Prognostic impact of ICG-PDR in patients with hypoxic hepatitis

Background: Hepatic impairment is found in up to 20 % in critically ill patients. Hypoxic/ischemic hepatitis (HH) is a diffuse hepatic damage associated with high morbidity and mortality. Indocyanine green plasma disappearance rate (ICG-PDR) is an effective tool assessing liver function in acute and chronic hepatic diseases. Aim of this study was to evaluate the prognostic impact of ICG-PDR in comparison to established parameters for risk stratification. Methods: Patients with HH were included in this prospective observational study and compared to cirrhosis, acute liver failure (ALF) and patients without underlying liver disease. ICG-PDR, measured non-invasively by finger pulse densitometry, was assessed on admission and in patients with HH serially and results were compared between groups. Diagnostic test accuracy of ICG-PDR predicting 28-day mortality was analyzed by receiver operating characteristics (ROC). Results: ICG-PDR on admission was significantly lower in patients with liver diseases than in patients without hepatic impairment (median 5.7 %/min, IQR 3.8-7.9 vs. 20.7 %/min, IQR 14.1-25.4 %/min;p = 9.0 %/min 48 h after admission. Conclusions: ICG-PDR is an independent predictor of mortality in patients with liver disease. Diagnostic test accuracy of ICG-PDR was superior to standard liver function parameters and established scoring systems in patients with HH

Charakteristika und Outcome von 70 beatmeten COVID-19-Patienten : Bilanz nach der ersten Welle an einem universitären Zentrum

BACKGROUND In a pandemic situation the overall mortality rate is of considerable interest; however, these data must always be seen in relation to the given healthcare system and the availability of local level of care. A recently published German data evaluation of more than 10,000 COVID-19 patients treated in 920 hospitals showed a high mortality rate of 22% in hospitalized patients and of more than 50% in patients requiring invasive ventilation. Because of the high infection rates in Bavaria, a large number of COVID-19 patients with considerable severity of disease were treated at the intensive care units of the LMU hospital. The LMU hospital is a university hospital and a specialized referral center for the treatment of patients with acute respiratory distress syndrome (ARDS). OBJECTIVE Data of LMU intensive care unit (ICU) patients were systematically evaluated and compared with the recently published German data. METHODS Data of all COVID-19 patients with invasive and noninvasive ventilation and with completed admission at the ICU of the LMU hospital until 31 July 2020 were collected. Data were processed using descriptive statistics. RESULTS In total 70 critically ill patients were included in the data evaluation. The median SAPS II on admission to the ICU was 62~points. The median age was 66 years and 81% of the patients were male. More than 90% were diagnosed with ARDS and received invasive ventilation. Treatment with extracorporeal membrane oxygenation (ECMO) was necessary in 10% of the patients. The median duration of ventilation was 16 days, whereby 34.3% of patients required a tracheostomy. Of the patients 27.1% were transferred to the LMU hospital from external hospitals with reference to our ARDS/ECMO program. Patients from external hospitals had ARDS of higher severity than the total study population. In total, nine different substances were used for virus-specific treatment of COVID-19. The most frequently used substances were hydroxychloroquine and azithromycin. Immunomodulatory treatment, such as Cytosorb® (18.6%) and methylprednisolone (25.7%) were also frequently used. The overall in-hospital mortality rate of ICU patients requiring ventilation was 28.6%. The mortality rates of patients from external hospitals, patients with renal replacement therapy and patients with ECMO therapy were 47.4%, 56.7% and 85.7%, respectively. CONCLUSION The mortality rate in the ventilated COVID-19 intensive care patients was considerably different from the general rate in Germany. The data showed that treatment in an ARDS referral center could result in a lower mortality rate. Low-dose administration of steroids may be another factor to improve patient outcome in a preselected patient population. In the authors' opinion, critically ill COVID-19 patients should be treated in an ARDS center provided that sufficient resources are available.ZUSAMMENFASSUNG HINTERGRUND: Eine aktuelle, deutschlandweite Datenerhebung zeigte bei beatmeten Patienten mit COVID-19 eine Letalität von über 50 %. Auch am LMU Klinikum wurde eine große Anzahl an Patienten mit COVID-19 mit teils erheblicher Erkrankungsschwere intensivmedizinisch behandelt. FRAGESTELLUNG Die Daten der am LMU-Klinikum behandelten COVID-19-Patienten wurden systematisch ausgewertet und mit den deutschlandweiten Daten verglichen. METHODIK Für die vorliegende Studie wurden die Daten aller Patienten, die bis zum 31.07.2020 am LMU-Klinikum aufgrund von COVID-19 invasiv und nichtinvasiv beatmet wurden und deren Krankenhausaufenthalt zum Zeitpunkt der Auswertung bereits abgeschlossen war, analysiert und mittels deskriptiver Statistik aufgearbeitet. ERGEBNISSE Insgesamt wurden 70 kritisch kranke, beatmete Patienten (SAPS-II-Median: 62 Punkte) analysiert (Altersmedian: 66 Jahre, 81 % männlich). Über 90 % wurden wegen eines akuten Lungenversagens (ARDS) unterschiedlicher Schweregrade behandelt. Eine Therapie mittels extrakorporaler Membranoxygenierung (ECMO) war bei 10 % erforderlich. Die Übernahme von externen Kliniken im Rahmen einer ARDS/ECMO-Anfrage erfolgte bei 27,1 % der Patienten. Häufig eingesetzte immunmodulatorische Therapien waren die Behandlung mit Cytosorb® (18,6 %) und die prolongierte Gabe von Methylprednisolon (25,7 %). Die krankenhausinterne Letalität betrug 28,6 %. FAZIT Trotz erheblicher Erkrankungsschwere lag die Letalität bei beatmeten COVID-19-Intensivpatienten im LMU-Kollektiv deutlich unter der deutschlandweit erhobenen Letalität. Ein möglicher Faktor ist die Behandlung in einem Zentrum für ARDS

High prevalence of falsely declaring nicotine abstinence in lung transplant candidates

Tobacco use after lung transplantation is associated with adverse outcome. Therefore, active smoking is regarded as a contraindication for lung transplantation and should be excluded prior to placement on the waiting list. The aim of the study was to compare self-reporting with a systematic cotinine based screening approach to identify patients with active nicotine abuse. Nicotine use was systematically assessed by interviews and cotinine test in all lung transplant candidates at every visit in our center. Patients were classified according to the stage prior to transplantation and cotinine test results were compared to self-reports and retrospectively analyzed until June 2019. Of 620 lung transplant candidates, 92 patients (14.8%) had at least one positive cotinine test. COPD as underlying disease (OR 2.102, CI 1.110-3.981;p = 0.023), number of pack years (OR 1.014, CI 1.000-1.028;p = 0.047) and a time of cessation less than one year (OR 2.413, CI 1.410-4.128;p = 0.001) were associated with a positive cotinine test in multivariable regression analysis. The majority of non-COPD patients (n = 13, 72.2%) with a positive test had a cessation time of less than one year. 78 patients (84.7%) falsely declared not consuming any nicotine-based products prior to the test. Finally, all never smokers were test negative. In conclusion, our data demonstrate that active nicotine use is prevalent in transplant candidates with a high prevalence of falsely declaring nicotine abstinence. COPD was the main diagnosis in affected patients. Short cessation time and a high number of pack years are risk factors for continued nicotine abuse

Dynamics of urinary and respiratory shedding of Severe acute respiratory syndrome virus 2 (SARS-CoV-2) RNA excludes urine as a relevant source of viral transmission

PURPOSE To investigate the expression of the receptor protein ACE-2 alongside the urinary tract, urinary shedding and urinary stability of SARS-CoV-2 RNA. METHODS Immunohistochemical staining was performed on tissue from urological surgery of 10 patients. Further, patients treated for coronavirus disease (COVID-19) at specialized care-units of a university hospital were assessed for detection of SARS-CoV-2 RNA in urinary samples via PCR, disease severity (WHO score), inflammatory response of patients. Finally, the stability of SARS-CoV-2 RNA in urine was analyzed. RESULTS High ACE-2 expression (3/3) was observed in the tubules of the kidney and prostate glands, moderate expression in urothelial cells of the bladder (0-2/3) and no expression in kidney glomeruli, muscularis of the bladder and stroma of the prostate (0/3). SARS-CoV-2 RNA was detected in 5/199 urine samples from 64 patients. Viral RNA was detected in the first urinary sample of sequential samples. Viral RNA load from other specimen as nasopharyngeal swabs (NPS) or endotracheal aspirates revealed higher levels than from urine. Detection of SARS-CoV-2 RNA in urine was not associated with impaired WHO score (median 5, range 3-8 vs median 4, range 1-8, p = 0.314), peak white blood cell count (median 24.1 × 1000/ml, range 5.19-48.1 versus median 11.9 × 1000/ml, range 2.9-60.3, p = 0.307), peak CRP (median 20.7~mg/dl, 4.2-40.2 versus median 11.9~mg/dl, range 0.1-51.9, p = 0.316) or peak IL-6 levels (median: 1442~ng/ml, range 26.7-3918 versus median 140~ng/ml, range 3.0-11,041, p = 0.099). SARS-CoV-2 RNA was stable under different storage conditions and after freeze-thaw cycles. CONCLUSIONS SARS-CoV-2 RNA in the urine of COVID-19 patients occurs infrequently. The viral RNA load and dynamics of SARS-CoV-2 RNA shedding suggest no relevant route of transmission through the urinary tract

Gamma-glutamyltransferase is a strong predictor of secondary sclerosing cholangitis after lung transplantation for COVID-19 ARDS

Background: Lung transplantation (LTx) can be considered for selected patients suffering from COVID-19 acute respiratory distress syndrome (ARDS). Secondary sclerosing cholangitis in critically ill (SSC-CIP) patients has been described as a late complication in COVID-19 ARDS survivors, however, rates of SSC-CIP after LTx and factors predicting this detrimental sequela are unknown. Methods: This retrospective analysis included all LTx performed for post-COVID ARDS at 8 European LTx centers between May 2020 and January 2022. Clinical risk factors for SSC-CIP were analyzed over time. Prediction of SSC-CIP was assessed by ROC-analysis. Results: A total of 40 patients were included in the analysis. Fifteen patients (37.5%) developed SSC-CIP. GGT at the time of listing was significantly higher in patients who developed SSC-CIP (median 661 (IQR 324-871) vs 186 (109-346); p = 0.001). Moreover, higher peak values for GGT (585 vs 128.4; p < 0.001) and ALP (325 vs 160.2; p = 0.015) were found in the ‘SSC’ group during the waiting period. Both, GGT at the time of listing and peak GGT during the waiting time, could predict SSC-CIP with an AUC of 0.797 (95% CI: 0.647-0.947) and 0.851 (95% CI: 0.707-0.995). Survival of ‘SSC’ patients was severely impaired compared to ‘no SSC’ patients (1-year: 46.7% vs 90.2%, log-rank p = 0.004). Conclusions: SSC-CIP is a severe late complication after LTx for COVID-19 ARDS leading to significant morbidity and mortality. GGT appears to be a sensitive parameter able to predict SSC-CIP even at the time of listing

Percutaneous dilatational tracheotomy in high-risk ICU patients

BACKGROUND Percutaneous dilatational tracheotomy (PDT) has become an established procedure in intensive care units (ICU). However, the safety of this method has been under debate given the growing number of critically ill patients with high bleeding risk receiving anticoagulation, dual antiplatelet therapy (DAPT) or even a combination of both, i.e. triple therapy. Therefore, the purpose of this study, including such a high proportion of patients on antithrombotic therapy, was to investigate whether PDT in high-risk ICU patients is associated with elevated procedural complications and to analyse the risk factors for bleeding occurring during and after PDT. METHODS PDT interventions conducted in ICUs at 12 European sites between January 2016 and October 2019 were retrospectively analysed for procedural complications. For subgroup analyses, patient stratification into clinically relevant risk groups based on anticoagulation and antiplatelet treatment regimens was performed and the predictors of bleeding occurrence were analysed. RESULTS In total, 671 patients receiving PDT were included and stratified into four clinically relevant antithrombotic treatment groups: (1) intravenous unfractionated heparin (iUFH, prophylactic dosage) (n = 101); (2) iUFH (therapeutic dosage) (n = 131); (3) antiplatelet therapy (aspirin and/or P2Y12 receptor inhibitor) with iUFH (prophylactic or therapeutic dosage) except for triple therapy (n = 290) and (4) triple therapy (DAPT with iUFH in therapeutic dosage) (n = 149). Within the whole cohort, 74 (11%) bleedings were reported to be procedure-related. Bleeding occurrence during and after PDT was independently associated with low platelet count (OR 0.73, 95% CI 0.56, 0.92, p = 0.009), chronic kidney disease (OR 1.75, 95{\%} CI 1.01, 3.03, p = 0.047) and previous stroke (OR 2.13, 95{\%} CI 1.1, 3.97, p = 0.02). CONCLUSION In this international, multicenter study bronchoscopy-guided PDT was a safe and low-complication airway management option, even in a cohort of high risk for bleeding on cardiovascular ICUs. Low platelet count, chronic kidney disease and previous stroke were identified as independent risk factors of bleeding during and after PDT but not triple therapy

Pulmonary Hypertension in Adults with Congenital Heart Disease: Real-World Data from the International COMPERA-CHD Registry

Introduction: Pulmonary hypertension (PH) is a common complication in patients with congenital heart disease (CHD), aggravating the natural, post-operative, or post-interventional course of the underlying anomaly. The various CHDs differ substantially in characteristics, functionality, and clinical outcomes among each other and compared with other diseases with pulmonary hypertension. Objective: To describe current management strategies and outcomes for adults with PH in relation to different types of CHD based on real-world data. Methods and results: COMPERA (Comparative, Prospective Registry of Newly Initiated Therapies for Pulmonary Hypertension) is a prospective, international PH registry comprising, at the time of data analysis, >8200 patients with various forms of PH. Here, we analyzed a subgroup of 680 patients with PH due to CHD, who were included between 2007 and 2018 in 49 specialized centers for PH and/or CHD located in 11 European countries. At enrollment, the patients’ median age was 44 years (67% female), and patients had either pre-tricuspid shunts, post-tricuspid shunts, complex CHD, congenital left heart or aortic disease, or miscellaneous other types of CHD. Upon inclusion, targeted therapies for pulmonary arterial hypertension (PAH) included endothelin receptor antagonists, PDE-5 inhibitors, prostacyclin analogues, and soluble guanylate cyclase stimulators. Eighty patients with Eisenmenger syndrome were treatment-naïve. While at inclusion the primary PAH treatment for the cohort was monotherapy (70% of patients), with 30% of the patients on combination therapy, after a median observation time of 45.3 months, the number of patients on combination therapy had increased significantly, to 50%. The use of oral anticoagulants or antiplatelets was dependent on the underlying diagnosis or comorbidities. In the entire COMPERA-CHD cohort, after follow-up and receiving targeted PAH therapy (n = 511), 91 patients died over the course of a 5-year follow up. The 5-year Kaplan–Meier survival estimate for CHD associated PH was significantly better than that for idiopathic PAH (76% vs. 54%; p < 0.001). Within the CHD associated PH group, survival estimates differed particularly depending on the underlying diagnosis and treatment status. Conclusions: In COMPERA-CHD, the overall survival of patients with CHD associated PH was dependent on the underlying diagnosis and treatment status, but was significantly better as than that for idiopathic PAH. Nevertheless, overall survival of patients with PAH due to CHD was still markedly reduced compared with survival of patients with other types of CHD, despite an increasing number of patients on PAH-targeted combination therapy

Temperature responsive polymers for controlled oxygen evolution in silica micromotors

Micromotors are self-propelled devices in the nanometer to micrometer range. Their applications cover a wide range of scientific fields such as medicine, environmental analysis and many others. Besides metal-organic frameworks, the micro- or nanoparticles can also be synthesised out of silicate. These particles are then further functionalised and/or loaded to meet the requirements for various applications. Special types of such particles are micro- or nanomotors that contain a catalytically active transition metal, leads to the most important type of propulsion of such motors, the propulsion by bubble evolution. In most cases, on this transition metal sites oxygen bubbles are formed through catalytic decomposition of hydrogen peroxide, leading to a movement of the motors. However, the disadvantage of this kind of micromotors, through the simple synthesis, is the directional independence of the bubble development, since the peroxide can enter on each side of the particle and hence, the bubbles also can emerge from everywhere. In order to stop this movement, the migration of the peroxide molecules and thereby the decomposition has to be prevented. For this, microparticles can be further functionalised with a thermoresponsive polymer. This polymer possesses a lower critical solution temperature (LCST), which means that as soon as a certain temperature is exceeded, the polymer molecules precipitate out of the solution. The explanation behind this is that the hydrogen bonds are no longer sufficient to resist the intrinsic motion of the molecules and thus the polymers bind each other, rather than the solvent water. But if the polymer is covalently attached on the surface of the microparticles, the chains do not precipitate but instead collapse and so stop shielding the particle void surface from the peroxide migration and so start the bubble formation. In this work, different synthetic routes have been followed to synthesise these multifunctional tools. As backbone or framework, mesoporous silica microparticles type MCM-41 prepared by the “atrane” synthesis are used. Through various types of functionalisation approaches, by co-condensation and/or by grafting-to, with derived bipyridine units, different microparticles were synthesised, that can be further equipped with cobalt as catalytically active transition metal. The bipyridine acts as a complexing agent for the cobalt and because it is firmly anchored on the microparticles, the cobalt is preserved. In order to obtain the break function of these micromotors, they are further functionalised with a polymer based on polyphosphazenes. The thermo-responsiveness of the polymer comes from the substituted organic side chains, bound to the phosphorus backbone, bringing specific and adjustable critical solution temperatures. These side chains consist of Jeffamine M-2005, a polyether consisting of a statistical mixture of ethylene oxide and propylene oxide. While the polymers were characterised by 1H, 31P NMR and GPC, the LCST was measured by UV-vis transmittance changes with temperature and by DLS. The silica based-microparticles were characterised by TGA and BET analysis. The oxygen evolution and motion from the prepared microparticles were finally studied under an optical microscope. The different microparticles, those without cobalt, those with cobalt and the fully functionalised with polyphosphazene, were tested in aqueous dispersion and then in hydrogen peroxide solutions. In the final step they were analysed at different temperatures to observe the evolution of oxygen and the temperature depending on/off switch was successfully observed during the oxygen evolution experiment.submitted by Michael Kneidinger, BSc.Universität Linz, Masterarbeit, 2019(VLID)367832