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We report on a 38-year-old patient who presented with rapidly progressive interstitial lung disease (ILD), without any signs of muscular involvement. Antinuclear antibody testing by indirect immunofluorescence revealed a nuclear titer of 1:320 with a fine speckled and a cytoplasmic titer of 1:1’280 with a fine speckled pattern. Subsequent myositis-specific and myositis-associated antibody tests with commercial multiplex dot-immunoassays showed a strong positive result for anti-Ha antibodies, also confirmed by protein immunoprecipitation, establishing the diagnosis of anti-synthetase syndrome with associated ILD. Despite initial improvement after treatment with intravenous cyclophosphamide and high dose steroids, he relapsed shortly after, with additional muscular symptoms. Subsequent escalation of therapy with rituximab resulted in sustained remission. Considering the scarcity of data about the clinical presentation and prognosis of patients with anti-Ha antibodies, our report provides additional information on diagnostic challenges and therapeutic response in these patients.

Background Inpatient polysomnography (PSG) is the gold standard for the diagnosis of obstructive sleep apnoea (OSA), however, both complexity and costs limit the availability of this examination. Home sleep apnoea testing devices are a diagnostic alternative in patients with increased risk of OSA. We evaluated the diagnostic performance of a Doppler radar technology based, contactless sleep apnoea testing device (CSATD) in a cohort of patients with a clinically increased risk of OSA. Methods Monocentric prospective study. Sleep monitoring with the CSATD SleepizOne + without pulse oximetry (Sleepiz AG, Switzerland) was performed simultaneously with elective inpatient PSG. PSG was analysed blinded to the CSATD results and according to AASM 2012 criteria by certified sleep physicians. The CSATD data were analysed automatically and independently by a dedicated software. Results A total of 102 patients, 60.8% male, with an average age of 55 ± 15 years and body mass index of 30 ± 6 kg/m2 were included in the analysis. The sensitivity and specificity of the CSATD for a PSG apnoea-hypopnoea-index (AHI) of ≥ 5/h were 0.89 (95%CI: 0.83–0.96) and 0.88 (95%CI: 0.73-1.0). The negative and positive predictive values were 0.62 (95%CI: 0.42–0.82) and 0.97 (95%CI: 0.94-1.0). The diagnostic agreement for the diagnosis of OSA (defined as PSG AHI ≥ 5/h) was 89.8% and 100% using a CSATD AHI threshold of ≥ 5/h ( n  = 79/88) and ≥ 15/h ( n  = 61/61). However, the concordance was poor in the classification of OSA severity, with 50% (13/26) concordance for mild, 38% (10/26) for moderate, and 76% (25/33) for severe OSA respectively. Conclusion CSATD accurately identifies patients with OSA, particularly using an AHI threshold of ≥ 15/h. However, it performs subpar in disease severity stratification. Clinical trial registration This trial was registered on the International Clinical Trials Registry Platform, ISRCTN45778591.

Background Polysomnography (PSG) is the gold standard for the diagnosis of obstructive sleep apnoea (OSA). Home sleep apnoea testing with peripheral arterial tonometry (PAT) is a recommended diagnostic alternative for patients with an increased risk for OSA. In a large clinical cohort, we investigated concordance and predictors for discordance in diagnosing OSA using PAT and PSG, and three-year cardiovascular risk in patients with discordant OSA diagnosis. Methods Retrospective monocentric cohort study. Patients with a PAT AHI ≥ 5/h followed by an in-hospital PSG within three months were included. All patients with a PAT AHI ≥ 5/h but a PSG AHI < 5/h were classified as discordant. Patients with PAT and PSG AHI ≥ 5/h were classified as concordant. To ascertain cardiovascular risk, major adverse cardiovascular events (MACE) were analyzed in discordant patients and sex, age, body mass index (BMI) and cardiovascular disease-matched concordant patients over a follow-up time of 3.1 ± 0.06 years. Results A total of 940 patients, 66% male with an average age of 55 ± 0.4 years and BMI of 31 ± 0.2 kg/m 2 were included. Agreement in OSA diagnosis was observed in 80% of patients (55% in mild and 86% in moderate and severe OSA). Factors significantly associated with a discordant diagnosis were female sex, younger age and lower BMI, but not comorbidities. There was no significant difference in MACE ( p  = 0.920) between discordant patients ( n  = 155) and matched concordant patients ( n  = 274) with or without therapy. Conclusions Concordance between PAT and PSG diagnosis of sleep apnoea is good, particularly in moderate and severe OSA. Predictors for discordant results between PAT and PSG were age, sex and BMI. MACE risk is similar in those with OSA diagnosed by PAT or PSG.

Brown adipose tissue (BAT) dissipates nutritional energy as heat via the uncoupling protein-1 (UCP1) and BAT activity correlates with leanness in human adults. Here we profile G protein-coupled receptors (GPCRs) in brown adipocytes to identify druggable regulators of BAT. Twenty-one per cent of the GPCRs link to the G q family, and inhibition of G q signalling enhances differentiation of human and murine brown adipocytes. In contrast, activation of G q signalling abrogates brown adipogenesis. We further identify the endothelin/Ednra pathway as an autocrine activator of G q signalling in brown adipocytes. Expression of a constitutively active G q protein in mice reduces UCP1 expression in BAT, whole-body energy expenditure and the number of brown-like/beige cells in white adipose tissue (WAT). Furthermore, expression of G q in human WAT inversely correlates with UCP1 expression. Thus, our data indicate that G q signalling regulates brown/beige adipocytes and inhibition of G q signalling may be a novel therapeutic approach to combat obesity. Brown and beige adipose tissues contribute to organismal energy expenditure by generating heat. Here, Klepac et al. survey G protein-coupled receptors in brown fat and show that G q -coupled receptors inhibit expression of thermogenic proteins in mice and in human adipocytes.

Emotional facial expressions provide critical information for social interactions. Above all, angry faces are assumed to reflect potential social threat. We investigated event-related potentials (ERPs) triggered by natural and artificial faces expressing fear, anger, happiness or no emotion in participants with low and high levels of social anxiety. Overall, artificial faces elicited stronger P100 and N170 responses than natural faces. Additionally, the N170 component was larger for emotional compared to neutral facial expressions. Social anxiety was associated with an enhanced emotional modulation of the early posterior negativity (EPN) in response to fearful and angry facial expressions. Additionally, while the late positive potential (LPP) was larger for emotional than for neutral faces in low socially anxious participants, LPPs of higher socially anxious participants did not differ. LPPs might therefore be enhanced in higher socially anxious participants for both emotional and neutral faces. Furthermore, the modulations of the EPN and LPP were comparable between natural and artificial faces. These results indicate that social anxiety influences early perceptual processing of faces and that artificial faces are suitable for psychophysiological emotion research.

The aim of this guideline is to provide standards for the recommendation, performance, interpretation and reporting of 68 Ga-PSMA PET/CT for prostate cancer imaging. These recommendations will help to improve accuracy, precision, and repeatability of 68 Ga-PSMA PET/CT for prostate cancer essentially needed for implementation of this modality in science and routine clinical practice.

Background Physical exercise and nutritional treatment are promising measures to prevent muscle wasting that is frequently observed in advanced-stage cancer patients. However, conventional exercise is not always suitable for these patients due to physical weakness and therapeutic side effects. In this pilot study, we examined the effect of a combined approach of the novel training method whole-body electromyostimulation (WB-EMS) and individualized nutritional support on body composition with primary focus on skeletal muscle mass in advanced cancer patients under oncological treatment. Methods In a non-randomized controlled trial design patients (56.5% male; 59.9 ± 12.7 years) with advanced solid tumors (UICC III/IV, N  = 131) undergoing anti-cancer therapy were allocated to a usual care control group ( n  = 35) receiving individualized nutritional support or to an intervention group ( n  = 96) that additionally performed a supervised physical exercise program in form of 20 min WB-EMS sessions (bipolar, 85 Hz) 2×/week for 12 weeks. The primary outcome of skeletal muscle mass and secondary outcomes of body composition, body weight and hand grip strength were measured at baseline, in weeks 4, 8 and 12 by bioelectrical impedance analysis and hand dynamometer. Effects of WB-EMS were estimated by linear mixed models. Secondary outcomes of physical function, hematological and blood chemistry parameters, quality of life and fatigue were assessed at baseline and week 12. Changes were analyzed by t-tests, Wilcoxon signed-rank or Mann-Whitney-U-tests. Results Twenty-four patients of the control and 58 of the WB-EMS group completed the 12-week trial. Patients of the WB-EMS group had a significantly higher skeletal muscle mass (0.53 kg [0.08, 0.98]; p  = 0.022) and body weight (1.02 kg [0.05, 1.98]; p  = 0.039) compared to controls at the end of intervention. WB-EMS also significantly improved physical function and performance status ( p  < 0.05). No significant differences of changes in quality of life, fatigue and blood parameters were detected between the study groups after 12 weeks. Conclusions Supervised WB-EMS training is a safe strength training method and combined with nutritional support it shows promising effects against muscle wasting and on physical function in advanced-stage cancer patients undergoing treatment. Trial registration ClinicalTrials.gov NCT02293239 (Date: November 18, 2014).

Previous studies have indicated that glabellar botulinum toxin (BTX) injections may lead to a sustained alleviation of depression. This may be accomplished by the disruption of a facial feedback loop, which potentially mitigates the experience of negative emotions. Accordingly, glabellar BTX injection can attenuate amygdala activity in response to emotional stimuli. A prototypic condition with an excess of negative emotionality and impulsivity accompanied by elevated amygdala reactivity to emotional stimuli is borderline personality disorder (BPD). In order to improve the understanding of how glabellar BTX may affect the processing of emotional stimuli and impulsivity, we conducted a functional magnetic resonance imaging (fMRI) study. Our hypotheses were (1) glabellar BTX leads to increased activation in prefrontal areas during inhibition performance and (2) BTX decreases amygdala activity during the processing of emotional stimuli in general. Using an emotional go-/no-go paradigm during fMRI, the interference of emotion processing and impulsivity in a sample of n = 45 women with BPD was assessed. Subjects were randomly assigned to BTX treatment or serial acupuncture (ACU) of the head. After 4 weeks, both treatments led to a reduction in the symptoms of BPD. However, BTX treatment was specifically associated with improved inhibition performance and increased activity in the motor cortex. In addition, the processing of negative emotional faces was accompanied by a reduction in right amygdala activity. This study provides the first evidence that glabellar BTX injections may modify central neurobiological and behavioural aspects of BPD. Since the control treatment produced similar clinical effects, these neurobiological findings may be specific to BTX and not a general correlate of symptomatic improvement.

Background Severe COVID-19 induced acute respiratory distress syndrome (ARDS) often requires extracorporeal membrane oxygenation (ECMO). Recent German health insurance data revealed low ICU survival rates. Patient characteristics and experience of the ECMO center may determine intensive care unit (ICU) survival. The current study aimed to identify factors affecting ICU survival of COVID-19 ECMO patients. Methods 673 COVID-19 ARDS ECMO patients treated in 26 centers between January 1st 2020 and March 22nd 2021 were included. Data on clinical characteristics, adjunct therapies, complications, and outcome were documented. Block wise logistic regression analysis was applied to identify variables associated with ICU-survival. Results Most patients were between 50 and 70 years of age. PaO 2 /FiO 2 ratio prior to ECMO was 72 mmHg (IQR: 58–99). ICU survival was 31.4%. Survival was significantly lower during the 2nd wave of the COVID-19 pandemic. A subgroup of 284 (42%) patients fulfilling modified EOLIA criteria had a higher survival (38%) ( p  = 0.0014, OR 0.64 (CI 0.41–0.99)). Survival differed between low, intermediate, and high-volume centers with 20%, 30%, and 38%, respectively ( p  = 0.0024). Treatment in high volume centers resulted in an odds ratio of 0.55 (CI 0.28–1.02) compared to low volume centers. Additional factors associated with survival were younger age, shorter time between intubation and ECMO initiation, BMI > 35 (compared to < 25), absence of renal replacement therapy or major bleeding/thromboembolic events. Conclusions Structural and patient-related factors, including age, comorbidities and ECMO case volume, determined the survival of COVID-19 ECMO. These factors combined with a more liberal ECMO indication during the 2nd wave may explain the reasonably overall low survival rate. Careful selection of patients and treatment in high volume ECMO centers was associated with higher odds of ICU survival. Trial registration Registered in the German Clinical Trials Register (study ID: DRKS00022964, retrospectively registered, September 7th 2020, https://www.drks.de/drks_web/navigate.do?navigationId=trial.HTML&TRIAL_ID=DRKS00022964 . Graphical abstract

Background During the COVID-19 pandemic, non-COVID-19 related healthcare utilization declined in Germany, resulting in care delay, including delays and cancellations of routine, chronic, and even acute care. The aim of this study was to investigate factors (i.e. regional differences and participant characteristics) associated with care delay during the pandemic in Germany using a cross-sectional survey. Methods In October 2022, a total of 117,466 participants from the German National Cohort (NAKO) study completed an online questionnaire on pandemic-related topics, including care delay during the COVID-19 pandemic. Regional differences and participant characteristics associated with care delay were assessed using (multilevel) logistic regression. Results One third of participants reported having experienced care delay. Care delay did not differ across the 13 federal states or 32 districts in Germany for which sufficient data were available. In the medical practice setting, care delay was nearly equally provider- and patient-related and was reported mostly for routine check-ups. In the hospital setting, care delay was predominantly provider-related and reported for newly occurring conditions. The odds for care delay were higher in females vs. males (odds ratio (OR): 1.30; 95% confidence interval (CI): 1.27–1.34), and in participants with vs. without chronic conditions (e.g. mental disorders, OR: 1.41, 95%CI: 1.36–1.46 or cardiovascular diseases, OR: 1.20 95%CI: 1.16–1.24) and decreased with age (e.g. 70 + vs. 50–59 years, OR: 0.59, 95%CI: 0.57–0.62). Conclusion Care delay during the COVID-19 pandemic depended on participant characteristics including age, sex, and preexisting chronic conditions but not on regional (i.e. state and district-level) differences in Germany.