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Abstract Objective: To describe the speech pattern of patients with hereditary Spastic Paraplegia type 4 (SPG4) and correlated it with their clinical data. Methods: Cross-sectional study was carried out in two university hospitals in Brazil. Two groups participated in the study: the case group (n = 28) with a confirmed genetic diagnosis for SPG4 and a control group (n = 17) matched for sex and age. The speech assessment of both groups included: speech task recording, acoustic analysis, and auditory-perceptual analysis. In addition, disease severity was assessed with the Spastic Paraplegia Rating Scale (SPRS). Results: In the auditory-perceptual analysis, 53.5% (n = 15) of individuals with SPG4 were dysarthric, with mild to moderate changes in the subsystems of phonation and articulation. On acoustic analysis, SPG4 subjects’ performances were worse in measurements related to breathing (maximum phonation time) and articulation (speech rate, articulation rate). The articulation variables (speech rate, articulation rate) are related to the age of onset of the first motor symptom. Conclusion: Dysarthria in SPG4 is frequent and mild, and it did not evolve in conjunction with more advanced motor diseases. This data suggest that diagnosed patients should be screened and referred for speech therapy evaluation and those pathophysiological mechanisms of speech involvement may differ from the length-dependent degeneration of the corticospinal tract.

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Abstract Objectives: Although miR-653-5p has been validated to participate in the progression of multiple types of cancer, the functional role of exosomal miR-653-5p derived from Mesenchymal Stem Cells (MSCs) in Laryngeal Papilloma (LP) has still remained elusive. Hence, this study aimed to investigate the role of MSCs-derived exosomal miR-653-5p in LP. Methods: LP tissues (n = 15) and adjacent normal tissues (n = 10) were collected to examine the expression level of miR-653-5p. The expression level of miR-653-5p in LP cells and normal cells was also detected. Then, miR-653-5p was overexpressed or silenced to explore its effects on the proliferation, migration, invasion, and apoptosis of LP cells. Thereafter, the effects of exosomal miR-653-5p derived from MSCs on LP cell progression and the potential regulatory mechanism of miR-653-5p were assessed. Results: It was revealed that the expression level of miR-653-5p was downregulated in LP tissues and cells. In addition, miR-653-5p suppressed the proliferation, migration, invasion, and apoptosis of LP cells. Exosomes derived from MSCs played a suppressive role in LP development and mediated the transmission of miR-653-5p to LP cells. Further exploration identified Basic leucine Zipper and W2 domains 2 (BZW2) as the target of miR-653-5p. More importantly, the rescue experiments revealed that MSCs-secreted exosomal miR-653-5p efficiently inhibited the aggressive phenotypes of LP cells, which could be significantly reversed by BZW2 overexpression in LP cells. Conclusion: MSCs-derived exosomal miR-653-5p exerted inhibitory effects on LP progression through targeting BZW2, which provided a novel idea for the therapy of LP. Clinical Trial registration number: chictr-ior-17011021.

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ABSTRACT Objectives: We examined the expression of Lnc-ZFAS1 in osteosarcoma and comprehensively evaluated its effects on osteosarcoma in vitro and vivo. Moreover, we revealed the regulatory mechanism between Lnc-ZFAS1 and miR-520b/miR-520e-mediated RHOC and provided a novel clue for ameliorating osteosarcoma. Method: The expression of Long non-coding RNA Zinc Finger Antisense 1 (LncRNA ZFAS1) osteosarcoma tissues and normal tissues in the TCGA database was analyzed. Then, LncRNA ZFAS1 expression was further verified in clinical samples and osteosarcoma cell lines (U2OS and KHOS), as well as the human osteoblast cell line hFOB1.19 by qRT-PCR. Thereafter, LncRNA ZFAS1 was overexpressed or silenced to explore its effects on cell proliferation, apoptosis, migration, invasion, and Epithelial-Mesenchymal Transition (EMT). The fundamental mechanism through which Lnc-ZFAS1 affects osteosarcoma progression was further investigated and verified. Results: We found that LncRNA ZFAS1 was upregulated in osteosarcoma, and Lnc-ZFAS1 overexpression facilitated osteosarcoma cells proliferation, migration, invasion and EMT, while Lnc-ZFAS1 silence exerted reverse influence. Mechanistically, Lnc-ZFAS1 functionally acted as a sponger of microRNA-520b (miR-520b) and micro-RNA-520e (miR-520e) to up-regulate Ras Homologue C (RHOC). In addition, depleted Lnc-ZFAS1 restrained osteosarcoma cells proliferation, migration, and invasion, which could be rescued by RHOC overexpression. Lnc-ZFAS1 was upregulated in osteosarcoma and Lnc-ZFAS1 could exert promoted impact upon osteosarcoma cells proliferation, migration, invasion, and EMT in vitro. Conclusions: Lnc-ZFAS1 acted sponger of miR-520b and miR-520e to promote RHOC, indicating that Lnc-ZFAS1/miR-520b/RHOC and Lnc-ZFAS1/miR-520e/RHOC axes might serve as potential therapeutic strategies against osteosarcoma.

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Abstract Objective: Familial Adenomatous Polyposis is a complex hereditary disease that exposes the carrier to a great risk of Colorectal Cancer (CRC). After prophylactic surgery, intra-abdominal desmoid tumors are known to be one the most important cause of death. Therefore, recognition of increased-risk patients and modification of operative strategy may be crucial. Aim: The objective of this study was to estimate the desmoid tumor risk in relation to various surgical and clinical variables. Methods: Patients who had undergone polyposis since 1958 were included in the study. After exclusion criteria were met, those who had developed desmoid tumors were selected to undergo further evaluation. Results: The study revealed that the risk of developing desmoid tumors was associated with various factors such as sex ratio, colectomy, and reoperations. On the other hand, the type of surgery, family history, and surgical approach did not affect the risk of developing desmoid tumors. The data collected from 146 polyposis patients revealed that 16% had desmoid polyps. The sex ratio was 7:1, and the median age at colectomy was 28.6 years. Family history, multiple abdominal operations, and reoperations were some of the characteristics that were common in desmoid patients. Conclusion: Recognition of clinical (female sex) and surgical (timing of surgery and previous reoperations) data as unfavorable variables associated with greater risk may be useful during the decision-making process.

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Abstract Objectives: Lung cancer was one of the most common malignancies around the world. It has great significance in to search for the mechanism of occurrence and development of lung cancer. LIM Domain Binding protein 2 (LDB2) belongs to the LIM-domain binding family, it can be used as a binding protein that combined with other transcription factors to form the transcription complex for regulating the expression of target genes. The expression of microRNA-96-5p (miR-96-5p) has been investigated in various tumors. The aim of this study is to investigate the potential role of LDB2 and miR-96-5p in lung cancer. Methods: Real-time quantitative PCR was applied to detect the expression of LDB2 and miR-96-5p. The proliferation, invasion, and metastasis of H1299 cells were analyzed by CCK8, transwell, and wound healing assay after LDB2 or miR-96-5p transfection. Luciferase activities assay and western blot were used to reveal the targeted regulation between LDB2 and miR-96-5p. Results: Here the authors found LDB2 was down-regulated in lung cancer tissues and negatively correlated with miR-96-5p expression, it could promote or inhibit the proliferation, invasion and metastasis of H1299 cells after LDB2 knockdown or overexpression and regulate the expression of cyclinD1, MMP9, Bcl-2, and Bax via ERK1/2 signaling pathway. Furthermore, miR-96-5p exerted its function by directly binding to 3′-UTR of LDB2 and regulating expression of LDB2. miR-96-5p could promote the proliferation, invasion, and metastasis of H1299 cells. Conclusion: These findings demonstrate that LDB2 can act as a new regulator to inhibit cell proliferation, invasion, and metastasis via the ERK1/2 signaling pathway, and miR-96-5p may be a potential promising molecular by targeting LDB2 in lung cancer.

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Abstract Purpose: The authors aimed to develop a Machine-Learning (ML) algorithm that can predict positive blood culture in the neonatal intensive care unit, using complete blood count and C-reactive protein values. Methods: The study was based on patients’ electronic health records at a tertiary neonatal intensive care unit in São Paulo, Brazil. All blood cultures that had paired complete blood count and C-reactive protein measurements taken at the same time were included. To evaluate the machine learning model’s performance, the authors used accuracy, Area Under the Receiver Operating Characteristics (AUROC), recall, precision, and F1-score. Results: The dataset included 1181 blood cultures with paired complete blood count plus c-reactive protein and 1911 blood cultures with paired complete blood count only. The f1-score ranged from 0.14 to 0.43, recall ranged from 0.08 to 0.59, precision ranged from 0.29 to 1.00, and accuracy ranged from 0.688 to 0.864. Conclusion: Complete blood count parameters and C-reactive protein levels cannot be used in ML models to predict bacteremia in newborns.

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Abstract Objectives: To compare variables of access to healthcare between the LGBT+ population aged 50 and over and those non-LGBT+. Methods: A cross-sectional study was carried out in Brazil through a confidential online questionnaire. The use of the health system was characterized by the number of preventive tests performed and measured by the PCATool-Brasil scale (a 10-point scale in which higher scores were associated with better assistance in healthcare). The association between being LGBT+ and access to health was analyzed in Poisson regression models. Results: 6693 participants (1332 LGBT+ and 5361 non-LGBT+) with a median age of 60 years were included. In the univariate analysis, it was observed not only lower scores on the PCATool scale (5.13 against 5.82, p < 0.001), but a greater proportion of individuals among those classified with the worst quintile of access to healthcare (< 4 points), 31% against 18% (p < 0.001). Being LGBT+ was an independent factor associated with worse access to health (PR = 2.5, 95% CI 2.04‒3.06). The rate of screening cancer, for breast, colon, and cervical cancer was also found to be lower in the LGBT+ population. Conclusion: Healthcare access and health service experiences were worse in the LGBT+ group than in their non-LGBT peers. Inclusive and effective healthcare public policies are essential to promote healthy aging for all.

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Abstract Objective: To evaluate inactivated CoronaVac prime vaccination, antibody decay, booster dose, and safety in ANCA-Associated Vasculitis (AAV) patients. Methods: Fifty-three AAV patients and 106 Controls (CG) received CoronaVac on days: D0 (first dose), D28(second dose), and D210 (booster dose, 32 AAV: 32 CG). The primary outcome was immunogenicity after the second vaccine dose (day 69) assessed by Seroconversion Rates (SC) of anti-SARS-CoV-2 S1/S2 IgG and Neutralizing Antibodies (NAb). Secondary outcomes were safety, immunogenicity (D28/D240), 6-months antibody decay (D210) and the booster dose response (D240). Results: At D69 SC (65.1% vs. 96.8%, p = 0.0001), GMT (21.3 UA/mL vs. 67.7 UA/mL, p < 0.001) and NAb- positivity (53.7% vs. 80.6%, p = 0.001) were moderate but lower in naïve-AAV patients than CG. Patients without SC used more often IS (93.3% vs. 53.3%, p = 0.015), mycophenolate mofetil (20% vs. 0%, p = 0.037) and prednisone (60.0% vs. 28.6%, p = 0.057) than seroconverted. NAb negativity in AAV patients was associated with prednisone treatment (57.9% vs. 18.2%, p = 0.015) and IS (84.2% vs. 55.0%, p = 0.046). Logistic regression analysis models showed that only prednisone was associated with lower seroconversion (OR = 0.2, 0,95% CI 0.05–0.86, p = 0.030) and with lower NAb positivity (OR = 0.2, 0,95% CI 0.05–0.88, p = 0.034). After six months (D69–D210) a decrease in IgG positivity occurred in 32 AAV patients (15.7%, p = 0.074) and 32 CG (18.7%, p = 0.041). For the NAb positivity, the 6-month decrease was not significant (p = 0.114) whereas a major reduction occurred for CG (p < 0.001). A booster dose (D240) resulted in an increment in IgG-positivity (21.9%, p = 0.023) and NAb-positivity (34.4%, p = 0.006) in AAV patients. No moderate/severe adverse events attributable to the vaccine were observed. Conclusion: This study provides novel data on the excellent safety and moderate immunogenicity of CoronaVac in AAV patients. A six-month mild antibody waning was observed with a good response to the booster dose, although levels remained lower than CG (CoronavRheum-NCT04754698).

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Abstract In Malignant Hilar Biliary Stricture (MHBS) palliative biliary drainage is a frequent strategy, improving the quality of life, reducing pruritus, loss of appetite and relieving cholangitis. The endoscopic approach is an effective, although challenging procedure. This study aimed to evaluate technical and clinical success rates of biliary drainage by ERCP. This is a retrospective study including all patients with MHBS referred to Instituto do Cancer do Hospital de São Paulo (ICESP) submitted to biliary drainage by ERCP, between January 2010 and December 2017. Multivariable logistic regression was performed to evaluate predictors of clinical failure, as total bilirubin levels, Bismuth classification, number of hepatic sectors drained and presence of cholangitis. In total, 82 patients presenting unresectable MHBS were included in this study. 58.5% female and 41.5% male, with a mean age of 60±13 years. Bismuth classification grades II, IIIA, IIIB and IV were noted in 23.2%, 15.9%, 14.6% and 46.3%, respectively. Technical and clinical success was achieved in 92.7% and 53.7% respectively. At multivariable logistic-regression analyses, Bismuth IV strictures were related to higher clinical failure rates when compared to other strictures levels, with an Odds Ratio of 5.8 (95% CI 1.28‒20.88). In conclusion, endoscopic biliary drainage for malignant hilar biliary stricture had a high technical success but suboptimal clinical success rate. Proximal strictures (Bismuth IV) were associated with poor drainage outcomes.

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Abstract Introduction: The association of diabetes with subclinical thyroid diseases may increase the risk of cardiovascular diseases. We analyzed the association of subclinical hypothyroidism, diabetes, and both diseases with carotid Intima-Media Thickness (cIMT) as a surrogate maker for early cardiovascular disease in the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil). Methods: Cross-sectional analysis with data from the 3rd visit (2017‒2019). Linear regression models were used to evaluate the association of subclinical hypothyroidism, diabetes and of both diseases with a cIMT presented as Beta (95% Confidence Interval – 95% CI) without adjustment, with adjustment for sociodemographic variables (Model 1) and multivariable adjustment (Model 1 more cardiovascular risk factors). We also used logistic regression models to analyze the Odds Ratio (OR) and 95% CI for the association of both diseases using cIMT > P75%. Results: After the exclusion of patients with previous cardiovascular disease, 5,077 participants with no diseases, 1578 with diabetes, 662 with subclinical hypothyroidism, and 234 with both diseases were included in the analysis. Linear regression models showed an association of cIMT with only diabetes (β = 0.019; 95% CI 0.012 to 0.027; p < 0.0001) and subclinical hypothyroidism more diabetes (β = 0.03; 95% CI 0.010‒0.047, p < 0.0001). The logistic regression model reported an association between diabetes and CIMT higher than P75% (OR = 1.49, 95% CI 1.30‒1.71). No interaction between diabetes and subclinical hypothyroidism was detected using cIMT respectively as a continuous (p = 0.29) or as a categorical variable (p = 0.92). Discussion: Diabetes was associated with higher cIMT values. However, no additive effect of subclinical hypothyroidism associated with diabetes over cIMT was detected.

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Abstract FOXO3a dysregulation is frequently implicated in tumorigenesis, and its inhibition can occur by several molecular mechanisms. Among these, post-transcriptional suppression by miRNAs has been associated with various cancers initiation. Here, we assessed the expression profiles of the most relevant miRNAs for breast tumorigenesis, using Luminal A (LA) and Triple-Negative (TN) breast cancer from Brazilian patients, by the quantitative real time-PCR method. Their potential prognostic role for the patients was also evaluated. We identified the miRNAs miR-96-5p and miR-182-5p, de-scribed as negative regulators of FOXO3A, with differential expression both in LA and TN tumors when compared to normal tissue. The miR-96-5p and miR-182-5p miRNAs were upregulated in LA (7.82 times, p < 0.005; 6.12 times, p < 0.005, respectively) and TN breast cancer samples (9.42 times, p < 0.0001; 8.51 times, p < 0.0001) compared to normal tissues. The samples with higher miR-96-5p and miR-182-5p expression (FR ≥ 4) were submitted for FOXO3a immunostaining. Reduced protein detection was observed in all of the tumors compared to normal tissues. The most prominent miRNA expression and FOXO3a protein suppression were observed in TN samples (p < 0.001), indicating the relevant role of these molecules in this tumor biology and clinical behavior. Our results corroborate the literature regarding to the relevance of FOXO3a in the breast cancer, and they open new perspectives for alternative target therapy options for Brazilian patients expressing both FOXO3a and its regulatory miRNAs.

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Abstract Objective: This study monitors trends in access to cancer screening, focusing on mammography, Papanicolaou (Pap smear), and Prostate-Specific Antigen (PSA), assessing the magnitude of inequality in the city of São Paulo from 2003 to 2015 according to education level. Method: This is a cross-sectional population-based study conducted with data from the 2003, 2008, and 2015 editions of the Health Survey of the City of São Paulo (ISA-Capital). Outcome variables were the proportion of mammography, Papanicolaou (Pap smear), and Prostate-Specific Antigen (PSA) tests according to the protocols. Inequality was measured by education level according to years of study. For static analysis, Poisson regression was used to estimate proportion ratios. Results: The proportion of Pap smears remained stationary at a high level (>89%) throughout the study period, while access to mammography and PSA tests significantly increased in the 2003–2015 period. The present results indicate inequalities in access to cancer screening due to education, and being more expressive for mammography and PSA tests. However, this inequality significantly decreased over the period analyzed comparing the most educated individuals with those with the lowest educational level. In addition, an increase in the proportion of tests performed in the Brazilian Unified Health System was identified, especially for mammography and PSA tests, in the period 2003–2015. Conclusions: The inequalities observed in the access to preventive exams were influenced by the level of education. The offer of exams was expanded, more significantly for mammography and PSA, especially among the less educated group.

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Objective: Amygdala has been demonstrated as one of the brain sites involved in the control of cardiorespiratory functioning. The structural and physiological alterations induced by epileptic activity are also present in the amygdala and reflect functional changes that may be directly associated with a sudden unexpected death. Seizures are always associated with neuronal damage and changes in the expression of cation-chloride cotransporters and Na/K pumps. In this study, the authors aimed to investigate if these changes are present in the amygdala after induction of status epilepticus with pilocarpine, which may be directly correlated with Sudden Unexpected Death in Epilepsy (SUDEP). Methods: Pilocarpine-treated wistar rats 60 days after Status Epilepticus (SE) were compared with control rats. Amygdala nuclei of brain slices immunostained for NKCC1, KCC2 and α1-Na+/K+-ATPase, were quantified by optical densitometry. Results: The amygdaloid complex of the animals submitted to SE had no significant difference in the NKCC1 immunoreactivity, but KCC2 immunoreactivity reduced drastically in the peri-somatic sites and in the dendritic-like processes. The α1-Na+/K+-ATPase peri-somatic immunoreactivity was intense in the rats submitted to pilocarpine SE when compared with control rats. The pilocarpine SE also promoted intense GFAP staining, specifically in the basolateral and baso-medial nuclei with astrogliosis and cellular debris deposition. Interpretation: The findings revealed that SE induces lesion changes in the expression of KCC2 and α1-Na + /K + -ATPase meaning intense change in the chloride regulation in the amygdaloid complex. These changes may contribute to cardiorespiratory dysfunction leading to SUDEP.

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Abstract Purpose: To explore differences in the changes of clinical and CT manifestations related to liver abscess before and after CT-guided interventional therapy between patients with and without Diabetes Mellitus (DM). Materials and methods: Fifty-eight consecutive patients with liver abscesses were retrospectively enrolled in this study. All patients underwent upper abdominal contrast-enhanced CT scans before and after CT-guided interventional therapy. They were divided into two groups including the DM group (n = 30) and the Non-DM group (n = 28) if the liver abscess occurred in patients with and without DM, respectively. The changes in the clinical and CT manifestations related to liver abscess after CT-guided interventional therapy in both groups were statistically analyzed. Results: After CT-guided interventional therapy, the length of hospital stay, white blood cell recovery time and drainage tube removal time in the DM group were longer than in the Non-DM group (all p-values < 0.05). The incidence of postoperative complications in the DM group was higher than in the Non-DM group (p < 0.05). As shown on CT, the postoperative reduced percentage of maximum diameter of abscess cavity and the reduction rate of edema band surrounding the liver abscess in the DM group were smaller than in the Non-DM group (both p-values < 0.05). The time intervals of the previous characteristic changes on CT before and after interventional therapy in the DM group were longer than in the Non-DM group (all p-values < 0.05). Conclusions: The liver abscesses patients with DM could not have a faster recovery and better therapeutic effect than those without DM after the CT-guided interventional therapy.

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Abstract Objective: To assess factors associated with emotional changes and Hyperactivity/Inattention (HI) motivated by COVID-19 quarantine in adolescents with immunocompromising diseases. Methods: A cross-sectional study included 343 adolescents with immunocompromising diseases and 108 healthy adolescents. Online questionnaires were answered including socio-demographic data and self-rated healthcare routine during COVID-19 quarantine and validated surveys: Strengths and Difficulties Questionnaire (SDQ), Pittsburgh Sleep Quality Index (PSQI), Pediatric Quality of Life Inventory 4.0 (PedsQL4.0). Results: The frequencies of abnormal emotional SDQ scores from adolescents with chronic diseases were similar to those of healthy subjects (110/343 [32%] vs. 38/108 [35%], p = 0.548), as well as abnormal hyperactivity/inattention SDQ scores (79/343 [23%] vs. 29/108 [27%], p = 0.417). Logistic regression analysis of independent variables associated with abnormal emotional scores from adolescents with chronic diseases showed: female sex (Odds Ratio [OR = 3.76]; 95% Confidence Interval (95% CI) 2.00–7.05; p < 0.001), poor sleep quality (OR = 2.05; 95% CI 1.08–3.88; p = 0.028) and intrafamilial violence during pandemic (OR = 2.17; 95% CI 1.12–4.19; p = 0.021) as independently associated with abnormal emotional scores, whereas total PedsQL score was inversely associated with abnormal emotional scores (OR = 0.95; 95% CI 0.93–0.96; p < 0.0001). Logistic regression analysis associated with abnormal HI scores from patients evidenced that total PedsQL score (OR = 0.97; 95% CI 0.95–0.99; p = 0.010], changes in medical appointments during the pandemic (OR = 0.39; 95% CI 0.19–0.79; p = 0.021), and reliable COVID-19 information (OR = 0.35; 95% CI 0.16–0.77; p = 0.026) remained inversely associated with abnormal HI scores. Conclusion: The present study showed emotional and HI disturbances in adolescents with chronic immunosuppressive diseases during the COVID-19 pandemic. It reinforces the need to promptly implement a longitudinal program to protect the mental health of adolescents with and without chronic illnesses during future pandemics.

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Abstract Context: Many studies show the importance of evaluating the adaptation time of subjects in a virtual driving environment, looking forwards to a response as closest as a possible real vehicle. Objectives: This study aimed to identify and analyze the adaptation to the driving simulator in older adults and middle-aged adults with and without a distraction, and a secondary aim was to identify predictors of safe performance for older adults’ drives. Design: Male and female middle-aged adults (n = 62, age = 30.3 ± 7.1 years) and older adults (n = 102, age = 70.4 ± 5.8 years) were evaluated for braking time performance in a driving simulator; cognition performance assessment included the Mini-Mental State Examination; motor evaluation included ankle flexor muscle strength with the isokinetic dynamometer and handgrip strength; the postural balance was evaluated with Timed Up and Go test, with and without a cognitive distraction task. Results: Older adults (men and women) and middle-aged adult women require more time to adapt to the driving simulator. The distractor increases the adaptation time for all groups. The main predictors of braking time for older women are age, muscle strength, and postural balance associated with distraction, and for older men, muscle strength. Conclusions: Age, sex, and distractor interfere in the adaptation of the virtual task of driving in a simulator. The evaluation model developed with multi-domains demonstrated the ability to predict which skills are related to braking time with and without the presence of the distractor.

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Abstract Objective: Identify the one-year survival rate and major complications in patients submitted to pneumonectomy for infectious disease. Methods: Retrospective data from all cases of infectious disease pneumonectomy over the past 10 years were collected from two reference centers. The authors analyzed: patient demographics, etiology, laterality, bronchial stump treatment, presence of previous pulmonary resection, postoperative complications in the first 30 days, the treatment used in pleural complications, and one-year survival rate. Results: 56 procedures were performed. The average age was 44 years, with female predominance (55%). 29 cases were operated on the left side (51%) and the most frequent etiology was post-tuberculosis (51.8%). The overall incidence of complications was 28.6% and the most common was empyema (19.2%). Among empyema cases, 36.3% required pleurostomy, 27.3% required pleuroscopy and 36.3% underwent thoracoplasty for treatment. Bronchial stump fistula was observed in 10.7% of cases. From all cases, 16.1% were completion pneumonectomies and 62.5% of these had some complication, a significantly higher incidence than patients without previous surgery (p = 0.0187). 30-day in-hospital mortality was (7.1%) with 52 cases (92.9%) and 1-year survival. The causes of death were massive postoperative bleeding (1 case) and sepsis (3 cases). Conclusions: Pneumonectomy for benign disease is a high-risk procedure performed for a variety of indications. While morbidity is often significant, once the perioperative risk has passed, the one-year survival rate can be very satisfying in selected patients with benign disease.

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Abstract Objective: To investigate the safety and efficacy of short-term (7-day) Dual Antiplatelet Therapy (DAPT) with intensive rosuvastatin in Acute Ischemic Stroke (AIS). Methods: In this study, patients with AIS in the emergency department of the hospital from October 2016 to December 2019 were registered and divided into the control group (Single Antiplatelet Therapy [SAPT] + rosuvastatin) and the study group (7-day DAPT + intensive rosuvastatin) according to the therapy regimens. The generalized linear model was used to compare the National Institute of Health Stroke Scale (NIHSS) scores between the two groups during the 21-day treatment. A Cox regression model was used to compare recurrent ischemic stroke, bleeding events, Statin-Induced Liver Injury (SILI), and Statin-Associated Myopathy (SAM) between the two groups during the 90-day follow-up. Results: Comparison of NIHSS scores after 21-day treatment: NIHSS scores in the study group decreased significantly, 0.273-times as much as that in the control group (Odds Ratio [OR] 0.273; 95% Confidence Interval [95% CI] 0.208–0.359; p < 0.001). Comparison of recurrent ischemic stroke during the 90-day follow-up: The therapy of the study group reduced the risk of recurrent stroke by 65% (7.76% vs. 22.82%, Hazard Ratio [HR] 0.350; 95% CI 0.167–0.730; p = 0.005). Comparison of bleeding events: There was no statistical difference between the two groups (7.79% vs. 6.71%, HR = 1.076; 95% CI 0.424–2.732; p = 0.878). No cases of SILI and SAM were found. Conclusions: Short-term DAPT with intensive rosuvastatin effectively relieved the clinical symptoms and significantly reduced the recurrent stroke for patients with mild-to-moderate AIS within 90 days, without increasing bleeding events, SILI and SAM.

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ABSTRACT Objective: The tyrosine-protein kinase inhibitor, genistein, can inhibit cell malignant transformation and has an antitumor effect on various types of cancer. It has been shown that both genistein and KNCK9 can inhibit colon cancer. This research aimed to investigate the suppressive effects of genistein on colon cancer cells and the association between the application of genistein and KCNK9 expression level. Methods: The Cancer Genome Atlas (TCGA) database was used to study the correlation between the KCNK9 expression level and the prognosis of colon cancer patients. HT29 and SW480 colon cancer cell lines were cultured to examine the inhibitory effects of KCNK9 and genistein on colon cancer in vitro, and a mouse model of colon cancer with liver metastasis was established to verify the inhibitory effect of genistein in vivo. Results: KCNK9 was overexpressed in colon cancer cells and was associated with a shorter Overall Survival (OS), a shorter Disease-Specific Survival (DFS), and a shorter Progression-Free Interval (PFI) of colon cancer patients. In vitro experiments showed that downregulation of KCNK9 or genistein application could suppress cell proliferation, migration, and invasion abilities, induce cell cycle quiescence, promote cell apoptosis, and reduce epithelialmesenchymal transition of the colon cancer cell line. In vivo experiments revealed that silencing of KCNK9 or application of genistein could inhibit hepatic metastasis from colon cancer. Additionally, genistein could inhibit KCNK9 expression, thereby attenuating Wnt/β-catenin signaling pathway. Conclusion: Genistein inhibited the occurrence and progression of colon cancer through Wnt/β-catenin signaling pathway that could be mediated by KCNK9.

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ABSTRACT Introduction: The exponential growth of telehealth services during the COVID-19 pandemic led to the implementation of a telemedicine care service in a tertiary university pediatric hospital. It brought the need to develop a training aimed at remote care within the pediatric emergency rotation program. Objective: To describe the implementation of a telemedicine training for pediatric residents and present the preliminary results. Methods: Descriptive prospective study (pre and post), with 40 resident physicians of the first year of pediatrics. Reaction Assessments were applied before and after training, in addition to a resident physician perception questionnaire at the end of the training. Results: There was a significant difference in the resident’s perception of experience and safety after initial training. Most rated the proposal as good or excellent, considered teaching telemedicine relevant and that this experience contributed to their learning on the subject. Conclusion: This study describes an innovative proposal for training in telemedicine. The preliminary results were encouraging, demonstrating the program’s potential in training future pediatricians.

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ABSTRACT Background: Proximal humeral fractures can progress to osteonecrosis of the humeral head. Hertel developed a binary classification system (12 subtypes) and demonstrated that some patterns have more risk to develop osteonecrosis. Hertel described the prevalence and the risk factors for Humeral head osteonecrosis after osteosynthesis using a Deltopectoral approach. Few studies have evaluated the prevalence and the capacity of Hertel’s classification to predict Humeral Head osteonecrosis following osteosynthesis of proximal Humeral fractures through the anterolateral approach. The objectives of this study were to correlate osteonecrosis predictors established by the Hertel classification with the risk of developing osteonecrosis and its prevalence after osteosynthesis using the anterolateral approach. Methods: This was a retrospective study of patients who underwent osteosynthesis of proximal humerus fractures using an anterolateral approach. Patients were divided into two groups: high risk for necrosis (group 1) and low risk for necrosis (group 2) according to Hertel’s criteria. The overall prevalence of osteonecrosis and the prevalence in each group were calculated. A radiological examination was performed in the true anteroposterior (Grashey), scapular, and axillary views, before and after the operation (minimum 1 year after surgery). A KaplanMeier curve was used to assess the pattern of the temporal evolution of osteonecrosis. The groups were compared using the Chi-square test or Fisher’s exact test. The unpaired t-test (parametric variables - age) and the MannWhitney test (non-parametric time between trauma and surgery) were used. Results: In total, 39 patients were evaluated. The postoperative follow-up time was 14.5 ± 3.3 months. The time to onset of necrosis was 14.1 ± 3.9 months. Sex, age, and time between trauma and surgery did not influence the risk of necrosis. Type 2, 9, 10, 11, and 12, or fractures with posteromedial head extension less than or equal to 8 mm, or diaphysis deviation greater than 2 mm, as well as grouping did not influence the risk for osteonecrosis. Conclusions: Hertel’s criteria were not able to predict the development of osteonecrosis after osteosynthesis of proximal humerus fractures performed through the anterolateral approach. The total prevalence of osteonecrosis was 17.9% with a tendency toward an increased incidence after 1 year of surgical treatment.

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ABSTRACT Objectives: To analyze the perinatal outcomes of Perinatally acquired HIV Infection (PHIV) in pregnant women. Method: This retrospective cohort study included singleton pregnancies in Women Living with HIV (WLH) between 2006 and 2019. Patient charts were revised, and maternal characteristics, type of HIV infection (perinatal vs. behavioral), Antiretroviral Therapy (ART) exposure, and obstetric and neonatal outcomes were assessed. The HIV-related aspects considered were: Viral Load (VL), CD4+ cell count, opportunistic infections, and genotype testing. Laboratory analyses were performed at baseline (first appointment) and 34 weeks of gestation. Results: There were 186 WLH pregnancies, and 54 (29%) patients had PHIV. Patients with PHIV were younger (p < 0.001), had less frequently stable partnerships (p < 0.001), had more commonly serodiscordant partners (p < 0.001), had a longer time on ART (p < 0.001), and had lower rates of undetectable VL at baseline (p = 0.046) and at 34 weeks of gestation (p < 0.001). No association was observed between PHIV and adverse perinatal outcomes. Among patients with PHIV, third trimester anemia was associated with preterm birth (p = 0.039). Genotype testing was available only for 11 patients with PHIV, who presented multiple mutations related to ART resistance. Conclusions: PHIV did not seem to increase the risk of adverse perinatal outcomes. However, PHIV pregnancies have a higher risk of viral suppression failure and exposure to complex ARTs.

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Abstract Objectives: The incidence of cerebellar Glioblastoma Multiforme (cGBM) is rare. Database like TCGA have not distinguish cGBM from GBM, our knowledge on cGBM gene expression characteristics is limited. The expression status of Oligodendrocyte Lineage Transcription factor 2 (OLIG2) and its clinical significance in cGBM is still unclear. Methods: The clinical data and tissue specimens of 73 cGBM patients were retrospectively studied. The association between OLIG2 expression level and the demographic characteristics of cGBM patients was identified by the Chi-Square test. The survival curves were drawn by Kaplan-Meier analysis. The independent prognostic factors was calculated according to Cox regression analysis. Results: The OLIG2 high expression was observed in about 57.5% (42/73) of the cGBM patients. Patients with high OLIG2 expression levels had a higher alive ratio at the end of follow-up (alive ratio: 70.6% vs. 29.4%, p = 0.04). The median survival time was 21 months and 13 months for high and low expression of OLIG2 (p < 0 .05). Univariate analysis and Multivariate analysis indicated that EOR (HR = 3.89, 95% CI 1.23−12.26, p = 0.02), low OLIG2 expression (HR = 5.26, 95% CI 1.13−24.59, p = 0.04), and without adjuvant therapy (HR = 4.95, 95% CI 1.22−20.00, p = 0.03) were independent risk factors for the OS of cGBM patients. Conclusion: High expression level of OLIG2 could be used as an independent favorable prognosis indicator in cGBM patients and be recognized as a characteristic biomarker of cGBM.

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Abstract Objective: To explore the changes and clinical significance of serum Neuron-Specific Enolase (NSE) and Squamous Cell Carcinoma antigen (SCC) in patients with lung cancer before and after radiotherapy. Methods: 82 patients with lung cancer were treated with radiotherapy, and effective clinical intervention was given during the radiotherapy process. The patients were followed up for 1 year after radiotherapy and were divided into a recurrence and metastasis group (n = 28) and a non-recurrence and metastasis group (n = 54) according to their prognosis. Another 54 healthy volunteers examined in the present study’s hospital during the same period were selected as the control group. To compare the changes of NSE and SCC levels in serum in patients with lung cancer at admission and after radiotherapy, and to explore their clinical significance. Results: After intervention, NSE and SCC levels in the serum of the two groups of patients were significantly lower than those before intervention, and the levels of CD4+ and CD4+/CD8+ were significantly higher than those before intervention (p < 0.05); the level of CD8+ was not significantly different from that before intervention (p > 0.05). And NSE and SCC levels in the intervention group were significantly lower than those in the routine group, the levels of CD4+, CD4+/CD8+ were significantly higher than those in the routine group (p < 0.05). Conclusion: NSE and SCC in serum can preliminarily evaluate the effect of radiotherapy in patients with lung cancer and have a certain predictive effect on prognosis.

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Abstract Context: Transtibial Amputation (TA) predisposes to a sedentary lifestyle. Objectives: To evaluate the efficiency of a short-term (8-week) Concurrent Training (CT) program in Unilateral Transtibial Amputees (UTA) and to compare it with the physical condition of a group of Paralympic athletes in preparation for the Rio de Janeiro Paralympics. Design: This was a longitudinal, prospective and controlled trial study. Methods: Thirty-four male subjects with UTA and using prostheses for six months or more were selected for this study. They were divided into two groups: Group 1 (G1) – 17 non-athlete and untrained UTA and Group 2 (G2) – 17 paralympic athletes with active UTA in the training phase. G1 was evaluated before and after eight weeks of CT and G2 made a single evaluation for control. All were submitted to anamnesis, clinical evaluation (blood pressure, electrocardiogram, and heart rate) and cardiopulmonary exercise testing on a lower limb cycle ergometer, and isokinetic knee dynamometry. The CT of G1 included resistance exercise and aerobic interval training on a stationary bicycle and G2 followed the training of the Paralympic teams. Results: Patients were retested by the same methods after CT. The two most important central dependent variables (maximal oxygen uptake and muscular strength) increased by 22% and knee extensor and flexor strength by 106% and 97%, respectively. Conclusion: After eight weeks of CT, there was an improvement in general functional condition, muscle strength, and cardiorespiratory performance improving protection against chronic diseases and quality of life.

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Abstract Objective: Nasopharyngeal Carcinoma (NPC) is lethal cancer. Typically, relapse and metastasis are the outcomes of most patients. Against this backdrop, this study aimed to investigate the correlation between Circulating Tumor Cell (CTC) profiles and clinicopathological features in patients with NPC. Patients and methods: A total of 119 blood samples from 79 patients were collected from patients with NPC during treatment. CanPatrol™ CTC enrichment and RNA In Situ Hybridization (RNA-ISH) were used to characterize CTCs, including epithelial, Mesenchymal (MCTCs), and epithelial/mesenchymal mixed types according to their surface markers. Results: The number of CTCs and MCTCs in the pre-treatment group was significantly higher than that in the post-treatment group (p < 0.05). The total number of CTCs and MCTCs cell numbers was significant correlation with Tumor-Node-Metastasis (TNM) staging (p < 0.05), Progression-Free Survival (PFS), and Overall Survival (OS). The PFS of patients with > 7 CTCs or > 5 MCTCs per 5 mL blood was significantly shorter PFS than those patients with ≤ 7 CTCs or ≤ 5 MCTCs (p < 0.05). Patients treated with targeted therapy combined with chemoradiother-apy had poorer PFS and OS rates than those treated with chemoradiotherapy (p < 0.05). The Kaplan-Meier survival analysis also demonstrated that patients with changes in CTC > 4 were strongly associated with PFS and OS rates (p < 0.05). Conclusion: CTC and MCTC number detection in patients with NPC is a useful biomarker for predicting patient progress. Patients with more than 7 CTCs or 5 MCTCs in 5 mL of blood had shorter PFS and OS rates. CTC and MCTC count changes were also significantly associated with the patient’s therapy.

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Abstract Background: Elderly patients are more susceptible to Coronavirus Disease-2019 (COVID-19) and are more likely to develop it in severe forms, (e.g., Acute Respiratory Distress Syndrome [ARDS]). Prone positioning is a treatment strategy for severe ARDS; however, its response in the elderly population remains poorly understood. The main objective was to evaluate the predictive response and mortality of elderly patients exposed to prone positioning due to ARDS-COVID-19. Methods: This retrospective multicenter cohort study involved 223 patients aged ≥ 65 years, who received prone position sessions for severe ARDS due to COVID-19, using invasive mechanical ventilation. The PaO2/FiO2 ratio was used to assess the oxygenation response. The 20-point improvement in PaO2/FiO2 after the first prone session was considered for good response. Data were collected from electronic medical records, including demographic data, laboratory/image exams, complications, comorbidities, SAPS III and SOFA scores, use of anticoagulants and vasopressors, ventilator settings, and respiratory system mechanics. Mortality was defined as deaths that occurred until hospital discharge. Results: Most patients were male, with arterial hypertension and diabetes mellitus as the most prevalent comorbidities. The non-responders group had higher SAPS III and SOFA scores, and a higher incidence of complications. There was no difference in mortality rate. A lower SAPS III score was a predictor of oxygenation response, and the male sex was a risk predictor of mortality. Conclusion: The present study suggests the oxygenation response to prone positioning in elderly patients with severe COVID-19-ARDS correlates with the SAPS III score. Furthermore, the male sex is a risk predictor of mortality.

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Abstract Objectives: This study aimed to explore the effects of bone marrow-derived Mesenchymal Stem Cell-Conditioned Medium (MSC-CM) treating diabetic foot ulcers in rats. Methods: Models of T2DM rats were induced by a high-fat diet and intraperitoneal injection of STZ in SD rats. Models of Diabetic Foot Ulcers (DFUs) were made by operation on hind limbs in diabetic rats. Rats were divided into four groups (n = 6 for each group), i.e., Normal Control group (NC), Diabetes Control group (DM-C), MSC-CM group and Mesenchymal Stem Cells group (MSCs). MSC-CM group was treated with an injection of conditioned medium derived from preconditioned rats’ bone marrow MSCs around ulcers. MSCs group were treated with an injection of rats’ bone marrow MSCs. The other two groups were treated with an injection of PBS. After the treatment, wound closure, re-epithelialization (thickness of the stratum granulosums of the skin, by H&E staining), cell proliferation (Ki67, by IHC), angiogenesis (CD31, by IFC), autophagy (LC3B, by IFC and WB; autoly-sosome, by EM) and pyroptosis (IL-1β, NLRP3, Caspase-1, GSDMD and GSDMD-N, by WB) in ulcers were evaluated. Results: After the treatment wound area rate, IL-1β by ELISA, and IL-1β, Caspase-1, GSDMD and GSDMD-N by WB of MSC-CM group were less than those of DM group. The thickness of the stratum granulosums of the skin, proliferation index of Ki67, mean optic density of CD31 and LC3B by IFC, and LC3B by WB of MSC-CM group were more than those of DM group. The present analysis demonstrated that the injection of MSC-CM into rats with DFUs enhanced the wound-healing process by accelerating wound closure, promoting cell proliferation and angiogenesis, enhancing cell autophagy, and reducing cell pyroptosis in ulcers. Conclusions: Studies conducted indicate that MSC-CM administration could be a novel cell-free therapeutic approach to treat DFUs accelerating the wound healing process and avoiding the risk of living cells therapy.

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Abstract Introduction: Optimized allocation of medical resources to patients with COVID-19 has been a critical concern since the onset of the pandemic. Methods: In this retrospective cohort study, the authors used data from a Brazilian tertiary university hospital to explore predictors of Intensive Care Unit (ICU) admission and hospital mortality in patients admitted for COVID-19. Our primary aim was to create and validate prediction scores for use in hospitals and emergency departments to aid clinical decisions and resource allocation. Results: The study cohort included 3,022 participants, of whom 2,485 were admitted to the ICU; 1968 survived, and 1054 died in the hospital. From the complete cohort, 1,496 patients were randomly assigned to the derivation sample and 1,526 to the validation sample. The final scores included age, comorbidities, and baseline laboratory data. The areas under the receiver operating characteristic curves were very similar for the derivation and validation samples. Scores for ICU admission had a 75% accuracy in the validation sample, whereas scores for death had a 77% accuracy in the validation sample. The authors found that including baseline flu-like symptoms in the scores added no significant benefit to their accuracy. Furthermore, our scores were more accurate than the previously published NEWS-2 and 4C Mortality Scores. Discussion and conclusions: The authors developed and validated prognostic scores that use readily available clinical and laboratory information to predict ICU admission and mortality in COVID-19. These scores can become valuable tools to support clinical decisions and improve the allocation of limited health resources.

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Abstract Objectives: To evaluate the inconsistency between clinical diagnosis of death and autopsy findings in adolescents with chronic diseases. Methods: A cross-sectional study including a sample of adolescents’ autopsies who died in a pediatric and adolescent tertiary hospital over 18 consecutive years. During this period, there were n = 2912 deaths, and n = 581/2912(20%) occurred in adolescents. Of these, n = 85/581(15%) underwent autopsies and were analyzed. Further results were divided into two groups: Goldman classes I or II (high disagreement between main clinical diagnosis of death and anatomopathological findings, n = 26) and Goldman classes III, IV or V (low or no disagreement between these two parameters, n = 59). Results: Median age at death (13.5 [10‒19] vs. 13 [10‒19] years, p = 0.495) and disease duration (22 [0‒164] vs. 20 [0‒200] months, p = 0.931), and frequencies for males (58% vs. 44%, p = 0.247) were similar between class I/II vs. class III/IV/V. The frequency of pneumonia (73% vs. 48%, p = 0.029), pulmonary abscess (12% vs. 0%, p = 0.026), as well as isolation of yeast (27% vs. 5%, p = 0.008), and virus (15% vs. 2%, p = 0.029) identified in the autopsy, were significantly higher in adolescents with Goldman class I/II compared to those with Goldman class III/IV/V. In contrast, cerebral edema was significantly lower in adolescents of the first group (4% vs. 25%, p = 0.018). Conclusion: This study showed that 30% of the adolescents with chronic diseases had major discrepancies between clinical diagnosis of death and autopsy findings. Pneumonia, pulmonary abscess, as well as isolation of yeast and virus were more frequently identified at autopsy findings in the groups with major discrepancies.

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Abstract Objective: To analyze aspects of sexual life and fertility desire among 46, XY DSD people, including those who changed their gender. Methods: It is a cross-sectional study including 127 adults (> 16 years of age) with 46, XY DSD (83 females; 44 males) from a Single Brazilian Tertiary-Care Medical Center. Results: Sexual fantasies and masturbation were more frequent in 46, XY DSD males, whereas orgasm and sexual life satisfaction were similar in both genders. More 46, XY DSD men than women had a long-term romantic relationship. 46, XY DSD women with prenatal androgen exposure reported more fear of being romantically rejected. External genitalia appearance at birth did not impact the sexuality of 46, XY DSD women after surgical genital treatment had been completed. Overall, the sexual life was similar between 46, XY men assigned as males and those who changed to the male gender. Regarding sexual orientation, most self-reported as heterosexual (91% and 92% of women and men, respectively). The desire for fertility had a similar prevalence in both genders, but more women than men considered infertility a barrier to a long-term romantic relationship. Twelve individuals (7 males) had children; 10 out of 12 have adopted children. Conclusion: Fertility desire was shared among 46, XY DSD people, regardless of gender. Prenatal androgen exposure reduced the desire for motherhood in 46, XY women. 46, XY DSD people who changed from female to male gender presented similar sexual parameters as those assigned as males. Among females, virilized genitalia at birth did not affect sexuality once the surgical treatment is completed.

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Abstract Introduction: Crohn’s disease (CD) has been related to an increased prevalence of psychiatric disorders and suicide risk (SR). However, the nature of their relationship still deserves clarification. The aim of this study is to assess the prevalence of major depressive disorder (MDD) in patients with CD, and to investigate the relationship between MDD and CD outcomes. Methods: A cross-sectional study involving CD patients was performed. CD activity was evaluated by the Harvey-Bradshaw index and CD phenotype by the Montreal classification. The presence of MDD was assessed by the Patient Health Questionnaire score-9 (PHQ-9). Sociodemographic data and other characteristics were retrieved from electronic medical records. Results: 283 patients with CD were included. The prevalence of MDD was 41.7%. Females had a risk of MDD 5.3 times greater than males. CD disease duration was inversely correlated with MDD severity. Individuals with active CD were more likely to have MDD (OR = 796.0; 95% CI 133.7‒4738.8) than individuals with CD remission. MDD was more prevalent in inflammatory behavior (45.5%) and there were no statistical differences regarding the disease location. 19.8% of the sample scored positive for SR. Conclusion: The present results support data showing an increased prevalence of MDD in individuals with CD. Additionally, it indicates that MDD in CD might be related to the activity of CD. Prospective studies are warranted to confirm these results and to address whether MDD leads to CD activity, CD activity leads to MDD or both ways are existent.

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Abstract Objective: To explore whether the effect of β-catenin on MI and MI-induced cardiomyocyte apoptosis is YAP-dependent. Methods: The authors established an MI rat model by ligating the anterior descending branch of the left coronary artery, and an MI cell model by treating cardiomyocytes with H2O2. Results: β-catenin downregulation was observed in MI cardiac tissues and in H2O2-treated cardiomyocytes. Lentiviral-CTNNB1 was administered to MI rats to upregulate β-catenin expression in MI cardiac tissue. β-catenin recovery reduced the myocardial infarct area, fibrosis, and apoptotic cell death in MI rats. H2O2 treatment attenuated cell viability and induced cell death in cardiomyocytes, whereas β-catenin overexpression partially reversed these changes. Moreover, H2O2 treatment caused the deactivation of Yes-Associated Protein (YAP), as detected by increased YAP phosphorylation and reduced the nuclear localization of YAP. Upregulation of β-catenin expression reactivated YAP in H2O2-treated cardiomyocytes. Reactivation of YAP was achieved by administration of Mitochonic Acid-5 (MA-5) to H2O2-treated cardiomyocytes, and deactivation of YAP by CIL56 treatment in β-catenin-overexpressing H2O2-treated cardiomyocytes. MA-5 administration increased cell viability and repressed apoptosis in H2O2-treated cardiomyocytes, whereas CIL56 treatment counteracted the effects of β-catenin overexpression on cell survival and apoptosis. Conclusions: The present data indicate that β-catenin and YAP are effective treatment targets for MI, blocking the apoptotic death of cardiomyocytes.

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Abstract Objectives: To determine the main clinical and demographic outcomes related to Pulmonary Hypertension (PH) and adverse obstetric and fetal/neonatal outcomes. Methods: This study retrospectively analyzed the medical record data of 154 patients with PH who were admitted to the Third Affiliated Hospital of Guangzhou Medical University between January 2011 and December 2020. Results: According to the severity of elevated Pulmonary Artery Systolic Pressure (PASP), 82 women (53.2%) were included in the mild PH group, 34 (22.1%) were included in the moderate PH group, and 38 (24.7%) were included in the severe PH group. There were significant differences in the incidence of heart failure, premature delivery, Very-Low-Birth-Weight (VLBW) infants, and Small-for-Gestational-Age (SGA) infants among the three PH groups (p < 0.05). Five (3.2%) women died within 7-days after delivery, 7 (4.5%) fetuses died in utero, and 3 (1.9%) neonates died. The authors found that PASP was an independent risk factor for maternal mortality. After adjustment for age, gestational weeks, systolic blood pressure, Body Mass Index (BMI), mode of delivery, and anesthesia, the risk of maternal mortality in the severe PH group was 20.21 times higher than that in the mildmoderate PH group (OR = 21.21 [95% CI 1.7~264.17]), p < 0.05. All 131 (85.1%) patients were followed up for 12 months postpartum. Conclusions: The authors found that the risk of maternal mortality in the severe PH group was significantly higher than that in the mild-moderate group, highlighting the importance of pulmonary artery pressure screening before pregnancy, early advice on contraception, and multidisciplinary care.

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Abstract Objective: The authors investigated changes in vascular reactivity in rats following pilocarpine-induced status epilepticus. Method: Male Wistar rats weighing between 250g and 300g were used. Status epilepticus was induced using 385 mg/kg i.p. pilocarpine. After 40 days the thoracic aorta was dissected and divided into 4 mm rings and the vascular smooth muscle reactivity to phenylephrine was evaluated. Results: Epilepsy decreased the contractile responses of the aortic rings to phenylephrine (0.1 nM–300 mM). To investigate if this reduction was induced by increasing NO production with/or hydrogen peroxide L-NAME and Catalase were used. L-NAME (N-nitro-L arginine methyl ester) increased vascular reactivity but the contractile response to phenylephrine increased in the epileptic group. Catalase administration decreased the contractile responses only in the rings of rats with epilepsy. Conclusions: Our findings demonstrated for the first time that epilepsy is capable of causing a reduction of vascular reactivity in rat aortas. These results suggest that vascular reactivity reduction is associated with increased production of Nitric Oxide (NO) as an organic attempt to avoid hypertension produced by excessive sympathetic activation.

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Abstract Background: Hirschsprung’s Disease (HD) is characterized by intestinal sub-occlusion and the absence of enteric ganglion cells. A rectal biopsy examination is performed to confirm the diagnosis. In a recent study, we demonstrated that the analysis of 60 sections of rectal mucosa and submucosa stained by H&E may ensure a 90% diagnostic accuracy. Although the need to analyze so many sections makes the process of reading the slides more time-consuming, this encouraged us to study their distribution in the healthy rectal submucosa, to simplify the diagnosis. Objectives: To develop a method that facilitates HD diagnosis by studying the distribution of ganglion cells in the submucosal plexus. Methods: Using the calretinin technique, we studied the distribution of plexuses in 60 fragments of rectal submucosa from 19 cadavers. After the study, the reading method created was used for diagnosis in 47 cases of suspected HD, using H&E staining. The accuracy was verified by comparing the results obtained with H&E to those obtained with the acetylcholinesterase technique, the golden standard in our laboratory. Results: The study of submucosal plexus distribution showed that just by examining the submucosal region every 20 µm, approximately, it is possible to locate a ganglionic plexus, and we have already been able to diagnose HD with 93% accuracy. Conclusion: The study of ganglion cell distribution enabled the creation of a simplified method for reading the slides. The method applied achieved good accuracy and it can be used as an alternative method in HD diagnosis.

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Abstract Objective: To analyze the value of serum miRNA-122 expression in the diagnosis, severity, and prognosis of Acute Cerebral Infarction (ACI) and the correlation mechanism of serum miRNA-122 on the proliferation and apoptosis of vascular endothelial cells in ACI. Method: A total of 60 patients with ACI who were admitted to the emergency department of the Taizhou People’s Hospital from January 1, 2019, to December 30, 2019, and 30 healthy controls during the same period were selected. General clinical data of all patients at admission were collected. Including age, sex, medical history, and inflammatory factors (C-Reactive Protein [CRP], Interleukin-6 [IL-6], Procalcitonin [PCT], Neutrophil Gelatinase-Associated Lipid carrier protein [NGAL]). The National Institutes of Health Stroke Scale (NIHSS) score at admission and short-term prognosis (the Modified Rankin Score [mRS]) score at 3 months after onset were recorded. The expression level of miRNA-122 in the serum of patients with ACI and normal controls was detected by reverse-transcription quantitative Real-Time Polymerase Chain Reaction (RT-QPCR), and the correlation between the expression level of miRNA-122 in the serum of patients with ACI and the level of inflammatory factors, NIHSS and mRS scores were analyzed. The expression levels of miRNA-122 in the serum of patients with ACI, normal people, and Human Umbilical cord Endothelial Cells (HUVECs) cultured in a blank control group were detected by RT-QPCR and statistically analyzed. MTT and flow cytometry was used to compare the proliferation and apoptosis of vascular endothelial cells in the miRNA-122 mimics and inhibitors transfection groups and the corresponding negative control group. The mRNA and protein levels of apoptosis-related factors Bax, Bcl-2, Caspase-3, and angiogenesis-related proteins Hes1, Notch1, Vascular Endothelial Growth Factors (VEGF), and CCNG1 were detected by RT-QPCR and Western blot. Bioinformatics methods predicted CCNG1 to be the target of miRNA-122, and the direct targeting relationship between CCNG1 and miRNA-122 was verified by a dual-luciferase reporting assay. Result: Serum miRNA-122 expression in patients with ACI was significantly higher than that in healthy controls, with an area under the receiver operating characteristic curve of 0.929, 95% Confidence Interval of 0.875‒0.983, and an optimal cut-off value of 1.397. The expression levels of CRP, IL-6, and NGAL in patients with ACI were higher than those in healthy control groups, p < 0.05; miRNA-122 was positively correlated with CPR, IL-6, NIHSS score, and mRS score. At 48h and 72h, the proliferation rate of HUVECs cells in the miRNA-122 mimics group decreased and the apoptosis rate increased. Cell proliferation rate increased, and apoptosis rate decreased significantly in the groups transfected with miRNA-122 inhibitors. The mRNA and protein levels of pro-apoptotic factors Bax and caspase-3 were significantly increased in the miRNA-122 mimics transfection group, while those of anti-apoptotic factor Bcl-2 were significantly decreased compared to those of the control group. The expression of Bax and Caspase-3 decreased, and the expression of anti-apoptotic factor Bcl-2 increased in the transfected miRNA-122 inhibitors group. mRNA expression levels of Hes1, Notch1, VEGF, and CCNG1 in the miRNA-122 mimic transfected group were significantly decreased, while mRNA expression levels in the miRNA-122 inhibitors transfected group were significantly increased. Bioinformatics showed that there was a miRNA-122 binding site in the 3′UTR region of CCNG1, and dual luciferase assay confirmed that CCNG1 was the target of miRNA-122.

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Abstract Objectives: Isoflurane (ISO) is widely used in the clinic and research. The authors aimed to explore whether Neobaicalein (Neob) could protect neonatal mice from ISO-induced cognitive damage. Method: The open field test, Morris water maze test, and tail suspension test was performed to assess the cognitive function in mice. Enzyme-linked immunosorbent assay was used to evaluate inflammatory-related protein concentrations. Immunohistochemistry was used to assess Ionized calcium-Binding Adapter molecule-1 (IBA-1) expression. Hippocampal neuron viability was detected using the Cell Counting Kit-8 assay. Double immunofluorescence staining was employed to confirm the interaction between proteins. Western blotting was used to assess protein expression levels. Results: Neob notably improved cognitive function and exhibited anti-inflammatory effects; moreover, under isotreatment, it exhibited neuroprotective effects. Furthermore, Neob suppressed interleukin-1β, tumor necrosis factor-α, and interleukin-6 levels and upregulated interleukin-10 levels in ISO-treated mice. Neob significantly mitigated iso-induced increases in IBA-1 – positive cell numbers of the hippocampus in neonatal mice. Furthermore, it inhibited ISO-induced neuronal apoptosis. Mechanistically, Neob was observed to upregulate cAMP Response Element Binding protein (CREB1) phosphorylation and protected hippocampal neurons from ISO-mediated apoptosis. Moreover, it rescued ISO-induced abnormalities of synaptic protein. Conclusions: Neob prevented ISO anesthesia-induced cognitive impairment by suppressing apoptosis and inflammation through upregulating CREB1.

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Abstract Purposes: Braided and laser-cut stents both are efficacious and safe for coiling intracranial aneurysms. The study aimed to compare outcomes following braided stent-assisted coil embolization versus laser engraved stent-assisted coil embolization in 266 patients who were diagnosed with unruptured intracranial aneurysms of different types and locations. Methods: Patients with unruptured complex intracranial aneurysms underwent braided (BSE cohort, n = 125) or laser engraved (LSE cohort, n = 141) stent-assisted embolization. Results: The deployment success rate was higher for patients of the LSE cohort than those of the BSE cohort (140 [99%] vs. 117 [94%], p = 0.0142). Seventy-one (fifty-seven percentages) and 73 (52%) were coil embolization procedure success rates of the BSE and the LSE cohorts. Periprocedural intracranial hemorrhage was higher in patients of the BSE cohort than those of the LSE cohort (8 [6%] vs. 1 [1%], p = 0.0142). Four (three percentages) patients from the LSE cohort and 3 (2%) patients from the BSE cohort had in-stent thrombosis during embolization. Permanent morbidities were higher in patients of the LSE cohort than those of the BSE cohort (8 [6%] vs. 1 [1%], p = 0.0389). Higher successful procedures (76% vs. 68%) and fewer postprocedural intracranial hemorrhage (0% vs. 5%) and mortality (0% vs. 5%) were reported for patients of the BSE cohort in posterior circulation aneurysmal location than those of the LSE cohort. Laser engraved stent has fewer problems with deployment and may have better periprocedural and follow-up outcomes after embolization. Conclusions: Braided stent-assisted embolization should be preferred when the aneurysm is present in the posterior circulation.

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Abstract Objective: The present study purposed to determine characteristics of ovarian carcinoma and to analyze predictors of survival in patients with ovarian carcinoma. Method: A retrospective cohort study was conducted including the patients with diagnosed ovarian carcinoma treated at the Clinic for Operative Oncology, Oncology Institute of Vojvodina in the period from January 2012 to December 2016. Seventy-two women with ovarian carcinoma were included in the analysis. The data about the histological type of tumor, disease stage, treatment, lymphatic infiltration, and surgical procedure were collected retrospectively, using the database of the institution where the research was conducted (BirPis 21 SRC Infonet DOO – Information System Oncology Institute of Vojvodina). Descriptive statistics and multivariate analysis using Cox proportional hazards model were performed. Results: The univariate Cox regression analysis identified histology, tumor grade, FIGO (International Federation of Gynecology and Obstetrics) stage, NACT (Neoadjuvant Chemotherapy), number of therapy cycles, type of surgery, and chemotherapy response as independent predictors of mortality. Finally, the type of tumor and chemotherapy response had an increased hazard ratio for mortality in the multivariate Cox regression model. Herewith, the percentage of high-grade, advanced-stage ovarian cancer patients with complete response to chemotherapy, absence of recurrent disease, and lymphovascular space invasion were significant predictors of survival in patients with ovarian carcinoma. Conclusions: Herein, emerging data regarding precision medicine and molecular-based personalized treatments are promising and will likely modify the way the authors provide multiple lines of treatments in the near future.

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Abstract Background: Demand for donor hearts and lungs exceeds their supply. Extended Criteria Donor (ECD) organs are used to help meet this demand, but their impact on heart-lung transplantation outcomes is poorly characterized. Methods and results: The United Network for Organ Sharing was queried for data on adult heart-lung transplantation recipients (n = 447) from 2005‒2021. Recipients were stratified based on whether they received ECD hearts and/or lungs. Morbidity was analyzed using Kruskal-Wallis, chi-square, and Fisher’s exact tests. Mortality was analyzed using Kaplan-Meier estimation, log-rank tests and Cox regression. Sixty-five (14.5%) patients received two ECD organs, 134 (30.0%) received only an ECD lung, and 65 (14.5%) only an ECD heart. Recipients of two ECD organs were older, more likely to have diabetes, and more likely transplanted from 2015‒2021 (p < 0.05). Groups did not differ by pre-transplant diagnosis, intensive care unit disposition, life support use, or hemodynam-ics. Group five-year survival rates ranged from 54.5% to 63.2% (p = 0.428). Groups did not differ by 30-day mortality, strokes, graft rejection, or hospital length of stay. Conclusions: Using ECD hearts and/or lungs for heart-lung transplantation is not associated with increased mortality and is a safe strategy for increasing donor organ supply in this complex patient population.

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Highlights VTE COVID-19 patients were sicker, their hospital stay was longer, and they were more likely to die. VTE incidence is still considerable in COVID-19 patients even under pharmacological prophylaxis. Prophylaxis and treatment compliance are essential to achieve a low VTE incidence.

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Highlights The present results support the potential of TPPU to be a multi-functional therapeutic approach for oral ulcers by targeting soluble epoxide hydrolase. To provide a new idea for the treatment and prevention of clinical oral ulcers.

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Highlights Decision support systems that can predict the diagnosis of malignancy for pleural effusion will help physicians in patient management. Advances in computer-aided diagnostic analysis of CT images and obtaining a pre-diagnosis of pleural fluid may reduce the need for interventional procedures by guiding physicians about which patients may have malignancy. Image-based decision support systems enable early diagnosis and treatment by saving cost and time in patient management.

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Highlights FKBP10 proteins are highly expressed in lung adenocarcinoma, including brain metastasis tissue. FKBP10 is a valuable prognostic indicator for lung adenocarcinoma. FKBP10 is a potential clinical biomarker for lung adenocarcinoma.

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Highlights A8 treatment inhibits CFA-triggered inflammatory pain. A8 treatment exerts a significant inhibitory effect on the production of pain-associated pro-inflammatory cytokines. A8 increased the signal transduction of the TRPV1 and CGRP.

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Highlights ML can be a practical and effective early prediction method of AP complicated by ARDS. PaO2, CRP, PCT, LA, Ca2+, NLR, WBC, and AMY were used as the optimal subset of features to early identify AP patients with a high risk for developing ARDS in ML. BC was the superior predictive model and EDTs could be promising for predicting large samples.

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Highlights This study aimed to find the clinical significance of the extracapsular extension in sentinel lymph nodes on the number of additional involved axillary lymph nodes, overall survival, and disease-free survival. One hundred twenty-eight patients with positive sentinel lymph nodes were separated into two groups according to the presence or absence of ECE and following during 10 years. There was found a positive correlation between the presence of ECE and the number of additional positive lymph nodes. Therefore, this does not impact overall survival, and disease-free survival in a follow-up of 10 years.

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Highlights Clinical features, prognostic indexes and echocardiographic parameters may contribute together to better define survival chances in CDH. When antenatal factors are not available, postnatal factors can be good predicting tools and may suffice to assess the prognosis of CDH patients.

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Highlights To comprehensively assess the safety and efficacy of hypothermia in ischemic stroke. Articles published were searched from Google scholar, Baidu scholar and PubMed. The results showed that hypothermia treatment was correlated with mRS≤2 at 3 month.

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Highlights Perianal Crohn's disease is the main risk factor for anal cancer in IBD patients. Perianal Crohn's disease patient has a chance of HPV 3.29 time higher than control. High risk HPV is numerically twice as prevalent in perianal Crohn's disease patient.

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Highlights Experimental evidence suggested that hypoperfusion could impact organ viability. High eNOS-expression in female rats favored the maintenance of renal perfusion. BD-female rats showed progressive inflammatory responses.

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Highlights This is a pioneer study investigating VTE in breast surgery patients in Brazil. Patients undergoing SSM or NSM, immediate breast reconstruction - especially abdominal flap - and procedures longer than four hours had a higher incidence of VTE events. Neoadjuvant chemotherapy and LMWH were associated with a lower incidence of thrombotic events.

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Abstract Objectives Hospitalization during pregnancy and childbirth increases the risk of Venous Thromboembolism Risk (VTE). This study applied a VTE risk score to all hospitalized pregnant women to ascertain its effectiveness in preventing maternal death from VTE until 3 months after discharge. Methods In this interventional study, patients were classified as low- or high-risk according to the VTE risk score (Clinics Hospital risk score). High-risk patients (score ≥ 3) were scheduled for pharmacological Thromboprophylaxis (TPX). Interaction analysis of the main risk factors was performed using Odds Ratio (OR) and Poisson regression with robust variance. Results The data of 10694 cases (7212 patients) were analyzed; 1626 (15.2%, 1000 patients) and 9068 (84.8%, 6212 patients) cases were classified as high-risk (score ≥ 3) and low-risk (score < 3), respectively. The main risk factors (Odds Ratio, 95% Confidence Interval) for VTE were age ≥ 35 and < 40 years (1.6, 1.4-1.8), parity ≥ 3 (3.5, 3.0-4.0), age ≥ 40 years (4.8, 4.1-5.6), multiple pregnancies (2.1, 1.7-2.5), BMI ≥ 40 kg/m2 (5.1, 4.3-6.0), severe infection (4.1, 3.3-5.1), and cancer (12.3, 8.8-17.2). There were 10 cases of VTE: 7/1636 (0.4%) and 3/9068 (0.03%) in the high- and low-risk groups, respectively. No patient died of VTE. The intervention reduced the VTE risk by 87%; the number needed to treat was 3. Conclusions This VTE risk score was effective in preventing maternal deaths from VTE, with a low indication for TPX. Maternal age, multiparity, obesity, severe infections, multiple pregnancies, and cancer were the main risk factors for VTE.

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Highlights Signs and symptoms of COVID-19 at hospital admission are similar between patients infected with HIV and controls. Mortality from COVID-19 in patients infected with HIV was higher compared to the controls in 2020, but no difference in 2021. Similar rates of ICU and invasive mechanical ventilation were observed in the different waves.

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Highlights IL-1β and AMH were lower, and IL-6 was higher in the endometriosis group. The treatment significantly decreased dysmenorrhea, dyspareunia, and cyst diameter. The treatment had no significant effect on the IL-1β, IL-6, and AMH levels.

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Highlights Analysis of recovery from cardiopulmonary exercise testing reveals pathophysiology. Recovery of respiratory gases from peak exercise is hindered in heart failure. Recovery from peak exercise in heart failure is negatively correlated with peak VO2 but not baseline LVEF.

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Highlights GM1 has neuroprotective effects, but it may face difficulty with the blood-brain barrier. Intrathecal application in models of spinal cord injury induced in rats. Determination of optimal timing of GM1 application for best functional results.

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Highlights COVID-19 pandemic was associated with an increase in healthcare-associated infection. For the majority of microorganisms, the proportion of resistance did not increase. The large spectrum antibiotic consumption increased disproportionately during the pandemic.

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Highlights Elevated level of MLR associated with higher AAC score. Each 0.1 unit of increased MLR was associated with a 14% increased risk of severe AAC. This positive relationship between MLR and AAC score was stronger in the elderly and with diabetes.

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Highlights The seroprevalence of SARS-CoV-2 antibodies in Brazil in 2020 was 11%. Seroprevalence increased with time, 1% in the first and 83% in the last quarter of the year. Seroprevalence was higher in the Northern region, decreasing as one moves south.

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Highlights Acute lymphoid leukemia changes the central auditory pathway. Changes in the central auditory pathway in individuals with acute lymphoid leukemia are due to neurotoxicity.

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Highlights MEG3 expressed exceptionally low in the ectopic endometrial. Overexpression of MEG3 inhibits hESCs proliferation and invasion. MEG3 is a ceRNA that has regulatory effects on miR-21-5p/DNMT3B axis. DNMT3B inhibits Twist expression after upregulation of MEG3 action.

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Highlights Combination of clinical factors and radiomic features to construct models for predicting IDH1 gene mutations in glioma. Multiparametric and multiregional MR images were used to achieve more accurate prediction performance. The model performance with different regions of interest for different sequences was compared.

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Highlights Fructosamine and HbA1c are associated in individuals with diabetes and cancer, even on chemotherapy. HbA1c and fructosamine are associated with self-monitoring of blood glucose in cancer. The association between fructosamine and HbA1c occurs even in anemia and hypoproteinemia.

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Highlights MCP enhanced ARPE-19 CA, proliferation, migration, invasion, and cytokine expression. MCP can promote the further development of PVR. The inhibition of MCP may be the key to the treatment of PVR.

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Highlights Insufficient vitamin D levels and sufficient vitamin D levels had a lower risk of ICPP. The vitamin D levels in ICPP girls could affect by height, weight, breast stage, mother's height, and luteinizing hormone/follicle-stimulating hormone ratio. The results could affect by the imbalance of girls in vitamin D deficiency, insufficiency, and sufficiency groups.

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Highlights miRNA-seq analysis obtained 1,002 differentially expressed miRNAs. Differentially expressed miRNAs were mainly enriched in axon guidance, regulation of the actin cytoskeleton and the MAPK signaling pathway. 10 miRNAs (miR-1306-5p, miR-196b-5p, miR-19a-3p, miR-22-3p, miR-320b, miR-34a-5p, miR-485-3p, miR-489-3p, miR-501-3p, and miR-487-3p) were found to be associated with the most sensitive and specific pathways for MMD prediction.

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Highlights WWI was a potential predictor for cardiovascular mortality with a cut-off of 11.33. Higher WWI associated with an increased 95% risk for cardiovascular mortality. Higher WWI associated with an increased 68% risk for all-cause mortality.

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Highlights Exercise training can enhance motor function and improve the spinal cord. Exercise training can improve gastrocnemius muscle morphology. Exercise training can promote neurological recovery after spinal cord injury in rats.

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Highlights 6-OHDA lesioned striatum without changes in CCC cotransporters and Na+/K+-atpase. However, was observed astrocytic reactivity. Dopaminergic degeneration was followed by changes in connexin-36.

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Highlights Pharmacological modulation of cardiac receptors can be an efficient therapeutic strategy to increase life expectancy in Parkinson's disease.

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Highlights Aging impairs binaural interaction in cortical and subcortical regions, elderly people with hearing loss show differences in responses between the ears/electrodes. Elderly people without hearing loss show differences in responses between the hemispheres. Binaural interaction is more impaired in older adults with high-frequency hearing loss.

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Highlights Patients with opioid use disorder experience greater in-hospital mortality and readmissions following MI. Paradoxically, these patients experience superior cardiovascular outcomes compared to their counterparts. Opioid use disorder remains associated with high resource utilization and healthcare expenditures.

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Highlights HMG-CoA reductase inhibitor statins can inhibit vascular remodeling. The regulation of HDAC2/NF-κB signaling pathway can improve pulmonary vascular remodeling. Atorvastatin can be used in the early intervention of pulmonary vascular remodeling.

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Highlights m6A modification participates in the development of BPD. METTL3 promotes the pyroptosis of BEAS-2B cells. ETTL3-mediated m6A modification of ATG8 disrupts the interaction between ATG8 and GSDMD.

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Highlights MiR-15a/β1,4-GalT-I axis inhibits ECM degradation and senescence in chondrocytes. MiR-15a inhibits β1,4-GalT-I expression with post-transcriptional modifications. β1,4-GalT-I promotes NF-κB phosphorylation to exacerbate osteoarthritis. Intra-articular injection of miR-15a attenuates cartilage degeneration in vivo.

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Highlights Ultrasound-guided PTCD improves treatment effect for AOSC combined with septic shock. Ultrasound-guided PTCD reduces stress response for AOSC combined with septic shock. Ultrasound-guided PTCD assists patients smoothly to pass preoperative critical period.

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Highlights EGFR, POLE, and PB1 genes had high mutated frequency in the patients with relapse and metastatic cancer. PBRM1, BAP1, KDM5C, and BAP1 genes were critical for the overall survival. Wild-type PBRM1 and mutated BAP1 were key indications for the predication of OS.

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Highlights Gestational trophoblastic neoplasia responds to anti-PD-1 or anti-PD-L1 immunotherapy. Multi-drug resistant gestational trophoblastic neoplasia may achieve remission with pembrolizumab.

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Highlights Infertility is caused by heterogeneous risks, but most of them are unexplained. Sperm DFI diagnostic value was controversial as not rule out male sperm parameters. Whether DFI was a useful indicator for embryologists and clinicians in UEI couples.

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Highlights LEP may be associated with the development of PCOS. LEP may be a protective factor against apoptosis in GCs treated with insulin. LEP knockdown induced JAK1/STAT3 activation could be reversed by administration of curcumin.

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Highlights Temperature-Related Illness (TRI) describes physiologic aberrations that occur secondary to exposure to extreme cold or heat. Individuals with Atrial Fibrillation (AF) who present with TRI may be at increased risk of poor outcomes relative to patients without TRI. Our analysis shows that individuals with AF who develop a cold-related TRI face an increased risk of mortality as compared to those without TRI.

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Highlights A stent-assisted thrombectomy can use in symptomatic intracranial hemorrhage. Contact aspiration plus stent retriever catheters have high chances of reperfusion. Contact aspiration + stent retriever has fewer disease-related adverse effects. The reperfusion parameter should be used to evaluate mechanical thrombectomy. Failure attempts increased procedural time and procedural-adverse effects.

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Highlights Several environmental and genetic factors may cause oral clefts. Iron supplementation use of folic acid are protective factors for oral fissures. Passive smoking during pregnancy can be a risk factor for oral clefts.

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Highlights Studies have shown worse rotational stability in the presence of a supposed ALL injury combined with an ACL injury. However, there is no evidence, so far, on how individuals behave regarding muscle strength and functionality. Knee and hip muscular functions are impaired after an ACL injury and do not seem to be influenced or worsened in individuals with greater rotational instability with clinical indications for combined reconstruction of the anterior cruciate and the anterolateral ligaments of the knee. The ACL+ALL group showed a significantly shorter distance achieved in the Crossover Hop Test than the other groups, as well as the reports of more pain during the tests.

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Highlights Notch2 is important in trastuzumab-induced cardiomyocytes apoptosis through JAK2/STAT3 pathway. Trastuzumab promotes cell apoptosis and causes cardiomyocyte injury. Notch2 may be a potential target of trastuzumab-induced myocardial injury.

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Highlights Identification of potential candidates for hand surgery in Systemic Sclerosis. Presence of digital ulcers increases the likelihood of surgical indication. Development of a predictive tool to identify candidates for surgical treatment.

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Highlight miRNAs are associated with colorectal cancer, peritonitis carcinomatosis, and liver metastasis. The miR-99b, miR-135b, and Akt protein levels, which are highly expressed in peritonitis carcinomatosis and liver metastasis tissues in colorectal cancer play a fundamental role in carcinomatosis and metastasis. While miR-99b is highest in the primary tumor, its decrease in liver metastasis suggests that miR-99b may have a protective effect against liver metastasis. miR-135 in the highest peritonitis carcinomatosis and liver metastasis compared to the main tissue suggests that it progresses to carcinomatosis and metastasis.

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Highlights The oral glucose tolerance characteristics were analyzed. Effect of gestational diabetes on the pregnancy outcome of twins was analyzed. The influence of preconception BMI on twin pregnancy outcome was explored.

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Highlights Activation of the NFκB signaling pathway aggravates myocardial injury. Vav3 might exert an effect in MI model by repressing the NFκB signaling pathway. Vav3 exerted its cardio-protective function in a NFκB-dependent manner. CLINICS-D-23-00277_Original Article

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Highlights Cystic fibrosis related vascular complications. Survival of people with cystic fibrosis. Cystic fibrosis related vascular complications and metabolic complications.

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Highlights Dysphagia has a high incidence in post-stroke patients. Alternative long-term feeding method indication in post-stroke patients. Dysartrhia associated dysphagia in post-stroke patients.

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Highlights The involvement of TMEM26, a novel plasma membrane protein, in cancer EMT was examined for the first time. The discovery of TMEM26 and its regulation on the tight junction activates NF-κB signaling as a novel therapeutic target of metastatic ESCC. A mechanism that directly controls the assembly of tight junctions at the plasma membrane, which affects a plethora of signaling pathways, was discovered.

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Highlights Understanding the costs of neonatal sepsis helps to provide the problem's dimension. Mean hospital cost for neonatal sepsis was US$ 3345.59 per patient in 2008‒2018. Improvement in quality of care may decrease neonatal sepsis’ economic impact.

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Highlights This study describes the implementation of an organized colorectal cancer (CRC) screening in an urban low-income community. Quantitative fecal immunochemical test (FIT) followed by colonoscopy is an efficacious strategy to improve the adenoma detection rate and CRC. FIT followed by colonoscopy ensued a high participation rate, and high predictive positive value for adenoma and CRC.

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Highlights Score to predict successful RRT discontinuation in AKI. Timely catheter removal. Comparison among different strategies to assess. Creatinine variation.

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Abstract Objectives: Ad fontes, the status of the thyroid gland, and metabolic disturbance lead to the alteration of oxygenation. In pregnancy, it is particularly crucial to possess all predictive parameters. Methods: This cross-sectional study was conducted at the Clinic of Gynecology and Obstetrics, Clinical Center of Serbia, Belgrade, Serbia, between 2017 and 2021 which study included a total of 99 women who had been admitted for preterm delivery and had undergone thyroid analysis, detected Hashimoto thyroiditis, and Oral Glucose Tolerance Test (OGTT) 40 days after delivery and had pathological Homeostatic Model Assessment for Insulin Response (HOMA IR) indices. In the group of urgent patients with preterm delivery, we looked after not only routine Doppler of the umbilical artery, but we measured specific ratios such as the Cerebroplacental ratio (CP). Results: The mean maternal age was 32.23 ± 5.96 years and the mean gestational age was detected as 35.40 ± 2.39 weeks. The delivery was completed vaginally in 77 women (78%) and surgically in 22 (22%). The Mean APGAR score was 8.44 ± 1.18, the mean birth weight was 2666.87 ± 622.17g and the cases undergoing cesarean section had significantly higher values of pulsatility index (1.85 ± 0.27 vs. 1.34 ± 0.31) and CP (1.22 ± 0.26 vs. 0.47 ± 0.17). Conclusions: The introduction of Doppler sonography for blood flow assessment helps to form a complete clinical description of the patient, particularly in conditions where oxidative stress became provocative by the thyroid gland antibodies and gestational diabetes in Thyroidology.

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Abstract Background: Physical activity had been reported among doctors-in-training, with very few focusing on attending doctors. This study aimed to evaluate the physical activity, particularly exercise, of Thai doctors and features associated with low-level exercise. Materials and methods: Thai doctors who participated in the hospital’s CSR service, which was conducted between Feb 14, 2022, to Oct 31, 2022, were verbally informed along with an information sheet about this parallel study. The doctors who consented to participate provided their personal data on diets, work hours, illnesses, health surveillance, stress, state of well-being, and exercise. To investigate the association with clinical features, the exercise level was categorized as low-level (≤ 2 days/week) or high-level (≥ 3 days/week). Results: The median age of 1187 doctors was 45.0 years. Slightly over half were female (55.4%) or worked ≤ 40 hours/week (55.3%). The presence of illnesses was found in 55.9%, irregular health surveillance in 29.0%, no/low fiber diet in 19.2%, overweight/obesity in 28.0%, and moderate/severe stress in 25.9%. Among the doctors who provided exercise data, 29.8% had a high-level of exercise and 49.0% had a low-level. Independent features associated with low-level exercise were no/low fiber diet (aOR = 3.01), irregular health surveillance (aOR = 2.41), age ≤ 60 years (aOR = 1.82), female gender (aOR = 1.79), and work > 40 hours/week (aOR = 1.76). Conclusions: Only 30% of Thai doctors had a high level of exercise. The significant independent factors for low-level exercise were younger age, female, working load, irregular health surveillance, and no/ low fiber diet.

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Abstract Objectives: The aim of this study was to evaluate the effect of STS resection in the thigh on MS and the HRQoL. Methods: Fourteen adults patients with STS in the thigh who underwent wide resection and limb preservation were evaluated. The patients were submitted to the Mini-Mental State Examination (MMSE). A hand-held dynamometer was used to measure the MS the flexors, adductors, abductors, and extensors muscles of the operated and non-operated thighs and between the dominant and non-dominant operated sides. The Musculoskeletal Tumor Society (MSTS) and Short Form Health Survey-36 (SF-36) questionnaires were applied to quantify the psychometric properties of the HRQoL. The data were submitted to statistical analysis using the Wilcoxon test (MS), and Mann-Whitney and Spearman correlation (MSTS and SF-36) (α = 0.05). Results: There was no significant difference in MS between the operated side and the non-operated side, and between the dominant and non-dominant operated side (ρ > 0.05). The MSTS presented a significant difference in the emotional acceptance for patients submitted to radiotherapy (ρ = 0.029). The SF-36 showed significant differences in the emotional aspect for patients submitted to chemotherapy (ρ = 0.027) and in the social aspect between the dominant and non-dominant operated side (ρ = 0.024). Conclusions: The HRQoL of adult patients is hampered after the treatment of STS even when MS is maintained.

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ABSTRACT Objectives: Within the tertiary-case database, the authors tested for differences in long-term continence rates (≥ 12 months) between prostate cancer patients with extraprostatic vs. organ-confined disease who underwent Robotic-Assisted Radical Prostatectomy (RARP). Method: In the institutional tertiary-care database the authors identified prostate cancer patients who underwent RARP between 01/2014 and 01/2021. The cohort was divided into two groups based on tumor extension in the final RARP specimen: patients with extraprostatic (pT3/4) vs. organ-confined (pT2) disease. Additionally, the authors conducted subgroup analyses within both the extraprostatic and organ-confined disease groups to compare continence rates before and after the implementation of the new surgical technique, which included Full Functional-Length Urethra preservation (FFLU) and Neurovascular Structure-Adjacent Frozen-Section Examination (NeuroSAFE). Multivariable logistic regression models addressing long-term continence were used. Results: Overall, the authors identified 201 study patients of whom 75 (37 %) exhibited extraprostatic and 126 (63 %) organ-confined disease. There was no significant difference in long-term continence rates between patients with extraprostatic and organ-confined disease (77 vs. 83 %; p = 0.3). Following the implementation of FFLU+ NeuroSAFE, there was an overall improvement in continence from 67 % to 89 % (Δ = 22 %; p < 0.001). No difference in the magnitude of improved continence rates between extraprostatic vs. organ-confined disease was observed (Δ = 22 % vs. Δ = 20 %). In multivariable logistic regression models, no difference between extraprostatic vs. organ-confined disease in long-term continence was observed (Odds Ratio: 0.91; p = 0.85). Conclusion: In this tertiary-based institutional study, patients with extraprostatic and organ-confined prostate cancer exhibited comparable long-term continence rates.

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Abstract Introduction: Long QT Syndrome (LQTS) is an inherited disease with an abnormal electrical conduction system in the heart that can cause sudden death as a result of QT prolongation. LQT2 is the second most common subtype of LQTS caused by loss of function mutations in the potassium voltage-gated channel subfamily H member 2 (KCNH2) gene. Although more than 900 mutations are associated with the LQTS, many of these mutations are not validated or characterized. Methods and results: Sequencing analyses of genomic DNA of a family with LQT2 identified a putative mutation. i.e., KCNH2(NM_000238.3): c.3099_3112del, in KCNH2 gene which appeared to be a definite pathogenic mutation. The family pedigree information showed a gender difference in clinical features and T-wave morphology between male and female patients. The female with mutation exhibited recurring ventricular arrhythmia and syncope, while two male carriers did not show any symptoms. In addition, T-wave in females was much flatter than in males. The female proband showed a positive reaction to the lidocaine test. Lidocaine injection almost completely blocked ventricular arrhythmia and shortened the QT interval by ≥30 ms. Treatment with propranolol, mexiletine, and implantation of cardioverter-defibrillators prevented the sustained ventricular tachycardia, ventricular fibrillation, and syncope, as assessed by a 3-year follow-up evaluation. Conclusions: A putative mutation c.3099_3112del in the KCNH2 gene causes LQT2 syndrome, and the pathogenic mutation mainly causes symptoms in female progeny.

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Abstract Purpose: This study aimed to analyze the auditory processing behavior of children and adolescents diagnosed with stroke and compare it with that of typically developing individuals. Methods: This was an analytical cross-sectional study involving 48 participants aged between 7 and 17 years with adequate schooling for age and grade, allocated equally to two groups: Stroke (SG) and Control Groups (CG). For the SG, cases identified between 2003 and 2018 were considered. In the CG, school-aged participants with typical development were randomized. After screening for differential audiological assessment and confirmation of auditory pathway integrity at the brainstem level, binaural analyses of the auditory processing behavior were conducted using the Dichotic Digit Test (DDT), Frequency Pattern Test (FPT), and electrophysiological assessment (P300). The Shapiro-Wilk test for normality was conducted, followed by the T and Mann-Whitney tests, with a 95 % confidence level and significance offset at p < 0.05, using the SPSS software (IBM®, v. 22.) Results: The CG performed better in terms of auditory processing. These differences were significant (p < 0.0001) for the binaural integration of DDT, FPT humming and Labeling, and P300 latency. The P300 results were similar; however, with a greater amplitude in the SG. Conclusion: This study showed that children and adolescents with stroke performed worse in electrophysiological and behavioral tests of auditory processing assessed using the auditory evoked potentials. These data reinforce the hypothesis that stroke-related lesions compromise the neural mechanisms underlying auditory processing.

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Abstract Objective: With the aging of the population, more patients have complained of pain due to knee Osteoarthritis (OA), and the number of arthroplasties has also increased. The objective of this study is to evaluate the prevalence of the neuropathic pain component in candidates for Total Knee Replacement and the effects of this component on their quality of life. Methods: In this cross-sectional study, patients with OA candidates for knee arthroplasty in the present institution were evaluated using the pain detection questionnaire and the Visual Analog Pain (VAS) scale to measure the pain index and the presence of associated neuropathic pain. In addition, evaluation of the quality of life and functionality using the EQ5D and SF12 questionnaires and their relationship with cases of neuropathic pain were performed. Results: One hundred twenty-six patients were evaluated, and 71.4 % were female. The age ranged from 46 to 85 years, and about 70 % of the patients had some associated clinical comorbidity. Neuropathic pain was present in 28.6 % of the patients evaluated. Patients with neuropathic pain presented worse results in the VAS evaluation, in the care, pain, and anxiety domains of the EQ5D, and in the physical and mental scores of the SF12. Conclusion: Neuropathic pain was present in 28.6 % of the patients with knee OA who are candidates for arthro-plasty. Patients with associated neuropathic pain present a higher level of pain and worse quality of life scores. Recognizing this type of pathology is extremely important in fully monitoring gonarthrosis.

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Abstract Objectives: To evaluate Microablative Fractional Radiofrequency (MAFRF) as a possible option in treating vaginal atrophy. Methods: This was a randomized, controlled clinical trial with postmenopausal women diagnosed with vaginal atrophy. The treatment consisted of three sessions of MAFRF, compared to vaginal estrogen administration and an untreated control group. Assessments occurred at baseline and 90 days. The primary endpoints were sexual function, evaluated by the Female Sexual Function Index (FSFI), and vaginal health, assessed by the Vaginal Health Index (VHI). Secondary outcomes included vaginal microbiota composition (Nugent score) and epithelial cell maturation (Maturation Value ‒ MV). Results: One hundred and twenty women (40 in each group) were included. Concerning the FSFI, both groups, MAFRF (median 4.8 [3.6‒6.0]) and vaginal estrogen (mean 4.7 ± 1.1), experienced improved sexual desire when compared to the control group (median 3.6 [2.4‒4.8]). Regarding the total score of VHI, the authors observed an improvement in the mean of the MAFRF (23.7 ± 2.0) and vaginal estrogen groups (23.5 ± 1.9) when compared to the control (14.8 ± 2.9). The Nugent score was reduced in the MAFRF and estrogen groups (p < 0.01) compared to the control group. Lastly, the MV was modified after treatment with MAFRF (p < 0.01) and vaginal estrogen (p < 0.001). No differences existed between the MAFRF and vaginal estrogen groups in the studied variables. No adverse effects were reported following the MAFRF protocol. Conclusions: Radiofrequency was comparable in efficacy to estrogen administration for treating vulvovaginal atrophy. It deserves consideration as a viable option in managing this condition.

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Abstract Introduction: Stable angina develops during physical activity or stress, and it is typically an aspect of Coronary Heart Disease (CHD) that can lead to arrhythmia, heart failure and even sudden death. ANRIL, an Antisense Non-coding RNA gene in the INK4 Locus, is associated with multiple disorders including CHD; however, expressional levels of ANRIL in between patients with stable angina and myocardial infarction, one of the acute coronary syndrome, have not been clarified yet. Methods: The authors enrolled 62 patients with myocardial infarction and 59 with stable angina before primary percutaneous coronary intervention, as well as 48 healthy volunteers. Their peripheral blood was collected for analysis of ANRIL and cardiac troponin I, a traditional diagnostic index of CHD by real-time PCR. Results: The data showed that ANRIL is a better diagnostic indicator than cardiac troponin I in patients with stable angina and that the levels of ANRIL are higher in patients with stable angina than those with the myocardial infarction. Discussion: The levels of ANRIL in peripheral plasma could be used as a good biomarker for stable angina.

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Abstract Objectives: This study aimed to compare progression-free survival, overall survival, clinical benefits, and adverse effects in postmenopausal women with hormone receptor-positive and HER2-negative breast cancer who received buparlisib plus fulvestrant against those of women who received dalpiciclib plus fulvestrant, considering ribociclib plus letrozole treatment as the reference standard. Methods: Women received buparlisib plus fulvestrant (BF cohort, n = 108), dalpiciclib plus fulvestrant (DF cohort, n = 132), or ribociclib plus letrozole (RL cohort, n = 150) until unacceptable toxicity was observed. Results: A total of 117 (89 %), 80 (74 %), and 84 (56 %) women in the BF, DF, and RL cohorts, respectively, had clinical benefits. After treatment, the clinical benefits for women and after 42 months of follow-up progression-free survival and overall survival were higher in the DF cohort than in the BF and RL cohorts (p < 0.05 for all). Neutropenia, vomiting, constipation, nausea, diarrhea, and anorexia were reported higher in women of the DF and BF cohorts than in women of the RL cohort. Leukopenia and increased levels of alanine aminotransferase and aspartate aminotransferase were reported to be higher in women in the RL cohort than in women in the DF and BF cohorts. Depression, anxiety, and increased levels of alanine aminotransferase and aspartate aminotransferase were reported to be higher in women in the BF cohort than in women in the DF and RL cohorts. Conclusions: Dalpiciclib plus fulvestrant is effective and comparatively safe in postmenopausal women with hormone receptor-positive and HER2-negative breast cancers. Dalpiciclib, buparlisib, fulvestrant, and ribociclib cause neutropenia, severe depression, adverse gastroenterological effects, and adverse hepatological effects, respectively.

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ABSTRACT Purpose: To determine the predictive value of maternal White Blood Cells (WBC), neutrophils, and C-Reactive Protein (CRP) for diagnosing Histological Chorioamnionitis (HCA) among women with Preterm Premature Rupture of Membranes (PPROM) who underwent cervical cerclage. Methods: A retrospective cross-sectional study was conducted among women with singleton pregnancy and PPROM, who underwent cervical cerclage during 2018-2020. Results: A total of 55 eligible women were included in the final analysis, including 36 (61.02%) cases with HCA and 19 (38.98%) without HCA. Women with HCA had higher WBC count (12.31 ± 2.80) × 109/L and neutrophil count (9.67 ± 2.90)×109/L than those without HCA (10.35 ± 2.53) × 109/L and 7.82 ± 2.82 × 109/L, respectively) (both p < 0.05). The cut-off value of WBC count at 10.15×109/L was found to be the most effective in identifying HCA, with an Area Under Curve (AUC) of 0.707 (95% CI: 0.56-0.86; p = 0.012), sensitivity of 86.11%, specificity of 57.90%, Positive Predictive Value (PPV) of 79.49%, Negative Predictive Value (NPV) of 68.75%, and Youden index of 0.44. The combination of WBC + neutrophil had a slightly higher (AUC = 0.711, 95% CI: 0.57–0.86; p = 0.011), specificity (68.42%), and PPV (81.25%), but lower sensitivity (72.22%), than the WBC count alone. A cut-off value of neutrophil at 7.46 × 109/L was effective in identifying HCA, with an AUC of 0.689 (95% CI: 0.53-0.84; p = 0.022). Discussion: Combination use of WBC+neutrophil was found to be the most accurate predictor of HCA among women with PPROM after surgery of cervical cerclage.

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Abstract Objectives: To measure Quality of Life (QoL) and costs of Heart Failure (HF) outpatients in Brazil as an introduction to the Value-Based Health Care (VBHC) concept. Materials and methods: Cross-sectional study, patients with HF, with ejection fraction <50%, were recruited from three hospitals in Brazil. Two QoL (36-Item Short Form Survey [SF-36] and Minnesota Living with Heart Failure Questionnaire [MLHFQ]) and two anxiety/depression questionnaires were applied. SF-36 scores were stratified by domains. Treatment costs were calculated using the Time-Driven Activity-Based Costing (TDABC) method. Results were stratified by NYHA functional class and sex. Results: From October 2018 to January 2021, 198 patients were recruited, and the median MLHFQ (49.5 [IQR 21.0, 69.0]) and SF-36 scores demonstrated poor QoL, worse at higher NYHA classes. A third of patients had moderate/severe depression and anxiety symptoms, and women had higher anxiety scores. Mean costs of outpatient follow-up were US$ 215 ± 238 for NYHA I patients, US$ 296 ± 399 for NYHA II and US$ 667 ± 1012 for NYHA III/IV. Lab/exam costs represented 30% of the costs in NYHA I, and 74% in NYHA III/IV (US $ 63.26 vs. US$ 491.05). Conclusion: Patients with HF in Brazil have poor QoL and high treatment costs; both worsen as the NYHA classification increases. It seems that HF has a greater impact on the mental health of women. Costs increase mostly related to lab/exams. Accurate and crossed information about QoL and costs is essential to drive care and reimbursement strategies based on value.

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Abstract Objective: The aim of this study was to study the curative effect and the relative mechanism of modified photodynamic therapy combined with Taohong Siwu Decoction in the treatment of hyperplastic scar after severe burn, in order to provide a stable, safe and satisfactory scheme for scar repair. Methods: Forty cases with hyperplastic scars after severe burns admitted to the plastic surgery department from May 2021 to May 2022 were divided into a control group and an observation group by means of the random number table method. The control group was treated with ordinary laser therapy combined with Taohong Siwu Decoction, while the observation group was treated with modified photodynamic therapy combined with Taohong Siwu Decoction. The Vancouver Scar Scale (VSS) was assessed in both groups, and the clinical effectiveness of both groups was compared. HE-staining was performed on the scar tissue of the same patient before and after treatment to observe the changes in the arrangement of fibroblasts. The Vascular Endothelial Growth Factor (VEGF), β-Transforming Growth Factor (TGF-β), and Platelet-Derived Growth Factor (PDGF) in the tissue samples of both groups were detected by quantitative real-time PCR. The patients were followed up for 6 months, and their satisfaction, side effects, and scar recurrence were observed. Results: Compared with the control group, the VSS score in the observation group was lower (p < 0.05). The therapeutic effect of the observation group was superior to the control group after 3 months (p < 0.05). After 3-months of therapy, the arrangement of fibroblasts in the scar became looser in two groups, and the observation group was more looser. The VEGF, TGF-β and PDGF levels in tissue samples of the observation group were lower than those in the control group after 3 months of treatment (p < 0.05). The satisfaction of the observation group was higher than that of the control group (p < 0.05). The adverse reactions between the two groups showed no difference (p > 0.05), while the recurrence rate was lower in the observation group (p < 0.05). Conclusion: Modified photodynamic therapy combined with Taohong Siwu Decoction shows remarkable efficacy in patients with hyperplastic scars after severe burns. It can improve the color, thickness, vascular distribution, and softness of the scar, and reduce the level of cytokines related to tissue repair. At the same time, it can improve patients’ satisfaction with the aesthetic appearance and reduce the recurrence rate, providing a new comprehensive therapy that is safer and more effective, simple and quick, and easy to promote in the clinic.

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Abstract Objectives: This study explored the association between insomnia and the clinical outcome of large vessel occlusion Acute Ischemic Stroke (AIS) and attempted to explore its potential mechanisms from the perspectives of inflammation and oxidative stress. Methods: AIS patients who underwent endovascular treatment for large vessel occlusion at Binzhou Central Hospital from 2018 to 2022 (n = 508) were included. Patients were divided into an insomnia group and a non-insomnia group. Insomnia was judged by self-reported Athens Insomnia Scale score. Regression analysis was used to compare the differences in the 24-hour and 7-day National Institutes of Health Stroke Scale (NIHSS) score, Early Neurological Deterioration (END), early adverse event incidence, 90-day prognosis and mortality, and serum bio-markers levels. Results: The incidence of insomnia in the study population was 39.6% (n = 144, insomnia group; n = 364, non-insomnia group). Compared with the non-insomnia group, a worse prognosis outcome (63% vs. 49%, adjusted rate ratio: 1.8, 95% Confidence Interval: 1.2–3.7; p = 0.016), higher 24-h and 7-day NIHSS score (17 [9–36] vs. 13 [5–20]; p = 0.024, and 11 [4‒24) vs. 8 [2‒14]; p = 0.031, respectively), higher END (24% vs. 15%, p = 0.022), and higher incidence of adverse events were observed in the insomnia group (79% vs. 59%, p = 0.010). The 90-day mortality was higher in the insomnia group than that in the non-insomnia group (22% vs. 17%), however, such a difference was not statistically significant. Conclusion: Insomnia is closely related to the clinical outcome of AIS with large vessel occlusion, and inflammation and oxidative stress mechanisms may be involved.

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Abstract Objectives: Abdominal Aortic Aneurysm (AAA) is a complex disease with both genetic and environmental risk factors. This study aimed to examine the potential association of the +276G/T and −420C>G polymorphisms in the resistin gene with AAA susceptibility and progression. Method: We performed a retrospective study involving AAA patients and healthy controls, assessing the distribution of the +276G/T and −420C>G genotypes in both groups. Hardy-Weinberg equilibrium was assessed for both polymorphisms. Logistic regression was used to explore the influence of these genotypes on AAA occurrence and progression, adjusting for relevant confounders. Results: The distribution of +276G/T polymorphism did not significantly differ between AAA patients and controls. Conversely, a significant difference was observed in the genotype distribution of −420C>G polymorphism between the two groups. The CC genotype and CC/CG genotypes of −420C>G polymorphism were found to be associated with an increased risk and progression of AAA. Conclusions: The −420C>G polymorphism, particularly the CC genotype and CC/CG genotypes, might play a substantial role in AAA susceptibility and progression. The present findings underscore the need for further investigations to confirm these associations and fully elucidate the role of the resistin gene in AAA.

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Abstract Objective: MicroRNAs play crucial roles in the pathogenesis of cancers. MiRNA-218-5p may act as either an oncogene or a tumor suppressor, but its role in the pathogenesis of Breast Cancer (BC) remains unclear. Methods: Infiltrative breast ductal carcinoma as well as corresponding adjacent normal samples were collected from 30 patients. Mimics and inhibitors of miRNA-218-5p or corresponding negative controls were transfected into BC cells. miRNA-218-5p expression was detected by quantitative PCR. The effects of miRNA-218-5p on the malignant behaviors of BC were assessed. Dual-luciferase reporter assay was employed to evaluate the binding of miRNA-218-5p to LRIG1. Results: BC tissues showed higher miRNA-218-5p expression as compared to the adjacent normal tissues. Ectopic miRNA-218-5p expression accelerated the cell cycle, cell growth and migration of BC, while repressed cell apoptosis. Interestingly, ectopic miRNA-218-5p expression down-regulated LRIG1 expression, and miRNA-218-5p could bind to LRIG1. Also, our study indicated that miRNA-218-5p up-regulated ErbB2 and EGFR expression by targeting LRIG1, suggesting that the LRIG1-mediated signaling pathway contributed to the pro-tumor effects of miRNA-218-5p on BC. Conclusion: MiRNA-218-5p up-regulates ErbB2 and EGFR expression by suppressing LRIG1 expression, thus promoting the malignant behaviors of BC. miRNA-218-5p may exert a pro-tumor effect on BC and serve as a therapeutic target for BC treatment.

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Highlights The role of diet in NAFLD development is still uncertain in PCOS women. Anthropometry and sedentarism were different between PCOS women with and without NAFLD. Food intake and dietary patterns were similar between PCOS women with and without NAFLD.

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Highlights It is able to as the balance point between the blood pressure and bleeding event. It can reduce the bleeding amount and infusion volume and increase the cure rate of patients. Restrictive fluid resuscitation has a promising value in the treatment of HTS, which is worthy of promotion in clinical practice.

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Highlight Non-alcoholic fatty liver disease was associated with carotid intimal thickening and non-calcified plaque, highlighting an elevated cardiovascular risk. NAFLD fibrosis is an independent risk factor for CHD. Inflammation potentially serves as a complete mediator in the connection between NAFLD fibrosis and CHD.

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Highlights Butyrate could suppress IFN-γ-induced PD-L1 up-regulation in Colorectal Cancer (CRC) cells. Butyrate promoted the lysine acetylation of STAT1 to reduce STAT1 expression. Butyrate attenuated the IFN-γ-induced impairment of CD8+ T-cell cytotoxicity against CRC cells. Butyrate suppressed CRC tumor growth by enhancing CD8+ T-cell infiltration.

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Highlights HBO promoted a significant improvement in the clinical and histological statuses of the animals of this study experimental. HBO is effective for the treatment of colitis by increasing the activity of antioxidant enzymes. This study demonstrated a modulation of the immune response by reducing the expression of inflammatory cytokines and increasing the anti-inflammatory cytokines.

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Highlight Adverse cardiac events after primary PCI are still common in STEMI patients. Elevated serum bilirubin levels are independent predictors of adverse cardiac events in STEMI patients. Direct bilirubin has a better predictive value for adverse cardiac events in STEMI patients.

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Highlights KIF22 expression is upregulated in melanoma tissues and cells. KIF22 knockdown suppresses proliferation and facilitates apoptosis of melanoma cells. KIF22 knockdown inhibits tumor glycolysis in melanoma cells. KIF22 depletion suppresses proliferation, glycolysis and facilitates apoptosis of melanoma cells by inactivating EGFR/STAT3 signaling.

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Highlights LFR can improve blood hemodynamics parameters after traumatic hemorrhagic shock. LFR would influence serum inflammatory levels after traumatic hemorrhagic shock. Medium MAP can be employed as the optimal administrating strategy for LFR.

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Highlights miR-143 is related with more inflammation and edema of intestinal loops of gastroschisis rat model. Time of exposure of the amniotic fluid increases the intestinal damage. miR-143 is a possible marker of gut inflammation.

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Highlights Raloxifene effect on the CA1 hippocampus synaptic density. Differences between early and late hormonal treatment on CA1 hippocampus synaptic density. Estrogen action on the rat synaptic density is higher than one of raloxifene.

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Abstract This study aimed to perform a meta-analysis comparing the efficacy and safety of gefitinib in combination with chemotherapy versus gefitinib alone in patients with advanced Non-Small Cell Lung Cancer (NSCLC). We searched databases for clinical studies that reported the efficacy or safety of gefitinib plus chemotherapy in comparison with gefitinib alone. Raw data from included studies were extracted and pooled to calculate the Odds Ratio (OR) for Objective Response Rate (ORR) and Disease Control Rate (DCR), the Hazard Ratio (HR) for Progression-Free Survival (PFS) and Overall Survival (OS), and OR for complication ≥ Grade 3. A total of 10 studies containing 1,528 patients with NSCLC were identified and included in the analysis. Gefitinib plus chemotherapy showed significantly better efficacy in improving ORR (OR = 1.54; 95% CI [Confidence Interval], 1.13‒2.1; p = 0.006), DCR (OR = 1.62; 95% CI 1.14‒2.29; p = 0.007), PFS (HR=1.67; 95% CI 1.45‒1.94; p < 0.001) and OS (HR = 1.49; 95% CI 1.2‒1.87; p < 0.001) as compared with gefitinib alone. Consistent results were observed in the sub-population with positive EGFR mutation. The combination of gefitinib with chemotherapy had a significantly higher risk of complication (≥ Grade 3) with an OR of 3.29 (95% CI 2.57‒4.21; p < 0.001). The findings in the present study suggest that the combination of gefitinib with chemotherapy can provide better disease response and survival outcomes for patients with advanced NSCLC.

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Abstract Biliary drainage for Perihilar Cholangiocarcinoma (PCCA) can be performed either by endoscopic retrograde cholangiopancreatography or Percutaneous Transhepatic Biliary Drainage (PTBD). To date there is no consensus about which method is preferred. Taking that into account, the aim of this study is to compare Endoscopic Biliary Drainage (EBD) versus percutaneous transhepatic biliary drainage in patients with perihilar cholangiocarcinoma through a systematic review and metanalysis. A comprehensive search of multiple electronic databases was performed. Evaluated outcomes included technical success, clinical success, post drainage complications (cholangitis, pancreatitis, bleeding, and major complications), crossover, hospital length stay, and seeding metastases. Data extracted from the studies were used to calculate Mean Differences (MD). Seventeen studies were included, with a total of 2284 patients (EBD = 1239, PTBD = 1045). Considering resectable PCCA, the PTBD group demonstrated lower rates of crossover (RD = 0.29; 95% CI 0.07–0.51; p = 0.009 I2 = 90%), post-drainage complications (RD = 0.20; 95% CI 0.06–0.33; p < 0.0001; I2 = 78%), and post-drainage pancreatitis (RD = 0.10; 95% CI 0.05–0.16; p < 0.0001; I2 = 64%). The EBD group presented reduced length of hospital stay (RD = -2.89; 95% CI -3.35 - -2,43; p < 0.00001; I2 = 42%). Considering palliative PCCA, the PTBD group demonstrated a higher clinical success (RD = -0.19; 95% CI -0.27 - -0.11; p < 0.00001; I2 = 0%) and less post-drainage cholangitis (RD = 0.08; 95% CI 0.01-0.15; p = 0.02; I2 = 48%) when compared to the EBD group. There was no statistical difference between the groups regarding: technical success, post-drainage bleeding, major post-drainage complications, and seeding metastases.

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Abstract Background: The accuracy of diagnosis and the safety of treatment in colonoscopy depends largely on the quality of bowel cleansing. This study aimed to compare the efficacy and adverse reactions of Polyethylene Glycol (PEG) combined with lactulose with that of PEG alone in bowel preparation before colonoscopy. Methods: The authors searched a number of databases including EMBASE, MEDLINE, Cochrane Library, and China Academic Journals Full-text Database. The authors screened according to literature inclusion and exclusion criteria, assessed the quality of the included literature, and extracted the data. The meta-analysis of included literature used RevMan 5.3 and Stata 14.0 software. Results: A total of 18 studies, including 2274 patients, were enrolled. The meta-analysis showed that PEG combined with lactulose had a better efficacy (OR = 3.87, 95% CI 3.07‒4.87, p = 0.000, and I2 = 36.2% in the efficiency group; WMD = 0.86, 95% CI 0.69‒1.03, p = 0.032 and I2 = 0% in the BBPS score group) in bowel preparation for patients with or without constipation. Moreover, PEG combined with lactulose had fewer adverse reactions, including abdominal pain (OR = 1.42, 95% CI 0.94‒2.14, p = 0.094), nausea (OR = 1.60, 95% CI 1.13‒2.28, p = 0.009) and vomiting (OR = 1.77, 95% CI 1.14‒2.74, p = 0.011), than PEG alone. No significant reduction in the incidence of abdominal distention was observed. Conclusion: PEG combined with lactulose may be a better choice for bowel preparation before colonoscopy compared with PEG alone.

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Abstract Programmed Cell Death-1 (PCD-1) is a key immune checkpoint receptor, which mainly expresses on activated T, B, Dendritic (DC), Natural Killer (NK), and Treg cells. On the surface of activated T-cells, PCD-1 expression is upregulated after the recognition of peripherals antigens by T cells; subsequently, the elevated binding of PD-1 to Programmed Death Ligand-1 (PD-L1) and Programmed Death Ligand-2 (PD-L2) becomes a key step for downstream inhibitory signaling. Although the role of PD-L1 has been evaluated more thoroughly by clinical research, and PD-L1 has also been used more widely in the clinical setting, PD-L2 also plays an important role in the negative regulation of T-cells, one of the necessary conditions that lead to immune tolerance. Expression of PD-L1 either in tumors or in infiltrating immune cells has been verified predominantly by Immunohistochemistry (IHC) in a variety of tumors, suggesting a role for the PD-1/PD-L1 axis as a prognostic trait and therapeutic target across multiple histotypes. The complex interplay between these factors plays a major role in the diffusion and clinical application of PD-L1 IHC assays as predictive biomarkers of response to PD-1/PD-L1 inhibitors. Checkpoint blockades are registered for the treatment of various cancers, including gynecological malignancies.

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Abstract Background: Lung transplantation represents the definite treatment for CF patients with advanced-stage pulmonary disease. Recent major developments in the treatment of CF indicate the need for an evaluation of lung transplantation as the current best practice in end-stage disease. This systematic review was performed to evaluate the impact of lung transplantation on health-related quality of life in patients with CF. Methods: PubMed was searched for studies matching the eligibility criteria between January 2000 and January 2022. OVID (MEDLINE), Google Scholar, and EBSCOhost (EMBASE) as well as bibliographies of included studies were also reviewed. Applying predetermined eligibility criteria, the included studies were selected. Predetermined forms were used to conduct a quality appraisal and implement data tabulation. Results were synthesized by narrative review. This systematic review was prospectively registered in the PROSPERO register (CRD 42022341942). Results: Ten studies (1494 patients) were included. Lung transplantation results in improvements in HRQoL in CF patients relative to their baseline waitlisted state. Up to five years postoperatively CF patients retain their HRQoL at levels similar to the general population. There are several modulating factors that impact HRQoL outcomes in CF patients post-LTx. Compared to lung recipients with other diagnoses CF patients achieve either greater or equal levels of HRQoL. Conclusion: Lung transplantation conveys improved HRQoL to CF patients with the advanced-stage pulmonary disease for up to five years, and to levels comparable to the general population and non-waitlisted CF patients. This systematic review quantifies, using current evidence, the improvements in HRQoL gained by CF patients following lung transplantation.

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Abstract Despite having an organized mental health law and policy, a majority of patients with depression remain underreported and undertreated in Brazil. The study aimed to quantitatively map and identify the deficiencies in patient journey touchpoints in terms of awareness, screening, diagnosis, treatment, adherence, and control for depression in Brazil using a semi-systematic approach highlighting the knowledge gaps in the existing literature. A structured search of Embase, MEDLINE, and BIOSIS databases was conducted to identify the relevant studies published in English, Portuguese, and Spanish from 2006 to 2021. An unstructured search was also conducted on Google or government websites with no restrictions. To address the data gaps, anecdotal data were also considered. Weighted or simple means were calculated for the pooled data. Of 3175 articles retrieved, 10 articles met the inclusion criteria. Synthesized evidence indicates that the pooled prevalence of depression in Brazil ranged from 4.1% to 21.8%; 42.4% of patients had awareness of depression, 37.5% underwent screening, 18.7% had a diagnosis, and 54.4% received treatment. No data on adherence and control were available. The study findings highlight the need for more research to accurately estimate the common patient journey touchpoints for depression to achieve better clinical outcomes in Brazil.

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Abstract Objectives: Remdesivir is an antiviral agent with positive effects on the prognosis of Coronavirus Disease (COVID-19). However, there are concerns about the detrimental effects of remdesivir on kidney function which might consequently lead to Acute Kidney Injury (AKI). In this study, we aim to determine whether remdesivir use in COVID-19 patients increases the risk of AKI. Methods: PubMed, Scopus, Web of Science, the Cochrane Central Register of Controlled Trials, medRxiv, and bio-Rxiv were systematically searched until July 2022, to find Randomized Clinical Trials (RCT) that evaluated remdesivir for its effect on COVID-19 and provided information on AKI events. A random-effects model metaanalysis was conducted and the certainty of evidence was evaluated using the Grading of Recommendations Assessment, Development, and Evaluation. The primary outcomes were AKI as a Serious Adverse Event (SAE) and combined serious and non-serious Adverse Events (AE) due to AKI. Results: This study included 5 RCTs involving 3095 patients. Remdesivir treatment was not associated with a significant change in the risk of AKI classified as SAE (Risk Ratio [RR]: 0.71, 95% Confidence Interval [95% CI] 0.43‒1.18, p = 0.19, low-certainty evidence) and AKI classified as any grade AEs (RR = 0.83, 95% CI 0.52‒1.33, p = 0.44, low-certainty evidence), compared to the control group. Conclusion: Our study suggested that remdesivir treatment probably has little or no effect on the risk of AKI in COVID-19 patients.

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Abstract Colorectal Cancer (CRC) is the third most common type of cancer worldwide and ranks second in mortality. Screening programs for early detection and treatment have been implemented in several countries. Economic evaluations are an important tool to support decision-making about reimbursement and coverage decisions in health systems and, therefore, to support efficient resource allocation. The article aims to review the up-to-date evidence on economic evaluations of CRC screening strategies. MEDLINE, EMBASE, Web of Science, SCOPUS, SciELO, Lilacs, CRD databases, and lists of references were reviewed to identify relevant literature regarding full economic evaluations of CRC screening in asymptomatic average-risk individuals over 40 years old. Searches were conducted with no restriction to language, setting, or date. Qualitative syntheses described CRC screening strategies and comparators (baseline context), study designs, key parameter inputs and incremental cost-effectiveness ratios. Seventy-nine articles were included. Most of the studies were from high-income countries and a third-party payer perspective. Markov models were predominantly used, although microsimulation has been increasingly adopted in the last 15 years. The authors found 88 different screening strategies for CRC, which differed in the type of technique, the interval of screening, and the strategy, i.e., isolated or combined. The annual fecal immunochemical test was the most predominant screening strategy. All studies reported cost-effective results in their scenarios compared to no screening scenarios. One-quarter of the publications reported cost-saving results. It is still necessary to develop future economic evaluations in Low- and Middle-Income Countries (LMICs), which account for the high burden of disease.

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Abstract Objective: This study aimed to perform a meta-analysis to investigate the diagnostic safety and accuracy of Ultrasound-Guided Core Needle Biopsy (US-CNB) Axillary Lymph Nodes (ALNs) region in patients with Breast Cancer (BC). Methods: The authors searched the electronic databases PubMed, Scopus, Embase, and Web of Science for clinical trials about US-CNB for the detection of ALNs in breast cancer patients. The authors extracted and pooled raw data from the included studies and performed statistical analyses using Meta-DiSc 1.4 and Review Manager 5.3 software. A random effects model was used to calculate the data. At the same time, data from the Ultrasound-guided Fine-Needle Aspiration (US-FNA) were introduced for comparison with the US-CNB. In addition, the subgroup was performed to explore the causes of heterogeneity. (PROSPERO ID: CRD42022369491). Results: In total, 18 articles with 2521 patients were assessed as meeting the study criteria. The overall sensitivity was 0.90 (95% CI [Confidence Interval], 0.87‒0.91; p = 0.00), the overall specificity was 0.99 (95% CI 0.98‒ 1.00; p = 0.62), the overall area under the curve (AUC) was 0.98. Next, in the comparison of US-CNB and US-FNA, US-CNB is better than US-FNA in the diagnosis of ALNs metastases. The sensitivity was 0.88 (95% CI 0.84‒ 0.91; p = 0.12) vs. 0.73 (95% CI 0.69‒0.76; p = 0.91), the specificity was 1.00 (95% CI 0.99‒1.00; p = 1.00) vs. 0.99 (95% CI 0.67‒0.74; p = 0.92), and the AUC was 0.99 vs. 0.98. Subgroup analysis showed that heterogeneity may be related to preoperative Neoadjuvant Chemotherapy (NAC) treatment, region, size of tumor diameter, and the number of punctures. Conclusion: US-CNB has a satisfactory diagnostic performance with good specificity and sensitivity in the preoperative diagnosis of ALNs in BC patients.

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Highlights The prevalence of chronic pain in the adult population (35.70%) and older adults (47.32%). Differs from region to region and is associated with heterogeneous risk factors. Manifested mainly with moderate or severe intensity and with an elevated rate of disability.

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Highlights None of the analized studies related serious adverse effects or toxicity to IV ASCs administration. This review suggests optimism in IV ASCs for lung damage in severe COVID-19 ARDS. Further studies on IV ASCs in COVID-19 are needed for standard dosage.

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Highlights Improving the cellular environment is expected to further optimize the management of HF. Metabolic remodeling is the driving force of deteriorated cellular environment in HF. Targeting impaired energy provision is of great potential in the treatment of HF.

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Highlights CT radiomics could preoperatively predict MVI in HCC with an AUC of 0.87. Radiomics model based on 3D tumor segmentation, and deep learning model can be superior to predict MVI. Reproducibility of current radiomics models for clinical application may be uncertain.

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Abstract Lipolytic substance injections to reduce localized fat have been extensively used because it is a low-invasive method. This review aimed to evaluate the efficacy and safety of deoxycholic acid in submental fat reduction compared to a placebo and investigate the potential industry sponsorship bias in the results of randomized clinical trials on this topic. Ten electronic databases were extensively searched for randomized clinical trials without restriction on language and year of publication. Two reviewers extracted the data and assessed the individual risk of bias in the studies with the RoB 2.0 tool. The industry sponsorship bias was evaluated according to citations in the articles regarding industry funding/sponsorship throughout the texts. Fixed and random effects meta-analyses were performed, and the results were reported in Risk Ratio (RR) at a 95% Confidence Interval (95% CI). The initial search provided 5756 results, of which only five were included. Only two studies had a low risk of bias. All studies showed a potential industry bias. The meta-analysis showed that patients treated with deoxycholic acid had significant positive results for all efficacy outcomes and a higher risk of fibrosis, pain, erythema, numbness, swelling, edema, pruritus, nodules, headache, and paresthesia. The low to moderate certainty of evidence found allows concluding that deoxycholic acid is effective in submental fat reduction, causing well-tolerated adverse effects. However, all eligible studies showed a potential industry bias.

Resumo em Inglês:

Abstract Background: In recent years, more and more studies have shown that microRNA-29a (miRNA-29a) can be used as a potential biomarker for active tuberculosis, but the results of these studies are not consistent. Objective: To comprehensively evaluate the value of miRNA-29a in the diagnosis of active tuberculosis by meta-analysis. Methods: The databases of CNKI, WanFang, PubMed, The Cochrane Library, Web of Science and EMBASE were searched for relevant studies. Studies were screened strictly according to inclusion and exclusion criteria. QUA-DAS-2 scale was used to evaluate the quality of the included studies. Data were extracted and analyzed by Meta-DiSc 1.4 and Stata 16.0 software. Results: 13 articles were included, including a total of 1598 subjects, including 872 active tuberculosis patients and 726 controls. The combined sensitivity and specificity of miRNA-29a in the diagnosis of active tuberculosis were 78 % and 76 %, respectively, and the area under the overall summary receiver operating characteristic curve was 0.8564. Conclusion: miRNA-29a can be used as a biomarker for the diagnosis of active tuberculosis.

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Highlights Epigenetics, hypersensibility and asthma: what do we know so far? Asthma can be triggered from epigenetic changes. Early life exposures can contribute to the development and exacerbation of asthma. DNA methylation profile of certain genes is related to asthma and allergy. Nasal epithelium samples have shown promise as a tissue for studying DNA methylation changes related to asthma. To find biomarkers and standardized assays to advance the field of epigenetics in respiratory disorders are still a challenge.

Resumo em Inglês:

Highlights Bisphenola A (BPA) is an endocrine disruptor widely investigated as a possible environmental contributor to the pathogenesis of Polycystic Ovary Syndrome (PCOS). Due to its structural similarity with the Estrogen molecule (E2), it acts as a xenoestrogen, binding to genomic and non-genomic estrogen receptors, causing metabolic and hormonal changes that lead to PCOS (hyperandrogenism, insulin resistance, hyperinsulinemia, obesity, atherogenic dyslipidemia, anovulation, and ovarian cysts). The aim and of this review were to present the mechanisms of bisphenol A participation in the pathogenesis of Polycystic Ovary Syndrome.

Resumo em Inglês:

Highlights Homeopathy is based on heterodox and complementary four scientific assumptions. Pseudosceptics deny these assumptions and any scientific evidence that proves them. The dossier describes hundreds of clinical and experimental studies in homeopathy. The dossier demystifies the fallacy that “there isn't scientific evidence for homeopathy”.