Clinical progression and outcome of dysphagia following thermal burn injury: A prospective cohort study

The objectives of this study were 1) to establish clinical profiles of dysphagic and nondysphagic individuals following thermal burn injury and 2) to provide a clinical profile of the progression and outcome of dysphagia resolution by hospital discharge for a dysphagic cohort. A total of 438 consecutively admitted patients with thermal burns were included. All patients underwent a clinical swallowing examination. Medical parameters regarding burn presentation and its treatment and speech-language pathology specific variables from admission to discharge were collected for each participant. Dysphagia was identified in 49 patients via clinical assessment, and their course of recovery was followed up until the point of dysphagia resolution or discharge. No significant difference was observed between the dysphagic and nondysphagic groups in age, gender, and injury etiology. However, the dysphagic cohort was significantly different from the nondysphagic group in all variables pertaining to injury presentation and medical management. Individuals with dysphagia took significantly longer to start, and maintain, oral intake and required nonoral supplementation for three and a half times longer than those who were nondysphagic. Length of speech-language pathology intervention averaged 1 month for the dysphagics and increased with dysphagia severity. Return to normal fluid consistencies occurred in >75% of dysphagic individuals by week 7 after injury, although resumption of normal diet textures was more protracted, with 75% resuming normal oral intake by week 9. Dysphagia had resolved in 50% of the cohort by week 6, and by hospital discharge, 85% of the dysphagic individuals had resumed normal oral intake of thin fluids and a general diet. This is the first large prospective cohort study to establish clinical profiles of dysphagic and nondysphagic cohorts and document the nature of dysphagia and patterns of recovery within the thermal burn population. These current data will assist the allocation and planning of speech-language pathology services and provide baseline data on the course of dysphagia resolution in the adult thermal burn population

Mortality and pulmonary complications in patients undergoing surgery with perioperative SARS-CoV-2 infection: an international cohort study

Background: The impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on postoperative recovery needs to be understood to inform clinical decision making during and after the COVID-19 pandemic. This study reports 30-day mortality and pulmonary complication rates in patients with perioperative SARS-CoV-2 infection. Methods: This international, multicentre, cohort study at 235 hospitals in 24 countries included all patients undergoing surgery who had SARS-CoV-2 infection confirmed within 7 days before or 30 days after surgery. The primary outcome measure was 30-day postoperative mortality and was assessed in all enrolled patients. The main secondary outcome measure was pulmonary complications, defined as pneumonia, acute respiratory distress syndrome, or unexpected postoperative ventilation. Findings: This analysis includes 1128 patients who had surgery between Jan 1 and March 31, 2020, of whom 835 (74·0%) had emergency surgery and 280 (24·8%) had elective surgery. SARS-CoV-2 infection was confirmed preoperatively in 294 (26·1%) patients. 30-day mortality was 23·8% (268 of 1128). Pulmonary complications occurred in 577 (51·2%) of 1128 patients; 30-day mortality in these patients was 38·0% (219 of 577), accounting for 81·7% (219 of 268) of all deaths. In adjusted analyses, 30-day mortality was associated with male sex (odds ratio 1·75 [95% CI 1·28–2·40], p\textless0·0001), age 70 years or older versus younger than 70 years (2·30 [1·65–3·22], p\textless0·0001), American Society of Anesthesiologists grades 3–5 versus grades 1–2 (2·35 [1·57–3·53], p\textless0·0001), malignant versus benign or obstetric diagnosis (1·55 [1·01–2·39], p=0·046), emergency versus elective surgery (1·67 [1·06–2·63], p=0·026), and major versus minor surgery (1·52 [1·01–2·31], p=0·047). Interpretation: Postoperative pulmonary complications occur in half of patients with perioperative SARS-CoV-2 infection and are associated with high mortality. Thresholds for surgery during the COVID-19 pandemic should be higher than during normal practice, particularly in men aged 70 years and older. Consideration should be given for postponing non-urgent procedures and promoting non-operative treatment to delay or avoid the need for surgery. Funding: National Institute for Health Research (NIHR), Association of Coloproctology of Great Britain and Ireland, Bowel and Cancer Research, Bowel Disease Research Foundation, Association of Upper Gastrointestinal Surgeons, British Association of Surgical Oncology, British Gynaecological Cancer Society, European Society of Coloproctology, NIHR Academy, Sarcoma UK, Vascular Society for Great Britain and Ireland, and Yorkshire Cancer Research

Risk of performance errors due to sleep loss, circadian desynchronization, fatigue, and work overload. Human Research Program Requirements Document, HRP-47052, Rev

Fatigue occurs during spaceflight and will jeopardize health and performance. This risk may be influenced by artificial and transmitted light exposure, individual vulnerability t o sleep l oss a nd c ircadian d ynamics, a nd work/sleep schedules. Efforts are needed to improve sleep hygiene, and to identif y and improve conditions that interfere with sleep quality. R esearch areas m ay inc lude: de velopment of a sel f-assessment t ool f or cognitive function and fatigue, light therapy for phase shifting, alertness and mood disorders, and other means to improve sleep quality and reduce fatigue. Executive Summary Data that have been collected during space flight missions consistently indicate that sleep loss, circadian desynchronization, fatigue, and work overload occur, to varying degrees, for some individuals. Few studies of performance have been conducted in flight, however, and the findings that have been generated remain unclear as to how a crew member's performance during space flight is directly impacted by sleep loss. Extensive ground-based scientific literature, including controlled laboratory studies and data that have been gathered from industries, demonstrates that the degree of sleep and circadian disturbances that are often experienced by astronauts result in performance errors and may also impact long-term health. Space flight evidence regarding sleep loss primarily includes data that were collected through controlled studies (Category II 15 ) as well as through self-report (Category III). These evaluations, which have focused on short-duration (fewer than 30-day) missions, have provided data from astronauts' daily sleep logs, polysomnography, and actigraphy. These data have characterized sleep in space, overall, as shorter, less restful, and more interrupted than sleep on Earth. Circadian rhythms may also be misaligned due to scheduling constraints, with the result that fatigue (physical and mental) from work overload has been reported Questions, however, remain regarding the nature of sleep and circadian rhythms on long-duration space flight missions. Despite the fact that ISS construction has been under way for 9 years, systematic data collection to address this issue has only been undertaken recently. In light of ground-based evidence on sleep-loss-related performance effects, it is critical to understand the various factors that exist in the space flight and long-duration mission environment, and to identify ways in which sleep and circadian rhythms can be protected for crews who are flying on ISS and shuttle missions. NASA ground support personnel, as well as space flight crews, experience sleep loss, fatigue, circadian misalignment, and work overload. Ground teams that support robotic missions to Mars, as evidenced during the Mars Pathfinder, Spirit, Opportunity, and Phoenix missions, similarly face issues of sleep loss and circadian desynchronization. As human space flight transitions from LEO (e.g., shuttle, ISS) to Exploration missions to the moon and Mars, and as NASA continues to support robotic missions to Mars and beyond, it becomes more important to characterize human risk factors accurately and adequately and to identify the ways in which to mitigate this performance risk safely and effectively. The first short-duration lunar missions, which will be similar to the shuttle missions, will seem to be fast-paced sprints as compared to the marathon-like races of later, longer lunar outpost missions (and ISS increments). Docking will require shifting of schedules for those in flight and for their support teams on the ground; the hurried schedule will likely include heavy workloads. Longer lunar missions will pose additional challenges to crews, including perpetual non-terrestrial day-night cues, environmental constraints, and extended periods of high-intensity workload. As the evidence reveals, crews on short-and long-duration lunar missions will need to be well-equipped and prepared for the potential performance and long-term health effects of sleep loss and circadian shifting. 15 To help characterize the kind of evidence that is provided in each of the risk reports in this book, the authors were encouraged to label the evidence that they provided according to the "NASA Categories of Evidence." Category I data are based on at least one randomized controlled trial. Category II data are based on at least one controlled study without randomization, including cohort, case-controlled or subject operating as own control

Leucine-Rich Repeat Kinase 2 (LRRK2)-Deficient Rats Exhibit Renal Tubule Injury and Perturbations in Metabolic and Immunological Homeostasis

<div><p>Genetic evidence links mutations in the LRRK2 gene with an increased risk of Parkinson’s disease, for which no neuroprotective or neurorestorative therapies currently exist. While the role of LRRK2 in normal cellular function has yet to be fully described, evidence suggests involvement with immune and kidney functions. A comparative study of LRRK2-deficient and wild type rats investigated the influence that this gene has on the phenotype of these rats. Significant weight gain in the LRRK2 null rats was observed and was accompanied by significant increases in insulin and insulin-like growth factors. Additionally, LRRK2-deficient rats displayed kidney morphological and histopathological alterations in the renal tubule epithelial cells of all animals assessed. These perturbations in renal morphology were accompanied by significant decreases of lipocalin-2, in both the urine and plasma of knockout animals. Significant alterations in the cellular composition of the spleen between LRRK2 knockout and wild type animals were identified by immunophenotyping and were associated with subtle differences in response to dual infection with rat-adapted influenza virus (RAIV) and <i>Streptococcus pneumoniae</i>. Ontological pathway analysis of LRRK2 across metabolic and kidney processes and pathological categories suggested that the thioredoxin network may play a role in perturbing these organ systems. The phenotype of the LRRK2 null rat is suggestive of a complex biology influencing metabolism, immune function and kidney homeostasis. These data need to be extended to better understand the role of the kinase domain or other biological functions of the gene to better inform the development of pharmacological inhibitors.</p></div

Flow cytometric immunophenotyping of male LRRK2 wild type and deficient spleenocytes.

<p>The average percentage of splenocyte cells staining for (A) CD11b, (B) CD4, (C) CD8 and (D) CD3 in uninfected and infected male rats is presented. B-cell data is from uninfected animals only (N = 4 male LRRK2 wild type and deficient rats in uninfected animals and N = 5 in infected animals; a two-tailed Student’s T-test was used to assess significance between genotypes where * represents a P-value <0.05 and ** represents a P-value <0.01; standard deviations of the mean are provided).</p

Direct interaction network of LRRK2 with genes associated in the MetaCore disease ontology with nutritional and metabolic disorders.

<p>Compounds are represented by hexagons, proteins by solid shapes representing different classes of compound, and enzymatic reactions by gray rectangles. Protein-protein, compound-protein and compound-reaction interactions are shown as unidirectional arrows, and a mechanism of interaction represented by letters in hexagonal boxes over the arrows.</p