OBJECTIVE: Sphingosine 1-phosphate receptor modulators (S1PRMs) are an effective treatment for ulcerative colitis (UC). This review summarizes all available randomized trial data on the efficacy and safety of S1PRM therapy.
METHODS: Multiple publication databases were systematically searched for randomized control trials (RCTs) of adults with moderate to severe UC treated with S1PRMs. Random effects meta-analysis was performed. The risk of bias was assessed using the Cochrane Risk-of-Bias 2 tool, and the overall quality of evidence was rated using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) approach.
RESULTS: We identified 7 RCTs (1737 patients) involving the use of S1PRMs for moderate to severe UC. During induction, S1PRM therapy was efficacious when compared with placebo for clinical remission [RR: 2.65 (95% CI: 2.00, 3.53)], clinical response [RR: 1.68 (95% CI: 1.48, 1.91)], endoscopic improvement [RR: 2.17 (95% CI: 1.76, 2.68)], endoscopic normalization [RR: 2.56 (95% CI: 1.58, 3.83)], mucosal healing [RR: 2.88 (95% CI: 1.94, 4.26)], and histologic remission [RR: 2.42 (95% CI: 1.60, 3.66)]. Similar results were seen throughout the maintenance peroid, although fewer data were available to pool; notably, both sustained [RR: 3.57 (95% CI: 1.23, 10.35)] and steroid-free [RR: 2.92 (95% CI: 1.35, 6.33)] remission were significantly increased by S1PRM. There were no significant differences in adverse events [RR: 1.02 (95% CI: 0.90, 1.15)] and infections [RR: 1.15 (95% CI: 0.82, 1.60)] between S1PRM and placebo.
CONCLUSIONS: Pooling of RCT data confirms that S1PRM therapy is both effective and safe for patients with moderate to severe UC.

UNASSIGNED: Few studies have directly compared the cognitive characteristics of patients with mild autonomous cortisol secretion (MACS) and Cushing\'s syndrome (CS). The effect of surgical or conservative treatment on cognitive function in patients with MACS is still unclear.
UNASSIGNED: To compare the differences in cognitive function between patients with MACS and CS and evaluate the effect of surgery or conservative treatment on cognitive function.
UNASSIGNED: We prospectively recruited 59 patients with nonfunctional adrenal adenoma (NFA), 36 patients with MACS, and 20 patients with adrenal CS who completed the global cognition and cognitive subdomains assessments. Seventeen MACS patients were re-evaluated for cognitive function after a 12-month follow-up period; of these, eleven underwent laparoscopic adrenalectomy and six received conservative treatment.
UNASSIGNED: Patients with MACS and CS performed worse in the global cognition and multiple cognitive domains than those with NFA (all P<0.05). No statistical difference was found in cognitive functions between patients with MACS and CS. Logistic regression analysis showed that patients with MACS (odds ratio [OR]=3.738, 95% confidence intervals [CI]: 1.329-10.515, P=0.012) and CS (OR=6.026, 95% CI: 1.411-25.730, P=0.015) were associated with an increased risk of immediate memory impairment. Visuospatial/constructional, immediate and delayed memory scores of MACS patients were significantly improved at 12 months compared with pre-operation in the surgical treatment group (all P<0.05), whereas there was no improvement in the conservative treatment group.
UNASSIGNED: Patients with MACS have comparable cognitive impairment as patients with CS. Cognitive function was partially improved in patients with MACS after adrenalectomy. The current data support the inclusion of cognitive function assessment in the clinical management of patients with MACS.

Idiopathic nephrotic syndrome (NS) is a common glomerular disease in children throughout the world; however, the exact pathogenesis of the disease remains unknown. Several studies have shown that tumour necrosis factor-alpha (TNF-α), a proinflammatory cytokine, plays a significant role in the pathogenesis of NS. The literature lacks sufficient data to establish the relationship between TNF-α and NS. This prospective study was conducted on children aged 1-14 years diagnosed with idiopathic NS. All enrolled individuals were followed up from disease onset or relapse of NS until remission or at least 42 days with steroid therapy if remission was not achieved. Serum TNF-α levels were measured at presentation and remission or after 42 days of steroid therapy if remission was not achieved. The role of TNF-α levels in response to steroid therapy in NS was also assessed. One hundred and twelve children (68% boys) with idiopathic NS were enrolled. The median age (interquartile range) at enrolment was 58.5 (37-84.7) months, while the median age at symptom onset was 47.5 (24-60.7) months. The median TNF-α level at presentation was 7.5 (3.5-12.1) pg/ml, and that at remission was 5.25 (1.62-8.8) pg/ml. The median TNF-α levels among first-episode NS at presentation were 3.98 pg/ml and 1.88 pg/ml (P = .04) at remission, whereas in steroid-resistant NS, it was 6.59 pg/ml at presentation and 9.02 pg/ml at 42 days (P = .45). There was a significant negative correlation between the duration of steroid therapy and TNF-α levels, with a correlation factor of -0.021 and R2 of 0.154 (P≤.001). Serum TNF-α levels decrease with steroid therapy in children with steroid-sensitive NS, which correlates clinically with the achievement of remission.

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UNASSIGNED: Minimal change disease (MCD) is a common cause of adult nephrotic syndrome. Most adults with MCD achieve complete remission (CR) after initial steroid therapy. However, approximately 30% of adults who respond to steroids experience frequent relapses, becoming steroid-dependent and potentially developing refractory MCD. Treating refractory MCD in adults poses a significant challenge.
UNASSIGNED: A 37-year-old woman presented to the nephrology department with a 6-year history of MCD. The diagnosis of MCD was confirmed via renal biopsy. She initially achieved CR with steroid treatment but experienced relapse during steroid tapering. Subsequent CR was achieved with a regimen of steroids and tacrolimus although multiple relapses occurred. Rituximab led to another CR, but its maintenance lasted only 6 months. The response to subsequent rituximab treatments was unsatisfactory. Ultimately, obinutuzumab was selected, resulting in the induction and maintenance of CR for 12 months.
UNASSIGNED: This case demonstrates the successful treatment of frequently relapsed, steroid-dependent, and rituximab-resistant MCD with obinutuzumab. Obinutuzumab is a promising therapeutic option for rituximab-resistant MCD.

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OBJECTIVE: To investigate if patients with early rheumatoid arthritis responding insufficiently to initial methotrexate (MTX) and bridging glucocorticoids (GCs) could benefit from early but temporary etanercept introduction as a second remission-induction attempt.
METHODS: CareRA2020 (NCT03649061) was a 2-year, open-label, multicentre, pragmatic randomised controlled trial. Treatment-naïve patients started MTX and GC bridging (COBRA-Slim: CS). Within a time window from week (W) 8 until W32, early insufficient responders (28-joint Disease Activity Score - C-reactive Protein (DAS28-CRP) >3.2 between W8 and W32 or ≥2.6 at W32) were randomised to a Standard-CS strategy (adding leflunomide first) or Bio-induction-CS strategy (adding etanercept for 24 weeks). Additional treatment adaptations followed the treat-to-target principle. Longitudinal disease activity (DAS28-CRP) over 104 weeks (primary outcome), achievement of DAS28-CRP <2.6 28 weeks after randomisation, and biologic or targeted synthetic disease-modifying antirheumatic drug (b/tsDMARD) use at W104 were compared between randomisation groups.
RESULTS: Following CS treatment, 142 patients were early responders; 55 early insufficient responders received Standard-CS and 55 Bio-induction-CS. Superiority of Bio-induction-CS over Standard-CS could not be demonstrated (ß=-0.204, (95% CI -0.486 to 0.078), p=0.157) for the primary outcome. More patients on Bio-induction-CS achieved DAS28-CRP <2.6 at 28 weeks after randomisation (59% (95% CI 44% to 72%) vs 44% (95% CI 31% to 59%) in Standard-CS) and they were treated less frequently with b/tsDMARDs at W104 (19/55, 35%) compared with Standard-CS (29/55, 53%).
CONCLUSIONS: Half of the patients responded well to initial COBRA-Slim induction therapy. In early insufficient responders, adding etanercept for 6 months did not improve disease control over 104 weeks versus adding leflunomide first. However, temporary introduction of etanercept resulted in improved disease control early after randomisation and less patients on b/tsDMARDs at W104.
BACKGROUND: NCT03649061.
UNASSIGNED: S59474, EudraCT number: 2017-004054-41.

BACKGROUND: Periarteritis nodosa (PAN) is a vasculitis affecting medium-vessel and may be associated with myelodysplastic syndrome. This association needs a simultaneous treatment of the vascular and the hematological disease. However limited data are available on the benefit of hematological treatment, and in particular allogeneic stem cell transplantation, in this situation.
METHODS: A 32-year-old patient with refractory periarteritis nodosa and simultaneous myelodysplastic syndrome, was treated with chemotherapy followed by hematopoietic stem cell allograft. The symptoms relating to PAN improved, allowing to decrease the dose of prednisone down to 5mg/d. However, a hematological relapse occurred two months later leading to the patient\'s death.
CONCLUSIONS: Hematopoietic stem cell allograft may represent a therapeutic option in the management of severe or refractory autoimmune diseases when the hematological indication is retained.

BACKGROUND: In 2021, an EULAR task force published a definition of difficult-to-treat rheumatoid arthritis (D2T RA). Our current knowledge of D2T RA with the EULAR definition is based on European and Asian cohorts, and no North American cohort has yet to be published. The aim of this study was to compare D2T RA patients to non-D2T RA who are good responders to advanced therapy, and to describe their evolution in an university health center patient cohort.
METHODS: This is a retrospective single centre study of the medical records of all adults with RA on at least one biologic or target synthetic DMARD (b/tsDMARD). D2T RA group was defined according to the EULAR definition of D2T RA. The non-D2T RA group was defined as a b/tsDMARD good responder who had low-disease activity or remission for at least one year on 1 or 2 b/tsDMARD mechanism of action. We compared the patients\' comorbidities, and history of b/tsDMARD use. Descriptive statistics and proportions were calculated. Kaplan-Meier analysis with log-rank test was used to estimate and compare median survival.
RESULTS: Among the 417 patients, 101 (24%) were D2T RA and 316 (76%) were non-D2T RA. D2T RA group was slightly younger (63 ± 9 years versus 65 ± 12 years, p = 0.045), more likely to have concomitant non-inflammatory pain (28% versus 8%, p < 0.0001) and to discontinue at least one b/tsDMARD due to intolerance (39% versus 10%, p < 0.0001). In the D2T RA group, JAK inhibitors were associated with longer drug continuation when used as the third b/tsDMARD. Fewer patients were using corticosteroid at their most recent follow-up in this Canadian cohort compared to others (16% versus from 29 to 74%).
CONCLUSIONS: Concomitant non-inflammatory pain was more prevalent in D2T RA patients compared to b/tsDMARD good responder non-D2T RA patients. Steroid-sparing strategies is possible even in D2T RA patients. Future prospective research may compare JAK inhibitors with other mechanisms of action in D2T RA.