Cerebrospinal fluid tumor necrosis factor-alpha (TNF-α) levels in children with cerebral malaria.

This prospective cross-sectional study evaluated the diagnostic and prognostic role of cerebrospinal fluid (CSF) tumor necrosis factor-alpha (TNF-α) in children with cerebral malaria (CM) and its role in the differentiation of CM from non-cerebral severe malaria. CSF TNF-α was measured using a human TNF-α enzyme-linked immunosorbent assay kit of 39 cases of CM and 19 cases of non-cerebral severe malaria. CSF TNF-α levels were significantly higher in CM (p < 0.001). Based on the receiver operating characteristics curve, a cutoff value of CSF TNF-α was 5.7 pg/ml for diagnosis of CM with sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of 87.2%, 94.7%, 97.1% and 78.3% respectively. The cutoff value of CSF TNF-α was 13.7 pg/ml for predicting adverse outcomes in CM with sensitivity, specificity, PPV and NPV of 100%, 96.8%, 88.9% and 100%, respectively. However, the cutoff value of CSF TNF-α was 4.96 pg/ml for predicting adverse outcomes in non-cerebral severe malaria with a sensitivity, specificity, PPV and NPV of 100%, 94.1%, 88.9% and 100% respectively. So, CSF TNF-α is an excellent biomarker and can be used as a diagnostic and prognostic tool. More studies are needed to establish CSF TNF-α as a predictor of neurological sequelae.

Maternal and fetal outcomes of COVID-19 infection in pregnant women with chronic rheumatic heart disease in a South Asian population: A case series.

Rheumatic heart disease (RHD) is associated with an increased risk of adverse maternal, fetal, and neonatal outcomes, particularly in developing countries. The current COVID-19 pandemic has also affected pregnant women, probably increasing the adverse effects. It is speculated that COVID-19 infection in pregnant women would further increase the risk of complications. However, factual data is still lacking, especially from resource-constrained countries. We conducted a case series of 20 pregnant women with RHD and COVID-19 infection and compared their outcomes with 40 with RHD but without COVDI-19. We observed a high risk of adverse cardiac and pregnancy effects across the whole cohort of 60 patients. However, the comparative study between the two groups failed to show any incremental risk of complications due to COVID-19 infection. Although the sample size was limited; the results are encouraging, particularly for developing countries.

Toll-like receptor 3 (TLR-3), TLR-4 and CD80 expression in peripheral blood mononuclear cells and urinary CD80 levels in children with idiopathic nephrotic syndrome.

BACKGROUND: The aims of this study were (1) to detect toll-like receptor (TLR)-3, TLR-4 and CD80 expression in peripheral blood mononuclear cells (PBMCs) and estimate urinary CD80 levels in children with idiopathic nephrotic syndrome and (2) to investigate the utility of these markers to differentiate between biopsy-proven minimal change disease (MCD) and focal segmental glomeruloscelerosis (FSGS). METHODS: The study included 70 patients with idiopathic nephrotic syndrome (NS), of whom 40 had steroid-sensitive NS (SSNS; 25 with active NS, 15 in remission) and 30 had steroid-resistant NS (SRNS) patients, and 23 healthy controls. TLR-3, TLR- 4 and CD80 mRNA expression levels in PBMCs were determined and the urinary CD80 level estimated. RESULTS: Median TLR-3, TLR-4 and CD80 mRNA expression levels were higher in patients with active SSNS than in those with SRNS, and the latter patient group also had significantly lower expression levels than the controls. The expression levels of these markers were associated with reductions in remission. Patients with biopsy-proven MCD had higher median expression levels of these markers than those with FSGS, but the differences were not statistically significant. Median urinary CD80/creatinine values were significantly higher in patients with SSNS and SRNS than in the controls and steroid-sensitive patients in remission (p < 0.001). CD80 levels were also significantly higher in patients with MCD than in those with FSGS (p = 0.002). A cut-off level of >914.5 ng/g had a sensitivity of 86.6%, specificity 71.4% and area under the curve of 0.828 (95% confidence interval 0.678-0.978, p = 0.002) for the diagnosis of MCD. CONCLUSIONS: Increased expressions of TLR-3, TLR-4 and CD80 mRNA and the level of urinary CD80/creatinine could be useful markers to differentiate patients of SSNS in relapse from those with SRNS. Further these markers can also distinguish biopsy proven MCD from FSGS in SRNS patients.

Predictive ability of urinary biomarkers for outcome in children with acute kidney injury.

BACKGROUND: Urinary neutrophil gelatinase-associated lipocalin (NGAL), N-acetyl-beta-D-glucosaminidase (NAG), and interleukin 18 (IL-18) were found to be useful for early detection of acute kidney injury (AKI). The objective of this study was to determine the predictive ability of biomarkers for mortality and variation in levels in relation to different stages of AKI, need for dialysis, etiologies, and with duration of hospital stay. METHODS: Urinary NGAL, NAG, and IL-18 levels were measured in 50 children with AKI and 30 age- and gender-matched healthy controls. AKI was classified as per pediatric Risk, Injury, Failure, Loss, and End-stage (RIFLE) criteria. RESULTS: Median NGAL, NAG, and IL-18 values were significantly increased in AKI patients compared with controls (p < 0.001), with significant increase among risk, injury, and failure stages. Nonsurvivors had significantly higher median levels of NGAL (p = 0.008) and NAG (p = 0.018) than survivors. NGAL had highest area under the curve (AUC) at 0.750 [confidence interval (CI) 0.580-0.920], followed by NAG at 0.724 (CI 0.541-0.907), with sensitivity and specificity of 75 % each; and IL-18 (AUC 0.688, CI 0.511-0.864), with sensitivity 62.5 % and specificity 70.8 %, for predicting mortality. Values were significantly higher in patients who required peritoneal dialysis (PD) than in those in whom it was not indicated. Levels were comparable among different etiologies. Only NGAL level was found to be a significant risk factor associated with longer duration of hospital stay. CONCLUSIONS: Urinary NGAL and NAG had modest predictive ability for mortality. Children requiring dialysis had significantly raised levels, and the NGAL level had significant association with duration of hospital stay.

Serum immunoglobulin E and interleukin-13 levels in children with idiopathic nephrotic syndrome.

Serum IgE and IL-13 levels were estimated in 40 idiopathic nephrotic syndrome and 16 controls. There were 15 first episode nephrotic syndrome (FENS), 15 infrequent relapsing nephrotic syndrome (IRNS) and 10 patients belonged to frequent relapsing nephrotic syndrome (FRNS). Serum IgE and IL-13 levels were significantly increased in active nephrotic syndrome and its sub-groups as compared to controls and remission (p < 0.001). IgE levels did not differ significantly among different subgroups, while Il-13 was significantly higher in FRNS in comparison with FENS (p = 0.041). Both IgE and IL-13 levels were comparable in nephrotic patients with and without bronchial asthma. Serum IL-13 had significant positive correlation with IgE (r = 0.605, p < 0.001). Thus, raised levels of IgE and IL-13 are found in nephrotic syndrome and could have a role in the pathogenesis of disease.

NPHS2 R229Q polymorphism in steroid resistant nephrotic syndrome: is it responsive to immunosuppressive therapy?

Steroid-resistant nephrotic syndrome (SRNS) patients with NPHS2 gene mutations have been reported as non-responsive to immunosuppressive therapy. Inter-ethnic differences can have influence over the frequency of mutations. The present study was undertaken to find out the incidence and treatment response. Mutational analysis of NPHS2 gene was performed in 20 sporadic idiopathic SRNS, 90 steroid-sensitive nephrotic syndrome (SSNS) and 50 normal controls. NPHS2 gene analysis showed R229Q polymorphism in six SRNS (30%), four SSNS (4.4%) and 13 controls (26%). The polymorphism (G→A) showed Hardy-Weinberg distribution and risk allele (G) had strong association with the disease (odds ratio 3.14, 95% CI 1.33-7.43) than controls. Five cases of SRNS having polymorphism showed partial remission to cyclosporine and prednisolone. Overall, partial remission was achieved in 14(70%), complete remission in four (20%), one(5%) patient had no response and one(5%) died. Thus, NPHS2 gene showed R229Q polymorphism and patients achieved partial remission to therapy.

Can we predict relapses in children with idiopathic steroid-sensitive nephrotic syndrome?

The objective of the present study was to find out the predictors of relapse. One hundred fifty children with a first episode of idiopathic nephrotic syndrome were followed for 12 months after initial treatment. Sixty-one (40.7%) children had no relapse, and 89 (59.3%) had relapses. A significantly higher proportion of children with disease onset between 1 and 3 years were relapsers in comparison with those with disease onset at 4-6 (p < 0.03) and 7-13 (p < 0.001) years. Risk of relapse was 2.99 times higher in this 1-3 year age-group as compared with patients aged >6 years (p = 0.001). Children responding between 1 and 2 weeks after start of treatment had a 0.423 times lesser risk of relapse than those who responded after 4 weeks (p = 0.023). Relapsers had significantly higher incidence of infection at relapse than at other time points (p < 0.001). Onset of disease in younger age and delayed response to prednisolone therapy were found as significant predictors for relapse.

Clinical, biochemical and outcome profile of dengue fever in hospitalised children in Eastern Uttar Pradesh, India.

Dengue fever is an important cause of acute febrile illness in the postmonsoon season in India. This study was done to record the incidence of dengue in admitted patients with acute febrile illness in a hospital setting. The study also intends to record the clinical, biochemical and outcome profile of paediatric dengue cases admitted in tertiary centres in Eastern Uttar Pradesh, India. It was a prospective case record analysis at a tertiary care research hospital in Eastern Uttar Pradesh. The study recruited fifty-53 children (<18 years) with serology-proven diagnosis of dengue disease. Disease was confirmed by doing Ns1Ag, IgM antibody test by ELISA method. Six hundred children were screened and 53 met the inclusion criteria. The incidence of dengue disease in hospitalised acute febrile illness was 8.8%. There were thirty-one males. The mean age of presentation of the study population was 9.32 ± 5 years with a range of 0.25 - 17 years. Fever (94%), nausea and vomiting (59 %), abdominal pain (55%), persistent vomiting (49%), thrombocytopenia (<100,000 [66%]), and petechiae and purpura (43%) were the important clinical manifestations. Six required intensive care monitoring. There was only one death. Dengue fever is an important cause of acute febrile illness in children. Case fatality rate can be minimised with proper World Health Organisation classification and protocol-based management of cases.

Pediatric Renal Rickets at a Tertiary Center.

We report clinical and etiological profile of 19 children (10 males) with renal rickets managed in the years 2021-2022. Median (IQR) age of presentation was 60 (18-96) months. The commonest cause was renal tubular acidosis (n=8). Genetic analysis revealed the diagnosis in 83% subjects (5 out of 6 tested).

Outcomes of children with idiopathic steroid resistant nephrotic syndrome: a single centre observational study.

INTRODUCTION: Idiopathic steroid resistant nephrotic syndrome (SRNS) has variable outcomes in children. The primary objective of the present study was to assess the cumulative remission rate and the secondary objectives were to assess factors affecting the remission status, kidney function survival, and adverse effects of medications. METHODS: One hundred fourteen patients with SRNS were included. Calcineurin inhibitor-based treatment protocol along with prednisolone and angiotensin-converting enzyme inhibitor were used, and patients were followed over 5 years. RESULTS: Median age was 4.5 years; 53.5% of cases were between 1 to 5 years of age. Sixty-two patients (54.4%) were at initial stage and 52 (45.6%) were at a late SRNS stage. Median eGFRcr was 83.5 mL/min/1.73m2 at presentation. Of the 110 patients, 63 (57.3%) achieved remission [complete remission 30 (27.3%), partial remission 33 (30%)], and 47 (42.7%) had no remission. Kidney function survival was 87.3% and 14 cases (12.7%) had progression to CKD (G3-8, G4-3, G5-1, and G5D-2). Median duration of follow up was 36 months (IQR 24, 60). Age of onset, cyclosporine/tacrolimus, eGFRcr, and histopathology (MCD/FSGS) did not affect remission. Similarly, remission status in addition to age of onset, drug protocol, and histopathology did not significantly affect kidney function during a period of 5 years. Hypertension, cushingoid facies, short stature, cataract, and obesity were observed in 37.7, 29.8, 25.5, 17.5, and 0.7% of cases, respectively. CONCLUSION: About half of the cases achieved remission. Age of onset of disease, cyclosporine/tacrolimus use, and histopathological lesion neither affected remission status nor short-term kidney function survival in SRNS.

SARS-CoV-2 Infection in Children with Idiopathic Nephrotic Syndrome: A Multicentric Study.

A multicenter retrospective study was conducted to assess the clinical spectrum of 30 severe acute respiratory syndrome coronavirus (SARS-CoV-2)-positive children with idiopathic nephrotic syndrome. Difficult to treat nephrotic syndrome was found to be a high-risk group with a high incidence of acute kidney injury and mortality.

Risk factors for mortality in critically ill infants with acute kidney injury: A resource-limited setting experience.

Infants with acute kidney injury (AKI) who are critically ill often will have multiorgan dysfunctions. Objective of the present study was to find out mortality, recovery of kidney function at discharge and at 3 months, and to determine risk factors for mortality. Fifty-two infants (24 newborns and 28 postneonatal) with AKI were included. Staging was done as per Kidney Disease Improving Global Outcomes classification. Patients were subjected to medical treatment and peritoneal dialysis (PD), wherever indicated. Kidney function tests were performed at admission, discharge, and at 3 months follow-up. Median age of neonates was 8 days and postneonatal infants were 4.5 months. Stage 1, 2, and 3 AKI were present in 14 (26.9%), 16 (30.7%), and 22 (42.3%) cases, respectively. PD was required in 22 (42.3%) infants, and significantly higher in postneonatal than in neonates (57.1% vs. 25%, p < 0.05). Significant recovery of kidney function occurred at discharge and cases had normal parameters at 3 months. Mortality was 17.3%. Patients had significantly higher risk of mortality, if they had metabolic acidosis (OR 13.22, CI 2.33-74.94, p = 0.002) and needed ventilation (OR 14.93, 95% CI 1.7-130.97, p = 0.006) and PD (OR 6.53, 95% CI 1.20-35.48, p = 0.026). In logistic regression analysis, fluid overload (p < 001), hypotension (p < 0.01), and higher PRISM-III score (p < 0.05) were found as significant risk factors for mortality. Medical management including PD led to good recovery of kidney function. Presence of fluid overload, hypotension, and higher PRISM-III score adversely affected the outcome.

Persistence of behavioral abnormalities following corticosteroid therapy in children with initial episode of idiopathic nephrotic syndrome: a prospective longitudinal observation.

INTRODUCTION: Treatment of nephrotic syndrome with corticosteroid can cause several side- effects including behavioral abnormalities. The objectives of the study were to observe the proportion of non-relapsers having persistence of behavioral abnormalities after completion of treatment of initial episode and compare the abnormalities with relapsers, and to determine risk factors for persistence. METHODS: Seventy-five children with a first episode of idiopathic nephrotic syndrome and 60 normal children were rated by parents for behavioral problems using the Child Behavior Checklist. The Parenting Stress Index was also evaluated. The children were rated before treatment and 12 and 36 weeks after. RESULTS: Both relapsers and non-relapsers showed abnormalities in internalizing and externalizing domains at 12 weeks of steroid therapy. Non-relapsers had abnormal scores in the internalizing domain in 63.5 % and externalizing domain in 48.1% of cases at 36 weeks. Relapsers had abnormal scores in all the three behavior domains, but a significantly higher proportion of relapsers had abnormal scores regarding total behavior (65.2% vs 28.8%, p<0.01) and child domains (100% vs 57.7%, p<0.001) of Parenting Stress Index in comparison to non-relapsers at 36 weeks. Occurrence of relapse increased the risk (odds ratio 5.76, 95% CI 1.35-10.76, p< 0.001) for persistence of abnormal total behavior at 36 weeks follow-up. CONCLUSION: Persistence of abnormalities was observed not only in relapsers but also in non-relapsers. Relapse was found to be a significant risk factor for persistence of abnormal behaviors in these patients.

Fibroblast Growth Factor 23 Level and Cardiovascular Parameters in Children with Chronic Kidney Disease.

OBJECTIVE: To find out the serum fibroblast growth factor 23 (FGF-23) levels in different grades of CKD, and the prevalence of abnormal left ventricular mass index (LVMI), carotid intima-medial thickness (cIMT), and central pulse wave velocity (cPWV) and the risk factors including FGF-23 for these abnormalities. METHODS: Fifty-nine patients of CKD with G2 to G5, aged 2-18 y were included. The LVMI, cIMT, and cPWV were measured using standard techniques, and serum intact FGF-23 levels were estimated at enrollment. RESULTS: Median FGF-23 levels were significantly raised in all the grades of CKD than controls (p < 0.001), and also in G4 and G5 in comparison to G2&3 and in G5D than G5. Increased LVMI in 42 (71.2%), elevated cIMT in 30 (57.7%), and cPWV in 14 (26.9%) patients were found. The FGF-23 showed significant negative correlation with eGFRcr and positive with serum iPTH, phosphate and alkaline phosphatase levels, but had no correlations with LVMI, cIMT SDS, and cPWV SDS. Only systolic BP SDS (odds ratio 1.5, 95% CI 1.008-2.231, p = 0.046) was observed as a significant predictor for increased cIMT, while no variables had any association with abnormal LVMI and cPWV. CONCLUSIONS: Serum FGF-23 showed higher levels with increasing grades of CKD, but no significant association with cardiovascular parameters. Systolic BP SDS was found as a significant risk factor for increased cIMT in children with CKD.

Congenital heart disease in harlequin ichthyosis: Case series.

Harlequin ichthyosis (HI) is the most severe form of congenital ichthyosis and inherited in an autosomal recessive manner. The disease is marked by severe thickened and scaly skin on the entire body. It is a lethal disease, but patients can rarely survive for several months or years with treatment. We present here seven cases of HI, where cardiac evaluation was done by echocardiography. To our knowledge, this is the first study to report associated cardiac abnormalities in such patients.

Double outlet right ventricle and aortopulmonary window in a neonate with Bohring-Opitz (Oberklaid-Danks) syndrome: First case report.

Bohring-Opitz syndrome (BOS) is a rare, sporadic genetic disorder, characterized by feeding difficulties, developmental delay, flexion abnormalities, dysmorphic facial features and typical body posture (BOS posture). This syndrome is diagnosed on the basis of distinctive clinical features with or without confirmation by genetic studies. Cardiac abnormalities are seen in almost half of the patients, but are nonspecific. We present a case of a 3-week-old male baby with BOS who was referred to our hospital with congestive heart failure, seizures and failure to thrive. He was diagnosed to have double outlet right ventricle and aortopulmonary window (DORV and APW). To our knowledge, this is the first case of Bohring-Opitz Syndrome ever reported with such clinical presentation.

Cytotoxic T- Lymphocyte Antigen-4 (CTLA4) Gene Expression and Urinary CTLA4 Levels in Idiopathic Nephrotic Syndrome.

OBJECTIVES: To detect Cytotoxic T- Lymphocyte Antigen-4 (CTLA4) single nucleotide polymorphisms (SNPs) at +49A/G (rs231775) and -318C/T (rs5742909) positions in children with idiopathic nephrotic syndrome (INS) and also assay urinary soluble CTLA4 (sCTLA4) levels in children with minimal change disease (MCD), focal segmental glomerulosclerosis (FSGS) and steroid sensitive nephrotic syndrome (SSNS) in remission. METHODS: The study included 59 patients of INS (MCD-23, FSGS-15 and SSNS in remission-21) and 35 healthy controls. The CTLA4 SNPs profiling was done in peripheral blood mononuclear cells and urinary sCTLA4 level was assayed by ELISA kit. RESULTS: Although frequency of homozygous +49 GG (rs4553808) genotype (26.3% vs. 11.4%; p = 0.231) and G allele (52.6% vs. 40%; p = 0.216) were found to be higher in INS as compared to controls, the differences were statistically non-significant. Genotypes GG, AG, AA and alleles A and G frequencies were comparable among MCD, FSGS and controls. SNP at -318 C/T (rs5742909) did not show homozygous TT genotype both in INS as well as controls. Median urinary sCTLA4/creatinine level was significantly higher in MCD as compared to FSGS (p = 0.027), SSNS in remission (p = 0.001) and controls (p = 0.003). CONCLUSIONS: The positive associations of +49 GG genotype and G allele in patients with nephrotic syndrome were not observed. The frequencies did not differ significantly among MCD, FSGS and controls. Urinary sCTLA4 level was significantly increased in MCD; suggesting its possible role in the pathogenesis of disease.