Kamalakshi G. Bhat

Significance of interleukin-6 (IL-6) and C-reactive protein (CRP) in children and young adults with febrile neutropenia during chemotherapy for cancer: a prospective study.

Objectives: We evaluated the usefulness of interleukin-6 (IL-6) and C-reactive protein (CRP) at the onset of febrile neutropenia and 72 hours later, in identifying risk groups and assessing response to antibiotic therapy. Methods: All episodes of febrile neutropenia were divided in 3 study groups—microbiologically documented infection (MDI), clinically documented infection (CDI), and fever of unknown origin (FUO). Three outcome groups were defined as those responding to first-line antibiotics (R1), those responding to second-line antibiotics (R2), and those requiring antifungal therapy (RAF). Median values of IL-6 and CRP were compared between the groups. Results: There were 57 episodes of febrile neutropenia among 26 patients younger than 25 years during 1 year of study period. On day 1, median IL-6 level was significantly lower in FUO group compared with CDI+MDI groups combined (P<0.001). Rise in CRP on day 3 was highly significant to differentiate MDI group from other 2 groups (P<0.001). The CRP also increased significantly on day 3 in RAF (P<0.001) and R2 (P=0.002) groups than in R1 group. Conclusions: Low level of IL-6 may help differentiate patients with FUO from those with documented infections. A rising CRP is indicative of serious infection.

Significance of 5,10-methylenetetrahydrofolate reductase gene variants in acute lymphoblastic leukemia in Indian population: an experimental, computational and meta-analysis

Abstract Acute lymphoblastic leukemia (ALL) arises due to several genetic alterations in progenitor cells, and methotrexate is frequently used as part of the treatment regimen. Although there is evidence for an effect of 5,10-methylenetetrahydrofolate reductase gene (MTHFR) C677T and A1298C variations on drug response in ALL, its risk association for ALL is still unresolved. In a case–control study of 203 patients with ALL and 246 controls and meta-analysis in the Indian population, we showed an insignificant association of MTHFR C677T and A1298C genotypes with childhood and adult ALL. Comprehensive in silico characterization of non-synonymous single nucleotide polymorphisms (nsSNPs) and SNPs of the 3′ untranslated region (UTR) revealed nine nsSNPs as deleterious, and three SNPs in the 3′UTR could possibly alter the binding of miRNAs. The study revealed that several overlooked SNPs may contribute to the risk of ALL susceptibility and further studies of these SNPs with functional characterization in a large sample size are required to understand the significant role of MTHFR in ALL development.

Recurrent and novel GLB1 mutations in India.

GM1 gangliosidosis is a lysosomal storage disorder caused by mutations in the GLB1 gene, leading to the deficiency of the enzyme β-d-galactosidase. In this study, we report molecular findings in 50 Asian Indian families with GM1 gangliosidosis. We sequenced all the exons and flanking intronic sequences of GLB1 gene. We identified 33 different mutations (20 novel and 13 previously reported). The novel mutations include 12 missense (p.M1?, p.E129Q, p.G134R, p.L236P, p.G262E, p.L297F, p.Y331C, p.G414V, p.K493N, p.L514P, p.P597L, p.T600I), four splicing (c.246-2A>G, c.397-2A>G, c.552+1G>T, c.956-2A>G), three indels (p.R22Qfs*8, p.L24Cfs*47, p.I489Qfs*4) and one nonsense mutation (p.Q452*). Most common mutations identified in this study were c.75+2InsT (14%) and p.L337P (10%). Known mutations accounted for 67% of allele frequency in our cohort of patients, suggesting that these mutations in GLB1 are recurrent across different populations. Twenty three mutations were localized in the TIM barrel domain, β-domain 1 and β-domain 2. In silico sequence and structure analysis of GLB1 reveal that all the novel mutations affect the function and structure of the protein. We hereby report on the largest series of patients with GM1 gangliosidosis and the first from India.

Successful treatment of vincristine induced ptosis and polyneuropathy with pyridoxine and pyridostigmine in a child with acute lymphoblastic leukemia

Vincristine is used in the treatment of solid tumors, lymphoma and leukemia in children. The dose-limiting toxicity is its neurotoxicity. We describe a 2-year-old girl with acute lymphoblastic leukemia who developed vincristine-induced polyneuropathy with bilateral ptosis and recovered on treatment with pyridoxine and pyridostigmine.

TRANSIENT MYELOPROLIFERATIVE DISORDER AND EOSINOPHILIC PERICARDIAL EFFUSION IN A DOWN SYNDROME NEONATE

Transient myeloproliferative disorder seen in neonates with Down syndrome is often thought to have a benign course. The authors describe the clinical and laboratory profile of a neonate with Down phenotype and transient myeloproliferative disorder with pericardial effusion as co-morbidity. Pericardial fluid analysis showed eosinophils. Pericardial effusion resolved with prednisolone therapy. Regression in hepatosplenomegaly with clearance of blasts was seen by third week of illness. The clinical course suggested a benign infiltration of the pericardium. Presence of eosinophils supports the differentiating capability of the blast cells in transient myeloproliferative disorders.

Effect of long-term transfusion therapy on the glycometabolic status and pancreatic beta cell function in patients with beta Thalassemia major

Background: Diabetes mellitus is a major complication of iron overload in patients with beta thalassemia major. Design: This is a descriptive study conducted in a Tertiary Care Teaching Hospital to analyze beta cell function and insulin resistance, and their relation to iron overload status in beta thalassemia major. Fasting glucose, two-hour post load glucose, fasting insulin, alanine amino transaminase (ALT), and ferritin were used as outcome measures. The homeostatic model assessment (HOMA model) was used to calculate the beta cell function and insulin resistance index. Results: Of the 30 cases, 20% had impaired fasting glucose, 3.3% had impaired glucose tolerance, and none had diabetes. Fasting glucose was not significant between the cases and controls (P = 0.113). Fasting insulin (P = 0.001), ferritin (P = 0.001), and ALT (P = 0.001) levels were significantly high in the cases. Insulin resistance index was significantly higher in the cases (P = 0.001) as also the beta cell function (P = 0.001). With increase in age and the number of units transfused there is a decline in beta cell function, fasting insulin, and insulin resistance after attaining the maximum level. This suggests that initial insulin resistance is followed by insulin depletion due to loss of beta cell function, leading to diabetes mellitus. Conclusion: Impaired glucose tolerance (IGT) and insulin resistance precede the onset of insulin-dependent diabetes and adequate chelation therapy is essential for delaying the onset or for prevention of diabetes.

Guillain–Barre syndrome with hyperreflexia: A variant

Guillain–Barre syndrome (GBS) is a common cause of acute peripheral neuropathy and is characterized by hyporeflexia or areflexia. Hyperreflexia has been rarely reported with acute motor axonal neuropathy. A 10-year-old boy presented with asymmetrical weakness of upper and lower limbs and change of voice. Weakness progressed in the hospital with involvement of multiple cranial nerves, preserved deep tendon jerks with extensor plantar, and normal abdominal reflexes. He was treated with IV immunoglobulin and IV methylprednisolone. He was able to walk with support with normal voice at the time of discharge. GBS should be a differential diagnosis in patients with acute quadriparesis even if there are preserved deep tendon reflexes.

Problem-based learning as an effective learning tool in community medicine: Initiative in a private medical college of a developing country

Background: Knowledge of community medicine is essential for health care professionals to function as efficient primary health care physicians. Medical students learning Community Medicine as a subject are expected to be competent in critical thinking and generic skills so as to analyze community health problems better. However, current teaching by didactic lectures fails to develop these essential skills. Problem-based learning (PBL) could be an effective strategy in this respect. This study was hence done to compare the academic performance of students who were taught Community Medicine by the PBL method with that of students taught by traditional methods, to assess the generic skills of students taught in a PBL environment and to assess the perception of students toward PBL methodology. Materials and Methods: This study was conducted among seventh-semester final-year medical students between June and November 2014. PBL was introduced to a randomly chosen group of students, and their performance in an assessment exam at the end of postings was compared with that of the remaining students. Generic skills and perception toward PBL were also assessed using standardized questionnaires. Results: A total of 77 students took part in the brainstorming session of PBL. The correlation between self-assigned scores of the participants and those assigned by the tutor in the brainstorming session of PBL was significant (r = 0.266, P = 0.05). Out of 54 students who took part in the presentation session, almost all 53 (98.1%) had good perception toward PBL. Demotivational scores were found to be significantly higher among males (P = 0.024). The academic performance of students (P < 0.001) and success rates (P = 0.05) in the examination were higher among students who took part in PBL compared to controls. Conclusion: PBL helped improve knowledge of students in comparison to those exposed only to didactic lectures. As PBL enabled students to identify the gaps in their knowledge and enhanced their group functioning and generic skills, we recommend PBL sessions: They would help optimize the training in Community Medicine at medical schools. Good correlation of tutor and self-assessment scores of participants in the brainstorming session suggests that the role of tutors could be restricted to assessment in presentation sessions alone. Demotivation, which hinders group performance in PBL, needs to be corrected by counselling and timely feedback by the tutors.

Diagnostic and Prognostic Validity of Proadrenomedullin among Neonates with Sepsis in Tertiary Care Hospitals of Southern India

Introduction To evaluate Proadrenomedullin (Pro-ADM) as the diagnostic and prognostic marker in neonatal sepsis. Materials and Methods In this cross-sectional study, Pro-ADM levels were estimated in 54 neonates with clinical sepsis and positive sepsis screen (cases) and 54 controls without clinical sepsis. Repeat Pro-ADM levels were estimated after 72 hours in cases. Pro-ADM levels were compared with the clinical outcome. Results and Discussion Median Pro-ADM levels in cases were 31.8 (IQR: 27.8-39.4) pmol/ml which was significantly higher than controls 5.1 (IQR; 3.1-7.7) pmol/ml. From the constructed ROC curve, a value of 14.5 pmol/ml was taken as the cut-off for sepsis. Pro-ADM had 100% sensitivity, specificity, and positive predictive values (PPV) in detecting sepsis at 14.5 pmol/ml. Among cases, a decrease in Pro-ADM level by 10 pmol/ml was associated with 99% survival. Pro-ADM value of 35 pmol/ml had 100% specificity and PPV in predicting mortality. Conclusion Pro-ADM can be used as a single biomarker for detecting neonatal sepsis, predicting clinical outcome and prognosis.

Study of Insulin Resistance in Patients with β Thalassemia Major and Validity of Triglyceride Glucose (TYG) Index

Complications like impaired glucose tolerance and diabetes mellitus due to iron overload need early identification in thalassemia. We studied the proportion of insulin resistance in thalassemia major patients on chronic transfusion, identified insulin resistance using homeostasis model assessment of insulin resistance (HOMA-IR) and triglyceride glucose (TYG) index, compared them and validated TYG index. In total, 73 thalassemia patients on regular transfusion for 3 years with serum ferritin >1500 ng/mL were studied. Serum ferritin, fasting blood glucose, triglycerides, and insulin levels were measured, HOMA-IR, and TYG index calculated and analyzed. Mean fasting glucose, triglyceride, and serum insulin values were 104 mg/dL, 164.18 mg/dL, and 19.6 m IU/mL, respectively. Mean serum ferritin was 5156 ng/mL. Insulin resistance was prevalent in one third of thalassemia patients and showed increase with age and serum ferritin. Insulin resistance by HOMA-IR was 32% as against 16% by TYG index with a cut-off value of 4.3. Using receiver operating charecteristic curve analysis, it was found that, by lowering the value of TYG index to 4.0215, sensitivity improved to 78.3% (from 39.13%) with specificity of 70%. Hence, we recommend a newer lower cut-off value of 4.0215 for TYG index for better sensitivity and specificity in identifying insulin resistance.