Intermitted pharmacologic pretreatment by xenon, isoflurane, nitrous oxide, and the opioid morphine prevents tumor necrosis factor alpha-induced adhesion molecule expression in human umbilical vein endothelial cells

BACKGROUND: The barrier properties of the endothelium are of critical importance during pathophysiologic processes. These barrier properties depend on an intact cytoskeleton and are regulated by cell adhesion molecules. Tumor necrosis factor alpha (TNF-alpha) is known to induce cell adhesion molecule expression. In myocardium, the protective effect by xenon and isoflurane preconditioning was found to be linked to the cytoskeleton. The authors investigated the impact of different anesthetics and morphine on TNF-alpha-induced endothelial cell adhesion molecule expression. METHODS: Human umbilical vein endothelial cells were isolated from three different preparations. Cells were either left untreated or pretreated with xenon, nitrous oxide, isoflurane (each 0.43 minimum alveolar concentration), or morphine (100 ng/ml) and stimulated with 10 ng/ml TNF-alpha. Reverse-transcription polymerase chain reaction and fluorescence-activated cell sorting of intracellular cell adhesion molecule 1, vascular cell adhesion molecule 1, and E-selectin were performed. Transcriptional activity of nuclear factor kappaB was assessed by infrared electrophoretic mobility shift assay. RESULTS: Tumor necrosis factor alpha significantly induced messenger RNA (mRNA) and protein expression of cell adhesion molecules as well as transcriptional activity of nuclear factor kappaB. All four agents prevented TNF-alpha-induced mRNA and protein expression of intracellular cell adhesion molecule 1. Vascular cell adhesion molecule 1 expression was only blocked by the inhalational anesthetics and not by morphine. None of the four agents had an effect on TNF-alpha induced E-selectin expression. TNF-alpha-induced transcriptional activity of nuclear factor kappaB was decreased by all four agents. CONCLUSION: These results suggest a protective effect of anesthetics on TNF-alpha-induced endothelial cell damag

Current Trends in Inpatient Care and In-Hospital Mortality of Cholangiocarcinoma in Germany: A Systematic Analysis between 2010 and 2019

Background: Cholangiocarcinoma (CCA) is a rare malignant disease of the biliary tract with an increasing incidence and a high mortality worldwide. Systematic data on epidemiological trends, treatment strategies, and in-hospital mortality of CCA in Germany are largely missing. However, the evaluation and careful interpretation of these data could help to further improve the treatment strategies and outcome of CCA patients in the future. Methods: Standardized hospital discharge data from the German Federal Statistical Office were used to evaluate epidemiological and clinical trends as well as the in-hospital mortality of CCA in Germany between 2010 and 2019. Results: A total of 154,515 hospitalized CCA cases were included into the analyses. The number of cases significantly increased over time (p < 0.001), with intrahepatic CCA (62.5%) being the most prevalent tumor localization. Overall, in-hospital mortality was 11.4% and remained unchanged over time. In-hospital mortality was significantly associated with patients’ age and tumor localization. The presence of clinical complications such as (sub)acute liver failure, acute respiratory distress syndrome (ARDS), or acute renal failure significantly increased in-hospital mortality up to 77.6%. In-hospital mortality was significantly lower among patients treated at high annual case volume centers. Finally, treatment strategies for CCA significantly changed over time and showed decisive differences with respect to the hospitals’ annual case volume. Conclusions: Our data provide a systematic overview on hospitalized CCA patients in Germany. We identified relevant clinical and epidemiological risk factors associated with an increased in-hospital mortality that could help to further improve framework conditions for the management of CCA patients in the future

Invasive treatment for esophageal motility disorder in Germany between 2011 and 2019.

(A) The total number of performed procedures increases between 2011 and 2019 over time. (B) Most patients are male (54.9%). (C) Most patients are aged between 31 and 70 years. (D) Achalasia of cardia (K22.0) represents the major treatment indication (95.7%). (E) There are significant differences regarding the regional distribution of performed procedures (BB: Brandenburg, BE: Berlin, BW: Baden-Württemberg, BY: Bavaria, HE: Hesse, HB: Bremen, HH: Hamburg, MV: Mecklenburg-Western Pomerania, NI: Lower Saxony, NW: North Rhine-Westphalia, RP: Rhineland-Palatinate, SH: Schleswig-Holstein, SL: Saarland, SN: Saxony, ST: Saxony-Anhalt, TH: Thuringia).</p

Post-interventional clinical course following invasive treatment for esophageal motility disorder.

(A) The mean duration of post-interventional mechanical ventilation is significantly lower in patients undergoing POEM (29.4 hours) compared to OHM (274.0 hours) and LHM (91.9 hours). (B) The mean duration of hospitalization is 5.7 days following POEM, which is significantly lower compared to patients undergoing OHM (13.7 days) or LHM (7.7 days). (C) The duration of hospitalization decreased from 9.5 days (2011) to 7.7 days (2019) for LHM and remained unchanged with respect to OHM and POEM. (D) The overall hospital mortality of all procedure combined was 0.2%.</p

Detailed description of study population from 2011 to 2019.

Detailed description of study population from 2011 to 2019.</p

Characteristics of study population.

Background/AimsWhile surgery remains a standard treatment for primary esophageal motility disorders (PEMDs), per-oral endoscopic myotomy (POEM) has recently evolved as an alternative. Systematic data on current trends of invasive procedures for PEMDs in Germany are missing.MethodsHospital discharge data were used to evaluate trends and mortality of invasive treatment options for PEMDs in Germany between 2011 and 2019.Results4543 cases of PEMDs (achalasia: n = 4349, dyskinesia of the esophagus: n = 194) receiving open surgery (n = 200), minimal invasive surgery (n = 2366), or POEM (n = 1977) were identified. The relative proportion of POEM significantly increased from 10.9% (2011) to 65.7% (2019). Hospital mortality was 0.2%. The median duration of mechanical ventilation was significantly lower in POEM patients (29.4 hours) compared to open (274.0 hours) or minimal invasive (91.9 hours) surgery. The duration of hospitalization was lowest among POEM patients (5.7 days) compared to surgical procedures (13.7 and 7.7 days).ConclusionWhile the low in-hospital mortality of all procedures combined confirms the solid safety profile of invasive procedures in general, our findings show that POEM has the lowest duration of mechanical ventilation and hospitalization compared to invasive surgical options.</div

Surgical vs. endoscopic treatment of esophageal motility disorder.

(A) Within the study period, the majority of patients (52.1%) underwent LHM followed by POEM (43.5%), while OHM was only rarely performed (4.4%). (B) The relative proportion of POEM shows a stepwise increase from only 10.9% in 2011 to 65.7% in 2019, with 2016 being the year POEM surpassed LHM in number for the first time. (C) The sex ratio of each procedure is comparable. (D) There is a higher proportion of POEM in patients older than 70 years (50.3%), compared to younger age groups (<18 years: 26.1%, 18–30 years: 42.1%, 31–50 years: 42.0%, 51–70 years: 44.4%).</p