Effectiveness of Intravenous Corticosteroid in Patients with Ulcerative Colitis after Oral Corticosteroid Failure: Differences by Prior Response to Oral Therapy in a Multicenter Cohort Study

Introduction: Mepolizumab is a treatment option in patients with severe eosinophilic asthma, which inhibits interleukin-5. The aim of this study was to evaluate the clinical features and laboratory data of patients with severe eosinophilic asthma who were classified as super-responders, partial responders, or nonresponders to mepolizumab treatment. Methods: In this retrospective real-life study, the clinical features and laboratory data were compared between groups of patients with severe eosinophilic asthma who were classified as super-responders, partial responders, or nonresponders to mepolizumab treatment. Results: Evaluation was made of a total of 55 patients, comprising 17 (30.9%) males and 38 (69.1%) females with a mean age of 51.28 ± 14.32 years. All the patients were receiving mepolizumab treatment for severe eosinophilic asthma, with 17 (30.9%) patients evaluated as super-responders, 26 (47.3%) as partial responders, and 12 (21.8%) as nonresponders. After mepolizumab treatment, there was a statistically significant decrease in asthma exacerbations, the number of oral corticosteroids (OCSs) used, the rate of hospitalization due to asthma attacks, and the eosinophil count (cells/µL) (p < 0.001, p < 0.001, p < 0.001, and <0.001, respectively). A statistically significant increase was determined in the forced expiratory volume in 1 s (FEV1) value (p = 0.010) and asthma control test (ACT) score (p < 0.001) after mepolizumab treatment. The baseline eosinophil count, eosinophil/lymphocyte ratio and FEV1 (%) values were significantly higher in the super-responder and partial responder groups (p < 0.001, p = 0.002, and p = 0.002, respectively). The baseline ACT score and the rate of chronic sinusitis with nasal polyps were significantly higher in the partial responder group (p = 0.004, p = 0.015, respectively). The rate of regular OCS use before mepolizumab treatment was significantly higher in the nonresponder group (p = 0.049). As a result of the receiver operating characteristics curve analysis, the blood eosinophil count (area under the curve [AUC]: 0.967, p < 0.001), eosinophil/lymphocyte ratio (AUC: 0.921, p < 0.001), and FEV1 (%) (AUC: 0.828, p = 0.002) were found to have diagnostic value in predicting the response to mepolizumab treatment in patients with severe eosinophilic asthma. Conclusion: Baseline eosinophil count, eosinophil/lymphocyte ratio, and FEV1 (%) were found to be important predictors of response to mepolizumab treatment. Further studies are needed to define the characterization of mepolizumab responders in the real world.

Treatment of Acute Visual Loss in Giant Cell Arteritis

Factors associated with early outcomes following standardised therapy in children with ulcerative colitis (PROTECT): a multicentre inception cohort study

Liver histology was compared in patients with chronic hepatitis C to note the differences between responders and non-responders to interferon treatment. Fifty-eight patients were administered interferon in varying doses and over various periods, and were then followed up for 1 year. According to the improvement status of serum alanine aminotransferase (ALT) levels during this period, the patients were classified into complete responders who showed complete normalization of ALT; partial responders who exhibited a significant decrease, but not complete normalization of ALT; and non-responders who did not reveal any significant decrease of ALT. Before application of the interferon treatment, liver biopsies were analyzed in four parameters and given scores from 0 to 5 for three groups in cord with no prior knowledge of the efficacy. The parameters included necroinflammation, fibrosis/lobular distortion, portal lymphocytic reaction and portal (or fibrous septal) outline destruction. Results indicated that there were no significant differences in the score of necroinflammation and portal lymphocytic reaction between the complete responder group and the non-responder group. In contrast, the complete responder group exhibited weaker fibrosis/lobular distortion and less portal outline destruction than the non-responder group. The partial responder group was more akin to the former group in these parameters. Thus, it is safe to conclude that liver histology may predict the efficacy of interferon treatment.

Real-time fMRI neurofeedback amygdala training may influence kynurenine pathway metabolism in major depressive disorder

Background: Therapeutic adjustment is of major importance in the treat to target strategy proposed for rheumatoid arthritis (RA). This aspect can be challenged in teleconsultation given the multiplicity of treatments,...

Once-Daily, High-Concentration MMX Mesalamine in Active Ulcerative Colitis

A Meta-Analysis of the Placebo Rates of Remission and Response in Clinical Trials of Active Ulcerative Colitis

Appendicectomy versus switching to a JAK inhibitor in inducing remission in patients with active ulcerative colitis after biologic therapy failure (COSTA): 1-year results of a multicentre, prospective, cohort study.

Background This study aimed to evaluate the efficacy of appendectomy in inducing remission in patients with moderately to severely active ulcerative colitis (UC), despite biological or small molecule therapy. Methods This multicentre, prospective cohort study included patients aged ≥16 years with moderately to severely active UC (total Mayo score [TMS] ≥5; endoscopic subscore of ≥2) despite optimised prior treatment with advanced medical therapy (i.e. biological/small molecule exposed). Eligible patients where those for whom the next treatment step was considered to be switching to a Janus kinase (JAK) inhibitor or undergoing (procto)colectomy. Enrolled patients were counselled (patient-preference model) to either undergo laparoscopic appendectomy (study intervention) or continue standard step-up therapy, which included: 1) switching to a JAK inhibitor or 2) undergoing staged restorative proctocolectomy with ileoanal pouch. The primary outcome was the proportion of patients achieving clinical remission (TMS≤2 with no subscore &amp;gt;1) at 12 months without therapy failure. Therapy failure was defined as (re)start of oral corticosteroids, switch of advanced therapy, start trial medication or proctocolectomy. Patients without therapy failure and pMS≤2 at 12 months without endoscopic follow-up were considered failures for the primary outcome. Primary analyses will be conducted based on a modified intention-to-treat (mITT) principle. Patients who received the assigned intervention (appendectomy in the intervention group, proctocolectomy in the control group) or at least one dose of the assigned medication (JAK-inhibitor in the control group) will be analysed. The last patient 12-month follow-up visit was completed in September 2024. Results A total of 120 patients were included in the mITT analysis (appendectomy group: n=65, JAK-inhibitor group: n=50, proctocolectomy group: n=5). Numerical baseline differences across groups (appendectomy vs JAK-i vs proctocolectomy) were: male gender (35.4% vs 54.0% vs 20.0%, p=0.08), family history of IBD (33.8% vs 12.0% vs 0%, p=0.02), current smoking (13.8% vs 2.0% vs 0%, p=0.22), disease extent (E3: 41.5% vs 60.0% vs 80.0%, p=0.18), TMS (median 9 [IQR, 7-10] vs 9 [IQR, 8-10] vs 10 [0-.], p=0.16) and concomitant oral corticosteroids (26.2% vs 46.0% vs 80.0%, p=0.01). The appendectomy group had a significantly higher proportion of patients in clinical remission at 12 months without therapy failure after appendectomy, compared to the JAK inhibitor group (33.8% vs 12.0%, p=0.007, Figure 1.). Final analysis are scheduled for Q4 2024 and Q1 2025. Conclusion Appendectomy may be an effective treatment option for inducing clinical remission in moderately to severely active UC. Final analyses are expected in Q1 2025.

A Phase I Study of Visilizumab, a Humanized Anti-CD3 Monoclonal Antibody, in Severe Steroid-Refractory Ulcerative Colitis

To evaluate the clinical presentations of traumatic optic neuropathy and to assess the visual outcome of three groups of patients managed differently (conservative, intravenous corticosteroids only and combination of intravenous and oral corticosteroids) at an academic tertiary care referral centre. A retrospective study was conducted involving 24 consecutive patients (27 eyes) with traumatic optic neuropathy attending Hospital Universiti Sains Malaysia from January 2007 till December 2009. Twenty-four patients (27 eyes) were included. All cases involved were males. Mean age was 33 years old. Motor vehicle accident was the major cause (83.3%). Both eyes were equally involved. Most of the eyes had poor vision on presentation (HM-NPL, 81.5%) with associated periorbital haematoma (22 eyes) and subconjunctival haemorrhage (20 eyes). Majority of patients (19 patients, 79.2%) presented with more than one bony fracture of skull or orbit and 5 patients (20.8%) had no fractures. None of the patients had evidence of optic nerve compression on CT scans or MRI done. Eleven patients (45.8%) had been treated with intravenous and oral corticosteroids. The other 7 patients (29.2%) were treated conservatively and the third group (6 patients, 25.0%) was on intravenous corticosteroids only. Eleven of 12 eyes (91.7%) treated with intravenous and oral corticosteroids had shown 1 line improvement of visual acuity. Those eyes treated conservatively (77.8%) had shown 1 line improvement of visual acuity. As for patients treated with intravenous corticosteroids only, four patients remained NPL, one patient had mild visual improvement and the other one's vision remained the same. The visual improvement in patients treated with conservative management was not significant (P=0.386). Patients treated with intravenous corticosteroids alone have shown no visual improvement statistically(P<0.05). Patients treated with intravenous followed by oral corticosteroids had significant visual improvement (P<0.05). There was no statistically significant difference in visual outcome between patients treated with corticosteroids and patients treated conservatively (P=0.368). No patient underwent surgical decompression of the optic nerve. In this series, the follow up ranges from 6 months to 3 years. Most of the traumatic optic neuropathy patients presented with periorbital haematoma, subconjunctival haemorrhage and orbital wall fractures. Patients treated with intravenous followed by oral corticosteroids have better visual outcome compared to conservative management.

Background: Fecal microbiota transplantation (FMT) may contribute to disease remission in ulcerative colitis (UC). We studied the microbiota change and its regulation on T cells after FMT. Methods: Patients with mild to moderately active UC were included to receive FMT. The intestinal histopathological changes and barrier function were evaluated. The fecal samples of donors and patients were analyzed by 16S rRNA gene-based microbiota analysis, and the colon Th17 and Treg cells were assessed. Results: Fifteen patients completed the 8-week-follow-up. A total of 10 patients (66.7%) were in the responders (RE) group and five in the non-responders (NR) group. The Nancy histological index and fecal calprotectin decreased (p < 0.001, p = 0.06, respectively) and Occludin and Claudin1 increased in the RE group. The abundance of Faecalibaterium increased significantly by 2.3-fold in the RE group at week 8 (p = 0.043), but it was suppressed in the NR group. Fecal calprotectin (r = −0.382, p = 0.003) and Nancy index (r = −0.497, p = 0.006) were correlated inversely with the abundance of Faecalibacterium, respectively. In the RE group the relative mRNA expression of RORγt decreased and Foxp3 increased. Significantly decreased CD4+ RORγt+ Th17 and increased CD4+ Foxp3+ Treg were also observed in the RE group. The relative abundance of Faecalibacterium correlated with CD4+ RORγt+ Th17 (r = −0.430, p = 0.018) and CD4+ Foxp3+ Treg (r = 0.571, p = 0.001). Conclusions: The long-term Faecalibaterium colonization following FMT plays a crucial role in UC remission by alleviating intestinal inflammation. This anti-inflammatory effect of Faecalibacterium may be achieved by regulating the imbalance of Th17/Treg levels in UC.

Purpose To compare post‐operative inflammation and development of cystoid macular oedema (CMO) in uveitis patients undergoing cataract surgery and intraocular lens (IOL) implantation who had either pre‐operative oral or intra‐venous (IV) corticosteroid. Methods Retrospective case note study comparing uveitis patients undergoing phakoemulsification cataract surgery and implantation of an acrylic IOL (performed by one surgeon), having either oral corticosteroid (usually 40mg prednisolone two weeks prior to surgery and tapered by 5‐10mg weekly post‐operatively) or a single 500mg IV methylprednisolone pulse one hour prior to surgery. Results 30 procedures (35 patients) were identified where pre‐operative oral corticosteroid had been given, and 93 procedures (76 patients) where IV corticosteroid was given. In the oral corticosteroid cohort there were 2 (7%) episodes of fibrinous uveitis and 4 (13%) episodes of CMO within 90 days of the surgery. In the IV cohort there were 3 (3%) episodes of fibrinous uveitis and 16 (17%) episodes of CMO within 90 days of surgery. There was no statistically significant difference in the number of episodes of fibrinous uveitis or CMO between the two groups. Conclusion There was no difference in the incidence of post‐operative fibrinous uveitis or CMO in patients who were given either pre‐operative oral or IV corticosteroid. A single pulse of 500mg IV methylprednisolone appears a reasonable alternative to a course of oral prednisolone in uveitis patients undergoing cataract surgery.

The interruption of mother-to-child transmission (MTCT) is considered important to decrease the individual and population morbidity of hepatitis B virus (HBV) infection as well as the global burden of hepatitis B. Serum vitamin D (VD) is associated with hepatitis B. To assess whether baseline VD levels and single nucleotide polymorphisms of the VD receptor gene (VDR SNPs) are associated with the efficacy of tenofovir disoproxil fumarate (TDF) in the prevention of MTCT in pregnant women with high HBV viral loads. Thirty-eight pregnant women who were at high risk for MTCT of HBV (those with an HBV DNA level ≥ 2 × 105 IU/mL during 12-24 wk of gestation) receiving antiviral therapy of TDF between June 1, 2019 and June 30, 2021 in Mianyang were included in this retrospective study. The women received 300 mg TDF once daily from gestational weeks 24-28 until 3 mo after delivery. To further characterize the clinical relevance of maternal serum HBV DNA levels, we stratified patients according to HBV DNA level as follows: Those with levels < 2 × 105 (full responder group) vs those levels ≥ 2 × 105 IU/mL (partial responder group) at delivery. Serum levels of 25-hydroxyvitamin D [25(OH)D], liver function markers, virological parameters, VDR SNPs and other clinical parameters were collected to analyze their association with the efficacy of TDF. The Mann-Whitney U test or t test was used to analyze the serum levels of 25(OH)D in different groups. Multiple linear regressions were utilized to analyze the determinants of the maternal HBV DNA level at delivery. Univariate and multivariate logistic regression analyses were employed to explore the association of targeted antiviral effects with various characteristics at baseline and delivery. A total of 38 pregnant women in Mianyang City at high risk for MTCT of HBV were enrolled in the study. The MTCT rate was 0%. No mother achieved hepatitis B e antigen or hepatitis B surface antigen (HBsAg) clearance at delivery. Twenty-three (60.5%) participants were full responders, and 15 (39.5%) participants were partial responders according to antiviral efficacy. The present study showed that a high percentage (76.3%) of pregnant women with high HBV viral loads had deficient (< 20 ng/mL) or insufficient (≥ 20 but < 31 ng/mL) VD levels. Serum 25(OH)D levels in partial responders appeared to be significantly lower than those in full responders both at baseline (25.44 ± 9.42 vs 17.66 ± 5.34 ng/mL, P = 0.006) and delivery (26.76 ± 8.59 vs 21.24 ± 6.88 ng/mL, P = 0.044). Serum 25(OH)D levels were negatively correlated with maternal HBV DNA levels [log(10) IU/mL] at delivery after TDF therapy (r = -0.345, P = 0.034). In a multiple linear regression analysis, maternal HBV DNA levels were associated with baseline maternal serum 25(OH)D levels (P < 0.0001, β = -0.446), BMI (P = 0.03, β = -0.245), baseline maternal log10 HBsAg levels (P = 0.05, β = 0.285) and cholesterol levels at delivery (P = 0.015, β = 0.341). Multivariate logistic regression analysis showed that baseline serum 25(OH)D levels (OR = 1.23, 95%CI: 1.04-1.44), maternal VDR Cdx2 TT (OR = 0.09, 95%CI: 0.01-0.88) and cholesterol levels at delivery (OR = 0.39, 95%CI: 0.17-0.87) were associated with targeted antiviral effects (maternal HBV DNA levels < 2 × 105 at delivery). Maternal VD levels and VDR SNPs may be associated with the efficacy of antiviral therapy in pregnant women with high HBV viral loads. Future studies to evaluate the therapeutic value of VD and its analogs in reducing the MTCT of HBV may be justified.