Dual-Energy CT muscle fat fraction as a new imaging biomarker of body composition and survival predictor in critically ill patients.

OBJECTIVE: To analyze changes in the muscular fat fraction (FF) during immobilization at the intensive care unit (ICU) using dual-energy CT (DECT) and evaluate the predictive value of the DECT FF as a new imaging biomarker for morbidity and survival. METHODS: Immobilized ICU patients (n = 81, 43.2% female, 60.3 ± 12.7 years) were included, who received two dual-source DECT scans (CT1, CT2) within a minimum interval of 10 days between 11/2019 and 09/2022. The DECT FF was quantified for the posterior paraspinal muscle by two radiologists using material decomposition. The skeletal muscle index (SMI), muscle radiodensity attenuation (MRA), subcutaneous-/ visceral adipose tissue area (SAT, VAT), and waist circumference (WC) were assessed. Reasons for ICU admission, clinical scoring systems, therapeutic regimes, and in-hospital mortality were noted. Linear mixed models, Cox regression, and intraclass correlation coefficients were employed. RESULTS: Between CT1 and CT2 (median 21 days), the DECT FF increased (from 20.9% ± 12.0 to 27.0% ± 12.0, p = 0.001). The SMI decreased (35.7 cm2/m2 ± 8.8 to 31.1 cm2/m2 ± 7.6, p < 0.001) as did the MRA (29 HU ± 10 to 26 HU ± 11, p = 0.009). WC, SAT, and VAT did not change. In-hospital mortality was 61.5%. In multivariable analyses, only the change in DECT FF was associated with in-hospital mortality (hazard ratio (HR) 9.20 [1.78-47.71], p = 0.008), renal replacement therapy (HR 48.67 [9.18-258.09], p < 0.001), and tracheotomy at ICU (HR 37.22 [5.66-245.02], p < 0.001). Inter-observer reproducibility of DECT FF measurements was excellent (CT1: 0.98 [0.97; 0.99], CT2: 0.99 [0.96-0.99]). CONCLUSION: The DECT FF appears to be suitable for detecting increasing myosteatosis. It seems to have predictive value as a new imaging biomarker for ICU patients. CLINICAL RELEVANCE STATEMENT: The dual-energy CT muscular fat fraction appears to be a robust imaging biomarker to detect and monitor myosteatosis. It has potential for prognosticating, risk stratifying, and thereby guiding therapeutic nutritional regimes and physiotherapy in critically ill patients. KEY POINTS: The dual-energy CT muscular fat fraction detects increasing myosteatosis caused by immobilization. Change in dual-energy CT muscular fat fraction was a predictor of  in-hospital morbidity and mortality. Dual-energy CT muscular fat fraction had a predictive value superior to established CT body composition parameters.

Characteristics and Outcome Analysis for Intensive Care Patients Undergoing Decompressive Laparotomy for Abdominal Compartment Syndrome: Impact of Extracorporeal Membrane Oxygenation Support.

(1) Background: Abdominal compartment syndrome (ACS) is a life-threatening situation and is associated with high mortality in the intensive care unit (ICU). Decompressive laparotomy represents the last therapeutic option. This cohort study aims to optimize the selection of ICU patients suffering from ACS who benefit from decompressive laparotomy. (2) Methods: All available data from adult patients treated at the 12 ICUs of a university hospital between 2011 and 2019 were included. Outcome parameters for patients with and without extracorporeal membrane oxygenation (ECMO) were compared. (3) Results: 207 ICU patients with ACS undergoing surgery were identified. Laparotomy resulted in immediate improvement of organ functions in 15% of patients, who then survived more frequently. The overall mortality rate in our cohort was 69%. The group of ECMO patients-including va- and vv-ECMO-showed significantly less organ function improvement and a higher mortality rate of 79% compared to a better postoperative improvement and a lower mortality rate of 62% in non-ECMO patients. (4) Conclusions: There are ICU patients who benefit from decompressive laparotomy-nevertheless, mortality is high. Non-ECMO patients have a better prognosis than ECMO patients. Our findings can support clinical decision-making on emergency surgery and the development of future guidelines.

Effect of Hemadsorption Therapy in Critically Ill Patients with COVID-19 (CYTOCOV-19): A Prospective Randomized Controlled Pilot Trial.

INTRODUCTION: Immunomodulatory therapies have shown beneficial effects in patients with severe COVID-19. Patients with hypercytokinemia might benefit from the removal of inflammatory mediators via hemadsorption. METHODS: Single-center prospective randomized trial at the University Medical Center Hamburg-Eppendorf (Germany). Patients with confirmed COVID-19, refractory shock (norepinephrine ≥0.2 µg/kg/min to maintain a mean arterial pressure ≥65 mm Hg), interleukin-6 (IL-6) ≥500 ng/L, and an indication for renal replacement therapy or extracorporeal membrane oxygenation were included. Patients received either hemadsorption therapy (HT) or standard medical therapy (SMT). For HT, a CytoSorb® adsorber was used for up to 5 days and was replaced every 18-24 h. The primary endpoint was sustained hemodynamic improvement (norepinephrine ≤0.05 µg/kg/min ≥24 h). RESULTS: Of 242 screened patients, 24 were randomized and assigned to either HT (N = 12) or SMT (N = 12). Both groups had similar severity as assessed by SAPS II (median 75 points HT group vs. 79 SMT group, p = 0.590) and SOFA (17 vs. 16, p = 0.551). Median IL-6 levels were 2,269 (IQR 948-3,679) and 3,747 (1,301-5,415) ng/L in the HT and SMT groups at baseline, respectively (p = 0.378). Shock resolution (primary endpoint) was reached in 33% (4/12) versus 17% (2/12) in the HT and SMT groups, respectively (p = 0.640). Twenty-eight-day mortality was 58% (7/12) in the HT compared to 67% (8/12) in the SMT group (p = 1.0). During the treatment period of 5 days, 6/12 (50%) of the SMT patients died, in contrast to 1/12 (8%) in the HT group. CONCLUSION: HT was associated with a non-significant trend toward clinical improvement within the intervention period. In selected patients, HT might be an option for stabilization before transfer and further therapeutic decisions. This finding warrants further investigation in larger trials.

Outcomes of critically ill coronavirus disease 2019 patients requiring kidney replacement therapy: A retrospective cohort study.

Background: Coronavirus disease 2019 (COVID-19) has resulted in high hospitalization rates worldwide. Acute kidney injury (AKI) in patients hospitalized for COVID-19 is frequent and associated with disease severity and poor outcome. The aim of this study was to investigate the incidence of kidney replacement therapy (KRT) in critically ill patients with COVID-19 and its implication on outcome. Methods: We retrospectively analyzed all COVID-19 patients admitted to the Department of Intensive Care Medicine at the University Medical Center Hamburg-Eppendorf (Germany) between 1 March 2020 and 31 July 2021. Demographics, clinical parameters, type of organ support, length of intensive care unit (ICU) stay, mortality and severity scores were assessed. Results: Three-hundred critically ill patients with COVID-19 were included. The median age of the study population was 61 (IQR 51-71) years and 66% (n = 198) were male. 73% (n = 219) of patients required invasive mechanical ventilation. Overall, 68% (n = 204) of patients suffered from acute respiratory distress syndrome and 30% (n = 91) required extracorporeal membrane oxygenation (ECMO). We found that 46% (n = 139) of patients required KRT. Septic shock (OR 11.818, 95% CI: 5.941-23.506, p < 0.001), higher simplified acute physiology scores (SAPS II) (OR 1.048, 95% CI: 1.014-1.084, p = 0.006) and vasopressor therapy (OR 5.475, 95% CI: 1.127-26.589, p = 0.035) were independently associated with the initiation of KRT. 61% (n = 85) of patients with and 18% (n = 29) without KRT died in the ICU (p < 0.001). Cox regression found that KRT was independently associated with mortality (HR 2.075, 95% CI: 1.342-3.208, p = 0.001) after adjusting for confounders. Conclusion: Critically ill patients with COVID-19 are at high risk of acute kidney injury with about half of patients requiring KRT. The initiation of KRT was associated with high mortality.

Importance of computed tomography muscle quality and continuous versus cut-off-based sarcopenia detection in major hepatic surgery.

Background: The role of the computed tomography (CT)-derived skeletal muscle index (SMI) as a parameter of muscle quantity on the outcome after major liver resection remains contradictory and that of the muscle radiodensity attenuation (MRA) as a parameter of muscle quality has not been sufficiently evaluated. This observational study aimed to investigate the influence of metric SMI and MRA values and cut-off-based CT sarcopenia detection on liver-surgery specific complications measured by the new FABIB (liver failure, ascites, biliary leakage, infection, bleeding) score and survival after hemihepatectomy. Methods: A total of 183 patients with major hepatectomy were retrospectively included. The SMI and MRA were determined from the abdominal muscle area of preoperative CT scans. Patients were classified as sarcopenic by the SMI and MRA cut-off values of Prado et al., Martin et al., and van der Werf et al. Postoperative complications were documented according to the Clavien-Dindo classification and FABIB score. The relation of the continuous, non-categoric SMI and MRA values and of the cut-off-based sarcopenia detection to the postoperative complications and survival was analyzed by multivariable linear, logistic, and Cox proportional hazards regression. Results: A higher MRA was associated with less severe postoperative complications in the Clavien-Dindo [-0.59 (95% CI: -0.95 to -0.23), P=0.002] and the FABIB score [-0.65 (95% CI: -1.19 to -0.12), P=0.017]. An increase of the SMI did not result in less severe complications in the Clavien-Dindo [0.14 (95% CI: -0.27 to 0.55), P=0.503] or FABIB score [0.17 (95% CI: -0.42 to 0.76), P=0.572]. For patients classified as sarcopenic by the cut-off-based systems no relevant relation to postoperative complications was found. Overall survival was better for a higher MRA [hazard ratio (HR): 0.75 (95% CI: 0.58-0.97), P=0.029], as long-term survival was for a higher SMI [HR: 0.68 (95% CI: 0.47-0.96), P=0.031]. Only below van der Werf's MRA cut-off the probability of overall and long-term survival was reduced [HR: 2.32 (95% CI: 1.18-4.54), P=0.015; 2.68 (95% CI: 1.25-5.74), P=0.011]. Conclusions: The MRA has a stronger influence on complications in the Clavien-Dindo classification and the liver-surgery specific FABIB score than the SMI. Continuous, non-categoric MRA and SMI values are superior to cut-off-based systems in predicting the outcome after major hepatic surgery.

Blunt traumatic right coronary artery dissection presenting with second-degree atrioventricular block and late-onset severe cardiogenic shock.

BACKGROUND: Blunt chest injury may induce several cardiovascular traumata, requiring immediate care. Right coronary artery dissection (RCA) is an extremely rare sequela in this setting and is associated with high mortality, if it remains undiagnosed. Case presentation We present the case of an RCA dissection after blunt chest trauma in a 16-year-old patient, who initially presented with a second-degree atrioventricular block as solitary manifestation on admission. Typical electrocardiographic findings, such as ST segmental changes or pathological Q waves were absent. Serial echocardiograms excluded segmental motion abnormalities, pericardial effusion or right ventricular strain. Nevertheless, a complementary computed tomography coronary angiography revealed this potentially lethal condition several hours later. The patient underwent an emergency surgical myocardial revascularization under the circulatory support of veno-arterial extracorporeal membrane oxygenation and suffered a prolonged right ventricular insufficiency with severe late-onset cardiogenic shock, due to an extensive myocardial infarction of the inferoseptal ventricular wall. CONCLUSION: Right coronary artery dissection after high-speed blunt chest injury constitutes a diagnostic challenge, especially in the absence of typical electrocardiographic and echocardiographic findings in young patients. This condition may dramatically deteriorate in time, leading to severe cardiogenic shock and life-threatening arrhythmias.

Surgical correction of a percutaneous dilatational tracheostomy: A case report.

INTRODUCTION AND IMPORTANCE: Percutaneous dilatational tracheostomy (PDT) has become a routine procedure in intensive care, because of its multiple advantages over surgical tracheostomy (ST). CASE PRESENTATION: We present the case of a 72-year-old patient with SARS-CoV-2 pneumonia, who received a PDT in the 6th tracheal ring with a lateral puncture of the trachea. This atypical placement of tracheostomy was due to a massive left-pronounced goiter, causing a tracheal shift to the right. To avoid dislocation of the tracheal cannula and prevent recurrent bleeding, surgical revision was decided. After left hemithyroidectomy, oral intubation was temporarily necessary, in order to remove the old tracheostomy. Then suturing of the left lateral tracheal defect and standard ST in the 2nd tracheal cartilage was performed. The patient was successfully weaned and decannulated and his swallowing function remained intact. CLINICAL DISCUSSION: In our case left hemithyroidectomy was necessary, in order to enable an optimal surgical tracheostomy in the 2nd tracheal cartilage. Because mechanical ventilation was carried out proximal to the large tracheal defect after PCT, a secondary closing approach was not an option. The endotracheal cuff was placed above the defect, in order to prevent acute or chronic intraluminal pressure trauma. Postoperative x-ray and bronchoscopy insured the sufficient sealing of the tracheal suturing. CONCLUSION: We describe an unusual placement of percutaneous dilatational tracheostomy through a thyroid goiter and our approach to perform a correction surgical tracheostomy.

Chronic Critical Illness in Patients with COVID-19: Characteristics and Outcome of Prolonged Intensive Care Therapy.

The spread of SARS-CoV-2 caused a worldwide healthcare threat. High critical care admission rates related to Coronavirus Disease 2019 (COVID-19) respiratory failure were observed. Medical advances helped increase the number of patients surviving the acute critical illness. However, some patients require prolonged critical care. Data on the outcome of patients with a chronic critical illness (CCI) are scarce. Single-center retrospective study including all adult critically ill patients with confirmed COVID-19 treated at the Department of Intensive Care Medicine at the University Medical Center Hamburg-Eppendorf, Germany, between 1 March 2020 and 8 August 2021. We identified 304 critically ill patients with COVID-19 during the study period. Of those, 55% (n = 167) had an ICU stay ≥21 days and were defined as chronic critical illness, and 45% (n = 137) had an ICU stay <21 days. Age, sex and BMI were distributed equally between both groups. Patients with CCI had a higher median SAPS II (CCI: 39.5 vs. no-CCI: 38 points, p = 0.140) and SOFA score (10 vs. 6, p < 0.001) on admission. Seventy-three per cent (n = 223) of patients required invasive mechanical ventilation (MV) (86% vs. 58%; p < 0.001). The median duration of MV was 30 (17-49) days and 7 (4-12) days in patients with and without CCI, respectively (p < 0.001). The regression analysis identified ARDS (OR 3.238, 95% CI 1.827-5.740, p < 0.001) and referral from another ICU (OR 2.097, 95% CI 1.203-3.654, p = 0.009) as factors significantly associated with new-onset of CCI. Overall, we observed an ICU mortality of 38% (n = 115) in the study cohort. In patients with CCI we observed an ICU mortality of 28% (n = 46) compared to 50% (n = 69) in patients without CCI (p < 0.001). The 90-day mortality was 28% (n = 46) compared to 50% (n = 70), respectively (p < 0.001). More than half of critically ill patients with COVID-19 suffer from CCI. Short and long-term survival rates in patients with CCI were high compared to patients without CCI, and prolonged therapy should not be withheld when resources permit prolonged therapy.

Necrotizing Soft Tissue Infections in Intensive Care.

BACKGROUND: Necrotizing soft tissue infections (NSTIs) are typically characterized by extensive soft tissue destruction with systemic signs of toxicity, ranging from sepsis to septic shock. Our aim was to analyze the clinical characteristics, microbiological results, laboratory data, therapies, and outcome of patients with NSTIs admitted to an intensive care unit (ICU). METHODS: A monocentric observational study of patients admitted to the ICU of a university hospital between January 2009 and December 2017. The demographic characteristics, comorbidities, clinical features, microbiology and laboratory results, organ dysfunctions, therapies, and outcome were retrospectively analyzed. RESULTS: There were 59 patients and 70% males. The mean age (± SD) was 55 ± 18; type II (monomicrobial) NSTI was present in 36 patients (61%); the most common isolated pathogen was Streptococcus pyogenes in 28 patients (48%). Septic shock was diagnosed in 41 patients (70%). The most common organ dysfunctions were circulatory and renal in 42 (71%) and 38 patients (64%). The mean value (± SD) of serum lactate at admission to the ICU was 4.22 ± 5.42 mmol/l, the median SOFA score and SAPS II were 7 (IQR 4 - 10) and 46 (IQR 30.5 - 53). ICU mortality rate was 25%. Both SOFA score and serum lactate demonstrated a good prognostic value regarding ICU outcome (OR 1.29, 95%CI 1.07-1.57, P < 0.007 and OR 1.53, 95%CI 1.19-1.98, P < 0.001). A cut-off value for serum lactate of 6.55 mmol/L positively predicted mortality with 67% sensitivity and 97% specificity. CONCLUSION: NSTIs carry a high risk of septic shock and multiple organ dysfunction syndrome and thus are still associated with high mortality. In our study, the value of serum lactate at admission to the ICU correlated well with mortality. This easy-to-measure parameter could play a role in the decision-making process regarding prognosis and continuation of care.

Single-dose of adrecizumab versus placebo in acute cardiogenic shock (ACCOST-HH): an investigator-initiated, randomised, double-blinded, placebo-controlled, multicentre trial.

BACKGROUND: Cardiogenic shock has a high mortality on optimal therapy. Adrenomedullin is released during cardiogenic shock and is involved in its pathophysiological processes. This study assessed treatment with the humanised, monoclonal, non-neutralising, adrenomedullin antibody adrecizumab, increasing circulating concentrations of adrenomedullin in cardiogenic shock. METHODS: In this investigator-initiated, placebo-controlled, double-blind, multicentre, randomised trial (ACCOST-HH), patients were recruited from four university hospitals in Germany. Patients were eligible if they were 18 years old or older and hospitalised for cardiogenic shock within the last 48 h. Exclusion criteria were resuscitation for longer than 60 min and cardiogenic shock due to sustained ventricular tachycardia or bradycardia. Adult patients in cardiogenic shock were randomly assigned (1:1) to intravenous adrecizumab (8 mg/kg bodyweight) or placebo using an internet-based software. A block randomisation procedure was applied with stratification by age (older vs younger than 65 years), sex (male vs female), and type of underlying cardiogenic shock (acute myocardial infarction vs other entities). Investigators, patients, and medical staff involved in patient care were masked to group assignment. The primary endpoint was number of days up to day 30 without the need for cardiovascular organ support, defined as vasopressor therapy, inotropes, or mechanical circulatory support (or both) assessed in the intention-to-treat population. Safety outcomes included therapy-emergent serious adverse events, severe adverse events, adverse events, suspected unexpected serious adverse reactions, study drug-related mortality, and total mortality. The trial was registered at ClinicalTrials.gov, NCT03989531, and EudraCT, 2018-002824-17, and is now complete. FINDINGS: Between April 5, 2019, and Jan 13, 2021, 150 patients were enrolled: 77 (51%) were randomly assigned to adrecizumab and 73 (49%) to placebo. All patients received the allocated treatment. The number of days without the need for cardiovascular organ support was not different between patients receiving adrecizumab or placebo (12·37 days [95% CI 9·80-14·94] vs 14·05 [11·41-16·69]; adjusted mean difference -1·69 days [-5·37 to 2·00]; p=0·37). Serious adverse events occurred in 59 patients receiving adrecizumab and in 57 receiving placebo (odds ratio 0·92 [95% CI 0·43-1·98]; p=0·83). Mortality was not different between groups at 30 days (hazard ratio 0·99 [95% CI 0·60-1·65]; p=0·98) or 90 days (1·10 [0·68-1·77]; p=0·71). INTERPRETATION: Adrecizumab was well tolerated in patients with cardiogenic shock but did not reduce the need for cardiovascular organ support or improve survival at days 30 and 90. FUNDING: Adrenomed AG and University Hospital of Hamburg.

Clinical Characteristics, Complications and Outcomes of Patients with Severe Acute Respiratory Distress Syndrome Related to COVID-19 or Influenza Requiring Extracorporeal Membrane Oxygenation-A Retrospective Cohort Study.

Extracorporeal membrane oxygenation (ECMO) represents a viable therapy option for patients with refractory acute respiratory distress syndrome (ARDS). Currently, veno-venous (vv) ECMO is frequently used in patients suffering from coronavirus disease 2019 (COVID-19). VV-ECMO was also frequently utilised during the influenza pandemic and experience with this complex and invasive treatment has increased worldwide since. However, data on comparison of clinical characteristics and outcome of patients with COVID-19 and influenza-related severe ARDS treated with vv-ECMO are scarce. This is a retrospective analysis of all consecutive patients treated with vv/(veno-arterial)va-ECMO between January 2009 and January 2021 at the University Medical Centre Hamburg-Eppendorf in Germany. All patients with confirmed COVID-19 or influenza were included. Patient characteristics, parameters related to ICU and vv/va-ECMO as well as clinical outcomes were compared. Mortality was assessed up to 90 days after vv/va-ECMO initiation. Overall, 113 patients were included, 52 (46%) with COVID-19 and 61 (54%) with influenza-related ARDS. Median age of patients with COVID-19 and influenza was 58 (IQR 53-64) and 52 (39-58) years (p < 0.001), 35% and 31% (p = 0.695) were female, respectively. Charlson Comorbidity Index was 3 (1-5) and 2 (0-5) points in the two groups (p = 0.309). Median SAPS II score pre-ECMO was 27 (24-36) vs. 32 (28-41) points (p = 0.009), and SOFA score was 13 (11-14) vs. 12 (8-15) points (p = 0.853), respectively. Median P/F ratio pre-ECMO was 64 (46-78) and 73 (56-104) (p = 0.089); pH was 7.20 (7.16-7.29) and 7.26 (7.18-7.33) (p = 0.166). Median days on vv/va-ECMO were 17 (7-27) and 11 (7-20) (p = 0.295), respectively. Seventy-one percent and sixty-nine percent had renal replacement therapy (p = 0.790). Ninety-four percent of patients with COVID-19 and seventy-seven percent with influenza experienced vv/va-ECMO-associated bleeding events (p = 0.004). Thirty-four percent and fifty-five percent were successfully weaned from ECMO (p = 0.025). Ninety-day mortality was 65% and 57% in patients with COVID-19 and influenza, respectively (p = 0.156). Median length of ICU stay was 24 (13-44) and 28 (16-14) days (p = 0.470), respectively. Despite similar disease severity, the use of vv/va-ECMO in ARDS related to COVID-19 and influenza resulted in similar outcomes at 90 days. A significant higher rate of bleeding complications and thrombosis was observed in patients with COVID-19.

Characteristics and Risk Factors for Intensive Care Unit Cardiac Arrest in Critically Ill Patients with COVID-19-A Retrospective Study.

The severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) causing the coronavirus disease 2019 (COVID-19) led to an ongoing pandemic with a surge of critically ill patients. Very little is known about the occurrence and characteristic of cardiac arrest in critically ill patients with COVID-19 treated at the intensive care unit (ICU). The aim was to investigate the incidence and outcome of intensive care unit cardiac arrest (ICU-CA) in critically ill patients with COVID-19. This was a retrospective analysis of prospectively recorded data of all consecutive adult patients with COVID-19 admitted (27 February 2020-14 January 2021) at the University Medical Centre Hamburg-Eppendorf (Germany). Of 183 critically ill patients with COVID-19, 18% (n = 33) had ICU-CA. The median age of the study population was 63 (55-73) years and 66% (n = 120) were male. Demographic characteristics and comorbidities did not differ significantly between patients with and without ICU-CA. Simplified Acute Physiological Score II (SAPS II) (ICU-CA: median 44 points vs. no ICU-CA: 39 points) and Sequential Organ Failure Assessment (SOFA) score (median 12 points vs. 7 points) on admission were significantly higher in patients with ICU-CA. Acute respiratory distress syndrome (ARDS) was present in 91% (n = 30) with and in 63% (n = 94) without ICU-CA (p = 0.002). Mechanical ventilation was more common in patients with ICU-CA (97% vs. 67%). The median stay in ICU before CA was 6 (1-17) days. A total of 33% (n = 11) of ICU-CAs occurred during the first 24 h of ICU stay. The initial rhythm was non-shockable (pulseless electrical activity (PEA)/asystole) in 91% (n = 30); 94% (n = 31) had sustained return of spontaneous circulation (ROSC). The median time to ROSC was 3 (1-5) minutes. Patients with ICU-CA had significantly higher ICU mortality (61% vs. 37%). Multivariable logistic regression showed that the presence of ARDS (odds ratio (OR) 4.268, 95% confidence interval (CI) 1.211-15.036; p = 0.024) and high SAPS II (OR 1.031, 95% CI 0.997-1.065; p = 0.077) were independently associated with the occurrence of ICU-CA. A total of 18% of critically ill patients with COVID-19 suffered from a cardiac arrest within the intensive care unit. The occurrence of ICU-CA was associated with presence of ARDS and severity of illness.

Are muscle parameters obtained by computed tomography associated with outcome after esophagectomy for cancer?

BACKGROUND & AIMS: Esophageal cancer patients often suffer from cancer-related malnutrition and, as a result, sarcopenia. Whether sarcopenia worsens the outcome after esophagectomy is unclear. Inconsistent study results are partly caused by varying cut-off values used for defining sarcopenia. To overcome this challenge, a new statistical approach is proposed in this study: analyzing the linear association of computer tomography derived muscle parameters with important clinical short- and long-term outcomes post esophagectomy, regardless of cut-offs. METHODS: Skeletal muscle index (SMI), quantifying muscle mass, was assessed with computed tomography (CT) in 98 patients undergoing esophagectomy. Muscle radiation attenuation (MRA) was measured to evaluate muscle quality. To evaluate the influence of the SMI and MRA on post-surgery complications, logistic regression models were used. To analyze the relationship of lengths of stay to muscle parameters, the competing risk approach introduced by Fine and Gray was applied. For survival analysis, log-rank test and Cox proportional hazards regression modeling were used. RESULTS: Neither a relevant association of SMI nor MRA with pneumonia and esophagoenteric leak were observed. Furthermore, no relevant association to lengths of stay in intensive care or hospital were detected. If the SMI increased, the odds for pleural effusion and pleural empyema decreased, but the odds of a pulmonary embolism increased. Univariate, unadjusted long-term survival analysis revealed that lower MRA and lower SMI were associated with shorter survival (P = 0.03). However, if the analysis was adjusted for confounders, e.g., Charlson Comorbidity Index, no relevant association regarding long-term survival was detected. CONCLUSION: Consequently, poor muscle status, determined by CT imaging, does not justify denying a patient an oncologic resection. The Charlson Comorbidity Index, however, was superior for preoperative risk stratification.

Multi-dimensional and longitudinal systems profiling reveals predictive pattern of severe COVID-19.

COVID-19 is a respiratory tract infection that can affect multiple organ systems. Predicting the severity and clinical outcome of individual patients is a major unmet clinical need that remains challenging due to intra- and inter-patient variability. Here, we longitudinally profiled and integrated more than 150 clinical, laboratory, and immunological parameters of 173 patients with mild to fatal COVID-19. Using systems biology, we detected progressive dysregulation of multiple parameters indicative of organ damage that correlated with disease severity, particularly affecting kidneys, hepatobiliary system, and immune landscape. By performing unsupervised clustering and trajectory analysis, we identified T and B cell depletion as early indicators of a complicated disease course. In addition, markers of hepatobiliary damage emerged as robust predictor of lethal outcome in critically ill patients. This allowed us to propose a novel clinical COVID-19 SeveriTy (COST) score that distinguishes complicated disease trajectories and predicts lethal outcome in critically ill patients.

Severe liver dysfunction complicating course of COVID-19 in the critically ill: multifactorial cause or direct viral effect?

BACKGROUND: SARS-CoV-2 caused a pandemic and global threat for human health. Presence of liver injury was commonly reported in patients with coronavirus disease 2019 (COVID-19). However, reports on severe liver dysfunction (SLD) in critically ill with COVID-19 are lacking. We evaluated the occurrence, clinical characteristics and outcome of SLD in critically ill patients with COVID-19. METHODS: Clinical course and laboratory was analyzed from all patients with confirmed COVID-19 admitted to ICU of the university hospital. SLD was defined as: bilirubin ≥ 2 mg/dl or elevation of aminotransferase levels (> 20-fold ULN). RESULTS: 72 critically ill patients were identified, 22 (31%) patients developed SLD. Presenting characteristics including age, gender, comorbidities as well as clinical presentation regarding COVID-19 overlapped substantially in both groups. Patients with SLD had more severe respiratory failure (paO2/FiO2: 82 (58-114) vs. 117 (83-155); p < 0.05). Thus, required more frequently mechanical ventilation (95% vs. 64%; p < 0.01), rescue therapies (ECMO) (27% vs. 12%; p = 0.106), vasopressor (95% vs. 72%; p < 0.05) and renal replacement therapy (86% vs. 30%; p < 0.001). Severity of illness was significantly higher (SAPS II: 48 (39-52) vs. 40 (32-45); p < 0.01). Patients with SLD and without presented viremic during ICU stay in 68% and 34%, respectively (p = 0.002). Occurrence of SLD was independently associated with presence of viremia [OR 6.359; 95% CI 1.336-30.253; p < 0.05] and severity of illness (SAPS II) [OR 1.078; 95% CI 1.004-1.157; p < 0.05]. Mortality was high in patients with SLD compared to other patients (68% vs. 16%, p < 0.001). After adjustment for confounders, SLD was independently associated with mortality [HR3.347; 95% CI 1.401-7.999; p < 0.01]. CONCLUSION: One-third of critically ill patients with COVID-19 suffer from SLD, which is associated with high mortality. Occurrence of viremia and severity of illness seem to contribute to occurrence of SLD and underline the multifactorial cause.

MR-proAdrenomedullin as a predictor of renal replacement therapy in a cohort of critically ill patients with COVID-19.

BACKGROUND: About 20% of ICU patients with COVID-19 require renal replacement therapy (RRT). Mid-regional pro-adrenomedullin (MR-proADM) might be used for risk assessment. This study investigates MR-proADM for RRT prediction in ICU patients with COVID-19. METHODS: We analysed data of consecutive patients with COVID-19, requiring ICU admission at a university hospital in Germany between March and September 2020. Clinical characteristics, details on AKI, and RRT were assessed. MR-proADM was measured on admission. RESULTS: 64 patients were included (49 (77%) males). Median age was 62.5y (54-73). 47 (73%) patients were ventilated and 50 (78%) needed vasopressors. 25 (39%) patients had severe ARDS, and 10 patients needed veno-venous extracorporeal membrane oxygenation. 29 (45%) patients required RRT; median time from admission to RRT start was 2 (1-9) days. MR-proADM on admission was higher in the RRT group (2.491 vs. 1.23 nmol/l; p = 0.002) and showed the highest correlation with renalSOFA. ROC curve analysis showed that MR-proADM predicts RRT with an AUC of 0.69 (95% CI: 0.543-0.828; p = 0.019). In multivariable logistic regression MR-proADM was an independent predictor (OR: 3.813, 95% CI 1.110-13.102, p<0.05) for RRT requirement. CONCLUSION: AKI requiring RRT is frequent in ICU patients with COVID-19. MR-proADM on admission was able to predict RRT requirement, which may be of interest for risk stratification and management.

Mechanical ventilation and mortality among 223 critically ill patients with coronavirus disease 2019: A multicentric study in Germany.

BACKGROUND: There are large uncertainties with regard to the outcome of patients with coronavirus disease 2019 (COVID-19) and mechanical ventilation (MV). High mortality (50-97%) was proposed by some groups, leading to considerable uncertainties with regard to outcomes of critically ill patients with COVID-19. OBJECTIVES: The aim was to investigate the characteristics and outcomes of critically ill patients with COVID-19 requiring intensive care unit (ICU) admission and MV. METHODS: A multicentre retrospective observational cohort study at 15 hospitals in Hamburg, Germany, was performed. Critically ill adult patients with COVID-19 who completed their ICU stay between February and June 2020 were included. Patient demographics, severity of illness, and ICU course were retrospectively evaluated. RESULTS: A total of 223 critically ill patients with COVID-19 were included. The majority, 73% (n = 163), were men; the median age was 69 (interquartile range = 58-77.5) years, with 68% (n = 151) patients having at least one chronic medical condition. Their Sequential Organ Failure Assessment score was a median of 5 (3-9) points on admission. Overall, 167 (75%) patients needed MV. Noninvasive ventilation and high-flow nasal cannula were used in 31 (14%) and 26 (12%) patients, respectively. Subsequent MV, due to noninvasive ventilation/high-flow nasal cannula therapy failure, was necessary in 46 (81%) patients. Renal replacement therapy was initiated in 33% (n = 72) of patients, and owing to severe respiratory failure, extracorporeal membrane oxygenation was necessary in 9% (n = 20) of patients. Experimental antiviral therapy was used in 9% (n = 21) of patients. Complications during the ICU stay were as follows: septic shock (40%, n = 90), heart failure (8%, n = 17), and pulmonary embolism (6%, n = 14). The length of ICU stay was a median of 13 days (5-24), and the duration of MV was 15 days (8-25). The ICU mortality was 35% (n = 78) and 44% (n = 74) among mechanically ventilated patients. CONCLUSION: In this multicentre observational study of 223 critically ill patients with COVID-19, the survival to ICU discharge was 65%, and it was 56% among patients requiring MV. Patients showed high rate of septic complications during their ICU stay.

Autopsy Findings and Venous Thromboembolism in Patients With COVID-19: A Prospective Cohort Study.

BACKGROUND: The new coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has caused more than 210 000 deaths worldwide. However, little is known about the causes of death and the virus's pathologic features. OBJECTIVE: To validate and compare clinical findings with data from medical autopsy, virtual autopsy, and virologic tests. DESIGN: Prospective cohort study. SETTING: Autopsies performed at a single academic medical center, as mandated by the German federal state of Hamburg for patients dying with a polymerase chain reaction-confirmed diagnosis of COVID-19. PATIENTS: The first 12 consecutive COVID-19-positive deaths. MEASUREMENTS: Complete autopsy, including postmortem computed tomography and histopathologic and virologic analysis, was performed. Clinical data and medical course were evaluated. RESULTS: Median patient age was 73 years (range, 52 to 87 years), 75% of patients were male, and death occurred in the hospital (n = 10) or outpatient sector (n = 2). Coronary heart disease and asthma or chronic obstructive pulmonary disease were the most common comorbid conditions (50% and 25%, respectively). Autopsy revealed deep venous thrombosis in 7 of 12 patients (58%) in whom venous thromboembolism was not suspected before death; pulmonary embolism was the direct cause of death in 4 patients. Postmortem computed tomography revealed reticular infiltration of the lungs with severe bilateral, dense consolidation, whereas histomorphologically diffuse alveolar damage was seen in 8 patients. In all patients, SARS-CoV-2 RNA was detected in the lung at high concentrations; viremia in 6 of 10 and 5 of 12 patients demonstrated high viral RNA titers in the liver, kidney, or heart. LIMITATION: Limited sample size. CONCLUSION: The high incidence of thromboembolic events suggests an important role of COVID-19-induced coagulopathy. Further studies are needed to investigate the molecular mechanism and overall clinical incidence of COVID-19-related death, as well as possible therapeutic interventions to reduce it. PRIMARY FUNDING SOURCE: University Medical Center Hamburg-Eppendorf.

Upregulation of SPDEF is associated with poor prognosis in prostate cancer.

SAM pointed domain-containing Ets transcription factor (SPDEF), a member of the ETS transcription factor family, has been associated with prostate cancer development; however, its role in tumour development and progression is controversial. In the present study, SPDEF expression was analysed on a tissue microarray with >12,000 prostate cancer samples. SPDEF expression levels were higher in most prostate cancer samples than in normal prostate epithelium, suggesting SPDEF was upregulated in cancer. Nuclear SPDEF expression was identified in 80% of prostate cancer samples, and considered weak in 26.4%, moderate in 40.1% and strong in 13.5% of cases. SPDEF positivity was significantly associated with tumour stage, Gleason grade, lymph node metastasis and PSA recurrence (all P<0.0001). SPDEF overexpression was more common in ERG positive (94%) than in ERG negative cancer (69%; P<0.0001). Elevated SPDEF expression predicted poor prognosis independent from established prognostic parameters, including Gleason grade, pT, pN, serum PSA level and nodal status (P<0.01). In summary, SPDEF overexpression was associated with aggressive behaviour, particularly in ERG negative prostate cancer, and may have potential for clinical application.