In-hospital survival of critically ill COVID-19 patients treated with glucocorticoids: a multicenter real-world data study.

The COVID-19 pandemic has posed a major challenge to healthcare systems globally. Millions of people have been infected, and millions of deaths have been reported worldwide. Glucocorticoids have attracted worldwide attention for their potential efficacy in the treatment of COVID-19. Various glucocorticoids with different dosages and treatment durations have been studied in patients with different severities, with a suitable dosage and treatment duration not yet defined. This study aimed to investigate whether in-hospital survival differs between critically ill patients treated with low-dose glucocorticoids, high-dose glucocorticoids or no glucocorticoids. All critically ill patients admitted to the intensive care unit of the Charité Hospital-Universitätsmedizin Berlin between February 2020 and December 2021 with COVID-19 pneumonia receiving supplemental oxygen were eligible to participate in this multicenter real-world data study. Patients were retrospectively assigned to one of three groups: the high corticosteroid dose (HighC) group (receiving 6 mg parenteral dexamethasone or an equivalent corticosteroid dosage for ten days), the low corticosteroid dose (LowC) group (receiving less than 6 mg parenteral dexamethasone or an equivalent corticosteroid dosage for ten days), or the no corticosteroid (NoC) group. Overall survival and risk effects were compared among groups within the total observation period, as well as at 35 days after the onset of COVID-19 symptoms. Adjusted multivariable Cox proportional hazard regression analysis was performed to compare the risk of death between the treatment groups. Out of 1561 critically ill COVID-19 patients, 1014 were included in the baseline analysis. In the survival study, 1009 patients were assigned to the NoC (n = 346), HighC (n = 552), or LowC group (n = 111). The baseline characteristics were balanced between groups, except for age, BMI, APACHE II score, SOFA and SAPS II. While the 35-day survival did not show any differences, a landmark analysis of the patients surviving beyond 35 days revealed differences between groups. The restricted mean survival time was 112 days in the LowC group [95% CI: 97 - 128], 133 days in the HighC group [95% CI: 124 - 141] and 144 days in the NoC group [95% CI: 121 - 167]. The multivariable-adjusted Cox proportional hazard analysis indicated that, regardless of age, sex, health status or invasive oxygenation, a low-dose treatment increased the hazard of death of critically ill COVID-19 patients by a factor of 2.09 ([95% CI: 0.99, 4.4], p = 0.05) and a high-dose corticosteroid treatment increased the risk by a factor of 1.07 ([95% CI: 0.53, 2.15], p = 0.85) compared to no treatment with glucocorticoids. The analysis reveals that corticosteroid treatment does not influence the survival of critically ill COVID-19 patients in the intensive care unit within 35 days. Our evaluations further suggest that regardless of ventilation status, the decision-making process for administering corticosteroid therapy should account for the individual severity of the illness.

Cross-regulation of antibody responses against the SARS-CoV-2 Spike protein and commensal microbiota via molecular mimicry.

The commensal microflora provides a repertoire of antigens that illicit mucosal antibodies. In some cases, these antibodies can cross-react with host proteins, inducing autoimmunity, or with other microbial antigens. We demonstrate that the oral microbiota can induce salivary anti-SARS-CoV-2 Spike IgG antibodies via molecular mimicry. Anti-Spike IgG antibodies in the saliva correlated with enhanced abundance of Streptococcus salivarius 1 month after anti-SARS-CoV-2 vaccination. Several human commensal bacteria, including S. salivarius, were recognized by SARS-CoV-2-neutralizing monoclonal antibodies and induced cross-reactive anti-Spike antibodies in mice, facilitating SARS-CoV-2 clearance. A specific S. salivarius protein, RSSL-01370, contains regions with homology to the Spike receptor-binding domain, and immunization of mice with RSSL-01370 elicited anti-Spike IgG antibodies in the serum. Additionally, oral S. salivarius supplementation enhanced salivary anti-Spike antibodies in vaccinated individuals. Altogether, these data show that distinct species of the human microbiota can express molecular mimics of SARS-CoV-2 Spike protein, potentially enhancing protective immunity.

Interdisciplinary perspectives on computed tomography in sepsis: survey among medical doctors at a large university medical center.

OBJECTIVES: This study aims to describe physicians' perspectives on the use of computed tomography (CT) in patients with sepsis. METHODS: In January 2022, physicians of a large European university medical center were surveyed using a web-based questionnaire asking about their views on the role of CT in sepsis. A total of 371 questionnaires met the inclusion criteria and were analyzed using work experience, workplace, and medical specialty of physicians as variables. Chi-square tests were performed. RESULTS: Physicians considered the ability to detect an unknown focus as the greatest benefit of CT scans in sepsis (70.9%, n = 263/371). Two clinical criteria - "signs of decreased vigilance" (89.2%, n = 331/371) and "increased catecholamine demand" (84.7%, n = 314/371) - were considered highly relevant for a CT request. Elevated procalcitonin (82.7%, n = 307/371) and lactate levels (83.6%, n = 310/371) were consistently found to be critical laboratory values to request a CT. As long as there is evidence of infection in one organ region, most physicians (42.6%, n = 158/371) would order a CT scan based on clinical assessment. Combined examination of the chest, abdomen, and pelvis was favored (34.8%, n = 129/371) in cases without clinical clues of an infection source. A time window of ≥ 1-6 h was preferred for both CT examinations (53.9%, n = 200/371) and CT-guided interventions (59.3%, n = 220/371) in patients with sepsis. CONCLUSION: Despite much consensus, there are significant differences in attitudes towards the use of CT in septic patients among physicians from different workplaces and medical specialties. Knowledge of these perspectives may improve patient management and interprofessional communication. KEY POINTS: Despite interdisciplinary consensus on the use of CT in sepsis, statistically significant differences in the responses are apparent among physicians from different workplaces and medical specialties. The detection of a previously unknown source of infection and the ability to plan interventions and/or surgery based on CT findings are considered key advantages of CT in septic patients. Timing of CT reflects the requirements of specific disciplines.

Cytolytic CD8+ T cell response to SARS-CoV-2 and non-SARS-CoV-2-related viruses is associated with severe manifestation of COVID-19.

Little is known about the CD8+ T cell functionality in the coronavirus disease 2019 (COVID-19). Therefore, we examined twenty-five hospitalized COVID-19 patients with moderate (MD) or severe disease (SD) as well as seventeen SARS-CoV-2-unexposed persons regarding the cytolytic and cytokine-producing reactivity of their CD8+ T cells. Reactive CD8+ T cells were detectable in 90% of the unexposed persons, confirming high cross-reactive immune memory in the general population. Compared to unexposed persons and MD patients, SD patients had higher numbers of SARS-CoV-2 reactive CD8+ T cells with cytolytic function that can simultaneously produce inflammatory cytokines. In addition, SD patients showed higher CD8+ T cell reactivity against non-SARS-CoV-2-related viruses, which was mainly mediated by cytolytic response. Sequence alignments showed that cross-reactivities with the Spike protein could contribute to the expansion of such cells. Since insufficiently regulated cytolytic CD8+ T cells can damage peripheral and vascular tissue structures, high levels of both SARS-CoV-2-reactive and heterologously activated cytolytic CD8+ T cells could favor severe disease progression.

Identification of Perioperative Procedural and Hemodynamic Risk Factors for Developing Colonic Ischemia after Ruptured Infrarenal Abdominal Aortic Aneurysm Surgery: A Single-Centre Retrospective Cohort Study.

(1) Background: This retrospective study evaluated perioperative and intensive care unit (ICU) variables to predict colonic ischemia (CI) after infrarenal ruptured abdominal aortic aneurysm (RAAA) surgery. (2) Materials and Methods: We retrospectively analyzed the data of the patients treated for infrarenal RAAA from January 2011 to December 2020 in our hospital. (3) Results: A total of 135 (82% male) patients were admitted to ICU after treatment of infrarenal RAAA. The median age of all patients was 75 years (IQR 68-81 years). Of those, 24 (18%) patients developed CI, including 22 (92%) cases within the first three postoperative days. CI was found more often after open repair compared to endovascular treatment (22% vs. 5%, p = 0.021). Laboratory findings in the first seven PODs revealed statistically significant differences between CI and non-CI patients for serum lactate, minimum pH, serum bicarbonate, and platelet count. Norepinephrine (NE) was used in 92 (68%) patients during ICU stay. The highest daily dose of norepinephrine was administered to CI patients at POD1. Multivariable analysis revealed that NE > 64 µg/kg (RD 0.40, 95% CI: 0.25-0.55, p < 0.001), operating time ≥ 200 min (RD 0.18, 95% CI: 0.05-0.31, p = 0.042), and pH < 7.3 (RD 0.21, 95% CI: 0.07-0.35, p = 0.019), significantly predicted the development of CI. A total of 23 (17%) patients died during the hospital stay, including 8 (33%) patients from the CI group and 15 (7%) from the non-CI group (p = 0.032). (4) Conclusions: CI after RAAA is a sever complication occurring most frequently within the first 3 postoperative days. Our study identified many surrogate markers associated with colonic ischemia after aortic RAAA, including norepinephrine dose > 64 µg/kg, operating time ≥ 200 min, and PH < 7.3. Future studies are needed to support these results.

Serum TGF-ß as a predictive biomarker for severe disease and fatality of COVID-19.

For targeted intervention in coronavirus disease 2019 (COVID-19), there is a high medical need for biomarkers that predict disease progression and severity in the first days after symptom onset. This study assessed the utility of early transforming growth factor ß (TGF-ß) serum levels in COVID-19 patients to predict disease severity, fatality, and response to dexamethasone therapy. Patients with severe COVID-19 had significantly higher TGF-ß levels (416 pg/mL) as compared to patients with mild (165 pg/mL, p < 0.0001) or moderate COVID-19 (241 pg/mL; p < 0.0001). Receiver operating characteristics area under the curve values were 0.92 (95% confidence interval [CI] 0.85-0.99, cut-off: 255 pg/mL) for mild versus severe COVID-19, and 0.83 (95% CI 0.65-1.0, cut-off: 202 pg/mL) for moderate versus severe COVID-19. Patients who died of severe COVID-19 had significantly higher TGF-ß levels (453 pg/mL) as compared to convalescent patients (344 pg/mL), and TGF-ß levels predicted fatality (area under the curve: 0.75, 95% CI 0.53-0.96). TGF-ß was significantly reduced in severely ill patients treated with dexamethasone (301 pg/mL) as compared to untreated patients (416 pg/mL; p < 0.05). Early TGF-ß serum levels in COVID-19 patients predict, with high accuracy, disease severity, and fatality. In addition, TGF-ß serves as a specific biomarker to assess response to dexamethasone treatment.

First successful treatment of Clostridium perfringens-associated emphysematous hepatitis: a case report.

Emphysematous diseases of the abdomen are rare with an often inconspicuous presentation of symptoms and rapid lethal outcome if untreated. We report the first successfully treated case of Clostridium perfringens-associated emphysematous hepatitis. In the emergency room, a 79-year-old man presented with shortness of breath and deteriorated general condition since the morning of admission. Initial CT scans showed a small but rapidly expanding gas collection in liver segment 6. Emergency surgery with atypical liver resection was performed immediately. With early resection and prolonged administration of antibiotics in the presence of sepsis, the patient recovered successfully and was discharged 37 days after admission. As in our case, prompt diagnosis with early surgical treatment is crucial for the management of emphysematous hepatitis.

A prospective phase IIA multicenter double-blinded randomized placebo-controlled clinical trial evaluating the efficacy and safety of inhaled Tobramycin in patients with ventilator-associated pneumonia (iToVAP).

OBJECTIVE: Treatment of ventilated pneumonia is often unsuccessful, even when patients are treated according to current guidelines. Therefore, we aimed to investigate the efficacy of the adjunctive inhaled Tobramycin in patients with pneumonia caused by Gram-negative pathogens in addition to the standard systemic treatment. DESIGN: Prospective, multicenter, double-blinded, randomized, placebo-controlled clinical trial. SETTING: 26 patients in medical and surgical ICUs. PATIENTS: Patients with ventilator-associated pneumonia caused by Gram-negative pathogens. MEASUREMENT AND MAIN RESULTS: Fourteen patients were assigned to the Tobramycin Inhal group and 12 patients to the control group. The microbiological eradication of the Gram-negative pathogens was significantly higher in the intervention group than in the control group (p < 0.001). The probability of eradication was 100% in the intervention group [95% Confidence Interval: 0.78-1.0] and 25% in the control group [95% CI: 0.09-0.53]. The increased eradication frequency was not associated with increased patient survival. CONCLUSION: Inhaled aerosolized Tobramycin demonstrated clinically meaningful efficacy in patients with Gram-negative ventilator-associated pneumonia. The probability of eradication in the intervention group was 100%. However, the successful eradication was not associated with a reduction in systemic anti-infective therapy, a shorter ICU stay, or even a survival benefit. In the presence of multidrug-resistant Gram-negative pathogens that are sensitive only to colistin and/or aminoglycosides, supplemental inhaled therapy with nebulizers suitable for this purpose should be considered in addition to systemic antibiotic therapy.

Mobilisation practices during the SARS-CoV-2 pandemic: A retrospective analysis (MobiCOVID).

BACKGROUND: Corona Virus Disease 2019 (COVID-19) patients display risk factors for intensive care unit acquired weakness (ICUAW). The pandemic increased existing barriers to mobilisation. This study aimed to compare mobilisation practices in COVID-19 and non-COVID-19 patients. METHODS: This retrospective cohort study was conducted at Charité-Universitätsmedizin Berlin, Germany, including adult patients admitted to one of 16 ICUs between March 2018, and November 2021. The effect of COVID-19 on mobilisation level and frequency, early mobilisation (EM) and time to active sitting position (ASP) was analysed. Subgroup analysis on COVID-19 patients and the ICU type influencing mobilisation practices was performed. Mobilisation entries were converted into the ICU mobility scale (IMS) using supervised machine learning. The groups were matched using 1:1 propensity score matching. RESULTS: A total of 12,462 patients were included, receiving 59,415 mobilisations. After matching 611 COVID-19 and non-COVID-19 patients were analysed. They displayed no significant difference in mobilisation frequency (0.4 vs. 0.3, p = 0.7), maximum IMS (3 vs. 3; p = 0.17), EM (43.2% vs. 37.8%; p = 0.06) or time to ASP (HR 0.95; 95% CI: 0.82, 1.09; p = 0.44). Subgroup analysis showed that patients in surge ICUs, i.e., temporarily created ICUs for COVID-19 patients during the pandemic, more commonly received EM (53.9% vs. 39.8%; p = 0.03) and reached higher maximum IMS (4 vs. 3; p = 0.03) without difference in mobilisation frequency (0.5 vs. 0.3; p = 0.32) or time to ASP (HR 1.15; 95% CI: 0.85, 1.56; p = 0.36). CONCLUSION: COVID-19 did not hinder mobilisation. Those treated in surge ICUs were more likely to receive EM and reached higher mobilisation levels.

[Anaesthesiological management of postmortem organ donors - What Evidence is Out There?] / Anästhesiologisches Management von postmortalen Organspendern.

The transplantation of organs from postmortem organ donors has been a lifesaving and quality-of-life-improving therapy for patients with irreversible organ failure for many years. In Germany, however, there has been an imbalance between the number of organs donated postmortem and the number of patients on the waiting list for years. The anesthesiological management of multiple organ harvesting (MOE) in postmortem organ donors is not an everyday challenge for various reasons: A lack of practical expertise due to the small number of MOE, even at university hospitals (usually < 20 per year), complex pathophysiological changes in the cardiovascular system and other organ functions of the postmortem organ donor and the lack of guidelines complicate anesthesiological management. This paper compiles the existing literature and reviews whether evidence-based recommendations can be derived for anesthesiologic management for MOE.

Mobilisation of critically ill patients receiving norepinephrine: a retrospective cohort study.

BACKGROUND: Mobilisation and exercise intervention in general are safe and feasible in critically ill patients. For patients requiring catecholamines, however, doses of norepinephrine safe for mobilisation in the intensive care unit (ICU) are not defined. This study aimed to describe mobilisation practice in our hospital and identify doses of norepinephrine that allowed a safe mobilisation. METHODS: We conducted a retrospective single-centre cohort study of 16 ICUs at a university hospital in Germany with patients admitted between March 2018 and November 2021. Data were collected from our patient data management system. We analysed the effect of norepinephrine on level (ICU Mobility Scale) and frequency (units per day) of mobilisation, early mobilisation (within 72 h of ICU admission), mortality, and rate of adverse events. Data were extracted from free-text mobilisation entries using supervised machine learning (support vector machine). Statistical analyses were done using (generalised) linear (mixed-effect) models, as well as chi-square tests and ANOVAs. RESULTS: A total of 12,462 patients were analysed in this study. They received a total of 59,415 mobilisation units. Of these patients, 842 (6.8%) received mobilisation under continuous norepinephrine administration. Norepinephrine administration was negatively associated with the frequency of mobilisation (adjusted difference -0.07 mobilisations per day; 95% CI - 0.09, - 0.05; p ≤ 0.001) and early mobilisation (adjusted OR 0.83; 95% CI 0.76, 0.90; p ≤ 0.001), while a higher norepinephrine dose corresponded to a lower chance to be mobilised out-of-bed (adjusted OR 0.01; 95% CI 0.00, 0.04; p ≤ 0.001). Mobilisation with norepinephrine did not significantly affect mortality (p > 0.1). Higher compared to lower doses of norepinephrine did not lead to a significant increase in adverse events in our practice (p > 0.1). We identified that mobilisation was safe with up to 0.20 µg/kg/min norepinephrine for out-of-bed (IMS ≥ 2) and 0.33 µg/kg/min for in-bed (IMS 0-1) mobilisation. CONCLUSIONS: Mobilisation with norepinephrine can be done safely when considering the status of the patient and safety guidelines. We demonstrated that safe mobilisation was possible with norepinephrine doses up to 0.20 µg/kg/min for out-of-bed (IMS ≥ 2) and 0.33 µg/kg/min for in-bed (IMS 0-1) mobilisation.

Successful treatment of severe COVID-19 pneumonia, a case series with simultaneous interleukin-1 and interleukin-6 blockade with 1-month follow-up.

Interleukin (IL)-6 and IL-1 blockade showed beneficial results in patients with severe COVID-19 pneumonia and evidence of cytokine release at the early disease stage. Here, we report outcomes of open-label therapy with a combination of blocking IL-6 with tocilizumab 8 mg/kg up to 800 mg and IL-1 receptor antagonist anakinra 100-300 mg over 3-5 days. Thirty-one adult patients with severe COVID-19 pneumonia and signs of cytokine release, mean age 54 (30-79) years, 5 female, 26 male, and mean symptom duration 6 (3-10) days were treated. Patients with more than 10 days of symptoms, evidence of bacterial infection/elevated procalcitonin and other severe lung diseases were excluded. Computed tomography (CT) scans of the lung were performed initially and after 1 month; inflammatory activity was assessed on a scale 0-25. Twenty-five patients survived without intubation and mechanical lung ventilation, two patients died. C-reactive protein decreased in 19/31 patients to normal ranges. The mean activity CT score decreased from 14 (8-20) to 6 (0-16, n = 16). In conclusion, most of our patients recovered fast and sustained, indicating that early interruption of cytokine release might be very effective in preventing patients from mechanical ventilation, death, and long-term damage.

Anti-SARS-CoV2 antibody-mediated cytokine release syndrome in a patient with acute promyelocytic leukemia.

BACKGROUND: Passive immunization against SARS-CoV-2 limits viral burden and death from COVID-19; however, it poses a theoretical risk of disease exacerbation through antibody-dependent enhancement (ADE). ADE after anti-SARS-CoV2 antibody treatment has not been reported, and therefore the potential risk and promoting factors remain unknown. CASE PRESENTATION: A 75-year-old female was admitted to the emergency room with recurrent, unexplained bruises and leukocytopenia, anemia, and thrombocytopenia. Evaluation of a bone marrow biopsy established the diagnosis of an acute promyelocytic leukemia (APL). SARS-CoV-2 RT-PCR testing of nasal and throat swabs on admission was negative. During the routine SARS-CoV-2 testing of inpatients, our patient tested positive for SARS-CoV-2 on day 14 after admission without typical COVID-19 symptoms. Due to disease- and therapy-related immunosuppression and advanced age conferring a high risk of progressing to severe COVID-19, casirivimab and imdevimab were administered as a preemptive approach. The patient developed immune activation and cytokine release syndrome (CRS) occurring within four hours of preemptive anti-SARS-CoV2 antibody (casirivimab/imdevimab) infusion. Immune activation and CRS were evidenced by a rapid increase in serum cytokines (IL-6, TNFα, IL-8, IL-10), acute respiratory insufficiency, and progressive acute respiratory distress syndrome. DISCUSSION AND CONCLUSION: The temporal relationship between therapeutic antibody administration and the rapid laboratory, radiological, and clinical deterioration suggests that CRS was an antibody-related adverse event, potentially exacerbated by APL treatment-mediated differentiation of leukemic blasts and promyelocytes. This case highlights the need for careful assessment of life-threatening adverse events after passive SARS-CoV-2 immunization, especially in the clinical context of patients with complex immune and hematological landscapes.

Quantification of ceftazidime/avibactam in human plasma and dried blood spots: Implications on stability and sample transport.

Ceftazidime is an established third-generation cephalosporin antibiotic frequently administered to intensive care patients. To overcome drug resistance of pathogens, it is combined with the newly developed non-ß-lactam ß-lactamase inhibitor avibactam under the brand name Zavicefta®. To facilitate therapeutic drug monitoring (TDM), we developed a method for the simultaneous quantification of these substances by LC-MS/MS. A problem for TDM is the low stability of the analytes in plasma, requiring transport times of less than 6 h at 23 °C. Thus, we evaluated dried blood spots (DBS) as matrix for better stability. For both analytes, stable isotope labelled internal standards were applied. Plasma samples were prepared by protein precipitation, DBS by liquid extraction. The chromatographic separation took place on a polar-modified C18 column, and detection was achieved by tandem mass spectrometry with ESI ionization in positive mode for ceftazidime and negative mode for avibactam. Calibration was linear in the ranges of 5 - 100 µg/mL for ceftazidime and 1.25 - 25 µg/mL for avibactam in plasma and 2.5 - 50 µg/mL and 0.625 - 12.5 µg/mL in DBS, respectively. Precision was better than 7 % and accuracy better than 10% for plasma as well as for DBS. The stability of ceftazidime and avibactam was better in DBS than in plasma or full blood, extending maximal transport times at 23 °C from 6 h in plasma or full blood to 24 h for DBS samples. However, robust estimation of plasma concentrations from DBS measurements requires validation by future clinical studies.

Corticosteroids as risk factor for COVID-19-associated pulmonary aspergillosis in intensive care patients.

PURPOSE: Corticosteroids, in particular dexamethasone, are one of the primary treatment options for critically ill COVID-19 patients. However, there are a growing number of cases that involve COVID-19-associated pulmonary aspergillosis (CAPA), and it is unclear whether dexamethasone represents a risk factor for CAPA. Our aim was to investigate a possible association of the recommended dexamethasone therapy with a risk of CAPA. METHODS: We performed a study based on a cohort of COVID-19 patients treated in 2020 in our 13 intensive care units at Charité Universitätsmedizin Berlin. We used ECMM/ISHM criteria for the CAPA diagnosis and performed univariate and multivariable analyses of clinical parameters to identify risk factors that could result in a diagnosis of CAPA. RESULTS: Altogether, among the n = 522 intensive care patients analyzed, n = 47 (9%) patients developed CAPA. CAPA patients had a higher simplified acute physiology score (SAPS) (64 vs. 53, p < 0.001) and higher levels of IL-6 (1,005 vs. 461, p < 0.008). They more often had severe acute respiratory distress syndrome (ARDS) (60% vs. 41%, p = 0.024), renal replacement therapy (60% vs. 41%, p = 0.024), and they were more likely to die (64% vs. 48%, p = 0.049). The multivariable analysis showed dexamethasone (OR 3.110, CI95 1.112-8.697) and SAPS (OR 1.063, CI95 1.028-1.098) to be independent risk factors for CAPA. CONCLUSION: In our study, dexamethasone therapy as recommended for COVID-19 was associated with a significant three times increase in the risk of CAPA. TRIAL REGISTRATION: Registration number DRKS00024578, Date of registration March 3rd, 2021.

Isolated Ruptured Paravisceral Penetrating Aortic Ulcers.

BACKGROUND: The goal of this study is to investigate the clinical presentation, treatment options, and outcomes of the patients with isolated ruptured paravisceral penetrating aortic ulcers (PV-PAU). METHODS: All patients presenting with acute aortic syndrome from 2015 to 2020 were screened, of which patients with isolated ruptured PV-PAU were included in this retrospective study. Study endpoints were the assessment of treatment options, technical success, and clinical outcome. Outcome measures included major perioperative complications and mortality. RESULTS: Sixteen patients (11 men; median age 68; IQR 60 - 75 years) presented with isolated ruptured PV-PAU were included in this study. The median follow-up was 25 months (range 1 - 51). Ruptured PV-PAUs represented 12.3% of the ruptured aortic aneurysms in all locations. PV-PAUs were found in segment A (n = 8, 50%), segment B (n = 5, 31%), and segment C (n = 3, 19%). PV-PAUs showed a mean protrusion distance of 27±10 mm, a mean neck diameter of 21 ± 7 mm, and maximal aortic diameter of 50 ± 11 mm. Five patients (31%) showed hemodynamic instability on admission and needed intense fluid resuscitation. Of those, 2 patients needed urgent laparotomy with a fast transabdominal supraceliac aortic clamping, one needed an aortic balloon occlusion to obtain rapid aortic control. The open aortic repair was the most frequently performed surgery (11/16, 69%), followed by hybrid procedures (3/16) and parallel graft chimney technique (2/16). Two patients died during the follow-up, calculating for in-hospital and 1-year mortality rates of 6 - 12%, respectively. The postoperative morbidity rate was 31%. Postoperative complications included acute renal failure (31%), pneumonia (25%), and 1case of ischemic colitis (6%). No spinal cord ischemia was reported. CONCLUSIONS: Ruptured PV-PAU is a rare and challenging diagnostic and therapeutic entity. Open aortic repair seems to be a reliable option in treating patients with isolated ruptured PV-PAUs. Hybrid procedures and parallel stent-graft techniques can only be used in selected patients.

Untimely TGFß responses in COVID-19 limit antiviral functions of NK cells.

SARS-CoV-2 is a single-stranded RNA virus that causes COVID-19. Given its acute and often self-limiting course, it is likely that components of the innate immune system play a central part in controlling virus replication and determining clinical outcome. Natural killer (NK) cells are innate lymphocytes with notable activity against a broad range of viruses, including RNA viruses1,2. NK cell function may be altered during COVID-19 despite increased representation of NK cells with an activated and adaptive phenotype3,4. Here we show that a decline in viral load in COVID-19 correlates with NK cell status and that NK cells can control SARS-CoV-2 replication by recognizing infected target cells. In severe COVID-19, NK cells show defects in virus control, cytokine production and cell-mediated cytotoxicity despite high expression of cytotoxic effector molecules. Single-cell RNA sequencing of NK cells over the time course of the COVID-19 disease spectrum reveals a distinct gene expression signature. Transcriptional networks of interferon-driven NK cell activation are superimposed by a dominant transforming growth factor-ß (TGFß) response signature, with reduced expression of genes related to cell-cell adhesion, granule exocytosis and cell-mediated cytotoxicity. In severe COVID-19, serum levels of TGFß peak during the first two weeks of infection, and serum obtained from these patients severely inhibits NK cell function in a TGFß-dependent manner. Our data reveal that an untimely production of TGFß is a hallmark of severe COVID-19 and may inhibit NK cell function and early control of the virus.

Preoperative and ICU Scoring Models for Predicting the In-Hospital Mortality of Patients With Ruptured Abdominal Aortic Aneurysms.

OBJECTIVES: This study's objective was to compare several preoperative and intensive care unit (ICU) prognostic scoring systems for predicting the in-hospital mortality of ruptured abdominal aortic aneurysms (RAAAs). DESIGN: Retrospective cohort study. SETTING: Single tertiary university center. PARTICIPANTS: The study comprised 157 patients. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: A total of 157 patients (82% male) presented with RAAA at Charité University Hospital from January 2011 to December 2020. The mean age was 74 years (standard deviation ten years). In-hospital mortality was 29% (n = 45), of whom nine patients (6%) died en route to the operating room, 13 (8%) on the operating table, and 23 (15%) in the ICU. A total of 135 patients (86%) were admitted to the ICU. All six models demonstrated good discriminating performance between survivors and nonsurvivors. Overall, the area under the curve (AUC) for RAAA preoperative scores was greater than those for ICU scores. The largest AUC was achieved with the Vascular Study Group of New England (VSGNE) RAAA risk score (AUC = 0.87 for all patients, AUC = 0.84 for patients admitted to the ICU), followed by Hardman Index (AUC = 0.83 for all patients, AUC = 0.81 for patients admitted to the ICU), and Glasgow Aneurysm Score (AUC = 0.74 for all patients, AUC = 0.83 for patients admitted to the ICU). The largest AUC for ICU scores (only patients admitted to the ICU) was achieved with Simplified Acute Physiology Score II (0.75), followed by Sepsis-related Organ Failure Assessment (0.73), and Acute Physiology and Chronic Health Evaluation II (0.71). CONCLUSIONS: Preoperative and ICU scores can predict the mortality of patients presenting with RAAA. In addition, the discriminatory ability of preoperative scores between survivors and nonsurvivors was larger than that for ICU scores.