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BackgroundWorldwide, idiopathic nephrotic syndrome (INS) is the most common glomerular disorder in children. Limited studies are available on quality of life (QOL) in children with NS, especially from developing countries. The aim of the current study was to compare the QOL of children having INS with that of matched healthy controls and to evaluate the effects of sub-types on domain scores.MethodsThis single-center, cross-sectional analytical study was conducted in children between 2 and 18 years with primary INS, at a tertiary care center in India, from September 2018 to November 2018. QOL data were collected using PedsQL™4.0 Generic Core Scales “Hindi-for-India” version (child self-report and parent-report). A total of 102 cases with equal number of matched healthy controls were included.ResultsThe mean total PedsQL scores were lower in NS children compared to healthy controls (p-0.0004). They had statistically lower scores in physical (p- < 0.0001), social (p-0.026), and school domains (p- < 0.0001); however, no such difference was noted in emotional functioning. School functioning was the most impacted domain overall, and also across all the clinical types. Worst scores were seen in children with steroid-resistant NS in all domains. Older age-at-enrolment, higher number of relapses, prevalent NS, steroid-resistant disease, calcineurin inhibitor (CNI) use, and higher number of immunosuppressant use were important predictors of poor total QOL scores. On multivariable regression, higher number of immunosuppressant use (p-0.015) and older age-at-enrolment (p-0.016) were main predictors of impaired total scores. Cases with edema and current/previous CNI use were more likely to have impaired emotional (p-0.028) and social (p-0.040) domain sub-scores, respectively.ConclusionNS has a significant impact on the QOL of children in different domains of functioning, based on their as well as parents’ perspective.Trial registration noEC/08/18/1414; Date: 30/08/2018.

Atypical hemolytic uremic syndrome (aHUS), an important cause of acute kidney injury (AKI), is characterized by dysregulation of the alternative complement pathway. Autoantibodies to factor H (FH), a chief regulator of this pathway, account for a distinct subgroup. While high anti-FH titers predict relapse, they do not correlate well with disease activity and their functional characterization is required. Of 781 patients <18-year-old of aHUS in the nationwide database from 2007 to 2018, 436 (55.8%) had anti-FH antibodies. Clinical features and outcome of patients managed in the last 6-year ( = 317) were compared to before ( = 119). In plasma samples of 44 patients, levels of serial circulating FH immune complexes (CIC), free FH, soluble terminal complement complex (sC5b-9), sheep red blood cell (SRBC) lysis and epitope specificity ( = 8) were examined. Functional renal reserve, ambulatory hypertension, left ventricular hypertrophy (LVH), and proteinuria were evaluated in a subset. Patients presented with markedly elevated anti-FH titers (10,633.2 ± 998.5 AU/ml). Management varied by center, comprising plasma exchange (PEX; 77.5%) and immunosuppression (73.9%). Patients managed in the last 6-year showed better renal survival at mean 28.5 ± 27.3 months (log rank = 0.022). Mean anti-FH titers stayed 700-1,164 AU/ml during prolonged follow-up, correlating with CIC. Patients with relapse had lower free-FH during remission [Generalized estimating equations (GEE), = 0.001]; anti-FH levels ≥1,330 AU/ml and free FH ≤440 mg/l predicted relapse (hazards ratio, HR 6.3; = 0.018). Epitope specificity was similar during onset, remission and relapse. Antibody titer ≥8,000 AU/ml (HR 2.23; = 0.024), time to PEX ≥14 days (HR 2.09; = 0.071) and PEX for <14 days (HR 2.60; = 0.017) predicted adverse renal outcomes. Combined PEX and immunosuppression improved long-term outcomes (HR 0.37; = 0.026); maintenance therapy reduced risk of relapses (HR 0.11; < 0.001). At 4.4±2.5 year, median renal reserve was 15.9%; severe ambulatory, masked and pre-hypertension were found in 38, 30, and 18%, respectively. Proteinuria and LVH occurred in 58 and 28% patients, respectively. Prompt recognition and therapy with PEX and immunosuppression, is associated with satisfactory outcomes. Free-FH predicts early relapses in patients with high anti-FH titers. A significant proportion of impaired functional reserve, ambulatory hypertension, proteinuria and LVH highlight the need for vigilant long-term follow-up.

Gastric acid-reducing medications (ARMs) such as proton pump inhibitors (PPIs) and histamine type 2 receptor blockers (H2 blockers) are crucial in pediatric care for treating various gastrointestinal conditions. These medications are frequently used to treat erosive esophagitis, peptic ulcer disease, and gastroesophageal reflux disease (GERD). ARMs are essential to the administration of eosinophilic esophagitis and infection. Additionally, literature also supports its use in alleviating drug-induced dyspepsia, preventing stress-related mucosal damage, and lowering the risk of acid aspiration syndrome during anesthesia in critical care settings. Despite the widespread indications of ARMs, PPIs, the most potent acid suppressants, present concerns regarding safety and their inappropriate use in pediatrics. This paper aims to address these gaps by providing comprehensive, practical recommendations for ARM use in pediatric settings. The methodology involved a structured literature review and opinions from 24 pediatric specialists across India, including neonatologists, general pediatricians, pediatric gastroenterologists, a pediatric hepatologist, pediatric nephrologists, a pediatric pulmonologist, and a pediatric intensivist on the appropriate choice of ARM use in various clinical scenarios. They emphasized the benefits of H2 receptor antagonists (H2RAs) over PPIs, particularly in neonates and infants, where H2RAs offer a safer alternative due to their lower risk of adverse effects. The paper outlines the effective application of H2RAs in managing GERD, preventing stress ulcers, and treating drug-induced dyspepsia. It also provides guidelines for appropriate ARM use, stressing the need for careful patient evaluation to minimize the risk of unnecessary ARM use. Pediatricians also provided a view on the use of H2RAs beyond gastrointestinal indications, such as in urticaria, where they show promising clinical application when combined with H1-antihistamines. This paper offers valuable insights and recommendations for optimizing the use of ARM in pediatric practice. By highlighting the advantages of H2RAs and addressing the limitations and risks associated with PPIs, the paper aims to guide clinicians in making informed, evidence-based decisions. The goal is to improve clinical outcomes, promote the rational use of ARM, and enhance the quality of pediatric care.

Antibodies to complement factor H are an uncommon cause of hemolytic uremic syndrome (HUS). Information on clinical features and outcomes in children is limited. In order to explore this we studied a multicenter cohort of 138 Indian children with anti-complement factor H antibody associated HUS, constituting 56% of patients with HUS. Antibody titers were high (mean 7054 AU/ml) and correlated inversely with levels of complement C3, but not complement factor H. Homozygous deletion of the CFHR1 gene was found in 60 of 68 patients. Therapies included dialysis in 119 children, 105 receiving plasma exchanges and 26 intravenous immunoglobulin. Induction immunosuppression consisted of 87 children receiving prednisolone with or without intravenous cyclophosphamide or rituximab. Antibody titers fell significantly following plasma exchanges and increased during relapses. Adverse outcome (stage 4-5 CKD or death) was seen in 36 at 3 months and 41 by last follow up, with relapse in 14 of 122 available children. Significant independent risk factors for adverse outcome were an antibody titer over 8000AU/ml, low C3 and delay in plasma exchange. Combined plasma exchanges and induction immunosuppression resulted in significantly improved renal survival: one adverse outcome prevented for every 2.6 patients treated. Maintenance immunosuppressive therapy, of prednisolone with either mycophenolate mofetil or azathioprine, significantly reduced the risk of relapses. Thus, prompt use of immunosuppressive agents and plasma exchanges are useful for improving outcomes in pediatric patients with anti-complement factor H-associated HUS.

To determine whether or not Darbepoetin alpha (DA) was non-inferior to recombinant human erythropoietin (rHuEPO) in the treatment of anemia in children with chronic kidney disease (CKD) stage 3–5 (on or not on dialysis). This was a randomized, open-label, two-arm, parallel group, active-controlled, non-inferiority trial conducted at a tertiary care center in New Delhi, India. Fifty patients of either gender (aged 1–18 years) with CKD stage 3–5 (on or not on dialysis) who had baseline hemoglobin (Hb) between 9 and 12 g/dL and were on stable erythropoietin therapy for at least 8 weeks were randomized (1:1) to either continue rHuEPO or switch to DA therapy for a period of 28 weeks. Doses were titrated in the initial 23 weeks to maintain the Hb between 11 and 12 g/dL, and efficacy was assessed between weeks 24 and 28. The primary efficacy outcome was the mean change in Hb between baseline and the evaluation period. In the intention-to-treat population ( n  = 50), the adjusted between-group difference in mean Hb change between the baseline and the evaluation period was 0.131 g/dL (95% CI: − 0.439 to 0.719, p  = 0.629). The lower limit of the two-sided 95% CI for the difference in the mean change in Hb between the two treatment groups was well above the pre-specified non-inferiority margin of − 1.0 g/dL. Similar pattern of non-inferiority was seen for per protocol population. The safety profile of DA and rHuEPO was also comparable (injection site pain:rHuEPO-3, DA-7; p -0.296).     Conclusion : DA is non-inferior to rHuEPO for the treatment of anemia of CKD (stage 3–5) in pediatric population with a comparable safety profile.     Trial registration : ClinicalTrials.gov Identifier: NCT04959578 (retrospectively registered), Date: July 13, 2021. What is Known: • Limited studies showing darbepoetin alpha is effective in children as an erythropoiesis stimulating agent. • No RCT from Indian subcontinent addressing this topic. What is New: • Darbepoetin alpha is non inferior to recombinant human erythropoietin for treatment of anemia in children with CKD stage 3-5 (on or not on dialysis) with safety comparable to recombinant human erythropoietin. • A cost reduction of approximately 8.6% per patient by shifting to darbepoetin alpha.

Scanty literature is available regarding continuous renal replacement therapy (CRRT) utility in severe sepsis with multiorgan dysfunction syndrome (MODS) from developing countries. Author unit's experience in pediatric CRRT is described and outcome of early initiation of CRRT with sepsis and MODS is assessed. Children aged <16 years with sepsis and MODS who required CRRT from September 2010 to February 2015 were analyzed on demographic factors, timing of initiation of CRRT, mode of CRRT, effect of CRRT onhemodynamics, oxygenation parameters, and outcome. Twenty-seven children required CRRT (male - 16). The median age was 11 years (range 1.1-16). Twenty-one had severe sepsis with MODS. Eighteen patients were given CRRT within 48 h of admission to Intensive Care Unit (ICU). Statistically significant improvement in the P/F ratio, decrement in plateau pressure and vasoactive-inotropic score were noted in survivor group compared to nonsurvivor group (P = 0.022, 0.00, and 0.03, respectively). There was no statistically significant difference in duration of ICU stay, fluid overload, CRRT duration, PRISM score at 12 and 24 h, percentage of decrease in inotrope score, plateau pressure, and percentage of increase in P/F ratio in relation to timing of CRRT initiation. However, the survival rate was 61.1% (11/18) who received CRRT within 48 h of ICU admission compared to 33.3% (3/9) who received after 48 h (P = 0.0001). Our study emphasizes the CRRT role in improving the oxygenation status and hemodynamics. Survival benefit may be expected in those children who receive CRRT early in the course of sepsis. However, multicenter RCTs are required to prove mortality benefit.

How does a user's prior experience with deep learning impact accuracy? We present an initial study based on 31 participants with different levels of experience. Their task is to perform hyperparameter optimization for a given deep learning architecture. The results show a strong positive correlation between the participant's experience and the final performance. They additionally indicate that an experienced participant finds better solutions using fewer resources on average. The data suggests furthermore that participants with no prior experience follow random strategies in their pursuit of optimal hyperparameters. Our study investigates the subjective human factor in comparisons of state of the art results and scientific reproducibility in deep learning.

Both transient elastography (TE)-based and non-TE-based criteria exist for detection of varices needing treatment (VNT) in patients with asymptomatic advanced chronic liver disease (CLD). However, their performance in clinical settings at different risk thresholds of detection of VNT and in regions where elastography is not widely available is unknown. We aimed to validate existing noninvasive criteria in our patients with CLD and identify best TE- and non-TE-based criteria for VNT screening at usual risk thresholds. Patients with compensated advanced CLD (cACLD) who underwent esophagogastroduodenoscopy and TE within 3 months were included. Diagnostic performance of Baveno VI, expanded Baveno VI, platelet-model for end-stage liver disease, and platelet-albumin (Rete Sicilia Selezione Terapia-hepatitis C virus) criteria were estimated. Decision curve analysis was conducted for different predictors across range of threshold probabilities. A repeat analysis including all patients with compensated CLD (cACLD and non-cACLD) was performed to simulate absence of TE. A total of 1,657 patients (cACLD, 895; non-cACLD, 762) related to hepatitis B virus (38.2%), hepatitis C virus (33.4%), nonalcoholic steatohepatitis (14.7%), and alcohol (11.8%) were included. Baveno VI identified maximum VNT (97.3%) and had best negative predictive value (96.9%), followed by platelet-albumin criteria. Expanded Baveno VI and platelet-model for end-stage liver disease had intermediate performance. At threshold probability of 5%, Baveno VI criteria showed maximum net benefit, and platelet-albumin criteria was next best, with need for 95 additional elastographies to detect 1 additional VNT. Similar results were obtained on including all patients with compensated CLD irrespective of TE. Baveno VI criteria maximizes VNT yield at 5% threshold probability. An acceptable alternative is the platelet-albumin criteria in resource-limited settings.

Background and Aims Decompensated cirrhosis in autoimmune hepatitis has poor prognosis. Besides liver transplant, treatment for this entity is undefined. We explored the outcomes of autoimmune hepatitis (AIH)‐related decompensated cirrhosis with active disease on treatment with steroids. Methods In this retrospective analysis, clinical data, laboratory parameters, and prognostic scores, such as baseline model for end‐stage liver disease (MELD) scores, were compared among patients of AIH with decompensated cirrhosis with mild/no ascites (n = 38), gross ascites (n = 24), and compensated cirrhosis (n = 32) when administered steroids. The primary outcome was transplant‐free survival at 12 months. Biochemical remission rates and other adverse events were also assessed and compared between these groups. Results Steroids were initiated at lower doses (25 mg/day‐mild/no ascites, 20 mg/day‐gross ascites) in patients with decompensated cirrhosis and at 40 mg/day in those with compensated cirrhosis. Transplant‐free survival was 25.4%, 74.6%, and 96.9% (P = 0.001), and biochemical remission occurred in 5.1%, 49.0%, and 64.1% (P = 0.001) at 12 months in patients with gross ascites, mild/no ascites, and compensated cirrhosis, respectively. Infections were seen more frequently in decompensated cirrhosis, while other adverse events were comparable. Among decompensated cirrhosis, those with mild/no ascites had better prognostic scores, fewer posttreatment infections, and more frequent biochemical remission than those with gross ascites, achieving rates comparable to compensated cirrhosis. On multivariate analysis, the MELD score (subdistributional hazards ratio [sHR]; 95% confidence interval: 1.153 [1.07–1.24]; P = 0.001) and ascites (sHR: 2.556 [1.565–5.65]; P = 0.020) predicted survival. Conclusion Type and severity of decompensation affect outcomes in patients with AIH‐related cirrhosis. Those with mild/no ascites have comparable outcomes to those with compensated cirrhosis upon treatment with low‐dose steroids. A subset of autoimmune hepatitis‐associated decompensated cirrhosis with only mild ascites/isolated variceal bleed achieves comparable biochemical remission to those having compensated cirrhosis when treated with steroids.