Viral infections in critical care: a narrative review

Viral infections form a substantial part of the intensive care workload, even before the recent and ongoing COVID-19 pandemic. The growing availability of molecular diagnostics for viral infections has led to increased recognition of these pathogens. This additional information, however, provides new challenges for interpretation and management. As the SARS-CoV-2 pandemic has amply demonstrated, the emergence and global spread of novel viruses are likely to provide continued challenges for critical care physicians into the future. This article will provide an overview of viral infections relevant to the critical care physician, discussing the diagnosis and management of respiratory viral infections, blood borne and enteric viruses. We will also discuss herpesviridae complications, commonly seen due to reactivation of latent infections. Further, we explore some rarer and emerging viruses, including recognition of viral haemorrhagic fevers, and briefly discuss post-viral syndromes which may present to the intensive care unit. Finally, we will discuss infection control and its importance in preventing nosocomial viral transmission.     

STAG2 loss rewires oncogenic and developmental programs to promote metastasis in Ewing sarcoma

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Clinical Evaluation of Deep Learning and Atlas-Based Auto-Contouring of Bladder and Rectum for Prostate Radiation Therapy

PurposeAuto-contouring may reduce workload, interobserver variation, and time associated with manual contouring of organs at risk. Manual contouring remains the standard due in part to uncertainty around the time and workload savings after accounting for the review and editing of auto-contours. This preliminary study compares a standard manual contouring workflow with 2 auto-contouring workflows (atlas and deep learning) for contouring the bladder and rectum in patients with prostate cancer.Methods and MaterialsThree contouring workflows were defined based on the initial contour-generation method including manual (MAN), atlas-based auto-contour (ATLAS), and deep-learning auto-contour (DEEP). For each workflow, initial contour generation was retrospectively performed on 15 patients with prostate cancer. Then, radiation oncologists (ROs) edited each contour while blinded to the manner in which the initial contour was generated. Workflows were compared by time (both in initial contour generation and in RO editing), contour similarity, and dosimetric evaluation.ResultsMean durations for initial contour generation were 10.9 min, 1.4 min, and 1.2 min for MAN, DEEP, and ATLAS, respectively. Initial DEEP contours were more geometrically similar to initial MAN contours. Mean durations of the RO editing steps for MAN, DEEP, and ATLAS contours were 4.1 min, 4.7 min, and 10.2 min, respectively. The geometric extent of RO edits was consistently larger for ATLAS contours compared with MAN and DEEP. No differences in clinically relevant dose-volume metrics were observed between workflows.ConclusionAuto-contouring software affords time savings for initial contour generation; however, it is important to also quantify workload changes at the RO editing step. Using deep-learning auto-contouring for bladder and rectum contour generation reduced contouring time without negatively affecting RO editing times, contour geometry, or clinically relevant dose–volume metrics. This work contributes to growing evidence that deep-learning methods are a clinically viable solution for organ-at-risk contouring in radiation therapy.     

A multi-centre,randomised, double-blind,placebo-controlled clinical trial of methylphenidate in the initial treatment of acute mania (MEMAP study)

Based on many clinical and preclinical findings the ‘vigilance regulation model of mania’ postulates that an unstable regulation of wakefulness is a pathogenetic factor in both mania and Attention Deficit Hyperactivity Disorder (ADHD) and induces hyperactivity and sensation seeking as an autoregulatory attempt to stabilize wakefulness. Accordingly, stimulant medications with their vigilance stabilizing properties could have rapid antimanic effects similar to their beneficial effects in ADHD. The MEMAP study – a multi-center, double-blind, placebo-controlled and randomized clinical trial (RCT) – assessed the antimanic efficacy and safety of a 2.5-day treatment with methylphenidate (20–40 mg/day). Of 157 screened patients with acute mania, 42 were randomly assigned to receive 20–40 mg per day of methylphenidate in one or two applications, or placebo. The primary outcome was the change in Young Mania Rating Scale (YMRS) sum scores from baseline to day 2.5 in the methylphenidate group compared to the placebo group. A group sequential design was chosen to justify early RCT termination based on efficacy or futility at an interim analysis after inclusion of 40 patients. In the interim analysis, the change from baseline in the YMRS total score at day 2.5 was not significantly different between both groups (F(1,37)=0.23; p=0.64). Thus, futility was declared for methylphenidate and the RCT was stopped. In summary, although methylphenidate was well tolerated and safe in the full analysis set, it failed to show efficacy in the treatment of acute mania. Trial registration: clinicaltrials.gov (URL: http://www.clinicaltrials.gov; registration number: NCT01541605).     

Quality of life of older women living with HIV: comparative assessment of physical and mental health-related markers using a large Canadian Sexual and Reproductive Health Cohort Study

Objective: This study assessed and compared physical and mental health components of quality of life (QoL) for older and younger women living with HIV (WLWH).

Method: Using survey data from the Canadian HIV Women's Sexual and Reproductive Health Cohort Study, demographic, well-being, and physical and mental health-related QoL (HR-QoL) variables were compared between older (≥50 years) and younger (<50 years) WLWH. As the only significantly different QoL component, bivariate analyses and linear regression were used to assess factors associated with physical HR-QoL of older women.

Results: The sample frame comprised 1,422 women (28.0% older women). Younger WLWH’s mean age was 37.8 years (SD = 7.4) compared to older WLWH (55.8 years, SD = 5.3). Compared to younger WLWH, older WLWH had poorer physical HR-QoL (40.0 vs. 50.7; p?p?>?0.001). Older WLWH had lower social support (p?Discussion: Compared to younger WLWH, older WLWH had poorer physical HR-QoL, which was associated with resilience, food insecurity and mental health factors, highlighting the complex interactions of health-related social-ecological factors impacting aging WLWH.     

Viadent, ethanol, and pH effects upon gingival epithelial-like cells, in vitro

Interest has recently been directed towards the use of antiplaque mouthrinses. Most published material concerns the antimicrobial effects of these agents rather than their effects upon oral tissue. This study was conducted to evaluate the effect of a sanguinarine-containing mouthrinse called Viadent upon epithelial-like gingival cells. The cells were grown for 24 hours in supplemented Earle's medium, with and without different Viadent dilutions. Cell counts were made with a hematocytometer. It was found that 50% of the cells were inhibited at 1.2% Viadent. In similar studies, it was found that 70% ethanol and two pH buffers were less toxic than Viadent. Exposure of preformed cell monolayers to Viadent also showed significant inhibition. The relative toxicity of different antiplaque agents may be compared using such cells as a model system. In conclusion, it was observed that Viadent significantly affected gingival cell growth in vitro, that viable cell numbers were greatly reduced by short time exposure, and that the toxic effect of Viadent could only partially be accounted for by ethanol content and/or pH.     

Colchicine inhibits pressure-induced tumor cell implantation within surgical wounds and enhances tumor-free survival in mice

Iatrogenic tumor cell implantation within surgical wounds can compromise curative cancer surgery. Adhesion of cancer cells, in particular colon cancer cells, is stimulated by exposure to increased extracellular pressure through a cytoskeleton-dependent signaling mechanism requiring FAK, Src, Akt, and paxillin. Mechanical stimuli during tumor resection may therefore negatively impact patient outcome. We hypothesized that perioperative administration of colchicine, which prevents microtubule polymerization, could disrupt pressure-stimulated tumor cell adhesion to surgical wounds and enhance tumor-free survival. Ex vivo treatment of Co26 and Co51 colon cancer cells with colchicine inhibited pressure-stimulated cell adhesion to murine surgical wounds and blocked pressure-induced FAK and Akt phosphorylation. Surgical wound contamination with pressure-activated Co26 and Co51 cells significantly reduced tumor-free survival compared with contamination with tumor cells under ambient pressure. Mice treated with pressure-activated Co26 and Co51 cells from tumors preoperatively treated with colchicine in vivo displayed reduced surgical site implantation and significantly increased tumor-free survival compared with mice exposed to pressure-activated cells from tumors not pretreated with colchicine. Our data suggest that pressure activation of malignant cells promotes tumor development and impairs tumor-free survival and that perioperative colchicine administration or similar interventions may inhibit this effect.