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Synchronous bilateral breast cancer (sBBC) occurs after both breasts have been affected by the same germline genetics and environmental exposures. Little evidence exists regarding immune infiltration and response to treatment in sBBCs. Here we show that the impact of the subtype of breast cancer on levels of tumor infiltrating lymphocytes (TILs, n = 277) and on pathologic complete response (pCR) rates (n = 140) differed according to the concordant or discordant subtype of breast cancer of the contralateral tumor: luminal breast tumors with a discordant contralateral tumor had higher TIL levels and higher pCR rates than those with a concordant contralateral tumor. Tumor sequencing revealed that left and right tumors (n = 20) were independent regarding somatic mutations, copy number alterations and clonal phylogeny, whereas primary tumor and residual disease were closely related both from the somatic mutation and from the transcriptomic point of view. Our study indicates that tumor-intrinsic characteristics may have a role in the association of tumor immunity and pCR and demonstrates that the characteristics of the contralateral tumor are also associated with immune infiltration and response to treatment.

Endoscopic retrograde cholangiopancreatography (ERCP) is the mainstay for interventional treatment of biliopancreatic diseases, and guidewires are decisive for successful treatment.A randomized, multicenter, open-label study was conducted in patients in whom a guidewire was required in ERCP. Success rate and duration of the investigation were evaluated by randomly applying hydrophilic guidewires with a straight tip (ST) or an angled tip (AT) configuration, with normal (type NF) or enhanced (type EF) flexibility. Randomization was stratified by indication, i.e., stricture of the intra-hepatic bile ducts, stricture of the extrahepatic bile ducts, obstruction by bile duct stones, or interventions involving the pancreas. Cross-over was allowed if the initially allocated guidewire did not result in treatment success.Four hundred fifty-three patients were included, and 422 were finally analyzed. In 363 procedures (86%), the initially allocated wirés use resulted in treatment success. The success rate for using a guidewire with an angled tip configuration was 87.5 vs. 79.9% in a straight tip configuration (ERCP guidewires with an angled tip were more frequently successful when compared to straight tipped wires and most successful in treating intrahepatic strictures. Guidewires with standard vs. enhanced tip flexibility showed equal success rates in all indications.

To evaluate the diagnostic accuracy of the app-based diagnostic tool Ada and the impact on patient outcome in the emergency room (ER).Artificial intelligence-based diagnostic tools can improve targeted processes in health care delivery by integrating patient information with a medical knowledge base and a machine learning system, providing clinicians with differential diagnoses and recommendations.Patients presenting to the ER with abdominal pain self-assessed their symptoms using the Ada-App under supervision and were subsequently assessed by the ER physician. Diagnostic accuracy was evaluated by comparing the App-diagnoses with the final discharge diagnoses. Timing of diagnosis and time to treatment were correlated with complications, overall survival, and length of hospital stay.In this prospective, double-blinded study, 450 patients were enrolled and followed up until day 90. Ada suggested the final discharge diagnosis in 52.0% (95% CI [0.47, 0.57]) of patients compared with the classic doctor-patient interaction, which was significantly superior with 80.9% (95% CI [0.77, 0.84], P0.001). However, when diagnostic accuracy of both were assessed together, Ada significantly increased the accuracy rate (87.3%, P0.001), when compared with the ER physician alone. Patients with an early time point of diagnosis and rapid treatment allocation exhibited significantly reduced complications ( P0.001) and length of hospital stay ( P0.001).Currently, the classic patient-physician interaction is superior to an AI-based diagnostic tool applied by patients. However, AI tools have the potential to additionally benefit the diagnostic efficacy of clinicians and improve quality of care.

Zusammenfassung Hintergrund und Fragestellung Die Severe acute respiratory syndrome coronavirus type 2(SARS-CoV-2)-Pandemie hat die Ausbildung von Medizinstudierenden grundlegend verändert. Die Notwendigkeit von Kontaktbeschränkungen und die damit einhergehende Forderung nach Distanzunterricht hat dazu geführt, dass innerhalb kurzer Zeit digitale Lehrformate umgesetzt werden mussten. Ziel dieser Arbeit war die Auswertung der studentischen Evaluationsergebnisse für virtuellen Unterricht im Fach Hals-Nasen-Ohren-Heilkunde während der SARS-CoV-2-Pandemie und ein Vergleich mit den zuvor erhobenen Evaluationsergebnissen unter Präsenzbedingungen. Material und Methoden Untersucht wurden die Evaluationsergebnisse für die Blockpraktika im Wintersemester 2020/21 und im Sommersemester 2021, die in einem virtuellen Format mit kurzer Präsenzphase durchgeführt wurden, sowie die der komplett im konventionellen Präsenzformat durchgeführten Praktika von Sommersemester 2018 bis Wintersemester 2019/20. Die anonyme Befragung der Studierenden bezog sich auf verschiedene Aspekte der Lehrveranstaltung, wie z. B. Organisation, Didaktik und Lernatmosphäre. Ergebnisse Von 16 abgefragten Kategorien zeigten 14 (87,5%) signifikant bessere Evaluationsergebnisse für die virtuellen Praktika verglichen mit den zuvor im Präsenzformat durchgeführten Praktika. Diese sehr positive Bewertung des digitalen Lehrangebots zeigte im Pandemieverlauf über die Dauer von zwei Semestern keine signifikante Änderung. Schlussfolgerung Die vorliegenden Daten belegen die hohe Akzeptanz eines digitalen Lehrangebots im Fach HNO-Heilkunde für Studierende. Auch wenn unerlässliche Bestandteile der ärztlichen Ausbildung, wie der Unterricht am Patienten und das Erlernen klinisch-praktischer Fertigkeiten, weiterhin nur im Präsenzformat realisiert werden können, legen die Ergebnisse nahe, dass digitale Elemente auch nach der SARS-CoV-2-Pandemie eine Rolle im Medizinstudium spielen könnten.

The main disadvantage of plastic stents is the high rate of stent occlusion. The usual replacement interval of biliary plastic stents is 3 months. This study aimed to investigate if a shorter interval of 6-8 weeks impacts the median premature exchange rate (mPER) in benign and malignant biliary strictures.All cases with endoscopic retrograde cholangiopancreatography (ERCP) and plastic stent placement were retrospectively analyzed since establishing an elective replacement interval of every 6-8 weeks at our institution and mPER was determined.A total of 3979 ERCPs (1199 patients) were analyzed, including 1262 (31.7%) malignant and 2717 (68.3%) benign cases, respectively. The median stent patency (mSP) was 41 days (range 14-120) for scheduled stent exchanges, whereas it was 17 days (1-75) for prematurely exchanged stents. The mPER was significantly higher for malignant (28.1%, 35-50%) compared with benign strictures (15.2%, 10-28%), P 0.0001, respectively. mSP was significantly shorter in cases with only one stent (34 days [1-87] vs 41 days [1-120]) and in cases with only a 7-Fr stent (28 days [2-79]) compared with a larger stent (34 days [1-87], P = 0.001). Correspondingly, mPER was significantly higher in cases with only one stent (23% vs 16.2%, P 0.0001) and only a 7-Fr stent (31.3% vs 22.4%, P = 0.03).A shorter replacement interval does not seem to lead to a clinically meaningful reduction of mPER in benign and malignant strictures. Large stents and multiple stenting should be favored as possible.

Penile squamous cell carcinomas are rare tumor entities throughout Europe. Early lymphonodal spread urges for aggressive therapeutic approaches in advanced tumor stages. Therefore, understanding tumor biology and its microenvironment and correlation with known survival data is of substantial interest in order to establish treatment strategies adapted to the individual patient. Fifty-five therapy naïve squamous cell carcinomas, age range between 41 and 85 years with known clinicopathological data, were investigated with the use of tissue microarrays (TMA) regarding the tumor-associated immune cell infiltrate density (ICID). Slides were stained with antibodies against CD3, CD8 and CD20. An image analysis software was applied for evaluation. Data were correlated with clinicopathological characteristics and overall survival. There was a significant increase of ICID in squamous cell carcinomas of the penis in relation to tumor adjacent physiological tissue. Higher CD3-positive ICID was significantly associated with lower tumor stage in our cohort. The ICID was not associated with overall survival. Our data sharpens the view on tumor-associated immune cell infiltrate in penile squamous cell carcinomas with an unbiased digital and automated cell count. Further investigations on the immune cell infiltrate and its prognostic and possible therapeutic impact are needed.

Background Before performing endoscopy to remove prophylactic pancreatic stents placed in patients with high risk of post‐endoscopic retrograde cholangiopancreatography pancreatitis (PEP), X‐ray imaging is recommended to confirm the stents position in the pancreatic duct. Objectives The aim of the present study was to investigate the feasibility of prophylactic pancreatic stent detection by transabdominal ultrasonography, to reduce the burden of X‐ray imaging, which is currently the golden standard. Methods All patients who received a pancreatic stent for PEP prophylaxis were included in the present prospective trial. First, stent position was determined by transabdominal ultrasonography. Afterwards, it was verified by X‐ray imaging. Retained stents were removed by esophagogastroduodenoscopy. Dislocated stents needed no further intervention. Results Fourty‐one patients were enrolled in this study. All prophylactic pancreatic stents were straight 6 cm long 5 Fr stents with external flap. All stents were removed between day 1 and 10 (median: 3 days) in all cases. In 34 of 41 cases (83.0%), the pancreatic stent was still in place on the day of examination. Twenty‐nine of 34 (85.3%) stents were detected correctly by transabdominal ultrasonography. Overlying gas prevented visualization of the pancreas in 3/41 (7.3%) cases. Sensitivity of sonographic detection of the stent was 93.5% (29/31). Six of seven stents were determined correctly as dislocated by ultrasonography. Here, specificity was 85.7%. A positive predictive value of 96.7% (29/30) was examined. The negative predictive value was 75.0% (6/8). Conclusion Transabdominal ultrasonography detects the majority of prophylactic pancreatic stents. Thereby, it helps to identify patients with an indication for endoscopy sufficiently. X‐ray imaging could subsequently be omitted in about 70% of examinations, reducing the radiation exposure for the patient and the endoscopy staff.

IntroductionMajor surgery is associated with a high risk for postoperative complications, leading to an increase in mortality and morbidity, particularly in frail patients with a reduced cardiopulmonary reserve. Prehabilitation, including aerobic exercise training, aims to improve patients’ physical fitness before major surgery and reduce postoperative complications, length of hospital stay and costs. The purpose of the study is to assess the usability, validity and safety of an app-based endurance exercise software in accordance with the Medical Device Regulation using wrist-worn wearables to measure heart rate (HR) and distance.Methods and analysisThe PROTEGO MAXIMA trial is a prospective, interventional study with patients undergoing major elective surgery, comprising three tasks. Tasks I and II aim to assess the usability of the app, using evaluation questionnaires and usability scenarios. In Task IIIa, patients will undergo a structured risk assessment by the Patronus App, which will be correlated with the occurrence of postoperative complications after 90 days (non-interventional). In Task IIIb, healthy students and patients will perform a supervised 6 min walking test and a 37 min interval training on a treadmill based on HR reserve, wearing standard ECG limb leads and two smartwatches, which will be driven by the test software. The aim of this task is to assess the accuracy of HR measurement by the wearables and the safety, using specific alarm settings of the devices and lab testing of the participants (interventional).Ethics and disseminationEthical approval was granted by the Institutional Review Board of the University Hospital of Frankfurt and by the Federal Institute for Pharmaceuticals and Medical Products (BfArM, reference number 94.1.04-5660-13655) on 7 February 2022. The results from this study will be submitted to peer-reviewed journals and reported at suitable national and international meetings.Trial registration numbersEuropean Database on Medical Devices (CIV-21-07-037311) and German Clinical Trial Registry (DRKS00026985).

OBJECTIVES The four-dimensional ultrasound (4D-US) enables imaging of the aortic segment and simultaneous determination of the wall expansion. The method shows a high spatial and temporal resolution, but its in vivo reliability is so far unknown for low-measure values. The present study determines the intraobserver repeatability and interobserver reproducibility of 4D-US in the atherosclerotic and non-atherosclerotic infrarenal aorta. METHODS In all, 22 patients with non-aneurysmal aorta were examined by an experienced examiner and a medical student. After registration of 4D images, both the examiners marked the aortic wall manually before the commercially implemented speckle tracking algorithm was applied. The cyclic changes of the aortic diameter and circumferential strain were determined with the help of custom-made software. The reliability of 4D-US was tested by the intraclass correlation coefficient (ICC). RESULTS The 4D-US measurements showed very good reliability for the maximum aortic diameter and the circumferential strain for all patients and for the non-atherosclerotic aortae (ICC >0.7), but low reliability for circumferential strain in calcified aortae (ICC = 0.29). The observer- and masking-related variances for both maximum diameter and circumferential strain were close to zero. CONCLUSIONS Despite the low-measured values, the high spatial and temporal resolution of the 4D-US enables a reliable evaluation of cyclic diameter changes and circumferential strain in non-aneurysmal aortae independent from the observer experience but with some limitations for calcified aortae. The 4D-US opens up a new perspective with regard to noninvasive, in vivo assessment of kinematic properties of the vessel wall in the abdominal aorta.

Stenosis of the biliary anastomosis predisposes liver graft recipients to bacterial cholangitis. Antibiotic therapy (AT) is performed according to individual clinical judgment, but duration of AT remains unclear.All liver graft recipients with acute cholangitis according to the Tokyo criteria grade 1 and 2 after endoscopic retrograde cholangiography (ERC) were included. Outcome of patients treated with short AT (7 days) was compared to long AT (6 days). Recurrent cholangitis (RC) within 28 days was the primary end point.In total, 30 patients were included with a median of 313 (range 34-9849) days after liver transplantation until first proven cholangitis. Among 62 cases in total, 51/62 (82%) were graded as Tokyo-1 and 11/62 (18%) as Tokyo-2. Overall median duration of AT was 6 days (1-14) with 36 cases (58%) receiving short AT and 26 (42%) receiving long AT. RC was observed in 10 (16%) cases, without significant difference in occurrence of RC in short versus long AT cases. CRP and bilirubin were significantly higher in patients with long AT, while low serum albumin and low platelets were associated with risk of RC.A shorter antibiotic course than 7 days shows good results in selected, ERC-treated patients for post-transplantation biliary strictures.

To prospectively evaluate the therapy response of third-line TACE with DSM or lipiodol in the treatment of CRLM using MRI. In this prospective, randomized, single-center trial, patients were randomly assigned to receive TACE therapy with either lipiodol or DSM as the embolization agent. Therapy response was evaluated using MRI. Local tumor response was determined according to RECIST 1.1, and survival data was analyzed using the Kaplan-Meier estimator. Fifty patients (35 male, 15 female) were randomized and included in the survival analysis, whereas 31 patients completed therapy and were considered for evaluation of tumor responses (cTACE: n = 13, DSM-TACE: n = 18). In the cTACE group, PR was observed in 23%, SD in 15%, and PD in 62%. In the DSM-TACE-group, PR was observed in 22% of patients, SD in 56%, and PD in 22% (p = 0.047). In addition, the DSM-TACE group showed statistically significant tumor volume reduction (p = 0.006). Median apparent diffusion coefficient values were not significantly different between both groups at baseline (p = 0.26) and study endpoint (p = 0.83). Median survival in the cTACE group was 13 months (95% confidence interval, range 5–40 months) compared to 16 months (95% confidence interval, range 1–48 months) in the DSM-TACE group, exhibiting no statistically significant difference (p = 0.75). DSM-TACE showed a significant difference reducing tumor volume and in tumor response according to RECIST 1.1 compared to cTACE. Thus, patients with CRLM might not only benefit from short embolization effect of DSM-TACE but also from better tumor responses. Apparent diffusion coefficients were not significantly different between both groups and cannot be used as a biomarker for monitoring for therapeutic effect of TACE. • To our knowledge, this is the first prospective study that directly compared cTACE and DSM-TACE in patients with CRLM. • DSM-TACE showed a significant difference reducing tumor volume (p = 0.006) and in tumor response according to RECIST 1.1 (p = 0.047) compared to cTACE. • Survival analysis showed a median survival of 13 months in the cTACE group compared to 16 months in the DSM-TACE group (p = 0.75).

Objective:To investigate the association of radiochemotherapy-induced cytopenia with sex of glioma patients and its potential impact on survival.Methods:We retrospectively analyzed cytopenia during temozolomide-based concomitant radiochemotherapy (RCT) in 492 glioma patients. Histological grading, molecular pathology, surgical procedures, adjuvant chemotherapy subsequent to the RCT phase and overall survival (OS) were recorded. The extent of cytopenia was correlated with sex and outcome.Results:Treatment-induced severe cytopenia (leuko-, lympho-, neutro- and thrombocytopenia) was more frequent in women than men (44 vs. 18%, p-value 0.0002). In women with IDH-wildtype high-grade astrocytomas there was a negative correlation of severe cytopenia in general and thrombocytopenia in specific during temozolomide RCT with OS independent from other predictors (92 (77-111) vs. 73 (21-127) weeks, p-values Conclusions:Our analysis of treatment-induced cytopenia in a large cohort of glioma patients (i) confirms that women are at higher risk and (ii) demonstrates an association of cytopenia in women with shortened survival.Classification of Evidence:This study provides class II evidence that women with glioma treated with temozolomide-based concomitant radiochemotherapy have more frequent treatment-induced severe cytopenia than men and that severe myelosuppression correlates with worse OS in women.

BackgroundTo study neoadjuvant chemoradiotherapy (nCRT) and potential predictive factors for response in locally advanced oral cavity cancer (LA-OCC).MethodsThe INVERT trial is an ongoing single-center, prospective phase 2, proof-of-principle trial. Operable patients with stage III-IVA squamous cell carcinomas of the oral cavity were eligible and received nCRT consisting of 60 Gy with concomitant cisplatin and 5-fluorouracil. Surgery was scheduled 6-8 weeks after completion of nCRT. Explorative, multiplex immunohistochemistry (IHC) was performed on pretreatment tumor specimen, and diffusion-weighted magnetic resonance imaging (DW-MRI) was conducted prior to, during nCRT (day 15), and before surgery to identify potential predictive biomarkers and imaging features. Primary endpoint was the pathological complete response (pCR) rate.ResultsSeventeen patients with stage IVA OCC were included in this interim analysis. All patients completed nCRT. One patient died from pneumonia 10 weeks after nCRT before surgery. Complete tumor resection (R0) was achieved in 16/17 patients, of whom 7 (41%, 95% CI: 18-67%) showed pCR. According to the Clavien-Dindo classification, grade 3a and 3b complications were found in 4 (25%) and 5 (31%) patients, respectively; grade 4-5 complications did not occur. Increased changes in the apparent diffusion coefficient signal intensities between MRI at day 15 of nCRT and before surgery were associated with better response (p=0.022). Higher abundances of programmed cell death protein 1 (PD1) positive cytotoxic T-cells (p=0.012), PD1+ macrophages (p=0.046), and cancer-associated fibroblasts (CAFs, p=0.036) were associated with incomplete response to nCRT.ConclusionnCRT for LA-OCC followed by radical surgery is feasible and shows high response rates. Larger patient cohorts from randomized trials are needed to further investigate nCRT and predictive biomarkers such as changes in DW-MRI signal intensities, tumor infiltrating immune cells, and CAFs.

Scarce data exist for therapy regimens other than somatostatin analogues (SSA) and peptide receptor radiotherapy (PRRT) for siNET. We analyzed real world data for differences in survival according to therapy.Analysis of 145 patients, diagnosed between 1993 and 2018 at a single institution, divided in treatment groups. Group (gr.) 0: no treatment (45.5% female, median age 60 years (range, 27-84). A total of 125/145 patients with a resection of the primary tumor. For all patients, 1-year OS (%) was 93.8 (95%-CI: 90-98), 3-year OS = 84.3 (CI: 78-90) and 5-year OS = 77.5 (CI: 70-85). For analysis of survival according to therapy, only stage IV patients (baseline) that received treatment were included. Compared with reference gr. 2 (SSA only), HR for OS was 1.49 (For stage IV patients in this analysis (limited by low patient numbers in co. 3/4), multimodal treatment did not significantly improve survival over SSA treatment alone. A resection of primary tumor significantly improves survival.

Intracranial haemorrhage (ICH) is associated with permanent neurological disability resulting in deterioration of the quality of life (QoL). Our study assesses QoL in patients with ruptured arteriovenous malformation (AVM) in long-term follow-up at least five years after ICH and compares their QoL with the QoL of patient with non-ruptured AVM.Using the Quality of Life Scale (QOLS), the Patient Health Questionnaire (PHQ-9) for depressive symptoms, and the socioeconomic status (SES), a prospective assessment was performed. The modified Rankin Scale (mRS) was assessed for outcome.Of 73 patients, 42 (57.5%) had ruptured (group 1) and 31 (42.5%) a non-ruptured AVM (group 2). Mean follow-up time was 8.6 ± 3.9 years (8.5 ± 4.2 years in group 1 and 8.9 ± 3.7 years in group 2). Favourable outcome (mRS 0-1) was assessed in 60 (83.3%) and unfavourable in 12 (16.7%) patients. Thirty-one of 42 patients (73.8%) in group 1 and 29 of 30 patients in group 2 (96.7%) had favourable outcomes. Mean QOLS was 85.6 ± 14.1 (group 1 86.1 ± 15.9, group 2 84.9 ± 11.4). Patients in group 1 did not show a significant difference in QoL compared to patients in group 2 (p = 0.23). Additional analyses in group 2 (rho = - 0.73; p 0.01) and in untreated AVM patients (rho = - 0.81; p 0.01) showed a strong correlation between QOLS and PHQ-9.Long-term follow-up showed no difference in the QoL between patients with and without ICH caused by brain AVM. Outcome- and QoL-scores were high in both groups. Further studies are necessary to evaluate depression and anxiety symptoms in patients with AVM.

Background & Aims: Ongoing transmission of HCV infections is associated with risk factors such as drug injection, needlestick injuries, and men who have sex with men (MSM). Ways of transmission, the course of acute infection, changes of virologic features, and incidence over time are not well known. Methods: Over a period of 10 years, n = 161 patients with recently acquired HCV infection (RAHC) (median follow-up 6.8 years) were prospectively enrolled. NS5B sequencing was performed to re-evaluate the HCV genotype (GT) and for phylogenetic analyses. Results: Patients with RAHC were mainly male (92.5%), MSM (90.1%), and HIV-coinfected (86.3%). Transmission risk factors for MSM and non-MSM were sexual risk behaviour (100 and 6.3%, respectively), injection drug use (9.7 and 37.5%, respectively), and nasal drug use (15.2 and 0%, respectively). Spontaneous and interferon- or direct-acting antiviral-based clearance rates were 13.6, 84.3 and 93.4%, respectively. Mean RAHC declined from 19.8 in the first to 13.2 in the past five study years. Although the majority of infections was caused by HCV GT1a, the frequency of HCV GT4d and slightly HCV GT3a increased over time. No relevant clustering of HCV isolates was observed in non-MSM. However, 45% of HCV GT1a and 100% of HCV GT4d MSM cases clustered with MSM isolates from other countries. Travel-associated infections were supported by personal data in an MSM subgroup. No international clustering was detected in MSM with HCV GT1b or HCV GT3a. Conclusions: RAHCs were mainly diagnosed in HIV-coinfected MSM patients and were associated with sexual risk behaviour. Spontaneous clearance rates were low, and phylogenetic clusters were observed in the majority of patients. Impact and Implications: We evaluated the occurrence and transmission of recently acquired HCV infections (RAHCs) over a period of 10 years. Our data demonstrate that the presence of RAHC was mainly found in HIV-coinfected MSM, with internationally connected transmission networks being observed in the majority of patients. Spontaneous clearance rates were low, and reinfection rates increased mainly driven by a small subset of MSM patients with high-risk behaviour., JHEP Reports, 5 (7)

To investigate the association of radiochemotherapy-induced cytopenia with sex and its potential effect on survival in patients with glioma.We retrospectively analyzed cytopenia during temozolomide-based concomitant radiochemotherapy in 492 patients with glioma. Histologic grading, molecular pathology, surgical procedures, adjuvant chemotherapy subsequent to the radiochemotherapy phase, and overall survival (OS) were recorded. The extent of cytopenia was correlated with sex and outcome.Treatment-induced severe cytopenia (leukocytopenia, lymphocytopenia, neutropenia, and thrombocytopenia) was more frequent in women than men (44 vs 18%;Our analysis of treatment-induced cytopenia in a large cohort of patients with glioma confirms that women are at higher risk and demonstrates an association of cytopenia with shortened survival in women.This study provides Class II evidence that women with glioma treated with temozolomide-based concomitant radiochemotherapy have more frequent treatment-induced severe cytopenia than men and that severe myelosuppression correlates with worse OS in women.

A lack of vitamin D seems to be related to autoimmune diseases including autoimmune thyroiditis (AIT). This study intends to determine the correlation between improvement of 25-hydroxyvitamin D [25(OH)D] levels and AIT in patients from an outpatient endocrine clinic in Frankfurt, Germany. This study included 933 patients with thyroid peroxidase antibodies (anti-TPO-Ab) ≥34 kIU/l, including most patients with clear AIT due to a concurrent sonographic evidence of reduced echogenicity. We performed clinical evaluation and laboratory analysis at five points in time within two years retrospectively. Due to a high dropout rate within the observation period, we excluded the last two time points from analysis. Data from 933 AIT patients revealed 89% having vitamin D deficiency or insufficiency [25(OH)D 0.2). We discovered 58 patients having initially a 25(OH)D level

Mortality rates after liver surgery are not well documented in Germany. More than 1000 hospitals offer liver resection, but there is no central regulation of infrastructure requirements or outcome quality.Hospital mortality rates after liver resection were analysed using the standardized hospital discharge data (Diagnosis-Related Groups, ICD-10 and German operations and procedure key codes) provided by the Research Data Centre of the Federal Statistical Office and Statistical Offices of the Länder in Wiesbaden, Germany.A total of 110 332 liver procedures carried out between 2010 and 2015 were identified. The overall hospital mortality rate for all resections was 5·8 per cent. The mortality rate among 17 574 major hepatic procedures was 10·4 per cent. Patients who had surgery for colorectal liver metastases (CRLMs) had the lowest mortality rate among those with malignancy (5·5 per cent), followed by patients with gallbladder cancer (7·1 per cent), hepatocellular carcinoma (9·3 per cent) and intrahepatic cholangiocarcinoma (11·0 per cent). Patients with extrahepatic cholangiocarcinoma had the highest mortality rate (14·6 per cent). The mortality rate for extended hepatectomy was 16·2 per cent and the need for a biliodigestive anastomosis increased this to 25·5 per cent. Failure to rescue after complications led to mortality rates of more than 30 per cent in some subgroups. There was a significant volume-outcome relationship for CRLM surgery in very high-volume centres (mean 26-60 major resections for CRLMs per year). The mortality rate was 4·6 per cent in very high-volume centres compared with 7·5 per cent in very low-volume hospitals (odds ratio 0·60, 95 per cent c.i. 0·42 to 0·77; P 0·001).This analysis of outcome data after liver resection in Germany suggests that hospital mortality remains high. There should be more focused research to understand, improve or justify factors leading to this result, and consideration of centralization of liver surgery.En Alemania, los datos de mortalidad después de la cirugía no están bien documentados. En más de 1.000 hospitales se realizan resecciones hepáticas, pero no existe una regulación central de los prerrequisitos estructurales necesarios y de la calidad de los resultados. MÉTODOS: Las tasas de mortalidad hospitalaria relacionadas con las resecciones hepáticas se analizaron utilizando los datos estandarizados del alta hospitalaria (Diagnóstico de grupos relacionados, DRG), la clasificación internacional de enfermedades 10 (ICD10) y la clave de procedimientos y operaciones (códigos OPS) proporcionados por el RDC de la Oficina Federal de Estadística y Oficinas de Estadística de Länder en Wiesbaden, Alemania.Se identificaron un total de 110.332 procedimientos hepáticos (de 2010 a 2015). La tasa global de mortalidad hospitalaria para todas las resecciones fue del 5,8%. Las resecciones hepáticas mayores (n = 15.333) presentaron una mortalidad del 10,4%. Los pacientes con metástasis hepáticas colorrectales (colorectal liver metastases, CRLM) tuvieron la mortalidad más baja de entre los pacientes con neoplasias malignas (5,5%), seguidos de los pacientes con cáncer de vesícula biliar (7,1%), colangiocarcinoma intrahepático (intrahepatic colangiocarcinoma, iCC) (11,0%) y carcinoma hepatocelular (hepatocellular carcinoma, HCC) (9,3%). Los pacientes con colangiocarcinoma extrahepático (extrahepatic cholangiocarcinoma, eCC) presentaron la mortalidad más alta (14,6%). Las hepatectomías extendidas (16,2%) y la necesidad de una anastomosis biliodigestiva (biliodigestive anastomosis, BDA) aumentaron la mortalidad a un 25,5%. La falta de solución de algunas complicaciones llevó a tasas de mortalidad de más del 30% en algunos subgrupos. Hubo una relación significativa volumen-resultado para las CRLM en centros de alto volumen (25,3 a 59,7 resecciones mayores/año; razón de oportunidades, odds ratio, OR 0,60, i.c. del 95%: 0,42-0,77; P0,001), lo que resultó en una disminución en las tasas de mortalidad de 7,5/6,4/7,5/6,5% a 4,6%. CONCLUSIÓN: El análisis de los resultados después de la resección hepática en Alemania muestra una alta mortalidad hospitalaria inesperada. Este análisis indica la necesidad de efectuar una investigación más específica para comprender, mejorar o justificar los factores que determinan estos hallazgos.

Vitamin K antagonists (VKAs) have been used in 1% of the world’s population for prophylaxis or treatment of thromboembolic events for 64 years. Impairment of osteoblast function and osteoporosis has been described in patients receiving VKAs. Given the involvement of cells of the bone marrow microenvironment (BMM), such as mesenchymal stem cells (MSCs) and macrophages, as well as other factors such as the extracellular matrix for the maintenance of normal hematopoietic stem cells (HSCs), we investigated a possible effect of VKAs on hematopoiesis via the BMM. Using various transplantation and in vitro assays, we show here that VKAs alter parameters of bone physiology and reduce functional HSCs 8-fold. We implicate impairment of the functional, secreted, vitamin K-dependent, γ-carboxylated form of periostin by macrophages and, to a lesser extent, MSCs of the BMM and integrin β3-AKT signaling in HSCs as at least partly causative of this effect, with VKAs not being directly toxic to HSCs. In patients, VKA use associates with modestly reduced leukocyte and monocyte counts, albeit within the normal reference range. VKAs decrease human HSC engraftment in immunosuppressed mice. Following published examples that alteration of the BMM can lead to hematological malignancies in mice, we describe, without providing a causal link, that the odds of VKA use are higher in patients with vs without a diagnosis of myelodysplastic syndrome (MDS). These results demonstrate that VKA treatment impairs HSC function via impairment of the BMM and the periostin/integrin β3 axis, possibly associating with increased MDS risk.

Background and aim A number of studies were able to show a reduction of hypoxemia episodes during procedural sedation through the use of capnography (CA). The present study investigates the number of episodes of hypoxemia during percutaneous endoscopic gastrostomy (PEG) placement with propofol sedation comparing standard monitoring (SM) versus SM with additional CA surveillance. Methods In this single center randomized controlled trial, 150 patients were prospectively randomized 1:1 in either the SM group or the CA group after stratification for ASA class, PEG method (push or pull method), presence of head and neck tumor, and tracheostomy. CA analysis was performed for all patients but was blinded for the endoscopic team in the SM group. Results In the SM group, 57% episodes of hypoxemia (SpO2 15 s) and 41% episodes of severe hypoxemia (SpO2 15 s) were observed in comparison with 28% and 20% in the CA group, respectively. Odds ratios for hypoxemia and severe hypoxemia were 0.29 (confidence interval 0.15-0.57; P = 0.0005) and 0.35 (confidence interval 0.17-0.73; P = 0.008) in favor of the CA group. On average, CA was able to detect imminent mild and severe hypoxemia 83 and 99 s before standard monitoring. Standard monitoring represented an independent risk factor for hypoxemia and severe hypoxemia. Conclusions Respiratory complications of sedation during PEG placement are frequent events. CA is able to detect imminent hypoxemia at an early time point. This allows an early intervention and consecutively the avoidance of mild and severe hypoxemia. Therefore, CA monitoring can be recommended particularly during PEG insertion procedures.

Liver cirrhosis is a systemic disease that substantially impacts the body's physiology, especially in advanced stages. Accordingly, the outcome of patients with cirrhosis requiring intensive care treatment is poor. We aimed to analyze the impact of cirrhosis on mortality of intensive care unit (ICU) patients compared to other frequent chronic diseases and conditions. In this retrospective study, patients admitted over three years to the ICU of the Department of Medicine of the University Hospital Frankfurt were included. Patients were matched for age, gender, pre-existing conditions, simplified acute physiology score (SAPS II), and therapeutic intervention scoring system (TISS). A total of 567 patients admitted to the ICU were included in the study; 99 (17.5 %) patients had liver cirrhosis. A total of 129 patients were included in the matched cohort for the sensitivity analysis. In-hospital mortality was higher in cirrhotic patients than non-cirrhotic patients (p 0.0001) in the entire and matched cohort. Liver cirrhosis remained one of the strongest independent predictors of in-hospital mortality (entire cohort p = 0.001; matched cohort p = 0.03) along with dialysis and need for transfusion in the multivariate logistic regression analysis. Furthermore, in the cirrhotic group, the need for kidney replacement therapy (p 0.001) and blood transfusion (p 0.001) was significantly higher than in the non-cirrhotic group. CONCLUSIONS: In the presented study, liver cirrhosis was one of the strongest predictors of in-hospital mortality in patients needing intensive care treatment along with dialysis and the need for ventilation. Therefore, concerted efforts are needed to improve cirrhotic patients' outcomes, prevent disease progression, and avoid complications with the need for ICU treatment in the early stages of the disease. Die Leberzirrhose ist eine systemische Erkrankung mit erheblichen Auswirkungen auf die Physiologie des Körpers, insbesondere in fortgeschrittenen Stadien. Dementsprechend schlecht ist das Outcome von Patienten mit Zirrhose in Abhängigkeit von der intensivmedizinischen Behandlung. Ziel unserer Studies war es, den Einfluss der Zirrhose auf die Mortalität von Patienten auf der Intensivstation (ICU) im Vergleich zu anderen häufigen chronischen Krankheiten und Zuständen zu analysieren. In diese retrospektive Studie wurden Patienten eingeschlossen, die in einem Zeitraum von drei Jahren auf der Intensivstation der Medizinischen Klinik des Universitätsklinikums Frankfurt aufgenommen wurden. Die Patienten wurden hinsichtlich Alter, Geschlecht, Vorerkrankungen, Simplified acute physiology score (SAPS II) und Therapeutic intervention scoring system (TISS) gematcht. Insgesamt wurden 567 Patienten, die auf der Intensivstation aufgenommen wurden, in die Studie aufgenommen; 99 (17,5 %) Patienten hatten eine Leberzirrhose. Für die Sensitivitätsanalyse wurden insgesamt 129 Patienten in die gematchte Kohorte aufgenommen. Die In-Hospital-Mortalität war bei zirrhotischen Patienten höher als bei nicht-zirrhotischen Patienten (p 0,0001) in der gesamten und gemachten Kohorte. Die Leberzirrhose blieb einer der stärksten unabhängigen Prädiktoren für die In-Hospital-Mortalität (gesamte Kohorte p = 0,001; gematchte Kohorte p = 0,03) zusammen mit Dialyse und Transfusionsbedarf in der multivariaten logistischen Regressionsanalyse. Darüber hinaus war in der zirrhotischen Gruppe der Bedarf an Nierenersatztherapie (p 0,001) und Bluttransfusion (p 0,001) signifikant höher als in der nicht zirrhotischen Gruppe. In der vorliegenden Studie war die Leberzirrhose einer der stärksten Prädiktoren für die In-Hospital-Mortalität bei Patienten, die eine intensivmedizinische Behandlung benötigten, zusammen mit Dialyse und Beatmungsbedarf. Daher sind konzertierte Anstrengungen erforderlich, um die Ergebnisse von zirrhotischen Patienten zu verbessern, ein Fortschreiten der Erkrankung zu verhindern und Komplikationen mit der Notwendigkeit einer intensivmedizinischen Behandlung bereits in den frühen Stadien der Erkrankung zu vermeiden.

Purpose Colorectal cancer (CRC) is the second most common cancer in Germany. Around 60,000 people were diagnosed CRC in 2016 in Germany. Since 2019, screening colonoscopies are offered in Germany for men by the age of 50 and for women by the age of 55. It is recently discussed if women should also undergo a screening colonoscopy by the age of 50 and if there are any predictors for getting CRC. Methods Colonoscopies of 1553 symptomatic patients younger than 55 years were compared with colonoscopies of 1075 symptomatic patients older than 55 years. We analyzed if there are any significant differences between those two groups in the prevalence of CRC and its precursor lesions or between symptomatic men and women. We evaluated if there is a correlation between abdominal symptoms and the prevalence of CRC. Results In 164/1553 symptomatic patients, 194 (12.5%) polyps were detected. In total, six colorectal carcinomas (0.4%) were detected. There were no significant differences between men and women. In symptomatic patients ≥ 55 years, significantly more polyps were found (pp=0.03, OR=2.73 95%-CI [1.11;6.70]), but with only low sensitivity (44%). Conclusion Due to no significant differences in men and women, we recommend screening colonoscopies also for women by the age of 50.

To prospectively evaluate the therapy response of third-line TACE with DSM or lipiodol in the treatment of CRLM using MRI.In this prospective, randomized, single-center trial, patients were randomly assigned to receive TACE therapy with either lipiodol or DSM as the embolization agent. Therapy response was evaluated using MRI. Local tumor response was determined according to RECIST 1.1, and survival data was analyzed using the Kaplan-Meier estimator.Fifty patients (35 male, 15 female) were randomized and included in the survival analysis, whereas 31 patients completed therapy and were considered for evaluation of tumor responses (cTACE: n = 13, DSM-TACE: n = 18). In the cTACE group, PR was observed in 23%, SD in 15%, and PD in 62%. In the DSM-TACE-group, PR was observed in 22% of patients, SD in 56%, and PD in 22% (p = 0.047). In addition, the DSM-TACE group showed statistically significant tumor volume reduction (p = 0.006). Median apparent diffusion coefficient values were not significantly different between both groups at baseline (p = 0.26) and study endpoint (p = 0.83). Median survival in the cTACE group was 13 months (95% confidence interval, range 5-40 months) compared to 16 months (95% confidence interval, range 1-48 months) in the DSM-TACE group, exhibiting no statistically significant difference (p = 0.75).DSM-TACE showed a significant difference reducing tumor volume and in tumor response according to RECIST 1.1 compared to cTACE. Thus, patients with CRLM might not only benefit from short embolization effect of DSM-TACE but also from better tumor responses. Apparent diffusion coefficients were not significantly different between both groups and cannot be used as a biomarker for monitoring for therapeutic effect of TACE.• To our knowledge, this is the first prospective study that directly compared cTACE and DSM-TACE in patients with CRLM. • DSM-TACE showed a significant difference reducing tumor volume (p = 0.006) and in tumor response according to RECIST 1.1 (p = 0.047) compared to cTACE. • Survival analysis showed a median survival of 13 months in the cTACE group compared to 16 months in the DSM-TACE group (p = 0.75).

Colorectal cancer (CRC) is the second most common cancer in Germany. Screening colonoscopies are considered an effective tool for early detection and prevention of CRC and are recommended in Germany for citizens over the age of 55. To increase the participation rate for screening colonoscopies, an invitation procedure was initiated in parts of Germany for patients between the ages of 55 and 75 who had never undergone a screening colonoscopy before.We examined the number of participating patients before, during, and after the invitation procedure and compared the number of the participating patients who received a cover letter with the participating patients from the control group. Additionally, we classified the findings of the colonoscopies including CRC, advanced adenomas, and polyps.During the invitation period, the participation rate of the invitation group increased from 220 patients to 531 patients compared to 1256 to 1693 in the control group. The increase was significantly greater in patients with cover letters (+141% vs.+35%,Our study clearly indicates that personal invitation letters are an effective measure to increase overall participation rates in screening colonoscopies.

Objectives On the basis of the immunomodulatory actions of vitamin D (VD), we investigated the effects of high-dose VD therapy over a 3 mo period on the immune response in patients with Addison's disease (AD). Methods This randomized, controlled, crossover trial included 13 patients with AD who received either cholecalciferol (4000 IU/d) for 3 mo followed by 3 mo placebo oil or the sequential alternative placebo followed by verum. Glucocorticoid replacement doses remained stable. The primary outcome measures were changes in 25-hydroxyvitamin D3 (25(OH)D3) levels and immune cells including T helper cells (Th; CD3+CD4+), late-activated Th cells (CD3+CD4+HLA-DR+), regulatory T cells (CD3+CD4+CD25brightCD127dim/neg), cytotoxic T cells (Tc; CD3+CD8+), late-activated Tc cells (CD3+CD8+HLA-DR+), and monocytes. The explorative analysis included the correlation of changes with VD-related gene polymorphisms and 21-hydroxylase antibody titers. Results Ten of 13 patients (77%) were VD deficient. Median 25(OH)D3 concentrations increased significantly to 41.5 ng/ml (median changes: 19.95 ng/ml; P = 0.0005) after 3 mo of cholecalciferol treatment. Within the T-cells, only the late-activated Th (median changes: 1.6%; P = 0.02) and late-activated Tc cells (median changes: 4.05%; P = 0.03) decreased, whereas monocytes (median changes: 1.05%; P = 0.008) increased after VD therapy. T-cell changes were associated with two polymorphisms (CYP27B1-rs108770012 and VDR-rs10735810), but no changes in the 21-hydroxylase antibody titers were observed. Conclusions Three months of treatment with cholecalciferol achieved sufficient 25(OH)D3 levels and can regulate late-activated T-cells and monocytes in patients with AD. Explorative analysis revealed potential genetic contributions. This pilot trial provides novel insights about immunomodulation in AD.

Background and Aims: Treatment of anastomotic biliary strictures (ABSs) after orthotopic liver transplantation by endoscopic insertion of multiple plastic stents (MPSs) is well established. The use of covered self-expandable metal stents (cSEMSs) for this indication is less investigated. Methods: In an open-label, multicenter, randomized trial, patients with confirmed ABSs were randomly assigned 1:1 to receive either an MPS or a cSEMS. The primary endpoint was the number of endoscopic interventions until ABS resolution. Secondary endpoints were frequency of adverse events, treatment success rates, and time to treatment success and recurrence of ABS during follow-up of at least 1 year. Results: Fifty-eight patients were included between 2012 and 2015, and 48 patients completed follow-up. Patients receiving MPS (n = 24) underwent a median of 4 (range, 3-12) endoscopic retrograde cholangiography examinations, whereas those in the cSEMS group (n = 24) underwent a median of 2 (range, 2-12) sessions until ABS resolution (P

3D imaging is an upcoming technology in laparoscopic surgery, and recent studies have shown that the modern 3D technique is superior in an experimental setting. However, the first randomized controlled clinical trial in this context dates back to 1998 and showed no significant difference between 2D and 3D visualization using the first 3D generation technique, which is now more than 15 years old. Positive results measured in an experimental setting considering 3D imaging on surgical performance led us to initiate a randomized controlled pragmatic clinical trial to validate our findings in daily clinical routine. Standard laparoscopic operations (cholecystectomy, appendectomy) were preoperatively randomized to a 2D or 3D imaging system. We used a surgical comfort scale (Likert scale) and the Raw NASA Workload TLX for the subjective assessment of 2D and 3D imaging; the duration of surgery was also measured. The results of 3D imaging were statistically significant better than 2D imaging concerning the parameters “own felt safety” and “task efficiency”; the difficulty level of the procedures in the 2D and 3D groups did not differ. Overall, the Raw NASA Workload TLX showed no significance between the groups. 3D imaging could be a possible advantage in laparoscopic surgery. The results of our clinical trial show increased personal felt safety and efficiency of the surgeon using a 3D imaging system. Overall of the procedures, the findings assessed using Likert scales in terms of own felt safety and task efficiency were statistically significant for 3D imaging. The individually perceived workload assessed with the Raw NASA TLX shows no difference. Although these findings are subjective impressions of the performing surgeons without a clear benefit for 3D technology in clinical outcome, we think that these results show the capability that 3D laparoscopy can have a positive impact while performing laparoscopic procedures.

Background and Aims: The IL-12/23 inhibitor ustekinumab (UST) opened up new treatment options for patients with Crohn’s disease (CD). Due to the recent approval, real-world German data on long-term efficacy and safety are lacking. This study aimed to assess the clinical course of CD patients under UST therapy and to identify potential predictive markers. Methods: Patients with CD receiving UST treatment in three hospitals and two outpatient centers were included and retrospectively analyzed. Rates for short- and long-term remission and response were analyzed with the help of clinical (Harvey–Bradshaw Index (HBI)) and biochemical (C-reactive protein (CRP), Fecal calprotectin (fCal)) parameters for disease activity. Results: Data from 180 patients were evaluated. One-hundred-and-six patients had a follow-up of at least eight weeks and were included. 96.2% of the patients were pre-exposed to anti- TNFα agents and 34.4% to both anti-TNFα and anti-integrin antibodies. The median follow-up was 49.1 weeks (95% CI 42.03-56.25). At week 8, 51 patients (54.8%) showed response to UST, and 24 (24.7%) were in remission. At week 48, 48 (51.6%) responded to UST, and 25 patients (26.9%) were in remission. Steroid-free response and remission at week eight was achieved by 30.1% and 19.3% of patients, respectively. At week 48, 37.6% showed steroid-free response to UST, and 20.4% of the initial patient population was in steroid-free remission. Conclusion: Our study confirms short- and long-term UST effectiveness and tolerability in a cohort of multi-treatment-exposed patients.

Background Patients with head and neck cancer (HNC) are at high risk for malnutrition because of tumour localisation and therapy. Prophylactic percutaneous endoscopic gastrostomy (PEG) tube placement is common practice to prevent malnutrition. Objective To investigate the benefits of prophylactic PEG tube placement for HNC patients in terms of the influence on patients' nutritional status, utilisation rate, complications and to identify the predictors of PEG tube utilisation. Methods All consecutive HNC patients who underwent prophylactic PEG tube insertion between 1 January 2011 and 31 December 2012 prior to therapy were enrolled. The PEG tube utilisation rate, complications, the patients' nutritional status and tumour therapy were evaluated with the help of electronic patient charts and telephone interviews. Results A total of 181 patients (48 female, median 67.5 years) were included. The PEG utilisation rate in the entire cohort was 91.7%. One hundred and forty-nine patients (82.3%) used the PEG tube for total enteral nutrition, 17 patients (9.4%) for supplemental nutrition and 15 patients (8.3%) made no use of the PEG tube. Peristomal wound infections were the most common complications (40.3%) in this study. A high Nutritional Risk Screening (NRS) score prior to tube insertion was found to be independently associated with PEG utilisation. No significant weight changes were observed across the three patient subgroups. Conclusions The overall PEG tube utilisation rate was high in this study. However, given the high rate of infections, diligent patient selection is crucial in order to determine which patients benefit most from prophylactic PEG tube insertion.

Background Although the therapeutic array has significantly widened, over the past decades predicting treatment persistence in IBD patients is still a challenge. In this study we collected longitudinal data to determine drug survival on the medications currently available for IBD. Methods Patients treated in the IBD outpatient clinic of the Goethe University Hospital were retrospectively analyzed. Laboratory parameters and data on treatment adherence were collected via the electronic patient file. We investigated how many patients continued on the respective substances after the induction period and after the 1-year mark. Results A total of 601 patients were included. 321 patients were female (53.4), 280 patients were male (46.6). The median age was 43 (range 19–86). The median disease duration was 14 years (range 1–52). 320 patients (53.2) suffered from CD and 281 (46,8) patients suffered from UC. 95 patients were treated with Infliximab (IFX) with a median duration of 912 days (20–5273). 91 patients (96.8) were still on IFX after the induction period. 73 patients (76.8) patients reached the 1-year mark. At the endpoint of this investigation, 39 patients (41.9) were still on IFX. 172 patients were started on Adalimumab (ADA) with a median of 1054 (48–4458) days on the medication. Of this collective, 172 (100%) patients continued on ADA after the end of the induction period. 136 patients (79.1) reached the 1-year mark. At the endpoint of this investigation, 90 patients (52.3) were still on ADA. Of the entire cohort, 124 patients were treated with Vedolizumab (VDZ) with a median of 745.50 (0-2204) days on the medication. After the induction period for this medication, 123 patients (99.2%) were still on VDZ. 89 patients (71.8%) achieved the 1-year mark. At the endpoint of this investigation, 82 patients (66.1%) were still on VDZ. Lastly, 66 patients were treated with Ustekinumab (UST) with a median duration of 720 days (50–1777). 64 patients (98.5%) achieved clinical remission. 48 patients (72.7%) achieved the 1-year mark. At the endpoint of this investigation, 54 patients (83.1%) were still on UST. As we provided longitudinal data some patients have been exposed to several medications which in part explains the lower patient numbers in the more recently approved drugs. Conclusion Conclusion: The majority of patients were still on the medication after the respective induction in all treatment groups. 1-year treatment persistence was higher for and ADA in comparison to VDZ and UST. Our study provides further evidence on drug survival in IBD and may aid in advising patients in this matter.

Background Short bowel syndrome (SBS) is a rare condition, and providing care for these patients can be challenging. Investigating the serologic sphingolipid profile has enhanced the understanding of various pathophysiologic conditions. However, data on the serologic sphingolipid profile in patients with SBS are –to date- not available. Methods Serum probes from patients with SBS treated in the outpatient clinic of the Department of Gastroenterology and Hepatology of the University Hospital Frankfurt were included and analyzed retrospectively. Serologic sphingolipid (SL) and especially ceramide (Cer) levels were assessed by LC-MS/MS and correlated with clinical and laboratory chemical parameters. Results A total of 37 (16 male) patients with SBS were included, 11 with Crohn’s disease (CD) (29.73%). Patients’ median age was 62 (24–88), with a median weight of 59 kilograms (42–75). Patients with less than 100 centimeters of small intestine had significantly higher creatinine and lower total protein levels, whereas the serologic SL-profile was not significantly affected. Furthermore, Sphingosine-1-Phosphate (S1P) and C18-Cer were increased in patients with SBS with CD as the underlying etiology. No significant differences in the sphingolipidomic profile were observed between patients on total parenteral nutrition than patients with oral and parenteral nutrition and patients with associated elevation of the liver enzymes. Conclusion Conclusion: Our study provides first insights into the serologic SL profile of patients with SBS. We showed that patients with CD present with an altered SL profile compared to other aetiologies, while the occurrence of liver disease in this single-center cohort does not appear to affect the serologic SL profile in respective patients.

IntroductionOccurrence of inaccurate or delayed diagnoses is a significant concern in patient care, particularly in emergency medicine, where decision making is often constrained by high throughput and inaccurate admission diagnoses. Artificial intelligence-based diagnostic decision support system have been developed to enhance clinical performance by suggesting differential diagnoses to a given case, based on an integrated medical knowledge base and machine learning techniques. The purpose of the study is to evaluate the diagnostic accuracy of Ada, an app-based diagnostic tool and the impact on patient outcome.Methods and analysisThe eRadaR trial is a prospective, double-blinded study with patients presenting to the emergency room (ER) with abdominal pain. At initial contact in the ER, a structured interview will be performed using the Ada-App and both, patients and attending physicians, will be blinded to the proposed diagnosis lists until trial completion. Throughout the study, clinical data relating to diagnostic findings and types of therapy will be obtained and the follow-up until day 90 will comprise occurrence of complications and overall survival of patients. The primary efficacy of the trial is defined by the percentage of correct diagnoses suggested by Ada compared with the final discharge diagnosis. Further, accuracy and timing of diagnosis will be compared with decision making of classical doctor–patient interaction. Secondary objectives are complications, length of hospital stay and overall survival.Ethics and disseminationEthical approval was received by the independent ethics committee (IEC) of the Goethe-University Frankfurt on 9 April 2020 including the patient information material and informed consent form. All protocol amendments must be reported to and adapted by the IEC. The results from this study will be submitted to peer-reviewed journals and reported at suitable national and international meetings.Trial registration numberDRKS00019098.

This prospective study investigated viral and host markers after stopping long-term therapy with nucleos(t)ide analogues in noncirrhotic patients with hepatitis B e antigen-negative chronic hepatitis B. After stopping therapy, 13 of 15 patients experienced a virological relapse. Rebound of hepatitis B virus DNA and hepatitis B core-related antigen was associated with induction of plasma tumor necrosis factor, interleukin (IL) 10 , IL-12p70, CXCL10 and subsequent decline in hepatitis B surface antigen (HBsAg), with 20% HBsAg loss after long-term follow-up. The peak levels of hepatitis B virus DNA and hepatitis B core-related antigen after cessation of therapy were positively correlated with the level of HBsAg decline at week 48. Thus, stopping or interrupting NA treatment should be further investigated as a strategy to accelerate HBsAg loss.

The value of bevacizumab (BEV) in recurrent glioblastoma is unclear. Imaging parameters and progression-free survival (PFS) are problematic endpoints. Few data exist on clinical factors influencing overall survival (OS) in unselected patients with recurrent glioblastoma exposed to BEV. We retrospectively analyzed 174 patients with recurrent glioblastoma treated with BEV at two German brain tumor centers. We evaluated general patient characteristics, MGMT status, pretreatment, concomitant oncologic treatment and overall survival. Karnofsky performance score, number of prior chemotherapies, number of prior recurrences and combined treatment with irinotecan (IRI) were significantly associated with OS in univariate analysis. We did not find differences in OS related to sex, age, histology, MGMT status, prior surgical treatment or number of prior radiotherapies. Combined treatment with IRI and higher KPS both remained significantly associated with prolonged survival in multivariate analysis, but patients receiving IRI co-treatment had less advanced disease. Grouping into clinically relevant categories revealed an OS of 16.9 months from start of BEV in patients with first recurrence and KPS ≥ 80 % (n = 25). In contrast, in patients with second recurrence and KPS

Background The IL-12/23 inhibitor ustekinumab (UST) opened up new treatment options for patients with Crohn’s disease (CD). Due to the recent approval, Real-World German data on long-term efficacy and safety are lacking. This study aimed to assess the clinical course of CD patients under UST therapy and to identify potential predictive markers. Methods Patients with CD receiving UST treatment in three hospitals and two outpatient centres were included and retrospectively analysed. Rates for short- and long-term remission and response were analysed with the help of clinical (Harvey–Bradshaw Index [HBI]) and biochemical (C-reactive protein [CRP], faecal calprotectin [fCal]) parameters for disease activity. Results Data from 180 patients were evaluated. One hundred six patients had a follow-up of at least 8 weeks and were included. 96.2% of the patients were pre-exposed to anti- TNFα agents and 34.4% to both anti-TNFα and anti-integrin. The median follow-up was 49.1 weeks (95% CI 42.03–56.25). At week 8, 51 patients (54.8%) showed response to UST, and 24 (24.7%) were in remission. At week 48, 39 (41.9%) responded to UST, and 20 patients (21.5%) were in remission. Steroid-free response and remission at week eight were achieved by 30.1%, and 19.3% of patients. At week 48, 26.9% showed steroid-free response to UST, and 15.1% of the initial patient population was in steroid-free remission. Clinical response at week 16 was independently associated with remission at week 48. Conclusion Our study confirms short- and long-term UST effectiveness and tolerability in a cohort of multi-treatment exposed patients.