N-Terminal Pro-Brain Natriuretic Peptide Levels in Kawasaki Disease, Sepsis and Other Febrile Illnesses.

OBJECTIVE: To compare the values of N-Terminal Pro-Brain Natriuretic Peptide (NT-proBNP) in acute phase of Kawasaki disease (KD), sepsis and other acute febrile illnesses. METHODS: We conducted a cross-sectional study on 40 KD patients and 40 age- and sex-matched controls with sepsis and other febrile illnesses between January, 2019 and June, 2020. Complete blood count, C-reactive protein (CRP), liver and renal function tests, serum electrolytes, chest X-ray, NT-proBNP level, Bactec blood culture, urine microscopy and culture along with detailed physical examination was done for all cases and control. RESULTS: Mean (SD) values of NT-proBNP levels in acute KD was higher than sepsis/other febrile illnesses (914.9 vs 219 pg/mL; P=0.001). Also, the number of KD patients whose NT-proBNP was elevated were significantly higher compared to controls (70% vs 32.5%; P<0.001). CONCLUSION: NT-proBNP may be useful as a biomarker in the diagnosis of acute phase KD.

Single- versus Divided-Dose Prednisolone for the First Episode of Nephrotic Syndrome in Children: An Open-Label RCT.

BACKGROUND: Early morning single-dose prednisolone has a hypothetical advantage of less hypothalamic-pituitary-adrenal (HPA) axis suppression, but lack of robust evidence has resulted in variation in practice, with divided-dose prednisolone still commonly used. We conducted this open-label randomized control trial to compare HPA axis suppression between single-dose or divided-dose prednisolone among children with first episode of nephrotic syndrome. METHODS: Sixty children with first episode of nephrotic syndrome were randomized (1:1) to receive prednisolone (2 mg/kg per day), either as single or two divided doses for 6 weeks, followed by single alternative daily dose of 1.5 mg/kg for 6 weeks. The Short Synacthen Test was conducted at 6 weeks, with HPA suppression defined as postadrenocorticotropic hormone cortisol <18 µ mg/dl. RESULTS: Four children (single=1 and divided dose=3) did not attend the Short Synacthen Test and were hence excluded from analysis. Remission was induced in all, and no relapse postremission was noted during the 6+6 weeks of steroid therapy. After 6 weeks of daily steroids, HPA suppression was greater in divided (100%) versus single dose (83%) ( P = 0.02). Time to remission and final relapse rates were similar, but for those children who relapsed within 6 months of follow-up period, time to first relapse was shorter for divided dose (median 28 versus 131 days) P = 0.002. CONCLUSIONS: Among children with first episode of nephrotic syndrome, single-dose and/or divided-dose prednisolone were equally effective in inducing remission with similar relapse rates, but single dose had less HPA suppression and longer time to first relapse. CLINICAL TRIAL REGISTRY NAME AND REGISTRATION NUMBER: CTRI/2021/11/037940. PODCAST: This article contains a podcast at https://dts.podtrac.com/redirect.mp3/www.asn-online.org/media/podcast/CJASN/2023_10_09_CJN0000000000000216.mp3.

The clinical relevance of native vitamin D in pediatric kidney disease.

Hypovitaminosis D has been reported to be common in chronic kidney disease (CKD) as well as in proteinuric disorders. We reviewed available evidence to assess clinically relevant effects of low vitamin D status and native vitamin D (NVD) therapy, in pediatric renal diseases. Online medical databases were searched for articles related to vitamin D status, associations of hypovitaminosis D and effects of NVD therapy in kidney disease. Hypovitaminosis D was associated with worse skeletal, cardiovascular, inflammatory, and renal survival outcomes in CKD. Low serum 25 hydroxy-vitamin D (25[OH]D) levels correlated positively with glomerular filtration rate and negatively with serum parathyroid (PTH) levels. However, to date, evidence of benefit of NVD supplementation is restricted mainly to improvements in serum PTH, and biochemical 25[OH]D targets form the basis of clinical practice recommendations for NVD therapy. In nephrotic syndrome (NS) relapse, studies indicate loss of 25[OH]D along with vitamin D binding protein in urine, and serum total 25[OH]D levels are low. Preliminary evidence indicates that free 25[OH]D may be a better guide to the biologically active fraction. NVD therapy in NS does not show consistent results in improving skeletal outcomes and hypercalciuria has been reported when total 25[OH]D levels were considered as indication for therapy. NVD formulations should be regularised, and therapy monitored adequately to avoid adverse effects.

Effect of deletions in the α-globin gene on the phenotype severity of ß-thalassemia.

Thalassemia is the most common inherited hemoglobinopathy worldwide. Variation of clinical symptoms in this hemoglobinopathy entails differences in disease-onset and transfusion requirements. The aim of this study was to investigate the role of α-globin gene deletions in modulating the clinical heterogeneity of ß-thalassemia (ß-thal) syndromes. A total number 270 ß-thal subjects were enrolled. Hematological parameters were recorded. ß-Globin mutations were determined by amplified refractory mutation system-polymerase chain reaction (ARMS-PCR), gap-PCR and Sanger sequencing. α-Globin gene deletions were determined by multiplex PCR. Out of 270 ß-thal subjects, 19 carried ß+/ß+, 74 had ß0/ß0 and 177 had the ß0/ß+ genotype. When we determined the severity of the different ß-thal subjects in coinherited with the α gene deletion, it was revealed that, 84.2% ß+/ß+ subjects carried a non severe phenotype and did not have an α gene deletion. Of the ß0/ß0 individuals, 95.9% presented a severe phenotype, irrespective of α-globin gene deletions. In cases with the ß0/ß+ genotype, 19.2% subjects also carried a deletion on the α gene. Of these, 61.8% presented a non severe phenotype and 38.2% were severely affected. Only in the ß0/ß+ category did α gene deletions make a significant contribution (p < 0.001) toward alleviation of clinical severity. Therefore, it can be stated that α-globin gene deletions play a role in ameliorating the phenotype in patients with a ß+/ß0 genotype.

Whole-exome sequencing and variant spectrum in children with suspected inherited renal tubular disorder: the East India Tubulopathy Gene Study.

BACKGROUND: Inherited tubulopathies are a heterogeneous group of genetic disorders making whole-exome sequencing (WES) the preferred diagnostic methodology. METHODS: This was a multicenter descriptive study wherein children (< 18 years) with clinically suspected tubular disorders were recruited for molecular testing through WES. Multiplex ligation-dependent probe amplification (MLPA) and Sanger sequencing were done when required. Variants were classified as per American College of Medical Genetics 2015 guidelines and pathogenic (P)/likely pathogenic (LP) variants were considered causative. RESULTS: There were 77 index cases (male =73%). Median age at diagnosis was 48 months (IQR 18.5 to 108 months). At recruitment, the number of children in each clinical group was as follows: distal renal tubular acidosis (dRTA) = 25; Bartter syndrome = 18; isolated hypophosphatemic rickets (HP) = 6; proximal tubular dysfunction (pTD) = 12; nephrogenic diabetes insipidus (NDI) = 6; kidney stone/nephrocalcinosis (NC) = 6; others = 4. We detected 55 (24 novel) P/LP variants, providing genetic diagnoses in 54 children (70%). The diagnostic yield of WES was highest for NDI (100%), followed by HP (83%; all X-linked HP), Bartter syndrome (78%), pTD (75%), dRTA (64%), and NC (33%). Molecular testing had a definite impact on clinical management in 24 (31%) children. This included revising clinical diagnosis among 14 children (26% of those with a confirmed genetic diagnosis and 18% of the overall cohort), detection of previously unrecognized co-morbidities among 8 children (sensorineural deafness n = 5, hemolytic anemia n = 2, and dental changes n = 1) and facilitating specific medical treatment for 7 children (primary hyperoxaluria n = 1, cystinosis n = 4, tyrosinemia n = 2). CONCLUSION: WES is a powerful tool in the diagnosis and management of children with inherited tubulopathies in the Indian population. A higher resolution version of the Graphical abstract is available as Supplementary information.

A comparative study of IL-6, CRP and NT-proBNP levels in post-COVID multisystem inflammatory syndrome in children (MISC) and Kawasaki disease patients.

BACKGROUND: Post-COVID multisystem hyperinflammatory syndrome in children (MISC) has clinical and laboratory similarities with Kawasaki disease (KD). Inflammatory markers like C-reactive protein (CRP), interleukin 6 (IL6) as well as N-terminal probrain natriuretic peptide (NT-proBNP) are elevated in both. This study attempts a comparative analysis of the 3 markers in an attempt at early differentiation for planning appropriate management. METHODOLOGY: This analytical study conducted at the Institute of Child Health, Kolkata, India compared the levels of the above 3 markers at admission between 72 patients with KD, 30% of whom had coronary artery lesions (CALs) collected over a period of 18 months (Jan 2017-June 2018), with 71 MISC patients over a period of 6 months (July 2020-December 2020). The non-parametric Mann-Whitney U test was used to test for similarity in distributions of the samples of CRP, NT-proBNP and IL6 in KD and MISC patients using correction factor for similar ranks. The 3 parameters were compared using receiver operating characteristic (ROC) curve analysis. RESULTS: Mean IL6 value in KD was 83.22 pg/mL and in MISC 199.91 pg/mL, which was not found to be statistically significant (P = .322 > .05).However mean NT-proBNP (914.91 pg/mL) with CRP level (96.32 mg/L) in KD was significantly lower (P < .05 for both cases) than that in MISC (9141.16 pg/mL and 145.66 mg/L respectively). ROC analysis showed NT-proBNP has the best sensitivity and specificity in predicting MISC. CONCLUSION: NT-proBNP and CRP are significantly higher among MISC patients; ROC analysis shows levels >935.7 pg/mL and >99.55 mg/L respectively might act as a guide to differentiate between them.

Lipid Profile in Children With Thalassemia: A Prospective Observational Study From Eastern India.

This was a prospective observational study to evaluate abnormalities in lipid profile in 50 children with transfusion dependent thalassemia. Dyslipidemia characterized by high triglycerides, low high density lipoprotein (HDL), and high total cholesterol: HDL ratio was noted. These pro atherogenic risk factors may be lead to significant cardiovascular morbidity in these patients.

Langerhans cell histiocytosis in children: A retrospective case series of 126 cases.

BACKGROUND/OBJECTIVES: Langerhans cell histiocytosis (LCH), a rare neoplasm of hematopoietic myeloid precursor cells, is clinically characterized by spontaneously resolving lesions to a progressive life-threatening multisystem disorder. Diagnosing LCH in children is challenging as it mimics other skin disorders. This study describes the varied clinical presentation and disease course in children less than 18 years diagnosed with LCH. METHODS: We performed a retrospective observational study of all cases diagnosed with LCH presenting to a children's hospital in the last 26 years. Data on history, cutaneous and systemic examination, and laboratory evaluation performed, were recorded. RESULTS: A total of 126 children diagnosed with LCH were included in the study. There were 68% cases limited only to skin, and 32% children with multisystem involvement at the initial presentation. Scaly papules were the most common morphologic finding in skin. The skeletal system was the second most common organ system to be affected. Failure to thrive was a common symptom. Progression of skin to systemic involvement was seen in 27.9%. In 76.7%, skin lesions cleared over a period of 2 to 4 years. Complete remission was seen in 56.9% of children over a period of 3 to 7 years, while 8.1% children died of complicationsand 31.8% were lost to follow-up. CONCLUSIONS: Long-term follow-up in this study has shown cutaneous LCH without systemic involvement has a good prognosis. Skin involvement,along with failure to thrive, was the most common clinical presentation in our study. The skeletal system was the second most common organ system involved.

Evaluation of immunogenicity, safety and breakthrough following administration of live attenuated varicella vaccine in two doses three months apart regimen in Indian children.

BACKGROUND: In India, where varicella outbreaks are reported at a younger age, a two-dose vaccine schedule administered at an early age could be highly efficacious in preventing varicella infection. The aim of this study was to evaluate the immunogenicity and safety of live attenuated varicella vaccine (VR 795 Oka strain) in a two-dose, 3 months apart regimen. METHODOLOGY: Healthy children (⩾ 12 months and ⩽12 years; mean age: 4.4 years) of either sex were included. Geometric mean titers (GMT) were measured at baseline and 28 days post first- and second-dose, and seroprotection rates were measured 28 days post first and second dose. The incidence of breakthrough (BT) infections post vaccination was determined from 42 days post first and second dose of vaccine up to 12 months. Adverse events (AEs) were monitored and recorded throughout the study period. RESULTS: Of 305 subjects enrolled, 217 were seronegative. The seroconversion rate (a change from a seronegative to a seropositive condition) was 93.3% post first-dose and 100% post two-doses. High levels (9 times) of GMT were reported since post first-dose to post second-dose in children aged 12-18 months, 18-60 months (99.43%); and in and above 60 months (99.02%). The extent of rise of anti-VZV IgG antibody titer post 28 days of first-dose at two-fold, three-fold and four-fold rise was 93.39%, 90.56% and 80.66%, respectively and 100% 4-fold rise post second-dose. A single case, a day after the first-dose of vaccination of mild BT infection, was observed after close contact with a severe case. AEs were mild and none of the serious AEs were related to the study drug. CONCLUSION: The two-dose schedule of varicella vaccine was safe and immunogenic when given 3 months apart. However, further comparative studies and follow up for both dosing schedules are needed to validate the advantage of early dosing.

Free vitamin D levels in steroid-sensitive nephrotic syndrome and healthy controls.

INTRODUCTION: Body stores of vitamin D are measured as "total" serum 25-hydroxy vitamin D (25(OH)D). Its largest component is protein bound and lost in urine in nephrotic syndrome (NS). Our study investigates whether "free" 25(OH)D levels are a better guide to bone health and need for vitamin D supplementation in patients with steroid-sensitive NS (SSNS). METHODS: A cross-sectional study was performed in children with SSNS and healthy controls. Blood was tested for albumin, creatinine, calcium, phosphate, ALP, total and free (by direct ELISA) 25(OH)D, iPTH, and urine for protein-creatinine ratio. RESULTS: Seventy-nine NS patients (48 in relapse, 31 in remission) and 60 healthy controls were included. The levels of total 25(OH)D were significantly different (lowest in NS relapse and highest in controls) (p < 0.001). Corrected calcium and phosphate levels were normal, and there were no differences in free 25(OH)D, ALP, or iPTH levels between groups. Only total and not free 25(OH)D correlated significantly and negatively with urinary protein creatinine ratios (rs = - 0.42 vs. 0.04). Free 25(OH)D values of 3.75 and 2.85 pg/ml corresponded to total 25(OH)D levels of 20 and 12 ng/ml, respectively, in healthy controls. CONCLUSION: These results confirm that total 25(OH)D levels are low in NS and related to degree of proteinuria. However levels of free 25(OH)D, ALP, and iPTH did not change in relapse or remission in comparison with healthy controls. Our results suggest that in proteinuric renal diseases, free 25(OH)D rather than total 25(OH)D levels should be used to diagnose vitamin D deficiency and guide therapy.

A comparison of serum IL6 and CRP levels with respect to coronary changes and treatment response in Kawasaki disease patients: a prospective study.

To evaluate serum levels of IL6 in patients with Kawasaki disease and compare it with CRP, and to assess the role of these biomarkers in predicting coronary changes and resistance to the first-line therapy of this disease in a subset of Indian population. A single centre prospective observational study was conducted amongst all Kawasaki disease patients for a period of 18 months from January 2017 at Institute of Child Health, Kolkata. Serum IL6 and CRP were compared at diagnosis and after 48 h of administering IVIG in patients who developed coronary changes with those who did not and also among the responders and non-responders to IVIG, the first-line therapy given to these patients. Out of total 72 patients of KD [mean age of presentation: 24 months, M:F = 1.22:1], 30% (n = 22) had coronary artery involvement (CALs), and 15% (n = 11) were IVIG non-responders. Mean IL6 prior to IVIG in those with CALs was 143.60 pg/ml, which was about three times higher than in those without CALs (mean = 52.90 pg/ml), the difference being significant (p < 0.01). Mean CRP values also were significantly raised in patients with CALs (p < 0.01) whereas post-IVIG levels of mean serum IL6 was found to be 108.15 pg/ml in non-responders which was about 17 times raised than that in the responders (mean IL6 = 6.22),the difference again was statistically significant (p < 0.001).Also, ROC analysis revealed a sensitivity and specificity of 81.0% and 82.0%, respectively, for IL6; 72% and 74%, respectively, for CRP for predicting CALs. This study also shows a sensitivity of 72% and specificity of 68% for IL6 in predicting IVIG resistance whereas that of CRP being 90% sensitive and 36% specific. These results suggest that higher levels of IL-6 and CRP at diagnosis are associated with occurrence of CALs and IVIG resistance in KD patients. Using the cutoff for IL6 and CRP from our study, chances of developing CALs and IVIG resistance can be predicted, which might prevent the development of future complications like aneurysms in such patients.

Recognizing missed opportunities to diagnose and treat iron deficiency anemia: A study based on prevalence of anemia among children in a teaching hospital.

BACKGROUND: In developing world, anemia is a significant cause of mortality and morbidity in children under 5 years of age. Iron deficiency anemia (IDA) is a very important causative factor for childhood anemia. The aim of this study was to find the prevalence of anemia in different age group, sex, and its pattern of severity in hospitalized children. MATERIALS AND METHODS: A cross-sectional study was carried out in a teaching hospital in Kolkata between April 2016 and September 2016. Children 1-168 months of age were included in the study. RESULTS: Of 697 children, 296 (42.5%) had anemia as per the World Health Organization criteria. Males outnumbered the females with a ratio of 1.6:1. The median age of presentation was 29.6 months. The majority were from 1-5 years of age. About 73.3% of children had moderate anemia, whereas 21.3% had severe anemia and only 5% had mild anemia. The mean hemoglobin, mean mean corpuscular volume, mean mean corpuscular hemoglobin concentration, and mean red cell distribution width were 9.3 ± 1.4 g/dL, 73.6 ± 8.8 (fL), 32.2 ± 2.6, and 16.3 ± 3.4 (%), respectively. Microcytic hypochromic anemia (71.3%) was the most common morphological type in all age groups, whereas macrocytic anemia was the least common among them. Prevalence of IDA was 69%. IDA was documented in close to 80% of children with microcytic hypochromic anemia. Interestingly, IDA was also documented in almost half of the children with normocytic normochromic anemia. CONCLUSION: The high prevalence of IDA among these hospitalized children indicates the role of early screening for IDA in all children with anemia. This early diagnosis and prompt management can prevent the mortality and morbidity related to IDA.

Hyperferritinemia in Hemophagocytic Lymphohistiocytosis: A Single Institution Experience in Pediatric Patients.

Hemophagocytic lymphohistiocytosis (HLH) is an inflammatory condition that may run a rapid fatal course and calls for prompt diagnosis. Early intervention with steroids and other immunosuppressive drugs can contain the disease process and favours positive outcome. Ferritin ≥500 ng/ml is a HLH diagnostic criterion. We evaluated the diagnostic potential of admission ferritin, in children with HLH. Pediatric patients of a referral teaching hospital from Feb 2010-Oct 2013 having been investigated for ferritin on admission were included. HLH was confirmed when patients had clinical features and met 5/8 diagnostic criteria of the revised 2004 HLH guidelines. Ferritin was estimated on Cobas e411 by electrochemiluminiscence, with a measuring range of 0.5-2000 ng/ml. Dilutions were made when linearity exceeded and absolute values were reported. 905 on-admission ferritin investigations were reviewed out of which 346 values ≥500 ng/ml. Hyperferritinemia was seen in HLH/MAS (macrophage activation syndrome) [HLH group, median age 4 year 4 month, 59% male] and in systemic lupus erythematosus, sepsis, juvenile idiopathic arthritis, impending HLH, haemolytic anemias and malignancy [non-HLH group, median age 4 year 6 month, 60% male]. Of 346, 72 cases of hyperferritinemia were diagnosed with secondary HLH while one patient had primary HLH. 13/73 patients expired. The median ferritin level of the HLH group was significantly higher [6556 (2402-11,734) ng/ml] compared to non-HLH group [median 1175 (943-2000) ng/ml] (p < 0.0001). Receiver operator characteristics curve analysis revealed optimal admission ferritin of 3120 ng/ml as the cut-off with sensitivity of 70% and specificity of 88.9% for HLH diagnosis, exceeding the currently prescribed cut-off of 500 ng/ml. Hyperferritinemia below 3120 ng/ml has higher negative predictive value to rule out secondary HLH on admission in the study population of children predominantly diagnosed with infection associated HLH than the prescribed cut-off as per the 2004 guidelines. This may prove to be beneficial to alert physicians for prompt intervention which considerably decreases mortality in this often fatal condition.

The effect of vitamin D and calcium supplementation in pediatric steroid-sensitive nephrotic syndrome.

BACKGROUND: Low serum levels of total 25-hydroxycholecalciferol (25(OH)D) occur in nephrotic syndrome (NS). We aimed to assess the effects of vitamin D3 and calcium supplementation on 25(OH)D levels, bone mineralization, and NS relapse rate in children with steroid-sensitive NS. METHODS: A randomized controlled trial (RCT) was performed in children with steroid-sensitive NS. The treatment group received vitamin D3 (60,000 IU orally, weekly for 4 weeks) and calcium supplements (500 to 1,000 mg/day for 3 months) after achieving NS remission. Blood samples for bone biochemistry were taken during relapse (T0), after 6 weeks (T1) and 6 months (T2) of randomization, whereas a lumbar DXA scan was performed at T0 and T2. Renal ultrasound was performed after study completion in the treatment group and in all patients with hypercalciuria. RESULTS: Of the 48 initial recruits, 43 patients completed the study. Post-intervention, 25(OH)D levels showed significant improvements in the treatment group compared with controls at T1 (p < 0.001) and T2 (p < 0.001). However, this was not associated with differences in bone mineral content (BMC) (p = 0.44) or bone mineral density (BMD) (p = 0.64) between the groups. Additionally, there was no reduction in relapse number in treated patients (p = 0.54). Documented hypercalciuria occurred in 52% of patients in the treatment group, but was not associated with nephrocalcinosis. CONCLUSIONS: Although supplementation with calcium and vitamin D improved 25(OH)D levels significantly, there was no effect on BMC, BMD or relapse rate over a 6-month follow-up. Occurrence of hypercalciuria mandates caution and appropriate monitoring if using such therapy. Appropriate dosage of vitamin D3 remains uncertain and studies examining biologically active vitamin D may provide answers.

Prevalence of vitamin d deficiency in a pediatric hospital of eastern India.

Vitamin D deficiency is highly prevalent in Indian children of northern, western and southern states. Serum 25 hydroxy cholecalferol (ng/ml) was analyzed in 310 children and adolescents of pediatric hospital of Kolkata, India. Serum calcium (mg/dl), phosphorous (mg/dl) and alkaline phosphatase (IU/L) data was obtained. Median 25(OH)D was 19 ng/ml. 19.2 % of population had serum 25(OH)D < 10 ng/ml (severe deficiency), 52.9 % had <20 ng/ml (deficiency), 24.5 % had 20-29 ng/ml (insufficiency) and 22.6 % had >30 ng/ml (optimum). Deficiency was highest in adolescents (86.1 %), followed by school children (61.0 %), lowest in pre-school children (41.6 %). 25(OH)D concentrations was lowest in winters (P = 0.002) and spring (P = 0.03) compared to summer. There was no correlation with calcium (P = 0.99), phosphorous (P = 0.23) and ALP (P = 0.63). There is high prevalence of vitamin D deficiency in children and adolescents of eastern India. Prevalence was lower in younger subjects. 25(OH)D did not correlate with bone mineral markers.

Vitamin D in nephrotic syndrome remission: a case-control study.

BACKGROUND: Vitamin D deficiency may contribute to osteoporosis in nephrotic syndrome (NS). METHODS: A cross-sectional case-control study was performed to investigate 25 hydroxycholecalciferol [25(OH)D] status in 40 patients with NS in remission and 40 healthy controls. Serum levels of 25(OH)D, calcium, phosphate, alkaline phosphatase (ALP), and intact parathyroid hormone (PTH) were assayed. NS patients were segregated by age at onset, current age, type and duration of NS, months since relapse and current drug therapy. RESULTS: Levels of 25(OH)D showed a positive correlation with months elapsed since last NS relapse (r s = +0.4, p = 0.012) and were lower in NS patients within 3 months of relapse but similar to that of controls in patients in remission for >3 months [median 14.23 (interquartile range 12.19-17.63) vs. 19.75 (14.04-28.38) ng/ml, respectively; p = 0.039]. There was no correlation of 25(OH)D levels with other disease characteristics or drug therapy. ALP levels were also lowest after relapse (r s = +0.34, p = 0.036). Overall, 25(OH)D levels of <20 ng/ml occurred in 62.5 % of NS patients + controls, and correlated negatively with age (r s = -0.24, p = 0.037) but showed no significant correlation with calcium, phosphate, or PTH levels. CONCLUSIONS: In our patients with NS, vitamin D stores remained low for 3 months after NS relapse but showed an increase with longer remission time to control levels. Vitamin D stores were not influenced by disease characteristics or therapy. Longitudinal studies are required to confirm these findings and evaluate the effect of vitamin D on bones, particularly in frequent relapsers.

Evaluation of sweat production by pilocarpine iontophoresis: a noninvasive screening tool for hypohidrosis in ectodermal dysplasia.

Ectodermal dysplasia (ED) is a genetic disorder affecting the skin, hair, nails, teeth and sweat glands. The clinical presentation is heterogenous; however, hypohidrotic (reduced sweat) ectodermal dysplasia (HED) being the commonest. Also known as anhidrotic ED, sweat glands are sparse or rudimentary, leading to dysregulation of body temperature and episodes of uncontrolled hyperthermia due to reduced sweating. Of the many aids to document hypohidrosis in HED, we present here the technique of pilocarpine iontophoresis to induce, collect and measure sweat. Evaluation of sweat generated (against normally obtained values) is a non-invasive alternative to establish hypohidrosis in disorders such as HED. This augments clinical decision levels to plan skin biopsy for confirmation of diagnosis and facilitates patient management and early discharge. We present two cases of HED that were primarily diagnosed with sweat gland dysplasia using pilocarpine iontophoresis, and later confirmed with skin biopsy findings.

Vitamin B(12) Immunoassay on Roche Elecsys 2010: Effects of High Excess Concentration of Serum Vitamin B(12) in CKD Patients on Parenteral Administration.

Vitamin B(12) being water soluble is excreted in the urine when administered in excess. The probability of finding an abnormally excess serum concentration would be almost surreal. We report a peculiar clinical situation that may impact the vitamin B(12) immunoassay on the Roche Elecsys 2010 due to excess analyte concentration. In separate episodes (Feb and June 2010), the Biochemistry laboratory of a tertiary-care hospital, Kolkata, India, encountered two critically ill patients with background chronic kidney disease (CKD), low urine output, and on cyanocoabalamin supplementation, who had serum vitamin B(12) concentrations far exceeding expected values; even post dialysis. The B(12) assays (pmol/l) were performed using electrochemiluminiscence immunoassay on Roche Elecsys 2010, the assay validity confirmed by concomitant quality control runs. The immunoassays failed to deliver results, flagged with "signal level below limit". Biotin therapy was ruled out as a possible interferent. In the first episode, re-assay of a repeat draw yielded same outcome; outsourcing on Immulite provided concentration of >738 pmol/l. Serial dilution gave result of >29520 pmol/l on Elecsys 2010. In the second, we gained from past experience. Vitamin B(12) concentration >59040 pmol/l was conveyed to the treating nephrologist the very day. The B(12) immunoassay on the Elecsys 2010 employs sequential incubation steps for competitive binding that is compromised in the event of abnormally excess B(12) concentration in patient sera akin to the prozone effect. This knowledge may be beneficial while assaying sera of CKD patients to avoid financial loss due unnecessary repeats and delay in turnaround time.

Microalbuminuria: A novel biomarker of sepsis.

CONTEXT: Diffused endothelial dysfunction in sepsis leads to an increase in systemic capillary permeability, the renal component manifesting as microalbuminuria. The degree of microalbuminuria correlates with the severity of the acute insult, the quantification of which may serve to predict sepsis and mortality in critically ill patients. AIMS: To evaluate whether the degree of microalbuminuria could differentiate patients with sepsis from those without and predict mortality in critically ill patients. SETTINGS AND DESIGN: Prospective, non-interventional study in a 20-bed Intensive Care Unit (ICU) of a tertiary care hospital. METHODS AND MATERIALS: After exclusions, between Jan-May 2007, 94 consecutive adult patients were found eligible. Albumin-creatinine ratio (ACR, mg/g) was measured in urine samples collected on ICU admission (ACR1) and at 24 hours (ACR2). RESULTS: PATIENTS WERE CLASSIFIED INTO TWO GROUPS: those with sepsis, severe sepsis and septic shock (n = 30) and those without sepsis [patients without systemic inflammatory response syndrome (SIRS) and with SIRS due to noninfectious causes] (n = 64). In the sepsis group, median ACR1 [206.5 (IQR129.7-506.1)] was significantly higher compared to the non sepsis group [76.4 (IQR29-167.1)] (P = 0.0016, Mann Whitney). The receiver operating characteristics (ROC) curve analysis showed that at a cut off value 124 mg/g, ACR1 may be able to discriminate between patients with and without sepsis with a sensitivity of 80%, specificity of 64.1%, positive predictive value (PPV) of 51.1% and negative predictive value (NPV) of 87.3%. The median ACR2 [154 (IQR114.4-395.3)] was significantly higher (P = 0.004) in nonsurvivors (n = 13) as compared to survivors [50.8 (IQR 21.6-144.7)]. The ROC curve analysis revealed that ACR2 at a cut-off of 99.6 mg/g could predict ICU mortality with sensitivity of 85%, specificity of 68% with a NPV of 97% and PPV of 30%. CONCLUSION: Absence of significant microalbuminuria on ICU admission is unlikely to be associated with sepsis. At 24 hours, absence of elevated levels of microalbuminuria is strongly predictive of ICU survival, equivalent to the time-tested APACHE II scores.