Roland M. Schmid

Cardiac Index (CI) is a key-parameter of hemodynamic monitoring. Indicator-dilution is considered as gold standard and can be obtained by pulmonary arterial catheter or transpulmonary thermodilution (TPTD; CItd). Furthermore, CI can be estimated by Pulse-Contour-Analysis (PCA) using arterial wave-form analysis (CIpc). Obviously, adjustment of CIpc to CItd initially improves the accuracy of CIpc. Despite uncertainty after which time accuracy of CIpc might be inappropriate, recalibration by TPTD is suggested after a maximum of 8 h. We hypothesized that accuracy of CIpc might not only depend on time to last TPTD, but also on changes of the arterial wave curve detectable by PCA itself. Therefore, we tried to prospectively characterize predictors of accuracy and precision of CIpc (primary outcome). In addition to “time to last TPTD” we evaluated potential predictors detectable solely by pulse-contour-analysis. Finally, the study aimed to develop a pulse-contour-derived “calibration-index” suggesting recalibration and to validate these results in an independent collective. In 28 intensive-care-patients with PiCCO-monitoring (Pulsion Medical-Systems, Germany) 56 datasets were recorded. CIpc-values at baseline and after intervals of 1 h, 2 h, 4 h, 6 h and 8 h were compared to CItd derived from immediately subsequent TPTD. Results from this evaluation-collective were validated in an independent validation-collective (49 patients, 67 datasets). Mean bias values CItd-CIpc after different intervals ranged between -0.248 and 0.112 L/min/m2. Percentage-error after different intervals to last TPTD ranged between 18.6% (evaluation, 2 h-interval) and 40.3% (validation, 6 h-interval). In the merged data, percentage-error was below 30% after 1 h, 2 h, 4 h and 8 h, and exceeded 30% only after 6 h. “Time to last calibration” was neither associated to accuracy nor to precision of CIpc in any uni- or multivariate analysis. By contrast, the height of CIpc and particularly changes in CIpc compared to last thermodilution-derived CItd(base) univariately and independently predicted the bias CItd-CIpc in both collectives. Relative changes of CIpc compared to CItd(base) exceeding thresholds derived from the evaluation-collective (-11.6% < CIpc-CItd(base)/CItd(base) < 7.4%) were confirmed as significant predictors of a bias |CItd-CIpc| ≥ 20% in the validation-collective. Recalibration triggered by changes of CIpc compared to CItd(base) derived from last calibration should be preferred to fixed intervals.

The detection of adenomatous lesions is a major indicator for quality and competence in colonoscopy. Little is known about adenoma detection rates (ADR) of endoscopy trainees. The aim of our study was to investigate the performance of trainee colonoscopists in detecting adenomas and to depict the shape of adenoma detection learning curves during apprenticeship. We retrospectively investigated a prospectively maintained database of a single tertiary referral center to reveal colonoscopies performed by trainee endoscopists during 2001 and 2013. Colonoscopy reports were chronologically retrieved and separately analyzed for each trainee. Using cumulative curves, courses of trainee’s Adenoma detection rates (ADR) during apprenticeship were displayed. Additionally, procedural data including cecal intubation rate and occurrence of complications were assessed. We retrospectively analyzed 4354 colonoscopies conducted by 10 trainee endoscopists (TE). A median number of 371 investigations were performed by each apprentice. Group ADR was 23%. No significant difference between aggregated ADRs at the beginning (23%) and at the end (22%) of apprenticeship could be determined (p = 0.70). However, individual learning curves showed considerable different slopes. Personal ADR values ranged between 17% and 31%. Overall cecum intubation rate was 99.0 %. Complication rates were low and fulfilled quality requirements recommended in guidelines. From the beginning of education, trainee colonoscopists are capable to provide high-quality investigations considering the detection of adenomas as a benchmark quality indicator. Nevertheless, performance differs markedly between investigators. Therefore, individual detection rates should be reviewed regularly to reveal further need for training.

While HIV, AIDS and atypical Mycobacterium infections are closely linked, the use of Integrase-Inhibitor based cART, notably raltegravir-based regimens is more widespread. RAL should be double-dosed to 800 mg semi-daily in situation of rifampicin co-medication, because RAL is more rapidly metabolized due to rifampicin-induced Uridine-5’-diphosph- gluronosyl-transferase (UGT1A1). Recently, it was speculated that chewed RAL might lead to increased absorption, which might compensate the inductive effect of rifampicin-rapid metabolized RAL, as part of cost-saving effects in countries with high-tuberculosis prevalence and less economic power. We report measurement of raltegravir pharmacokinetics in a 34-year AIDS-patient suffering from disseminated Mycobacterium avium infection with necessity of parenteral rifampicin treatment. RAL levels were measured with HPLC (internal standard: carbamazepine, LLQ 11 ng/ml, validation with Valistat 2.0 program (Arvecon, Germany)). For statistical analysis, a two-sided Wilcoxon signed rank test for paired samples was used. High intra-personal variability in raltegravir serum levels was seen. Comparable Cmax concentrations were found for 800 mg chewed and swallowed RAL, as well as for 400 mg chewed and swallowed RAL. While Cmax seems to be more dependent from overall RAL dosing than from swallowed or chewed tablets, increased AUC12 is clearly linked to higher RAL dosages per administration. Anyway, chewed raltegravir showed a rapid decrease in serum levels. We found no evidence that chewed 400 mg semi-daily raltegravir in rifampicin co-medication leads to optimized pharmacokinetics. There is need for more data from randomized trials for further recommendations.

Transpulmonary thermodilution (TPTD) derived parameters are used to direct fluid management in ICU-patients. Extravascular lung water EVLW and its ratio to pulmonary blood volume (pulmonary vascular permeability index PVPI) have been associated with mortality. In single indicator TPTD pulmonary blood volume (PBV) is estimated to be 25% of global end-diastolic volume (GEDV). A recent study demonstrated marked overestimation of GEDV indexed to body-surface area (BSA; GEDVI) when using a femoral central venous catheter (CVC) for indicator injection due to the additional volume measured in the vena cava inferior. Therefore, a correction formula derived from femoral TPTD and biometric data has been suggested. Consequence, one of the commercially available TPTD-devices (PiCCO; Pulsion Medical Systems, Germany) requires information about CVC site. Correction of GEDVI for femoral CVC can be assumed. However, there is no data if correction also pertains to unindexed GEDV, which is used for calculation of PBV and PVPI. Therefore, we investigated, if also GEDV, PBV and PVPI are corrected by the new PiCCO-algorithm.

Monitoring cardiovascular function in acutely ill patients in the emergency department (ED) is of paramount importance. Arterial pressure (AP) is usually monitored using intermittent oscillometric measurements with an upper arm cuff. The vascular unloading technique (VUT) allows continuous noninvasive AP monitoring. In this study, we compare continuous AP measurements obtained by VUT with intermittent oscillometric AP measurements in ED patients. In addition, we aimed to investigate whether continuous noninvasive AP monitoring allows detection of relevant hypotensive episodes that might be missed with intermittent AP monitoring.

Cystic lesions of the pancreas are detected more frequently due to the improvement of imaging technologies. Their prevalence increases with age. In 95 % of cases, the spectrum of cystic neoplasia includes intraductal papillary mucinous neoplasia (IPMN), mucinous cystic neoplasia (MCN), serous cystic neoplasia, and solid pseudopapillary neoplasia (SPN). Diagnostic procedures aim to distinguish between neoplastic cystic and non‐neoplastic cystic lesions as well as serous and mucinous lesions because of their different malignant potential. In most cases,cystic lesions are detected incidentally by computed tomography and magnetic resonance imaging (MRI) performed for other reasons. In our opinion, MRI/magnetic resonance cholangiopancreatography (MRCP) and endoscopic ultrasound (EUS) are complementary diagnostic procedures. In doubtful cases, cyst fluid analysis might be performed. The most frequent lesions are IPMNs. MRI/MRCP allows the detection of the number of cystic lesions, the relation to the main pancreatic duct, and the size of the lesion. EUS is superior to evaluate mural nodules. The relation to the main pancreatic duct can more easily appreciated with secretin MRI, MCN, SPN as well as main-duct type IPMN and BD-IPMN with “high-risk stigmata” for malignancy should be resected. Asymptomatic BD-IPMN without mural nodules, no main duct involvement, and a size less than 30 mm can be followed with a watchful waiting strategy. Durch die Entwicklung und Verfügbarkeit neuer Bildgebungsverfahren werden zystische Läsionen des Pankreas häufiger diagnostiziert. Die Prävalenz steigt mit dem Alter an. Intraduktale papilläre muzinöse Neoplasien (IPMN), muzinöse zystische Neoplasien (MCN), seröse zystische Neoplasien und solid pseudopapilläre Neoplasien (SPN) machen 95 % des Spektrums der zystischen Neoplasien aus. Die diagnostischen Maßnahmen zielen darauf ab neoplastische von nicht neoplastischen zystischen Läsionen und seröse von muzinösen Läsionen zu unterschieden, da diese ein unterschiedliches malignes Potential aufweisen. In der Mehrzahl der Fälle werden zystische Läsionen zufällig durch CT und MRT Untersuchung entdeckt. Unserer Erfahrung nach sind die MRT/MRCP und der endoskopische Ultraschall komplementäre diagnostische Methoden. Bei unklaren Fällen kann die durch Punktion gewonnene Zystenflüssigkeit untersucht werden. Die häufigste Läsion ist die IPMN. Die MRT/MRCP erlaubt die Detektion der Zahl der zystischen Läsionen, die Beziehung zum Pankreashauptgang und die Größe der Läsion. Der endoskopische Ultraschall ist in der Erkennung muraler Knoten und der Beziehung der Läsion zum Pankreashauptgang bei Seitengang-IPMNs überlegen. MCN, SPN und Hauptgang-IPMNs sowie Seitengang-IPMNs mit Hochrisikozeichen sollten reseziert werden. Asymptomatische Seitengang-IPMNs ohne murale Knoten, ohne Hauptgangbeteiligung und einer Größe von kleiner 3 cm können überwacht werden.

Sexually transmitted diseases and most notably syphilis-infections are rising amongst men who have sex with men. In HIV-co-infected patients, an accelerated clinical course of syphilis neurological involvement is known.

The aim of the study was to investigate the effect of red blood cell (RBC) transfusion on hemodynamic parameters including transpulmonary thermodilution (TPTD)-derived variables.

Histone deacetylases (HDACs) control fundamental physiological processes such as proliferation and differentiation. HDAC inhibitors (HDACi) induce cell cycle arrest and apoptosis of tumor cells. Therefore, they represent promising cancer therapeutics that appear particularly useful in combination therapies. Although HDACi are tested in current clinical trials, the molecular mechanisms modulating the cellular responses toward HDACi are incompletely understood. To gain insight into pathways that limit HDACi efficacy in gastric cancer, we treated a panel of gastric cancer cells with the clinically relevant HDACi suberoylanilide hydroxamic acid (SAHA). We report that higher expression levels of the anti-apoptotic BCL2 family members MCL1 and BCLXL were detectable in cells with high inhibitory concentration 50 (IC50) values for SAHA. Using RNAi, we show that MCL1 and BCLXL lower the efficacy of SAHA. To find strategies to interfere with MCL1 and BCLXL expression, we investigated molecular regulation of both proteins. We show that specific siRNAs against c-MYC as well as pharmacological inhibition of this cancer-relevant transcription factor reduced MCL1 and BCLXL expression. Subsequently, we observed an increase in SAHA efficacy. Our data furthermore demonstrate that two different molecular mechanisms are responsible for the modulation of these factors. Whereas c-MYC controls transcription of MCL1 directly, regulation of BCLXL was due to c-MYC’s capability to regulate the eIF4E gene, which encodes a rate-limiting factor of eukaryotic translation. Our data reveal a new molecular mechanism for how c-MYC controls cell autonomous apoptosis and provide a rationale for a concerted inhibition of HDACs and c-MYC in gastric cancer.