Dual-Energy CT muscle fat fraction as a new imaging biomarker of body composition and survival predictor in critically ill patients.

OBJECTIVE: To analyze changes in the muscular fat fraction (FF) during immobilization at the intensive care unit (ICU) using dual-energy CT (DECT) and evaluate the predictive value of the DECT FF as a new imaging biomarker for morbidity and survival. METHODS: Immobilized ICU patients (n = 81, 43.2% female, 60.3 ± 12.7 years) were included, who received two dual-source DECT scans (CT1, CT2) within a minimum interval of 10 days between 11/2019 and 09/2022. The DECT FF was quantified for the posterior paraspinal muscle by two radiologists using material decomposition. The skeletal muscle index (SMI), muscle radiodensity attenuation (MRA), subcutaneous-/ visceral adipose tissue area (SAT, VAT), and waist circumference (WC) were assessed. Reasons for ICU admission, clinical scoring systems, therapeutic regimes, and in-hospital mortality were noted. Linear mixed models, Cox regression, and intraclass correlation coefficients were employed. RESULTS: Between CT1 and CT2 (median 21 days), the DECT FF increased (from 20.9% ± 12.0 to 27.0% ± 12.0, p = 0.001). The SMI decreased (35.7 cm2/m2 ± 8.8 to 31.1 cm2/m2 ± 7.6, p < 0.001) as did the MRA (29 HU ± 10 to 26 HU ± 11, p = 0.009). WC, SAT, and VAT did not change. In-hospital mortality was 61.5%. In multivariable analyses, only the change in DECT FF was associated with in-hospital mortality (hazard ratio (HR) 9.20 [1.78-47.71], p = 0.008), renal replacement therapy (HR 48.67 [9.18-258.09], p < 0.001), and tracheotomy at ICU (HR 37.22 [5.66-245.02], p < 0.001). Inter-observer reproducibility of DECT FF measurements was excellent (CT1: 0.98 [0.97; 0.99], CT2: 0.99 [0.96-0.99]). CONCLUSION: The DECT FF appears to be suitable for detecting increasing myosteatosis. It seems to have predictive value as a new imaging biomarker for ICU patients. CLINICAL RELEVANCE STATEMENT: The dual-energy CT muscular fat fraction appears to be a robust imaging biomarker to detect and monitor myosteatosis. It has potential for prognosticating, risk stratifying, and thereby guiding therapeutic nutritional regimes and physiotherapy in critically ill patients. KEY POINTS: The dual-energy CT muscular fat fraction detects increasing myosteatosis caused by immobilization. Change in dual-energy CT muscular fat fraction was a predictor of  in-hospital morbidity and mortality. Dual-energy CT muscular fat fraction had a predictive value superior to established CT body composition parameters.

Fat quantification in dual-layer detector spectral CT: How to handle iron overload, varying tube voltage and radiation dose Indices.

OBJECTIVES: Opposed to other spectral CT techniques, fat quantification in dual-layer detector CT (dlCT) has only recently been developed. The impact of concomitant iron overload and dlCT-specific protocol settings such as the dose right index (DRI), a measure of image noise and tube current, on dlCT fat quantification was unclear. Further, spectral information became newly available <120 kV. Therefore, this study's objective was to evaluate the impact of iron, changing tube voltage, and DRI on dlCT fat quantification. MATERIAL AND METHODS: Phantoms with 0 and 8mg/cm3 iron; 0 and 5mg/cm3 iodine; 0, 10, 20, 35, 50, and 100% fat and liver equivalent, respectively, were scanned with a dlCT (CT7500, Philips, the Netherlands) at 100kV/20DRI, 120kV/20DRI, 140kV/20DRI, and at 120kV/16DRI, 120kV/24DRI. Material decomposition was done for fat, liver, and iodine (A1); for fat, liver, and iron (A2); and for fat, liver, and combined reference values of iodine and iron (A3). All scans were analyzed with reference values from 120kV/20DRI. For statistics, the intraclass correlation coefficient (ICC) and Bland-Altman analyses were used. RESULTS: In phantoms with iron and iodine, results were best for A3 with a mean deviation to phantom fat of 1.3±2.6% (ICC 0.999 [95%-confidence interval 0.996-1]). The standard approach A1 yielded a deviation of -2.5±3.0% (0.998[0.994-0.999]), A2 of 6.1±4.8% (0.991[0.974-0.997]). With A3 and changing tube voltage, the maximal difference between quantified fat and the phantom ground truth occurred at 100kV with 4.6±2.1%. Differences between scans were largest between 100kV and 140kV (2.0%[-7.1-11.2]). The maximal difference of changing DRI occurred between 16 and 24 DRI with 0.4%[-2.2-3.0]. CONCLUSION: For dlCT fat quantification in the presence of iron, material decomposition with combined reference values for iodine and iron delivers the most accurate results. Tube voltage-specific calibration of reference values is advisable while the impact of the DRI on dlCT fat quantification is neglectable.

Influencing factors on the time to CT in suspected pulmonary embolism: an explorative investigation.

Pulmonary embolism is a potentially fatal condition with increased mortality if anticoagulation is delayed. This study aimed to find influencing factors on the duration from requesting a computed tomography (CT) pulmonary angiography (CTPA) to performing a CTPA in suspected acute pulmonary embolism. In 1849 cases, automatically generated time data were extracted from the radiological information system. The impact of the distance to the scanner, case-related features (sector of patient care, triage), and workload (demand for CTs, performed CTs, available staff, hospital occupancy) were investigated retrospectively using multiple regression. The time to CTPA was shorter in cases from the emergency room (ER) than in inpatients and outpatients at distances below 160 m and 240 m, respectively. While requests from the ER were also performed faster than cases from regular wards (< 180 m), no difference was found between the ER and intensive care units. Compared to "not urgent" cases, the workflow was shorter in "urgent" (- 17%) and "life-threatening" (- 67%) situations. The process was prolonged with increasing demand (+ 5%/10 CTs). The presented analysis identified relevant in-hospital influences on the CTPA workflow, including the distance to the CT together with the sector of patient care, the case triage, and the demand for imaging.

Finding a balance in reduced toxicity hematopoietic stem cell transplantation for thalassemia: role of infused CD3+ cell count and immunosuppression.

We performed a retrospective analysis on 124 patients with transfusion-dependent thalassemia who were registered in the German pediatric registry for stem cell transplantation. All patients underwent first allogeneic hematopoietic stem cell transplantation (HSCT) between 2011 and 2020 and belonged mainly to Pesaro risk class 1-2. Four-year overall (OS) and thalassemia-free survival (TFS) were 94.5% ± 2.9% and 88.0% ± 3.4% after treosulfan-fludarabine-thiotepa- and 96.9% ± 3.1% (P = 0.763) and 96.9% ± 3.1% (P = 0.155) after busulfan-fludarabine-based conditioning. Mixed chimerism below 75% occurred predominantly in treosulfan-based regimens (27.5% versus 6.2%). OS and TFS did not differ significantly between matched sibling, other matched family and matched unrelated donor (UD) HSCTs (OS: 100.0%, 100.0%, 96.3% ± 3.6%; TFS: 96.5% ± 2.4%, 90.0% ± 9.5%, 88.9% ± 6.0%). However, mismatched UD-HSCTs performed less favorable (OS: 84.7% ± 7.3% (P = 0.029); TFS: 79.9% ± 7.4% (P = 0.082)). We generated a scoring system reflecting the risk to develop mixed chimerism in our cohort. The main risk-reducing factors were a high CD3+ cell count (≥6 × 107/kg) in the graft, busulfan-conditioning, pre-conditioning therapy and low-targeted ciclosporin A trough levels. Acute GvHD grade III-IV in treosulfan-based concepts predominantly occurred in patients with UD and reduced GvHD prophylaxis but not in the context of high CD3+ cell doses. Taken together, this information might be used to develop more risk-adapted HSCT regimens for thalassemia patients.

Anticoagulation with edoxaban in patients with long atrial high-rate episodes ≥24†h.

BACKGROUND AND AIMS: Patients with long atrial high-rate episodes (AHREs) ≥24 h and stroke risk factors are often treated with anticoagulation for stroke prevention. Anticoagulation has never been compared with no anticoagulation in these patients. METHODS: This secondary pre-specified analysis of the Non-vitamin K antagonist Oral anticoagulants in patients with Atrial High-rate episodes (NOAH-AFNET 6) trial examined interactions between AHRE duration at baseline and anticoagulation with edoxaban compared with placebo in patients with AHRE and stroke risk factors. The primary efficacy outcome was a composite of stroke, systemic embolism, or cardiovascular death. The safety outcome was a composite of major bleeding and death. Key secondary outcomes were components of these outcomes and electrocardiogram (ECG)-diagnosed atrial fibrillation. RESULTS: Median follow-up of 2389 patients with core lab-verified AHRE was 1.8 years. AHRE ≥24 h were present at baseline in 259/2389 patients (11%, 78 ± 7 years old, 28% women, CHA2DS2-VASc 4). Clinical characteristics were not different from patients with shorter AHRE. The primary outcome occurred in 9/132 patients with AHRE ≥24 h (4.3%/patient-year, 2 strokes) treated with anticoagulation and in 14/127 patients treated with placebo (6.9%/patient-year, 2 strokes). Atrial high-rate episode duration did not interact with the efficacy (P-interaction = .65) or safety (P-interaction = .98) of anticoagulation. Analyses including AHRE as a continuous parameter confirmed this. Patients with AHRE ≥24 h developed more ECG-diagnosed atrial fibrillation (17.0%/patient-year) than patients with shorter AHRE (8.2%/patient-year; P < .001). CONCLUSIONS: This hypothesis-generating analysis does not find an interaction between AHRE duration and anticoagulation therapy in patients with device-detected AHRE and stroke risk factors. Further research is needed to identify patients with long AHRE at high stroke risk.

Does breast cancer modify the long-term relationship between lifestyle behaviors and mortality? A prospective analysis of breast cancer survivors and population-based controls.

BACKGROUND: Modifiable lifestyle factors are known to impact survival. It is less clear whether this differs between postmenopausal women ever diagnosed with breast cancer and unaffected women. METHODS: Women diagnosed with breast cancer and unaffected women of comparable age were recruited from 2002 to 2005 and followed up until 2020. Using baseline information, a lifestyle adherence score (range 0-8; categorized as low [0-3.74], moderate [3.75-4.74], and high [≥4.75]) was created based on the 2018 World Cancer Research Fund/American Institute for Cancer Research (WCRF/AICR) cancer prevention recommendations. Cox regression and competing risks analysis were used to analyze the association of adherence to WCRF/AICR lifestyle recommendations with overall mortality and with death due to cardiovascular diseases and cancer, respectively. RESULTS: A total of 8584 women were included (2785 with breast cancer and 5799 without). With a median follow-up of 16.1 years there were 2006 total deaths. Among the deaths of known causes (98.6%), 445 were cardiovascular-related and 1004 were cancer-related. The average lifestyle score was 4.2. There was no differential effect of lifestyle score by case-control status on mortality. After adjusting for covariates, moderate (hazard ratio [HR], 0.66; 95% confidence interval [CI], 0.57-0.76) and high (HR, 0.54; 95% CI, 0.47-0.63) adherence to WCRF/AICR lifestyle recommendations were significantly associated with a decrease in overall mortality. Similarly, in competing risks analysis, moderate and high adherence were associated with decreased mortality from cardiovascular diseases and from cancer. CONCLUSIONS: A healthy lifestyle can substantially reduce mortality risk in women. With low adherence to all WCRF/AICR guidelines in about a third of study participants, health interventions are warranted.

Preoperative TIPS and in-hospital mortality in patients with cirrhosis undergoing surgery.

Background & Aims: Cirrhosis is associated with an increased surgical morbidity and mortality. Portal hypertension and the surgery type have been established as critical determinants of postoperative outcome. We aim to evaluate the hypothesis that preoperative transjugular intrahepatic portosystemic shunt (TIPS) placement in patients with cirrhosis is associated with a lower incidence of in-house mortality/liver transplantation (LT) after surgery. Methods: A retrospective database search for the years 2010-2020 was carried out. We identified 64 patients with cirrhosis who underwent surgery within 3 months after TIPS placement and 131 patients with cirrhosis who underwent surgery without it (controls). Operations were categorised into low-risk and high-risk procedures. The primary endpoint was in-house mortality/LT. We analysed the influence of high-risk surgery, preoperative TIPS placement, age, sex, baseline creatinine, presence of ascites, Chronic Liver Failure Consortium Acute Decompensation (CLIF-C AD), American Society of Anesthesiologists (ASA), and model for end-stage liver disease (MELD) scores on in-house mortality/LT by multivariable Cox proportional hazards regression. Results: In both the TIPS and the control cohort, most patients presented with a Child-Pugh B stage (37/64, 58% vs. 70/131, 53%) at the time of surgery, but the median MELD score was higher in the TIPS cohort (14 vs. 11 points). Low-risk and high-risk procedures amounted to 47% and 53% in both cohorts. The incidence of in-house mortality/LT was lower in the TIPS cohort (12/64, 19% vs. 52/131, 40%), also when further subdivided into low-risk (0/30, 0% vs. 10/61, 16%) and high-risk surgery (12/34, 35% vs. 42/70, 60%). Preoperative TIPS placement was associated with a lower rate for postoperative in-house mortality/LT (hazard ratio 0.44, 95% CI 0.19-1.00) on multivariable analysis. Conclusions: A preoperative TIPS might be associated with reduced postoperative in-house mortality in selected patients with cirrhosis. Impact and implications: Patients with cirrhosis are at risk for more complications and a higher mortality after surgical procedures. A transjugular intrahepatic portosystemic shunt (TIPS) is used to treat complications of cirrhosis, but it is unclear if it also helps to lower the risk of surgery. This study takes a look at complications and mortality of patients undergoing surgery with or without a TIPS, and we found that patients with a TIPS develop less complications and have an improved survival. Therefore, a preoperative TIPS should be considered in selected patients, especially if indicated by ascites.

Anticoagulation with Edoxaban in Patients with Atrial High-Rate Episodes.

BACKGROUND: Device-detected atrial high-rate episodes (AHREs) are atrial arrhythmias detected by implanted cardiac devices. AHREs resemble atrial fibrillation but are rare and brief. Whether the occurrence of AHREs in patients without atrial fibrillation (as documented on a conventional electrocardiogram [ECG]) justifies the initiation of anticoagulants is not known. METHODS: We conducted an event-driven, double-blind, double-dummy, randomized trial involving patients 65 years of age or older who had AHREs lasting for at least 6 minutes and who had at least one additional risk factor for stroke. Patients were randomly assigned in a 1:1 ratio to receive edoxaban or placebo. The primary efficacy outcome was a composite of cardiovascular death, stroke, or systemic embolism, evaluated in a time-to-event analysis. The safety outcome was a composite of death from any cause or major bleeding. RESULTS: The analysis population consisted of 2536 patients (1270 in the edoxaban group and 1266 in the placebo group). The mean age was 78 years, 37.4% were women, and the median duration of AHREs was 2.8 hours. The trial was terminated early, at a median follow-up of 21 months, on the basis of safety concerns and the results of an independent, informal assessment of futility for the efficacy of edoxaban; at termination, the planned enrollment had been completed. A primary efficacy outcome event occurred in 83 patients (3.2% per patient-year) in the edoxaban group and in 101 patients (4.0% per patient-year) in the placebo group (hazard ratio, 0.81; 95% confidence interval [CI], 0.60 to 1.08; P = 0.15). The incidence of stroke was approximately 1% per patient-year in both groups. A safety outcome event occurred in 149 patients (5.9% per patient-year) in the edoxaban group and in 114 patients (4.5% per patient-year) in the placebo group (hazard ratio, 1.31; 95% CI, 1.02 to 1.67; P = 0.03). ECG-diagnosed atrial fibrillation developed in 462 of 2536 patients (18.2% total, 8.7% per patient-year). CONCLUSIONS: Among patients with AHREs detected by implantable devices, anticoagulation with edoxaban did not significantly reduce the incidence of a composite of cardiovascular death, stroke, or systemic embolism as compared with placebo, but it led to a higher incidence of a composite of death or major bleeding. The incidence of stroke was low in both groups. (Funded by the German Center for Cardiovascular Research and others; NOAH-AFNET 6 ClinicalTrials.gov number, NCT02618577; ISRCTN number, ISRCTN17309850.).

Disentangling pharmacological and expectation effects in antidepressant discontinuation among patients with fully remitted major depressive disorder: study protocol of a randomized, open-hidden discontinuation trial.

BACKGROUND: Antidepressants are established as an evidence-based, guideline-recommended treatment for Major Depressive Disorder. Prescriptions have markedly increased in past decades, with a specific surge in maintenance prescribing. Patients often remain on antidepressants longer than clinically necessary. When attempting to stop, many patients experience adverse discontinuation symptoms. Discontinuation symptoms can be debilitating and hinder successful discontinuation. While discontinuation symptoms can result from pharmacological effects, evidence on nocebo-induced side effects of antidepressant use suggests that patients' expectations may also influence occurrence. METHODS: To disentangle pharmacological and expectation effects in antidepressant discontinuation, patients with fully remitted Major Depressive Disorder who fulfill German guideline recommendations to discontinue will either remain on or discontinue their antidepressant. Participants' expectations will be manipulated by varying verbal instructions using an open-hidden paradigm. Within the open trial arms, participants will receive full information about treatment, i.e., high expectation. Within the hidden trial arms, participants will be informed about a 50% chance of discontinuing versus remaining on their antidepressant, i.e., moderate expectation. A total of N = 196 participants will be randomly assigned to either of the four experimental groups: open discontinuation (OD; n = 49), hidden discontinuation (HD; n = 49), open continuation (OC; n = 49), or hidden continuation (HC; n = 49). Discontinuation symptom load during the 13-week experimental phase will be our primary outcome measure. Secondary outcome measures include discontinuation symptom load during the subsequent 39-week clinical observation phase, recurrence during the 13-week experimental period, recurrence over the course of the complete 52-week trial evaluated in a time-to-event analysis, and stress, anxiety, and participants' attentional and emotional processing at 13 weeks post-baseline. Blood and saliva samples will be taken as objective markers of antidepressant blood serum level and stress. Optional rsfMRI measurements will be scheduled. DISCUSSION: Until today, no study has explored the interplay of pharmacological effects and patients' expectations during antidepressant discontinuation. Disentangling their effects has important implications for understanding mechanisms underlying adverse discontinuation symptoms. Results can inform strategies to manage discontinuation symptoms and optimize expectations in order to help patients and physicians discontinue antidepressants more safely and effectively. TRIAL REGISTRATION: ClinicalTrials.gov (NCT05191277), January 13, 2022.

CNS Manifestations in Mucolipidosis Type II-A Retrospective Analysis of Longitudinal Data on Neurocognitive Development and Neuroimaging in Eleven Patients.

Mucolipidosis type II (MLII), an ultra-rare lysosomal storage disorder, manifests as a fatal multi-systemic disease. Mental inhibition and progressive neurodegeneration are commonly reported disease manifestations. Nevertheless, longitudinal data on neurocognitive testing and neuroimaging lack in current literature. This study aimed to provide details on central nervous system manifestations in MLII. All MLII patients with at least one standardized developmental assessment performed between 2005 and 2022 were included by retrospective chart review. A multiple mixed linear regression model was applied. Eleven patients with a median age of 34.0 months (range 1.6-159.6) underwent 32 neurocognitive and 28 adaptive behaviour assessments as well as 14 brain magnetic resonance imagings. The scales used were mainly BSID-III (42%) and VABS-II (47%). Neurocognitive testing (per patient: mean 2.9, standard deviation (SD) 2.0) performed over 0-52.1 months (median 12.1) revealed profound impairment with a mean developmental quotient of 36.7% (SD 20.4) at last assessment. The patients showed sustained development; on average, they gained 0.28 age-equivalent score points per month (confidence interval 0.17-0.38). Apart from common (63%) cervical spinal stenosis, neuroimaging revealed unspecific, non-progressive abnormalities (i.e., mild brain atrophy, white matter lesions). In summary, MLII is associated with profound developmental impairment, but not with neurodegeneration and neurocognitive decline.

Nasendoscopy to Predict Difficult Videolaryngoscopy: A Multivariable Model Development Study.

BACKGROUND: Transnasal videoendoscopy (TVE) is the standard of care when staging pharyngolaryngeal lesions. This prospective study determined if preoperative TVE improves the prediction of difficult videolaryngoscopic intubation in adults with expected difficult airway management in addition to the Simplified Airway Risk Index (SARI). METHODS: 374 anesthetics were included (252 with preoperative TVE). The primary outcome was a difficult airway alert issued by the anesthetist after Macintosh videolaryngoscopy. SARI, clinical factors (dysphagia, dysphonia, cough, stridor, sex, age and height) and TVE findings were used to fit three multivariable mixed logistic regression models; least absolute shrinkage and selection operator (LASSO) regression was used to select co-variables. RESULTS: SARI predicted the primary outcome (odds ratio [OR] 1.33; 95% confidence interval [CI] 1.13-1.58). The Akaike information criterion for SARI (327.1) improved when TVE parameters were added (311.0). The Likelihood ratio test for SARI plus TVE parameters was better than for SARI plus clinical factors (p < 0.001). Vestibular fold lesions (OR 1.82; 95% CI 0.40-8.29), epiglottic lesions (OR 3.37; 0.73-15.54), pharyngeal secretion retention (OR 3.01; 1.05-8.63), restricted view on rima glottidis <50% (OR 2.13; 0.51-8.89) and ≥50% (OR 2.52; 0.44-14.56) were concerning. CONCLUSION: TVE improved prediction of difficult videolaryngoscopy in addition to traditional bedside airway examinations.

Systematic comparison of approaches to analyze clustered competing risks data.

BACKGROUND: In many clinical trials the study interest lies in the comparison of a treatment to a control group regarding a time to event endpoint like time to myocardial infarction, time to relapse, or time to a specific cause of death. Thereby, an event can occur before the primary event of interest that alters the risk for or prohibits observing the latter, i.e. a competing event. Furthermore, multi-center studies are often conducted. Hence, a cluster structure might be observed. However, commonly only the aspect of competing events or the aspect of the cluster structure is modelled within primary analysis, although both are given within the study design. Methods to adequately analyze data in such a design were recently described but were not systematically compared yet. METHODS: Within this work we provide a systematic comparison of four approaches for the analysis of competing events where a cluster structure is present based on a real life data set and a simulation study. The considered methods are the commonly applied cause-specific Cox proportional hazards model with a frailty, the Fine and Gray model for considering competing risks, and extensions of the latter model by Katsahian et al. and Zhou et al. RESULTS: Based on our simulation results, the model by Katsahian et al. showed the best performance in bias, square root of mean squared error, and power in nearly all scenarios. In contrast to the other three models this approach allows both unbiased effect estimation and prognosis. CONCLUSION: The provided comparison and simulations help to guide applied researchers to choose an adequate method for the analysis of competing events where a cluster structure is present. Based on our simulation results the approach by Katsahian et al. can be recommended.

Higher Risk of HEV Transmission and Exposure among Blood Donors in Europe and Asia in Comparison to North America: A Meta-Analysis.

BACKGROUND AND AIMS: The increasing number of diagnosed hepatitis E virus (HEV) infections in Europe has led to the implementation of the testing of blood products in various countries. Many nations have not yet implemented such screening. To assess the need for HEV screening in blood products worldwide, we conducted a systematic review and meta-analysis assessing HEV RNA positivity and anti-HEV seroprevalence in blood donors. METHODS: Studies reporting anti-HEV IgG/IgM or HEV RNA positivity rates among blood donors worldwide were identified via predefined search terms in PubMed and Scopus. Estimates were calculated by pooling study data with multivariable linear mixed-effects metaregression analysis. RESULTS: A total of 157 (14%) of 1144 studies were included in the final analysis. The estimated HEV PCR positivity rate ranged from 0.01 to 0.14% worldwide, with strikingly higher rates in Asia (0.14%) and Europe (0.10%) in comparison to North America (0.01%). In line with this, anti-HEV IgG seroprevalence in North America (13%) was lower than that in Europe (19%). CONCLUSIONS: Our data demonstrate large regional differences regarding the risk of HEV exposure and blood-borne HEV transmission. Considering the cost-benefit ratio, this supports blood product screening in high endemic areas, such as Europe and Asia, in contrast to low endemic regions, such as the U.S.

Gender differences and cooperation in medical authorships - an analysis of the recent ten years in five key medical disciplines.

BACKGROUND: Career prospects in academic medicine are strongly linked to scientific authorship and this marker has been widely used as an indicator of gender equity in academia. However, direct comparisons of medical disciplines regarding their proportion of female physicians (FP) in different countries are missing. This study examines the gender parity and gender cooperation using first authorships (FA) and senior authorships (SA) of scientific publications in five medical disciplines and six different OECD countries over a 10-year time-trend. METHODS: Articles from three high-impact journals in each of the medical discipline radiology, urology, surgery, gynecology, and pediatrics from the years 2007/8 and 2017/18 were retrospectively reviewed. The gender and affiliation location of the FA and SA of original research articles and reviews were assigned and compared with the proportion of in each discipline for the United States of America, Canada, United Kingdom, France, Germany, and Japan. Mantel-Haenszel test and multinomial logistic regression models were used to calculate differences in proportions of women authors and FP and to assess trends and proportions of FA and SA. RESULTS: 30,803 articles were evaluated. Equally, with rising proportions of FP in all disciplines, the number of women authors increased across years. The shares of women FAs were either significantly higher (urology/surgery/gynecology) or balanced (pediatrics/radiology) compared to the proportion of FP. In contrast, the shares of women SA were balanced only in disciplines with a low proportion of FP (urology and surgery) and otherwise reduced. Women same-gender cooperation was as common as men same-gender cooperation and preferred over a women-led mixed gender cooperation in disciplines where this seemed to be practicable due to the high proportions of FP. CONCLUSION: In contrast to FA, a significant disparity persists in SA, particularly in disciplines with a high proportion of FP. The discrepancy between FA and SA may reflect, among others, dropout from an academic career in early or mid-academic levels, for example, due to structural inequality; together with the findings on gender preference in authorship collaborations, this may inform future strategies for promoting equal career advancement for women physicians.

The Freestyle Valve in Severe Necrotizing Aortic Root Endocarditis: Comorbidity Upon Outcome.

BACKGROUND: Treatment of severe necrotizing aortic root endocarditis (SNARE) carries a substantial perioperative risk. As an alternative to homografts, we assessed short-term outcome and future prognosis in patients undergoing root replacement using the Freestyle valve. METHODS: Between 2000 and 2018, a total of 45 patients (mean age 70.9 ± 8.3 years, 66% men) underwent aortic root replacement for SNARE using the Freestyle valve. Mean Society of Thoracic Surgeons mortality score and EuroScore II were 22.6% ± 17.1 and 29.3% ± 20.9, respectively. Prosthetic endocarditis was present in 70.1%, and aortic annulus patch repair was performed in 64% of the patients. Median follow-up was 3.6 years (range: 0.1-14.5) and was 100% complete. RESULTS: The 30-day mortality was 15.5%. During follow-up, there were no reoperations, while reinfection was suspected in one patient. Survival was significantly inferior to the general population with a standardized mortality ratio of 10.7 (95% confidence interval [CI]: 9.1-12.6) (p < 0.0001). In 30-day survivors and after correction for significant comorbidities in a Cox proportional hazards model, estimated survival probabilities at 1, 5, and 10 years were 98.7 (95% CI: 92.5-99.8%), 94.1 (77.9-98.5%), and 63.8 (28.4-85.2%). Estimated mean difference in survival probability was better for the general population after postoperative year 6, but within the 95% CI for no difference. CONCLUSION: Use of the Freestyle valve is reliable solution for the most complex cases with a low rate of reinfection. Early mortality is substantial and caused by the patient's condition and severity of the infection. Excess late mortality can be attributed to patient-specific comorbidities.

Study protocol of a randomized controlled trial evaluating home treatment with peer support for acute mental health crises (HoPe).

BACKGROUND: Home treatment (HT) is a treatment modality for patients with severe mental illness (SMI) in acute mental crises. It is frequently considered equivalent to psychiatric inpatient treatment in terms of treatment outcome. Peer Support (PS) means that people with lived experience of a mental illness are trained to support others on their way towards recovery. While PS is growing in international importance and despite a growing number of studies supporting its benefits, it is still not comprehensively implemented into routine care. The HoPe (Home Treatment with Peer Support) study investigates a combination of both - HT and PS - to provide further evidence for a recovery-oriented treatment of psychiatric patients. METHODS: In our randomized controlled trial (RCT), HT with PS is compared with HT without PS within a network of eight psychiatric clinical centers from the North, South and East of Germany. We investigate the effects of a combination of both approaches with respect to the prevention of relapse/recurrence defined as first hospitalization after randomization (primary outcome), disease severity, general functioning, self-efficacy, psychosocial health, stigma resistance, recovery support, and service satisfaction (secondary outcomes). A sample of 286 patients will be assessed at baseline after admission to HT care (data point t0) and randomized into the intervention (HT + PS) and control arm (HT). Follow-Up assessments will be conducted 2, 6 and 12 months after admission (resulting in three further data points, t1 to t3) and will be analyzed via intention-to-treat approach. DISCUSSION: This study may determine the positive effects of PS added to HT, prove additional evidence for the efficacy of PS and thereby facilitate its further implementation into psychiatric settings. The aim is to improve quality of mental health care and patients' recovery as well as to reduce the risk of relapses and hospitalizations for patients with SMI. TRIAL REGISTRATION: The trial is registered with ClinicalTrials.gov: NCT04336527 , April 7, 2020.

The pandemic coping scale - validity and reliability of a brief measure of coping during a pandemic.

This study assessed the validity and reliability of the Pandemic Coping Scale (PCS), a new brief measure of coping with pandemic-related stressors. Methods: The PCS was administered to N = 2316 German participants during the COVID-19 pandemic. Exploratory and confirmatory factor analysis was applied among random splits of the sample. Global goodness of fit (χ 2, RMSEA, SRMR, CFI, TLI), local goodness of fit (factor loadings, communalities, factor reliability, discriminant validity) and additional test quality criteria (internal consistency, item discrimination and difficulty) were evaluated for a four-factor model vs. a four-factor model combined with a second-order general factor. Convergent and divergent validity were examined by Pearson correlations of the PCS subscales with the Brief-COPE subscales; criterion validity was evaluated by correlations with wellbeing (WHO-5), depressive (PHQ-9) and anxiety symptoms (GAD-2). Results: Exploratory factor analysis suggested a four-factor solution ('Healthy Lifestyle', 'Joyful Activities', 'Daily Structure', 'Prevention Adherence'). Confirmatory factor analysis showed a sufficient global fit for both specified models which did not differ in their fit to the data. Local goodness of fit indices showed moderate to large factor loadings and good factor reliabilities except for the subscale 'Prevention Adherence'. Internal consistencies were good for the PCS total scale (α = .83), the 'Healthy Lifestyle' (α = .79) and the 'Daily Structure' (α = .86) subscales, acceptable for 'Joyful Activities' (α = .60), and low for 'Prevention Adherence' (α = .52). The four subscales evidenced convergent and divergent validity with the Brief-COPE subscales. The subscales 'Healthy lifestyle', 'Joyful activities' and 'Daily structure' showed criterion validity with wellbeing, depressive and anxiety symptoms. Conclusions: The PCS is a reliable and valid measure to assess pandemic-specific coping behavior in the domains of 'Healthy Lifestyle', 'Joyful Activities', and 'Daily Structure'. The PCS subscale 'Prevention Adherence' might be improved by adding items with varying item difficulties.

Comparison of four diagnostic criteria for invasive pulmonary aspergillosis-A diagnostic accuracy study in critically ill patients.

BACKGROUND: In the absence of lung biopsy, there are various algorithms for the diagnosis of invasive pulmonary aspergillosis (IPA) in critically ill patients that rely on clinical signs, underlying conditions, radiological features and mycology. The aim of the present study was to compare four diagnostic algorithms in their ability to differentiate between probable IPA (i.e., requiring treatment) and colonisation. METHODS: For this diagnostic accuracy study, we included a mixed ICU population with a positive Aspergillus culture from respiratory secretions and applied four different diagnostic algorithms to them. We compared agreement among the four algorithms. In a subgroup of patients with lung tissue histopathology available, we determined the sensitivity and specificity of the single algorithms. RESULTS: A total number of 684 critically ill patients (69% medical/31% surgical) were included between 2005 and 2020. Overall, 79% (n = 543) of patients fulfilled the criteria for probable IPA according to at least one diagnostic algorithm. Only 4% of patients (n = 29) fulfilled the criteria for probable IPA according to all four algorithms. Agreement among the four diagnostic criteria was low (Cohen's kappa 0.07-0.29). From 85 patients with histopathological examination of lung tissue, 40% (n = 34) had confirmed IPA. The new EORTC/MSGERC ICU working group criteria had high specificity (0.59 [0.41-0.75]) and sensitivity (0.73 [0.59-0.85]). CONCLUSIONS: In a cohort of mixed ICU patients, the agreement among four algorithms for the diagnosis of IPA was low. Although improved by the latest diagnostic criteria, the discrimination of invasive fungal infection from Aspergillus colonisation in critically ill patients remains challenging and requires further optimization.

Metabolic Syndrome Is Associated with Impaired Survival after Surgery for Pancreatic Neuroendocrine Tumors.

INTRODUCTION: Pancreatic neuroendocrine tumors (pNETs) are a heterogeneous group of neoplasms. Surgery is the only curative treatment option. However, our understanding of predictors of survival after surgery remains incomplete. The aim of the study was to evaluate metabolic syndrome (MetS) as a prognostic factor in pNET. METHODS: In a retrospective single-center cohort study, we examined the influence of MetS in 120 patients with curative intended resection of pNETs on overall survival (OS), recurrence-free survival, and outcome after recurrence. RESULTS: MetS was present in 32 patients (26.6%). Patients with MetS had an impaired OS after curative intended surgery compared to patients without MetS (median OS 72 months [95% CI 13.3-130.7] vs. not reached, p < 0.001). The shortest survival was observed in patients with MetS in the presence of oligometastatic disease at time of surgery. In a multivariable Cox regression analysis, MetS was identified as an independent risk factor for mortality (hazard ratio [HR] = 4.54, 95% CI [1.88-11.00], p = 0.01). In our dataset, MetS was not associated with tumor recurrence or recurrence-free survival. Nevertheless, in patients with recurrence, MetS was associated with shorter time to recurrence (median 3.4 months, 95% CI [2.48-4.24], vs. 20.1 months, 95% CI [10.8-29.49], p < 0.001), and poor outcome (HR = 5.03, 95% CI [1.25-20.20], p = 0.01). CONCLUSIONS: We identified MetS as a negative prognostic factor after curative intended surgery for pNET. In particular, patients with oligometastatic disease might not benefit from extensive surgery in the presence of MetS. Furthermore, MetS had a strong impact on survival after recurrence.