Background: Mobilization of intensive care patients is a multi-professional task. Aim of this study was to explore how different professions working at Intensive Care Units (ICU) estimate the mobility capacity using the ICU Mobility Score in 10 different scenarios.

Methods: Ten fictitious patient-scenarios and guideline-related knowledge were assessed using an online survey. Critical care team members in German-speaking countries were invited to participate. All datasets including professional data and at least one scenario were analyzed. Kruskal Wallis test was used for the individual scenarios, while a linear mixed-model was used over all responses.

Results: In total, 515 of 788 (65%) participants could be evaluated. Physicians (p = 0.001) and nurses (p = 0.002) selected a lower ICU Mobility Score (-0.7 95% CI -1.1 to -0.3 and -0.4 95% CI -0.7 to -0.2, respectively) than physical therapists, while other specialists did not (p = 0.81). Participants who classified themselves as experts or could define early mobilization in accordance to the "S2e guideline: positioning and early mobilisation in prophylaxis or therapy of pulmonary disorders" correctly selected higher mobilization levels (0.2 95% CI 0.0 to 0.4, p = 0.049 and 0.3 95% CI 0.1 to 0.5, p = 0.002, respectively).

Conclusion: Different professions scored the mobilization capacity of patients differently, with nurses and physicians estimating significantly lower capacity than physical therapists. The exact knowledge of guidelines and recommendations, such as the definition of early mobilization, independently lead to a higher score. Interprofessional education, interprofessional rounds and mobilization activities could further enhance knowledge and practice of mobilization in the critical care team.

Introduction: Arterial brain vessel assessment is crucial for the diagnostic process in patients with cerebrovascular disease. Non-invasive neuroimaging techniques, such as time-of-flight (TOF) magnetic resonance angiography (MRA) imaging are applied in the clinical routine to depict arteries. They are, however, only visually assessed. Fully automated vessel segmentation integrated into the clinical routine could facilitate the time-critical diagnosis of vessel abnormalities and might facilitate the identification of valuable biomarkers for cerebrovascular events. In the present work, we developed and validated a new deep learning model for vessel segmentation, coined BRAVE-NET, on a large aggregated dataset of patients with cerebrovascular diseases. Methods: BRAVE-NET is a multiscale 3-D convolutional neural network (CNN) model developed on a dataset of 264 patients from three different studies enrolling patients with cerebrovascular diseases. A context path, dually capturing high- and low-resolution volumes, and deep supervision were implemented. The BRAVE-NET model was compared to a baseline Unet model and variants with only context paths and deep supervision, respectively. The models were developed and validated using high-quality manual labels as ground truth. Next to precision and recall, the performance was assessed quantitatively by Dice coefficient (DSC); average Hausdorff distance (AVD); 95-percentile Hausdorff distance (95HD); and via visual qualitative rating. Results: The BRAVE-NET performance surpassed the other models for arterial brain vessel segmentation with a DSC = 0.931, AVD = 0.165, and 95HD = 29.153. The BRAVE-NET model was also the most resistant toward false labelings as revealed by the visual analysis. The performance improvement is primarily attributed to the integration Hilbert et al. Fully-Automated Arterial Brain Vessel Segmentation of the multiscaling context path into the 3-D Unet and to a lesser extent to the deep supervision architectural component. Discussion: We present a new state-of-the-art of arterial brain vessel segmentation tailored to cerebrovascular pathology. We provide an extensive experimental validation of the model using a large aggregated dataset encompassing a large variability of cerebrovascular disease and an external set of healthy volunteers. The framework provides the technological foundation for improving the clinical workflow and can serve as a biomarker extraction tool in cerebrovascular diseases.

Background: Adverse childhood experiences (ACE) are associated with an increased risk of major depressive disorder (MDD) and hypothalamic-pituitary-adrenal (HPA) axis dysregulation. Within the HPA axis, corticotropin-releasing hormone and vasopressin (AVP) synergistically stimulate the release of adrenocorticotropic hormone, which promotes cortisol release. The cleavage product copeptin is produced during AVP synthesis and is a surrogate marker of AVP release. Children with ACE and young adults with depressive symptoms have higher levels of copeptin than healthy controls. Objective: To uncover the effects of MDD and ACE on copeptin levels in adult females. Methods: We recruited 94 women (mean age: 34.0 +/- 3.6 years): 23 with MDD and ACE, 24 with MDD without ACE, 22 with ACE without MDD, and 25 healthy controls. ACE was defined as repeated sexual or physical abuse at least once a month over at least one year before the age of 18 years. MDD was defined by the DSM-IV criteria. Copeptin plasma levels were measured with an immunoluminometric assay. Results: The four groups did not differ in demographic variables. We found a significant negative correlation between body mass index (BMI) and copeptin plasma levels (r = -.21; p = .045). Copeptin plasma levels did not differ between the four groups after controlling for BMI. Conclusion: Neither MDD nor ACE was associated with altered plasma copeptin levels. Thus, copeptin does not seem to play a major role in MDD and ACE in adult females.

Heart failure (HF) affects at least 26 million people worldwide, so predicting adverse events in HF patients represents a major target of clinical data science. However, achieving large sample sizes sometimes represents a challenge due to difficulties in patient recruiting and long follow-up times, increasing the problem of missing data. To overcome the issue of a narrow dataset cardinality (in a clinical dataset, the cardinality is the number of patients in that dataset), population-enhancing algorithms are therefore crucial. The aim of this study was to design a random shuffle method to enhance the cardinality of an HF dataset while it is statistically legitimate, without the need of specific hypotheses and regression models. The cardinality enhancement was validated against an established random repeated-measures method with regard to the correctness in predicting clinical conditions and endpoints. In particular, machine learning and regression models were employed to highlight the benefits of the enhanced datasets. The proposed random shuffle method was able to enhance the HF dataset cardinality (711 patients before dataset preprocessing) circa 10 times and circa 21 times when followed by a random repeated-measures approach. We believe that the random shuffle method could be used in the cardiovascular field and in other data science problems when missing data and the narrow dataset cardinality represent an issue.

Immunofluorescence staining is the most frequently applied technique to detect and visualize various molecules in biological samples. Many protocols can be found in the literature and the websites of commercial antibody producers. This can result in a time-consuming and costly methodical work to establish "simple" antibody staining. We here summarize in a stepwise manner an easy-to-follow immunofluorescence staining protocol with an improved specific fluorescent signal and a reduced background and non-specific binding signal. This will help scientists to save time, effort, and antibody costs during the application of such a valuable technique.

PURPOSE

The purpose of this study was to evaluate associations among use of walking aids, mobility status, and occurrence of urinary incontinence (UI) in geriatric patients residing in nursing homes, and to examine associations between UI severity (frequency and amount) and its impact on health-related quality of life (QoL).

DESIGN

Multicenter descriptive cross-sectional prevalence study.

SUBJECTS AND SETTING

A total of 2044 patients from nursing homes were included in the study. A majority were female (72.0%), the mean age of participants was 82.1 years (SD 11.2), their mean body mass index was 26.1 (SD 5.4), and their mean Care Dependency Scale score was 46.0 (SD 18.2), indicating a medium to high care dependency. The study setting was 30 nursing homes throughout Germany from 2014 to 2015.

METHODS

Data were collected by trained nurses using a standardized data collection form to collect information about demographic characteristics, health conditions, mobility status measured according to the Elderly Mobility Scale (EMS), UI, and QoL measured using the International Consultation of Incontinence Questionnaire Short Form (ICIQ-SF).

RESULTS

The prevalence of UI was 69.7% (n = 1804). Analysis of variance showed that, in 1659 nursing home residents with information on UI, 572 reported a medium amount of leakage with a mean impact on health-related QoL of 2.2 (SD 2.2, P < .001) on a scale from 0 (no impact) to 10 (very high impact). The mean of the impact on QoL in 235 residents who reported a large amount of leakage was 2.4 (SD 3.0, P < .001). In 1741 residents with information on the frequency of UI, 637 reported being urinary incontinent more than once a day with a mean impact on QoL of 2.2 (SD 2.1, P < .001) and 359 residents with permanent UI stated a mean impact on QoL of 2.1 (SD 2.8, P < .001). According to the bivariate association of UI with use of walking aids, the highest prevalence of UI (61.2%) was in patients who did not use any walking aids. The Chi-square Automatic Interaction Detector (CHAID) of the relationship between mobility according to the EMS and UI indicated that 71.1% of all patients with UI did not use any walking aids, although their mobility status had been reduced.

CONCLUSIONS

Findings indicate a significant association between impaired mobility and UI in nursing home residents. Chronic, severe urinary incontinence exerted the greatest impact on health-related QoL. Therefore, we recommend measures to preserve or regain mobility to minimize or prevent UI in geriatric residents and patients and, thus, increase their health-related QoL.

BACKGROUND

There is a well-established link between maternal depression and child mental health. Similar effects have been found for maternal history of early life maltreatment (ELM). However, studies investigating the relationship of children's quality of life and maternal depression are scarce and none have been conducted for the association with maternal ELM. The aim of the present study was to investigate the effects of maternal history of ELM and depression on children's health-related quality of life and to identify mediating factors accounting for these effects.

METHODS

Our study involved 194 mothers with and without history of depression and/or ELM and their children between five and 12 years. Children's health-related quality of life was assessed by maternal proxy- and child self-ratings using the KIDSCREEN. We considered maternal sensitivity and maternal parenting stress as potential mediators.

RESULTS

We found an effect of maternal history of depression but not of maternal history of ELM on health-related quality of life. Maternal stress and sensitivity mediated the effects of maternal depression on child global health-related quality of life, as well as on the dimensions Autonomy & Parent Relation, School Environment (maternal and child rating), and Physical Wellbeing (child rating).

LIMITATION

Due to the cross-sectional design of the study, causal interpretations must be made with caution. Some scales yielded low internal consistency.

CONCLUSIONS

Maternal impairments in areas of parenting which possibly developed during acute depression persist even after remission of acute affective symptoms. Interventions should target parenting stress and sensitivity in parents with prior depression.

OBJECTIVE

This study investigates associations of subjective hearing ability, physical comorbidities, and mental comorbidities with bothersome (vs. non-bothersome) tinnitus and mediating effects between these influences.

METHODS

The Swedish LifeGene cohort was used to sample cross-sectional survey data (collected 2009-2016) of 7615 participants with tinnitus, 697 (9.2%) of whom rated their tinnitus as bothersome. Associations between bothersome tinnitus and subjective hearing ability, physical and mental comorbidities were investigated by separate age- and gender-adjusted multiple logistic regression models. Interrelationships between these associations were investigated by logistic mediation models.

RESULTS

Compared to non-bothersome tinnitus, bothersome tinnitus was associated with higher age, reduced subjective hearing ability, hearing-related difficulties in social situations, cardiovascular disease, chronic shoulder pain, thyroid disease, Ménière's disease, depression, anxiety syndrome, and social anxiety. Subjective hearing impairment or hearing-related difficulties mediated 13-36% of the effects of mental comorbidities on bothersome tinnitus. Depression or anxiety syndrome mediated 5-8% of most relationships between physical comorbidities and bothersome tinnitus. Depression, anxiety syndrome, or social anxiety mediated 2-4% of the effects of subjective hearing impairment or hearing-related difficulties on bothersome tinnitus.

CONCLUSION

Psychological factors, subjective hearing impairment, and hearing-related difficulties in social situations play key roles in predicting bothersome (vs. non-bothersome) tinnitus in a large population sample. Psychological factors contribute to explaining the impact of physical comorbidities and hearing-related effects on bothersome tinnitus. This highlights their transdiagnostic importance for aggravating varied physical symptom clusters. Interventions to improve or prevent high tinnitus burden should be interdisciplinary/multimodal and target auditory, physical, and psychological factors.

Objectives: The study reports longitudinal changes in grip strength, muscle mass and muscle power of lower extremities. The aim is to identify early muscular changes to improve the diagnosis and treatment of sarcopenia.

Methods: Grip strength was measured by hand dynamometer, muscle mass by dual-energy X-ray absorptiometry and muscle power by performing a chair rise test and two-leg jumps (2LJP) on the Leonardo Mechanograph®. Longitudinal changes were analysed using paired t-tests by age group and sex. Differences between groups in terms of the annual change were tested by Analysis of Variance and the Dunnett's test. Comparisons between the variables were performed using one sample t-tests.

Results: Six-year changes were determined in 318 randomly selected healthy participants aged 20-90 years from Berlin. 2LJP declined significantly earlier in 20-39 years old women (-3.70 W/kg) and men (-5.97 W/kg, both p<0.001). This is an absolute annual decline of -0.46 W/kg in females and -0.75 W/kg in males. In the oldest age group, 2LJP showed the highest absolute annual loss with -0.99 W/kg in women and -0.88 W/kg in men. 2LJP was significantly different compared to all variables of muscle mass and strength (p<0.01).

Conclusions: The results underline the importance of assessing muscle power using 2LJP during aging.

During pregnancy, the body's hyperestrogenic state alters hepatic metabolism and synthesis. While biochemical changes related to liver function during normal pregnancy are well understood, pregnancy-associated alterations in biophysical properties of the liver remain elusive. In this study, we investigated 26 ex vivo fresh liver specimens harvested from pregnant and non-pregnant rats by diffusion-weighted imaging (DWI) and magnetic resonance elastography (MRE) in a 0.5-Tesla compact magnetic resonance imaging (MRI) scanner. Water diffusivity and viscoelastic parameters were compared with histological data and blood markers. We found livers from pregnant rats to have (i) significantly enlarged hepatocytes (26 ± 15%, p < 0.001), (ii) increased liver stiffness (12 ± 15%, p = 0.012), (iii) decreased viscosity (-23 ± 14%, p < 0.001), and (iv) increased water diffusivity (12 ± 11%, p < 0.001). In conclusion, increased stiffness and reduced viscosity of the liver during pregnancy are mainly attributable to hepatocyte enlargement. Hypertrophy of liver cells imposes fewer restrictions on intracellular water mobility, resulting in a higher hepatic water diffusion coefficient. Collectively, MRE and DWI have the potential to inform on structural liver changes associated with pregnancy in a clinical context.

Simple Summary: Hepatocellular carcinoma remains a leading cause of cancer-related death and the most common primary hepatic malignancy in the Western hemisphere. Previous research found that angiogenesis-related cytokines and elevated levels of interleukin 8 and vascular endothelial growth factor (VEGF) shorten the expected time of survival. Moreover, factors of tumor angiogenesis- and hypoxia-driven signaling pathways are already associated with worse outcome in disease-free survival in several tumor entities. Our study investigates the prognosis of hepatocellular carcinoma patients based on a selection of ten different single-nucleotide polymorphisms from angiogenesis, carcinogenesis, and hypoxia pathways. Our study with 127 patients found supporting evidence that polymorphisms in angiogenesis-associated pathways corelate with disease-free survival and clinical outcome in patients with hepatocellular carcinoma.

Abstract: Tumor angiogenesis plays a pivotal role in hepatocellular carcinoma (HCC) biology. Identifying molecular prognostic markers is critical to further improve treatment selection in these patients. The present study analyzed a subset of 10 germline polymorphisms involved in tumor angiogenesis pathways and their impact on prognosis in HCC patients undergoing partial hepatectomy in a curative intent. Formalin-fixed paraffin-embedded (FFPE) tissues were obtained from 127 HCC patients at a German primary care hospital. Genomic DNA was extracted, and genotyping was carried out using polymerase chain reaction (PCR)-restriction fragment length polymorphism-based protocols. Polymorphisms in interleukin-8 (IL-8) (rs4073; p = 0.047, log-rank test) and vascular endothelial growth factor (VEGF C + 936T) (rs3025039; p = 0.045, log-rank test) were significantly associated with disease-free survival (DFS). After adjusting for covariates in the multivariable model, IL-8 T-251A (rs4073) (adjusted p = 0.010) and a combination of "high-expression" variants of rs4073 and rs3025039 (adjusted p = 0.034) remained significantly associated with DFS. High-expression variants of IL-8 T-251A may serve as an independent molecular marker of prognosis in patients undergoing surgical resection for HCC. Assessment of the patients' individual genetic risks may help to identify patient subgroups at high risk for recurrence following curative-intent surgery.

Background: During the COVID-19 pandemic people are facing risks of adverse health effects due to the restrictions implemented such as quarantine measures, reduced social contact, and self-isolation. In this qualitative review, we collected data on potential preventive and therapeutic health benefits of Complementary and Integrative Medicine (CIM) that might be useful during the COVID-19 pandemic. We have reviewed the scientific literature to summarize CIM practices that could be beneficial for improving physical and mental health and well-being of the population under the current pandemic circumstances. It must be noted that this review is not SARS-CoV-2 specific and we explicitly do not intend to make any SARS-CoV-2 specific health claims in this article.

Methods and Findings: A qualitative, non-systematic literature review was conducted in Medline to identify literature describing preventive and therapeutic CIM approaches for strengthening mental and physical health. For a variety of CIM approaches clinical evidence was identified, indicating beneficial effects. CIM approaches include specific dietary measures and selected micronutrients, physical activity, techniques from Mind-Body Medicine, single botanicals or botanical compounds, and spending time in nature among others. The effects of CIM measures on conditions like obesity and hypertension are of special relevance here, as these conditions are considered as risk factors for a severe course of COVID-19. Moreover, a possibly direct effect of CIM approaches on immune functions and clinical parameters in respiratory tract infections, such as influenza, were identified. The findings of this review could be helpful for clinicians, patients, and the general population during the current pandemic when discussing and/or considering CIM options.

Conclusions: CIM offers a variety of preventive and therapeutic options for strengthening physical and mental resilience, which could also be useful in the current COVID-19 pandemic. The evidence of CIM approaches with a potential benefit in the COVID-19 pandemic in different areas is worth to be analyzed. While this qualitative review has several obvious limitations, it might serve as useful starting point for further research on this topic.

(1) Background: Improved surgical techniques and implants in total knee arthroplasty (TKA) have led to broader indications for surgical interventions of osteoarthritis of the knee. There is a growing young and active patient subgroup with high return to sports (RTS) expectations after TKA. The current lack of evidence regarding RTS capacity in this patient cohort, requires the consolidation of experts' opinions and experiences to address the special needs among these patients. The aim of this study was to assess current expert opinions in regard to preoperative patient assessment, surgical technique and decision-making and patient counseling for these patients. (2) Methods: We performed a survey among surgeons specialized in arthroplasty with a questionnaire designed to assess current recommendations, surgical techniques, and implant preferences as well as patient counseling in patients with high expectations for RTS after TKA. (3) Results: The majority of surgeons are in favor of return to low-impact sports after TKA within 3 to 6 months. Some even recommend return to high-impact sports. Despite improvement of surgical techniques and implants, we observed no clear preference for a single surgical technique or implant specification in active patients. (4) Conclusions: Current evidence for sports-associated complications after TKA is scarce. Despite a growing array of surgical techniques and implants, the available literature is still controversial with no single surgical technique or TKA design distinguishing itself clearly from others. Surgeons' recommendations are mostly based on their experience and training. Nonetheless, we observed growing faith in modern implants with some surgeons even recommending high-impact sports after TKA.

Human campylobacteriosis represents an infectious enteritis syndrome caused by Campylobacter species, mostly Campylobacter jejuni. Given that C. jejuni infections are rising worldwide and antibiotic treatment is usually not indicated, novel treatment options for campylobacteriosis are needed. Urolithin-A constitutes a metabolite produced by the human gut microbiota from ellagitannins and ellagic acids in berries and nuts which have been known for their health-beneficial including anti-inflammatory effects since centuries. Therefore, we investigated potential pathogen-lowering and immunomodulatory effects following oral application of synthetic urolithin-A during acute campylobacteriosis applying perorally C. jejuni infected, microbiota-depleted IL-10-/- mice as preclinical inflammation model. On day 6 post infection, urolithin-A treated mice harbored slightly lower pathogen loads in their ileum, but not colon as compared to placebo counterparts. Importantly, urolithin-A treatment resulted in an improved clinical outcome and less pronounced macroscopic and microscopic inflammatory sequelae of infection that were paralleled by less pronounced intestinal pro-inflammatory immune responses which could even be observed systemically. In conclusion, this preclinical murine intervention study provides first evidence that oral urolithin-A application is a promising treatment option for acute C. jejuni infection and paves the way for future clinical studies in human campylobacteriosis.

Obesity and bowel gas are known to impair image quality in abdominal ultrasound (US). The present study aims at identifying individual factors in B-mode US that influence contrast-enhanced US (CEUS) image quality to optimize further imaging workup of incidentally detected focal renal masses. We retrospectively analyzed renal CEUS of focal renal masses <= 4 cm performed at our center in 143 patients between 2016 and 2020. Patient and lesion characteristics were tested for their influence on focal and overall image quality assessed by two experienced radiologists using Likert scales. Effects of significant variables were quantified by receiver operating characteristics (ROC) curve analysis with area under the curve (AUC), and combined effects were assessed by binary logistic regression. Shrunken kidney, kidney depth, lesion depth, lesion size, and exophytic lesion growth were found to influence focal renal lesion image quality, and all factors except lesion size also influenced overall image quality. Combination of all parameters except kidney depth best predicted good CEUS image quality showing an AUC of 0.91 (p < 0.001, 95%-CI 0.863-0.958). The B-mode US parameters investigated can identify patients expected to have good CEUS image quality and thus help select the most suitable contrast-enhanced imaging strategy for workup of renal lesions.

We propose a mathematical model of the human cardiovascular system. The model allows one to simulate the main heart rate, its variability under the influence of the autonomic nervous system, breathing process, and oscillations of blood pressure. For the first time, the model takes into account the activity of the cerebral cortex structures that modulate the autonomic control loops of blood circulation in the awake state and in various stages of sleep. The adequacy of the model is demonstrated by comparing its time series with experimental records of healthy subjects in the SIESTA database. The proposed model can become a useful tool for studying the characteristics of the cardiovascular system dynamics during sleep.

The development of chimeric antigen receptor (CAR) T cell therapy has introduced a new and effective strategy to guide and promote the immune response against tumors in the clinic. More recently, in an attempt to enhance its utility, this method has been expanded to novel cell types. One of the more successful variants has proven to be the expression of CARs in Natural Killer (NK) cells (CAR-NK). Gene engineering NK cells to express an exogenous CAR receptor allows the innate anti-tumor ability of NK cells to be harnessed and directed against a target tumor antigen. In addition, the biology of NK cells allows the development of an allogeneic cell therapeutic product useable with most or all patient haplotypes. NK cells cause little or no graft versus host disease (GvHD) and are therefore suitable for development of an "off the shelf" therapeutic product. Initial trials have also shown that CAR-NK cells rarely cause cytokine release syndrome. However, despite their potential NK cells have proven to be difficult to engineer, with high sensitivity to apoptosis and low levels of gene expression. The creation of optimized methods to introduce genes into NK cells will promote the widespread application of CAR-NK in research laboratories and the clinics.

Aspergillus fumigatus (Af) frequently colonizes the respiratory tract of patients with cystic fibrosis (CF). Af is associated with loss of pulmonary function and allergic bronchopulmonary aspergillosis (ABPA), a hypersensitivity fungal lung disease. Environmental factors have impact on CF patients' lung function variation. The aim of this nationwide questionnaire survey was to investigate the amount of CF patients with frequent pet contact including pet species and to examine the potential impact of frequent pet contact on the occurrence of Af colonization and ABPA diagnosis in these patients. The survey was carried out in 31 German CF centers in 2018. A total of 1232 who completed the surveys were included, and statistical analysis was performed by chi-squared test. Within the study cohort 49.8% of subjects (n = 614; CF patients < 18years: 49.4%, n = 234; ≥ 18years: 50.1%, n = 380) reported frequent contact to pets, of which 60.7% reported frequent contact to dogs, 42.3% to cats and other animals. Of those with frequent pet contact, 71.8% (n = 441) had contact to one pet or more pets from the same family. Af colonization was not significantly associated with frequent pet contact. ABPA diagnosis was documented in 16.7% (n = 206) of all included CF patients and was significantly associated with frequent pet contact (18.9%, n = 116, p = 0.042), confirming previous single center examinations. Particularly, patients with frequent contact to dogs showed an increased ABPA prevalence of 21.3%. Frequent pet contact might be a risk factor for ABPA. CF patients who are sensitized to Af should be informed about the increased risk to develop an ABPA by frequent pet contact. Patients with recurrent onset of ABPA should be evaluated in terms of frequent pet contact.