T Cell Lymphoma: A Rough Road to Diagnosis

Introduction: Lymphoproliferative disorders are well known for their variable presentation. Peripheral T cell lymphoma not otherwise specified (PTCL-NOS) is one subtype which is especially notorious. It has a variable age of onset, predominantly a nodal presentation and immunohistochemistry (IHC) depicting mature T cells.Presentation of case: We share our experience of a 33 year old patient who presented with mediastinal mass with pericardial effusion. However the histopathology revealed PTCL-NOSConclusion: This case in one of the manifestations of heterogeneity encompassing T cell neoplasms where discordance in clinical and pathological behaviour caused not only diagnostic confusion but also complicated treatment decisions.

Engraftment Syndrome: A Retrospective Analysis of the Experience at a Tertiary Care Institute

Engraftment syndrome (ES) is a clinical syndrome that occurs in the early neutrophil recovery phase following hematopoietic stem cell transplant (HSCT). Although also described for allogenic HSCT, it is basically diagnosed in the context of autologous HSCT. We retrospectively reviewed 171 consecutive HSCTs performed between January 2013 and January 2015 in our Bone Marrow Transplant (BMT) unit and analyzed all cases of noninfectious fever and strong clinical features suggestive of ES in the peri-engraftment period for up to 7 days. We observed the incidence of ES to be 12.3% (16/130) in the autologous and 4.8% (2/41) in the allogeneic cohort. Among plasma cell disorders, which constitute 50% of our study population, the incidence of ES was 19.7%. Among the ES cases of autologous transplants, 81.2% (13/16) patients satisfied the Maiolino criteria (MC) and 87.5% (14/16) patients the Spitzer diagnostic criteria (SC). A total of 68.7% (11/16) patients satisfied both MC and SC, and two patients (12.5%) did not satisfy either (MC− SC−). There was no significant difference in days of hospitalization and usage of supportive care between ES and non-ES patients, and there was no mortality due to ES. On univariate analysis, female patients (p < 0.013) and those with diagnosis of a plasma cell disorder (p < 0.03) had higher risk of ES. In conclusion, the incidence of ES in our study population is consistent with that of many others, but severity evaluation needs exploration in larger cohorts with pragmatically modified diagnostic criteria

Comprehensive mutations analyses of FTO (fat mass and obesity-associated gene) and their effects on FTO’s substrate binding implicated in obesity

An excessive amount of fat deposition in the body leads to obesity which is a complex disease and poses a generic threat to human health. It increases the risk of various other diseases like diabetes, cardiovascular disease, and multiple types of cancer. Genomic studies have shown that the expression of the fat mass obesity (FTO) gene was highly altered and identified as one of the key biomarkers for obesity. This study has been undertaken to investigate the mutational profile of the FTO gene and elucidates its effect on the protein structure and function. Harmful effects of various missense mutations were predicted using different independent tools and it was observed that all mutations were highly pathogenic. Molecular dynamics (MD) simulations were performed to study the structure and function of FTO protein upon different mutations and it was found that mutations decreased the structure stability and affected protein conformation. Furthermore, a protein residue network analysis suggested that the mutations affected the overall residues bonding and topology. Finally, molecular docking coupled with MD simulation suggested that mutations affected FTO substrate binding by changing the protein-ligand affinity. Hence, the results of this finding would help in an in-depth understanding of the molecular biology of the FTO gene and its variants and lead to the development of effective therapeutics against associated diseases and disorders

Different prognostic impact of recurrent gene mutations in chronic lymphocytic leukemia depending on IGHV gene somatic hypermutation status: a study by ERIC in HARMONY

Recent evidence suggests that the prognostic impact of gene mutations in patients with chronic lymphocytic leukemia (CLL) may differ depending on the immunoglobulin heavy variable (IGHV) gene somatic hypermutation (SHM) status. In this study, we assessed the impact of nine recurrently mutated genes (BIRC3, EGR2, MYD88, NFKBIE, NOTCH1, POT1, SF3B1, TP53, and XPO1) in pre-treatment samples from 4580 patients with CLL, using time-to-first-treatment (TTFT) as the primary end-point in relation to IGHV gene SHM status. Mutations were detected in 1588 (34.7%) patients at frequencies ranging from 2.3-9.8% with mutations in NOTCH1 being the most frequent. In both univariate and multivariate analyses, mutations in all genes except MYD88 were associated with a significantly shorter TTFT. In multivariate analysis of Binet stage A patients, performed separately for IGHV-mutated (M-CLL) and unmutated CLL (U-CLL), a different spectrum of gene alterations independently predicted short TTFT within the two subgroups. While SF3B1 and XPO1 mutations were independent prognostic variables in both U-CLL and M-CLL, TP53, BIRC3 and EGR2 aberrations were significant predictors only in U-CLL, and NOTCH1 and NFKBIE only in M-CLL. Our findings underscore the need for a compartmentalized approach to identify high-risk patients, particularly among M-CLL patients, with potential implications for stratified management

SARS-CoV-2 B.1.617.2 Delta variant replication and immune evasion

Abstract: The B.1.617.2 (Delta) variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was first identified in the state of Maharashtra in late 2020 and spread throughout India, outcompeting pre-existing lineages including B.1.617.1 (Kappa) and B.1.1.7 (Alpha)1. In vitro, B.1.617.2 is sixfold less sensitive to serum neutralizing antibodies from recovered individuals, and eightfold less sensitive to vaccine-elicited antibodies, compared with wild-type Wuhan-1 bearing D614G. Serum neutralizing titres against B.1.617.2 were lower in ChAdOx1 vaccinees than in BNT162b2 vaccinees. B.1.617.2 spike pseudotyped viruses exhibited compromised sensitivity to monoclonal antibodies to the receptor-binding domain and the amino-terminal domain. B.1.617.2 demonstrated higher replication efficiency than B.1.1.7 in both airway organoid and human airway epithelial systems, associated with B.1.617.2 spike being in a predominantly cleaved state compared with B.1.1.7 spike. The B.1.617.2 spike protein was able to mediate highly efficient syncytium formation that was less sensitive to inhibition by neutralizing antibody, compared with that of wild-type spike. We also observed that B.1.617.2 had higher replication and spike-mediated entry than B.1.617.1, potentially explaining the B.1.617.2 dominance. In an analysis of more than 130 SARS-CoV-2-infected health care workers across three centres in India during a period of mixed lineage circulation, we observed reduced ChAdOx1 vaccine effectiveness against B.1.617.2 relative to non-B.1.617.2, with the caveat of possible residual confounding. Compromised vaccine efficacy against the highly fit and immune-evasive B.1.617.2 Delta variant warrants continued infection control measures in the post-vaccination era