Risk Factors for Cerebral Edema and Acute Kidney Injury in Children with Diabetic Ketoacidosis.

OBJECTIVES: To study the clinical profile and risk factors of cerebral edema and acute kidney injury in children with diabetic ketoacidosis. DESIGN: Retrospective review of medical records. PATIENTS: Fifty consecutive patients (age <18 years) admitted to our pediatric intensive care unit with a diagnosis of diabetic ketoacidosis over 5 years. MATERIALS AND METHODS: Retrospective analysis of medical records was done, and data including patients' age, sex, presenting features, biochemical profile including blood glucose, osmolality, urea, creatinine, and venous blood gas, electrolytes were recorded at admission, at 12 and 24 hours. Treatment details including fluid administration, rate of fall of glucose, time to resolution of diabetic ketoacidosis were noted. Complications such as cerebral edema and acute kidney injury were recorded. Patients with and without cerebral edema and acute kidney injury were compared. Variables that were significant on univariate analysis were entered in a multiple logistic regression analysis to determine the independent predictors for cerebral edema and acute kidney injury. Odds ratio and 95% confidence interval were calculated using SPSS version 22. MEASUREMENTS AND MAIN RESULTS: Between November 2015 and 2020, 48 patients were admitted for a total of 50 episodes of diabetic ketoacidosis. Two patients had recurrent diabetic ketoacidosis. Median age was 9.5 years (range 1-17). Thirty-one patients (62%) had new-onset type I diabetes mellitus. Twenty-two patients (44%) presented with severe diabetic ketoacidosis. Cerebral edema and acute kidney injury were seen in 11 (22%) and 15 (30%) patients, respectively. On multiple logistic regression analysis, higher blood urea level, lower serum bicarbonate level, and higher corrected sodium levels at admission were identified to be variables independently associated with risk of cerebral edema. CONCLUSIONS: Higher corrected sodium, higher urea level, and lower serum bicarbonate levels at admission are predictive of cerebral edema in patients presenting with diabetic ketoacidosis. The severity of dehydration and acidosis in DKA appears to be a common factor responsible for the development of dysfunction of both brain and kidney. HOW TO CITE THIS ARTICLE: Raghunathan V, Jevalikar G, Dhaliwal M, Singh D, Sethi SK, Kaur P, et al. Risk Factors for Cerebral Edema and Acute Kidney Injury in Children with Diabetic Ketoacidosis. Indian J Crit Care Med 2021;25(12):1446-1451.

Novel mutations of the arylsulphatase B (ARSB) gene in Indian patients with mucopolysaccharidosis type VI.

BACKGROUND & OBJECTIVES: Mucopolysaccharidosis type VI (MPS VI) is a rare, autosomal recessive lysosomal storage disorder caused by deficient enzymatic activity of N-acetyl galactosamine-4-sulphatase resulting from mutations in the arylsulphatase B (ARSB) gene. The ARSB gene is located on chromosome 5q11-q13 and is composed of eight exons. More than hundred ARSB mutations have been reported so far, but the mutation spectrum of MPS VI in India is still unknown. Hence, the aim of the present study was to identify the mutational spectrum in patients with MPS VI in India and to study the genotype-phenotype association and functional outcomes of these mutations. METHODS: Molecular characterization of the ARSB gene by Sanger sequencing was done for 15 patients (aged 15 months to 11 yr) who were enzymatically confirmed to have MPS VI. Age of onset, clinical progression and enzyme activity levels in each patient were studied to look for genotype-phenotype association. Haplotype analysis performed for unrelated patients with the recurring mutation W450C, was suggestive of a founder effect. Sequence and structural analyses of the ARSB protein using standard software were carried out to determine the impact of detected mutations on the function of the ARSB protein. RESULTS: A total of 12 mutations were identified, of which nine were novel mutations namely, p.D53N, p.L98R, p.Y103SfsX9, p.W353X, p.H393R, p.F166fsX18, p.I220fsX5, p.W450L, and p.W450C, and three were known mutations (p.D54N, p.A237D and p.S320R). The nine novel sequence variants were confirmed not to be polymorphic variants by performing sequencing in 50 unaffected individuals from the same ethnic population. INTERPRETATION & CONCLUSIONS: Nine novel mutations were identified in MPS VI cases from India in the present study. The study also provides some insights into the genotype-phenotype association in MPS VI.

Rapidly evolving hypopituitarism in a boy with multiple autoimmune disorders.

A 10-year-old boy with acute onset cranial diabetes insipidus and multiple autoimmune disorders had evolving panhypopituitarism, thought to be due to autoimmune hypophysitis. Over 18 months, a dramatic clinical course with progressive hypopituitarism and development of type 1 diabetes mellitus was evident. Serial brain imaging showed changes suggestive of germinoma.

Pediatric Ectopic Cushing Syndrome Caused by Hepatic Neoplasms: A Case Report and Systematic Review.

Ectopic adrenocorticotropic hormone (ACTH) syndrome (EAS) is rare in children, and localizing the source of EAS is often challenging. Here, we report EAS in an adolescent boy who presented with Cushingoid features and had endogenous ACTH-dependent hypercortisolism on hormonal evaluation. Abdominal ultrasound and CT revealed a hepatic lesion with characteristics suggestive of hemangioma, whereas the lesion was tracer non-avid on 68Ga-DOTANOC positron emission tomography/CT. A regional sampling of ACTH was done to confirm the hepatic lesion as the source of EAS, and a definitive ACTH gradient was observed between the hepatic vein and the right internal jugular vein. Further, a preoperative biopsy of the lesion revealed a small round cell tumor with positive immunostaining for ACTH and synaptophysin, suggestive of a neuroendocrine tumor. The patient was managed with partial hepatectomy, resulting in hormonal and clinical remission of Cushing syndrome. In a systematic review of pediatric EAS due to primary hepatic tumors (n = 11), calcifying nested stromal epithelial cell tumors were the most common. EAS-associated hepatic tumors were larger (≥10 cm) except benign primary hepatic neuroendocrine tumors (PHNET). The latter were misdiagnosed as hemangioma in two cases by anatomical imaging but correctly diagnosed by somatostatin receptor scintigraphy. Hepatic tumors causing EAS in children required extensive resection, except benign PHNET. Nevertheless, all benign tumors with an uncomplicated perioperative course demonstrated disease-free survival over a median follow-up period of two years.

Video Consultation Versus In-Person Clinic Visit for Glycemic Control in Type 2 Diabetes during COVID-19 Pandemic (VIP-CD Study).

Objectives: To compare the efficacy of video consultation (VC) for prospective glycemic control against that of in-person clinic visit (IPV) in individuals with type 2 diabetes. Materials and Methods: This is a retrospective, cohort study of 96 individuals with type 2 diabetes followed up for a period of ≤6 months. The cohort was divided into two groups depending on the mode of consultation, namely IPV (n = 48) and VC (n = 48). Baseline and follow-up characteristics including glycemic profile and lipid profile were compared. Results: The cohort had a mean age of 55.4 ± 13.8 years, median diabetes duration of 8 (0.3-70) years, a mean body mass index (BMI) of 28.8 ± 5.8 kg/m2, 44 (46.3%) females, and uncontrolled hyperglycemia (HbA1c 8.7% ± 1.9%). Both groups were adequately matched at baseline. At the time of first visit, cessation of previous medications was more frequent in the IPV group (37.5% vs 8.3%; P = 0.001) than in the VC group. Follow-up was earlier in the VC group as compared to the IPV group (43.2 vs 87.9 days; P = 0.000). During the follow-up period, both groups had similar and adequate glycemic (mean HbA1c 7% ± 1%) and lipid profile control. Cox regression model showed that the VC group achieved glycemic control quicker as compared to the IPV group. Conclusions: Telemedicine is an effective mode of consultation for attaining glycemic control during COVID-19 pandemic, possibly owing to the quicker follow-up without the risk of potential in-clinic/hospital exposure to COVID-19.

High prevalence of diabetes and other comorbidities in hospitalized patients with COVID-19 in Delhi, India, and their association with outcomes.

BACKGROUND AND AIMS: To study the prevalence and impact of diabetes mellitus and other comorbidities among hospitalized patients with COVID-19. METHODS: In a prospective, observational study including consecutive adults hospitalized with COVID-19, clinical outcomes and inflammatory markers were compared in those with and without diabetes. Participants were classified as having mild or severe COVID-19 disease using the WHO ordinal scale. RESULTS: 401 patients (125 females) with median age of 54 years (range 19-92) were evaluated. Of them 189 (47.1%) had pre-existing diabetes and21 (5.2%) had new-onset hyperglycaemia. Overall, 344 (85.8%) and 57 (14.2%) cases had mild and severe COVID-19 disease respectively. The group with diabetes had a higher proportion of severe cases (20.1% vs 9%, p-0.002), mortality (6.3 vs 1.4%, p-0.015), ICU admission (24.3 vs 12.3%, p-0.002), and oxygen requirement (53.4 vs 28.3%, p < 0.001). Baseline Hba1c (n = 331) correlated significantly with outcome severity scores (r 0.136, p-0.013) and 12/15 (80%) of those who succumbed had diabetes. Hypertension, coronary artery disease, and chronic kidney disease were present in 164 (40.9%), 35 (8.7%) and 12 (2.99%) patients respectively. Hypertension was associated with a higher proportion of severe cases, mortality, ICU admission and oxygen administration. CONCLUSIONS: We report a high prevalence of diabetes in a hospitalized COVID-19 population. Patients with diabetes or hypertension had more severe disease and greater mortality.

Low FT3 is an independent marker of disease severity in patients hospitalized for COVID-19.

AIM: To study the prevalence of thyroid dysfunction and its association with disease severity in hospitalized patients of coronavirus disease-19 (COVID-19). METHODS: In this retrospective cohort study, thyroid function tests (TFT) of 236 hospitalized patients of COVID-19 along with demographic, comorbid, clinical, biochemical and disease severity records were analysed. Patients were divided into previous euthyroid or hypothyroid status to observe the effect of prior hypothyroidism on the severity of COVID-19. RESULTS: TFT abnormalities were common. Low free T3 (FT3), high thyroid-stimulating hormone (TSH) and low TSH were seen in 56 (23.7%), 15 (6.4%) and 9 (3.8%) patients, respectively. The median levels of TSH (2.06 vs 1.26 mIU/mL, P = 0.001) and FT3 (2.94 vs 2.47 pg/mL, P < 0.001) were significantly lower in severe disease. Previous hypothyroid status (n = 43) was associated with older age, higher frequency of comorbidities, higher FT4 and lower FT3. TFT did not correlate with markers of inflammation (except lactate dehydrogenase); however, FT3 and TSH negatively correlated with outcome severity score and duration of hospital stay. Cox regression analysis showed that low FT3 was associated with severe COVID-19 (P = 0.032, HR 0.302; CI 0.101-0.904), irrespective of prior hypothyroidism. CONCLUSIONS: Functional thyroid abnormalities (low FT3 and low TSH) are frequently seen in hospitalized patients of COVID-19. Although these abnormalities did not correlate with markers of inflammation, this study shows that low FT3 at admission independently predicts the severity of COVID-19.

Lack of association of baseline 25-hydroxyvitamin D levels with disease severity and mortality in Indian patients hospitalized for COVID-19.

Vitamin D deficiency (VDD) owing to its immunomodulatory effects is believed to influence outcomes in COVID-19. We conducted a prospective, observational study of patients, hospitalized with COVID-19. Serum 25-OHD level < 20 ng/mL was considered VDD. Patients were classified as having mild and severe disease on basis of the WHO ordinal scale for clinical improvement (OSCI). Of the 410 patients recruited, patients with VDD (197,48.2%) were significantly younger and had lesser comorbidities. The levels of PTH were significantly higher in the VDD group (63.5 ± 54.4 vs. 47.5 ± 42.9 pg/mL). The proportion of severe cases (13.2% vs.14.6%), mortality (2% vs. 5.2%), oxygen requirement (34.5% vs.43.4%), ICU admission (14.7% vs.19.8%) was not significantly different between patients with or without VDD. There was no significant correlation between serum 25-OHD levels and inflammatory markers studied. Serum parathormone levels correlated with D-dimer (r 0.117, p- 0.019), ferritin (r 0.132, p-0.010), and LDH (r 0.124, p-0.018). Amongst VDD patients, 128(64.9%) were treated with oral cholecalciferol (median dose of 60,000 IU). The proportion of severe cases, oxygen, or ICU admission was not significantly different in the treated vs. untreated group. In conclusion, serum 25-OHD levels at admission did not correlate with inflammatory markers, clinical outcomes, or mortality in hospitalized COVID-19 patients. Treatment of VDD with cholecalciferol did not make any difference to the outcomes.

Cutaneous mucormycosis as a presenting feature of type 1 diabetes in a boy - case report and review of the literature.

BACKGROUND: Mucormycosis is a potentially fatal complication of diabetes. The rhino-orbito-cerebral form is the most common presentation, however, rarely other types can also be seen. CASE PRESENTATION: We describe the case of a 4½ -year-old boy not previously known to be a diabetic who presented to the plastic surgery department for gangrene of the left middle finger with surrounding erythema and induration. After the diagnosis of diabetes and initial treatment, pus from the wound showed broad aseptate hyphae suggestive of mucormycosis which was further confirmed on culture. Aggressive surgical debridement including amputation, antifungal treatment and glycemic control achieved a complete cure. CONCLUSIONS: Cutaneous mucormycosis is a rare complication of type 1 diabetes mellitus and can even be seen at the onset of diabetes. High index of suspicion, timely antifungal treatment and aggressive surgical debridement usually lead to recovery in the localized form of the disease.

Effect of Empagliflozin on Liver Fat in Patients With Type 2 Diabetes and Nonalcoholic Fatty Liver Disease: A Randomized Controlled Trial (E-LIFT Trial).

OBJECTIVE: Sodium-glucose cotransporter 2 (SGLT-2) inhibitors have been shown to reduce liver fat in rodent models. Data regarding the effect of SGLT-2 inhibitors on human liver fat are scarce. This study examined the effect of empagliflozin (an SGLT-2 inhibitor) on liver fat in patients with type 2 diabetes and nonalcoholic fatty liver disease (NAFLD) by using MRI-derived proton density fat fraction (MRI-PDFF). RESEARCH DESIGN AND METHODS: Fifty patients with type 2 diabetes and NAFLD were randomly assigned to either the empagliflozin group (standard treatment for type 2 diabetes plus empagliflozin 10 mg daily) or the control group (standard treatment without empagliflozin) for 20 weeks. Change in liver fat was measured by MRI-PDFF. Secondary outcome measures were change in alanine transaminase (ALT), aspartate transaminase (AST), and γ-glutamyl transferase (GGT) levels. RESULTS: When included in the standard treatment for type 2 diabetes, empagliflozin was significantly better at reducing liver fat (mean MRI-PDFF difference between the empagliflozin and control groups -4.0%; P < 0.0001). Compared with baseline, significant reduction was found in the end-of-treatment MRI-PDFF for the empagliflozin group (16.2% to 11.3%; P < 0.0001) and a nonsignificant change was found in the control group (16.4% to 15.5%; P = 0.057). The two groups showed a significant difference for change in serum ALT level (P = 0.005) and nonsignificant differences for AST (P = 0.212) and GGT (P = 0.057) levels. CONCLUSIONS: When included in the standard treatment for type 2 diabetes, empagliflozin reduces liver fat and improves ALT levels in patients with type 2 diabetes and NAFLD.

Efficacy and safety of a single monthly dose of cholecalciferol in healthy school children.

BACKGROUND: This study aimed to evaluate the efficacy and safety of a single monthly dose of cholecalciferol in healthy school children. METHODS: A total of 118 children of class VI of a residential school were selected to receive vitamin D supplementation in the form of oral cholecalciferol 60,000 IU monthly. Serum calcium and 25-hydroxyvitamin D (25OHD) levels were estimated at 0 and 12 months. The proportion of subjects achieving vitamin D sufficiency was assessed. RESULTS: The mean 25OHD levels increased significantly from 12.04±5.27 ng/mL at baseline to 32.6±7.05 ng/mL after 12 months of supplementation (p<0.001). None developed hypercalcemia. CONCLUSIONS: Vitamin D supplementation in the doses of 60,000 IU monthly is a reasonable, safe and cost-effective regimen for children to attain and maintain vitamin D sufficiency.

Acute Respiratory Distress Syndrome: A Rare Complication in Pediatric Diabetic Ketoacidosis.

Cerebral edema (CE) and non cardiogenic pulmonary edema (acute respiratory distress syndrome, ARDS) are life-threatening complications of diabetic ketoacidosis (DKA). In contrast to CE complicating DKA, which is primarily reported in pediatric patients, ARDS is rarely described in this age group. Here, the authors present a child with DKA who developed both cerebral edema and ARDS during the course of her management. It is feasible that severe acidosis, hypotension, azotemia, hypoalbuminemia and the superimposed aggressive intravenous fluid administration were important risk factors for the development of cerebral edema and ARDS in the index patient. The report highlights the importance of early diagnosis and aggressive therapy in the management of ARDS, and summarizes the published literature on this rarely reported complication of pediatric DKA.

Childhood and Youth Onset Diabetes: A Single Centre Experience.

OBJECTIVES: To identify proportion of various types of diabetes and differences between type 1 and type 2 diabetes in patients with youth onset diabetes (onset below 25 completed years of age). In addition, concurrent autoimmune diseases in type 1 diabetes were studied in a subset of patients. METHODS: A total of 577 patients (192 girls) with diabetes onset at median age of 14 y (range 1 mo-25 y) with median duration of 1 y (range day of diagnosis- 43 y) were included. Clinical details, investigations and complications were recorded in a proforma. Diabetes was classified using clinical criteria supported by laboratory tests of C peptide and anti GAD-65 antibody in a subset of patients. RESULTS: Type 1 diabetes accounted for 368/421 (87.4 %) patients with age of onset <18 y and 99/156 (63.5 %) of patients with onset between 19 and 25 y of age. Proportion of type 2 diabetes was 36/421 (8.5 %) and 41/156 (26.2 %) in these two groups. Older age at onset, diabetes in one or both parents, absence of ketosis /weight loss and presence of acanthosis were significant predictors of type 2 diabetes. Hypothyroidism (TSH >10) and biopsy proven celiac disease was found in 11.6 and 9.7 % of type 1 diabetes patients respectively. CONCLUSIONS: Type 1 diabetes is the most common type of diabetes in youth, however, a significant proportion of youth have type 2 diabetes. In these patients a combination of clinical factors, biochemical parameters and course over few months helps to guide the diagnosis.

From cerebral salt wasting to diabetes insipidus with adipsia: case report of a child with craniopharyngioma.

UNLABELLED: Craniopharyngioma is associated with a wide and interesting variety of sodium states both by itself and following surgical resection. These are often challenging to diagnose, especially given their dynamic nature during the perioperative course. We present the case of a boy with craniopharyngioma who had hyponatremia due to cerebral salt wasting preoperatively, developed diabetes insipidus (DI) intraoperatively and proceeded to develop hypernatremia with adipsic DI. CONCLUSION: Cerebral salt wasting is a rare presenting feature of craniopharyngioma. Postoperative DI can be associated with thirst abnormalities including adipsia due to hypothalamic damage; careful monitoring and a high index of suspicion are required for its detection. Adipsic DI is a difficult condition to manage; hence a conservative surgical approach is suggested.

Turner syndrome patients with bicuspid aortic valves and renal malformations exhibit abnormal expression of X-linked inhibitor of apoptosis protein (XIAP).

OBJECTIVE: We analyzed mRNA expression of X-linked inhibitor of apoptosis protein (XIAP) in patients with Turner syndrome (TS) and examined its association with phenotypic features. SUBJECTS AND METHODS: XIAP mRNA expression levels were investigated in 98 patients with TS in total RNA extracted from blood leucocytes by real time quantitative polymerase chain reaction. RESULTS: Levels of XIAP mRNA were significantly lower in patients with bicuspid aortic valves (BAV; n=13) than those without (log XIAP -1.17±0.3 vs. -0.94±0.2, p=0.002). Significantly higher expression of XIAP mRNA was seen in patients with a mosaic karyotype and renal malformations (log XIAP -0.79±0.3 vs. -1.0±0.3, p=0.03). No correlations were seen between XIAP and other manifestations. CONCLUSION: Abnormal expression of XIAP may be an important underlying mechanism in the development of BAV and renal malformations in TS. However, abnormal XIAP mRNA expression, as determined from peripheral mononuclear cells, does not appear to explain all the somatic and visceral stigmata of TS.

Long-term outcomes of pediatric Graves' disease.

BACKGROUND: Remission rates with antithyroid drugs (ATDs) in pediatric Graves' disease (GD) are low. Very few studies report long-term follow-up of GD especially into adulthood. OBJECTIVES: We studied long-term outcomes of pediatric onset GD, including a follow-up into adulthood and factors associated with need for definitive therapy. METHODS: Sixty-five patients (57 females) with GD, with onset <18 years (median 13, range, 3.5-17) and duration ≥2 years (median 7; range, 2-22) since diagnosis, were included. Medical records were reviewed, and current details were recorded in a questionnaire by telephonic interview. RESULTS: All patients were initially treated with ATDs. Fifty-three patients were treated for ≥2 years. Amongst these, outcomes included relapse after initial remission (n=38), failure of remission (n=8) and long-term remission, defined as remission lasting ≥4 years (n=6). One patient had carbimazole and surgery but died of hepato-renal failure secondary to systemic vasculitis. A total of 44/65 patients were managed with definitive treatment. Those needing definitive treatment had higher mean free T4 (54.6±23.7 vs. 39.5±20.5 pmol/L, p=0.02) and thyrotropin receptor antibody (TRAB) titers (34.1±19.3 vs. 13.8±9.9 IU/L p<0.0001). Long-term sequelae included need for thyroxine replacement (n=42, 64.6%), persistent goiter (12/62, 19.3%) and persistent ophthalmopathy (19/40, 47.5%). CONCLUSIONS: Long-term remission rates of pediatric onset GD with ATDs are very low, especially with longer follow-up. Higher pretreatment free T4 and high TRAB titers predict need for definitive treatment.

A guide to understanding the steroid pathway: new insights and diagnostic implications.

Steroid analysis has always been complicated requiring a clear understanding of both the clinical and analytical aspects in order to accurately interpret results. The literature relating to this specialised area spans many decades and the intricacies of the steroid pathway have evolved with time. A number of key changes, including discovery of the alternative androgen pathway, have occurred in the last decade, potentially changing our understanding and approach to investigating disorders of sexual development. Such investigation usually occurs in specialised paediatric centres and although preterm infants represent only a small percentage of the patient population, consideration of the persistence of the foetal adrenal zone is an additional important consideration when undertaking steroid hormone investigations. The recent expanded role of mass spectrometry and molecular diagnostic methods provides significant improvements for accurate steroid quantification and identification of enzyme deficiencies. However analysis of steroids and interpretation of results remain complicated. This review aims to provide an insight into the complexities of steroid measurement in children and offers an updated guide to interpretation, of serum and urine steroids through the presentation of a refined steroid pathway.

Usage of pioglitazone at Medanta, the Medicity.

Pioglitazone improves glycemic control by acting as an insulin sensitizer and is used in the management of Type 2 diabetes mellitus. Pioglitazone has recently been at the center of a controversy with regards to its safety. There is no clear consensus on how, when and in what dose the drug should be used in the management of diabetes. We have summarized our strategy on pioglitazone use in Type 2 diabetes in a large private tertiary care center - Medanta, the Medicity- which may help in generating further thought about positioning of this anti-diabetic molecule. We use pioglitazone as the fourth in the pecking order of oral anti-diabetic agents. We typically use pioglitazone in a dose of 15 mg/day. We avoid using pioglitazone with insulin. We do not use pioglitazone under following situations: In the presence of significant or proven cardiac disease, in patients who are struggling with their weight or need to lose weight, in patients at high risk for osteoporotic fractures, in patients with macular edema, in patients with pre-existing bladder cancer and would discontinue in case hematuria or any other symptom of bladder cancer develops. We continue to use the drug in patients well controlled on it without any evident side-effects or contraindications.