Search

Background: Whether the access site influences the comparative efficacy and safety of ticagrelor and prasugrel in patients with acute coronary syndrome (ACS) undergoing invasive treatment strategy remains unstudied. Methods: This post-hoc analysis included ACS patients undergoing invasive treatment via radial or femoral access and randomized to either ticagrelor or prasugrel in the ISAR-REACT 5 trial. The primary efficacy endpoint was the composite of death, myocardial infarction (MI) or stroke, safety endpoint was BARC 3 to 5 bleeding. Outcomes were assessed out to 12 months after randomization. Results: Out of 4018 patients, 3984 underwent invasive treatment via radial or femoral access. 1479 had coronary angiography via radial access (ticagrelor, N = 748; prasugrel, N = 731) and 2505 via femoral access (ticagrelor, N = 1245; prasugrel, N = 1260). There was no interaction between access route and assignment to either ticagrelor or prasugrel regarding the primary efficacy or safety endpoints (P for interaction≥0.616). In the radial group, the primary efficacy endpoint (7.6% versus 5.8%, HR: 1.32 [0.88–1.97], P = 0.151) and the safety endpoint (4.3% versus 3.0%, HR: 1.36, [0.73–1.31], P = 0.300) were not statistically different in patients receiving either ticagrelor or prasugrel. In the femoral group, the primary efficacy endpoint occurred more frequently in patients assigned to ticagrelor as compared to prasugrel (10.3% versus 7.3%, HR: 1.44 [1.10–1.88], P = 0.006) without significant difference in terms of safety endpoint (6.4% versus 5.8%, HR: 1.14, [0.81–1.60], P = 0.470). Conclusions: In patients with ACS undergoing an invasive treatment strategy, the access route does not influence the comparative efficacy and safety of ticagrelor and prasugrel.

Different immunohistochemical programmed death-ligand 1 (PD-L1) assays and scorings have been reported to yield variable results in triple-negative breast cancer (TNBC). We compared the analytical concordance and reproducibility of four clinically relevant PD-L1 assays assessing immune cell (IC) score, tumor proportion score (TPS), and combined positive score (CPS) in TNBC. Primary TNBC resection specimens (n = 104) were stained for PD-L1 using VENTANA SP142, VENTANA SP263, DAKO 22C3, and DAKO 28–8. PD-L1 expression was scored according to guidelines on virtual whole slide images by four trained readers. The mean PD-L1 positivity at IC-score ≥1% and CPS ≥1 ranged between 53% and 75% with the highest positivity for SP263 and comparable levels for 22C3, 28–8, and SP142. Inter-assay agreement was good between 28–8 and 22C3 across all scores and cut-offs (kappa 0.68–0.74) and for both assays with SP142 at IC-score ≥1% and CPS ≥1 (kappa 0.61–0.67). The agreement between SP263 and all other assays was substantially lower for all scores. Inter-reader agreement for each assay was good to excellent for IC-score ≥1% (kappa 0.73–0.78) and CPS ≥1 (kappa 0.68–0.74), fair to good for CPS ≥10 (kappa 0.52–0.67) and TPS ≥1% (kappa 0.53–0.72). The percentage of overlapping cases in the positive/negative category was >90% between IC-score ≥1% and CPS ≥1 but below when comparing IC-score ≥1% with CPS ≥10. We demonstrate an overall good inter-reader agreement for all PD-L1 assays in TNBC along with assay specific differences in positivity and concordances, which may aid to select the right test strategy in routine diagnostics., Highlights • Different PD-L1 IHC assays and scorings may show variable results in TNBC. • Overall good assay concordance between SP142, 22C3, and 28–8 at IC-score 1%. • Overall good assay concordance between SP142, 22C3, and 28–8 at CPS 1. • SP142 is less optimal for CPS assessment at higher cut-offs. • SP263 assay is not interchangeable with the other three PD-L1 assays.

Background The efficacy and safety of ticagrelor versus prasugrel in patients with acute coronary syndrome and prior myocardial infarction (MI) remain unstudied. We aimed to assess the treatment effect of ticagrelor versus prasugrel according to prior MI status in patients with ACS. Methods and Results Patients with acute coronary syndrome planned for an invasive strategy and randomized to ticagrelor or prasugrel in the ISAR‐REACT (Intracoronary Stenting and Antithrombotic Regimen: Rapid Early Action for Coronary Treatment) 5 trial were included. The primary end point was the composite of 1‐year all‐cause death, MI, or stroke; the secondary safety end point was the composite of 1‐year Bleeding Academic Research Consortium type 3 to 5 bleeding. The study included 4015 patients (prior MI=631 patients; no prior MI=3384 patients). As compared with patients without prior MI, the primary end point occurred more frequently in patients with prior MI (12.6% versus 7.2%; hazard ratio [HR], 1.78 [95% CI, 1.38–2.29]); the secondary safety end point appears to differ little between patients with and without prior MI (5.8% versus 5.7%, respectively; HR, 1.02 [95% CI, 0.71–1.45]). With regard to the primary end point, ticagrelor versus prasugrel was associated with an HR of 1.62 (95% CI, 1.03–2.55) in patients with prior MI and an HR of 1.28 (95% CI, 0.99–1.65) in patients without prior MI ( P int =0.37). With regard to the secondary safety end point, ticagrelor versus prasugrel was associated with an HR of 1.28 (95% CI, 0.56–2.91) in patients with prior MI and an HR of 1.13 (95% CI, 0.82–1.55) in patients without prior MI ( P int =0.79). Conclusions Patients with acute coronary syndrome and prior MI are at higher risk for recurrent ischemic but not bleeding events. Prasugrel is superior to ticagrelor in reducing the risk of ischemic events without a tradeoff in bleeding regardless of prior MI status. Registration URL: https://www.clinicaltrials.gov ; Unique identifier: NCT01944800.

Background Case-based group discussions (CBGD) are a specific, interaction-focused format dedicated to fostering medical students’ skills in applying basic biomedical knowledge to patient cases. Existing conceptions of CBGD suggest that a gradient towards increased opportunities for students to make elaborative verbal contributions is an important element of such seminars. To verify this assumption, we investigate empirically if clinical teachers progress from more basic, knowledge-oriented questions towards more advanced, elaboration-oriented questions in such seminars. Methods We videotaped 21 different clinical teachers and 398 medical students in 32 CBGD-seminars on surgery and internal medicine. We coded closed-reproductive and open-elaborative teacher questions as well as reproductive and elaborative student responses to these questions. Inter-rater reliability was satisfactory. To determine trends regarding the teacher questions / student responses, we compared eight time-segments of equal duration per seminar. Results Overall, clinical teachers asked more closed-reproductive than open-elaborative questions. Students gave more reproductive than elaborative responses. Regarding the frequencies of these forms of teacher questions / student responses, we found no significant differences over time. Conclusions Clinical teachers did not deliberately modify the types of questions over time to push students towards more elaborative responses. We conclude that the critical question to which degree promising teaching approaches are actually put into clinical teaching practice should be raised more purposefully in medical education research.

Objectives The aim of this study was to assess the safety and efficacy of ticagrelor versus prasugrel for patients with acute coronary syndrome (ACS) according to their estimated glomerular filtration rates (eGFRs). Background The outcomes of ticagrelor versus prasugrel in patients with ACS according to eGFR have not been defined. Methods Patients (n = 4,012) were categorized into 3 groups: low eGFR ( Results Patients with low eGFRs had a higher risk for the primary endpoint compared with patients with intermediate eGFRs (adjusted HR: 1.89; 95% CI: 1.46-2.46]) and those with high eGFRs (adjusted HR: 2.33; 95% CI: 1.57-3.46). A risk excess for low eGFR was also observed for bleeding (adjusted HR: 1.55 [95% CI: 1.12-2.13] vs intermediate eGFR; adjusted HR: 1.59 [95% CI: 1.01-2.50] vs high eGFR). However, eGFR did not affect the relative efficacy and safety of ticagrelor versus prasugrel. In patients with low eGFR, the primary endpoint occurred in 20.5% with ticagrelor and in 14.7% with prasugrel (HR: 1.47; 95% CI: 1.04-2.08; P = 0.029); there was no significant difference in bleeding. Conclusions These results show that among patients with ACS, reduction of eGFR is associated with increased risk for ischemic and bleeding events but has no significant impact on the relative efficacy and safety of ticagrelor versus prasugrel. (Prospective, Randomized Trial of Ticagrelor Versus Prasugrel in Patients With Acute Coronary Syndrome [ISAR-REACT 5]; NCT01944800 )

Background Lung emphysema is an important phenotype of chronic obstructive pulmonary disease (COPD), and CT scanning is strongly recommended to establish the diagnosis. This study aimed to identify criteria by which physicians with limited technical resources can improve the diagnosis of emphysema. Methods We studied 436 COPD patients with prospective CT scans from the COSYCONET cohort. All items of the COPD Assessment Test (CAT) and the St George’s Respiratory Questionnaire (SGRQ), the modified Medical Research Council (mMRC) scale, as well as data from spirometry and CO diffusing capacity, were used to construct binary decision trees. The importance of parameters was checked by the Random Forest and AdaBoost machine learning algorithms. Results When relying on questionnaires only, items CAT 1 & 7 and SGRQ 8 & 12 sub-item 3 were most important for the emphysema- versus airway-dominated phenotype, and among the spirometric measures FEV1/FVC. The combination of CAT item 1 (≤ 2) with mMRC (> 1) and FEV1/FVC, could raise the odds for emphysema by factor 7.7. About 50% of patients showed combinations of values that did not markedly alter the likelihood for the phenotypes, and these could be easily identified in the trees. Inclusion of CO diffusing capacity revealed the transfer coefficient as dominant measure. The results of machine learning were consistent with those of the single trees. Conclusions Selected items (cough, sleep, breathlessness, chest condition, slow walking) from comprehensive COPD questionnaires in combination with FEV1/FVC could raise or lower the likelihood for lung emphysema in patients with COPD. The simple, parsimonious approach proposed by us might help if diagnostic resources regarding respiratory diseases are limited. Trial registration ClinicalTrials.gov, Identifier: NCT01245933, registered 18 November 2010, https://clinicaltrials.gov/ct2/show/record/NCT01245933. Supplementary Information The online version contains supplementary material available at 10.1186/s12931-021-01837-2.

Background: The relative efficacy and safety of more potent P2Y 12 inhibitors in patients with acute coronary syndrome and high bleeding risk (HBR) undergoing percutaneous coronary intervention remains unclear. We aimed to study the treatment effect of ticagrelor and prasugrel in percutaneous coronary intervention patients presenting with acute coronary syndrome and HBR. Methods: This post hoc analysis of the ISAR-REACT 5 trial (Intracoronary Stenting and Antithrombotic Regimen: Rapid Early Action for Coronary Treatment 5) included patients with acute coronary syndrome undergoing percutaneous coronary intervention, randomized to ticagrelor or prasugrel, in whom HBR was defined as per Academic Research Consortium criteria. The primary (efficacy) end point was the composite of all-cause death, myocardial infarction, or stroke. The secondary (safety) end point was Bleeding Academic Research Consortium type 3 to 5 bleeding. Outcomes were assessed 12 months after randomization. Results: Out of the 3239 patients included in this analysis, 486 fulfilled the criteria for Academic Research Consortium-HBR definition (HBR group; ticagrelor, n=230 and prasugrel, n=256), while 2753 did not (non-HBR group; ticagrelor, n=1375 and prasugrel, n=1378). Compared with the non-HBR group, the HBR group had a higher risk for the primary (hazard ratio [HR]=3.57 [95% CI, 2.79–4.57]; P P P for interaction=0.12) or secondary ( P for interaction=0.80) end points. Conclusions: In patients with acute coronary syndrome undergoing percutaneous coronary intervention, HBR status increased both ischemic and bleeding risk without significant impact on the relative efficacy and safety of either ticagrelor or prasugrel. These results warrant confirmation in larger cohorts. Registration: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT01944800.

ObjectivesTo estimate the treatment incidence of post-COVID syndrome (postinfectious sequelae present at least 12 weeks following infection) in the context of ambulatory care in Bavaria, Germany, and to establish whether related diagnoses occur more frequently than in patients with no known history of COVID-19.DesignRetrospective cohort analysis of routinely collected claims data.SettingAmbulatory care in Bavaria, Germany, observed from January 2020 to March 2022 (data accessed May 2022).Participants391 990 patients with confirmed COVID-19 diagnosis, 62 659 patients with other respiratory infection and a control group of 659 579 patients with no confirmed or suspected diagnosis of COVID-19.Primary and secondary outcome measuresPrimary outcome is diagnosis of post-COVID syndrome documented in ambulatory care. Secondary outcomes are: chronic fatigue syndrome, psychological disorder, fatigue, mild cognitive impairment, disturbances of taste and smell, dyspnoea, pulmonary embolism and myalgia.ResultsAmong all patients with confirmed COVID-19, 14.2% (95% CI 14.0% to 14.5%) received a diagnosis of a post-COVID syndrome, and 6.7% (95% CI 6.5% to 6.9%) received the diagnosis in at least two quarterly periods during a 2-year follow-up. Compared with patients with other respiratory infections and with controls, patients with COVID-19 more frequently received a variety of diagnoses including chronic fatigue syndrome (1.6% vs 0.6% and 0.3%, respectively), fatigue (13.3% vs 9.2% and 6.0%), dyspnoea (9.9% vs 5.1% and 3.2%) and disturbances of taste and smell (3.2% vs 1.2% and 0.5%). The treatment incidence of post-COVID syndrome was highest among adults aged 40–59 (19.0%) and lowest among children aged below 12 years (2.6%).ConclusionsOur results demonstrate a moderately high incidence of post-COVID syndrome 2 years after COVID-19 diagnosis. There is an urgent need to find efficient and effective solutions to help patients with dyspnoea, fatigue, cognitive impairment and loss of smell. Guidelines and treatment algorithms, including referral criteria, and occupational and physical therapy, require prompt and coherent implementation.

Asthma education programs (AEPs) have been shown to increase quality of life and reduce emergency treatments and hospital admissions. Despite the proven benefits, only a minority of asthma patients attend such programs. To increase the number of educated patients, an online education program (electronic AEP, eAEP) for asthma patients has been developed. The present study aims to investigate the effectiveness of the eAEP in terms of asthma knowledge, asthma control and emergency treatments in general practice settings.This is a cluster randomized controlled trial including 100 patients with bronchial asthma from 20 general practices in Bavaria, Germany. General practices will be randomly assigned to either the intervention or control group. Patients in the intervention group will receive access to the eAEP and instructions to complete this program within two weeks. Patients in the control group will receive usual care including a referral to face-to-face AEP (fAEP) by a certified primary care physician or a pulmonologist according to guideline recommendations. Furthermore, patients of both the intervention and control groups will be invited to a follow-up consultation in their general practice after completion of the eAEP and fAEP (three weeks and twelve weeks after study inclusion, respectively) to discuss any open issues. Outcomes for both groups will be assessed at baseline (tThe results of the present trial will provide knowledge about the effectiveness of an online education program for asthma patients compared to usual care in primary care.German Clinical Trials Register (DRKS), DRKS00028805 . Registered 22 April 2022.

Aims Dynamic retinal vessel analysis (DVA) provides a noninvasive way to asses microvascular function in patients and potentially to improve predictions of individual cardiovascular (CV) risk. The aim of our study was to use untargeted machine learning on DVA in order to improve CV mortality prediction and to identify corresponding response alterations. Methods and results We adopted a workflow consisting of noise reduction and extraction of independent components within DVA signals. Predictor performance was assessed in survival random forest models. Applying our technique to the prediction of all-cause mortality in a cohort of 214 hemodialysis patients resulted in the selection of a component which was highly correlated to maximal venous dilation following flicker stimulation (vMax), a previously identified predictor, confirming the validity of our approach. When fitting for CV mortality as the outcome of interest, a combination of three components derived from the arterial signal resulted in a marked improvement in predictive performance. Clustering analysis suggested that these independent components identified groups of patients with substantially higher CV mortality. Conclusions Our results provide a machine learning workflow to improve the predictive performance of DVA and identify groups of hemodialysis patients at high risk of CV mortality. Our approach may also prove to be promising for DVA signal analysis in other CV disease states. Translational perspective DVA is a noninvasive technique which can help to assess microvascular dysfunction, one of the driving factors of CV disease. This study demonstrates a machine learning method which improves DVA interpretation for the estimation of CV risk in hemodialysis patients. Similar techniques can help doctors to identify high risk patients for timely therapeutic interventions and to monitor the effects of these interventions.

Tumour budding (TB) has been associated with adverse clinicopathological factors and poor survival in a plethora of therapy-naïve carcinoma entities including gastric adenocarcinoma (GC). As conventional histopathological grading is usually omitted in the post-neoadjuvant setting of GC, our study aimed to investigate the prognostic impact of TB in GCs resected after neoadjuvant therapy. We evaluated TB according to the criteria from the International Tumour Budding Consensus Conference (ITBCC) in 167 post-neoadjuvant resections of intestinal-type GC and correlated the results with overall survival (OS) and clinicopathological parameters. GCs were categorised into Bd1 (0-4 buds, low TB), Bd2 (5-9 buds, intermediate TB), and Bd3 (≥10 buds, high TB). Carcinomas with intermediate and high TB were significantly enriched in higher ypTNM stages and strongly associated with reduced 5-year OS in univariable analyses (p 0.001). In multivariable analyses including sex, age, resection status, UICC stage, and tumour regression grading, TB remained a stage-independent predictor of survival (p 0.001, hazard ratio Bd2: 2.60, Bd3: 4.74). The assessment of TB according to the ITBCC criteria provides valuable prognostic information in the post-neoadjuvant setting of intestinal-type GC and may be a considerable substitute for the conventional grading system in GCs after neoadjuvant therapy.

Background: Subgroup analyses are frequently used to assess heterogeneity of treatment effects in randomised clinical trials. Inconsistent, improper and incomplete implementation, reporting and interpretation have been identified as ongoing challenges. Further, subgroup analyses were frequently criticised because of unreliable or potentially misleading results. More recently, recommendations and guidelines have been provided to improve the reporting of data in this regard. Methods: This systematic review was based on a literature search within the digital archives of three selected medical journals, The New England Journal of Medicine, The Lancet and Circulation. We reviewed articles of randomised clinical trials in the domain of cardiovascular disease which were published in 2015 and 2016. We screened and evaluated the selected articles for the mode of implementation and reporting of subgroup analyses. Results: We were able to identify a total of 130 eligible publications of randomised clinical trials. In 89/130 (68%) articles, results of at least one subgroup analysis were presented. This was dependent on the considered journal (p Conclusion: Compared to previous reviews in this context, we observed improvements in the reporting of subgroup analyses of cardiovascular randomised clinical trials. Nonetheless, critical shortcomings, such as inconsistent reporting of the implementation and insufficient pre-specification, persist.

Background After the ‘first wave’ in spring 2020, opinions regarding the threat and measures against COVID-19 seemed to vary among German general practitioners (GPs). Objectives To systematically investigate opinions and to identify subgroups of GPs sharing similar views. Methods A questionnaire was sent to all 210 practices accredited for undergraduate teaching of family medicine at the Medical Faculty of the Technical University of Munich. Questions addressed personal opinions regarding risks, dilemmas, restrictions and their relaxation associated with COVID-19, and personal fears, symptoms of depression and anxiety. Patterns of strong opinions (‘archetypes’) were identified using archetypal analysis, a statistical method seeking extremal points in the multidimensional data. Results One hundred and sixty-one GPs sent back a questionnaire (response rate 77%); 143 (68%) with complete data for all 38 relevant variables could be included in the analysis. We identified four archetypes with subgroups of GPs tending in the direction of these archetypes: a small group of ‘Sceptics’ (n = 12/8%) considering threats of COVID-19 as overrated and measures taken as exaggerated; ‘Hardliners’ (n = 34/24%) considering threats high and supporting strong measures; ‘Balancers’ (n = 77/54%) who also rated the threats high but were more critical about potentially impairing the quality of life of elderly people and children; and ‘Anxious’ GPs (n = 20/14%) tending to report more fear, depressive and anxiety symptoms. Conclusion Among the participants in this survey, opinions regarding the threat and the measures taken against COVID-19 during the ‘first wave’ in Germany in spring 2020 varied greatly.

Background: Data on the comparative efficacy and safety of ticagrelor versus prasugrel in patients with ST-segment–elevation myocardial infarction undergoing primary percutaneous coronary intervention are limited. We assessed the efficacy and safety of ticagrelor versus prasugrel in a head-to-head comparison in patients with ST-segment–elevation myocardial infarction undergoing primary percutaneous coronary intervention. Methods: In this prespecified subgroup analysis, we included 1653 patients with ST-segment–elevation myocardial infarction randomized to receive ticagrelor or prasugrel in the setting of the ISAR REACT-5 trial (Intracoronary Stenting and Antithrombotic Regimen: Rapid Early Action for Coronary Treatment 5). The primary end point was the incidence of death, myocardial infarction, or stroke at 1 year after randomization. The secondary end point was the incidence of bleeding defined as BARC (Bleeding Academic Research Consortium) type 3 to 5 bleeding at 1 year after randomization. Results: The primary end point occurred in 83 patients (10.1%) in the ticagrelor group and in 64 patients (7.9%) in the prasugrel group (hazard ratio, 1.31 [95% CI, 0.95–1.82]; P =0.10). One-year incidence of all-cause death (4.9% versus 4.7%; P =0.83), stroke (1.3% versus 1.0%; P =0.46), and definite stent thrombosis (1.8% versus 1.0%; P =0.15) did not differ significantly in patients assigned to ticagrelor or prasugrel. One-year incidence of myocardial infarction (5.3% versus 2.8%; hazard ratio, 1.95 [95% CI, 1.18–3.23]; P =0.010) was higher with ticagrelor than with prasugrel. BARC type 3 to 5 bleeding occurred in 46 patients (6.1%) in the ticagrelor group and in 39 patients (5.1%) in the prasugrel group (hazard ratio, 1.22 [95% CI, 0.80–1.87]; P =0.36). Conclusions: In patients with ST-segment–elevation myocardial infarction undergoing primary percutaneous coronary intervention, there was no significant difference in the primary end point between prasugrel and ticagrelor. Ticagrelor was associated with a significant increase in the risk for recurrent myocardial infarction. Registration: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT01944800.

Bone volume changes following vascularized bone flaps and possible confounding factors over time are described in the literature with some controversy. The purpose of this study was to evaluate the bone volume behavior of two frequently used free flaps.Computed tomography (CT) scans were examined with regard to bone volume using the software program ITK-SNAP for all patients who required mandibular reconstruction with a free fibula flap (FFF, conventionally vs assisted by computer-aided design/computer-aided manufacturing (CAD/CAM)) or iliac crest flap (DCIA) following mandibular resection because of benign or malign processes, between August 2010 and August 2015. Clinical data, complication rates, and CT scans were analyzed retrospectively. Additionally, complication rates (microvascular revision, flap loss, postoperative fistula or dehiscence, and postoperative bone exposure) were compared within early (≤30 days), late (31st-100th day), and overall (≤100th day) postoperative time intervals.113 cases, comprizing 89 FFF and 24 DCIA cases, were included. FFF showed superior bone volume behavior over the DCIA flap. Multivariable regression models assessed the relationships between the following and bone volume behavior: interval between operation and CT scan (p 0.683), age (p = 0.004), gender (p = 0.006), BMI (p = 0.400), adjuvant radiation therapy (p = 0.334), reconstruction with DCIA flap (p 0.0001), number of segments (p = 0.02), and incidence of dental implant insertion (p = 0.45).The bone volume of FFFs remains stable. DCIA flaps show a higher bone volume reduction, but the postoperative course might be associated with fewer complications. Time interval between operation and CT scan, age, gender, reconstruction with DCIA flap, and number of fibula segments contributed significantly to bone volume behavior.

The authors discuss minimally invasive and noninvasive cardiac output monitoring technologies available in the clinical practice and how to evaluate these systems objectively.

Objective Ward rounds are an essential part of physicians' daily routine. Existing studies suggest that their practical implementation is inconsistent. Therefore, developing interventions to train ward round competence and assessing if they are effective educational tools are crucial goals for research. Methods We analysed a simulation-based tutorial dedicated to fourth-year medical students, including casework and ward round simulation. We investigated the effectiveness of this intervention regarding ward round competence through a randomized controlled trial. Performance was assessed with the modified/validated surgical ward round assessment tool by two blinded and trained raters. Supplementary, motivation during the ward round tutorial was assessed for all students at different time points. Results Analysis of the ratings show that, in contrast to the control group (pre: 66.1 vs. post: 64.8 points, p = 0.72), the ward round competence of the intervention group (pre: 62.6 vs. post: 69.6 points, p = 0.0169) improved significantly after participating in the ward round tutorial. Conclusion The results show that our simulation-based training is an effective way to improve competence of medical students in conducting surgical ward rounds. Practice implications Participation in ward round trainings is a valuable tool to prepare students for their future professional practise.

BACKGROUND Invasive coronary angiography (ICA) still causes a significant amount of radiation exposure for patients and operators. In February 2017, the Azurion system was introduced, a new-generation fluoroscopy image acquisition and processing system. Radiation exposure in patients undergoing ICA was assessed comparing the novel Azurion 7 F12 angiography system to its predecessor Allura Xper in a randomized manner. METHODS Radiation exposure was prospectively analyzed in 238 patients undergoing diagnostic ICA. Patients were randomly assigned to the novel Azurion system (119 patients) or its predecessor Allura Xper system (119 patients). In each patient, 8 predefined standard projections (5 left coronary artery, 3 right coronary artery) were performed. Image quality was quantified by grading of the images on the basis of a 5-point grading system. RESULTS Radiation dose area product was significantly lower in the Azurion group 109 (interquartile range [IQR 75-176] cGy cm) compared with the Allura Xper group 208 [IQR 134-301] cGy cm (P

Cardiac output (CO) is a key determinant of oxygen delivery, but choosing the optimal method to obtain CO in pediatric patients remains challenging. The pressure recording analytical method (PRAM), implemented in the MostCareUp system (Vygon), is an invasive uncalibrated pulse wave analysis (PWA) method to measure CO. The objective of this study is to compare CO measured by PRAM (PRAM-CO; test method) with CO simultaneously measured by transesophageal Doppler echocardiography (TEE-CO; reference method) in pediatric patients.In this prospective observational method comparison study, PRAM-CO and TEE-CO were assessed in pediatric elective cardiac surgery patients at 2 time points: after anesthesia induction and after surgery. The study was performed in a German university medical center from March 2019 to March 2020. We included pediatric patients scheduled for elective cardiac surgery with arterial catheter and TEE monitoring. PRAM-CO and TEE-CO were compared using Bland-Altman analysis accounting for repeated measurements per subject, and the percentage error (PE).We included 52 PRAM-CO and TEE-CO measurement pairs of 30 patients in the final analysis. Mean ± SD TEE-CO was 2.15 ± 1.31 L/min (range 0.55-6.07 L/min), and mean PRAM-CO was 2.21 ± 1.38 L/min (range 0.55-5.90 L/min). The mean of the differences between TEE-CO and PRAM-CO was -0.06 ±0.38 L/min with 95% limits of agreement (LOA) of 0.69 (95% confidence interval [CI], 0.53-0.82 L/min) to -0.80 L/min (95% CI, -1.00 to -0.57 L/min). The resulting PE was 34% (95% CI, 27%-41%).With a PE of45%, PRAM-CO shows clinically acceptable agreement with TEE-CO in hemodynamically stable pediatric patients before and after cardiac surgery.

Survivors of an acute myocardial infarction with diabetes mellitus retain an increased mortality risk. Reliable assessment of individual risk is required for effective and cost-efficient medical care in these patients. The Polyscore is a previously established risk predictor consisting of seven autonomic tests derived from electrocardiogram, blood pressure, and respiration. The Polyscore allows classification of survivors of myocardial infarction in groups at low, intermediate and high mortality risk. The aim of this study was to investigate the prognostic value of the Polyscore in diabetic survivors of acute myocardial infarction, which may be impaired by the presence of diabetic autonomic neuropathy. Survivors of an acute myocardial infarction were included in a prospective cohort study during hospitalisation due to the index event at two university hospitals in Munich, Germany. The Polyscore was determined from simultaneous non-invasive 30-min recordings of electrocardiogram, continuous arterial blood pressure, and respiration which were performed in all participants. Patients were followed for 5 years. The primary and secondary outcomes were all-cause mortality and cardiac mortality. 184 of 941 enrolled patients (19.6%) suffered from diabetes mellitus. 5-year-mortality was higher in diabetic patients (15.2%) compared to non-diabetic patients (5.8%). A multivariable Cox regression model confirmed the Polyscore as a strong predictor of mortality in diabetic post-MI patients (intermediate risk: HR 6.56, 95% CI 1.61–26.78, p = 0.004, mortality 22.8%; high risk: HR 18.76, 95% CI 4.35–80.98, p

Background: Pregnancies have an impact on the disease course of multiple sclerosis (MS), but their relationship with MS risk is yet unclear. Objective: To determine the relationships of pregnancies and gynecological diagnoses with MS risk. Methods: In this retrospective case–control study, we assessed differences in gynecological International Classification of Diseases, 10th Revision (ICD-10) code recording rates between women with MS ( n = 5720), Crohn’s disease ( n = 6280), or psoriasis ( n = 40,555) and women without these autoimmune diseases ( n = 26,729) in the 5 years before diagnosis. Results: Twenty-eight ICD-10 codes were recorded less frequently for women with MS as compared to women without autoimmune disease, 18 of which are pregnancy-related. After adjustment for pregnancies, all codes unrelated to pregnancies were still negatively associated with MS. In a sensitivity analysis excluding women with evidence for possible demyelinating events before diagnosis, all associations were more pronounced. In comparison to women with psoriasis, most associations could be confirmed; that was not true in comparison to women with Crohn’s disease. Conclusion: Our findings provide evidence for a possible protective effect of pregnancies on MS risk likely independent of or in addition to a previously suggested reversed causality. The negative associations of gynecological disorders with disease risk need further investigation. The associations might be shared by different autoimmune diseases.

Understanding immune responses to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is crucial to contain the COVID-19 pandemic. Using a multiplex approach, serum IgG responses against the whole SARS-CoV-2 proteome and the nucleocapsid proteins of endemic human coronaviruses (HCoVs) were measured in SARS-CoV-2-infected donors and healthy controls. COVID-19 severity strongly correlated with IgG responses against the nucleocapsid (N) of SARS-CoV-2 and possibly with the number of viral antigens targeted. Furthermore, a strong correlation between COVID-19 severity and serum responses against N of endemic alpha- but not betacoronaviruses was detected. This correlation was neither caused by cross-reactivity of antibodies, nor by a general boosting effect of SARS-CoV-2 infection on pre-existing humoral immunity. These findings raise the prospect of a potential disease progression marker for COVID-19 severity that allows for early stratification of infected individuals.

Perioperative antibiotic prophylaxis is an established concept to reduce the risk of surgical-site infections; however, the optimal treatment duration in prosthetic breast reconstruction is still controversial. This study evaluated a potential association between the perioperative antibiotic prophylaxis duration (≤24 hours versus24 hours) and incidence of postoperative surgical-site infections in immediate implant-based breast reconstruction in breast cancer patients.A descriptive, retrospective analysis of surgical-site infections after immediate implant-based breast reconstruction in breast cancer patients between January of 2011 and December of 2018 was performed. The incidence of postoperative surgical-site infections in patients with more than 24 hours of perioperative antibiotic prophylaxis was compared to patients treated for 24 hours or less.A total of 240 patients who met criteria were included. There were no relevant epidemiologic, clinical, or histopathologic differences between groups. Surgical-site infections as defined by the Centers for Disease Control and Prevention criteria occurred in 25.8 percent. A risk factor-adjusted analysis by a prespecified multiple logistic regression model showed that 24 hours or less of perioperative antibiotic prophylaxis was not inferior to treatment for more than 24 hours. The upper limit of the one-sided 95 percent confidence interval of the risk difference was 9.4 percent (below the prespecified noninferiority margin of 10 percent leading to statistical significance). Risk factors for a surgical-site infection included obesity and postoperative wound complications.The study found no association between short-course perioperative antibiotic prophylaxis (≤24 hours) and an increased rate of postoperative surgical-site infection. This is of high clinical relevance because short-course treatment can help reduce side effects and the emergence of antimicrobial resistance and prevent surgical-site infections as effectively as a prolonged perioperative antibiotic prophylaxis course.Therapeutic, III.

We investigated the clinical impact of elevated microsatellite instability at selected tetranucleotide (EMAST) repeats in the context of neoadjuvant chemotherapy (CTx) in gastric/gastro-oesophageal adenocarcinomas. We analysed 583 resected tumours (272 without and 311 after CTx) and 142 tumour biopsies before CTx. If at least two or three of the five tetranucleotide repeat markers tested showed instability, the tumours were defined as EMAST (2+) or EMAST (3+), respectively. Expression of mismatch repair proteins including MSH3 was analysed using immunohistochemistry. Microsatellite instability (MSI) and Epstein-Barr virus (EBV) positivity were determined using standard assays. EMAST (2+) and (3+) were detected in 17.8 and 11.5% of the tumours, respectively. The frequency of EMAST (2+) or (3+) in MSI-high (MSI-H) tumours was 96.2 or 92.5%, respectively, demonstrating a high overlap with this molecular subtype, and the association of EMAST and MSI status was significant (each overall p 0.001). EMAST (2+ or 3+) alone in MSI-H and EBV-negative tumours demonstrated only a statistically significant association of EMAST (2+) positivity and negative lymph node status (42.3% in EMAST (2+) and 28.8% in EMAST negative, p = 0.045). EMAST alone by neither definition was significantly associated with overall survival (OS) of the patients. The median OS for EMAST (2+) patients was 40.0 months (95% confidence interval [CI] 16.4-63.6) compared with 38.7 months (95% CI 26.3-51.1) for the EMAST-negative group (p = 0.880). The median OS for EMAST (3+) patients was 46.7 months (95% CI 18.2-75.2) and 38.7 months (95% CI 26.2-51.2) for the negative group (p = 0.879). No statistically significant association with response to neoadjuvant CTx was observed (p = 0.992 and p = 0.433 for EMAST (2+) and (3+), respectively). In conclusion, our results demonstrate a nearly complete intersection between MSI-H and EMAST and they indicate that EMAST alone is not a distinct instability type associated with noticeable clinico-pathological characteristics of gastric carcinoma patients.

Background: Institutional programs such as antibiotic stewardship (ABS) programs offer possibilities to monitor and modify antibiotic usage with the aim of reducing antibiotic resistance. In orthop...

Cardiac output (CO) is a key hemodynamic variable that can be minimally invasively estimated by pulse wave analysis. Multi-beat analysis is a novel pulse wave analysis method. In this prospective observational clinical method comparison study, we compared CO estimations by multi-beat analysis with CO measured by intermittent pulmonary artery thermodilution (PATD) in adult patients treated in the intensive care unit (ICU) after off-pump coronary artery bypass surgery (OPCAB). We included patients after planned admission to the ICU after elective OPCAB who were monitored with a radial arterial catheter and a pulmonary artery catheter. At seven time points, we determined CO using intermittent PATD (PATD-CO; reference method) and simultaneously recorded the radial arterial blood pressure waveform that we later used to estimate CO using multi-beat analysis (MBA-CO; test method) with the Argos monitor (Retia Medical; Valhalla, NY, USA). Blood pressure waveforms impaired by inappropriate damping properties or artifacts were excluded. We compared PATD-CO and MBA-CO using Bland–Altman analysis accounting for repeated measurements, the percentage error, and the concordance rate derived from four-quadrant plot analysis (15% exclusion zone). We analyzed 167 CO values of 31 patients. Mean PATD-CO was 5.30 ± 1.22 L/min and mean MBA-CO was 5.55 ± 1.82 L/min. The mean of the differences between PATD-CO and MBA-CO was 0.08 ± 1.10 L/min (95% limits of agreement: − 2.13 L/min to + 2.29 L/min). The percentage error was 40.7%. The four-quadrant plot-derived concordance rate was 88%. CO estimation by multi-beat analysis of the radial arterial blood pressure waveform (Argos monitor) shows reasonable agreement compared with CO measured by intermittent PATD in adult patients treated in the ICU after OPCAB.

Pulse wave analysis enables stroke volume to be estimated from an arterial blood pressure waveform. Multi-beat analysis is a novel pulse wave analysis method. We aimed to investigate cardiac output (CO) estimations using multi-beat analysis of the radial arterial blood pressure waveform in patients undergoing off-pump coronary artery bypass surgery (OPCAB) using intermittent pulmonary artery thermodilution (PATD) as the reference method. This was a prospective clinical method comparison study. In 58 patients, we measured CO using PATD (PATD-CO; reference method) and simultaneously recorded the radial arterial blood pressure waveform that we used for off-line estimation of CO based on multi-beat analysis (MBA-CO; test method) using the Argos CO monitor (Retia Medical; Valhalla, NY, USA). The final analysis was performed using 572 paired CO measurements. We performed Bland–Altman analysis accounting for multiple observations per patient. To describe the ability of the test method to track changes in CO over time we computed four-quadrant plots using a central exclusion zone of 15% and calculated the concordance rate. Mean PATD-CO was 4.13 ± 1.26 L/min and mean MBA-CO was 4.31 ± 1.25 L/min. The mean of the differences between PATD-CO and MBA-CO was − 0.20 L/min with a standard deviation of ± 1.14 L/min and 95% limits of agreement of − 2.48 to + 2.08 L/min. The concordance rate for CO changes between PATD-CO and MBA-CO was 89%. CO estimations using multi-beat analysis (Argos monitor) show reasonable agreement and trending ability compared with PATD-CO as the reference method in adult patients during OPCAB.

Objectives The purpose of the study was to investigate the impact of oral anticoagulation (OAC) type on clinical outcomes 1 year after transcatheter aortic valve replacement (TAVR). Background Non–vitamin K oral anticoagulants (NOACs) are superior to vitamin K antagonists (VKAs) in nonvalvular atrial fibrillation (AF), while their comparative performance among patients in need of OAC undergoing TAVR is underinvestigated. Methods The study enrolled 962 consecutive patients who underwent TAVR in 4 tertiary European centers and were discharged on either NOACs (n = 326) or VKAs (n = 636). By using propensity scores for inverse probability of treatment weighting (IPTW), the comparison of treatment groups was adjusted to correct for potential confounding. Results Mean age and Society of Thoracic Surgeons score of the population were 81.3 ± 6.3 years and 4.5% (interquartile range: 3.0% to 7.3%); 52.5% were women and a balloon-expandable valve was used in 62.7% of cases. The primary outcome of interest, combined incidence of all-cause mortality, myocardial infarction, and any cerebrovascular event at 1-year after TAVR, was 21.2% with NOACs versus 15.0% with VKAs (hazard ratio [HR]: 1.44; 95% confidence interval [CI]: 1.00 to 2.07; p = 0.050, IPTW-adjusted). The 1-year incidence of any Bleeding Academic Research Consortium bleeds and all-cause mortality were comparable between the NOAC and VKA groups, 33.9% versus 34.1% (HR: 0.97; 95% CI: 0.74 to 1.26; p = 0.838, IPTW-adjusted) and 16.5% versus 12.2% (HR: 1.36; 95% CI: 0.90 to 2.06; p = 0.136, IPTW-adjusted), respectively. Conclusions Chronic use of both NOACs and VKAs among patients in need of OAC after TAVR are comparable regarding 1-year bleeding risk. The higher ischemic event rate observed with NOACs needs to be evaluated in large randomized trials.

BACKGROUND AND AIM In contrast to the first peak of multi-organ failure in acute pancreatitis, the second peak is mostly triggered by septic complications. Our aim was to analyze the spectrum of pathogens and antimicrobial resistance development in relation to the time-course of the disease and its clinical outcome. METHODS One hundred twenty-two patients with acute necrotizing pancreatitis undergoing pancreas puncture at two tertiary academic medical centers in Germany were retrospectively analyzed. RESULTS At species level, there was a change in spectrum from Enterococcus faecalis (∆d150 - d1 = 14.6% - 16.7% = -2.1%) to Enterococcus faecium (∆d150 - d1 = 93.1% - 16.3% = 76.8%) (P

Objectives To assess the ability of multislice detector computed tomography (MDCT) to differentiate old versus acute/subacute vertebral fractures (VF) and to identify characteristic MDCT imaging signs. Methods 74 consecutive patients demonstrated 192 VF that were classified as either acute/subacute or old based on magnetic resonance imaging, MDCT, and clinical information as reference standard. Classification as acute/subacute versus old fractures based on MDCT alone was evaluated on a Likert scale by 2 independent radiologists. Morphologic MDCT features of fractures, such as trabecular compaction or fracture line, were recorded. Receiver operating characteristic analyses and Cohen's κ were used to assess the discriminatory power of the MDCT and interrater agreement, respectively. Results Out of all 192 VF, 148 fractures were acute/subacute and 44 were old according to the reference standard. Receiver operating characteristic analyses of sole MDCT assessment showed very good identification of acute/subacute VF, with areas under the curve of 0.854 and 0.861 for readers 1 and 2, respectively. When indeterminate findings were treated as acute/subacute fractures, sensitivity and specificity were 97.2% and 58.1% for reader 1 and 94.5% and 65.1% for reader 2. Interrater agreement regarding fracture age was good (weighted Cohen's κ = 0.607). Trabecular compression/callus distinct from the cortex (double compaction sign) was present in approximately half of acute/subacute VF and highly specific for acute/subacute VF (specificity = 93.2% and 88.6% for readers 1 and 2, respectively). Conclusion The acuity of VF can be assessed by MDCT alone with high sensitivity and in case of a double compaction sign with high specificity.

Background Screening questionnaires are not sufficient to improve diagnostic quality of depression in primary care. The additional consideration of the general practitioner’s (GP’s) assessment could improve the accuracy of depression diagnosis. The aim of this study was to examine whether the GP rating supports a reliable depression diagnosis indicated by the PHQ-9 over a period of three months. Methods We performed a secondary data analysis from a previous study. PHQ-9 scores of primary care patients were collected at the time of recruitment (t1) and during a follow-up 3 months later (t2). At t1 GPs independently made a subjective assessment whether they considered the patient depressive (yes/no). Two corresponding groups with concordant and discordant PHQ-9 and GP ratings at t1 were defined. Reliability of the PHQ-9 results at t1 and t2 was assessed within these groups and within the entire sample by Cohen’s Kappa, Pearson’s correlation coefficient and Bland-Altman plots. Results 364 consecutive patients from 12 practices in the region of Upper Bavaria/Germany participated in this longitudinal study. 279 patients (76.6%) sent back the questionnaire at t2. Concordance of GP rating and PHQ-9 at t1 led to higher replicability of PHQ-9 results between t1 and t2. The reliability of PHQ-9 was higher in the concordant subgroup (κ = 0.507) compared to the discordant subgroup (κ = 0.211) (p = 0.064). The Bland-Altman Plot showed that the deviation of PHQ-9 scores at t1 and t2 decreased by about 15% in the concordant subgroup. Pearson’s correlation coefficient between PHQ-9 scores at t1 and t2 increased significantly if the GP rating was concordant with the PHQ-9 at t1 (r = 0.671) compared to the discordant subgroup (r = 0.462) (p = 0.044). Conclusions The combination of PHQ-9 and GP rating might improve diagnostic decision making regarding depression in general practices. PHQ-9 positive results might be more reliable and accurate, when a concordant GP rating is considered.

Postinduction and intraoperative hypotension are associated with organ injury in non-cardiac surgery patients. Automated ambulatory blood pressure monitoring can identify chronic arterial hypertension and nocturnal blood pressure non-dipping. We tested the hypotheses that: a) chronic arterial hypertension and nocturnal non-dipping are independent risk factors for postinduction and intraoperative hypotension; and b) adding information on chronic arterial hypertension and nocturnal non-dipping improves hypotension prediction models based on readily available preoperative clinical information.Prediction model development based on a secondary analysis of a prospective observational study.German university medical center.366 non-cardiac surgery patients who had preoperative automated ambulatory blood pressure monitoring.Multivariable analyses to identify risk factors for postinduction and intraoperative hypotension. Area under receiver operating characteristics curves (AUROC) and likelihood-ratio tests to test whether adding information on chronic arterial hypertension and nocturnal non-dipping improves hypotension prediction models based on readily available preoperative clinical information.Risk factors for postinduction hypotension were age in years (odds ratio: 1.06 (95% confidence interval: 1.03 to 1.10), P = 0.001), American Society of Anesthesiologists physical status class (1.85 (1.02 to 3.35), P = 0.043), preoperative use of angiotensin-converting enzyme inhibitors or angiotensin II receptor blockers (15.19 (1.76 to 131.46), P = 0.013), chronic arterial hypertension (2.54 (1.49 to 4.34), P = 0.001), and nocturnal non-dipping (3.61 (2.09 to 6.23), P 0.001). The model's AUROC was 0.76 (95% confidence interval: 0.71 to 0.81) with and 0.67 (0.62 to 0.73) without information on chronic arterial hypertension and nocturnal non-dipping (P 0.001). Risk factors for intraoperative hypotension were male sex (1.73 (1.07 to 2.80), P = 0.025), chronic arterial hypertension (4.35 (2.33 to 8.14), P 0.001), and nocturnal non-dipping (3.56 (2.07 to 6.11), P 0.001). The model's AUROC was 0.76 (0.70 to 0.81) with and 0.63 (0.57 to 0.69) without information on chronic arterial hypertension and nocturnal non-dipping (P 0.001).Chronic arterial hypertension and nocturnal non-dipping are independent risk factors for postinduction and intraoperative hypotension in non-cardiac surgery patients. Adding information on chronic arterial hypertension and nocturnal non-dipping moderately improved hypotension prediction models based on preoperative clinical information.

The competence centre for Residency Training in Family Medicine Bavaria (CCRTB) was established to improve the quality of postgraduate medical education by offering training and mentoring programmes for residents, and by providing train-the-trainer and mentoring courses for supervisors. Beyond that, regional Residency Training Networks (RTN) on avoluntary basis were developed to facilitate structured and efficient clinical rotation programs. Primary aim was to investigate the burden of burnout and the development of professionalism among CCRTB-residencies within a cross-sectional study. Secondary aim was to evaluate differences between CCRTB-residents with and without participation in aregional RTN. Burnout was determined with the Maslach Burnout Inventory (MBI), comprising the scales emotional exhaustion, depersonalization, and personal accomplishment. Ambulatory professionalization was evaluated using the German Professional Scale (Pro-D), comprising the scales professionalism towards the patient, towards other professionals, towards society, and towards oneself. Statistical significance of group differences was calculated by nonparametric tests. Multivariable linear regression modelling was performed to estimate the independent impact of professionalization and RTN participation on burnout scores. 347 CRRTB residents in ambulatory postgraduate training were invited, 212 (61.1%) participated, and 197 (92.9%) were included in our analyses. Lower emotional exhaustion and depersonalization, and increased personal accomplishment was associated with increased professionalisation, which was significant for nearly all Pro-D scales (p ≤ 0.05). RTN residents showed higher professionalism towards the patient (p = 0.031), other professionals (p = 0.012), and towards the society (p = 0.007) than residents of unstructured programs, and higher levels of personal accomplishment (p < 0.05). Early and efficient professionalization might be akey to reduce burnout and to establish asatisfying career in family medicine. Train-the-trainer and mentoring concepts should be implemented regularly for the training of residents. Thus, increased engagement in medical didactics should be aprerequisite for accreditation as atraining practice for residents.

Background The Cancer Genome Atlas (TCGA) consortium described EBV positivity(+), high microsatellite instability (MSI-H), genomic stability (GS) and chromosomal instability (CIN) as molecular subtypes in gastric carcinomas (GC). We investigated the predictive and prognostic value of these subtypes with emphasis on CIN in the context of neoadjuvant chemotherapy (CTx) in GC. Methods TCGA subgroups were determined for 612 resected adenocarcinomas of the stomach and gastro-oesophageal junction (291 without, 321 with CTx) and 143 biopsies before CTx. EBV and MSI-H were analysed by standard assays. CIN was detected by multiplex PCRs analysing 22 microsatellite markers. Besides the TCGA classification, CIN was divided into four CIN-subgroups: low, moderate, substantial, high. Mutation profiling was performed for 52 tumours by next-generation sequencing. Results EBV(+) (HR, 0.48; 95% CI, 0.23–1.02), MSI-H (HR, 0.56; 95% CI, 0.35–0.89) and GS (HR, 0.72; 95% CI, 0.45–1.13) were associated with increased survival compared to CIN in the resected tumours. Considering the extended CIN-classification, CIN-substantial was a negative prognostic factor in uni- and multivariable analysis in resected tumours with CTx (each p p = 0.026), but was not prognostically relevant. Conclusion A refined CIN classification reveals tumours with different biological characteristics and potential clinical implications.

Importance It is unclear whether ticagrelor or prasugrel hydrochloride is superior for patients with acute coronary syndrome (ACS) treated with percutaneous coronary intervention (PCI). Objective To assess the safety and efficacy of ticagrelor vs prasugrel for patients with ACS treated with PCI. Design, Setting, and Participants A prespecified analysis was performed of a postrandomization subgroup of 3377 patients who presented with ACS and were treated with PCI in the investigator-initiated, multicenter, phase 4, open-label Intracoronary Stenting and Antithrombotic Regimen: Rapid Early Action for Coronary Treatment 5 randomized clinical trial, conducted from September 1, 2013, to February 28, 2018. Statistical analysis was performed from September 1, 2020, to January 30, 2021. Analysis was performed according to the intention-to-treat principle. Interventions Patients were randomly assigned to a ticagrelor-based or prasugrel-based strategy. This analysis focuses on the subgroup of patients who underwent PCI that was formed after randomization. Main Outcomes and Measures The primary end point was a composite consisting of all-cause death, myocardial infarction, or stroke at 12 months. The safety end point was Bleeding Academic Research Consortium (BARC) type 3 to 5 bleeding. Results The ticagrelor group comprised 1676 patients (1323 men [78.9%]; mean [SD] age, 64.4 [12.0] years), and the prasugrel group comprised 1701 patients (1341 men [78.8%]; mean [SD] age, 64.7 [12.0] years). The primary end point occurred for 162 patients (9.8%) in the ticagrelor group and 120 patients (7.1%) in the prasugrel group (hazard ratio [HR], 1.41; 95% CI, 1.11-1.78;P = .005). Myocardial infarction occurred in 88 patients (5.3%) in the ticagrelor group compared with 55 patients (3.8%) in the prasugrel group (HR, 1.67; 95% CI, 1.19-2.34;P = .003). The safety end point, BARC type 3 to 5 bleeding, occurred in 84 of 1672 patients (5.3%) in the ticagrelor group and 78 of 1680 patients (4.9%) in the prasugrel group (HR; 1.10; 95% CI, 0.81-1.50;P = .54). Conclusions and Relevance Among patients presenting with ACS who were treated with PCI, the incidence of the primary composite end point occurred less frequently for patients who received prasugrel compared with those who received ticagrelor. The incidence of bleeding events was comparable between the 2 groups. These results suggest that, for patients presenting with ACS who undergo PCI, a prasugrel-based strategy is superior to a ticagrelor-based strategy. However, because these observations are based on a postrandomization subgroup, these findings should be regarded as hypothesis generating and dedicated randomized clinical trials may be warranted to confirm these findings. Trial Registration ClinicalTrials.gov Identifier:NCT01944800

The study aimed to evaluate the diagnostic accuracy of contact history and clinical symptoms and to develop decision rules for ruling-in and ruling-out SARS-CoV-2 infection in family practice. We performed a prospective diagnostic study. Consecutive inclusion of patients coming for COVID-PCR testing to 19 general practices. Contact history and self-reported symptoms served as index test. PCR testing of nasopharyngeal swabs served as reference standard. Complete data were available from 1141 patients, 605 (53.0%) female, average age 42.2 years, 182 (16.0%) COVID-PCR positive. Multivariable logistic regression showed highest odds ratios (ORs) for “contact with infected person” (OR 9.22, 95% CI 5.61–15.41), anosmia/ageusia (8.79, 4.89–15.95), fever (4.25, 2.56–7.09), and “sudden disease onset” (2.52, 1.55–4.14). Patients with “contact with infected person” or “anosmia/ageusia” with or without self-reported “fever” had a high probability of COVID infection up to 84.8%. Negative response to the four items “contact with infected person, anosmia/ageusia, fever, sudden disease onset” showed a negative predictive value (NPV) of 0.98 (95% CI 0.96–0.99). This was present in 446 (39.1%) patients. NPV of “completely asymptomatic,” “no contact,” “no risk area” was 1.0 (0.96–1.0). This was present in 84 (7.4%) patients. To conclude, the combination of four key items allowed exclusion of SARS-CoV-2 infection with high certainty. With the goal of 100% exclusion of SARS-CoV-2 infection to prevent the spread of SARS-CoV-2 to the population level, COVID-PCR testing could be saved only for patients with negative response in all items. The decision rule might also help for ruling-in SARS-CoV-2 infection in terms of rapid assessment of infection risk.

Importance The assessment of new antithrombotic agents with a favorable safety profile is clinically relevant. Objective To test the efficacy and safety of revacept, a novel, lesion-directed antithrombotic drug, acting as a competitive antagonist to platelet glycoprotein VI. Design, Setting, and Participants A phase 2 randomized clinical trial; patients were enrolled from 9 centers in Germany from November 20, 2017, to February 27, 2020; follow-up ended on March 27, 2020. The study included patients with stable ischemic heart disease (SIHD) undergoing elective percutaneous coronary intervention (PCI). Interventions Single intravenous infusion of revacept, 160 mg, revacept, 80 mg, or placebo prior to the start of PCI on top of standard antithrombotic therapy. Main Outcomes and Measures The primary end point was the composite of death or myocardial injury, defined as an increase in high-sensitivity cardiac troponin to at least 5 times the upper limit of normal within 48 hours from randomization. The safety end point was bleeding type 2 to 5 according to the Bleeding Academic Research Consortium criteria at 30 days. Results Of 334 participants (median age, 67.4 years; interquartile range, 60-75.1 years; 253 men [75.7%]; and 330 White participants [98.8%]), 120 were allocated to receive the 160-mg dose of revacept, 121 were allocated to receive the 80-mg dose, and 93 received placebo. The primary end point showed no significant differences between the revacept and placebo groups: 24.4%, 25.0%, and 23.3% in the revacept, 160 mg, revacept, 80 mg, and placebo groups, respectively (P = .98). The high dose of revacept was associated with a small but significant reduction of high-concentration collagen-induced platelet aggregation, with a median 26.5 AU × min (interquartile range, 0.5-62.2 AU × min) in the revacept, 160 mg, group; 43.5 AU × min (interquartile range, 22.8-99.5 AU × min) in the revacept, 80 mg, group; and 41.0 AU × min (interquartile range, 31.2-101.0 AU × min) in the placebo group (P = .02), while adenosine 5′-diphosphate–induced aggregation was not affected. Revacept did not increase Bleeding Academic Research Consortium type 2 or higher bleeding at 30 days compared with placebo: 5.0%, 5.9%, and 8.6% in the revacept, 160 mg, revacept, 80 mg, and placebo groups, respectively (P = .36). Conclusions and Relevance Revacept did not reduce myocardial injury in patients with stable ischemic heart disease undergoing percutaneous coronary intervention. There were few bleeding events and no significant differences between treatment arms. Trial Registration ClinicalTrials.gov Identifier:NCT03312855

Objective Dealing with uncertainty is a core competence for physicians. To evaluate the impact of an educational intervention on family medicine residents’ (FMRs’) intention to request diagnostic tests and their attitudes toward uncertainty. Methods Nonrandomized controlled trial. Intervention group (IG) FMRs participated in interactive “dealing with uncertainty” seminars comprising statistical lessons and diagnostic reasoning. Control group (CG) FMRs participated in seminars without in-depth diagnostic lessons. FMRs completed the Dealing with Uncertainty Questionnaire (DUQ), comprising the Diagnostic Action and Diagnostic Reasoning scales. The Physicians’ Reaction to Uncertainty (PRU) questionnaire, comprising 4 scales (Anxiety Due to Uncertainty, Concern about Bad Outcomes, Reluctance to Disclose Uncertainty to Patients, and Reluctance to Disclose Mistakes to Physicians) was also completed. Follow-up was performed 3 months later. Differences were calculated with repeated-measures analysis of variance. Results In total, 107 FMRs of the IG and 102 FMRs of the CG participated at baseline and follow-up. The mean (SD) Diagnostic Action scale score decreased from 24.0 (4.8) to 22.9 (5.1) in the IG and increased in the CG from 23.7 (5.4) to 24.1 (5.4), showing significant group difference ( P = 0.006). The Diagnostic Reasoning scale increased significantly ( P = 0.025) without a significant group difference ( P = 0.616), from 19.2 (2.6) to 19.7 (2.4) in the IG and from 18.1 (3.3) to 18.8 (3.2) in the CG. The PRU scale Anxiety Due to Uncertainty decreased significantly ( P = 0.029) without a significant group difference ( P = 0.116), from 20.5 (4.8) to 18.5 (5.5) in the IG and from 19.9 (5.5) to 19.0 (6.0) in the CG. Conclusion The structured seminar reduced self-rated diagnostic test requisition. The change in Anxiety Due to Uncertainty and Diagnostic Reasoning might be due to an unspecific accompanying effect of the extra-occupational seminars for residents.

Background Risk factors of severe COVID-19 have mainly been investigated in the hospital setting. We investigated pre-defined risk factors for testing positive for SARS-CoV-2 infection and cardiovascular or pulmonary complications in the outpatient setting. Methods The present cohort study makes use of ambulatory claims data of statutory health insurance physicians in Bavaria, Germany, with polymerase chain reaction (PCR) test confirmed or excluded SARS-CoV-2 infection in first three quarters of 2020. Statistical modelling and machine learning were used for effect estimation and for hypothesis testing of risk factors, and for prognostic modelling of cardiovascular or pulmonary complications. Results A cohort of 99 811 participants with PCR test was identified. In a fully adjusted multivariable regression model, dementia (odds ratio (OR) = 1.36), type 2 diabetes (OR = 1.14) and obesity (OR = 1.08) were identified as significantly associated with a positive PCR test result. Significant risk factors for cardiovascular or pulmonary complications were coronary heart disease (CHD) (OR = 2.58), hypertension (OR = 1.65), tobacco consumption (OR = 1.56), chronic obstructive pulmonary disease (COPD) (OR = 1.53), previous pneumonia (OR = 1.53), chronic kidney disease (CKD) (OR = 1.25) and type 2 diabetes (OR = 1.23). Three simple decision rules derived from prognostic modelling based on age, hypertension, CKD, COPD and CHD were able to identify high risk patients with a sensitivity of 74.8% and a specificity of 80.0%. Conclusions The decision rules achieved a high prognostic accuracy non-inferior to complex machine learning methods. They might help to identify patients at risk, who should receive special attention and intensified protection in ambulatory care.

IntroductionThe measurement of fractional exhaled nitric oxide (FeNO) is promising for diagnosing asthma and might substitute for bronchial provocation (BP) tests. To evaluate the diagnostic accuracy of FeNO within a confirmatory study, the following hypotheses will be tested: (1) A FeNO cut-off >50 ppb (parts per billion) is suitable for diagnosing asthma (sensitivity 35%, specificity 95%); (2) If the clinical symptoms ‘allergic rhinitis’ and ‘wheezing’ are present, asthma can be diagnosed at FeNO >33 ppb with a positive predictive value (PPV) >70% and (3) A FeNO >33 ppb can predict responsiveness to inhaled corticosteroid (ICS) with a PPV >70%.Methods and analysisA prospective diagnostic study will be conducted in three practices of pneumologists in Germany. 300 patients suspected of suffering from asthma will be included. As an index test, patients perform FeNO measurement with the device NIOX VERO. As reference a test, patients are examined with whole bodyplethysmography and BP, if necessary. After 3 months, patients with an asthma diagnosis will be examined again to verify the diagnosis and evaluate ICS responsiveness. Patients who did not receive an asthma diagnosis at the initial examination will be phoned after 3 months and asked about persistent respiratory symptoms to exclude false negative findings. As a primary target, sensitivity and specificity of FeNO >50 ppb will be determined. As a secondary target the PPV for asthma at FeNO >33 ppb, when the symptoms ‘allergic rhinitis’ and ‘wheezing’ are present, will be calculated. Regarding ICS responsiveness, the PPV of FeNO >33 ppb will be determined.Ethics and disseminationThe study was approved by the Ethical Committee of the Technical University of Munich (Reference number 122/20 S). The major results will be published in peer-reviewed academic journals and disseminated through conferences.Trial registration numberDRKS00021125.

OBJECTIVES: The objective of the study is to determine the impact of changing reference standards (RS), namely spirometry vs. whole-body plethysmography (WBP), on estimation of the diagnostic accuracy of fractional exhaled nitric oxide (FeNO) and clinical signs and symptoms (CSS) as index tests regarding asthma diagnosis. STUDY DESIGN AND SETTING: This was a diagnostic study conducted in 393 patients attending a private practice of pneumologists with complaints suspicious of asthma. First, the index tests were compared with the diagnostic results of spirometry in terms of forced expiratory volume in the first second (FEV1) responsiveness. Second, the index tests were compared with the results of WBP in terms of specific airway resistance and FEV1 responsiveness. Areas under the curve (AUC) were compared with a generalized estimating equation approach based on binary logistic regression. RESULTS: FeNO values and CSS 'wheezing' and 'allergic rhinitis' showed higher specificities (P

Aims Present society is constantly ageing and elderly frequently suffer from conditions that are difficult and/or costly to treat if detected late. Effective screening of the elderly is therefore needed so that those requiring detailed clinical work-up are identified early. We present a prospective validation of a screening strategy based on a Polyscore of seven predominantly autonomic, non-invasive risk markers. Methods and results Within a population-based survey in Germany (INVADE study), participants aged ≥60 years were enrolled between August 2013 and February 2015. Seven prospectively defined Polyscore components were obtained during 30-min continuous recordings of electrocardiogram, blood pressure, and respiration. Out of 1956 subjects, 168 were excluded due to atrial fibrillation, implanted pacemaker, or unsuitable recordings. All-cause mortality over a median 4-year follow-up was prospectively defined as the primary endpoint. The Polyscore divided the investigated population (n = 1788, median age: 72 years, females: 58%) into three predefined groups with low (n = 1405, 78.6%), intermediate (n = 326, 18.2%), and high risk (n = 57, 3.2%). During the follow-up, 82 (4.6%) participants died. Mortality in the Polyscore-defined risk groups was 3.4%, 7.4%, and 17.5%, respectively (P Conclusion The Polyscore-based mortality risk assessment from short-term non-invasive recordings is effective in the elderly general population, especially those aged 60–74 years. Implementation of a comprehensive Polyscore screening of this age group is proposed to advance preventive medical care.

Background The efficacy and safety of a reduced dose of prasugrel versus a standard dose of ticagrelor in elderly patients or those with a low body weight presenting with an acute coronary syndrome (ACS) are unknown. Objective To investigate the effect of an age- and weight-adapted dose of prasugrel versus a standard dose of ticagrelor in patients with ACS. (ClinicalTrials.gov: NCT01944800). Design Prespecified analysis of the multicenter, randomized ISAR-REACT 5 trial. Setting 23 centers in Germany and Italy. Patients 3997 patients with ACS planned for invasive management. Intervention Participants were randomly assigned to receive a standard dose of ticagrelor or prasugrel (reduced dose in the elderly or low-weight group and standard dose in the neither elderly nor low-weight group). Measurements The efficacy end point was a composite of death, myocardial infarction, or stroke, and the safety end point was bleeding, both at 12 months. Results In the elderly or low-weight group, the efficacy end point occurred in 12.7% of patients assigned to receive prasugrel and 14.6% of those assigned to receive ticagrelor (hazard ratio [HR], 0.82 [95% CI, 0.60 to 1.14]); in the neither elderly nor low-weight group, the efficacy end point occurred in 4.8% of patients assigned to receive prasugrel and 7.3% of those assigned to receive ticagrelor (HR, 0.65 [CI, 0.48 to 0.88]; P for interaction > 0.2). In the elderly or low-weight group, Bleeding Academic Research Consortium type 3 to 5 bleeding occurred in 8.1% of patients assigned to receive prasugrel and 10.6% of those assigned to receive ticagrelor (HR, 0.72 [0.46 to 1.12]), and in 3.7% and 3.8%, respectively, of patients in the neither elderly nor low-weight group (HR, 0.98 [CI, 0.65 to 1.47]; P for interaction > 0.2). Limitation The study is a subgroup analysis. Conclusion In elderly or low-weight patients with ACS, a reduced dose of prasugrel compared with the standard dose of ticagrelor is associated with maintained anti-ischemic efficacy while protecting these patients against the excess risk for bleeding. Primary funding source German Center for Cardiovascular Research and Deutsches Herzzentrum Munchen.

Background Invasive pulse wave analysis is used in peri-operative settings to estimate cardiac output (CO). The 'pressure recording analytical method' (PRAM) implemented in the MostCareUp CO monitor is an invasive pulse wave analysis method using high-frequency sampling and analysis of the pulse wave to directly estimate the arterial impedance as a key variable of the proprietary CO estimation algorithm. Objective To compare CO estimated by PRAM (PRAM-CO; test method) with CO measured by pulmonary artery thermodilution (PATD-CO; reference method). Design Prospective observational method comparison study. PRAM-CO and PATD-CO were assessed simultaneously at five time points with at least 20 min between measurements. Arterial pressure waveforms were carefully checked for damping artefacts and a proprietary electronic filter of the MostCareUp CO monitor was used to optimise waveform quality. Setting ICU of a German university hospital from August 2018 until April 2019. Patients We included adult patients admitted to the ICU after elective off-pump coronary artery bypass surgery who were monitored with a radial arterial catheter and a pulmonary artery catheter. Patients with severe heart valve insufficiency or persistent arrhythmia were excluded. Main outcome measures and analysis PATD-CO and PRAM-CO were compared using Bland-Altman analysis accounting for repeated measurements, the percentage error and trending analysis (four-quadrant plot, concordance rate). Results We analysed 195 paired CO values of 41 patients. Mean PATD-CO and PRAM-CO were 4.99 ± 1.02 and 4.92 ± 1.05 l min, respectively. PATD-CO and PRAM-CO ranged from 3.04 to 8.74 and 2.79 to 8.01 l min, respectively. The mean of the differences between PATD-CO and PRAM-CO was -0.08 ± 0.74 l min with 95% limits of agreement of -1.55 to +1.40 l min. The percentage error was 29.8%. The concordance rate in four-quadrant plot analysis was 92%. Conclusion Using the system's electronic waveform filter PRAM-CO shows good agreement and trending ability compared with PATD-CO in adults after off-pump coronary artery bypass surgery.

A crucial mode of action of trastuzumab is the labeling of HER2-positive (HER2

Introduction In mice there might be an association between sleep deprivation and amyloid β plasma levels. Hence, we examined whether amyloid plasma levels are associated with sleep duration or fragmentation in 17 psychiatrists on-call. Methods Amyloid β (Aβ)42, Aβ40, and soluble amyloid precursor protein β (sAPP-β) plasma concentrations were measured at the beginning and end of 90 on-call nights, and analyzed using generalized linear models. Results In on-call nights, a 10.7% reduction of Aβ42 was revealed overnight. Every single short sleep interruption diminished this reduction by 5.4%, as well as every pg/mL of sAPP-β by 1.2%, each copy of APOE e4 by 10.6%, and each year of professional experience by 3.0%. Discussion The extent of sleep fragmentation diminishes the physiological overnight reduction of Aβ42 but not Aβ40 plasma levels in the same direction as the enzyme for Aβ42 production, the genetic risk factor for Alzheimer's disease (AD), and on-call experience. Might on-call duty and sleep fragmentation in general alter the risk for AD?

Introduction and aims. We aimed to explore the impact of infection diagnosed upon admission and of other clinical baseline parameters on mortality of cirrhotic patients with emergency admissions. Material and methods. We performed a prospective observational monocentric study in a tertiary care center. The association of clinical parameters and established scoring systems with short-term mortality up to 90 days was assessed by univariate and multivariable Cox regression analysis. Akaike’s Information Criterion (AIC) was used for automated variable selection. Statistical interaction effects with infection were also taken into account. Results. 218 patients were included. 71.2% were male, mean age was 61.1 ± 10.5 years. Mean MELD score was 16.2 ± 6.5, CLIF-consortium Acute on Chronic Liver Failure-score was 34 ± 11. At 28, 90 and 365 days, 9.6%, 26.0% and 40.6% of patients had died, respectively. In multivariable analysis, respiratory organ failure [Hazard Ratio (HR) = 0.15], albumin substitution (HR = 2.48), non-HCC-malignancy (HR = 4.93), CLIF-C-ACLF (HR = 1.10), HCC (HR = 3.70) and first episode of ascites (HR = 0.11) were significantly associated with 90-day mortality. Patients with infection had a significantly higher 90-day mortality (36.3 vs. 20.1%, p = 0.007). Cultures were positive in 32 patients with resistance to cephalosporins or quinolones in 10, to ampicillin/sulbactam in 14 and carbapenems in 6 patients. Conclusion. Infection is common in cirrhotic ED admissions and increases mortality. The proportion of resistant microorganisms is high. The predictive capacity of established scoring systems in this setting was low to moderate.

Magnetic resonance imaging (MRI), including diffusion-weighted imaging (DWI), is an excellent tool for diagnosing intracranial infection, with limitations in previous neurosurgical intervention. This study aimed to evaluate the accuracy of DWI in the diagnosis of postoperative intracranial infection.We retrospectively evaluated all consecutive patients with intracranial infection undergoing a neurosurgical intervention who had preoperative MRI, including DWI. Patients were divided into 2 groups: spontaneous intracranial infection (SI) and postoperative intracranial infection (PI). A control group (CG) of patients who had undergone brain surgery without any signs of subsequent infection was also included. Qualitatively, MRI data were evaluated for the presence of intracranial infection. Sensitivity, specificity, and positive and negative predictive values for PI as opposed to no infection were determined. Quantitatively, areas with diffusion restriction within the surgery/abscess cavity were identified for the 3 groups using semiautomated segmentation. Group differences regarding apparent diffusion coefficient (ADC) ratios were evaluated. Receiver operating characteristic curve analysis was used to identify a point in time beyond which ADC ratios might show reasonable discriminatory power between the PI and CG groups.A total of 78 patients were included (38 in the SI group, 20 in the PI group, 20 in the CG group). Sensitivity, specificity, and positive and negative predictive values in the diagnosis of PI were 80%, 95%, 4%, and 100%, respectively. Median ADC was significantly higher in the PI group compared with the SI group (0.98 vs. 0.69; P0.001) but lower compared with the CG group (1.24; P = 0.16). The analysis suggested a possible differentiation of PI and CG after a time interval of approximately 100 days/3 months.DWI is of limited value in evaluating postoperative brain infection. Our data show a trend toward DWI regaining its validity at approximately 3 months after surgery.

Background Use of a side-viewing endoscope is currently mandatory to examine the major duodenal papilla; however, previous studies have used cap-assisted endoscopy for complete examination of the papilla. The aim of this study was to compare cap-assisted endoscopy with side-viewing endoscopy for examination of the major duodenal papilla. Methods This was a prospective, randomized, blinded, controlled, noninferiority crossover study. Patients were randomized to undergo either side-viewing endoscopy followed by cap-assisted endoscopy or cap-assisted endoscopy followed by side-viewing endoscope. Photographs of the major duodenal papilla were digitally edited to mask the cap area before they were evaluated by three blinded external examiners. Our primary end point was complete visualization of the major duodenal papilla. Secondary end points were the ability to examine the mucosal pattern, the overview of the periampullary region, overall satisfaction, and time to locate the papilla. Results 62 patients completed the study. Complete visualization of the major duodenal papilla was achieved in 60 examinations by side-viewing endoscopy and in 59 by cap-assisted endoscopy (97 % vs. 95 %). The difference between the two examinations was 1.6 % with a two-sided 95 % confidence interval of −4.0 % to 7.3 %, which did not exceed the noninferiority margin of 8 %. Cap-assisted endoscopy achieved better scores regarding the examination of mucosal pattern and overall satisfaction, whereas side-viewing endoscopy had a better overview score (P Conclusion Cap-assisted endoscopy and side-viewing endoscopy had similar success rates for complete visualization of the major duodenal papilla. Cap-assisted endoscopy is superior to side-viewing endoscopy regarding the mucosal pattern and overall satisfaction. Side-viewing endoscopy gives a better overview of the periampullary region.