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Congenital omphalocele is among the most common antenatally diagnosed anomalies. As additional abnormalities are found in majority of cases, antenatal investigations target the search for additional structural anomalies and genetic disorders, including aneuploidy. Antenatal management focuses on the assessment of fetal well-being. Unfortunately, antenatal prediction of postnatal and long-term outcomes represents 2 less well-documented but crucial facets of this pathology. A large part of the prognosis relies on aspects that are difficult to predict such as quality of life, neurological development, and autonomy, which cause significant anxiety in expectant parents.This article offers a comprehensive review of antenatal management of omphalocele with a specific focus on predictive factors and long-term outcomes.We conducted an extensive literature review targeting management of fetal omphalocele. We had a specific interest in factors predictive of fetal and neonatal outcome as well as long-term consequences of omphalocele. Fetuses with large defects and those containing the liver are at higher risk of having a complicated postnatal course. Neonates may experience pulmonary hypoplasia, pulmonary hypertension, and gastroesophageal reflux. In selected cases, motor and cognitive delay may be present, but the overall life-long prognosis and quality of life is good.A multidisciplinary approach should be encouraged after the diagnosis of fetal omphalocele. In addition to clinical team experience, antenatal counseling should be based on objective and gestational age-dependent criteria and should include long-term outcomes.

Purpose Osteopenia is common in postmenopausal women and effective interventions increasing or stabilizing bone mineral density (BMD) to prevent fractures are urgently needed. Methods Sixty-five postmenopausal women diagnosed with osteopenia (T-score between -1.0 and -2.5) were randomly assigned to either a vibration training group (VT), a resistance training group (RT), or a control group (CG). BMD T-score values (primary endpoint) were assessed at baseline (T0) and after 12 months (T12), secondary endpoints (muscle strength, postural control, and health-related quality of life) at baseline (T0), after 6 months (T6), after 12 months (T12), and as follow-up after 15 months (T15). Results After the intervention period, neither the VT nor the RT showed any significant changes in BMD T-score values compared to the CG. Isokinetic strength improved significantly within all training groups, with the exception of the flexors of VT at an angular velocity of 240°/s. Health-related quality of life as well as postural control improved significantly for the RT only. Conclusions We conclude that participants of all three groups were able to maintain their BMD. The improvements in quality of life and postural control after resistance training are nevertheless meaningful for postmenopausal osteopenic women and support the importance of regular loadings of the musculoskeletal system. This study was retrospectively registered in January 2022 at the DRKS (S00027816) as clinical trial.

OBJECTIVE Women experience higher risk for PTSD following trauma compared with men. Fluctuations in ovarian hormones might contribute to this greater vulnerability, given that estradiol is associated with affect and stress reactivity. Our objective was to test the relations between menstrual cycle-related changes in estradiol, affect, stress reactivity, and trauma-related symptoms. METHOD We assessed trauma-related symptoms in ethnically diverse naturally cycling women with a history of trauma during a clinical interview. Participants also completed a 10-day ecological momentary assessment (EMA) that included lower- and higher-estradiol phases. We tested associations between estradiol and PTSD symptoms and stress reactivity to a trauma reminder using Spearman correlation and Wilcoxon rank-sum tests. We tested the effect of menstrual cycle day on daily affect using multilevel modeling. RESULTS Estradiol was negatively associated with symptom severity (rs = -.36), and participants in low- versus high-estradiol cycle phases at interview had higher sympathetic (r = .35) and lower hypothalamic-pituitary-adrenal axis (r = .41) reactivity. Across the EMA period, participants showed a decrease in daily PTSD symptoms (b = -.39), negative (b = -.11) and positive (b = -.24) affect, and variability in daily valence (b = -.07) and arousal (b = -.08), from the low- to high-estradiol phase. CONCLUSIONS Consistent with prior evidence of more aversive affective experiences in low-estradiol states, lower estradiol was associated with higher trauma-related symptoms. In addition, trauma-exposed women showed a discordant pattern of stress reactivity to a trauma reminder, higher daily symptoms, and greater affective lability in a low-estradiol phase. Given that our sample consisted of high-functioning trauma-exposed women, these results should be replicated in women with PTSD. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

Summary Background Computer-assisted teaching is becoming increasingly more important to acquire new knowledge and skills in medical curricula. The consequence of gender-characteristic personality traits on academic performance in e‑learning examinations are difficult to forecast. This study investigated gender-related differences in examination behavior among undergraduate medical students taking a web-based quiz. Methods A total of 1315 4th grade medical students at the Medical University of Vienna completing the compulsory online moodle-based ECG quiz 2017/2018 were enrolled into this observational study. Individual data of examination behavior and quiz results as well as results of the final annual exam were extracted. Students were grouped into 10 strata according to academic performance. Variables between both sexes were compared using a nonparametrical test. Examination variables were correlated to performance. Results Of the total study population 686 (52%) were female and 629 (48%) were male. The time until the first attempt and number of attempts performed was comparable between both sexes, however female students spent more time on the first attempt compared to their male colleagues (1592 sec [Q1–Q3: 999–2536] vs 1405 sec [Q1–Q3: 828–2395], p = 0.002), suggesting a higher self-discipline and risk-aversity. There was no difference regarding quiz scores or final ECG examination scores between female and male students (p = 0.869 and p = 0.396). Students who accessed the quiz earlier and less time spent for the first attempt tended to perform better at the final examination (rs = 0.20, p s = −0.15, p Conclusions Gender-related differences in examination behavior already described for nononline based examinations are similarly observable in e‑learning. For this test, gender-immanent traits seem not to twist final examination results and impact academic performance.

Background Depression is an important nonmotor symptom of Parkinson's disease (PD) and has been associated with the motor symptoms in these individuals. Objectives To determine whether there are relationships between depressive symptoms and abnormalities in axial postural alignment and axial motor deficits, especially postural instability, and trunk rigidity in PD. Methods In this cross-sectional study, 65 individuals were evaluated using the Beck Depression Inventory-II (BDI-II) for the analysis of depressive symptoms and underwent a postural assessment of head, trunk, and hip sagittal alignment through computerized photogrammetry. The MDS-UPDRS was used to assess clinical aspects of PD, the Trunk Mobility Scale was used to assess axial rigidity, and the MiniBESTest to assess balance. To determine the relationship between depressive symptoms and postural alignment, multiple linear regression analysis was performed. Results The participants with depressive symptoms had more severe motor deficits as well as greater trunk rigidity and worse postural instability (p < 0.05). When the postural angles were compared between men and women using Student's t-test, it was found that men had greater flexion angles of the head (p = 0.003) and trunk (p = 0.017). Using multiple linear regression analysis corrected for the age and sex of the participants, we verified that the anterior trunk inclination was significantly larger in the PD population with depressive symptoms (R2 = 0.453, β = 0.116, and p = 0.045). Conclusion PD individuals with depressive symptoms have more severe flexed trunk posture, mainly in older men. Additionally, more severe depressive symptoms are associated with worsening postural instability, trunk rigidity and motor deficits in this population. Resumo Antecedentes A depressão é um sintoma não motor importante da doença de Parkinson (DP) e tem sido associada aos sintomas motores nesses indivíduos. Objetivos Determinar se existem relações entre sintomas depressivos e anormalidades no alinhamento postural axial e déficits motores axiais, especialmente instabilidade postural e rigidez de tronco na DP. Métodos Neste estudo transversal, 65 indivíduos foram avaliados pelo BDI-II para análise de sintomas depressivos e submetidos à avaliação postural do alinhamento sagital de cabeça, tronco e quadril por meio de fotogrametria computadorizada. A MDS-UPDRS avaliou os aspectos clínicos, TMS avaliou rigidez axial e o MiniBESTest equilíbrio. Para determinar a relação entre sintomas depressivos e alinhamento postural, realizou-se uma análise de regressão linear múltipla. Resultados Os participantes com sintomas depressivos apresentaram déficits motores mais graves, bem como maior rigidez de tronco e pior instabilidade postural (p < 0,05). Quando comparados os ângulos posturais entre homens e mulheres pelo teste t de Student, verificou-se que os homens apresentaram maiores graus de flexão da cabeça (p = 0,003) e do tronco (p = 0,017). Por meio da análise de regressão linear múltipla corrigida para a idade e sexo dos participantes, verificamos que a inclinação anterior do tronco foi significativamente maior nos indivíduos com DP com sintomas depressivos do que sem sintomas depressivos (R2 = 0,453, β = 0,116 e p = 0,045) Conclusão Indivíduos com DP com sintomas depressivos apresentam postura de tronco flexionado mais severa, principalmente em homens mais idosos. Além disso, os sintomas depressivos mais graves pioram significativamente a instabilidade postural, a rigidez do tronco e os déficits motores nessa população.

Thiopurines are in widespread clinical use for the treatment of immunological disorders and certain cancers. However, treatment failure due to resistance or adverse drug reactions are common, asking for new therapeutic strategies. We investigated the potential of 6-thioguanosine monophosphate (6sGMP) prodrugs to overcome resistance to 6-thioguanine. We successfully developed synthetic routes toward diverse 6sGMP prodrugs, tested their proliferation inhibitory potential in different cell lines, and examined their mode of action. Our results show that 4-acetyloxybenzyl- and

Early pregnancy is frequently accompanied by abnormal symptoms such as pelvic pain and metrorrhagia. In these situations, it is quite frequent to be unable to identify the pregnancy and in particular its location, even if the pregnancy test is clearly positive. Many clinical, biological and ultrasound approaches have been proposed to try to predict the location and development of the suspected pregnancy, without the individualization of a truly reliable tool. Currently the HCG dosage at 48 heures-interval remains one of the best tools available, but it is challenged by mathematical models such as the M6 model. The M6 model has shown in our experience a very good predictive value with also an ability to reduce the follow-up of patients with low progressive risk, thus allowing a reduction in costs and anxiety for patients and caregivers.Le début des grossesses est fréquemment accompagné de symptômes anormaux tels que douleurs pelviennes et métrorragies. Dans ces situations, il n’est pas rare de ne pas pouvoir identifier la grossesse et, en particulier, sa localisation même si le test de grossesse est nettement positif. De nombreuses approches clinique, biologique et échographique ont été proposées pour essayer de prédire la localisation et l’évolutivité de la grossesse suspectée, sans individualisation d’un outil vraiment fiable. Actuellement, le dosage de HCG à 48 heures d’intervalle reste un des meilleurs outils disponibles, mais il est concurrencé par des modèles mathématiques comme le M6. Ce dernier a démontré, selon notre expérience, une très bonne valeur prédictive avec aussi une capacité à réduire le suivi des patientes à faible risque évolutif, en permettant ainsi une baisse des coûts et de l’anxiété des patientes et soignants.

Ileocolic resection for Crohn's disease traditionally does not include a high ligation of the ileocolic pedicle, and most commonly is performed with a stapled side-to-side ileocolic anastomosis. The mesentery has recently been implicated in the pathophysiology of Crohn's disease. Two techniques have been developed and are associated with reduced postoperative recurrence: the Kono-S anastomosis that excludes diseased mesentery and extended mesenteric excision that resects diseased mesentery. We aimed to assess the technical feasibility and safety of a novel combination of techniques: mesenteric excision and exclusion.This initial report is a single-center descriptive study of consecutive adults who underwent mesenteric excision and exclusion for primary or recurrent ileocolic Crohn's disease from September 2020 to June 2021. Medication exposure and endoscopic balloon dilation before surgery were recorded. Phenotype was classified using the Montreal Classification. Thirty-day outcomes were reported. A video of the mesenteric excision and exclusion including the Kono-S anastomosis is presented.Twenty-two patients with ileocolic Crohn's disease underwent mesenteric excision and exclusion: 100% had strictures, 59% had fistulas, 81% were on biologics, and 27% had previous ileocolic resection(s). Seventy-two percent underwent laparoscopic procedures, a mesenteric defect was closed in 86%, omental flaps were fashioned in 77%, and 3 patients were diverted. Median operative time was 175 minutes. Median postoperative stay was 4 days. At 30 days, there were 2 readmissions for reintervention: 1 seton placement and 1 percutaneous drainage of a sterile collection. There were no cases of intra-abdominal sepsis or anastomotic leak.Mesenteric excision and exclusion represents an innovative, progressive, and promising approach that appears to be highly feasible and safe. Further study is warranted to determine if mesenteric excision and exclusion is associated with reduced postoperative recurrence of ileocolic Crohn's disease.

Objectives Pedunculated lipofibromas are soft, compressible, skin-colored nodules that typically present as an acquired solitary lesion, predominantly located on the buttocks and thighs. We aimed to differentiate between pedunculated lipofibromas and nevus lipomatosus superficialis. Although benign, this may be important as treatment options vary. Methods We describe 3 cases of solitary pedunculated lipofibromas occurring in older, obese adults that required clinicopathologic correlation for the correct diagnosis. Results The histopathologic features of pedunculated lipofibromas include a broad-based lesion with aggregates of mature adipocytes extending upwards into the dermis without an associated inflammatory infiltrate. The primary histopathologic differential diagnoses include fibroepithelial polyps with adipocytes and nevus lipomatosus superficialis, which is more frequently found in children or young adults and is typically characterized clinically by multiple lesions with a cerebriform to verrucoid surface. Conclusions While the precise relationship between pedunculated lipofibromas and nevus lipomatosus is still unknown, we propose using pedunculated lipofibroma as a more specific clinical term to refer to solitary pedunculated or broad-based fatty lesions with a smooth surface that occur in older patients and in a wide anatomic distribution.

ObjectiveExploration of a novel therapeutic drug monitoring (TDM) strategy to personalise use of ibuprofen for closure of patent ductus arteriosus (PDA) in preterm neonates.DesignProspective, single-centre, open-label, pharmacokinetics study in preterm neonates.SettingNeonatal intensive care unit at McMaster Children’s Hospital.PatientsNeonates with a gestational age ≤28+6 weeks treated with oral ibuprofen for closure of a PDA.MethodsPopulation pharmacokinetic parameters, concentration-time profiles and exposure metrics were obtained using pharmacometric modelling and simulation.Main outcome measureAssociation between ibuprofen plasma concentrations measured at various sampling time points on the first day of treatment and attainment of the target exposure over the first 3 days of treatment (AUC0–72h >900 mg·hour/L).ResultsTwenty-three preterm neonates (median birth weight 780 g and gestational age 25.9 weeks) were included, yielding 155 plasma ibuprofen plasma samples. Starting from 8 hours’ postdose on the first day, a strong correlation between ibuprofen concentrations and AUC0–72h was observed. At 8 hours after the first dose, an ibuprofen concentration >20.5 mg/L was associated with a 90% probability of reaching the target exposure.ConclusionWe designed a novel and practical TDM strategy and have shown that the chance of reaching the target exposure (AUC0–72h >900 mg·hour/L) can be predicted with a single sample collection on the first day of treatment. This newly acquired knowledge can be leveraged to personalise ibuprofen dosing regimens and improve the efficacy of ibuprofen use for pharmacological closure of a PDA.

SUMMARY The ATP-dependent chromatin remodeling factor CHD1 is essential for the assembly of variant histone H3.3 into paternal chromatin during sperm chromatin remodeling in fertilized eggs. It remains unclear, however, if CHD1 has a similar role in normal diploid cells. Using a specifically tailored quantitative mass spectrometry approach, we show that Chd1 disruption results in reduced H3.3 levels in heads of Chd1 mutant flies. Chd1 deletion perturbs brain chromatin structure in a similar way as H3.3 deletion and leads to global de-repression of transcription. The physiological consequences are reduced food intake, metabolic alterations, and shortened lifespan. Notably, brain-specific CHD1 expression rescues these phenotypes. We further demonstrate a strong genetic interaction between Chd1 and H3.3 chaperone Hira. Thus, our findings establish CHD1 as a factor required for the assembly of H3.3-containing chromatin in adult cells and suggest a crucial role for CHD1 in the brain as a regulator of organismal health and longevity., Graphical abstract, In brief In postmitotic brain cells, histones lost during transcription must be replenished by replication-independent mechanisms. Schoberleitner et al. show that the chromatin remodeling factor CHD1 is involved in this process. CHD1 loss results in reduced histone H3.3 levels, global chromatin perturbation, transcriptional dysregulation, and defects in feeding behavior, metabolism, and lifespan.

Background and Aims Emerging evidence points to a link between creeping fat and the pathogenesis of Crohn’s disease [CD]. Non-invasive assessment of the severity of creeping fat on cross-sectional imaging modality has seldom been investigated. This study aimed to develop and characterize a novel mesenteric creeping fat index [MCFI] based on computed tomography [CT] in CD patients. Methods MCFI was developed based on vascular findings on CT in a retrospective cohort [n = 91] and validated in a prospective cohort [n = 30]. The severity of creeping fat was graded based on the extent to which mesenteric fat extended around the intestinal circumference using the vessels in the fat as a marker. The accuracy of MCFI was assessed by comparing it with the degree of creeping fat observed in surgical specimens. The relationship between MCFI and fibrostenosis was characterized by determining if these correlated. The accuracy of MCFI was compared with other radiographic indices [i.e. visceral to subcutaneous fat area ratio and fibrofatty proliferation score]. Results In the retrospective cohort, MCFI had moderate accuracy in differentiating moderate–severe from mild fibrostenosis (area under the receiver operating characteristic [ROC] curve [AUC] = 0.799; p = 0.000). ROC analysis in the retrospective cohort identified a threshold MCFI of > 3 which accurately differentiated fibrostenosis severity in the prospective cohort [AUC = 0.756; p = 0.018]. An excellent correlation was shown between MCFI and the extent of fat wrapping in specimens in the prospective cohort [r = 0.840, p = 0.000]. Neither visceral to subcutaneous fat area ratio nor fibrofatty proliferation score correlated well with the degree of intestinal fibrosis. Conclusions MCFI can accurately characterize the extent of mesenteric fat wrapping in surgical specimens. It may become another non-invasive measure of CD fibrostenosis.

A role for addiction psychiatry in aesthetic treatment-seeking behavior has been evidenced for ultraviolet light tanning.We aim to demonstrate an initial proof of concept for the presence of addictive behaviors in cosmetic procedure use.Adults visiting a cosmetic dermatology practice with history of at least 1 cosmetic procedure and consideration of at least 1 cosmetic procedure in the past 12 months were included. Two previously validated instruments in the detection of alcohol use disorder, the Cut Down, Annoyed, Guilty, Eye-Opener (CAGE) questionnaire, and Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-V) criteria were modified to evaluate participants for a substance-related disorder (SRD) in cosmetic procedures.Of 153 adults, 34 (22.2%) met modified CAGE criteria, and 40 (26.1%) met modified DSM-V criteria. Results from both instruments were significantly associated (P .0002). Significant differences in consideration and use of cosmetic treatments were found in SRD positive versus negative groups (P .0001 and P = .009, respectively).Preliminary criteria for SRD in cosmetic procedure use in this study has not yet been validated.A type of SRD involving cosmetic procedures may exist, and qualifying individuals may have increased cosmetic treatment use. Future efforts to rigorously validate an instrument for SRD detection in cosmetic procedures use are warranted for future research and clinical application.

Aims This study aims to investigate the efficacy of transcutaneous tibial nerve home stimulation for overactive bladder (OAB) in women with Parkinson's disease (PD). Methods The current study is a prospective, randomized, double-blind, sham-controlled trial. Home intervention was carried out and assessments were conducted at a tertiary hospital in South Brazil. Women with PD and OAB symptoms were included in the study. Patients were randomly divided into two groups: (1) stimulation and (2) sham. Both groups underwent intervention at home for 12 weeks. Patients were evaluated at baseline and at 12 weeks (end of intervention), 30- and 90-day follow-up. The primary outcome was the mean reduction in the number of urgency incontinence episodes, and secondary outcomes included daytime and nighttime urinary frequency, urinary urgency episodes, use of pad (reported in a 24-h bladder diary), OAB-V8 and King's Health Questionnaire scores, and maintenance of symptom relief after discontinuation of the intervention. Results In total, 30 consecutive patients completed the study (15/group). The stimulation group showed a reduction in nighttime urinary frequency (0.9 ± 0.6), urinary urgency (1.0 ± 1.2), urgency incontinence episodes (0.5 ± 0.6), use of pads (1.3 ± 1.2), and OAB-V8 (1.3 ± 1.2) and King's Health Questionnaire scores. In a 30-day and 90-day follow-up, 8 (53.3%) and 5 (33.3%) stimulation patients, respectively, reported full maintenance of symptom relief after discontinuation of the intervention. Stimulation patients presented a statistically significant improvement of symptoms as compared with sham patients (p = .001). Conclusions Transcutaneous tibial nerve home stimulation can be used in clinical practice as an effective nonpharmacological resource for the reduction of OAB symptoms in women with PD, and the resulting relief seems to persist in the follow-up (30 and 90 days).

The question about how to resume typical orthopaedic care during a pandemic, such as coronavirus disease 2019, should be framed not only as a logistic or safety question but also as an ethical question. The current published guidelines from surgical societies do not explicitly address ethical dilemmas, such as why public health ethics requires a cessation of nonemergency surgery or how to fairly allocate limited resources for delayed surgical care. We propose ethical guidance for the resumption of care on the basis of public health ethics with a focus on clinical equipoise, triage tiers, and flexibility. We then provide orthopaedic surgery examples to guide physicians in the ethical resumption of care.

The Coronavirus disease 2019 pandemic has been an unprecedented challenge to healthcare systems and clinicians around the globe. As the virus has spread, critical questions arose about how to best deliver health care in emergency situations where material and personnel resources become scarce. Clinicians who excel at caring for the individual patient at the bedside are now being reoriented into a system where they are being asked to see the collective public as their responsibility. As such, the clinical ethics that clinicians are accustomed to practicing are being modified by a framework of public health ethics defined by the presence of a global pandemic. There are many unknowns about Coronavirus disease 2019, which makes it difficult to provide consistent recommendations and guidelines that uniformly apply to all situations. This lack of consensus leads to the clinicians' confusion and distress. Real-life dilemmas about how to allocate resources and provide care in hotspot cities make explicit the need for careful ethical analysis, but the need runs far deeper than that; even when not trading some lives against others, the responsibilities of both individual clinicians and the broader healthcare system are changing in the face of this crisis.

Objective Individuals with Parkinson's disease (PD) and freezing of gait (FOG) present peripheral and central sensitivity disturbances that impair motor performance. This study aimed to investigate long-term effects of plantar sensory stimulation on brain activity, brain connectivity, and gait velocity of individuals with PD and FOG. Methods Twenty-five participants were enrolled in this clinical trial (NCT02594540). Plantar sensory stimulation was delivered using the Automated Mechanical Peripheral Stimulation therapy (AMPS). Volunteers were randomly assigned to real or placebo AMPS groups and received eight sessions of treatment. The primary outcome was brain activity (task-based fMRI-active ankle dorsi-plantar flexion). Secondary outcomes were brain connectivity (resting state-RS fMRI) and gait velocity. fMRI was investigated on the left, right, and mid-sensory motor regions, left and right basal ganglia. Results No changes in brain activity were observed when task-based fMRI was analyzed. After real AMPS, RS functional connectivity between basal ganglia and sensory-related brain areas increased (insular and somatosensory cortices). Gait velocity also increased after real AMPS. A positive correlation was found between gait velocity and the increased connectivity between sensory, motor and supplementary motor cortices. Conclusion Plantar sensory stimulation through AMPS was not able to modify brain activity. AMPS increased the RS brain connectivity mainly in areas related to sensory processing and sensorimotor integration. Plantar stimulation could be a way to improve plantar sensitivity and consequently ameliorate gait performance. However, the mechanisms behind the way AMPS influences brain pathways are still not completely known.

Summary Purpose Subthalamic nucleus deep brain stimulation (STN-DBS) parameters, for example the frequency of stimulation, seem to affect speech and voice aspects. However, this influence is not well understood. This study aimed to investigate the impact of low- and high-frequency STN-DBS on voice and speech for people with Parkinson's disease. Methods Nineteen individuals with Parkinson's disease who received bilateral STN-DBS were assessed for motor performance (Unified Parkinson's Disease Rating Scale-III), perceptual evaluation of voice (grade, roughness, breathiness, asthenia, strain, and instability [GRBASI]), dysarthria assessment, and computerized acoustic analysis of voice upon receiving low-frequency (60 Hz) and high-frequency (130 Hz) STN-DBS. Results In the GRBASI protocol, asthenia, and instability were significantly better at 130 Hz of stimulation. In the dysarthria evaluation, the phonation aspect, articulation, and grade of dysarthria showed deterioration at the same high-frequency condition. There was no significant difference for any vocal acoustic measures. Conclusion The high-frequency of STN-DBS may affect speech and voice differently, leading to an amelioration of the vocal production, but with adverse effects in the speech control.

Background The implementation of quality of life (QoL) concepts in routine care, is still an open matter. We followed the Medical Research Council framework for complex interventions to implement a model of QoL diagnosis and therapeutic options, and investigated its effectiveness in patients with colorectal cancer. Methods This randomised, single-blind, multicentre, clinical trial enrolled patients diagnosed with primary colorectal cancer aged 18 years or older who were surgically treated in one of four recruiting hospitals in Germany. All patients received aftercare from one of 178 coordinating practitioners (CPs) who had access to 75 healthcare professionals providing tailored therapies. QoL was measured (EORTC QLQ-C30, QLQ-CR29) in all patients after surgery (baseline) and during aftercare (3, 6, 12, 18 months). Patients were randomised (1:1) into two groups: a care pathway, including QoL-profiles consisting of 13 QoL scales plus specific therapeutic recommendations forwarded to the patient’s CP or standard postoperative care adhering to the German national guideline for colorectal cancer (control). The primary endpoint was the proportion of patients in each group with a need for QoL therapy 12 months after surgery. Analyses were done in the intention-to-treat population. This trial is registered with ClinicalTrials.gov , number NCT02321813 and closed to accrual. Findings Between Jan 13, 2014, and Oct 28, 2015, 220 patients were enrolled and randomly assigned (n = 110 per group). At baseline (in hospital after surgery), a need for QoL therapy was diagnosed in 92/103 (89%) of intervention and 86/104 (83%) of control group patients. At 12 months (primary endpoint) the proportion of patients with a need for QoL therapy was 35/83 (42%; 95% CI 31–54%) in the intervention group versus 50/87 (57%; 95% CI: 46–68%) in the control group (p = 0·046, number needed to treat = 7; 95% CI 3–225). Interpretation Patients profited from the diagnosis of QoL deficits and tailored therapeutic options in their treatment of colorectal cancer. This trial confirmed the results of a previous RCT in breast cancer patients. The implementation of QoL concepts should become standard in treatment guidelines on cancer care. Funding Federal Ministry of Education and Research (BMBF; grant no. 01GY1339). Clinical trial information NCT02321813.

Low fruit and vegetable (F&V) intake, sedentary behavior, excessive alcohol consumption, and smoking are risk factors for the development of non-communicable diseases. This study describes the patterns and factors of nutrition (F&V and alcohol intake), physical activity (PA), obesity, and other chronic diseases of 10,053 adult farmers (52.7% female) in Austria, based on the cross-sectional survey from the Austrian Social Insurance Institution for the Self-Employed and compared with the results of the general Austrian population from 2019 (n = 14,606; 53.7% female). Compared to the general Austrian population, farmers showed a higher prevalence of overweight and obesity (42.8% vs. 36.5%; 18.8% vs. 17.1%), as well as hypertension, hypercholesterolemia, and diabetes mellitus. Additionally, farmers ate less F&V (0 servings/day 39.7% vs. 14.0%; 1–4 servings/day 55.5% vs. 80.8%) and only 4.8% vs. 5.1% (p < 0.001) fulfilled the F&V recommendations. Lower participation in endurance training (38.3% vs. 52.1%) was found, whereas farmers did more strength training (64.1% vs. 27.6%). Those who failed to fulfill the PA recommendations reported worse health status (OR: 3.14; 95%-CI: 2.08–4.76) and a higher chance for obesity (OR: 1.68; 95%-CI: 1.38–2.05). Since obesity rates among farmers are high and recommendations have rarely been met, every opportunity should be taken to promote healthy eating and adequate PA.

Risk factors for intervention in terminal ileal (TI) stricturing Crohn's disease (CD) are poorly defined. Novel and rigorous definitions for TI strictures recently became available.We aimed to describe the rates of symptoms or need for endoscopic balloon dilation (EBD) or surgery as well as risk factors of progression in a well-defined stricturing CD cohort.Consecutive adult patients with non-penetrating stricturing TI CD, as defined by centrally-read magnetic resonance enterography CONSTRICT criteria, were separated into a derivation and validation cohort. Clinical and imaging characteristics were collected following prespecified scoring conventions. Primary outcome was a composite endpoint of EBD or surgery ("intervention"). Multivariable analysis was performed.Eighty-six patients (48.8% female, median age 36 years) met selection criteria, 17.4% had prior EBD, 59.3% previously received biologics and 58.1% of strictures were anastomotic. Median follow-up was 63.4 [95% CI: 57, 68.9] months. In the derivation cohort, at 12 and 48 months, 26% and 45% of patients had intervention, respectively. Multivariable analysis showed obstructive symptoms (Hazard ratio [HR] 1.444; 95% CI 1.126-1.852), stricture duration (HR 0.974; 95% CI, 0.954-0.995) and length (HR 1.039; 95% CI, 1.011-1.069) predicted intervention. The concordance index for split-sample validation was 0.74 and 0.67, respectively. Biologics were not associated with intervention. An online risk calculator was constructed.In patients with TI stricturing CD, 26% and 45% required intervention at 1 and 4 years. Obstructive symptoms, stricture duration and length were independent and validated predictors of the need for intervention. These findings are important for clinical practice and aid in the design of future trials for CD strictures.

Drug reaction with eosinophilia and systemic symptoms (DRESS) is a rare, drug-induced severe adverse reaction that usually occurs 3-6 weeks after initial exposure to certain drugs. It affects mainly adults and children to a lesser extent. Clinical features include fever, facial oedema, generalized skin rash, lymphadenopathy, haematological abnormalities and internal organ involvement. The objective was to investigate the clinical and laboratory features of patients with DRESS in our centre.We retrospectively describe and analyse 19 cases of DRESS whose diagnosis was based on the RegiSCAR criteria (≥6 points) that occurred from January 2009 to December 2019.Patient age ranged from 4 to 76 years (4 children/15 adults); 10 were female (52.3%). The most common culprit drugs were antibiotics (74%) and anticonvulsants (21%). The most common comorbidities were epilepsy (26%) and hypertension (26%). All patients developed cutaneous manifestations and of those, 58% presented facial oedema. Liver function tests, urea/creatinine and troponin elevation were present in 74, 32 and 42%, respectively. The median time to develop the skin rash after the drug exposure was 3.7 weeks (interquartile range 2.4-4.2 wk). Eosinophilia (≥0.7 × 10DRESS is a serious condition with significant morbidity and mortality, which requires more research for a better understanding.

The Y chromosome is a valuable genetic marker for studying the origin and influence of paternal lineages in populations. In this study, we conducted Y-chromosomal lineage-tracing in Arabian horses. First, we resolved a Y haplotype phylogeny based on the next generation sequencing data of 157 males from several breeds. Y-chromosomal haplotypes specific for Arabian horses were inferred by genotyping a collection of 145 males representing most Arabian sire lines that are active around the globe. These lines formed three discrete haplogroups, and the same haplogroups were detected in Arabian populations native to the Middle East. The Arabian haplotypes were clearly distinct from the ones detected in Akhal Tekes, Turkoman horses, and the progeny of two Thoroughbred foundation sires. However, a haplotype introduced into the English Thoroughbred by the stallion Byerley Turk (1680), was shared among Arabians, Turkomans, and Akhal Tekes, which opens a discussion about the historic connections between Oriental horse types. Furthermore, we genetically traced Arabian sire line breeding in the Western World over the past 200 years. This confirmed a strong selection for relatively few male lineages and uncovered incongruences to written pedigree records. Overall, we demonstrate how fine-scaled Y-analysis contributes to a better understanding of the historical development of horse breeds.

Background The burden of long-term symptoms (ie, long COVID) in patients after mild COVID-19 is debated. Within a cohort of healthcare workers (HCWs), frequency and risk factors for symptoms compatible with long COVID are assessed. Methods Participants answered baseline (August/September 2020) and weekly questionnaires on SARS-CoV-2 nasopharyngeal swab (NPS) results and acute disease symptoms. In January 2021, SARS-CoV-2 serology was performed; in March, symptoms compatible with long COVID (including psychometric scores) were asked and compared between HCWs with positive NPS, seropositive HCWs without positive NPS (presumable asymptomatic/pauci-symptomatic infections), and negative controls. The effect of time since diagnosis and quantitative anti-spike protein antibodies (anti-S) was evaluated. Poisson regression was used to identify risk factors for symptom occurrence. Results Of 3334 HCWs (median, 41 years; 80% female), 556 (17%) had a positive NPS and 228 (7%) were only seropositive. HCWs with positive NPS more frequently reported ≥1 symptom compared with controls (73% vs 52%, P 6 months ago; anti-S titers correlated with high symptom scores. Acute viral symptoms in weekly questionnaires best predicted long-COVID symptoms. Physical activity at baseline was negatively associated with neurocognitive impairment and fatigue scores. Conclusions Seropositive HCWs without positive NPS are only mildly affected by long COVID. Exhaustion/burnout is common, even in noninfected HCWs. Physical activity might be protective against neurocognitive impairment/fatigue symptoms after COVID-19.

Background Timely acquisition of 12-lead Electrocardiogram (ECG) in the emergency department (ED) is crucial and recommended by current guidelines. Objectives To evaluate the association of medical history of coronary artery disease (hCAD) on door-to-ECG time in the ED. Methods In this single center, retrospective cohort study, patients admitted to ED for cardiac evaluation were grouped according to hCAD and no hCAD. The primary outcome was door-to-ECG time. A multivariate analysis adjusted for the cofounders sex, age, type of referral and shift was performed to evaluate the association of hCAD with door-to-ECG time. Results 1101 patients were included in this analysis. 362 patients (33%) had hCAD. Patients with hCAD had shorter door-to-ECG time (20 min. [Inter Quartile Range [IQR] 13–30] vs. 22 min. [IQR 14–37]; p p = 0.007; 95% confidence Interval [CI] − 5.16 to − 0.84 min]). Conclusion In this single center registry, hCAD was associated with shorter door-to-ECG time. In patients presenting in ED for cardiac evaluation, timely ECG diagnostic should be facilitated irrespective of hCAD.

Purpose Neoadjuvant radiochemotherapy (RCTH) is proven to be highly effective in the treatment of esophageal cancer (EC). We investigated oncological outcome and morbidity in patients treated with a modified CROSS protocol followed by esophagectomy at our institution. Methods Patients with EC receiving neoadjuvant RCTH with paclitaxel and carboplatin and concurrent radiotherapy (46 Gy) followed by esophagectomy were included in this retrospective analysis. Histopathological response, overall survival (OS) and recurrence-free interval (RFI) as well as perioperative morbidity were investigated. Results Thirty-six patients (86.1% male, mean age 61.3 years, standard deviation 11.52) received neoadjuvant RCTH before surgery. Sixteen patients (44.4%) were treated for squamous cell cancer, whereas 20 patients (55.6%) had adenocarcinoma. The majority (75%) underwent abdominothoracic esophageal resection. Major complications occurred in 7 patients (19.5%) including anastomotic leakage in 4 patients (11.1%). A R0 resection was achieved in 97.2%. A complete pathological remission was seen in 13 patients (36.1%). Major response, classified as Mandard tumor regression grade 1 and 2, was found in 26 patients (72.2%). Median OS and RFI were not reached. Conclusions Neoadjuvant radiotherapy with 46 Gy and concomitant chemotherapy with paclitaxel and carboplatin for the treatment of locally advanced esophageal carcinoma is safe and effective. The results of this modified radiotherapy protocol are encouraging and should be considered in future patient treatment and study designs.

Purpose The aims of this study were to evaluate a semi-automatic segmentation software for assessment of ablation zone geometry in computed tomography (CT)-guided microwave ablation (MWA) of liver tumors and to compare two different MWA systems. Material and Methods 27 patients with 40 hepatic tumors (primary liver tumor n = 20, metastases n = 20) referred for CT-guided MWA were included in this retrospective IRB-approved study. MWA was performed using two systems (system 1: 915 MHz; n = 20; system 2: 2.45 GHz; n = 20). Ablation zone segmentation and ellipticity index calculations were performed using SAFIR (Software Assistant for Interventional Radiology). To validate semi-automatic software calculations, results (2 perpendicular diameters, ellipticity index, volume) were compared with those of manual analysis (intraclass correlation, Pearson’s correlation, Mann–Whitney U test; p

Intestinal strictures are a frequent complication in patients with Crohn’s Disease (CD) and the presence of fibrosis within strictures impacts the therapeutic treatment approach. Here, we evaluate quantitative phase imaging (QPI) using digital holographic microscopy (DHM) for the evaluation of fibrosis within CD strictures. 30 full thickness resection specimens were obtained from non-stenotic and stenotic tissue areas of 15 CD patients. Cryostat sections were analyzed by DHM to measure the spatial distribution of the refractive index (RI) to quantify tissue density. Complementary, histopathological evaluation of H&E staining and immunofluorescence (IF) targeting fibrosis markers served as the gold standard. Moreover, tissue stiffness was evaluated by elastography. RI values assessed by DHM were significantly higher in stenotic compared to non-stenotic tissue areas (p

Animal models recapitulating features of chronic colitis, such as ulcerative colitis, Crohn’s disease, or HIV infection, are critical to study disease pathogenesis and test novel therapeutics. In this study, we used a proteomics approach to explore the molecular intestinal response in two rhesus macaque (RM) animal models of experimentally induced colitis using dextran sulfate sodium (DSS) and simian immunodeficiency virus (SIV) infection. Proteomic analysis detected more than 2500 proteins in colonic tissue collected from 30 RMs. Differential protein expression analysis revealed a protein expression pattern in DSS-treated RMs resembling the proteome of human ulcerative colitis. In a group of 12 DSS-treated RMs compared to 6 with no treatment, decrease in expression of proteins related to mitochondrial energy metabolism, including fatty acid metabolism was noted, while innate immune activation pathways, including complement and coagulation proteins were upregulated. SIV infection of RMs resulted in increased innate immune responses related to viral defense. Proteomic signatures of barrier damage were apparent in both DSS treatment or SIV infection. These results demonstrate that DSS treatment in a non-human primate model resembles features of human ulcerative colitis, making this a promising tool to study important immunological mechanisms in inflammatory bowel disease.

Gait and postural control deficiencies in Parkinson's disease (PD) involve several specific motor aspects. The aim of this study was to identify and compare the main changes in gait kinematics and postural control with dopaminergic loss in the striatum region. This is a cross-sectional study that included 42 individuals with PD at different motor stages, according to the Hoehn & Yahr scale (H&Y). Motor subsection of the Movement Disorder Society-Unified Parkinson Disease Rating Scale-part III (MDS-UPDRS III) was used to evaluate general motor aspects. Gait kinematics was assessed using a three-dimensional motion capture system. Postural control was assessed by stabilometry using force platforms. Dopamine depletion was verified through 99mTc-TRODAT-1 (SPECT-CT) examination. We included 12, 15 and 15 individuals classified as H&Y I, II and III, respectively. We identified worse values of dopamine transporter uptake, MDS-UPDRS III, gait parameters (velocity, step length and stride length) and center of pressure displacement as the disease progressed. Our results indicate that higher dopaminergic loss and gait and postural control deficits occur between the H&Y levels II and III.

Purpose: PD-(L)1–blocking antibodies have clinical activity in metastatic non–small cell lung cancer (NSCLC) and mediate durable tumor remissions. However, the majority of patients are resistant to PD-(L)1 blockade. Understanding mechanisms of primary resistance may allow prediction of clinical response and identification of new targetable pathways. Experimental Design: Peripheral blood mononuclear cells were collected from 35 patients with NSCLC receiving nivolumab monotherapy. Cellular changes, cytokine levels, gene expression, and polymorphisms were compared between responders and nonresponders to treatment. Findings were confirmed in additional cohorts of patients with NSCLC receiving immune checkpoint blockade. Results: We identified a genetic variant of a killer cell immunoglobulin-like receptor (KIR) KIR3DS1 that is associated with primary resistance to PD-1 blockade in patients with NSCLC. This association could be confirmed in independent cohorts of patients with NSCLC. In a multivariate analysis of the pooled cohort of 135 patients, the progression-free survival was significantly associated with presence of the KIR3DS1 allele (HR, 1.72; 95% confidence interval, 1.10–2.68; P = 0.017). No relationship was seen in cohorts of patients with NSCLC who did not receive immunotherapy. Cellular assays from patients before and during PD-1 blockade showed that resistance may be due to NK-cell dysfunction. Conclusions: We identified an association of the KIR3DS1 allelic variant with response to PD-1–targeted immunotherapy in patients with NSCLC. This finding links NK cells with response to PD-1 therapy. Although the findings are interesting, a larger analysis in a randomized trial will be needed to confirm KIRs as predictive markers for response to PD-1–targeted immunotherapy.

Patients with Crohn’s disease commonly develop ileal and less commonly colonic strictures, containing various degrees of inflammation and fibrosis. While predominantly inflammatory strictures may benefit from a medical anti-inflammatory treatment, predominantly fibrotic strictures currently require endoscopic balloon dilation or surgery. Therefore, differentiation of the main components of a stricturing lesion is key for defining the therapeutic management. The role of endoscopy to diagnose the nature of strictures is limited by the superficial inspection of the intestinal mucosa, the lack of depth of mucosal biopsies and by the risk of sampling error due to a heterogeneous distribution of inflammation and fibrosis within a stricturing lesion. These limitations may be in part overcome by cross-sectional imaging techniques such as ultrasound, CT and MRI, allowing for a full thickness evaluation of the bowel wall and associated abnormalities. This systematic literature review provides a comprehensive summary of currently used radiologic definitions of strictures. It discusses, by assessing only manuscripts with histopathology as a gold standard, the accuracy for diagnosis of the respective modalities as well as their capability to characterise strictures in terms of inflammation and fibrosis. Definitions for strictures on cross-sectional imaging are heterogeneous; however, accuracy for stricture diagnosis is very high. Although conventional cross-sectional imaging techniques have been reported to distinguish inflammation from fibrosis and grade their severity, they are not sufficiently accurate for use in routine clinical practice. Finally, we present recent consensus recommendations and highlight experimental techniques that may overcome the limitations of current technologies.

Analysis of the Y chromosome is the best-established way to reconstruct paternal family history in humans. Here, we applied fine-scaled Y-chromosomal haplotyping in horses with biallelic markers and demonstrate the potential of our approach to address the ancestry of sire lines. We de novo assembled a draft reference of the male-specific region of the Y chromosome from Illumina short reads and then screened 5.8 million basepairs for variants in 130 specimens from intensively selected and rural breeds and nine Przewalski's horses. Among domestic horses we confirmed the predominance of a young'crown haplogroup' in Central European and North American breeds. Within the crown, we distinguished 58 haplotypes based on 211 variants, forming three major haplogroups. In addition to two previously characterised haplogroups, one observed in Arabian/Coldblooded and the other in Turkoman/Thoroughbred horses, we uncovered a third haplogroup containing Iberian lines and a North African Barb Horse. In a genealogical showcase, we distinguished the patrilines of the three English Thoroughbred founder stallions and resolved a historic controversy over the parentage of the horse 'Galopin', born in 1872. We observed two nearly instantaneous radiations in the history of Central and Northern European Y-chromosomal lineages that both occurred after domestication 5,500 years ago. ispartof: SCIENTIFIC REPORTS vol:9 issue:1 ispartof: location:England status: published

In advanced cancer care, early communication about palliative care (PC) and end-of-life (EoL)-related issues is recommended, but is often impeded by physicians' communication insecurities. We investigated the effect of a newly developed compact communication skills training 'PALLI-COM' on oncologists' competencies to early address PC/EoL-related issues.We conducted a randomized, controlled trial (RCT) with an intervention group (IG; 2 × 90 min training) and a wait list control group (CG) at five sites. At two assessment points, participating oncologists led videotaped medical consultations with simulated patients (SPs) via a privacy compliant video conference platform. SPs were represented by trained actors. The taped conversations were rated for primary outcome (communication skills assessed by adapted COM-ON-checklist and COM-ON-coaching rating scales) by raters blinded for study group. Secondary outcomes included oncologists' self-reported communication skills (Self-Efficacy in Palliative Care Scale, Thanatophobia-Scale, Communication about End of Life Survey, study-specific items) as well as external rating of the SPs. Univariate analyses of covariance with baseline adjustment were used to analyze intervention effects.A total of 141 oncologists [age: mean (standard deviation) = 32.7 (6.3) years, 60% female (nFindings indicate that the compact communication skills training PALLI-COM increases oncologists' competencies in early addressing PC/EoL-related issues from different perspectives. Implementation in routine oncology residency might improve advanced cancer care by strengthening these communication skills.

Background There is insufficient evidence regarding the role of respirators in the prevention of SARS-CoV-2 infection. We analysed the impact of filtering facepiece class 2 (FFP2) versus surgical masks on the risk of SARS-CoV-2 acquisition among Swiss healthcare workers (HCW). Methods Our prospective multicentre cohort enrolled HCW from June to August 2020. Participants were asked about COVID-19 risk exposures/behaviours, including preferentially worn mask type when caring for COVID-19 patients outside of aerosol-generating procedures. The impact of FFP2 on (1) self-reported SARS-CoV-2-positive nasopharyngeal PCR/rapid antigen tests captured during weekly surveys, and (2) SARS-CoV-2 seroconversion between baseline and January/February 2021 was assessed. Results We enrolled 3259 participants from nine healthcare institutions, whereof 716 (22%) preferentially used FFP2. Among these, 81/716 (11%) reported a SARS-CoV-2-positive swab, compared to 352/2543 (14%) surgical mask users; seroconversion was documented in 85/656 (13%) FFP2 and 426/2255 (19%) surgical mask users. Adjusted for baseline characteristics, COVID-19 exposure, and risk behaviour, FFP2 use was non-significantly associated with decreased risk for SARS-CoV-2-positive swab (adjusted hazard ratio [aHR] 0.8, 95% CI 0.6–1.0) and seroconversion (adjusted odds ratio [aOR] 0.7, 95% CI 0.5–1.0); household exposure was the strongest risk factor (aHR 10.1, 95% CI 7.5–13.5; aOR 5.0, 95% CI 3.9–6.5). In subgroup analysis, FFP2 use was clearly protective among those with frequent (> 20 patients) COVID-19 exposure (aHR 0.7 for positive swab, 95% CI 0.5–0.8; aOR 0.6 for seroconversion, 95% CI 0.4–1.0). Conclusions Respirators compared to surgical masks may convey additional protection from SARS-CoV-2 for HCW with frequent exposure to COVID-19 patients. Supplementary Information The online version contains supplementary material available at 10.1186/s13756-022-01070-6.

Methylprednisolone is a glucocorticoid and can negatively influence immune defense mechanisms. During bacterial infections in the dog, neutrophils infiltrate infected tissue and mediate antimicrobial effects with different mechanisms such as phagocytosis and neutrophil extracellular trap (NET) formation. Here, we investigated the influence of methylprednisolone on canine NET formation and neutrophil killing efficiency of Gram positive and Gram negative bacteria. Therefore, canine blood derived neutrophils were treated with different concentrations of methylprednisolone over time. The survival factor of Staphylococcus pseudintermedius, Streptococcus canis or Escherichia coli was determined in presence of stimulated neutrophils. Additionally, free DNA and nucleosomes as NET marker were analyzed in supernatants and neutrophils were assessed for NET formation by immunofluorescence microscopy. Methylprednisolone concentrations of 62.5 and 625 µg/mL enhanced the neutrophil killing of Gram positive bacteria, whereas no significant influence was detected for the Gram negative Escherichia coli. Interestingly, higher amounts of free DNA were detected under methylprednisolone stimulation in a concentration dependency and in the presence of Streptococcus canis and Escherichia coli. The nucleosome release by neutrophils is induced by bacterial infection and differs depending on the concentration of methylprednisolone. Furthermore, immunofluorescence microscopy analysis identified methylprednisolone at a concentration of 62.5 µg/mL as a NET inducer. In summary, methylprednisolone enhances NET-formation and time-dependent and concentration-dependent the bactericidal effect of canine neutrophils on Gram positive bacteria.

OBJECTIVE This work was undertaken in order to identify Parkinson's disease (PD) risk variants in a Latino cohort, to describe the overlap in the genetic architecture of PD in Latinos compared to European-ancestry subjects, and to increase the diversity in PD genome-wide association (GWAS) data. METHODS We genotyped and imputed 1,497 PD cases and controls recruited from nine clinical sites across South America. We performed a GWAS using logistic mixed models; variants with a p-value

In consequence of a car accident a 20-year-old woman with bilateral fractures of the femur and an unilateral lower leg fracture was treated with external fixation. Afterwards she was soporific with signs of impaired consciousness and required intubation and intensive medical care surveillance. A cerebral fat embolism syndrome could be detected as the reason, which was characterized by acute respiratory insufficiency, neurological symptoms and petechiae. Subsequently, definitive treatment was performed by intramedullary nailing. After neurological and orthopedic rehabilitation no performance inhibiting limitations remained.Eine 20-jährige Frau wurde nach einem Pkw-Unfall bei beidseitiger Oberschenkel- und einer einseitigen Unterschenkelfraktur mit mehreren Fixateur externe versorgt und unter intensivmedizinischer Überwachung soporös und intubationspflichtig. Ursächlich konnte ein zerebrales Fettemboliesyndrom nachgewiesen werden, welches durch akute respiratorische Insuffizienz, neurologische Symptomatik und Petechien gekennzeichnet war. Im Verlauf erfolgte eine definitive Versorgung mittels Marknagelosteosynthese. Nach neurologischer und orthopädischer Rehabilitation verblieben keine Einschränkungen der Leistungsfähigkeit.

Older age is a substantial risk factor for serious illness from COVID-19. Moreover, isolation and quarantine are more likely to cause physical, mental and social deprivation in older age. Information and Communication Tools are means to prevent such consequences.This study aimed therefore to investigate the impact of the COVID-19 lockdown measures on the usage of an innovative technical support system deployed in Austria (AT) and Luxembourg (LU) consisting of several tools that allow independent living in older age.Thirty-nine older adults (11 male; 28 female) with a mean age of 74.3 (SD 7.3) years were included in the study. In total, 18 older people were recruited in AT and 21 in LU. Descriptive statistics were computed, and longitudinal models were fitted for technology use and self-reported mood.The number of older adults using the system significantly decreased from the time before lockdown (39 [100%]) to during lockdown (26 [67%]) and thereafter (23 [59%]; p 0.001). Multiple comparisons revealed a significant reduction in the average number of events for calendar and medication tools, but a substantial increase in communication and messaging events. Self-reported well-being declined during the lockdown and increased afterwards back to baseline levels.Communication was the main reason for using the support system. In addition, strategies and interventions are essential to support older adults when using information technology in the prolonged phases of the pandemic to sustain independent living.The DAPAS protocol was published at www.researchgate.net. DOI: 10.13140/RG.2.2.24233.34401.

Background & Aims: Cancer-associated fibroblasts (CAFs) play an important role in colorectal cancer (CRC) progression and predict poor prognosis in CRC patients. However, the cellular origins of CAFs remain unknown, making it challenging to therapeutically target these cells. Here, we aimed to identify the origins and contribution of colorectal CAFs associated with poor prognosis. Methods: To elucidate CAF origins, we used a colitis-associated CRC mouse model in 5 different fate-mapping mouse lines with 5-bromodeoxyuridine dosing. RNA sequencing of fluorescence-activated cell sorting–purified CRC CAFs was performed to identify a potential therapeutic target in CAFs. To examine the prognostic significance of the stromal target, CRC patient RNA sequencing data and tissue microarray were used. CRC organoids were injected into the colons of knockout mice to assess the mechanism by which the stromal gene contributes to colorectal tumorigenesis. Results: Our lineage-tracing studies revealed that in CRC, many ACTA2+ CAFs emerge through proliferation from intestinal pericryptal leptin receptor (Lepr)+ cells. These Lepr-lineage CAFs, in turn, express melanoma cell adhesion molecule (MCAM), a CRC stroma-specific marker that we identified with the use of RNA sequencing. High MCAM expression induced by transforming growth factor β was inversely associated with patient survival in human CRC. In mice, stromal Mcam knockout attenuated orthotopically injected colorectal tumoroid growth and improved survival through decreased tumor-associated macrophage recruitment. Mechanistically, fibroblast MCAM interacted with interleukin-1 receptor 1 to augment nuclear factor κB–IL34/CCL8 signaling that promotes macrophage chemotaxis. Conclusions: In colorectal carcinogenesis, pericryptal Lepr-lineage cells proliferate to generate MCAM+ CAFs that shape the tumor-promoting immune microenvironment. Preventing the expansion/differentiation of Lepr-lineage CAFs or inhibiting MCAM activity could be effective therapeutic approaches for CRC.

Veno-venous extracorporeal membrane oxygenation (V-V ECMO) is a last resort treatment option for patients with acute respiratory failure (acute respiratory distress syndrome [ARDS]). Cytokine adsorption has been incorporated in the management of some of these patients on an individual basis to control the imbalance of danger-associated molecular patterns and proinflammatory cytokines. However, little is known about the combination of V-V ECMO and cytokine adsorption as earlier reports contained mixed patient cohorts in terms of disease and mode of ECMO, veno-venous and veno-arterial. We here report single-center registry data of nine all-comers with severe ARDS treated with V-V ECMO and cytokine adsorption using the CytoSorb adsorber compared with a control group of nine propensity score matched patients undergoing V-V ECMO support without cytokine adsorption. Even though Respiratory ECMO Survival Prediction and PRedicting dEath for SEvere ARDS on V-V ECMO scores predicted a higher mortality in the cytokine adsorption group, mortality was numerically reduced in the patients undergoing V-V ECMO and cytokine removal compared with V-V ECMO alone. The need for fluid resuscitation and vasopressor support as well as lactate levels dropped significantly in the cytokine adsorption group within 72 hours, whereas vasopressor need and lactate levels did not decrease significantly in the control group. Therefore, our data suggest that cytokine adsorption might be beneficial in patients with severe ARDS requiring V-V ECMO support.

Early prediction of patient mortality risks during a pandemic can decrease mortality by assuring efficient resource allocation and treatment planning. This study aimed to develop and compare prognosis prediction machine learning models based on invasive laboratory and noninvasive clinical and demographic data from patients’ day of admission. Three Support Vector Machine (SVM) models were developed and compared using invasive, non-invasive, and both groups. The results suggested that non-invasive features could provide mortality predictions that are similar to the invasive and roughly on par with the joint model. Feature inspection results from SVM-RFE and sparsity analysis displayed that, compared with the invasive model, the non-invasive model can provide better performances with a fewer number of features, pointing to the presence of high predictive information contents in several non-invasive features, including SPO2, age, and cardiovascular disorders. Furthermore, while the invasive model was able to provide better mortality predictions for the imminent future, non-invasive features displayed better performance for more distant expiration intervals. Early mortality prediction using non-invasive models can give us insights as to where and with whom to intervene. Combined with novel technologies, such as wireless wearable devices, these models can create powerful frameworks for various medical assignments and patient triage.

Measures implemented to reduce the spread of SARS-CoV-2 have resulted in a decrease in physical activity (PA) while sedentary behaviour increased. The aim of the present study was to explore associations between PA and mental health in Austria during COVID-19 social restrictions. In this web-based cross-sectional study (April–May 2020) moderate-to-vigorous physical activity (MVPA), sitting time, and time spent outdoors were self-reported before and during self-isolation. Mental well-being was assessed with the Warwick-Edinburgh Mental Well-being Scale, and the Beck depression and anxiety inventories. The majority of the participants (n = 652) were female (72.4%), with a mean age of 36.0 years and a standard deviation (SD) of 14.4. Moreover, 76.5% took part in ≥30 min/day of MVPA, 53.5% sat ≥10 h/day, and 66.1% spent ≥60 min/day outdoors during self-isolation. Thirty-eight point five percent reported high mental well-being, 40.5% reported depressive symptoms, and 33.9% anxiety symptoms. Participating in higher levels of MVPA was associated with higher mental well-being (odds ratio = OR: 3.92, 95% confidence interval = 95%CI: 1.51–10.15), less depressive symptoms (OR: 0.44, 95%CI: 0.29–0.66) and anxiety symptoms (OR = 0.62, 95%CI: 0.41–0.94), and less loneliness (OR: 0.46, 95%CI: 0.31–0.69). Participants sitting &lt, 10 h/day had higher odds of mental well-being (OR: 3.58, 95%CI: 1.13–11.35). Comparable results were found for spending ≥60 min/day outdoors. Maintaining one’s MVPA levels was associated with higher mental well-being (OR = 8.61, 95%CI: 2.68–27.62). In conclusion, results show a positive association between PA, time spent outdoors and mental well-being during COVID-19 social restrictions. Interventions aiming to increase PA might mitigate negative effects of such restrictions.