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The coronavirus disease 2019 (COVID-19) pandemic has heavily impacted medical care of patients with Parkinson's disease (PwP).ObjectiveTo assess the longitudinal impact of the COVID-19 pandemic on PwP and their relatives in Germany.MethodsTwo online, nationwide, cross-sectional surveys were conducted from December 2020 to March 2021 and from July to September 2021.ResultsA total of 342 PwP and 113 relatives participated. Despite partial resumption of social and group activities, healthcare was continuously disrupted during times of loosened restrictions. Respondents’ willingness to use telehealth infrastructure increased, yet the availability remained low. PwP reported worsened symptoms and further deterioration during the pandemic, resulting in an increase in new symptoms and relatives’ burden. We identified patients at particular risk: young patients and those with long disease duration.ConclusionsThe COVID-19 pandemic persistently disrupts the care and quality of life of PwP. Although willingness to use telemedicine services has increased, its availability needs to be improved.

Background. Extensive physical activity (PA; ≥18 MET ∗ h/week, MET metabolic equivalent of tasks hours) postcancer diagnosis has shown favorable effects on colorectal cancer disease-free survival. However, the feasibility of introducing this high volume of PA in this patient group is unclear. Therefore, the aim of the F-PROTECT study was to evaluate the feasibility of extensive and prolonged PA (≥18 MET ∗ h/week over 12 months) in colorectal cancer patients with the primary objectives to (1) recruit 50 patients within 12 months and (2) reach an attendance rate of ≥70%. Methods. Single-armed, bicentric, prospective intervention study in colorectal cancer patients (≤80 years; UICC II/III Union for International Cancer Control) after histopathological confirmed R0-resection who were consecutively recruited from visceral surgery units of 10 clinics in Germany. Recruitment rates were calculated using screening logs. Intervention was a 12-month endurance-focused exercise program with supervised and home-based training. Attendance rates defined as ≥70% participation in training sessions were calculated by training diaries. Results. Out of 521 patients who were screened for eligibility, 50 (23 female; 59 ± 10 years, UICC 44% II, 56% III; adjuvant chemotherapy 60%) were recruited within 15 months. Mean duration between surgery and first training was 103 ± 57 days. Training attendance rate was 64% (including 9 dropouts). Six (12%) participants reached ≥18 MET ∗ h/week in ≥70% of training sessions between 4–12 months. 28 adverse events (n = 9 serious) occurred, however, were not assessed as training related. Conclusions. The present intervention involving a combination of supervised and home-based exercise training in postsurgical colorectal cancer patients was not feasible. Strategies specifically designed for this patient group must be developed and investigated to motivate long-term PA. Registration. The study was prospectively registered at clinicaltrials.gov (NCT01991847).

Purpose The diagnostic criteria of prosthetic joint infection (PJI) recommended by the most commonly used diagnostic algorithms can be obscured or distorted by other inflammatory processes or aseptic pathology. Furthermore, the most reliable diagnostic criteria are garnered during revision surgery. A robust, reliable addition to the preoperative diagnostic cascade is warranted. Calprotectin has been shown to be an excellent diagnostic marker for PJI. In this study, we aimed to evaluate a lateral flow test (LFT) in the challenging patient cohort of a national referral centre for revision arthroplasty. Methods Beginning in March 2019, we prospectively included patients scheduled for arthroplasty exchange of a total hip (THA) or knee arthroplasty (TKA). Synovial fluid samples were collected intra-operatively. We used the International Consensus Meeting of 2018 (ICM) score as the gold standard. We then compared the pre-operative ICM score with the LFT result to calculate its diagnostic accuracy as a standalone pre-operative marker and in combination with the ICM score as part of an expanded diagnostic workup. Results A total of 137 patients with a mean age of 67 (± 13) years with 53 THA and 84 TKA were included. Ninety-nine patients (72.8%) were not infected, 34 (25.0) were infected, and four (2.9%) had an inconclusive final score and could not be classified after surgery. The calprotectin LFT had a sensitivity (95% confidence interval) of 0.94 (0.80–0.99) and a specificity of 0.87 (0.79–0.93). The area under the receiver operating characteristic curve (AUC) for the calprotectin LFT was 0.94 (0.89–0.99). In nine cases with an inconclusive pre-operative ICM score, the calprotectin LFT would have led to the correct diagnosis of PJI. Conclusions The synovial fluid calprotectin LFT shows excellent diagnostic metrics both as a rule-in and a rule-out test, even in a challenging patient cohort with cases of severe osteolysis, wear disease, numerous preceding surgeries, and poor soft tissue conditions, which can impair the common diagnostic criteria. As it is available pre-operatively, this test might prove to be a very useful addition to the diagnostic algorithm.

The diagnosis of device infections, especially pocket infections, is challenging and relies primarily on clinical presentation. The prospective DIRT (Device associated Infections Role of new diagnostic Tools) study identified procalcitonin (PCT) as the most promising biomarker among other 14 biomarkers to aid the diagnosis of pocket infection. It also identified an optimized cut-off value of 0.05 ng/ml for a localized generator pocket infection.The present study aims to validate the proposed PCT cut-off value of 0.05 ng/ml for the diagnosis of pocket infection in an independent cohort.We prospectively enrolled 81 patients with pocket infections and 81 controls matched for age and renal function presenting for elective device exchange or lead revision. Patients with concomitant infectious or inflammatory diseases, end-stage renal failure, current active malignancy, or receiving immunosuppressive therapy were excluded.An elevated PCT over 0.05 ng/ml was found in 68% (n = 55) of pocket infections and 24% (n = 19) of controls, corresponding to a sensitivity of 68% and a specificity of 77% for diagnosing a pocket infection. In receiver operating characteristic (ROC) analysis, PCT showed an area under the curve of 0.75 (95% confidence interval, 0.68-0.83; P0.001). Sensitivity remained high with antibiotic pretreatment (65% compared to 69% without pretreatment) and in cases with minimal inflammatory signs (67% compared to 70% with extensive inflammation).Our study validates the cut-off value of 0.05 ng/ml PCT for diagnosis of a pocket infection, even in patients pre-treated with antibiotics or with minimal clinical signs of inflammation.

Background: The COVID-19 pandemic has led to a flood of—often contradictory—evidence. HCWs had to develop strategies to locate information that supported their work. We investigated the information-seeking of different HCW groups in Germany. Methods: In December 2020, we conducted online surveys on COVID-19 information sources, strategies, assigned trustworthiness, and barriers—and in February 2021, on COVID-19 vaccination information sources. Results were analyzed descriptively; group comparisons were performed using χ2-tests. Results: For general COVID-19-related medical information (413 participants), non-physicians most often selected official websites (57%), TV (57%), and e-mail/newsletters (46%) as preferred information sources—physicians chose official websites (63%), e-mail/newsletters (56%), and professional journals (55%). Non-physician HCWs used Facebook/YouTube more frequently. The main barriers were insufficient time and access issues. Non-physicians chose abstracts (66%), videos (45%), and webinars (40%) as preferred information strategy; physicians: overviews with algorithms (66%), abstracts (62%), webinars (48%). Information seeking on COVID-19 vaccination (2700 participants) was quite similar, however, with newspapers being more often used by non-physicians (63%) vs. physician HCWs (70%). Conclusion: Non-physician HCWs more often consulted public information sources. Employers/institutions should ensure the supply of professional, targeted COVID-19 information for different HCW groups.

We analyse interactions between teachers and students during video-recorded bedside teaching sessions in internal medicine, orthopaedics and neurology. Multiple raters used a high-inference categorical scheme on 36 sessions. Our research questions concern the types of student mistakes, clinical teachers’ reactions to them and if they use different strategies to address different types of mistakes. We used a Poisson model and generalized mixed models to analyse these research questions. Most frequently, students made reproduction mistakes. Relatively high rates of rejection and a similar prevalence of low and high levels of elaboration and correction time for students were observed. Reproduction mistakes were associated with the highest level of rejection and the lowest level of elaboration. High levels of elaboration were observed when students were applying skills in new situations. Students were most often allowed time to correct when mistakes in the areas of analysis or application of skills and knowledge had occurred. There is a decrease in the rate of making mistakes for neurology and orthopaedics compared to internal medicine. Reproduction mistakes influence significantly the outcome feedback compared to application mistakes. Analytic and reproduction mistakes influence elaboration significantly compared to application mistakes. We found a significant effect whether the lecturer allows time for correction of reproduction mistakes compared to application mistakes. These results contribute to the understanding of interactive, patient-centred clinical teaching as well as student mistakes and how teachers are reacting to them. Our descriptive findings provide an empirical basis for clinical teachers to react to student mistakes in didactically fruitful ways.

Aim Retinal vessel diameters are candidate biomarkers of mortality prediction in large population-based studies. We aimed to investigate the predictive value of retinal vessel diameters and flicker-induced retinal arteriolar and venular dilation on all-cause mortality in long-term follow-up of haemodialysis patients. Methods and results Retinal vessel diameters as well as maximum arteriolar (aMax) and venular dilation (vMax) were investigated in 275 and 214 haemodialysis patients, respectively. Patients were observed in a long-term follow-up for a median period of 73 months. About 36% (76/214) and 41% (113/275) of patients died. Arteriolar and venular diameters were 175 ± 19 and 208 ± 20 µm, respectively. Median aMax and vMax were 1.6 (0.3–3.3) and 3.2 (2.0–5.1)%. Patients within the lowest tertile of vMax showed lower 5-year survival rates compared with the highest tertile (50.6 vs. 82.1%) and also exhibited a higher incidence of infection-related deaths (21.7 vs. 4.0%). Univariate hazard ratio (HR) per standard deviation increase of vMax for all-cause mortality was 0.69 (0.54–0.88) and was even more pronounced for infection-related mortality [HR 0.53 (0.33–0.83)]. Regarding all-cause mortality, multivariate adjustment for eight non-retinal mortality predictors including interleukin-6 did not attenuate the HR relevantly [0.73 (0.54–0.98)]. Arteriolar and venular diameters did not predict all-cause nor cardiovascular and infection-related mortality. Conclusions Long-term follow-up of patients on haemodialysis demonstrated the potential of retinal venular dilation capacity for mortality prediction, which was most pronounced for infection-related mortality. In the same cohort, retinal arteriolar and venular diameters showed no predictive value for hard endpoints. Retinal venular dilation but not arteriolar and venular diameters is a valuable diagnostic biomarker for risk prediction in patients with end-stage renal disease and should be considered for monitoring of critically ill patients.

Purpose Radiation-induced cognitive deficits have a severe negative impact on pediatric brain tumor patients. The severity of cognitive symptoms is related to the age of the child when radiation was applied, with the most severe effects seen in the youngest. Previous studies using whole-brain irradiation (WBRT) in mice confirmed these findings. To understand ipsilateral and contralateral changes in the hippocampus after partial-brain irradiation (PBRT) of the left hemisphere we assessed the neuroplasticity and changes in the microvasculature of the irradiated and non-irradiated hippocampus in juvenile mice. Methods and materials The left hemispheres of 5-week old mice were irradiated with 2, 8, 20 Gray (Gy) and a fractionated dose of 8 Gy in 2 fractions (8 Gy/2f) using a Computed Tomography (CT)-image guided Small Animal Radiation Research Platform (SARRP). Long-Term Potentiation (LTP) has been monitored ex vivo in the hippocampal Cornu Ammonis 1 (CA1) region and was assessed 3 days, 5 and 10 weeks after PBRT in both hemispheres and compared to a sham group. Irradiation effects on the hippocampus microvasculature were quantified by Efficient tissue clearing and Multi-Organ Volumetric Imaging (EMOVI). Results LTP in irradiated hippocampal slices of juvenile mice declines 3 days after radiation, lasts up to 10 weeks in the irradiated part of the hippocampus and correlates with a significantly reduced microvasculature length. Specifically, LTP inhibition is sustained in the irradiated (20 Gy, 8 Gy/2f, 8 Gy, 2 Gy) hippocampus, whereas the contralateral hippocampus remains unaffected after PBRT. LTP inhibition in the irradiated hemisphere after PBRT might be associated with an impaired microvascular network. Conclusion PBRT induces a long-lasting impairment in neuroplasticity and microvessel network of the irradiated hippocampus, whereas the contralateral hippocampus remains unaffected. These findings provide insight into the design of PBRT strategies to better protect the young developing brain from cognitive decline.

Late-onset small-for-gestational-age (SGA) fetuses usually show normal uterine artery Doppler and were long considered to have a good peri- and postnatal outcome. Recently, these fetuses were identified to have a risk factor for cardiovascular disease. The aim of our study was to evaluate former SGA children concerning their cardiovascular risk and nutrition behavior at the age of 1 year.We performed a prospective longitudinal cohort study at the University Hospital "Klinikum rechts der Isar" of the Technical University of Munich. Singleton pregnancies from 32 weeks with suspicion of SGA and healthy control pregnancies were included.A total of 100 former SGA children and 113 controls with normal weight (AGA) were examined at 1 year of age. Drop-out for 1-year follow-up was 27%. SGA children had significantly higher systolic (92.8 ± 9.8 mmHg vs. 87.5 ± 10.7 mmHg, p = 0.001), diastolic (63.1 ± 8.5 mmHg vs. 60.0 ± 10.3 mmHg, p = 0.028) and mean (73.0 ± 7.8 vs. 69.2 ± 9.7 mmHg, p = 0.004) blood pressure than AGA children. Comparing two breastfeeding periods (0-4 months vs. 7 months), a downward trend in blood pressure values for longer breastfeeding periods was shown.Our study showed that even late-onset small-for-gestational-age fetuses seem to have cardiovascular problems, although they were previously thought to be "healthy". Up to now, blood pressure measurement is not part of indicated health checks in former SGA or even fetal growth-restricted children which should be changed. Further studies are needed to investigate cardiovascular prevention programs in children.

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Purpose:Non–small cell lung cancer (NSCLC) is a fatal disease with poor prognosis. A membrane-bound form of Hsp70 (mHsp70) which is selectively expressed on high-risk tumors serves as a target for mHsp70-targeting natural killer (NK) cells. Patients with advanced mHsp70-positive NSCLC may therefore benefit from a therapeutic intervention involving mHsp70-targeting NK cells. The randomized phase II clinical trial (EudraCT2008-002130-30) explores tolerability and efficacy of ex vivo–activated NK cells in patients with NSCLC after radiochemotherapy (RCT).Patients and Methods:Patients with unresectable, mHsp70-positive NSCLC (stage IIIa/b) received 4 cycles of autologous NK cells activated ex vivo with TKD/IL2 [interventional arm (INT)] after RCT (60–70 Gy, platinum-based chemotherapy) or RCT alone [control arm (CTRL)]. The primary objective was progression-free survival (PFS), and secondary objectives were the assessment of quality of life (QoL, QLQ-LC13), toxicity, and immunobiological responses.Results:The NK-cell therapy after RCT was well tolerated, and no differences in QoL parameters between the two study arms were detected. Estimated 1-year probabilities for PFS were 67% [95% confidence interval (CI), 19%–90%] for the INT arm and 33% (95% CI, 5%–68%) for the CTRL arm (P = 0.36, 1-sided log-rank test). Clinical responses in the INT group were associated with an increase in the prevalence of activated NK cells in their peripheral blood.Conclusions:Ex vivo TKD/IL2-activated, autologous NK cells are well tolerated and deliver positive clinical responses in patients with advanced NSCLC after RCT.

Supplementary Figure 1. Summary and survival of murine cohort used in the study. Supplementary Figure 2 Consort diagram of the patient distribution of surgical subcohort 1. Supplementary Figure 3. Consort diagram of the patient distribution of surgical subcohort 2. Supplementary Figure 4. Consort diagram of the patient distribution of surgical subcohort 3. Supplementary Figure 5. Schematic of relative tumor cell and stroma contribution in PDAChigh Supplementary Table 1. Statistics of the patients used in surgical subcohort 1. Supplementary Table 2. Statistics of the patients used in surgical subcohort 2. Supplementary Table 3. Statistics of the patients used in surgical subcohort 3. Supplementary Table 4. Results of a multivariable Cox regression model fit to the data of subcohort 2 that assess whether PDAC is associated with overall survival after adjustment for common predictors. Supplementary Table 5. The permutation test analysis revealing association between overall survival and lowest ADC stratified by each of the relevant categorical variables. Data used for analysis are derived from surgical subcohort 3.

Purpose: Tumor heterogeneity is a hallmark of pancreatic ductal adenocarcinoma (PDAC). It determines tumor biology including tumor cellularity (i.e., amount of neoplastic cells and arrangement into clusters), which is related to the proliferative capacity and differentiation and the degree of desmoplasia among others. Given the close relation of tumor differentiation with differences in progression and therapy response or, e.g., the recently reported protective role of tumor stroma, we aimed at the noninvasive detection of PDAC groups, relevant for future personalized approaches. We hypothesized that histologic differences in PDAC tissue composition are detectable by the noninvasive diffusion weighted- (DW-) MRI-derived apparent diffusion coefficient (ADC) parameter.Experimental design: PDAC cellularity was quantified histologically and correlated with the ADC parameter and survival in genetically engineered mouse models and human patients.Results: Histologic analysis showed an inverse relationship of tumor cellularity and stroma content. Low tumor cellularity correlated with a significantly prolonged mean survival time (PDAClow = 21.93 months vs. PDACmed = 12.7 months; log-rank P < 0.001; HR = 2.23; CI, 1.41–3.53). Multivariate analysis using the Cox regression method confirmed tumor cellularity as an independent prognostic marker (P = 0.034; HR = 1.73; CI, 1.04–2.89). Tumor cellularity showed a strong negative correlation with the ADC parameter in murine (r = −0.84; CI, −0.90– −0.75) and human (r = −0.79; CI, −0.90 to −0.56) PDAC and high preoperative ADC values correlated with prolonged survival (ADChigh = 41.7 months; ADClow = 14.77 months; log rank, P = 0.040) in PDAC patients.Conclusions: This study identifies high tumor cellularity as a negative prognostic factor in PDAC and supports the ADC parameter for the noninvasive identification of PDAC groups. Clin Cancer Res; 23(6); 1461–70. ©2016 AACR.

Data about the influence of short-term lifestyle intervention in children with obesity on long-term follow-up body weight, adipokines and cardiometabolic risk parameters is scarce.In a subgroup of the LOGIC-trial (Long-term Effects of Lifestyle Intervention in Obesity and Genetic Influence in Children), we assessed anthropometry (BMI, BMI-SDS (Standard Deviation Score), adipokines (omentin-1, chemerin, leptin, adiponectin) and cardiometabolic risk parameters, (e.g. hsCRP) in children with overweight/obesity after 4 weeks of lifestyle intervention (n = 156, 14.0 ± 1.8 yrs) and after one year follow-up (n = 50). Data were compared to normal weight children (JuvenTUM school cohort; n = 152, 13.3 ± 0.7 yrs).Short-term lifestyle intervention was associated with a significant reduction in BMI and BMI-SDS (p 0.001), with significant reductions in hsCRP, leptin, and chemerin levels, and an increase in adiponectin and omentin-1 levels (p 0.001 for all). After one year follow-up a significant reduction in BMI and BMI-SDS was observed in children from the LOGIC-trial (p 0.001). Improvements in adiponectin (p = 0.025) and chemerin levels (p = 0.027) were seen in children with clear weight loss success (BMI-SDS reduction ≥ 0.2), whereas children with no or only mild weight loss success showed an increase in leptin levels (p 0.001). An increase in omentin-1 levels was observed after 1 year independent of weight change (p 0.001).Effects of short-term weight reduction on mean BMI and BMI-SDS persist over one year. Improvements in omentin-1 levels were independent of short-term or long-term weight loss.ClinicalTrials.gov: LOGIC-trial: NCT01067157, JuvenTUM-trial: NCT00988754.

IMPORTANCEThe rapid genetic evolution of SARS-CoV-2 and in particular the highly contagious Omicron variant of concern (VoC) may pose problems for rapid and accurate diagnosis of infection.OBJECTIVEDetermine the diagnostic accuracy and robustness of a second generation rapid antigen tests compared to gold-standard, PCR-based diagnostics, for detection of infection with different SARS-CoV-2 Omicron VoC sub lineages in health care workers.DESIGN, SETTING, AND PARTICIPANTSThe study included 428 health care workers from the University Hospital Munich Rechts der Isar of the Technical University of Munich who either reported recent onset of COVID-19 associated symptoms or completed routine diagnostic testing between 24thof May and 22ndof September 2022. All participants gave written informed consent to participate in this study and completed a questionnaire on infection-associated symptoms, prior SARS-CoV-2 infections and vaccination status.INTERVENTIONSDuring the first visit, two nasal swabs and one oropharyngeal swab were taken to perform two rapid antigen tests and a SARS-CoV-2 PCR-assay, respectively. A second set of nasal swabs was taken by the participants themselves two days later to repeat the two rapid antigen tests.MAIN OUTCOMES AND MEASURESThe accuracy for detection of infection with different SARS-CoV-2 Omicron VoCs with two rapid antigen tests (Test IandTest II) was determined and compared to quantitative SARS-CoV-2 RNA levels detected by PCR.RESULTSIn a side-by-side comparison, we found thatTest Idetected viral nucleocapsids from Omicron VoC (BA.5.2.3) at higher dilutions compared toTest II. In the 428 health care workers,Test Iand Test II detected PCR-confirmed SARS-CoV-2 infection with different Omicron VoCs (BA.2, BA.4, BA.5) with a sensitivity of 89.4% (95% CI 81.9% - 94.6%) and 83.7% (95% CI 75.12% - 90.18%), respectively. Increased sensitivity ofTest Iwas also reflected by earlier detection of SARS-CoV-2 infection. The lower test sensitivity ofTest IIcould be compensated for by a repeated test performed two days later.CONCLUSIONS AND RELEVANCEOur study demonstrates that rapid antigen tests are suited to detect infection with the SARS-CoV-2 Omicron VoC and reveal an advantage of a lower detection limit for earlier detection of infection in health care workers.

Background Industrially processed trans-fatty acids (IP-TFA) have been linked to altered lipoprotein metabolism, inflammation and increased NT-proBNP. In patients with heart failure with preserved ejection fraction (HFpEF), associations of TFA blood levels with patient characteristics are unknown. Methods This is a secondary analysis of the Aldo-DHF-RCT. From 422 patients, individual blood TFA were analyzed at baseline in n = 404 using the HS-Omega-3-Index® methodology. Patient characteristics were: 67 ± 8 years, 53% female, NYHA II/III (87/13%), ejection fraction ≥ 50%, E/e′ 7.1 ± 1.5; NT-proBNP 158 ng/L (IQR 82–298). A principal component analysis was conducted but not used for further analysis as cumulative variance for the first two PCs was low. Spearman’s correlation coefficients as well as linear regression analyses, using sex and age as covariates, were used to describe associations of whole blood TFA with metabolic phenotype, functional capacity, echocardiographic markers for LVDF and neurohumoral activation at baseline and after 12 months. Results Blood levels of the naturally occurring TFA C16:1n-7t were inversely associated with dyslipidemia, body mass index/truncal adiposity, surrogate markers for non-alcoholic fatty liver disease and inflammation at baseline/12 months. Conversely, IP-TFA C18:1n9t, C18:2n6tt and C18:2n6tc were positively associated with dyslipidemia and isomer C18:2n6ct with dysglycemia. C18:2n6tt and C18:2n6ct were inversely associated with submaximal aerobic capacity at baseline/12 months. No significant association was found between TFA and cardiac function. Conclusions In HFpEF patients, higher blood levels of IP-TFA, but not naturally occurring TFA, were associated with dyslipidemia, dysglycemia and lower functional capacity. Blood TFAs, in particular C16:1n-7t, warrant further investigation as prognostic markers in HFpEF. Graphical abstract Higher blood levels of industrially processed TFA, but not of the naturally occurring TFA C16:1n-7t, are associated with a higher risk cardiometabolic phenotype and prognostic of lower aerobic capacity in patients with HFpEF.

Objectives To evaluate associations of omega-3 fatty acid (O3-FA) blood levels with cardiometabolic risk markers, functional capacity and cardiac function/morphology in patients with heart failure with preserved ejection fraction (HFpEF). Background O3-FA have been linked to reduced risk for HF and associated phenotypic traits in experimental/clinical studies. Methods This is a cross-sectional analysis of data from the Aldo-DHF-RCT. From 422 patients, the omega-3-index (O3I = EPA + DHA) was analyzed at baseline in n = 404 using the HS-Omega-3-Index® methodology. Patient characteristics were; 67 ± 8 years, 53% female, NYHA II/III (87/13%), ejection fraction ≥ 50%, E/e′ 7.1 ± 1.5; median NT-proBNP 158 ng/L (IQR 82–298). Pearson’s correlation coefficient and multiple linear regression analyses, using sex and age as covariates, were used to describe associations of the O3I with metabolic phenotype, functional capacity, echocardiographic markers for LVDF, and neurohumoral activation at baseline/12 months. Results The O3I was below ( 11%) than the target range in 374 (93%), 29 (7%), and 1 (0.2%) patients, respectively. Mean O3I was 5.7 ± 1.7%. The O3I was inversely associated with HbA1c (r = − 0.139, p = 0.006), triglycerides-to-HDL-C ratio (r = − 0.12, p = 0.017), triglycerides (r = − 0.117, p = 0.02), non-HDL-C (r = − 0.101, p = 0.044), body-mass-index (r = − 0.149, p = 0.003), waist circumference (r = − 0.121, p = 0.015), waist-to-height ratio (r = − 0.141, p = 0.005), and positively associated with submaximal aerobic capacity (r = 0.113, p = 0.023) and LVEF (r = 0.211, p β = 15.614, p β = 0.399, p = 0.005) and LVEF (β = 0.698, p = 0.007) at 12 months. Conclusions Higher O3I was associated with a more favorable cardiometabolic risk profile and predictive of higher submaximal/maximal aerobic capacity and lower BMI/truncal adiposity in HFpEF patients. Graphic abstract Omega-3 fatty acid blood levels are inversely associated with cardiometabolic risk factors in HFpEF patients. Higher O3I was associated with a more favorable cardiometabolic risk profile and aerobic capacity (left) but did not correlate with echocardiographic markers for left ventricular diastolic function or neurohumoral activation (right). An O3I-driven intervention trial might be warranted to answer the question whether O3-FA in therapeutic doses (with the target O3I 8–11%) impact on echocardiographic markers for left ventricular diastolic function and neurohumoral activation in patients with HFpEF. This figure contains modified images from Servier Medical Art (https://smart.servier.com) licensed by a Creative Commons Attribution 3.0 Unported License.

Additional treatment options for coronavirus disease (COVID-19) are urgently needed, particularly for populations at high risk of severe disease. This cross-sectional, retrospective study characterized the outcomes of 43 patients with nosocomial severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection with and without treatment using monoclonal SARS-CoV-2 spike antibodies (bamlanivimab or casirivimab/imdevimab). Our results indicate that treatment with monoclonal antibodies results in a significant decrease in disease progression and mortality when used for asymptomatic patients with early SARS-CoV-2 infection. Supplementary Information The online version contains supplementary material available at 10.1007/s15010-021-01657-y.

Systemic pan-tumor analyses may reveal the significance of common features implicated in cancer immunogenicity and patient survival. Here, we provide a comprehensive multi-omics data set for 32 patients across 25 tumor types by combining proteogenomics with phenotypic and functional analyses. By using an optimized computational approach, we discovered a large number of novel tumor-specific and tumor-associated antigens including shared common target candidates. To create a pipeline for the identification of neoantigens in our cohort, we combined deep DNA and RNA sequencing with MS- based immunopeptidomics of tumor specimens, followed by the assessment of their immunogenicity. In fact, we could detect a broad variety of non-wild type HLA-binding peptides in the majority of patients and confirmed the immunogenicity of 24 neoantigens. Most interestingly, the majority of total and immunogenic neoantigens originated from variants identified in the RNA dataset, illustrating the importance of RNA as a still understudied source of cancer antigens. Moreover, the amount of these mainly RNA-based immunogenic neoantigens correlated positively with overall CD8+ tumor-infiltrating T cells. This study therefore underlines the importance of RNA-centered variant detection for the identification of shared biomarkers and potentially relevant neoantigen candidates.Statement of significanceThe significance of this study lies not only in the potential of our optimized proteogenomic workflow for the discovery of neoantigens (in particular RNA-derived neoantigens) for clinical application, but sheds light on the entity-agnostic prevalence of HLA class I peptide presentation of RNA processing events to be used for tumor targeting.

To describe the perinatal outcome of a prospective cohort of late-onset small-for-gestational-age (SGA) fetuses and to test adverse perinatal outcome (APO) prediction using Doppler measurements. Singleton pregnancies from 32 weeks with suspicion of SGA (followed-up each 2 weeks) and randomly selected healthy controls at a university hospital were included. The whole SGA group was divided into the FGR subgroup or SGA percentile 3-10 subgroup. The following Doppler measurements were evaluated prospectively: umbilical artery (UA) pulsatility index (PI), middle cerebral artery (MCA) PI, cerebro-placental ratio (CPR), and mean uterine artery (mUtA) PI. APO was defined as arterial cord blood pH ≤ 7.15 and/or 5-minute Apgar ≤ 7 and/or emergency operative delivery and/or admission to the neonatal unit. Induction of labor was indicated according to a stage-based protocol. A total of 149 SGA and 143 control fetuses were included. The number of operative deliveries was similar between both groups (control: 29 %, SGA: 28 %), especially the cesarean delivery rate after the onset of labor (11 % vs. 10 %). Most SGA cases ended up in induction of labor (61 % vs. 31 %, p 0.001). The areas under the curve (AUC) for APO prediction were similar using the last UA PI, MCA PI, CPR, and mUtA PI and barely reached 0.60. The AUC was best for the FGR subgroup, using the minimal CPR or maximum mUtA PI z-score of all longitudinal measurements (AUC = 0.63). SGA fetuses do not have a higher rate of operative delivery if managed according to a risk stratification protocol. Prediction of APO is best for SGA and FGR using the "worst" CPR or mUtA PI but it remains moderate.ZIEL: Beschreibung des perinatalen Outcomes einer prospektiven Kohorte von „small for gestational age“ (SGA)-Feten sowie Vorhersage eines schlechten perinatalen Outcomes (APO) mittels longitudinaler Dopplermessungen. Eingeschlossen wurden Einlingsschwangerschaften ab 32 + 0 Schwangerschaftswochen mit Verdacht auf SGA (Untersuchungen alle 2 Wochen) und gesunde Kontrollen. Die folgenden Dopplermessungen wurden ermittelt: Pulsatilitätsindex (PI) der Nabelschnurarterie (UA), PI der mittleren Zerebralarterie (MCA-PI), die zerebroplazentare Ratio (CPR) und mittlerer PI der Uterinarterien (mUtA-PI). APO wurde definiert als arterieller Nabelschnurblut-pH-Wert ≤ 7,15 und/oder 5-Minuten-Apgar ≤ 7 und/oder operative Notfall-Entbindung und/oder Aufnahme auf die Neugeborenenstation. Eine Geburtseinleitung bei SGA wurde nach Protokoll indiziert. Insgesamt wurden 149 SGA- und 143 Kontrollfeten eingeschlossen. Die Anzahl der operativen Entbindungen war in beiden Gruppen ähnlich, insbesondere die sekundäre Sectiorate (11 % vs. 10 %). Bei den meisten SGA-Fällen wurde die Geburt eingeleitet (61 % vs. 31 %; p 0,001). Die Fläche unter der Kurve (AUC) für die APO-Vorhersage war unter Verwendung des letzten UA, MCA-PI, CPR und mUtA PI ähnlich und erreichte kaum 0,60; am besten war sie für die FGR-Subgruppe unter Verwendung der minimalen CPR oder des maximalen mUtA-PI (AUC = 0,63). SGA-Feten haben keine erhöhte operative Entbindungsrate, wenn sie nach einem Risikostratifizierungsprotokoll überwacht und entbunden werden. Die Vorhersage des APO ist am besten mit der „schlechtesten“ CPR oder mUtA-PI, aber sie ist insgesamt moderat.

PURPOSE: The effects of orthognathic surgery (OGS) on the temporomandibular joint (TMJ) are still controversial. Based on a high-volume uniform collective, the function and clinical symptoms of the TMJ and the dysfunction index (Di) by Helkimo were evaluated prior and up to 2 years after OGS. METHODS: A longitudinal cohort study was performed between 2006 and 2016. A comprehensive examination focusing on TMJ function, temporomandibular disorder (TMD) symptoms, and the Di had been performed preopertaively (T0) and postoperatively at 6 weeks (T1), 6 months (T2), 1 year (T3), and 2 years (T4). The predictor variables used were sex, age, skeletal class, type of surgery, and amount of dysfunction or number of TMD complaints before treatment. The outcome of this study was TMD symptoms and the Di. Descriptive and bivariate statistics were computed, and the significance level was set at P

Background: Advanced stages of dementia are characterized by severe cognitive and physical impairment. It has not yet been investigated whether persons with young onset dementia (YOD) and late onset dementia (LOD) differ in advanced disease stages. Objectives: To compare quality of life (QoL) between persons with advanced YOD and LOD; to explore the determinants of QoL; to investigate whether YOD and LOD differ with regard to symptoms and care. Methods: The study was performed in the context of EPYLOGE (IssuEs in Palliative care for persons in advanced and terminal stages of YOD and LOD in Germany). Persons with advanced dementia (PWAD) were assessed and caregivers were interviewed. QoL was measured with the proxy rating Quality of Life in Late Stage Dementia (QUALID) scale. Results: 93 persons with YOD and 98 with LOD were included. No significant differences in QoL were detected. Determinants of QoL were similar in YOD and LOD. Behavioral and psychological symptoms of dementia (BPSD), suffering and other distressing symptoms were associated with a lower QoL. In YOD but not in LOD antipsychotic treatment was associated with low QoL. The group of persons who were younger than 65 years at the time of the study visit experienced significantly more distressing symptoms than older PWAD. Conclusion: Overall, persons with advanced YOD do not appear to be disadvantaged compared to old and oldest PWAD. Special attention, however, must be paid to the group of the very young persons who seem to be particularly vulnerable.