Clinicopathological and oncological outcomes in upper extremity Ewing's sarcoma: A single institutional experience.

Background: Ewing's sarcoma is highly aggressive bone tumor having predilection for younger age groups with t (11,22) translocation, recombines the FLI-1 and EWS genes on chromosome 22. This disease requires multi-disciplinary treatment withneo-adjuvant chemotherapy followed by surgery or radiotherapy and adjuvant chemotherapy. This study was aimed to assess the demographic distribution, clinical behaviour and oncological outcome of Ewings Sarcoma involving upper extremity. Methods: From 2015 to 2022, 45 patients of upper extremity Ewing's sarcoma underwent treatment at a territory cancer centre. A total of 26 patients treated with surgical management were included in the study comprising 15 males (57.7 %) and 11 females (42.3 %). Mean age of presentation was 26 years (3-43 years). The most common site for Ewings sarcoma of upper extremity was Humerus(42 %) followed by Scapula(27 %), Radius(15 %), Ulna(8 %), Metacarpals(4 %) and Clavicle(4 %). Out of 26 cases, 19 (73%) underwent limb salvage surgery and 7 (27%) underwent ampuation surgery. Results: In limb salvage group reconstruction with Extra-corporeal radiotherapy (ECRT), Ulna centralization, Megaprosthesis and 3D printed scapula was performed following wide resection of tumor. In Amputation group ray resection in one case and forequarter amputation was performed in six cases. Mean serum LDH value was 335 IU/L (2.3X Normal value) and serum albumin was 4.04 gm/dl. Mean tumour necrosis after neo-adjuvant chemotherapy was 68 %. Out of 26 cases, 19(73 %) cases underwent limb salvage and 7 patients underwent amputation surgery. Out of 26, 13 (50 %) patients developed metastasis on follow up. The Event free survival (EFS) in current study was 70 % at 12 months and 40 % at 24 months. Mean Event free survival (EFS) in current study was 33.5 months (22.3-44.6) and Median Event free survival (EFS) in current study was 25 months (19.7-30.2). Conclusion: This study characterises demographic and oncologic outcomes of upper extremity ewings sarcoma in Indian subpopulation. Pain and swelling were prominent clinical findings at presentation in patients with upper extremity Ewing's sarcoma. The survival rate following limb salvage surgery in Ewings sarcoma of upper extremity was comparable to that of patients with amputation surgery. Ewings sarcoma of upper extremity was associated with higher LDH level which was raised more than twice the normal range and can led to worse oncologic outcomes. A comparative study on upper extremity and lower extremity ewings sarcoma will be of help to improve literature on this rare disease.

Clinical Profile and Outcome of Young Infants With Hypernatremic Dehydration Presenting to the Emergency Department.

OBJECTIVES: The aim of this study was to evaluate the clinical profile and outcome of young infants presenting to the pediatric emergency department with hypernatremic dehydration. METHODS: A prospective observational study was conducted at a tertiary care teaching hospital over a period of 18 months. All outborn sick young infants aged 2 months or younger who presented to the emergency department with symptoms and signs of possible sepsis and/or dehydration were screened, and those with hypernatremia were enrolled in the study. Those infants born at less than 37 weeks of gestation and gross congenital anomaly were excluded. Hypernatremic dehydration was defined as serum sodium levels (Se Na+)higher than 145 mEq/L. Variables used in the study were defined as per standard definitions. Acute kidney injury was defined and staged using serum creatinine as per modified neonatal Kidney Disease Improving Global Outcome guidelines. Clinical presentation, laboratory parameters, and comorbidities were compared among outcome groups (survived and died). RESULTS: Of 1124 outborn young infants who met the eligibility criteria for screening, 63 were diagnosed to have hypernatremic dehydration and 55 were enrolled. The hospital-based period prevalence of hypernatremic dehydration in young infants was 4.89%. The median age of presentation was 17 days (10-30). Male-to-female ratio was 1.1:1. Seventy-three percent were first in birth order. Feeding pattern showed 61.8%, 30.9%, and 7.3% of infants were exclusively breastfed, top fed, and mixed fed, respectively. The median serum sodium at the time of admission was 160 (153.5-167) mg/dL. Three (5.5%) infants had mild, 39 (70.9%) had moderate, and 13 (23.6%) had severe hypernatremic dehydration. There was statistically significant correlation between median platelet count with severity of hypernatremic dehydration. The mean time taken to correct serum sodium level was 3.30 ± 1.60 days. The case fatality rate was 41.8%. Those who died had statistically more severe hypernatremic dehydration, acute kidney injury, sepsis, and need for ventilation. CONCLUSIONS: Acute kidney injury stage 3, shock, and need for ventilation are associated with poor outcome in infants with hypernatremic dehydration.

Role of bone scintigraphy (bone scan) in skeletal osteosarcoma: A retrospective audit and review from tertiary oncology centre.

Introduction: Bone scan is a investigation which uses radionuclide phosphonate compound for whole skeletal survey. In this current study we have done the analysis of the role of bone scan in skeletal osteosarcoma at tertiary oncology care centre. Material & methods: This is a retrospective study conducted in a tertiary oncology centre from January 2022 to February 2023. A total of 92 patients with skeletal OGS were included in our study undergone 99 mTCcMDP whole body bone scan. 99 mTc MDP was prepared freshly every morning and dose for each patient were calculated as per EANM guidelines. Images were acquired 2-3 h of post injection. All images were acquired at GE infinia dual head machine with peak setting at 140Kev and LEAP collimator. Suspicious lesions on planer bone scan were correlated with SPECT fused with CT. All the bone scans were reviewed retrospectively by two independent nuclear medicine physicians. Results: In this study group, 86 patients with biopsy proven skeletal OGS underwent 99 mTCcMDP bone scan of which 63 were males and 23 were females (2.7:1) with age of study group ranging from 7years to 48years. Patients referred for bone scan were retrospectively categorized in two groups, first group patients (52) were referred for initial staging of disease and second group of patients (34) were referred for follow-up or re-staging of the disease. Total 09 patients showed distant skeletal metastases on bone scan, out of which 05 were in initial staging group and 04 in follow up group. Conclusion: Osteosarcoma has propensity to metastasize to many sites in the body however most common site being lung followed by skeletal, nodal and rarely soft tissue metastasis. Bone scan enjoys a optimal sensitivity in case of osteosarcoma to detect skeletal metastasis but have low specificity. However being a cost effective and faster investigation makes it a wise investigation of choice in case of osteosarcoma for skeletal metastasis evaluation.

SARS-CoV-2 infection in children with chronic kidney disease.

BACKGROUND: Information on the course of SARS-CoV-2 infection in children with chronic kidney disease (CKD) is limited. METHODS: We retrospectively reviewed the presentation and outcomes of SARS-CoV-2 infection in patients with CKD followed at any of the four pediatric nephrology centers in New Delhi from April 2020 to June 2021. Outcomes, including cardiopulmonary and renal complications, were reported in relation to underlying disease category and illness severity at presentation. RESULTS: Underlying illness in 88 patients included nephrotic syndrome (50%), other CKD stages 1-4 (18.2%), CKD 5D (17%), and CKD 5T (14.8%). Thirty-two of 61 patients with symptomatic COVID-19 and 9/27 asymptomatic patients were admitted for median 10 (interquartile range 7-15) days. Seventeen (19.3%) patients developed moderate or severe COVID-19. Systemic complications, observed in 30 (34.1%), included acute kidney injury (AKI, 34.2%), COVID-19 pneumonia (15.9%), unrelated pulmonary disease (2.3%), and shock (4.5%). Nineteen (21.6%) had severe complications (AKI stage 2-3, encephalopathy, respiratory failure, shock). Eight (11%) of twelve (16.4%) patients with severe AKI required dialysis. Three (3.4%) patients, two with steroid-resistant nephrotic syndrome in relapse and one with CKD 1-4, died due to respiratory failure. Univariate logistic regression indicated that patients presenting with nephrotic syndrome in relapse or moderate to severe COVID-19 were at risk of AKI (respective odds ratio, 95%CI: 3.62, 1.01-12.99; 4.58, 1.06-19.86) and/or severe complications (respective odds ratio, 95%CI: 5.92, 1.99-17.66; 61.2, 6.99-536.01). CONCLUSIONS: Children with CKD presenting with moderate-to-severe COVID-19 or in nephrotic syndrome relapse are at risk of severe complications, including severe AKI and mortality. A higher resolution version of the Graphical abstract is available as Supplementary information.

Clinical and Histopathological Profile of Adolescent onset Idiopathic Nephrotic Syndrome in North Indian Children.

Adolescent onset idiopathic nephrotic syndrome (INS) is marked by increased incidence atypical features and non-minimal change disease in histopathology. The objective of the study was to analyze the clinical features and histopathological spectrum of adolescent-onset INS. It was conducted in a Pediatric nephrology clinic of a tertiary care hospital in North India. We retrospectively evaluated clinical features, biochemical investigations and histopathology of 33 adolescents with idiopathic NS registered in pediatric nephrology clinic. Twenty-three (70.0%) adolescents had steroid resistant nephrotic syndrome. Hematuria was present in 39%, hypertension 36% and acute kidney injury (AKI) in 27%. Three-fourth of adolescents who underwent biopsy had non-minimal change disease in histopathology. Adolescent onset INS have increased incidence of AKI, hypertension, and non-minimal change disease.

TELEPRO: Patient-Reported Carcinoid Syndrome Symptom Improvement Following Initiation of Telotristat Ethyl in the Real World.

BACKGROUND: When carcinoid syndrome (CS) diarrhea (CSD) is inadequately controlled with long-acting somatostatin analogs (SSAs), clinical practice guidelines recommend addition of the tryptophan hydroxylase inhibitor telotristat ethyl (TE). In a 12-week multinational, randomized controlled trial, TE added to SSA reduced peripheral serotonin and the frequency of CSD. We evaluated real-world effectiveness of TE using patient-reported data from a nurse support program over 3 months. MATERIALS AND METHODS: This study used a deidentified data set of patients initiating TE who opted into a nurse support program between March and November 2017 and reported CS symptom burden at baseline and at least one follow-up time point at months 1, 2, and 3. Patients reported demographic and medical history information as well as frequency of bowel movements (BMs) and flushing episodes, severity of nausea, urgency and abdominal pain (0 "no/not at all" to 100 "worst imaginable/very urgent"), and stool form (1 "very hard" to 10 "watery"). Mean changes from baseline in CS symptom burden were reported using paired-sample t tests and Wilcoxon signed-rank tests. RESULTS: Most patients initiating TE enrolled in the nurse program (791/898, 88%), of whom 369 (47%) were included in the analysis. Patients treated with TE reported significant reductions in CSD and other CS symptoms (all p < .001). At least half of patients treated with TE experienced ≥30% improvement from baseline in BM frequency and an average reduction of at least two BMs per day within 3 months. CONCLUSION: Patients taking SSA therapy showed substantial burden of disease before initiating TE and significant improvements with the addition of TE treatment in this real-world effectiveness study. IMPLICATIONS FOR PRACTICE: Patients with carcinoid syndrome diarrhea uncontrolled by high doses of long-acting somatostatin analogs may be candidates for additional therapy with the tryptophan hydroxylase inhibitor telotristat ethyl. Understanding the real-world prevalence of uncontrolled symptoms and the effectiveness of telotristat ethyl in clinical practice may further support clinical and policy decisions for these patients. This study investigated self-reported carcinoid syndrome symptom burden and improvements among patients initiating telotristat ethyl and participating in a voluntary nurse support program. Disease burden and off-label somatostatin analog treatment before initiating telotristat ethyl were high, and symptoms improved markedly over 1, 2, and 3 months of treatment.

Mycophenolate Sodium for Children with Frequently Relapsing or Steroid Dependent Nephrotic Syndrome.

In this retrospective study, patients with idiopathic frequently-relapsing nephrotic syndrome (FRNS) (n=27) and steroid dependent nephrotic syndrome (SDNS) (n=13) who received enteric coated mycophenolate sodium (ECMS) for at least 6 months, were included for analysis. Primary outcome was response to ECMS, which was defined as complete if there were no relapses, partial response if there was 1 relapse and no response if there were 2 or more relapses within 6 months of initiation. The mean (SD) dose of ECMS was 985.24 (190.82) mg/m2/day. Thirty patients(75%) had complete response, eight (20%) had partial and two (5%) patients did not respond at 6 months. ECMS seems to be a safe and effective as steroid sparing agent in children with FRNS/SDNS.

Proteinuria in HIV-infected Indian children.

Chronic kidney disease (CKD) is a major cause of morbidity and mortality among individuals with HIV infection. Screening for proteinuria in HIV-infected children will help in early detection and treatment, and thus prevention and progression to CKD to end-stage kidney disease (ESRD). We screened 139 HIV-infected children aged 18 months to 18 years for proteinuria by urinary dipstick and confirmed by spot urine protein-to-creatinine ratio. If proteinuria was absent by the above methods, patients were screened for microalbuminuria by urinary albumin to creatinine ratio. We found proteinuria in 11.5% and microalbuminuria in 10.6% of our study population. The prevalence of proteinuria was higher in the advanced stages; 8.05% in stage 1, 12.12% in stage 2 and 26.32% in stages 3 + 4.

Meningitis and intracranial bleed in a child with steroid-resistant nephrotic syndrome.

Meningitis and associated intracranial bleeding have been rarely reported in patients with steroid-resistant nephrotic syndrome. We present such a case with raised intracranial tension in a 13-year-old child and discuss the management issues. Prompt recognition and appropriate treatment of these complications can be life saving in a child with nephrotic syndrome.

Circular right upper quadrant mass, not intussusception.

Point-of-care ultrasound is fast becoming a routine diagnostic tool in the pediatric emergency department, including in resource-limited settings. We describe a case where a patient was initially diagnosed with intussusception and admitted to a hospital. While serving as a patient model for a point-of-care ultrasound course, he was found to have a liver abscess. We discuss the manner in which the ultrasound study for ileocolic intussusception is performed and potential mimickers of ileocolic intussusception.

Endothelial dysfuntion in children with idiopathic nephrotic syndrome.

BACKGROUND: Impaired endothelial function is the initial step in atherogenesis, which is largely responsible for ischaemic heart disease and thrombotic strokes decades later. METHODS: Fourty two children with first episode nephrotic syndrome (FENS) aged 1-16 years and 40 controls were enrolled. Soluble thrombomodulin (sTM), tissue plasminogen activator (t-PA), plasminogen activator inhibitor -1 (PAI-1) and von-willebrand factor (vWF) levels were measured in plasma in FENS, at 12 weeks of drug induced remission and in steroid resistant nephrotic syndrome (SRNS) patients at diagnosis. RESULTS: PAI-1, sTM, vWF and t-PA were significantly raised at the onset of nephrotic syndrome (p<0.0001). All the markers had a fall after 12 weeks of steroid treatment, but were still raised. Children with SRNS had higher levels of sTM, tPA, vWF as compared to infrequent relapsers, at onset and at 4 weeks of steroid treatment. CONCLUSION: Children with idiopathic nephrotic syndrome have endothelial dysfunction which is largely dependent upon disease activity.

Homocysteine metabolism in children with idiopathic nephrotic syndrome.

BACKGROUND: Homocysteine metabolism is altered in children with idiopathic nephrotic syndrome. Hyperhomocysteinemia is a risk factor of early atherosclerosis and glomerulosclerosis and may occur at time of first occurrence of idiopathic nephrotic syndrome. METHODS: Thirty children with first episode of idiopathic nephrotic syndrome (FENS) aged 1-16 years along with 30 age- and sex-matched healthy controls were enrolled in this study. Homocysteine and cysteine were measured with HPLC; vitamin B12 and folic acid were measured with electro-chemilumiscence immunoassay. Primary outcome measure was plasma homocysteine level in children with FENS and in controls. Secondary outcome measures were (1) plasma and urine homocysteine and cysteine levels in children with FENS at 12 weeks and 1 year (remission) and (2) plasma and urine levels of vitamin B12 and folic acid in children with FENS, at 12 weeks and 1 year (remission). RESULTS: Plasma homocysteine and cysteine levels were comparable to controls in children with FENS, at 12 weeks and 1-year remission. Plasma levels of vitamin B12 and folic acid were significantly decreased compared to controls in FENS due to increased urinary excretion, which normalize during remission at 12 weeks and 1 year. Urinary homocysteine and cysteine levels were significantly raised in FENS compared to controls and continued to be raised even at 12-week and 1-year remission. CONCLUSION: Homocysteine metabolism is deranged in children with FENS. Renal effects of long-term raised urinary homocysteine levels need to be studied.

Subclinical non-autoimmune hypothyroidism in children with steroid resistant nephrotic syndrome.

BACKGROUND: Thyroid status has not been studied well in children with steroid resistant nephrotic syndrome (SRNS). METHODS: In this cross sectional study we recruited 20 children aged 1-16 years with SRNS and similar number of controls. Serum levels of FT3, FT4 and TSH were measured in all the subjects. Overt hypothyroidism was defined as low FT4 (normal values: 0.7-2.0 ng/mL) and elevated serum TSH above reference values (0.45-4.5 mIU/L). Subclinical hypothyroidism (SH) was defined as an elevation in serum TSH with a normal serum FT4 concentration. The primary outcome measure was serum levels of FT3, FT4 and TSH in children with SRNS. RESULTS: Thirty per cent of the children (n = 6) with SRNS had non-autoimmune subclinical hypothyroidism (2 children each with grade I, II and III). Children with SRNS had a median TSH value [3.9 mIU/L (0.5-13)] within normal range, but levels were high as compared to controls. Out of 6 children with SH, 3 were in partial remission, 3 were in complete remission. The TSH levels normalized on thyroxine supplementation in grades II and III subclinical hypothyroidism. CONCLUSION: Subclinical non-autoimmune hypothyroidism is present in a significant proportion of children with SRNS despite partial or complete remission. Thyroid profile should be evaluated routinely in this subset of patients.