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Background: Programmed cell death‐ligand 1 (PD‐L1) expression is a well‐established biomarker for predicting responses to immune checkpoint inhibitors and certain targeted therapies. As a result, treatment strategies for patients vary based on their PD‐L1 expression status. Understanding the clinical features of patients with distinct PD‐L1 levels is crucial for personalized treatment approaches. Methods: Demographic and clinicopathological characteristics of 227 patients (54% male, mean age 67 ± 9.9 years) newly diagnosed with non‐small‐cell lung cancer (NSCLC) between April 2020 and December 2022 were retrospectively compared among three groups based on the PD‐L1 expression: PD‐L1 Tumor Proportion Score (TPS) negative, 1–50%, and ≥50%. Logistic regression analysis was performed to evaluate predictors for high PD‐L1 expression ≥50%. Results: PD‐L1 expression levels were distributed as follows: negative in 29% of patients, between 1% and 50% in 41%, and greater than 50% (high) in 29%. In comparison to negative PD‐L1 expression, low and high PD‐L1 expression was associated with female sex (32.9% vs. 52.7% vs. 50.7%, p = 0.031), with the absence of epidermal growth factor receptor (EGFR) mutations (83.6% vs. 91.1% vs. 98.1% p = 0.029), and with the absence of ERBB2 (HER2) tyrosine kinase mutations (90.9% vs. 100% vs. 98.1% p = 0.007), respectively. Age, smoking status, histological subtype, and disease stage showed no significant differences among the three patient groups. In the univariate logistic regression, EGFR mutation appeared to be the only predictor for PD‐L1 expression, although it did not reach statistical significance (p = 0.06). Conclusion: Although sex and genomic alterations are associated with PD‐L1 expression in patients with NSCLC, no clinical characteristics seem to predict PD‐L1 expression significantly. [ABSTRACT FROM AUTHOR]

Objective: To evaluate whether locally applied vaginal estrogen affects prolapse‐associated complaints compared with placebo treatment in postmenopausal women prior to surgical prolapse repair. Design: Randomised, double‐masked, placebo‐controlled, multicentre study. Setting: Urogynaecology unit at the Medical University of Vienna and University Hospital of Tulln. Population: Postmenopausal women with symptomatic pelvic organ prolapse and planned surgical prolapse repair. Methods: Women were randomly assigned local estrogen cream or placebo cream 6 weeks preoperatively. Main outcome measures: The primary outcome was differences in subjective prolapse‐associated complaints after 6 weeks of treatment prior to surgery, assessed with the comprehensive German pelvic floor questionnaire. Secondary outcomes included differences in other pelvic floor‐associated complaints (bladder, bowel or sexual function). Results: Out of 120 women randomised, 103 (86%) remained for the final analysis. After 6 weeks of treatment the prolapse domain score did not differ between the estrogen and the placebo groups (4.4 ± 0.19 versus 4.6 ± 0.19; mean difference, −0.21; 95% CI −0.74 to 0.33; P = 0.445). Multivariate analysis, including only women receiving the intervention, showed that none of the confounding factors modified the response to estradiol. Conclusions: These results demonstrate that preoperative locally applied estrogen does not ameliorate prolapse‐associated symptoms in postmenopausal women with symptomatic pelvic organ prolapse. Preoperative local estrogen does not ameliorate prolapse‐associated symptoms in postmenopausal women with pelvic organ prolapse. Preoperative local estrogen does not ameliorate prolapse‐associated symptoms in postmenopausal women with pelvic organ prolapse. [ABSTRACT FROM AUTHOR]

Background: Coronavirus disease 2019 (COVID‐19) interferes with the vascular endothelium. It is not known whether COVID‐19 additionally affects arterial stiffness. Methods: This case–control study compared brachial‐ankle pulse wave (baPWV) and carotid‐femoral pulse wave velocities (cfPWV) of acutely ill patients with and without COVID‐19. Results: Twenty‐two COVID‐19 patients (50% females, 77 [67–84] years) were compared with 22 age‐ and sex‐matched controls. In COVID‐19 patients, baPWV (19.9 [18.4–21.0] vs. 16.0 [14.2–20.4], P = 0.02) and cfPWV (14.3 [13.4–16.0] vs. 11.0 [9.5–14.6], P = 0.01) were higher than in the controls. In multiple regression analysis, COVID‐19 was independently associated with higher cfPWV (β = 3.164, P = 0.004) and baPWV (β = 3.532, P = 0.003). PWV values were higher in nonsurvivors. In survivors, PWV correlated with length of hospital stay. Conclusion: COVID‐19 appears to be related to an enhanced PWV reflecting an increase in arterial stiffness. Higher PWV might be related to an increased length of hospital stay and mortality. [ABSTRACT FROM AUTHOR]

ABSTRACTObjective:Recent studies have tried to find a reliable way of predicting the development of Alzheimer´s Disease (AD) among patients with mild cognitive impairment (MCI), often focusing on olfactory dysfunction or semantic memory. Our study aimed to validate these findings while also comparing the predictive accuracy of olfactory and semantic assessments for this purpose.Method: Six hundred fifty patients (median age 68, 58% females) including controls, SCD (subjective cognitive decline), non-amnestic MCI (naMCI), amnestic MCI (aMCI), and AD patients were tested for olfactory dysfunction by means of odor identification testing and semantic memory. Of those 650 patients, 120 participants with SCD, naMCI, or aMCI at baseline underwent a follow-up examination after two years on average. Of these 120 patients, 12% had developed AD at follow-up (converters), while 88% did not develop AD at follow-up (non-converters).Results: Analysis showed a significant difference only for initial olfactory identification between converters and non-converters. Sensitivity of impairment of olfactory identification for AD prediction was low at 46.2%, although specificity was high at 81.9%. Semantic memory impairment at baseline was not significantly related to AD conversion, although, when naming objects, significant differences were found between AD patients and all other groups and between naMCI and aMCI patients compared to controls and SCD patients.Conclusions: Objective olfactory assessments are promising instruments for predicting the conversion to AD among MCI patients. However, due to their low sensitivity and high specificity, a combination with other neuropsychological tests might lead to an improved predictive accuracy. Further longitudinal studies with more participants are required to investigate the usefulness of semantic memory tests in this case. [ABSTRACT FROM AUTHOR]

Objectives: Nailfold capillaroscopy (NC) and laboratory tests for antinuclear antibodies (ANA) are routinely used in parallel for detection of emerging connective tissue disease (CTD) in patients with Raynaud's phenomenon (RP). The aim of this study was to assess the associations between distinct nailfold capillary abnormalities and concomitant autoantibodies in patients with incipient RP without previously known CTD. Method: Patients with incipient RP without previously known CTD were included in this retrospective analysis. We analysed the association of particular capillary abnormalities (reduced density, avascular fields, dilations, giant capillaries, haemorrhages, tortuosity, ramifications, oedema) with ANA and ANA subsets (anti-Scl-70, anti-CENP-B, anti-U1-RNP, anti-dsDNA, anti-SSA(Ro), anti-SSB(La), anti-Sm, and anti-Jo-1 antibodies). We also developed a score that allows the estimation of each patient's individual probability for the presence of an ANA titre ≥ 1:160. Results: The final analysis comprised 2971 patients. Avascular fields, giant capillaries, reduced capillary density, and capillary oedema were closely related to an ANA titre ≥ 1:160. Both giant capillaries and avascular fields were associated with anti-Scl-70 and anti-CENP-B antibodies. Only a weak association was found between giant capillaries and anti-U1-RNP antibodies. Each patient's individual probability for the presence of an ANA titre ≥ 1:160 can be represented by a sum score comprising giant capillaries, reduced density, avascular fields, ramifications, and oedema as well as patients' sex and age. Conclusion: In patients with incipient RP, anti-Scl-70 and anti-CENP-B antibodies are related most specifically to distinct capillary alterations. Although a sum score can represent the patient's probability for elevated ANA titres, NC cannot substitute for immunological tests in patients with incipient RP. [ABSTRACT FROM AUTHOR]

Background: Clinical subtypes of mild cognitive impairment (MCI) were assigned as potential prodromes to various types of dementia. Amnestic MCI (aMCI) is said to have a high likelihood of progressing to Alzheimer's dementia (AD) and non-amnestic MCI (naMCI) subtypes are assumed to have a higher likelihood of progressing to non-AD dementia. The aim of this study was to investigate the prognostic accuracy of aMCI and naMCI for the development of AD, vascular dementia (VaD), and mixed dementia.Methods: In this longitudinal study, 487 subjects without dementia (cognitively healthy: n = 387; MCI cases: n = 115) aged 75 years at baseline, who participated in a population-based cohort study (Vienna Transdanube Aging study), were available for analysis. The observation period was 90 months. The diagnoses of the clinical MCI subtypes were made according to common criteria. The outcome (AD, VaD, mixed dementia) was described for both MCI subtypes. Diagnostic values of aMCI and naMCI according to incident AD, VaD, and mixed dementia were determined.Results: AD was the most common type of dementia following both MCI subtypes. Participants with aMCI were more likely to progress to AD than participants with naMCI. The proportion of incident VaD and mixed dementia did not differ concerning the MCI subtypes. The positive predictive value for both MCI subtypes was low (range: 1%–46%), whereas the negative predictive value was high (range: 86%–99%).Conclusions: The increased risk of clinical MCI subtypes for a particular type of dementia could only be confirmed for aMCI and incident AD. [ABSTRACT FROM PUBLISHER]

Background: To date, no single instrument has proved to be adequate for screening for Alzheimer's dementia (AD). The aim of this study was to identify a combination of instruments which were highly sensitive for screening late onset AD. Methods: Subjects were drawn from the Vienna TransDanube Aging (VITA) study. This is an interdisciplinary, longitudinal community-based cohort study of the 21st and 22nd district of Vienna (Austria). Data refer to the cohort of 478 individuals at age 78 who took part in the first follow-up investigation of the VITA study. The psychometric instruments which were investigated were: the Ten-Point Clock Test, the Human-Figure Drawing Test, a Delayed Selective Reminding Test, Naming, the Trail Making Test-B, and Verbal Fluency. Further instruments were the Pocket Smell Test, and Subjective Memory Complaints. Data were analyzed using logistic regression analyses and cross validation. Results: A combination of the Delayed Selective Reminding Test and Verbal Fluency was best for screening AD (R2 = 0.38, main model). An area under the ROC curve of 0.829 was reached. This model discriminated between subjects with incident AD and subjects who did not have incident AD with a sensitivity of 91% and a specificity of 56%. Conclusion: The combination of an episodic memory test and a test of verbal fluency was an effective way of screening for AD. [ABSTRACT FROM AUTHOR]

Background Mild cognitive impairment (MCI) is defined to diagnose prodromal dementia and prodromal Alzheimer dementia, in particular. Objective The main aim of this study is to identify subtypes of MCI in comparison to the frequency of Petersen's MCI-amnestic in an elderly age-cohort. Participants The study is based on the cross sectional data from the Vienna-Transdanube-Aging (VITA) study. The data refer to the age cohort of 592 individuals at age 75 to 76 years who completed extensive neuropsychological examination. Results Dementia was present in 15 subjects (2.5%, CI: 1.4–4.1). 141 subjects (23.8%, CI: 20.4–27.5) of the entire age cohort 75 (n = 592) showed cognitive impairment without dementia concerning one or more cognitive functions (1.5 SD paradigm). These subjects were assigned to three subtypes of MCI: Selective Memory Impairment: n = 22 (3.7%, CI: 2.3–5.6), Memory Impairment+Non-Memory Impairment: n = 31 (5.2%, CI: 3.6–7.4) and Non-Memory Impairment: n = 88 (14.9%, CI: 12.1–18.0). Conclusions The frequency of MCI-amnestic, the so-called prestage of AD according to Petersen, was very low (0.5%, CI: 0.1–1.5) compared to the estimated incidence rates of AD at this age. Established criteria of MCI could be modified in order to include a higher percentage of high-risk subjects for later developing Alzheimer dementia. Copyright © 2005 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Abstract: Background: Neurotrophic factors are known to play an important role in the survival and differentiation of many types of neurons during development. Both brain-derived neurotrophic factor (BDNF) and ciliary neurotrophic factor (CNTF) may act cooperatively in modulating the development and functioning of synapses. Both these neurotrophic factors were intensely investigated with regard to depression without conclusive results. Methods: We have investigated the possible use of both CNTF null-mutation and BDNF polymorphism C270T as biomarkers for depression in the Vienna Transdanube Aging (VITA) study. The VITA is a prospective community-based cohort study of all 75 years old inhabitants of a geographical region of Vienna. Results: We found no association between CNTF null-mutation and BDNF C270T polymorphism to any depressive symptoms after exclusion of demented subjects. Conclusion: These results call in question the hypothesis that either BDNF or CNTF can be used as molecular markers for depression or late onset depression in the elderly. [Copyright &y& Elsevier]

Measuring disease progression in clinical trials for testing novel treatments for multifaceted diseases as progressive supranuclear palsy (PSP), remains challenging. In this study we assess a range of statistical approaches to compare outcomes as measured by the items of the progressive supranuclear palsy rating scale (PSPRS). We consider several statistical approaches, including sum scores, a modified PSPRS rating scale that had been recommended by FDA in a pre-IND meeting, multivariate tests, and analysis approaches based on multiple comparisons of the individual items. In addition, we propose two novel approaches which measure disease status based on Item Response Theory models. We assess the performance of these tests under various scenarios in an extensive simulation study and illustrate their use with a re-analysis of the ABBV-8E12 clinical trial. Furthermore, we discuss the impact of the FDA-recommended scoring of item scores on the power of the statistical tests. We find that classical approaches as the PSPRS sum score demonstrate moderate to high power when treatment effects are consistent across the individual items. The tests based on Item Response Theory (IRT) models yield the highest power when the simulated data are generated from an IRT model. The multiple testing based approaches have a higher power in settings where the treatment effect is limited to certain domains or items. The study demonstrates that there is no one-size-fits-all testing procedure for evaluating treatment effects using PSPRS items; the optimal method varies based on the specific effect size patterns. The efficiency of the PSPRS sum score, while generally robust and straightforward to apply, varies depending on the specific patterns of effect sizes encountered and more powerful alternatives are available in specific settings. These findings can have important implications for the design of future clinical trials in PSP and similar multifaceted diseases., (© 2024. The Author(s).)

The closure principle is a powerful approach to constructing efficient testing procedures controlling the familywise error rate in the strong sense. For small numbers of hypotheses and the setting of independent elementary p -values we consider closed tests where each intersection hypothesis is tested with a p -value combination test. Examples of such combination tests are the Fisher combination test, the Stouffer test, the Omnibus test, the truncated test, or the Wilson test. Some of these tests, such as the Fisher combination, the Stouffer, or the Omnibus test, are not consonant and rejection of the global null hypothesis does not always lead to rejection of at least one elementary null hypothesis. We develop a general principle to uniformly improve closed tests based on p -value combination tests by modifying the rejection regions such that the new procedure becomes consonant. For the Fisher combination test and the Stouffer test, we show by simulations that this improvement can lead to a substantial increase in power., Competing Interests: Declaration of conflicting interestsThe authors declared no potential conflicts of interest with respect to the research, authorship and/or publication of this article.

RN Braun observed that frequencies of health disorders in general practice are so consistent that he called his discovery "Case Distribution Law". Our study compares morbidity data from methodologically similar surveys in primary care practices over a period of fifty years. Frequency ranks were determined for each observation period and the first 150 ranks were compared with Spearman's correlation coefficients. All correlations were consistently positive. Frequency ranks were strikingly similar for surveys carried out at approximately the same time, especially when nomenclatural matching had been carried out before data collection. Ranks were also very similar where clear disease classifications were possible, but less so for non-specific symptoms.The consistency of the distribution of health disorders helps develop diagnostic strategies (diagnostic protocols) and appropriate labeling for non-specific, diagnostically open symptom classifications. According to Braun's considerations, the regularity of case distribution plays an important role in the professionalization of primary care., (© 2024. The Author(s).)

Background: Asthma is increasingly recognized as heterogeneous, characterized by different endotypes, with obesity not only a distinct phenotype but a risk factor for severe asthma., Objective: We sought to understand the associations of obesity with relevant parameters of severe asthma, including asthma control, disease burden, and lung function., Methods: The German Asthma Net registry is a multicenter international real-life registry capturing long-term follow-up data. This analysis included 2213 patients (52 ± 16 years, 58% female, 29% with obesity [body mass index ≥30 kg/m 2 ], 4.2 ± 4.3 exacerbations/year). The primary analysis assessed relationships between BMI and variables through univariate tests, followed by a multiple regression model. Secondary outcomes regarded clinically relevant variables in relation to weight groups., Results: Patients with obesity were more frequently female, more likely to have depression and gastroesophageal reflux, and suffered from worse asthma control, lower quality of life, reduced static lung volumes, more pronounced hypoxemia, and higher blood neutrophil counts, all statistically significant. Blood eosinophils, exhaled nitric oxide, and total IgE were independent of obesity. In the multiple regression analysis, obesity was significantly associated with more frequent reflux and depression, reduced static lung function values, older age, poor asthma control, and long-acting muscarinic antagonist therapy, and inversely associated with bronchiectasis and nonsmoking status., Conclusion: In this large, well-characterized cohort, we identified the association of obesity with a significantly higher disease burden and a similar portfolio of inflammation type 2 markers in patients with and without obesity; therefore, patients with obesity seem similarly eligible for the treatment with biologics targeting these disease endotypes., (Copyright © 2023 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Purpose: To determine the diagnostic accuracy of preinterventional imaging modalities in patients being evaluated for iliocaval venous recanalization and stent placement., Methods: Consecutive patients with iliocaval postthrombotic obstructions or nonthrombotic iliac vein lesions (NIVL), who were scheduled for recanalization, underwent duplex ultrasound (DUS), magnetic resonance venography (MRV), multiplanar venography (MPV), and intravascular ultrasound (IVUS). The diagnostic accuracies of DUS, MRV, and MPV were analyzed using IVUS as reference., Results: A total of 216 limbs in 108 patients (80 patients with postthrombotic obstructions, 28 patients with NIVL) were examined. In patients with postthrombotic obstructions, the diagnostic sensitivities for the detection of lesions of the common femoral vein were 81% (95% CI 71-89%) for DUS, 76% (95% CI 65-85%) for MRV, and 86% (95% CI 76-93%) for MPV. The sensitivities for detecting lesions of the iliac veins were 96% (95% CI 89-99%) for DUS, 99% (95% CI 92-100%) for MRV, and 100% (95% CI 94-100%) for MPV. Regarding the inferior vena cava, the sensitivities were 44% (95% CI 24-65%) for DUS, 52% (95% CI 31-73%) for MRV, and 70% (95% CI 47-86%) for MPV. The sensitivities for detecting NIVL were 58% (95% CI 34-79%) for DUS, 90% (95% CI 68-97%) for MRV, and 95% (95% CI 73-99%) for MPV., Conclusion: In patients scheduled for recanalization of iliocaval postthrombotic obstructions, the sensitivities of DUS, MRV, and MPV were similar. In patients with suspected inferior vena cava involvement and in patients with NIVL, additional imaging with MR or conventional venography is required.

Background: Dynamic MELD deterioration (Delta MELD) during waiting time was shown to have significant impact on post-transplant survival. The aim of this study was to analyze the impact of MELD-Na score alterations on waiting list outcomes in liver transplant candidates., Method: 36,806 patients listed at UNOS for liver transplantation in 2011-2015 were analyzed according to their delisting reasons. Several different MELD-Na alterations during waiting time were analyzed (e.g., maximal change, last change before delisting/transplantation). Outcome estimates were calculated according to MELD-Na scores at listing and Delta MELD., Results: Patients who died while on the waiting list showed a significantly higher deterioration in MELD-Na during the waiting time (6.8 ± 8.4 points) than stable patients who remained actively listed (-0.1 ± 5.2 points; p < 0.01). Patients who were considered too healthy for transplantation improved by more than 3 points on average during the waiting time. The mean peak MELD-Na alteration during the waiting time was 10.0 ± 7.6 for patients who died on the waiting list, compared to 6.6 ± 6.1 in the group of patients who finally underwent transplantation., Conclusions: Deterioration of MELD-Na during waiting time and maximal MELD-Na deterioration have a significant negative impact on the liver transplant waiting list outcome.

Background and Objectives: Gender inequality in medicine remains an issue. Despite the increasing proportion of female physicians, women still appear underrepresented in interventional pulmonology (IP) careers. To date, no data are available on the gender distribution in IP., Method: An online survey was sent to pulmonary physicians internationally between July and December 2022. The survey included questions on gender diversity in the pulmonology departments, such as the proportion of male, female, and gender diverse physicians performing bronchoscopy, career progression, and social life., Results: Responses from 92 physicians (mean age 45 ± 10 years) from 47 hospitals across 17 countries were analysed, of whom 52% were women. Overall, 79% of the respondents were pulmonologists and 83% perform bronchoscopy. Although men continue to dominate bronchoscopy (65 vs. 43%) and are more likely to be involved in research (89 vs. 77%), the observed difference is statistically not significant (p = 0.135 and p = 0.281). Leading positions are held by 60% of male respondents and 23% of female respondents (p = 0.002). Men are also more often reported to have academic awards. Discrimination based on gender was reported by 5.3% of all men and 26.8% of all women (p = 0.023)., Conclusions: Men and women are almost equally involved in IP, especially in female-led bronchoscopy units. However, leading positions and academic awards are still predominantly held by men., (© 2023 S. Karger AG, Basel.)

When testing multiple hypotheses, a suitable error rate should be controlled even in exploratory trials. Conventional methods to control the False Discovery Rate assume that all p -values are available at the time point of test decision. In platform trials, however, treatment arms enter and leave the trial at different times during its conduct. Therefore, the actual number of treatments and hypothesis tests is not fixed in advance and hypotheses are not tested at once, but sequentially. Recently, for such a setting the concept of online control of the False Discovery Rate was introduced. We propose several heuristic variations of the LOND procedure (significance Levels based On Number of Discoveries) that incorporate interim analyses for platform trials, and study their online False Discovery Rate via simulations. To adjust for the interim looks spending functions are applied with O'Brien-Fleming or Pocock type group-sequential boundaries. The power depends on the prior distribution of effect sizes, for example, whether true alternatives are uniformly distributed over time or not. We consider the choice of design parameters for the LOND procedure to maximize the overall power and investigate the impact on the False Discovery Rate by including both concurrent and non-concurrent control data.

Introduction: People with epilepsy (PWE) have a higher prevalence of psychiatric disorders. Some individuals with drug-resistant epilepsy might benefit from surgical interventions. The aim of this study was to perform an assessment of psychiatric comorbidities with a follow-up period of 12 months in patients with drug-resistant epilepsy, comparing those who underwent surgery to those who did not., Material and Methods: We assessed psychiatric comorbidities at baseline, after 4 months and after 12 months. Psychiatric symptoms and diagnoses were assessed using SCID-Interview, Hamilton Rating Scale for Depression, Beck-Depression Inventory, Hamilton Anxiety Rating Scale, Prodromal-Questionnaire and the Global Assessment of Functioning Scale., Results: Twenty-five patients were included in the study, 12 underwent surgery, 11 were esteemed as being neurologically unqualified for surgery and two refused surgery. Patients in the no-surgery group were significantly older, reported more substance use, had significantly higher levels of anxiety and were more often diagnosed with a personality disorder. Age and levels of anxiety were significant predictors of being in the surgery or the no-surgery group. The described differences between surgery and no-surgery patients did not change significantly over the follow-up period., Discussion: These data point toward a higher expression of baseline psychiatric symptoms in drug-resistant PWE without surgery. Further studies are warranted to further elucidate these findings and to clarify potential psychotropic effects of epilepsy itself, drug-resistant epilepsy and of epilepsy surgery and their impact on psychopathology. Clinically, it seems highly relevant to include psychiatrists in an interdisciplinary state-of-the-art perioperative management of drug-resistant PWE., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Friedrich, Pataraia, Aull-Watschinger, Zehetmayer, Weitensfelder, Watschinger and Mossaheb.)

Purpose: At least half of surgical complications can be avoided by using surgical checklists. However, universal implementation and compliance have been reported as being variable. Patients undergoing urgent surgical intervention are at increased risk for complications. The aim of this study was to evaluate the checklist compliance together with the complication rate during day and night shifts in a European University hospital., Methods: 51 and 52 consecutive patients who had surgery during day and night shifts were included. The primary outcome measures were compliance and completeness of the WHO safety checklist. The occurrence of postoperative complications was investigated., Results: The analysis included 103 surgical procedures. The mean compliance rate of use was 93% and the mean completeness rate was 22%. After operations were broken down by day or night shift, we found that checklists were less often available in night shifts compared to day shifts. The completeness of the checklist and the occurrence of postoperative complications did not differ between day and night shifts., Conclusion: This study reports worse checklists availability in night shifts when compared to day shifts, but complication rates did not increase. Further studies are warranted to investigate postoperative complication rates together with checklist compliance in day versus night shifts., (© 2022. The Author(s).)

Background: Diagnosis of food allergies is challenging, as combining information from specific IgE (sIgE)-sensitization pattern and skin prick tests (SPTs) with clinical history is necessary for a personalized management of allergic patients. The aim of this study was to compare two molecular tests, the ImmunoCAP ISAC (ISAC) and the Allergy Explorer, version 2 (ALEX 2 ) in the context of pollen food syndrome (PFS) diagnosis in a real-life scenario, to assess the benefit of multiplex testing in PFS patients., Methods: Diagnosis of food allergy was performed in 53 patients. Allergen-sIgE concentrations were measured with ISAC and ALEX 2 . Results for sIgE were statistically compared with each other, with SPT results and with clinical presentation of the patients., Results: Using ISAC as reference test for sIgE measurements, the average sensitivity of ALEX 2 for PR-10 allergens was 83.2% and the average specificity 88.0%. If only low sIgE concentrations were included, the sensitivity was 60.8% and the specificity 91.1%. Apple and hazelnut sensitizations were confirmed in most patients by concordance of sIgE and SPT results. Significant correlations were shown between clinical symptoms and Mal d 1- and Gly m 4-sIgE levels measured by both tests and for Cor a 1-sIgE levels measured by ALEX 2 . In eight patients, profilin related symptoms were supported by Hev b 8-sensitization., Conclusion: Multiplex testing is beneficial to understand patient-specific individual sensitization profiles and to providing personalized management recommendations. In the future, custom-designed test kits might enable reducing costs of multiplex testing for specific patient groups without compromising the diagnostic value., (© 2022 The Authors. Allergy published by European Academy of Allergy and Clinical Immunology and John Wiley & Sons Ltd.)

Background: In RNA-sequencing studies a large number of hypothesis tests are performed to compare the differential expression of genes between several conditions. Filtering has been proposed to remove candidate genes with a low expression level which may not be relevant and have little or no chance of showing a difference between conditions. This step may reduce the multiple testing burden and increase power., Results: We show in a simulation study that filtering can lead to some increase in power for RNA-sequencing data, too aggressive filtering, however, can lead to a decline. No uniformly optimal filter in terms of power exists. Depending on the scenario different filters may be optimal. We propose an adaptive filtering strategy which selects one of several filters to maximise the number of rejections. No additional adjustment for multiplicity has to be included, but a rule has to be considered if the number of rejections is too small., Conclusions: For a large range of simulation scenarios, the adaptive filter maximises the power while the simulated False Discovery Rate is bounded by the pre-defined significance level. Using the adaptive filter, it is not necessary to pre-specify a single individual filtering method optimised for a specific scenario., (© 2022. The Author(s).)

Purpose: Hypofractionated radiotherapy for prostate cancer is well established for definitive treatment, but not well defined in the postoperative setting. The purpose of this analysis was to assess oncologic outcomes and toxicity in a large cohort of patients treated with conventionally fractionated three-dimensional (3D) conformal radiotherapy (CF) and hypofractionated volumetric modulated arc therapy (HF) after radical prostatectomy., Methods: Between 1994 and 2019, a total of 855 patients with prostate carcinoma were treated by postoperative radiotherapy using CF (total dose 65-72 Gy, single fraction 1.8-2 Gy) in 572 patients and HF (total dose 62.5-63.75 Gy, single fraction 2.5-2.55 Gy) in 283 patients. The association of treatment modality with biochemical control, overall survival (OS), and gastrointestinal (GI) and genitourinary (GU) toxicity was assessed using logistic and Cox regression analysis., Results: There was no difference between the two modalities regarding biochemical control rates (77% versus 81%, respectively, for HF and CF at 24 months and 58% and 64% at 60 months; p = 0.20). OS estimates after 5 years: 95% versus 93% (p = 0.72). Patients undergoing HF had less frequent grade 2 or higher acute GI or GU side effects (p = 0.03 and p = 0.005, respectively). There were no differences in late GI side effects between modalities (hazard ratio 0.99). Median follow-up was 23 months for HF and 72 months for CF (p < 0.001)., Conclusion: For radiation therapy of resected prostate cancer, our analysis of this largest single-centre cohort (n = 283) treated with hypofractionation with advanced treatment techniques compared with conventional fractionation did not yield different outcomes in terms of biochemical control and toxicities. Prospective investigating of HF is merited., (© 2022. The Author(s).)

Background: Long-lasting symptoms following SARS-CoV2-infection have been described in several studies. However, there is only limited knowledge about the ongoing pathophysiology and the association with pathological findings in medical examinations., Methods: In this post hoc analysis of a prospective trial, 135 patients following COVID-19 were enrolled and grouped with respect to the presence or absence of respiratory ongoing symptoms following COVID-19. Pulmonary function test (PFT), diffusion capacity measurement (TLCO SB and TLCO/VA), blood gas analysis (BGA), laboratory tests and high-resolution computed tomography (HRCT) of patients with persistent respiratory symptoms were compared to those of asymptomatic patients., Results: In this analysis, 71% (96/135) of all patients (mean age 49 years; range 20-91 years) reported long-lasting symptoms after a median (IQR) of 85 days (60-116) following COVID-19 whereby 57.8% (78/135) complained about persistent pulmonary symptoms. Pathological findings in blood test, PFT, TLCO, BGA and/or HRCT were found in 71.8% and 64.1% of patients with and without long-lasting respiratory symptoms respectively. Patients with persistent respiratory symptoms were significantly younger and presented a significant lower FVC (%), TLC (L), and TLCO SB compared to asymptomatic patients (p < 0.05). The multiple logistic regression results in a significant effect of age (p = 0.004) and TLCO SB (p = 0.042)., Conclusion: Following COVID-19, a large proportion of patients experience ongoing symptoms, whereby the respiratory symptoms are the predominant complaints. Compared to asymptomatic patients, patients with ongoing symptoms were younger and presented a significant lower FVC, TLC and TLCO SB. The multiple logistic regression demonstrated only a significant association between the TLCO SB as the only PFT parameter and the perceived symptoms., (© 2022. The Author(s).)

Objective: To increase knowledge of discrete symptoms shall help to avoid misinterpretation of test results and to gain better understanding of associations between early symptoms and severe disease to provide additional criteria for targeted early interventions., Design: Retrospective observational study., Setting: Austrian GP practices in the year 2020, patients above 18 years were included., Participants: We recruited 25 practices which included 295 participants with a positive SARS-CoV‑2 test., Main Outcome Measures: Data collection comprised basic demographic data, risk factors and the recording of symptoms at several points in time in the course of the illness. Descriptive analyses for possible associations between demographics and symptoms were conducted by means of cross tabulation. Group differences (hospitalized yes/no) were assessed using Fisher's exact test. The significance level was set to 0.05; due to the observational character of the study, no adjustment for multiplicity was performed., Results: Only one third of patients report symptoms generally understood to be typical for COVID‑19. Most patients presented with unspecific complaints. We found symptoms indicating complicated disease, depending on when they appear. The number of symptoms may be a predictor for the need of hospital care. More than 50% of patients still experience symptoms 14 days after onset., Conclusion: Unspecific symptoms are valuable indicators in the detection of early COVID‑19 disease that practitioners and the general public should be aware of also in the interpretation of low sensitivity tests. Monitoring patients using the indicators we identified may help to identify patients who are likely to profit from early intervention., (© 2022. The Author(s).)

Hemodialysis (HD) patients have an increased risk of severe SARS-CoV-2 infection. In this study, we assess the impact of a third vaccine dose (3D) on antibody levels and T cell response in HD patients and a healthy control group in a prospective cohort study consisting of 60 HD patients and 65 healthy controls. Each participant received two doses of the BNT-162b2 mRNA vaccine and an mRNA vaccine 3D. The SARS-CoV-2 antibody response was measured 6 months after the second vaccine dose and 6 to 8 weeks after the 3D. We assessed INF-γ secretion 6-8 weeks post 3D in 24 healthy controls, 17 HD patients with a normal response, and 20 low responder HD patients. The groups were compared using univariate quantile regressions and multiple analyses. After the 3D, the SARS-CoV-2-specific antibody and INF-γ titers of most HD patients were comparable to those of healthy controls. A subgroup of HD patients who had shown a diminished antibody response after the first two vaccine doses developed a significantly lower antibody and INF-γ response compared to responder HD patients and controls even after the 3D. A new strategy is needed to protect low/non-responder HD patients from severe SARS-CoV-2 infection.

Objective: To evaluate whether locally applied vaginal estrogen affects prolapse-associated complaints compared with placebo treatment in postmenopausal women prior to surgical prolapse repair., Design: Randomised, double-masked, placebo-controlled, multicentre study., Setting: Urogynaecology unit at the Medical University of Vienna and University Hospital of Tulln., Population: Postmenopausal women with symptomatic pelvic organ prolapse and planned surgical prolapse repair., Methods: Women were randomly assigned local estrogen cream or placebo cream 6 weeks preoperatively., Main Outcome Measures: The primary outcome was differences in subjective prolapse-associated complaints after 6 weeks of treatment prior to surgery, assessed with the comprehensive German pelvic floor questionnaire. Secondary outcomes included differences in other pelvic floor-associated complaints (bladder, bowel or sexual function)., Results: Out of 120 women randomised, 103 (86%) remained for the final analysis. After 6 weeks of treatment the prolapse domain score did not differ between the estrogen and the placebo groups (4.4 ± 0.19 versus 4.6 ± 0.19; mean difference, -0.21; 95% CI -0.74 to 0.33; P = 0.445). Multivariate analysis, including only women receiving the intervention, showed that none of the confounding factors modified the response to estradiol., Conclusions: These results demonstrate that preoperative locally applied estrogen does not ameliorate prolapse-associated symptoms in postmenopausal women with symptomatic pelvic organ prolapse., Tweetable Abstract: Preoperative local estrogen does not ameliorate prolapse-associated symptoms in postmenopausal women with pelvic organ prolapse., (© 2021 The Authors. BJOG: An International Journal of Obstetrics and Gynaecology published by John Wiley & Sons Ltd.)

Background: Elevated D-dimer is known as predictor for severity of SARS-CoV2-infection. Increased D-dimer is associated with thromboembolic complications, but it is also a direct consequence of the acute lung injury seen in COVID-19 pneumonia., Objectives: To evaluate the rate of persistent elevated D-dimer and its association with thromboembolic complications and persistent ground glass opacities (GGO) after recovery from COVID-19., Methods: In this post hoc analysis of a prospective multicenter trial, patients underwent blood sampling, measurement of diffusion capacity, blood gas analysis, and multidetector computed tomography (MDCT) scan following COVID-19. In case of increased D-dimer (>0,5 μg/ml), an additional contrast medium-enhanced CT was performed in absence of contraindications. Results were compared between patients with persistent D-dimer elevation and patients with normal D-dimer level., Results: 129 patients (median age 48.8 years; range 19-91 years) underwent D-Dimer assessment after a median (IQR) of 94 days (64-130) following COVID-19. D-dimer elevation was found in 15% (19/129) and was significantly more common in patients who had experienced a severe SARS-CoV2 infection that had required hospitalisation compared to patients with mild disease (p = 0.049). Contrast-medium CT (n = 15) revealed an acute pulmonary embolism in one patient and CTEPH in another patient. A significant lower mean pO2 (p = 0.015) and AaDO2 (p = 0.043) were observed in patients with persistent D-Dimer elevation, but the rate of GGO were similar in both patient groups (p = 0.33)., Conclusion: In 15% of the patients recovered from COVID-19, persistent D-dimer elevation was observed after a median of 3 months following COVID-19. These patients had experienced a more severe COVID and still presented more frequently a lower mean pO2 and AaDO2., Competing Interests: NO authors have competing interests.

Background: Adaptive interpersonal emotion regulation (iER) is a vital tool for positive relations. During early adolescence, peer relations become increasingly important, making this age group a relevant target group for interventions promoting positive interactions with each other, yet no evidence-based intervention exists for iER and early adolescents specifically., Methods: This randomised controlled trial (RCT) aims to test effectiveness and feasibility of a serious game training iER skills in early adolescents by comparing outcomes with a control group playing a game without psychoeducational content in a pre- and post-test design. German- and English-speaking early adolescents (10-14 years) are eligible for participation. IER skills improvement as assessed by a vignette task is the primary outcome and will be analysed with a chi-square test. Secondary outcomes include feasibility and acceptability, emotional competence, personal emotion regulation, gender, and sex., Discussion: This RCT will test whether playing a serious game about iER strategies results in an improvement of iER skills and whether the game is feasible and acceptable for early adolescents with the ultimate aim to implement the game in schools and help early adolescents achieve positive peer relationships., Trial Registration: ClinicalTrials.gov NCT04808102 , Registered on 19 March 2021., (© 2021. The Author(s).)

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a severe multi-systemic disease characterized by debilitating fatigue that is not relieved by rest. The causes of the disease are still largely unexplained, and no causative treatment is currently available. Changes in the immune response are considered as fundamental in the development of ME/CFS. Thus, we aimed to evaluate the immunological profile of ME/CFS patients in a retrospective data analysis. As part of the routine workup for ME/CFS patients, a differential blood count, leukocyte subtyping, and quantification of immunoglobulins and IgG subclasses, as well as a complement analysis, was performed. Out of 262 ME/CFS patients, 64.9% had a reduction or deficiency in at least one of the listed immune parameters. In contrast, 26.3% showed signs of immune activation or inflammation. A total of 17.6% of the ME/CFS patients had an unclassified antibody deficiency, with IgG3 and IgG4 subclass deficiencies as the most common phenotypes. Reduced MBL (mannose-binding lectin) levels were found in 32% of ME/CFS patients, and MBL deficiency in 7%. In summary, the present results confirmed the relevance of immune dysfunction in ME/CFS patients underlining the involvement of a dysfunctional immune response in the disease. Thus, immune parameters are relevant disease biomarkers, which might lead to targeted therapeutic approaches in the future.

Background: Haemodialysis (HD) patients are exposed to a high risk due to the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic. They are prone to acquiring the infection and are threatened by high mortality rates in case of infection. However, HD patients were not included in the efficacy trials of the SARS-CoV-2 vaccines. Such efficacy data would have been critical because HD patients show decreased responses against various other vaccines and this could translate to the SARS-CoV-2 vaccines as well., Methods: We conducted a prospective cohort study that contained a group of 81 HD patients and 80 healthy controls. All of them had been vaccinated with the BioNTech/Pfizer mRNA vaccine (two doses, as per the manufacturer's recommendation). The anti-SARS-CoV-2 spike (S) antibody response was measured for all participants 21 days after the second dose. The groups were compared using univariate quantile regressions and a multivariate analysis. The adverse events (AEs) of the vaccination were assessed via a questionnaire. Finally, a correlation between the HBs-antibody response and the SARS-CoV-2 antibody response in the HD patients was established., Results: The HD patients had significantly lower anti-SARS-CoV-2 S antibody titres than the control patients 21 days after vaccination (median was 171 U/mL for dialysis patients and 2500 U/mL for the controls). Further, the HD group presented fewer AEs than the control group. No correlation was found between the antibody response to previous Hepatitis B vaccination and that of the SARS-CoV-2 vaccine., Conclusions: HD patients present highly diminished SARS-CoV-2 S antibody titres compared with a cohort of controls. Therefore, they could be much less protected by SARS-CoV-2 mRNA vaccinations than expected. Further studies to test alternative vaccination schemes should be considered., (© The Author(s) 2021. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.)

Introduction and Hypothesis: Triage has become a valid tool to reduce workload during the first consultation in a specialized clinic. A nurse-led telephone intervention prior to the first urogynecologic visit reduces visit duration and increases patients' and physicians' satisfaction., Methods: All patients scheduled for their very first visit were recruited. They were randomized into an intervention group (prior contact by a specialized urogynecology nurse) and a control group (no contact). The intervention included a questionnaire about history and symptoms. Patients were prompted to complete a bladder diary. Primary outcome was duration of the consultation; secondary outcomes were patients' and physicians' satisfaction with the intervention., Results: Fifty-five patients were allocated to the intervention group and 53 to the control group with no difference regarding age, BMI, parity, menopausal status and primary diagnosis. Mean duration of the telephone call was 10.8 min (SD 4.4). The consultation was significantly shorter in the intervention group than in the control group (mean difference: 4 min and 8 s, p = 0.017). In the intervention group, 79% of the patients found the consultation quality "excellent," 86% would return, and 77% would recommend our clinic to a relative or friend compared with 68%, 67% and 66%, respectively, in the control group. Physicians were "very satisfied" or "satisfied" with the patient preparation., Conclusions: A nurse-led intervention reduces the duration of the first uroynecologic consultation and is associated with high patient and physician satisfaction. Further research should evaluate whether it also decreases the number of follow-up visits and further referrals.

Despite being located close to the European epicenter of the COVID-19 pandemic in Italy, Austria has managed to control the first wave. In Austria, the largest health insurance fund covers 7 million people and has 12,000 employees, including 3700 healthcare workers (HCW). For patient and staff safety, transmission control measures were implemented and mass testing of employees for SARS-CoV-2 antibodies was conducted. An IgG SARS-CoV-2 rapid test on fingerstick blood was used as a screening test (ST), followed by serologic studies with 3 different immunoassays and confirmatory testing by a neutralization test (NT). Among 7858 employees, 144 had a positive ST and 88 were confirmed by a NT (1.12%, CI: 0.9-1.38%). The positive predictive value (PPV) of the ST was 69.3% (CI: 60.5-77.2). Interestingly, 40% of the NT positive serum samples were tested negative in all 3 immunoassays. Of the total sample, 2242 HCW (28.5%) were identified. Unexpectedly, there was no difference in the prevalence of NT positives in HCW compared to non-HCW (23/2242 vs. 65/5301, p = 0.53). SARS-CoV-2 antibody prevalence was not increased among HCW. Although HCW are at potentially increased risk for SARS-CoV-2 infection, transmission control measures in healthcare facilities appear sufficient to limit transmission of infection.

Objective: To assess the effect of patient's sex on response to neoadjuvant chemotherapy (NAC) in patients with clinically nonmetastatic muscle-invasive bladder cancer (MIBC)., Methods: Complete pathologic response, defined as ypT0N0 at radical cystectomy, and downstaging were evaluated using sex-adjusted univariable and multivariable logistic regression modeling. We used interaction terms to account for age of menopause and smoking status. The association of sex with overall survival and cancer-specific survival was evaluated using Cox regression analyses., Results: A total of 1,031 patients were included in the analysis, 227 (22%) of whom were female. Female patients had a higher rate of extravesical disease extension (P = 0.01). After the administration of NAC, ypT stage was equally distributed between sexes (P = 0.39). On multivariable logistic regression analyses, there was no difference between the sexes or age of menopause with regards to ypT0N0 rates or downstaging (all P > 0.5). On Cox regression analyses, sex was associated with neither overall survival (hazard ratio 1.04, 95% confidence interval 0.75-1.45, P = 0.81) nor cancer-specific survival (hazard ratio 1.06, 95% confidence interval 0.71-1.58, P = 0.77)., Conclusion: Our study generates the hypothesis that NAC equalizes the preoperative disparity in pathologic stage between males and females suggesting a possible differential response between sexes. This might be the explanation underlying the comparable survival outcomes between sexes despite females presenting with more advanced tumor stage., (Copyright © 2020 Elsevier Inc. All rights reserved.)