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Most published prediction models for Coronavirus Disease 2019 (COVID-19) were poorly reported, at high risk of bias, and heterogeneous in model performance. To tackle methodological challenges faced in previous prediction studies, we investigated whether model updating and extending improves mortality prediction, using the Intensive Care Unit (ICU) as a proxy. All COVID-19 patients admitted to seven ICUs in the Euregio-Meuse Rhine during the first pandemic wave were included. The 4C Mortality and SEIMC scores were selected as promising prognostic models from an external validation study. Five predictors could be estimated based on cohort size. TRIPOD guidelines were followed and logistic regression analyses with the linear predictor, APACHE II score, and country were performed. Bootstrapping with backward selection was applied to select variables for the final model. Additionally, shrinkage was performed. Model discrimination was displayed as optimism-corrected areas under the ROC curve and calibration by calibration slopes and plots. The mortality rate of the 551 included patients was 36%. Discrimination of the 4C Mortality and SEIMC scores increased from 0.70 to 0.74 and 0.70 to 0.73 and calibration plots improved compared to the original models after updating and extending. Mortality prediction can be improved after updating and extending of promising models., (© 2024. The Author(s).)

Objective: To examine if peritoneal conditioning with an altered insufflation gas mixture is associated with reduced postoperative pain intensity compared to the standard insufflation gas (i.e., 100% CO 2 )., Design: A prospective, single-centre, randomized, double-blind, superiority trial was performed., Setting: This study was conducted between 4 April 2019 and 10 February 2022 at the Jessa Hospital, Hasselt, Belgium., Population: Patients scheduled for elective gynaecologic laparoscopic surgery., Methods: Seventy-four patients scheduled for elective gynaecologic laparoscopic surgery were randomised to receive either the standard insufflation gas with 100 CO 2 (n = 37; control group) or the altered gas mixture of 86% CO 2 , 10% N 2 O and 4% O 2 (n = 37; experimental group)., Main Outcome Measures: Postoperative pain was assessed at 4, 8 and 24 hours after surgery and on postoperative day (POD) 7 by an 11-point Numeric Rating Scale, with 0 indicating no pain and 10 indicating worst imaginable pain., Results: No significant differences were found between the control and experimental groups regarding postoperative pain at 4, 8 and 24 h after surgery, as well as on POD7. In addition, the median (25% and 75%) total amount of IV piritramide consumption during the first 24 h after surgery was not significantly different between groups (control group: 18.0 [10.0, 27.0] mg vs. experimental group: 17.0 [10.0, 34.0] mg, p = 0.62)., Conclusion: The alternative insufflation gas mixture comprising 86% CO 2 , 10% N 2 O and 4% O 2 used for the pneumoperitoneum during gynaecologic laparoscopic surgery does not appear to reduce postoperative pain compared to the standard insufflation gas of 100% CO 2 ., (© 2024 John Wiley & Sons Ltd.)

Introduction: Serratus anterior plane block has been proposed to reduce opioid requirements after minimally invasive cardiac surgery, but high-quality evidence is lacking., Methods: This prospective, double-blinded, randomized controlled trial recruited patients undergoing totally endoscopic aortic valve replacement. Patients in the intervention arm received a single-injection serratus anterior plane block on arrival to the intensive care unit added to standard of care. Patients in the control group received routine standard of care, including patient-controlled intravenous analgesia. Primary outcome was piritramide consumption within the first 24 hours after serratus anterior plane block placement. We hypothesized that compared with no block, patients in the intervention arm would consume 25% less opioids., Results: Seventy-five patients were analyzed (n=38 in intervention arm, n=37 in control arm). When comparing the serratus anterior plane group with the control group, median 24-hour cumulative opioid use was 9 (IQR 6-19.5) vs 15 (IQR 11.3-23.3) morphine milligram equivalents, respectively (p<0.01). Also, pain scores at 4, 8 and 24 hours were lower in the intervention arm at 4, 8 and 24 hours, respectively., Conclusion: Combined deep and superficial single-injection serratus anterior plane block is superior to standard of care in reducing opioid requirements and postoperative pain intensity up to 24 hours after totally endoscopic aortic valve replacement., Trial Registration Number: NCT04699422., Competing Interests: Competing interests: None declared., (© American Society of Regional Anesthesia & Pain Medicine 2024. Re-use permitted under CC BY-NC. No commercial re-use. Published by BMJ.)

Background: Several regional anesthesia (RA) techniques have been described for distal upper limb surgery. However, the best approach in terms of RA block success rate and safety is not well recognized. Objective: To assess and compare the surgical anesthesia and efficacy of axillary brachial plexus block with other RA techniques for hand and wrist surgery. The attainment of adequate surgical anesthesia 30 min after block placement was considered a primary outcome measure. Additionally, successful block outcomes were required without the use of supplemental local anesthetic injection, systemic opioid analgesia, or the need to convert to general anesthesia. Methods: We performed a systematic search in the following databases: MEDLINE, EMBASE, Cochrane Database of Systematic Reviews, and CENTRAL. RCTs comparing axillary blocks with other brachial plexus block techniques, distal peripheral forearm nerve block, intravenous RA, and the wide-awake local anesthesia no tourniquet (WALANT) technique were included. Results: In total, 3070 records were reviewed, of which 28 met the inclusion criteria. The meta-analysis of adequate surgical anesthesia showed no significant difference between ultrasound-guided axillary block and supraclavicular block (RR: 0.94 [0.89, 1.00]; p = 0.06; I 2 = 60.00%), but a statistically significant difference between ultrasound-guided axillary block and infraclavicular block (RR: 0.92 [0.88, 0.97]; p < 0.01; I 2 = 53.00%). Ultrasound-guided infraclavicular blocks were performed faster than ultrasound-guided axillary blocks (SMD: 0.74 [0.30, 1.17]; p < 0.001; I 2 = 85.00%). No differences in performance time between ultrasound-guided axillary and supraclavicular blocks were demonstrated. Additionally, adequate surgical anesthesia onset time was not significantly different between ultrasound-guided block approaches: ultrasound-guided axillary blocks versus ultrasound-guided supraclavicular blocks (SMD: 0.52 [-0.14, 1.17]; p = 0.12; I 2 = 86.00%); ultrasound-guided axillary blocks versus ultrasound-guided infraclavicular blocks (SMD: 0.21 [-0.49, 0.91]; p = 0.55; I 2 = 92.00%). Conclusions: The RA choice should be individualized depending on the patient, procedure, and operator-specific parameters. Compared to ultrasound-guided supraclavicular and infraclavicular block, ultrasound-guided axillary block may be preferred for patients with significant concerns of block-related side effects/complications. High heterogeneity between studies shows the need for more robust RCTs.

Background: Efforts to identify therapies to treat hospitalised patients with COVID-19 are being continued. Alkaline phosphatase (AP) dephosphorylates pro-inflammatory adenosine triphosphate (ATP) into anti-inflammatory adenosine., Methods: In a randomised controlled trial, we investigated the safety and efficacy of AP in patients with SARS-CoV-2 infection admitted to the ICU. AP or a placebo was administered for four days following admission to the ICU. The primary outcome was the duration of mechanical ventilation. Mortality in 28 days, acute kidney injury, need for reintubation, safety, and inflammatory markers relevant to the described high cytokine release associated with SARS-CoV-2 infection were the secondary outcomes., Results: Between December 2020 and March 2022, 97 patients (of the intended 132) were included, of which 51 were randomised to AP. The trial was terminated prematurely based on meeting the threshold for futility. Compared to the placebo, AP did not affect the duration of mechanical ventilation (9.0 days vs. 9.3 days, p = 1.0). No safety issues were observed. After 28 days, mortality was 9 (18%) in the AP group versus 6 (13%) in the placebo group ( p = 0.531). Additionally, no statistically significant differences between the AP and the placebo were observed for the other secondary outcomes., Conclusions: Alkaline phosphatase (AP) therapy in COVID-19 ICU patients showed no significant benefits in this trial.

Introduction: We aimed to identify risk factors associated with ICU mortality in critically ill patients with COVID-19 pneumonia treated with Extracorporeal membrane oxygenation (ECMO). We also aimed to assess protocol violations of the local eligibility criteria of ECMO initiation., Methods: All 31 consecutive adult patients with confirmed COVID-19 pneumonia admitted to ICU and treated with ECMO from March 13th 2020 to 8 December 2021 were enrolled. Eligibility criteria for ECMO initiation were: P/F-ratio<50 mmHg >3 hours, P/F-ratio<80 mmHg >6 hours or pH<7.25 + PaCO2>60 mmHg >6 hours, despite maximal protective invasive ventilation. Primary outcome was ICU mortality. Univariate logistic regression analyses were performed to identify predictors of ICU mortality., Results: 12 out of 31 patients (38.7%) did not survive ECMO treatment in ICU. Half of the non-survivors suffered from acute kidney failure compared to 3 out of 19 survivors (15.79%) ( p = .04). Half of the non-survivors required CRRT treatment versus 1 patient in the survivor group (5.3%) ( p < .01). Higher age (2.45 (0.97-6.18), p = .05), the development of AKI (5.33 (1.00-28.43), p = .05), need of CRRT during ICU stay (18.00 (1.79-181.31), p = .01) and major bleeding during ECMO therapy (0.51 (0.19-0.89), p < .01) were identified to be predictors of ICU mortality., Conclusion: Almost 60% of patients could be treated successfully with ECMO with sustained results at 3 months. Predictors for ICU mortality were development of AKI and need of CRRT during ICU stay, higher age category and major bleeding. Inadvertent ECMO allocation was noted in almost one in five patients., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

The immune response in patients with Coronavirus Disease 2019 (COVID-19) is highly variable and is linked to disease severity and mortality. However, antibody and cytokine responses in the early disease stage and their association with disease course and outcome are still not completely understood. In this large, multi-centre cohort study, blood samples of 434 Belgian COVID-19 hospitalized patients with different disease severities (ranging from asymptomatic/mild to critically ill) from the first wave of the COVID-19 pandemic were obtained. Baseline antibody and cytokine responses were characterized and associations with several clinical outcome parameters were determined. Anti-spike immunoglobulin (Ig)G and IgM levels were elevated in patients with a more severe disease course. This increased baseline antibody response however was associated with decreased odds for hospital mortality. Levels of the pro-inflammatory cytokines IL-6, IP-10 and IL-8, the anti-inflammatory cytokine IL-10 and the antiviral cytokines IFN-α, IFN-β and IFN-λ1 were increased with disease severity. Remarkably, we found significantly lower levels of IFN-λ2,3 in critically ill patients compared to patients of the moderate and severe disease category. Finally, levels of IL-8, IL-6, IP-10, IL-10, IFN-α, IFN-β, IFN-γ and IFN-λ1 at baseline were positively associated with mortality, whereas higher IFN-λ2,3 levels were negatively associated with mortality., (© 2023. The Author(s).)

Patients infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) who have been admitted to the intensive care unit (ICU) often face months of physical disability after discharge. To optimize recovery, it is important to understand the role of musculoskeletal alterations in critically ill patients infected with SARS-CoV-2. The main aim of the present study was to describe the presence and morphology of nemaline bodies found in the skeletal muscle tissue from critically ill patients infected with SARS-CoV-2. In n = 7 patients infected with SARS-CoV-2, ultrastructural characteristics of vastus lateralis muscle obtained on days 1-3 and days 5-8 following ICU admission were investigated in more detail with electron microscopy. Those muscle biopsies consistently showed variable degrees of myofiber necrosis and myofibrillar disorganization. In 4/7 (57%) patients on days 5-8, the Z-line material accumulated into nemaline bodies with a typical lattice-like appearance at higher magnification, similar to that found in nemaline myopathy. This study is the first to describe the disintegration of myofibrils and the accumulation of Z-line material into nemaline bodies in the skeletal muscle tissue obtained from critically ill coronavirus disease-19 patients following ICU admission, which should be interpreted primarily as a non-specific pathological response of extreme myofibrillar disintegration associated with myofiber necrosis., (© The Author(s) 2023. Published by Oxford University Press on behalf of The Japanese Society of Microscopy. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Randomized, controlled trials have shown both benefit and harm from tight blood-glucose control in patients in the intensive care unit (ICU). Variation in the use of early parenteral nutrition and in insulin-induced severe hypoglycemia might explain this inconsistency., Methods: We randomly assigned patients, on ICU admission, to liberal glucose control (insulin initiated only when the blood-glucose level was >215 mg per deciliter [>11.9 mmol per liter]) or to tight glucose control (blood-glucose level targeted with the use of the LOGIC-Insulin algorithm at 80 to 110 mg per deciliter [4.4 to 6.1 mmol per liter]); parenteral nutrition was withheld in both groups for 1 week. Protocol adherence was determined according to glucose metrics. The primary outcome was the length of time that ICU care was needed, calculated on the basis of time to discharge alive from the ICU, with death accounted for as a competing risk; 90-day mortality was the safety outcome., Results: Of 9230 patients who underwent randomization, 4622 were assigned to liberal glucose control and 4608 to tight glucose control. The median morning blood-glucose level was 140 mg per deciliter (interquartile range, 122 to 161) with liberal glucose control and 107 mg per deciliter (interquartile range, 98 to 117) with tight glucose control. Severe hypoglycemia occurred in 31 patients (0.7%) in the liberal-control group and 47 patients (1.0%) in the tight-control group. The length of time that ICU care was needed was similar in the two groups (hazard ratio for earlier discharge alive with tight glucose control, 1.00; 95% confidence interval, 0.96 to 1.04; P = 0.94). Mortality at 90 days was also similar (10.1% with liberal glucose control and 10.5% with tight glucose control, P = 0.51). Analyses of eight prespecified secondary outcomes suggested that the incidence of new infections, the duration of respiratory and hemodynamic support, the time to discharge alive from the hospital, and mortality in the ICU and hospital were similar in the two groups, whereas severe acute kidney injury and cholestatic liver dysfunction appeared less prevalent with tight glucose control., Conclusions: In critically ill patients who were not receiving early parenteral nutrition, tight glucose control did not affect the length of time that ICU care was needed or mortality. (Funded by the Research Foundation-Flanders and others; TGC-Fast ClinicalTrials.gov number, NCT03665207.)., (Copyright © 2023 Massachusetts Medical Society.)

Regional anaesthesia (RA) has an important and ever-expanding role in ambulatory surgery. Specific practices vary depending on the preferences and resources of the anaesthesia team and hospital setting. It is used for various purposes, including as primary anaesthetic technique for surgery but also as postoperative analgesic modality. The limited duration of action of currently available local anaesthetics limits their application in postoperative pain control and enhanced recovery. The search for the holy grail of regional anaesthetics continues. Current evidence suggests that a peripheral nerve block performed with long-acting local anaesthetics in combination with intravenous or perineural dexamethasone gives the longest and most optimal sensory block. In this review, we outline some possible blocks for ambulatory surgery and additives to perform RA. Moreover, we give an update on local anaesthesia drugs and adjuvants, paediatric RA in ambulatory care and discuss the impact of RA by COVID-19., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Objective: Minimally invasive procedures have been developed to reduce surgical trauma after cardiac surgery. Clinical recovery is the main focus of most research. Still, patient-centred outcomes, such as the quality of life, can provide a more comprehensive understanding of the impact of the surgery on the patient's life. This systematic review aims to deliver a detailed summary of all available research investigating the quality of recovery, assessed with quality of life instruments, in adults undergoing minimally invasive cardiac surgery., Methods: All randomised trials, cohort studies, and cross-sectional studies assessing the quality of recovery in patients undergoing minimally invasive cardiac surgery compared to conventional cardiac surgery within the last 20 years were included, and a summary was prepared., Results: The randomised trial observed an overall improved quality of life after both minimally invasive and conventional surgery. The quality of life improvement in the minimally invasive group showed a faster course and evolved to a higher level than the conventional surgery group. These findings align with the results of prospective cohort studies. In the cross-sectional studies, no significant difference in the quality of life was seen except for one that observed a significantly higher quality of life in the minimally invasive group., Conclusions: This systematic review indicates that patients may benefit from minimally invasive and conventional cardiac surgery, but patients undergoing minimally invasive cardiac surgery may recover sooner and to a greater extent. However, no firm conclusion could be drawn due to the limited available studies. Therefore, randomised controlled trials are needed., Competing Interests: Conflict of interestThe authors declare that they have no conflicting interests., (© The Author(s) 2023.)

Literature regarding monitoring and consequences of distal limb ischemia due to femoral artery cannulation for Minimally Invasive Cardiac Surgery (MICS) remains limited. The primary objective was to determine its incidence, defined as a ≥ 15% difference in regional Oxygen Saturation (rSO 2 ) lasting ≥ four consecutive minutes between the cannulated and non-cannulated limb. The secondary objectives included: determination of distal limb ischemia, defined as a Tissue Oxygenation Index (TOI) < 50% in the cannulated limb, identification of predictors for distal limb ischemia, determination of a possible association of NIRS-diagnosed ischemia with acute kidney injury, and the need for vascular surgery up to six months after cardiac surgery. A prospective, observational cohort study with blinded rSO 2 -measurements to prevent intraoperative clinical decision-making. A single-center, community-hospital, clinical study. All consecutive patients ≥ 18 years old, and scheduled for predefined MICS. Patients underwent MICS with bilateral calf muscle rSO 2 -measurements conducted by Near-Infrared Spectroscopy (NIRS). In total 75/280 patients (26.79%) experienced distal limb ischemia according to the primary objective, while 18/280 patients (6.42%) experienced distal limb ischemia according to the secondary objective. Multivariate logistic regression showed younger age to be an independent predictor for distal limb ischemia (p = 0.003). None of the patients who suffered intraoperative ischemia required vascular surgery within the follow-up period. The incidence of NIRS-diagnosed ischemia varied from 6.4% to 26.8% depending on the used criteria. Short and long-term vascular sequelae, however, are limited and not intraoperative ischemia related. The added value of intraoperative distal limb NIRS monitoring for vascular reasons seems limited. Future research on femoral artery cannulation in MICS should shift focus to other outcome parameters such as acute kidney injury, postoperative pain or paresthesias., (© 2023. The Author(s).)

Patient-centred outcomes have grown in popularity over recent years in surgical care research. These patient-centred outcomes can be measured through the health-related quality of life (HRQL) without professional interpretations. In May 2022, a study regarding patient-centred outcomes up to 90 days postoperatively was published. Fourteen days after surgery, the HRQL decreased and returned to baseline levels after 30 days. Next, the HRQL significantly improved 90 days postoperatively. However, this study only focuses on a short-term follow-up of the patients. Hence, this follow-up study aims to assess the HRQL one year after totally endoscopic cardiac surgery. At baseline, 14, 30, and 90 days, and one year after surgery, the HRQL was evaluated using a 36-item short form and 5-dimensional European QoL questionnaires (EQ-5D). Using the 36-item short form questionnaire, a physical and mental component score is calculated. Over the period of one year, this physical and mental component score and the EQ-5D index value significantly improve. According to the visual analogue scale of the EQ-5D, patients score their health significantly higher one year postoperatively. In conclusion, after endoscopic cardiac surgery, the HRQL is significantly improved 90 days postoperatively and remains high one year afterward.

Background: In patients with severe respiratory failure from COVID-19, extracorporeal membrane oxygenation (ECMO) treatment can facilitate lung-protective ventilation and may improve outcome and survival if conventional therapy fails to assure adequate oxygenation and ventilation. We aimed to perform a confirmatory propensity-matched cohort study comparing the impact of ECMO and maximum invasive mechanical ventilation alone (MVA) on mortality and complications in severe COVID-19 pneumonia., Materials and Methods: All 295 consecutive adult patients with confirmed COVID-19 pneumonia admitted to the intensive care unit (ICU) from March 13 th , 2020, to July 31 st , 2021 were included. At admission, all patients were classified into 3 categories: (1) full code including the initiation of ECMO therapy (AAA code), (2) full code excluding ECMO (AA code), and (3) do-not-intubate (A code). For the 271 non-ECMO patients, match eligibility was determined for all patients with the AAA code treated with MVA. Propensity score matching was performed using a logistic regression model including the following variables: gender, P/F ratio, SOFA score at admission, and date of ICU admission. The primary endpoint was ICU mortality., Results: A total of 24 ECMO patients were propensity matched to an equal number of MVA patients. ICU mortality was significantly higher in the ECMO arm (45.8%) compared with the MVA cohort (16.67%) (OR 4.23 (1.11, 16.17); p =0.02). Three-month mortality was 50% with ECMO compared to 16.67% after MVA (OR 5.91 (1.55, 22.58); p < 0.01). Applied peak inspiratory pressures (33.42 ± 8.52 vs. 24.74 ± 4.86 mmHg; p < 0.01) and maximal PEEP levels (14.47 ± 3.22 vs. 13.52 ± 3.86 mmHg; p =0.01) were higher with MVA. ICU length of stay (LOS) and hospital LOS were comparable in both groups., Conclusion: ECMO therapy may be associated with an up to a three-fold increase in ICU mortality and 3-month mortality compared to MVA despite the facilitation of lung-protective ventilation settings in mechanically ventilated COVID-19 patients. We cannot confirm the positive results of the first propensity-matched cohort study on this topic. This trial is registered with NCT05158816., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2023 Björn Stessel et al.)

Background: There is growing evidence that the analgesic effect of metamizole is mediated at least partly by central mechanisms, including the endocannabinoid/endovanilloid system. Consequently, metamizole may have additive or even synergistic analgesic effects with paracetamol and nonsteroidal anti-inflammatory drugs (NSAID)., Objective: This study aimed to assess if triple therapy with metamizole, ibuprofen and paracetamol (MIP) is superior to double therapy with ibuprofen and paracetamol (i.p.) in treating pain at home after ambulatory arthroscopic shoulder surgery., Design/setting/patients/intervention: In this double-blind, controlled, high-volume single centre, superiority trial, 110 patients undergoing elective ambulatory arthroscopic shoulder surgery were randomised to receive either MIP ( n  = 55) or i.p. ( n  = 55) orally for 4 days between December 2019 and November 2021. Pain intensity at movement and rest, using a numeric rating scale (NRS), perceived pain relief, use of rescue medication and adverse effects of study medication were recorded at the post-anaesthesia care unit (PACU) and on postoperative day (POD) 1 to 4 and 7. Quality of Recovery (QoR) and satisfaction with study medication were measured at POD 7 with telephone follow-up., Main Outcome Measure: The primary outcome measure was postoperative pain intensity on movement measured by an 11-point NRS (where 0 = no pain and 10 = worst pain imaginable) on POD 1., Results: For the primary outcome, superiority of MIP in reducing postoperative pain at movement on POD 1 was not confirmed: mean difference NRS [95% confidence interval (CI), -0.08 (-1.00 to 0.84)]. For pain on movement and at rest, no significant differences were found between groups in the PACU nor on POD 1 to 4 or day 7. Nausea was reported significantly more frequently in the metamizole group (22.6 vs. 58.5; P  < 0.001). Other adverse effects of study medication, rescue opioid consumption, perceived pain relief, QoR at POD 7, and overall patient satisfaction were similar in both groups., Conclusion: Clinically, triple oral treatment with metamizole, paracetamol and ibuprofen is not superior to oral paracetamol and ibuprofen in multimodal pain treatment at home after ambulatory arthroscopic shoulder surgery., Trial Registration: European Union Clinical Trials Register 2019-002801-23 and Clinicaltrials.gov NCT04082728., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the European Society of Anaesthesiology and Intensive Care.)

Objectives: Many prediction models for coronavirus disease 2019 (COVID-19) have been developed. External validation is mandatory before implementation in the intensive care unit (ICU). We selected and validated prognostic models in the Euregio Intensive Care COVID (EICC) cohort., Study Design and Setting: In this multinational cohort study, routine data from COVID-19 patients admitted to ICUs within the Euregio Meuse-Rhine were collected from March to August 2020. COVID-19 models were selected based on model type, predictors, outcomes, and reporting. Furthermore, general ICU scores were assessed. Discrimination was assessed by area under the receiver operating characteristic curves (AUCs) and calibration by calibration-in-the-large and calibration plots. A random-effects meta-analysis was used to pool results., Results: 551 patients were admitted. Mean age was 65.4 ± 11.2 years, 29% were female, and ICU mortality was 36%. Nine out of 238 published models were externally validated. Pooled AUCs were between 0.53 and 0.70 and calibration-in-the-large between -9% and 6%. Calibration plots showed generally poor but, for the 4C Mortality score and Spanish Society of Infectious Diseases and Clinical Microbiology (SEIMC) score, moderate calibration., Conclusion: Of the nine prognostic models that were externally validated in the EICC cohort, only two showed reasonable discrimination and moderate calibration. For future pandemics, better models based on routine data are needed to support admission decision-making., (Copyright © 2022 The Author(s). Published by Elsevier Inc. All rights reserved.)

Transcutaneous medium-frequency alternating electrical current is defined as an alternating current between 1 and 10 kHz and is capable of producing an instant, reversible block. This study aims to evaluate the efficacy of sensory perception and force production of the index and middle finger after transcutaneous medium-frequency alternating electrical current stimulation of the distal median nerve. A single-center prospective interventional cohort study was conducted in adult healthy volunteers at the Jessa Hospital, Hasselt, Belgium. Two different electrodes (PALS & 3M) were placed on the distal median nerve, which was located using a Sonosite X-Porte Ultrasound transducer, with the first electrode being placed on the skin at the level of the transverse carpal ligament and the second electrode 7 cm proximally to the first electrode. The tactile sensation was evaluated with Semmes-Weinstein monofilament test and sensation of pressure/pain was evaluated with an algometer. Peak force production was assessed with an electronic dynamometer. All measurements were performed at baseline and tMFAEC stimulation frequencies of 2 and 10 kHz in a randomized manner. Statistical analysis was performed with a one-way ANOVA with repeated measures test or a Friedman rank sum test, followed by the Wilcoxon signed rank test adjusted with Bonferroni correction. A p-value &lt; 0.05 was considered statistically significant. From 9 to 13th of April 2021, 25 healthy volunteers were included in the Jessa Hospital, Hasselt, Belgium. A statistically significant reduction in tactile sensation during 2 kHz and 10 kHz stimulation compared to baseline was observed (2.89 ± 0.22 (PALS2); 3.35 ± 0.25 (3M2) and 2.14 ± 0.12 (PALS10); 2.38 ± 0.12 (3M10) versus - 1.75 ± 0.09 (baseline), p &lt; 0.0001). 3M electrodes showed a tendency towards the elevation of pressure pain threshold compared to baseline. No significant difference in mean peak forces of the index and middle fingers after transcutaneous medium-frequency alternating electrical current stimulation with 2 and 10 kHz was found. This study demonstrates that transcutaneous medium-frequency alternating electrical current stimulation on the distal median nerve inhibits tactile sensory nerve activity in the index and middle finger when stimulation of 2 kHz and, to a lesser extent, 10 kHz was applied. A reduction of motor nerve activity was not observed but force production measurements may be prone to error.Trial registration: clinicaltrials.gov on 01/04/2021. NCT-Number: NCT04827173., (© 2022. The Author(s).)

Background: Acute kidney injury (AKI) has been reported as a frequent complication of critical COVID-19. We aimed to evaluate the occurrence of AKI and use of kidney replacement therapy (KRT) in critical COVID-19, to assess patient and kidney outcomes and risk factors for AKI and differences in outcome when the diagnosis of AKI is based on urine output (UO) or on serum creatinine (sCr)., Methods: Multicenter, retrospective cohort analysis of patients with critical COVID-19 in seven large hospitals in Belgium. AKI was defined according to KDIGO within 21 days after ICU admission. Multivariable logistic regression analysis was used to explore the risk factors for developing AKI and to assess the association between AKI and ICU mortality., Results: Of 1286 patients, 85.1% had AKI, and KRT was used in 9.8%. Older age, obesity, a higher APACHE II score and use of mechanical ventilation at day 1 of ICU stay were associated with an increased risk for AKI. After multivariable adjustment, all AKI stages were associated with ICU mortality. AKI was based on sCr in 40.1% and UO in 81.5% of patients. All AKI stages based on sCr and AKI stage 3 based on UO were associated with ICU mortality. Persistent AKI was present in 88.6% and acute kidney disease (AKD) in 87.6%. Rapid reversal of AKI yielded a better prognosis compared to persistent AKI and AKD. Kidney recovery was observed in 47.4% of surviving AKI patients., Conclusions: Over 80% of critically ill COVID-19 patients had AKI. This was driven by the high occurrence rate of AKI defined by UO criteria. All AKI stages were associated with mortality (NCT04997915)., (© 2022. The Author(s).)

Over the past years, minimally invasive procedures have been developed to reduce surgical trauma after cardiac surgery. The value of patient-centered outcomes, including the quality of recovery after hospital discharge, is increasingly recognized. Identifying meaningful changes in postoperative function that might have a negative impact on patients without noticeable complications can provide a more comprehensive understanding of the impact on the patient's life. In total, 209 patients were included in this trial. Of these, 193 patients underwent totally endoscopic cardiac surgery, 8 underwent cardiac surgery through a sternotomy, and 8 underwent transcatheter aortic valve implantation. Patients who previously underwent cardiac surgery were excluded. Quality of life was determined through the Short Form 36 and European Quality of Life-5 Dimensions questionnaires before the surgery and 14, 30, and 90 days afterward. In patients who underwent totally endoscopic cardiac surgery, the quality of life improved over the three time periods. The different domains of the questionnaire evolved in a positive manner. However, 14 days postoperatively, a decline in quality of life was noted, followed by a return to baseline at 30 days and an increase at 90 days. In conclusion, totally endoscopic cardiac surgery improves the quality of life 90 days after surgery.

Objectives: To investigate healthcare system-driven variation in general characteristics, interventions, and outcomes in coronavirus disease 2019 (COVID-19) patients admitted to the ICU within one Western European region across three countries., Design: Multicenter observational cohort study., Setting: Seven ICUs in the Euregio Meuse-Rhine, one region across Belgium, The Netherlands, and Germany., Patients: Consecutive COVID-19 patients supported in the ICU during the first pandemic wave., Interventions: None., Measurements and Main Results: Baseline demographic and clinical characteristics, laboratory values, and outcome data were retrieved after ethical approval and data-sharing agreements. Descriptive statistics were performed to investigate country-related practice variation. From March 2, 2020, to August 12, 2020, 551 patients were admitted. Mean age was 65.4 ± 11.2 years, and 29% were female. At admission, Acute Physiology and Chronic Health Evaluation II scores were 15.0 ± 5.5, 16.8 ± 5.5, and 15.8 ± 5.3 (p = 0.002), and Sequential Organ Failure Assessment scores were 4.4 ± 2.7, 7.4 ± 2.2, and 7.7 ± 3.2 (p < 0.001) in the Belgian, Dutch, and German parts of Euregio, respectively. The ICU mortality rate was 22%, 42%, and 44%, respectively (p < 0.001). Large differences were observed in the frequency of organ support, antimicrobial/inflammatory therapy application, and ICU capacity. Mixed-multivariable logistic regression analyses showed that differences in ICU mortality were independent of age, sex, disease severity, comorbidities, support strategies, therapies, and complications., Conclusions: COVID-19 patients admitted to ICUs within one region, the Euregio Meuse-Rhine, differed significantly in general characteristics, applied interventions, and outcomes despite presumed genetic and socioeconomic background, admission diagnosis, access to international literature, and data collection are similar. Variances in healthcare systems' organization, particularly ICU capacity and admission criteria, combined with a rapidly spreading pandemic might be important drivers for the observed differences. Heterogeneity between patient groups but also healthcare systems should be presumed to interfere with outcomes in coronavirus disease 2019., Competing Interests: The authors have disclosed that they do not have any potential conflicts of interest., (Copyright © 2022 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the Society of Critical Care Medicine and Wolters Kluwer Health, Inc.)

Background: Patients infected with severe acute respiratory syndrome coronavirus (SARS-CoV-2) can develop severe illness necessitating intensive care admission. Critically ill patients are susceptible for the development of secondary bacterial infections. Due to a combination of virus- and drug-induced immunosuppression, critically ill patients with corona virus disease 2019 (COVID-19) may even have a higher risk of developing a secondary infection. These secondary infections can aggravate the severity of illness and increase the risk of death. Further research on secondary infections in COVID-19 patients is essential. Therefore, the objective of this study was to investigate the incidence and associated risk factors of secondary bacterial infections and to identify the most common groups of pathogens in critically ill COVID-19 patients., Methods: This mono-center, retrospective observational cohort study was performed at the intensive care unit (ICU) of the Jessa Hospital, Hasselt, Belgium. All adult COVID-19 patients admitted to the ICU from 13th March 2020 until 17th October 2020, were eligible for inclusion in the study. Data from the resulting 116 patients were prospectively entered into a customized database. The resulting database was retrospectively reviewed to investigate three types of secondary bacterial infections (secondary pneumonia, bloodstream infections of unknown origin, catheter-related sepsis)., Results: Of 94 included patients, 68% acquired at least one of the studied secondary bacterial infections during their ICU stay. Almost two thirds of patients (65.96%, n = 62) acquired a secondary pneumonia, whereas 29.79% (n = 28) acquired a bacteremia of unknown origin and a smaller proportion of patients (14.89%, n = 14) acquired a catheter-related sepsis. Male gender (P = 0.05), diabetes mellitus (P = 0.03) and the cumulative dose of corticosteroids (P = 0.004) were associated with increased risk of secondary bacterial infection. The most common pathogens detected in the cultures of patients with secondary pneumonia were Gram-negative bacilli. Bacteremia of unknown origin and catheter-related sepsis were mostly caused by Gram-positive cocci., Conclusion: This study confirms that the incidence of secondary bacterial infections is very high in critically ill COVID-19 patients. These patients are at highest risk of developing secondary pneumonia. Male gender, a history of diabetes mellitus and the administration of corticosteroids were associated with increased risk of secondary bacterial infection., (© 2022. The Author(s).)

Although male Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) patients have higher Intensive Care Unit (ICU) admission rates and a worse disease course, a comprehensive analysis of female and male ICU survival and underlying factors such as comorbidities, risk factors, and/or anti-infection/inflammatory therapy administration is currently lacking. Therefore, we investigated the association between sex and ICU survival, adjusting for these and other variables. In this multicenter observational cohort study, all patients with SARS-CoV-2 pneumonia admitted to seven ICUs in one region across Belgium, The Netherlands, and Germany, and requiring vital organ support during the first pandemic wave were included. With a random intercept for a center, mixed-effects logistic regression was used to investigate the association between sex and ICU survival. Models were adjusted for age, Acute Physiology and Chronic Health Evaluation II (APACHE II) score, comorbidities, and anti-infection/inflammatory therapy. Interaction terms were added to investigate effect modifications by sex with country and sex with obesity. A total of 551 patients (29% were females) were included. Mean age was 65.4 ± 11.2 years. Females were more often obese and smoked less frequently than males (p-value 0.001 and 0.042, respectively). APACHE II scores of females and males were comparable. Overall, ICU mortality was 12% lower in females than males (27% vs 39% respectively, p-value < 0.01) with an odds ratio (OR) of 0.62 (95%CI 0.39-0.96, p-value 0.032) after adjustment for age and APACHE II score, 0.63 (95%CI 0.40-0.99, p-value 0.044) after additional adjustment for comorbidities, and 0.63 (95%CI 0.39-0.99, p-value 0.047) after adjustment for anti-infection/inflammatory therapy. No effect modifications by sex with country and sex with obesity were found (p-values for interaction > 0.23 and 0.84, respectively). ICU survival in female SARS-CoV-2 patients was higher than in male patients, independent of age, disease severity, smoking, obesity, comorbidities, anti-infection/inflammatory therapy, and country. Sex-specific biological mechanisms may play a role, emphasizing the need to address diversity, such as more sex-specific prediction, prognostic, and therapeutic approach strategies., (© 2022. The Author(s).)

Background: The Sequential Organ Failure Assessment (SOFA) score has been developed to score the severity of organ dysfunction in critically ill sepsis patients and has been proven to have a high predictive value for intensive care unit (ICU) mortality in severely ill patients. Our goal was to evaluate the prognostic value of the SOFA score as well as trends in SOFA score for ICU mortality in COVID-19 patients., Methods: All consecutive patients with confirmed COVID-19 pneumonia admitted to the ICU between March 13th, 2020, and October 17th, 2020 were included in this retrospective cohort study. The worst SOFA score was evaluated daily. Multiple logistic regression models were used to evaluate the predictive value of SOFA in ICU mortality., Results: 103 patients were included in this study. 30 patients (29%) died during their ICU stay and 73 (71%) patients were discharged alive. The ICU admission SOFA score was 5.2 ± 3.3 in ICU non-survivors vs. 4.3 ± 2.9 in ICU survivors (P = 0.15). The maximum SOFA score in ICU non-survivors was 11.7 ± 4.7 vs. 7.4 ± 4.3 in ICU survivors. SOFA scores increased the first week in both survivors and non-survivors, but the increase was less pronounced in survivors. In the multiple logistic regression models, neither admission SOFA score nor combination with delta SOFA in the first 48 hours was statistically significantly related to ICU mortality. Only the maximum SOFA score remained significant (OR = 1.23, 95% CI: 1.11-1.37, P < 0.001) in the multiple logistic models with an AUC of 0.91., Conclusions: Evaluation of SOFA scores in the first 48 hours after ICU admission is not a good prognostic indicator in COVID-19 patients. Only the maximum SOFA score was predictive for ICU mortality.

Background: To minimise the risk of COVID-19 transmission, an ambulant screening protocol for COVID-19 in patients before admission to the hospital was implemented, combining the SARS CoV-2 reverse-transcriptase polymerase chain reaction (RT-PCR) on a nasopharyngeal swab, a chest computed tomography (CT) and assessment of clinical symptoms. The aim of this study was to evaluatethe diagnostic yield and the proportionality of this pre-procedural screeningprotocol., Methods: In this mono-centre, prospective, cross-sectional study, all patients admitted to the hospital between 22nd April 2020 until 14th May 2020 for semi-urgent surgery, haematological or oncological treatment, or electrophysiological investigationunderwent a COVID-19 screening 2 days before their procedure. At a 2-week follow-up, the presence of clinical symptoms was evaluated by telephone as a post-hoc evaluation of the screening approach.Combined positive RT-PCR assay and/or positive chest CT was used as gold standard. Post-procedural outcomes of all patients diagnosed positive for COVID-19 were assessed., Results: In total,528 patients were included of which 20 (3.8%) were diagnosed as COVID-19 positive and 508 (96.2%) as COVID-19 negative. 11 (55.0%) of COVID-19 positive patients had only a positive RT-PCR assay, 3 (15.0%) had only a positive chest CT and 6 (30%) had both a positive RT-PCR assay and chest CT. 10 out of 20 (50.0%) COVID-19 positive patients reported no single clinical symptom at the screening. At 2 week follow-up, 50% of these patients were still asymptomatic. 37.5% of all COVID-19 negative patients were symptomatic at screening. In the COVID-19 negative group without symptoms at screening, 78 (29.3%) patients developed clinical symptoms at a 2-week follow-up., Conclusion: This study suggests that routine chest CT and assessment of self-reported symptoms have limited value in the preprocedural COVID-19 screening due to low sensitivity and/or specificity.

Study Objective: This study aimed to assess if a forearm (FA) intravenous regional anesthesia (IVRA) with a lower, less toxic, local anesthetic dosage is non-inferior to an upper arm (UA) IVRA in providing a surgical block in patients undergoing hand and wrist surgery., Design: Observer-blinded, randomized non-inferiority study., Setting: Operating room., Patients: 280 patients undergoing hand surgery were randomly assigned to UA IVRA (n = 140) or FA IVRA (n = 140)., Interventions: Forearm IVRA or upper arm IVRA in patients undergoing hand and wrist surgery., Measurements: The primary outcome was block success rate of both techniques. Block success was defined as no need of additional analgesics. A second, alternative non-inferiority outcome was defined as no need of conversion to general anesthesia. A difference in success rate of <5% was considered non-inferior. Secondary endpoints were tourniquet pain measured with a Numerical Rating Scale (0-10), satisfaction of patients and surgeons, onset time, surgical time and total OR time., Main Results: Non-inferiority of block success rate, defined as no need of additional analgesics or conversion to general anesthesia was inconclusive (5.24%, 95% CI:-4.34%,+14.82%). Non-inferiority of no need of conversion to general anesthesia was confirmed (+0.73%, 95% CI:-0.69%,+2.15%). No differences were observed in onset time (FA: 5 (5, 8) vs UA: 6 (5, 7) min, p = 0.74), surgical time (FA: 8 (5, 12) vs UA: 7 (5, 11) min, p = 0.71), nor total OR stay time (FA: 34 (27, 41) vs UA: 35 (32, 39) min, p = 0.09). Tourniquet pain after 10 min was significantly lower after FA IVRA compared to UA IVRA (FA: 2.00 (0.00, 4.00) vs UA: 3.00 (1.00,5.00) min, p = 0.003)., Conclusion: We failed to demonstrate non-inferiority of forearm IVRA with a lower dosage of LA in providing a surgical block without rescue opioids and LA. Non-inferiority of no need of conversion to general anesthesia was confirmed., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background: Severity scoring systems are inherent to ICU practice for multiple purposes. Acute Physiology and Chronic Health Evaluation (APACHE) scoring systems are designed for ICU mortality prediction. This study aims to validate APACHE IV in COVID-19 patients admitted to the ICU., Methods: All COVID-19 patients admitted to the ICU between March 13, 2020, and October 17, 2020, were retrospectively analyzed. APACHE II and APACHE IV scores as well as SOFA scores were calculated within 24 hours after admission. Discrimination for mortality of all three scoring systems was assessed by receiver operating characteristic curves. Youden index was determined for the scoring system with the best discriminative performance. The Hosmer-Lemeshow goodness-of-fit test was used to assess calibration. All analyses were performed for both the overall population as in a subgroup treated with anti-Xa adjusted dosages of LMWHs., Results: 116 patients were admitted to our ICU during the study period. 13 were excluded for various reasons, leaving 103 patients in the statistical analysis of the overall population. 57 patients were treated with anti-Xa adjusted prophylactic dosages of LMWH and were supplementary analyzed in a subgroup analysis. APACHE IV had the best discriminative power of the three scoring systems, both in the overall population (APACHE IV ROC AUC 0.67 vs. APACHE II ROC AUC 0.63) as in the subgroup (APACHE IV ROC AUC 0.82 vs. APACHE II ROC AUC 0.7). This model exhibits good calibration. Hosmer-Lemeshow p values for APACHE IV were 0.9234 for the overall population and 0.8017 for the subgroup. Calibration p values of the APACHE II score were 0.1394 and 0.6475 for the overall versus subgroup, respectively., Conclusions: APACHE IV provided the best discrimination and calibration of the considered scoring systems in critically ill COVID-19 patients, both in the overall group and in the subgroup with anti-Xa adjusted LMWH doses. Only in the subgroup analysis, discriminative abilities of APACHE IV were very good. This trial is registered with NCT04713852., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2021 Jeroen Vandenbrande et al.)

Background and Objectives: Distal upper extremity surgery is commonly performed under regional anaesthesia, including intravenous regional anaesthesia (IVRA) and ultrasound-guided forearm nerve block. This study aimed to investigate if ultrasound-guided forearm nerve block is superior to forearm IVRA in producing a surgical block in patients undergoing carpal tunnel release., Methods: In this observer-blinded, randomized controlled superiority trial, 100 patients undergoing carpal tunnel release were randomized to receive ultrasound-guided forearm nerve block (n = 50) or forearm IVRA (n = 50). The primary outcome was anaesthetic efficacy evaluated by classifying the blocks as complete vs incomplete. Complete anaesthesia was defined as total sensory block, incomplete anaesthesia as mild pain requiring more analgesics or need of general anaesthesia. Pain intensity on a numeric rating scale (0-10) was recorded. Surgeon satisfaction with hemostasis, surgical time, and OR stay time were recorded. Patient satisfaction with the quality of the block was assessed at POD 1., Results: In total, 43 (86%) of the forearm nerve blocks were evaluated as complete, compared to 33 (66%) of the forearm IVRA (p = 0.019). After the forearm nerve block, pain intensity was lower at discharge (-1.76 points lower, 95% CI (-2.92, -0.59), p = 0.0006) compared to patients treated with forearm IVRA. No differences in pain experienced at the start of the surgery, during surgery, and at POD1, nor in surgical time or total OR stay were observed between groups. Surgeon (p = 0.0016) and patient satisfaction (p = 0.0023) were slightly higher after forearm nerve block., Conclusion: An ultrasound-guided forearm nerve block is superior compared to forearm IVRA in providing a surgical block in patients undergoing carpal tunnel release., Trial Registration: This trial was registered as NCT03411551., Competing Interests: The authors have declared that no competing interests exist.

Background/objectives: This study aimed to study one-month recovery profile and to identify predictors of Quality of Recovery (QOR) after painful day surgery and investigate the influence of pain therapy on QOR., Methods/design: This is a secondary analysis of a single-centre, randomised controlled trial of 200 patients undergoing ambulatory haemorrhoid surgery, arthroscopic shoulder or knee surgery, or inguinal hernia repair between January 2016 and March 2017. Primary endpoints were one-month recovery profile and prevalence of poor/good QOR measured by the Functional Recovery Index (FRI), the Global Surgical Recovery index and the EuroQol questionnaire at postoperative day (POD) 1 to 4, 7, 14 and 28. Multiple logistic regression analysis was performed to determine predictors of QOR at POD 7, 14, and 28. Differences in QOR between pain treatment groups were analysed using the Mann-Whitney U test., Results: Four weeks after haemorrhoid surgery, inguinal hernia repair, arthroscopic knee and arthroscopic shoulder surgery, good QOR was present in 71%, 76%, 57% and 24% respectively. Poor QOR was present in 5%, 0%, 7% and 29%, respectively. At POD 7 and POD 28, predictors for poor/intermediate QOR were type of surgery and a high postoperative pain level at POD 4. Male gender was another predictor at POD 7. Female gender and having a paid job were also predictors at POD 28. Type of surgery and long term fear of surgery were predictors at POD 14. No significant differences in total FRI scores were found between the two different pain treatment groups., Conclusions: The present study shows a procedure-specific variation in recovery profile in the 4-week period after painful day surgery. The best predictors for short-term (POD 7) and long-term (POD 28) poor/intermediate QOR were a high postoperative pain level at POD 4 and type of surgery. Different pain treatment regimens did not result in differences in recovery profile., Trial Registration: European Union Clinical Trials Register 2015-003987-35., Competing Interests: The authors have declared that no competing interests exist.

Background/objectives: Endoscopic coronary artery bypass grafting (Endo-CABG) is a minimally invasive CABG procedure with retrograde arterial perfusion. The main objective of this study is to assess neurocognitive outcome after Endo-CABG., Methods/design: In this prospective observational cohort study, patients were categorised into: Endo-CABG (n = 60), a comparative Percutaneous Coronary Intervention (PCI) group (n = 60) and a healthy volunteer group (n = 60). A clinical neurological examination was performed both pre- and postoperatively, delirium was assessed postoperatively. A battery of 6 neurocognitive tests, Quality of life (QoL) and the level of depressive feelings were measured at baseline and after 3 months. Patient Satisfaction after Endo-CABG was assessed at 3-month follow-up. Primary endpoints were incidence of postoperative cognitive dysfunction (POCD), stroke and delirium after Endo-CABG. Secondary endpoints were QOL, patient satisfaction and the incidence of depressive feelings after Endo-CABG., Results: In total, 1 patient after Endo-CABG (1.72%) and 1 patient after PCI (1.67%) suffered from stroke during the 3-month follow-up. POCD in a patient is defined as a Reliable Change Index ≤-1.645 or Z-score ≤-1.645 in at least two tests, and was found in respectively 5 and 6 patients 3 months after Endo-CABG and PCI. Total incidence of POCD/stroke was not different (PCI: n= 7 [15.9%]; Endo-CABG: n= 6 [13.0%], p = 0.732). ICU delirium after Endo-CABG was found in 5 (8.6%) patients. QoL increased significantly three months after Endo-CABG and was comparable with QoL level after PCI and in the control group. Patient satisfaction after Endo-CABG and PCI was comparable. At follow-up, the level of depressive feelings was decreased in all groups., Conclusions: The incidence of poor neurocognitive outcome, including stroke, POCD and postoperative ICU delirium until three months after Endo-CABG is low and comparable with PCI., Trial Registration: Registered on ClinicalTrials.gov (NCT02979782)., Competing Interests: The authors have declared that no competing interests exist.