EEG connectivity and network analyses predict outcome in patients with disorders of consciousness - A systematic review and meta-analysis.

Outcome prediction in prolonged disorders of consciousness (DOC) remains challenging. This can result in either inappropriate withdrawal of treatment or unnecessary prolongation of treatment. Electroencephalography (EEG) is a cheap, portable, and non-invasive device with various opportunities for complex signal analysis. Computational EEG measures, such as EEG connectivity and network metrics, might be ideal candidates for the investigation of DOC, but their capacity in prognostication is still undisclosed. We conducted a meta-analysis aiming to compare the prognostic power of the widely used clinical scale, Coma Recovery Scale-Revised - CRS-R and EEG connectivity and network metrics. We found that the prognostic power of the CRS-R scale was moderate (AUC: 0.67 (0.60-0.75)), but EEG connectivity and network metrics predicted outcome with significantly (p = 0.0071) higher accuracy (AUC:0.78 (0.70-0.86)). We also estimated the prognostic capacity of EEG spectral power, which was not significantly (p = 0.3943) inferior to that of the EEG connectivity and graph-theory measures (AUC:0.75 (0.70-0.80)). Multivariate automated outcome prediction tools seemed to outperform clinical and EEG markers.

A Systematic Review and Meta-Analysis of microRNA Profiling Studies in Chronic Kidney Diseases.

Chronic kidney disease (CKD) represents an increasing health burden. Evidence suggests the importance of miRNA in diagnosing CKD, yet the reports are inconsistent. This study aimed to determine novel miRNA biomarkers and potential therapeutic targets from hypothesis-free miRNA profiling studies in human and murine CKDs. Comprehensive literature searches were conducted on five databases. Subgroup analyses of kidney diseases, sample types, disease stages, and species were conducted. A total of 38 human and 12 murine eligible studies were analyzed using Robust Rank Aggregation (RRA) and vote-counting analyses. Gene set enrichment analyses of miRNA signatures in each kidney disease were conducted using DIANA-miRPath v4.0 and MIENTURNET. As a result, top target genes, Gene Ontology terms, the interaction network between miRNA and target genes, and molecular pathways in each kidney disease were identified. According to vote-counting analysis, 145 miRNAs were dysregulated in human kidney diseases, and 32 were dysregulated in murine CKD models. By RRA, miR-26a-5p was significantly reduced in the kidney tissue of Lupus nephritis (LN), while miR-107 was decreased in LN patients' blood samples. In both species, epithelial-mesenchymal transition, Notch, mTOR signaling, apoptosis, G2/M checkpoint, and hypoxia were the most enriched pathways. These miRNA signatures and their target genes must be validated in large patient cohort studies.

Burden of Childhood Cancer and the Social and Economic Challenges in Adulthood: A Systematic Review and Meta-Analysis.

Importance: Significant advancements in pediatric oncology have led to a continuously growing population of survivors. Although extensive research is being conducted on the short-, medium-, and long-term somatic effects, reports on psychosocial reintegration are often conflicting; therefore, there is an urgent need to synthesize the evidence to obtain the clearest understanding and the most comprehensive answer. Objective: To provide a comprehensive review and analysis of the socioeconomic attainment of childhood cancer survivors (CCSs) compared with their unaffected peers. Data Sources: A systematic review and meta-analysis was conducted using data obtained from a comprehensive search of MEDLINE (via PubMed), Embase, and CENTRAL (Cochrane Central Register of Controlled Trials) databases on October 23, 2021; the search was updated until July 31, 2023. Study Selection: Eligible articles reported on educational attainment, employment, family formation, quality of life (QoL), or health-risk behavior-related outcomes of CCSs, and compared them with their unaffected peers. Study selection was performed in duplicate by 4 blinded independent coauthors. Data Extraction and Synthesis: Data extraction was performed in duplicate by 4 independent authors following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Outcome measures were odds ratios (ORs) and mean differences with 95% CIs; data were pooled using a random-effects model. Results: The search identified 43 913 articles, 280 of which were eligible for analysis, reporting data on a total of 389 502 survivors. CCSs were less likely to complete higher levels of education (OR, 0.69; 95% CI, 0.40-1.18), had higher odds of health-related unemployment (OR, 2.94; 95% CI, 1.90-4.57), and showed lower rates of marriage (OR, 0.72; 95% CI, 0.63-0.84) and parenthood (OR, 0.60; 95% CI, 0.49-0.74) compared with population-based controls. Conclusion and Relevance: Study findings suggest that CCSs face several socioeconomic difficulties; as a result, the next goal of pediatric oncology should be to minimize adverse effects, as well as to provide lifelong survivorship support aimed at maximizing social reintegration.

Comparison of Executive Function Skills between Patients with Cerebral Palsy and Typically Developing Populations: A Systematic Review and Meta-Analysis.

Background: Children with CP show deficits in executive function compared to their typically developing peers, based on the majority of the available evidence. However, the magnitude of these deficits, as well as the proportions of the shortfalls in the three main components, have not yet been examined. This is the first meta-analysis to synthesize evidence on the magnitude of differences between patients with cerebral palsy (CP) and typically developing populations in different components of executive function skills (working memory, inhibitory control and cognitive flexibility), and thus makes recommendations on which areas of executive functioning are in greatest need of intervention. Methods: We conducted a systematic literature search of four databases for studies that measured executive functions in these two groups until 31 August 2023. We calculated the standardized mean difference (Hedges' g), an average effect size overall, and for the three components of executive function skills separately, we used several moderator analyses, including methodological differences between the primary studies. Results: Fifteen articles were included in the meta-analysis. The average mean difference in executive functioning overall was large (g+ = -0.82). Furthermore, large significant differences were found in working memory (g+ = -0.92) and inhibitory control (g+ = -0.82) and a moderate difference was identified in cognitive flexibility (g+ = -0.57). In addition, results of moderator analyses reveal the importance of a rigorous matching of control group participants and CP patients. Conclusions: The results demonstrate a severe impairment in all executive functions among CP patients compared to typically developing peers, which do not decrease over time.

Magnetic Resonance Imaging in Prostate Cancer Screening: A Systematic Review and Meta-Analysis.

Importance: Prostate magnetic resonance imaging (MRI) is increasingly integrated within the prostate cancer (PCa) early detection pathway. Objective: To systematically evaluate the existing evidence regarding screening pathways incorporating MRI with targeted biopsy and assess their diagnostic value compared with prostate-specific antigen (PSA)-based screening with systematic biopsy strategies. Data Sources: PubMed/MEDLINE, Embase, Cochrane/Central, Scopus, and Web of Science (through May 2023). Study Selection: Randomized clinical trials and prospective cohort studies were eligible if they reported data on the diagnostic utility of prostate MRI in the setting of PCa screening. Data Extraction: Number of screened individuals, biopsy indications, biopsies performed, clinically significant PCa (csPCa) defined as International Society of Urological Pathology (ISUP) grade 2 or higher, and insignificant (ISUP1) PCas detected were extracted. Main Outcomes and Measures: The primary outcome was csPCa detection rate. Secondary outcomes included clinical insignificant PCa detection rate, biopsy indication rates, and the positive predictive value for the detection of csPCa. Data Synthesis: The generalized mixed-effect approach with pooled odds ratios (ORs) and random-effect models was used to compare the MRI-based and PSA-only screening strategies. Separate analyses were performed based on the timing of MRI (primary/sequential after a PSA test) and cutoff (Prostate Imaging Reporting and Data System [PI-RADS] score ≥3 or ≥4) for biopsy indication. Results: Data were synthesized from 80 114 men from 12 studies. Compared with standard PSA-based screening, the MRI pathway (sequential screening, PI-RADS score ≥3 cutoff for biopsy) was associated with higher odds of csPCa when tests results were positive (OR, 4.15; 95% CI, 2.93-5.88; P ≤ .001), decreased odds of biopsies (OR, 0.28; 95% CI, 0.22-0.36; P ≤ .001), and insignificant cancers detected (OR, 0.34; 95% CI, 0.23-0.49; P = .002) without significant differences in the detection of csPCa (OR, 1.02; 95% CI, 0.75-1.37; P = .86). Implementing a PI-RADS score of 4 or greater threshold for biopsy selection was associated with a further reduction in the odds of detecting insignificant PCa (OR, 0.23; 95% CI, 0.05-0.97; P = .048) and biopsies performed (OR, 0.19; 95% CI, 0.09-0.38; P = .01) without differences in csPCa detection (OR, 0.85; 95% CI, 0.49-1.45; P = .22). Conclusion and relevance: The results of this systematic review and meta-analysis suggest that integrating MRI in PCa screening pathways is associated with a reduced number of unnecessary biopsies and overdiagnosis of insignificant PCa while maintaining csPCa detection as compared with PSA-only screening.

Early onset of abnormal glucose tolerance in patients with cystic fibrosis: A systematic review and meta-analysis.

BACKGROUND: Despite translational evidences suggesting that cystic fibrosis-related abnormal glucose tolerance (CF-related AGT) may begin early in life and is known to be associated with increased morbidity and mortality, current guidelines recommend screening for AGT only from 10 years of age, thus missing the opportunity for early detection and intervention. METHODS: A systematic review and meta-analysis (PROSPERO number: CRD42021282516) was conducted on studies that reported data on the prevalence of AGT or its subtypes in CF populations. Pooled proportions, risk, and odds ratios with 95 % confidence intervals (CI) were calculated. One-stage dose-response random-effect meta-analysis was used to assess the effect of age on CF-related diabetes (CFRD). RESULTS: The quantitative analysis included 457 studies and data from 520,544 patients. Every third child with CF (chwCF) (0.31 [95 % CI 0.25-0.37]) and every second adult with CF (awCF) (0.51 [95 % CI 0.45-0.57]) were affected by AGT. Even in the 5-10 years of age subgroup, the proportion of AGT was 0.42 [95 % CI 0.34-0.51]. The prevalence of prediabetes remained unchanged (impaired glucose tolerance in chwCF:0.14 [95 % CI 0.10-0.18]) vs. awCF:0.19 [95 % CI 0.14-0.25]), whereas the proportion of CFRD increased with age (0-5: 0.005 [95 % CI 0.0001-0.15]; 5-10: 0.05 [95 % CI 0.01-0.27]; 10-18: 0.11 [95 % CI 0.08-0.14]; >18 years of age: 0.27 [95 % CI 0.24-0.30]). CONCLUSION: CF-related AGT is common under 10 years of age. Our study suggests considering earlier AGT screening, starting from 5 years of age. This highlights the imperative for additional research for guideline adjustments and provides the opportunity for early intervention.

Diagnostic Accuracy of Transvaginal Ultrasound and Magnetic Resonance Imaging for the Detection of Myometrial Infiltration in Endometrial Cancer: A Systematic Review and Meta-Analysis.

In endometrial cancer (EC), deep myometrial invasion (DMI) is a prognostic factor that can be evaluated by various imaging methods; however, the best method of choice is uncertain. We aimed to compare the diagnostic performance of two-dimensional transvaginal ultrasound (TVS) and magnetic resonance imaging (MRI) in the preoperative detection of DMI in patients with EC. Pubmed, Embase and Cochrane Library were systematically searched in May 2023. We included original articles that compared TVS to MRI on the same cohort of patients, with final histopathological confirmation of DMI as reference standard. Several subgroup analyses were performed. Eighteen studies comprising 1548 patients were included. Pooled sensitivity and specificity were 76.6% (95% confidence interval (CI), 70.9-81.4%) and 87.4% (95% CI, 80.6-92%) for TVS. The corresponding values for MRI were 81.1% (95% CI, 74.9-85.9%) and 83.8% (95% CI, 79.2-87.5%). No significant difference was observed (sensitivity: p = 0.116, specificity: p = 0.707). A non-significant difference between TVS and MRI was observed when no-myometrium infiltration vs. myometrium infiltration was considered. However, when only low-grade EC patients were evaluated, the specificity of MRI was significantly better (p = 0.044). Both TVS and MRI demonstrated comparable sensitivity and specificity. Further studies are needed to assess the presence of myometrium infiltration in patients with fertility-sparing wishes.

Prediction performance of scoring systems after out-of-hospital cardiac arrest: A systematic review and meta-analysis.

INTRODUCTION: Ongoing changes in post resuscitation medicine and society create a range of ethical challenges for clinicians. Withdrawal of life-sustaining treatment is a very sensitive, complex decision to be made by the treatment team and the relatives together. According to the guidelines, prognostication after cardiopulmonary resuscitation should be based on a combination of clinical examination, biomarkers, imaging, and electrophysiological testing. Several prognostic scores exist to predict neurological and mortality outcome in post-cardiac arrest patients. We aimed to perform a meta-analysis and systematic review of current scoring systems used after out-of-hospital cardiac arrest (OHCA). MATERIALS AND METHODS: Our systematic search was conducted in four databases: Medline, Embase, Central and Scopus on 24th April 2023. The patient population consisted of successfully resuscitated adult patients after OHCA. We included all prognostic scoring systems in our analysis suitable to estimate neurologic function as the primary outcome and mortality as the secondary outcome. For each score and outcome, we collected the AUC (area under curve) values and their CIs (confidence iterval) and performed a random-effects meta-analysis to obtain pooled AUC estimates with 95% CI. To visualize the trade-off between sensitivity and specificity achieved using different thresholds, we created the Summary Receiver Operating Characteristic (SROC) curves. RESULTS: 24,479 records were identified, 51 of which met the selection criteria and were included in the qualitative analysis. Of these, 24 studies were included in the quantitative synthesis. The performance of CAHP (Cardiac Arrest Hospital Prognosis) (0.876 [0.853-0.898]) and OHCA (0.840 [0.824-0.856]) was good to predict neurological outcome at hospital discharge, and TTM (Targeted Temperature Management) (0.880 [0.844-0.916]), CAHP (0.843 [0.771-0.915]) and OHCA (0.811 [0.759-0.863]) scores predicted good the 6-month neurological outcome. We were able to confirm the superiority of the CAHP score especially in the high specificity range based on our sensitivity and specificity analysis. CONCLUSION: Based on our results CAHP is the most accurate scoring system for predicting the neurological outcome at hospital discharge and is a bit less accurate than TTM score for the 6-month outcome. We recommend the use of the CAHP scoring system in everyday clinical practice not only because of its accuracy and the best performance concerning specificity but also because of the rapid and easy availability of the necessary clinical data for the calculation.

Persistently High Procalcitonin and C-Reactive Protein Are Good Predictors of Infection in Acute Necrotizing Pancreatitis: A Systematic Review and Meta-Analysis.

Infected necrotizing pancreatitis (INP) is associated with an increased risk of organ failure and mortality. Its early recognition and timely initiation of antibiotic therapy can save patients' lives. We systematically searched three databases on 27 October 2022. In the eligible studies, the presence of infection in necrotizing pancreatitis was confirmed via a reference test, which involved either the identification of gas within the necrotic collection through computed tomography imaging or the examination of collected samples, which yielded positive results in Gram staining or culture. Laboratory biomarkers compared between sterile necrotizing pancreatitis and INP were used as the index test, and our outcome measures included sensitivity, specificity, the receiver operating characteristic (ROC) curve and area under the ROC curve (AUC). Within the first 72 hours (h) after admission, the AUC of C-reactive protein (CRP) was 0.69 (confidence interval (CI): 0.62-0.76), for procalcitonin (PCT), it was 0.69 (CI: 0.60-0.78), and for white blood cell count, it was 0.61 (CI: 0.47-0.75). After the first 72 h, the pooled AUC of CRP showed an elevated level of 0.88 (CI: 0.75-1.00), and for PCT, it was 0.86 (CI: 0.60-1.11). The predictive value of CRP and PCT for infection is poor within 72 h after hospital admission but seems good after the first 72 h. Based on these results, infection is likely in case of persistently high CRP and PCT, and antibiotic initiation may be recommended.

The Effect of Additional Whole-Body Vibration on Musculoskeletal System in Children with Cerebral Palsy: A Systematic Review and Meta-Analysis of Randomized Clinical Trials.

Nowadays, whole-body vibration (WBV) has become increasingly popular as an additional therapy in the intervention of patients with cerebral palsy (CP). However, the impact of WBV remains a subject of debate. Consequently, a systematic review and meta-analysis were undertaken to evaluate the effects of WBV on the musculoskeletal system in children with CP. Randomized controlled trials (RCTs) were sought in the most frequent databases. The intervention studied was WBV combined with conventional physiotherapy (PT) compared with conventional PT as the control; the main outcomes were changes in the musculoskeletal system. Weighted mean differences with 95%CIs were calculated. A random-effects model was applied, and the publication bias was checked using funnel plots. On the basis of the inclusion and exclusion criteria, 16 articles, including 414 patients, were considered in the final analysis. The improvement in walking performance (speed and step length) was statistically significant (p < 0.05), and although there were no significant differences in the further outcomes, a clear positive tendency was visible in the case of improved muscle strength, decreased spasticity, enhanced gross motor functions, and overall stability. Based on the findings, a clear assessment of the usefulness of this intervention cannot be made; nonetheless, due to the promising results, it would be worthwhile to conduct additional RCTs to enhance the available evidence in this field. Due to the wide range of vibration configurations, including varying durations and intensities, it is suggested to establish guidelines and a strategy for the incorporation of this additional treatment.

The histologic fetal inflammatory response and neonatal outcomes: systematic review and meta-analysis.

OBJECTIVE: This study aimed to investigate the prognostic role of concomitant histological fetal inflammatory response with chorioamnionitis on neonatal outcomes through a systematic review and meta-analysis of existing literature. DATA SOURCES: The primary search was conducted on October 17, 2021, and it was updated on May 26, 2023, across 4 separate databases (MEDLINE, the Cochrane Central Register of Controlled Trials, Embase, and Scopus) without using any filters. STUDY ELIGIBILITY CRITERIA: Observational studies reporting obstetrical and neonatal outcomes of infant-mother dyads with histological chorioamnionitis and histological fetal inflammatory response vs infant-mother dyads with histological chorioamnionitis alone were eligible. Studies that enrolled only preterm neonates, studies on neonates born before 37 weeks of gestation, or studies on neonates with very low birthweight (birthweight <1500 g) were included. The protocol was registered with the International Prospective Register of Systematic Reviews (registration number: CRD42021283448). METHODS: The records were selected by title, abstract, and full text, and disagreements were resolved by consensus. Random-effect model-based pooled odds ratios with corresponding 95% confidence intervals were calculated for dichotomous outcomes. RESULTS: Overall, 50 studies were identified. A quantitative analysis of 14 outcomes was performed. Subgroup analysis using the mean gestational age of the studies was performed, and a cutoff of 28 weeks of gestation was implemented. Among neonates with lower gestational ages, early-onset sepsis (pooled odds ratio, 2.23; 95% confidence interval, 1.76-2.84) and bronchopulmonary dysplasia (pooled odds ratio, 1.30; 95% confidence interval, 1.02-1.66) were associated with histological fetal inflammatory response. Our analysis showed that preterm neonates with a concomitant histological fetal inflammatory response are more likely to develop intraventricular hemorrhage (pooled odds ratio, 1.54; 95% confidence interval, 1.18-2.02) and retinopathy of prematurity (pooled odds ratio, 1.37; 95% confidence interval, 1.03-1.82). The odds of clinical chorioamnionitis were almost 3-fold higher among infant-mother dyads with histological fetal inflammatory response than among infant-mother dyads with histological chorioamnionitis alone (pooled odds ratio, 2.99; 95% confidence interval, 1.96-4.55). CONCLUSION: This study investigated multiple neonatal outcomes and found association in the case of 4 major morbidities: early-onset sepsis, bronchopulmonary dysplasia, intraventricular hemorrhage, and retinopathy of prematurity.

Hemoadsorption as Adjuvant Therapy in Acute Respiratory Distress Syndrome (ARDS): A Systematic Review and Meta-Analysis.

BACKGROUND: Acute respiratory distress syndrome (ARDS) is often a consequence of a dysregulated immune response; therefore, immunomodulation by extracorporeal cytokine removal has been increasingly used as an adjuvant therapy, but convincing data are still missing. The aim of this study was to investigate the effects of adjunctive hemoadsorption (HA) on clinical and laboratory outcomes in patients with ARDS. METHODS: We performed a systematic literature search in PubMed, Embase, CENTRAL, Scopus, and Web of Science (PROSPERO: CRD42022292176). The population was patients receiving HA therapy for ARDS. The primary outcome was the change in PaO2/FiO2 before and after HA therapy. Secondary outcomes included the before and after values for C-reactive protein (CRP), lactate, interleukin-6 (IL-6), and norepinephrine (NE) doses. RESULTS: We included 26 publications, with 243 patients (198 undergoing HA therapy and 45 controls). There was a significant improvement in PaO2/FiO2 ratio following HA therapy (MD = 68.93 [95%-CI: 28.79 to 109.06] mmHg, p = 0.005) and a reduction in CRP levels (MD = -45.02 [95%-CI: -82.64; -7.39] mg/dL, p = 0.026) and NE dose (MD = -0.24 [95%-CI: -0.44 to -0.04] µg/kg/min, p = 0.028). CONCLUSIONS: Based on our findings, HA resulted in a significant improvement in oxygenation and a reduction in NE dose and CRP levels in patients treated with ARDS. Properly designed RCTs are still needed.

Effect of Chitosan on the Number of Streptococcus mutans in Saliva: A Meta-Analysis and Systematic Review.

We conducted a meta-analysis and systematic review to investigate the efficacy of chitosan-containing chewing gums, and to test their inhibitory effects on Streptococcus mutans. The systematic search was performed in three databases (Cochrane Library, EMBASE, and PubMed) and included English-language randomized-controlled trials to compare the efficacy of chitosan in reducing the number of S. mutans. To assess the certainty of evidence, the GRADE tool was used. Mean differences were calculated with a 95% confidence interval for one outcome: bacterial counts in CFU/mL. The protocol of the study was registered on PROSPERO, registration number CRD42022365006. Articles were downloaded (n = 6758) from EMBASE (n = 2255), PubMed (n = 1516), and Cochrane (n = 2987). After the selection process, a total of four articles were included in the qualitative synthesis and three in the quantitative synthesis. Our results show that chitosan reduced the number of bacteria. The difference in mean quantity was -4.68 × 105. The interval of the random-effects model was [-2.15 × 106; 1.21 × 106] and the prediction interval was [1.03 × 107; 9.40 × 106]. The I2 value was 98% (p = 0.35), which indicates a high degree of heterogeneity. Chitosan has some antibacterial effects when used as a component of chewing gum, but further studies are needed. It can be a promising antimicrobial agent for prevention.

ORGANOLEPTIC AND HALITOMETRIC ASSESSMENTS DO NOT CORRELATE WELL IN INTRA-ORAL HALITOSIS: A SYSTEMATIC REVIEW AND META-ANALYSIS.

BACKGROUND: The gold standard method for diagnosing oral halitosis is the subjective organoleptic measurement. Device-supported methods are also widespread worldwide. The challenges and safety concerns around performing organoleptic measurements during pandemics and the diversity of measuring device alternatives raised our clinical question: which halitometer is the most suitable for diagnosing halitosis? METHODS: This systematic review was registered in PROSPERO (ID CRD42022320024). The search was performed on March 23, 2022 in the following electronic databases: MEDLINE, Embase, Scopus, Web of Science, and CENTRAL. Adult populations with or without halitosis were included, and patients with systemic diseases were excluded. Organoleptic (subjective) measurement and the device-supported (objective) methods were compared; the primary outcome was the correlation coefficient, and the secondary was the specificity and sensitivity of the devices. QUADAS-2 and QUADAS-C were used to evaluate the risk of bias in the studies. Random-effects meta analyses were performed on the outcomes, and the secondary outcomes were plotted on a common ROC plot. RESULTS: A total of 1231 records were found in the 5 databases. After the selection process, 76 articles were eligible for the systematic review, and 14,635 patients were involved in the qualitative analysis. The pooled Spearman's correlation coefficient (c.c.) for sulfide monitors was 0.65; 95% CIs: [0.53-0.74]; I2 = 95%, P < .01. The pooled Spearman's c.c. for portable gas chromatographs was 0.69; 95% CIs: [0.63-0.74]; I2 = 12%, P < .01. The pooled Spearman's c.c. for gas chromatographs was 0.76; 95% CIs: [0.67-0.83]; I2 = 0%, P < .01. DISCUSSION: None of the most commonly used halitometers proved to be significantly superior to the others. Halimeter and OralChroma measurements did not correlate well with the organoleptic level of oral halitosis in adults. Therefore, better halitometers need to be developed as an alternative to organoleptic measurements.

Poly (ADP-ribose) Polymerase Inhibitors Have Comparable Efficacy with Platinum Chemotherapy in Patients with BRCA-positive Metastatic Castration-resistant Prostate Cancer. A Systematic Review and Meta-analysis.

CONTEXT: Testing for mutations in Breast Cancer Gene 1/2 (BRCA) has emerged as a novel decision-making tool for clinicians. Patients with metastatic castration-resistant prostate cancer (mCRPC) harboring pathogenic BRCA mutations can benefit from poly (ADP-ribose) polymerase inhibitor (PARPi) and platinum treatments, whereas the impact of the mutation on sensitivity to cabazitaxel and prostate-specific membrane antigen (PSMA)-ligand therapy is currently unknown. OBJECTIVE: To assess the efficacy of PARPi, platinum, cabazitaxel, and PSMA-ligand therapies in BRCA-positive mCRPC. EVIDENCE ACQUISITION: Databases were queried in February 2022. We performed data synthesis by using both proportional and individual patient data. For prostate-specific antigen (PSA) response rate (≥50% decrease from baseline [PSA50]) evaluation, we pooled event rates with 95% confidence intervals (CIs). Progression-free (PFS) and overall (OS) survival analyses with individual patient data were performed with the mixed-effect Cox proportional hazard model and single-arm random-effect analysis, providing pooled medians. EVIDENCE SYNTHESIS: We included 23 eligible studies with 901 BRCA-positive mCRPC patients. PSA50 response rates for PARPi and platinum were 69% (CI: 53-82%), and 74% (CI: 49-90%), respectively. Analyses of OS data showed no difference between PARPi and platinum treatments (hazard ratio: 0.86; CI: 0.49-1.52; p = 0.6). The single-arm OS and PFS analyses revealed similarities among different PARPis; pooled PFS and OS medians were 9.7 mo (CI: 8.1-12.5) and 17.4 mo (CI: 12.7-20.1), respectively. CONCLUSIONS: Our data revealed that different PARPis were similarly effective in terms of PFS and OS. Moreover, we found that PARPi and platinum therapy were comparable in terms of PSA50 response rate and OS, highlighting that platinum is a valid treatment option for BRCA-positive mCRPC patients. However, prospective interventional studies comparing these agents are essential to provide a higher level of evidence. PATIENT SUMMARY: In this report, we found that different poly (ADP-ribose) polymerase inhibitors had similar efficacy, and platinum was a valid treatment option in BRCA-positive metastatic castration-resistant prostate cancer patients.

Teledentistry: A Future Solution in the Diagnosis of Oral Lesions: Diagnostic Meta-Analysis and Systematic Review.

Introduction: Teledentistry (TD) can offer a wide range of possibilities in the field of oral medicine. Oral potentially malignant disorders (OPMDs) are hard to detect, and even harder to diagnose correctly. With the help of TD, OPMDs can be detected and diagnosed by a remote specialist. Our aim was to investigate whether TD could provide a reliable diagnostic method compared with clinical oral examination (COE) in the diagnosis of OPMDs. Methods: A systematic search was conducted in three databases (Medline, EMBASE, CENTRAL) until November 2021. We included studies that compared telediagnosis and COE, both made by experts. Pooled specificity and sensitivity were calculated and visualized on a two-dimensional plot. Risk of bias was assessed using the QUADAS-2 tool, and the level of evidence is shown with the Grades of Recommendation, Assessment, Development and Evaluation (GRADE) tool. Results: Of the 7,608 studies, 13 were included in the qualitative and 9 in the quantitative synthesis. Using TD tools in the detection of oral lesions (OLs) showed high specificity (0.92 confidence interval [95% CI] = 0.59-0.99) and sensitivity (0.93 95% CI = 0.17-1.00). In the differential diagnosis of lesions, we found high sensitivity and specificity (0.942 95% CI = 0.826-0.982 and 0.982 95% CI = 0.913-0.997), respectively. We summarized the available data on time-effectiveness, screening person, referral decision, and technical settings. Conclusion: Detecting OLs with TD tools might lead to earlier diagnosis, treatment, and stricter follow-up of OPMD. TD may offer a great substitution for COE in the diagnosis of OLs, and thus, fewer referrals could be made to special care, resulting in a greater number of treated OPMDs.

Safety Analysis of Preoperative Anti-TNF-α Therapy in Pediatric IBD After Intestinal Resection: A Systematic Review and Meta-analysis.

BACKGROUND: Biological agents have transformed the management of inflammatory bowel disease (IBD). However, intestinal resection is still unavoidable in complicated IBD. It is still under debate whether antitumor necrosis factor (TNF)-α is related to higher postoperative complications in children with IBD. Therefore, we aimed to analyze data on preoperative anti-TNF-α and postoperative complications in pediatric IBD. METHODS: We conducted a systematic literature search in 4 databases for studies that compared the incidence of postoperative complications between children with IBD who received anti-TNF-α treatment within 12 weeks prior to intestinal resection and who did not receive anti-TNF-α before the operation. To analyze this question, pooled odds ratios (ORs) were calculated with 95% confidence intervals (CIs). Odds ratios higher than 1 mean higher complication rate among children treated with preoperative anti-TNF-α, whereas an OR lower than 1 means lower complication rate. The I² value was calculated to measure the strength of the between-study heterogeneity, where a smaller percentage means the lower heterogeneity. RESULTS: We found 8 eligible articles with 526 pediatric patients with IBD. The primary outcome was the overall complication. The pooled OR of overall complications was 1.38 (95% CI, 0.10-18.76; P = .65; I2 = 34%) in contrast, the OR of infectious and noninfectious complications were 0.59 (95% CI, 0.21-1.69; P = .16; I2 = 0%) and 0.48 (95% CI, 0.18-1.25; p = .09; I2 = 0%), although both showed a nonsignificant result. CONCLUSION: There is no significant association between preoperative anti-TNF-α therapy and postoperative complications in children with IBD after intestinal resection. However, the evidence is low due to the low number of studies investigating this question.

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.

Hemoadsorption Therapy for Critically Ill Patients with Acute Liver Dysfunction: A Meta-Analysis and Systematic Review.

Critically ill patients are at risk of developing acute liver dysfunction as part of multiorgan failure sequelae. Clearing the blood from toxic liver-related metabolites and cytokines could prevent further organ damage. Despite the increasing use of hemoadsorption for this purpose, evidence of its efficacy is lacking. Therefore, we conducted this systematic review and meta-analysis to assess the evidence on clinical outcomes following hemoadsorption therapy. A systematic search conducted in six electronic databases (PROSPERO registration: CRD42022286213) yielded 30 eligible publications between 2011 and 2023, reporting the use of hemoadsorption for a total of 335 patients presenting with liver dysfunction related to acute critical illness. Of those, 26 are case presentations (n = 84), 3 are observational studies (n = 142), and 1 is a registry analysis (n = 109). Analysis of data from individual cases showed a significant reduction in levels of aspartate transaminase (p = 0.03) and vasopressor need (p = 0.03) and a tendency to lower levels of total bilirubin, alanine transaminase, C-reactive protein, and creatinine. Pooled data showed a significant reduction in total bilirubin (mean difference of -4.79 mg/dL (95% CI: -6.25; -3.33), p = 0.002). The use of hemoadsorption for critically ill patients with acute liver dysfunction or failure seems to be safe and yields a trend towards improved liver function after therapy, but more high-quality evidence is crucially needed.

The influence of air pollution on respiratory allergies, asthma and wheeze in childhood in Hungary.

BACKGROUND: Higher exposure to air pollution may contribute to the increased prevalence of allergic diseases in children. The study investigated the associations between the prevalence of childhood respiratory diseases and long-term exposure to NO2, SO2, PM10, especially some surrogates in schoolchildren in Hungary. We also analyzed the possible modification effects of some confounders by interaction analysis. METHODS: A total of 6771 children aged 8-9-year-old residing at their current addresses since their births with air pollution monitoring stations were selected into this analysis. Health outcomes and their possible determinants, as well as surrogates of air pollution were surveyed by using a standardized questionnaire. Long-term exposure to PM10, NO2, and SO2 was calculated at settlement level derived from daily average concentrations of pollutants. Descriptive and analytical statistical methods were applied. RESULTS: NO2 levels were positively associated with respiratory allergies and asthma. Decreased risk for ragweed, any other pollen, house dust mite and animal fur allergy was detected with PM10 level. There were significant associations between respiratory allergies to ragweed, any other pollen, house dust mite, animal fur, wheeze symptoms and living or attending school nearby a factory, power station or bus station as well as living in a home with intensive noise or vibration. Gender, parental atopy, home mold and early respiratory infection were significant effect modifiers in some cases. CONCLUSIONS: The results of this study indicate that respiratory health in children is adversely affected by air pollutants.