Preoperative Exercise Training to Prevent Postoperative Pulmonary Complications in Adults Undergoing Major Surgery. A Systematic Review and Meta-analysis with Trial Sequential Analysis.

Rationale: Poor preoperative physical fitness and respiratory muscle weakness are associated with postoperative pulmonary complications (PPCs) that result in prolonged hospital length of stay and increased mortality.Objectives: To examine the effect of preoperative exercise training on the risk of PPCs across different surgical settings.Methods: We searched MEDLINE, Web of Science, Embase, the Physiotherapy Evidence Database, and the Cochrane Central Register, without language restrictions, for studies from inception to July 2020. We included randomized controlled trials that compared patients receiving exercise training with those receiving usual care or sham training before cardiac, lung, esophageal, or abdominal surgery. PPCs were the main outcome; secondary outcomes were preoperative functional changes and postoperative mortality, cardiovascular complications, and hospital length of stay. The study was registered with PROSPERO (International Prospective Register of Systematic Reviews).Results: From 29 studies, 2,070 patients were pooled for meta-analysis. Compared with the control condition, preoperative exercise training was associated with a lower incidence of PPCs (23 studies, 1,864 patients; relative risk, 0.52; 95% confidence interval [CI], 0.41 to 0.66; grading of evidence, moderate); Trial Sequential Analysis confirmed effectiveness, and there was no evidence of difference of effect across surgeries, type of training (respiratory muscles, endurance or combined), or preoperative duration of training. At the end of the preoperative period, exercise training resulted in increased peak oxygen uptake (weighted mean difference [WMD], +2 ml/kg/min; 99% CI, 0.3 to 3.7) and higher maximal inspiratory pressure (WMD, +12.2 cm H <sub>2</sub> O; 99% CI, 6.3 to 18.2). Hospital length of stay was shortened (WMD, -2.3 d; 99% CI, -3.82 to -0.75) in the intervention group, whereas no difference was found in postoperative mortality.Conclusions: Preoperative exercise training improves physical fitness and reduces the risk of developing PPCs while minimizing hospital resources use, regardless of the type of intervention and surgery performed.Systematic review registered with https://www.crd.york.ac.uk/prospero/ (CRD 42018096956)

Blasts in context:the impact of the immune environment on acute myeloid leukemia prognosis and treatment

Acute myeloid leukemia (AML) is a cancer that originates from the bone marrow (BM). Under physiological conditions, the bone marrow supports the homeostasis of immune cells and hosts memory lymphoid cells. In this review, we summarize our present understanding of the role of the immune microenvironment on healthy bone marrow and on the development of AML, with a focus on T cells and other lymphoid cells. The types and function of different immune cells involved in the AML microenvironment as well as their putative role in the onset of disease and response to treatment are presented. We also describe how the immune context predicts the response to immunotherapy in AML and how these therapies modulate the immune status of the bone marrow. Finally, we focus on allogeneic stem cell transplantation and summarize the current understanding of the immune environment in the post-transplant bone marrow, the factors associated with immune escape and relevant strategies to prevent and treat relapse.</p

Cross-intolerance with bosutinib after prior tyrosine kinase inhibitors for Philadelphia chromosome-positive leukemia: long-term analysis of a phase I/II study

No abstract availabl

The Importance of Time Congruity in the Organisation.

In 1991 Kaufman, Lane, and Lindquist proposed that time congruity in terms of an individual's time preferences and the time use methods of an organisation would lead to satisfactory performance and enhancement of quality of work and general life. The research reported here presents a study which uses commensurate person and job measures of time personality in an organisational setting to assess the effects of time congruity on one aspect of work life, job-related affective well-being. Results show that time personality and time congruity were found to have direct effects on well-being and the influence of time congruity was found to be mediated through time personality, thus contributing to the person–job (P–J) fit literature which suggests that direct effects are often more important than indirect effects. The study also provides some practical examples of ways to address some of the previously cited methodological issues in P–J fit research

Evaporation from three water bodies of different sizes and climates: Measurements and scaling analysis

Evaporation from small reservoirs, wetlands, and lakes continues to be a theoretical and practical problem in surface hydrology and micrometeorology because atmospheric flows above such systems can rarely be approximated as stationary and planar-homogeneous with no mean subsidence (hereafter referred to as idealized flow state). Here, the turbulence statistics of temperature(T)and water vapor (q)most pertinent to lake evaporation measurementsover three water bodies differing in climate, thermal inertia and degree of advective conditions are explored. The three systems included Lac Le´man in Switzerland (high thermal inertia, near homogeneous conditions with no appreciable advection due to long upwind fetch), Eshkol reservoir in Israel (intermediate thermal inertia, frequent strong advective conditions) and Tilopozo wetland in Chile (low thermal inertia, frequent but moderate advection). The data analysis focused on how similarity constants for the flux-variance approach, CT/Cq, and relative transport efficiencies RwT/Rwq, are perturbed from unity with increased advection or the active role of temperature. When advection is small and thermal inertia is large, CT/Cq 1)primarily due to the active role of temperature, which is consistent with a large number of studies conducted over bare soil and vegetated surfaces. However, when advection is significantly large, then CT/Cq >1 (orRwT/Rwq < 1). When advection is moderate and thermal inertia is low, then CT/Cq �1. This latter equality, while consistent with Monin–Obukhov similarity theory (MOST), is due to the fact that advection tends to increase CT/Cq above unity while the active role of temperature tends to decrease CT/Cq below unity. A simplified scaling analysis derived from the scalar variance budget equation, explained qualitatively how advection could per¬turb MOST scaling (assumed to represent the idealized flow state)

Efficacy of Dupilumab in a Phase 2 Randomized Trial of Adults With Active Eosinophilic Esophagitis.

Eosinophilic esophagitis (EoE) is an allergen-mediated inflammatory disease with no approved treatment in the United States. Dupilumab, a VelocImmune-derived human monoclonal antibody against the interleukin (IL) 4 receptor, inhibits IL4 and IL13 signaling. Dupilumab is effective in the treatment of allergic, atopic, and type 2 diseases, so we assessed its efficacy and safety in patients with EoE. We performed a phase 2 study of adults with active EoE (2 episodes of dysphagia/week with peak esophageal eosinophil density of 15 or more eosinophils per high-power field), from May 12, 2015, through November 9, 2016, at 14 sites. Participants were randomly assigned to groups that received weekly subcutaneous injections of dupilumab (300 mg, n = 23) or placebo (n = 24) for 12 weeks. The primary endpoint was change from baseline to week 10 in Straumann Dysphagia Instrument (SDI) patient-reported outcome (PRO) score. We also assessed histologic features of EoE (peak esophageal intraepithelial eosinophil count and EoE histologic scores), endoscopically visualized features (endoscopic reference score), esophageal distensibility, and safety. The mean SDI PRO score was 6.4 when the study began. In the dupilumab group, SDI PRO scores were reduced by a mean value of 3.0 at week 10 compared with a mean reduction of 1.3 in the placebo group (P = .0304). At week 12, dupilumab reduced the peak esophageal intraepithelial eosinophil count by a mean 86.8 eosinophils per high-power field (reduction of 107.1%; P &lt; .0001 vs placebo), the EoE-histologic scoring system (HSS) severity score by 68.3% (P &lt; .0001 vs placebo), and the endoscopic reference score by 1.6 (P = .0006 vs placebo). Dupilumab increased esophageal distensibility by 18% vs placebo (P &lt; .0001). Higher proportions of patients in the dupilumab group developed injection-site erythema (35% vs 8% in the placebo group) and nasopharyngitis (17% vs 4% in the placebo group). In a phase 2 trial of patients with active EoE, dupilumab reduced dysphagia, histologic features of disease (including eosinophilic infiltration and a marker of type 2 inflammation), and abnormal endoscopic features compared with placebo. Dupilumab increased esophageal distensibility and was generally well tolerated. ClinicalTrials.gov, Number: NCT02379052

Rituximab in B-Cell Hematologic Malignancies: A Review of 20 Years of Clinical Experience

Rituximab is a human/murine, chimeric anti-CD20 monoclonal antibody with established efficacy, and a favorable and well-defined safety profile in patients with various CD20-expressing lymphoid malignancies, including indolent and aggressive forms of B-cell non-Hodgkin lymphoma. Since its first approval 20 years ago, intravenously administered rituximab has revolutionized the treatment of B-cell malignancies and has become a standard component of care for follicular lymphoma, diffuse large B-cell lymphoma, chronic lymphocytic leukemia, and mantle cell lymphoma. For all of these diseases, clinical trials have demonstrated that rituximab not only prolongs the time to disease progression but also extends overall survival. Efficacy benefits have also been shown in patients with marginal zone lymphoma and in more aggressive diseases such as Burkitt lymphoma. Although the proven clinical efficacy and success of rituximab has led to the development of other anti-CD20 monoclonal antibodies in recent years (e.g., obinutuzumab, ofatumumab, veltuzumab, and ocrelizumab), rituximab is likely to maintain a position within the therapeutic armamentarium because it is well established with a long history of successful clinical use. Furthermore, a subcutaneous formulation of the drug has been approved both in the EU and in the USA for the treatment of B-cell malignancies. Using the wealth of data published on rituximab during the last two decades, we review the preclinical development of rituximab and the clinical experience gained in the treatment of hematologic B-cell malignancies, with a focus on the well-established intravenous route of administration. This article is a companion paper to A. Davies, et al., which is also published in this issue

Acute myeloid leukemia patients’ clinical response to idasanutlin (RG7388) is associated with pre-treatment MDM2 protein expression in leukemic blasts

In translational research described, we investigated biomarker expression by flow cytometry for MDM2 antagonist clinical response association in relapsed/refractory AML patients treated with idasanutlin-based therapy (Clinicaltrials.gov identifier: NCT01773408)

Risk of progression in chronic phase-chronic myeloid leukemia patients eligible for tyrosine kinase inhibitor discontinuation: Final analysis of the TFR-PRO study

Disease progression to accelerated/blast phase (AP/BP) in patients with chronic phase chronic myeloid leukemia (CP-CML) after treatment discontinuation (TD) has never been systematically reported in clinical trials. However, recent reports of several such cases has raised concern. To estimate the risk of AP/BP among TD-eligible patients, we conducted TFR-PRO, a cohort retro-prospective study: 870 CP-CML patients eligible for TD formed a discontinuation cohort (505 patients) and a reference one (365 patients). The primary objective was the time adjusted rate (TAR) of progression in relation to TD. Secondary endpoints included the TAR of molecular relapse, that is, loss of major molecular response (MMR). With a median follow up of 5.5 years and 5188.2 person-years available, no events occurred in the TD cohort. One event of progression was registered 55 months after the end of TD, when the patient was contributing to the reference cohort. The TAR of progression was 0.019/100 person-years (95% CI [0.003-0.138]) in the overall group; 0.0 (95% CI [0-0.163]) in the discontinuation cohort; and 0.030 (95% CI [0.004-0.215]) in the reference cohort. These differences are not statistically significant. Molecular relapses occurred in 172/505 (34.1%) patients after TD, and in 64/365 (17.5%) patients in the reference cohort, p &lt; .0001. Similar rates were observed in TD patients in first, second or third line of treatment. CML progression in patients eligible for TD is rare and not related to TD. Fears about the risk of disease progression among patients attempting TD should be dissipated