Very young and advanced maternal age strongly elevates the occurrence of nonchromosomal congenital anomalies: a systematic review and meta-analysis of population-based studies.

BACKGROUND: Nonchromosomal congenital anomalies (NCAs) are the most common cause of infant mortality and morbidity. The role of maternal age is well known, although the specifics are not thoroughly elucidated in the literature. OBJECTIVE: To evaluate the role of maternal age in the incidence of NCAs and to pinpoint age groups at higher risk to refine screening protocols. STUDY DESIGN: A systematic review and meta-analysis were conducted following the PRISMA 2020 guidelines and Cochrane Handbook. Searches were performed on October 19, 2021, across MEDLINE (via PubMed), Cochrane Library (CENTRAL), and Embase. Population-based studies assessing the impact of maternal age on the incidence of NCAs in pregnant women were included, without restrictions on age range, country, or comorbidities. A random-effects model was used for pooling effect sizes, considering the heterogeneity across studies. RESULTS: From 15,547 studies, 72 were synthesized. Maternal age >35 showed an increased NCA risk (risk ratio [RR]: 1.31, confidence interval [CI]: 1.07 -1.61), rising notably after>40 (RR: 1.44, CI: 1.25 -1.66). The latter changes to 1.25 (CI: 1.08 -1.46) if the co-occurrence of chromosomal aberrations is excluded. Specific anomalies like cleft lip/palate (>40, RR: 1.57, CI: 1.11 -2.20) and circulatory system defects (>40, RR: 1.94, CI: 1.28 -2.93) were significantly associated with advanced maternal age. Conversely, gastroschisis was linked to mothers <20 (RR: 3.08, CI: 2.74 -3.47). CONCLUSION: The study confirms that both very young and advanced maternal ages significantly increase the risk of NCAs. There is a pressing need for age-specific prenatal screening protocols to better detect these anomalies, especially considering the current trend of delayed childbearing. Further research is required to fully understand the impact of maternal age on the prevalence of rarer NCAs.

COVID-19 mortality prediction in Hungarian ICU settings implementing random forest algorithm.

The emergence of newer SARS-CoV-2 variants of concern (VOCs) profoundly changed the ICU demography; this shift in the virus's genotype and its correlation to lethality in the ICUs is still not fully investigated. We aimed to survey ICU patients' clinical and laboratory parameters in correlation with SARS-CoV-2 variant genotypes to lethality. 503 COVID-19 ICU patients were included in our study beginning in January 2021 through November 2022 in Hungary. Furthermore, we implemented random forest (RF) as a potential predictor regarding SARS-CoV-2 lethality among 649 ICU patients in two ICU centers. Survival analysis and comparison of hypertension (HT), diabetes mellitus (DM), and vaccination effects were conducted. Logistic regression identified DM as a significant mortality risk factor (OR: 1.55, 95% CI 1.06-2.29, p = 0.025), while HT showed marginal significance. Additionally, vaccination demonstrated protection against mortality (p = 0.028). RF detected lethality with 81.42% accuracy (95% CI 73.01-88.11%, [AUC]: 91.6%), key predictors being PaO2/FiO2 ratio, lymphocyte count, and chest Computed Tomography Severity Score (CTSS). Although a smaller number of patients require ICU treatment among Omicron cases, the likelihood of survival has not proportionately increased for those who are admitted to the ICU. In conclusion, our RF model supports more effective clinical decision-making among ICU COVID-19 patients.

Investigating the role of ultrasound-based shear wave elastography in kidney transplanted patients: correlation between non-invasive fibrosis detection, kidney dysfunction and biopsy results-a systematic review and meta-analysis.

INTRODUCTION: Interstitial fibrosis and tubular atrophy are leading causes of renal allograft failure. Shear wave elastography could be a promising noninvasive method for providing information on the state of the kidney, with specific regard to fibrosis but currently available data in the literature are controversial. Our study aimed to analyze the correlation between shear wave elastography and various kidney dysfunction measures. METHODS: This review was registered on PROSPERO (CRD42021283152). We systematically searched three major databases (MEDLINE, Embase, and CENTRAL) for articles concerning renal transplant recipients, shear wave elastography, fibrosis, and kidney dysfunction. Meta-analytical calculations for pooled Pearson and Spearman correlation coefficients (r) were interpreted with 95% confidence intervals (CIs). Heterogeneity was tested with Cochran's Q test. I2 statistic and 95% CI were reported as a measurement of between-study heterogeneity. Study quality was assessed with the QUADAS2 tool. RESULTS: In total, 16 studies were included in our meta-analysis. Results showed a moderate correlation between kidney stiffness and interstitial fibrosis and tubular atrophy, graded according to BANFF classification, on biopsy findings for pooled Pearson (r = 0.48; CI: 0.20, 0.69; I2 = 84%) and Spearman correlations (r = 0.57; CI: 0.35, 0.72; I2 = 74%). When compared to kidney dysfunction parameters, we found a moderate correlation between shear wave elastography and resistive index (r = 0.34 CI: 0.13, 0.51; I2 = 67%) and between shear wave elastography and estimated Glomerular Filtration Rate (eGFR) (r = -0.65; CI: - 0.81, - 0.40; I2 = 73%). All our outcomes had marked heterogeneity. CONCLUSION: Our results showed a moderate correlation between kidney stiffness measured by shear wave elastography and biopsy results. While noninvasive assessment of kidney fibrosis after transplantation is an important clinical goal, there is insufficient evidence to support the use of elastography over the performance of a kidney biopsy.

PARP inhibitor era in ovarian cancer treatment: a systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: Ovarian cancer is the eighth leading cause of cancer-related death among women, characterized by late diagnosis and a high relapse rate. In randomized controlled trials, we aimed to evaluate the efficacy and safety of PARP inhibitors (PARPi) in treating advanced ovarian cancer. METHODS: This review was registered on PROSPERO (CRD42021283150), included all phase II and phase III randomized controlled trials (RCTs) assessing the effect of PARPi on ovarian cancer until the 13th of April, 2022. The main outcomes were progression- free survival (PFS), overall survival (OS), and adverse events (AEs). Pooled hazard ratios (HRs), and risk ratios (RRs) were calculated with 95% confidence intervals (95% CI). The random-effects model was applied in all analyses. RESULTS: In the meta-analysis, 16 eligible RCTs were included, with a total of 5,815 patients. In recurrent ovarian cancer, PARPi maintenance therapy showed a significant PFS benefit over placebo in the total population (HR 0.34, CI 0.29-0.40), BRCA mutant (HR 0.24, CI 0.18-0.31), germline BRCA mutant (HR 0.23, CI 0.18-0.30), and BRCA wild-type cases (HR 0.50, CI 0.39-0.65). PARPi monotherapy also improved PFS (HR 0.62, CI 0.51-0.76) compared with chemotherapy in BRCAm patients with recurrent ovarian cancer. The use of PARPi maintenance therapy resulted in an improvement in PFS over placebo in newly-diagnosed cancers in the overall population (HR 0.46, CI 0.30-0.71) and the BRCAm population (HR 0.36, CI 0.29-0.44). Although the risk of severe AEs was increased by PARPi therapy compared to placebo in most settings investigated, these side effects were controllable with dose modification, and treatment discontinuation was required in the minority of cases. CONCLUSIONS: PARPis are an effective therapeutic option for newly-diagnosed and recurrent ovarian cancer. Despite a minor increase in the frequency of serious adverse effects, they are generally well tolerated.

An overlooked phenomenon: complex interactions of potential error sources on the quality of bacterial de novo genome assemblies.

BACKGROUND: Parameters adversely affecting the contiguity and accuracy of the assemblies from Illumina next-generation sequencing (NGS) are well described. However, past studies generally focused on their additive effects, overlooking their potential interactions possibly exacerbating one another's effects in a multiplicative manner. To investigate whether or not they act interactively on de novo genome assembly quality, we simulated sequencing data for 13 bacterial reference genomes, with varying levels of error rate, sequencing depth, PCR and optical duplicate ratios. RESULTS: We assessed the quality of assemblies from the simulated sequencing data with a number of contiguity and accuracy metrics, which we used to quantify both additive and multiplicative effects of the four parameters. We found that the tested parameters are engaged in complex interactions, exerting multiplicative, rather than additive, effects on assembly quality. Also, the ratio of non-repeated regions and GC% of the original genomes can shape how the four parameters affect assembly quality. CONCLUSIONS: We provide a framework for consideration in future studies using de novo genome assembly of bacterial genomes, e.g. in choosing the optimal sequencing depth, balancing between its positive effect on contiguity and negative effect on accuracy due to its interaction with error rate. Furthermore, the properties of the genomes to be sequenced also should be taken into account, as they might influence the effects of error sources themselves.

Myoinositols Prevent Gestational Diabetes Mellitus and Related Complications: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

Although gestational diabetes mellitus (GDM) has several short- and long-term adverse effects on the mother and the offspring, no medicine is generally prescribed to prevent GDM. The present systematic review and meta-analysis aimed to investigate the effect of inositol supplementation in preventing GDM and related outcomes. Systematic search was performed in CENTRAL, MEDLINE, and Embase until 13 September 2023. Eligible randomized controlled trials (RCTs) compared the efficacy of inositols to placebo in pregnant women at high risk for GDM. Our primary outcome was the incidence of GDM, whereas secondary outcomes were oral glucose tolerance test (OGTT) and maternal and fetal complications. (PROSPERO registration number: CRD42021284939). Eight eligible RCTs were identified, including the data of 1795 patients. The incidence of GDM was halved by inositols compared to placebo (RR = 0.42, CI: 0.26-0.67). Fasting, 1-h, and 2-h OGTT glucose levels were significantly decreased by inositols. The stereoisomer myoinositol also reduced the risk of insulin need (RR = 0.29, CI: 0.13-0.68), preeclampsia or gestational hypertension (RR = 0.38, CI: 0.2-0.71), preterm birth (RR = 0.44, CI: 0.22-0.88), and neonatal hypoglycemia (RR = 0.12, CI: 0.03-0.55). Myoinositol decrease the incidence of GDM in pregnancies high-risk for GDM. Moreover, myoinositol supplementation reduces the risk of insulin need, preeclampsia or gestational hypertension, preterm birth, and neonatal hypoglycemia. Based on the present study 2-4 g myoinositol canbe suggested from the first trimester to prevent GDM and related outcomes.

Routine screening of abnormal vaginal flora during pregnancy reduces the odds of preterm birth: a systematic review and meta-analysis.

Prematurity is the leading cause of perinatal mortality and the morbidity among children under the age of 5. The prevalence of preterm birth is between 5 and 18% worldwide. Approximately 30% of preterm deliveries occur as a consequence of fetal or maternal infections. Bacterial vaginosis can increase the risk of ascending infections. However, there is no recommendation or protocol for screening of abnormal vaginal flora. The aim of this systematic review was to investigate the effectiveness of routine screening of abnormal vaginal flora during pregnancy care. We conducted our systematic search in the following databases: MEDLINE via PubMed, Embase, and Cochrane Library. Studies reporting on pregnant women with no symptoms of bacterial vaginosis were included in our analysis if they provided data on the outcome of their pregnancy. The intervention group went through screening of abnormal vaginal flora in addition to routine pregnancy care. Odds ratio (OR) with 95% confidence intervals (CIs) was used as effect size measure. From each study the total number of patients and number of events was extracted in both the intervention and control arm to calculate OR. Altogether we included 13 trials with 143,534 patients. The screening methods were Gram stain, pH screening, pH self-screening and pH screening combined with Gram stain. Regular screening of vaginal flora compared to no screening significantly reduces the odds of preterm birth before 37 weeks (8.98% vs 9.42%; OR 0.71, CI 0.57-0.87), birthweight under 2500 g (6.53% vs 7.24%; OR 0.64, CI 0.50-0.81), preterm birth before 32 weeks (1.35% vs 2.03%; OR 0.51, CI 0.31-0.85) and birthweight under 1000 g (0.86% vs 2.2%; OR 0.33, CI 0.19-0.57). In conclusion, the routine screening of abnormal vaginal flora might prevent preterm birth, extreme preterm birth, low birthweight deliveries and very low birthweight deliveries. Further research is needed to assess the problem more accurately.

Hungarian Linguistic, Cross-Cultural and Age Adaptation of Transition Specific Questionnaires in Patients with Inflammatory Bowel Disease.

Objective: In the TRANS-IBD clinical trial, the outcomes are measured with selected validated questionnaires. Cross-cultural and age adaptations of the Self-Efficacy Scale for adolescents and young adults (IBD-SES), the Transition Readiness Assessment Questionnaire (TRAQ), and the Self-Management and Transition Readiness Questionnaire (STARx) were performed. Methods: Linguistic and cultural adaptation was carried out with the usage of reliability coefficients (Cronbach's α coefficients, Spearman's rank correlation), and with confirmatory factor analysis (CFA; root Mean Square Error of Approximation [RMSEA], Comparative Fit Index [CFI], and Tucker-Lewis Index [TLI]). Results: 112 adolescents participated in the study (45.5% male, mean age 17 ± 1.98 years). CFA was acceptable in the IBD-SES and the TRAQ. Internal consistency was acceptable in IBD-SES and good in TRAQ (0.729; 0.865, respectively). Test-retest reliability was good in IBD-SES, but below the acceptable threshold in TRAQ (ρ = 0.819; ρ = 0.034). In STARx tools, RMSEA showed poor fit values, CFI and TLI were below acceptable fit values, and internal consistency was not satisfied (0.415; 0.693, respectively), while test-retest reliabilities were acceptable (ρ = 0.787; ρ = 0.788, respectively). Conclusions: Cross-cultural, age-specific adaptation was successfully completed with IBD-SES and TRAQ. Those are comparable to the original validated versions. The adaption of the STARx tools was not successful.

Detailed Characteristics of Post-discharge Mortality in Acute Pancreatitis.

BACKGROUND & AIMS: The in-hospital survival of patients suffering from acute pancreatitis (AP) is 95% to 98%. However, there is growing evidence that patients discharged after AP may be at risk of serious morbidity and mortality. Here, we aimed to investigate the risk, causes, and predictors of the most severe consequence of the post-AP period: mortality. METHODS: A total of 2613 well-characterized patients from 25 centers were included and followed by the Hungarian Pancreatic Study Group between 2012 and 2021. A general and a hospital-based population was used as the control group. RESULTS: After an AP episode, patients have an approximately threefold higher incidence rate of mortality than the general population (0.0404 vs 0.0130 person-years). First-year mortality after discharge was almost double than in-hospital mortality (5.5% vs 3.5%), with 3.0% occurring in the first 90-day period. Age, comorbidities, and severity were the most significant independent risk factors for death following AP. Furthermore, multivariate analysis identified creatinine, glucose, and pleural fluid on admission as independent risk factors associated with post-discharge mortality. In the first 90-day period, cardiac failure and AP-related sepsis were among the main causes of death following discharge, and cancer-related cachexia and non-AP-related infection were the key causes in the later phase. CONCLUSION: Almost as many patients in our cohort died in the first 90-day period after discharge as during their hospital stay. Evaluation of cardiovascular status, follow-up of local complications, and cachexia-preventing oncological care should be an essential part of post-AP patient care. Future study protocols in AP must include at least a 90-day follow-up period after discharge.

Metabolic-associated fatty liver disease is associated with acute pancreatitis with more severe course: Post hoc analysis of a prospectively collected international registry.

INTRODUCTION: Non-alcoholic fatty liver disease (NAFLD) is a proven risk factor for acute pancreatitis (AP). However, NAFLD has recently been redefined as metabolic-associated fatty liver disease (MAFLD). In this post hoc analysis, we quantified the effect of MAFLD on the outcomes of AP. METHODS: We identified our patients from the multicentric, prospective International Acute Pancreatitis Registry of the Hungarian Pancreatic Study Group. Next, we compared AP patients with and without MAFLD and the individual components of MAFLD regarding in-hospital mortality and AP severity based on the revised Atlanta classification. Lastly, we calculated odds ratios (ORs) with 95% confidence intervals (CIs) using multivariate logistic regression analysis. RESULTS: MAFLD had a high prevalence in AP, 39% (801/2053). MAFLD increased the odds of moderate-to-severe AP (OR = 1.43, CI: 1.09-1.89). However, the odds of in-hospital mortality (OR = 0.89, CI: 0.42-1.89) and severe AP (OR = 1.70, CI: 0.97-3.01) were not higher in the MAFLD group. Out of the three diagnostic criteria of MAFLD, the highest odds of severe AP was in the group based on metabolic risk abnormalities (OR = 2.68, CI: 1.39-5.09). In addition, the presence of one, two, and three diagnostic criteria dose-dependently increased the odds of moderate-to-severe AP (OR = 1.23, CI: 0.88-1.70, OR = 1.38, CI: 0.93-2.04, and OR = 3.04, CI: 1.63-5.70, respectively) and severe AP (OR = 1.13, CI: 0.54-2.27, OR = 2.08, CI: 0.97-4.35, and OR = 4.76, CI: 1.50-15.4, respectively). Furthermore, in patients with alcohol abuse and aged ≥60 years, the effect of MAFLD became insignificant. CONCLUSIONS: MAFLD is associated with AP severity, which varies based on the components of its diagnostic criteria. Furthermore, MAFLD shows a dose-dependent effect on the outcomes of AP.

Trichomonas vaginalis infection is associated with increased risk of cervical carcinogenesis: A systematic review and meta-analysis of 470 000 patients.

BACKGROUND: Trichomonas vaginalis infection is the most prevalent non-viral sexually transmitted infection (STI) in women and has been suggested as a risk factor for developing cervical cancer. OBJECTIVE: We aimed to investigate the associations between T. vaginalis infection and cervical carcinogenesis. SEARCH STRATEGY: A comprehensive systematic search was conducted in five databases on 21 October 2021. SELECTION CRITERIA: Studies assessing the relationship between T. vaginalis infection, HPV co-infections, cervical dysplasia, and cervical cancer were found eligible. DATA COLLECTION AND ANALYSIS: Summary estimates for pooled odds ratios (ORs) and their 95% confidence intervals (CIs) were calculated with a random-effects model. Statistical heterogeneity was measured with I2 and Cochran's Q tests. MAIN RESULTS: The 29 articles included 473 740 women, of whom 8518 were T. vaginalis-positive. Our results showed that T. vaginalis-infected women had 1.79 times higher odds of being diagnosed with HPV co-infection (95% CI 1.27-2.53; I2 95%). We also found that T. vaginalis infection was associated with high-grade squamous intraepithelial lesion diagnosis (OR 2.34, 95% CI 1.10-4.95; I2 75%) and cervical cancer (OR 5.23, 95% CI 3.03-9.04; I2 3%). CONCLUSIONS: Our results showed an association between T. vaginalis and cervical carcinogenesis in sexually active women.

Inositol is an effective and safe treatment in polycystic ovary syndrome: a systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: Metformin is the gold standard insulin sensitizer, which is widely used to treat insulin resistance in polycystic ovary syndrome (PCOS). However, metformin may induce gastrointestinal side effects. OBJECTIVE: Inositols have long been debated as a potential alternative for metformin in treating PCOS. Therefore, the present systematic review aimed to evaluate the efficacy and safety of inositols in treating PCOS. METHODS: The present systematic search was performed in CENTRAL, MEDLINE, and Embase from the inception until October 20th, 2021. Eligible randomized controlled trials (RCTs) included women diagnosed with PCOS and compared any inositols with metformin or placebo. Our primary outcome was cycle normalization, whereas secondary outcomes were body mass index (BMI), parameters of carbohydrate metabolism and clinical and laboratory hyperandrogenism. Results are reported as risk ratios or mean differences (MDs) with 95% confidence intervals (CIs). RESULTS: Twenty-six RCTs were identified, including data of 1691 patients (806 inositol, 311 with placebo, and 509 metformin groups). In patients treated with inositols, the risk (CI: 1.13; 2.85) of having a regular menstrual cycle was found by 1.79 higher than in the case of placebo. Moreover, the inositols showed non-inferiority compared to metformin in this outcome. In the case of BMI (MD = -0.45; CI: -0.89; -0.02), free testosterone (MD = -0,41, CI: -0.69; -0.13), total testosterone (MD = -20.39, CI: -40.12; -0.66), androstenedione (MD = -0.69, CI: -1,16; -0.22), glucose (MD = -3.14; CI: -5.75; -0.54) levels and AUC insulin (MD = -2081.05, CI: -2745.32; -1416.78) inositol treatment induced greater decrease compared to placebo. Inositol increased sex-hormone-binding globulin significantly compared to placebo (MD = 32.06, CI:1.27; 62.85). CONCLUSION: Inositol is an effective and safe treatment in PCOS. Moreover, inositols showed non-inferiority in most outcomes compared to the gold standard treatment; metformin. TRIAL REGISTRATION: PROSPERO registration number: CRD42021283275.

Lifestyle-, environmental-, and additional health factors associated with an increased sperm DNA fragmentation: a systematic review and meta-analysis.

INTRODUCTION: Infertility affects one in every six couples in developed countries, and approximately 50% is of male origin. In 2021, sperm DNA fragmentation (SDF) testing became an evidence-based test for fertility evaluations depicting fertility more clearly than standard semen parameters. Therefore, we aimed to summarize the potential prognostic factors of a higher SDF. METHODS: We conducted a systematic search in three medical databases and included studies investigating any risk factors for SDF values. We calculated mean differences (MD) in SDF with 95% confidence interval (CI) for exposed and non-exposed individuals. RESULTS: We included 190 studies in our analysis. In the group of associated health conditions, varicocele (MD = 13.62%, CI: 9.39-17.84) and impaired glucose tolerance (MD = 13.75%, CI: 6.99-20.51) had the most significant increase in SDF. Among malignancies, testicular tumors had the highest impact, with a maximum of MD = 11.3% (CI: 7.84-14.76). Among infections, the overall effects of both Chlamydia and HPV were negligible. Of lifestyle factors, smoking had the most disruptive effect on SDF - an increase of 9.19% (CI: 4.33-14.06). Different periods of sexual abstinence did not show significant variations in SDF values. Age seemed to have a more drastic effect on SDF from age 50 onwards, with a mean difference of 12.58% (CI: 7.31-17.86). Pollution also had a detrimental effect - 9.68% (CI: 6.85-12.52). CONCLUSION: Of the above risk factors, varicocele, impaired glucose tolerance, testicular tumors, smoking, pollution, and paternal age of over 50 were associated with the highest SDF. TRIAL REGISTRATION: CRD42021282533.

Anaemia Is Associated with an Increased Risk of Fractures, a Systematic Review, and Meta-Analysis.

BACKGROUND: Anaemia and osteoporotic fractures are both major health problems among older adults worldwide. OBJECTIVES: Previous studies suggest that anaemia may be associated with elevated fracture risk among older adults; however, the exact relationship between them is unknown. We aimed to investigate the association between anaemia and fracture risk. METHODS: A comprehensive literature search was performed in four medical databases. We included articles that were published from inception to February 18, 2021. Odds ratios (ORs), hazard ratios (HRs) with 95% confidence intervals (CIs), and original raw incidences from studies comparing fracture rates in anaemic versus non-anaemic patients were extracted and pooled with the random-effects model. I2 test was used to assess heterogeneity. Risk of bias assessment was performed using the Quality of Prognostic Studies tool. PROSPERO: CRD42021241109. RESULTS: A total of 13 studies were identified; 8 of them were included in the quantitative synthesis. Anaemia was found to be a risk factor for fracture compared to non-anaemia. Anaemia increased hip fracture risk in both older men (HR = 1.71; CI: 1.46-2.00, p< 0.001, I2 = 83.2%) and women (HR = 1.31; CI: 1.13-1.52, p< 0.001), but the fracture risk was more increased among men. There was also an increased chance of hip fracture in the presence of anaemia in populations, including both older men and women (OR = 1.64; CI: 1.35-2.01, p< 0.001, I2 = 61.1%). Anaemia was also associated with increased vertebral (HR = 1.21; CI: 1.04-1.40, p = 0.012) and all-type (HR = 1.49; CI: 1.19-1.86, p< 0.001) fracture risk in older men. CONCLUSION: Our results suggest that there is a significant relationship between anaemia and fracture risk in older adults. This association is stronger among older men than women and differs in the different types of fractures.

Therapeutic sensitivity to standard treatments in BRCA positive metastatic castration-resistant prostate cancer patients-a systematic review and meta-analysis.

BACKGROUND: Recent oncology guidelines recommend BRCA1/2 testing for a wide range of prostate cancer (PCa) patients. In addition, PARP inhibitors are available for mutation-positive metastatic castration-resistant PCa (mCRPC) patients following prior treatment with abiraterone, enzalutamide or docetaxel. However, the question of which of these standard treatments is the most effective for BRCA1/2 positive mCRPC patients remains to be answered. The aim of this meta-analysis was to assess the efficacy of abiraterone, enzalutamide and docetaxel in BRCA1/2 mutation-positive mCRPC patients in terms of PSA-response (PSA50), progression-free survival (PFS) and overall survival (OS). METHODS: As no interventional trials are available on this topic, we performed the data synthesis of BRCA1/2 positive mCRPC patients by using both proportional and individual patient data. For PSA50 evaluation, we pooled event rates with 95% confidence intervals (CI), while for time-to-event (PFS, OS) analyses we used individual patient data with random effect Cox regression calculations. RESULTS: Our meta-analysis included 16 eligible studies with 348 BRCA1/2 positive mCRPC patients. In the first treatment line, response rates for abiraterone, enzalutamide and docetaxel were 52% (CI: 25-79%), 64% (CI: 43-80%) and 55% (CI: 36-73%), respectively. Analyses of individual patient data revealed a PFS (HR: 0.47, CI: 0.26-0.83, p = 0.010) but no OS (HR: 1.41, CI: 0.82-2.42, p = 0.210) benefit for enzalutamide compared to abiraterone-treated patients. CONCLUSIONS: Our PSA50 analyses revealed that all the three first-line treatments have therapeutic effect in BRCA1/2 positive mCRPC; although, based on the results of PSA50 and PFS analyses, BRCA positive mCRPC patients might better respond to enzalutamide treatment. However, molecular marker-driven interventional studies directly comparing these agents are crucial for providing higher-level evidence.

Pre-treatment soluble PD-L1 as a predictor of overall survival for immune checkpoint inhibitor therapy: a systematic review and meta-analysis.

INTRODUCTION: Immune checkpoint inhibitors (ICI) such as anti-PD-L1 and anti-PD-1 agents have been proven to be effective in various cancers. However, the rate of non-responders is still high in all cancer entities. Therefore, the identification of biomarkers that could help to optimize therapeutic decision-making is of great clinical importance. Soluble PD-L1 (sPD-L1) and PD-1 (sPD-1) are emerging blood-based biomarkers and were previously shown to be prognostic in various clinical studies. OBJECTIVE: We aimed to evaluate the prognostic relevance of sPD-L1 and sPD-1 in patients with different tumor entities who underwent ICI therapy. METHODS: We searched for articles in PubMed via Medline, Embase, Scopus, and Cochrane databases. The primary outcome was overall survival (OS) and progression-free survival (PFS); furthermore, we analyzed on-treatment serum level changes of sPD-L1 and sPD-1 during ICI therapy. RESULTS: We synthesized the data of 1,054 patients with different cancer types from 15 articles. Pooled univariate analysis showed that elevated levels of sPD-L1 were significantly associated with inferior OS (HR = 1.67; CI:1.26-2.23, I2 = 79%, p < 0.001). The strongest association was found in non-small cell lung cancer, whereas weaker or no association was observed in melanoma as well as in renal cell and esophageal cancers. Pooled multivariate analysis also showed that elevated levels of sPD-L1 correlated with worse OS (HR = 1.62; CI: 1.00-2.62, I2 = 84%, p = 0.05) and PFS (HR = 1.71; CI:1.00-2.94, I2 = 82%, p = 0.051). Furthermore, we observed that one or three months of anti-PD-L1 treatment caused a strong (27.67-fold) elevation of sPD-L1 levels in malignant mesothelioma and urothelial cancer. CONCLUSIONS: We found significantly inferior OS in ICI-treated cancer patients with elevated pre-treatment sPD-L1 levels, but this association seems to be tumor type dependent. In addition, sPD-L1 increases during anti-PD-L1 therapy seems to be therapy specific.

First-Trimester Influenza Infection Increases the Odds of Non-Chromosomal Birth Defects: A Systematic Review and Meta-Analysis.

Viral infections during pregnancy raise several clinical challenges, including birth defects in the offspring. Thus, this systematic review and meta-analysis aims to prove and highlight the risk of birth defects after first-trimester maternal influenza infection. Our systematic search was performed on 21 November 2022. Studies that reported maternal influenza infection in the first trimester and non-chromosomal congenital abnormalities were considered eligible. We used odds ratios (OR) with 95% confidence intervals (CIs) to measure the effect size. Pooled ORs were calculated with a random effects model. Heterogeneity was measured with I² and Cochran's Q tests. We found that first-trimester maternal influenza was associated with increased odds of developing any type of birth defects (OR: 1.5, CI: 1.30-1.70). Moreover, newborns were more than twice as likely to be diagnosed with neural tube defects (OR: 2.48, CI: 1.95-3.14) or cleft lip and palate (OR: 2.48, CI: 1.87-3.28). We also found increased odds of developing congenital heart defects (OR: 1.63, CI: 1.27-2.09). In conclusion, influenza increases the odds of non-chromosomal birth defects in the first trimester. The aim of the present study was to estimate the risk of CAs in the offspring of mothers affected by first-trimester influenza infection.

Inflammatory bowel disease does not alter the clinical features and the management of acute pancreatitis: A prospective, multicentre, exact-matched cohort analysis.

OBJECTIVE AND AIMS: Acute pancreatitis in inflammatory bowel disease occurs mainly as an extraintestinal manifestation or a side effect of medications. We aimed to investigate the prognostic factors and severity indicators of acute pancreatitis and the treatment of patients with both diseases. DESIGN: We performed a matched case-control registry analysis of a multicentre, prospective, international acute pancreatitis registry. Patients with both diseases were matched to patients with acute pancreatitis only in a 1:3 ratio by age and gender. Subgroup analyses were also carried out based on disease type, activity, and treatment of inflammatory bowel disease. RESULTS: No difference in prognostic factors (laboratory parameters, bedside index of severity in acute pancreatitis, imaging results) and outcomes of acute pancreatitis (length of hospitalization, severity, and local or systemic complications) were detected between groups. Significantly lower analgesic use was observed in the inflammatory bowel disease population. Antibiotic use during acute pancreatitis was significantly more common in the immunosuppressed group than in the non-immunosuppressed group (p = 0.017). However, none of the prognostic parameters or the severity indicators showed a significant difference between any subgroup of patients with inflammatory bowel disease. CONCLUSION: No significant differences in the prognosis and severity of acute pancreatitis could be detected between patients with both diseases and with pancreatitis only. The need for different acute pancreatitis management is not justified in the coexistence of inflammatory bowel disease, and antibiotic overuse should be avoided.

Rapid genotyping of targeted viral samples using Illumina short-read sequencing data.

The most important information about microorganisms might be their accurate genome sequence. Using current Next Generation Sequencing methods, sequencing data can be generated at an unprecedented pace. However, we still lack tools for the automated and accurate reference-based genotyping of viral sequencing reads. This paper presents our pipeline designed to reconstruct the dominant consensus genome of viral samples and analyze their within-host variability. We benchmarked our approach on numerous datasets and showed that the consensus genome of samples could be obtained reliably without further manual data curation. Our pipeline can be a valuable tool for fast identifying viral samples. The pipeline is publicly available on the project's GitHub page (https://github.com/laczkol/QVG).

Diagnostic accuracy of SARS-CoV-2 Panbio™ rapid antigen diagnostic tests in a 4,440-case clinical follow-up.

Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) Rapid Antigen Detection Testing (RADT) has been subjected to several evaluations in reference to diagnostic accuracy, ranging from small scale up to large population studies including nation-wide community-based studies. All confirmed the diagnostic accuracy of the tests which were strongly dependent upon the infection's population prevalence. In our retrospective study, parallel SARS-CoV-2 Panbio™ RADT assay, including real-time reverse transcription quantitative polymerase chain reaction (RT-qPCR) tests, were aimed to evaluate diagnostic performance regarding the rapid antigen diagnostic testing. Out of 4,440 paired tests, 609 samples tested positive using RT-qPCR, resulting in a prevalence of 13.7%. Panbio detected 251 (5.7%) positive tested samples. Overall sensitivity was 41.2% (95% CI 37.4-45.2%) and overall specificity was 99.7% (95% CI 99.4-99.8%). Positive predictive value (PPV) was 95.1% (95% CI 91.8-97.1%) and the negative predictive value (NPV) was 91.4% (95% CI 90.5-92.2%). RADT sensitivity increased with stratification in reference to the results according to PCR Cycle threshold (Ct) and presence of the symptoms considerably influenced PPV and NPV. Sensitivity in the group of Ct values ≤ 20 was 91.2%, 68.6% within the Ct range of 20-25, 47.9% in the group of Ct values between 25 and 30, and 12.6% in the group of Ct values between 30 and 35. A follow-up of the positive cases aligned with RT-qPCR testing and comparison of the general population enrolled in the testing in which the fatal cases occurred enabled us to estimate real clinical diagnostic performance regarding the SARS-CoV-2 Panbio RADT. Based upon our results, we recommend the SARS-CoV-2 Panbio RADT tests be carried out as the primary test, without parallel PCR testing, only among high population prevalence rates of the infection and to be used for symptomatic individuals with average or low severe disease developmental risk. In the case of high risk regarding the development of severe infection complications, a parallel SARS-CoV-2 RT-qPCR is needed to be carried out to attain proper diagnostic accuracy and avoid delaying appropriate medical care.