Search

Background: Symptomatic patients with femoroacetabular impingement (FAI) have limitations in daily activities and sports and report the exacerbation of hip pain in deep flexion. Yet, the exact impingement location in deep flexion and the effect of femoral version (FV) are unclear. Purpose: To investigate the acetabular and femoral locations of intra- or extra-articular hip impingement in flexion in patients with FAI with and without femoral retroversion. Study Design: Cross-sectional study; Level of evidence, 3. Methods: An institutional review board–approved retrospective study involving 84 hips (68 participants) was performed. Of these, symptomatic patients (37 hips) with anterior FAI and femoral retroversion (FV Results: In maximal hip flexion, femoral impingement was located anterior-inferior at 4 o’clock (57%) and 5 o’clock (32%) in patients with femoral retroversion and mostly at 5 o’clock in patients without femoral retroversion (69%) and in asymptomatic controls (76%). Acetabular intra-articular impingement was located anterior-superior (2 o’clock) in all 3 groups. In 125° of flexion, patients with femoral retroversion had a significantly ( P < .001) higher prevalence of anterior extra-articular subspine impingement (54%) and anterior intra-articular impingement (89%) compared with the control group (29% and 62%, respectively). Conclusion: Knowing the exact location of hip impingement in deep flexion has implications for surgical treatment, sports, and physical therapy and confirms previous recommendations: Deep flexion (eg, during squats/lunges) should be avoided in patients with FAI and even more in patients with femoral retroversion. Patients with femoral retroversion may benefit and have less pain when avoiding deep flexion. For these patients, the femoral location of the impingement conflict in flexion was different (anterior-inferior) and distal to the cam deformity compared with the location during the anterior impingement test (anterior-superior). This could be important for preoperative planning and bone resection (cam resection or acetabular rim trimming) during hip arthroscopy or open hip preservation surgery to ensure that the region of impingement is appropriately identified before treatment.

OBJECTIVES To assess the vertical discrepancy between implant-supported crowns and adjacent teeth in the maxillary anterior region at least 8 years after implant placement and to evaluate the influence of this discrepancy on the level of aesthetic awareness of patients. MATERIAL AND METHODS The sample consisted of 23 adult individuals evaluated at least 8 years after placement of an implant-supported central or lateral single tooth-fixed partial denture. Patients had their crowns delivered at a mean age of 47.8 years (range: 18.9-65.8). The vertical discrepancy was measured by comparing initial and follow-up periapical radiographs using the implant as a stable structure. The patients' satisfaction with their anterior teeth condition and awareness of the possible vertical problem were evaluated using a questionnaire. The aesthetic outcome and patient awareness were related to the objective measurement of the vertical discrepancy. RESULTS The implant showed a mean infraocclusion of 0.62 mm (range: 0.15-1.63 mm). The vertical discrepancy was not associated with the patient's gender, age at implant placement, and duration between initial and recall radiograph. Patients were generally satisfied with the long-term aesthetic outcome of their smile (mean: 3.9 on a 1-5 scale, 1 unsatisfied, and 5 completely satisfied). Out of 23 patients, 8 noticed the implant infraocclusion and 4 of them found the problem severe enough to be willing to improve the situation. The amount of vertical discrepancy was not associated with the patient's perception of the discrepancy and the pink aesthetic score. CONCLUSION Implant-supported crowns in the anterior region may suffer infraocclusion over the long term. The amount of vertical discrepancy was not dependent on the gender and age of the patient. Patients were generally satisfied with the aesthetic result of the restoration. The amount of vertical discrepancy, at least in the range we have measured, was not perceived by the patients as a complication.

Objectives To evaluate the 5-year results of single and multiple recession type (RT) 1 and 2 (Miller I to III) recessions treated with the modified coronally advanced tunnel (MCAT) and connective tissue graft (CTG) with or without an enamel matrix derivative (EMD). The main outcome variable was the stability of obtained root coverage from 6 months to 5 years. Materials and methods In 24 patients, both complete and mean root coverage (CRC and MRC) and gain of keratinised tissue (KT) were assessed at 6 months and 5 years after recession coverage by means of MCAT and CTG with or without EMD. Aesthetic outcomes after 5 years were evaluated using the root coverage aesthetic score (RES). Results At 5 years, 24 patients with a total of 43 recessions were evaluated. Eight patients (57.14%) of the test and 6 (60.0%) of the control group showed complete root coverage. MRC revealed no statistically significant differences between the two groups, with 73.87 ± 26.83% (test) and 75.04 ± 22.06% (control), respectively. KT increased from 1.14 ± 0.57 mm to 3.07 ± 2.27 mm in the test group and from 1.24 ± 0.92 mm to 3.02 ± 1.55 mm in the control group, respectively. Conclusion Treatment of single and multiple RT 1 and 2 recessions by means of MCAT and CTG with or without EMD yielded comparable clinical improvements which could be maintained over a period of 5 years. The additional use of EMD did not influence the clinical outcomes. Clinical relevance The use of MCAT + CTG yielded successful coverage of single and multiple RT 1 and 2 gingival recessions, while the additional application of EMD did not seem to influence the results.

The aim of this study was to investigate the diagnostic accuracy and reader confidence for late-gadolinium enhancement (LGE) detection of a novel free-breathing, image-based navigated 3D whole-heart LGE sequence with fat–water separation, compared to a free-breathing motion-corrected 2D LGE sequence in patients with ischemic and non-ischemic cardiomyopathy. Cardiac MRI patients including the respective sequences were retrospectively included. Two independent, blinded readers rated image quality, depiction of segmental LGE and documented acquisition time, SNR, CNR and amount of LGE. Results were compared using the Friedman or the Kruskal–Wallis test. For LGE rating, a jackknife free-response receiver operating characteristic analysis was performed with a figure of merit (FOM) calculation. Forty-two patients were included, thirty-two were examined with a 1.5 T-scanner and ten patients with a 3 T-scanner. The mean acquisition time of the 2D sequence was significantly shorter compared to the 3D sequence (07:12 min vs. 09:24 min; p

If increasing practitioners’ diagnostic accuracy, medical artificial intelligence (AI) may lead to better treatment decisions at lower costs, while uncertainty remains around the resulting cost-effectiveness. In the present study, we assessed how enlarging the data set used for training an AI for caries detection on bitewings affects cost-effectiveness and also determined the value of information by reducing the uncertainty around other input parameters (namely, the costs of AI and the population’s caries risk profile). We employed a convolutional neural network and trained it on 10%, 25%, 50%, or 100% of a labeled data set containing 29,011 teeth without and 19,760 teeth with caries lesions stemming from bitewing radiographs. We employed an established health economic modeling and analytical framework to quantify cost-effectiveness and value of information. We adopted a mixed public–private payer perspective in German health care; the health outcome was tooth retention years. A Markov model, allowing to follow posterior teeth over the lifetime of an initially 12-y-old individual, and Monte Carlo microsimulations were employed. With an increasing amount of data used to train the AI sensitivity and specificity increased nonlinearly, increasing the data set from 10% to 25% had the largest impact on accuracy and, consequently, cost-effectiveness. In the base-case scenario, AI was more effective (tooth retention for a mean [2.5%–97.5%] 62.8 [59.2–65.5] y) and less costly (378 [284–499] euros) than dentists without AI (60.4 [55.8–64.4] y; 419 [270–593] euros), with considerable uncertainty. The economic value of reducing the uncertainty around AI’s accuracy or costs was limited, while information on the population’s risk profile was more relevant. When developing dental AI, informed choices about the data set size may be recommended, and research toward individualized application of AI for caries detection seems warranted to optimize cost-effectiveness.

BACKGROUND There is limited information on the effects of statins on the outcomes of liver transplantation (LT), regarding either their use by LT recipients or donors. AIM To analyse the association between statin exposure and recipient and graft survival. METHODS We included adult LT recipients with deceased donors in a nationwide prospective database study. Using a multistate modelling approach, we examined the effect of statins on the transition hazard between LT, biliary and vascular complications and death, allowing for recurring events. The observation time was 3 years. RESULTS We included 998 (696 male, 70%, mean age 54.46 ± 11.14 years) LT recipients. 14% of donors and 19% of recipients were exposed to statins during the study period. During follow-up, 141 patients died; there were 40 re-LT and 363 complications, with 66 patients having two or more complications. Treatment with statins in the recipient was modelled as a concurrent covariate and associated with lower mortality after LT (HR = 0.35; 95% CI 0.12-0.98; p = 0.047), as well as a significant reduction of re-LT (p = 0.004). However, it was not associated with lower incidence of complications (HR = 1.25; 95% CI = 0.85-1.83; p = 0.266). Moreover, in patients developing complications, statin use was significantly associated with decreased mortality (HR = 0.10; 95% CI = 0.01-0.81; p = 0.030), and reduced recurrence of complications (HR = 0.43; 95% CI = 0.20-0.93; p = 0.032). CONCLUSIONS Statin use by LT recipients may confer a survival advantage. Statin administration should be encouraged in LT recipients when clinically indicated.

Introduction. Lower HbA1c targets and increasingly complex diabetes management with substantially increasing costs dominate today’s type 1 diabetes therapy in children and adolescents. Objective. To evaluate metabolic control in children and adolescents with type 1 diabetes and assess associated factors, evaluate determinants for frequency of healthcare contacts, and compare actual with historical data. Method. This cross-sectional observational study collected data on 178 children and adolescents with type 1 diabetes treated at the University Children’s Hospital in Bern. Results. Mean HbA1c was 7.9% (63 mmol/mol), 33.1% (59/178) of children reached the target of HbA 1 c < 7.5 % ( HbA 1 c value < 7.0 % (

OBJECTIVE To assess the impact of operating room (OR) ventilation quality on surgical site infections (SSI) using a novel ventilation index. SUMMARY BACKGROUND DATA Previous studies compared laminar air flow with conventional ventilation, thereby ignoring many parameters that influence air flow properties. METHODS In this cohort study, we surveyed hospitals participating in the Swiss SSI surveillance and calculated a ventilation index for their ORs, with higher values reflecting less turbulent air displacement. For procedures captured between 01/2017-12/2019, we studied the association between ventilation index and SSI rates using linear regression (hospital-level analysis) and with the individual SSI risk using generalized linear mixed-effects models (patient-level analysis). RESULTS We included 47 hospitals (182 ORs). Among the 163'740 included procedures, 6791 SSIs were identified. In hospital-level analyses, a 5-unit increase in the ventilation index was associated with lower SSI rates for knee and hip arthroplasty (-0.41 infections per 100 procedures, CI -0.69 to -0.13), cardiac (-0.89, -1.91 to 0.12), and spine surgeries (-1.15, -2.56 to 0.26). Similarly, patient-level analyses showed a lower SSI risk with each 5-unit increase in ventilation index (adjusted odds ratio 0.71, CI 0.58 to 0.87 for knee and hip; 0.72, 0.49 to 1.06 for spine; 0.82, 0.69 to 0.98 for cardiac surgery). Higher index values were mainly associated with a lower risk for superficial and deep incisional SSIs. CONCLUSIONS Better ventilation properties, assessed with our ventilation index, are associated with lower rates of superficial and deep incisional SSIs in orthopedic and cardiac procedures. OR ventilation quality appeared to be less relevant for other surgery types.

An increasing number of elderly people retain their natural teeth into old age and further, the prevalence of endosseous implants for supporting oral prosthesis is ever increasing. These teeth and implants now present a considerable challenge in terms of maintenance, especially when patients become dependent on care. Periodontal and peri-implant diseases are more prevalent in elderly than in younger age cohorts. There are distinct differences related to the inflammatory response between periodontal and peri-implant tissues, both in young and old age. The age-related reasons for the increase in periodontal infections may be related to poor oral hygiene because of a loss of dexterity or vision, but also to immunosenescence. This term describes the aging of the immune system and the decline of its effectiveness with age. Low-grade infections, like chronic periodontitis, may cause low-grade inflammation and subsequently increase the likelihood of developing chronic diseases. In return, treatment of periodontitis may improve general health, as demonstrated for diabetes. A second mechanism illustrating how poor oral health translates into systemic disease is the risk of developing aspiration pneumonia. The treatment options in old age should be evaluated with regard to the issues of general health and maintenance. Systematic periodontal maintenance therapy, as performed in younger age cohorts, may be difficult to implement in elderly people experiencing institutional or hospital confinement because of logistics, barriers related to patients and caregivers, or cost. The scale of periodontal disease in old age represents a public health issue.

Background Whether seminal vesicles play a role in sexual activity in men is unknown. No study so far has compared the neural processing of visual sexual stimuli in men depending on the filling state of the seminal vesicles. Objective To evaluate potential specific cortical activation by visual sexual stimuli with distended and empty seminal vesicles. Design setting and participants A prospective case-control trial was conducted. Six male individuals underwent two visits on 2 consecutive days for hormone analyses; Derogatis Interview for Sexual Functioning (DISF) questionnaire; functional magnetic resonance imaging (fMRI) with passively viewing sexual, neutral, positive, and negative emotional pictures; and structural pelvic MRI. After the first visit, the participants had to empty seminal vesicles by masturbation. During fMRI, every participant viewed alternating blocks of sexual, neutral, positive, and negative emotional pictures. Outcome measurements and statistical analysis Comparisons between days 1 and 2 were evaluated using paired t tests. Results and limitations No significant differences were observed regarding hormone analyses, DISF questionnaire score, and arousal scoring between days 1 and 2. Seminal vesicle volume was significantly lower on day 2 (p = 0.003). Significantly higher activation was observed in the right precentral gyrus, middle frontal gyrus, and right superior temporal sulcus when contrasted for sexual over neutral (p

Sarcopenia, defined as progressive and generalized loss of muscle mass and strength, is common in chronic liver disease. It significantly impacts the quality of life and increases the risk of liver-related complications and mortality in cirrhotic patients. Moreover, recent studies showed a negative impact of sarcopenia on patients awaiting liver transplantation (LT), on post-LT outcomes, and on response to hepatocellular carcinoma therapies. Data about the influence of sex on the incidence, prevalence, diagnosis and treatment of sarcopenia in chronic liver diseases are poor and conflicting. The aims of this review of the literature are to define sex differences in sarcopenic cirrhotic patients and to highlight the necessity of a sex stratified analysis in future studies. This analysis of the literature showed that most of the studies are retrospective, with a higher prevalence of sarcopenia in males, probably due to anatomical differences between the sexes. Moreover, diagnostic criteria for sarcopenia are different between studies, as there is not a defined cut-off and, as a consequence, no comparable results. In conclusion, sex seems to have an impact on sarcopenia, and future studies must accurately investigate its role in identifying and treating high-risk patients, reducing the negative impact of sarcopenia on the survival and quality of life of cirrhotic patients.

PURPOSE The first convincing evidence for a causal relationship between bacterial infection and lymphomagenesis came from the link between gastric lymphoma and chronic Helicobacter pylori gastritis. This review will summarize the current epidemiological, clinical, and biological evidence of a causative role of bacteria in the development of malignant lymphomas, particularly, the extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue type. RECENT FINDINGS Other microorganisms have been associated with specific extranodal lymphoma sites with variable and not always definitive, evidence, including Chlamydia psittaci, Borrelia burgdorferi, Campylobacter jejuni and, most recently, Coxiella Burnetii. According to most plausible models, lymphoma growth is a consequence of continuous antigenic stimulation induced by chronic infection. However, some evidence of a direct oncogenic role of H. pylori has been provided, too. SUMMARY Lymphomas are not the result of a single cause but multifactorial diseases, influenced by a variety of genetic and environmental elements. Hence, ascertaining the specific contribution of bacterial infections is not always easy. Nevertheless, the eradication of the associated chronic infection may result in sustained lymphoma regression. Moreover, the association between infections and lymphoma may offer opportunities for reducing lymphoma incidence by preventing the predisposing infections or treating them early.

BackgroundSARS-CoV-2 mRNA vaccination of healthy individuals is highly immunogenic and protective against severe COVID-19. However, there are limited data on how disease-modifying therapies (DMTs) alter SARS-CoV-2 mRNA vaccine immunogenicity in patients with autoimmune diseases.MethodsAs part of a prospective cohort study, we investigated the induction, stability and boosting of vaccine-specific antibodies, B cells and T cells in patients with multiple sclerosis (MS) on different DMTs after homologous primary, secondary and booster SARS-CoV-2 mRNA vaccinations. Of 126 patients with MS analysed, 105 received either anti-CD20-based B cell depletion (aCD20-BCD), fingolimod, interferon-β, dimethyl fumarate, glatiramer acetate, teriflunomide or natalizumab, and 21 were untreated MS patients for comparison.ResultsIn contrast to all other MS patients, and even after booster, most aCD20-BCD- and fingolimod-treated patients showed no to markedly reduced anti-S1 IgG, serum neutralising activity and a lack of receptor binding domain-specific and S2-specific B cells. Patients receiving fingolimod additionally lacked spike-reactive CD4+T cell responses. The duration of fingolimod treatment, rather than peripheral blood B and T cell counts prior to vaccination, determined whether a humoral immune response was elicited.ConclusionsThe lack of immunogenicity under long-term fingolimod treatment demonstrates that functional immune responses require not only immune cells themselves, but also access of these cells to the site of inoculation and their unimpeded movement. The absence of humoral and T cell responses suggests that fingolimod-treated patients with MS are at risk for severe SARS-CoV-2 infections despite booster vaccinations, which is highly relevant for clinical decision-making and adapted protective measures, particularly considering additional recently approved sphingosine-1-phosphate receptor antagonists for MS treatment.

Background Several studies have suggested that proton pump inhibitors (PPIs) may reduce the antiplatelet effects of clopidogrel and/or aspirin, possibly leading to cardiovascular events. Aims We aimed to investigate the association between PPI and clinical outcomes in patients treated with ticagrelor monotherapy or conventional antiplatelet therapy after percutaneous coronary intervention (PCI). Methods This is a subanalysis of the randomized GLOBAL LEADERS trial, comparing the experimental antiplatelet arm (23-month ticagrelor monotherapy following 1-month dual antiplatelet therapy [DAPT]) with the reference arm (12-month aspirin monotherapy following 12-month DAPT) after PCI. Patient-oriented composite endpoints (POCEs: all-cause mortality, myocardial infarction, stroke, or repeat revascularization) and its components were assessed stratified by PPI use as a time-dependent covariate in patients with the experiment or reference antiplatelet arm. Results Among 15,839 patients, 2115 patients (13.5%) experienced POCE at 2 years. In the reference arm, the use of PPIs was independently associated with POCE (hazard ratio [HR]: 1.27; 95% confidence interval [CI]: 1.12-1.44) and its individual components, whereas it was not in the experimental arm (HR: 1.04; 95% CI: 0.92-1.19; p(interaction) = 0.035). During the second-year follow-up, patients taking aspirin with PPIs had a significantly higher risk of POCE compared to those on aspirin without PPIs (HR: 1.57; 95% CI: 1.27-1.94), whereas the risk did not differ significantly irrespective of PPI in ticagrelor monotherapy group (HR: 1.03; 95% CI: 0.83-1.28; p(interaction) = 0.008). Conclusions In contrast to conventional antiplatelet strategy, there were no evidence suggesting the interaction between ticagrelor monotherapy and PPIs on increased cardiovascular events, which should be confirmed in further studies. Clinical Trial Registration URL: The GLOBAL LEADERS trial was supported by unrestricted grants from AstraZeneca, Biosensors, and The Medicines Company. ECRI (European Cardiovascular Research Institute) was formally the sponsor of the study. GLOBAL LEADERS was sponsored by the European Clinical Research Institute, which received funding from Biosensors International, AstraZeneca, and the Medicines Company. P. J. is a Tier 1 Canada Research Chair in Clinical Epidemiology of Chronic Diseases. This study was completed, in part, with funding from the Canada Research Chairs Program. Open access funding provided by IReL.

Aim To assess the effects of 1- or ≥3-month dual antiplatelet therapy (DAPT) in high bleeding risk (HBR) patients who received biodegradable-polymer sirolimus-eluting stents for complex percutaneous coronary intervention (PCI) and/or acute coronary syndrome (ACS). Methods and results In the MASTER DAPT trial, 3383 patients underwent non-complex (abbreviated DAPT, n = 1707; standard DAPT, n = 1676) and 1196 complex (abbreviated DAPT, n = 588; standard DAPT, n = 608) PCI. Co-primary outcomes at 335 days were net adverse clinical events [NACE; composite of all-cause death, myocardial infarction, stroke, and bleeding academic research consortium (BARC) 3 or 5 bleeding events]; major adverse cardiac or cerebral events (MACCE; all-cause death, myocardial infarction, and stroke); and Types 2, 3, or 5 BARC bleeding. Net adverse clinical events and MACCE did not differ with abbreviated vs. standard DAPT among patients with complex [hazard ratio (HR): 1.03, 95% confidence interval (CI): 0.69–1.52, and HR: 1.24, 95% CI: 0.79–1.92, respectively] and non-complex PCI (HR: 0.90, 95% CI: 0.71–1.15, and HR: 0.91, 95% CI: 0.69–1.21; Pinteraction = 0.60 and 0.26, respectively). BARC 2, 3, or 5 was reduced with abbreviated DAPT in patients with and without complex PCI (HR: 0.64; 95% CI: 0.42–0.98, and HR: 0.70; 95% CI: 0.55–0.89; Pinteraction = 0.72). Among the 2816 patients with complex PCI and/or ACS, NACE and MACCE did not differ and BARC 2, 3, or 5 was lower with abbreviated DAPT. Conclusion In HBR patients free from recurrent ischaemic events at 1 month, DAPT discontinuation was associated with similar NACE and MACCE and lower bleeding rates compared with standard DAPT, regardless of PCI or patient complexity. Clinical Trial Registration This trial is registered with ClinicalTrials.gov, number NCT03023020, and is closed to new participants, with follow-up completed.

Objectives The aim of this study is to gain experienced nursing perspective on current and future complication reporting and grading in Urology, establish the CAMUS CCI and quality control the use of the Clavien-Dindo Classification (CDC) in nursing staff. Subjects and Methods The 12-part REDCap-based Delphi survey was developed in conjunction with expert nurse, urologist and methodologist input. Certified local and international inpatient and outpatient nurses specialised in urology, perioperative nurses and urology-specific advanced practice nurses/nurse practitioners will be included. A minimum sample size of 250 participants is targeted. The survey assesses participant demographics, nursing experience and opinion on complication reporting and the proposed CAMUS reporting recommendations; grading of intervention events using the existing CDC and the proposed CAMUS Classification; and rating various clinical scenarios. Consensus will be defined as ≥75% agreement. If consensus is not reached, subsequent Delphi rounds will be performed under Steering Committee guidance. Results Twenty participants completed the pilot survey. Median survey completion time was 58 min (IQR 40-67). The survey revealed that 85% of nursing participants believe nurses should be involved in future complication reporting and grading but currently have poor confidence and inadequate relevant background education. Overall, 100% of participants recognise the universal demand for reporting consensus and 75% hold a preference towards the CAMUS System. Limitations include variability in nursing experience, complexity of supplemental grades and survey duration. Conclusion The integration of experienced nursing opinion and participation in complication reporting and grading systems in a modern and evolving hospital infrastructure may facilitate the assimilation of otherwise overlooked safety data. Incorporation of focused teaching into routine nursing education will be essential to ensure quality control and stimulate awareness of complication-related burden. This, in turn, has the potential to improve patient counselling and quality of care.

Hand hygiene is at the core of effective infection prevention and control (IPC) programmes. 10 years after the development of the WHO Multimodal Hand Hygiene Improvement Strategy, we aimed to ascertain the level of hand hygiene implementation and its drivers in health-care facilities through a global WHO survey.From Jan 16 to Dec 31, 2019, IPC professionals were invited through email and campaigns to complete the online Hand Hygiene Self-Assessment Framework (HHSAF). A geospatial clustering algorithm selected unique health-care facilities responses and post-stratification weighting was applied to improve representativeness. Weighted median HHSAF scores and IQR were reported. Drivers of the HHSAF score were determined through a generalised estimation equation.3206 unique responses from 90 countries (46% WHO Member States) were included. The HHSAF score indicated an intermediate hand hygiene implementation level (350 points, IQR 248-430), which was positively associated with country income level and health-care facility funding structure. System Change had the highest score (85 points, IQR 55-100), whereby alcohol-based hand rub at the point of care has become standard practice in many health-care facilities, especially in high-income countries. Institutional Safety Climate had the lowest score (55 points, IQR 35-75). From 2015 to 2019, the median HHSAF score in health-care facilities participating in both HHSAF surveys (n=190) stagnated.Most health-care facilities had an intermediate level of hand hygiene implementation or higher, for which health-care facility funding and country income level were important drivers. Availability of resources, leadership, and organisational support are key elements to further improve quality of care and provide access to safe care for all.WHO, Geneva University Hospitals and Faculty of Medicine, and WHO Collaborating Center on Patient Safety, Geneva, Switzerland.

Background Triage refers to the process of patient prioritisation in the emergency department (ED). This is based on the severity of the patient’s illness and is performed by emergency nurses (ENs). This has a pivotal role in ensuring patient safety and in ensuring that the ED operates smoothly – so continuous and accurate training are essential. As Emergency Nursing has been formally established in Greece since 2019, it is of the uppermost importance that all Greek ENs should be trained in the use of a standardised triage system. The present study aimed to evaluate the effect of triage training of ENs in the use of the Swiss Triage System (STS) after an intervention of one week. Methods The effect of triage training was studied experimentally by comparing performance before and one week after training. A sample of thirty-six ENs from the University Department of Emergency Medicine at AHEPA University Hospital took part. The role of training in triage by the STS was assessed by completing the same self-administered questionnaire before and after a 45-minute e-learning program (presentation video of STS but with simulation scenarios) which was available during the period of a week. The post-training test was taken 2 weeks later, after the training process. Results The most promising finding was that there was a significant improvement in the number of correct answers after the training in triage (p<0.001). A significant improvement was also detected (p<0.001) in the questions that tested vigilance in providing safe health services by ENs, whereas there was no significant association between the number of correct answers and years of emergency experience or level of education, - either before or after the intervention. Conclusions Triage training seems to successfully improve effective and efficient triage. To the best of our knowledge, this is the first study that has demonstrated that triage training has a significant positive impact on triage performance by ENs in Greece. It is planned to support these findings by real time studies in an ED.

SUMO ist ein am Robert Koch-Institut entwickeltes und betriebenes System, welches Gesundheitsdaten für Public Health-Surveillance verarbeitet und bereitstellt. Der Notaufnahmesurveillance Wochenbericht enthält Daten der Routinedokumentation aus einer Auswahl deutscher Notaufnahmen und bildet die aktuelle Inanspruchnahme dieser Notaufnahmen ab., SUMO is a system that has been developed and implemented at the Robert Koch Institute. It processes and provides health data for surveillance and public health research. The emergency department weekly report presents data from the routine documentation of selected emergency departments in Germany, and shows the current utilisation of those emergency departments.

Blood-brain barrier (BBB) breakdown and immune cell infiltration into the central nervous system (CNS) are early hallmarks of multiple sclerosis (MS). High numbers of CD8+ T cells are found in MS lesions, and antigen (Ag) presentation at the BBB has been proposed to promote CD8+ T cell entry into the CNS. Here, we show that brain endothelial cells process and cross-present Ag, leading to effector CD8+ T cell differentiation. Under physiological flow in vitro, endothelial Ag presentation prevented CD8+ T cell crawling and diapedesis resulting in brain endothelial cell apoptosis and BBB breakdown. Brain endothelial Ag presentation in vivo was limited due to Ag uptake by CNS-resident macrophages but still reduced motility of Ag-specific CD8+ T cells within CNS microvessels. MHC class I-restricted Ag presentation at the BBB during neuroinflammation thus prohibits CD8+ T cell entry into the CNS and triggers CD8+ T cell-mediated focal BBB breakdown.

Hintergrund: Ein kontinuierliches bundesweites Gesundheitsmonitoring ist wichtig, um das Wohlbefinden von Kindern und Jugendlichen im Blick zu behalten und Entwicklungsverläufe abzubilden. Anhand der Ergebnisse von 3 ausgewählten epidemiologischen Studien werden Entwicklungen zum kindlichen Wohlbefinden der letzten 20 Jahre vorgestellt. Methodik: Datengrundlage bilden (1.) die bevölkerungsbezogene BEfragung zum seeLischen WohLbefinden und VerhAlten (BELLA-Studie, 2003–2017, N = 1500–3000), die ein Modul der KiGGS-Studie ist, (2.) die COrona und PSYche Studie (COPSY, 2020–2022, N = 1600–1700), die auf der BELLA-Studie aufbaut, und (3.) die internationale Health-Behaviour in School-aged Children Studie (HBSC, 2002–2018, N = 4300–7300). Das Wohlbefinden wurde bei 7‑ bis 17-Jährigen mittels der Indikatoren gesundheitsbezogene Lebensqualität (KIDSCREEN-10), Lebenszufriedenheit (Cantril Ladder) und psychische Auffälligkeiten (Strenghts and Difficulties Questionnaire (SDQ), Screen for Child Anxiety Related Emotional Disorders (SCARED) und Center for Epidemiological Studies Depression Scale for Children (CES-DC)) erfasst. Ergebnisse: Insgesamt zeigen Kinder und Jugendliche präpandemisch (2002–2018) eine konstant hohe gesundheitsbezogene Lebensqualität und eine hohe allgemeine Lebenszufriedenheit, die sich mit Beginn der COVID-19-Pandemie 2020 zunächst verschlechterte. 2 Jahre später zeigen sich Verbesserungen, die jedoch noch nicht das Ausgangsniveau erreichen. Psychische Auffälligkeiten, ängstliche und depressive Symptome nahmen mit Pandemiebeginn um bis zu 12 Prozentpunkte zu und zeigen auch 2 Jahre nach Pandemiebeginn noch höhere Werte als präpandemische Studien. Diskussion: Die Epidemiologie kindlichen Wohlbefindens bietet eine notwendige Datengrundlage, um den Unterstützungsbedarf von Kindern und Jugendlichen zu erfassen und auf dieser Basis Maßnahmen der Gesundheitsförderung, Prävention und Intervention zu entwickeln.

Objectives: We aimed to assess the predictive value of the total metabolic tumor burden prior to treatment in patients with advanced non-small-cell lung cancer (NSCLC) receiving immune checkpoint inhibitors (ICIs). Methods: Pre-treatment 2-deoxy-2-[18F]fluoro-D-glucose positron emission tomography/computed tomography (PET/CT) scans performed in two consecutive years for staging in adult patients with confirmed NSCLC were considered. Volume, maximum/mean standardized uptake value (SUVmax/SUVmean), metabolic tumor volume (MTV) and total lesion glycolysis (TLG) were assessed per delineated malignant lesion (including primary tumor, regional lymph nodes and distant metastases) in addition to the morphology of the primary tumor and clinical data. Total metabolic tumor burden was captured by totalMTV and totalTLG. Overall survival (OS), progression-free survival (PFS) and clinical benefit (CB) were used as endpoints for response to treatment. Results: A total of 125 NSCLC patients were included. Osseous metastases were the most frequent distant metastases (n = 17), followed by thoracal distant metastases (pulmonal = 14 and pleural = 13). Total metabolic tumor burden prior to treatment was significantly higher in patients treated with ICIs (mean totalMTV ± standard deviation (SD) 72.2 ± 78.7; mean totalTLG ± SD 462.2 ± 538.9) compared to those without ICI treatment (mean totalMTV ± SD 58.1 ± 233.8; mean totalTLG ± SD 290.0 ± 784.2). Among the patients who received ICIs, a solid morphology of the primary tumor on imaging prior to treatment was the strongest outcome predictor for OS (Hazard ratio HR 28.04, p < 0.01), PFS (HR 30.89, p < 0.01) and CB (parameter estimation PE 3.46, p < 0.01), followed by the metabolic features of the primary tumor. Interestingly, total metabolic tumor burden prior to immunotherapy showed a negligible impact on OS (p = 0.04) and PFS (p = 0.01) after treatment given the hazard ratios of 1.00, but also on CB (p = 0.01) given the PE < 0.01. Overall, biomarkers on pre-treatment PET/CT scans showed greater predictive power in patients receiving ICIs, compared to patients without ICI treatment. Conclusions: Morphological and metabolic properties of the primary tumors prior to treatment in advanced NSCLC patients treated with ICI showed great outcome prediction performances, as opposed to the pre-treatment total metabolic tumor burdens, captured by totalMTV and totalTLG, both with negligible impact on OS, PFS and CB. However, the outcome prediction performance of the total metabolic tumor burden might be influenced by the value itself (e.g., poorer prediction performance at very high or very low values of total metabolic tumor burden). Further studies including subgroup analysis with regards to different values of total metabolic tumor burden and their respective outcome prediction performances might be needed.

Die COVID-19-Impfempfehlungen der STIKO ha¬ben seit Beginn der Impfkampagne im Winter 2020/2021 das vordringliche Ziel, schwere Verläufe und Langzeit¬folgen von COVID-19 zu verhindern sowie Beschäf¬tigte in der medizinischen und pflegenden Versor¬gung vor SARS-CoV-2-Infektionen zu schützen. Die STIKO hat ihre COVID-19-Impfempfehlung seit der Erstpublikation im Dezember 2020 unter der Berücksichtigung neuer Daten und wei¬teren Impfstoffzulassungen fortlaufend angepasst. Beim Übergang von der pandemischen in die ende¬mische Phase des Infektionsgeschehens hat sich die STIKO mit der Überführung der bisherigen Emp¬fehlungen in eine längerfristige COVID-19-Impfempfehlung befasst. Im Epidemiologischen Bulletin 21/2023 wird die dazugehörige wissenschaftliche Begründung der aktualisierten Empfehlung und der Integration in den Impfkalender veröffentlicht. Die neue Empfehlung ersetzt die 25. Aktualisierung der COVID-19-Impfempfehlung von Februar 2023, die nicht mehr länger gültig ist.

Introduction The humanized anti-α4 integrin blocking antibody natalizumab (NTZ) is an effective treatment for relapsing–remitting multiple sclerosis (RRMS) that is associated with the risk of progressive multifocal leukoencephalopathy (PML). While extended interval dosing (EID) of NTZ reduces the risk for PML, the minimal dose of NTZ required to maintain its therapeutic efficacy remains unknown. Objective Here we aimed to identify the minimal NTZ concentration required to inhibit the arrest of human effector/memory CD4+ T cell subsets or of PBMCs to the blood–brain barrier (BBB) under physiological flow in vitro. Results Making use of three different human in vitro BBB models and in vitro live-cell imaging we observed that NTZ mediated inhibition of α4-integrins failed to abrogate T cell arrest to the inflamed BBB under physiological flow. Complete inhibition of shear resistant T cell arrest required additional inhibition of β2-integrins, which correlated with a strong upregulation of endothelial intercellular adhesion molecule (ICAM)-1 on the respective BBB models investigated. Indeed, NTZ mediated inhibition of shear resistant T cell arrest to combinations of immobilized recombinant vascular cell adhesion molecule (VCAM)-1 and ICAM-1 was abrogated in the presence of tenfold higher molar concentrations of ICAM-1 over VCAM-1. Also, monovalent NTZ was less potent than bivalent NTZ in inhibiting T cell arrest to VCAM-1 under physiological flow. In accordance with our previous observations ICAM-1 but not VCAM-1 mediated T cell crawling against the direction of flow. Conclusion Taken together, our in vitro observations show that high levels of endothelial ICAM-1 abrogate NTZ mediated inhibition of T cell interaction with the BBB. EID of NTZ in MS patients may thus require consideration of the inflammatory status of the BBB as high levels of ICAM-1 may provide an alternative molecular cue allowing for pathogenic T cell entry into the CNS in the presence of NTZ.

Aims Current long QT syndrome (LQTS) therapy, largely based on beta-blockade, does not prevent arrhythmias in all patients; therefore, novel therapies are warranted. Pharmacological inhibition of the serum/glucocorticoid-regulated kinase 1 (SGK1-Inh) has been shown to shorten action potential duration (APD) in LQTS type 3. We aimed to investigate whether SGK1-Inh could similarly shorten APD in LQTS types 1 and 2. Methods and results Human-induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) and hiPSC-cardiac cell sheets (CCS) were obtained from LQT1 and LQT2 patients; CMs were isolated from transgenic LQT1, LQT2, and wild-type (WT) rabbits. Serum/glucocorticoid-regulated kinase 1 inhibition effects (300 nM–10 µM) on field potential durations (FPD) were investigated in hiPSC-CMs with multielectrode arrays; optical mapping was performed in LQT2 CCS. Whole-cell and perforated patch clamp recordings were performed in isolated LQT1, LQT2, and WT rabbit CMs to investigate SGK1-Inh (3 µM) effects on APD. In all LQT2 models across different species (hiPSC-CMs, hiPSC-CCS, and rabbit CMs) and independent of the disease-causing variant (KCNH2-p.A561V/p.A614V/p.G628S/IVS9-28A/G), SGK1-Inh dose-dependently shortened FPD/APD at 0.3–10 µM (by 20–32%/25–30%/44–45%). Importantly, in LQT2 rabbit CMs, 3 µM SGK1-Inh normalized APD to its WT value. A significant FPD shortening was observed in KCNQ1-p.R594Q hiPSC-CMs at 1/3/10 µM (by 19/26/35%) and in KCNQ1-p.A341V hiPSC-CMs at 10 µM (by 29%). No SGK1-Inh-induced FPD/APD shortening effect was observed in LQT1 KCNQ1-p.A341V hiPSC-CMs or KCNQ1-p.Y315S rabbit CMs at 0.3–3 µM. Conclusion A robust SGK1-Inh-induced APD shortening was observed across different LQT2 models, species, and genetic variants but less consistently in LQT1 models. This suggests a genotype- and variant-specific beneficial effect of this novel therapeutic approach in LQTS.

Die Aktivität akuter Atemwegserkrankungen (ARE-Rate) in der Bevölkerung (GrippeWeb) ist in der 19. KW im Vergleich zur Vorwoche leicht gesunken. Die aktuelle ARE-Rate lag über den Werten der vorpandemi-schen Jahre zu dieser Zeit. Im ambulanten Bereich (Arbeitsgemeinschaft Influenza) ist die Zahl der Arztbesuche wegen ARE im Vergleich zur Vorwoche weiter gesunken. Auch die Zahl der Arztbesuche lag über dem Wertebereich der vorpandemischen Jahre zu dieser Zeit. Im NRZ für Influenzaviren wurden in der 19. KW 2023 in insgesamt 28 (47 %) der 60 eingesandten Sentinelproben respiratorische Viren identifiziert, darunter zehn (17 %) Proben mit humanen saisonalen Coronaviren (hCoV), acht (13 %) mit Rhinoviren, sechs (10 %) mit Influenzaviren, drei (5 %) mit Parainfluenzaviren (PIV) und drei (5 %) Proben mit SARS-CoV-2. Humane Metapneumoviren (hMPV) und Respiratorische Synzytialviren (RSV) wurden in der 19. KW nicht nachgewiesen. Im Rahmen der ICD-10-Code basierten Krankenhaussurveillance (ICOSARI) ist die Zahl schwerer akuter respiratorischer Infektionen (SARI) in den letzten Wochen gesunken und lag in der 19. KW 2023 weiterhin auf einem niedrigen Niveau. Insgesamt ist der Anteil der mit einer schweren Atemwegserkrankung hospitalisierten Patientinnen und Patienten mit einer COVID-19-Diagnose in der 19. KW 2023 erneut leicht gesunken und lag bei 9 %. Der Anteil an Influenza-Diagnosen bzw. an RSV-Diagnosen lag in der 19. KW 2023 jeweils bei 1 %. Die ARE-Aktivität in der Bevölkerung ist für die Jahreszeit in der 19. KW 2023 immer noch vergleichsweise hoch. Sie ist auf die Zirkulation unterschiedlicher Viren zurückzuführen, insbesondere auf hCoV, Rhinoviren und Influenzaviren. Die Zahl schwer verlaufender Atemwegsinfektionen liegt weiterhin auf einem niedrigen Niveau.

Nachdem die für die Bevölkerung in Deutschland geschätzte Gesamt-ARE-Rate von der 9. Kalenderwoche (KW) bis zur 16. KW gesunken war, stieg die Rate in der 17. KW 2023 wieder an und ist seitdem relativ stabil. Im Vergleich zur Vorwoche ist die Gesamt-ARE-Rate in der 19. KW leicht gesunken (5,7 %; Vorwoche: 6,0 %). Dabei ist die ARE-Rate bei den Kleinkindern bis 4 Jahren leicht gestiegen, in den anderen Altersgruppen ab 5 Jahren ist die ARE-Rate stabil geblieben oder gesunken. Die Gesamt-ILI-Rate ist mit 1,1 % in der 19. KW im Vergleich zur Vorwoche stabil geblieben. Die Gesamt-ARE-Rate lag in der 19. KW 2023 über dem Wertebereich der vorpandemischen Jahre zu dieser Zeit, die Gesamt-ILI-Rate lag im oberen Wertebereich. Die für die Bevölkerung in Deutschland geschätzten Raten für die 19. KW 2023 beruhen auf den Angaben von 6.004 GrippeWeb-Teilnehmenden, von diesen meldeten 345 eine ARE und 73 eine ILI (Datenstand: 16.5.2023, 0:00 Uhr). Durch Nachmeldungen, die bis zu vier Wochen lang möglich sind, können sich noch Änderungen ergeben.

Die STIKO empfiehlt, für die Standardimpfung gegen Pneumokokken im Säuglingsalter einen Pneu-mokokken-Konjugatimpfstoff (PCV) zu verwenden. Sie empfiehlt kein bestimmtes Impfstoffprodukt. Wie das Epidemiologische Bulletin 20/2023 ausführt, wird hingegen für die Indikationsimpfung von Kindern ab 2 Jahren mit bestimmten Vorerkrankungen bisher eine sequenzielle Impfung mit dem 13-valenten PCV (PCV13) gefolgt vom 23-valenten Polysacchari-dimpfstoff (PPSV23) im Mindestabstand von 6 Monaten empfohlen. Da der zusätzliche Nutzen des in Deutschland seit Anfang 2022 zugelassenen 15-valenten PCV (PCV15) im Vergleich zu PCV13 unter Berücksichtigung der aktuellen Serotypenverteilung gering ist, können für die Grundimmunisierung bei Säuglingen beide Impfstoffe zur Anwendung kommen. Von dem 20-valenten PCV (PCV20) ist im Vergleich zu PCV13 und PCV15 durch die breitere Serotypenabdeckung ein deutlicher Zusatznutzen zu erwarten. Der Impfstoff sollte jedoch im Kindesalter noch nicht eingesetzt werden, solange er hierfür nicht zugelassen ist.

Identifying areas with high and low infection rates can provide important etiological clues. Usually, areas with high and low infection rates are identified by aggregating epidemiological data into geographical units, such as administrative areas. This assumes that the distribution of population numbers, infection rates, and resulting risks is constant across space. This assumption is, however, often false and is commonly known as the modifiable area unit problem. This article develops a spatial relative risk surface by using kernel density estimation to identify statistically significant areas of high risk by comparing the spatial distribution of address-level COVID-19 cases and the underlying population at risk in Berlin-Neukölln. Our findings show that there are varying areas of statistically significant high and low risk that straddle administrative boundaries. The findings of this exploratory analysis further highlight topics such as, e.g., Why were mostly affluent areas affected during the first wave? What lessons can be learned from areas with low infection rates? How important are built structures as drivers of COVID-19? How large is the effect of the socio-economic situation on COVID-19 infections? We conclude that it is of great importance to provide access to and analyse fine-resolution data to be able to understand the spread of the disease and address tailored health measures in urban settings. Deutsche Forschungsgemeinschaft

Clinical reasoning is a core ability in the health professions, but the term is conceptualised in multiple ways within and across professions. For interprofessional teamwork it is indispensable to recognise the differences in understanding between professions. Therefore, our aim was to investigate how nurses, physicians, and medical and nursing students define clinical reasoning. We conducted 43 semi-structured interviews with an interprofessional group from six countries and qualitatively analysed their definitions of clinical reasoning based on a coding guide. Our results showed similarities across professions, such as the emphasis on clinical skills as part of clinical reasoning. But we also revealed differences, such as a more patient-centered view and a broader understanding of the clinical reasoning concept in nurses and nursing students. The explicit sharing and discussion of differences in the understanding of clinical reasoning across health professions can provide valuable insights into the perspectives of different team members on clinical practice and education. This understanding may lead to improved interprofessional collaboration, and our study's categories and themes can serve as a basis for such discussions.

ObjectivePreclinical studies have shown that cognitive impairments following spinal cord injury (SCI), such as impaired spatial memory, are linked to inflammation, neurodegeneration, and reduced neurogenesis in the right hippocampus. This cross-sectional study aims to characterize metabolic and macrostructural changes in the right hippocampus and their association to cognitive function in traumatic SCI patients.MethodsWithin this cross-sectional study, cognitive function was assessed in 28 chronic traumatic SCI patients and 18 age-, sex-, and education-matched healthy controls by a visuospatial and verbal memory test. A magnetic resonance spectroscopy (MRS) and structural MRI protocol was performed in the right hippocampus of both groups to quantify metabolic concentrations and hippocampal volume, respectively. Group comparisons investigated changes between SCI patients and healthy controls and correlation analyses investigated their relationship to memory performance.ResultsMemory performance was similar in SCI patients and healthy controls. The quality of the recorded MR spectra was excellent in comparison to the best-practice reports for the hippocampus. Metabolite concentrations and volume of the hippocampus measured based on MRS and MRI were not different between two groups. Memory performance in SCI patients and healthy controls was not correlated with metabolic or structural measures.ConclusionThis study suggests that the hippocampus may not be pathologically affected at a functional, metabolic, and macrostructural level in chronic SCI. This points toward the absence of significant and clinically relevant trauma-induced neurodegeneration in the hippocampus.

Background Numerical 4D phantoms, together with associated ground truth motion, offer a flexible and comprehensive data set for realistic simulations in radiotherapy and radiology in target sites affected by respiratory motion. Purpose We present an openly available upgrade to previously reported methods for generating realistic 4DCT lung numerical phantoms, which now incorporate respiratory ribcage motion and improved lung density representation throughout the breathing cycle. Methods Density information of reference CTs, toget her with motion from multiple breathing cycle 4DMRIs have been combined to generate synthetic 4DCTs (4DCT(MRI)s). Inter-subject correspondence between the CT and MRI anatomy was first established via deformable image registration (DIR) of binary masks of the lungs and ribcage. Ribcage and lung motions were extracted independently from the 4DMRIs using DIR and applied to the corresponding locations in the CT after post-processing to preserve sliding organ motion. In addition, based on the Jacobian determinant of the resulting deformation vector fields, lung densities were scaled on a voxel-wise basis to more accurately represent changes in local lung density. For validating this process, synthetic 4DCTs, referred to as 4DCT(CT)s, were compared to the originating 4DCTs using motion extracted from the latter, and the dosimetric impact of the new features of ribcage motion and density correction were analyzed using pencil beam scanned proton 4D dose calculations. Results Lung density scaling led to a reduction of maximum mean lung Hounsfield units (HU) differences from 45 to 12 HU when comparing simulated 4DCT(CT)s to their originating 4DCTs. Comparing 4D dose distributions calculated on the enhanced 4DCT(CT)s to those on the original 4DCTs yielded 2%/2 mm gamma pass rates above 97% with an average improvement of 1.4% compared to previously reported phantoms. Conclusions A previously reported 4DCT(MRI) workflow has been successfully improved and the resulting numerical phantoms exhibit more accurate lung density representations and realistic ribcage motion., Medical Physics, ISSN:0094-2405, ISSN:2473-4209, ISSN:1522-8541

ImportanceOtologic disease is common among people with primary ciliary dyskinesia (PCD), yet little is known about its spectrum and severity.ObjectiveTo characterize otologic disease among participants with PCD using data from the Ear-Nose-Throat Prospective International Cohort.Design, Setting, and ParticipantsThis cross-sectional analysis of baseline cohort data from February 2020 through July 2022 included participants from 12 specialized centers in 10 countries. Children and adults with PCD diagnoses; routine ear, nose, and throat examinations; and completed symptom questionnaires at the same visit or within 2 weeks were prospectively included.ExposuresPotential risk factors associated with increased risk of ear disease.Main Outcomes and MeasuresThe prevalence and characteristics of patient-reported otologic symptoms and findings from otologic examinations, including potential factors associated with increased risk of ear inflammation and hearing impairment.ResultsA total of 397 individuals were eligible to participate in this study (median [range] age, 15.2 [0.2-72.4] years; 186 (47%) female). Of the included participants, 204 (51%) reported ear pain, 110 (28%) reported ear discharge, and 183 (46%) reported hearing problems. Adults reported ear pain and hearing problems more frequently when compared with children. Otitis media with effusion—usually bilateral—was the most common otoscopic finding among 121 of 384 (32%) participants. Retracted tympanic membrane and tympanic sclerosis were more commonly seen among adults. Tympanometry was performed for 216 participants and showed pathologic type B results for 114 (53%). Audiometry was performed for 273 participants and showed hearing impairment in at least 1 ear, most commonly mild. Season of visit was the strongest risk factor for problems associated with ear inflammation (autumn vs spring: odds ratio, 2.40; 95% CI, 1.51-3.81) and age 30 years and older for hearing impairment (41-50 years vs ≤10 years: odds ratio, 3.33; 95% CI, 1.12-9.91).Conclusion and RelevanceIn this cross-sectional study, many people with PCD experienced ear problems, yet frequency varied, highlighting disease expression differences and possible clinical phenotypes. Understanding differences in otologic disease expression and progression during lifetime may inform clinical decisions about follow-up and medical care. Multidisciplinary PCD management should be recommended, including regular otologic assessments for all ages, even without specific complaints.

Thermodilution is the gold standard for cardiac output measurement in critically ill patients. Its application in extracorporeal therapy is limited, as a portion of the thermal indicator is drawn into the extracorporeal circuit. The behaviour of thermodilution signals in extracorporeal circuits is unknown. We investigated thermodilution curves within a closed-circuit and assessed the impact of injection volume, flow and distance on the behaviour of the thermodilution signals and catheter constants. We injected 3, 5, 7 and 10 ml of thermal indicator into a heated closed circuit. Thermistors at distances of 40, 60, 80, and 100 cm from the injection port recorded the thermodilution signals (at flow settings of 0.5, 1, 1.5, and 2 L/min). Area under the curve (AUC), rise time, exponential decay and catheter constants were analysed. Linear mixed-effects models were used to evaluate the impact of circuit flow, distance and injection volume. Catheter positioning did not influence AUC (78 injections). Catheter constants were independent of flow, injection volume or distance to the injection port. The distance to the injection port increased peak temperature and rise time and decreased exponential time constant significantly. The distance to the injection port did not influence catheter constants, but the properties of the thermodilution signal itself. This may influence measurements that depend on the exponential decay of the thermodilution signal such as right ventricular ejection fraction.

Background Bipolar voltage (BV) electrograms for left atrial (LA) substrate characterization depend on catheter design and electrode configuration. Aims The aim of the study was to investigate the relationship between the BV amplitude (BVA) using four catheters with different electrode design and to identify their specific LA cutoffs for scar and healthy tissue. Methods and results Consecutive high-resolution electroanatomic mapping was performed using a multipolar-minielectrode Orion catheter (Orion-map), a duo-decapolar circular mapping catheter (Lasso-map), and an irrigated focal ablation catheter with minielectrodes (Mifi-map). Virtual remapping using the Mifi-map was performed with a 4.5 mm tip-size electrode configuration (Nav-map). BVAs were compared in voxels of 3 × 3 × 3 mm3. The equivalent BVA cutoff for every catheter was calculated for established reference cutoff values of 0.1, 0.2, 0.5, 1.0, and 1.5 mV. We analyzed 25 patients (72% men, age 68 ± 15 years). For scar tissue, a 0.5 mV cutoff using the Nav corresponds to a lower cutoff of 0.35 mV for the Orion and of 0.48 mV for the Lasso. Accordingly, a 0.2 mV cutoff corresponds to a cutoff of 0.09 mV for the Orion and of 0.14 mV for the Lasso. For healthy tissue cutoff at 1.5 mV, a larger BVA cutoff for the small electrodes of the Orion and the Lasso was determined of 1.68 and 2.21 mV, respectively. Conclusion When measuring LA BVA, significant differences were seen between focal, multielectrode, and minielectrode catheters. Adapted cutoffs for scar and healthy tissue are required for different catheters.

Das Polymyxin-Antibiotikum Colistin ist in Deutschland seit 2012 als (Last-Line-)Antibiotikum für die systemische Therapie schwerer Infektionen mit multiresistenten Erregern zugelassen. 2016 wurde erstmals das Plasmid-vermittelte Colistinresistenzgen mcr-1 bei Menschen und Nutztieren beschrieben. Somit ist eine horizontale und speziesübergreifende Übertragung von mcr-1 und mrc-2 denkbar und es wurden seitdem weltweit zahlreiche bakterielle Isolate von Mensch und Tier z. T. auch retrospektiv auf das Vor¬handensein dieser neuen Resistenzgene untersucht. Eine weite Verbreitung von mcr-1/-2 wurde bestätigt. Vor diesem Hintergrund führte das Niedersächsische Landesgesundheitsamt in Kooperation mit der Westfälischen Wilhelms-Universität Münster und dem Nieder¬sächsischen Landesamt für Verbraucherschutz und Lebensmittelsicherheit eine Studie zur Verbreitung der mcr-vermittelten Colistinresistenz auf putenhaltenden Betrieben in Niedersachsen durch. Im Epidemiologischen Bulletin 19/2023 werden die Ergebnisse zusammengefasst und diskutiert.

Mit der Studie „Kindergesundheit in Deutschland aktuell“ (KIDA) untersucht das Robert Koch-Institut seit Februar 2022, wie sich die Gesundheit und das Gesundheitsverhalten von Kindern und Jugendlichen im Alter von 3 bis 17 Jahren im Verlauf der COVID-19-Pandemie darstellen und entwickeln. In der Studie werden über einen Zeitraum von 14 Monaten fortlaufend Informationen zu Gesundheit, Wohlbefinden und Gesundheitsverhalten sowie Daten zur Kenntnis und Nutzung von Beratungs- und Versorgungsangeboten erhoben. Dabei werden Eltern von Kindern im Alter von 3 bis 15 Jahren und Jugendliche im Alter von 16 bis 17 Jahren zunächst telefonisch befragt. Im Anschluss werden die Teilnehmenden eingeladen, zusätzlich an einer vertiefenden Online-Befragung teilzunehmen. Die so gewonnenen Daten werden im Kontext zu den jeweils vorherrschenden Pandemiebedingungen (z. B. Eindämmungsmaßnahmen, altersspezifische Inzidenzen, Testkonzepte) interpretiert und die Ergebnisse vierteljährlich in Form schriftlicher Berichte auf der Website des Robert Koch-Instituts veröffentlicht. KIDA wird finanziert aus Mitteln des Bundesministeriums für Gesundheit. Der vorliegende 1. Teil des 4. Quartalsberichts fasst die Ergebnisse der zwischen dem 20. April 2022 und dem 12. März 2023 durchgeführten Online-Befragungen zusammen. Gegenstand des 2. Teils werden Trendauswertungen der Telefonbefragungen sein. Der Erhebungszeitraum war zum Start der Onlineerhebung (KW16 2022) bereits durch stark abnehmende Neuerkrankungsraten unter Kindern und Jugendlichen gekennzeichnet, die nach einer Sommerwelle bis zum Ende des Erhebungszeitraums weiter sanken. Während der Erhebung gab es nur noch geringe pandemiebedingte Einschränkungen des öffentlichen Lebens, die im Verlauf des Erhebungszeitraums weiter abnahmen.

Nachdem die für die Bevölkerung in Deutschland geschätzte ARE-Rate von der 9. Kalenderwoche (KW) bis zur16. KW gesunken war, stieg die Rate in der 17. KW wieder auf 6,3 % an (Vorwoche: 4,9 %). Im Vergleich zur Vorwoche ist die ARE-Rate insbesondere bei den Kindern bis 14 Jahre deutlich angestiegen, aber auch bei den Erwachsenen ab 15 Jahre war ein leichter Anstieg zu verzeichnen. Bei der Gesamt-ILI-Rate war ebenfalls ein leichter Anstieg auf 1,3 % in der 17. KW zu beobachten (Vorwoche: 1,2 %). Die Gesamt-ARE-Rate lag in der 17. KW 2023 über dem Wertebereich der vorpandemischen Jahre zu dieser Zeit, die Gesamt-ILI-Rate lag im oberen Wertebereich. Die für die Bevölkerung in Deutschland geschätzten Raten für die 17. KW 2023 beruhen auf den Angaben von 5.246 GrippeWeb-Teilnehmenden, von diesen meldeten 324 eine ARE und 66 eine ILI (Datenstand: 2.5.2023, 0:00 Uhr). Durch Nachmeldungen, die bis zu vier Wochen lang möglich sind, können sich noch Änderungen ergeben.

Der von der Weltgesundheitsorganisation initiierte „Internationale Tag der Händehygiene“ soll alljährlich am 5. Mai die Aufmerksamkeit auf die Händehygiene vor allem in medizinischen und pfle-gerischen Einrichtungen lenken. Aus diesem Anlass wird in diesem Jahr im Epidemiologischen Bulletin 18/2023 die indikationsgerechte Nutzung medizinischer Einmalhandschuhe in Einrichtungen des Gesundheitswesens thematisiert und auf bestehende Probleme bei der Händehygiene-Compliance hingewiesen.

Synaptic vesicle (SV) fusion with the plasma membrane (PM) proceeds through intermediate steps that remain poorly resolved. The effect of persistent high or low exocytosis activity on intermediate steps remains unknown. Using spray-mixing plunge-freezing cryo-electron tomography we observe events following synaptic stimulation at nanometer resolution in near-native samples. Our data suggest that during the stage that immediately follows stimulation, termed early fusion, PM and SV membrane curvature changes to establish a point contact. The next stage—late fusion—shows fusion pore opening and SV collapse. During early fusion, proximal tethered SVs form additional tethers with the PM and increase the inter-SV connector number. In the late-fusion stage, PM-proximal SVs lose their interconnections, allowing them to move toward the PM. Two SNAP-25 mutations, one arresting and one disinhibiting spontaneous release, cause connector loss. The disinhibiting mutation causes loss of membrane-proximal multiple-tethered SVs. Overall, tether formation and connector dissolution are triggered by stimulation and respond to spontaneous fusion rate manipulation. These morphological observations likely correspond to SV transition from one functional pool to another. Synaptic vesicle (SV) fusion with the plasma membrane (PM) proceeds through intermediate steps that remain poorly resolved. The effect of persistent high or low exocytosis activity on intermediate steps remains unknown. Using spray-mixing plunge-freezing cryo-electron tomography we observe events following synaptic stimulation at nanometer resolution in near-native samples. Our data suggest that during the stage that immediately follows stimulation, termed early fusion, PM and SV membrane curvature changes to establish a point contact. The next stage—late fusion—shows fusion pore opening and SV collapse. During early fusion, proximal tethered SVs form additional tethers with the PM and increase the inter-SV connector number. In the late-fusion stage, PM-proximal SVs lose their interconnections, allowing them to move toward the PM. Two SNAP-25 mutations, one arresting and one disinhibiting spontaneous release, cause connector loss. The disinhibiting mutation causes loss of membrane-proximal multiple-tethered SVs. Overall, tether formation and connector dissolution are triggered by stimulation and respond to spontaneous fusion rate manipulation. These morphological observations likely correspond to SV transition from one functional pool to another.

Abundant studies have examined mental health in the early periods of the COVID-19 pandemic. However, empirical work examining the mental health impact of the pandemic’s subsequent phases remains limited. In the present study, we investigated how mental vulnerability and resilience evolved over the various phases of the pandemic in 2020 and 2021 in Germany. Data were collected (n = 3522) across seven measurement occasions using validated and self-generated measures of vulnerability and resilience. We found evidence for an immediate increase in vulnerability during the first lockdown in Germany, a trend towards recovery when lockdown measures were eased, and an increase in vulnerability with each passing month of the second lockdown. Four different latent trajectories of resilience–vulnerability emerged, with the majority of participants displaying a rather resilient trajectory, but nearly 30% of the sample fell into the more vulnerable groups. Females, younger individuals, those with a history of psychiatric disorders, lower income groups, and those with high trait vulnerability and low trait social belonging were more likely to exhibit trajectories associated with poorer mental well-being. Our findings indicate that resilience–vulnerability responses in Germany during the COVID-19 pandemic may have been more complex than previously thought, identifying risk groups that could benefit from greater support. Social Neuroscience Lab of the Max Planck Society Berlin University Alliance (BUA) Max Planck Society

Background & Aims: HBV coinfection is common among people living with HIV (PLWH) and is the most important cause of hepatocellular carcinoma (HCC). While risk prediction tools for HCC have been validated in patients with HBV monoinfection, they have not been evaluated in PLWH. Thus, we performed an external validation of PAGE-B in people with HIV/HBV coinfection.Methods: We included data on PLWH from four European cohorts who were positive for HBsAg and did not have HCC before starting tenofovir. We estimated the predictive performance of PAGE-B for HCC occurrence over 15 years in patients receiving tenofovir-containing antiretroviral therapy. Model discrimination was assessed after multiple imputation using Cox regression with the prognostic index as a covariate, and by calculating Harrell's c-index. Calibration was assessed by comparing our cumulative incidence with the PAGE-B derivation study using Kaplan-Meier curves.Results: In total, 2,963 individuals with HIV/HBV coinfection on tenofovir-containing antiretroviral therapy were included. PAGE-B was Conclusions: For individuals with HIV/HBV coinfection, PAGE-B is a valid tool to determine the need for HCC screening. Impact and implications: Chronic HBV infection is the most important cause of hepatocellular carcinoma (HCC) among people living with HIV. Valid risk prediction may enable better targeting of HCC screening efforts to high-risk individuals. We aimed to validate PAGE-B, a risk prediction tool that is based on age, sex, and platelets, in 2,963 individuals with HIV/HBV coinfection who received tenofovir-containing antiretroviral therapy. In the present study, PAGE-B showed good discrimination, adequate calibration, and a cut-off of

BACKGROUND AND AIM Liver graft utilization rates are a hot topic due to the worldwide organ shortage and an increasing number of transplant candidates on waiting lists. Liver perfusion techniques have been introduced in several countries, and may help to increase the organ supply, as they potentially allow the assessment of livers before use. METHODS Liver offers were counted from donation after circulatory death (DCD) donors (Maastricht-type-III) arising during the past decade in eight countries, including Belgium, France, Italy, the Netherlands, Spain, Switzerland, UK, and US. Initial DCD-type-III liver offers were correlated with accepted, recovered and implanted livers. RESULTS A total number of 34`269 DCD livers were offered, resulting in 9`780 liver transplants (28.5%). The discard rates were highest in UK and US, ranging between 70 and 80%. In contrast, much lower DCD liver discard rates, e.g., between 30-40%, were found in Belgium, France, Italy, Spain and Switzerland. In addition, large differences were recognized in the use of various machine perfusion techniques, and in terms of risk factors in the cohorts of implanted livers. For example, the median donor age and functional donor warm ischemia were highest in Italy, e.g., >40minutes, followed by Switzerland, France, and the Netherlands. Importantly, such varying risk profiles of accepted DCD livers between countries did not translate into large differences in five-year graft survival rates, which ranged between 60-82% in this analysis. CONCLUSIONS We highlight a significant number of discarded and consequently unused DCD liver offers. Countries with more routine use of in- and ex-situ machine perfusion strategies showed better DCD utilization rates without compromised outcome. IMPACT AND IMPLICATIONS A significant number of Maastricht type III DCD livers are discarded across Europe and North America today. The overall utilization rate among eight Western countries is 28.5%, but varies significantly between 18.9% and 74.2%. For example, the median DCD III liver utilization in five countries, e.g., Belgium, France, Italy, Switzerland, and Spain is 65%, in contrast to 24% in the Netherlands, UK and US. Despite this, and despite different rules and strategies for organ acceptance and preservation, the one and five-year graft survival remains currently relatively comparable among all participating countries. Factors which impact on DCD liver acceptance rates include the national pre-selections of donors, before the offer is made, as well as cutoffs for key risk factors, including donor age and donor warm ischemia time. In addition, a highly varying experience with modern machine perfusion technology is noticed. In situ and ex situ liver perfusion concepts, and assessment tools for type III DCD livers before transplantation may be one key part for the observed differences in better DCD III utilization.

PURPOSE The aims of this work are (1) to explore deep learning (DL) architectures, spectroscopic input types, and learning designs toward optimal quantification in MR spectroscopy of simulated pathological spectra; and (2) to demonstrate accuracy and precision of DL predictions in view of inherent bias toward the training distribution. METHODS Simulated 1D spectra and 2D spectrograms that mimic an extensive range of pathological in vivo conditions are used to train and test 24 different DL architectures. Active learning through altered training and testing data distributions is probed to optimize quantification performance. Ensembles of networks are explored to improve DL robustness and reduce the variance of estimates. A set of scores compares performances of DL predictions and traditional model fitting (MF). RESULTS Ensembles of heterogeneous networks that combine 1D frequency-domain and 2D time-frequency domain spectrograms as input perform best. Dataset augmentation with active learning can improve performance, but gains are limited. MF is more accurate, although DL appears to be more precise at low SNR. However, this overall improved precision originates from a strong bias for cases with high uncertainty toward the dataset the network has been trained with, tending toward its average value. CONCLUSION MF mostly performs better compared to the faster DL approach. Potential intrinsic biases on training sets are dangerous in a clinical context that requires the algorithm to be unbiased to outliers (i.e., pathological data). Active learning and ensemble of networks are good strategies to improve prediction performances. However, data quality (sufficient SNR) has proven as a bottleneck for adequate unbiased performance-like in the case of MF.