To investigate the immune response and mechanisms associated with severe coronavirus disease 2019 (COVID-19), we performed single-cell RNA sequencing on nasopharyngeal and bronchial samples from 19 ...clinically well-characterized patients with moderate or critical disease and from five healthy controls. We identified airway epithelial cell types and states vulnerable to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. In patients with COVID-19, epithelial cells showed an average three-fold increase in expression of the SARS-CoV-2 entry receptor ACE2, which correlated with interferon signals by immune cells. Compared to moderate cases, critical cases exhibited stronger interactions between epithelial and immune cells, as indicated by ligand-receptor expression profiles, and activated immune cells, including inflammatory macrophages expressing CCL2, CCL3, CCL20, CXCL1, CXCL3, CXCL10, IL8, IL1B and TNF. The transcriptional differences in critical cases compared to moderate cases likely contribute to clinical observations of heightened inflammatory tissue damage, lung injury and respiratory failure. Our data suggest that pharmacologic inhibition of the CCR1 and/or CCR5 pathways might suppress immune hyperactivation in critical COVID-19.
In coronavirus disease 2019 (COVID-19), hypertension and cardiovascular diseases are major risk factors for critical disease progression. However, the underlying causes and the effects of the main ...anti-hypertensive therapies-angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs)-remain unclear. Combining clinical data (n = 144) and single-cell sequencing data of airway samples (n = 48) with in vitro experiments, we observed a distinct inflammatory predisposition of immune cells in patients with hypertension that correlated with critical COVID-19 progression. ACEI treatment was associated with dampened COVID-19-related hyperinflammation and with increased cell intrinsic antiviral responses, whereas ARB treatment related to enhanced epithelial-immune cell interactions. Macrophages and neutrophils of patients with hypertension, in particular under ARB treatment, exhibited higher expression of the pro-inflammatory cytokines CCL3 and CCL4 and the chemokine receptor CCR1. Although the limited size of our cohort does not allow us to establish clinical efficacy, our data suggest that the clinical benefits of ACEI treatment in patients with COVID-19 who have hypertension warrant further investigation.
Extracorporeal Membrane Oxygenation (ECMO) use is increasing despite limited evidence. The aim of this study was to demonstrate heterogeneity of ECMO use and its association with hospital size and ...annual frequency in Germany.
This is a database analysis of all ECMO cases in Germany from 2010 to 2016 using the German Diagnosis Related Groups (DRG) coding system for ECMO.
During the study period, 510 hospitals performed 29,929 ECMO runs (12,572 vvECMO, 11,504 vaECMO, 1993 pECLA) with an increase over time. Mortality ranged between 58% and 66% for vaECMO cases and 66% and 53% for vvECMO cases. 304 (61%) hospitals performed only one ECMO per year. 78%% of all ECMO runs were performed in centres with more than 20 cases per year and more than half of all ECMO runs were performed in hospitals with >1.000 beds. Mortality for vv and vaECMO was highest in very small hospitals (< 200 beds; 70%; 74%) and very large hospitals (>1000 beds; 60%; 62%).
Use of ECMO is still increasing and a substantial proportion of hospitals performs very few ECMO runs. Small hospitals had a significantly higher mortality, but dependence on hospital size and ECMO mortality was irregular.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Hydroxyethyl starch (HES) was part of "triple-H" therapy for prophylaxis and therapy of vasospasm in patients with subarachnoid haemorrhage (SAH). The European Medicines Agency restricted the use of ...HES in 2013 due to an increase of renal failure in critically ill patients receiving HES compared to crystalloid fluids. The occurrence of renal insufficiency in patients with SAH due to HES is still uncertain. The purpose of our study was to evaluate whether there was an association with renal impairment in patients receiving HES after subarachnoid haemorrhage.
Medical records of all non-traumatic SAH patients treated at the Departments of Anaesthesiology and Neurosurgery, University Hospital of Leipzig, Germany, between January 2009 and December 2014 were analysed. Patients received either HES 6% and/or 10% (HES group, n = 183) or exclusively crystalloids for fluid therapy (Crystalloid group, n = 93). Primary outcome was the incidence of acute kidney injury.
The study groups had similar characteristics except for initial SAPS scores, incidence of vasospasm and ICU length of stay. Patients receiving HES fulfilled significantly more often SIRS (systemic inflammatory response syndrome) criteria. 24.6% (45/183) of the patients in the HES group had acute kidney injury (KDIGO 1-3) at any time during their ICU stay compared to 26.9% (25/93) in the crystalloid group (p = 0.679). Only few patients needed renal replacement therapy with no significant difference between groups (Crystalloid group: 4.3%; HES group: 2.2%; p = 0.322). The incidence of vasospasm was increased in the HES group when compared to the crystalloid group (33.9% vs. 17.2%; p = 0.004).
In the presented series of patients with non-traumatic SAH we found no significant association between HES therapy and the incidence of acute kidney injury. Treatment without HES did not worsen patient outcome.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
AIM: To analyze differences in patients’ clinical course, we compared two regimes of either preemptive therapy or prophylaxis after liver transplantation.METHODS: This retrospective study was ...reviewed and approved by the institutional review board of the University of Leipzig. Cytomegalovirus(CMV) prophylaxis with valganciclovir hydrochloride for liver transplant recipients was replaced by a preemptive strategy in October 2009. We retrospectively compared liver transplant recipients 2 years before and after October 2009. During the first period, all patients received valganciclovir daily. During the second period all patients included in the analysis were treated following a preemptive strategy. Outcomes included one year survival and therapeutic intervention due to CMV viremia or infection.RESULTS: Between 2007 and 2010 n = 226 patients underwent liver transplantation in our center. n = 55 patients were D~+/R~- high risk recipients and were excluded from further analysis. A further 43 patients had to be excluded since CMV prophylaxis/preemptive strategy was not followed although there was no clinical reason for the deviation. Of the remaining 128 patients whose data were analyzed, 60 receivedprophylaxis and 68 were treated following a preemptive strategy. The difference in overall mortality was not significant, nor was it significant for one-year mortality where it was 10%(95%CI: 8%-28%, P = 0.31) higher for the preemptive group. No significant differences in blood count abnormalities or the incidence of sepsis and infections were observed other than CMV. In total, 19 patients(14.7%) received ganciclovir due to CMV viremia and/or infections. Patients who were treated according to the preemptive algorithm had a significantly higher rate risk of therapeutic intervention with ganciclovir n = 16(23.5%) vs n = 3(4.9%), P = 0.003).CONCLUSION: These data suggest that CMV prophylaxis is superior to a preemptive strategy in patients undergoing liver transplantation.
Background: Sleep deprivation and disturbances in circadian rhythms may hinder surgical performance and decision-making capabilities. Solid organ transplantations, which are technically demanding and ...often begin at uncertain times, frequently during nighttime hours, are particularly susceptible to these effects. This study aimed to assess how transplant operations conducted during daytime versus nighttime influence both patient and graft outcomes and function. Methods: simultaneous pancreas–kidney transplants (SPKTs) conducted at the University Hospital of Leipzig from 1998 to 2018 were reviewed retrospectively. The transplants were categorized based on whether they began during daytime hours (8 a.m. to 6 p.m.) or nighttime hours (6 p.m. to 8 a.m.). We analyzed the demographics of both donors and recipients, as well as primary outcomes, which included surgical complications, patient survival, and graft longevity. Results: In this research involving 105 patients, 43 SPKTs, accounting for 41%, took place in the daytime, while 62 transplants (59%) occurred at night. The characteristics of both donors and recipients were similar across the two groups. Further, the rate of (surgical) pancreas graft-related complications and reoperations (daytime 39.5% versus nighttime 33.9%; p = 0.552) were also not statistically significant between both groups. In this study, the five-year survival rate for patients was comparable for both daytime and nighttime surgeries, with 85.2% for daytime and 86% for nighttime procedures (p = 0.816). Similarly, the survival rates for pancreas grafts were 75% for daytime and 77% for nighttime operations (p = 0.912), and for kidney grafts, 76% during the day compared to 80% at night (p = 0.740), indicating no significant statistical difference between the two time periods. In a multivariable model, recipient BMI > 30 kg/m2, donor age, donor BMI, and cold ischemia time > 15 h were independent predictors for increased risk of (surgical) pancreas graft-related complications, whereas the timepoint of SPKT (daytime versus nighttime) did not have an impact. Conclusions: The findings from our retrospective analysis at a big single German transplant center indicate that SPKT is a reliable procedure, regardless of the start time. Additionally, our data revealed that patients undergoing nighttime transplants have no greater risk of surgical complications or inferior results concerning long-term survival of the patient and graft. However, due to the small number of cases evaluated, further studies are required to confirm these results.
Objectives: Adequate organ perfusion, as well as appropriate blood pressure levels at the time of unclamping, is crucial for early and long-term graft function and outcome in simultaneous ...pancreas−kidney transplantation (SPKT). However, the optimal intraoperative mean arterial pressure (MAP) level has not well been defined. Methods: From a prospectively collected database, the medical data of 105 patients undergoing SPKT at our center were retrospectively analyzed. A receiver operating characteristic (ROC) analysis was preliminarily performed for optimal cut-off value for MAP at reperfusion, to predict early pancreatic graft function. Due to these results, we divided the patients according to their MAP values at reperfusion into <91 mmHg (n = 47 patients) and >91 mmHg (n = 58 patients) groups. Clinicopathological characteristics and outcomes, as well as early graft function and long-term survival, were retrospectively analyzed. Results: Donor and recipient characteristics were comparable between both groups. Rates of postoperative complications were significantly higher in the <91 mmHg group than those in the >91 mmHg group (vascular thrombosis of the pancreas: 7 (14%) versus 2 (3%); p = 0.03; pancreatitis/intraabdominal abscess: 10 (21%) versus 4 (7%); p = 0.03; renal delayed graft function (DGF): 11 (23%) versus 5 (9%); p = 0.03; postreperfusion urine output: 106 ± 50 mL versus 195 ± 45 mL; p = 0.04). There were no significant differences in intraoperative volume repletion, central venous pressure (CVP), use of vasoactive inotropic agents, and the metabolic outcome. Five-year pancreas graft survival was significantly higher in the >91 mmHg group (>91 mmHg: 82% versus <91 mmHg: 61%; p < 0.01). No significant differences were observed in patient and kidney graft survival at 5 years between both groups. Multivariate Cox regression analysis affirmed MAP < 91 mmHg as an independent prognostic predictor for renal DGF (HR 3.49, 1.1−10.8, p = 0.03) and pancreas allograft failure (HR 2.26, 1.0−4.8, p = 0.01). Conclusions: A MAP > 91 mmHg at the time point of reperfusion was associated with a reduced rate of postoperative complications, enhancing and recovering long-term graft function and outcome and thus increasing long-term survival in SPKT recipients.
Background: Despite recent advances in surgical procedures and immunosuppressive regimes, early pancreatic graft dysfunction, mainly specified as ischemia–reperfusion injury (IRI)—Remains a common ...cause of pancreas graft failure with potentially worse outcomes in simultaneous pancreas-kidney transplantation (SPKT). Anesthetic conditioning is a widely described strategy to attenuate IRI and facilitate graft protection. Here, we investigate the effects of different volatile anesthetics (VAs) on early IRI-associated posttransplant clinical outcomes as well as graft function and outcome in SPKT recipients. Methods: Medical data of 105 patients undergoing SPKT between 1998–2018 were retrospectively analyzed and stratified according to the used VAs. The primary study endpoint was the association and effect of VAs on pancreas allograft failure following SPKT; secondary endpoint analyses included “IRI- associated posttransplant clinical outcome” as well as long-term graft function and outcome. Additionally, peak serum levels of C-reactive protein (CRP) and lipase during the first 72 h after SPKT were determined and used as further markers for “pancreatic IRI” and graft injury. Typical clinicopathological characteristics and postoperative outcomes such as early graft outcome and long-term function were analyzed. Results: Of the 105 included patients in this study three VAs were used: isoflurane (n = 58 patients; 55%), sevoflurane (n = 22 patients; 21%), and desflurane (n = 25 patients, 24%). Donor and recipient characteristics were comparable between both groups. Early graft loss within 3 months (24% versus 5% versus 8%, p = 0.04) as well as IRI-associated postoperative clinical complications (pancreatitis: 21% versus 5% versus 5%, p = 0.04; vascular thrombosis: 13% versus 0% versus 5%; p = 0.09) occurred more frequently in the Isoflurane group compared with the sevoflurane and desflurane groups. Anesthesia with sevoflurane resulted in the lowest serum peak levels of lipase and CRP during the first 3 days after transplantation, followed by desflurane and isoflurane (p = 0.039 and p = 0.001, respectively). There was no difference with regard to 10-year pancreas graft survival as well as endocrine/metabolic function among all three VA groups. Multivariate analysis revealed the choice of VAs as an independent prognostic factor for graft failure three months after SPKT (HR 0.38, 95%CI: 0.17–0.84; p = 0.029). Conclusions: In our study, sevoflurane and desflurane were associated with significantly increased early graft survival as well as decreased IRI-associated post-transplant clinical outcomes when compared with the isoflurane group and should be the focus of future clinical studies evaluating the positive effects of different VA agents in patients receiving SPKT.
Background: Despite recent advances and refinements in perioperative management of kidney transplantation (KT), early renal graft injury (eRGI) remains a critical problem with serious impairment of ...graft function as well as short- and long-term outcome. Serial monitoring of peripheral blood innate immune cells might be a useful tool in predicting post-transplant eRGI and graft outcome after KT. Methods: In this prospective study, medical data of 50 consecutive patients undergoing KT at the University Hospital of Leipzig were analyzed starting at the day of KT until day 10 after the transplantation. The main outcome parameter was the occurrence of eRGI and other outcome parameters associated with graft function/outcome. eRGI was defined as graft-related complications and clinical signs of renal IRI (ischemia reperfusion injury), such as acute tubular necrosis (ATN), delayed graft function (DGF), initial nonfunction (INF) and graft rejection within 3 months following KT. Typical innate immune cells including neutrophils, natural killer (NK) cells, monocytes, basophils and dendritic cells (myeloid, plasmacytoid) were measured in all patients in peripheral blood at day 0, 1, 3, 7 and 10 after the transplantation. Receiver operating characteristics (ROC) curves were performed to assess their predictive value for eRGI. Cutoff levels were calculated with the Youden index. Significant diagnostic immunological cutoffs and other prognostic clinical factors were tested in a multivariate logistic regression model. Results: Of the 50 included patients, 23 patients developed eRGI. Mean levels of neutrophils and monocytes were significantly higher on most days in the eRGI group compared to the non-eRGI group after transplantation, whereas a significant decrease in NK cell count, basophil levels and DC counts could be found between baseline and postoperative course. ROC analysis indicated that monocytes levels on POD 7 (AUC: 0.91) and NK cell levels on POD 7 (AUC: 0.92) were highly predictive for eRGI after KT. Multivariable analysis identified recipient age (OR 1.53 (95% CI: 1.003−2.350), p = 0.040), recipient body mass index > 25 kg/m2 (OR 5.6 (95% CI: 1.36−23.9), p = 0.015), recipient cardiovascular disease (OR 8.17 (95% CI: 1.28−52.16), p = 0.026), donor age (OR 1.068 (95% CI: 1.011−1.128), p = 0.027), <0.010), deceased-donor transplantation (OR 2.18 (95% CI: 1.091−4.112), p = 0.027) and cold ischemia time (CIT) of the renal graft (OR 1.005 (95% CI: 1.001−1.01), p = 0.019) as clinically relevant prognostic factors associated with increased eRGI following KT. Further, neutrophils > 9.4 × 103/μL on POD 7 (OR 16.1 (95% CI: 1.31−195.6), p = 0.031), monocytes > 1150 cells/ul on POD 7 (OR 7.81 (95% CI: 1.97−63.18), p = 0.048), NK cells < 125 cells/μL on POD 3 (OR 6.97 (95% CI: 3.81−12.7), p < 0.01), basophils < 18.1 cells/μL on POD 10 (OR 3.45 (95% CI: 1.37−12.3), p = 0.02) and mDC < 4.7 cells/μL on POD 7 (OR 11.68 (95% CI: 1.85−73.4), p < 0.01) were revealed as independent biochemical predictive variables for eRGI after KT. Conclusions: We show that the combined measurement of immunological innate variables (NK cells and monocytes on POD 7) and specific clinical factors such as prolonged CIT, increased donor and recipient age and morbidity together with deceased-donor transplantation were significant and specific predictors of eRGI following KT. We suggest that intensified monitoring of these parameters might be a helpful clinical tool in identifying patients at a higher risk of postoperative complication after KT and may therefore help to detect and—by diligent clinical management—even prevent deteriorated outcome due to IRI and eRGI after KT.
PurposeThis executive summary of a national living guideline aims to provide rapid evidence based recommendations on the role of drug interventions in the treatment of hospitalized patients with ...COVID-19.MethodsThe guideline makes use of a systematic assessment and decision process using an evidence to decision framework (GRADE) as recommended standard WHO (2021). Recommendations are consented by an interdisciplinary panel. Evidence analysis and interpretation is supported by the CEOsys project providing extensive literature searches and living (meta-) analyses. For this executive summary, selected key recommendations on drug therapy are presented including the quality of the evidence and rationale for the level of recommendation.ResultsThe guideline contains 11 key recommendations for COVID-19 drug therapy, eight of which are based on systematic review and/or meta-analysis, while three recommendations represent consensus expert opinion. Based on current evidence, the panel makes strong recommendations for corticosteroids (WHO scale 5–9) and prophylactic anticoagulation (all hospitalized patients with COVID-19) as standard of care. Intensified anticoagulation may be considered for patients with additional risk factors for venous thromboembolisms (VTE) and a low bleeding risk. The IL-6 antagonist tocilizumab may be added in case of high supplemental oxygen requirement and progressive disease (WHO scale 5–6). Treatment with nMABs may be considered for selected inpatients with an early SARS-CoV-2 infection that are not hospitalized for COVID-19. Convalescent plasma, azithromycin, ivermectin or vitamin D3 should not be used in COVID-19 routine care.ConclusionFor COVID-19 drug therapy, there are several options that are sufficiently supported by evidence. The living guidance will be updated as new evidence emerges.
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