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Background: Patients aged 80 years and older who require cardiac surgical procedures are an increasing population and usually present with considerable comorbidity. Detailed operative risk stratification versus long-term survival and quality of life after surgery is mandatory. Methods: A retrospective analysis was performed on 1,003 patients aged 82.3 years (range, 80 to 94 years) who underwent aortic valve replacement (n = 303), coronary artery bypass grafting (n = 403), or aortic valve replacement with coronary artery bypass grafting (n = 297) between 1987 and 2006. Preoperative data, operative outcome, long-term survival, and predictors for early and late mortality were analyzed. Furthermore, the Short Form 36 Health Status questionnaire was used to evaluate the quality of life. Results: Overall in-hospital mortality was 7.1%. Overall actuarial survival at 1, 5, and 10 years was 81.6% ± 1.2%, 60.4% ± 1.9%, and 23.3% ± 2.6% (mean survival time, 6.25 ± 0.2 years) and showed no significant difference compared with an age- and sex-matched general population. Multivariate analysis showed that preoperative creatinine concentration greater than 1.3 mg/dL (p < 0.001), preoperative atrial fibrillation (p < 0.005), and postoperative prolonged ventilation (p < 0.001) were independent predictors for poor long-term survival. The physical health summarized score of the Short Form 36 Health Status questionnaire was significantly increased in the study population compared with a German standard population aged 80 years and older (p < 0.05). Conclusions: Despite an increased operative mortality, octogenarians showed a considerable quality of life and an excellent long-term survival. To further improve surgical outcome in octogenarians, patient selection should be done with consideration of the identified independent preoperative risk factors. [ABSTRACT FROM AUTHOR]

Epithelial ovarian cancer is a highly metastatic disease and the leading cause of death among cancer of the female genital tract. Abnormal epidermal growth factor receptor (EGFR) signalling has been shown to be involved in epithelial-mesenchymal transition (EMT), an early step during metastasis. Additionally, over-expression of the E-cadherin repressor Snail, a key regulator of EMT, has previously been found to be associated with unfavourable prognostic features. Thus, the aim of our study was to elucidate the role of EGFR-dependent signalling pathways for Snail expression in ovarian cancer. For this purpose, we analysed 25 formalin-fixed and paraffin-embedded (FFPE) primary tumours and their corresponding metastases for the expression of 25 signalling pathway molecules by reverse phase protein arrays. We found a significant correlation of Snail with EGFR((Tyr1086)) and p38 MAPK((Thr180/Tyr182)) in primary ovarian carcinoma and with EGFR((Tyr1086)) in their corresponding metastasis. Additionally, we showed that high expression levels of Snail in primary tumours combined with high expression levels of the phosphorylated p38 MAPK((Thr180/Tyr182)) in metastasis lead to an increased risk for death in ovarian carcinoma patients. Thus, for future combinatorial cancer therapy, drug combinations that best target the deregulated protein network in each individual patient should be selected. [ABSTRACT FROM AUTHOR]

Background: Histone deacetylases (HDACs) modulate chromatin and may influence the effect of DNA-damaging drugs. We investigated HDAC1 and -2 expression in gastric carcinomas (GCs) for an association of patient outcome with conventional neoadjuvant chemotherapy. In vitro, HDAC inhibitors were evaluated as alternative treatment options. Methods: HDAC1/2 expression was analyzed immunohistochemically in 127 pretherapeutic biopsy samples of neoadjuvant (platinum/5-fluorouracil) chemotherapy-treated GC patients and correlated with response and overall survival (OS). Chemosensitivity of four GC cell lines to cisplatin and the HDAC inhibitors suberoylanilide hydroxamic acid (SAHA) and valproic acid was determined by XTT assays. Efficiencies of combined drug schedules were analyzed. Results: High expression of HDAC1/2 was found in 69 (54%) of 127 and 108 (85%) of 127 carcinomas, respectively, and was not associated with response or OS. In patients whose disease responded to therapy, high HDAC1 expression was associated with worse OS ( P = 0.005). In cell lines, sequential treatment with SAHA and cisplatin showed synergistic effects irrespective of the initial cisplatin sensitivity. Conclusions: HDAC1 and -2 expression is not suitable to predict response or survival for neoadjuvant-treated GC patients, but HDAC1 expression may be used for risk stratification in patients whose disease responds to therapy. Sequential treatment with SAHA and cisplatin may represent an alternative treatment option for GC patients. [ABSTRACT FROM AUTHOR]

In this explorative mixed-method pilot study, we set out to have a closer look at the largely under-recognized and under-investigated symptom of thick mucus in patients with ALS and its impact on patients and relatives. Thick mucus is a highly distressing symptom for both patients and caregivers. It complicates the use of non-invasive ventilation and is therefore an important prognostic factor of survival. Methods: In our preliminary study, we used a cross-sectional design, including ten ALS patients with thick mucus who were matched to ten ALS patients without thick mucus. Lung function tests and laboratory and sputum analysis were performed and questionnaires administered in order to determine associated factors of thick mucus accumulation. In a qualitative study using semi-structured interviews, we analysed the impact of thick mucus on patients and caregivers. Results: Reduced respiratory parameters as well as a higher degree of bulbar impairment were associated with the presence of thick mucus. Quality of life of patients and caregivers was strongly impaired by thick mucus accumulation. Conclusions: Thick mucus in patients with ALS has a strong impact on quality of life. Reduced cough flow and severely impaired bulbar function appear to be indicative parameters. We suggest that healthcare providers actively explore the presence of thick mucus in their patients and that it becomes included in commonly used screening tools. [ABSTRACT FROM AUTHOR]

In contemporary healthcare, effective risk stratification in the general population is vital amidst rising chronic disease rates and an ageing demographic. Deceleration Capacity of the heart rate (DC), derived from 24-hour Holter electrocardiograms, holds promise in risk stratification for cardiac patients. However, the potential of short-term electrocardiograms of five minutes duration for population screening has not been fully explored. Our study aims to investigate the utility of Deceleration Capacity derived from short-term electrocardiograms as a scalable, fully-automated screening tool for predicting long-term mortality risk in the general population. Within a cohort of a representative population-based survey in Germany (KORA-KMC-study), 823 participants with sinus rhythm aged 27 to 76 years at enrollment (females 47.4%) were followed for a median of 13.4 years (IQR 13.1–13.6). All-cause mortality was defined as the primary endpoint and observed in 159 participants. Deceleration Capacity was calculated from 5-minute 12-lead electrocardiograms by a fully automated approach. Participants were divided into three predefined risk categories: DCcategory0 – low-risk (> 4.5ms); DCcategory1 – intermediate-risk (2.5-4.5ms); and DCcategory2 – high-risk (≤ 2.5ms). More than two-thirds of the participants (n = 564, 68.5%) fell into DCcategory0, about one-fifth (n = 168, 20.4%) into DCcategory1, and about one-tenth (n = 91, 11.1%) into DCcategory2. Estimated 13-years mortality in the risk groups was 16.7%, 23.5%, and 49.1%, respectively (p < 0.001). Adjusting for age, life-style-related risk factors, and comorbidities, increased mortality risk was observed for DCcategory2 (HR 2.34, 95%-CI 1.56–3.50). Deceleration Capacity, derived automatically from brief 5-minute electrocardiogram recordings, emerges as a robust, feasible, and independent predictor of long-term mortality risk in the general population. [ABSTRACT FROM AUTHOR]

This study evaluated the association between pediatric multiple sclerosis and vaccinations within 5 years before diagnosis using German ambulatory claims data. Children with multiple sclerosis (n = 346) aged 9–17 were analyzed with logistic and Poisson regression. Control groups included children with Crohn's disease, psoriasis, and no autoimmune diseases. The results indicated a negative association between vaccinations and pediatric multiple sclerosis, with no significant risk identified. This negative relationship was consistent in sensitivity and clinically isolated syndrome analyses. Overall, the study's findings do not support the hypothesis that vaccination is a risk factor for pediatric multiple sclerosis. [ABSTRACT FROM AUTHOR]

Simple Summary: Here we report a sex- and age-specific analysis of 717 patients with gastric/gastro-esophageal adenocarcinomas treated with or without neoadjuvant chemotherapy (CTx) regarding overall survival (OS) and response to CTx. The analysis was also performed in molecular subtypes determined previously. Females demonstrated a significantly increased OS particularly in the group of patients treated with neoadjuvant CTx. Specifically in this patient group and taken into account the molecular subtypes, females with high microsatellite instability (MSI-H) showed the best survival followed by the male MSI-H, the female microsatellite stable (MSS) group and the male MSS group. Thus, we show an effect of sex on OS in gastric/gastro-esophageal cancer in particular for patients treated with neoadjuvant CTx. The superior survival of women with MSI-H tumors among the CTx patients implies that the combined consideration of these factors could contribute to an individualized treatment of the patients. We aimed to investigate patients with gastric/gastro-esophageal adenocarcinomas for sex- and age-specific differences regarding overall survival (OS) and response to neoadjuvant chemotherapy (CTx) under consideration of tumor specific molecular subtypes. Overall, 717 patients were analyzed, including 426 patients treated with and 291 treated without neoadjuvant CTx. Microsatellite instability (MSI) and Epstein-Barr virus positivity (EBV+) were determined previously. Females demonstrated a significantly increased OS (p = 0.035), particularly in the subgroup treated with CTx (p = 0.054). No significant differences regarding age were found. In the molecular subgroups, no sex-related differences were observed in the non-CTx group. However in the CTx group, females with MSI-high (H) tumors showed the best OS (p = 0.043), followed by the male MSI-H (p = 0.198) and female MSS (p = 0.114) compared to the male MSS group as reference. The interaction between sex and MSI in this patient group was noticeable (p = 0.053) and was included as a relevant factor in multivariable analyses. In conclusion, our results show an effect of sex on OS in gastric/gastro-esophageal cancer specifically for patients treated with neoadjuvant CTx. The superior survival of women with MSI-H tumors after neoadjuvant CTx implies that combined consideration of these factors could contribute to an individualized treatment of the patients. [ABSTRACT FROM AUTHOR]

Background: Safe diagnosis of periprosthetic joint infection (PJI) is of utmost importance for successful exchange arthroplasty. However, current diagnostic tools show insufficient accuracy in the clinically common and challenging chronic low-grade infections. To close this diagnostic gap, reliable (bio)markers display the most promising candidates. Antimicrobial peptides (AMPs) are part of the innate immune response towards microbial growth. Recently we could show significant intraarticular levels of human cathelicidin LL-37 and β-defensin-3 (HBD-3) with high diagnostic accuracy in PJI synovial fluid. Consequently, these promising biomarkers were evaluated in PJI synovial membrane and synoviocytes, which may significantly facilitate histological diagnosis of PJI to improve outcome of septic joint replacement. Methods: In this prospective single-center controlled clinical study (diagnostic level II), consecutive patients with total hip (THR) and knee (TKR) replacements were included undergoing primary arthroplasty (n = 8), surgical revision due to aseptic loosening (n = 9) and septic arthroplasty with coagulase-negative staphylococci (n = 8) according to the criteria of the Musculoskeletal Infection Society (MSIS). Semiquantitative immunohistochemical (IHC) analysis of LL-37, HBD-3 and HBD-2 in synovial membrane and isolated synoviocytes based on Total Allred Score (TS) and Immunoreactive Remmele and Stegner score (IRS) was performed. For statistical analysis, SPSS 26.0/R3.6.3 (p < 0.05) was used. Results: The AMPs LL-37 and HBD-3 were significantly elevated (up to 20×) in synovial membranes from PJI compared to aseptic loosening or primary arthroplasty. The area under the curve (AUC) in a receiver operating characteristic curve analysis was equal to 1.0 for both scores revealing excellent diagnostic accuracy. Isolated synoviocytes as cellular AMP source showed comparable results with a significant LL-37/HBD-3-increase up to 3 × in PJI. In contrast, local HBD-2 levels were negligible (p > 0.23) upon PJI with a lower diagnostic accuracy (AUC = 0.65) in analogy to our previous findings with synovial fluid. Conclusions: Our results implicate AMPs as promising and specific biomarkers for the histological diagnosis of PJI. [ABSTRACT FROM AUTHOR]

We investigated the prognostic and predictive impact of p53 expression for gastric cancer (GC) patients treated without or with preoperative chemotherapy (CTx) and its relationship with specific molecular GC subtypes. Specimens from 694 GC patients (562 surgical resection specimens without or after CTx, 132 biopsies before CTx) were analyzed by p53 immunohistochemistry. High (H) and low (L) microsatellite instability (MSI) and Epstein–Barr virus positivity were determined previously. Our results show that aberrant p53 expression was a negative prognostic factor in uni- and multivariable analysis in the resection specimens cohort (each p < 0.01). Subgroup analysis showed the strongest prognostic effect for patients with distally located tumors or no CTx treatment. In the biopsy cohort before CTx, p53 did not predict response or survival. p53 expression was significantly different among the molecular subtypes in surgical resection and bioptic specimens with strong association of altered p53 with MSI-L. Patients with MSI-H and aberrant p53 showed the worst survival in the biopsy cohort. In conclusion, the prognostic impact of p53 in GC differs according to tumor localization and CTx. Altered p53 is characteristic for MSI-L, and the p53 status in biopsies before CTx delineates MSI-H subtypes with inverse prognostic impact. [ABSTRACT FROM AUTHOR]

An amendment to this paper has been published and can be accessed via a link at the top of the paper. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the incidence of cancer within the first 15 years of life in children who underwent cardiac catheterization under the age of one year. Methods: In this retrospective, single center study, 2770 infants (7.8% with trisomy 21) were studied. All infants underwent cardiac catheterization under one year of age between January 1980 and December 1998. Newly diagnosed cancer in the first 15 years of life was assessed through record linkage to the German Childhood Cancer Registry (GCCR). Cancer risk in study patients was compared to the GCCR population of children less than 15 years. Patients with trisomy 21 were compared to the Danish Cytogenic Register for trisomy 21. Effective radiation doses were calculated for each tumor patient and 60 randomly selected patients who did not develop cancer. Results: In total, 24,472.5 person-years were analyzed. Sixteen children developed cancer, while 3.64 were expected (standardized incidence ratio (SIR) = 4.4, 95% confidence interval (CI): 2.5–7.2, p < 0.001). There was no preferred cancer type. The observed incidence of leukemia and solid tumors in trisomy 21 was only slightly higher (1 in 476 py) than expected (1 in 609 py, p = 0.64). There was no direct relationship between the radiation dose and the incidence of cancer. Conclusion: Cardiac catherization in the first year of life was associated with a significantly increased cancer risk in a population with congenital heart disease. [ABSTRACT FROM AUTHOR]

Background and Aim: Patients with liver cirrhosis often face a grave threat from infected ascites (IA). However, a well‐established prognostic model for this complication has not been established in routine clinical practice. Therefore, we aimed to assess mortality risk in patients with liver cirrhosis and IA. Methods: We conducted a retrospective study across three tertiary hospitals, enrolling 534 adult patients with cirrhotic liver and IA, comprising 465 with spontaneous bacterial peritonitis (SBP), 34 with bacterascites (BA), and 35 with secondary peritonitis (SP). To determine the attributable mortality risk linked to IA, these patients were matched with 122 patients with hydropic decompensated liver cirrhosis but without IA. Clinical, laboratory, and microbiological parameters were assessed for their relation to mortality using univariable analyses and a multivariable random forest model (RFM). Least absolute shrinkage and selection operator (Lasso) regression model was used to establish an easy‐to‐use mortality prediction score. Results: The in‐hospital mortality risk was highest for SP (39.0%), followed by SBP (26.0%) and BA (25.0%). Besides illness severity markers, microbiological parameters, such as Candida spp., were identified as the most significant indicators for mortality. The Lasso model determined 15 parameters with corresponding scores, yielding good discriminatory power (area under the receiver operating characteristics curve = 0.89). Counting from 0 to 83, scores of 20, 40, 60, and 80 corresponded to in‐hospital mortalities of 3.3%, 30.8%, 85.2%, and 98.7%, respectively. Conclusion: We developed a promising mortality prediction score for IA, highlighting the importance of microbiological parameters in conjunction with illness severity for assessing patient outcomes. [ABSTRACT FROM AUTHOR]

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 orthopedic units that treat peri-prosthetic joint infections (PJIs), ABS programs are still rare, however, there is extensive use of high-risk antibiotic agents and an increased risk for the occurrence of Clostridium difficile infections (CDIs). Patients and Methods: An ABS program was implemented at the Department of Orthopedic Surgery at a university hospital. Quarterly antibiotic consumption was measured in defined daily doses (DDDs) per 100 patient-days (PDs) at 10 quarters before the intervention and seven quarters after the intervention. The effect of the new antibiotic policy on drug use rates was evaluated using an interrupted time-series analysis. Estimated changes over time in the incidence of CDIs (cases per 1,000 PDs) were analyzed. Results: A remarkable percentual reduction in second-generation cephalosporin use of 83% (p < 0.001; pre-intervention level, 81.486 DDDs/100 patient-days; post-intervention level, 13.751 DDDs/100 PDs) and clindamycin administration of 78% (p < 0.001; pre-intervention level, 18.982 DDDs/100 PDs; post-intervention level, 4.216 DDDs/100 PDs) was observed after implementation of ABS interventions. Total antibiotic use declined by 25% (p < 0.001; pre-intervention level, 129.078 DDDs/100 PDs; post-intervention level, 96.826 DDDs/100 PDs). Conclusions: This research assessed the positive impact of an intensified ABS program at an orthopedic department specializing in PJIs. Antibiotic stewardship program interventions encourage the reduction of total antibiotic usage and especially high-risk antibiotic agents, associated with the development of antimicrobial resistance. [ABSTRACT FROM AUTHOR]

Aims Dynamic retinal vessel analysis (DVA) provides a non-invasive way to assess 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 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 haemodialysis 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. Conclusion Our results provide a machine learning workflow to improve the predictive performance of DVA and identify groups of haemodialysis patients at high risk of CV mortality. Our approach may also prove to be promising for DVA signal analysis in other CV disease states. [ABSTRACT FROM AUTHOR]

Background: This study aimed to investigate the knowledge, attitudes, behaviors, and COVID-19 vaccine hesitancy of people with migratory backgrounds among Turkish- and German-speaking patients in Munich.Methods: Primary outcomes were the intention to get vaccinated for COVID-19 and COVID-19 knowledge levels (25 true/false items). Other variables included demographics, attitudes to COVID-19 and vaccination (7 items), and behaviors regarding COVID-19 (7 items). The attitude and behavior questions had 5-point Likert scales. Of the 10 Turkish-speaking family physicians in Munich, six agreed to administer Turkish or German questionnaires to consecutive patients in February 2021. Furthermore, participants with either citizenship, country of origin, native language, or place of birth being non-German were categorized as "Having a migratory background." Data from 420 respondents were analyzed.Results: Women constituted 41.4% (n = 174), the mean age was 42.2 ± 15.5 years, 245 (58.3%) preferred the Turkish questionnaire, 348 (82.9%) had a migratory background, and 197 (47.9%) intended to be vaccinated. The mean knowledge, attitude, and behavioral scores were 21.5 ± 3.2 (max = 25), 3.7 ± 0.8 (max = 5), and 4.0 ± 0.5 (max = 5). While 42.3% (n = 145) of the participants with a migratory background considered getting vaccinated, this proportion was 76.5% (n = 52) for non-immigrant Germans (Chi-square = 26.818, p < 0.001). Non-migratory background (odds ratio (OR): 3.082), high attitude scores (OR: 2.877), male sex (OR: 2.185), years of schooling (OR: 1.064), and age (OR: 1.022) were positively associated with vaccination intention.Conclusions: We suggest initiating or supporting projects run by persons or groups with immigrant backgrounds to attempt to elaborate and change their vaccination attitudes. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background: Case-based learning (CBL) is a highly interactive instructional format widely used in medical education. One goal of CBL is to integrate basic biomedical knowledge and its application to concrete patient cases and their clinical management. In this context, we focus the role of teacher questions as triggers for reproductive vs. elaborative student responses. Specifically, our research questions concern the kinds of questions posed by clinical teachers, the kinds of responses given by students, the prediction of student responses based upon teacher questions, and the differences between the two medical disciplines in focus of our study, internal medicine and surgery. Methods: We analyse 19 videotaped seminars (nine internal medicine, ten surgery) taught by clinicians and attended by advanced medical students. Multiple raters performed a low-inference rating process using a theory-based categorical scheme with satisfactory interrater-reliability. Results: We found that medical teachers mostly posed initial (instead of follow-up) questions and that their questions were more often closed (instead of open). Also, more reasoning (than reproductive) questions were posed. A high rate of student non-response was observed while elaborative and reproductive student responses had a similar prevalence. In the prediction context, follow-up reasoning questions were associated with low non-response and many elaborative answers. In contrast, the highest student non-response rate followed open reproduction questions and initial reasoning questions. Most reproductive statements by students were made following closed reproduction questions. Conclusions: These results deepen our understanding of interactive, questions-driven medical teaching and provide an empirical basis for clinical teachers to use questions in didactically fruitful ways. [ABSTRACT FROM AUTHOR]

The aims of our study were to determine first circadian influences on central concentrations of the neuropeptides oxytocin and arginine-vasopressin and second to investigate if these central concentrations are associated with those in the peripheral compartments blood and saliva in neurocritical care patients. We therefore included patients with external ventricular drain who attended a neurosurgical intensive care unit and were not exposed to painful or stressful stimuli during the sampling period. For this purpose, blood, cerebrospinal fluid and saliva were collected in a 24-hour-interval at the timepoints 06:00, 12:00, 18:00 and 24:00. In none of the three body fluids examined, significant time-dependent fluctuations of oxytocin and arginine-vasopressin concentrations could be detected during the 24-hour sampling period. The only exception was the subgroup of postmenopausal women whose oxytocin concentrations in cerebrospinal fluid at 12:00 were significantly higher than at 18:00. Correlations of blood and cerebrospinal fluid and blood and saliva neuropeptide levels were very weak to weak at each timepoint. Cerebrospinal fluid and saliva oxytocin levels showed a moderate correlation at 06:00 but did correlate very weak at the other timepoints. Central as well as peripheral oxytocin and arginine-vasopressin concentrations in neurocritical care patients did not show significant diurnal fluctuations. No strong correlations between central and peripheral neuropeptide concentrations could be detected under basal conditions. If investigators even though decide to use saliva concentrations as surrogate parameter for central neuropeptide activity, they have to consider that correlations of cerebrospinal fluid and saliva oxytocin seem to be highest in the early morning. • Diurnal variations of central neuropeptide concentrations have been described in several species including humans • We could not show circadian rhythmicity of central OXT and AVP levels in neurocritical care patients under basal conditions • No strong correlations between central and peripheral neuropeptide concentrations could be detected • Correlations of oxytocin CSF and saliva levels may depend on the timepoint of sampling [ABSTRACT FROM AUTHOR]

Background: Neuroactive steroids seem to be implicated in a variety of neurophysiological and behavioral processes, such as sleep, learning, memory, stress, feeding and aging. Numerous studies have also addressed this implication in various cerebral disorders and diseases. Yet, the correlation and association between steroids in the periphery, e.g. blood, and the central compartments, e.g. cerebrospinal fluid (CSF), have not yet been comprehensively assessed. As the brain is not directly accessible, and the collection of human CSF usually requires invasive procedures, easier accessible compartments, such as blood, have always attracted attention. However, studies in humans are scarce. In the present study we determined estradiol, progesterone and testosterone levels in CSF and serum of 22 males without cerebral disorders or diseases.Results: Samples were taken under conditions corresponding closest to basal conditions with patients expecting only spinal anesthesia and minor surgery. All samples per patient were collected concomitantly. Total estradiol, progesterone and testosterone concentrations were measured by electro-chemiluminescence immunoassay. The strength of correlation was assessed by Spearman's rank correlation coefficient. Correlation analysis revealed merely weak to very weak correlations for estradiol, progesterone and testosterone respectively between the CSF and serum compartments.Conclusions: Total steroid levels of estradiol, progesterone and testosterone in CSF and serum of males without neurological disorders were determined. Weak to very weak correlations between CSF and serum were found thus suggesting that concentrations in the periphery do not parallel concentrations in the central compartments. Further research is needed to clarify to what extent and under which conditions serum levels of estradiol, progesterone and testosterone may possibly serve as a biomarker reflecting the respective concentrations in the CSF or in the brain. [ABSTRACT FROM AUTHOR]

Background: The influence of lifestyle factors on the quality of life, incidence and tumor recurrence has been evaluated in several studies and is gaining increasing importance in cancer research. However, the extent of the influence of such lifestyle factors on the quality of life of cancer patients remains largely unclear, as does the number of patients actually pursuing these lifestyle changes. The purpose of this study was to examine the prevalence and predictors of lifestyle changes in patients with gynecological cancer.Methods: The survey consisted of a pseudonymous questionnaire that was conducted from January to May 2014 via a telephone interview with 141 patients with a gynaecological malignancy who had undergone surgery at our Department of Gynaecology and Obstetrics. Lifestyle factors (diet, physical activity, stress level, alcohol and nicotine consumption) prior to and after the diagnosis of cancer were evaluated.Results: 89% (n = 125) of the patients reported lifestyle changes after being diagnosed with cancer. There was a significant association between the implementation of lifestyle changes and age as well as the use of complementary medicine. Nutrition: 66% of the patients (n = 93) consumed more fruit and vegetables and 65% ate less meat (n = 92). Physical activity: 37% (n = 52) reported no change in their exercise routine, 36% (n = 51) described a decrease, 27% (n = 38) an increase in their physical activity. Subjective feeling of stress: 77% of the patients (n = 108) described a reduction in their perceived level of stress. Nicotine consumption: 63% (n = 12) of the 19 patients who were smokers at the time of the diagnosis quit or reduced smoking thereafter. Alcohol consumption: 47% (n = 61/129) of the patients reduced their alcohol consumption.Conclusions: Most of the patients from our study group implemented lifestyle changes after being diagnosed with cancer. Prospective randomized trials are needed in order to determine the benefit of lifestyle changes (physical activity, dietary habits and stress reduction) for cancer survivors. The potential impact of lifestyle on the quality of life and the trajectory of the disease should be discussed with all oncological patients. [ABSTRACT FROM AUTHOR]

Purpose: Prospectively collected outcome data of patients (pts) whose adjuvant systemic therapy recommendation was based on the clinico-molecular test EndoPredict® (EP) are presented. Methods: Pts with ER-positive, HER2-negative early breast cancer with 0–3 positive lymph nodes were enrolled. The EP was carried out on all tumor samples. Pts were evaluated for treatment compliance, local recurrence, distant metastases and overall survival. Censored time-to-event outcomes were analysed by Cox proportional hazards models. Additional estimates of the event-free-survival were calculated by the Kaplan–Meier method. Hypothesis testing was conducted on two-sided exploratory 5% significance levels. Results: 373 consecutive pts were enrolled. EP classified 238 pts (63.8%) as low risk and 135 pts (36.2%) as high risk. Median follow-up was 41.6 months. Risk for disease recurrence or death in EPclin high-risk patients was twofold higher in comparison with EPclin low-risk patients (hazard ratio (HR) 2.05 (95% CI 0.85–4.96; p = 0.110). Patients with EPclin high risk were at significant higher risk of distant metastases than patients with EPclin low risk (HR 5.18; 95% CI 1.04–25.74; p = 0.0443). EPclin high-risk patients who actually underwent adjuvant CTX had a 3-year-DFS of 96.3% (95% CI 92.2–100) in contrast to EPclin high-risk patients without CTX (3-year-DFS: 91.5% (95% CI 82.7–100%); HR 0.32; 95% CI 0.10–1.05; p = 0.061). Conclusion: These first prospective outcome results show that EP, in clinical routine, is a valid clinico-molecular test, to predict DFS and to guide decision of adjuvant CTX use in ER-positive, HER2-negative early breast cancer pts with 0–3 positive lymph nodes. Adjuvant CTX seems to be beneficial for EPclin high-risk patients. [ABSTRACT FROM AUTHOR]

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

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. [ABSTRACT FROM AUTHOR]

Identification of relevant biomarkers that are associated with a treatment effect is one requirement for adequate treatment stratification and consequently to improve health care by administering the best available treatment to an individual patient. Various statistical approaches were proposed that allow assessing the interaction between a continuous covariate and treatment. Nevertheless, categorization of a continuous covariate, e.g., by splitting the data at the observed median value, appears to be very prevalent in practice. In this article, we present a simulation study considering data as observed in a randomized clinical trial with a time-to-event outcome performed to compare properties of such approaches, namely, Cox regression with linear interaction, Multivariable Fractional Polynomials for Interaction (MFPI), Local Partial-Likelihood Bootstrap (LPLB), and the Subpopulation Treatment Effect Pattern Plot (STEPP) method, and of strategies based on categorization of continuous covariates (splitting the covariate at the median, splitting at quartiles, and using an "optimal" split by maximizing a corresponding test statistic). In different scenarios with no interactions, linear interactions or nonlinear interactions, type I error probability and the power for detection of a true covariate-treatment interaction were estimated. The Cox regression approach was more efficient than the other methods for scenarios with monotonous interactions, especially when the number of observed events was small to moderate. When patterns of the biomarker-treatment interaction effect were more complex, MFPI and LPLB performed well compared to the other approaches. Categorization of data generally led to a loss of power, but for very complex patterns, splitting the data into multiple categories might help to explore the nature of the interaction effect. Consequently, we recommend application of statistical methods developed for assessment of interactions between continuous biomarkers and treatment instead of arbitrary or data-driven categorization of continuous covariates. [ABSTRACT FROM AUTHOR]

Background: Infections are discussed as risk factor for multiple sclerosis (MS) development and relapses. This may lead to decreased vaccination frequency in newly diagnosed patients. Objective: The aim of this study was to evaluate the relation of MS diagnosis to subsequent vaccination frequency. Methods: Based on German ambulatory claims data from 2005 to 2019, regression models were used to assess the relation of MS diagnosis (n = 12,270) to vaccination. A cohort of patients with MS was compared to control cohorts with Crohn's disease, psoriasis, and without these autoimmune diseases (total n = 198,126) in the 5 years after and before diagnosis. Results: Patients with MS were less likely to be vaccinated compared to persons without the autoimmune diseases 5 years after diagnosis (odds ratio = 0.91, p < 0.001). Exceptions were vaccinations against influenza (1.29, p < 0.001) and pneumococci (1.41, p < 0.001). Differences were strong but less pronounced after than before diagnosis (p < 0.001). The likelihood of vaccination was also lower compared to patients with Crohn's disease or psoriasis. Conclusions: Patients with MS were not adequately vaccinated despite guideline recommendations. Increasing awareness about the importance of vaccination is warranted to reduce the risk of infection, in particular, in patients with MS receiving immunotherapies. [ABSTRACT FROM AUTHOR]

Background Quick symptomatic remission after the onset of psychotic symptoms is critical in schizophrenia treatment, determining the subsequent disease course and recovery. In this context, only every second patient with acute schizophrenia achieves symptomatic remission within three months of initiating antipsychotic treatment. The potential indication extension of clozapine—the most effective antipsychotic—to be introduced at an earlier stage (before treatment-resistance) is supported by several lines of evidence, but respective clinical trials are lacking. Methods Two hundred-twenty patients with acute non-treatment-resistant schizophrenia will be randomized in this double-blind, 8-week parallel-group multicentric trial to either clozapine or olanzapine. The primary endpoint is the number of patients in symptomatic remission at the end of week 8 according to international consensus criteria ('Andreasen criteria'). Secondary endpoints and other assessments comprise a comprehensive safety assessment (i. e., myocarditis screening), changes in psychopathology, global functioning, cognition, affective symptoms and quality of life, and patients' and relatives' views on treatment. Discussion This multicentre trial aims to examine whether clozapine is more effective than a highly effective second-generation antipsychotics (SGAs), olanzapine, in acute schizophrenia patients who do not meet the criteria for treatment-naïve or treatment-resistant schizophrenia. Increasing the likelihood to achieve symptomatic remission in acute schizophrenia can improve the overall outcome, reduce disease-associated burden and potentially prevent mid- and long-term disease chronicity. [ABSTRACT FROM AUTHOR]

Purpose: To investigate the prognostic role of microsatellite instability (MSI) in association with sex of patients treated with platinum/fluoropyrimidine neoadjuvant chemotherapy (CTx) with or without a taxane-containing compound. Methods: Of the 505 retrospectively analyzed patients with gastric or gastroesophageal adenocarcinoma, 411 patients were treated without taxane and 94 patients with a taxane-containing compound. MSI was determined using standard assays. Results: Females demonstrated a better overall survival (OS) than males in the non-taxane group (HR, 0.59; 95% CI 0.41–0.86; p = 0.005), whereas no significant difference was found in the taxane group (HR 1.22; 95% CI 0.55–2.73, p = 0.630). MSI-High (-H) was associated with a better prognosis in both groups (without taxane: HR 0.56; 95% CI 0.33–0.97; p = 0.038; with taxane: HR 0.28; 95% CI 0.04–2.02, p = 0.204). In the non-taxane group, female MSI-H patients showed the best OS (HR 0.18, 95% CI 0.05–0.73; p = 0.016), followed by the female microsatellite stable (MSS) (HR 0.67, 95% CI 0.46–0.98, p = 0.040) and the male MSI-H group (HR 0.76; 95% CI 0.42–1.37, p = 0.760) taken the male MSS group as reference. In the taxane group, female and male MSI-H patients demonstrated the best OS (female MSI-H: HR 0.05, 95% CI 0.00–240.46; male MSI-H: HR 0.45, 95% CI 0.61–3.63, p = 0.438), whereas the female MSS group showed a decreased OS (HR 1.39 95% CI 0.62–3.12, p = 0.420) compared to male MSS patients. Conclusion: OS in gastric/gastroesophageal cancer after CTx might depend on sex and MSI status and may differ between patients treated with or without a taxane compound in the chemotherapeutic regimen. [ABSTRACT FROM AUTHOR]

Background: Adjuvant therapy decisions in early breast cancer are based on accurate risk assessment. Urokinase plasminogen activator (uPA) and plaminogen activator inhibitor-1 (PAI-1) have been the first biomarkers in hormone receptor (HR) positive breast cancer to reach highest level of evidence. The EndoPredict test (EPclin) combines gene expression information with nodal status and tumor size. The aim of this prospective study was to compare uPA/PAI-1 and EPclin as prognostic biomarkers with regard to feasibility, risk stratification and impact on adjuvant therapy recommendation. Materials and method: 395 patients with HR positive, HER2 negative, intermediate risk breast cancer were enrolled. Relations and concordance of histologic grading as well as EPclin and uPA/PAI-1 values were assessed by Spearman’s rank correlation coefficient and Cohen’s Kappa. To compare decision impact of EPclin and uPA/PAI-1 three independent case discussions were held: One with known uPA/PAI-1 and EPclin results, one blinded to EPclin alone and another one blinded to both EPclin and uPA/PAI-1. Results: EPclin could be determined in all 395 (100%), uPA/PAI-1 in 190 (48%) of the tumor samples. EPclin allocated 250 patients (63%) to the low-risk group and 145 patients (37%) to the high-risk group, whereas uPA/PAI-1 allocated 88 patients (46%) to the low-risk group and 102 patients (54%) to the high-risk group. In 59% of cases, both tests showed concordant results. EPclin resulted more frequently in a change of therapy recommendation than the uPA/PAI-1 test (46% vs 24%). Recommendation of adjuvant chemotherapy (CTX) was abandoned twice as often by EPclin (45%) compared to uPA/PAI-1 (22%). Conclusion: In this first prospective comparison of EPclin and uPA/PAI-1 we found, that EPclin is superior to uPA/PAI-1 with respect to feasibility and decision impact. This leads to substantial avoidance of adjuvant CTX in endocrine-sensitive, HER2-negative breast cancer. Data collection for patients´ clinical outcome is ongoing. [ABSTRACT FROM AUTHOR]

• This study shows that the continuous presence of a trained neurologist is associated with a lower seizure frequency in people with epilepsy. • The continuous presence of a neurologist is also associated with a higher likelihood of reporting and detecting side effects. • Investing in specialist services in addition to primary healthcare may reduce brain health inequities faced by PWE in Africa. With an estimated lifetime prevalence of epilepsy of 7.6 per 1,000 people, epilepsy represents one of the most common neurological disorders worldwide, with the majority of people with epilepsy (PWE) living in low-income and middle-income countries (LMICs). Adequately treated, up to 70 % of PWE will become seizure-free, however, as many as 85% of PWE worldwide, mostly from LMICs, do not receive adequate treatment. To assess the impact of the presence of a neurologist on the management of PWE in Tanzania. Two epilepsy clinics in rural Tanzania, one continuously attended by a neurologist, and one mainly attended by nurses with training in epilepsy and supervised intermittently by specialist doctors (neurologists/psychiatrists) were comparatively analyzed by multivariable linear and logistic regression models with regard to the outcome parameters seizure frequency, the occurrence of side effects of antiepileptic medication and days lost after a seizure. The presence of a neurologist significantly reduced the mean number of seizures patients experienced per month by 4.49 seizures (p < 0.01) while leading to an increase in the occurrence of reported side effects (OR: 2.15, p = 0.02). The presence of a neurologist may play a substantial role in reducing the burden of the disease of PWE in LMICs. Hence, specialist training should be encouraged, and relevant context-specific infrastructure established. [ABSTRACT FROM AUTHOR]

Simple Summary: The major histocompatibility complex (MHC) class I genes, encompassing the human leukocyte antigen (HLA) class I and the beta-2 microglobulin (B2M) genes, play a key role in neoantigens presentation to the immune system. We analyzed allelic imbalance (AI) of the respective chromosomal regions by multiplex PCRs using microsatellite markers in biopsies of 158 patients with gastric/gastroesophageal adenocarcinoma before neoadjuvant platinum/fluoropyrimidine chemotherapy (CTx) for an association with clinical outcome of the patients. AI with no marker was significantly associated with response or survival. However, subgroup analysis revealed interesting differences. Of note, AI at markers of the HLA region was associated with a decreased survival only in responding but not in non-responding patients. No associations were observed for B2M markers. Our results underline the importance of intact neoantigen presentation specifically for responding patients and may help explain an unexpectedly poor survival of a patient despite significant tumor regression after neoadjuvant CTx. We aimed to determine the clinical and prognostic relevance of allelic imbalance (AI) of the major histocompatibility complex (MHC) class I genes, encompassing the human leukocyte antigen (HLA) class I and beta-2 microglobulin (B2M) genes, in the context of neoadjuvant platinum/fluoropyrimidine chemotherapy (CTx). Biopsies before CTx were studied in 158 patients with adenocarcinoma of the stomach or gastroesophageal junction. The response was histopathologically evaluated. AI was detected by multiplex PCRs analysis of four or five microsatellite markers in HLA and B2M regions, respectively. AI with no marker was significantly associated with response or survival. However, subgroup analysis revealed differences. AI at marker D6S265, close to the HLA-A gene, was associated with an obvious increased risk in responding (HR, 3.62; 95% CI, 0.96–13.68, p = 0.058) but not in non-responding patients (HR, 0.92; 95% CI, 0.51–1.65, p = 0.773). Markers D6S273 and D6S2872 showed similar results. The interaction between AI at D6S265 and response to CTx was significant in a multivariable analysis (p = 0.010). No associations were observed for B2M markers. Our results underline the importance of intact neoantigen presentation specifically for responding patients and may help explain an unexpectedly poor survival of a patient despite significant tumor regression after neoadjuvant platinum/fluoropyrimidine CTx. [ABSTRACT FROM AUTHOR]

Blood pressure drops during endovascular treatment of acute ischemic stroke have been associated with worse outcomes for stroke patients. We aimed to evaluate this observation in our patient population. Retrospective study. University hospital. Records from patients who underwent endovascular treatment of acute ischaemic stroke under general anaesthesia at a university hospital from 2017 to 2020 were screened. 586 patients aged 78 years (interquartile range [IQR] 67–84) with a mean National Institutes of Health Stroke Scale score of 15 (IQR 8–19) were included. None. Good functional outcome was defined as a three-month modified Rankin Scale (mRS) value between 0 and 2, or a mRS value less than or equal to the pre-stroke baseline. In addition to well-established predictors, blood pressure before reperfusion was found to be associated with good functional outcomes. Per five minutes that systolic arterial pressure spent below 140 mmHg, the odds of good outcome decreased by 11.1 %. In this retrospective study of general anaesthesia for endovascular stroke therapy, blood pressure drops during the intervention were associated with reduced odds of a good functional outcome three months later. Before a clinical recommendation can be made, a prospective study must clarify effective and safe target ranges of blood pressure support and augmentation. • Anaesthesiologists can enhance the success of endovascular stroke thrombectomy. • A number of patient and procedure characteristics are associated with outcome. • The duration and magnitude of blood pressure drops correlate with worse outcome. [ABSTRACT FROM AUTHOR]

Asthma education programs (AEPs) for patients are known to be important to provide skills to effectively manage the disease. We developed an electronic AEP (eAEP) and assessed the extent to which patients with asthma in primary care are capable to use the eAEP and whether asthma knowledge improved after eAEP. A single-arm pilot study was performed between November 2019 and December 2020 in 12 general practices in Upper Bavaria, Germany. Asthma knowledge was assessed by the Asthma Knowledge Test (AKT) at baseline, 2 weeks after completion of the eAEP, as well as after 3 and 6 months. AKT sum scores at baseline and follow-up were compared with each other using the Wilcoxon test. In total, 72 patients with asthma were included, of whom all participated in the 2-week follow-up, while data on the 3- and 6-month follow-up was available in 62 and 51 patients, respectively. The eAEP was well accepted and positively evaluated by participants. The mean AKT score significantly (p <.001) increased from 22.8 ± 11.0 at baseline to 44.6 ± 8.3 two weeks after completion of the eAEP. After 3 months, the mean score was still 41.8 ± 7.6, and after 6 months it was 40.2 ± 9.3 (p <.001 each compared to baseline). The internet-based asthma education program was well accepted by primary care patients and resulted in a major increase of asthma knowledge. Thus, it has the potential to be an important adjunct in the treatment of patients with asthma in general practice. [ABSTRACT FROM AUTHOR]

In an interesting and quite exhaustive review on Random Forests (RF) methodology in bioinformatics Touw et al. address--among other topics--the problem of the detection of interactions between variables based on RF methodology. We feel that some important statistical concepts, such as 'interaction', 'conditional dependence' or 'correlation', are sometimes employed inconsistently in the bioinformatics literature in general and in the literature on RF in particular. In this letter to the Editor, we aim to clarify some of the central statistical concepts and point out some confusing interpretations concerning RF given by Touw et al. and other authors. [ABSTRACT FROM AUTHOR]

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.Clinical Trial Registration: NCT01944800. [ABSTRACT FROM AUTHOR]

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 < 0.001, mortality 68.8%). There was no interaction between diabetes mellitus and the Polyscore regarding mortality prediction (p = 0.775). Interestingly, in contrast to the groups at intermediate and high risk (73 patients, 39.7%), the Polyscore identified a majority of diabetic patients (111, 60.3%) with a low mortality risk, comparable to that of low-risk non-diabetic patients (3.6% and 2.1%, respectively, p = 0.339). Consistent results were observed for cardiac mortality. This analysis shows that the Polyscore predicts all-cause and cardiac mortality in diabetic survivors of acute myocardial infarction. Within these patients it identifies a large population not affected by the excess mortality associated with diabetes in this setting. Thus, the Polyscore may facilitate risk-adapted follow-up strategies in diabetic survivors of myocardial infarction. [ABSTRACT FROM AUTHOR]

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 < 0.05). In biopsies before CTx, CIN-high predicted tumour regression (p = 0.026), but was not prognostically relevant.Conclusion: A refined CIN classification reveals tumours with different biological characteristics and potential clinical implications. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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 . [ABSTRACT FROM AUTHOR]