Shorter Survival of SDF1-3′A/3′A Homozygotes Linked to CD4+ T Cell Decrease in Advanced Human Immunodeficiency Virus Type 1 Infection

The SDF-1 3′A allelic polymorphism has been reported to influence either positively or negatively the progression of human immunodeficiency virus type 1 (HIV-1) disease. Therefore, the SDF-1 genotype of 729 HIV-1-infected individuals pooled from 3 distinct cohorts was determined. A statistically nonsignificant association between the SDF1-3′A/3′A genotype and accelerated disease progression was evident among seroconverters (n = 319), but a striking correlation of decreased survival after either diagnosis of AIDS according to the 1993 definition or loss of CD4+ T cell counts <200 was observed. The relative hazards for SDF1-3′A/3′A homozygotes, compared with heterozygotes and wild-type homozygotes were 2.16 (P = .0047), for time from diagnosis according to the 1993 Centers for Disease Control and Prevention AIDS case definition (AIDS-'93) to death, and 3.43 (P = .0001), for time from CD4+ T cells <200 to death. Because no difference in survival was observed after diagnosis according to AIDS-'87, the association of the SDF1-3′A/3′A genotype with the accelerated progression of late-stage HIV-1 disease appears to be explained for the most part by the loss of CD4+ T lymphocyte

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

Clinical performance of lung ultrasound in predicting ARDS morphology

Abstract Background To assess diagnostic performance of lung ultrasound (LUS) in identifying ARDS morphology (focal vs non-focal), compared with the gold standard computed tomography. Methods Mechanically ventilated ARDS patients undergoing lung computed tomography and ultrasound were enrolled. Twelve fields, were evaluated. LUS score was graded from 0 (normal) to 3 (consolidation) according to B-lines extent. Total and regional LUS score as the sum of the four ventral (LUSV), intermediate (LUSI) or dorsal (LUSD) fields, were calculated. Based on lung CT, ARDS morphology was defined as (1) focal (loss of aeration with lobar distribution); (2) non-focal (widespread loss of aeration or segmental loss of aeration distribution associated with uneven lung attenuation areas), and diagnostic accuracy of LUS in discriminating ARDS morphology was determined by AU-ROC in training and validation set of patients. Results Forty-seven patients with ARDS (25 training set and 22 validation set) were enrolled. LUSTOT, LUSV and LUSI but not LUSD score were significantly lower in focal than in non-focal ARDS morphologies (p < .01). The AU-ROC curve of LUSTOT, LUSV, LUSI and LUSD for identification of non-focal ARDS morphology were 0.890, 0.958, 0.884 and 0.421, respectively. LUSV value ≥ 3 had the best predictive value (sensitivity = 0.95, specificity = 1.00) in identifying non-focal ARDS morphology. In the validation set, an LUSV score ≥ 3 confirmed to be highly predictive of non-focal ARDS morphology, with a sensitivity and a specificity of 94% and 100%. Conclusions LUS had a valuable performance in distinguishing ARDS morphology

Plan optimization for mediastinal radiotherapy: Estimation of coronary arteries motion with ECG-gated cardiac imaging and creation of compensatory expansion margins

BACKGROUND AND PURPOSE: Inadvertent heart and coronary arteries (CA) irradiation may increase the risk of coronary artery disease (CAD) in patients receiving thoracic irradiation. To date, the entity of cardiac-related CA displacement and the possible margins to be used for planning organs at risk volume (PRV) have been poorly described. Aim of this study was to quantify CA displacement and to estimate PRV through the use of ECG-gated computed tomography (CT) scans. MATERIAL AND METHODS: Eight patients received an ECG-gated intravenous contrast enhanced CT for non-cancer related reasons. Nine data sets were reconstructed over the entire R-R cycle with a dedicated retrospective algorithm and the following structures were delineated: Left main trunk (LM), left anterior descending (LAD), left circumflex (CX) and right coronary artery (RCA). CA displacements across the different cardiac phases were evaluated in left-right (X), cranio-caudal (Y) and anteroposterior (Z) directions using the McKenzie-van Herk formula (1.3 * Σ + 0.5 * σ). RESULTS: The following CA displacements were found in X, Y and Z coordinates: 3.6, 2.7 and 2.7 mm for LMT, respectively; 2.6, 5.0 and 6.8 mm for LAD, respectively; 3.5, 4.5 and 3.7 mm for CX, respectively; 3.6, 4.6 and 6.9 mm for RCA, respectively. Based on the mean displacements, we created a PRV of 3 mm for LM, 4 mm for CX and 5 mm for LAD and RCA. CONCLUSION: CA showed relevant displacements over the heart cycle, suggesting the need for a specific PRV margin to accurately estimate the dose received by these structures and optimize the planning process

Structure and membrane interactions of chionodracine, a piscidin-like antimicrobial peptide from the icefish Chionodraco hamatus

AbstractChionodracine (Cnd) is a 22-residue peptide of the piscidin family expressed in the gills of the Chionodraco hamatus as protection from bacterial infections. Here, we report the effects of synthetic Cnd on both Psychrobacter sp. TAD1 and Escherichia coli bacteria, as well as membrane models. We found that Cnd perforates the inner and outer membranes of Psychrobacter sp. TAD1, making discrete pores that cause the cellular content to leak out. Membrane disruption studies using intrinsic and extrinsic fluorescence spectroscopy revealed that Cnd behaves similarly to other piscidins, with comparable membrane partition coefficients. Membrane accessibility assays and structural studies using NMR in detergent micelles show that Cnd adopts a canonical topology of antimicrobial helical peptides, with the hydrophobic face toward the lipid environment and the hydrophilic face toward the bulk solvent. The analysis of Cnd free energy of binding to vesicles with different lipid contents indicates a preference for charged phospholipids and a more marked binding to native E. coli extracts. Taken with previous studies on piscidin-like peptides, we conclude that Cnd first adsorbs to the membrane, and then forms pores together with membrane fragmentation. Since Cnd has only marginal hemolytic activity, it constitutes a good template for developing new antimicrobial agents