Trends of humoral immune responses to heterologous antigenic exposure due to vaccination & omicron SARS-CoV-2 infection: Implications for boosting

Background & objectives: Vaccination and natural infection can both augment the immune responses against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), but how omicron infection has affected the vaccine-induced and hybrid immunity is not well studied in Indian population. The present study was aimed to assess the durability and change in responses of humoral immunity with age, prior natural infection, vaccine type and duration with a minimum gap of six months post-two doses with either ChAdOx1 nCov-19 or BBV152 prior- and post-emergence of the omicron variant. Methods: A total of 1300 participants were included in this observational study between November 2021 and May 2022. Participants had completed at least six months after vaccination (2 doses) with either ChAdOx1 nCoV-19 or an inactivated whole virus vaccine BBV152. They were grouped according to their age (? or ?60 yr) and prior exposure of SARS-CoV-2 infection. Five hundred and sixteen of these participants were followed up after emergence of the Omicron variant. The main outcome was durability and augmentation of the humoral immune response as determined by anti-receptor-binding domain (RBD) immunoglobulin G (IgG) concentrations, anti-nucleocapsid antibodies and anti-omicron RBD antibodies. Live virus neutralization assay was conducted for neutralizing antibodies against four variants – ancestral, delta and omicron and omicron sublineage BA.5. Results: Before the omicron surge, serum anti-RBD IgG antibodies were detected in 87 per cent participants after a median gap of eight months from the second vaccine dose, with a median titre of 114 [interquartile range (IQR) 32, 302] BAU/ml. The levels increased to 594 (252, 1230) BAU/ml post- omicron surge (P<0.001) with 97 per cent participants having detectable antibodies, although only 40 had symptomatic infection during the omicron surge irrespective of vaccine type and previous history of infection. Those with prior natural infection and vaccination had higher anti-RBD IgG titre at baseline, which increased further [352 (IQR 131, 869) to 816 (IQR 383, 2001) BAU/ml] (P<0.001). The antibody levels remained elevated after a mean time gap of 10 months, although there was a decline of 41 per cent. The geometric mean titre was 452.54, 172.80, 83.1 and 76.99 against the ancestral, delta, omicron and omicron BA.5 variants in the live virus neutralization assay. Interpretation & conclusions: Anti-RBD IgG antibodies were detected in 85 per cent of participants after a median gap of eight months following the second vaccine dose. Omicron infection probably resulted in a substantial proportion of asymptomatic infection in the first four months in our study population and boosted the vaccine-induced humoral immune response, which declined but still remained durable over 10 months

A Comparative Study of the Patterns of Mortality in COVID-19 Patients in Juxtaposition with Non-COVID-19 Mortality in the First and Second Waves of the Pandemic

Background and objectives: The Coronavirus disease 2019 (COVID-19) pandemic has posed an unprecedented challenge to the public healthcare system worldwide like none before, producing far-reaching global economic, humanitarian, and social crises. It is estimated to have affected more than 1.8 million people worldwide. India has faced two phases of the pandemic, being the country with 2nd most number of deaths with varying mortality patterns across the two waves. In this study, we compare the patterns of mortality between the two phases of pandemics in association with COVID-19 and non-COVID-19 deaths. Materials and Methods: A retrospective observational study at a tertiary care center in Central India was carried out. Demographic patterns of mortality have been studied in each of the groups, and a comparative analysis was done between COVID-19 and non-COVID-19 mortality patterns in each phase of the study, that is, from 20th March 2020 to 19th September 2020 and from 20th September 2020 to May 2021, as well as between the two phases. Results: The case fatality rate of COVID-19 positive patients in the second phase of the study was 22.04%, whereas the those of non-COVID-19 patients in the second phase were found to be 15.95%. A maximum number of COVID-19 positive deaths during the first wave of the pandemic occurred in September 2020 and during the second wave in April 2021. In the first phase of the study, 69.6% of patients who died were males, and 30.3% were females, whereas in the second phase among COVID-19 positive subjects, 65% deaths were among males, and 35% deaths were among females. COVID-19 positive mortality in the second phase showed, 26.53% to be hypertensive, while 13.8% were diabetic. Conclusion: It was found that most of the deaths in both phases of COVID-19 amongst COVID-19 positive patients and non-COVID patients were amongst the elderly population (>60 years) with male predominance. Most deaths in both populations occurred during the first 3 days of admission whereas it was relatively less in the second phase. Noncommunicable diseases like systemic hypertension, and DM had a significant influence on all-cause mortality and morbidity in both COVID-19 positive and non-COVID-19 patients in the first and second waves of COVID-19. Noncommunicable diseases thus played a major role in mortality among both the populations under study.

Study of intrauterine fetal death cases in a tertiary care center

Background: The death of a fetus is a tragic event not only for the parents but also a great cause of stress for the caregiver. It is thus vital to identify specific probable causes of fetal death to determine the risk of recurrence, prevention or corrective action.Methods: This retrospective observational study was carried out in department of obstetrics and gynaecology, Jhalawar Medical College, Jhalawar, from July 2019 to October 2019. Intrauterine fetal death was confirmed either with ultrasound or on clinical examination. The details of complaints, obstetrics history, examination findings, mode of delivery, fetal outcomes and investigation reports were recorded.Results: A total of 114 intrauterine fetal deaths were reported amongst 2982 deliveries conducted during the study period. The incidence rate of IUFD was 38.22/1000 live births. 85.96% deliveries were unbooked. 59.64% belonged to rural population. 59.64% fetal deaths occurred in women between 20 to 25 years of age. 45.61% women were primigravida. 41.2% IUFD occurred between 26 to 31 weeks of gestation. Among the identifiable cause’s hypertensive disorders (23.68) and placental causes (19.29%) were most common.Conclusions: Unexplained causes, PIH and abruptio placentae were major causes of IUFD. Majority of fetal wastage can be prevented with universal and improved antenatal care.

Study of Corrected QT Dispersion in Acute ST-elevation Myocardial Infarction (Thrombolysed/ Non-Thrombolysed) Patients and its Prognostic Significant During Hospital Stay

Introduction: In the electrocardiogram, the QT interval reflects the duration of depolarization and repolarization of the ventricularmyocardium thus reflects changes in local myocardial milieu. Dispersion of repolarization is thought to reflect regional heterogeneityof the recovery process within the myocardium, which believed to be important in the genesis of ventricular arrhythmias.Purpose of Study: The purpose of the present study was to predict the risk of life-threatening ventricular arrhythmias andother cardiac complications after acute ST-elevation myocardial infarction (STEMI) event with using rate adjusted corrected QT(QTc) dispersion as one of the cheapest modalities and non-invasive investigation, which may reflect as a prognostic marker.Materials and Methods: The present study had been carried out in the Department of Medicine, NSCB. Medical College andassociated Hospital, Jabalpur, Madhya Pradesh, India, from March 2017 to August 2018. This was a case–control prospectiveobservational study. The targeted populations were 60 cases of both sexes with the age group of ≥18–≤70 years, and age- andsex-matched 60 apparently healthy control subjects.Results: Mean QTc dispersion was increased in patients of acute MI compared to control subjects; which were found statisticallyhighly significant. The mean QTc dispersion remained consistently high in a group of patients with cardiac complications incomparison to patients without cardiac complications on day 1 up to discharge. The mean QTc dispersion was found high inpatients who were died compared to who were survived on day 1.Conclusion: It could be concluded that QTc dispersion measurement may provide a potentially simple, cheap, and non-invasivemethod of identification of patients with acute MI (STEMI) at risk of development of ventricular arrhythmias and also relates tothe prognosis in that patients and the future may prove to be an independent predictor of death.

Genomic classification of acute myeloid leukaemia: An incessantly evolving concept.

Papaemmanuil E, Gerstung M, Bullinger L, Gaidzik VI, Paschka P, Roberts ND, Potter NE, Heuser M, Thol F, Bolli N, Gundem G, Van Loo P, Martincorena I, Ganly P, Mudie L, McLaren S, O’Meara S, Raine K, Jones DR, Teague JW, Butler AP, Greaves MF, Ganser A, Döhner K, Schlenk RF, Döhner H, Campbell PJ. (Cancer Genome Project, Wellcome Trust Sanger Institute; European Bioinformatics Institute; European Molecular Biology Laboratory, Hinxton; Centre for Evolution and Cancer, Institute of Cancer Research, London; and Department of Haematology, University of Cambridge, Cambridge—all in the UK; Departments of Epidemiology and Biostatistics and Cancer Biology; Center for Molecular Oncology and Center for Hematologic Malignancies, Memorial Sloan Kettering Cancer Center, New York, USA; Department of Internal Medicine III, Ulm University, Ulm;

Autologous stem cell transplantation for multiple myeloma: Long-term results .

Background. Survival of myeloma patients has improved considerably in the past decade. However, limited data are available on their long-term outcome. We analysed the data of 225 consecutive patients who underwent autologous stem cell transplantation (ASCT) at our centre. Methods. Between April 1990 and December 2013, a total of 225 patients with multiple myeloma (median age 53 years, range 27–67 years, 69.3% men) underwent ASCT. High-dose melphalan 200 mg/m2 was used for conditioning. Before transplant, the patients received induction therapy with novel agents (thalidomide and dexamethasone, or lenalidomide and dexamethasone, or bortezomib and dexamethasone); or vincristine, doxorubicin, dexamethasone; or alkylating agents (vincristine, melphalan, cyclophosphamide and prednisolone; or melphalan and prednisolone). The response to transplant was evaluated using the European Bone Marrow Transplant criteria, and an intention-to-treat analysis was done. Results. Four-fifths (79.6%) of our patients had Durie Salmon Stage (DSS) IIIA and nearly a quarter (24%) of them had International Stage III disease. Before the transplant, 80.4% of patients had chemosensitive disease. The median interval from diagnosis to transplant was 10 months (range 2–128 months). Following ASCT, 197 (87.5%) patients responded. Complete response was obtained in 54.7%, very good partial response in 19% and partial response in 13.8%. At a median follow-up of 90 months (range 18–266 months), the median progression-free survival (PFS) and overall survival (OS) were 32 and 85.5 months, respectively. The estimated PFS and OS at 10 years were 29.7% and 43.6%, respectively. On multivariate analysis, the presence of extramedullary disease (HR 3.05, p<0.001), and ISS III (HR 0.50, p<0.02)

High fms-like tyrosine kinase-3 (FLT3) receptor surface expression predicts poor outcome in FLT3 internal tandem duplication (ITD) negative patients in adult acute myeloid leukaemia: a prospective pilot study from India.

Background & objectives: Mutations in fms-like tyrosine kinase 3 (FLT3) receptor have significant role in assessing outcome in patients with acute myeloid leukaemia (AML). Data for FLT3 surface expression in relation to FLT3 internal tandem duplication (ITD) status and outcome are not available from India. The objective of the current study was to investigate adult patients with AML for FLT3 expression and FLT3 ITD mutation, and their association with long-term outcome. Methods: Total 51 consecutive de novo AML patients aged 18-60 yr were enrolled in the study. FLT3 ITD was detected by polymerase chain reaction (PCR); flowcytometry and qPCR (Taqman probe chemistry) were used for assessment of FLT3 protein and transcript, respectively. Kaplan Meier curves were obtained for survival analysis followed by log rank test. Results: FLT3 ITD was present in eight (16%) patients. Complete remission was achieved in 33 (64.6%) patients. At 57.3 months, event free survival (EFS) was 26.9±6.3 per cent, disease free survival (DFS) 52.0±9.2 per cent, and overall survival event (OS) 34.5±7.4 per cent. FLT3 surface expression was positive (>20%) by flow-cytometry in 38 (88%) of the 51 patients. FLT3 surface expression and transcripts were not associated with FLT3 ITD status. FLT3 expression was significantly associated with inferior EFS (P=0.026) and OS (P=0.018) in those who were negative for FLT3 ITD. Interpretation & conclusions: This study evaluated FLT3 ITD mutation along with FLT3 expression in AML patients, and associated with survival. Negative impact of FLT3 surface expression on survival was observed in AML patients who were FLT3 ITD negative.

Bilateral Symmetrical Basal Ganglia Calcification with Atypical Presentation: A Case Series.

Physiological intracranial calcification is asymptomatic and is detected incidentally by neuroimaging. Pathological basal ganglia calcification (BGC) is caused by various causes such as metabolic disorders, infectious and genetic diseases, and others. The most common causes of pathological BGC are hypoparathyroidism and pseudohypoparathyroidism. We present three cases of bilaterally symmetrical BGC associated with hypoparathyroidism. All of them presented with seizures as the only presentation without any signs of hypocalcemia and without extrapyramidal features. One should not rule out hypoparathyroidism in the absence of other signs of hypocalcemia and extrapyramidal features. Biochemical analysis pertaining to hypoparathyroidism must be done. Timely treated patients can have a good prognosis.

Emergence of Resistance in Community-acquired Enteric Fever.

We present a retrospective analysis of 225 blood culture-proven pediatric patients with the sensitivity pattern represented in the Antibiogram obtained by Vitek-2 Systems. Resistance to typhoid fever with commonly used oral antibiotics (Ciprofloxacin 41.4%, Amoxy-clavulonic acid 44.1% and Cotrimoxazole 32.7%) was common.

Ventilatory Impairment In Petrol Pump Workers.

The lung functions of 133 subjects (33 controls and 100 petrol pump workers) were studied. The study group comprised of healthy non-smoking males in the age group of 20-40 years working in different petrol pumps in Jammu city and its outskirts within a radius of 10 km for more than one year. The control group comprised of 33 healthy non-smoking adult males between the age group of 20-40 years working in the hospital. The results show that ventilatory efficiency of lung is decreased in petrol pump workers. The decline in lung functions in petrol pump workers could be due to exposure to petrol fuel vapours, diesel exhaust and airborne particulate matter at petrol pumps.

Nonleukemic granulocytic sarcoma of kidney with mixed phenotype blasts: A diagnostic dilemma.

Granulocytic sarcoma (GS) usually presents concomitantly with or after the onset of acute myeloid leukemia, blastic phase of chronic myeloid leukemia (CML), or myelodysplastic syndromes. Rarely, it may present even before the onset of overt leukemia and when so, it is often misdiagnosed. We are reporting a case of GS of kidney presenting as an isolated renal mass with normal laboratory investigations including a normal peripheral blood smear. It was initially misdiagnosed as lymphoma as the blasts, in addition to the morphological similarity with lymphoma cells, also showed positive immunohistochemistry for B cell markers. Based on further investigations including immunophenotyping and cytogenetic studies, a final diagnosis of CML-blast crisis (mixed phenotype) presenting initially as GS was made. To the best of our knowledge, this is the first antemortem report of nonleukemic GS presenting as kidney mass that later on progressed to CML-blast crisis with mixed phenotype blasts.

Childhood Chronic Myeloid Leukemia with Monocytosis.

We report two cases of chronic myeloid leukemia (CML) in childhood presenting with monocytosis. History, physical examination and laboratory findings were in favor of juvenile myelomonocytic leukemia in both the cases, but reverse transcriptase polymerase chain reaction (RT-PCR) detected b2a2 and b3a2 transcript of p210 bcr-abl protein characteristic of major BCR breakpoint. Presence of monocytosis in early childhood suggests a viral infection or JMML but a possibility of CML with monocytosis needs to be considered.

Colloidion Baby.

A two day old male baby, third issue of a second degree consanguineously married couple with clinical features of colloidion baby is being presented. Early recognition of this clinical entity and early institution of appropriate therapy can definitely reduce morbidity and mortality in neonates.

Bilateral Pulmonary Cyst in a Child.

A four year old male child presented with history of cough for last six months. Chest skiagram and CT scan of mediastinum revealed bilateral pulmonary hydatid cyst. Serology did authenticate diagnosis. The child was prescribed albendazole for 6 months and was advised to come for follow up. The case of bilateral pulmonary hydatid cyst is being presentated because of rarity.

Splenic lymphoma with villous lymphocytes.

Splenic lymphoma with villous lymphocytes (SLVL) is a rare disorder that comprises less than 1% of lymphoid neoplasms. It is the leukemic counterpart of splenic marginal zone lymphoma (SMZL) and is characterized by splenomegaly, often with no lymphadenopathy, moderate lymphocytosis and villous lymphocytes on peripheral blood smear. Here, we report a case of SLVL in a 56-year-old male with very high leukocyte counts, massive splenomegaly and relatively few leukemic cells with subtle villous projections on the surface. This disorder is often confused with other chronic lymphoproliferative disorders, especially chronic lymphocytic leukemia (CLL) and hairy cell leukemia and should be differentiated from them. We are reporting this case to highlight the diagnostic pitfalls associated with this disorder.

Immunophenotypic patterns in precursor T-cell neoplasm.

T-cell lymphoproliferative disorders are a heterogeneous group of lymphoid neoplasm that can mimic both benign conditions and non-hematopoietic tumors. In routine clinical practice, morphology and immunophenotyping forms the basis of their diagnosis. In this retrospective analysis, we evaluate the utility of flow cytometric immunophenotyping patterns in diagnosis of precursor T-cell neoplasm. Aberrant expression of T-cell antigens was found in all the cases of precursor T-cell neoplasm. The residual normal T-lymphocytes, identifiable in majority of cases, were found to be useful in evaluation of quantitative differences in antigen expression by leukemic cells. A careful analysis of flow cytometric immunophenotyping data can provide additional information which is useful for diagnosis of precursor T-cell neoplasm. This information can be further utilized for analysis of minimal residual disease in these tumors.

Turner Syndrome

Turner Syndrome is one of the important chromosomal disorders characterised by loss (total or part) of sex chromosome. The manifestations being peripheral edema, short stature, extra skin fold, webbing of neck, renal and cardiovascular anomalies, sexual infantilism, learning disability etc. We present here a one month female baby who had classical features of Turner Syndrome. The karyotape analysis was consistent with the diagnosis.

Primary Hodgkin's disease of spleen--a case report.

Primary malignant lymphoma of spleen is rare with primary Hodgkin's disease (HD) of spleen being rarer. The diagnosis of primary splenic HD is usually made on the histopathological examination of the splenectomy specimen. We report an interesting case of primary HD of spleen in a child emphasizing its rarity and the role of fine needle aspirate cytology in early diagnosis and non-surgical management of this entity.