Trends in the profile of non hodgkins lymphoma in North and South India: a study from two tertiary care hospitals in India

Background: A number of environmental and chemical factors have been thought to been implicated in the occurrence of Non-Hodgkin’s Lymphomas (NHLs).To fill the knowledge gap in various aspect of the disease, this study was undertaken at this tertiary care centre in Delhi and Bangalore.Methods: This was a prospective observational study conducted in two defenses medical centre in India among patients of Non Hodgkins Lymphoma, registered at Command hospital Airforce Bangalore and Army Hospital (Research and Referral), New Delhi, between March 2016 and March 2019.Results: The disease showed a bimodal onset in both centres with 26 (26%) and 24 (24%) cases occurring in the age group of 31-40 years and 24 (24%) and 25 (25%) cases occurring in the age group of >60 years at CHAF (B) and AH (RR) respectively. B cell Lymphoma was the most common type of NHL seen in 85% and 89% patients, whereas T-cell lymphomas constituted 13% and 11% at CHAF (B) and AH (RR).  32(32%) patients presented with an Ann Arbor Stage 1 or 2 disease whereas 68(68%) patients were with Stage 3 or 4 disease at both the centers. IPI score was ≥3 in 45 % and 43% patients.Conclusions: NHL in India is a homogeneous and uniform disease. But there was increased detection of hepatosplenomegaly and associated hepatitis B/C in the southern part of India. Also, the occurrence of Cutaneous T cell lymphoma was only seen in the south India centre. The early stage NHLs has better survival and increase chance of complete response.

Lefamulin: novel pleuromutilin drug for community acquired bacterial pneumonia

The advent and spread of antimicrobial resistance has led to a global public health emergency necessitating development of new antimicrobial drugs. Community acquired bacterial pneumonia (CABP) contributes a major portion of societal burden with increasing morbidity due to evolution of drug resistant strains. Lefamulin is a novel pleuromutilin antibiotic with unique mechanism of action through inhibition of protein synthesis by binding to the peptidyl transferase center of the 50s bacterial ribosome. The drug displays activity against Gram positive and atypical organisms associated with CABP (i.e., Streptococcus pneumoniae, Haemophilus influenzae, Mycoplasma pneumonia, Legionella pneumophila, and Chlamydophila pneumoniae), with an expanded Gram-positive spectrum including Staphylococcus aureus (i.e., methicillin-resistant, vancomycin-intermediate, and heterogeneous strains). Lefamulin is available in both intravenous (IV) and per oral (PO) formulation, exhibits high nonlinear plasma protein binding with low unbound concentrations, higher concentrations in lung epithelial lining fluid (ELF) than in plasma, and a half-life of approximately 10 hour. The recommended IV dose is 150 mg twice daily over 1 hour or a PO dose of 600 mg twice daily. Most common adverse drug reactions injection site reactions, hepatic enzyme elevation, nausea, diarrhoea, hypokalemia, insomnia, and headache. Clinical trials for lefamulin have been positive and Phase 3 data suggest similar efficacy when compared to moxifloxacin with or without linezolid in CABP. Also, the documented resistance and cross-resistance with other Gram-positive antibacterials remains low. With Nabrivia Pharmaceuticals having already received US FDA approval in August 2019, lefamulin may soon be a new addition to the mounting armoury of drugs against CABP.

Side scatter versus CD45 flow cytometric plot can distinguish acute leukaemia subtypes.

Background & objectives: Flow cytometry is an important tool to diagnose acute leukaemia. Attempts are being made to find the minimal number of antibodies for correctly diagnosing acute leukaemia subtypes. The present study was designed to evaluate the analysis of side scatter (SSC) versus CD45 flow dot plot to distinguish acute myeloid leukaemia (AML) from acute lymphoblastic leukaemia (ALL), with minimal immunological markers. Methods: One hundred consecutive cases of acute leukaemia were evaluated for blast cluster on SSC versus CD45 plots. The parameters studied included visual shape, CD45 and side scatter expression, continuity with residual granulocytes/lymphocytes/monocytes and ratio of maximum width to maximum height (w/h). The final diagnosis of ALL and AML and their subtypes was made by morphology, cytochemistry and immunophenotyping. Two sample Wilcoxon rank-sum (Mann Whitney) test and Kruskal-Wallis equality-of-populations rank tests were applied to elucidate the significance of the above ratios of blast cluster for diagnosis of ALL, AML and their subtypes. Receiver operating characteristic (ROC) curves were generated and the optimal cut-offs of the w/h ratio to distinguish between ALL and AML determined. Results: Of the 100 cases, 57 of ALL and 43 cases of AML were diagnosed. The median w/h ratio of blast population was 3.8 for ALL and 1 for AML (P<0.001). ROC had area under curve of 0.9772.The optimal cut-off of the w/h ratio for distinction of ALL from AML was found to be 1.6. Interpretation & conclusions: Our findings suggest that if w/h ratio on SSC versus CD45 plot is less than 1.6, AML may be considered, and if it is more than 1.6, ALL may be diagnosed. Using morphometric analysis of the blast cluster on SSC versus CD45, it was possible to distinguish between ALL and AML, and their subtypes.

Heparin Co-factor II Thrombin Complex as a Biomarker for Mucopolysaccharidosis: Indian Experience.

Background: Serum heparin cofactor II-thrombin complex (HCII-T) is an emerging biomarker for mucopolysaccharidosis disease (MPS I and MPS II). Methods: Seventeen cases (6 MPS I and 11 MPS II) and sixty healthy controls were enrolled in study, conducted from September 2008 to December 2012. The mean ± SD age of MPS1 (n=6, 5 males) and MPS II was 7.02 ± 3.25 and 5.2 ± 2.15 years, respectively. Disease status was confirmed by clinical features and enzyme assay. Urinary glycosaminoglycans were measured in spot urine samples and expressed in relation to creatinine content. HCIIT measurement was done using sandwich ELISA at enrolment and after 12 and 24 months of recruitment. Results: Urinary glycosaminoglycans and HCIIT were elevated in all patients compared to their healthy controls. Both markers could not discriminate between the type of mucopolysaccharidosis. Conclusion: Heparin Cofactor II Thrombin Complex is a good biomarker for mucopolysaccharidosis I and II.

Consensus Statement of the Indian Academy of Pediatrics on Integrated Management of Severe Acute Malnutrition.

Justification: Severe acute malnutrition (SAM) is a major public health issue. It afflicts an estimated 8.1 million under-five children in India causing nearly 0.6 million deaths. The improved understanding of pathophysiology of SAM as well as new internationally accepted growth charts and newer modalities of integrated intervention have necessitated a relook at IAP recommendations. Process: A National Consultative Meeting on Integrated Management of Severe Acute Malnutrition was held in Mumbai on 16th and 17th October, 2010. It was attended by the invited experts in the field. Extensive discussions were held as per the program. The participants were then divided into six groups for detailed discussions. The groups deliberated on various issues pertaining to the task assigned and presented recommendations of the groups in a plenary session. The participants made a list of recommendations after extensive discussions. A Writing Committee was formed and was entrusted with the task of drawing a Consensus Statement on the basis of these Recommendations. After multiple deliberations, the following Consensus Statement was adopted. Objectives: To critically evaluate the current global evidence to formulate a consensus among stakeholders regarding diagnosis and management of SAM. Recommendations: An integrated management of malnutrition is likely to yield more dividends. Thus, management of SAM should constitute an important component of Integrated Management of Neonatal and Childhood Illnesses (IMNCI) program. Determination of SAM on the basis of Z-scores using WHO Growth charts is considered statistically more appropriate than cut-offs based on percentage weight deficit of the median. Considering the fact that many children with SAM can be successfully managed on outpatient basis and even in the community, it is no more considered necessary to advise admission of all children with SAM to a healthcare facility. Management of SAM should not be a stand-alone program. It should integrate with community management therapeutic programs and linkages with child treatment center, district hospitals and tertiary level centers offering inpatient management for SAM and include judicious use of ready-to-use-therapeutic Food (RUTF). All sections of healthcare providers need to be trained in the integrated management of SAM.

Prevalence of celiac disease in north indian children.

Celiac disease (CD) is being increasingly reported from the wheat-eating population of north India. However, the exact prevalence of CD in children is not known as population screening studies are scarce. Our study aimed to determine the prevalence of CD in 400 children, 6 months to 12 years of age attending pediatrics department of a tertiary care hospital in north India. The study population was screened for anti-tissue transglutaminase (tTG) antibodies. Endoscopic duodenal biopsy was done in the anti–tTG positive subjects. Four patients were diagnosed with CD as per the modified ESPGHAN criteria. The prevalence of CD thus was 1%, which was in concordance with screening studies using serological markers conducted in the West.

Current trends in the management of beta thalassemia.

The management of Beta Thalassemia, the commonest form of hemolytic anemia in children, has changed significantly in the last few years. With the availability of better transfusion regimen, iron chelation therapy, proper management of complications and good supportive care, it is now possible for a thalassemic child to have a near normal life span with a good quality of life.

Deferasirox: the new oral iron chelator.

Deferasirox is a new tridentate oral iron chelator developed by computer remodeling recently approved by FDA for children above 2 years. Phase II/III trials have demonstrated similar efficacy to desferrioxamine and better chelation efficiency. Adverse events were minor and growth remained unaffected. Data on cardiac iron chelation is limited although some studies have shown it comparable to deferiprone. The benefit to risk profile of deferasirox is favorable. This promising new drug might decrease the burden of subcutaneous or intravenous infusion improving compliance and hence the life expectation in thalassemic patients.

Safety and reactogenicity of a low dose diphtheria tetanus acellular pertussis vaccine (Boostrix) in pre-school Indian children.

OBJECTIVE: To evaluate the safety and reactogenicity of a reduced-antigen-content combined Diphtheria Tetanus Acellular Pertussis (dTpa) vaccine in Indian preschool children. METHODS: GlaxoSmithKline Biologicals combination dTpa vaccine was administered as a single booster dose to 347 children aged 46 years in seven centers across India. All children were subsequently followed up for two weeks for safety and reactogenicity assessment. RESULTS: A total of 345 subjects completed the study and two subjects were lost to follow-up. One serious adverse event (head injury) unrelated to vaccination was reported. Otherwise, all subjects were in good health throughout the study period. Three subjects (0.9%) reported transient general symptoms (such as irritability and drowsiness), which prevented normal activity. Pain at injection site, swelling and redness was reported in 31.1%, 18.2% and 8.9% subjects respectively. Five subjects (1.4%) reported severe pain preventing normal movement. This resolved within 48 hours in all cases. There were no other severe local reactions including large injection site reactions. CONCLUSION: The reduced antigen content combined dTpa vaccine is safe and well tolerated in Indian pre-school children.

Peripheral gangrene: an uncommon manifestation of disseminated tuberculosis.

Peripheral gangrene as a manifestation of tuberculosis is very uncommon. An 8 year old male child presented with non-healing ulcer over the sole of left foot, left inguinal tubercular lymphadenopathy with scrofloderma, tubercular pleural effusion and gangrene of the right fore foot. The child improved on antitubercular treatment.

Anti-HCV seropositivity among multiple transfused patients with beta thalassaemia.

Hepatitis C virus is considered to be the main aetiological agent responsible for the occurrence of post-transfusion hepatitis. Patients with thalassaemia acquire hepatitis most often from viruses contracted through blood transfusions. The present study was undertaken to evaluate the prevalence of hepatitis C virus (HCV) in thalassaemic patients with multiple blood transfusions. The association of HCV seropositivity with number of blood transfusions and liver enzyme profile was also analysed. The study group consisted of fifty patients (40 males and 10 females) attending the thalassaemic unit of Lok Nayak Hospital, a tertiary care hospital at Delhi, within the age group of 1-25 years. Thirty patients (60%) were found to be seropositive for HCV antibodies while one patient (2%) was co-infected with HCV antibodies and hepatitis B surface antigen. Study of liver enzyme profile showed aspartate aminotransferase levels to be significantly higher, although the level of serum alanine aminotransferase, alkaline phosphatase, total protein, bilirubin and albumin were not significantly altered in these patients. It is inferred from this study that 60% of the thalassaemics were infected with HCV and this was directly related to the number of blood transfusions received by them. The regularised national blood policy followed by blood banks for providing safe blood along with better screening method of donated blood in blood banks would bring down the incidence of hepatitis C in such high risk group.

Nutritional parameters in children with malignancy.

Nutritional status of 44 children with newly diagnosed malignancy was evaluated by anthropometric, hematological and biochemical parameters before initiating therapy and response to therapy was assessed during follow up. Malnutrition was seen in 56.8% children by weight for age criteria (WFA <-2 z). Low hemoglobin was found in 82% children, 25% had low total proteins (<5.7 g/dL), 20.5% low serum albumin (<3.2 g/dL), 27.3% low serum transferrin (<210 mg/dL) and 16.3% low serum iron (<60 ug/dL). Mean anthropometric and biochemical parameters were higher among the survivors compared to non-survivors. Significant difference between the well nourished and the malnourished group was detected in the achievement of remission/response (69.5% vs 38.1%), delays in therapy (8. 7% vs 38.1%) and mortality (30.5% vs 61.9%). Complications like febrile neutropenia and bleeding were more in the malnourished group. A statistically significant higher incidence of infection was seen in children with serum iron<60 ug/dL than those with higher values of serum iron (42.8% vs 8%). Malnutrition is a major determining factor in treatment planning, complication rates, response to therapy and survival.

Measles, mumps, rubella (MMR) vaccine.

MMR is a live attenuated vaccine. Indian children show almost 90% seroconversion against measles and rubella and 90% against mumps. Several adverse effects have been reported. Epidemiological studies do not support a causative link between MMR and autism, IBD or GBS. There is an association between the Urabe strain of mumps vaccine and viral meningitis. Vaccine associated thrombocytopenia has been reported. Severe hypersensitivity reactions occur, mainly due to the gelatin component. Outbreaks of measles occur in areas of high measles vaccine coverage, when susceptible individuals accumulate. A second dose is given mainly to vaccinate those who missed the first dose or had primary vaccine failure, rather than to boost waning antibody levels. The possibility or eradication of mumps with a second dose of mumps vaccine is being considered.

Febrile episodes in childhood malignancies.

The objectives of the present report were to study the site of infections and pathogenic organisms during febrile episodes in different childhood malignant conditions, to correlate febrile episode with Absolute Neutrophil Count (ANC) and to know the sensitivity pattern of bacteria to different antibiotics so as to know the most appropriate antibiotic regimen in these children. The study material comprised of forty two febrile episodes occurring in children aged lt 12 years with various malignancies. All the episodes were worked up in detail including complete history, physical examination and relevant hematological, microbiological and radiological investigations. Out of the 42 episodes, 15 (36%) occurred in children with acute leukemias, 20 (48%) in children with lymphomas and 7(17%) in children with solid tumors. 26 (62%) episodes were seen in children during chemotherapy, while 12% each in freshly diagnosed and remission and 14% in relapse cases. 12 (28%) episodes occurred in children with ANC < 500/mm3. 36% were microbiologically confirmed. Klebsiella species was the commonest organism isolated followed by E. coli. Maximum sensitivity (75%) was seen with ciprofloxacin against both Klebsiella species and E.coli.