Proceedings of the 3rd Indian Cancer Genome Atlas Conference 2022: Biobanking to Omics: Collecting the Global Experience.

On January 13th and 14th 2022, the Center for Translational Cancer Research organized the virtual third Indian Cancer Genome Atlas (ICGA) Conference 2022 "Biobanking to Omics - Collecting the Global Experience." This conference was planned as the steppingstone to help ICGA understand the road ahead and the probable roadblocks in its preparatory phase as ICGA begins to streamline the tumor tissue biobanking and multi-omics efforts in the Indian subcontinent. The first day of the conference was dedicated to updates on the current status of ICGA, the future prospect, and the global understanding of multi-omics efforts. The key highlights included two keynote speeches by Dr Wui Jin Koh, Senior Vice President and Chief Medical Office, National Comprehensive Cancer Network, and by Dr Christina Curtis, Associate Professor, Stanford University School of Medicine. The first day ended with an intriguing panel discussion on "ICGA updates and Future Steps." The second day focused on biobanking practices across the globe and several aspects of biobank setup such as infrastructure, maintenance, quality control, patient consent, and lessons learned from established biobanking setups. The talk by Rosita Kammler, Head, Translational Research Coordination, International Breast Cancer Study Group, Switzerland, and Ruhul Amin, Director, Bangladesh Medical Research Council were the key highlights. The second day also ended with an engaging panel discussion on "Tumor tissue biobanking - national and international perspectives." Overall, the conference was well received and had good attendance from national and international students, researchers, and faculty from academia as well as industry.

Once-a-Day Ceftriaxone-Amikacin Combination as Empiric Antibiotic Therapy to Enable Outpatient Management of Febrile Neutropenia in Children-16-Year Experience from a Single Institute.

Shailesh KanvindeBackground To enable outpatient department (OPD) management of febrile neutropenia (FN), we used once-a-day (OD) ceftriaxone-amikacin (CFT-AMK) as empiric antibiotic therapy. Our experience over 16-year period is presented. Methods This was a retrospective study conducted from January2002 to December2017. Inclusion criteria were <18 years of age, undergoing cancer chemotherapy, and having FN. Exclusion criteria were FN after palliative chemotherapy, bone marrow transplantation, or at diagnosis of malignancy. Empiric CFT-AMK was used in all, except those having respiratory distress, hypotension, altered sensorium, paralytic ileus, or clinical evidence of peritonitis. Admission criteria were age <1 year, acute myeloid leukemia (AML) chemotherapy, poor performance status, need for blood transfusions, convenience, insurance, or persistent fever >48 to 72 hours after CFT-AMK. Outcomes analyzed were response (defervescence within 48-72 hours), OPD management, antibiotic upgrade, and mortality. AML diagnosis, >7 days to absolute neutrophil count >0.5 × 10 9 /L, poor performance status, and malignancy not in remission were considered high-risk FN criteria. Results CFT-AMK was given in 877/952 (92.2%) FN episodes. Seventy-six percent had hematolymphoid malignancies. Response, antibiotic upgrade, and mortality were seen in 85.7 and 65.5% ( p < 0.0001), 15 and 45.5% ( p < 0.0001), and 0 and 2% ( p = 0.003) of low- and high-risk patients, respectively. Treatment was started in OPD in 52%, of which 21.6% required subsequent admission. Of those initially admitted, early discharge (hospital stay < 5 days) was possible in 24.6%. Forty-one percent episodes were managed entirely on OPD. Overall, 80% of low-risk and 42% of high-risk episodes received treatment wholly or partially on OPD. Conclusion Our results show empiric OD CFT-AMK allows OPD management for most of the low-risk and a proportion of high-risk FN following chemotherapy in children, without compromising clinical outcomes.

Self-reported Wheat Sensitivity in Irritable Bowel Syndrome and Healthy Subjects: Prevalence of Celiac Markers and Response to Wheat-free Diet.

BACKGROUND/AIMS: Most patients with irritable bowel syndrome (IBS) report food-related aggravation of symptoms. Wheat/gluten is one of the most commonly incriminated. We studied the prevalence of self-reported wheat sensitivity in patients with IBS and in a healthy population from a region in India consuming mixed-cereal diets, correlated it with serological and human leukocyte antigen (HLA) markers of celiac disease, and evaluated the response to a wheat-free diet. METHODS: We surveyed 204 patients with IBS and 400 healthy persons for self-reported wheat sensitivity. Testing for IgA anti-tissue transglutaminase and HLA DQ2 or DQ8 was done in individuals who reported wheat sensitivity. Consenting persons with wheat sensitivity were put on wheat-free diet and monitored for symptom change. RESULTS: Twenty-three of 204 patients with IBS (11.3%) and none of the healthy subjects self-reported wheat sensitivity. Of 23 patients, 14 (60.9%) were positive for HLA DQ2 or DQ8 and none for anti-tissue transglutaminase antibody. After 6 weeks on wheat-free diet, all 19 participating patients reported clinical improvement; fewer patients had bloating, diarrhea, constipation, and easy fatigue. CONCLUSIONS: Eleven percent of patients with IBS self-reported wheat sensitivity. None of them had positive celiac serology; 60.9% were positive for HLA DQ2 and DQ8, suggesting a possible genetic basis. All of them improved symptomatically on a wheat-free diet.

Molecular epidemiology of Canine parvovirus shows CPV-2a genotype circulating in dogs from western India.

Canine parvovirus (CPV) has emerged as an acute pathogen of young canine causing haemorrhagic enteritis and myocarditis. It is widely distributed and underreported in India. Therefore the study was conducted to type the CPV circulating in western Maharashtra. The faecal samples (n = 150) from clinically ill dogs showing diarrhoea and vomition were collected and subjected to haemagglutination (HA) with porcine RBC's. The DNA was extracted from the samples showing HA titres above 64 and subjected for amplification of VP2 gene fragment by PCR. The amplicons were subjected for restriction fragment length polymorphism (RFLP), sequencing and BEAST phylogenetic analysis. The results revealed 6% positivity by PCR. The RFLP results indicated single cleavage site for ApaLI and HinfI with an exception of two sites for HinfI. The nucleotide sequences showed nonfunctional nucleotide changes at different locations. The sequence analysis indicated that the nucleotide divergence within isolates under study was 0.00-0.42%, while the nucleotide homology was 99.58-100%. The most recent common ancestor was determined by molecular clock analysis using Bayesian methods. The sequence and phylogenetic analysis suggested the isolates as CPV-2a and KATN1 (KU866391, 2014) isolate from Tamilnadu, India as time to most recent common ancestor (TMRCA). The results revealed the circulating CPV in canines from western India as CPV2a genotype.

Anti-M antibodies: Biphasic (reactive at room temperature and at 37°C): A case series.

Anti-M antibody, which is not reactive at 37°C, is not clinically significant. Reports of clinically significant anti-M antibodies causing hemolytic disease of the fetus and the newborn (HDFN) and delayed hemolytic transfusion reaction (DHTR) are available. We report 13 cases of anti-M antibodies reactive at room temperature (RT) and at 37°C. These were found in patients of varied age groups (11 months to 85 years) with varied clinical diagnosis. All the female patients were multigravida. In all cases, antibody screening was positive at RT as well as at the indirect antiglobulin test (IAT) phase. Providing "M"-antigen negative transfusions is the best therapy in this situation. Provision of red blood cell (RBC) antigen phenotyped donor registry shall ensure quick provision of antigen-negative blood for transfusion in emergency situations.

Data structure and movement for lattice-based simulations.

We show that for the lattice Boltzmann model, the existing paradigm in computer science for the choice of the data structure is suboptimal. In this paper we use the requirements of physical symmetry necessary for recovering hydrodynamics in the lattice Boltzmann description to propose a hybrid data layout for the method. This hybrid data structure, which we call a structure of an array of structures, is shown to be optimal for the lattice Boltzmann model. Finally, the possible advantages of establishing a connection between group theoretic symmetry requirements and the construction of the data structure is discussed in the broader context of grid-based methods.

HGV-HCV/HBV co-infection in India: A pilot study.

BACKGROUND: Hepatitis G virus (HGV) is newly identified virus, transmitted by infected blood and blood products. Effect of HGV infection on liver diseases is not well known. AIMS: Co-infection of HGV with hepatitis B virus (HBV) and hepatitis C virus (HCV) infection has been reported however; very limited data is available from India. Therefore, we have performed a pilot study for the presence of co-infection of HGV in chronic liver disease patients. SETTING AND DESIGN: The study was performed in research laboratory at P.D. Hinduja National hospital and Medical research center, Mahim, Mumbai. Prospective study was designed. METHODS AND MATERIALS: Forty HBV, HCV related chronic liver disease patients were studied. Forty randomly selected voluntary healthy blood donors visiting our blood bank were included as controls. Serum bilirubin, alanine aminotransferase (ALT), Aspartate aminotransferase (AST) and alkaline phosphatase (ALP) were estimated. HGV infection was detected by using reverse transcriptase molony murine leukemia virus (M-MLV) with the help of HGV 340/625IC kit (Sacace, Italy). RESULTS AND CONCLUSION: One HCV positive patient had infection with HGV among 40 HBV/HCV chronic liver disease patients.

Balancing efficacy and bleeding risk in the prevention of stroke due to atrial fibrillation with newer oral anticoagulants.

With the evaluation and approval of newer oral anticoagulants such as the factor IIa inhibitor, dabigatran etexilate and the factor Xa inhibitors, rivaroxaban and apixaban, strategies for stroke prevention in atrial fibrillation need a thorough re-evaluation of current options. Clinicians are naturally excited about the imminent introduction of these newer drugs that do not need international normalized ratio (INR) monitoring, besides having no drug-food and minimal drug-drug interactions. However, as with all new drugs, it is always prudent to use these judiciously so that they stay in our therapeutic armamentarium for a long time. More than 56 years after the introduction of warfarin we now have three drugs, viz., dabigatran 150 mg bid, rivaroxaban 20 mg od, and apixaban 5 mg bid which were effective in comparison with warfarin in reducing the risk of stroke and bleeding in the landmark trials, RE-LY, ROCKET-AF, and ARISTOTLE respectively. There is a thin dividing line between physiological hemostasis and pathological thrombosis. Routine INR monitoring may not be required but in special situations, such as prior to major surgery, overdose, non-compliance or stroke while on the anticoagulant, one may wish to know whether there are any laboratory measures of efficacy or means of reversal of over anticoagulation. Similar questions may be raised about other situations such as renal dysfunction, cardioversion, ablation procedures, post-stenting, or switch to and from warfarin, heparin or LMWH? This document is an attempt to address these concerns based on available evidence and give physicians a perspective and practice guidelines on how best to use these agents, both old and new, for optimal patient outcomes, maximizing efficacy and minimizing risk.

Correlation of HLA B27 subtypes with clinical features of ankylosing spondylitis.

AIM: The aim of the present study was to identify the B*27 subtypes associated with ankylosing spondylitis (AS) in our population and correlate them with clinical features of AS. METHOD: Whole blood samples were collected from 81 HLA-B27 positive AS patients and 29 controls (asymptomatic healthy unrelated individuals) positive for HLA-B27. Clinical details of the patients were recorded which included history of inflammatory back pain, sacroiliitis, spine involvement, enthesitis, peripheral arthritis and uveitis. HLA-B27 subtypes were detected using commercially available techniques. Fisher's exact test was used for statistical analysis. RESULTS: The subtypes observed in AS patients were B*2705 (67.9%, 55/81), B*2704 (28.4%, 23/81), B*2707 (2/81) and B*2702 (1/81). Subtypes in the controls were B*2705 (62.07%, 18/29), B*2707 (27.59%, 8/29) and B*2704 (10.34%, 3/29). Uveitis was observed more in B*2704-positive AS patients (34.78%, 8/23) compared to B*2705-positive AS patients (16.36%, 9/55). However, the difference was not statistically significant (P = 0.130). No major differences were found between B*2705 and B*2704 for other clinical features. CONCLUSION: B*2705 was the main subtype observed in both patient and control groups. Frequency of B*2704 was more in AS patients compared to controls. Occurrence of AS-associated uveitis was more often in B*2704-positive AS patients compared to B*2705-positive ones.

Massive retinal gliosis: an unusual case with immunohistochemical study.

Massive retinal gliosis (MRG) is a rare, benign intraocular condition that results from the proliferation of well-differentiated glial cells. Immunohistochemically, these cells show positivity for glial fibrillary acid protein (GFAP), neuron specific enolase (NSE), and S-100 protein. We encountered a case of a 45-year-old female with loss of vision in the left eye. She had a history of trauma to that eye two years ago. Enucleation was carried out, because malignancy was suspected due to retinal calcification. On the basis of light microscopy and immunohistochemistry (IHC) performed on the enucleated eye, it was diagnosed as massive retinal gliosis.

Case of TTP with cerebral infarct secondary to platelet transfusion.

BACKGROUND: Thrombotic thrombocytopenic purpura (TTP) is a rare disease in children with significant mortality in cases who do not receive appropriate treatment. CASE: The author describe a 3-year-old child who presented with skin bleeds, microangiopathic anemia, thrombocytopenia and right sided hemi paresis with aphasia and altered sensorium following platelet transfusion. CONCLUSION: A diagnosis of thrombotic thrombocytopenic purpura was made and the child recovered dramatically after giving fresh frozen plasma and steroids.

Comparative evaluation of efficacy and safety of cefotaxime-sulbactam with amoxicillin-clavulanic acid in children with lower respiratory tract infections.

OBJECTIVE: Beta-lactamase producing bacteria present a major problem in treating lower respiratory tract infections. The objective of this study was to evaluate efficacy and safety of cefotaxime-sulbactam combination versus amoxicillin-clavulanic acid injection as an alternative therapeutic option for treatment of lower respiratory tract infections in pediatric patients. METHODS: This randomized, multicentric, comparative study enrolled 102 inpatients with lower respiratory tract infections, in the age range of 3 months - 12 years. Patients received cefotaxime-sulbactam or amoxicillin-clavulanic acid injection intravenously for up to 7 days. RESULTS: There was no difference between the two groups in demography or disease characteristics (p > 0.05) at baseline. Efficacy was evaluated in a total of 96 patients. Both the treatment groups were comparable in response rate at the end of the therapy (p > 0.05). Clinical success rate was 93.6% and 89.8%, respectively for cefotaxime-sulbactam and co-amoxiclav. One patient from the cefotaxime-sulbactam group reported convulsions, which were probably not related to the study medication in the opinion of the investigator. Except for this serious adverse event, both the study medications were safe and well tolerated in the study population. CONCLUSION: In conclusion, cefotaxime-sulbactam administered 3 times a day for up to 7 days was found to be as effective as co-amoxiclav therapy. However, further studies with a large number of patients are required to confirm these findings with more robust microbiological evaluation.