Background Psoriasis vulgaris (PsV) and psoriatic arthritis (PsA) are complex, multifactorial diseases significantly impacting health and quality of life. Predicting treatment response and disease ...progression is crucial for optimizing therapeutic interventions, yet challenging. Automated machine learning (AutoML) technology shows promise for rapidly creating accurate predictive models based on patient features and treatment data. Objective This study aims to develop highly accurate machine learning (ML) models using AutoML to address key clinical questions for PsV and PsA patients, including predicting therapy changes, identifying reasons for therapy changes, and factors influencing skin lesion progression or an abnormal Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) score. Methods Clinical study data from 309 PsV and PsA patients were extensively prepared and analyzed using AutoML to build and select the most accurate predictive models for each variable of interest. Results Therapy change at 24 weeks follow-up was modeled using the extreme gradient boosted trees classifier with early stopping (area under the receiver operating characteristic curve AUC of 0.9078 and logarithmic loss LogLoss of 0.3955 for the holdout partition). Key influencing factors included the initial systemic therapeutic agent, the Classification Criteria for Psoriatic Arthritis score at baseline, and changes in quality of life. An average blender incorporating three models (gradient boosted trees classifier, ExtraTrees classifier, and Eureqa generalized additive model classifier) with an AUC of 0.8750 and LogLoss of 0.4603 was used to predict therapy changes for 2 hypothetical patients, highlighting the significance of these factors. Treatments such as methotrexate or specific biologicals showed a lower propensity for change. An average blender of a random forest classifier, an extreme gradient boosted trees classifier, and a Eureqa classifier (AUC of 0.9241 and LogLoss of 0.4498) was used to estimate PASI (Psoriasis Area and Severity Index) change after 24 weeks. Primary predictors included the initial PASI score, change in pruritus levels, and change in therapy. A lower initial PASI score and consistently low pruritus were associated with better outcomes. BASDAI classification at onset was analyzed using an average blender of a Eureqa generalized additive model classifier, an extreme gradient boosted trees classifier with early stopping, and a dropout additive regression trees classifier with an AUC of 0.8274 and LogLoss of 0.5037. Influential factors included initial pain, disease activity, and Hospital Anxiety and Depression Scale scores for depression and anxiety. Increased pain, disease activity, and psychological distress generally led to higher BASDAI scores. Conclusions The practical implications of these models for clinical decision-making in PsV and PsA can guide early investigation and treatment, contributing to improved patient outcomes.
BackgroundRheumatic immune-related adverse events (R-irAEs) occur in 5–15% of patients receiving immune checkpoint inhibitors (ICI) and, unlike other irAEs, tend to be chronic. Herein, we investigate ...the factors influencing cancer and R-irAEs outcomes with particular focus on adverse effects of anti-inflammatory treatment.MethodsIn this prospective, multicenter, long-term, observational study, R-irAEs were comprehensively analyzed in patients with malignant melanoma (MM, n=50) and non-small cell lung cancer (NSCLC, n=41) receiving ICI therapy who were enrolled in the study between August 1, 2018, and December 11, 2022.ResultsAfter a median follow-up of 33 months, progressive disease or death occurred in 66.0% and 30.0% of MM and 63.4% and 39.0% of patients with NSCLC. Male sex (progression-free survival (PFS): p=0.013, and overall survival (OS): p=0.009), flare of a pre-existing condition (vs de novo R-irAE, PFS: p=0.010) and in trend maximum glucocorticoid (GC) doses >10 mg and particularly ≥1 mg/kg prednisolone equivalent (sex-adjusted PFS: p=0.056, OS: p=0.051) were associated with worse cancer outcomes. Patients receiving disease-modifying antirheumatic drugs (DMARDs) showed significantly longer PFS (n=14, p=0.011) and OS (n=20, p=0.018). Effects of these variables on PFS and/or OS persisted in adjusted Cox regression models. Additionally, GC treatment negatively correlated with the time from diagnosis of malignancy and the latency from ICI start until R-irAE onset (all p<0.05). R-irAE features and outcomes were independent of other baseline patient characteristics in both studied cancer entities.ConclusionMale sex, flare of pre-existing rheumatologic conditions and extensive GC treatment appeared to be linked with unfavorable cancer outcomes, while DMARD use had a favorable impact. These findings challenge the current dogma of restrictive DMARD use for R-irAE and thus may pave the way to better strategies and randomized controlled trials for the growing number of patients with R-irAE.
Bone marrow edema (BME) is a descriptive term for a common finding in magnetic resonance imaging (MRI). Although pain is the major symptom, BME differs in terms of its causal mechanisms, underlying ...disease, as well as treatment and prognosis. This complexity together with the lack of evidence-based guidelines, frequently makes the identification of underlying conditions and its management a major challenge. Unnecessary multiple consultations and delays in diagnosis as well as therapy indicate a need for interdisciplinary clinical recommendations. Therefore, an interdisciplinary task force was set up within our large osteology center consisting of specialists from internal medicine, endocrinology/diabetology, hematology/oncology, orthopedics, pediatrics, physical medicine, radiology, rheumatology, and trauma surgery to develop a consenus paper. After review of literature, review of practical experiences (expert opinion), and determination of consensus findings, an overview and an algorithm were developed with concise summaries of relevant aspects of the respective underlying disease including diagnostic measures, clinical features, differential diagnosis and treatment of BME. Together, our single-center consensus review on the management of BME may help improve the quality of care for these patients.
Zusammenfassung
Bei Patienten mit entzündlich rheumatischen Erkrankungen muss vor elektiven Eingriffen entschieden werden, ob die medikamentöse Therapie fortgeführt werden kann oder ob sie in der ...Dosis verändert oder pausiert werden muss. Die Deutsche Gesellschaft für Rheumatologie (DGRh) hat aktualisierte Empfehlungen für den Umgang mit „disease-modifying antirheumatic drugs“ (DMARDs) und Glukokortikoiden erarbeitet. Die Handlungsempfehlungen können auf die individuelle Situation angepasst und mit den interdisziplinär behandelnden Ärzten und Patienten abgestimmt werden. Glukokortikoide haben dosisabhängig ein hohes Infektionsrisiko und sollten präoperativ so niedrig wie möglich eingestellt werden. Die meisten konventionell synthetischen (cs) DMARDs können fortgeführt werden. Bei einer biologischen (b) DMARD-Therapie kann die Operation zum Ende des jeweiligen Therapieintervalls geplant werden. Für Januskinase(JAK)-Inhibitoren wird eine Pause von 3 bis 4 Tagen vor größeren Eingriffen empfohlen. Pausierte Medikamenteneinnahmen sollten so bald wie möglich – in Abhängigkeit der Wundheilung – fortgesetzt werden.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
ObjectiveThis study aims to (1) assess the perceived need for a postdoctoral (post-doc) mentoring programme in rheumatology, (2) describe the characteristics and organisational aspects of a pilot ...mentoring programme implemented by the EMerging European League Against Rheumatism NETwork (EMEUNET) and (3) report mentors’ and mentees’ evaluation of the pilot programme.MethodsAn online survey was conducted among young researchers in rheumatology to evaluate the need and preferred characteristics of a post-doc mentoring initiative. Informed by the survey, a pilot programme was designed and launched. The pilot programme was evaluated with 3-month, 6-moth and 12-month surveys and interviews with mentees and a 12-month survey among mentors, after completion.ResultsFrom 275 responses (43 countries, 86% from Europe) collected, analyses were restricted to the target population (total population=158; post-docs (n=103 (65%)) and PhD students (n=55 (35%))). There was a clear need (99% positive responses) for a post-doc mentoring programme. Discussions about current and new projects, and how to lead projects were ranked as priorities in post-doc mentoring. The most desired mentor attribute was generosity and interest in helping (86%), followed by research experience (68%) and having a well-established network (66%). The pilot programme included four mentees (through competitive application) allocated to three mentors. Evaluation surveys and interviews revealed that the programme organisation and content were well appreciated by mentees and mentors.ConclusionsThe EMEUNET post-doc mentoring programme addresses unmet need for mentoring, is viable and appreciated by mentors and mentees. The programme structure and content are transferable to other fields where there is need for academic career mentoring.
Different observations have suggested that patients with depression have a higher risk for a number of comorbidities and mortality. The underlying causes have not been fully understood yet.
The aim ...of our study was to investigate the association of a genetic depression risk score (GDRS) with mortality all-cause and cardiovascular (CV) and markers of depression (including intake of antidepressants and a history of depression) in the Ludwigshafen Risk and Cardiovascular Health (LURIC) study involving 3,316 patients who had been referred for coronary angiography.
The GDRS was calculated in 3,061 LURIC participants according to a previously published method and was found to be associated with all-cause (
= 0.016) and CV mortality (
= 0.0023). In Cox regression models adjusted for age, sex, body mass index, LDL-cholesterol, HDL-cholesterol, triglycerides, hypertension, smoking, and diabetes mellitus, the GDRS remained significantly associated with all-cause 1.18 (1.04-1.34,
= 0.013) and CV 1.31 (1.11-1.55,
= 0.001) mortality. The GDRS was not associated with the intake of antidepressants or a history of depression. However, this cohort of CV patients had not specifically been assessed for depression, leading to marked underreporting. We were unable to identify any specific biomarkers correlated with the GDRS in LURIC participants.
A genetic predisposition for depression estimated by a GDRS was independently associated with all-cause and CV mortality in our cohort of patients who had been referred for coronary angiography. No biomarker correlating with the GDRS could be identified.
The predominance of differentiated Th17 cells has been implied as a key driver of autoimmune arthritis, including early RA. Because accumulating evidence suggests that Th cell differentiation is a ...plastic process, we investigated plasticity and underlying molecular mechanisms to address the shift towards the Th17 phenotype in early RA.
A cohort of 61 patients with early, active, untreated RA and 45 age- and sex-matched healthy controls were studied. Viable in vitro- and in vivo-generated Th1, Th2 and Th17 cells were FACS-sorted and transdifferentiated under Th1-, Th2- or Th17-inducing conditions. The cytokine Th profile of the transdifferentiated cells was assessed by flow cytometry. Th cell-associated cytokine and transcription factor gene loci were analysed by chromatin immunoprecipitation assay and their expression by quantitative real-time PCR.
In vitro-generated Th cells showed substantial plasticity, which was similar between RA and healthy controls, whereas in vivo-derived Th1 and Th2 cells from RA patients demonstrated an enhanced plasticity towards IL-17-expressing phenotypes compared with healthy controls. Further, in vivo-generated Th17 cells from RA patients showed a resistance to transdifferentiate into Th1 or Th2 cells. The serum/glucocorticoid-regulated kinase 1-forkhead box protein O1-IL-23 receptor (SGK1-FOXO1-IL-23R) axis together with increased RORC expression was associated with the predominant Th17 phenotype in early RA.
Our data indicate that in vivo-originated Th subsets are prone to Th17 cell transdifferentiation in early RA, while Th17 cells are resistant to changes in their phenotype. Together, the data imply that an altered plasticity contributes to the Th17 shift in early RA.
Activated effector T cells induce the generation of suppressor T cells from bystander memory T cells via interactions involving LFA‐1 and its receptors.
We have shown previously that homotypic ...interaction of resting memory CD4 T cells with activated T cells induces the production of cytokines with immunoregulatory potential (IL‐10, IL‐4) from the former. Here, we analyzed the effector functions of these T cells stimulated by homotypic T cell interaction. T cells induced upon homotypic T cell interaction expressed CD25 and reduced levels of CD127 and produced TGF‐β. Functionally, homotypic T cell interaction‐induced T cells were anergic and inhibited the proliferation of CD25‐negative T cells as potently as naturally occurring CD25‐positive Tregs in vitro. They also prevented clonotypic expansion of OVA TCR tg T cells in BALB/c mice upon antigenic challenge in vivo. The generation of suppressor T cells by homotypic T cell contact is anchored and tuned through interactions of LFA‐1 and its ligands ICAM‐1, ICAM‐2, and ICAM‐3. Together, the data suggest a negative‐feedback mechanism of specific immunity involving bystander‐activated memory T cells.
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FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
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