A Cross-sectional Study on Fibroblast Growth Factor 23 and Other Markers of Mineral Metabolism in Healthy Children in India.

Fibroblast growth factor 23 (FGF23) plays a significant role in phosphate homeostasis but data on children are limited. We aimed to detect FGF23 levels in 107 healthy children aged 6-16 years and evaluate its correlation with markers of phosphate and calcium metabolism, and the dietary intake of calcium, phosphate, and proteins. Height, weight, and Tanner stages were measured, and dietary intake was calculated. Biochemical analyses of hemoglobin, serum calcium, phosphate, creatinine, Vitamin D, and plasma parathyroid hormone (PTH) and FGF23 levels were performed, alongside their associations with FGF23. Of the children, 65.4% were males. Their mean body mass index was 15.79 ± 2.96 for males and 16.5 ± SD 2.72 for females. The mean Vitamin D and PTH levels were 29.7 ± 1.1 ng/mL and 29.2 ± 1.2 pg/mL, respectively. The mean FGF23 levels were 159 ± 15.2 reference units (RU)/mL. The mean FGF23 levels were significantly higher in females (209.3 ± 31 RU/mL) than in males (132.3 ± 15.1 RU/mL). All biochemical parameters were within the normal range. FGF23 correlated with age, weight, and height, but not Vitamin D, PTH, or dietary calcium and phosphate. FGF23 showed a negative correlation with hemoglobin levels (r = -0.23). Since most children had a nonvegetarian diet, the FGF23 levels were not assessed in vegetarians. These observations were attributed to the rural lifestyle favoring adequate exposure to sunlight and physical activity. The increased FGF23 levels in females, the trends in urban settings, and the levels in strictly vegetarian diets need further study.

Cerebrospinal Fluid Procalcitonin-A Potential Biomarker for Post-Craniotomy Bacterial Meningitis.

Background: The literature regarding the utility of cerebrospinal fluid (CSF) procalcitonin (PCT) in the diagnosis of post-craniotomy bacterial meningitis and differentiating it from aseptic meningitis is sparse. Materials and Methods: CSF total WBC count, sugar, protein, and PCT were measured in febrile patients with suspected post-craniotomy meningitis during the first 30 days following an intradural cranial procedure for non-trauma indications. Patients were diagnosed as postoperative bacterial meningitis if CSF culture was positive (PBM, n = 28) or postoperative aseptic meningitis if CSF culture was sterile and there was no evidence of systemic infection (PAM, n = 31). CSF cytochemical parameters and PCT values were compared between the groups. Normal values of CSF PCT were obtained from 14 patients with noninfectious indications with hydrocephalus. Results: There was no significant difference in CSF total WBC count, sugar, and protein levels between PAM and PBM groups. The median PCT level in CSF in the normal group was 0.03 ng/mL (interquartile range [IQR] 0.02-0.07 ng/mL). CSF PCT in the PBM group (median 0.37 ng/mL, IQR 0.2-1.4 ng/mL) was significantly higher than normal values as well as PAM group (median 0.12 ng/mL, IQR 0.07-0.26 ng/mL (P = 0.0004). The area under the receiver operating characteristic (ROC) curve for CSF PCT was 0.767. A cutoff value of 0.12 ng/mL yielded a sensitivity of 85.7% (95% CI: 67.3% to 96%), specificity of 51.6% (95% CI: 33% to 69.9%), positive predictive value of 61.5% (95% CI: 51.9% to 70.3%), and negative predictive value of 80% (95% CI: 60.3.8% to 91.3%). Conclusions: CSF PCT assay in patients who are febrile during the first 30 days post-non-trauma neurosurgical procedures has a role in the early diagnosis of bacterial meningitis.

Calculated values of serum LDL-cholesterol (LDL-C) - for better or worse?

BACKGROUND AND AIMS: The use of Friedewald's formula to calculate serum low-density lipoprotein cholesterol (LDL-C) is well-known to have limitations. A modification of it, in 2013, has been proposed to be superior. However, it was not known whether LDL-C values (calculated by the modified formula) meet laboratory performance criteria for their estimation. This study aimed to evaluate this. METHODS AND RESULTS: LDL-C values were calculated for 129,821 lipid profiles, using both Friedewald's formula and its modified version. Kappa statistics and intra-class correlation coefficient (ICC) were used to determine degree of agreement between directly measured and calculated values for LDL-C. Bias and total percentage error of the values were calculated. LDL-C concentrations calculated by the modified formula showed a greater degree of agreement with directly measured values (kappa = 0.713) than those calculated by Friedewald's formula (kappa = 0.595). Both the formulae produced values with negative biases (-3.47 for the modified formula and -7.62 for Friedewald's formula) and total percentage errors above the recommended limit of 12% (15.57% for the modified formula and 21.77% for Friedewald's formula). ICC showed that values calculated by the modified formula showed a greater degree of agreement with directly measured values, across a range of LDL-C values. CONCLUSION: Calculated LDL-C values, using the modified formula, showed better agreement with directly measured values, and less bias and percentage total error than those obtained by use of Friedewald's formula. However, the percentage total error with use of the modified formula exceeded the recommended limit for LDL-C.

Vitamin D Levels and Associations in Indian Patients with Primary Sjögren's Syndrome.

INTRODUCTION: Vitamin D is a steroid hormone belonging to the class of secosteroids with myriad immune functions and has been implicated in aetiopathogenesis of various autoimmune diseases. Although, there have been various studies showing the association of vitamin D in rheumatoid arthritis and lupus in different populations, there have been limited studies on vitamin D and primary Sjögren's Syndrome (pSS). There are no studies on association of vitamin D and pSS from any tropical country including Indian subcontinent. AIM: The purpose of the study was to look for any association between 25-hydroxyvitamin D (25(OH)D) levels and disease manifestations in Indian patients with pSS. MATERIALS AND METHODS: This is a retrospective cross-sectional study done at a tertiary teaching hospital in southern India in 235 patients with pSS. Patients satisfying the American European Consensus Group (AECG) or American College of Rheumatology (ACR) 2012 for pSS between 2008 and 2015 were included if baseline 25(OH)D levels using electrochemiluminescence were available in hospital's laboratory record, 25(OH)D <20 ng/ml,20-30 ng/ml and >30 ng/ml was defined as deficiency, insufficiency and normal, respectively. Clinical laboratory data and disease activity scoring by EULAR Sjögren's syndrome disease activity index (ESSDAI) were retrieved retrospectively. Latitude corresponding to residence of each patient and the season of performing the assay were recorded. Chi-square statistics was done to find associations between categorized 25(OH)D and outcomes and was reported as odds ratio(95% confidence interval). RESULTS: Mean 25(OH)D for 235 patients with pSS was 19.98(12.55)ng/ml. A vitamin D deficiency, insufficiency and sufficiency was seen in 141(60%), 60(25.5%) and 34.0(14.5%), respectively. No association was noted between latitude or season of performing assay and the levels. pSS with 25(OH)D ≤30ng/ml had more than two fold risk of higher grading on lip biopsy as well as Rheumatoid Factor (RF) positivity. However, low 25(OH)D seemed to be associated with lower ESSDAI and less pulmonary involvement. CONCLUSION: Prevalence of 25(OH)D deficiency in Indian patients with pSS was comparable to that of general Indian population. Low 25(OH)D level ≤30ng/ml was associated with higher odds for RF positivity and positive grading on lip biopsy. Surprisingly, low 25(OH)D was associated with lower ESSDAI score.

Diagnostic accuracy of salivary and serum-free light chain assays in primary Sjögren's syndrome: a pilot study.

OBJECTIVE: To estimate levels of salivary and serum free light chains (FLCs) and explore its utility as a biomarker in primary Sjögren's syndrome (pSS). METHODS: Patients with pSS classified by American European Consensus group 2002 or American College of Rheumatology 2012 criteria between January 2015 and August 2015 were included. Healthy staff and non-first degree relatives of patients constituted controls. Serum and salivary FLCs were measured by immunoturbidometry using FREELITE™ Human Kappa(κ) and Lambda(λ) Free Kit (Binding site, Birmingham, UK), on a Roche Modular P800. FLCs were compared between cases and controls using the Mann-Whitney U-test. The receiver operator characteristic curve was constructed to analyze the discriminating ability of salivary and serum kappa and lambda FLCs. RESULTS: Salivary and serum FLCs were assayed in 15 patients and 13 patients, respectively, and in 15 controls. Median age of cases and controls was 34 years. Salivary kappa and lambda FLCs were higher in pSS as compared to controls (P < 0.05 and P < 0.001, respectively). Serum kappa and lambda FLCs were also higher in pSS (both P < 0.05). Salivary lambda levels were higher in pSS with ocular signs; serum kappa and lambda levels were higher in those with ocular symptoms. A cut off of ≥ 1.1 mg/L for salivary lambda FLC had a sensitivity and specificity of 73.3% and 93.3%, respectively, for the diagnosis of pSS. Serum kappa FLC ≥ 30 mg/L had a sensitivity and specificity of 92.3% and 73.3%, respectively. CONCLUSION: Serum and salivary FLCs and in particular the latter, are potential biomarkers in pSS. Larger studies are required for validating the findings.

Effect of Fortification and Additives on Breast Milk Osmolality.

This study evaluated the effect of fortification and commonly used additives on the osmolality of human milk. Osmolality after fortification with milk powder and human milk fortifier increased from 303 mOsmol/kg to 397 and 373 mOsmol/kg, respectively. The maximal increase in osmolality was seen with the addition of calcium gluconate.

Serum Vitamin D Status and Outcome among Critically Ill Children Admitted to the Pediatric Intensive Care Unit in South India.

OBJECTIVES: To determine the vitamin D status and the association between vitamin D status and the clinical outcome of critically ill children admitted to pediatric intensive care unit (PICU) in South India. METHODS: Fifty-four consecutive children with medical and surgical diagnoses were included with parental consent. Severity of illness was assessed using PIM-2 score; Sequential Organ Failure Assessment Cardiovascular Score (CV-SOFA) was used to describe vasopressor use. Serum for 25(OH) D levels was obtained as close as possible to the ICU admission. Vitamin D deficiency was defined as serum 25(OH) D level < 20 ng/ml (50 nmol/L). Primary outcome measures were serum 25(OH) D level and in-hospital all cause mortality. Secondary outcomes were illness severity, vasopressor requirement, use of mechanical ventilation and duration of ICU stay. RESULTS: Of the 54 children, two were excluded due to insufficient serum for vitamin D analysis. Median age was 17.5 mo (IQR = 4.5-78); 38.5 % were infants. Higher age was associated with low vitamin D levels (r s = -0.34; p 0.01). Median serum 25(OH) D level was 25.1 ng/ml (IQR = 16.2-34.2). Shock (30.8 %), CNS conditions (23.1 %) and respiratory illnesses (21.2 %) were the three most common reasons for admission to the PICU. Vitamin D deficiency was seen in 40.3 % of the critically ill children. Higher PIM score or SOFA score were associated with low vitamin levels (r s = -0.29, p 0.04 and r s = -0.29, p 0.05 respectively). Children who were mechanically ventilated had a significantly lower median serum 25(OH) D level than those who were not on ventilation [19.5 ng/ml (IQR = 14.6-27.7)] vs. 32.1 ng/ml[(IQR = 16.5-50.9), p 0.01]. Serum 25(OH) D level was also positively associated with serum calcium levels (r s = 0.32, p 0.03). The proportion of children who died or were discharged terminally at parental request was 23.8 % among those with serum 25(OH) D level < 20 ng/ml as compared to 16.1 % among those with serum 25(OH) D level > 20 ng/ml (p 0.49). CONCLUSIONS: Vitamin D deficiency is common among pediatric patients admitted to PICU in South India. Low serum 25(OH) D level was associated with higher severity of illness, need for mechanical ventilation, more vasopressor use and lower serum calcium levels. No association between vitamin D status and mortality was demonstrated.

Vitamin D status and adequacy of standard supplementation in preterm neonates from South India.

OBJECTIVE: The aim of this study was to assess vitamin D status of preterm babies at birth and adequacy of daily supplementation with vitamin D. METHODS: This prospective cohort study recruited 111 preterm babies, 25 to 32 weeks' gestation from a tertiary care perinatal center in south India. Cord blood was assayed for serum calcium, phosphate, alkaline phosphatase, and 25-hydroxyvitamin D (25(OH)D). All of the babies were fed unfortified breast-milk and supplemented daily with calcium, phosphate, and 400 IU of vitamin D. At 6 weeks serum calcium, phosphate, alkaline phosphatase, parathyroid hormone, and 25(OH)D levels were estimated. RESULTS: Of 111 preterm babies recruited, a total of 90 (81%) of the preterm babies were followed up until 6 weeks. The median (interquartile range) vitamin D level in the preterm group was 34.7 (25.6-50.1) and 19.3 (13.9-27.1) ng/mL at birth and 6 weeks, respectively. Using a cutoff value of <20 ng/mL to determine vitamin D insufficiency (VDI), it was observed that 12.6% of the babies were vitamin D insufficient at birth. This increased to 52.2% at 6 weeks despite the recommended supplementation with vitamin D (P < 0.001). CONCLUSIONS: The prevalence of VDI was not high at birth; however, a large proportion of preterm babies were vitamin D insufficient at 6 weeks despite being supplemented with vitamin D 400 IU/day. The recommended vitamin D supplementation of 400 IU appears to be inadequate to prevent VDI, and hence randomized controlled trials looking at higher doses of vitamin D supplementation are needed.

Elevated procalcitonin is associated with increased mortality in patients with scrub typhus infection needing intensive care admission.

CONTEXT: Procalcitonin is a biomarker of bacterial sepsis. It is unclear if scrub typhus, a rickettsial illness, is associated with elevated procalcitonin levels. AIM: To assess if scrub typhus infection is associated with high procalcitonin levels and whether high levels portend a poorer prognosis. SETTING AND DESIGN: Retrospective study of patients with severe scrub typhus infection, admitted to the medical intensive care unit of a tertiary care university affiliated teaching hospital. MATERIALS AND METHODS: Eighty-four patients with severe scrub typhus infection that also had procalcitonin levels were assessed. STATISTICAL ANALYSIS: Relationship between procalcitonin and mortality explored using univariate and multivariate analyses. RESULTS: The mean (±standard deviation) age was 40.0 ± 15.5 years. Patients were symptomatic for 8.3 ± 4.3 days prior to presentation. The median admission procalcitonin level was 4.0 (interquartile range 1.8 to 8.5) ng/ml; 59 (70.2%) patients had levels >2 ng/ml. Invasive mechanical ventilation was required in 65 patients; 20 patients died. On univariate analysis, admission procalcitonin was associated with increased odds of death [odds ratio (OR) 1.09, 95% confidence interval (CI) 1.03 to 1.18]. On multivariate logistic regression analysis including procalcitonin and APACHE-II score, the APACHE-II score was significantly associated with mortality (OR 1.16, 95% CI 1.06 to 1.30, P = 0.004) while a trend was observed with procalcitonin (OR 1.05, 95%CI 1.01 to 1.13, P = 0.09). The area under the receiver operating characteristic (ROC) curve, AUC, for mortality was 0.77 for procalcitonin and 0.78 for APACHE-II. CONCLUSIONS: Procalcitonin is elevated in severe scrub typhus infection and may be associated with higher mortality.

Spot urine cortisol-creatinine ratio - A useful screening test in the diagnosis of Cushing's syndrome.

INTRODUCTION: Although, there are several tests available, not one of them fulfils the criteria of being an ideal screening test. Continuing the search for an ideal screening test, we explored the use of urine spot cortisol-creatinine ratio as a novel method of evaluating patients with Cushing's syndrome. METHOD: A total of 35 subjects were studied and divided into 3 groups - 15 having cushings syndrome, 15 patients with obesity and 5 normal weight subjects. All patients with cushings syndrome were positive for the other screening tests. RESULTS: The mean (standard deviation) of cortisol:creatinine ratio among the 3 groups (cushings, obese and control subjects) was 36.00(24.74), 7.01(2.73) and 3.49(2.68) respectively. Using the cutoff of 12.27 nano mol/ micro mol(based on data of normal subjects) for the urine cortisol creatinine ratio we get a sensitivity of 93.75% and a specificity of 100%. Also the positive and negative predictive value as calculated with this cutoff is 100% and 93.3% respectively. CONCLUSION: In this study we found that UCCR is similar in both Obese and Non Obese subjects who did not have cushings syndrome. UCCR is significantly elevated in individuals with Cushing's syndrome as compared to those who do not have cushings syndrome. Also when a cut off of 12.27 nano mol/ micro mol was used this test had a higher sensitivity, however this test had a higher specificity at a cut off of 15.35.

Systemic inflammatory response syndrome in diseases of the skin.

BACKGROUND: A number of dermatological conditions present with features of systemic inflammatory response syndrome (SIRS). This study evaluated the incidence and outcome of SIRS in patients with dermatological diseases. STUDY DESIGN: Prospective cohort study. RESULTS: Patients admitted to a university hospital with a skin disease and fulfilling at least two SIRS criteria were included. The primary outcome measure was mortality. Secondary outcomes included incidence of multiple organ dysfunction syndrome (MODS), sepsis, severe sepsis and shock. Over 14 months, 2765 inpatients with skin related problems were examined. These included 721 patients admitted directly to the dermatology ward and 2044 patients referred from other departments within the hospital, with cutaneous manifestations. The incidence of SIRS in this cohort was 2.4% (n=67). The mean (SD) age was 32.6 (19.7) years with a male:female ratio of 1.2:1. Cutaneous adverse drug reaction (CADR) was the most common cause of SIRS (35.8%). During hospitalisation, 37 patients (55.2%) developed sepsis, 23 (34.4%) MODS, 15 (22.4%) severe sepsis and 6 (9%) shock. Methicillin sensitive Staphylococcus aureus was the most common skin isolate (41.4%) and Enterococcus the most common blood isolate. Overall mortality was 15% (10/67). Older age, low albumin, MODS, severe sepsis and shock were associated with an increased risk of death (p<0.03). Positive blood cultures, liver or lung involvement were also significantly associated with increased mortality (p<0.01). CONCLUSION: The incidence of SIRS was low in dermatological diseases. In this cohort, CADR was the most common cause of SIRS. Patients who developed sepsis or MODS had a poor outcome.

Sequential treatment of metformin and clomiphene citrate in clomiphene-resistant women with polycystic ovary syndrome: a randomized, controlled trial.

BACKGROUND: Recognition of the importance of insulin resistance in clomiphene-resistant women with polycystic ovary syndrome (PCOS) has led to the use of insulin sensitizers. METHODS: A randomized, controlled trial was conducted to compare efficacy of sequential treatment with metformin and clomiphene citrate with conventional gonadotrophins. Sixty clomiphene-resistant women with PCOS were randomized to two groups (n = 30 each), using computer-generated tables. Group I received metformin for 6 months, followed by ovulation induction with clomiphene citrate; group II received hMG for ovulation induction. Hormonal profiles were evaluated at the onset and after completion of treatment. RESULTS: There was no significant difference in pregnancy rates between the two groups (16.7 versus 23.3%). In group I, there was a significant improvement in menstrual function and ovulation after treatment (40%, P < 0.001; and 46.7%, P < 0.001), with a significant decrease in fasting insulin levels (P < 0.05). There were no changes in other biochemical parameters. The ovulation rate in group II was 43.3%, with a high drop-out rate. The cost-effective analysis for medications per pregnancy in group I was US$ 71 +/- 3 versus US$ 277 +/- 171 in group II. CONCLUSIONS: Sequential treatment with metformin and clomiphene citrate is an effective and safe option for clomiphene-resistant women with PCOS.

Post-transplant hyperglycaemia: a study of risk factors.

BACKGROUND: Post-transplant diabetes mellitus (PTDM) has several identifiable pre- and post-transplant risk factors. The link to nutritional status pre-transplant has not been explored previously. This study was conducted to identify risk factors for the development of PTDM, with emphasis on pre-transplant nutritional status and glucose tolerance. METHODS: Non-diabetic adult end-stage renal failure patients awaiting renal transplantation were studied prospectively. Their nutritional status was assessed as body mass index (BMI), serum albumin, and the evolution of these parameters over time prior to transplantation. An oral glucose tolerance test (OGTT) was performed pre- and serially post-transplant until 6 months. Pre- and post-transplant risk factors such as age, nutritional status, glucose tolerance parameters and immunosuppression were related to the development of PTDM or impaired glucose tolerance (IGT) post-transplant. RESULTS: The mean age of 174 patients studied over a 2-year period was 32.9 +/- 9.7 years. The mean post-transplant follow-up was 25.6 +/- 12.8 months. The mean BMI at recruitment was 18.3 +/- 2.4 kg/m(2). The rate of increase in BMI pre-transplant showed an inverse correlation with the baseline BMI (r = -0.34, P = 0.000) and formed an independent marker of nutritional status. PTDM developed in 21.4% patients and 24.1% had IGT. On univariate and multivariate analyses, the factors significantly associated with the development of PTDM were greater age, more rapid increase in dry weight after starting haemodialysis (HD), elevated pre-transplant OGTT responses and cyclosporin (CsA) and prednisolone doses early post-transplant. Additionally, on multivariate analysis, higher CsA trough level > 300 ng/ml at 3 months increased the risk for the development of PTDM. Of patients who developed PTDM, 57% had impairment of glucose tolerance pre-transplant (> 140 mg/dl at 2 h). Patients with a 1-h glucose value greater than the 50th percentile on pre-transplant OGTT had a 3.9-fold greater risk for the development of PTDM (P = 0.05, 95% CI = 1.03-11.1). In those patients with higher 1-h glucose (> 50th percentile) who also gained in dry weight rapidly pre-transplant, the risk increased to 5.3 (P = 0.02). Of 76 patients with abnormal OGTT early post-transplant, only 68% continued to have PTDM or IGT post-transplant, the remainder reverting to normal glucose tolerance. CONCLUSIONS: Persistent abnormal glucose tolerance after transplantation was seen in 45% of the patients. Pre-transplant factors including greater age, abnormal glucose tolerance parameters, and rapid gain in dry weight on HD, along with higher prednisolone and CsA doses early post-transplant were the important factors associated with the development of PTDM. Identification of patients with pre-transplant risks might allow modification of post-transplant immunosuppression with non-diabetogenic agents.