A retrospective study of antimicrobial usage in wound healing

Background: Chronic wounds are responsible for increase in burden to healthcare systems. The evidence concerning effectiveness of antibiotic therapy or optimal regimens is insufficient. Patients with chronic wounds receive significantly more systemic and topical antibiotics. Current guidelines for antibiotic prescribing for such wounds are often based on expert opinion rather than scientific fact. As there is increasing prevalence of antibiotic resistance, the relationships between antibiotic resistance and rationales for antibiotic therapy have to be determined. Current practice of antibiotic usage for chronic wounds and postoperative wounds in a tertiary care setting should be studied.Methods: Retrospective study was conducted from February 2017 to February 2018 using medical records of patients with wound admitted in surgical departments in HIMS, Hassan, Karnataka. The inpatient records were analysed, which includes duration of stay in the hospital, number of drugs/products per person, percentage of antibiotics prescribed, percentage of antibiotic injection prescribed, and other modalities used to treat wounds.Results: In present study, amongst 100 antimicrobial prescriptions, 26 females and 74 males. The most commonly prescribed parenteral antibiotic was ceftriaxone (58%), followed by metronidazole (56%). The average number of antibiotics per prescription was 2.8. The mean duration parenteral antibiotics given was 4.26 days during their hospital stay oral antibiotics were 5.18 days after the discharge from the hospital.Conclusions: The information generated shall be used to decide the policies to govern the prescription of antibiotics in the management of chronic wounds and post-operative wounds

Chronic lymphocytic leukemia therapy guided by measurable residual disease

Background:Ibrutinib (I) and venetoclax (V) improve chronic lymphocytic leukemia (CLL) outcomes compared to chemo-immunotherapy. We hypothesized I+V is more effective than fludarabine-cyclophosphamide-rituximab (FCR), and personalizing treatment duration, using measurable residual disease (MRD), would optimize outcomes.Methods:FLAIR, a phase III, multicenter, randomized, controlled, open-label platform trial for untreated CLL, compared I+V and I, to FCR. In I+V, after 2m I, V was added for up to 6y of therapy. The duration of I+V was defined by MRD assessed in peripheral blood (PB) and bone marrow (BM) and was double the time to undetectable MRD (uMRD). The primary endpoint was progression-free survival for I+V vs FCR, reported herein. Key secondary endpoints were overall survival, response, MRD and safety. Results:523 participants were randomized to FCR or I+V. At median 43.7m, there were 87 progressions (75 FCR, 12 I+V). The hazard ratio (HR) for progression-free survival for I+V vs FCR is 0.13 (95% confidence interval [CI], 0.07-0.24; P&lt;0.0001). There were 34 deaths (25 FCR, 9 I+V). The HR for overall survival for I+V vs FCR is 0.31 (95%CI, 0.15-0.67). At 3y, 58.0% I+V participants stopped therapy due to uMRD. After 5y of I+V, 65.9% and 92.7% participants were BM and PB uMRD, respectively. Infection rates were similar. There were more cardiovascular events with I+V (10.7%) vs FCR (0.4%). Conclusion:MRD-directed I+V improved progression-free survival and favored overall survival compared to FCR. (Funded by Cancer Research UK and others; Trial Registration number: ISRCTN01844152 and EudraCT, 2013-001944-76.) <br/

Results of a multicentre UK-wide compassionate use programme evaluating the efficacy of idelalisib monotherapy in relapsed, refractory follicular lymphoma.

Follicular lymphoma (FL) is an indolent B-cell malignancy with a variable course. Standard immuno-chemotherapy incorporate alkylator and anti-CD20 monoclonal antibody as first line (Rummel et al, 2013) commonly followed by 24 months rituximab maintenance (Salles et al, 2008). Anthracycline, purine analogue, and alkylator combination are used at relapse and younger patients may have remissions consolidated with autologous or allogeneic stem-cell transplantation (alloSCT) (Kothari et al, 2014). Relapsed or refractory (R/R) FL in patients unfit for transplantation or post-transplantation is incurable, and remains an unmet need

Brexucabtagene autoleucel for relapsed or refractory mantle cell lymphoma in the United Kingdom: A real‐world intention‐to‐treat analysis

Brexucabtagene autoleucel (brexu‐cel) is an autologous CD19 CAR T‐cell product, approved for relapsed/refractory (r/r) mantle cell lymphoma (MCL). In ZUMA‐2, brexu‐cel demonstrated impressive responses in patients failing ≥2 lines, including a bruton's tyrosine kinase inhibitor, with an overall and complete response rate of 93% and 67%, respectively. Here, we report our real‐world intention‐to‐treat (ITT) outcomes for brexu‐cel in consecutive, prospectively approved patients, from 12 institutions in the United Kingdom between February 2021 and June 2023, with a focus on feasibility, efficacy, and tolerability. Of 119 approved, 104 underwent leukapheresis and 83 received a brexu‐cel infusion. Progressive disease (PD) and/or manufacturing (MF) were the most common reasons for failure to reach harvest and/or infusion. For infused patients, best overall and complete response rates were 87% and 81%, respectively. At a median follow‐up of 13.3 months, median progression‐free survival (PFS) for infused patients was 21 months (10.1–NA) with a 6‐ and 12‐month PFS of 82% (95% confidence interval [CI], 71–89) and 62% (95% CI, 49–73), respectively. ≥Grade 3 cytokine release syndrome and neurotoxicity occurred in 12% and 22%, respectively. On multivariate analysis, inferior PFS was associated with male sex, bulky disease, ECOG PS > 1 and previous MF. Cumulative incidence of non‐relapse mortality (NRM) was 6%, 15%, and 25% at 6, 12, and 24 months, respectively, and mostly attributable to infection. Outcomes for infused patients in the UK are comparable to ZUMA‐2 and other real‐world reports. However, ITT analysis highlights a significant dropout due to PD and/or MF. NRM events warrant further attention

Genetic subtypes of smoldering multiple myeloma are associated with distinct pathogenic phenotypes and clinical outcomes

Smoldering multiple myeloma (SMM) is a precursor condition of multiple myeloma (MM) with significant heterogeneity in disease progression. Existing clinical models of progression risk do not fully capture this heterogeneity. Here we integrate 42 genetic alterations from 214 SMM patients using unsupervised binary matrix factorization (BMF) clustering and identify six distinct genetic subtypes. These subtypes are differentially associated with established MM-related RNA signatures, oncogenic and immune transcriptional profiles, and evolving clinical biomarkers. Three genetic subtypes are associated with increased risk of progression to active MM in both the primary and validation cohorts, indicating they can be used to better predict high and low-risk patients within the currently used clinical risk stratification models

Human Peripheral Blood Mononuclear Cells Exhibit Heterogeneous CD52 Expression Levels and Show Differential Sensitivity to Alemtuzumab Mediated Cytolysis

Alemtuzumab is a monoclonal antibody that targets cell surface CD52 and is effective in depleting lymphocytes by cytolytic effects in vivo. Although the cytolytic effects of alemtuzumab are dependent on the density of CD52 antigen on cells, there is scant information regarding the expression levels of CD52 on different cell types. In this study, CD52 expression was assessed on phenotypically distinct subsets of lymphoid and myeloid cells in peripheral blood mononuclear cells (PBMCs) from normal donors. Results demonstrate that subsets of PBMCs express differing levels of CD52. Quantitative analysis showed that memory B cells and myeloid dendritic cells (mDCs) display the highest number while natural killer (NK) cells, plasmacytoid dendritic cells (pDCs) and basophils have the lowest number of CD52 molecules per cell amongst lymphoid and myeloid cell populations respectively. Results of complement dependent cytolysis (CDC) studies indicated that alemtuzumab mediated profound cytolytic effects on B and T cells with minimal effect on NK cells, basophils and pDCs, correlating with the density of CD52 on these cells. Interestingly, despite high CD52 levels, mDCs and monocytes were less susceptible to alemtuzumab-mediated CDC indicating that antigen density alone does not define susceptibility. Additional studies indicated that higher expression levels of complement inhibitory proteins (CIPs) on these cells partially contributes to their resistance to alemtuzumab mediated CDC. These results indicate that alemtuzumab is most effective in depleting cells of the adaptive immune system while leaving innate immune cells relatively intact

Idelalisib treatment prior to allogeneic stem cell transplantation for patients with chronic lymphocytic leukemia: a report from the EBMT chronic malignancies working party

No studies have been reported so far on bridging treatment with idelalisib for patients with chronic lymphocytic leukemia (CLL) prior to allogeneic hematopoietic cell transplantation (alloHCT). To study potential carry-over effects of idelalisib and to assess the impact of pathway-inhibitor (PI) failure we performed a retrospective EBMT registry-based study. Patients with CLL who had a history of idelalisib treatment and received a first alloHCT between 2015 and 2017 were eligible. Data on 72 patients (median age 58 years) were analyzed. Forty percent of patients hadTP53(mut/del)CLL and 64% had failed on at least one PI. No primary graft failure occurred. Cumulative incidences of acute GVHD degrees II-IV and chronic GVHD were 51% and 39%, respectively. Estimates for 2-year overall survival (OS), progression-free survival (PFS), and cumulative incidences of relapse/progression (CIR) and non-relapse mortality NRM were 59%, 44%, 25%, and 31%. In univariate analysis, drug sensitivity was a strong risk factor. For patients who had failed neither PI treatment nor chemoimmunotherapy (CIT) the corresponding 2-year estimates were 73%, 65%, 15%, and 20%, respectively. In conclusion, idelalisib may be considered as an option for bridging therapy prior to alloHCT. Owing to the high risk for acute GVHD intensified clinical monitoring is warranted.Development and application of statistical models for medical scientific researc