Association of soluble suppression of tumorigenicity 2 with mortality and adverse outcomes in chronic kidney disease: a systematic review and meta-analysis.

BACKGROUND: Early risk stratification is necessary to prevent chronic kidney disease progression and complications. This systematic review aims to evaluate the association of soluble suppression of tumorigenicity 2 (sST2), a member of the interleukin-1 receptor family, with all-cause mortality, cardiovascular disease and renal function deterioration among chronic kidney disease patients. METHODS: PubMed, Scopus, Web of Science, CENTRAL and Google Scholar were systematically searched from inception to December 20, 2023. Cohort studies examining the prognostic role of sST2 levels in pre-dialysis and dialysis patients were included. In case of 3 or more studies per outcome, conventional and dose-response meta-analyses were conducted. RESULTS: Overall, 21 studies were included comprising 15,100 patients. In pre-dialysis patients, the qualitative synthesis of studies suggested that high sST2 is associated with significantly increased all-cause mortality, while evidence regarding cardiovascular events or kidney disease progression was conflicting. In the dialysis population, high sST2 was linked to an elevated risk of all-cause (Hazard ratio-HR: 3.00, 95% confidence intervals-CI: 1.95-4.61) and cardiovascular (HR: 2.38, 95% CI: 1.69-3.34) mortality. Dose-response meta-analysis suggested a log-linear association of sST2 with both all-cause (χ2: 34.65, p value < 0.001) and cardiovascular (χ2: 29.14, p value < 0.001) mortality, whereas findings regarding cardiovascular events were limited with mixed results. CONCLUSIONS: High sST2 values are associated with an increased risk of all-cause mortality in pre-dialysis and dialysis patients, as well as with an elevated risk of cardiovascular mortality in the dialysis population. Further studies are needed to elucidate its potential association with cardiovascular events and kidney disease progression.

Providing Positive End-Expiratory Pressure during Neonatal Resuscitation: A Meta-analysis.

Our objective was to conduct a systematic review and meta-analysis evaluating the effects of administering positive end-expiratory pressure (PEEP) during neonatal resuscitation at birth. Medline, Web of Science, Scopus, Cochrane Central Register of Controlled Trials, and Clinicaltrials.gov databases were systematically searched from inception to 15 December 2020. Randomized controlled trials and cohort studies were held eligible. Studies were included if they compared the administration of PEEP using either a T-piece resuscitator or a self-inflating bag with a PEEP valve versus resuscitation via a self-inflating bag without a PEEP valve. Data were extracted by two reviewers independently. The credibility of evidence was appraised with the Grading of Recommendations, Assessment, Development, and Evaluations approach. Random-effects models were fitted to provide pooled estimates of risk ratio (RR) and 95% confidence intervals (CIs). Overall, 10 studies were included, comprising 4,268 neonates. This included five randomized controlled trials, one quasi-randomized trial, and four cohort studies. The administration of PEEP was associated with significantly lower rates of mortality till discharge (odds ratio [OR]: 0.60, 95% CI: 0.49-0.74, moderate quality of evidence). The association was significant in preterm (OR: 0.57, 95% CI: 0.46-0.69) but not in term (OR: 1.03, 95% CI: 0.52-2.02) neonates. Low-to-moderate quality evidence suggests that providing PEEP during neonatal resuscitation is associated with lower rates of mortality in preterm neonates. Evidence regarding term neonates is limited and inconclusive. Future research is needed to determine the optimal device and shed more light on the long-term effects of PEEP administration during neonatal resuscitation. This study is registered with PROSPERO with registration number: CRD42020219956. KEY POINTS: · PEEP administration during neonatal resuscitation in the delivery room reduces mortality in preterm.. · Evidence regarding term neonates is limited and inconclusive.. · Future research is needed to determine the optimal device..

Tranexamic acid for the prevention of postpartum hemorrhage in women undergoing cesarean delivery: an updated meta-analysis.

OBJECTIVE: This study aimed to assess the efficacy and safety of prophylactic tranexamic acid administration vs standard uterotonic agents alone among women undergoing cesarean delivery. DATA SOURCES: MEDLINE, Scopus, Web of Science, Cochrane Central Register of Controlled Trials, ClinicalTrials.gov, and Google Scholar were systematically searched from inception to June 30, 2021. STUDY ELIGIBILITY CRITERIA: Randomized controlled trials comparing intravenous tranexamic acid administration with placebo in women undergoing cesarean delivery and receiving standard prophylactic uterotonic agents were held eligible. STUDY APPRAISAL AND SYNTHESIS METHODS: The risk of bias of individual studies was appraised with the Risk of Bias 2 tool. Meta-analysis was conducted by fitting random-effects models using restricted maximum likelihood. Subgroup analysis was performed on the basis of country, protocol availability, double-blinding, risk of bias, sample size, and tranexamic acid dose. A 1-stage meta-analysis was performed as a sensitivity analysis. The credibility of outcomes was appraised with the Grading of Recommendations Assessment, Development and Evaluation approach. RESULTS: Overall, 36 studies with 10,659 women were included. Tranexamic acid administration was associated with significantly lower total blood loss (mean difference, -189.44 mL; 95% confidence intervals, -218.63 to -160.25), lower hemoglobin drop (mean difference, 8.22%; 95% confidence interval, 5.54-10.90), decreased risk of blood loss of >1000 mL (odds ratio, 0.37; 95% confidence interval, 0.22-0.60), transfusion requirement (odds ratio, 0.41; 95% confidence interval, 0.26-0.65), and need of additional uterotonics (odds ratio, 0.36; 95% confidence interval, 0.25-0.52). Subgroup analysis indicated a greater effect of tranexamic acid on total blood loss reduction in low-middle income countries. The outcomes remained stable by separately evaluating women at low bleeding risk. The 1-stage meta-analysis demonstrated similar outcomes with the primary analysis. The quality of evidence was judged to be moderate regarding total blood loss and hemoglobin percentage change and low for the other outcomes. CONCLUSION: This meta-analysis suggested that prophylactic tranexamic acid administration is effective among women undergoing cesarean delivery in lowering postpartum blood loss and limiting hemoglobin drop. Further research is needed to test its efficacy in high-risk populations and verify its safety profile.

A past medical history of autoimmune disease predicts a future with fewer relapses in patients with ANCA-associated vasculitis.

OBJECTIVES: To explore the frequency and impact of an autoimmune disease past-medical history (PMH) in the clinical picture and outcomes of patients with antineutrophil cytoplasmic autoantibodies (ANCA) associated vasculitis (AAV). METHODS: This was a retrospective study of patients with biopsy-proven AAV, >16 years old, with detailed information about their PMH. Outcomes of interest included remission, treatment resistance, relapse, end-stage kidney disease (ESKD), and death. RESULTS: 206 patients with biopsy-proven AAV and available information regarding their PMH were studied. 63(30.6%) of them had a history of autoimmune disease prior to AAV diagnosis. The mean age overall was 54.1 years. One hundred and five patients (51%) were positive for PR3-ANCA, 101 (49%) for MPO-ANCA. Granulomatosis with polyangiitis was diagnosed in 79 (38.3%), microscopic polyangiitis in 97 (47.1%) and renal-limited vasculitis in 30 (14.6%) individuals. Remission rate was similar among patients with and without a PMH of autoimmune disease. Time-to-event analysis indicated that the relapse-free survival was significantly longer in patients with PMH of autoimmune disease (148.2 vs. 61.9 months, p-value <0.001). After adjusting for covariates, autoimmune disease history was associated with significantly lower risk of relapse (HR: 0.33, 95% CI: 0.15-0.72), which remained significant in males, patients ≥60 years old and those with C/PR3-ANCA, kidney and lung involvement. CONCLUSIONS: Patients with a PMH of autoimmune disease, prior to AAV diagnosis, experienced significantly fewer relapses after achievement of remission, compared to patients without such a history, underlining the importance of individualisation of maintenance immunosuppressive therapy, given the different aetiopathogenetic settings the disease was developed.

The impact of vaginal pH on induction of labour outcomes: a meta-analysis of observational studies.

The present meta-analysis evaluates the impact of an acidic vaginal pH on the progress of labour induction with dinoprostone and misoprostol. We searched Medline, Scopus, EMBASE, Cochrane Central Register of Controlled Trials CENTRAL, Clinicaltrials.gov and Google Scholar databases for relevant studies. Meta-analysis was performed with Rstudio using the meta function and trial sequential analysis was used to evaluate the adequacy of sample size. Nine studies were retrieved that involved 809 patients. An acidic vaginal pH did not influence the efficacy of misoprostol or dinoprostone in terms of accomplishing a successful vaginal delivery (OR 0.62, 95% CI 0.29, 1.30). The interval to delivery was unaffected by the acidity of vaginal pH (Mean Difference 4.18 h, 95% CI -2.09, 10.45). In conclusion, vaginal pH does not seem to affect the potency of vaginally administered prostaglandins; therefore, moistening of vaginal tables with acetic acid does not seem reasonable until further evidence becomes available.

Cephalad-caudad versus transverse blunt expansion of the low transverse hysterotomy during cesarean delivery decreases maternal morbidity: a meta-analysis.

OBJECTIVE: Cesarean delivery is the most prevalent surgical procedure worldwide, reaching approximately 29.7 million cases in 2015. It is directly associated with an increased risk of maternal and neonatal morbidity rates in the absence of malpresentation. Several techniques have been investigated, and there is evidence that cephalad-caudad expansion of the uterine incision might be associated with improved maternal outcomes compared with traditional transverse blunt expansion. The purpose of this meta-analysis was to evaluate the impact of cephalad-caudad expansion on adverse maternal outcomes, including intraoperative blood loss, risk of uterine vessel injury, and tearing of the lower uterine segment. DATA SOURCES: We searched Medline, Scopus, the Cochrane Central Register of Controlled Trials, Google Scholar, and Clinicaltrials.gov databases from inception to January 2021. STUDY ELIGIBILITY CRITERIA: Randomized controlled trials that assessed the impact of the cephalad-caudad blunt expansion of the low transverse uterine incision during cesarean delivery rather than those of transverse blunt expansion were selected for inclusion. METHODS: Effect sizes were calculated with the Hartung-Knapp-Sidik-Jonkman random-effects model in R. Trial sequential analysis was performed to evaluate the adequacy of sample sizes. RESULTS: Cephalad-caudad blunt expansion of the uterine incision was associated with a lower prevalence of unintended incision extension (relative risk, 0.62; 95% confidence interval, 0.45-0.86) and uterine vessel injury (relative risk, 0.55; 95% confidence interval 0.41-0.73). However, these complications were not accompanied by the increased need for additional suture placement (relative risk, 0.62; 95% confidence interval, 0.31-4.12) or transfusion rates (relative risk, 0.75; 95% confidence interval, 0.28-2.03). Similarly, the intraoperative duration was comparable with cases treated with transverse blunt expansion (mean difference = -0.45 minutes; 95% confidence interval -2.12 to 1.21) and the risk of intentional incision extension in the form of an inverted T (relative risk, 0.38; 95% confidence interval, 0.09-1.52). Trial sequential analysis revealed that the required sample size was reached in the unintended incision extension and uterine vessel injury outcomes. CONCLUSION: The findings of our study suggested that cephalad-caudad blunt expansion of the uterine incision is superior to transverse expansion in terms of reducing unintended incision extension and uterine vessel injury.

Markers of endothelial dysfunction and arterial stiffness in patients with early-stage autosomal dominant polycystic kidney disease: A meta-analysis.

OBJECTIVES: Autosomal dominant polycystic kidney disease (ADPKD) is characterised by increased rates of cardiovascular complications leading to significant morbidity and mortality. This meta-analysis aims to evaluate whether the disease is linked to endothelial dysfunction and arterial stiffness during its early stages. METHODS: Medline, Scopus, CENTRAL, Web of Science, Clinicaltrials.gov and Google Scholar databases comparing ADPKD patients with preserved renal function to healthy controls were included. The outcomes of interest were brachial flow-mediated dilatation, carotid-femoral pulse wave velocity, augmentation index, carotid intima-media thickness and central systolic blood pressure, plasma ADMA or homocysteine levels. Standardised mean differences (SMDs) were estimated by a random-effects model in R-3.6.3. RESULTS: A total of 27 studies were included, comprising 1967 individuals. ADPKD was linked to significantly lower flow-mediated dilatation (SMD: -1.44, 95% CI: [-2.35, -0.53]) and higher pulse wave velocity (SMD: 1.44, 95% CI: [0.22, 2.66]) and carotid intima-media thickness (SMD: 1.02, 95% CI: [0.57, 1.47]). No significant associations were noted regarding augmentation index (SMD: 0.62, 95% CI: [-0.19, 1.43]) and central systolic blood pressure (SMD: 1.84, 95% CI: [-0.12, 3.80]). Plasma homocysteine was significantly higher in ADPKD (SMD: 0.81, 95% CI: [0.16, 1.45]), while no difference was calculated for ADMA levels (SMD: 1.14, 95% CI: [-0.25, 2.53]). CONCLUSIONS: Early-stage ADPKD patients present increased vascular stiffness and endothelial dysfunction, as reflected by low flow-mediated dilatation and elevated values of pulse wave velocity, carotid intima-media thickness and plasma homocysteine. The exact effects of early arterial stiffness on long-term outcomes remain to be elucidated.

Serum LDH values in hypertensive disorders of pregnancy and their association with maternal and neonatal morbidity: A meta-analysis.

BACKGROUND: Serum lactate dehydrogenase has been extensively studied in hypertensive disorders of pregnancy. However, to date, its clinical usefulness in the field remains unknown. The present meta-analysis has been designed to evaluate differences in serum LDH values among patients with hypertensive disorders of pregnancy and to help determine its diagnostic accuracy as well its predictive accuracy in determining adverse pregnancy outcomes. METHODS: We searched Medline, Scopus, Clinicaltrials.gov, EMBASE, Cochrane Central Register of Controlled Trials CENTRAL and Google Scholar databases from their inception till 18 March 2021. Observational studies that assessed differences in serum LDH levels among women with hypertensive disorders of pregnancy and healthy controls were included. Meta-analysis was performed using Rstudio. Pooled mean differences (MD) were calculated with the Hartung-Knapp-Sidik-Jonkman. Meta-regression analyses, publication bias assessment and Trim and Fill function were also performed. The adequacy of the sample size was evaluated with Trial Sequential Analysis. RESULTS: Fifty-two articles were included that comprised 5340 women with hypertensive disorders of pregnancy and 2890 healthy controls. The meta-analysis revealed significant differences among patients with preeclampsia (either mild or severe) compared with controls, as well as among patients with mild and severe preeclampsia. Significant asymmetry was noted after examining funnel plots, however, and the trim and fill analysis revealed that differences were significant only among cases with severe preeclampsia and healthy controls. Morbidity outcomes increased with LDH levels >600 IU/L and particularly when these exceeded 800 IU/L. However, confidence and prediction intervals indicated an underpowered sample size for the accurate determination of the odds of developing maternal morbidity. CONCLUSION: Despite the extensive research in the field of hypertensive disorders of pregnancy, there is still lack of evidence concerning the diagnostic performance of serum LDH in clinical practice; hence, research should expand in this direction to evaluate its clinical utility.

Development of a novel risk score for the prediction of critical illness amongst COVID-19 patients.

OBJECTIVES: Coronavirus disease-19 (COVID-19) is associated with various clinical manifestations, ranging from asymptomatic infection to critical illness. The aim of this study is to evaluate the clinical and laboratory characteristics of hospitalised COVID-19 patients and construct a predictive model for the discrimination of patients at risk of disease progression. METHODS: A single-centre cohort study was conducted including consecutively patients with COVID-19. Demographic, clinical and laboratory findings were prospectively collected at admission. The primary outcome of interest was the intensive care unit admission. A risk model was constructed by applying a Cox's proportional hazard's model with elastic net penalty. Its diagnostic performance was assessed by receiver operating characteristic analysis and was compared with conventional pneumonia severity scores. RESULTS: From a total of 67 patients 15 progressed to critical illness. The risk score included patients' gender, presence of hypertension and diabetes mellitus, fever, shortness of breath, serum glucose, aspartate aminotransferase, lactate dehydrogenase, C-reactive protein and fibrinogen. Its predictive accuracy was estimated to be high (area under the curve: 97.1%), performing better than CURB-65, CRB-65 and PSI/PORT scores. Its sensitivity and specificity were estimated to be 92.3% and 93.3%, respectively, at the optimal threshold of 1.6. CONCLUSIONS: A10-variable risk score was constructed based on clinical and laboratory characteristics in order to predict critical illness amongst hospitalised COVID-19 patients, achieving better discrimination compared with traditional pneumonia severity scores. The proposed risk model should be externally validated in independent cohorts in order to ensure its prognostic efficacy.

Relationship of vancomycin trough levels with acute kidney injury risk: an exposure-toxicity meta-analysis.

OBJECTIVES: Nephrotoxicity represents a major complication of vancomycin administration, leading to high rates of morbidity and treatment failure. The aim of this meta-analysis was to evaluate the association between trough levels and risk of renal impairment, by defining an exposure-toxicity relationship and assessing its accuracy in predicting the development of acute kidney injury (AKI). METHODS: Medline, Scopus, CENTRAL, Clinicaltrials.gov and Google Scholar databases were systematically searched from inception. Studies examining the effects of trough levels on nephrotoxicity risk in adult patients were deemed eligible. RESULTS: The meta-analysis was based on 60 studies, including 13 304 patients. The development of AKI was significantly linked to both higher initial [standardized mean difference (SMD): 0.82; 95% CI: 0.65-0.98] and maximum (SMD: 1.06; 95% CI: 0.82-1.29) trough levels. Dose-response analysis indicated a curvilinear relationship between trough levels and nephrotoxicity risk (χ2 = 127.1; P value < 0.0001). A cut-off of 15 mg/L detected AKI with a sensitivity of 62.6% (95% CI: 55.6-69.2) and a specificity of 65.5% (95% CI: 58.9-71.6), while applying a 20 mg/L threshold resulted in a sensitivity of 42.9% (95% CI: 34-52.2) and a specificity of 82.5% (95% CI: 73.9-88.8). CONCLUSIONS: The present findings suggest that the development of vancomycin-induced AKI is significantly associated with higher initial and maximum trough levels. An exposure-response relationship was defined, indicating that increasing trough levels correlate with a significant rise of nephrotoxicity risk. Future studies should verify the effectiveness of individualized pharmacokinetic tools that would enable the attainment of trough level targets and minimize the risk of renal toxicity.

Efficacy and safety of colistin loading dose: a meta-analysis.

OBJECTIVES: Colistin represents a polypeptide used for the treatment of MDR microorganisms, although the optimal dosing strategy is under investigation. The present meta-analysis aims to determine whether the administration of a colistin loading dose in patients receiving high-dose maintenance regimens changes the rates of treatment success and the risk of nephrotoxicity. METHODS: Medline, Scopus, CENTRAL, Clinicaltrials.gov and Google Scholar were systematically searched from inception to 18 November 2019. Studies were considered eligible if they reported clinical outcomes among patients receiving high-dose colistin therapy with and without the administration of a loading dose. Meta-analysis was performed by fitting a random-effects model. RESULTS: Eight (three prospective and five retrospective cohort) studies were included, comprising 1115 patients. The administration of a colistin loading dose was associated with significantly higher microbiological [risk ratio (RR) = 1.23, 95% CI = 1.10-1.39] but not clinical (RR = 1.04, 95% CI = 0.87-1.24) success. No significant associations were calculated for nephrotoxicity (RR = 1.31, 95% CI = 0.90-1.91) and mortality (RR = 1.03, 95% CI = 0.82-1.29) risk. The results remained stable after adjustments for small sample size, credibility ceilings, publication bias and risk of bias. CONCLUSIONS: Observational evidence suggests that the administration of a colistin loading dose in patients receiving high maintenance dosage regimens is significantly associated with higher rates of microbiological response, but does not change clinical cure, mortality or nephrotoxicity risk. The dosing regimen that would provide the optimal balance between treatment efficacy and safety needs to be determined by future randomized controlled trials.

Comparative efficacy and safety of oral antihypertensive agents in pregnant women with chronic hypertension: a network metaanalysis.

OBJECTIVE DATA: Chronic hypertension is associated with adverse perinatal outcomes, although the optimal treatment is unclear. The aim of this network metaanalysis was to simultaneously compare the efficacy and safety of antihypertensive agents in pregnant women with chronic hypertension. STUDY: Medline, Scopus, CENTRAL, Web of Science, Clinicaltrials.gov, and Google Scholar databases were searched systematically from inception to December 15, 2019. Both randomized controlled trials and cohort studies were held eligible if they reported the effects of antihypertensive agents on perinatal outcomes among women with chronic hypertension. STUDY APPRAISAL AND SYNTHESIS METHODS: The primary outcomes were preeclampsia and small-for-gestational-age risk. A frequentist network metaanalytic random-effects model was fitted. The main analysis was based on randomized controlled trials. The credibility of evidence was assessed by taking into account within-study bias, across-studies bias, indirectness, imprecision, heterogeneity, and incoherence. RESULTS: Twenty-two studies (14 randomized controlled trials and 8 cohorts) were included, comprising 4464 women. Pooling of randomized controlled trials indicated that no agent significantly affected the incidence of preeclampsia. Atenolol was associated with significantly higher risk of small-for-gestational age compared with placebo (odds ratio, 26.00; 95% confidence interval, 2.61-259.29) and is ranked as the worst treatment (P-score=.98). The incidence of severe hypertension was significantly lower when nifedipine (odds ratio, 0.27; 95% confidence interval, 0.14-0.55), methyldopa (odds ratio, 0.31; 95% confidence interval, 0.17-0.56), ketanserin (odds ratio, 0.29; 95% confidence interval, 0.09-0.90), and pindolol (odds ratio, 0.17; 95% confidence interval, 0.05-0.55) were administered compared with no drug intake. The highest probability scores were calculated for furosemide (P-score=.86), amlodipine (P-score=.82), and placebo (P-score=.82). The use of nifedipine and methyldopa were associated with significantly lower placental abruption rates (odds ratio, 0.29 [95% confidence interval, 0.15-0.58] and 0.23 [95% confidence interval, 0.11-0.46], respectively). No significant differences were estimated for cesarean delivery, perinatal death, preterm birth, and gestational age at delivery. CONCLUSION: Atenolol was associated with a significantly increased risk for small-for-gestational-age infants. The incidence of severe hypertension was significantly lower when nifedipine and methyldopa were administered, although preeclampsia risk was similar among antihypertensive agents. Future large-scale trials should provide guidance about the choice of antihypertensive treatment and the goal blood pressure during pregnancy.

An arm-based network meta-analysis on treatments for vulvar lichen sclerosus and a call for development of core outcome sets.

OBJECTIVE: The purpose of the present systematic review is to evaluate the available medical treatments for vulvar lichen sclerosus, using an arm-based network meta-analysis protocol. DATA SOURCES: We searched Medline (1966-2019), Scopus (2004-2019), Cochrane Central Register of Controlled Trials CENTRAL (1999-2019), Clinicaltrials.gov (2008-2019) databases, and Google Scholar (2004-2019) database along with the reference list of all included studies. STUDY ELIGIBILITY CRITERIA: All observational, randomized, and single-arm studies that evaluated medical treatments for vulvar lichen sclerosus were considered eligible for inclusion in the present systematic review. STUDY APPRAISAL: A network meta-analysis was carried out in R 3.4.3 using the pcnetmeta package, which uses a Bayesian hierarchical model (based in Markov chain Monte Carlo convergence simulation). RESULTS: Sixteen studies were included in this present meta-analysis, which recruited 954 women with vulvar lichen sclerosus. Their quality was evaluated with the JADAD, Cochrane risk of bias, and risk of bias in nonrandomised studies of interventions-I tools. Clobetasol treatment ranked as the best treatment for disease remission after evaluating rank probabilities (40% chance of ranking first compared with tacrolimus [38%]). However, the density plot revealed partial overlapping with tacrolimus. The lowest probability of experiencing a relapse was observed with pimecrolimus (15% [2-48%]); however, the density plot revealed significant overlapping with mometasone furoate, testosterone, and clobetasol. CONCLUSION: Robust evidence concerning the superiority of potent steroids at least over calcineurin inhibitors is still lacking in the field of vulvar lichen sclerosus. On the other hand, the gross heterogeneity in terms of selected population, duration of treatment, administered regimen, outcome reporting, and selection of outcome measures leaves several fields unanswered.

Tolvaptan Response Improves Overall Survival in Patients with Refractory Ascites: A Meta-Analysis.

BACKGROUND AND AIMS: Refractory ascites represents a significant complication of decompensated cirrhosis, associated with increased mortality rates. The aim of this meta-analysis was to evaluate whether response to treatment with tolvaptan is associated with improved overall survival in cirrhotic patients with refractory ascites. METHODS: Medline, Scopus, Cochrane Central Register of Controlled Trials, Clinicaltrials.gov, and Google Scholar databases were systematically searched from inception to April 11, 2019. All studies that assessed the overall survival of patients with ascites depending on their response to tolvaptan were held eligible. RESULTS: Nine studies were included, with a total of 736 patients with cirrhosis and ascites. Response to tolvaptan was estimated to be linked to significantly improved overall survival (hazard ratio [HR] 0.42, 95% CI [0.31-0.58]). Subgroup analysis indicated that the same outcome was present when tolvaptan responsiveness was defined either as effective body weight loss (HR 0.44, 95% CI [0.30-0.63] or as effective sodium restoration (HR 0.35, 95% CI [0.20-0.61]. Sensitivity analysis suggested that the presence of hepatocellular carcinoma, the sample size, and the quality of the studies did not significantly affect the overall result of the meta-analysis. CONCLUSIONS: The outcomes of the meta-analysis support the prognostic role of tolvaptan response in patients with cirrhosis and refractory ascites, as it was shown to lead to significantly improved overall survival. These findings should be confirmed by future large-scale studies, while efficient biomarkers should be identified in order to accurately predict response to tolvaptan and discriminate patients that would benefit from its administration.

Predictors of tolvaptan short-term response in patients with refractory ascites: A meta-analysis.

BACKGROUND AND AIM: Tolvaptan represents an oral V2 -receptor antagonist, which has been suggested as a promising add-on diuretic treatment for refractory ascites. The present meta-analysis aims to accumulate current evidence and identify which clinical and laboratory factors are linked to short-term response to tolvaptan therapy. METHODS: Medline, Scopus, Cochrane Central Register of Controlled Trials, Clinicaltrials.gov, and Google Scholar databases were searched from inception. All observational studies reporting the correlation of patients' characteristics with tolvaptan response were selected. RESULTS: Tolvaptan response was associated with significantly higher baseline body weight (mean difference: 4.59 kg, 95% confidence interval [CI]: [3.58, 5.61]), presence of hepatitis C (odds ratio: 1.59 95% CI: [1.18, 2.14]), lower blood urea nitrogen (BUN) (mean difference: -6.88 mg/dL, 95% CI: [-8.13, -5.63]), lower serum creatinine (mean difference: -0.17 mg/dL, 95% CI: [-0.30, -0.05]), lower C-reactive protein (mean difference: -1.43 mg/dL, 95% CI: [-2.52, -0.35]), and higher sodium levels (mean difference: 1.00 mEq/L, 95% CI: [0.45, 1.55]). The outcomes of bodyweight, hepatitis C, BUN, and C-reactive protein remain significant independently of response definition and risk of bias. CONCLUSIONS: The present findings suggest bodyweight, BUN, C-reactive protein, and hepatitis C as potential predictive factors of tolvaptan short-term response in patients with refractory ascites. Future studies are needed to introduce cut-off values and construct an optimal combined screening model.

Association of postoperative fluid overload with adverse outcomes after congenital heart surgery: a systematic review and dose-response meta-analysis.

BACKGROUND: Pediatric cardiac surgery is commonly associated with acute kidney injury (AKI) and significant fluid retention, which complicate postoperative management and lead to increased rates of morbidity. This meta-analysis aimed to accumulate current literature evidence and evaluate the correlation of fluid overload degree with adverse outcome in patients undergoing congenital heart surgery. METHODS: Medline, Scopus, CENTRAL, Clinicaltrials.gov, and Google Scholar were systematically searched from inception. All studies reporting the effects of fluid overload on postoperative clinical outcomes were selected. A dose-response meta-analytic method using restricted cubic splines was implemented in R-3.6.1. RESULTS: Twelve studies were included, with a total of 3111 pediatric patients. Qualitative synthesis indicated that fluid overload was linked to significantly higher risk of mortality, AKI, prolonged hospital, and intensive care unit (ICU) stay, as well as with increased duration of mechanical ventilation, inotrope need, and infection rate. Meta-analysis demonstrated a linear correlation between fluid overload and the risk of mortality (χ2 = 6.22, p value = 0.01) and AKI (χ2 = 35.84, p value < 0.001), while a positive curvilinear relationship was estimated for the outcomes of hospital (χ2 = 18.84, p value = 0.0001) and ICU stay (χ2 = 63.69, p value = 0.0001). CONCLUSIONS: The present meta-analysis supports that postoperative fluid overload is significantly linked to elevated risk of prolonged hospital stay, AKI development, and mortality in pediatric patients undergoing cardiac surgery. These findings warrant replication by future prospective studies, which should define the optimal cutoff values and assess the effectiveness of therapeutic strategies to limit fluid overload in the postoperative setting.

Presence of amniotic fluid sludge and pregnancy outcomes: A systematic review.

INTRODUCTION: Several studies acknowledge that the presence of amniotic fluid sludge (AFS) is an independent predictive factor for preterm birth. In the present systematic review, we summarize research that focuses on the comparison of pregnancy outcomes among women with and without AFS. MATERIAL AND METHODS: Medline, Scopus, Clinicaltrials.gov, EMBASE, Cochrane Central Register of Controlled Trials (CENTRAL), and Google Scholar databases were systematically searched from inception. Both observational and randomized controlled studies were considered eligible provided that they reported data on pregnancy outcomes among women with and without AFS. Outcomes were not meta-analyzed because of the high heterogeneity in terms of selected population and outcome reporting. RESULTS: Seventeen studies of 2432 women were included in this review. Six studies evaluated women at high risk for preterm birth. Pregnancies complicated by AFS had a lower gestational age at delivery and increased incidence of preterm delivery at <37 weeks. Neonatal death rates and admission to the Neonatal Intensive Care Unit were also increased. Evidence in low-risk women, those with signs of preterm labor, in those carrying twins, and in women with cervical cerclage or Arabin pessary was extremely limited. CONCLUSIONS: Women with AFS seem to deliver at an earlier gestational age, and preterm birth rates are also increased. Limited data seem to point to neonatal morbidity and mortality being increased. However, the presence of a direct association should not be assumed because the evidence is not adjusted for the presence of confounders.

Systematic review found that using thin catheters to deliver surfactant to preterm neonates was associated with reduced bronchopulmonary dysplasia and mechanical ventilation.

AIM: Surfactant delivery is a cornerstone for managing respiratory distress in preterm neonates, but data on the best surfactant delivery methods have been conflicting. METHODS: A systematic literature review using the PubMed, Embase, Cochrane Library and Web of Science databases identified papers published up to November 5, 2019. Additional studies were identified from trial registries, conference proceedings and the reference lists of the selected papers. RESULTS: We identified 15 studies covering 4926 preterm infants. The randomised controlled trials (RCTs) and observational studies both showed significant reductions in early intubation rates with use of thin catheters. The relative risk (RR) was 0.63 and the 95% confidence interval (95% CI) was 0.55-0.72 (P < .01), with an odds ratio (OR) of 0.40 and 95% CI of 0.35-0.45 (P < .0001). The collective results from the RCTs revealed a significant decrease in bronchopulmonary dysplasia (BPD) rates in the thin catheter group (RR, 0.47; 95% CI 0.33-0.66; P < .01). These findings were consistent with the observational studies (OR 0.47; 95% CI 0.43-0.52; P < .01). CONCLUSION: Using thin catheters to deliver surfactant in comparison with intubate-surfactant-extubate (INSURE) to newborn preterm infants with respiratory distress was associated with a reduced incidence of BPD and less need for mechanical ventilation.

Progestogens for the prevention of preterm birth and risk of developing gestational diabetes mellitus: a meta-analysis.

BACKGROUND: Several articles have implied that progestogen supplementation during pregnancy to reduce the risk of preterm birth may increase the risk for developing gestational diabetes mellitus. OBJECTIVE: The purpose of the present meta-analysis was to accumulate existing evidence concerning this correlation. DATA SOURCES: We searched Medline (1966-2019), Scopus (2004-2019), Clinicaltrials.gov (2008-2019), EMBASE (1980-2019), Cochrane Central Register of Controlled Trials CENTRAL (1999-2019), and Google Scholar (2004-2019) databases. STUDY ELIGIBILITY CRITERIA: Randomized trials and observational studies were considered eligible for inclusion in the present meta-analysis. To minimize the possibility of article losses, we avoided language, country, and date restrictions. STUDY APPRAISAL AND SYNTHESIS METHODS: The methodological quality of included studies was evaluated with the Cochrane risk of bias and the Risk Of Bias In Non-Randomized Studies of Interventions (ROBINS-I) tool. Meta-analysis was performed with the RevMan 5.3 and secondary analysis with the Open Meta-Analyst software. Trial sequential analysis was conducted with the trial sequential analysis program. RESULTS: Overall, 11 studies were included in the present meta-analysis that recruited 8085 women. The meta-analysis revealed that women who received 17-alpha hydroxyprogesterone caproate had increased the risk of developing gestational diabetes mellitus (risk ratio, 1.73, 95% confidence interval, 1.32-2.28), whereas women who received vaginal progesterone had a decreased risk, although the effect did not reach statistical significance because of the unstable estimate of confidence intervals (risk ratio, 0.82, 95% confidence interval, 0.50-1.12). Meta-regression analysis indicated that neither the methodological rationale for investigating the prevalence of gestational diabetes mellitus (incidence investigated as primary or secondary outcome) (coefficient of covariance, -0.36, 95% confidence interval, -0.85 to 0.13, P = .154) nor the type of investigated study (randomized controlled trial/observational) (coefficient of covariance -0.361, 95% confidence interval, -1.049 to 0.327, P = .304) significantly altered the results of the primary analysis. Trial sequential analysis suggested that the meta-analysis concerning the correlation of 17-alpha hydroxyprogesterone caproate was of adequate power to reach firm conclusions, whereas this was not confirmed in the case of vaginal progesterone. CONCLUSION: The results of the present meta-analysis clearly indicate that women who receive supplemental 17-alpha hydroxyprogesterone caproate for the prevention of preterm birth have an increased risk of developing gestational diabetes mellitus. On the other hand, evidence concerning women treated with vaginal progesterone remains inconclusive.

Allopurinol Administration for the Prevention of Contrast-Induced Nephropathy: A Network Meta-analysis With Trial Sequential Analysis.

Contrast-induced nephropathy represents a major source of morbidity in patients undergoing coronary angiography. Various preventive measures have been proposed, although the optimal one remains still unknown. The aim of the present meta-analysis is to accumulate current literature knowledge and evaluate the renoprotective effects of allopurinol administration before contrast medium exposure. To achieve this, MEDLINE, Scopus, Cochrane Central Register of Controlled Trials, Clinicaltrials.gov, and Google Scholar databases were searched from inception to November 8, 2018. Statistical meta-analysis was conducted with Review Manager 5.3, TSA 0.9.5.5 and R-3.4.3. Six studies were included with a total of 918 patients. Quantitative synthesis revealed that allopurinol leads to significantly reduced incidence of contrast-induced nephropathy compared with hydration alone [odds ratio: 0.29, 95% confidence interval: (0.09-0.90)]. Trial sequential analysis suggested that Z-curve crossed the O'Brien-Fleming significance boundaries, although required information size was not reached. Network meta-analysis indicated that allopurinol had the highest probability (81.2%) to rank as the most effective intervention compared with hydration and N-acetyl cysteine; however, significant overlap with the rest treatments was noted. In conclusion, the present meta-analysis suggests that allopurinol may represent a promising measure for the prevention of acute kidney injury after coronary angiography. Future large-scale randomized controlled trials should verify this finding, while combinations of allopurinol with other novel interventions should be evaluated to define the most effective strategy to be implemented in the clinical setting.