Dynamics of disease characteristics and clinical management of critically ill COVID-19 patients over the time course of the pandemic: an analysis of the prospective, international, multicentre RISC-19-ICU registry.

BACKGROUND It remains elusive how the characteristics, the course of disease, the clinical management and the outcomes of critically ill COVID-19 patients admitted to intensive care units (ICU) worldwide have changed over the course of the pandemic. METHODS Prospective, observational registry constituted by 90 ICUs across 22 countries worldwide including patients with a laboratory-confirmed, critical presentation of COVID-19 requiring advanced organ support. Hierarchical, generalized linear mixed-effect models accounting for hospital and country variability were employed to analyse the continuous evolution of the studied variables over the pandemic. RESULTS Four thousand forty-one patients were included from March 2020 to September 2021. Over this period, the age of the admitted patients (62 [95% CI 60-63] years vs 64 [62-66] years, p < 0.001) and the severity of organ dysfunction at ICU admission decreased (Sequential Organ Failure Assessment 8.2 [7.6-9.0] vs 5.8 [5.3-6.4], p < 0.001) and increased, while more female patients (26 [23-29]% vs 41 [35-48]%, p < 0.001) were admitted. The time span between symptom onset and hospitalization as well as ICU admission became longer later in the pandemic (6.7 [6.2-7.2| days vs 9.7 [8.9-10.5] days, p < 0.001). The PaO2/FiO2 at admission was lower (132 [123-141] mmHg vs 101 [91-113] mmHg, p < 0.001) but showed faster improvements over the initial 5 days of ICU stay in late 2021 compared to early 2020 (34 [20-48] mmHg vs 70 [41-100] mmHg, p = 0.05). The number of patients treated with steroids and tocilizumab increased, while the use of therapeutic anticoagulation presented an inverse U-shaped behaviour over the course of the pandemic. The proportion of patients treated with high-flow oxygen (5 [4-7]% vs 20 [14-29], p < 0.001) and non-invasive mechanical ventilation (14 [11-18]% vs 24 [17-33]%, p < 0.001) throughout the pandemic increased concomitant to a decrease in invasive mechanical ventilation (82 [76-86]% vs 74 [64-82]%, p < 0.001). The ICU mortality (23 [19-26]% vs 17 [12-25]%, p < 0.001) and length of stay (14 [13-16] days vs 11 [10-13] days, p < 0.001) decreased over 19 months of the pandemic. CONCLUSION Characteristics and disease course of critically ill COVID-19 patients have continuously evolved, concomitant to the clinical management, throughout the pandemic leading to a younger, less severely ill ICU population with distinctly different clinical, pulmonary and inflammatory presentations than at the onset of the pandemic

Pressurized intraperitoneal aerosol chemotherapy (PIPAC) with cisplatin and doxorubicin in a woman with pseudomyxoma peritonei: A case report

• This is the first report of pressurized intraperitoneal aerosol chemotherapy (PIPAC) in a woman with pseudomyxoma peritonei. • PIPAC achieved clinical and histological disease remission. • PIPAC with cisplatin and doxorubicin may be effective in pseudomyxoma peritonei

Lower rate of delayed graft function is observed when epidural analgesia for living donor nephrectomy is administered

Abstract Background The beneficial effects of epidural analgesia (EDA) in terms of pain control and postoperative convalescence are widely known and led to a frequent use for patients who underwent living donor kidney nephrectomy. The objective of this study was to determine whether general anesthesia (GA) plus EDA compared to GA only, administered for living donor nephrectomy has effects on postoperative graft function in recipients. Methods In this monocentric, retrospective cohort analysis we analyzed the closed files of all consecutive donor- recipient pairs who underwent living donor kidney transplantations from 2008 to 2017. The outcome variable was delayed graft function (DGF), defined as at least one hemodialysis within seven days postoperatively, once hyperacute rejection, vascular or urinary tract complications were ruled out. Statistical analyses of continuous variables were calculated using the two-tail Student’s t test and Fisher exact test for categorical variables with a significance level of p < 0.05, respectively. Results The study enclosed 291 consecutive living donor kidney transplantations. 99 kidney donors received epidural analgesia whereas 192 had no epidural analgesia. The groups showed balanced pretransplantational characteristics and comparable donors´ and recipients’ risk factors. 9 out of all 291 recipients needed renal replacement therapy (RRT) during the first 7 days due to delayed graft function; none of these donors received EDA. The observed rate of DGF in recipients whose kidney donors received epidural analgesia was significantly lower (0% vs. 4.6%; p = 0.031). Conclusions In our cohort we observed a significantly lower rate of DGF when epidural analgesia for donor nephrectomy was administered. Due to restrictions of the study design this observation needs further confirmation by prospective studies

Surgical performance of large loop excision of the transformation zone in a training model

Large loop excision of the transformation zone (LLETZ) is one of the most common procedures in operative gynecology and it is a routine part of the surgical training program of residents. There is, however, no established and standardized method of teaching residents how to perform LLETZ. Here, we present a surgical training model and assessed the improvement of surgical skills during repeated hands-on trainings of LLETZ in this model. Surgical novices and experts were recruited and were shown a LLETZ training video and then performed 3 LLETZ training sessions on consecutive days. Surgical skills were assessed by Objective Structured Assessment of Technical Skills (OSATS). Global rating scale (GRS), confidence (CON), fragmentation rate (FR), performance time (PT), and OSATS scores were calculated. Intra- and interobserver variabilities were determined. The construct validity of OSATS was assessed comparing metric scores of novices with those of experts. Sixty-eight probands (58 novices, 10 experts) were recruited. GRS, 2.3$\pm$1.3 (median$\pm$SD) versus 1.4$\pm$0.6, P<.001; CON, 2.7$\pm$0.9 versus 1.6$\pm$0.6, P<.001; FR, 81% versus 100%, P<.001; PT, 152$\pm$33 versus 120$\pm$27seconds, P=.006; and OSATS scores, 18.8$\pm$1.3 versus 19.1$\pm$1.1, P=.16 of novices improved from session 1 to session 3. OSATS showed construct validity with metric scores (GRS, 1.1$\pm$0.3 vs 2.3$\pm$0.8, P<.001; CON, 1.0$\pm$0.0 vs 2.7$\pm$0.9, P<.001; PT 125$\pm$30 vs 152$\pm$33seconds, P=.02; OSATS scores, 19.6$\pm$0.7 vs. 18.8$\pm$1.3, P=.02) reliably discriminating between experts and novices. Intra- and interobserver variabilities across probands were 0.99$\pm$0.03 and 0.64$\pm$0.10, respectively. OSATS scores were independent of handedness, sex, and regular sports activity in univariate and multivariate analyses. Repeated hands-on trainings improve surgical performance of LLETZ in a surgical training model with construct validity. $\textbf {Abbreviations:}$ CON = confidence, FR = fragmentation rate, GRS = global rating scale, LLETZ = large loop excision of the transformation zone, OSATS = Objective Structured Assessment of Technical Skills, PT = performance time

Additional file 1: of Quality of websites of obstetrics and gynecology departments: a cross-sectional study

Questionnaire

Thiopental inhibits global protein synthesis by repression of eukaryotic elongation factor 2 and protects from hypoxic neuronal cell death.

Ischemic and traumatic brain injury is associated with increased risk for death and disability. The inhibition of penumbral tissue damage has been recognized as a target for therapeutic intervention, because cellular injury evolves progressively upon ATP-depletion and loss of ion homeostasis. In patients, thiopental is used to treat refractory intracranial hypertension by reducing intracranial pressure and cerebral metabolic demands; however, therapeutic benefits of thiopental-treatment are controversially discussed. In the present study we identified fundamental neuroprotective molecular mechanisms mediated by thiopental. Here we show that thiopental inhibits global protein synthesis, which preserves the intracellular energy metabolite content in oxygen-deprived human neuronal SK-N-SH cells or primary mouse cortical neurons and thus ameliorates hypoxic cell damage. Sensitivity to hypoxic damage was restored by pharmacologic repression of eukaryotic elongation factor 2 kinase. Translational inhibition was mediated by calcium influx, activation of the AMP-activated protein kinase, and inhibitory phosphorylation of eukaryotic elongation factor 2. Our results explain the reduction of cerebral metabolic demands during thiopental treatment. Cycloheximide also protected neurons from hypoxic cell death, indicating that translational inhibitors may generally reduce secondary brain injury. In conclusion our study demonstrates that therapeutic inhibition of global protein synthesis protects neurons from hypoxic damage by preserving energy balance in oxygen-deprived cells. Molecular evidence for thiopental-mediated neuroprotection favours a positive clinical evaluation of barbiturate treatment. The chemical structure of thiopental could represent a pharmacologically relevant scaffold for the development of new organ-protective compounds to ameliorate tissue damage when oxygen availability is limited

Quality of websites of obstetrics and gynecology departments

$\bf Background:$ The internet has become an easily accessible and widely used source of healthcare information. There are, however, no standardized or commonly accepted criteria for the quality of Obstetrics and Gynecology websites. In this study, we aimed to evaluate the quality of websites of Obstetrics and Gynecology departments in German-speaking countries and to compare websites nationally and internationally. $\bf Methods:$ We scored 672 websites from Germany (n = 566), Austria (n = 57), and Switzerland (n = 49) using the objective criteria: Google search rank (2 items), technical aspects (11 items), navigation (8 items), and content (6 items) for a 26 point score. Scores were compared nationally and inter nationally. Multivariable regression models assessed good quality scores ($\geq$50% of maximum) as the dependent variables and country, academic affiliation, being member of a healthcare consortium, confessional affiliation, and content management system (CMS) use as independent variables. $\bf Results:$ The mean score of websites was 13.8 $\pm$ 3.3. 4.2% were rated as good ($\geq$75% of maximum), 61.8% as fair (($\geq$50% of maximum). German (14.0 $\pm$ 3.2) and Swiss (13.8 $\pm$ 4.0) websites scored significantly higher compared to Austrian websites (11.6 $\pm$ 2.5) (P < 0.001 and P = 0.005, respectively). Within Germany, academic had higher scores than non-academic departments (14.9 $\pm$ 3.2 vs. 13.7 $\pm$ 3.1, P < 0.001). Single institutions had higher scores compared to healthcare consortium institutions (14.1 $\pm$ 3.2 vs. 13.2 $\pm$ 2.6, P = 0.003). Departments in Northern and Southern states had higher scores compared to Eastern states (14.4 $\pm$ 3.2 and 14.2 $\pm$ 3.2 vs. 13.0 $\pm$ 3.0, P < 0.001). In multivariate regression models, all subscores (all: P < 0.001) independently predicted a website’s reaching a good quality score, with navigation subscore as strongest predictor. Affiliations were predictors for some good individual subscores, but not for others. High content subscore was associated with good Google search rank, technical aspects, and navigation subscores. $\bf Conclusions:$ The quality of websites of Obstetrics and Gynecology departments varies widely. We found marked differences depending on country, affiliation, and region