Aplastic anemia (AA) is a rare, potentially life-threatening disorder characterized by immune-mediated destruction of hematopoietic stem cells, resulting in a hypocellular bone marrow and cytopenias. Patients typically present with fatigue, infections, and bleeding due to anemia, neutropenia, and thrombocytopenia. Diagnosis is established by demonstrating bone marrow hypocellularity with cytopenias and is classified using the modified Camitta et al. criteria. Compared to the Western world, AA occurs more frequently in Asian populations and at a relatively younger age at presentation. Acquired AA is primarily immune-mediated, involving cytotoxic T-cell destruction of CD34⁺ stem cells and cytokine-mediated suppression of hematopoiesis. Most cases are idiopathic, while secondary causes include infections, drugs, toxins, radiation, immune disorders, and pregnancy. Diagnosis of acquired AA requires exclusion of inherited bone marrow failure syndromes and screening for paroxysmal nocturnal hemoglobinuria (PNH) clones. Diagnosis of idiopathic AA requires careful exclusion of IBMFS and other causes of pancytopenia through detailed clinical assessment and bone marrow examination. It also involves cytogenetic and molecular studies along with screening for PNH clones. Management depends on disease severity, patient age, and donor availability. Hematopoietic stem cell transplantation (HSCT) from a matched sibling donor remains the preferred curative option in eligible patients, whereas immunosuppressive therapy with anti-thymocyte globulin and cyclosporine, often combined with eltrombopag, is recommended for patients ineligible for HSCT. Supportive care is essential for all the patients. These consensus guidelines provide evidence-based recommendations for the diagnosis and management of AA, including severity classification, evaluation for PNH clones, and exclusion of IBMFS. They also address the diagnostic approach and management principles of IBMFS while outlining contemporary treatment strategies such as immunosuppressive therapy and hematopoietic stem cell transplantation, with an emphasis on data from India and other resource-limited settings

Background Patients undergoing haematopoietic stem cell transplantation (HSCT) are highly susceptible to bloodstream infections (BSIs) caused by antimicrobial resistant (AMR) pathogens, yet the temporal dynamics and clinical relevance of intestinal AMR reservoirs remain poorly defined, particularly in high-burden settings. Methods We conducted prospective longitudinal surveillance of 81 HSCT recipients in India using targeted enrichment-based stool metagenomics, coupled with whole genome sequencing of bloodstream isolates and strain-level tracking. Results Across 252 samples, we identified a restructuring of the gut-associated resistome, characterised by depletion during conditioning and a marked post-engraftment expansion of non-efflux AMR determinants, including plasmid-borne carbapenemase and ESBL genes ( bla NDM, bla OXA). This expansion defined a previously underappreciated window of vulnerability during early immune recovery. Over 50% of patients harboured multidrug-resistant organisms, and carriage of bla NDM was associated with increased odds of subsequent infection. Strain-resolved analyses provided genomic evidence linking gut colonisation to bloodstream infection in a subset of cases, demonstrating the feasibility of non-invasive prediction of invasive disease. Patients with AMR-BSIs experienced high mortality (> 40%). Conclusions These findings establish that dynamic changes in the gut resistome following HSCT can identify periods of heightened infection risk and provide a foundation for predictive, genomics-guided surveillance and antimicrobial stewardship strategies in high-burden settings.

Severe aplastic anemia [SAA] is a serious illness characterized by pancytopenia with symptoms of hematopoietic failure and a hypocellular marrow. Both hematopoietic stem cell transplantation [HSCT] and immunosuppressive therapy [IST] with antithymocyte globulin [ATG] are the standard treatment options available. The process of HSCT can vary depending upon whether it is being offered for idiopathic AA or for inherited bone marrow failure syndromes [IBMFS]. For idiopathic AA, HSCT using a matched sibling [MSD] donor is the treatment of choice in patients below the age of 50 years. Alternate donor [matched unrelated donor and haplo-identical donor] transplants may be offered upfront in specific circumstances. Conditioning regimens used include a combination of Cyclophosphamide with ATG or Fludarabine with Cyclophosphamide and ATG. The preferred graft source is unmanipulated bone marrow [BM]; however, in low-income countries and in specific circumstances, the use of peripheral blood stem cells [PBSC] may be preferred. Graft-versus-host disease [GVHD] prophylaxis consists of a calcineurin inhibitor [CNI] – either Cyclosporine or Tacrolimus in combination with short course methotrexate. The overall survival after MSD transplants is close to 90

Antiemetic therapy is an essential component of supportive care following hematopoietic stem cell transplantation (HSCT). Chemotherapy and irradiation used in conditioning regimens frequently induce severe nausea and vomiting, which can significantly impair patients' quality of life. Although recent guidelines recommend a triple combination of a 5-hydroxytryptamine-3 (5-HT3) receptor antagonist, dexamethasone, and an neurokinin 1 (NK1) receptor antagonist, antiemetic practices vary widely across countries and regions. This study aimed to investigate current antiemetic policies among the Asia-Pacific Blood and Marrow Transplantation (APBMT) centers. A web-based questionnaire survey using SurveyMonkey was distributed via email from the APBMT office between December 7, 2021, and January 21, 2022. The survey addressed antiemetic strategies used in HSCT conditioning regimens. Responses were received from 28 centers across 14 countries. Among the participating centers, 93% reported that physicians were primarily responsible for antiemetic decision-making, with limited involvement from pharmacists or multidisciplinary teams. The most commonly used conditioning regimens for allogeneic HSCT were busulfan and cyclophosphamide (Bu-CY) (72%) and fludarabine and busulfan (Flu-Bu) (62%), whereas high-dose melphalan (83%) and carmustine (BCNU), etoposide, cytarabine arabinoside, and melphalan (BEAM) (69%) were predominant for autologous HSCT. Despite guidelines recommending olanzapine as an additional antiemetic in highly emetogenic chemotherapy, its routine implementation remains limited, even in high-risk settings. Notably, dexamethasone is frequently avoided in allogeneic HSCT, likely due to concerns about its immunosuppressive effects. The incidence of vomiting varied, with 36% of centers reporting rates of 10% or higher, even among those with institutional antiemetic policies. In conclusion, this survey highlighted substantial variation in antiemetic strategies across the APBMT centers. The limited use of olanzapine reflects ongoing concerns regarding its side effects, while the frequent avoidance of dexamethasone in allogeneic HSCT represents a deviation from current guideline recommendations. Given the complexity of HSCT and the varying side effect profiles of antiemetic agents, a multidisciplinary approach to treatment planning, including that of pharmacists and dietitians, could optimize supportive care. Future prospective studies are warranted to evaluate the safety, efficacy, and feasibility of olanzapine- and steroid-sparing antiemetic strategies to improve patient outcomes.

PURPOSE:Invasive aspergillosis (IA) is an important cause of mortality in haemato-oncology patients. Polymerase chain reaction (PCR) and galactomannan (GM) enzyme immunoassays are two key laboratory tests in the diagnosis of IA. METHODS:An in-house qualitative real-time PCR (Aspergillus PCR) for the detection of IA, and galactomannan assay were performed on serum samples collected from haemato-oncology patients at-risk of Invasive Aspergillosis. Patients were categorized into proven or probable or possible IA according to the revised EORTC/MSGERC (2020) definitions. RESULTS:The in-house Aspergillus PCR had a sensitivity, specificity, PPV, and NPV of 82.00%, 56.76%, 71.93%, and 70.00% respectively when compared with a galactomannan assay. Among the study participants, two patients had proven, 37 had probable and 48 had possible IA. When the Aspergillus PCR was evaluated against those with proven/probable IA (as per the EORTC/MSGERC 2020 definition), the test showed sensitivity, specificity, PPV, and NPV of 69.23%, 52.08%, 54.00%, and 67.57% respectively. When combined positive results of either PCR or galactomannan were compared against proven/probable IA as per the EORTC 2020 definition, sensitivity, specificity, PPV and NPV were 97.44%, 37.50%, 55.88%, and 94.74% respectively. CONCLUSION:Aspergillus PCR from single serum sample as a standalone screening test in those at-risk patients for IA has moderate sensitivity and specificity. Combining molecular testing with serological testing for antigen detection has good diagnostic sensitivity and hence IA PCR needs to be included as part of the screening tests.

As effects of plateletpheresis on donor haematopoiesis are contradictory, the present study investigated changes in haematological parameters during and after apheresis, and the impact of iron parameters in platelet recovery. Blood samples collected from 32 consenting donors were used to analyse haematological parameters in a pilot study. Serum samples were isolated for estimation of iron parameters in 10 donors, within 30 min after initiation, and after 48 h, 96 h, day 7 and day 10. The Paired t-test or repeated measure analysis of variance (ANOVA) were used to compare parameters between 2/more time points. Changes in platelet recovery and iron parameters were compared by the paired t-test, and associations between them were assessed by Pearson’s/ Spearman’s correlation analyses. Platelet recovery between donor groups classified by their iron content was compared by the student’s t test. Transient changes in different haematological parameters during apheresis were not observed after 48 h. Platelet counts decreased (p < 0.001), mean platelet volume (MPV) increased (p < 0.001) after 48 h. Mean platelet recovery exceeded baseline counts on day 10 (p < 0.001). Serum iron (SI) declined from day 7 (p < 0.001), after initially increasing. Platelet recovery showed significant association with changes in sTfR (r = 0.31, p < 0.05). No differences in platelet recovery were observed between donor groups, classified by their iron content. Changes in haematological parameters during plateletpheresis are transient, and the time required for platelet recovery is dependent on pre-donation counts. The effect of iron profile in influencing platelet recovery was explored.

Background:Abnormal coagulation and thrombotic complications prompted many guidelines to recommend thromboprophylaxis for patients hospitalised with COVID-19, but the dose required for prophylaxis remains unclear. This systematic review (SR) analyses the safety and efficacy of therapeutic dose anticoagulation (TDA) versus non-therapeutic dose anticoagulation (NDA) in COVID-19 patients. Methods:According to the Cochrane Handbook of Systematic Review of Interventions, we performed an SR. The protocol is registered in Prospero (CRD42021269197, date 12 August 2021). Results:In this SR of 18 studies, TDA was shown to reduce all-cause mortality (risk ratio [RR] 0.83; 95% confidence interval [95% CI] 0.70, 0.99) in COVID-19 infection. TDA also reduced thrombosis (RR 0.55; 95% CI 0.48, 0.72) but increased major bleeding (RR 1.87; 95% CI 1.29, 2.69). A stratified analysis according to severity revealed that, in non-critical patients, TDA resulted in mortality benefit (RR 0.79; 95% CI 0.67, 0.94). In critical patients, TDA did not affect all-cause mortality (RR 1.03; 95% CI 0.89, 1.18) but reduced thrombosis (RR 0.65; 95% CI 0.48, 0.86) and increased major bleeding (RR 1.85; 95% CI 1.06, 3.23). Conclusion:TDA significantly reduced all-cause mortality and thrombosis in non-critical COVID-19 patients at the expense of increased major bleeding. In critical COVID-19, this mortality benefit was not observed.

Fludarabine (Flu) in combination with Treosulfan (Treo) and Thiotepa (Thio) (TFT) has been used as a toxicity-reduced conditioning regimen in patients with high-risk β-Thalassemia undergoing HCT, resulting in better outcomes in patients compared to the Bu/Cy-based regimen (Mathews et al., 2013). Our group has previously reported the PK and PD of Flu/Treo-containing regimen (Mohanan et al., 2019; Pai et al., 2023). More recently, there has been an increase in the use of TFT regimen, especially in high-risk Thal at our center, hence the need to explore the impact of Flu PK on HCT outcomes in this group, which has not been reported. Fludarabine exposure and dose optimization in HCT has been attempted by few groups (Ivaturi et al., 2017, Dekker et al., 2024, Scordo et al., 2023). Here, we compared the association between Flu exposure with transplant outcomes in patients with β- Thal. A total of 245 Class III low-risk or high-risk patients who received TFT as a conditioning regimen were enrolled between 2012 and 2024. All patients received Thio 8mg/kg/day x 1 day (day -1) Flu 40mg/m2/day x 4 days (day – 5 to -2) as a 1-hr infusion and Treo as 14g/m2/day x 3 days at the rate of 5g/hr (day -5 to -3) infused post Flu). Plasma samples were collected and stored at various points (pre infusion, end of infusion, and 2hr, 6hr and 24 post infusion) for Flu PK analysis using LC-MS. Non-linear mixed effects modeling analysis was performed with Monolix (version 2023R1) using the SEAM method. A two-compartment PK model was used to describe the data. The individual post hoc parameter values were used to estimate the area under the concentration curve (AUC). The inter-individual variability of the parameters was assumed to be log-normally distributed. A proportional residual error model was used with an assumed normal distribution of the residuals. Patient characteristics and post-transplant outcomes up to one year were documented from the clinical databases. Engraftment was achieved at a median of 16 days (11- 43 days) in 233 (95%) patients. Any deaths occurring within the first 100 days post-HCT were regarded as transplant-related mortality (TRM). Early TRM (TRM≤D30) are deaths occurring within 30 days post-HCT. One-year thalassemia-free survival (TFS) was defined as the time from transplant to the occurrence of an event (rejection or death within a year). Patients were characterized into three groups based on Flu exposure: low AUC (<18 mg*h/L), optimal AUC (18-20 mg*h/L), and high AUC (>20 mg*h/L) (Scordo et al., 2023). Flu exposure cut-off for Allo HCT in Thalassemia has not been previously described and therefore we chose target AUC based on available literature. Descriptive statistics and Pearson Chi-Square analysis were performed to assess the association of Flu exposure with transplant outcomes. In our cohort, 142 patients (58%) were in the low AUC, 23 (9%) in the optimal AUC and 80 (33%) in the high AUC groups. Rejection occurred in a total of 13 patients (5.3%), 8 of whom were in the low AUC group, and 5 in the high AUC, and this association was not statistically significant (p=0.474). Incidence of GvHD was recorded in a total of 67 (27.3%) patients, of which 41 patients were in the low AUC group with no significant difference in Flu AUC among the three groups (p=0.259). TRM day ≤30 occurred in a total of 19 patients (7.8%), of which 10 deaths were in the low AUC group with no statistically significant differences between the three groups as tested by Chi-square analysis (p=0.595). We also observed that Flu exposure had no direct effect on influencing 1yr OS (p=0.817) and TFS (p=0.748). We then compared the outcomes between patients with Flu AUC below or above median (median AUC 15.2mg*hr/L). Similar analysis was done comparing the association of Flu AUC with outcomes, in those above (n=121) and below (n=124) median. However, this too revealed no differences in outcomes based on exposure. Our study suggests that Flu exposure does not directly influence transplant outcomes in high-risk patients with Thalassemia receiving the Thio/Flu/Treo regimen. However, low exposure to Flu may be a surrogate indicator of poor outcomes. More robust patient-specific parameters (pre-transplant risk factors), the role of concomitantly administered drugs such a Treo and other pharmacodynamic measures should be considered along with the PK of Flu to better explain and predict transplant outcomes.

INTRODUCTION:Anti-fungal stewardship (AFS) is a neglected aspect of antimicrobial stewardship programs. This study aimed to examine the effectiveness of an AFS program to ensure rational prescribing of antifungals via a post-prescription review and feedback method. METHODS:In this prospective, interrupted time series analysis, AFS was done on adult patients admitted to the department of hematology in a tertiary care hospital in South India. In the pre-intervention phase, patients on anti-fungal therapy for more than 48 h were identified and baseline data was collected. In the intervention phase, patients on antifungals for >48 h were assessed by an AFS team including an infectious diseases specialist and appropriate recommendations were made regarding modification or discontinuation of the antifungals where required. Acceptance of the intervention by the treating team and clinical outcomes were recorded. RESULTS:A total of 193 courses of antifungal therapy in 152 patients were analyzed over 6 months, of which 107 courses belonged to the pre-intervention phase and 86 were in the intervention phase. In the intervention phase, the AFS teams recommended that 15 (17.44 %) of antifungal prescriptions be modified. Among these, 66 % of the recommendations were accepted by the treating physician. Days of therapy per 1000 patient days were calculated for each individual anti-fungal drug and there was a significant reduction in consumption of antifungals, particularly voriconazole, posaconazole and echinocandins in the intervention phase. There was no statistically significant difference in the in-hospital mortality [26.16 % vs 23. 25 % (p = 0.64)] between the two groups. CONCLUSION:In this study, a focused post prescription review and feedback in an antifungal stewardship program appeared to significantly decrease the prescription of antifungal medication without adversely affecting patient outcomes.

Background/objectives: The outcome of refractory/relapsed systemic Anaplastic Large Cell Lymphoma (R/R-sALCL), especially for anaplastic lymphoma kinase-1 (ALK-1)-negative disease, remains dismal even after autologous hematopoietic stem cell transplantation (AHSCT). The intensification of both salvage and conditioning regimens, without increasing the toxicity, could improve the outcome of AHSCT in R/R-sALCL. Methods: Based on the successful experience of the incorporation of antiD20 monoclonal antibodies in the treatment of B-Cell Lymphomas, we designed a salvage and conditioning regimen incorporating the antiCD30-conjugated antibody (Brentuximab Vedotin, BV) to standard chemotherapy regimens, and we describe herein the clinical course of a patient with AKL-ve, R/R-sALCL, who received salvage regimen BV + DHAP, followed by AHSCT with preparative regimen consisted of BV plus standard BEAM. Results: The novel regimen was well tolerated, and no severe adverse effects were noticed. The engraftment was prompt and successful. The patient remained in complete metabolic remission for almost 12 months post-transplant. Conclusions: The proposed treatment approach, which combines antiCD30-conjugated antibody with standard salvage and conditioning regimens, demonstrated a completely acceptable toxicity with promising efficacy.

A BSTRACT Objectives: Nearly 8.9% of the total Indian population is constituted by tribal groups. The burden of haemoglobinopathies, especially β-thalassaemia, is more prominent among these populations than non-tribal populations. β-Thalassaemia major is a public health challenge that requires proven health strategies to minimise the effect of the same on the communities. This study was conducted to estimate the prevalence of β-thalassaemia trait among the school-going children from Jawadhi Hills of Tamil Nadu. Methods: This cross-sectional study was conducted among school-going children between 8 th to 12 th standards from four different higher secondary schools in Jawadhi Hills. We adopted a unique bag and ball technique for health education, and the participants who consented to the study were screened for β-thalassaemia trait using a complete blood count (CBC) profile and high-performance liquid chromatography (HPLC). Results: A total of 1980 school-going children within the age group 13–19 years were screened for the β-thalassaemia trait, of which 12.3% were positive. The prevalence of anaemia among normal children was 29.5%, whereas the prevalence among β-thalassaemia traits was 56.5%. Conclusion: The prevalence of the β-thalassaemia trait is high among the tribal populations of Jawadhi Hills. Widespread use of proven strategies, including health education followed by screening, is necessary for behavioural changes, which are essential for reducing the burden in the long run.

Post-transplant Cyclophosphamide (PTCy) based Graft versus Host disease (GvHD) prophylaxis has improved the success of Haploidentical transplantation (HaploHCT) in recent years. Along with PtCy, Mycophenolate Mofetil (MMF) is used concomitantly with calcineurin inhibitors (Cyclosporine A (CsA) or Tacrolimus (Tac)) interchangeably. Due to the unavailability of IV Tac at our center, we use PTCy/MMF/CsA based-GvHD prophylaxis for HaploHCT. In our previous pilot MMF Pharmacokinetic (PK) study (Pai et al. Blood, 2022), we observed low MPA (Mycophenolic acid) systemic exposure in all patients, possibly due to potential drug-drug interaction (DDI) with concomitant CsA administration. In the present study, we evaluated the PK and pharmacogenetics (PG) of MMF in a larger cohort, and we attempted to recommend the optimal MMF dosing for HaploHCT in patients receiving PTCy/MMF/CsA based-GvHD prophylaxis. Ninety patients with various underlying diagnoses who underwent HaploHCT between October 2021 and March 2024 were enrolled. All patients received uniform GvHD prophylaxis comprising Cy (I.V. 50 mg/kg/day x 2 days (day +3 to day +4) and i.v. CsA (2.5mg/kg, Q12H) with oral MMF (15 mg/kg/dose Q8H) from day +5 post-HCT. Plasma was separated from the peripheral blood collected at pre-determined time points at day+8 post HCT. Plasma MPA levels were measured using a validated HPLC-UV method, and MPA systemic exposure and clearance were calculated using nonlinear mixed effects modeling via Monolix (version 2023R2). MPA exposure was compared with HaploHCT outcomes using GraphPad Prism8. For PG analysis, we screened for genetic variants using the Infinium Global Screening Array (Illumina, CA, USA), and the effect of genetic variants on MPA PK was then compared. MPA levels were available for all ninety patients. In concordance with our previous findings, we observed low systemic MPA exposure in all patients [Median AUC: 8.7 (1.0 - 27.3) μg*hr/mL) less than the lower limit of the suggested therapeutic range of 30 μg*hr/mL. None of the covariates explained the large variability in MPA PK. We also did not observe any significant association between genetic variants in MPA metabolic pathway-related genes and MPA exposure. The lack of pharmacogenetic associations may be attributed to DDI with CsA, which may mask the effects of any genetic variation on MPA PK. Of 90 patients, seven (8%) died before engraftment. Twenty-nine (32.2%) experienced acute GvHD (Grade I/II-16, III/IV - 13 patients), and at a mean follow-up of 12.3 ± 9.9 months, there were thirty-six deaths (40%). There was no difference in the MPA exposure amongst patients with or without GVHD. No associations were observed with clinical outcomes, including neutrophil engraftment, transplant-related mortality, or survival. We then attempted simulation studies using the current patient data set to identify optimum MMF dosing using different dosing strategies (2g/day TID, 3g/day TID, 500mg/m2 TID, and 750mg/m2 TID). We observed that patients achieved higher MPA exposure when oral MMF is dosed with 750mg/m2 twice daily (15.2±7.1 μg*hr/mL, p<0.0001) and 3g/day flat-dosing (20.2±16.3 μg*hr/mL, p<0.0001) compared to actual dosing (9.3±4.1 μg*hr/mL). Our study suggests that dose intensification is recommended for MMF when used concomitantly with CsA for HaploHCT to achieve therapeutic exposure. Pharmacogenomic associations were not observed with MPA exposure due to the DDI phenomenon with CsA. Simulation studies demonstrated the need for a higher MMF dosage. However, prospective trials with drug monitoring are warranted to address the safety concerns, including toxicities.

Background Anti-CD19 CAR T-cells are an effective therapeutic modality against chemorefractory B-cell leukemia and lymphomas. Decentralized manufacturing using fresh products and a short vein-to-vein time can potentially improve access and efficacy of CAR T-cell therapy, especially in low or middle-income countries (LMIC). We present the results of the phase 1 clinical trial using onsite CAR-T manufacture. Methods The anti-CD19 CAR T-cells were manufactured through the CliniMACS Prodigy system using a second-generation lentiviral vector LTG1563, Lentigen, Miltenyi Biotec, and a 9-day culture protocol. The phase 1 study was designed with a dose escalation strategy using a 3+3 design. Results A total of 10 patients with R/R B-ALL (n=6) and DLBCL (n=4) were enrolled, with a median age of 45 years (range: 6-59). CAR T-cell product manufacture was successful in all patients. The median transduction rate was 38% (range: 16-55%), and the median culture expansion was 15-fold (range: 1-33). Immunophenotypic characterization demonstrated an increase in central memory cells followed by effector cells. All the patients were infused with fresh CAR T-cells. The cell dose was 0.5x106/kg (n=3), 1x106/kg (n=3), and 2x106/kg (n=4). CAR-T persistence by flow cytometry demonstrated a peak in peripheral blood MNCs between days 14 and 21. Adverse events of special interest reported were CRS (grade 2: n=1/6, grade 3: n=1/6; 33% in B-ALL, and 0% in DLBCL, with overall 20%). None of the patients developed ICANS of any grade. Early hematological toxicity (ICAHT) was common and 3 patients had grade 2/3 neutropenia (30%). Among 10 patients evaluable for response, 6/6 B-ALL patients (100%) achieved MRD negativity by day 90. Among the DLBCL patients, 2/4 (50%) achieved complete remission, 1 patient had a partial response, and 1 patient in the first cohort with the lowest cell dose did not respond and died due to progressive disease. At a median follow-up of 6 months, 9/10 patients remain without disease progression. Conclusion The phase 1 data demonstrated the feasibility, safety, and efficacy of decentralized manufactured CAR T-cells. This product's safety profile was comparable to other CAR-T therapies, with high CR rates across different doses in a heavily pretreated cohort of patients.

Osteopetrosis is a clinically and genetically heterogeneous group of inherited bone disorders that is caused by defects in osteoclast formation or function. Treatment options vary with the disease severity and an accurate molecular diagnosis helps in prognostication and treatment decisions. We investigated the genetic causes of osteopetrosis in 31 unrelated patients of Indian origin. Screening for the genetic variants was done by Sanger sequencing or next generation sequencing in 48 samples that included 31 samples from index patients, 16 from parents’ and 1 chorionic villus sample. A total of 30 variants, including 29 unique variants, were identified in 26 of the 31 patients in the study. TCIRG1 was the most involved gene (n = 14) followed by TNFRSF11A (n = 4) and CLCN7 (n = 3). A total of 17 novel variants were identified. Prenatal diagnosis was done in one family and the foetus showed homozygous c.807 + 2T > G variant in TCIRG1 . Molecular diagnosis of osteopetrosis aids in therapeutic decisions including the need for a stem cell transplantation and gives a possible option of performing prenatal diagnosis in affected families. Further studies would help in understanding the genetic etiology in patients where no variants were identified.

CVB3 infection is associated with the development of end-stage heart diseases. Lack of effective anti-viral treatments and vaccines for CVB3 necessitates comprehensive understanding of the molecular players during CVB3 infection. miRNAs have emerged as promising targets for anti-viral strategies. Here, we demonstrate that miR-22-3p binds to 5′ UTR and inhibits viral RNA translation at the later stage of infection to promote viral RNA replication. Conversely, as host response, it targets PCDH1, a proviral factor, to discourage viral propagation. miR-22-3p also influences CVB3 tissue tropism. Deciphering the multifaced role of miR-22-3p during CVB3 infection unravels the necessary molecular insights, which can be exploited for novel intervening strategies to curb infection and restrict viral pathogenesis.