Routine biomarker profile for the prediction of clinical phenotypes of adult-onset Still's disease using unsupervised clustering algorithm.

AIM: This study addresses the challenge of predicting the course of Adult-onset Still's disease (AoSD), a rare systemic autoinflammatory disorder of unknown origin. Precise prediction is crucial for effective clinical management, especially in the absence of specific laboratory indicators. METHODS: We assessed the effectiveness of combining traditional biomarkers with the k-medoids unsupervised clustering algorithm in forecasting the various clinical courses of AoSD-monocyclic, polycyclic, or chronic articular. This approach represents an innovative strategy in predicting the disease's course. RESULTS: The analysis led to the identification of distinct patient profiles based on accessible biomarkers. Specifically, patients with elevated ferritin levels at diagnosis were more likely to experience a monocyclic disease course, while those with lower erythrocyte sedimentation rate could present with any of the clinical courses, monocyclic, polycyclic, or chronic articular, during follow-up. CONCLUSION: The study demonstrates the potential of integrating traditional biomarkers with unsupervised clustering algorithms in understanding the heterogeneity of AoSD. These findings suggest new avenues for developing personalized treatment strategies, though further validation in larger, prospective studies is necessary.

Balancing risks and benefits in the use of hydroxychloroquine and glucocorticoids in systemic lupus erythematosus.

INTRODUCTION: Hydroxychloroquine (HCQ) and glucocorticoids (GCs) constitute the oldest and more used drugs in the treatment of systemic lupus erythematosus (SLE). Despite this long experience, both are still subject to a number of uncertainties, mainly regarding the dose. AREAS COVERED: We review the main mechanisms of action, the clinical and toxic effects of HCQ and GCs and analyze the recommendations for the use of both in guidelines published since 2018. We offer a set of recommendations based on the pharmacology, mechanisms of action and clinical evidence. EXPERT OPINION: HCQ is the backbone therapy for SLE, and a judicious use must be accomplished, using doses that allow a good control of lupus without compromising the safety of treatments very much prolonged over the time. Stable doses of 200 mg/day seem to accomplish both conditions. GCs should be used more judiciously, with methyl-prednisolone pulses as the main therapy for inducing rapid remission and doses ≤5-2.5 mg/day be never exceeded in long-term maintenance treatments.

Intravenous cyclophosphamide improves functional outcomes in interstitial lung disease related to idiopathic inflammatory myopathies.

OBJECTIVE: To compare the efficacy, toxicity and glucocorticoid (GC)-sparing effects of intravenous cyclophosphamide (iv CYC) with other immunosuppressive regimes as the induction treatment for Idiopathic Inflammatory Myopathy-Related Interstitial Lung Disease (IIM-ILD). METHODS: Observational comparative study of patients with IIM-ILD from the EPIMAR and Cruces cohorts. The main efficacy outcome was a 6 to 12-month improvement >10% in the forced vital capacity (FVC) from baseline. RESULTS: Overall, 47 patients were included: 22 (47%) in the CYC group and 25 (53%) in the non-CYC group (32% azathioprine, 28% GC alone, 20% mycophenolate, 16% calcineurin-inhibitors and methotrexate and 4% rituximab). 81% patients were female with a mean age of 50.4 years. FVC improvement was achieved by 64% patients in the CYC group vs. 32% in the non-CYC group (p = 0.03). In the logistic regression model, CYC was identified as the only independent predictor of FVC improvement (OR=3.97, 95% CI 1.07-14.75). Patients in the CYC group received more methyl-prednisolone pulses (MP) (59% vs. 28% in the non-CYC group, p = 0.03), less initial GCs doses >30 mg/d (19% vs. 77%, p = 0.001) and lower 6-month average doses of prednisone (11 mg/d vs. 31.1 mg/d, p = 0.001). CONCLUSION: iv CYC showed better functional outcomes than other immunosuppressants in IIM-ILD. The additional use of MP is likely to potentiate the effects of CYC and allows lowering prednisone doses. Therefore, CYC in combination with MP could be considered as the first line induction therapy in IIM-ILD, without limiting its use to rapidly progressive, life-threatening or refractory disease.

Anti-phospholipid antibodies do not predict damage in SLE patients in the 21st century-an observational study from the Lupus-Cruces cohort.

OBJECTIVE: To compare the influence of aPLs on global and cardiovascular damage in patients with SLE diagnosed before and after the year 2000. METHODS: Two hundred and eighty-six patients from the Lupus-Cruces cohort with a minimum follow-up of 5 years were divided into two subcohorts according to the date of diagnosis, before 2000 (less than 2000) and from 2000 on (2000 or more). We compared the mean Systemic Lupus Erythematosus International Collaborating Clinics-American College of Rheumatology (SLICC-ACR) Damage Index score and global and cardiovascular damage-free survival rates in the presence or absence of aPL in both subcohorts. Variables potentially modulating damage among aPL-positive patients were analysed. RESULTS: The subcohorts were comparable for demographic and lupus-related variables except for treatment variables: the 2000 or more subcohort received lower doses of prednisone and more HCQ, low-dose aspirin, statins, immunosuppressive agents and vitamin D. aPL-positive patients in the less than 2000, but not in the 2000 or more subcohort, accrued more damage compared with aPL-negative patients. In the less than 2000 subcohort, the adjusted hazard ratios (HRs) for global and cardiovascular damage in aPL-positive vs aPL-negative patients were 1.98 (95% CI 1.24, 3.14) and 9.3 (95% CI 3.24, 26.92), respectively. No differences in damage were seen between aPL-positive and aPL-negative patients in the 2000 or more subcohort. Hypertension (HR = 4.64, 95% CI 1.33, 16.19), LA (HR = 3.85, 95% CI 1.1, 13.41) and the number of months on HCQ (HR = 0.97, 95% CI 0.95, 0.99) were independent predictors of vascular damage in the combined analysis of all aPL-positive patients. CONCLUSION: The effects of aPL on damage accrual in SLE patients have been reduced over recent years. The widespread use of HCQ and a better thromboprophylaxis are likely causing this change.

Burn-out syndrome in Spanish internists during the COVID-19 outbreak and associated factors: a cross-sectional survey.

OBJECTIVES: The objective of this study is to evaluate the impact of the COVID-19 outbreak on mental health and burn-out syndrome in Spanish internists and the factors that could be related to its appearance. DESIGN: We performed an observational, cross-sectional, descriptive study for which we designed a survey that was distributed in May 2020. SETTING: We included internists who worked in Spain during the COVID-19 outbreak. PARTICIPANTS: A total of 1015 internists responded to the survey. Of those 62.9% were women. RESULTS: Of 1015 people, 58.3% presented with high emotional exhaustion, 61.5% had a high level of depersonalisation and 67.6% reported low personal fulfilment. 40.1% presented with the 3 criteria described, and therefore burn-out syndrome.Burn-out syndrome was independently related to the management of patients with SARS-CoV-2 (HR: 2.26; 95% CI 1.15 to 4.45), the lack of availability of personal protective equipment (HR: 1.41; 95% CI 1.05 to 1.91), increased responsibility (HR: 2.13; 95% CI 1.51 to 3.01), not having received financial compensation for overtime work (HR: 0.43; 95% CI 0.31 to 0.62), not having rested after 24-hour shifts (HR: 1.61; 95% CI 1.09 to 2.38), not having had holidays in the previous 6 months (HR: 1.36; 95% CI 1.01 to 1.84), consumption of sleeping pills (HR: 1.83; 95% CI 1.28 to 2.63) and higher alcohol intake (HR: 1.95; 95% CI 1.39 to 2.73). CONCLUSIONS: During the COVID-19 outbreak, 40.1% of Internal Medicine physicians in Spain presented with burn-out syndrome, which was independently related to the assistance of patients with SARS-CoV-2, overworking without any compensation and the fear of being contagious to their relatives. Therefore, it is imperative to initiate programmes to prevent and treat burn-out in front-line physicians during the COVID-19 outbreak.

Update on antimalarials and systemic lupus erythematosus.

PURPOSE OF REVIEW: The purpose of this review is highlighting the most recent evidence on the clinical efficacy and toxicity of antimalarials in systemic lupus erythematosus (SLE). RECENT FINDINGS: New data confirm the effects of antimalarials in preventing SLE activity, damage and infections and in decreasing mortality. An important reduction in use of health resources is related to continued antimalarial use. Hydroxychloroquine (HCQ) may prevent preeclampsia in pregnant women with SLE. HCQ ocular toxicity is infrequent and could be associated with blood levels. Gastrointestinal and skin toxicity are underrecognized and could influence adherence. Prolongation of QT interval is extremely unusual with HCQ. Doses of HCQ of 200 mg/day seem to offer a good efficacy/toxicity balance. HCQ protection against herpes zoster and Pneumocystis jirovecii infection has been shown. On the contrary, HCQ prescription by doctors and adherence by patients are both under recommended standards. The recent coronavirus disease 2019 pandemic has resulted in a significant shortage of HCQ in many countries with possible consequences in the correct treatment of lupus patients. SUMMARY: Recent evidence reinforces the central role of HCQ in SLE therapy. The reduction in activity, damage accrual and mortality is consistent across studies, countries and ethnical groups. On the contrary, and despite the well established beneficial effects of prolonged regular HCQ therapy, many SLE patients do never take this drug or it is eventually stopped in the setting of severe flares, pregnancy or presumed toxicity. Every effort must be made to assure the correct prescription of HCQ and not to withdraw the drug unless unequivocal signs of toxicity are present.