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Rheumatoid arthritis (RA) is a systemic autoimmune disease characterized by chronic inflammation of the joints. Untreated RA leads to a destruction of joints through the erosion of cartilage and bone. The loss of physical function is the consequence. Early treatment is important to control disease activity and to prevent joint destruction. Nowadays, different classes of drugs with different modes of action are available to control the inflammation and to achieve remission. In this review, we want to discuss differences and similarities of these different drugs.

To quantify the impact of depression measured by self-reports and depression measured by clinical interview on all-cause mortality in individuals with diabetes and to analyze the strength of both associations, the influence of covariates, and possible differences between studies assessing self-rated depressive symptoms and those using a clinical interview to measure depression as predictors of mortality. PUBMED and PsycINFO were searched up to July 2013 for prospective studies assessing depression, diabetes and mortality. The pooled hazard ratios were calculated using random-effects models. Sixteen studies met the inclusion criteria. After adjustment for demographic variables depression measured by self-reports was associated with an increased all-cause mortality risk (pooled HR = 2.56, 95% CI 1.89-3.47), and the mortality risk remained high after additional adjustment for diabetes complications (HR = 1.76, 95% CI 1.45-2.14,). Six studies reporting adjusted HRs for depression measured by clinical interviews supported the results of the other models (HR = 1.49, 95% CI 1.15-1.93). Both depression measured by self-report and depression measured by clinical interview have an unfavorable impact on mortality in individuals with diabetes. The results, however, are limited by the heterogeneity of the primary studies. It remains unclear whether self-reports or clinical interviews for depression are the more precise predictor.

Onychomycosis (OM) is a common fungal nail infection. Based on the rich mycobial diversity in healthy toenails, we speculated that this is lost in OM due to the predominance of a single pathogen. We used next generation sequencing to obtain insights into the biodiversity of fungal communities in both healthy individuals and OM patients. By sequencing, a total of 338 operational-taxonomic units were found in OM patients and healthy controls. Interestingly, a classifier distinguished three distinct subsets: healthy controls and two groups within OM patients with either a low or high abundance of Trichophyton . Diversity per sample was decreased in controls compared to cases with low Trichophyton abundance (LTA), while cases with a high Trichophyton abundance (HTA) showed a lower diversity. Variation of mycobial communities between the samples showed shifts in the community structure between cases and controls—mainly driven by HTA cases. Indeed, LTA cases had a fungal β-diversity undistinguishable from that of healthy controls. Collectively, our data provides an in-depth characterization of fungal diversity in health and OM. Our findings also suggest that onychomycosis develops either through pathogen-driven mechanisms, i.e., in HTA cases, or through host and/or environmental factors, i.e., in cases with a low Trichophyton abundance.

Background Previous studies in quality of life (QOL) in individuals with disorders/differences of sex development (DSD) have been restricted to subpopulations of the condition. We describe QOL in adult persons with DSD compared to country specific references and assess the impact of diagnosis. Methods The multicentre cross-sectional clinical evaluation (dsd-LIFE) took place in 14 specialized clinics in six European countries. Adolescents (≥16 years) and adults having a DSD condition were included from 02/2014 to 09/2015. The main outcome QOL was measured by the WHOQOL-BREF (domains of physical health , psychological , social relationships , and environment ). QOL was compared to country specific reference populations by using unpaired t-tests. Linear regression models explained the additional variance of the diagnosis on QOL. Results Three hundred one individuals with Turner Syndrome, 219 with Klinefelter Syndrome (including XYY), 226 with 46,XX CAH and 294 with rare DSD conditions (gonadal dysgenesis, androgen insensitivity syndrome, severe hypospadias, and androgen synthesis errors or other diagnosis) took part. Compared to healthy European populations, QOL was similar in psychological , slightly worse in physical health , and slightly better in environment . In social relationships, QOL was significantly poorer compared to healthy and non-healthy reference populations. In linear regression models health status was the most important predictor of QOL; additional variance was explained by feelings about household’s income in all domains, and the relationship status in social relationships . Diagnosis explained nearly no additional variance. Conclusions Except for social relationships, most people with DSD adapt well to their life circumstances and report a good QOL. Not diagnosis, but the individual’s health status is much more important than previously thought. Therefore care for people with DSD should focus more on chronic physical or mental health problems both related and unrelated to the diagnosis itself. Trial registration German Clinical Trials Register DRKS00006072 .

The term differences of sex development (DSDs; also known as disorders of sex development) refers to a heterogeneous group of congenital conditions affecting human sex determination and differentiation. Several reports highlighting suboptimal physical and psychosexual outcomes in individuals who have a DSD led to a radical revision of nomenclature and management a decade ago. Whereas the resulting recommendations for holistic, multidisciplinary care seem to have been implemented rapidly in specialized paediatric services around the world, adolescents often experience difficulties in finding access to expert adult care and gradually or abruptly cease medical follow-up. Many adults with a DSD have health-related questions that remain unanswered owing to a lack of evidence pertaining to the natural evolution of the various conditions in later life stages. This Consensus Statement, developed by a European multidisciplinary group of experts, including patient representatives, summarizes evidence-based and experience-based recommendations for lifelong care and data collection in individuals with a DSD across ages and highlights clinical research priorities. By doing so, we hope to contribute to improving understanding and management of these conditions by involved medical professionals. In addition, we hope to give impetus to multicentre studies that will shed light on outcomes and comorbidities of DSD conditions across the lifespan.

We determined microbial decomposition of dissolved organic carbon (DOC) over 3.7 year long dark bioassays of six Swedish lake waters. The overall lost DOC fraction was similar in clearwater lakes (34.8 ± 2.4%) and in brownwater lakes (37.8 ± 1.9%). Reactivity continuum modeling revealed that the most labile DOC fraction, degrading at rates >0.01 d−1, was larger in the clearwater lakes (11.1 ± 1.2%) than in the brownwater lakes (0.8 ± 0.1%). The initial apparent first‐order decay coefficientk was fivefold larger in the clearwater lakes (0.0043 ± 0.0012 d−1) than in the brownwater lakes (0.0009 ± 0.0003 d−1). Over time, k decreased more steeply in the clearwater lakes than in the brownwater lakes, reaching the k of the brownwater lakes within 5 months. Finally, k averaged 0.0001 d−1 in both lake categories. In the brownwater lakes, colored dissolved organic matter (CDOM) absorption decayed with an initial k twice as large (0.0018 ± 0.0008 d−1) as that of DOC. The initial kwas inversely correlated with initial specific UV absorption and CDOM absorption and positively correlated with initial tryptophan‐like fluorescence as proxy for autochthonous DOC. Exposure to simulated sunlight at the end of the incubations caused loss of color in the clearwater lakes and loss of DOC in the brownwater lakes, where subsequent mineralization was also stimulated. The DOC lost in the absence of photochemical processes fell below previously reported watershed‐scale losses in Sweden by 25% at most. This suggests that a major part of the in situ DOC loss could potentially be attributed to dark reactions alone. Key Points Allochthonous and autochthonous DOC were similarly bioavailable in the long term Optical properties predicted initial differences in bioavailability Substantial mineralization of allochthonous DOC without solar irradiation

Circulating CAR T cells expanded and peaked on day 10 (figure A; appendix pp 3, 5), as observed in previous studies.4,5 Peak expansion (19·8 cells per μL) was moderate, most likely due to previous rituximab exposure with no circulating B cells at baseline (figure A). [...]despite a lower pool of circulating B cells, as evidenced by no circulating B cells at baseline presumed to be due to the previous rituximab exposure and the presence of dexamethasone, concentrations of CAR T cells increased showing target cell engagement and proliferation. SK has received consulting fees and honoraria for lectures from Sobi and BMS and travel grants from Janssen, BMS, Sobi, Novartis, and Kite/Gilead; and participated in a data safety monitoring board for BMS. Supplementary Materials Supplementary appendix Supplementary Video 1 Functional neurologic status of the patient at baseline examination https://youtu.be/U_zEPe0EGmQ Supplementary Video 2 Functional neurologic status 3 weeks after treatment with CAR T cells https://youtu.be/EF7c9QmBqsU Supplementary Video 3 Functional neurologic status 4 weeks after treatment with CAR T cells https://youtu.be/rU-RRJewgRk Supplementary Video 4 Functional neurologic status 7 weeks after treatment with CAR T

ABSTRACT BACKGROUND Disorders of sex development (DSD) are a heterogeneous group of rare genetic disorders of sex determination or differentiation. Evidence-based guidelines concerning gender assignment and surgical and hormonal treatment are limited for many DSD entities, and health care is highly fragmented across various sub-specialties and settings. A lack of informed consent, secrecy about the condition, shame, and impaired sexual and psychosocial functioning may affect satisfaction with care. OBJECTIVES The main goal of this study was to describe satisfaction with care in individuals with DSD and to identify factors associated with low satisfaction with care. METHODS / MAIN MEASURES Using both biological (chromosomes) and social categories (sex of rearing), we classified participants according to the nomenclature of the European Society for Pediatric Endocrinology/Lawson Wilkins Pediatric Endocrine Society (ESPE/LWPES) consensus statement. We used standardized measures to assess satisfaction with care (CSQ-8), health-related quality of life (SF-36), psychological symptoms (BSI), and gender identity (FGI), in addition to self-constructed questionnaires probing experiences with health care and access to self-help groups. PARTICIPANTS A total of 110 adults were recruited between January 2005 and December 2007 in four study centers in Germany, Austria, and German-speaking Switzerland. RESULTS Reports of half the participants scored below the cut-off indicating low quality of care. Women with XX DSD conditions and virilization (i.e., congenital adrenal hyperplasia) reported the highest scores for satisfaction with care, and women with XY DSD conditions and complete lack of androgen effects reported the lowest scores. Satisfaction with care was positively associated with indicators of psychological well-being. CONCLUSIONS Satisfaction with care is lowest among participants with the rarest conditions, highlighting the lack of evidence-based recommendations and the lack of coordination of care. Associations of satisfaction and well-being indicate the need to ensure access to mental health services.

Disorders/diversity of sex development (dsd) is an umbrella term for congenital conditions often diagnosed within childhood. As most parents are unprepared for this situation, psychological support (PsySupp) is recommended. The aim of this study was to analyse the extent to which parents express a need for PsySupp. Three hundred twenty-nine parents of children with dsd were included; 40.4 % of the parents indicated to have a need for PsySupp, only 50 % of this group received it adequately. The diagnoses partial gonadal dysgenesis, partial androgen insensitivity syndrome (pAIS) and disorders of androgen synthesis are associated with a high need for PsySupp in parents (54, 65, and 50 %). Sex assignment surgery neither reduced nor increased the need for PsySupp. Taking a picture, radiography, laparoscopy, gonadal biopsy, gonadectomy and hormonal puberty induction are associated with a high need for PsySupp. There was no association between the need for PsySupp and the parents’ perception of the appearance of the genitalia. Conclusion : Having a child with dsd is associated with a high need for PsySupp in parents. In particular, parents of children with XY-dsd with androgen effects other than hypospadias expressed a high need of PsySupp. PsySupp for parents should be an obligatory part of interdisciplinary care to reduce fears and concerns. What is known • In parents, having a child with dsd provokes insecurities and fears. Hence, psychological support is recommended as part of the interdisciplinary care . What is new • This is the first study investigating the subjective need for psychological support in a large sample of parents of children with dsd in Germany. We present data on the subjective need for psychological support of the parents, related diagnoses and factors, which should be considered in psychological counselling .

To investigate clinical symptoms and genetic variants in patients from the German anti-IL-1 registry for autoinflammatory orphan diseases (GARROD) between 2013 and 2022. Multicentre, retrospective analysis of demographic, clinical and genetic data of patients with autoinflammatory diseases (AID) who received anti-IL-1 targeted therapy. The cohort comprised 152 patients with familial Mediterranean fever (FMF; n = 71), cryopyrin-associated periodic syndromes (CAPS; n = 43), TNF-receptor associated periodic syndrome (TRAPS; n = 19), mevalonate kinase deficiency (MKD; n = 3) and unclassified AID (uAID; n = 16). Inflammatory attacks started in 61.2% of the patients before the age of 18 years. The delay between the first AID attack and anti-IL-1 therapy was 17.8 years. Monogenetic AIDs were diagnosed by clinical symptoms. Genetic analyses confirmed the diagnosis in 87.3% of patients with FMF, 65.2% with CAPS and 94.8% with TRAPS. Among this group, heterozygous MEFV variants and variants of unknown significance (VUS) were detected in 22.5% of patients with FMF, 51.2% with CAPS and 47.4% with TRAPS. Patients with VUS were older at disease onset which is consistent with a milder phenotype. Twenty-four patients had secondary AA amyloidosis (AA) at initiation of anti-IL-1 therapy. The mean age of these patients was 16.4 years at their first attack and 44.9 years at the time of AA diagnosis. Turkish-Armenian ancestry correlated with MEFV variants and higher FMF disease activity compared to German ancestry. Molecular genetic analyses should substantiate the clinical diagnosis of a monogenetic AID. Our data support the concept of variable penetrance of VUS which can be associated with late-onset AID.