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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.

Background: Non-anastomotic biliary strictures (NAS) are a common cause of morbidity and mortality after liver transplantation. Methods: All patients with NAS from 2008 to 2016 were retrospectively analyzed. The success rate and overall mortality of an ERCP-based stent program (EBSP) were the primary outcomes. Results: A total of 40 (13.9%) patients with NAS were identified, of which 35 patients were further treated in an EBSP. Furthermore, 16 (46%) patients terminated EBSP successfully, and nine (26%) patients died during the program. All deaths were caused by cholangitis. Of those, one (11%) patient had an extrahepatic stricture, while the other eight patients had either intrahepatic (3, 33%) or combined extra- and intrahepatic strictures (5, 56%). Risk factors of overall mortality were age (p = 0.03), bilirubin (p < 0.0001), alanine transaminase (p = 0.006), and aspartate transaminase (p = 0.0003). The median duration of the stent program was 34 months (ITBL: 36 months; IBL: 10 months), and procedural complications were rare. Conclusions: EBSP is safe, but lengthy and successful in only about half the patients. Intrahepatic strictures were associated with an increased risk of cholangitis.

BACKGROUND: Genesis and the prognostic value of olfactory dysfunction (OD) in COVID-19 remain partially described. The objective of our study was to characterize OD during SARS-CoV-2 infection and to examine whether testing of OD may be a useful tool in clinical practice in order to early identify patients with SARS-CoV-2 infection. METHODS: Olfactory function assessment was objectively carried out using the u-Smell-it® test. In a cross-sectional study part, we evaluated this test in a control cohort of SARS-CoV-2 negative tested patients, who attended the University Hospital Frankfurt between May 2021 and March 2022. In a second longitudinal study part, sensitivity and specificity of OD was evaluated as a diagnostic marker of a SARS-CoV-2 infection in Frankfurt am Main, Germany in SARS-CoV-2 infected patients and their close contacts. RESULTS: Among 494 SARS-CoV-2 negative tested patients, OD was detected in 45.7% and was found to be significantly associated with the male gender (p < 0.001), higher age (p < 0.001), cardiovascular and pulmonary comorbidities (p < 0.001; p = 0.03). Among 90 COVID-19 positive patients, OD was found in 65.6% and was significantly associated with male gender and positive smoking status (p = 0.04 each). Prevalence and severity of OD were significantly increased in infections with the Delta variant (B.1.617.2) compared to those with the Omicron variant (BA.1.1.529). Diagnostic sensitivity and specificity of OD for diagnosis of SARS-CoV-2 infection were 69% and 64%, respectively. CONCLUSION: OD is common in COVID-19 negative and positive tested patients with significantly different prevalence rates observed between different variants. Diagnostic accuracy of OD is not high enough to implement olfactory testing as a tool in diagnostic routine to early identify patients with a SARS-CoV-2 infection.

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.

Introduction: 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. Patients and methods: Analysis of 145 patients, diagnosed between 1993 and 2018 at a single institution, divided in treatment groups. Group (gr.) 0: no treatment (n = 10), gr 1: TACE and/or PRRT (n = 26), gr. 2: SSA (n = 32), gr. 3: SSA/PRRT (n = 8), gr. 4: chemotherapy (n = 8), gr. 5: not metastasized (at diagnosis), surgery only (n = 53), gr. 6 = metastasized (at diagnosis), surgery only (n = 10). Results: 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 (p = 0.47) for gr. 1, 0.72 (p = 0.69) for gr. 3, 2.34 (p = 0.19) for gr. 4. The 5 y OS rate of patients whose primary tumor was resected (n = 125) was 73.1%, and without PTR was 33.3% (HR: 4.31; p = 0.003). Individual patients are represented in swimmer plots. Conclusions: 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.

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.

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.

Effective antibiotic therapy of cerebral infections such as meningitis or ventriculitis is hindered by low penetration into the cerebrospinal fluid (CSF). Because continuous infusion of meropenem and vancomycin and routine therapeutic drug monitoring (TDM) have been proposed to optimize antimicrobial exposure in ventriculitis patients, an individualized dosing strategy was implemented in our department. We present a retrospective analysis of meropenem and vancomycin concentrations in serum and CSF in the first nine ventriculitis patients treated with continuous infusion and TDM-guided dose optimization aiming at 20–30 mg/L. Median initial dosing was 8.8 g/24 h meropenem and 4.25 g/24 h vancomycin, respectively, resulting in median serum concentrations of 21.3 mg/L for meropenem and 24.5 mg/L for vancomycin and CSF concentrations of 3.4 mg/L for meropenem and 1.7 mg/L for vancomycin. Median CSF penetration was 15% for meropenem and 7% for vancomycin. With initial dosing, all but one patient achieved CSF concentrations above 1 mg/L. Dose adjustment according to TDM ensured sufficient CSF concentrations in all patients within 48 h of treatment. Given the limited penetration, continuous infusion of meropenem and vancomycin based on renal function and TDM-guided dose optimization appears a reasonable approach to attain sufficient CSF concentrations in ventriculitis patients.

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.