Histone methyltransferase NSD3 also known KMT3F, is an epigenetic regulator that methylates histone H3 at lysine 36, a mark associated with gene activation. Functionally, NSD3 is crucial for supporting various cellular and developmental processes, and its deregulation can lead to various disease conditions, including solid and hematological cancers. However, the role of NSD3 in regulating normal hematopoiesis remains elusive. In the present study, we have investigated the role of NSD3 in regulating human erythropoiesis, the process of red blood cell production from hematopoietic stem cells (HSCs). To achieve this, we isolated CD34+ HSCs from a healthy donor and subjected them to ex-vivo erythroid differentiation. Using a combination of lentiviral transduction and small hairpin RNA-mediated knockdown approaches, we targeted NSD3 depletion during the early phases of erythroid differentiation. Our results demonstrated that depleting NSD3 on days 2 and 7 of ex-vivo erythroid differentiation resulted in notable disruptions of erythropoiesis process. Specifically, NSD3 downregulation resulted in a decreased megakaryocyte-erythroid progenitors, reduced colony formation, and a significant decrease in erythroid differentiation markers. Furthermore, NSD3 depletion altered erythroid differentiation by favouring basophilic erythroblasts over ortho/polychromatic erythrocytes. At the transcriptomic level, NSD3 depletion led to the downregulation of key hematopoiesis-specific transcription factors and genes associated with erythroid differentiation and hemoglobin synthesis. Additionally, NSD3 depletion also induced apoptosis and hindered cell proliferation, accompanied by altered expression of genes involved in these pathways. Our findings uncover a previously undescribed role of histone methyltransferase NSD3 in regulating human erythropoiesis.

Background Occupational injuries continue to pose a significant public health challenge worldwide, particularly in low- and middle-income countries such as India, where industrial safety measures frequently fail to keep pace with rapid infrastructural development. Railway wagon repair workers constitute a vulnerable population due to their exposure to mechanical, ergonomic, and environmental hazards. Objective The objective of the study is to assess the prevalence and severity of occupational injuries and identify associated sociodemographic and occupational factors among railway wagon repair workers in Datia, Madhya Pradesh. Methods A cross-sectional study was conducted from July 2023 to June 2024 among 327 railway wagon repair workers who had sustained work-related injuries. Data were collected using a structured questionnaire and analyzed with Jamovi software. Injury severity was assessed using a custom 10-point scale. Multivariate linear and binary logistic regression models were employed to identify predictors of injury severity and injury occurrence, respectively. Results The prevalence of occupational injuries was 59.0% (N = 193). Male workers, older age groups, and unskilled workers reported a higher incidence of injury; however, these associations were not statistically significant. Only the type of occupation significantly predicted injury severity, with unskilled workers experiencing more severe injuries (β = 1.165; p = 0.008). No variable significantly predicted injury occurrence. Model fit for both severity (adjusted R² = 0.0134) and occurrence (McFadden's R² = 0.0178) was poor, suggesting that the identified factors explain only a small portion of the variability and that severity and occurrence are likely influenced by multiple unmeasured factors. These findings should, therefore, be interpreted with caution regarding their predictive value. Conclusion Unskilled workers face a higher risk of sustaining severe occupational injuries in railway wagon repair settings. Although no single factor independently predicted injury occurrence, the findings highlight the need for improved occupational safety practices, particularly through targeted skill development, strict enforcement of personal protective equipment (PPE) use, and customized safety training programs. Longitudinal studies using validated injury assessment tools are recommended to further clarify causal pathways.

Multiple myeloma (MM) is a clonal plasma cell disorder that commonly presents with anemia, renal failure, hypercalcemia, and lytic bone lesions. MM is also frequently associated with thrombotic complications; however, it may rarely present with bleeding diathesis. We report a case of a 42-year-old gentleman with relapsed immunoglobulin G lambda MM who presented with epistaxis, gingival bleeding, and oozing at the venepuncture site. Routine tests of coagulation revealed a prolonged prothrombin time (PT), activated partial thromboplastin time (aPTT), and thrombin time. The PT and aPTT failed to correct with pooled normal plasma and the patient was thus diagnosed to have an acquired heparin-like anticoagulant (HLAC). The source of this HLAC has long been debated, but recent data have demonstrated that this HLAC may be the paraproteins produced by the malignant plasma cells. The patient was treated with intravenous protamine sulfate, repeated cycles of plasma exchange, and a daratumumab-based quadruplet regimen but eventually succumbed to an intracranial hemorrhage. HLAC is a rare but potentially fatal complication of MM that must be considered when patients with MM present with bleeding diathesis.

Spondyloenchondrodysplasia with immune dysregulation(SPENCDI) is a rare genetic disorder resulting from suboptimal Tartrate Resistant Acid Phosphatase (TRAP) activity which key regulates functioning of immune effector cells and osteoclasts. This leads to autoimmune cytopenias along with skeletal system and neurological manifestations. Refractory autoimmune haemolysis is frequently encountered and manifest at a younger age demanding attention of a paediatric haematologist. Here we report the typical evolution of multi-systemic symptoms in a 7 year old child and difficult to manage haemolysis with use of sirolimus for attaining clinical remission.

Background Published data on outcomes ofpediatric mature B-cell non-Hodgkin lymphoma (B-NHL) from India is limited and difficult to interpret due to small sample size and non-uniform treatment protocols.This study aims to do a pooled analysis of published patient data from multiplecenters across India to provide a clearer understanding of survival rates and treatment-related toxicities with respect to the treatment protocols in this population. Methods A pooled analysis of patient-level data from 505 children with mature B-NHL, including Burkitt lymphoma (n=395), diffuse large B-cell lymphoma (DLBCL, n=52), and other subtypes (n=58), treated from 2000 to 2022 at seven major cancer centers in India, was conducted. Outcomes assessed were grade 3/4 toxicities, toxic deaths, relapse/progression, and survival rates. Results Most patients (401/505) presented with advanced disease; bone marrow and CNS involvement were observed in 13.9% and 6.9% of cases, respectively. Treatment protocols primarily included LMB (n=208), BFM (n=191), and MCP (n=61). Grade 3/4 toxicities were reported in 79.2% of patients, with higher rates observed with LMB protocol (92.1%) compared to BFM (70.8%) and MCP (70.1%) (p<0.001). Toxic death rates were similar across protocols. Overall survival (OS) and event-free survival (EFS) at a median follow-up of 17 months were 69.4±2.2% and 64.9±2.2%, respectively, with no significant differences in relapse/progression rates or stage-specific OS between protocols (p=0.28 and 0.51). Conclusions This pooled analysis shows that although treatment-related toxicities differ by protocol, overall survival outcomes were similar across the LMB, BFM, and MCP regimens, despite being lower than those reported in Western studies.Uniform standardized protocols may further improve outcomes for pediatric B-NHL in India.

BACKGROUND:Recurrent somatic mutations in the JAK2 , CALR , and the MPL genes are noted in BCR:ABL1 negative classic myeloproliferative neoplasms (MPN) that includes polycythemia vera (PV), essential thrombocytosis (ET), and primary myelofibrosis (PMF). MATERIALS AND METHODS:Mutation profile and clinical features of MPN cases diagnosed at a tertiary care center in North India are being described. JAK2V617F mutation was screened using ARMS PCR, and CALR mutation was screened using allele-specific PCR followed by fragment analysis. MPL and JAK2 Exon 12 mutations were screened by Sanger sequencing. Some of the samples were also screened using commercial kits based on single-plex RT PCR. RESULTS:A total of 378 cases (including 124 PV, 121 ET, and 133 PMF cases) were screened over 6.5 years. JAK2V617F mutation was noted in 90.3%, 61.1%, and 69.2% of cases of PV, ET, and PMF, respectively. In PV, JAK2V617F wild-type cases were associated with a significantly lower age (44 yrs vs 54 yrs; P = 0.001), lower TLC (6.3 vs 16.9; P = 0.001), and a lower platelet count (188 × 109/L vs 435 × 109/L; P = 0.009) as compared to the JAK2V617F mutated cases. CALR and MPL mutations were noted in 17.4% and 12% and 0.8% and 5.3% of ET and PMF cases, respectively. Type 1 CALR mutations were commoner in both ET and PMF. The triple negative cases constituted 20.7% and 13.5% cases of ET and PMF, respectively. In ET, the triple negative cases were found to have a significantly lower median age of presentation (42 yrs vs 52 yrs; P = 0.001), lower median TLC (10.2 × 109/L vs 13.2 × 109/L; P = 0.024), and a higher median platelet count (1238 × 109/L vs 906 × 109/L; P = 0.001) as compared to driver genes mutated cases. In PMF, the triple negative cases were found to have a significantly lower hemoglobin level (7.9 g/dl vs 11.0 gl/dl; P = 0.001) and a significant female preponderance ( P = 0.05) as compared to the mutated cases. CALR mutations were found to have a significantly lower median age (43 yrs vs 56 yrs; P = 0.001) and lower hemoglobin (9.6 g/dl vs 11.3 g/dl) as compared to the JAK2 mutations. CONCLUSION:Our data on the driver gene mutational profile of BCR:ABL1 negative MPN is one of the largest patient cohorts. The prevalence and clinicopathological features corroborate with that of other Asian studies.

Topic: 4. Acute myeloid leukemia - Clinical Background: Venetoclax in combination with azacytidine, decitabine or low dose ARA-C has been approved as an upfront therapy for elderly patients (75 years or above) of AML or those who are ineligible for intensive induction therapy based on the results of Viale A and Viale C phase 3 trials. However, the criteria of ineligibility for intensive induction in LMICs is not just age. Many younger patients could not be given intensive induction due to baseline serious infections, financial issues and/or lack of social support. Aims: To study the efficacy and cost effectiveness of Venetoclax and Hypomethylating agent-based induction in newly diagnosed and relapsed refractory Acute myeloid leukemia. Methods: This retrospective single centre study was conducted at a tertiary care institute in India between 2020 and 2022 where 57 patients of newly diagnosed (Age>60 years, Baseline non-resolving infection, lack of financial resources, diagnosed during second covid wave) or relapsed refractory AML received off label VEN-HMA based induction therapy. The results were compared with 27 patients receiving Intensive Induction therapy (ARM B) at our centre during the same period. Informed consent was taken from all patients <75 years for off label use of VEN-HMA. The cut-off date for last follow up was September 2022 Results: Between April 2020 and June 2022, 57 patients, median age 48 years (Range 11-78), of Acute myeloid leukemia (35 newly diagnosed and 22 relapsed refractory) were treated with Venetoclax and Hypomethylating agents (Azacytidine/Decitabine). The Overall complete response rate (ORR) was 72.7% with Complete Remission (CR), Complete Remission with incomplete count recovery (CRi) rates of 57.9% and 15.8% respectively, was statistically comparable to ORR of patients receiving intensive induction 62.96% (p value-0.251). The median number of cycles of VEN-HMA for CR/CRi was 1(1-3). Median overall survival (OS) in VEN-HMA patients was 19 months which was statistically superior to OS of 13±2.78 months in ARM B (log rank test-0.025) while Median progression free survival (PFS) was superior in ARM B (17months vs 14 months in VEN- HMA arm, p-value-0.020). Median OS and PFS were significantly superior in newly diagnosed (OS-19 months, pvalue-0.044, PFS-14±1.1 months, p value-0.011) when compared with relapsed/refractory patients(OS-12±2.2 months, PFS-9±1.7 months). Median time from diagnosis to treatment was significantly lower (p value-0.016),13 days (0-29) in VEN-HMA arm vs 35(3-165) days in ARM B. Grade 3-4 adverse events were lower in VEN-HMA arm. 48(84.21) vs 27(100%) in ARM B. Induction deaths in VEN-HMA arm was 8/57(14%) while in ARM B it was 8/27 (30%). Duration of hospital stay in VEN-HMA in cycle 1 was 7 days (1-22) compared to 27 days (14-68) in ARM B (p value <0.001) and cost of therapy in VEN-HMA arm ($1429.9±132.5) was significantly lower than in ARM B ($3927.2±823.9) (p value<0.001) In this study patients who received consolidation with Allogenic stem cell transplant(N=5) or high dose cytarabine(N=6) post attainment of CR with VEN-HMA had superior OS (Mean OS-18.40±0.80 vs 12.97±1.0 months, p-value-0.029) and PFS(Mean 16.60±0.82 vs 10.44±1.0 months, p-value-0.034) as compared to those who were continued on VEN-HMA. Summary/Conclusion: Venetoclax and hypomethylating agent outpatient-based induction for AML is a feasible approach in both newly diagnosed and relapsed refractory cases especially in LMICs due to lower cost, less duration of hospital stay, less delay in therapy, decreased transfusion requirement. However, research should focus on appropriate consolidation strategy in fit patients who achieve CR post VEN-HMA.Keywords: Acute myeloid leukemia

Pediatric Blood & CancerVolume 70, Issue 2 e29896 LETTER TO THE EDITOR When “milky fluid” was aspirated from the bone: Gorham–Stout syndrome—A report of a rare entity Ruchi Gupta, Corresponding Author Ruchi Gupta ruchipgi@yahoo.co.in Department of Haematology, Sanjay Gandhi Post Graduate Institute of Medical Sciences (SGPGIMS), Lucknow, Uttar Pradesh, India Correspondence Ruchi Gupta, Department of Haematology, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Lucknow, Uttar Pradesh, India. Email: ruchipgi@yahoo.co.inSearch for more papers by this authorSeema Biswas, Seema Biswas Department of Haematology, Sanjay Gandhi Post Graduate Institute of Medical Sciences (SGPGIMS), Lucknow, Uttar Pradesh, IndiaSearch for more papers by this authorPrateek Das, Prateek Das Department of Haematology, Sanjay Gandhi Post Graduate Institute of Medical Sciences (SGPGIMS), Lucknow, Uttar Pradesh, IndiaSearch for more papers by this authorPrakhar Gupta, Prakhar Gupta Department of Haematology, Sanjay Gandhi Post Graduate Institute of Medical Sciences (SGPGIMS), Lucknow, Uttar Pradesh, IndiaSearch for more papers by this authorKusum Gupta, Kusum Gupta Department of Haematology, Sanjay Gandhi Post Graduate Institute of Medical Sciences (SGPGIMS), Lucknow, Uttar Pradesh, IndiaSearch for more papers by this authorMathiyazhagan Gopinathan, Mathiyazhagan Gopinathan Department of Haematology, Sanjay Gandhi Post Graduate Institute of Medical Sciences (SGPGIMS), Lucknow, Uttar Pradesh, IndiaSearch for more papers by this authorAnshul Gupta, Anshul Gupta Department of Haematology, Sanjay Gandhi Post Graduate Institute of Medical Sciences (SGPGIMS), Lucknow, Uttar Pradesh, IndiaSearch for more papers by this authorZafar Neyaz, Zafar Neyaz Department of Radiodiagnosis, Sanjay Gandhi Post Graduate Institute of Medical Sciences (SGPGIMS), Lucknow, Uttar Pradesh, IndiaSearch for more papers by this authorManish Ora, Manish Ora Department of Nuclear Medicine, Sanjay Gandhi Post Graduate Institute of Medical Sciences (SGPGIMS), Lucknow, Uttar Pradesh, IndiaSearch for more papers by this author Ruchi Gupta, Corresponding Author Ruchi Gupta ruchipgi@yahoo.co.in Department of Haematology, Sanjay Gandhi Post Graduate Institute of Medical Sciences (SGPGIMS), Lucknow, Uttar Pradesh, India Correspondence Ruchi Gupta, Department of Haematology, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Lucknow, Uttar Pradesh, India. Email: ruchipgi@yahoo.co.inSearch for more papers by this authorSeema Biswas, Seema Biswas Department of Haematology, Sanjay Gandhi Post Graduate Institute of Medical Sciences (SGPGIMS), Lucknow, Uttar Pradesh, IndiaSearch for more papers by this authorPrateek Das, Prateek Das Department of Haematology, Sanjay Gandhi Post Graduate Institute of Medical Sciences (SGPGIMS), Lucknow, Uttar Pradesh, IndiaSearch for more papers by this authorPrakhar Gupta, Prakhar Gupta Department of Haematology, Sanjay Gandhi Post Graduate Institute of Medical Sciences (SGPGIMS), Lucknow, Uttar Pradesh, IndiaSearch for more papers by this authorKusum Gupta, Kusum Gupta Department of Haematology, Sanjay Gandhi Post Graduate Institute of Medical Sciences (SGPGIMS), Lucknow, Uttar Pradesh, IndiaSearch for more papers by this authorMathiyazhagan Gopinathan, Mathiyazhagan Gopinathan Department of Haematology, Sanjay Gandhi Post Graduate Institute of Medical Sciences (SGPGIMS), Lucknow, Uttar Pradesh, IndiaSearch for more papers by this authorAnshul Gupta, Anshul Gupta Department of Haematology, Sanjay Gandhi Post Graduate Institute of Medical Sciences (SGPGIMS), Lucknow, Uttar Pradesh, IndiaSearch for more papers by this authorZafar Neyaz, Zafar Neyaz Department of Radiodiagnosis, Sanjay Gandhi Post Graduate Institute of Medical Sciences (SGPGIMS), Lucknow, Uttar Pradesh, IndiaSearch for more papers by this authorManish Ora, Manish Ora Department of Nuclear Medicine, Sanjay Gandhi Post Graduate Institute of Medical Sciences (SGPGIMS), Lucknow, Uttar Pradesh, IndiaSearch for more papers by this author First published: 28 July 2022 https://doi.org/10.1002/pbc.29896Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinkedInRedditWechat No abstract is available for this article. Volume70, Issue2February 2023e29896 RelatedInformation

Objectives Methotrexate (MTX) has anticancer therapeutic potential with multiple doses-related adverse effects and toxicities. Immunoassays for therapeutic monitoring of serum MTX have their own limitations. Liquid chromatography-tandem mass spectrometry (LC-MS/MS) is considered as the reference method; however, commer-cially availability of them is limited. We aimed to adapt/develop an in-house LC-MS/MS method for therapeutic monitoring of serum MTX.Materials and Methods Serum protein precipitation was performed using acetoni-trile-water containing 250 mu M solution of aminoacetophenone as internal standard (IS). Chromatographic separation was achieved on a C18 column with mobile phase of 0.1% solution of formic acid (solvent A) and acetonitrile (solvent B) at a flow rate of 0.4 mL/min. MS was performed under positive ion mode with mass transition for MTX and IS as m/z 455.1 -> 308.1 and 136.2 -> 94.1, respectively. The method was validated by following Bioanalytical Method Validation Guidance for Industry, 2018 and applied on leukemia patients' samples on MTX therapy.Results The correlation coefficient of eight serially diluted calibration standards of 0.09 to 12.5 mu M was > 0.99 and had linearity with > 95% precision and accuracy at analytical quality control levels. The lower limit of MTX quantification achieved was 0.09 mu M with good intensity and sharp peak as compared with blank sample. The total run time of the assay was 5 minutes. The serum MTX levels obtained by this method in leukemia patients exhibited clinical correlation and an excellent agreement with commercial immunoassay used in parallel.Conclusion We were able to develop a rapid, sensitive, and cost-effective LC-MS/MS method suitable for therapeutic drug monitoring of MTX in routine clinical diagnostic laboratories.

Immune dysregulation plays a key role in determining COVID-19 disease severity. We aimed to analyze the T cell activation profile in COVID − 19 cases and its predictive role in disease severity and outcome. This was a prospective observational pilot study from a tertiary care COVID-19 hospital. Peripheral blood samples obtained between the fifth and seventh day of COVID-19 illness, were subjected to lymphocyte subset analysis using multicolor flowcytometry using a single tube, 8 antibodies (CD45, CD19, CD3, CD4, CD8, CD38, HLADR, and CD56) analysis. Correlation between lymphocyte subset analysis and clinical profile was determined. 26 patients including 11 with mild disease and 15 with severe disease were enrolled. The median age was 58 years (range: 33–81), with a male: female ratio of 1.36:1. Significant lymphopenia was observed in the severe group compared to the mild group (p < 0.02). The absolute numbers of CD3+, CD4+, CD8 + T cells, B cells, and NK cells were significantly reduced in the severe group as compared to the mild group (p < 0.05). In patients with severe disease, the proportion of CD8 + and CD4 + T cells were significantly higher than those in patients with mild disease (p = 0.0372). Using ROC analysis, a CD4:8 T cell ratio of ≥ 2.63 and an activated (CD38 + HLA-DR+) CD8 T cell proportion of > 15.85

Background Computed tomography (CT)-guided biopsy is emerging as a preferred method for obtaining tissue samples from retroperitoneal lesions due to clear visualization of needle and vessels. Purpose To assess diagnostic yield and safety of CT-guided biopsy of retroperitoneal lesions and compare CT findings in different disease categories. Material and Methods This retrospective analytical study included 86 patients with retroperitoneal lesions who underwent CT-guided biopsy from December 2010 to March 2020. All procedures were performed with co-axial technique and multiple cores were obtained and subjected to histopathology. Additional tests like immunohistochemistry or microbiological analysis were done depending on clinical suspicion. Diagnostic yield calculation and comparison of imaging findings was done by one-way ANOVA, chi-square, and Fisher’s exact tests. Results CT-guided biopsy was technically successful in all cases with a diagnostic yield of 91.9%. Minor complications in the form of small hematomas were seen in two patients. Major disease categories on final diagnosis were lymphoma, tuberculosis, and metastases. A variety of malignant and benign soft-tissue neoplasms were also noted less commonly. With help of immunohistochemistry, lymphoma subtype was established in 88.8% of cases. Addition of microbiological tests like the GeneXpert assay helped in the diagnosis of tuberculosis in some cases. A mass-like appearance and vascular encasement was common in metastatic group and lymphoma. Conclusion Percutaneous CT-guided biopsy is a safe method for the sampling of retroperitoneal lesions with high diagnostic yield. Imaging findings are mostly overlapping; however, some features are more common in a particular disease condition.

High-dose methotrexate (HD-MTX) that is given in the form of continuous infusion over 24hours forms an essential part of extra compartmental therapy pediatric-inspired protocols for treatment of acute lymphoblastic leukemia (ALL). Dermatological eruptions due to HD-MTX are rarely reported as compared with low-dose MTX (LD-MTX) therapy given for immunodermatological disorders. Defects in skin and muco-sa pave way for bacterial invasion and sepsis in a neutropenic patient adding up to complications and contributing to morbidity due to ALL. We report a 24-year-old female diagnosed as Philadel-phia positive B cell ALL treated with Berlin-Frank-Mun-chester-95 protocol, who developed severe methotrexate-induced dermatological eruption post fi rst HD-MTX infusion. She had an uneventful induction course with docu-mented minimal residual disease negativity post induction. After documenting baseline normal complete blood count and biochemistry values, hydration along with alkalinization was started as per institute ’ s protocol. Interacting medications such as dasatinib, septran, 6-mercaptopurine, and folate were stopped. HD-MTX was administered at a dose of 5 gm/m 2 as a 24-hour infusion. Her maximum serum level of MTX at 36 hours was 1.38

The outcome of acute myeloid leukemia (AML) in low-middle-income countries (LMIC) is dismal due to delayed clinical presentation and infection-related complications. We aimed to analyze the outcome of patients with AML and the factors associated with its prognosis. A retrospective observational study was conducted at a tertiary care university hospital in North India from January 2015 to December 2019. A total of 137 AML patients (median age 32 year (3–66 years) received intensive chemotherapy during study period. The median delay from diagnosis to treatment was 45 days (6–177 days). Among the 352 febrile neutropenia (FN) episodes analyzed, 175 (49.7%) were culture positive; Gram-negative multi-drug resistant organism (MDRO) sepsis during induction being 57.4% with 34.5% infections due to carbapenem-resistant Enterobacteriaceae (CRE) leading to a mortality rate of 14.6%. The median EFS and OS were 12.0 ± 1.57 (95% CI 8.91–15.08) and 15.0 ± 2.44 (95% CI 10.21–19.78) months respectively. Multivariable analysis revealed significant difference in median OS between favorable vs high risk AML groups (20.0 (95% CI: 12.50–27.49) vs 9.0 (95% CI: 2.99–15.01) months; p = 0.002); time from diagnosis to treatment (< 30 days vs ≥ 30 days; not reached vs 9.0 (95% CI: 6.81–11.18) months; p = 0.001), performance status (1 vs 2 vs 3; not reached vs 12.0 (95% CI: 10.32–13.67) vs 4.0 (95% CI:2.77–5.22); p = 0.001), and attainment of complete remission vs induction failure (not reached vs 6.0 (95% CI: 3.78–8.21); p = 0.002). Patient-related factors like delayed treatment initiation and high incidence of MDRO-associated sepsis are critical determinants of AML outcome in LMIC.

COVID‐19‐associated pulmonary aspergillosis (CAPA) has been widely reported but homogenous large cohort studies are needed to gain real‐world insights about the disease.

Circular RNAs (circRNAs) have been reported to play critical roles in the malignant progression of diverse human cancers, including multiple myeloma (MM). This study aimed to explore the functional role and underlying mechanism of circ_SEC61A1 in MM progression.Quantitative real-time polymerase chain reaction (qRT-PCR) assay was performed to detect the expression levels of circ_SEC61A1, microRNA (miR)-660-5p and cyclin-dependent kinase 6 (CDK6) mRNA. The localization of circ_SEC61A1 in MM cells was tested by the subcellular fractionation location assay. Actinomycin D assay was conducted to determine the characteristics of circ_SEC61A1. Cell proliferation was evaluated by colony formation assay, 5-ethynyl-2’-deoxyuridine (EdU) incorporation assay and 3-(4, 5-Dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) assay. Western blot assay was exploited to examine the expression of proteins. Cell migration and invasion were tested via transwell assay, and cell apoptosis was measured by flow cytometry analysis. Dual-luciferase reporter assay was utilized to confirm the interaction between miR-660-5p and circ_SEC61A1 or CDK6.Circ_SEC61A1 level was increased in MM tissues and cells. Circ_SEC61A1 was a stable circRNA and mainly located in cytoplasm. Circ_SEC61A1 silence restrained the proliferation, metastasis and expedited the apoptosis in MM cells. CDK6 was identified as the target of miR-660-5p, and circ_SEC61A1 sponged miR-660-5p to positively regulate CDK6 expression. The inhibitory impacts of circ_SEC61A1 knockdown on the progression of MM cells were mitigated by miR-660-5p inhibition. MiR-660-5p overexpression blocked the malignant phenotypes of MM cells by targeting CDK6.Our study manifested that circ_SEC61A1 could accelerate MM progression at least partially through modulating miR-660-5p/CDK6 axis.

Primary myelofibrosis in childhood is a rare occurrence. We report a case of 12-year-old female who had a three year history of progressive abdominal distension with two months history of increasing pallor and associated symptoms. On evaluation she was found to have primary myelofibrosis with a novel frameshift deletion in the Calreticulin gene leading to premature truncation of the protein. Patient responded to hydroxyurea and low dose steroid therapy. Our case highlights the typical adult like presentation with a novel mutation in CALR gene, emphasizing the need to perform mutational analysis in pediatric myelofibrosis with no secondary etiology

Musculoskeletal manifestations as the sole presentation in acute leukemia is rare in adults. Acute promyelocytic leukemia (APML) is a subtype of acute myeloid leukemia (AML) with reported incidence of 10 to 15% of total AML cases. APML presenting as polyarticular arthritis has never been reported in the literature. We present an interesting case of 20-year-old male patient who manifested with polyarticular arthritis mainly of small joints as the initial presentation, followed by pancytopenia and eventually was diagnosed as a case of APML on bone marrow morphology and molecular analysis for PML-RARα transcript. He was successfully treated with all-trans-retinoic acid (ATRA) and arsenic trioxide (ATO). Arthritis also resolved with complete remission of APML. Arthritis in a case with pancytopenia should promptly be evaluated prior to treatment with steroids and anti-metabolites. Arthritis can be a presenting manifestation of APML and responds to prompt management of leukemia as in other cases of leukemic arthritis.

Ralstonia mannitolilytica is a Gram-negative, nonfermentative, soil bacterium that is reported to cause opportunistic infections in immunocompromised patients in nosocomial settings. After extensive review of literature, it was found that this is second outbreak reported from India. This study is a retrospective analysis of the clinical features, outcome, and source identification of R. mannitolilytica infection outbreak in a hemato-oncology unit of a tertiary care center of North India between February 2020 and March 2020. We report an outbreak of R. mannitolilytica bacteremia (with or without septic shock) in five patients admitted in hemato-oncology unit at a tertiary care institute in North India for 1 month period. Four patients were cured after administration of appropriate antibiotics as per sensitivity reports, while one patient died of septicemia due to delayed diagnosis. Environmental cultures revealed multidose saline bottles used for administration of drugs as the source of outbreak. Following implementation of use of single dose diluents and flushing solutions in patients with central venous catheter, no new case was reported. Clinicians and microbiologists should keep high index of suspicion to identify these organisms as timely diagnosis is the only key to improve outcomes.