Abstract Background/Introduction Alcohol use disorder (AUD) is associated with the development of psychiatric conditions as well as alcoholic liver disease (ALD). Ethanol toxicity but also the intestinal microbiota are important drivers of fibrogenesis in the liver and eventually also of the myocardium. Purpose The aim of our study was the investigation of simultaneous development of fibrosis in liver and heart in patients with early ALD. Methods The HALFWAY-Study is a cohort study, recruiting patients with ALD during a detoxification program. Liver stiffness was measured by non-invasive elastography (ARFI, Acoustic Radiation Force Impulse). Echocardiographic measured E/e' (early ventricle filling velocity, E / mitral annular early diastolic velocity, e') and left atrial volume (LaVol) were used as surrogate markers for atrial filling pressure, which in case of normal de-loading of the left ventricle, correlates with diastolic dysfunction. Results 50 patients were included into the study (females n=27, males n=23). Participants were young (mean age 43.3 years ± 7.3), non-obese (body mass index; BMI 23.9 kg/m2 ±3.9) and non-diabetic (HbA1c 5.1% ± 0.3), ruling out metabolic disease. All patients displayed normal ejection fraction (EF; 61.3% ± 9.1) a global longitudinal strain (4 chamber view) of −15.03±3.7 and NTproBNP (50 pg/ml; IQR 46.5). 95% of patients reported alcohol consumption more than four times a week, with 65% drinking 7–8 drinks per day and 25% consuming more than daily 10 drinks. The mean liver stiffness was 6.5 kPa ± 4.2, whereby in 18% of participants a significant liver fibrosis was diagnosed. We could observe a significant correlation between non-invasive liver stiffness measurements (ARFI) and E/e' (p=0.019, R=0.338) as well as LaVol (p=0.043, R=0.29). In a multivariate linear regression model using ARFI, EF, LaVol and global strain as independent variables, using the backward selection method (R2=0.114, p=0.022 for the final model), we identified ARFI as the only significant predictor of E/e' (B=0,337; p=0.022). Conclusion In patients with early ALD liver stiffness (measured by ARFI) independently predicts E/e' which might indicate simultaneous fibrogenesis of liver and heart. Funding Acknowledgement Type of funding sources: Foundation. Main funding source(s): ÖGGH

Introduction Alcoholic liver disease (ALD) is the hepatic manifestation of alcohol overconsumption (alcohol use disorder, AUD). Ethanol toxicity, systemic pro-inflammatory cytokines as well as the intestinal microbiota contribute to progression of inflammation and fibrosis in the liver. Fibrogenesis in the heart, with impaired myocardial relaxation, is clinically characterized as diastolic heart dysfunction. The goal of our study is the investigation of circulating metabolites, microbiota signature and clinical characteristics associated with the simultaneous development of liver and heart fibrosis in patients with AUD.

Introduction Excessive alcohol consumption remains a global health issue, leading to the development of alcoholic liver disease (ALD), which comprises a spectrum of liver injuries including steatosis, steatohepatitis, fibrosis and, ultimately, cirrhosis. Ethanol toxicity, pro-inflammatory cytokines as well as the microbiota influence the development of ALD. The aim of our study was to investigate whether there is a measurable relation between different types of diets and the development of alcohol-induced injuries on the liver.

•High gradients along a stenosed aortic valve are the cause of Heyde syndrome.•With high-output cardiac failure, even mild aortic stenosis can cause Heyde syndrome.•When anemia causes a high-output state, this can worsen blood bloss in Heyde syndrome.

Background: Fibroblast growth factor-23 produced by osteocytes regulates calcium and phosphate homeostasis which are cornerstones for bone integrity. Recently, FGF23 was also found to be directly related with both severity and prognosis of heart failure. However, the mechanism of FGF23 regulation in heart failure, particularly in patients with preserved renal function is poorly understood. Methods: In this retrospective single center trial we assessed the association of systemic inflammation (surrogated by CRP) and FGF23 regulation in 221 stable non-ischemic heart failure patients (age ≥ 18) with reduced ejection fraction and an estimated glomerular filtration rate of more than 60 ml/min/1.73m². Furthermore, we analyzed the prognostic ability of FGF23 and CRP in this population. Fasting ct-FGF23, highly sensitive CRP and a comprehensive panel of further biomarkers, as well as invasive hemodynamic measures from right heart catheterization, were used for univariate and multivariate regression analysis. Results: In bivariate correlation analysis ct-FGF23 was correlated with Cardiac output (r= -0.42); NTproBNP (r=0.34) and CRP (r=0.31); for all of those p < 0.001. Multivariate linear regression analysis revealed CRP and CO as independently associated with ct-FGF23 (total model fit; r²=0.32; p <0.001). In time to event analysis ct-FGF23 was the only independent parameter predicting transplant-free survival. Conclusion: Our data indicate an association of systemic inflammation and FGF23 in heart failure independent from renal function and supports the hypothesis that FGF23 may be directly involved in heart failure.

Purpose: Chronic inflammation, even at subclinical levels, is associated with adverse long-term outcome. Patients and Methods: In this prospective, observational study, 66 critically ill patients surviving to hospital discharge were included. C-reactive protein (CRP) levels were determined at hospital discharge, 1, 2, and 6 weeks after hospital discharge. All the patients were repeatedly screened for adverse events resulting in rehospitalization or death for 1.5 years. Results: After hospital discharge, over two-thirds of the patients exhibited elevated CRP levels (>2.0 mg/L). During the first week, CRP decreased compared with hospital discharge (P < 0.001) but did not change after week 1 (P = 0.67). Age (P = 0.24), surgical status (P = 0.95), or sepsis (P = 0.77) did not influence the CRP course. The latter differed between patients with (n = 15) and without (n = 51) adverse events (P = 0.003). CRP levels of patients without adverse events persistently decreased after hospital discharge (P = 0.03), whereas those of patients with adverse events did not (P = 0.86) but rebounded early. Conclusions: Plasma CRP levels in critically ill patients decreased during the first week after hospital discharge but remained unchanged during the subsequent 5 weeks. Over two-thirds of the patients exhibited elevated CRP levels compatible with chronic sub-clinical inflammation. Persistently elevated CRP levels after hospital discharge are associated with higher risk of rehospitalization.

Zusammenfassung Die lebensbedrohliche Hyperthermie wird durch eine primär schwere Störung des autonomen Nervensystems einhergehend mit einem Hypermetabolismus der quergestreiften Muskulatur verursacht. Kerntemperaturen erreichen dabei praktisch immer die 40 °C und mehr. Auslöser sind in den meisten Fällen Psychopharmaka (Antidepressiva, Neuroleptika), aber auch eine Reihe anderer Medikamente (Antihistaminika, Antibiotika, Parkinsonmittel, Schmerzmittel) und schließlich volatile Anästhetika. In seltenen Fällen führen Stress, Hitze und körperliche Anstrengungen („non drug induced“) zu einem Hyperthermie-Syndrom. Die Leitsymptome betreffen das zentrale und periphere autonome Nervensystem (Neurotransmitter) sowie in praktisch allen Fällen die quergestreifte Muskulatur. Dies geschieht entweder durch Dysregulation der motorischen Endplatte (Serotonin, Anticholinergika) oder durch intrazelluläre Kalziumüberladung (volatile Anästhetika, Succinylcholin). Die schwere Hyperthermie führt schließlich zu einem Zusammenbruch des autonomen Nervensystems, zu einer Rhabdomyolyse mit Verbrauchskoagulopathie und letztendlich zum Multiorganversagen. Therapeutisch gelten neben dem Absetzen des auslösenden Agens die symptomatologisch, intensivmedizinischen Maßnahmen zur Stabilisierung der Organfunktionen und gehen fließend über in die Therapie der Multiorgandysfunktion. Die Therapie des „Leitsymptoms“ Hyperthermie gelingt nur durch physikalische Maßnahmen, beginnend mit einfachen pflegerischen Maßnahmen bis hin zum Einsatz invasiver Kühlsysteme, eventuell begleitet durch die Gabe von nicht depolarisierenden Muskelrelaxantien.

Die lebensbedrohliche Hyperthermie wird durch eine primär schwere Störung des autonomen Nervensystems einhergehend mit einem Hypermetabolismus der quergestreiften Muskulatur verursacht. Kerntemperaturen erreichen dabei praktisch immer die 40 °C und mehr. Auslöser sind in den meisten Fällen Psychopharmaka (Antidepressiva, Neuroleptika), aber auch eine Reihe anderer Medikamente (Antihistaminika, Antibiotika, Parkinsonmittel, Schmerzmittel) und schließlich volatile Anästhetika. In seltenen Fällen führen Stress, Hitze und körperliche Anstrengungen („non drug induced“) zu einem Hyperthermie-Syndrom. Die Leitsymptome betreffen das zentrale und periphere autonome Nervensystem (Neurotransmitter) sowie in praktisch allen Fällen die quergestreifte Muskulatur. Dies geschieht entweder durch Dysregulation der motorischen Endplatte (Serotonin, Anticholinergika) oder durch intrazelluläre Kalziumüberladung (volatile Anästhetika, Succinylcholin). Die schwere Hyperthermie führt schließlich zu einem Zusammenbruch des autonomen Nervensystems, zu einer Rhabdomyolyse mit Verbrauchskoagulopathie und letztendlich zum Multiorganversagen. Therapeutisch gelten neben dem Absetzen des auslösenden Agens die symptomatologisch, intensivmedizinischen Maßnahmen zur Stabilisierung der Organfunktionen und gehen fließend über in die Therapie der Multiorgandysfunktion. Die Therapie des „Leitsymptoms“ Hyperthermie gelingt nur durch physikalische Maßnahmen, beginnend mit einfachen pflegerischen Maßnahmen bis hin zum Einsatz invasiver Kühlsysteme, eventuell begleitet durch die Gabe von nicht depolarisierenden Muskelrelaxantien.

Die lebensbedrohliche Hyperthermie wird durch eine primär schwere Störung des autonomen Nervensystems einhergehend mit einem Hypermetabolismus der quergestreiften Muskulatur verursacht. Kerntemperaturen erreichen dabei praktisch immer 40 °C und mehr. Auslöser sind in den meisten Fällen Psychopharmaka (Antidepressiva, Neuroleptika), aber auch ein Reihe anderer Medikamente (Antihistaminika, Antibiotika, Parkinson-Mittel, Schmerzmittel) und schließlich volatile Anästhetika („drug induced“). In seltenen Fällen führt Stress, Hitze und körperliche Anstrengung („non drug induced“) zu einem Hyperthermiesyndrom. Die Leitsymptome betreffen das zentrale und periphere autonome Nervensystem (Neurotransmitter) und in praktisch allen Fällen die quergestreifte Muskulatur entweder durch Dysregulation der motorischen Endplatte (Serotonin, Anticholinergika) oder durch intrazelluläre Kalziumüberladung (volatile Anästhetika, Succinylcholin). Die schwere Hyperthermie führt schließlich zu einem Zusammenbruch des autonomen Nervensystems, zu einer Rhabdomyolyse mit Verbrauchskoagulopathie und letzten Endes zum Multiorganversagen. Therapeutisch gelten neben dem Absetzten des auslösenden Agens, je nach Schweregrad, die symptomatologischen intensivmedizinischen Maßnahmen zur Stabilisierung der Organfunktionen. Sie gehen fließend in die Therapie der Multiorgandysfunktion über. Die Therapie des Leitsymptoms Hyperthermie gelingt nur durch physikalische Interventionen beginnend mit einfachen pflegerischen Maßnahmen bis hin zum Einsatz invasiver Kühlsysteme eventuell begleitend von Einsatz nicht depolarisierender Muskelrelaxanzien.

Malignant hyperthermia is a life-threatening disease caused by derangement of the autonomic nerve system and hypermetabolism of the peripheral musculature. Commonly body core temperatures of more than 40 °C will be found in this disease which is caused mostly by psychopharmacological drugs like antidepressants, neuroleptics but also antibiotics, pain killers, anti-Parkinson drugs, and volatile anesthetics. The inducers of malignant hyperthermia interact with postsynaptic receptors (serotonin, anticholinergics) or muscular intracellular structures responsible for calcium utilization (volatile anesthetics, succinylcholine). Rarely malignant hyperthermia is a consequence of mental stress or vigorous exercise and or heat. Malignant hyperthermic syndromes lead to a severe dysbalance of the autonomic nerve system accompanied by rhabdomyolysis, disseminated intravascular coagulopathy, and finally multi-organ failure. Accordingly, medical management is primarily directed to stabilize vital functions, withdrawal of the causing drug, and if possible antagonizing toxic substances. The leading symptom hyperthermia needs to be treated physically with available cooling systems.

Background Intravenous thrombolysis for ischaemic stroke remains underused worldwide. We aimed to assess whether our statewide comprehensive stroke management programme would improve thrombolysis use and clinical outcome in patients.Methods In 2008-09, we designed the Tyrol Stroke Pathway, which provided information campaigns for the public and standardised the entire treatment pathway from stroke onset to outpatient rehabilitation. It was commenced in Tyrol, Austria, as a long-term routine-care programme and aimed to include all patients with stroke in the survey area. We focused on thrombolysis use and outcome in the first full 4 years of implementation (2010-13).Findings We enrolled 4947 (99%) of 4992 patients with ischaemic stroke who were admitted to hospitals in Tyrol; 675 (14%) of the enrollees were treated with alteplase. Thrombolysis administration in Tyrol increased after programme implementation, from 160 of 1238 patients (12-9%, 95% CI 11.1-14-9) in 2010 to 213 of 1266 patients (16.8%, 14-8-19.0) in 2013 (p(trent) (2010-13) < 0.0001). Differences in use of thrombolysis in the nine counties of Tyrol in 2010 (range, 2.2-22.6%) were reduced by 2013 (12.1-22-5%). Median statewide door-to-needle time decreased from 49 min (IQR 35-60) in 2010 to 44 min (29-60) in 2013; symptomatic post-thrombolysis intracerebral haemorrhages occurred in 28 of 675 patients (4.1%, 95% CI 2.8-5.9) during 2010-13. In four Austrian states without similar stroke programmes, thrombolysis administration remained stable or declined between 2010 and 2013 (mean reduction 14.4%, 95% CI 10.9-17.9). Although the 3-month mortality was not affected by our programme (137 [13%] of 1060 patients in 2010 vs 143 [13%] of 1069 patients in 2013), 3-month functional outcome significantly improved (modified Rankin Scale score 0-1 in 375 [40%] of 944 patients in 2010 vs 493 [53%] of 939 in 2013; score 0-2 in 531 [56%] patients in 2010 and 615 [65%] in 2013; Ptrend2010-13 <0.0001).Interpretation During the period of implementation of our comprehensive stroke management programme, thrombolysis administration increased and clinical outcome significantly improved, although mortality did not change. We hope that these results will guide health authorities and stroke physicians elsewhere when implementing similar programmes for patients with stroke.

In critically ill children, in-line microfilters may reduce the incidence of the systemic inflammatory response syndrome (SIRS), the overall complication and organ dysfunction rate. No data on the use of in-line microfilters exist in critically ill adults.

Background In this multi-centre, randomised, placebo-controlled pilot trial, we investigated the clinical and haemodynamic effects of the endothelin-receptor blocker Bosentan in patients with heart failure, preserved ejection fraction and pulmonary hypertension (PH-HFpEF).Materials and Methods Eligible patients received either 12 weeks of Bosentan therapy, or a placebo drug. Patients were thereafter followed for a further period of 12 weeks without the study medication. At three points during the study (study Commencement, Week 12 and Week 24), a six-minute walk test (6MWT), echocardiographic and laboratory assessments were performed, as well as a quality of life survey. Right heart catheterisation (RHC) was undertaken at commencement only. The study was aborted early, after an interim analysis favoured the placebo.Results Six-minute walk distance (6MWD) did not change in the Bosentan group (309.7 +/- 96.3m (Commencement), 317.0 +/- 126.1m (Week 12), 307.0 +/- 84.4m (Week 24); p = 0.86), but almost reached statistical significance in the placebo group from 328.8 +/- 79.6m, to 361.6 +/- 98.2m and 384.0 +/- 74.9m (Week 24); p = 0.075. In the placebo group, estimated systolic pulmonary artery pressure (measured via echocardiography) significantly decreased (from 62.3 +/- 16.7 mmHg [Commencement], 45.3 +/- 13.9 mmHg [Week 12], to 44.6 +/- 14.5 mmHg [Week 24]; p = 0.014) as did right atrial pressure (13.1 +/- 5.3 [Commencement], 10.0 +/- 3.8 [Week 12], to 9.4 +/- 3.2 [Week 24]; p = 0.046).Conclusion Despite this study's limited sample size and premature cessation, it nevertheless suggests that endothelin receptor blockade in patients with PH-HFpEF may have no beneficial effects and could even be detrimental in comparison to a placebo.

A heart rate >90 bpm serves as one of four characteristics defining the systemic inflammatory response syndrome and is used in scoring systems to predict in-hospital mortality of intensive care unit (ICU) patients. Despite its central role in critical illness, specific data regarding the relationship between heart rate and outcome are rare.

Exercise capacity in patients with dilated cardiomyopathy has low correlation to resting left ventricular function. Dysfunctional autonomic activity, cardiomechanics and inflammation are associated with exercise capacity but were investigated under inhomogeneous situations. It remains essentially unclear which factor mainly determines exercise capacity in dilated cardiomyopathy.

ABSTRACT Prospective studies addressing the clinical value of broad-range PCR using the internal transcribed spacer region (ITS) for diagnosis of microscopy-negative fungal infections in nonselected patient populations are lacking. We first assessed the diagnostic performance of ITS rRNA gene PCR compared with that of routine microscopic immunofluorescence examination. Second, we addressed prospectively the impact and clinical value of broad-range PCR for the diagnosis of infections using samples that tested negative by routine microscopy; the corresponding patients' data were evaluated by detailed medical record reviews. Results from 371 specimens showed a high concordance of >80% for broad-range PCR and routine conventional methods, indicating that the diagnostic performance of PCR for fungal infections is comparable to that of microscopy, which is currently considered part of the “gold standard.” In this prospective study, 206 specimens with a negative result on routine microscopy were analyzed with PCR, and patients' clinical data were reviewed according to the criteria of the European Organization for Research and Treatment of Cancer/Invasive Fungal Infections Cooperative Group and the National Institute of Allergy and Infectious Diseases Mycoses Study Group. We found that broad-range PCR showed a sensitivity, specificity, positive predictive value, and negative predictive value of 57.1%, 97.0%, 80%, and 91.7%, respectively, for microscopy-negative fungal infections. This study defines a possible helpful role of broad-range PCR for diagnosis of microscopy-negative fungal infections in conjunction with other tests.