Adjunctive Midodrine Therapy for Vasopressor-Dependent Shock in the ICU: A Systematic Review and Meta-Analysis.

Objectives: To summarize the efficacy of midodrine as an adjunctive therapy in critically ill patients. Safety of midodrine was assessed as a secondary outcome.

Data Sources: We performed a systematic review and meta-analysis using a peer-reviewed search strategy combining the themes of vasopressor-dependent shock, critical care, and midodrine and including MEDLINE, Ovid Embase, CINAHL, and Cochrane library databases until September 14, 2023.

ATP citrate lyase is an essential player in the metabolic rewiring induced by PTEN loss during T-ALL development.

Alterations inactivating the tumor suppressor gene PTEN drive the development of solid and hematological cancers, such as T-cell acute lymphoblastic leukemia (T-ALL), whereby PTEN loss defines poor-prognosis patients. We investigated the metabolic rewiring induced by PTEN loss in T-ALL, aiming at identifying novel metabolic vulnerabilities. We showed that the enzyme ATP citrate lyase (ACLY) is strictly required for the transformation of thymic immature progenitors and for the growth of human T-ALL, which remain dependent on ACLY activity even upon transformation.

Global view of haematolymphoid tumor classifications and their application in low- and middle-income countries.

The accurate diagnosis of haematolymphoid malignancies is crucial for effective cancer care, but major obstacles to diagnosis exist in low- and middle-income countries (LMICs). This article explores the global applicability of current haematolymphoid classification systems, which are predominantly derived from data generated in high-income countries (HICs). Although disproportionately burdened with poor cancer outcomes, LMICs are generally faced with limited diagnostic resources, suboptimal access to therapeutics, and inadequate healthcare infrastructure.

DNA methylation as a new tool for the differential diagnosis between T-LBL and lymphocyte-rich thymoma.

T-lymphoblastic lymphoma (T-LBL) and thymoma are two rare primary tumors of the thymus deriving either from T-cell precursors or from thymic epithelial cells, respectively. Some thymoma subtypes (AB, B1, and B2) display numerous reactive terminal deoxynucleotidyl transferase-positive (TdT) T-cell precursors masking epithelial tumor cells. Therefore, the differential diagnosis between T-LBL and TdT T-lymphocyte-rich thymoma could be challenging, especially in the case of needle biopsy.

The influence of threat on visuospatial perception, affordances, and protective behaviour: A systematic review and meta-analysis.

Perception has been conceptualised as an active and adaptive process, based upon incoming sensory inputs, which are modified by top-down factors such as cognitions. Visuospatial perception is thought to be scaled based on threat, with highly threatening objects or contexts visually inflated to promote escape or avoidance behaviours. This meta-analytical systematic review quantified the effect and evidence quality of threat-evoked visuospatial scaling, as well as how visuospatial scaling relates to affordances (perceived action capabilities) and behavioural avoidance/escape outcomes.

Painful distortions: people with painful knee osteoarthritis have biased visuospatial perception of the environment.

Visuospatial perception is thought to be adaptive-ie, hills are perceived as steeper when capacity is low, or threat is high-guiding appropriate interaction with the environment. Pain (bodily threat) may similarly modulate visuospatial perception, with the extent of modulation influenced by threat magnitude (pain intensity, fear) and associated with behaviour (physical activity). We compared visuospatial perception of the environment between 50 people with painful knee osteoarthritis and 50 age-/sex-matched pain-free control participants using 3 virtual reality tasks (uphill steepness estimation, downhill steepness estimation, and a distance-on-hill measure), exploring associations between visuospatial perception, clinical characteristics (pain intensity, state and trait fear), and behaviour (wrist-worn accelerometry) within a larger knee osteoarthritis group (n = 85).

Waiting in Pain II: An Updated Analysis of the Multidisciplinary Staffing Levels and Clinical Activity in Australian Specialist Persistent Pain Services.

This study provides an update on multidisciplinary staffing and clinical activity in Australian specialist persistent pain services. Of the 109 services identified, 57 responded, met inclusion criteria and completed a study-specific questionnaire detailing service characteristics, staff resources, and clinical activities. Where possible, data were compared between the 'Waiting in Pain' (WIP) investigations (WIP-I: Dec'08-Jan'10, WIP-II: Jul'16-Feb'18).

Predictive Value of Minimal Residual Disease for Efficacy of Rituximab Maintenance in Mantle Cell Lymphoma: Results From the European Mantle Cell Lymphoma Elderly Trial.

Purpose: The outcome of older patients with mantle cell lymphoma (MCL) has improved by the introduction of immunochemotherapy, followed by rituximab (R)-maintenance. Assessment of minimal residual disease (MRD) represents a promising tool for individualized treatment decisions and was a prospectively planned part of the European MCL Elderly trial. We investigated how MRD status influenced the efficacy of R-maintenance and how MRD can enable tailored consolidation strategies.

PHF6-altered T-ALL Harbor Epigenetic Repressive Switch at Bivalent Promoters and Respond to 5-Azacitidine and Venetoclax.

Purpose: To assess the impact of PHF6 alterations on clinical outcome and therapeutical actionability in T-cell acute lymphoblastic leukemia (T-ALL).

Experimental Design: We described PHF6 alterations in an adult cohort of T-ALL from the French trial Group for Research on Adult Acute Lymphoblastic Leukemia (GRAALL)-2003/2005 and retrospectively analyzed clinical outcomes between PHF6-altered (PHF6ALT) and wild-type patients. We also used EPIC and chromatin immunoprecipitation sequencing data of patient samples to analyze the epigenetic landscape of PHF6ALT T-ALLs.

Performance of baseline FDG-PET/CT radiomics for prediction of bone marrow minimal residual disease status in the LyMa-101 trial.

The prognostic value of F-Fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT) at baseline or the predictive value of minimal residual disease (MRD) detection appear as potential tools to improve mantle cell lymphoma (MCL) patients' management. The LyMa-101, a phase 2 trial of the LYSA group (ClinicalTrials.gov:NCT02896582) reported induction therapy with obinutuzumab, a CD20 monoclonal antibody.

TREC mediated oncogenesis in human immature T lymphoid malignancies preferentially involves ZFP36L2.

The reintegration of excised signal joints resulting from human V(D)J recombination was described as a potent source of genomic instability in human lymphoid cancers. However, such molecular events have not been recurrently reported in clinical patient lymphoma/leukemia samples. Using a specifically designed NGS-capture pipeline, we here demonstrated the reintegration of T-cell receptor excision circles (TRECs) in 20/1533 (1.

Systemic Nonsteroidal Anti-Inflammatories for Analgesia in Postoperative Critical Care Patients: A Systematic Review and Meta-Analysis of Randomized Control Trials.

Unlabelled: While opioids are part of usual care for analgesia in the ICU, there are concerns regarding excess use. This is a systematic review of nonsteroidal anti-inflammatory drugs (NSAIDs) use in postoperative critical care adult patients.

Data Sources: We searched Medical Literature Analysis and Retrieval System Online, Excerpta Medica database, Cumulative Index to Nursing and Allied Health Literature, Cochrane Library, trial registries, Google Scholar, and relevant systematic reviews through March 2023.

ESMO-Magnitude of Clinical Benefit Scale for haematological malignancies (ESMO-MCBS:H) version 1.0.

Background: The European Society for Medical Oncology (ESMO)-Magnitude of Clinical Benefit Scale (MCBS) has been accepted as a robust tool to evaluate the magnitude of clinical benefit reported in trials for oncological therapies. However, the ESMO-MCBS hitherto has only been validated for solid tumours. With the rapid development of novel therapies for haematological malignancies, we aimed to develop an ESMO-MCBS version that is specifically designed and validated for haematological malignancies.

Distinct subsets of multi-lymphoid progenitors support ontogeny-related changes in human lymphopoiesis.

Changes in lymphocyte production patterns occurring across human ontogeny remain poorly defined. In this study, we demonstrate that human lymphopoiesis is supported by three waves of embryonic, fetal, and postnatal multi-lymphoid progenitors (MLPs) differing in CD7 and CD10 expression and their output of CD127 early lymphoid progenitors (ELPs). In addition, our results reveal that, like the fetal-to-adult switch in erythropoiesis, transition to postnatal life coincides with a shift from multilineage to B lineage-biased lymphopoiesis and an increase in production of CD127 ELPs, which persists until puberty.

Lessons learned from implementing a surge capacity support program for COVID-19 contact management in Ontario.

Setting: In Ontario, local public health units (PHUs) are responsible for leading case investigations, contact tracing, and follow-up. The workforce capacity and operational requirements needed to maintain this public health strategy during the COVID-19 pandemic were unprecedented.

Intervention: Public Health Ontario's Contact Tracing Initiative (CTI) was established to provide a centralized workforce.