Splenic Dysfunction in Children With Sickle Cell Disease: A Single Centre Experience From Central India.

OBJECTIVE: To assess the incidence and predictors of splenic dysfunction in children with sickle cell disease (SCD). METHODS: A cross-sectional study was conducted between June 2019 and December 2020 where children aged 1 to 15 years of age with SCD were screened for splenic dysfunction. Children who were splenectomised, those with other diseases known to affect splenic function like congenital malformations, immunodeficiencies, and chronic diseases like tuberculosis, nephrotic syndrome, diabetes mellitus, chronic liver disease, celiac disease or malignancy were excluded. Splenic size was assessed by clinical examination and ultrasonography. Splenic dysfunction was assessed using splenic scintigraphy using Technetium-99m (99mTc) labeled autologous RBCs and by the presence of Howell Jolly bodies in the peripheral smear. Laboratory and clinical predictors of splenic dysfunction were assessed by multiple logistic regression. RESULTS: We evaluated 66 children with SCD with a mean (SD) age of 7.41 (3.3) years. Impaired and absent splenic function as assessed by 99mTc scintigraphy was found in 13 (19.7%), and 3 (4.6%) children, respectively. Howell Jolly bodies in peripheral smear were found in 5 (7.5%) children; 3 of them had abnormal uptake on scintigraphy; all five had splenomegaly. Age > 5 years, > 4 episodes of vaso-occlusive crisis (VOC), > 3 hospitalization events in the past, > 5 blood transfusions, children not receiving hydroxyurea, reticulocyte count > 4%, and HbS > 70% were independent predictors of splenic dysfunction. CONCLUSION: The prevalence of splenic dysfunction in children with SCD in Central India is lower than that reported from the West. The decision to start antibiotic prophylaxis can be individualized in these children.

A Novel Mutation in Cystic Fibrosis Presenting as Pseudo Bartter Syndrome: A Case Report.

Pseudo-Bartter's (PB) syndrome is characterized by hypokalemic metabolic alkalosis and failure to thrive which constitutes a rare but typical presentation of cystic fibrosis (CF) in children. The most common mutation of CF is F508del, due to loss of 3 base pairs, causing deletion of phenylalanine, at position 508. We present a case of CF presenting with failure to thrive, dehydration, PB syndrome associated with urosepsis and primo-colonization with Escherichia coli suggesting the role of epigenetic factors. The heterozygous state for Phe508del mutation in Exon 11 combination with Glu92Ala in Exon 4 resulted in epigenetic effect on atypical phenotype as PBS, a novel mutation identified in our case.

A Real-World Study of Safety, Immunogenicity and Efficacy of Bevacizumab in Patients With Solid Malignancies: A Phase IV, Post-Marketing Study in India.

Objective: The aim of this study was to evaluate the post-marketing safety, tolerability, immunogenicity and efficacy of Bevacizumab (manufactured by Hetero Biopharma) in a broader population of patients with solid tumors. Patients And Methods: This phase IV, prospective, multi-centric clinical study was carried out in Indian patients with solid malignancies (metastatic colorectal cancer, non-squamous non-small-cell lung cancer, metastatic renal cell carcinoma) treated with Bevacizumab between April 2018 and July 2019. This study included 203 patients from 16 tertiary care oncology centers across India for safety assessment, of which a subset of 115 patients who have consented were also evaluated for efficacy and immunogenicity. This study was prospectively registered in the Clinical Trial Registry of India (CTRI), and was commenced only after receiving approval from the competent authority (Central Drugs Standard Control Organization, CDSCO). Results: Out of the 203 enrolled patients, 121 (59.6%) patients reported 338 adverse events (AEs) during this study. Of 338 reported AEs, 14 serious adverse events (SAEs) were reported by 13 patients including 6 fatal SAEs, assessed as unrelated to the study medication and 7 non-fatal SAEs, 5 assessed as related, and 3 unrelated to Bevacizumab. Most AEs reported in this study (33.9%) were general disorders and administration site conditions, followed by gastrointestinal disorders (29.1%). The most frequently reported AEs were diarrhea (11.3%), asthenia (10.3%), headache (8.9%), pain (7.4%), vomiting (7.9%), and neutropenia (5.9%). At the end of the study, 2 (1.75%) of 69 patients reported antibodies to Bevacizumab without affecting safety and efficacy. However, at the end of 12 months, no patient had reported antibodies to Bevacizumab. Complete response (CR), partial response (PR), stable disease (SD), and progressive disease (PD) were reported in 18.3%, 22.6%, 9.6%, and 8.7% of patients, respectively. The overall response rate (CR + PR) was reported in 40.9% of patients at the end of the study. Disease control rate (DCR), also known as the clinical benefit rate (CBR) was reported in 50.4% of patients. Conclusions: Bevacizumab (Cizumab, Hetero Biopharma) was observed to be safe, well tolerated, lacking immunogenicity, and efficacious in the treatment of solid tumors. The findings of this phase IV study of Bevacizumab, primarily as a combination therapy regimen suggest its suitability and rationality for usage in multiple solid malignancies. Clinical Trial Registry Number: CTRI/2018/4/13371 [Registered on CTRI http://ctri.nic.in/Clinicaltrials/advsearch.php : 19/04/2018]; Trial Registered Prospectively.

Cutaneous manifestations associated with COVID-19 in children: A systematic review.

Cutaneous manifestation of COVID 19 in children has not yet been reviewed systematically. Hence, this review gives the clinicians a future direction to be vigilant for skin presentations during pandemics. The Pubmed database used for literature search with keywords COVID 19, children, and skin in different combinations. Articles published in English with cases of age one month to 18 years were eligible. The outcome included varied aspects of cutaneous and COVID 19 infection. The authors did not register review protocol. Of 51 publications identified, 13 studies containing 149 children met the eligibility criteria. Acrally located erythematous maculopapular lesion was the most common finding in 138 children. The researcher reported Erythema multiforme, varicella like exanthem, and Kawasaki disease like presentations in the rest of the cases. The duration of the skin lesion was 1 2 weeks in 43%. Skin biopsy done in 18 patients revealed superficial and deep perivascular and peri eccrine lymphocytic infiltrate and lymphocytic vasculitis. RT PCR was positive13.8% cases. Serological markers for HSV, parvovirus B19 analyzed across various studies, were negative, except positive mycoplasma pneumonia in 2 of 20 cases tested. Clinicopathologic analysis established chilblains like lesion in 43% cases with no confirmed etiology like cold exposure, autoimmune dysfunction, drug reaction, or viral infection. The usual cephalo caudal spread of a viral exanthem was also missing. However, a low number of discussed cases was a limitation of the study. The absence of any confirmed etiology for such cutaneous manifestations, the possibility of COVID 19, should be explored and thoroughly evaluated and isolated during such a pandemic.

Sickle Cell Trait Presenting as Chronic Calcific Pancreatitis with Pseudocyst- A Case Report.

Sickle cell disease is known to cause acute pancreatitis either due to gall stones obstructing the pancreatic duct or by vaso-occlusive mechanism. However chronic pancreatitis is a very rare complication in sickle cell anemia. We report a case of sickle cell trait presenting with chronic pancreatitis with pseudo cyst. USG abdomen and CT abdomen confirmed the diagnosis of chronic calcific pancreatitis with pseudocyst. Etiological work up for other causes did not reveal anything except sickle cell trait. This case represents a rare association between chronic calcific pancreatitis and sickle cell trait.

PET-CT scan-based maximum standardized uptake value as a prognostic predictor in oropharynx squamous cell cancer.

INTRODUCTION: Positron emission tomography with 2-deoxy-2-[fluorine-18]fluoro-D-glucose integrated with computed tomography (18F-FDG PET-CT) is clinically useful and extensively used in initial staging and follow-up of patients with head and neck squamous cell carcinoma (HNSCC). We studied the potential prognostic significance of primary tumor maximum standard uptake value (SUVmax) by 18F-FDG PET-CT in oropharyngeal cancer. METHODS: Sixty patients with early and locally advanced histopathologically proven oropharyngeal squamous cell cancer were staged using FDG PET-CT at diagnosis. All patient received radiation therapy and concurrent chemotherapy (in stage III and IVA disease) and were assessed prospectively for treatment outcome. Groups were created based on stage and cut off for SUVmax. The association of SUVmax of primary tumour and stage with disease-free survival and overall survival was analyzed by univariate and multivariate statistics. RESULTS: In univariate analysis, a primary tumour SUVmax of greater than 13.0 and advanced stage (IVA) predicted inferior disease-free survival (P=0.0241 and 0.0005, respectively) and overall survival (P=0.0510, toward significance and 0.0003, respectively). In proportional hazards analysis, stage was significant only when adjusted for primary SUVmax. CONCLUSION: SUVmax failed to demonstrate predictive significance in oropharyngeal cancer, and an increase in primary tumor uptake is possibly a direct effect of advanced disease and consequently increased metabolic activity and aggressiveness.

Temporal changes in plasma profile of pregnancy-associated glycoprotein, progesterone and estrone sulfate associated with fetal number during early- and mid-pregnancy in goats.

This study was designed to investigate plasma profile of pregnancy-associated glycoprotein (PAG), progesterone (P4) and estrone sulfate (E1S) during early- and mid-pregnancy. The goal was to explore the relationships with values for reproductive variables, to detect the most reliable predictor variable, and to identify the most desirable time point for blood collection for determining fetal number in goats. After ultrasonographic examination at d35-40 post-mating, blood sampling of 15 pregnant goats (total 18) was continued until d114. The PAG profile was characterized by gradual increase during early pregnancy from d26 to d51 and thereafter concentrations were relatively constant until d114 of gestation. The effect of fetal number on plasma PAG, P4 and E1S was first evident on d28, d51 and d26, respectively. During mid-pregnancy, does with twins had a greater (P < 0.05) PAG (S-N = 2.54 ± 0.12 compared with 1.59 ± 0.11), P4 (18.91 ± 0.67 compared with 14.51 ± 0.47 ng/mL) and E1S (16.34 ± 0.76 compared with 11.32 ± 0.44 ng/dL) as compared with does with a singleton fetus. Plasma PAG but not P4 and E1S was positively correlated with fetal number and birth weight of kids during early pregnancy. Multivariate linear regression and discriminant function analyzes allowed for identification of plasma PAG as the most reliable predictor for fetal number and birth weight of kids. Furthermore, d58 was the most suitable single time point for prediction of fetal number using PAG as a biomarker. In conclusion, plasma profile of PAG, P4 and E1S was affected by fetal count. Plasma PAG was identified as the most reliable predictor variable of fetal number and birth weight of kids as compared to plasma P4 and E1S.

Radiofrequency ablation of atrial fibrillation during mitral valve surgery.

Twenty-three patients underwent endocardial radiofrequency ablation of atrial fibrillation (AF) during mitral valve procedures with a previously described left atrial lesion pattern. A temperature-controlled 7-coil surgical probe delivered 60-second lesions at 80 degrees C. The left atrial appendage was oversewn after ablation. Ages ranged from 28 to 88 years. Nineteen patients had chronic AF that was present for over 1 year in 74%; 12 patients had rheumatic mitral stenosis. Mean left atrial diameter was 5.4 +/- 0.7 cm. There was 1 operative death unrelated to the ablation, and no strokes or ablation-related complications were observed. At mean follow-up of 32.5 weeks, 86% of the 22 survivors were in sinus rhythm. All 18 patients with left atrial diameter <6 cm are in sinus rhythm. All postoperative atrial flutter was transient, and no patients required subsequent transcatheter ablation. This lesion pattern is safe and effective when applied in the method described here. It appears to be a reasonable alternative to the complete Maze 3 lesion pattern in patients with mitral valve disease.