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Abstract Introduction International guidelines recommend definitive combination antibiotic therapy for the management of serious infections involving carbapenem-resistant Acinetobacter (CRAB) species. The commonly available combination options include high-dose sulbactam, polymyxins, tetracyclines, and cefiderocol. Scanty prospective data exist to support this approach. Methods Patients with CRAB bacteraemia, ventilator-associated pneumonia (VAP), or both were categorized based on whether they received combination therapy or monotherapy. The 30-day mortality was compared between the two groups. Inverse probability treatment weighting (IPTW) was done using propensity score (PS) for a balanced comparison between groups. Results Between January 2021 and May 2023, of the 161 patients with CRAB bacteraemia (n = 55, 34.2%), VAP (n = 46, 28.6%), or both (n = 60, 37.3%) who received appropriate intravenous antibiotic therapy, 70% (112/161) received monotherapy, and the rest received combination therapy. The overall 30-day mortality was 62% (99/161) and not different (p = 0.76) between the combination therapy (31/49, 63.3%) and monotherapy (68/112, 60.7%) groups. The propensity score matching using IPTW did not show a statistical difference (p = 0.47) in 30-day mortality for receiving combination therapy with an adjusted odds ratio (OR) P of 1.29 (0.64, 2.58). Conclusion Combination therapy for CRAB infections needs further study in a randomised controlled trial, as this observational study showed no difference in 30-day mortality between monotherapy and combination therapy.

Abstract The survival of leukemic cells is significantly influenced by the bone marrow microenvironment, where stromal cells play a crucial role. While there has been substantial progress in understanding the mechanisms and pathways involved in this crosstalk, limited data exist regarding the impact of leukemic cells on bone marrow stromal cells and their potential role in drug resistance. In this study, we identify that leukemic cells prime bone marrow stromal cells towards osteoblast lineage and promote drug resistance. This biased differentiation of stroma is accompanied by dysregulation of the canonical Wnt signaling pathway. Inhibition of Wnt signaling in stroma reversed the drug resistance in leukemic cells, which was further validated in leukemic mice models. This study evaluates the critical role of leukemic cells in establishing a drug-resistant niche by influencing the bone marrow stromal cells. Additionally, it highlights the potential of targeting Wnt signaling in the stroma by repurposing an anthelmintic drug to overcome the microenvironment-mediated drug resistance.

Background: Violence in psychiatric patients is a major concern to both public and mental health professionals. Risk of violence (ROV) in patients can cause a high degree of psychological stress on caregivers that may predispose them to various psychological problems. Aim: To estimate the ROV in patients with severe mental illness and to estimate the relationship between the ROV among severely mentally ill and the psychiatric morbidity in their primary caregivers. Methods: A cross-sectional study was conducted at a tertiary care center involving 308 patient subjects and their caregivers. Socio-demographic data were collected using a proforma, and caregivers were diagnosed based on the International Classification of Diseases-10 using Mini International Neuropsychiatric Interview (MINI)-Plus. ROV was assessed using Historical Clinical Risk Management (HCR)-20, Version 3. Statistical analysis was done using the Chi-square test for association and odds ratio and its 95% confidence interval for the strength of association. Results: High ROV was found in 32.5% of the severely mentally ill. Caregivers reported a high rate of psychiatric disorders (44.8%), of which 71.7% were mood disorders. A significant association was found between ROV in patients and psychiatric morbidity in their caregivers (p = 0.001). Conclusion: ROV is high among the severely mentally ill. There is a high rate of psychiatric morbidity among caregivers of patients with a high ROV. There is a significant association between psychiatric morbidity in caregivers and ROV in patients.

Abstract Introduction The objective of this study was to examine the evolution of carbapenem-resistant Klebsiella pneumoniae (CRKp) infections and their impact at a tertiary care hospital in South India. Methods A comparative analysis of clinical data from two prospective cohorts of patients with CRKp bacteremia (C1, 2014–2015; C2, 2021–2022) was carried out. Antimicrobial susceptibilities and whole genome sequencing (WGS) data of selected isolates were also analyzed. Results A total of 181 patients were enrolled in the study, 56 from C1 and 125 from C2. CRKp bacteremia shifted from critically ill patients with neutropenia to others (ICU stay: C1, 73%; C2, 54%; p = 0.02). The overall mortality rate was 50% and the introduction of ceftazidime-avibactam did not change mortality significantly (54% versus 48%; p = 0.49). Oxacillinases (OXA) 232 and 181 were the most common mechanisms of resistance. WGS showed the introduction of New Delhi metallo-β-lactamase-5 (NDM-5), higher genetic diversity, accessory genome content, and plasmid burden, as well as increased convergence of hypervirulence and carbapenem resistance in C2. Conclusions CRKp continues to pose a significant clinical threat, despite the introduction of new antibiotics. The study highlights the evolution of resistance and virulence in this pathogen and the impact on patient outcomes in South India, providing valuable information for clinicians and researchers.

Introduction: Post hematopoietic stem cell transplant (HSCT), kidney can be subjected to injury by various causes. Of these, graft versus host disease (GvHD) affecting the kidney is an under-recognized entity with no clear guidelines on its diagnosis, clinicopathological manifestations, and outcomes. Material and Methods: Out of 2,930 patients who underwent HSCT at our center between 2005 and 2020, kidney biopsy was performed in 19 allogenic and 5 autologous recipients. Results: The mean age of the cohort at transplant was 33.2 ± 7 years, and 15 (62%) were males. Median time to kidney biopsy from HSCT was 14 (IQR, 9–30) months. Aplastic anemia was the most common underlying hematological disease (54.2%). All 19 allogenic recipients were classified based on clinicopathological manifestations into either thrombotic microangiopathy (TMA, 12/19 [63%]) or nephrotic syndrome (NS, 7/19 [37%]) pattern. Glomerular tuft “mesangiolysis” was the dominant pattern of injury noted in 9/12 cases of TMA pattern. There was a predominance of acute microangiopathic changes restricted primarily to the glomerular compartment. Of the 7 patients with NS pattern, membranous nephropathy was seen in 4 (57%) and minimal change disease in 3 (43%) patients. Thirty-nine percent (7/18) stained positive for C4d which was predominantly glomerular. Allogenic recipients who did not receive immunosuppression (IS) for renal disease had a lower eGFR at biopsy, a longer latency between withdrawal of GvHD prophylaxis and biopsy, and were significantly at a higher risk of kidney failure (IS: 2/11, 18.1% vs. no IS: 2/6, 33.3%, p = 0.04). “Associated extra-renal GvHD” occurred in 11/19 (57.9%) allogenic recipients. Patients with “associated extra-renal GvHD” had significantly more deaths (6/11, 60% vs. 0, p = 0.02) but comparable renal outcomes. Conclusion: Renal GvHD can present with or without “associated extra-renal GvHD” after a prolonged period of withdrawal of GvHD prophylaxis, requiring careful diagnostic vigilance and consideration of IS.

Refractory acute myeloid leukemia (AML), defined as failure of two cycles of induction therapy at diagnosis or of one cycle at relapse, represents a subgroup with poor outcomes. Haploidentical natural killer cell (NK) therapy is a strategy that is being explored in refractory malignancies. Historically, at our center, patients with refractory AML have been treated with cytoreductive therapy (fludarabine + cytosine + granulocyte colony-stimulating factor ± idarubicin or mitoxantrone + etoposide) followed by 1-week rest and then reduced-intensity transplant with fludarabine + melphalan. We used the same backbone for this trial (CTRI/2019/02/017505) with the addition of CD56-positive cells from a family donor infused 1 day after the completion of chemotherapy. CD56-positive selection was done using a CliniMACS Prodigy system (Miltenyi Biotec, Bergisch Gladbach, Germany) followed by overnight incubation in autologous plasma with 2 micromolar arsenic trioxide and 500 U/mL of interleukin-2. From February 2019, 14 patients with a median age of 29 years (interquartile range [IQR]: 16.5–38.5) were enrolled in this trial. Six were females. Six had primary refractory AML while eight had relapsed refractory AML. The median CD56-cell dose infused was 46.16 × 106/kg (IQR: 25.06–70.36). One patient withdrew consent after NK cell infusion. Of the 13 patients who proceeded to transplant, five died of immediate post-transplant complications while two did not engraft but were in morphologic leukemia-free state (both subsequently died of infective complications after the second transplant). Of the remaining six patients who engrafted and survived beyond 1 month of the transplant, two developed disease relapse and died. The remaining four patients are alive and relapse free at the last follow-up (mean follow-up duration of surviving patients is 24 months). The 2-year estimated overall survival for the cohort was 28.6% ± 12.1% while the treatment-related mortality (TRM) with this approach was 38.5% ± 13.5%. Haploidentical NK cell therapy as an adjunct to transplant is safe and needs further exploration in patients with AML. For refractory AML, post-transplant NK infusion and strategies to reduce TRM while using pre-transplant NK infusion merit exploration.

Abstract Purpose Identifying persistent bacteremia early in patients with neutropenia may improve outcome. This study evaluated the role of follow-up blood cultures (FUBC) positivity in predicting outcomes among patients with neutropenia and carbapenem-resistant gram-negative bloodstream infections (CRGNBSI). Methods This retrospective cohort study conducted between December 2017 and April 2022 included patients more than 15 years old with neutropenia and CRGNBSI, who survived for ≥ 48 h, receiving appropriate antibiotic therapy and had FUBCs. Patients with polymicrobial bacteremia within 30 days were excluded. The primary outcome was 30 day mortality. Persistent bacteremia, septic shock, recovery from neutropenia, prolonged or profound neutropenia, requirement of intensive care and dialysis, and initiation of appropriate empirical therapy were also studied. Results In our study cohort of 155 patients, the 30 day mortality rate was 47.7%. Persistent bacteremia was common in our patient cohort (43.8%). Carbapenem resistant isolates identified in the study were K.pneumoniae (80%), E.coli (12.26%), P.aeruginosa (5.16%), A.baumanii (1.94%) and E.cloacae (0.65%). The median time for sending a FUBC was 2 days (IQR, 1–3 days). Patients with persistent bacteremia had higher mortality than those without (56.76% versus 32.1%; p

Classifying diffuse large B cell lymphomas, not otherwise specified (DLBCL, NOS), is based on their cell-of-origin (COO) which is included in the WHO classification (2016), is essential to characterize them better in context of prognostication. While gene expression profiling (GEP) considered the gold standard and more recently, the Nanostring-based approach, classify these tumors accurately, many laboratories with limited resources and instrumentation need an alternate approach that is reliable, inexpensive, and with a reasonable turnaround. The Reverse Transcriptase Multiplex Ligation Dependant Probe Amplification (RT-MLPA) to subtype DLBCL, NOS cases, as designed by CALYM group appears to provide a good alternative but needs to be validated in other centres. Therefore, this study evaluated DLBCL, NOS and compared the results of RT-MLPA to that obtained by immunohistochemistry using the Hans algorithm. Materials and Methods: Sixty-five DLBCL, NOS cases were included and the RT-MLPA was set up and standardized using probes that were designed by the CALYM study group. Briefly, RNA was extracted converted to cDNA and the 21-gene expression classifier that also included probes to detect MYD88 mutations and EBER mRNA was performed by MLPA. The results were analyzed by the open home grown software designed by the same group and compared to the results obtained by IHC. Results: Forty-four of the sixty-five cases provided concordant results (k = 0.35) and if the MYD88 results were to be used as a classifier the concordance would have improved from 67.7% to 82%. The 21 discordant cases were divided into five categories to provide a possible explanation for the discordance. Further 26% and 31% of the samples tested were positive for MYD88 mutations and EBER mRNA, respectively. The test had a turnaround of three days. Conclusion: The test provided moderate (67.7%) concordance when compared with IHC and perhaps would have provided higher concordance if compared with GEP. The test also has the advantage of providing information on the MYD88 and EBV infection status. It was found to be reliable, easy to perform and standardize, requiring only routine instruments available in most molecular laboratories. The RT-MLPA assay therefore provides an alternative for laboratories that would require subtyping of DLBCL, NOS cases in the absence of an access to GEP or other instrument intensive methods.

Hyperacute GVHD (HaGVHD) is a rare complication of hematopoietic stem cell transplantation (HSCT) occurring before engraftment, a syndrome commonly involving skin and/or gut and/or liver, with increased morbidity and mortality. Myeloablative conditioning (MAC) regimes and mismatched donor transplants have an increased risk for HaGVHD. There is a higher chance of steroid-refractoriness and chronic GVHD in those who develop HaGVHD. There is limited literature about HaGVHD, especially in the paediatric age group. This retrospective single-centre case series included five paediatric patients who underwent HSCT between 1st April 2013 and 31st July 2015 at a tertiary care centre in South India, who fulfilled the criteria for HaGVHD as per criteria by Kim et al. and whose follow up data was available. We noted their risk factors, clinical course and prognosis. There were five paediatric HaGVHD patients. The risk factors noted among them were MAC regimen in three and mismatched unrelated donor sources in three. Two had steroid-refractory disease, four went on to develop chronic GVHD and three died of GVHD or treatment-related complications. A high index of suspicion is necessary to recognize HaGVHD, especially in patients with known risk factors developing a fever with rash post-HSCT.

Background: Hematopoietic stem cell transplantation [HSCT] is the only curative option for Fanconi Anemia (FA) patients with hematological abnormalities. Materials and Methods: This is a retrospective analysis of patients with FA who underwent a matched-related donor HSCT. Results: Sixty patients underwent 65 transplants between 1999-2021 using a fludarabine-based low-intensity conditioning regimen. The median age at transplant was 11 years (range: 3-37). Aplastic anemia (AA) was the underlying diagnosis in 55 (84.6%) while 8 (12.4%) had myelodysplastic syndrome (MDS) and 2 (3%) had acute myeloid leukemia (AML). The conditioning regimen used was fludarabine with low-dose cyclophosphamide for aplastic anemia and Fludarabine with low-dose busulfan for MDS/AML. Graft versus host disease (GVHD)prophylaxis consisted of cyclosporine and methotrexate. Peripheral blood stem cells was the predominant graft source (86.2%). Engraftment occurred in all but 1 patient. The median time to neutrophil and platelet engraftment was 13 days (range: 9-29) & 13 days (range: 5-31), respectively. Day 28 chimerism analysis showed complete chimerism in 75.4 % and mixed chimerism in 18.5%. Secondary graft failure was encountered in 7.7%. Grade II–IV acute GVHD occurred in 29.2% while Grade III-IV acute GVHD occurred in 9.2%. Chronic GVHD was seen in 58.5% and was limited in most patients. The median follow-up is 55 months [range: 2-144] & the 5-year estimated overall survival (OS) is 80.2 ± 5.1%. Secondary malignancies were noted in 4 patients. The 5-year OS was significantly higher in patients undergoing HSCT for AA (86.6 + 4.7%) as compared to MDS/AML (45.7+16.6%) (p= 0.001). Conclusion: SCT using a fully matched donor provides good outcomes with low-intensity conditioning regimens in patients with FA who have an aplastic marrow.

Abstract Purpose Immune thrombocytopenia (ITP) is primarily considered a bleeding disorder; its impact on patients’ health-related quality of life (HRQoL) is under-recognized. We aimed to assess how aligned patient and physician perceptions are regarding ITP-associated symptoms, HRQoL, and disease management in India. Methods Patients and physicians (hematologists/hemato-oncologists) from India who participated in the global ITP World Impact Survey (I-WISh) were included in this subgroup analysis (survey). Physicians were recruited via a local, third party recruiter in India. In addition to completing a survey themselves, physicians were asked to invite consulting patients on a consecutive basis to complete a survey. All surveys were completely independently by the respondents online in English. The respondents took 30 min to complete the questionnaire. Patients also completed the newly developed ITP Life Quality Index (ILQI) that included 10 questions on the impact of ITP on the following: work or studies, time taken off work or education, ability to concentrate, social life, sex life, energy levels, ability to undertake daily tasks, ability to provide support, hobbies, and capacity to exercise. Results A total of 65 patients and 21 physicians were included in this study. Average disease duration from diagnosis-to-survey-completion was 5.3 years. The most severe symptoms reported by patients at diagnosis were menorrhagia (15 of 19 patients [79%]), anxiety surrounding unstable platelet counts (17 of 28 patients [61%]), and fatigue (27 of 46 patients [59%]); these were also the key symptoms they wanted to be resolved. In contrast, physicians perceived petechiae (19 of 21 patients [90%]), bleeding-from-gums (8 of 21 patients [86%]), and purpura (16 of 21 patients [76%]) as the most common symptoms. While the important treatment goals for patients were healthy blood counts (42 of 65 patients [65%]), improved QoL (35 of 65 patients [54%]), and prevention of worsening of ITP (33 of 65 patients [51%]), physicians’ goals were reduction in spontaneous bleeding (17 of 21 physicians [81%]), better QoL (14 of 21 physicians [67%]), and symptom improvement (9 of 21 physicians [43%]). More than half the patients reported that ITP affected their work life/studies, social life, and energy levels, thereby negatively impacting their QoL. Patients were almost entirely dependent on family and friends for support. Conclusions This survey highlights the substantial discrepancy in patients’ and physicians’ perceptions regarding ITP-associated symptoms and treatment goals in India. Based on the identified gaps, educating physicians on aspects of ITP beyond bleeding, and highlighting patients’ under-recognized symptoms/needs through support-systems should be prioritized in the future.

Background and Aim: Anaplastic lymphoma kinase (ALK)-positive large B-cell lymphomas (ALK+-LBCLs) are aggressive CD20-negative lymphomas, accounting for

Introduction: BK polyomavirus-associated hemorrhagic cystitis (BKPyV-HC) is a well-recognized infective complication of hematopoietic cell transplant (HCT) with increased organ dysfunction and mortality. This study was performed to describe the local incidence, risk factors, and outcomes of BKPyV infection. Methods: This retrospective case–control study was conducted between 2007 and 2016 from a tertiary hospital in South India. We identified HCT recipients diagnosed with BKPyV-HC and compared them with recipients over the same period who did not develop BK virus infection matched for age, sex, diagnosis, and donor type. We collected data from central electronic medical records and databases maintained in the departments of hematology and virology. Results: Over the study period, 1276 transplants were performed, of which 262 patients (20.5%) developed HC and 105 (8.2%) were BKPyV-positive. Grade 3 HC was most commonly (57.1%) seen, and the median time to develop BKPyV-HC was 35 (range 0–858) days. Survival was significantly lower in the cases (42.9% vs. 61%, P < 0.05). On univariate analysis, the protective effect of nonmyeloablative conditioning (P = 0.04), residual disease at the time of transplant in malignant conditions (P = 0.001), lower CD34 dose (P = 0.006), presence of acute graft versus host disease (GVHD, P < 0.001), reactivation of cytomegalovirus infection (P < 0.001), and presence of bacterial urinary tract infection (UTI) (P < 0.001) were significant factors. Multivariate logistic regression confirmed the presence of acute GVHD (P = 0.041), bacterial UTI (P < 0.001), and residual disease (P = 0.009) at HCT as significant risk factors for BKPyV-HC. Conclusions: Our study affirms the homogeneity of BKPyV-HC disease in low- and middle-income HCT settings with prior reports and the need for therapeutic strategies to reduce its resultant mortality.

Health care workers are at the frontline for management and containment of COVID-19 infection which has put them at additional risk of the disease. Infection and subsequent quarantine of contacts among HCW may produce considerable strain on the health care system. It is essential that we study the modes by which HCW may get infected in the work environment. Methods: All HCW testing positive for SARS COV 2 from 1st March 2020 to 31st Jan 2021 were included in the study. Data regarding possible source of infection, details of symptoms along with demographic details were collected. Results: A total of 390 health-care workers tested positive for SARS CoV-2 in the institution. The mean age of affected health-care workers was 32.82 (±10.6) years (range 20–65 years), and 61.3% were female 33% of the positive HCW were doctors and 19.5% nurses. 29% of the infections occurred during patient care of which majority were from the non-COVID areas of the hospital. Interactions with infected colleagues constituted 27.4% of the infections. Symptomatics constituted 67% and the predominant symptoms included Fever, myalgia and severe headache. 57.2% of those followed up reported persistence of symptoms, commonly fatigue (53%), dyspnea on exertion (48%) and myalgia (18%). Conclusion and Recommendation: Infection control practices in non-COVID areas of the hospital needs to be stepped up. Adherence to masking and personal protection during clinical interactions and with colleagues needs to be maintained. Physical distancing at workplace and during mealtimes needs to be ensured by the system.

Hematopoietic cell transplantation is an established curative treatment option for various hematological malignant, and non-malignant diseases. However, the success of HCT is still limited by life-threatening early complications post-HCT, such as Graft Versus Host Disease (GVHD), Sinusoidal Obstruction Syndrome (SOS), and transplant-associated microangiopathy, to name a few. A decade of research in the discovery and validation of novel blood-based biomarkers aims to manage these early complications by using them for diagnosis or prognosis. Advances in this field have also led to predictive biomarkers to identify patients’ likelihood of response to therapy. Although biomarkers have been extensively evaluated for different complications, these are yet to be used in routine clinical practice. This review provides a detailed summary of various biomarkers for individual early complications post-HCT, their discovery, validation, ongoing clinical trials, and their limitations. Furthermore, this review also provides insights into the biology of biomarkers and the challenge of obtaining a universal cut-off value for biomarkers.

Introduction: BK Polyomavirus induced Haemorrhagic Cystitis (BKPyV-HC), a well-recognised complication following Haematopoietic Cell Transplantation (HCT), is associated with increased organ dysfunction and mortality. The treatment is a multipronged strategy which includes manipulating immunosuppression and antiviral therapy along with newer advances of virus specific cellular therapy. Cidofovir is a nucleotide analogue of Cytosine that is effective against many Deoxyribonucleic Acid (DNA) viruses and its use has been limited in the past because of cost and toxicity. Aim: To capture real world data on the use of cidofovir in BKPyVHC, post HCT especially with regard to dosage, efficacy, toxicity and predictors of response to therapy. The study compared the efficacy and safety of the innovator molecule of cidofovir with Generic versions. Materials and Methods: This study was a retrospective cohort of 67 patients, who were diagnosed with BKPyV-HC post haematopoietic stem cell transplant, and were treated with cidofovir. The study was conducted at a tertiary care centre at Vellore, Tamil Nadu, India, between 2015 and 2021. BKPyV Polymerase Chain Reaction (PCR) was checked in urine routinely in alternate donor transplants, and if there were typical lower urinary tract symptoms or haematuria in any other transplant setting. Treatment with cidofovir (initially innovator and subsequently generic) was as per physician’s discretion. The descriptive data were reported as means with Standard Deviation (SD) or frequencies with percentages as appropriate. Results: Total 985 patients underwent Allogeneic HCT during the study period, of which 67 had BKPyV-HC and were treated with cidofovir (47 with Innovator molecule, 20 with Generic molecule). There was clinical resolution in 47 (70.1%) and mortality in 32 (47.8%) of the cohort. On univariate analysis, risk factors associated with mortality were an absence of clinical resolution (p9×106/Kg (p=0.029), partial remission of malignancy at the time of transplant (p=0.001), ≤3 doses of cidofovir used (p=0.036), BK log value >log 7 at the time of stopping cidofovir (p=0.021) and toxicity with cidofovir (p=0.036). However, only the absence of clinical resolution was significantly associated (p

Due to the limited availability of Root-Zone Soil Moisture (RZSM) information at the regional scale, this paper explores the use of thermal infrared remote sensing to estimate RZSM in agricultural fields. This study presents the Crop Water Stress Index (CWSI) derived from thermal infrared data used as an indicator to estimate root zone soil moisture. Theoretical limits were calculated using canopy and air temperature difference, which is related to vapor pressure deficit. An empirical model was developed using continuous remotely sensed optical, thermal infrared data with limited meteorological data collected from a wheat site, the Dookie experimental farm, Victoria, Australia during 2012 and 2013. Linear and exponential models predicting RZSM using CWSI were constructed and compared in two different cropping seasons. Cross-validation results demonstrate that the linear model predicted RZSM with an error of 3.9% in 2012 and 5.3% in 2013 cropping seasons. The proposed method is applied to another root-zone soil moisture dataset collected during 2002–04 cropping seasons from a corn field site in the Optimizing Production Inputs for Economic and Environmental Enhancement (OPE3) site in the USA. Validation results showed that the model produces reasonable RZSM estimates, except for the high rainfall distribution during cropping seasons even though the crop types of the calibration and validation sites were different. The efficacy of canopy temperature in RZSM estimations was demonstrated using Dookie and OPE3 RZSM dataset. The potential limitation is that sparse vegetation in the initial growth stages produces negative values in CWSI due to the dominant soil surface. Overall, the results support the potential role of the theoretical crop water stress index in root-zone soil moisture estimations.

In this study, the physical and economic impacts of four policy measures (crop diversification, improved watershed development, canal lining and reducing the level of reliability) all designed to improve bulk water supply, are assessed in a case study of the Musi catchment of India. The aim is to compare the impacts these policy measures have on the amount of bulk water supplied and the net economic returns across a complex multi-nodal catchment. It is argued that because it is policymakers who make decisions regarding these measures, an assessment of the private benefits to a subset of users would not be adequate. Rather, the society wide costs and benefits need to be considered. Using a hydroeconomic model of the catchment it was found that reducing the level of reliability was the most beneficial outcome from both a physical and economic perspective. The other three measures were found to have some adverse impacts on regions not directly affected by the measure.

BackgroundHypervirulent variants of Klebsiella pneumoniae (HvKp) were typically associated with a broadly antimicrobial susceptible clone of sequence type (ST) 23 at the time of its emergence. Concerningly, HvKp is now also emerging within multidrug-resistant (MDR) clones, including ST11, ST15, and ST147. MDR-HvKp either carry both the virulence and resistance plasmids or carry a large hybrid plasmid coding for both virulence and resistance determinants. Here, we aimed to genetically characterize a collection of MDR-HvKp ST2096 isolates haboring hybrid plasmids carrying both antimicrobial resistance (AMR) and virulence genes.MethodsNine K. pneumoniae ST2096 isolated over 1 year from the blood sample of hospitalized patients in southern India that were MDR and suspected to be HvKp were selected. All nine isolates were subjected to short-read whole-genome sequencing; a subset (n = 4) was additionally subjected to long-read sequencing to obtain complete genomes for characterization. Mucoviscosity assay was also performed for phenotypic assessment.ResultsAmong the nine isolates, seven were carbapenem-resistant, two of which carried blaNDM-5 on an IncFII plasmid and five carried blaOXA-232 on a ColKP3 plasmid. The organisms were confirmed as HvKp, with characteristic virulence genes (rmpA2, iutA, and iucABCD) carried on a large (~320 kbp) IncFIB–IncHI1B co-integrate. This hybrid plasmid also carried the aadA2, armA, blaOXA-1, msrE, mphE, sul1, and dfrA14 AMR genes in addition to the heavy-metal resistance genes. The hybrid plasmid showed about 60% similarity to the IncHI1B virulence plasmid of K. pneumoniae SGH10 and ~70% sequence identity with the first identified IncHI1B pNDM-MAR plasmid. Notably, the hybrid plasmid carried its type IV-A3 CRISPR-Cas system which harbored spacer regions against traL of IncF plasmids, thereby preventing their acquisition.ConclusionThe convergence of virulence and AMR is clinically concerning in K. pneumoniae. Our data highlight the role of hybrid plasmids carrying both AMR and virulence genes in K. pneumoniae ST2096, suggesting that MDR-HvKp is not confined to selected clones; we highlight the continued emergence of such genotypes across the species. The convergence is occurring globally amidst several clones and is of great concern to public health.

We report here the draft genome sequence of two rare Salmonella serotypes, isolated from human faecal samples in India. The isolates were identified as Salmonella enterica subsp. enterica serovar Ceyco and serovar Hillegersberg by Wole genome sequencing (WGS) based serotype prediction. The genomic similarity of study isolates was identified by clustering with the global collection of Salmonella sp. available in EnteroBase and SISTR based on their cgMLST profile. Phylogenetic analysis showed the study isolates were closer to S. Detmold and other unknown serovars from serogroup D2. The information generated from genome sequencing of two rare S. enterica serovar will improve the overall understanding of the epidemiology of this clinically relevant pathogen.

Abstract Early complications post hematopoietic stem cell transplantation (HSCT) such as sinusoidal obstruction syndrome (SOS) and graft versus host disease (GVHD) can be life threatening. Although several biomarkers have been identified to correlate with these complications and their response to treatment, these are yet to be used in clinical practice. Here, we evaluated circulating endothelial cells (CECs) (n = 26) and plasma biomarkers (ST2, REG3α, VCAM1, ICAM1, TIM3) (N = 210) at early time points, to determine their association with early complications post‐HSCT. Elevated CEC counts at the end of conditioning was associated with GVHD, indicating endothelial damage during HSCT. Plasma levels of REG3α, VCAM1, ICAM1, and TIM3 on day 14 (D14) and D14 ICAM1 and D28 ST2 were significantly higher in patients with SOS and aGVHD, respectively. Upon sub‐group analysis, D28 ST2, D14/D28 REG3α, and D14 ICAM1 levels were significantly higher in patients with gastrointestinal GVHD, while D28 ST2 was higher in those with skin/liver GVHD. High ST2 levels on D28 was significantly associated with non‐relapse mortality (NRM) and overall survival. Our results suggest that elevated ST2 levels on D28 could predict the likelihood of developing aGVHD and could influence NRM and OS.

Abstract The standard‐of‐care for patients with acute promyelocytic leukemia (APL) relapsing after upfront arsenic trioxide (ATO) therapy is not defined. The present study was undertaken to evaluate the safety of addition of bortezomib to ATO in the treatment of relapsed APL based on our previously reported preclinical data demonstrating synergy between these agents. This was an open label, nonrandomized, phase II, single‐center study. We enrolled 22 consecutive patients with relapsed APL. The median age was 26.5 years (interquartile range 17.5 to 41.5). The median time from initial diagnosis to relapse was 23.1 months (interquartile range 15.6 to 43.8). All patients achieved hematological remission at a median time of 45 days (range 40‐63). Nineteen patients were in molecular remission at the end of induction. Grade 3 adverse events occurred in eight instances with one patient requiring discontinuation of therapy for grade 3 neuropathy. Twelve (54.5%) patients underwent autologous transplantation (auto‐SCT) in molecular remission while the rest opted for maintenance therapy. The median follow‐up was 48 months (range 28‐56.3). Of the patients undergoing auto‐SCT, all except one was alive and relapse free at last follow‐up. Of the patients who opted for maintenance therapy, three developed a second relapse. For treatment of APL relapsing after upfront ATO therapy, addition of bortezomib to a standard ATO‐based salvage regimen is safe and effective. This trial was registered at www.clinicaltrials.gov as NCT01950611.

Context: Repeated trauma involving extremities (in the setting of peripheral neuropathy) and poor vascularity that impairs wound healing are important causes of disability and deformity in leprosy patients. Nail changes can serve as indicators of trophic changes due to leprosy. Aims: To describe the onychoscopy findings in leprosy cases and to identify any specific findings in leprosy patients in comparison to controls. Settings and Design: The first 30 leprosy patients and 30 age and sex-matched controls who attended our tertiary care center from 1 August 2018 were included in this cross-sectional study. Materials and Methods: Onychoscopy examination of all fingernails was performed at 50× magnification using dinolite dermoscope AM4113ZT under non-polarizing light to document surface changes and under polarizing light to document pigmentation and vascular changes. Statistical Analysis: The observed nail changes in cases and controls were compared using Pearson's Chi-square test. Results: Statistically significant association with leprosy was found for pitting, onycholysis, melanonychia, transverse lines, nail pallor, and onychauxis. Nail pallor was unique to leprosy patients. Limitations: Small sample size and not evaluating toenails were the major limitations of the study. Conclusions: Studies with large sample size are needed to assess the significance of nail pallor as a specific onychoscopy finding in leprosy.

Abstract: Allogeneic bone marrow transplantation (BMT) is curative therapy for the treatment of patients with severe aplastic anemia (SAA). However, several conditioning regimens can be used for BMT. We evaluated transplant conditioning regimens for BMT in SAA after HLA-matched sibling and unrelated donor BMT. For recipients of HLA-matched sibling donor transplantation (n = 955), fludarabine (Flu)/cyclophosphamide (Cy)/antithymocyte globulin (ATG) or Cy/ATG led to the best survival. The 5-year probabilities of survival with Flu/Cy/ATG, Cy/ATG, Cy ± Flu, and busulfan/Cy were 91%, 91%, 80%, and 84%, respectively (P = .001). For recipients of 8/8 and 7/8 HLA allele-matched unrelated donor transplantation (n = 409), there were no differences in survival between regimens. The 5-year probabilities of survival with Cy/ATG/total body irradiation 200 cGy, Flu/Cy/ATG/total body irradiation 200 cGy, Flu/Cy/ATG, and Cy/ATG were 77%, 80%, 75%, and 72%, respectively (P = .61). Rabbit-derived ATG compared with equine-derived ATG was associated with a lower risk of grade II to IV acute graft-versus-host disease (GVHD) (hazard ratio [HR], 0.39; P < .001) but not chronic GVHD. Independent of conditioning regimen, survival was lower in patients aged >30 years after HLA-matched sibling (HR, 2.74; P < .001) or unrelated donor (HR, 1.98; P = .001) transplantation. These data support Flu/Cy/ATG and Cy/ATG as optimal regimens for HLA-matched sibling BMT. Although survival after an unrelated donor BMT did not differ between regimens, use of rabbit-derived ATG may be preferred because of lower risks of acute GVHD.

Background: Delay in early diagnosis of Specific learning disorder (SLD) is influenced by various factors, including the lack of simple yet validated tools for assessment. Objective: We aimed to develop and validate a screening questionnaire in English and Malayalam for SLD in children aged 7-11 years, which can be used easily. This paper deals with the initial development and preliminary validation of the tool, which was subsequently validated in a larger sample and had already been published. Materials and methods: The tool was validated using a case-control methodology. It was developed after ensuring face and content validity, and suitable modifications were done based on the internal consistency measure and factor analysis results. The tool was applied in children with SLD and two groups of controls. ROC curve analysis was done to find the optimum cut-off, and validity parameters were estimated. Results: A total of 21 SLD, 42 normal and 37 borderline intelligence children, were studied. The final tool with 26 items had good Cronbach’s alpha (0.95) and area under the curve values (0.96). The tool had good sensitivity (100 %) and specificity (77.2%), i.e., if the score is

Abstract: We studied 1110 patients with β-thalassemia major aged ≤25 years who received transplants with grafts from HLA-matched related (n = 677; 61%), HLA-mismatched related (n = 78; 7%), HLA-matched unrelated (n = 252; 23%), and HLA-mismatched unrelated (n = 103; 9%) donors between 2000 and 2016. Ninety percent of transplants were performed in the last decade. Eight-five percent of patients received ≥20 transfusions and 88% were inadequately chelated. All patients received myeloablative-conditioning regimen. Overall and event-free survival were highest for patients aged ≤6 years and after HLA-matched related and HLA-matched unrelated donor transplantation. The 5-year probabilities of overall survival for patients aged ≤6 years, 7 to 15 years, and 16 to 25 years, adjusted for donor type and conditioning regimen were 90%, 84%, and 63%, respectively (P < .001). The corresponding probabilities for event-free survival were 86%, 80%, and 63% (P < .001). Overall and event-free survival did not differ between HLA-matched related and HLA-matched unrelated donor transplantation (89% vs 87% and 86% vs 82%, respectively). Corresponding probabilities after mismatched related and mismatched unrelated donor transplantation were 73% vs 83% and 70% vs 78%. In conclusion, if transplantation is considered as a treatment option it should be offered early (age ≤6 years). An HLA-matched unrelated donor is a suitable alternative if an HLA-matched relative is not available.

Objectives: Chronic alcohol consumption is associated with nutritional deficiency including micronutrients such as magnesium. Alcohol dependent patients often develop delirium during withdrawal. The relationship between low magnesium levels and delirium tremens has not been well studied. This study aims to estimate serum magnesium levels in alcohol withdrawal state and to study its association with severity of delirium. Methodology: This is a prospective study that involved 60 alcohol dependent patients in withdrawal state. Diagnosis was made using the tenth revision of the International Statistical Classification of Diseases and Related Health Problems (ICD-10) criteria. Alcohol withdrawal symptoms were rated using the revised clinical institute withdrawal assessment for alcohol scale (CIWA-Ar). The severity of delirium was rated using the Delirium Rating Scale-revised-98 (DRS-R-98). Serum magnesium was estimated using colorimetric end point method. Results: Twenty per cent (n=12) of the subjects in alcohol withdrawal state had shown hypomagnesaemia. A significant increase in serum magnesium was seen from day one to day five. No significant relationship was noticed for serum magnesium level and severity of delirium. Conclusion: A significant number of alcohol dependent patients during withdrawal demonstrate hypomagnesaemia. Correction of serum magnesium level may be considered in patients with delirium tremens.

Background: Carotid sinus syndrome accounts for one third of patients who presents with unexplained syncope. Prevalence of carotid sinus hypersensitivity (CSH) in Indians has not been studied till now. Objectives: To assess the prevalence and associations of CSH in symptomatic patients above 50 years and to study its prognostic significance pertaining to sudden cardiac death, syncope, recurrent pre syncope and falls on 1 year follow up. Methods: Patients above 50 years who presented with unexplained syncope, recurrent syncope or falls were considered cases and those without these symptoms were considered as controls. All the patients underwent carotid sinus massage and their responses noted. All symptomatic patients were followed up and observed for events like sudden cardiac death, syncope, recurrent pre syncope and falls during 1 year follow up. Patients with recurrent syncope and predominant cardioinhibitory syncope were advised permanent pacemaker implantation. Results: A total of 252 patients were screened, 130 patients constituted cases and 49 patients constituted controls. CSH was demonstrable in 32% (n = 42) of cases as compared to 8% (n = 4) in controls (p

Background: An outbreak of the rare and highly pathogenic Nipah virus infection occurred in Kozhikode, Kerala, India, during May 2018. Methodology: Outbreak control activities included laboratory case confirmation and isolation. Contact surveillance was initiated and close contacts were home quarantined for the maximum incubation period of the disease. Field visits and verbal autopsy of the deaths were done to elicit the details of exposure. Results: Of the 18 confirmed cases, 16 succumbed (case fatality rate, 88.8%). The mean incubation period was 9 days. The transmission was person to person wherein the primary case served as a point source for 15 other cases including 2 health-care workers. The mean age of the affected cases was 41 years with male preponderance. More than 2600 contacts were under surveillance. The outbreak was contained within 3 weeks and declared closed by July the same year. Conclusion: Early detection of the outbreak and prompt isolation of cases along with strengthening of infection control practices and barrier nursing helped in containing the outbreak.

Introduction: In India, a large majority of patients with craniofacial microsomia are unable to undergo complex reconstructions owing to unaffordability, lack of access to good craniofacial centers, or reluctance of parents to accept the surgical risk. There is also considerable social stigma attached to the resultant facial scars of surgery, especially in a girl child. Hence, we have explored autologous fat graft transfer as a “stand-alone” reconstructive option for soft tissue camouflage and aesthetic correction of facial deformity in unilateral craniofacial microsomia of Pruzansky–Kaban Grades I and II. Materials and Methods: Twelve patients who were seeking aesthetic correction of facial deformity in unilateral craniofacial microsomia of Pruzansky–Kaban Grades I and II, and who had adequate fat in the preferred donor sites of lower abdomen and antero-medial thighs, were selected. Patients with Grade III deformity, facial palsy, and previous skeletal surgeries were excluded. Autologous fat harvesting was done with the standardized Coleman’s technique and injected after decantation. Volumetric augmentation was assessed by clinical comparison with normal side for facial symmetry, skin pinch thickness at four reference points, and by two-dimensional analysis of pre- and postoperative standardized photographs at periodic intervals. Results and Analysis: Eleven of our patients were female and one was a male (N = 12). In each session, 20–40mL (mean 28.75 ± standard deviation [SD] 5.69) fat was aspirated and 12–35mL (mean 23.67 ± SD 6.07) fat was injected. The average operating time was 35min (mean 32.91 ± SD 4.05). Majority of our patients needed three sessions (mean 2.8 ± SD 1.03) of serial fat injections to achieve bilateral facial symmetry. Increase in skin pinch thickness was 6.4167 ± 1.31 mm. The mean patient satisfaction score was 8.83 ± SD .717. Conclusion: Based on our results, we conclude that autologous fat transfer, when used for soft tissue camouflage, is a versatile, easy, effective, and inexpensive method for obtaining consistent long-term aesthetic goals in mild to moderate cases of craniofacial microsomia.

Background: Systemic autoinflammatory diseases (SAID) are rare inherited disorders involving genes regulating innate immune signaling and are characterized by periodic or chronic multi-systemic inflammation.Objective: To describe spectrum of clinical, immunological, molecular features, and outcomes of patients with SAID in India.Methods: Request to share data was sent to multiple centers in India that are involved in care and management of patients with Inborn Errors of Immunity. Six centers provided requisite data that were compiled and analyzed.Results: Data on 107 patients with SAID were collated—of these, 29 patients were excluded due to unavailability of complete information. Twelve patients (15%) had type 1 interferonopathies, 21 (26%) had diseases affecting inflammasomes, 30 patients (41%) had non-inflammasome related conditions and 1five patients (19%) had Periodic Fever, Aphthous Stomatitis, Pharyngitis, Adenitis (PFAPA). Type1 interferonopathies identified in the cohort included patients with Deficiency of Adenosine Deaminase 2 (DADA2) (six patients; five families); STING-associated vasculopathy infantile-onset (SAVI) (three patients, one family); Spondyloenchondro-dysplasia with Immune Dysregulation (SPENCD) (two patients). Diseases affecting inflammasomes include Mevalonate Kinase Deficiency (eight patients); Cryopyrin-Associated Periodic Syndromes (CAPS) (seven patients); NLR Family, Pyrin domain-containing 12 (NLRP12) (two patients); Familial Mediterranean fever (FMF) (two patients); Autoinflammation and PLCG2-associated antibody deficiency and immune dysregulation (APLAID) (two patients). TNF receptor-associated periodic syndrome (TRAPS) (three patients); A20 haploinsufficiency (four patients); Deficiency of Interleukin 1 Receptor Antagonist (DIRA) (two patients) were categorized as non-inflammasome related conditions. There were significant delays in diagnosis Corticosteroids and other immunosuppressive agents were used for treatment as anti-IL-1 drugs and other biological agents were and still are not available in India. Eight (16.3%) patients had so far succumbed to their illness.Conclusions: This is the first nationwide cohort of patients with SAID from India. Clinical manifestations were diverse. Overlapping of clinical features with other relatively common rheumatological disorders often resulted in delays in diagnosis. More nationwide efforts are needed to enhance awareness of SAID among health care professionals and there is an urgent need to make targeted immunotherapies universally available.

BackgroundSevere Combined Immune Deficiency (SCID) is an inherited defect in lymphocyte development and function that results in life-threatening opportunistic infections in early infancy. Data on SCID from developing countries are scarce.ObjectiveTo describe clinical and laboratory features of SCID diagnosed at immunology centers across India.MethodsA detailed case proforma in an Excel format was prepared by one of the authors (PV) and was sent to centers in India that care for patients with primary immunodeficiency diseases. We collated clinical, laboratory, and molecular details of patients with clinical profile suggestive of SCID and their outcomes. Twelve (12) centers provided necessary details which were then compiled and analyzed. Diagnosis of SCID/combined immune deficiency (CID) was based on 2018 European Society for Immunodeficiencies working definition for SCID.ResultsWe obtained data on 277 children; 254 were categorized as SCID and 23 as CID. Male-female ratio was 196:81. Median (inter-quartile range) age of onset of clinical symptoms and diagnosis was 2.5 months (1, 5) and 5 months (3.5, 8), respectively. Molecular diagnosis was obtained in 162 patients - IL2RG (36), RAG1 (26), ADA (19), RAG2 (17), JAK3 (15), DCLRE1C (13), IL7RA (9), PNP (3), RFXAP (3), CIITA (2), RFXANK (2), NHEJ1 (2), CD3E (2), CD3D (2), RFX5 (2), ZAP70 (2), STK4 (1), CORO1A (1), STIM1 (1), PRKDC (1), AK2 (1), DOCK2 (1), and SP100 (1). Only 23 children (8.3%) received hematopoietic stem cell transplantation (HSCT). Of these, 11 are doing well post-HSCT. Mortality was recorded in 210 children (75.8%).ConclusionWe document an exponential rise in number of cases diagnosed to have SCID over the last 10 years, probably as a result of increasing awareness and improvement in diagnostic facilities at various centers in India. We suspect that these numbers are just the tip of the iceberg. Majority of patients with SCID in India are probably not being recognized and diagnosed at present. Newborn screening for SCID is the need of the hour. Easy access to pediatric HSCT services would ensure that these patients are offered HSCT at an early age.

BackgroundChronic granulomatous disease (CGD) is an inherited defect in phagocytic respiratory burst that results in severe and life-threatening infections in affected children. Single center studies from India have shown that proportion of autosomal recessive (AR) CGD is more than that reported from the West. Further, affected patients have high mortality rates due to late referrals and difficulties in accessing appropriate treatment. However, there is lack of multicentric collaborative data on CGD from India.ObjectiveTo describe infection patterns, immunological, and molecular features of CGD from multiple centers in India.MethodsA detailed proforma that included clinical and laboratory details was prepared and sent to multiple centers in India that are involved in the care and management of patients with inborn errors of immunity. Twelve centers have provided data which were later pooled together and analyzed.ResultsOf the 236 patients analyzed in our study, X-linked and AR-CGD was seen in 77 and 97, respectively. Male female ratio was 172:64. Median age at onset of symptoms and diagnosis was 8 and 24 months, respectively. Common infections documented include pneumonia (71.6%), lymphadenitis (31.6%), skin and subcutaneous abscess (23.7%), blood-stream infection (13.6%), osteomyelitis (8.6%), liver abscess (7.2%), lung abscess (2.9%), meningoencephalitis (2.5%), splenic abscess (1.7%), and brain abscess (0.9%). Forty-four patients (18.6%) had evidence of mycobacterial infection. Results of molecular assay were available for 141 patients (59.7%)—CYBB (44.7%) gene defect was most common, followed by NCF1 (31.9%), NCF2 (14.9%), and CYBA (8.5%). While CYBA variants were documented only in Southern and Western parts of India, a common dinucleotide deletion in NCF2 (c.835_836delAC) was noted only in North Indian population. Of the 174 patients with available outcome data, 67 (38.5%) had expired. Hematopoietic stem cell transplantation was carried out in 23 patients, and 12 are doing well on follow-up.ConclusionsIn India, proportion of patients with AR-CGD is higher as compared to Western cohorts, though regional differences in types of AR-CGD exist. Clinical profile and mortality rates are similar in both X-linked and AR-CGD. However, this may be a reflection of the fact that milder forms of AR-CGD are probably being missed.

Mendelian Susceptibility to Mycobacterial diseases (MSMD) are a group of innate immune defects with more than 17 genes and 32 clinical phenotypes identified. Defects in the IFN-γ mediated immunity lead to an increased susceptibility to intracellular pathogens like mycobacteria including attenuated Mycobacterium bovis-Bacillus Calmette-Guérin (BCG) vaccine strains and non-tuberculous environmental mycobacteria (NTM), Salmonella, fungi, parasites like Leishmania and some viruses, in otherwise healthy individuals. Mutations in the IL12RB1 gene are the commonest genetic defects identified. This retrospective study reports the clinical, immunological, and molecular characteristics of a cohort of 55 MSMD patients from 10 centers across India. Mycobacterial infection was confirmed by GeneXpert, Histopathology, and acid fast bacilli staining. Immunological workup included lymphocyte subset analysis, Nitro blue tetrazolium (NBT) test, immunoglobulin levels, and flow-cytometric evaluation of the IFN-γ mediated immunity. Genetic analysis was done by next generation sequencing (NGS). Disseminated BCG-osis was the commonest presenting manifestation (82%) with a median age of presentation of 6 months due to the practice of BCG vaccination at birth. This was followed by infection with Salmonella and non-typhi Salmonella (13%), Cytomegalovirus (CMV) (11%), Candida (7%), NTM (4%), and Histoplasma (2%). Thirty-six percent of patients in cohort were infected by more than one organism. This study is the largest cohort of MSMD patients reported from India to the best of our knowledge and we highlight the importance of work up for IL-12/IL-23/ISG15/IFN-γ circuit in all patients with BCG-osis and suspected MSMD irrespective of age.

BackgroundHematopoietic stem cell transplantation (HSCT) is the curative option for many primary immune deficiency disorders (PID). In the last 5 years, increased awareness, availability of diagnostics based on flow cytometry, genetic testing, improved supportive care, use of reduced toxicity conditioning, and success of haploidentical donor HSCT have improved access to HSCT for children with PID in India. We present results on children with PID who underwent HSCT across India and the factors that influenced outcome.Patients and MethodsWe collected retrospective data on the outcome of HSCT for PID from seven centers. We analyzed the impact of the type of PID, conditioning regimen, time period of HSCT- before or after January 2016, graft versus host disease prophylaxis, cause of mortality and overall survival.ResultsA total of 228 children underwent HSCT for PID at a median age of 12 months (range, 1 to 220 months) with a median follow up of 14.4 months. Infants accounted for 51.3% of the cohort and the male female ratio was 3:1. SCID (25%) and HLH (25%) were the more frequent diagnoses. Matched family donor was available in 36.4% and 44.3% children had a haploidentical HSCT. Reduced and myeloablative conditioning regimens were used with 64% children receiving a treosulfan based conditioning regimen. Peripheral blood stem cells were the predominant graft source at 69.3%. The survival in infants (60.2%) was inferior to children aged over 1 year (75.7% p value = 0.01). Children with Wiskott Aldrich syndrome (74.3%) and chronic granulomatous disease (82.6%) had the best outcomes. The survival was superior in children receiving HSCT from a matched sibling (78%) versus an alternate donor HSCT (61% p value = 0.04). In the cohort transplanted after January 2016 survival improved from 26.8% to 77.5% (p value = 0.00). Infection remains the main cause of mortality at in over 50% children. The 5-year overall survival rate was 68%.ConclusionSurvival of children with PID undergoing HSCT in India has improved dramatically in last 5 years. Alternate donor HSCT is now feasible and has made a therapeutic option accessible to all children with PID.

There is limited data on iron reduction therapy (IRT) after successful allogeneic haematopoietic stem cell transplantation (aHSCT) for patients with thalassemia major (TM). We present the long term outcome of IRT in 149 patients with TM who underwent aHSCT during January, 2001-December, 2012. The median age was 7 years (range:1-18) and 92 (61.7%) belonged to Pesaro class 3 with a median ferritin at aHSCT of 2480ng/ml (range:866-8921). IRT was reinitiated post-aHSCT at a median of 14 months (range:5-53) post aHSCT with phlebotomy alone in 10 (6.7%) patients or iron chelation alone in 60 (40.3%) patients while 79 (53%) were treated with the combination. Reduction in serum ferritin/month [absolute quantity (ng/ml/month) was as follows: 87 (range:33-195), 130 (range:17-1012) and 147 (range:27.7-1427) in the phlebotomy, chelation and combination therapy groups, respectively (p = 0.038). With a median follow up of 80 months (range:37-182), target ferritin level of 2500ng/ml) were associated with delayed responses to IRT. Our data shows that IRT may be needed for very long periods in ex-thalassaemics to achieve target ferritin levels and should therefore be carefully planned and initiated as soon as possible after aHSCT. A combination of phlebotomy and iron chelators is more effective in reducing iron overload.

Background: India has the second-largest population of elderly in the world. Serious mental illness (SMI) is a subset of the mental disorders that result in significant functional impairment and is usually long term. Persons with SMI face several challenges in their old age that are different from the issues faced by younger people with SMI. Understanding the problems faced by elderly individuals suffering from SMI is fundamental for planning programs to address them. The SENIOR ( S upport Systems E valuation of N europsychiatric I llness in O ld age) project is a study aimed at evaluating the problems faced in obtaining mental health care by elderly persons having SMI in the Kerala state of India. Aim: To describe the scientific methodology of the SENIOR project. Methods: This study employs mixed-methods cross-sectional design among a minimum sample of 768 SMI patients identified through cluster sampling from three districts, and Focus Group Discussion among mental health program officials. Discussion: This paper presents a methodological model to assist researchers in future field epidemiological studies on mental illness. Assessing service needs and barriers to access for the most vulnerable among the mentally ill will help the policymakers make evidence-based decisions to improve their quality of life.

Cytogenetic risk stratification at diagnosis has long been one of the most useful tools to assess prognosis in acute lymphoblastic leukemia (ALL). To examine the prognostic impact of cytogenetic abnormalities on outcomes after allogeneic hematopoietic cell transplantation, we studied 1731 adults with Philadelphia-negative ALL in complete remission who underwent myeloablative or reduced intensity/non-myeloablative conditioning transplant from unrelated or matched sibling donors reported to the Center for International Blood and Marrow Transplant Research. A total of 632 patients had abnormal conventional metaphase cytogenetics. The leukemia-free survival and overall survival rates at 5 years after transplantation in patients with abnormal cytogenetics were 40% and 42%, respectively, which were similar to those in patients with a normal karyotype. Of the previously established cytogenetic risk classifications, modified Medical Research Council-Eastern Cooperative Oncology Group score was the only independent prognosticator of leukemia-free survival (P=0.03). In the multivariable analysis, monosomy 7 predicted post-transplant relapse [hazard ratio (HR)=2.11; 95% confidence interval (95% CI): 1.04-4.27] and treatment failure (HR=1.97; 95% CI: 1.20-3.24). Complex karyotype was prognostic for relapse (HR=1.69; 95% CI: 1.06-2.69), whereas t(8;14) predicted treatment failure (HR=2.85; 95% CI: 1.35-6.02) and overall mortality (HR=3.03; 95% CI: 1.44-6.41). This large study suggested a novel transplant-specific cytogenetic scheme with adverse [monosomy 7, complex karyotype, del(7q), t(8;14), t(11;19), del(11q), tetraploidy/near triploidy], intermediate (normal karyotype and all other abnormalities), and favorable (high hyperdiploidy) risks to prognosticate leukemia-free survival (P=0.02). Although some previously established high-risk Philadelphia-negative cytogenetic abnormalities in ALL can be overcome by transplantation, monosomy 7, complex karyotype, and t(8;14) continue to pose significant risks and yield inferior outcomes.

Back Ground: Personality disorders especially Emotionally Unstable Personality Disorder (EUPD) may lead to significant marital discord. Though the incidence of separation and divorce are on the rise the problem of underlying personality factors are not given much significance and inadequately studied. Among the personality disorders EUPD is the one that is more likely to be associated with marital discord and separation. Objective To study the marital adjustments of patients with emotionally unstable personality disorder Methodology This cross-sectional study was done in individuals between 18 to 45 years and diagnosed as having EUPD as per ICD 10 DCR criteria, currently staying with their spouse, attending psychiatry department during the study period. Details were collected, Locke Wallace marital adjustment scale was administered, and Chi-square test was used to compare the relevant variables. Results 35 % of the the Sample (n= 34) EUPD subjects reported significant marital dissatisfaction. Co morbid psychiatric disorders were obtained in 23.5% of sample. Association between type of marriage and marital adjustment was found to be significant .41.2% received some kind of psychosocial intervention. 70.6% of the spouses had history of substance use and 23.5 % had history of psychiatric illness. No significant difference in MAT severity was found between EUPD subtypes. Conclusion Study found high level of marital maladjustment among subjects with EUPD.

Purpose: Limited data exist on intensifying chemotherapy regimens in the treatment of adult acute lymphoblastic leukemia (ALL) outside the setting of a clinical trial. Materials and Methods: Retrospectively, data from 507 consecutive adults (age ≥ 15 years) with a diagnosis of ALL treated at our center were analyzed. Standard-risk (SR) patients were offered treatment with a modified German Multicenter ALL (GMALL) regimen, whereas high-risk (HR) patients were offered intensification of therapy with hyperfractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone (HCVAD). Because of resource constraints, a proportion of HR patients opted to receive the same treatment regimen as used for SR patients. Results: There were 344 SR patients (67.8%) and 163 HR patients (32.2%) at diagnosis. Among the HR patients, 53 (32.5%) opted to receive intensification with the HCVAD regimen. The SR cohort showed a superior 5-year event-free survival rate compared with the HR cohort (47.3% v 23.6%, respectively; P < .001). Within the HR subgroup, there was no statistically significant difference in overall survival or event-free survival between patients who received the modified GMALL regimen (n = 59) and patients who received HCVAD (n = 53). Conclusion: Intensified therapy in the HR subset was associated with a significant increase in early treatment-related mortality and cost of treatment. A modified GMALL regimen was found to be cost-effective with clinical outcomes comparable to those achieved with more intensive regimens.

Objectives: The primary objective of the study was to assess the association between central aortic blood pressure indices and coronary artery disease (CAD) in patients undergoing elective angiography and the secondary objective was to study whether any association exists between central aortic pressure indices and the incidence of major adverse cardiovascular events (MACE) in the same patients during a 6-month follow-up period. Methods: We conducted a prospective observational study in consecutive patients undergoing coronary angiography. Central and peripheral pressures were invasively recorded and CAD was classified into obstructive and nonobstructive group. CAD severity was graded using the Gensini score and patients were divided into tertiles. Patients were followed up, and the role of central aortic pressure indices in the prediction of cardiovascular events was analyzed. Results: A total of 623 patients were enrolled. Central pulsatility was found to be most closely associated with severity of CAD by univariate analysis, with age, sex, and smoking status being important predictors of pulsatility. A positive correlation was found between the central and peripheral mean and pulse pressures. No significant association was noted between the central aortic pressures and MACE on short-term follow-up. Conclusions: Of the various central aortic pressure indices studied, central pulsatility was found to be most closely associated with the severity of CAD.

Allogeneic stem cell transplantation (allo-SCT) is the only currently available curative treatment for thalassemia major. Since it was first done in 1981, several thousand patients have benefited from it and it is now possible to offer this treatment in different parts of the world with good results. With better risk stratification and supportive care, the results of allo-SCT are now very good even in high risk patients who have significant iron overload related organ dysfunction. The improvements have mainly been in the conditioning strategies with less toxic myeloablation and management of the complications of SCT. However, several challenges remain. Transplant related complications still cause significant morbidity and mortality. There is data to show that the results of transplantation as best if done in well transfused and chelated patients

Purpose: There are limited data from developing countries on the role and cost-effectiveness of allogeneic stem cell transplantation (allo-SCT) for patients with acute myeloid leukemia (AML). Patients and Methods: We undertook a retrospective descriptive study of all patients with AML who underwent allo-SCT from 1994 to 2013 at our center to evaluate the clinical outcomes and cost-effectiveness of this therapeutic modality. Results: Two hundred fifty-four consecutive patients, median age 34 years, who underwent allo-SCT at our center were included in this study. There were 161 males (63.4%). The 5-year overall survival (OS) and event-free survival for the entire cohort was 40.1 ± 3.5% and 38.7 ± 3.4%, respectively. The 5-year OS for patients in first (CR1), second, and third complete remission and with disease/refractory AML was 53.1 ± 5.2%, 48.2 ± 8.3%, 31.2 ± 17.8%, and 16.0 ± 4.4%, respectively (P < .001). From 2007, reduced intensity conditioning (RIC) with fludarabine and melphalan (Flu/Mel) was used in a majority of patients in CR1 (n = 67). Clinical outcomes were compared with historical conventional myeloablative conditioning regimens (n = 38). Use of Flu/Mel was associated with lower treatment-related mortality at 1 year, higher incidence of chronic graft-versus-host-disease, and comparable relapse rates. The 5-year OS and event-free survival for Flu/Mel and myeloablative conditioning group was 67.2 ± 6.6% versus 38.1 ± 8.1% (P = .003) and 63.8 ± 6.4% versus 32.3 ± 7.9% (P = .002), respectively. Preliminary cost analysis suggests that in our medical cost payment system, RIC allo-SCT in CR1 was likely the most cost-effective strategy in the management of AML. Conclusion: In a resource-constrained environment, Flu/Mel RIC allo-SCT for AML CR1 is likely the most efficacious and cost-effective approach in a subset of newly diagnosed young adult patients.