Open Access

Bei der chronisch obstruktiven Lungenerkrankung handelt es sich um eine pulmonale Erkrankung mit persistierender respiratorischer Symptomatik. Für die Erkrankung pathognomonisch ist eine Atemflussminderung aufgrund einer progressiven Atemwegsobstruktion. Trotz individueller Krankheitsverläufe und verschiedenen klinischen Phänotypen resultiert häufig eine chronisch respiratorische Insuffizienz mit obstruktiver Ventilationsstörung, welche sich limitierend auf die Überlebenszeit auswirkt und die Wahrscheinlichkeit für wiederholte Hospitalisierungen erhöht. Die nichtinvasive Beatmung stellt seit Jahren eine etablierte und anerkannte Therapieoption der akuten respiratorischen Insuffizienz bei COPD-Patienten da. Weniger eindeutig verhält sich jedoch die Studienlage bezüglich der Etablierung einer langfristigen außerklinischen NIV-Therapie bei COPD-Patienten mit chronisch respiratorischer Insuffizienz. Kurz- und Langzeiteffekte dieser Therapieoption bei chronisch respiratorischer Insuffizienz wurden in den letzten 20 Jahren nur in wenigen Publikationen untersucht und es konnte kein Vorteil hinsichtlich des Überlebens von Patienten mit Überleitung auf eine LTH-NIV-Therapie gezeigt werden. Ziel dieser retrospektiven Studie war es, die Auswirkungen der NIV-Therapie auf das Langzeitüberleben und die Rehospitalisierung zu untersuchen und mögliche Einflussfaktoren bzw. Prädiktoren auf diese zu identifizieren. Zur Beantwortung der Fragestellung wurden 151 Patienten in die Studie eingeschlossen, welche sich in dem Zeitraum vom 01.01.2012 bis 30.06.2019 aufgrund einer akuten nicht-invasiven Beatmungsnotwenigkeit bei AECOPD in den Abteilungen für innere Medizin der UMG in Behandlung befanden. Vom Gesamtkollektiv wurden 83 Patienten im Anschluss an den Indexkrankenhausaufenthalt direkt auf eine LTH-NIV-Therapie eingestellt. Die Non-NIV-Gruppe bildeten 68 Patienten, welche ohne Überleitung auf eine LTH-NIV-Therapie nach dem Indexaufenthalt aus dem Krankenhaus entlassen wurden. Über ein Follow-up von zwei Jahren wurden Blutgasanalysen, Beatmungsparameter, Rehospitalisierungen und die Mortalität betrachtet. Es wurden eine Überlebenszeitanalyse nach der Kaplan-Meier-Methode sowie eine Cox-Regression zur Analyse mehrerer Einflussgrößen auf das Überleben im Gruppenvergleich durchgeführt. In der vorliegenden retrospektiven Datenauswertung von COPD-Patienten mit akuter nicht-invasiver Beatmungsnotwendigkeit im Rahmen einer AECOPD, konnte gezeigt werden, dass die Einstellung auf eine LTH-NIV-Therapie das Überleben in einem zweijährigen Beobachtungszeitraum signifikant (p=0,027) verbessert. Das 24-Monats-Risiko einer Rehospitalisierung lag in der LTH-NIV-Gruppe bei 41% gegenüber 55,9% in der Non-NIV-Gruppe. Dieses Ergebnis verfehlte nur knapp die statistische Signifikanz (p=0,053). In der statistischen Testung ergab sich ein verringertes Mortalitätsrisiko bei den Patienten, die im direkten Anschluss an eine AECOPD auf eine LTH-NIV-Therapie übergeleitet wurden [HR: 0,37 (0,17; 0,79)].

Acute pancreatitis (AP) is one of the most common and widely increasing gastrointestinal diseases leading to hospitalization without specifically available therapy. Among various etiologies, biliary origin is the most common cause. However, the effects of BAs, given systemically, on AP remains elusive. A detailed characterization of the mechanisms through which BAs contribute to the pathogenesis and severity of AP will greatly improve our understanding of the underlying pathophysiology and may facilitate the development of treatment, early identification of complications, and prevention for AP. In this view, the roles of different circulating BAs using in vitro-to-in vivo models were investigated and the underlying mechanisms through which BAs modulate the severity of AP were addressed. The impact of hydrophobic and hydrophilic BAs on both, isolated acinar cells and different animal models induced by repetitive injections of caerulein or L-arginine, ligation of the pancreatic duct (PDL) or combined bile and pancreatic duct ligation (BPDL), were tested. Disease severity was assessed by biochemical and histological parameters. Serum CCK concentrations were determined by enzyme immunoassay. The binding of CCK1 receptor was measured using fluorescent-labeled CCK. Human BA profiles in AP patients were quantified and that were correlated with etiology as well as clinical course. In acinar cells, hydrophobic BAs mitigated the damaging effects of CCK. The same BAs further enhanced pancreatitis in L-arginine and PDL-based pancreatitis whereas they ameliorated pancreatic damage in the caerulein and BPDL models, in which CCK was involved. The chemical effect of BAs on protease trypsin was also observed, however, it was similar between hydrophobic and hydrophilic compounds. Mechanistically, the binding affinity of the CCK1 receptor was significantly reduced by hydrophobic BAs. In patients, the sum of hydrophobic but not hydrophilic BAs correlated with the etiology and severity of AP. Post-endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis (PEP) was reported to be related with CCK and several pharmaceutical agents have been used to prevent this most common and potentially severe complication, but those are of limited benefit. In this regard, our multicenter multinational randomized control trial was designed to compare the efficacy of indomethacin and N-acetylcysteine (NAC) for the prevention of PEP. A total of 432 ERCP patients from 6 countries were recruited and randomly assigned to receive either NAC (group A, 84 cases), indomethacin (group B, 138 cases), NAC + indomethacin (group C, 115 cases) or placebo (group D, 95 cases) two hours before procedure. The rate of PEP in groups A, B and C in comparison with placebo were 10.7%, 17.4%, 7.8% vs 20% (p = 0.08, 0.614 & 0.01, respectively). Among complications of AP, infection of pancreatic necrosis is one of the most severe consequence that mostly necessitates interventional therapy. A model to identify parameters that are useful for the prediction of infected necrosis at an early stage was developed. A retrospective analysis was conducted in 705 AP patients, who underwent contrast-enhanced computed tomography (CT scan). Both laboratory and clinical parameters were analyzed for an association with infected pancreatic necrosis, which was microbiologically confirmed. A logistic regression analysis with stepwise inclusion of significant variables was used to develop a prediction model. We tested the model quality by receiver operating characteristics analysis. We found a significant association between 11 parameters with an infection including albumin, creatinine, C-reactive protein (CRP), and alcoholic etiology, which were independent variables in the final predictive model with an area under the curve of 0.819. In the same cohort in which we developed the prediction model above, 89 AP cases with necrotic complications diagnosed by CT scan were identified. These complications with high morbidity and mortality required endoscopic drainage, which possibly accompanies severe adverse events. All complications which occurred in patients who underwent those procedures and their associated features were retrospectively analyzed. Positive necrosis cultures and a larger diameter of the intervened necroses were significant factors associated with the occurrence of adverse events, in which the former was the most significant predictor with Odds Ratio of 6.1. The entire work demonstrated that hydrophobicity of BAs and the involvement of CCK are relevant for the clinical course of AP. Systemic BAs may affect the severity of AP by interfering with the binding of the CCK1 receptor. Oral NAC is effective for prevention of PEP and the combination of NAC plus indomethacin resulted in the lowest PEP rate. A model using albumin, creatinine, CRP, and alcoholic etiology can differentiate infected and sterile pancreatic necrosis and control of infection is crucial for successful endoscopic drainage therapy in complicated AP. The exact pathophysiologic mechanisms, especially in CCK-related pathways, and the potential impact of BAs in human AP, in particular in preventing PEP, need to be investigated in further studies.

In dieser retrospektiven Studie sind ausgehend von 527 der Gesamtkohorte 345 Patienten mit einer CTEPH analysiert worden. Die Stratifizierung der Patienten erfolgte in zwei Gruppen: Der konventionellen Gruppe, in der Patienten eine medikamentöse PH-Therapie erhalten haben, und der interventionellen Gruppe, in der Patienten eine Intervention in Form einer pulmonalen Endarteriektomie (PEA) oder einer pulmonalen Ballonangioplastie (BPA) erhalten haben. Der Beobachtungszeitraum erstreckte sich vom 01.01.2002 bis zum 31.12.2020. In der gesamten Nachbeobachtungszeit (Median: 3.5 Jahre; mean ± SD, 4.4 ± 3.6 Jahre) starben ins-gesamt 78 Patienten, entsprechend einem Prozentsatz von 22.6 % (n = 345), davon in der konventionellen Gruppe 29 % (n = 60) und in der interventionellen Gruppe 13 % (n = 18). Die wichtigste Schlussfolgerung der vorliegenden Arbeit ist der prädiktive Vorhersagewert der Überlebenswahrscheinlichkeit der mittels CPET bestimmten maximal Sauerstoffaufnahme VO2 (Peak) für Patienten, die aus verschiedensten Gründen keiner interventionellen Therapie im Sinne der etablierten pulmonale Endarteriektomie (PEA) oder der pulmonale Ballonangioplastie (BPA) zugänglich sind. Die in dieser Studie untersuchten Parameter, die zu Beginn des Beobachtungszeitraums. d. h. vor der Intervention, erhoben wurden, lassen in der interventionellen Gruppe keine verlässliche Vorhersage für das Überleben zu. In der konventionellen Gruppe konnten in der vorliegenden Arbeit jedoch eine Vielzahl an prognoserelevanten Parametern identifiziert werden. Maßgeblich sind dies neben der bereits erwähnten VO2 (Peak) [% SW] die Parameter PET CO2 in Ruhe und an der AT, die VE/VCO2 in Ruhe und an der AT. Der VE/VCO2-Slope und die PET CO2 (Peak) sind ebenso prognoserelevant. Größere Studienkollektive mit einem längeren Beobachtungszeitraum könnten sich mit einer höheren Sensitivität auch der Frage widmen, ob es nicht doch einen relevanten CPET-Parameter zur Prognoseabschätzung auch bei interventionell versorgten Patienten gibt. Ein Ansatz da-für wäre CPET-Untersuchungen in definierten Zeitintervallen nach der operativen Intervention. Weiterführende Studien sollten zudem unter diesem Aspekt auch die Frage des Einsatzes der CPET über die Basisdiagnostik hinaus als Verlaufsparameter untersuchen und außerdem auf längere Beobachtungsphasen ausgedehnt werden, um weitere Langzeitdaten erheben zu können.

Background Previous work has focused on speckle-tracking echocardiography (STE)-derived global longitudinal and circumferential peak strain as potential superior prognostic metric markers compared with left ventricular ejection fraction (LVEF). However, the value of regional distribution and the respective orientation of left ventricular wall motion (quantified as strain and derived from STE) for survival prediction have not been investigated yet. Moreover, most of the recent studies on risk stratification in primary and secondary prevention do not use neural networks for outcome prediction. Purpose To evaluate the performance of neural networks for predicting all cause-mortality with different model inputs in a moderate-sized general population cohort. Methods All participants of the second cohort of the population-based Study of Health in Pomerania (SHIP-TREND-0) without prior cardiovascular disease (CVD; acute myocardial infarction, cardiac surgery/intervention, heart failure and stroke) and with transthoracic echocardiography exams were followed for all-cause mortality from baseline examination (2008-2012) until 2019. A novel deep neural network architecture ‘nnet-Surv-rcsplines’, that extends the Royston-Parmar- cubic splines survival model to neural networks was proposed and applied to predict all-cause mortality from STE-derived global and/or regional myocardial longitudinal, circumferential, transverse, and radial strain in addition to the components of the ESC SCORE model. The models were evaluated by 8.5-year area-under-the-receiver-operating-characteristic (AUROC) and (scaled) Brier score [(S)BS]and compared to the SCORE model adjusted for mortality rates in Germany in 2010. Results In total, 3858 participants (53 % female, median age 51 years) were followed for a median time of 8.4 (95 % CI 8.3 – 8.5) years. Application of ‘nnet-Surv-rcsplines’ to the components of the ESC SCORE model alone resulted in the best discriminatory performance (AUROC 0.9 [0.86-0.91]) and lowest prediction error (SBS 21[18-23] %). The latter was significantly lower (p <0.001) than the original SCORE model (SBS 11 [9.5 - 13] %), while discrimination did not differ significantly. There was no difference in (S)BS (p= 0.66) when global circumferential and longitudinal strain were added to the model. Solely including STE-data resulted in an informative (AUROC 0.71 [0.69, 0.74]; SBS 3.6 [2.8-4.6] %) but worse (p<0.001) model performance than when considering the sociodemographic and instrumental biomarkers, too. Conclusion Regional myocardial strain distribution contains prognostic information for predicting all-cause mortality in a primary prevention sample of subjects without CVD. Still, the incremental prognostic value of STE parameters was not demonstrated. Application of neural networks on available traditional risk factors in primary prevention may improve outcome prediction compared to standard statistical approaches and lead to better treatment decisions.

Low risk prostate cancer does not always necessitate aggressive or invasive intervention and is best monitored through active surveillance, but in daily practice a majority of men seek a more proactive approach. Therefore, tertiary chemoprevention is an attractive option for men seeking a way to slow disease progression. Several natural anti-carcinogens have been identified in soy beans, especially isoflavones. Case series have been published, demonstrating a positive influence of isoflavones on PSA serum levels in prostate cancer. Therefore, a systematic review of the effect of isoflavones versus placebo on PSA levels in localized prostate cancer was conducted, following the recommendations of the Cochrane Handbook of systematic Reviews. On the whole, the primary aim of this review is to summarize the evidence for the use of isoflavones in localized prostate cancer in terms of PSA response. In total, we identified four relevant RCTs involving 298 treated men. The result of this synopsis was that none of the studies showed a significant effect on serum PSA levels, suggesting that isoflavone intake has no effect on biochemical progression. The influence of isoflavones on overall survival in localized prostate cancer remains unclear. Nevertheless, there are indications that isoflavones may be clinically beneficial, for example regarding lipid metabolism and cholesterol. Isoflavones represent a safe therapeutic option with few side effects, where further interdisciplinary research is needed.