Coronary artery bypass grafting in octogenarians: a nomogram for predicting all-cause mortality.

BACKGROUND: The benefits and risks of coronary artery bypass grafting (CABG) in octogenarians remain unclear. This study aimed to identify the predictors of increased risk of all-cause mortality in octogenarian patients after CABG. METHODS: We retrospectively analyzed the data of 1636 octogenarians who underwent isolated elective on-pump CABG between 2007 and 2016. The primary endpoint was mortality from any cause. The Kaplan-Meier curve was generated for mortality. A univariate Cox regression was performed for preprocedural and procedural variables. The Akaike information criterion (AIC) using the Cox proportional hazard model was applied to determine the strongest predictors. We designed a nomogram based on the selected variables to calculate the mortality risk after one, five, and ten years. The bootstrap resampling based on the C-index was performed to validate the final model. Calibration plots were created at different time points. RESULTS: The mean age of the patients was 82.03 years (SD = 1.74), and 74% were male. In a median follow-up of 9.2 (95% CI 9.0,9.5) years, 626 (38.2%) patients died. After the selection of best predictors based on AIC, the multivariable Cox regression showed that ejection fraction < 40 (HR 1.41, 95% CI 1.21-1.65, P < 0.001), two-vessel disease (HR: 0.59, 95% CI 0.40-0.89, P = 0.012), peripheral vascular disease (HR 1.52, 95% CI 1.05-2.21, P = 0.027), and valvular heart disease (HR 1.45, 95% CI 1.24-1.69, P < 0.001) were the significant predictors of all-cause mortality. CONCLUSION: Octogenarians who undergo CABG have a high mortality risk, influenced by several preprocedural and procedural risk factors. The proposed nomogram can be considered for optimizing the management of this vulnerable age group. Clinical registration number IR.TUMS.THC.REC.1400.081.

Localized Administration of Mesenchymal Stem Cell-Derived Exosomes for the Treatment of Refractory Perianal Fistula in Crohn's Disease Patients: A Phase II Clinical Trial.

BACKGROUND: Crohn's disease perianal fistulae are often resistant to standard anti-TNF-α therapies. Mesenchymal stem cell (MSC)-derived exosomes are extracellular vesicles that have highly potent anti-inflammatory effects, and the previous phase of this study demonstrated their safety in the treatment of refractory perianal fistulas. OBJECTIVE: To evaluate the efficacy of mesenchymal stem cell-derived exosomes for the treatment of refractory perianal fistulas. DESIGN: Nonrandomized, nonblinded single-center phase II clinical trial. SETTINGS: Tertiary university hospital. PATIENTS: Twenty-three patients were enrolled, 20 of whom completed the study. Refractory perianal fistula was defined as resistance to at least one course of treatment with anti-tumor necrosis facto-α therapy. INTERVENTIONS: After clinical assessment and magnetic resonance imaging, the patients were subjected to general anesthesia, and 5 mL of exosome solution was injected directly into the fistula tracts. The injections were repeated three times at 2-month intervals, and patients were followed monthly for 6 months after the last injection. Tissue samples from the tracts were obtained before each injection and subjected to immunohistopathological assessment. MRI data were obtained before and six months after the last injection. MAIN OUTCOME MEASURES: The primary outcome of this study was fistula tract closure on clinical examination and magnetic resonance imaging. The secondary outcome was an improvement in the discharge from the tracts. RESULTS: Fistula tracts were fully closed in 12 (60%) of the patients. Four patients showed clinical improvement, with some tracts remaining open, and four patients were completely resistant to treatment. A total of 43 fistula tracts were treated during the trial, 30 (69.7%) of which showed complete closure. Histopathological analysis revealed substantial reductions in local inflammation and signs of enhanced tissue regeneration. Immunohistochemical analysis of cluster of differentiation-68, 20 and 31 reaffirmed these results. CONCLUSIONS: MSC-derived exosomes are safe and effective for treating refractory perianal fistulas in patients with Crohn's disease. See Video Abstract.

Predictive value of flexible proctosigmoidoscopy and laboratory findings for complete clinical responses after neoadjuvant chemoradiotherapy in patients with locally advanced primary rectal cancer: a retrospective cohort study.

PURPOSE: Colorectal cancer is the second leading cause of cancer death worldwide. Standard treatments for locally advanced rectal cancer include neoadjuvant chemoradiotherapy and total mesorectal excision (TME), which are associated with significant morbidity. After neoadjuvant therapy, one-third of patients achieve a pathological complete response (pCR) and are eligible for a watch-and-wait approach without TME. The purpose of this study was to determine the potential predictors of pCR before surgery. METHODS: The demographic, clinical, and endoscopic data of 119 patients with primary locally advanced rectal cancer without distant metastasis who underwent restaging endoscopy and TME 6-8 weeks after the end of neoadjuvant therapy were collected. The absence of tumor cells in the histological examination of the TME specimen after neoadjuvant therapy was considered pCR. Binary logistic regression and receiver operating characteristic curves were utilized for analysis. RESULTS: According to the multivariate logistic regression analysis, flattening of marginal tumor swelling (p value < 0.001, odds ratio = 100.605) emerged as an independent predictor of pCR in rectal cancer patients. Additionally, receiver operating characteristic curve analysis revealed that lower preoperative carcinoembryonic antigen and erythrocyte sedimentation rate levels predict pCR, with cutoffs of 2.15 ng/ml and 19.0 mm/h, respectively. CONCLUSION: Carcinoembryonic antigen and erythrocyte sedimentation rate, along with the presence of flattening of marginal tumor swelling, can predict pCR after neoadjuvant chemoradiotherapy in patients with primary rectal cancer. These factors offer a potential method for selecting candidates for conservative treatment based on endoscopic and laboratory findings.

Association between pre-diabetes or diabetes and cognitive impairment in a community-dwelling older population: Bushehr Elderly Health (BEH) program.

Background: Persistent uncontrolled hyperglycemia is recognized as one of the risk factors for cognitive disorders. Accordingly, both type 1 and type 2 diabetes may predispose individuals to cognitive impairment, particularly in cases where glycemic control is insufficient. The objective of this comprehensive study is to separately assess cognitive dysfunctions in diabetic and non-diabetic older adults. Methods: This cross-sectional study is part of phase 2 of the Bushehr elderly health program (BEHP). Cognitive function was evaluated using the Mini-cog and categorical verbal fluency tests (CFTs). Patients were classified as non-diabetics, pre-diabetics, or diabetics based on the diagnostic criteria for diabetes mellitus (DM). To compare the means of the two groups, we utilized the t-test or the Mann-Whitney test. Additionally Multivariable logistic regression models were used to determine the association between pre-diabetes or DM and cognitive impairment. Results: Out of 1533 participants, 693 (45.2%) were identified as having cognitive impairment. The average hemoglobin A1C was higher in participants with cognitive impairment compared to those without cognitive impairment. (5.8 ± 1.6% vs. 5.5 ± 1.4%, P = 0.004). Furthermore, the mean blood glucose levels were found to be more elevated in cases of cognitive impairment (108.0 ± 47.4 mg/dL vs. 102.1 ± 0.35 mg/dL, P = 0.002). After adjusting for age, gender, body mass index (BMI), waist circumference, amount of physical activity, and smoking, the multivariable logistic regression model, declared an association between diabetes and cognitive impairment (OR = 1.48, P = 0.003). In addition, older patients, females, widows, and individuals with elevated LDL-Cs and those with high blood pressure were found to be more vulnerable to cognitive impairment. Conclusion: The Bushehr Elderly Health Program (BEHP) study revealed that individuals affected with cognitive impairment may exhibit higher levels of HbA1c. This suggests a positive correlation between elevated HbA1c and cognitive impairment.

Exploring the metabolomics profile of frailty- a systematic review.

Background: Frailty is a multifaceted geriatric syndrome characterized by an increased vulnerability to stressful events. metabolomics studies are valuable tool for better understanding the underlying mechanisms of pathologic conditions. This review aimed to elucidate the metabolomics profile of frailty. Method: This systematic review was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) 2020 statement. A comprehensive search was conducted across multiple databases. Initially, 5027 results were retrieved, and after removing duplicates, 1838 unique studies were subjected to screening. Subsequently, 248 studies underwent full-text screening, with 21 studies ultimately included in the analysis. Data extraction was performed meticulously by two authors, and the quality of the selected studies was assessed using the Critical Appraisal Skills Program (CASP) checklist. Results: The findings revealed that certain Branched-chain amino acids (BCAAs) levels were lower in frail subjects compared to robust subjects, while levels of glutamate and glutamine were higher in frail individuals. Moreover, sphingomyelins and phosphatidylcholines (PC) displayed a decreasing trend as frailty advanced. Additionally, other metabolic derivatives, such as carnitine, exhibited significant associations with frailty. These metabolites were primarily interconnected through biochemical pathways related to the tricarboxylic acid and urea cycles. Notably, frailty was associated with a decrease in metabolic derivatives, including carnitine. Conclusion: This study underscores the intricate relationship between essential metabolites, including amino acids and lipids, and their varying levels in frail individuals compared to their robust counterparts. It provides a comprehensive panel of metabolites, shedding light on their potential associations with frailty and expanding our understanding of this complex syndrome.

Comparing the effectiveness of letrozole versus methotrexate for treatment of ectopic pregnancy: A randomized controlled trial.

OBJECTIVE: To evaluate the efficacy of two different regimens of Letrozole, an aromatase inhibitor, in the management of ectopic pregnancy compared to methotrexate. STUDY DESIGN: This randomized controlled trial was conducted on 88 women diagnosed with ectopic pregnancy with a baseline level of serum beta-human chorionic gonadotropin under 3000 mIU/mL between June 30, 2023, and December 30, 2023, at the Department of Obstetrics and Gynecology of the Vali-e-Asr Hospital affiliated with Tehran University of Medical Sciences. Participants were allocated into either methotrexate (n = 43), 5-day course Letrozole (n = 24), or 10-day course Letrozole (n = 21) treatments. The methotrexate group received a single dose of 50 mg/m2 dosage intramuscular methotrexate. The 5-day Letrozole group received a 2.5 mg Letrozole tablet three times daily for 5 days, whereas the 10-day Letrozole group received a 2.5 mg Letrozole tablet twice daily for 10 days. The primary outcome was the treatment response, defined as the achievement of a negative serum beta-human chorionic level without the need for additional methotrexate treatment or surgery. The secondary outcomes were the need for additional methotrexate dose or laparoscopic surgery intervention. The trial protocol was prospectively registered in ClinicalTrials.gov with code NCT05918718. RESULTS: The treatment response rates in methotrexate, 5-day Letrozole, and 10-day Letrozole groups were 76.7 %, 75.0 %, and 90.5 %, respectively, with no significant differences between the groups (P-value = 0.358). A total of 10 (23.3 %) patients from the methotrexate group, 3 (12.5 %) from the 5-day Letrozole group, and 2 (9.5 %) from the 10-day Letrozole group required an additional methotrexate dose, with no significant differences between the groups (P-value = 0.307). Furthermore, only 3 (12.5 %) patients, all from the 5-day Letrozole group, were suspected of tubal rupture and underwent surgery (P-value = 0.016). CONCLUSION: Our findings suggest Letrozole as a safe alternative to methotrexate in treating stable ectopic pregnancies, with a favorable treatment response rate. However, there is still a need for future larger studies to determine the applicability of Letrozole in the EP management. Also, the non-significant higher effectiveness of the 10-day Letrozole regimen than the 5-day Letrozole group underscores the need for future research to determine the optimal Letrozole regimen for the management of ectopic pregnancy.

Diagnostic Performance of Ultrasonography for Identification of Small Bowel Obstruction; a Systematic Review and Meta-analysis.

Introduction: Small bowel obstruction (SBO) is known as a common cause of acute abdominal complaints in the emergency department (ED). The modality of choice for the diagnosis of SBO has not yet been established. This systematic review and meta-analysis aimed to investigate the accuracy of ultrasonography for the diagnosis of SBO. Methods: Systematic search was performed on five electronic databases including Medline, Scopus, Web of Sciences, Embase, and Cochrane Library, and the retrieval period was from the inception of each database to November 2023. The quality of the included studies were investigated using the Quality Assessment of Diagnostic Accuracy Studies 2 (QUADAS-2). The pooled values of diagnostic characteristics for ultrasonography were estimated using meta-Disc and Stata statistical software. Results: Twenty-one studies with a total of 1977 patients were included in the meta-analysis. The pooled estimate for sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic odds ratio (DOR), and area under the summary ROC curve of ultrasonography for diagnosing SBO were 0.93 (95% CI: 0.91-0.95), 0.8 (95% CI: 0.77-0.83), 5.69 (95% CI: 3.64-8.89), 0.1 (95% CI: 0.07-0.16), 83.51 (95% CI: 18.12-182.91) and 0.96, respectively. Conclusion: The findings of this meta-analysis showed that the utilization of ultrasonography holds promise as a diagnostic imaging for SBO with high accuracy. However, additional worldwide studies are essential to get more evidence on the value of ultrasonography for the diagnosis of SBO.

Enhanced antibacterial activity of porous chitosan-based hydrogels crosslinked with gelatin and metal ions.

Addressing the increasing drug resistance in pathogenic microbes, a significant threat to public health, calls for the development of innovative antibacterial agents with versatile capabilities. To enhance the antimicrobial activity of non-toxic biomaterials in this regard, this study focuses on novel, cost-effective chitosan (CS)-based hydrogels, crosslinked using gelatin (GEL), formaldehyde, and metallic salts (Ag+, Cu2+, and Zn2+). These hydrogels are formed by mixing CS and GEL with formaldehyde, creating iminium ion crosslinks with metallic salts without hazardous crosslinkers. Characterization techniques like FTIR, XRD, FESEM, EDX, and rheological tests were employed. FTIR analysis showed metal ions binding to amino and hydroxyl groups on CS, enhancing hydrogelation. FESEM revealed that freeze-dried hydrogels possess a crosslinked, porous structure influenced by various metal ions. Antibacterial testing against gram-negative and gram-positive bacteria demonstrated significant bacterial growth inhibition. CS-based hydrogels containing metal ions showed reduced MIC and MBC values against Staphylococcus aureus (0.5, 8, 16 µg/mL) and Escherichia coli (1, 16, 8 µg/mL) for CS-g-GEL-Ag+, CS-g-GEL-Cu2+, and CS-g-GEL-Zn2+. MTT assay results confirmed high biocompatibility (84.27%, 85.24%, 84.96% viability at 10 µg/mL) for CS-based hydrogels towards HFF-1 cells over 48 h. Therefore, due to their non-toxic nature, these CS hydrogels are promising for antibacterial applications.

Postoperative complications and unanticipated healthcare encounters following mini-laparotomy vs. laparoscopic/robotic-assisted sacrocolpopexy: a comparative retrospective study.

BACKGROUND: Pelvic organ prolapse is a debilitating condition impacting lives of millions of women worldwide. Sacrocolpopexy (SCP) is considered an effective and durable surgical technique for treatment of apical prolapse. The aim of this study was to compare short-term outcomes including postoperative complications and unanticipated healthcare encounters between patients who underwent SCP with a mini-laparotomy approach compared to patients treated with laparoscopic and robotic-assisted laparoscopic SCP. METHODS: This was a retrospective cohort study including patients treated for apical prolapse at a university affiliated urogynecology practice. Patients over the age of 18 who underwent abdominal SCP between 2019 and 2023 were included. The cohort was formed into two groups: (1) Patients who underwent SCP through a mini-laparotomy incision (Mini-lap group); (2) Patients who underwent laparoscopic or robotic-assisted laparoscopic SCP (Lap/Robot group). RESULTS: A total of 116 patients were included in the final analysis. Ninety patients underwent either laparoscopic or robotic-assisted SCP, whereas 26 patients underwent SCP with a mini-laparotomy approach. Study participants exhibited a mean age of 63.1 ± 10.3 years, mean body mass index (BMI) of 25.8 ± 4.9 Kg/m2, and 77.6% of them identified as Caucasian. Upon comparison of demographic and past medical history between groups there were no statistically significant differences in age, BMI, menopausal status, race, parity or comorbid conditions. Patients in the Mini-lap group were less likely to have undergone previous abdominal surgery (11.5% vs. 50.6%, p < 0.001) and had more severe apical prolapse (stage 4 prolapse, 40% vs. 21.2%, p < 0.001) than their counterparts in the Lap/robot group. Regarding intraoperative parameters, length of surgery was significantly shorter in the Mini-lap group compared to the Lap/robot group (97.3 ± 35.0 min vs. 242.0 ± 52.6 min, p < 0.001). When focusing on the primary outcome, postoperative complications within the first 30 days after surgery, there were no differences noted between groups. Additionally, the number of unanticipated healthcare encounters, such as phone calls, clinic visits, emergency department visits, urgent care visits, readmissions and reoperations were similar between groups. CONCLUSIONS: Mini-laparotomy approach for SCP is safe with comparable intra- and postoperative complications, and unanticipated healthcare encounters compared to conventional minimally invasive methods.

Cesarean Scar Pregnancy: Results of Treatment Using a Double-Balloon Cervical Ripening Catheter.

Background: Being considered a life-threatening condition, cesarean scar pregnancy (CSP) leads to loss of fertility, severe bleeding, and even maternal mortality. We intended to assess the effect of double-balloon cervical ripening catheter insertion on CSP termination before nine weeks of gestation. Method: All participants were diagnosed CSP by abdominal and transvaginal ultrasound. The cases were treated with a sterile, double-balloon cervical ripening catheter inserted with real-time transabdominal ultrasound guidance and removed three days later. The control group consisted of patients treated with systemic methotrexate with or without fetal reduction. Results: Thirty-five patients were eligible for double-balloon ripening and 32 for MTX therapy; the treatment in cases failed in five of the patients. Success rate difference between two methods was insignificant (Pearson Chi-square: 0.383, p-value: 0.536). There were significant differences regarding the time to normal menstruation (OR: 1.303) and the thickness of the myometrium after surgery (OR: 4.721), but there was no significant difference in the time resolve of either ß-HCG or residue of pregnancy. Conclusion: Double-balloon cervical ripening insertion yields acceptable results for terminating CSP. This strategy does not cause bleeding and even prevents it with its tamponade properties. Additionally, this treatment is minimally invasive simple with low morbidity.

Structured Workshop for Repair of High-Grade Perineal Lacerations Among Obstetrics and Gynecology Residents, The Need for Repetition and Retraining.

Objective: The objective of this study was to evaluate the effectiveness of structured workshops in improving the knowledge and skills of obstetrics and gynecology residents for repairing high-grade perineal lacerations. Materials and methods: This quasi-experimental multicenter study evaluated the baseline knowledge of obstetrics and gynecology residents using an online patient-management problem (PMP) tool. After the initial evaluation, a workshop was conducted using sponge models to teach the practical technique for repairing high-grade perineal lacerations, including external and internal anal sphincter repair. The residents' knowledge was reassessed by PMP exams at 3 and 6 months after the workshop, and the scores were compared to the baseline statistics. Result: Eighty residents participated in the study, including 26, 22, and 32 at the first, second, and third-year levels of residency, respectively. The total PMP scores significantly improved after three months of the workshop, with an increasing total score from 15.5 (baseline) to 31.3 (p = 0.027) (range of total score from - 63 to + 52). The senior residents performed better before and after three months of the intervention. However, in the six-month follow-up, the total PMP score of all residents decreased to 12.3 with no significant difference with pre-education scores at all levels. Similar significant results were also reported for each PMP question at all levels of residency. Conclusion: The study found that obstetrics and gynecology residents had substandard knowledge in repairing perineal lacerations. Although the training workshop significantly increased residents' knowledge, its effectiveness diminished over time, indicating a need for continuous or periodic training. Supplementary Information: The online version contains supplementary material available at 10.1007/s13224-023-01792-6.

Methotrexate as the first-line treatment of unruptured tubular ectopic pregnancies with high initial human chorionic gonadotropin levels: A retrospective cohort.

Objectives: To evaluate the effectiveness of the first-line medical management with Methotrexate (MTX) in the treatment of patients with stable tubal Ectopic Pregnancies (EPs) and varying ranges of Beta-Human Chorionic Gonadotropin (ß-HCG) levels. Materials and methods: In this retrospective cohort study, we reviewed the medical records of a total of 184 patients with the diagnosis of tubal EP, who received MTX as their first-line treatment. Patients with a baseline ß-HCG< 4800 mIU/mL received single-dose MTX (n = 136) and those with an initial ß-HCG≥ 4800 mIU/mL underwent the double-dose MTX regimen (n = 48). The treatment success was determined by evaluating the reported weekly ß-HCG levels of the patients. Results: Baseline ß-HCG and mass size in the single-dose group were 1895.1 ± 1463.4 mIU/mL and 2.2 ± 1.1 cm, respectively, compared to 17,867.6 ± 31,870.5 mIU/mL and 2.3 ± 1.1 cm in the double-dose group. Treatment duration was 30.6 ± 16.9 days for single dose and 41.0 ± 27.0 days for double dose, with additional MTX in 27.2% and 12.5% in respective groups. Single dose achieved a 92.6% success rate, and double dose, 81.3%, without serious adverse effects. No significant effects were seen for either baseline ß-HCG and mass size on the treatment success rates of both groups (p-value>0.05). However, the presence of Fetal Heart Rate (FHR) was associated with poorer responses only in the single-dose group (p-value=0.034). Conclusions: Medical management with MTX shows promise as a first-line treatment for tubal EPs with ß-HCG> 2000, suggesting a potential reassessment of existing guidelines in light of this emerging evidence. However, further research seems crucial in this field.

Development of preeclampsia in pregnant women with white-coat hypertension: a systematic review and meta-analysis.

OBJECTIVE: Hypertensive disorders during pregnancy are a significant cause of maternal and perinatal mortality and morbidity worldwide. White coat hypertension (WCH) is a hypertensive disease characterized by an increased clinic blood pressure but normal home or workplace blood pressure. Due to variable prevalence, a subset of women with WCH may be incorrectly diagnosed with chronic hypertension, highlighting the need for accurate diagnosis. Little is known about the role of WCH in pregnancy, but a meta-analysis aims to determine whether WCH increases the likelihood of developing preeclampsia. METHODS: A systematic review and meta-analysis was conducted to determine whether there is an association between WCH and the incidence of preeclampsia in pregnant women. The search included PubMed, Embase, and Scopus databases until February 2023, using PRISMA guidelines. Pregnant women with apparent office hypertension throughout pregnancy who underwent 24-hour ambulatory blood pressure monitoring or home blood pressure monitoring were included. Meta-analysis was performed using RevMan. RESULTS: This study included 12 studies with a total of 4,672 pregnant women and found that women with WCH have a higher risk of developing preeclampsia compared to normotensive women (RR: 2.29, 95% CI [1.18,4.43], P = 0.01). However, when compared with pregnant women with gestational hypertension or chronic hypertension, women with WCH had a significantly lower risk of developing preeclampsia ((RR: 0.39, [0.20,0.80], p=0.009) and (RR: 0.41, [0.27,0.62], P<0.001), respectively). CONCLUSION: The study recommends incorporating 24-hour ABPM into clinical practice to differentiate between chronic hypertension and WCH in early pregnancy and focus on special management for those who need it. The findings may guide future research on ABPM's role in diagnosing WCH and its effects on pregnancy outcomes.

Incidence and Outcomes Associated with Menopausal Status in COVID-19 Patients: A Systematic Review and Meta-analysis.

OBJECTIVE: Menopause causes several changes in the body that may affect the response to COVID -19. We aimed to investigate the possible association between menopausal status and incidence and outcomes in COVID-19 patients. METHODS: Combinations of keywordsCOVID-19, menopause, and estrogen were used to search the PubMed, Embase, Web-of-Science, and Scopus databases for articles reporting the incidence and outcomes of COVID-19 (discharge, length-of-admission, intensive care, or mortality) in premenopausal women, available through December 29, 2022. Data from studies comparing the incidence of COVID-19 infection with the age-matched male population were pooled and meta-analyzed using a random-effects model. RESULTS: Overall, 1,564 studies were retrieved, of which 12 were finally included in the systematic review to compare disease outcomes, and 6 were meta-analyzed for the incidence of COVID-19 in premenopausal and postmenopausal women. All studies reported better COVID-19-associated outcomes in premenopausal women compared with postmenopausal women. After adjusting for confounding factors, three studies found better outcomes in postmenopausal women, and two found no association between menopausal status and COVID-19 outcomes. Our meta-analysis found a higher incidence of COVID-19 infection among premenopausal women than postmenopausal women, when compared with age-matched men (odds ratio = 1.270; 95% confidence interval: 1.086-1.486; p = 0.003). CONCLUSION: The incidence of COVID-19 was significantly higher in premenopausal women than in postmenopausal women when compared with age-matched men. Although premenopausal women may have more favorable COVID-19-associated outcomes, the presumed preventive effect of estrogens on the incidence and related outcomes of COVID-19 in premenopausal women cannot be proven at present. Further longitudinal studies comparing pre- and post-menopausal women are required to provide further insight into this matter.

OBJETIVO: A menopausa causa diversas alterações no corpo que podem afetar a resposta ao COVID-19. Nosso objetivo foi investigar a possível associação entre o status da menopausa e a incidência e os resultados em pacientes com COVID-19. MéTODOS: Combinações de palavras-chave COVID-19, menopausa e estrogênio foram usadas para pesquisar os bancos de dados PubMed, Embase, Web-of-Science e Scopus para artigos relatando a incidência e os resultados do COVID-19 (alta, tempo de internação, tratamento intensivo cuidados ou mortalidade) em mulheres na pré-menopausa, disponível até 29 de dezembro de 2022. Dados de estudos comparando a incidência de infecção por COVID-19 com a população masculina da mesma idade foram agrupados e meta-analisados usando um modelo de efeitos aleatórios. RESULTADOS: No geral, 1.564 estudos foram recuperados, dos quais 12 foram finalmente incluídos na revisão sistemática para comparar os resultados da doença e 6 foram meta-analisados para a incidência de COVID-19 em mulheres na pré e pós-menopausa. Todos os estudos relataram melhores resultados associados ao COVID-19 em mulheres na pré-menopausa em comparação com mulheres na pós-menopausa. Após o ajuste para fatores de confusão, três estudos encontraram melhores resultados em mulheres na pós-menopausa e dois não encontraram associação entre o status da menopausa e os resultados do COVID-19. Nossa meta-análise encontrou uma maior incidência de infecção por COVID-19 entre mulheres na pré-menopausa do que mulheres na pós-menopausa, quando comparadas com homens da mesma idade (odds ratio = 1,270; intervalo de confiança de 95%: 1,086­1,486; p = 0,003). CONCLUSãO: A incidência de COVID-19 foi significativamente maior em mulheres na pré-menopausa do que em mulheres na pós-menopausa quando comparadas com homens da mesma idade. Embora as mulheres na pré-menopausa possam ter resultados mais favoráveis associados ao COVID-19, o efeito preventivo presumido dos estrogênios na incidência e nos resultados relacionados ao COVID-19 em mulheres na pré-menopausa não pode ser comprovado no momento. Mas estudos longitudinais comparando mulheres pré e pós-menopausa são necessários para fornecer mais informações sobre este assunto.

Incidence and Outcomes Associated with Menopausal Status in COVID-19 Patients: A Systematic Review and Meta-analysis / Incidência e resultados associados ao estado da menopausa em pacientes com COVID-19: Uma revisão sistemática e metanálise

Abstract Objective Menopause causes several changes in the body that may affect the response to COVID-19. We aimed to investigate the possible association between menopausal status and incidence and outcomes in COVID-19 patients. Methods Combinations of keywordsCOVID-19, menopause, and estrogen were used to search the PubMed, Embase, Web-of-Science, and Scopus databases for articles reporting the incidence and outcomes of COVID-19 (discharge, length-of-admission, intensive care, or mortality) in premenopausal women, available through December 29, 2022. Data from studies comparing the incidence of COVID-19 infection with the age-matched male population were pooled and meta-analyzed using a random-effects model. Results Overall, 1,564 studies were retrieved, of which 12 were finally included in the systematic review to compare disease outcomes, and 6 were meta-analyzed for the incidence of COVID-19 in premenopausal and postmenopausal women. All studies reported better COVID-19-associated outcomes in premenopausal women compared with postmenopausal women. After adjusting for confounding factors, three studies found better outcomes in postmenopausal women, and two found no association between menopausal status and COVID-19 outcomes. Our meta-analysis found a higher incidence of COVID-19 infection among premenopausal women than postmenopausal women, when compared with age-matched men (odds ratio = 1.270; 95% confidence interval: 1.086-1.486; p= 0.003). Conclusion The incidence of COVID-19 was significantly higher in premenopausal women than in postmenopausal women when compared with age-matched men. Although premenopausal women may have more favorable COVID-19-associated outcomes, the presumed preventive effect of estrogens on the incidence and related outcomes of COVID-19 in premenopausal women cannot be proven at present. Further longitudinal studies comparing pre- and post-menopausal women are required to provide further insight into this matter.

Resumo Objetivo A menopausa causa diversas alterações no corpo que podem afetar a resposta ao COVID-19. Nosso objetivo foi investigar a possível associação entre o status da menopausa e a incidência e os resultados em pacientes com COVID-19. Métodos Combinações de palavras-chave COVID-19, menopausa e estrogênio foram usadas para pesquisar os bancos de dados PubMed, Embase, Web-of-Science e Scopus para artigos relatando a incidência e os resultados do COVID-19 (alta, tempo de internação, tratamento intensivo cuidados ou mortalidade) em mulheres na pré-menopausa, disponível até 29 de dezembro de 2022. Dados de estudos comparando a incidência de infecção por COVID-19 com a população masculina da mesma idade foram agrupados e meta-analisados usando um modelo de efeitos aleatórios. Resultados No geral, 1.564 estudos foram recuperados, dos quais 12 foram finalmente incluídos na revisão sistemática para comparar os resultados da doença e 6 foram meta-analisados para a incidência de COVID-19 em mulheres na pré e pós-menopausa. Todos os estudos relataram melhores resultados associados ao COVID-19 em mulheres na pré-menopausa em comparação com mulheres na pós-menopausa. Após o ajuste para fatores de confusão, três estudos encontraram melhores resultados em mulheres na pós-menopausa e dois não encontraram associação entre o status da menopausa e os resultados do COVID-19. Nossa meta-análise encontrou uma maior incidência de infecção por COVID-19 entre mulheres na pré-menopausa do que mulheres na pós-menopausa, quando comparadas com homens da mesma idade (odds ratio = 1,270; intervalo de confiança de 95%: 1,086-1,486; p = 0,003). Conclusão A incidência de COVID-19 foi significativamente maior em mulheres na pré-menopausa do que em mulheres na pós-menopausa quando comparadas com homens da mesma idade. Embora as mulheres na pré-menopausa possam ter resultados mais favoráveis associados ao COVID-19, o efeito preventivo presumido dos estrogênios na incidência e nos resultados relacionados ao COVID-19 em mulheres na pré-menopausa não pode ser comprovado no momento. Mas estudos longitudinais comparando mulheres pré e pós-menopausa são necessários para fornecer mais informações sobre este assunto.

The impact of circular stapler size on the risk of anastomotic stricture following total mesorectal excision in rectal cancer patients: A retrospective cross-sectional study.

Introduction: Colorectal cancer (CRC) surgery complications are a major issue affecting morbidity and mortality rates. Anastomotic stricture, which occurs in almost 30% of patients after surgery for rectal cancer, is one of the most serious but underreported side effects. In this study, we tried to assess the effect of stapler size on anastomotic stricture rate. Materials and Methods: At our facility, all patients underwent low anterior resections (LAR) performed using an open laparotomy technique. A contour-curved stapler and an end-to-end anastomosis (EEA) circular stapler were used in the double stapling technique (DST). All patients also underwent a protective loop ileostomy. Patients who developed stricture following leakage were excluded. Results: This study comprised a total of 173 rectal cancer patients. A 29-mm circle stapler was used to anastomose 77 patients (44.5%), while a 31-mm circular stapler was used to anastomose 96 patients (55.5%). Six individuals experienced strictures; two had a 29 mm stamper and four (4.4%) had a 31 mm one. There was no significant difference between the two groups (p:0.575). On aggregate, 8 patients experienced leakage; 3 (3.8%) of these patients received treatment with a 29 mm stapler, whereas 5 (5.2%) received treatment with a 31 mm stapler. Conclusion: this study found no statistically significant difference in the stricture rates and stapler size. The findings of this study provide credibility to the notion that in rectal cancer patients having LAR, strictures can be safely avoided by performing the anastomoses with both staplers.

Evaluation of the effect of endometrial scratch by hysteroscopic scissors on frozen embryo transfer outcomes: A historical cohort study.

Background: Endometrial scratch (ES) has been suggested to improve assisted reproductive techniques success rates by investigating implantation failure. Objective: In this study, we evaluated the effect of ES on the outcomes of frozen embryo transfer (FET) in women with at least 2 failed embryo transfer cycles. Materials and Methods: In this historical cohort study, medical data of 236 infertile women who underwent in-vitro fertilization-FET at Ebne-sina Infertility Center, Tehran, Iran, from January 2015-December 2021 was extracted from their medical records. Based on having ES before FET, they were assigned to either the scratch (n = 118) or the no-scratch group (n = 118). We compared these groups regarding pregnancy rates and outcomes. Results: The demographic characteristics were similar in both groups regarding weight, body mass index, the number of previous embryo transfers, and the duration of infertility. However, the scratch group had a slightly higher mean age (32.31 vs. 29.96 yr, p < 0.001). No statistically significant difference was observed between groups regarding pregnancy rate (p = 0.89). No significant association was observed between scratch, infertility duration, the number of previous FET attempts, and the likelihood of pregnancy in a logistic regression model. No major complications were observed. Conclusion: Hysteroscopic endometrial scratching with scissors probably has no effect on FET outcomes, including pregnancy or live birth rates.

Role of autoantibodies targeting interferon type 1 in COVID-19 severity: A systematic review and meta-analysis.

Introduction: Impairment of the type I interferon (IFN-I) signaling pathway is associated with increased severity of COVID-19 disease. Here we have undertaken a systematic review and meta = analysis on the association between the severity of COVID-19 and IFN-1 autoantibodies (AAbs; aIFN-1, aIFN-α, aIFN-ω, and aIFN-ß). Methods: Four databases, including Medline [PubMed], Embase, Web of Science, and Scopus, were systematically searched to find papers on the role of aIFN-1 and its subtype AAbs in the severity of COVID-19 infection. Data on the prevalence of aIFN-1, aIFN-α, aIFN-ω, and aIFN-ß were pooled using random- or fixed-effects models. Subgroup analysis was performed based on disease severity. Odds ratios (OR) for COVID-19 disease outcome, including length of hospital stay, ICU admission and death, were calculated in relation to positive or negative plasma IFN-1 AAbs. Results: A total of 33 studies with 13023 patients were included. The overall prevalence of circulating aIFN-1, aIFN-α, and aIFN-ω AAbs was 17.8 % [13.8, 22.8], 7.2 % [4.7, 10.9], and 4.4 % [2.1, 8.6], respectively, and the overall prevalence of neutralizing aIFN-1, aIFN-α, aIFN-ω, and aIFN-ß AAbs was 7.1 % [4.9, 10.1], 7.5 % [5.9, 9.5], 8.0 % [5.7, 11.1] and 1.2 % [0.4, 3.5], respectively. Circulating aIFN-α (OR = 4.537 [2.247, 9.158]), neutralizing aIFN-α (O = 17.482 [8.899, 34.342]), and neutralizing aIFN-ω (OR = 12.529 [7.397, 21.222]) were significantly more frequent in critical/severe patients than in moderate/mild patients (p < 0.001 for all). Anti-IFN-1 was more common in male subjects (OR = 2.248 [1.366, 3.699], p = 0.001) and two COVID-19 outcomes including ICU admission (OR = 2.485 [1.409, 4.385], p = 0.002) and death (OR = 2.593 [1.199, 5.604], p = 0.015) occurred more frequently in patients with positive anti-IFN-1.Conclusion: aIFN-1 and its subtypes AAbs are associated with severe and critical COVID-19 disease and may be a predictive marker for a poor prognosis, particularly in men.

A rare case of prostate cancer initially presented by disseminated intravascular coagulation-related subdural hemorrhage.

BACKGROUND: Disseminated intravascular coagulation (DIC) has been reported in various solid malignancies and is a common coagulation-related complication in prostate cancer. However, DIC has been rarely reported as the initial presentation of prostate cancer. Herein, we reported a patient referring with subdural hemorrhage (SDH) and DIC with an unexplained cause who was later diagnosed with prostate cancer. CASE PRESENTATION: We presented a 68-year-old man who was referred to the hospital with a gradual deterioration of consciousness, dyspnea, and edema in the genitalia and lower limbs. His primary laboratory tests showed elevated prothrombin time (PT) and partial thromboplastin time (PTT) and a decreased fibrinogen level of 47 mg/dL [200-400 mg/dL]. The DIC score was 7, which was suggestive of DIC. Moreover, cranial imaging showed SDH. Further work-up revealed elevated prostate-specific antigen and prostate enlargement with a mass effect on the bladder with a bone lesion, which was suggestive of metastatic prostate cancer. CONCLUSION: This report highlights DIC as a possible initial presentation of an underlying malignancy, as well as the importance of treatment of underlying disease in the management of DIC. A comprehensive and systematic work-up is essential for early diagnosis in patients with DIC to avoid further complications and mortality.

Polyvinyl Alcohol (PVA)-Based Nanoniosome for Enhanced in vitro Delivery and Anticancer Activity of Thymol.

Introduction: There is an unmet need to develop potent therapeutics against cancer with minimal side effects and systemic toxicity. Thymol (TH) is an herbal medicine with anti-cancer properties that has been investigated scientifically. This study shows that TH induces apoptosis in cancerous cell lines such as MCF-7, AGS, and HepG2. Furthermore, this study reveals that TH can be encapsulated in a Polyvinyl alcohol (PVA)-coated niosome (Nio-TH/PVA) to enhance its stability and enable its controlled release as a model drug in the cancerous region. Materials and Methods: TH-loaded niosome (Nio-TH) was fabricated and optimized using Box-Behnken method and the size, polydispersity index (PDI) and entrapment efficiency (EE) were characterized by employing DLS, TEM and SEM, respectively. Additionally, in vitro drug release and kinetic studies were performed. Cytotoxicity, antiproliferative activity, and the mechanism were assessed by MTT assay, quantitative real-time PCR, flow cytometry, cell cycle, caspase activity evaluation, reactive oxygen species investigation, and cell migration assays. Results: This study demonstrated the exceptional stability of Nio-TH/PVA at 4 °C for two months and its pH-dependent release profile. It also showed its high toxicity on cancerous cell lines and high compatibility with HFF cells. It revealed the modulation of Caspase-3/Caspase-9, MMP-2/MMP-9 and Cyclin D/ Cyclin E genes by Nio-TH/PVA on the studied cell lines. It confirmed the induction of apoptosis by Nio-TH/PVA in flow cytometry, caspase activity, ROS level, and DAPI staining assays. It also verified the inhibition of metastasis by Nio-TH/PVA in migration assays. Conclusion: Overall, the results of this study revealed that Nio-TH/PVA may effectively transport hydrophobic drugs to cancer cells with a controlled-release profile to induce apoptosis while exhibiting no detectable side effects due to their biocompatibility with normal cells.