New recommendations to reduce unnecessary blood tests after robot-assisted radical prostatectomy.

Description to be added.Cannot be left empt

Robust estimation of bacterial cell count from optical density

Optical density (OD) is widely used to estimate the density of cells in liquid culture, but cannot be compared between instruments without a standardized calibration protocol and is challenging to relate to actual cell count. We address this with an interlaboratory study comparing three simple, low-cost, and highly accessible OD calibration protocols across 244 laboratories, applied to eight strains of constitutive GFP-expressing E. coli. Based on our results, we recommend calibrating OD to estimated cell count using serial dilution of silica microspheres, which produces highly precise calibration (95.5% of residuals <1.2-fold), is easily assessed for quality control, also assesses instrument effective linear range, and can be combined with fluorescence calibration to obtain units of Molecules of Equivalent Fluorescein (MEFL) per cell, allowing direct comparison and data fusion with flow cytometry measurements: in our study, fluorescence per cell measurements showed only a 1.07-fold mean difference between plate reader and flow cytometry data

Effect of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker initiation on organ support-free days in patients hospitalized with COVID-19

IMPORTANCE Overactivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19. Objective To determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19. DESIGN, SETTING, AND PARTICIPANTS In an ongoing, adaptive platform randomized clinical trial, 721 critically ill and 58 non–critically ill hospitalized adults were randomized to receive an RAS inhibitor or control between March 16, 2021, and February 25, 2022, at 69 sites in 7 countries (final follow-up on June 1, 2022). INTERVENTIONS Patients were randomized to receive open-label initiation of an ACE inhibitor (n = 257), ARB (n = 248), ARB in combination with DMX-200 (a chemokine receptor-2 inhibitor; n = 10), or no RAS inhibitor (control; n = 264) for up to 10 days. MAIN OUTCOMES AND MEASURES The primary outcome was organ support–free days, a composite of hospital survival and days alive without cardiovascular or respiratory organ support through 21 days. The primary analysis was a bayesian cumulative logistic model. Odds ratios (ORs) greater than 1 represent improved outcomes. RESULTS On February 25, 2022, enrollment was discontinued due to safety concerns. Among 679 critically ill patients with available primary outcome data, the median age was 56 years and 239 participants (35.2%) were women. Median (IQR) organ support–free days among critically ill patients was 10 (–1 to 16) in the ACE inhibitor group (n = 231), 8 (–1 to 17) in the ARB group (n = 217), and 12 (0 to 17) in the control group (n = 231) (median adjusted odds ratios of 0.77 [95% bayesian credible interval, 0.58-1.06] for improvement for ACE inhibitor and 0.76 [95% credible interval, 0.56-1.05] for ARB compared with control). The posterior probabilities that ACE inhibitors and ARBs worsened organ support–free days compared with control were 94.9% and 95.4%, respectively. Hospital survival occurred in 166 of 231 critically ill participants (71.9%) in the ACE inhibitor group, 152 of 217 (70.0%) in the ARB group, and 182 of 231 (78.8%) in the control group (posterior probabilities that ACE inhibitor and ARB worsened hospital survival compared with control were 95.3% and 98.1%, respectively). CONCLUSIONS AND RELEVANCE In this trial, among critically ill adults with COVID-19, initiation of an ACE inhibitor or ARB did not improve, and likely worsened, clinical outcomes. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT0273570

Reducing the environmental impact of surgery on a global scale: systematic review and co-prioritization with healthcare workers in 132 countries

Abstract Background Healthcare cannot achieve net-zero carbon without addressing operating theatres. The aim of this study was to prioritize feasible interventions to reduce the environmental impact of operating theatres. Methods This study adopted a four-phase Delphi consensus co-prioritization methodology. In phase 1, a systematic review of published interventions and global consultation of perioperative healthcare professionals were used to longlist interventions. In phase 2, iterative thematic analysis consolidated comparable interventions into a shortlist. In phase 3, the shortlist was co-prioritized based on patient and clinician views on acceptability, feasibility, and safety. In phase 4, ranked lists of interventions were presented by their relevance to high-income countries and low–middle-income countries. Results In phase 1, 43 interventions were identified, which had low uptake in practice according to 3042 professionals globally. In phase 2, a shortlist of 15 intervention domains was generated. In phase 3, interventions were deemed acceptable for more than 90 per cent of patients except for reducing general anaesthesia (84 per cent) and re-sterilization of ‘single-use’ consumables (86 per cent). In phase 4, the top three shortlisted interventions for high-income countries were: introducing recycling; reducing use of anaesthetic gases; and appropriate clinical waste processing. In phase 4, the top three shortlisted interventions for low–middle-income countries were: introducing reusable surgical devices; reducing use of consumables; and reducing the use of general anaesthesia. Conclusion This is a step toward environmentally sustainable operating environments with actionable interventions applicable to both high– and low–middle–income countries

Durable responses in acute lymphoblastic leukaemia with the use of FLT3 and IDH inhibitors

Data regarding the use of FMS-like tyrosine kinase 3 (FLT3) and isocitrate dehydrogenase 1/2 (IDH1/2) inhibitors in acute lymphoblastic leukaemia (ALL) are lacking. We identified 14 patients with FLT3- or IDH1/2-mutated ALL. Three early T-cell precursor-ALL patients received FLT3 or IDH2 inhibitors. Patient 1 maintains a complete remission (CR) with enasidenib after intolerance to chemotherapy. Patient 2 maintained a CR for 27 months after treatment with enasidenib for relapsed disease. Patient 3 was treated with venetoclax and gilteritinib at the time of relapse and maintained a CR with gilteritinib for 8 months. These cases suggest that FLT3 and IDH inhibitors could represent a viable therapeutic option for ALL patients with these mutations

Efficacy and tolerability of a modified pediatric‐inspired intensive regimen for acute lymphoblastic leukemia in older adults

Abstract Although acute lymphoblastic leukemia (ALL) is most common in pediatric and adolescent and young adult (AYA) patients, 20% of cases are diagnosed in patients ≥ 55 years old. Use of intensive pediatric regimens in AYA populations has demonstrated excellent tolerability and significant improvements in event‐free survival (EFS) and overall survival (OS). The backbone of pediatric regimens includes asparaginase and corticosteroids, both of which are associated with more toxicity in older patients and those with body mass index (BMI) ≥ 30 kg/m which leads to poor tolerance of these regimens. We tested the safety and efficacy of a dose‐modified The Cancer and Leukemia Group B 10403 regimen using reduced doses of pegylated (PEG)‐asparaginase (ASP) and corticosteroids (RD‐10403) in 30 patients with Philadelphia‐chromosome negative ALL who were ≥50‐year‐old and younger adults with significant metabolic or hepatic co‐morbidities. The complete remission rate on day 28 was 77%, 3‐year EFS was 54%, and estimated 3‐year OS was 55%. Grade 3+ toxicity was noted in 40% of patients during induction, and induction‐related mortality was 3%. Additional prospective evaluation of RD‐10403 is merited to determine efficacy and safety of this regimen and to serve as a framework for chemoimmunotherapy combination therapy

Outcomes of Patients with Accelerated/Blast-Phase MPNs That Received Allogeneic Stem-Cell Transplant in the Current Era of Myeloid Therapies

Background Patients (pts) with Philadelphia chromosome-negative (Ph-neg) myeloproliferative neoplasms (MPNs) that progress to an accelerated phase (AP) or blast phase (BP) have a median overall survival (mOS) of less than 1 year (Odenike, Blood 2018; Tam et al, JCO 2009). Allogeneic hematopoietic stem cell transplant (allo-HCT) is the only curative approach for MPN-AP/BP, but mOS remains about a year for pts with MPN-BP that undergo allo-HCT (2005-2019) (Orti et al, AJH 2023). We previously reported on outcomes of pts with MPN-AP/BP treated in the current era of myeloid therapies (2017 onward) and found a mOS of 0.73 years in a multi-center cohort of 80 pts (Patel et al, ASH 2022). We aim to characterize treatment patterns and outcomes of pts with MPN-AP/BP that underwent allo-HCT via a multi-center retrospective analysis. Methods Retrospective chart review was performed at 8 institutions to identify pts with pathology-confirmed Ph-neg MPN-AP/BP diagnosed in 2017 or later. All patients that met inclusion criteria were included. Response was assessed using 2017 European Leukemia Net AML (2017 ELN) criteria (Dohner et al, Blood 2017). OS from diagnosis of MPN-AP/BP and from time of allo-HCT was calculated utilizing Kaplan-Meier analysis. Results The full MPN-AP/BP cohort consists of 180 pts. This analysis includes 58 pts that underwent allo-HCT for MPN-AP/BP across 8 institutions. Median age at MPN-AP/BP diagnosiswas 64 years. The most common therapies for chronic-phase MPN included hydroxyurea (55%), JAK inhibitor (JAKi) (26%), interferon (9%), and hypomethylating agent (HMA, 4%). No patient previously received allo-HCT for chronic-phase MPN. Driver mutations included JAK2 (60%), CALR (22%), MPL (10%), but some pts had triple-negative disease (7%). Sixty-two percent of pts had high-risk disease by 2017 ELN criteria. Forty-four pts had next-generation sequencing performed at time of MPN-AP/BP diagnosis. The most frequently co-occurring mutations detected at time of MPN-AP/BP diagnosis were ASXL1 (30%), SRSF2 (23%), RUNX1 (23%), TP53 (18%), TET2 (16%), IDH2 (11%), U2AF1 (7%), EZH2 (7%), and IDH1 (9%). Additional characteristics are in Table 1. One pt proceeded directly to allo-HCT at time of MPN-AP/BP diagnosis. Frontline therapies (1L) for MPN-AP included intensive chemotherapy (IC) (n=26), hypomethylating agent (HMA) + venetoclax (VEN) (n=16), HMA monotherapy (n=14), and low-dose cytarabine (LDAC) + VEN + JAKi (n=1). Responses are summarized in Table 2A. Thirty-seven pts proceeded to allo-HCT after 1L therapy (17 after IC, 10 after HMA+VEN, 9 after HMA, 1 after LDAC+VEN+JAKi). Twenty pts proceeded to allo-HCT after 2 nd-line and beyond (2L+) therapies. Therapies utilized and responses are summarized in Table 2B. Transplant-specific characteristics include 15 pts receiving myeloablative conditioning while 43 received reduced-intensity conditioning. Donor source was matched unrelated donor for 33 pts, haploidentical donor for 10 pts, matched related donor for 9 patients, mismatched unrelated donor for 5 patients, and cord blood for 1 patient. Twenty-two pts developed acute GVHD while 15 developed chronic GVHD. Amongst the 58 pts that underwent allo-HCT, 19 had relapse of disease and 8 patients received treatment after relapse. Amongst the full cohort of 180 patients, mOS was 0.72 years from time of MPN-AP/BP diagnosis. The mOS for the 58 pts that underwent allo-HCT was 1.82 years from time of MPN-AP/BP diagnosis and 1.30 years from time of allo-HCT. Survival analysis by initial MPN-AP/BP therapy demonstrated a mOS from time of MPN-AP/BP diagnosis of 1.9 years for HMA-based therapy, 1.9 years for HMA + VEN, and 1.5 years for IC ( p=0.006). We also analyzed mOS by disease status prior to transplant. Thirty-four pts had a complete response (CR) or CR with incomplete count recovery (CRi) with mOS of 1.7 years from time of allo-HCT, 12 pts with a partial response (PR) or morphologic leukemia-free state (MLFS) had mOS of 1.8 years, and 11 pts with treatment failure (TF) had mOS of 0.47 years (p=0.82). Conclusions Our cohort of 180 pts with MPN-AP/BP treated in the current era of myeloid therapies had limited survival with a mOS of 0.72 years from MPN-AP/BP diagnosis. Amongst the 58 pts that underwent allo-HCT the mOS was 1.82 years with longer mOS seen in pts that received HMA or HMA + VEN as their 1L therapy when compared to IC. This underscores the need for novel management strategies even in pts eligible for allo-HCT