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Background: Is insulin initiation linked to increasing body mass index (BMI) in all patients with type-2-diabetes (T2D)? To determine distinct longitudinal patterns of BMI change over time. Materials and Methods: 5057 patients with T2D (55% males, median BMI [IQR]: 30.0 [26.9-33.3] kg/m2) aged ≥40 years at diabetes diagnosis and with ≥2 years of follow-up after insulin initiation irrespective of previous or concurrent use of metformin/dipeptidyl peptidase-4-inhibitor from the multicenter prospective diabetes registry DPV were studied. To identify subgroups following a similar pattern of BMI change after insulin initiation, longitudinal group-based trajectory modeling was applied. Multinomial logistic regression was then used to analyze covariates associated with group membership. Results: Three heterogeneous groups with either relevant BMI increase (delta-BMI: +4.0 kg/m2 after 2 years; 12% of patients); slight BMI increase (+0.4 kg/m2; 80%); or BMI decrease (-3.2 kg/m2; 8%) were identified. Patients with older age [OR (95% CI): 1.37 (1.11-1.69)] and obesity [2.05 (1.65-2.55)] before insulin start were more often in the BMI decreasing group, and less often in the BMI increasing class [0.80 (0.67-0.95); 0.82 (0.69-0.98)]. A worse HbA1c both at insulin start and during follow-up [1.90 (1.60-2.26); 1.17 (1.07-1.27)], a higher insulin dose [1.67 (1.33-2.10)], and severe hypoglycemic events [2.38 (1.60-3.53)] after insulin initiation were all linked with higher odds of belonging to the BMI increasing trajectory. Conclusions: Patient heterogeneity with respect to weight gain after initiation of insulin therapy in adult T2D was detected by an objective computer algorithm. Older people with obesity should not defer from insulin use due to fear of weight gain.

Background: Cardiovascular outcome trials have shown cardiovascular benefit with sodium-glucose co-transporter-2 (SGLT2) inhibitors in patients with type 2 diabetes, whereas dipeptidyl peptidase-4 (DPP-4) inhibitors have not shown an effect. We aimed to address knowledge gaps regarding the comparative effectiveness of SGLT2 inhibitor use in clinical practice (with DPP-4 inhibitor use as an active comparator) across a range of cardiovascular risks and in diverse geographical settings. Methods: In this comparative cohort study, we used data from clinical practice from 13 countries in the Asia-Pacific, Middle East, European, and North American regions to assess the risk of cardiovascular events and death in adult patients with type 2 diabetes newly initiated on SGLT2 inhibitors compared with those newly initiated on DPP-4 inhibitors. De-identified health records were used to select patients who were initiated on these drug classes between Dec 1, 2012, and May 1, 2016, with follow-up until Dec 31, 2014, to Nov 30, 2017 (full range; dates varied by country). Non-parsimonious propensity scores for SGLT2 inhibitor initiation were developed for each country and patients who were initiated on an SGLT2 inhibitor were matched with those who were initiated on a DPP-4 inhibitor in a 1:1 ratio. Outcomes assessed were hospitalisation for heart failure, all-cause death, myocardial infarction, and stroke. Hazard ratios (HRs) were estimated by country and then pooled in a weighted meta-analysis. Findings: Following propensity score matching, 193 124 new users of SGLT2 inhibitors and 193 124 new users of DPP-4 inhibitors were included in the study population. Participants had a mean age of 58 years (SD 12·2), 170 335 (44·1%) of 386 248 were women, and 111 933 (30·1%) of 372 262 had established cardiovascular disease. Initiation of an SGLT2 inhibitor versus a DPP-4 inhibitor was associated with substantially lower risks of hospitalisation for heart failure (HR 0·69, 95% CI 0·61–0·77; p

Summary Background With increasingly precise radiotherapy and advanced medical imaging, the concept of radiotherapy target volume planning might be redefined with the aim of improving outcomes. We aimed to investigate whether target volume reduction is feasible and effective compared with conventional planning in the context of radical chemoradiotherapy for patients with locally advanced non-small-cell lung cancer. Methods We did a multicentre, open-label, randomised, controlled trial (PET-Plan; ARO-2009-09) in 24 centres in Austria, Germany, and Switzerland. Previously untreated patients (aged older than 18 years) with inoperable locally advanced non-small-cell lung cancer suitable for chemoradiotherapy and an Eastern Cooperative Oncology Group performance status of less than 3 were included. Undergoing 18F-fluorodeoxyglucose (18F-FDG) PET and CT for treatment planning, patients were randomly assigned (1:1) using a random number generator and block sizes between four and six to target volume delineation informed by 18F-FDG PET and CT plus elective nodal irradiation (conventional target group) or target volumes informed by PET alone (18F-FDG PET-based target group). Randomisation was stratified by centre and Union for International Cancer Control stage. In both groups, dose-escalated radiotherapy (60–74 Gy, 2 Gy per fraction) was planned to the respective target volumes and applied with concurrent platinum-based chemotherapy. The primary endpoint was time to locoregional progression from randomisation with the objective to test non-inferiority of 18F-FDG PET-based planning with a prespecified hazard ratio (HR) margin of 1·25. The per-protocol set was included in the primary analysis. The safety set included all patients receiving any study-specific treatment. Patients and study staff were not masked to treatment assignment. This study is registered with ClinicalTrials.gov , NCT00697333 . Findings From May 13, 2009, to Dec 5, 2016, 205 of 311 recruited patients were randomly assigned to the conventional target group (n=99) or the 18F-FDG PET-based target group (n=106; the intention-to-treat set), and 172 patients were treated per protocol (84 patients in the conventional target group and 88 in the 18F-FDG PET-based target group). At a median follow-up of 29 months (IQR 9–54), the risk of locoregional progression in the 18F-FDG PET-based target group was non-inferior to, and in fact lower than, that in the conventional target group in the per-protocol set (14% [95% CI 5–21] vs 29% [17–38] at 1 year; HR 0·57 [95% CI 0·30–1·06]). The risk of locoregional progression in the 18F-FDG PET-based target group was also non-inferior to that in the conventional target group in the intention-to-treat set (17% [95% CI 9–24] vs 30% [20–39] at 1 year; HR 0·64 [95% CI 0·37–1·10]). The most common acute grade 3 or worse toxicity was oesophagitis or dysphagia (16 [16%] of 99 patients in the conventional target group vs 17 [16%] of 105 patients in the 18F-FDG PET-based target group); the most common late toxicities were lung-related (12 [12%] vs 11 [10%]). 20 deaths potentially related to study treatment were reported (seven vs 13). Interpretation 18F-FDG PET-based planning could potentially improve local control and does not seem to increase toxicity in patients with chemoradiotherapy-treated locally advanced non-small-cell lung cancer. Imaging-based target volume reduction in this setting is, therefore, feasible, and could potentially be considered standard of care. The procedures established might also support imaging-based target volume reduction concepts for other tumours. Funding German Cancer Aid (Deutsche Krebshilfe).

BACKGROUND Treatment of patients with type 1 diabetes requires experience and a specific infrastructure. Therefore, center size might influence outcome in diabetes treatment. OBJECTIVE To analyze the influence of center size on the quality of diabetes treatment in children and adolescents in Germany and Austria. PATIENTS AND METHODS In 2009 and 2018, we analyzed metabolic control, acute complications, and rates of recommended screening tests in the DPV cohort. Diabetes centers were classified according to the number of patients from "XS" to "XL" (

Most historical articles have named Johann Jacob Wepfer as the first author to describe a case of chronic subdural hematoma (CSDH). However, the question arises whether these cases truly describe CSDH. Two other names that appear in literature as the first authors to describe a case of CSDH are Thomas Willis and Giovanni Battista Morgagni. In our attempt to find the first description of a CSDH, we studied the original cases described by Willis, Wepfer, and Morgagni. The cases described by Willis and Wepfer cannot be interpreted as cases of CSDH. Willis’s university scholar is more likely to have experienced venous infarction with an underlying septic thrombosis than a CSDH. Wepfer’s cases seem to represent an intraparenchymal hemorrhage from the rupture of a branch or branches of the internal carotid artery, a subarachnoid hemorrhage complicated with hydrocephalus, and a hydrocephalus in tuberculous meningitis. Morgagni’s case described in Letter III, Article 20 in the Sedibus in 1761 seems to be the first accurate historical description of a CSDH, and we believe it should be cited as such. With these early cases of alleged CSDH, we emphasize the importance of misquotation and blind copying of references, which are important citation errors.

Background Human papillomavirus (HPV), primarily genotypes 6 and 11, cause the majority of cases of anogenital warts (AGW). Although benign, AGW are associated with a substantial economic and psychosocial burden. Several vaccines have been developed to prevent HPV. The objective of this study was to describe the epidemiology and healthcare resource utilization of AGW in Morocco, as well as the associated costs of treatment from the public healthcare perspective. Methods This was a descriptive analysis of questionnaire data obtained via a Delphi panel. The panel consisted of 9 physicians practicing in public hospitals in Morocco (4 dermatologists and 5 obstetricians/gynecologists). The questionnaire collected data on physician and practice characteristics, diagnostic tests and procedures, treatments, and follow-up (including recurrence) of patients with AGW. Questionnaire items on which ≥ 70% of respondents agreed were considered as having consensus. Costs associated with diagnosis, treatment, and follow-up were calculated in Moroccan dirham (MAD) and converted to euros (€) based on official national price lists for public hospitals and the HCRU estimates from the questionnaire. Results The physician-estimated prevalence of AGW in Morocco was 1.6%-2.6% in women and 2.0%-5.3% in men. A mean (median) of 6.4 (4) patients per month per physician sought medical attention for AGW. Simple observation was the most common diagnostic method for AGW in both men and women, and excision was the most prescribed therapy (75%), requiring a mean of 2 visits. Recurrence occurred in approximately 27% of patients. The cost per case of managing AGW, including recurrence, was estimated at 2182–2872 MAD (€207–272) for women and 2170–2450 MAD (€206–233) for men. The total annual cost of medical consultations for AGW in Morocco ranged from 3,271,877 MAD to 4,253,703 MAD (€310,828–404,102). Conclusions Expert consensus indicates that AGW represent a significant burden to the Moroccan public healthcare system. These data can inform policy makers regarding this vaccine-preventable disease.

ZusammenfassungDie interdisziplinäre Forschungskooperation COACH-Konsortium (Chronic Conditions in Adolescents – Implementation and Evaluation of Patient-centered Collaborative Healthcare) untersucht die psychosoziale Situation von Jugendlichen und jungen Erwachsenen mit chronischen körperlichen Erkrankungen. Zur Untersuchung der psychischen Komorbidität wurden bisher 1.023 Patienten mit Diabetes mellitus Typ 1 im Alter von 12–21 Jahren bei Routinevorstellungen in der Klinik bzw. Ambulanz mittels der Screening-Fragebogen Patient Health Questionnaire (PHQ-9) und Generalized Anxiety Disorder Scale-7 (GAD-7) zu Angst- und Depressionssymptomen befragt. 29,8 % der Jugendlichen und jungen Erwachsenen zeigten ein auffälliges Screening-Ergebnis. Dabei wurden 17,8 % der Fragebogen zu Angstsymptomen und 25,6 % der Fragebogen zu Depressionssymptomen auffällig mit Gesamtscore-Werten ≥ 7 in GAD-7 bzw. PHQ-9 beantwortet. Patienten mit erhöhten Depressions- und Angstwerten wiesen im Mittel einen deutlich höheren medianen HbA1c-Wert als Zeichen einer schlechteren Stoffwechseleinstellung auf (8,33 [8,09; 8,56]) als Patienten mit unauffälligem Screening (7,58 [7,48; 7,68]; p

Introduction The success of intensification and personalisation of the curative treatment of non-small cell lung cancer (NSCLC) is strongly associated with the precision in radiotherapy. Here, we evaluate the impact of radiotherapy protocol adherence in a prospective multicentre trial. Methods In the open-label, randomised, controlled PET-Plan trial, patients with inoperable NSCLC were randomized at a 1:1 ratio regarding the target volume delineation informed by 1F-FDG PET and CT plus elective nodal irradiation (arm A) or target volumes informed by PET alone (arm B) and received iso-toxically dose-escalated concurrent chemoradiation. The prospectively organised quality assurance program (RTQA) included individual case review by predefined criteria. For evaluation, protocol adherence was scored as per protocol (pP), with minor (miD), intermediate (inD) and major (maD) deviations. In order to exclude biases through patients who discontinued treatment, patients who received ≥60 Gy were additionally analysed. Results Between 05/2009–11/2016, 205 patients were randomized, 204 patients started treatment according to protocol of which 31 (15%) patients had maD. Patients with maD had an inferior overall survival (OS) (HR 2.9, 95% CI 1.8–4.4, p Conclusions Non-adherence to the radiotherapy protocol was associated with an inferior OS and loco-regional control. These results underline the importance of RTQA.

The role of steroids as an adjunct to surgery for chronic subdural hematoma (cSDH) remains unclear. We evaluated the effect of steroids as an adjunct to surgery on recurrence rates, complications, and mortality. We retrospectively collected data of 525 patients operated on for cSDH between January 2010 and April 2015 at the Amsterdam University Medical Centers and Erasmus Medical Center Rotterdam. Data from patients with and without steroid use as an adjunct to surgery were obtained from medical records and compared using the chi-square test, independent-samples t-test, and Mann-Whitney U test, where applicable. Associations between adjuvant steroid use and complications were analyzed with univariable (penalized likelihood) logistic regression analysis. Multi-variate logistic regression was performed to analyze the influence of adjuvant steroid use on recurrence. Propensity-score matching was used to assemble a cohort of patients with similar baseline characteristics. Two hundred seventy-eight of the 525 patients (53%) were treated with adjuvant steroids. Surgery for recurrences occurred less in patients of the steroid group (9% vs. 14%; odds ratio [OR] 0.57; 95% confidence interval [CI], 0.33-0.99), but the effect was not significant after correction for confounders (adjusted aOR, 0.59; 95% CI, 0.33-1.05). In the steroid group, delirium (10% vs. 3%; OR, 3.99; 95% CI, 1.72-9.29) and dysregulated glucose levels occurred more frequently (2% vs. 0%; OR, 11.81; 95% CI, 1.38-1542.79), but multi-variate analysis was not possible. After propensity-score matching, McNemar's chi-square test showed that adjuvant steroid use was not significantly associated with recurrence rate (p = 0.10). Steroids as an adjunct to surgery in patients with cSDH did not have a favorable effect on the recurrence rate in our data after controlling for confounders.

Available basal insulin regimes differ in pharmacokinetic profiles, which may be related to subsequent changes in anthropometry in patients with type 1 diabetes. This analysis elucidates the standardized height and body mass index development (height and BMI standard deviation score [height-SDS and BMI-SDS]) in pediatric type 1 diabetes patients depending on the choice of basal insulin.Longitudinal data of 10 338 German/Austrian patients from the Diabetes Prospective Follow-up (DPV, Diabetes Patienten Verlaufsdokumentation) database were analyzed. Patients aged 5.0 to 16.9 years were treated exclusively with neutral protamine Hagedorn (NPH), insulin detemir (IDet), insulin glargine (IGla), or continuous subcutaneous insulin infusion (CSII) for at least 3 years. Population-based German reference data were used to calculate height-SDS and BMI-SDS. Multiple linear regression was conducted.BMI-SDS increased significantly in all regimes (NPH P = .0365; IDet P = .0003; IGla P .0001; and CSII P .0001). Direct comparison of the therapies revealed a favorable association only for NPH vs IGla. A rise in BMI-SDS was observed for all insulins in females, but only for IGla in males. BMI-SDS increment was not observed before 8 years of age. Initially and at the end of the observation period, mean height was above the 50th percentile of the reference population. Across the cohort, height-SDS declined during the observation period, except for CSII. Apart from the 5.0- to 7.9-year-old subgroup, long-acting insulin analogues were associated with a significant loss of height-SDS.Choice of basal insulin regimen might influence height development. CSII appeared to have a favorable effect on growth trajectories. All therapies were associated with an increase of BMI-SDS, most evident in females.背景: 现有的基础胰岛素方案在药代动力学方面存在差异, 这可能与1型糖尿病患者后续的人体测量学变化有关。这项分析阐明了儿童1型糖尿病患者基于基础胰岛素的选择的标准化身高和体重指数BMI(身高和BMI标准差评分[身高-SDS和BMI-SDS])的发展。 方法: 对10338例德国/奥地利糖尿病进行前瞻性数据库中的纵向资料进行分析。年龄5.0~16.9岁的患者接受中性鱼精蛋白Hagedorn(NPH), 地特胰岛素(IDET), 甘精胰岛素(IGLA)或持续皮下胰岛素输注(CSII)治疗至少3年。以人群为基础的德国参考数据被用来计算身高-SDS和BMI-SDS。进行多元线性回归分析。 结果: BMI-SDS在所有方案中均显著升高(NPH P=.0365, IDET P=.0003, IGLA P.0001, CSII P.0001)。对这些疗法的直接比较显示, 仅对NPH和IGLA有有利的关联。在女性中观察到所有胰岛素的BMI-SDS升高, 但只在男性中观察到IGLA的升高。BMI-SDS在8岁前未见明显增加。 最初和在观察期结束时, 平均身高高于参考人口的第50个百分位数。在整个队列中, 除CSII外, 身高-SDS在观察期内均呈下降趋势。除了5.0到7.9岁的亚组外, 长效胰岛素类似物与身高-SDS显著降低相关。 结论: 基础胰岛素方案的选择可能影响身高发育。CSII似乎对增长轨迹有有利的影响。所有的治疗都与BMI-SDS的增加有关, 这在女性中最为明显。.

Die aktuelle COVID-19 Pandemie stellt eine große Herausforderung dar für die psychische Gesundheit der Allgemeinbevölkerung und speziell der Mitarbeiter*innen des Gesundheitssystems. In diesem Beitrag wird ein Überblick sowohl zu den allgemeinen psychischen Belastungsfaktoren wie zu den speziellen Herausforderungen für Gesundheitsfachkräfte im Rahmen der COVID-19 Pandemie gegeben. Daran anschließend werden psychosoziale und organisationale Handlungsempfehlungen für das Pflegemanagement im Rahmen der COVID-19 Pandemie vermittelt mit dem Ziel, psychische Belastungen der Mitarbeiter*innen des Gesundheitswesens in der aktuellen Hochbelastungsphase zu reduzieren und die psychische Nachsorge vorzubereiten. Supplementary Information Zusatzmaterial online: Zu diesem Beitrag sind unter 10.1007/s41906-021-1058-y für autorisierte Leser zusätzliche Dateien abrufbar.

Liver transplant recipients (LTRs) are at high risk for cardiovascular disease (CVD). We sought to characterize LTR, informal caregiver, and health care provider perceptions about CVD care after liver transplantation (LT) to inform the design of solutions to improve care. Participants included adult LTRs, their caregivers, and multispecialty health care providers recruited from an urban tertiary care network who participated in 90-minute focus groups and completed a brief survey. Focus group transcripts were analyzed using thematic analysis, and survey data were analyzed using descriptive statistics. A total of 17 LTRs, 9 caregivers, and 22 providers participated in 7 separate focus groups. Most (93.3%) LTRs and caregivers were unaware of the risk of CVD after LT. Although 54.5% of providers were confident discussing CVD risk factors with LTRs, only 36.3% were confident managing CVD risk factors in LTRs, and only 13.6% felt that CVD risk factors in their LTR patients were well controlled. Barriers to CVD care for LTRs included (1) lack of awareness of CVD risk after LT, (2) lack of confidence in an ability to provide proper CVD care to LTRs, (3) reluctance to provide CVD care without transplant provider review, and (4) complexity of communication with the multidisciplinary LTR care team about CVD care. Participant recommendations included improved education for LTRs and caregivers about CVD risk factors, electronic health record alerts for providers, clearly defined CVD care provider roles, increased use of the transplant pharmacist, and multidisciplinary provider meetings to discuss care plans for LTRs. Multiple barriers to CVD care after LT were identified, and targeted recommendations were proposed by participants. Transplant centers should integrate participants' recommendations when designing interventions to optimize CVD care for LTRs.

ZusammenfassungFür die Therapie kindlicher Aussprachestörungen ist die diagnostische Abgrenzung zwischen kindlicher Sprechapraxie (KSAX) und phonologischer Aussprachestörung (PAS) wichtig. Während für die Diagnostik einer PAS Diagnostikmaterial zur Verfügung steht, ist das Expertenurteil Goldstandard in der Diagnostik einer KSAX. Ziel des Beitrags ist die Definition von Testungen zur Differenzialdiagnostik von KSAX und PAS für deutschsprachige Kinder im Alter von 4;6–5;11 Jahren. Die Stichprobe umfasst 8 Kinder mit KSAX und 5 Kindern mit PAS. Es werden die Ergebnisse der PLAKSS-II mit Inkonsequenztest, Test zum Nachsprechen von Lauten, Test zu konsistenten Wiederholungen von Lauten und Wörtern und Test zu oralmotorischen Fähigkeiten, in denen signifikante Unterschiede zwischen den Gruppen (KSAX vs. PAS) vorliegen, vorgestellt. Daraus können konkrete Realisierungen zur Differenzialdiagnostik von KSAX und PAS für deutschsprachige Kinder abgeleitet werden. Die Erprobung der Testungen an einer größeren Stichprobe ist notwendig.

Background Both interferon beta-1b (IFN-β-1b) and interferon beta-1a (IFN-β-1a) are immunomodulators that require regular subcutaneous self-administration by patients with multiple sclerosis (MS). However, no electronic autoinjector is available for IFN-β-1a in the US. Objective This retrospective cohort study investigated adherence to two subcutaneous disease-modifying therapies, IFN-β-1b and IFN-β-1a, during two periods (before and after the introduction of the BETACONNECT® autoinjector for IFN-β-1b). Patients and Methods Data were evaluated from the MarketScan database for adults in the US with an MS diagnosis and a medical claim for subcutaneous IFN-β-1b or IFN-β-1a, either before (October 2013–September 2015) or after the introduction of BETACONNECT (October 2016–September 2018). Patient populations were propensity-score matched by demographic and clinical characteristics. Persistence was recorded, and adherence was evaluated by medication possession ratio (MPR). Results The study included 196 IFN-β-1b and 365 IFN-β-1a people with MS (PwMS) (pre-BETACONNECT period), and 126 IFN-β-1b and 223 IFN-β-1a PwMS (post-BETACONNECT period). In the pre-BETACONNECT period, the proportion with at least 80% MPR was higher for IFN-β-1a (90%) than for IFN-β-1b (83%), but in the post-BETACONNECT period the proportion with ≥ 80% MPR was higher for IFN-β-1b (92%) than for IFN-β-1a (86%). In the pre-BETACONNECT period, median persistence (in days) was higher for IFN-β-1a (199) than for IFN-β-1b (152), while in post-BETACONNECT period persistence was higher for IFN-β-1b (327) than for IFN-β-1a (229). Conclusions Following the introduction of BETACONNECT, this exploratory study suggested that PwMS taking IFN-β-1b were more adherent compared with those taking IFN-β-1a, with higher persistence, and more than 90% reached 80% MPR, a threshold commonly used to define good adherence. Supplementary Information The online version contains supplementary material available at 10.1007/s40801-021-00248-5.

Bisphenol F (BPF) is increasingly substituting bisphenol A in manufacturing polycarbonates and consumer products. The cardiometabolic effects of BPF in either humans or model organisms are not clear, and no studies to date have investigated the role of genetic background on susceptibility to BPF-induced cardiometabolic traits. The primary goal of this project was to determine if BPF exposure influences growth and adiposity in male N:NIH heterogeneous stock (HS) rats, a genetically heterogeneous population. Littermate pairs of male HS rats were randomly exposed to either vehicle (0.1% ethanol) or 1.125 µg/ml BPF in 0.1% ethanol for 5 weeks in drinking water starting at 3 weeks-of-age. Water consumption and body weight was measured weekly, body composition was determined using nuclear magnetic resonance, urine and feces were collected in metabolic cages, and blood and tissues were collected at the end of the study. BPF-exposed rats showed significantly increased body growth and abdominal adiposity, risk factors for cardiometabolic disease. Urine output was increased in BPF-exposed rats, driving a trend in increased creatinine clearance. We also report the first relationship between a bisphenol metabolizing enzyme and a bisphenol-induced phenotype. Preliminary heritability estimates of significant phenotypes suggest that BPF exposure may alter trait variation. These findings support BPF exposure as a cardiometabolic disease risk factor and indicate that the HS rat will be a useful model for dissecting gene by BPF interactions on metabolic health.

Background and Objective: Intermittent scanning continuous glucose monitoring (iscCGM) is increasingly used for glycemic monitoring in diabetes care. In this cross-sectional real-world analysis, is...

Host-mediated lung inflammation is present1, and drives mortality2, in the critical illness caused by coronavirus disease 2019 (COVID-19). Host genetic variants associated with critical illness may identify mechanistic targets for therapeutic development3. Here we report the results of the GenOMICC (Genetics Of Mortality In Critical Care) genome-wide association study in 2,244 critically ill patients with COVID-19 from 208 UK intensive care units. We have identified and replicated the following new genome-wide significant associations: on chromosome 12q24.13 (rs10735079,P=1.65×10−8) in a gene cluster that encodes antiviral restriction enzyme activators (OAS1,OAS2andOAS3); on chromosome 19p13.2 (rs74956615,P=2.3×10−8) near the gene that encodes tyrosine kinase 2 (TYK2); on chromosome 19p13.3 (rs2109069,P=3.98× 10−12) within the gene that encodes dipeptidyl peptidase 9 (DPP9); and on chromosome 21q22.1 (rs2236757,P=4.99×10−8) in the interferon receptor geneIFNAR2. We identified potential targets for repurposing of licensed medications: using Mendelian randomization, we found evidence that low expression ofIFNAR2, or high expression ofTYK2, are associated with life-threatening disease; and transcriptome-wide association in lung tissue revealed that high expression of the monocyte–macrophage chemotactic receptorCCR2is associated with severe COVID-19. Our results identify robust genetic signals relating to key host antiviral defence mechanisms and mediators of inflammatory organ damage in COVID-19. Both mechanisms may be amenable to targeted treatment with existing drugs. However, large-scale randomized clinical trials will be essential before any change to clinical practice.

Objective To perform an exploratory, descriptive pilot study of the systemic and local immune environment in patients with vesicoureteral reflux (VUR) and bladder-bowel dysfunction (BBD). Methods Consecutive children with VUR undergoing intravesical ureteral reimplantation were enrolled. Patients were assessed for presence of BBD by reported patient history and validated questionnaire. Fresh blood and bladder tissue, collected at the time of surgery, were immediately processed for analysis. Immune cell compositions were determined via flow cytometry. Immune cell activation was also defined at the time of analysis. LegendPlex assay analysis was utilized to define levels of circulating chemokines and cytokines. Results A total of 7 patients were enrolled. Although percentages of circulating immune cells in the blood of those with VUR/BBD and VUR alone were similar, within bladder tissue, VUR/BBD demonstrated increased immune infiltrates compared to VUR alone. Bladder sample analysis showed that B cells, and Effector Memory and Naive T cell percentages were significantly increased in VUR/BBD patients compared to VUR patients. T cell expression of PD1 was increased in bladder tissues of BBD/VUR. Additionally, analysis of circulating neutrophils displayed significantly increased upregulation of PDL-1 in patients with VUR/BBD vs those with VUR only. Conclusion These pilot data suggest an immune-rich microenvironment is present within VUR. Severity of inflammation appeared to correlate with presence of BBD. This implies that targeting pelvic inflammation may be a novel therapy for children with VUR- or non-VUR-related BBD. Follow-up studies are currently underway.

Background Previous MRI studies reported deep grey matter volume increases after electroconvulsive therapy (ECT) in patients with major depressive disorder (MDD). However, the clinical correlates of these changes are still unclear. It remains debated whether such volume changes are transient, and if they correlate with affective changes over time. We here investigated if ECT induces deep grey matter volume increases in MDD-patients; and, if so, whether volume changes persist over more than 9 months and whether they are related to the clinical outcome. Methods We examined 16 MDD-patients with 3Tesla MRI before (baseline) and after an ECT-series and followed 12 of them up for 10-36 months. Patients’ data were compared to 16 healthy controls. Affective scales were used to investigate the relationship between therapy-outcome and MRI changes. Results At baseline, MDD-patients had lower values in global brain volume, white matter and peripheral grey matter compared to healthy controls, but we observed no significant differences in deep grey matter volumes. After ECT, the differences in peripheral grey matter disappeared, and patients demonstrated significant volume increases in the right hippocampus and both thalami, followed by subsequent decreases after 10-36 months, especially in ECT-responders. Controls did not show significant changes over time. Limitations Beside the relatively small, yet carefully characterized cohort, we address the variability in time between the third scanning session and the baseline. Conclusions ECT-induced deep grey matter volume increases are transient. Our results suggest that the thalamus might be a key region for the understanding of the mechanisms of ECT action.

Male hypogonadism and major comorbidities such as type 2 diabetes mellitus, obesity, cardiovascular disease, and osteoporosis appear closely connected, forming a vicious cycle that leads to further hypogonadism. This narrative review provides a comprehensive overview of the current literature on the overall burden of male hypogonadism alongside related comorbidities, and how this may be alleviated through testosterone therapy. Observational and clinical data demonstrate that the interaction of male hypogonadism and its related comorbidities is associated with increased mortality, cardiovascular event risk and reduced quality of life. Evidence from epidemiological and registry-based studies shows that this clinical and humanistic burden translates to increased economic burden on health-care systems, through increased physician visits, medical claims, and drug costs. Male hypogonadism can be managed with testosterone therapy, which is intended to normalize testosterone concentrations and thereby reduce both hypogonadism symptoms and risk of comorbidities. Clinical and observational data suggest that in males with hypogonadism, testosterone therapy rapidly and sustainably improves glycemia, reduces risk of progression to diabetes, leads to significantly reduced waist circumference and fat mass, while providing significant positive effects on cardiovascular event risk and bone density. Significant and sustained improvement in patient-reported erectile function, urinary function, and aging male symptoms have also been shown. Economic evaluations have estimated that reduced comorbidity risk following testosterone therapy may lead to cost-savings, with one study estimating yearly inpatient savings of £3732 for treating comorbidities after intervention. A major unmet need exists in the area of male hypogonadism, particularly related to common comorbidities. Options for treatment include testosterone therapy, which has been shown to alleviate the clinical, economic, and humanistic burden associated with these conditions. As the prevalence of male hypogonadism is likely to increase globally, and this condition may be currently underdiagnosed, cost-saving testosterone therapies should be increasingly considered to manage hypogonadism.

Background: Diet modification has the potential to influence glycemic control and diabetes outcome in patients with type 1 diabetes (T1D). This cross-sectional study aimed to assess types of diets being reported by patients with T1D and documented in the Diabetes Patients Follow-Up Registry (DPV). Methods: The DPV registry was screened for additional free text entries containing information about certain diets and/or physician-based diagnoses requiring special diets e. g. celiac disease. Descriptive analysis and unadjusted comparisons between patients with T1D following at least one special diet and controls (T1D without diet) were performed. Results: Overall, 113,894 patients with T1D of all ages were included. In 2.3% (n = 2,595; median age 11.3 yrs [Q1; Q3: 7.0; 15.2]), at least one kind of diet was documented. These patients were significantly younger at diabetes onset than controls (median age 7.5 yrs [Q1; Q3: 3.9; 11.4] vs. 11.1 yrs [6.6; 16.7]; p < 0.001) and showed a significantly lower BMI-SDS (median [Q1; Q3]: 0.220 [−0.427;0.812] vs. 0.450 [−0.211;1.088]). Diet was more often reported in females (55.7% vs. 44.3%, p < 0.001). The three most common diets were gluten-free diet due to celiac disease, low-protein diet, and lactose-restricted diet due to lactoseintolerance. A combination of two diagnoses in one patient (n = 44, 1.7% of the entire diet group) was predominantly intolerance to both fructose and lactose. Among all diet subgroups the highest BMI-SDS was found in the group diets for weight loss. Conclusions: This study revealed a wide range of eating habits in patients with T1D. A special diet was more frequently documented in females. The main reason for adhering to a diet was a concomitant disease. As any diet modification could impact glycemic control, health care providers should be encouraged to regularly ask their patients about their eating habits and provide training and support by specialized dietitians.

Summary Background Although continuous subcutaneous insulin infusion therapy (ie, insulin pump therapy) is associated with improved metabolic control compared with multiple daily insulin injections in children with type 1 diabetes, it is unclear when it is best to start it after diagnosis. In this study, we aimed to compare the outcomes between early and delayed start of insulin pump therapy in young patients with type 1 diabetes. Methods We based the current study on data from the multicentre, prospective diabetes follow-up registry (ie, Diabetes-Patienten-Verlaufsdokumentation [DPV]). The DPV registry comprises 501 diabetes centres from Germany, Austria, Switzerland, and Luxembourg. We included patients diagnosed with type 1 diabetes between 2004 and 2014, who were aged between 6 months and 15 years at the time of diagnosis, who had started insulin pump therapy either within the first 6 months (ie, the early treatment group) or in the second to third year (ie, the delayed treatment group) after diabetes diagnosis, and who were treated with insulin pump therapy for at least 1 year. The outcome parameters included the glycated haemoglobin (HbA1c) values, the cardiovascular risk profile, and rates of acute complications and diabetes-associated hospital admissions (ie, hospitalisation) during the most recent documented treatment year with insulin pump therapy. Statistical models were adjusted for age at diabetes diagnosis, year of diagnosis, sex, immigrant background, use of continuous glucose monitoring, centre size, and the German Index of Socioeconomic Deprivation 2012 terciles. Findings Our study sample comprised 8332 patients from 311 diabetes centres in Germany, Austria, Switzerland, and Luxembourg. The early treatment group consisted of 4004 (48·1%) of 8332 patients, and the delayed treatment group consisted of 4328 (51·9%). The median diabetes duration during follow-up was 6·7 years (IQR 5·1–8·7 in the early group; 5·0–8·7 in the delayed group) in both groups. Patients with early initiation of insulin pump therapy compared with those with delayed initiation of insulin pump therapy had significantly lower estimated mean HbA1c values (7·9% [95% CI 7·8–7·9] and 62·6 mmol/mol [95% CI 62·1–63·2] vs 8·0% [8·0–8·1] and 64·1 mmol/mol [63·6–64·6]; p=0·0006), and lower rates of hypoglycaemic coma (incidence risk ratio 0·44 [95% CI 0·24–0·79]; p=0·0064) and hospitalisation (0·86 [95% CI 0·78–0·94]; p=0·0016). A better cardiovascular risk profile was observed in patients with early initiation of insulin pump therapy than in those with delayed initiation: an estimated mean systolic blood pressure of 117·6 mm Hg (95% CI 117·2–117·9) versus 118·5 mm Hg (118·2–118·9), p=0·0007; and HDL cholesterol of 62·8 mg/dL (95% CI 62·2–63·5) versus 60·6 mg/dL (60·0–61·2), p Interpretation Our findings provide evidence for improved clinical outcomes associated with the early initiation of insulin pump therapy in children with type 1 diabetes. Funding The German Center for Diabetes Research (Deutsches Zentrum fur Diabetesforschung), German Robert Koch Institute, German Diabetes Association, and Diabetes Agenda 2010.

Aim To determine the prevalence of inflammatory bowel disease (IBD) in patients with type 1 diabetes (T1D) and to characterise patients with both diseases. Methods Data of 65.147 patients with T1D ≤18 years of 379 centres in Germany and Austria participating in the DPV initiative were analysed. A total of 63 children had comorbid IBD; IBD prevalence was 0.1%. Regression models were used to analyse differences in metabolic control, acute complications and steroid intake. Results Mean BMI‐SDS in patients with T1D and IBD was lower (−0.15 ± 0.11) compared to patients with T1D only (0.27 ± 0.00, p

Die institutionelle Krippenbetreuung fur Kinder unter 3 Jahren (U3-Betreuung) wird aktuell offentlich und politisch kontrovers diskutiert. Eine systematische Uberprufung des bisherigen empirischen Forschungsstandes zu diesem Thema ist noch ausstehend und soll mit diesem Artikel erbracht werden. Mit der Methode der Preferred Reporting Items for Systematic Reviews and Meta-Analyses Guidelines (PRISMA-Richtlinien) erfolgte eine systematische Literaturrecherche und -analyse empirischer Peer-reviewed-Studien, die die folgenden Einschlusskriterien erfullten: 1) die untersuchte Stichprobe gehort dem Sauglings- und Kleinkindalter (zwischen 0 und 3 Jahren) an, 2) Untersuchungsschwerpunkt sind die Effekte der institutionellen Fruhbetreuung auf die kindliche Entwicklung, 3) die Ergebnisse werden mit einer Kontrollgruppe verglichen sowie 4) Messungen wurden mit validierten Messmethoden vollzogen. Es wurden 28 Studien eingeschlossen, die die Auswirkungen der institutionellen U3-Betreuung auf die kognitive/sprachliche, emotionale Entwicklung/Bindung und das Sozialverhalten von Kindern untersuchten. Die Synthese der Ergebnisse ergab, dass der Bindungsstil von Kindern eher von der Familie gepragt wird, aber Sprache, Kognitionen und auch Sozialverhalten von Kindern in U3-Einrichtungen bei Stabilitat der Betreuungskonstellation, gutem Betreuungsschlussel und hoher Qualitat der padagogischen Arbeit positiv unterstutzt werden konnen. Fazit: Auf der Grundlage der aktuellen empirischen Studien kann eine U3-Betreuung empfohlen werden, wenn sie den genannten Qualitatsmerkmalen entspricht.

We present the case of a patient with granulomatous endocarditis of the mitral valve leading to severe valve stenosis caused by granulomatosis with polyangiitis. Endocarditis is a rare complication of granulomatosis with polyangiitis that may be misdiagnosed as infectious endocarditis or, as in our case, thrombotic lesions. (Level of Difficulty: Intermediate.), Graphical abstract

ZusammenfassungZiel dieser Beobachtungsstudie ist die Beschreibung der aktuellen Nutzung von Diabetestechnologien bei Patienten/-innen mit Diabetes mellitus.Methode Auswertung von Daten des DPV-Registers zur Nutzung der Insulinpumpentherapie (CSII), kontinuierlicher Glukosemessung (CGM) und der Selbstmessung der Blutglukose (SMBG) aus 497 teilnehmenden Zentren in Deutschland, Österreich, Luxemburg und der Schweiz zwischen 1995 und 2019. Die Daten wurden bei Patienten/-innen mit Diabetes Typ 1 (Alter ≥ 0,5 Jahre) für 5 Altersgruppen ausgewertet. Zusätzlich wurden aktuelle (zwischen 2017 und 2019) Geschlechtsunterschiede in der Verwendung von Diabetestechnologie bei Typ-1-Patienten/-innen untersucht, ebenso wie die Nutzung von Insulinpumpen und CGM für Patienten/-innen mit Insulintherapie bei Typ-2-DM, bei zystischer Fibrose (CFRD), bei anderen Pankreaserkrankungen, neonatalem Diabetes und Maturity Onset Diabetes of the Young (MODY).Ergebnisse Es zeigte sich bei Patienten/-innen mit Diabetes Typ 1 ein Anstieg der CSII-Nutzung von 1995 bis 2019 von 1 % auf 55 % (2019: Zwischen 2017 und 2019 erfolgte eine Nutzung von Insulinpumpen und CGM bei neonatalem Diabetes (CSII 87 %; CGM 38 %), bei MODY (CSII 14 %; CGM 28 %) und bei CFRD (CSII 18 %; CGM 22 %). CGM und CSII wurden dagegen nur selten von Menschen mit Insulintherapie und Diabetes Typ 2 (CSII Schlussfolgerung Moderne Diabetestechnologien werden derzeit insbesondere von pädiatrischen Patienten/-innen mit Diabetes Typ 1, aber auch von Menschen mit neonatalem Diabetes breit genutzt, von Patienten/-innen mit MODY und CFRD sowie Erwachsenen mit Diabetes Typ 1 in etwas geringerem Maße mit ansteigendem Trend. Dagegen sind diese Technologien in der Therapie des Typ-2-Diabetes und bei anderen Pankreaserkrankungen zurzeit nur wenig verbreitet.

ZusammenfassungJugendliche und junge Erwachsene mit Typ-1-Diabetes sind häufig von komorbiden psychischen Störungen betroffen. Dabei zeigt die Studienlage zur Verbreitung ein heterogenes und inkonsistentes Bild. Diagnose und Behandlung der somatopsychischen Begleiterkrankungen beeinflussen den Behandlungs- und Krankheitsverlauf sowie die Lebensqualität der Betroffenen. Trotzdem wird dies in der klinischen Praxis selten frühzeitig berücksichtigt. Das multizentrische Verbundprojekt COACH verfolgt das Ziel, die Erkennung und Behandlung psychischer Komorbidität für diese Zielgruppe in der bundesweiten Routineversorgung zu optimieren.

Background Enhanced recovery protocols (ERPs) have been used to improve patient outcomes and resource utilization after surgery. These evidence-based interventions include patient education, standardized anesthesia protocols, and limited fasting, but their use among pediatric populations is lagging. We aimed to determine baseline recovery practices within pediatric surgery departments participating in an ERP implementation trial for elective inflammatory bowel disease (IBD) operations. Methods To measure baseline ERP adherence, we administered a survey to a staff surgeon in each of the 18 participating sites. The survey assessed demographics of each department and utilization of 21 recovery elements during patient encounter phases. Mixed-methods analysis was used to evaluate predictors and barriers to ERP element implementation. Results The assessment revealed an average of 6.3 ERP elements being practiced at each site. The most commonly practiced elements were using minimally invasive techniques (100%), avoiding intraabdominal drains (89%), and ileus prophylaxis (72%). The preoperative phase had the most elements with no adherence including patient education, optimizing medical comorbidities, and avoiding prolonged fasting. There was no association with number of elements utilized and total number of surgeons in the department, annual IBD surgery volume, and hospital size. Lack of buy-in from colleagues, electronic medical record adaptation, and resources for data collection and analysis were identified barriers. Conclusions Higher intervention utilization for IBD surgery was associated with elements surgeons directly control such as use of laparoscopy and avoiding drains. Elements requiring system-level changes had lower use. The study characterizes the scope of ERP utilization and the need for effective tools to improve adoption. Level of evidence Level III. Type of study Mixed-methods survey.

ZusammenfassungIm Rahmen der vorliegenden multizentrischen Auswertung mit 6.424 Pflegepatienten unter 500.973 Menschen mit Diabetes aus dem DPV-Register wird die Erkrankungssituation der Pflegebedürftigen im Vergleich zu Patienten ohne Pflegebedürftigkeit, differenziert nach Altersgruppen und Diabetestyp, dargestellt.15 % der Pflegebedürftigen haben einen Typ-1-Diabetes, darunter fallen 99,0 % der Kinder, 9,5 % der 18- bis 75-Jährigen und 2,4 % der über 75-Jährigen. Pflegebedürftigkeit ist bei Erwachsenen und Senioren insbesondere mit den Krankheitsbildern Demenz, Depression, Herzinsuffizienz, Durchblutungsstörungen der Hirngefäße/Schlaganfall sowie mit dem diabetischen Fußsyndrom/Amputationen assoziiert. In der diabetologischen Therapie des Typ-2-DM wird bei 77 % der Pflegebedürftigen und damit deutlich häufiger als in der Vergleichsgruppe mit 55 % Insulin eingesetzt. Trotz höherer HbA1c-Werte und höherer Nüchternglukose als bei Typ-2-Patienten ohne Pflege treten unter Pflegebedürftigen gleichzeitig signifikant häufiger Hypoglykämien mit und ohne Koma auf. Stoffwechselbedingte Entgleisungen führten bei 15 % der Pflegepatienten mit Typ-2-DM gegenüber nur 6 % der Menschen mit Typ-2-DM ohne Pflegebedarf zu Klinikaufnahmen.Im Rahmen der Versorgung sollte verstärkt auf die Vermeidung von Stoffwechselentgleisungen geachtet und präventiv auf einen späteren Eintritt der assoziierten Krankheitsbilder hingewirkt werden. Die Versorgungsstrukturen sollten regional auf die Begleitung der Betroffenen spezialisiert werden. In der Aus- und Weiterbildung von Pflegepersonal und Ärzten sollten die Besonderheiten von jungen und alten Menschen mit Typ-1- und Typ-2-Diabetes stärker beachtet werden.

BACKGROUND: In melanoma patients, microscopic tumor in the sentinel lymph node biopsy (SLN) increases the risk of distant metastases but the transition from tumor in the SLN to metastatic disease remains poorly understood. METHODS: Fluorescent staining for CD3, CD20, CD11c, and DNA was performed on SLN tissue and matching primary tumors. Regions of interest (ROI) were then chosen geometrically (e.g. tumor) or by fluorescent cell subset markers (e.g. CD11c). Each ROI was further analyzed using NanoString Digital Spatial Profiling high-resolution multiplex profiling. Digital counts for 59-panel immune related proteins were collected and normalized to account for system variation and ROI area. RESULTS: Tumor regions of SLNs had variable infiltration of CD3 cells among patients. The patient with overall survival (OS) > 8 years had the most CD11c- and CD3-expressing cells infiltrating the SLN tumor region. All patients had CD11c (dendritic cell, DC) infiltration into the SLN tumor region. Selecting ROI by specific cell subtype, we compared protein expression of CD11c cells between tumor and non-tumor/normal tissue SLN regions. Known markers of DC activation such as CD86, HLA-DR, and OX40L were lowest on CD11c cells within SLN tumor for the patient with OS < 1 year and highest on the patient with OS > 8 years. CONCLUSION: We demonstrate the feasibility of profiling the protein expression of CD11c cells within the SLN tumor. Identifying early regulators of melanoma control when the disease is microscopically detected in the SLN is beneficial and requires follow-up studies in a larger cohort of patients.

Background: To analyze key indicators of metabolic control in adults with type 1 diabetes (T1D) using real-time or intermittent scanning continuous glucose monitoring (rtCGM/iscCGM) during real-lif...

Objective To estimate the prevalence of diabetes due to diseases of the exocrine pancreas (DEP) using data of the multicentre diabetes patient follow-up registry. Moreover, we aimed at comparing individuals with diabetes due to DEP to individuals with type 1 and type 2 diabetes. Methods Individuals with DEP, type 1 or type 2 diabetes ≥18 years of age were studied. We aggregated the most recent treatment year per patient and used propensity scores to match diabetes due to DEP to type 1 and type 2 diabetes. Matching was conducted one-to-one with sex, age, diabetes duration, migration background and the German index of socioeconomic deprivation as covariates. Results We identified 7,093 (1.6%) individuals with diabetes due to DEP. In the matched cohort DEP-type 1 diabetes we observed a similar daily insulin dose (0.62 IU/kg (95% confidence interval:0.60–0.63), 0.60 IU/kg (0.58–0.62)) and significant differences regarding microvascular (41.0% (39.7–42.2), 45.3% (44.0–46.6)), and macrovascular disease (16.6% (15.7–17.6), 14.7% (13.8–15.6)). HbA1c (8.2% (8.1–8.3), 7.9% (7.8–8.0)), daily insulin dose (0.60 IU/kg (0.58–0.62), 0.56 IU/kg (0.54–0.58)) and event rates of severe hypoglycemia (23.9 events/100 PY (21.4–26.8), (9.5 events/100 PY (8.0–11.2)) were significantly higher in individuals with diabetes due to DEP compared to type 2 diabetes. Conclusions Using registry data, rare diabetes types such as diabetes due to DEP can be studied with a significant sample size. Our study identified differences and similarities between adult individuals with DEP related diabetes and type 1 or type 2 diabetes.

Background To explore, in a large group of patients with type-2 diabetes (T2DM), renal function decline in terms of the slope of the estimated glomerular filtration rate (eGFR) over time, and to find out how classical risk factors, such as the presence of hypertension, dyslipidemia and microalbuminuria, affect the renal function. Methods The analysis included 32,492 adult T2DM patients from the DIVE/DPV registries who had serial eGFR determinations and information on the presence of microalbuminuria, hypertension and dyslipidemia available. Results Patients had a mean age of 66.3 years, 52.6% were male with a mean BMI of 31.7 kg/m2. The mean eGFR was 78.4 ± 21.4 mL/min/1.73m2. The results showed that the prevalence of renal function impairment understood as chronic kidney disease (CKD) is considerable (53.0%) in a population of patients with T2DM and has a high incidence rate of 6.6% within a year. Serial determinations of the eGFR are, however, infrequent (7.8% of all patients) and these patients are characterised by the presence of a high-risk profile for CKD, such as hypertension (88.1%) and dyslipidemia (66.1%). Over a three-year time period, 30.9% of the patients had an eGFR slope of -12 mL/min/1.73m2 or more; and more than a doubled proportion of patients with an eGFR 2 (3.8% vs. 1.8%; p Conclusion CKD is highly prevalent in patients with T2DM. Serial surveillance of the glomerular filtration rate is, however, not established in clinical practice, which would be necessary as indicated by a doubling of patients with an eGFR 2 within 3 years. Moreover, the use of renin-angiotensin blocking agents was low, pointing at considerable room for improvement. Taken together we conclude that a closer surveillance of patients with diabetes based on the presence of further risk factors is mandatory combined with a mandatory prescription of RAS blocking agents once microalbuminuria and / or renal function deterioration develops.

Objective Long-term outcomes are rarely reported for patients with pediatric hydrocephalus. Ventriculoperitoneal shunting is the surgical standard; nevertheless, in selected patients, a ventriculoatrial shunt (VAS) remains an important alternative. This study aimed to analyze the causes of VAS revisions and complications. Methods Pediatric patients who underwent their first shunt operation between 1982 and 1992 were included. The timing, cause, and modality of VAS revisions were retrospectively determined. Results Overall, 138 patients were treated for hydrocephalus and 61 patients received a VAS during the follow-up period. A primary VAS was the first shunt type in 42 (68.85%) patients. In 19 (31.15%) patients, conversions to second-line VAS were carried out. The rates of VAS revisions performed for dysfunction or elective lengthening of a short atrial catheter were 52.2% and 22.9%, respectively. There was no difference in the number of VAS revisions between patients with primary VASs and second-line VASs. Age at VAS and etiology of hydrocephalus had no effect on the number of revisions. Specific VAS complications were observed in 2 patients. Deep positioning of the distal catheter led to asymptomatic tricuspid regurgitation that was reversible after shortening of the atrial catheter. Another patient presented with shunt nephritis and completely recovered after the atrial catheter was replaced with a peritoneal catheter. Conclusions VAS remains an appropriate second-line alternative in selected patients. Specific VAS complications were rarely observed and completely reversible after treatment. However, regular and specific follow-up examinations are strongly recommended to avoid cardiopulmonary or renal complications.

Aims To compare diabetes patients with hyperglycaemic hyperosmolar state (HHS), diabetic ketoacidosis (DKA), and patients without decompensation (ND). Methods In total, 500,973 patients with type 1 or type 2 diabetes of all ages registered in the diabetes patient follow-up (DPV) were included. Analysis was stratified by age (≤ / > 20 years) and by manifestation/follow-up. Patients were categorized into three groups: HHS or DKA—during follow-up according to the most recent episode—or ND. Results At onset of diabetes, HHS criteria were met by 345 (68.4% T1D) and DKA by 9824 (97.6% T1D) patients. DKA patients had a lower BMI(-SDS) in both diabetes types compared to ND. HbA1c was higher in HHS/DKA. During follow-up, HHS occurred in 1451 (42.2% T1D) and DKA in 8389 patients (76.7% T1D). In paediatric T1D, HHS/DKA was associated with younger age, depression, and dyslipidemia. Pump usage was less frequent in DKA patients. In adult T1D/T2D subjects, metabolic control was worse in patients with HHS/DKA. HHS and DKA were also associated with excessive alcohol intake, dementia, stroke, chronic kidney disease, and depression. Conclusions HHS/DKA occurred mostly in T1D and younger patients. However, both also occurred in T2D, which is of great importance in the treatment of diabetes. Better education programmes are necessary to prevent decompensation and comorbidities.

Das muskuloskeletale System unterliegt in Kindheit und Jugend bis zum Erreichen der Endgrose einem ausgepragten Langenwachstum. Zusatzlich muss sich das muskuloskeletale System kontinuierlich an die aktuellen auf Muskel und Knochen einwirkenden Beanspruchungen adaptieren. Uber die funktionelle Muskel-Knochen-Einheit wird im Sinne eines Regelkreises der Knochenaufbau und -abbau angepasst. Im Rahmen chronischer Erkrankungen (neurologische Erkrankungen, Knochenstoffwechselstorungen, rheumatisch-entzundliche Erkrankungen) aber auch im Rahmen einer kurzfristigen Immobilitat kommt es haufig direkt oder indirekt zu Veranderungen der funktionellen Muskel-Knochen-Einheit, der Gelenke oder der Bewegungsmuster, was letztlich in einer „Bewegungsstorung“ bzw. in veranderten Bewegungsmustern mundet. Unabhangig von der zugrunde liegenden Ursache scheinen die reduzierte Beweglichkeit, das veranderte Bewegungsmuster und die teilweise resultierende Immobilitat die Teilhabe der Betroffenen am Leben deutlich zu reduzieren, weswegen diesem Symptom eine hohe Wichtigkeit aus Sicht der Patienten zugeschrieben wird. Eine gezielte Diagnostik mit funktioneller Analyse der vorliegenden Bewegungsstorung erscheint unabdingbar, um ein interdisziplinar individuelles Betreuungskonzept, basierend auf der zugrunde liegenden Erkrankung, anbieten und dessen Wirksamkeit beurteilen zu konnen sowie die Lebensqualitat und Teilhabe der Betroffenen zu erhalten.

AIM To examine the control of cardiovascular risk factors in type 1 diabetes (T1D) registries from the United States and Germany/Austria. MATERIALS AND METHODS Data on individuals aged ≥12 years with T1D for ≥1 year, from the T1D Exchange Clinic Network (T1DX, United States) and the Prospective Diabetes Follow-up Registry (DPV, Germany/Austria) from 1 January 2016 to 31 March 2018 were analysed. Linear and logistic regression models adjusted for age groups, sex, duration of diabetes and minority status were used to compare clinical characteristics and achievement of diabetes management targets between registries. RESULTS The cohort consisted of 47 936 patients (T1DX, n = 19 442; DPV, n = 28 494). Achievement of HbA1c goals (

Zu den Grosgefasvaskulitiden zahlen 2 unterschiedliche Entitaten, die Riesenzellarteriitis (RZA) und die Takayasu-Arteriitis (TAK). Die RZA ist die haufigste Vaskulitis in Mitteleuropa und manifestiert sich im Alter von uber 50 Jahren, wohingegen die wesentlich seltenere TAK fast ausschlieslich junge Erwachsene und hierbei uberwiegend Frauen betrifft. Beide Vaskulitiden betreffen als granulomatose Arteriitiden hauptsachlich die Aorta und von ihr abgehende Arterienaste. RZA und TAK sind mit unterschiedlichen Genen des Haupthistokompatibilitatskomplexes assoziiert. Infektionen spielen moglicherweise eine Rolle bei der Initiierung von Grosgefasvaskulitiden. Die Aktivierung von dendritischen Zellen in der Adventitia induziert eine Chemokin- und Zytokin-vermittelte Rekrutierung und Reifung von T‑Helfer(Th)1- und Th17-Zellen und von Zytokin‑, Wachstumsfaktor- und Matrixmetalloproteinase-produzierenden Makrophagen. Bei der RZA werden uberwiegend CD4+-T-Helferzellen und Makrophagen im entzundlichen Infiltrat gefunden, bei der TAK auch zytotoxische CD8+-T-Zellen und γδ-T-Zellen. Dies konnte auf unterschiedliche antigene Trigger bei der RZA und TAK deuten. Die entzundliche Infiltration mit T‑Zellen und Makrophagen sowie die Aktivierung von Myofibroblasten und glatten muskularen Zellen fuhren zu vaskularen Umbauvorgangen mit Intimahyperplasie und Destruktion der Media. Der Umbau ist histologisch durch eine fortschreitende Arterienwandfibrose, Gefasstenosierung und Obstruktion gekennzeichnet. Zusammengefasst stellen die RZA und TAK zwei verschiedene Entitaten mit unterschiedlichem HLA(„human leukocyte antigen“)- und moglicherweise atiopathogenetischem Hintergrund dar. Klinisch imponieren entzundungsbedingte Allgemeinsymptome und Ischamiezeichen, einhergehend mit erhohten serologischen Entzundungsmarkern.

Purpose of Review Probiotics are living bacteria, which when ingested in adequate amounts, confer health benefits. Gut microbes are suggested to play a role in many psychiatric disorders and could be a potential therapeutic target. Between the gut and the brain, there is a bi-directional communication pathway called the microbiota-gut-brain axis. The purpose of this review is to examine data from recent interventional studies focusing on probiotics and the gut-brain axis for the treatment of depression, anxiety and schizophrenia. Recent Findings Probiotics are likely to improve depression but not schizophrenia. Regarding anxiety, there is only one trial which showed an effect of a multispecies probiotic. However, determinants like the duration of treatment, dosage and interactions have not been thoroughly investigated and deserve more scientific attention. Summary Microbiome-based therapies such as probiotics could be cautiously recommended for depression to enhance beneficial bacteria in the gut and to improve mood through the gut-brain axis.

Type 1 diabetes (T1D) is a known risk factor for fractures, but the underlying pathophysiology is still not fully understood. This study aims to define age peaks and frequent fracture sites of children and young adults with T1D. Additionally, associations of fractures with metabolic and lifestyle factors as well as with additional complications in individuals with T1D were analyzed. A total of 750 individuals with T1D aged ≤25 years with fractures were matched to 3750 patients with T1D without fractures by demographics and insulin regimen. Hemoglobin A1c (HbA1c) values were compared using linear regression, and logistic regression was used to calculate odds ratios (OR) for fractures in individuals with acute complications and diseases. Median (Q1–Q3) age was 12.7 (9.9 to 14.9) years in individuals with fractures and 16.3 (12.6 to 17.8) years in the entire control group with 65% versus 53% males. Peak age for fractures was 7 to

Many personality traits are influenced by genetic factors. Rodents models provide an efficient system for analyzing genetic contribution to these traits. Using 1,246 adolescent heterogeneous stock (HS) male and female rats, we conducted a genome-wide association study (GWAS) of behaviors measured in an open field, including locomotion, novel object interaction, and social interaction. We identified 30 genome-wide significant quantitative trait loci (QTL). Using multiple criteria, including the presence of high impact genomic variants and co-localization of cis-eQTL, we identified 13 candidate genes (Adarb2, Ankrd26, Cacna1c, Clock, Crhr1, Ctu2, Cyp26b1, Eva1a, Fam114a1, Kcnj9, Mlf2, Rab27b, Sec11a) for these traits. Most of these genes have been implicated by human GWAS of various psychiatric traits. For example, Cacna1c, a gene known to be critical for social behavior in rodents and implicated in human schizophrenia and bipolar disorder, is a candidate gene for distance to the social zone. In addition, the QTL region for total distance to the novel object zone, on Chr1 at 144 Mb, is syntenic to a hotspot on human Chr15 (82.5-90.8 Mb) that contains 14 genes associated with psychiatric or substance abuse traits. Although some of the genes identified by this study appear to replicate findings from prior human GWAS, others likely represent novel findings that can be the catalyst for future molecular and genetic insights into human psychiatric diseases. Together, these findings provide strong support for the use of the HS population to study psychiatric disorders.

Aims: This study assessed hemoglobin A1c (HbA1c) across the lifespan in people with type 1 diabetes (T1D) in Germany/Austria, Sweden, and the United States between 2011 and 2017 to ascertain tempor...

The global scale and unpredictable nature of the current COVID-19 pandemic have put a significant burden on health care and public health leaders, for whom preparedness plans and evidence-based guidelines have proven insufficient to guide actions. This article presents a review of empirical articles on the topics of “crisis leadership” and “pandemic” across medical and business databases between 2003 (since SARS) and—December 2020 and has identified 35 articles for detailed analyses. We use the articles’ evidence on leadership behaviors and skills that have been key to pandemic responses to characterize the types of leadership competencies commonly exhibited in a pandemic context. Task-oriented competencies, including preparing and planning, establishing collaborations, and conducting crisis communication, received the most attention. However, people-oriented and adaptive-oriented competencies were as fundamental in overcoming the structural, political, and cultural contexts unique to pandemics.

Supplemental Digital Content is available in the text., Background. Chronic kidney disease (CKD) is associated with cardiovascular (CV) events, a leading complication in liver transplant recipients (LTRs). Timely subspecialty care is associated with improved clinical outcomes in patients with CKD. This study sought to assess associations between nephrology comanagement and CV events among LTRs at risk for or with CKD. Methods. LTRs with CKD plus those at risk were identified in an inception cohort at a single tertiary care network between 2010 and 2016, using electronic health record data and manual chart review. CKD was defined as estimated glomerular filtration rate

Central obesity, high blood pressure, dyslipidemia, and insulin resistance are a collection of cardiovascular and metabolic risk factors that form the basis of the Metabolic Syndrome (MetS) and represent a major public health burden worldwide. The phenotypes that define MetS are all highly heritable, but their genetic complexity necessitates the use of animal models to tease apart novel pathways. The Lyon Hypertensive (LH) rat is a well-characterized model of MetS, exhibiting profound differences in features of MetS compared to its metabolically healthy control, the Lyon Normotensive (LN) rat. To understand the genomic causes of MetS, we developed a congenic rat model, where a portion of LN chromosome 17 is introgressed on the LH genomic background. Male and female LH congenic (CON) rats and LH controls were phenotyped for a variety of MetS characteristics, including body growth and composition by nuclear magnetic resonance (NMR), metabolic rate (Promethion system), and adipose tissue collection and histological examination. There were significant decreases in body weight in the CON rats of both sexes compared to LH. We also found significant female-specific increases in body fat and decreases in metabolic rate. Tissue collection revealed the source of the increased adiposity in the female CON rats was specific to perirenal white adipose tissue (PWAT) and was further explained by significant hypertrophy in those adipocytes. Genome resequencing of the parental strains identified a gene, C17h6orf52 , as a strong contender underlying the phenotype differences in the congenics, with predicted amino acid changes and the loss of Nr2f2 transcription factor binding sites.