Impact of broad-spectrum antibiotic exposures and multidrug-resistant gram-negative bacteremia on hematopoietic cell transplantation outcomes.

INTRODUCTION: There is a close association between the use of broad-spectrum antibiotics, gut microbiome alteration, multidrug resistant (MDR) gram-negative bacilli (GNB) bacteremia, graft versus host disease (GVHD), and mortality post-allogeneic hematopoietic cell transplantation (allo-HCT). This study reports the impact of the high use of carbapenems and colistin and MDR bacteremia pre- and post-HCT on HCT outcomes. METHODS: This was a single-center, partial retrospective, and prospective study from 2016 to 2020. Both pre- and post-HCT antibiotic exposures and blood culture/sensitivity were recorded. MDR GNB was defined as either non-susceptibility to third-generation cephalosporin or carbapenems. In the absence of positive cultures, the treating physician escalated antibiotics from third-generation cephalosporins to carbapenem and/or colistin as per clinical discretion. De-escalation policy was not strictly enforced. RESULTS: MDR GNB bacteremia was seen in 29 of 76 (38%) of patients peri-HCT. The utilization rates for carbapenems and colistin was significantly higher in the cohort with MDR GNB bacteremia pre-HCT (70% vs. 32%, p = 0.002 and 31% vs. 6.4%, p = 0.007, respectively) and post-HCT (100% vs. 74.5%, p = 0.002, and 55.2% vs. 8.5%, p < 0.0001, respectively). The cohort with MDR GNB bacteremia had significantly more severe acute GVHD at day+100 (45% vs. 17.5%, p = 0.009). The median survival was 204 days compared to not reached in the cohort without any MDR GNB bacteremia (p = 0.005). CONCLUSION: This study shows pre- and post-HCT MDR GNB bacteremia is associated with an increased risk of severe acute GVHD and mortality. Patients with MDR GNB bacteremia had higher exposure to pre- and post-HCT carbapenems and colistin.

Use of convalescent plasma for COVID-19 in India: A review & practical guidelines.

Convalescent plasma (CP) therapy is one of the promising therapies being tried for COVID-19 patients. This passive immunity mode involves separating preformed antibodies against SARS-CoV-2 from a recently recovered COVID-19 patient and infusing it into a patient with active disease or an exposed individual for prophylaxis. Its advantages include ease of production, rapid deployment, specificity against the target infectious agent, and scalability. In the current pandemic, it has been used on a large scale across the globe and also in India. However, unequivocal proof of efficacy and effectiveness in COVID-19 is still not available. Various CP therapy parameters such as donor selection, antibody quantification, timing of use, and dosing need to be considered before its use. The current review attempts to summarize the available evidence and provide recommendations for setting up CP protocols in clinical and research settings.

Demographic & clinical profile of patients with COVID-19 at a tertiary care hospital in north India.

BACKGROUND & OBJECTIVES: The COVID-19 pandemic emerged as a major public health emergency affecting the healthcare services all over the world. It is essential to analyze the epidemiological and clinical characteristics of patients with COVID-19 in different parts of our country. This study highlights clinical experience in managing patients with COVID-19 at a tertiary care centre in northern India. METHODS: Clinical characteristics and outcomes of consecutive adults patients admitted to a tertiary care hospital at Chandigarh, India, from April 1 to May 25, 2020 were studied. The diagnosis of SARS-CoV-2 infection was confirmed by real-time reverse transcriptase polymerase chain reaction (RT-PCR) on throat and/or nasopharyngeal swabs. All patients were managed according to the institute's consensus protocol and in accordance with Indian Council of Medical Research guidelines. RESULTS: During the study period, 114 patients with SARS-CoV-2 infection were admitted. The history of contact with COVID-19-affected individuals was available in 75 (65.8%) patients. The median age of the patients was 33.5 yr (13-79 yr), and there were 66 (58%) males. Of the total enrolled patients, 48 (42%) were symptomatic. The common presenting complaints were fever (37, 77%), cough (26, 54%) and shortness of breath (10, 20.8%). Nineteen (17%) patients had hypoxia (SpO2<94%) at presentation and 36 (31%) had tachypnoea (RR >24). Thirty four (29.8%) patients had an accompanying comorbid illness. Age more than 60 yr and presence of diabetes and hypertension were significantly associated with severe COVID-19 disease. Admission to the intensive care unit (ICU) was needed in 18 patients (52%), with three (2.6%) patients requiring assisted ventilation. Mortality of 2.6 per cent (3 patients) was observed. INTERPRETATION & CONCLUSIONS: Majority of the patients with COVID-19 infection presenting to our hospital were young and asymptomatic. Fever was noted only in three-fourth of the patients and respiratory symptoms in half of them. Patients with comorbidities were more vulnerable to complications. Triaged classification of patients and protocol-based treatment resulted in good outcomes and low case fatality.

Randomized controlled trial of twice-daily versus alternate-day oral iron therapy in the treatment of iron-deficiency anemia.

Recent studies in iron-depleted women have challenged the current approach of treating iron-deficiency anemia (IDA) with oral iron in divided daily doses. Alternate day dosing leads to more fractional absorption of iron. In this randomized controlled trial, we looked at the efficacy and safety of alternate-day (AD) versus twice-daily (BD) oral iron in all severity of IDA. Total of 62 patients were randomized, 31 patients in BD arm received 60 mg elemental iron twice daily while 31 patients in AD arm received 120 mg iron on alternate days. The primary endpoint of 2 g/dl rise in hemoglobin was met in significantly more patients in the BD arm at 3 weeks (32.3% vs. 6.5%, p < 0.0001) and 6 weeks (58% vs. 35.5%, p = 0.001). There was a significant rise in the median hemoglobin at 3 (1.6 vs. 1.1, p = 0.02) and 6 weeks (2.9 vs. 2.0 g/dl, p = 0.03) in the BD arm. However, the median hemoglobin rise in the AD arm at 6 weeks was not significantly different than the BD arm at 3 weeks. Alternate-day dosing for 6 weeks and twice-daily dosing for 3 weeks resulted in the provision of the same total amount of iron. There were more reports of nausea in the BD arm (p = 0.03). In conclusion, the choice of twice-daily or alternate-day oral iron therapy should depend on the severity of anemia, the rapidity of response desired, and patient preference to either regimen due to adverse events. Trial Registration: CTRI reg. no. CTRI/2018/07/015106 http://ctri.nic.in/Clinicaltrials/login.php.

Haploidentical Hematopoietic Stem Cell Transplantation for Patients with Severe Aplastic Anemia-Single-Centre Experience.

Severe aplastic anemia (SAA) is a life-threatening type of aplastic anemia for which allogeneic stem cell transplantation or immunosuppressive therapy are the principal treatment modalities. Only about 25-30% of patients have a matched sibling donor, and finding an unrelated donor in ethnic minorities is a challenge. The use of related haploidentical donor transplants in severe aplastic anemia is uncommon. We would like to report our experience with the first four patients who underwent haploidentical transplants for severe aplastic anemia. This is a retrospective study. We collected data from our transplant database of all haploidentical hematopoietic stem cell transplants for SAA from 1 January 2020 to 31 December 2021. The transplant protocol used was the Hopkins' protocol. There were three patients who underwent haploidentical transplants as primary therapy for SAA. A fourth patient received a haploidentical transplant after immunosuppressive therapy failure. The median age of the patients at transplant was 24 y (range 20-29). All patients were engrafted. Neutrophil engraftment occurred at a median of 21 days (range 17-22). Any active infections resolved with the recovery of blood counts. The median hospitalization time was 27 days (range 22-41). Only one patient had grade 2 acute GVHD involving the skin. There was no chronic GVHD. All patients had complete lymphoid and myeloid donor chimerism on day 60. Based on our experience and the emerging literature, haplo-identical transplantation should be considered for select young patients with SAA who have low chances of responding to immunosuppressive therapy.

Randomized controlled trial of pre-transplant zoledronate versus observation for prevention of bone loss in allogeneic hematopoietic cell transplantation.

Background: Approximately half of allogeneic hematopoietic cell transplantation (HCT) recipients experience significant bone loss in the early post-HCT period. Only recently have international guidelines started recommending early screening. However, the guidance for intervention remains conservative. In this study, we sought to evaluate the efficacy of pre-transplant prophylactic zoledronate in preventing early bone loss in allogeneic HCT recipients. Methods: This was an open-label, investigator-initiated, phase 2 randomized controlled trial (RCT) of prophylactic zoledronate versus observation to prevent bone loss in allogeneic HCT recipients. Recipients aged ≥ 18 years of age were included after informed consent and randomized to prophylactic zoledronate 4 mg pre-HCT or observation in a 1:1 ratio. The primary outcome of the study was bone mineral density (BMD) loss at the femoral neck (FN), total hip (TH), and lumbar spine (LS), as assessed using dual-energy X-ray absorptiometry (DXA) on day+100 post-HCT. The secondary outcomes included BMD loss on day+365 and Z scores on day+100 and day+365 at the FN, TH, and LS sites. Results: The trial was terminated because the interim analysis showed a significant benefit in the intervention arm, with 50% planned recruitment. A total of 40 patients were randomized to the zoledronate and control arms. Both arms were matched for age, sex, diagnosis, pre-HCT steroid exposure, body mass index, human leukocyte antigen (HLA) match, and conditioning intensity. The grade 2-4 acute graft versus host disease (GVHD) incidences were comparable. The primary endpoint of BMD loss at FN and TH at day+100 was significant (5.62% vs. -6.78%, p = 0.009, -1.59 vs. -3.98, p = 0.016, respectively). There was no difference in the secondary endpoint of BMD loss on day+365 compared to that on day+100 or baseline at any BMD site. There was no difference in the Z-scores at any site on day+100 or day+365. Conclusions: Prophylactic zoledronate prevented early bone loss on day+100. The indicated preemptive zoledronate beyond day+100 in recipients prevented further bone loss. Patients receiving prophylactic zoledronate may benefit from a supplementary dose of the indicated preemptive zoledronate.

Monocyte Distribution Width (MDW) in Patients with COVID-19: An Indicator of Disease Severity.

Identifying patients with Coronavirus disease-2019 (COVID-19) who may have a severe illness is essential for timely intervention and decreasing the fatality rate. In the present study, we evaluated the performance of Monocyte Distribution Width (MDW) as a prognostic marker for identifying disease severity in COVID-19 patients. We included 145 patients with PCR-confirmed COVID-19 infection in the study. The performance of MDW was evaluated by calculating the area under the receiver operating characteristic curve (AUC), specificity, sensitivity, negative predictive value, and positive predictive value. Further analysis was conducted for the disease outcome, comparing COVID-19 patients discharged (n = 135) to deceased COVID-19 patients (n = 10). As a marker of disease severity, MDW demonstrated an AUC of 0.702 (95% CI 0.620-0.775) in ROC analysis. If MDW is considered a marker of patient outcome, AUC was 0.916 (95% CI 0.862-0.953), comparing deceased COVID-19 patients vs. those who survived. At a cut-off of > 25.4 on admission, MDW correlates well with poor disease outcomes in COVID-19 patients. MDW can be considered a helpful parameter in predicting the severity of COVID-19 disease and patient outcomes. Its role and incorporation in the standard diagnostic algorithm and management of COVID-19 patients need further validation. Supplementary Information: The online version contains supplementary material available at 10.1007/s12288-023-01665-y.

Utility of eGVHD App for bedside GVHD assessment in a high-volume BMT center.

Assessing acute and chronic graft-versus-host disease (GVHD) is challenging because there are several classification systems. The European Society for Blood and Marrow Transplantation and the Center for International Bone Marrow Transplantation Registry task force recommends using the eGVHD application (App) to score acute GVHD according to the Mount Sinai Acute GvHD International Consortium (MAGIC) criteria and chronic GVHD according to the National Institutes of Health 2014 criteria. We prospectively used the eGVHD App at each follow-up visit in a large-volume bone-marrow transplant center in India from 2017 to 2021. We retrospectively evaluated the discrepancy in scoring GVHD severity by physicians not using the App from the same patient charts. The App user satisfaction and experience were recorded using the technology acceptance model (TAM) and the Post-Study System Usability Questionnaire (PSSUQ). In 100 consecutive allogeneic hematopoietic cell transplantation recipients, there was more discrepancy in scoring the severity of chronic GVHD (38%) than acute GVHD (9%) without using the App. The median TAM and PSSUQ scores were six (IQR:1) and two (IQR:1), respectively, indicating high perceived usefulness and user satisfaction. The eGVHD App is an excellent learning tool for hematology/BMT fellows and helps manage GVHD in high-volume BMT centers.

Adherence to long-term follow-up preventive practices in allogeneic hematopoietic cell transplantation survivors from North India.

Introduction: There are existing international guidelines for long-term follow-up (LTFU) care of allogeneic hematopoietic cell transplantation (allo-HCT) survivors. However, implementing these guidelines represents a unique challenge in resource-challenged settings. Methods: This study aimed to evaluate adherence to recommended surveillance in allo-HCT survivors at an academic center in North India and study the incidence of late effects. This single-center, retrospective study analyzed records of allo-HCT recipients from 2016 to 2020. Survivors were screened in our LTFU clinic at day +100 and +365 using cardiometabolic parameters (screening for hypertension, dyslipidemia, hyperglycemia, 24-hour urine protein, thyroid function), pulmonary function test (PFT), bone mineral density (BMD), and initiation of revaccination. Results: A total of 40/80 (50%) allo-HCT survivors were alive at a median of 888 days (IQR 515-1,306). The adherence to home-based screening parameters such as blood pressure and blood glucose was highest (>75%), followed by lab-based parameters (45-70%), and lowest for specialized tests such as PFT (<50%) at both day +100 and +365 time points. Adherence to the initiation of revaccination was only 67%. At least one cardiometabolic parameter was out of range in 55% and 63% of survivors at day +100 and +365, respectively. Conclusion: The adherence to recommended surveillance measures for allo-HCT survivors in an academic LTFU clinic at one year was only 75% overall. Cardiometabolic abnormalities were noted in more than half of the survivors. This study emphasizes the need for a structured LTFU clinic in all centers performing HCT.

Early bone loss in Indian patients undergoing allogeneic hematopoietic cell transplantation.

Background: There is a lack of prospective studies to address the issue of timing of bone mineral density (BMD) measurement and anti-resorptive therapy before and after allogeneic hematopoietic cell transplantation (allo-HCT), specifically in the younger population (age < 40 years). This study evaluated the incidence and risk factors of poor BMD in young Indian patients undergoing allogeneic hematopoietic cell transplant and the effect of anti-resorptive therapy in allogeneic transplant recipients who are at high risk for severe bone loss. Methods: This was a single-center, prospective study conducted from 2016 to 2019. All patients aged ≥ 12 years undergoing allo-HCT were included in the study. Data regarding the risk factors for osteoporosis, underlying diagnoses, and HCT characteristics were recorded. BMD was measured by dual-energy X-ray absorptiometry (DXA) (HOLOGIC Discovery A) at the lumbar spine (LS), femoral neck (FN), and total hip (TH) at pre-HCT, day+100, and day+365 post-HCT. Patients with Z-score ≤ -2 at day+100 were given one dose (4 mg) of intravenous zoledronate. Patients with moderate to severe chronic graft-versus-host disease (GVHD) also received a dose of zoledronate if they had not received it earlier. Results: The median age of our cohort was 24 years (IQR 18.5 - 39.5). Day+100 DXA was available for 25 (54.3%) patients, a paired day+100, and day+365 DXA was available for 15 patients. For pre-HCT, a Z-score ≤ -2 was seen in 30% of patients. For day+100 post-HCT, a Z-score ≤ -2 was seen in 44% of patients. Low body mass index was associated with a Z-score ≤ -2 (median 18 vs. 23 kg/m2, P = 0.04). Despite a single dose of zoledronate in this cohort, the median Δ BMD (day+365 - day+100) loss at FN and LS was -0.8% to -3.7%, respectively. Seven (64%) of these patients also had moderate-severe chronic GVHD. Conclusions: BMD below the expected range for age (Z-score ≤ -2) was present in one-third of young Indian patients undergoing allo-HCT in this single center study. Without intervention, up to half of the patients had a Z-score ≤ -2 at day+100 post-HCT. BMD loss at day+100 persisted at day+365 despite anti-resorptive therapy.

Xpert MTB/RIF for diagnosis of tubercular liver abscess. A case series.

Hepatic involvement is an infrequent manifestation of abdominal tuberculosis and could occur in form of granulomatous hepatitis, nodular involvement or abscess formation. Tubercular liver abscess (TLA) is uncommon, and diagnosing this entity is a challenge. Xpert MTB/RIF (Cepheid, Sunnyvale, CA, USA) assay has been widely used for diagnosing pulmonary tuberculosis (TB) and lymph nodal tuberculosis. Its utility in some forms of other extrapulmonary TB has also been studied. The role of Xpert MTB/RIF for diagnosis of tubercular liver abscess is not known. Here we present a series of four 4 cases of TLA, where the diagnosis was made on the basis of positive Xpert MTB/RIF assay tested on liver drained pus.