Kikuchi-Fujimoto disease, simultaneously diagnosed with systemic lupus erythematosus in an Arabic female: an agonizing combination.

Kikuchi-Fujimoto disease (KFD), also known as histiocytic necrotizing lymphadenitis, is a rare, benign condition affecting young Oriental-Asian females. It is characterized by fever and tender cervical lymphadenopathy with an unclear aetiology, and in most longitudinal reviews, KFD occurs before systemic lupus erythematosus (SLE). Herein, the case of a 28-year-old Kuwaiti female without any relevant past medical history, who was simultaneously diagnosed with KFD and SLE following an Ebstein-Barr virus infection, is reported. The patient was treated with oral prednisolone, hydroxychloroquine, cyclosporin, and belimumab and her response was clinically and biochemically favourable. Although KFD is prevalent in Asian populations, it may affect all races. Early diagnosis of KFD is difficult, particularly when simultaneously diagnosed with SLE, but crucial to preventing inappropriate therapy. Clinicians need to know about this rare disease, especially when patients present with fever and swollen lymph nodes, due to a risk of misdiagnosis with tuberculosis or lymphoma, as these are more often thought to be the cause of such symptoms.

Increasing the etanercept dose in a treat-to-target approach in juvenile idiopathic arthritis: does it help to reach the target? A post-hoc analysis of the BeSt for Kids randomised clinical trial.

BACKGROUND: Etanercept has been studied in doses up to 0.8 mg/kg/week (max 50 mg/week) in juvenile idiopathic arthritis (JIA) patients. In clinical practice higher doses are used off-label, but evidence regarding the relation with outcomes is lacking. We describe the clinical course of JIA-patients receiving high-dose etanercept (1.6 mg/kg/week; max 50 mg/week) in the BeSt for Kids trial. METHODS: 92 patients with oligoarticular JIA, RF-negative polyarticular JIA or juvenile psoriatic arthritis were randomised across three treat-to-target arms: (1) sequential DMARD-monotherapy (sulfasalazine or methotrexate (MTX)), (2) combination-therapy MTX + 6 weeks prednisolone and (3) combination therapy MTX + etanercept. In any treatment-arm, patients could eventually escalate to high-dose etanercept alongside MTX 10mg/m2/week. RESULTS: 32 patients received high-dose etanercept (69% female, median age 6 years (IQR 4-10), median 10 months (7-16) from baseline). Median follow-up was 24.6 months. Most clinical parameters improved within 3 months after dose-increase: median JADAS10 from 7.2 to 2.8 (p = 0.008), VAS-physician from 12 to 4 (p = 0.022), VAS-patient/parent from 38.5 to 13 (p = 0.003), number of active joints from 2 to 0.5 (p = 0.12) and VAS-pain from 35.5 to 15 (p = 0.030). Functional impairments (CHAQ-score) improved more gradually and ESR remained stable. A comparable pattern was observed in 11 patients (73% girls, median age 8 (IQR 6-9)) who did not receive high-dose etanercept despite eligibility (comparison group). In both groups, 56% reached inactive disease at 6 months. No severe adverse events (SAEs) occurred after etanercept dose-increase. In the comparison group, 2 SAEs consisting of hospital admission occurred. Rates of non-severe AEs per subsequent patient year follow-up were 2.27 in the high-dose and 1.43 in the comparison group. CONCLUSIONS: Escalation to high-dose etanercept in JIA-patients who were treated to target was generally followed by meaningful clinical improvement. However, similar improvements were observed in a smaller comparison group who did not escalate to high-dose etanercept. No SAEs were seen after escalation to high-dose etanercept. The division into the high-dose and comparison groups was not randomised, which is a potential source of bias. We advocate larger, randomised studies of high versus regular dose etanercept to provide high level evidence on efficacy and safety. TRIAL REGISTRATION: Dutch Trial Register; NTR1574; 3 December 2008; https://onderzoekmetmensen.nl/en/trial/26585 .

Effects of prednisolone tapering on effectiveness of infliximab in patients with ulcerative colitis: data from a retrospective cohort.

BACKGROUND AND OBJECTIVE: The influence of concomitant prednisolone on clinical outcomes and safety in infliximab-treated ulcerative colitis (UC) patients is unknown. DESIGN, SETTING, PARTICIPANTS AND OUTCOME MEASURES: A retrospective cohort study was performed, including 147 UC patients treated with infliximab at a tertiary inflammatory bowel disease (IBD) centre. Primary outcome was corticosteroid-free clinical remission (CFCR) at week 14 and week 52. Patients were grouped according to prednisolone tapering regimens: standard (≤5 mg/week), fast (>5 mg/week), direct discontinuation or no prednisolone. Patients intolerant to corticosteroids and patients stopping corticosteroids in preparation for surgery including colectomy during their initial admission were excluded. RESULTS: There was no overall association between prednisolone exposure or no exposure and CFCR at weeks 14 or 52 of infliximab. The proportion of patients with C reactive protein ≤5 mg/L was higher in the standard tapering at week 14 as compared with faster regimens or no prednisolone. In subgroup analyses, the standard tapering was associated with a higher rate of CFCR at week 14 compared with the fast-tapering regimen in patients receiving ≥40 mg prednisolone at initiation of infliximab (64.3% vs 26.3%, p=0.04) and among patients admitted with acute severe UC (66.6% vs 23.5%, p<0.05). Similar data were seen at week 52. Prednisolone did not affect infliximab trough levels but increased infection rates (10/77 vs 2/70, p=0.03), in particular C. difficile infection. CONCLUSION: In UC patients with limited disease burden, prednisolone did not affect effectiveness of infliximab. However, patients with increased disease burden seem to benefit from corticosteroid combination therapy.

Comparison of the effect of Everolimus, Prednisolone, and a combination of both on experimentally induced peritoneal adhesions in rats.

Postoperative intra-abdominal adhesions represent a significant post-surgical problem. Its complications can cause a considerable clinical and cost burden. Herein, our study aimed to investigate the effect of Everolimus on peritoneal adhesion formation after inducing adhesions in rats. In this experimental study, adhesion bands were induced by intraperitoneal injection of 3 ml of 10% sterile talc solution in 64 male albino rats. The first group served as the control group. The second one received oral Prednisolone (1 mg/kg/day), the third received Everolimus (0.1 mg/kg/day), and group four received both drugs with similar dosages for four consecutive weeks. The formation of adhesion bands was qualitatively graded according to the Nair classification. The rats in the control group had extensive adhesions between the abdominal wall and the organs. Regarding substantial adhesion formation, 50% (8/16) of animals in the control group had substantial adhesions, while this rate in the groups receiving Prednisolone, Everolimus, and combination treatment was 31%, 31%, and 31%, respectively. Also, 68.75% (5/11) of the Prednisolone recipients had insubstantial adhesions, the same as Everolimus recipients, while in the combination group, 66.66% (10/15) rats had insubstantial adhesions. Everolimus demonstrated satisfactory results in reducing the rates of induced peritoneal adhesion in an experimental model, similar to Prednisolone and superior to a combination regime.

Nivolumab-associated immune-related filamentary keratitis.

A woman in her late 50s presented to the ophthalmology clinic having bilateral eye pain and discharge for the last month. Her medical history was significant for lung adenocarcinoma, for which she was being treated with nivolumab. Filamentary keratitis was evident at the slit-lamp examination. Regardless of ophthalmic reasons, nivolumab was suspended. Prednisolone ointment was started, with a complete remission. We present a case of steroid-responsive filamentary keratitis triggered by nivolumab. We aim to highlight the importance of prompt ophthalmology referral and the use of therapies targeting ocular surface inflammation in immune checkpoint inhibition therapy.

[Improvement of tissue fibrosis in TAFRO syndrome by prednisolone monotherapy].

We report the case of a 48-year-old man who presented with fatigue and weight loss. A local physician observed elevated alkaline phosphatase levels, anemia, thrombocytopenia, and renal dysfunction. Fever also appeared, and the patient was admitted to our hospital. Computed tomography revealed hepatosplenomegaly, pleural and ascitic fluid, and left axillary lymphadenopathy. Bone marrow biopsy indicated hyperplasia with increased megakaryocytes and reticulin fibrosis. Axillary lymph node biopsy showed Castleman's disease-like features. Liver biopsy revealed proliferation of reticulin fibrosis. Therefore, TAFRO syndrome was diagnosed and treatment with 1 mg/kg prednisolone was started. Anemia and thrombocytopenia improved, and after 24 weeks of treatment, serum hyaluronic acid and type IV collagen decreased to the normal range. Bone marrow biopsy after 18 weeks of treatment showed decreased reticular fibers. In TAFRO syndrome, improvement of liver and bone marrow fibrosis can be expected with adequate intervention, and serum hyaluronic acid and type IV collagen are useful for evaluating fibrosis.

Evaluation of a multiagent chemotherapy protocol combining vincristine, cyclophosphamide, mitoxantrone and prednisolone (CMOP) for treatment of feline intermediate-large cell lymphoma.

OBJECTIVES: The aim of this study was to determine response rates, median progression-free intervals (PFIs) and median survival times (MSTs) for cats with intermediate-large cell lymphoma treated with a vincristine, cyclophosphamide, mitoxantrone and prednisolone (CMOP) protocol. A secondary objective was to determine the tolerability of mitoxantrone used within this multiagent protocol. METHODS: The medical records of 31 cats treated at a single institution between 2009 and 2022 were reviewed to identify suitable cases. Cats were included in the study if they had a confirmed diagnosis of intermediate-large cell lymphoma, had received a CMOP protocol as first-line treatment and had completed at least one 4-week cycle of this protocol. Modifications allowed in the protocol included the use of l-asparaginase, vinblastine substitution for vincristine, chlorambucil substitution for cyclophosphamide and dexamethasone or methylprednisolone substitution for prednisolone. RESULTS: The overall response rate was 74% (n = 23), with 45% (n = 14) achieving complete remission (CR), 29% (n = 9) achieving partial remission (PR) and 26% (n = 8) achieving stable disease (SD). The Kaplan-Meier median PFI and MST were 139 days and 206 days, respectively. Responders (CR or PR) had a significantly longer (P <0.001) median PFI and MST compared with non-responders (SD) (176 days vs 62 days, and 251 days vs 61 days, respectively). Cats that achieved CR had a significantly longer median PFI and MST (P <0.001) at 178 days and 1176 days, respectively. The 6-month and 1- and 2-year survival rates in cats with CR were 64%, 57% and 35%, respectively. Treatment with mitoxantrone was generally well tolerated, with no cats experiencing Veterinary Cooperative Oncology Group adverse effects above grade 2. CONCLUSIONS AND RELEVANCE: The CMOP protocol is an alternative and well-tolerated treatment for cats with intermediate-large cell lymphoma. As demonstrated with previous chemotherapy protocols, cats that respond to treatment, particularly those that achieve CR, are likely to have more durable responses.

Refractory and Recurrent Idiopathic Granulomatous Mastitis Treatment: Adaptive, Randomized Clinical Trial.

BACKGROUND: Idiopathic granulomatous mastitis (IGM) is mostly described as an autoimmune disease with higher prevalence among Middle Eastern childbearing-age women. This study aimed to evaluate the best treatment of choice in patients with resistant or recurrent IGM. STUDY DESIGN: Patients with established recurrent or resistant IGM who were referred to the Breast Cancer Research Center from 2017 to 2020 were randomly assigned to either one of the following treatment groups: A (best supportive care), B (corticosteroids: prednisolone), and C (methotrexate and low-dose corticosteroids). This adaptive clinical trial evaluated radiological and clinical responses, as well as the potential side effects, on a regular basis in each group, with patients followed up for a minimum of 2 years. RESULTS: A total of 318 participants, with a mean age of 33.52 ± 6.77 years, were divided into groups A (10 patients), B (78 patients), and C (230 patients). In group A, no therapeutic response was observed; group B exhibited a mixed response, with 14.1% experiencing complete or partial responses, 7.7% maintaining stability, and 78.2% experiencing disease progression. Accordingly, groups A and B were terminated due to inadequate response. In group C, 94.3% achieved complete response, 3% showed partial remission, and 2.7% had no response to therapy. Among the entire patient cohort, 11.6% tested positive for antinuclear antibodies, 3.5% for angiotensin-converting enzyme, and 12.3% for erythema nodosum. Notably, hypothyroidism was a prevalent condition among the patients, affecting 7.2% of the cohort. The incidence of common side effects was consistent across all groups. CONCLUSIONS: The most effective treatment option for patients with recurrent or resistant IGM is a combination therapy involving steroids and disease-modifying antirheumatic drugs such as methotrexate.

Biweekly vs Triweekly Cabazitaxel in Older Patients With Metastatic Castration-Resistant Prostate Cancer: The CABASTY Phase 3 Randomized Clinical Trial.

Importance: Many patients 65 years or older with metastatic castration-resistant prostate cancer (mCRPC) are denied taxane chemotherapy because this treatment is considered unsuitable. Objective: To determine whether biweekly cabazitaxel (CBZ), 16 mg/m2 (biweekly CBZ16), plus prophylactic granulocyte colony-stimulating factor (G-CSF) at each cycle reduces the risk of grade 3 or higher neutropenia and/or neutropenic complications (eg, febrile neutropenia, neutropenic infection, or sepsis) compared with triweekly CBZ, 25 mg/m2 (triweekly CBZ25), plus G-CSF (standard regimen). Design, Setting, and Participants: A total of 196 patients 65 years or older with progressive mCRPC were enrolled in this prospective phase 3 randomized clinical trial conducted in France (18 centers) and Germany (7 centers) between May 5, 2017, and January 7, 2021. All patients had received docetaxel and at least 1 novel androgen receptor-targeted agent. Interventions: Patients were randomly assigned 1:1 to receive biweekly CBZ16 plus G-CSF and daily prednisolone (experimental group) or triweekly CBZ25 plus G-CSF and daily prednisolone (control group). Main Outcome and Measures: The primary end point was the occurrence of grade 3 or higher neutropenia measured at nadir and/or neutropenic complications. Results: Among 196 patients (97 in the triweekly CBZ25 group and 99 in the biweekly CBZ16 group), the median (IQR) age was 74.6 (70.4-79.3) years, and 181 (92.3%) had an Eastern Cooperative Oncology Group performance status of 0 or 1. The median (IQR) follow-up duration was 31.3 (22.5-37.5) months. Relative dose intensities were comparable between groups (median [IQR], 92.7% [83.7%-98.9%] in the triweekly CBZ25 group vs 92.8% [87.0%-98.9%] in the biweekly CBZ16 group). The rate of grade 3 or higher neutropenia and/or neutropenic complications was significantly higher with triweekly CBZ25 vs biweekly CBZ16 (60 of 96 [62.5%] vs 5 of 98 [5.1%]; odds ratio, 0.03; 95% CI, 0.01-0.08; P < .001). Grade 3 or higher adverse events were more common with triweekly CBZ25 (70 of 96 [72.9%]) vs biweekly CBZ16 (55 of 98 [56.1%]). One patient (triweekly CBZ25 group) died of a neutropenic complication. Conclusions and Relevance: In this randomized clinical trial, compared with the standard regimen, biweekly CBZ16 plus G-CSF significantly reduced by 12-fold the occurrence of grade 3 or higher neutropenia and/or neutropenic complications, with comparable clinical outcomes. The findings suggest that biweekly CBZ16 regimen should be offered to patients 65 years or older with mCRPC for whom the standard regimen is unsuitable. Trial Registration: ClinicalTrials.gov Identifier: NCT02961257.

High-dose (40†mg) versus low-dose (20†mg) prednisolone for treating sarcoidosis: a randomised trial (SARCORT trial).

BACKGROUND: Current guidelines recommend 20-40 mg·day-1 of oral prednisolone for treating pulmonary sarcoidosis. Whether the higher dose (40 mg·day-1) can improve outcomes remains unknown. METHODS: We conducted an investigator-initiated, single-centre, open-label, parallel-group, randomised controlled trial (ClinicalTrials.gov identifier NCT03265405). Consecutive subjects with pulmonary sarcoidosis were randomised (1:1) to receive either high-dose (40 mg·day-1 initial dose) or low-dose (20 mg·day-1 initial dose) oral prednisolone, tapered over 6 months. The primary outcome was the frequency of relapse or treatment failure at 18 months from randomisation. Key secondary outcomes included the time to relapse or treatment failure, overall response, change in forced vital capacity (FVC, in litres) at 6 and 18 months, treatment-related adverse effects and health-related quality of life (HRQoL) scores using the Sarcoidosis Health Questionnaire and Fatigue Assessment Scale. FINDINGS: We included 86 subjects (43 in each group). 42 and 43 subjects completed treatment in the high-dose and low-dose groups, respectively, while 37 (86.0%) and 41 (95.3%), respectively, completed the 18-month follow-up. 20 (46.5%) subjects had relapse or treatment failure in the high-dose group and 19 (44.2%) in the low-dose group (p=0.75). The mean time to relapse/treatment failure was similar between the groups (high-dose 307 days versus low-dose 269 days, p=0.27). The overall response, the changes in FVC at 6 and 18 months and the incidence of adverse effects were also similar. Changes in HRQoL scores did not differ between the study groups. INTERPRETATION: High-dose prednisolone was not superior to a lower dose in improving outcomes or the HRQoL in sarcoidosis and was associated with similar adverse effects.

Case Report: A Rare Case of Elderly-Onset Adult-Onset Still's Disease in a Patient With Systemic Lupus Erythematosus.

The rare systemic inflammatory disorder 'adult-onset Still's disease (AOSD)' is characterized by recurrent fever, evanescent rash, arthralgia, and leukocytosis with neutrophilia. The Yamaguchi criteria are widely used to diagnose AOSD; these criteria can be used for diagnosis after a wide range of infectious, rheumatic, and neoplastic diseases have been excluded. AOSD generally does not overlap with other rheumatic diseases. We present the rare case of an 80-year-old Japanese woman who presented with arthralgia, fever, and skin rash during treatment for systemic lupus erythematosus (SLE), which was finally diagnosed as an overlap of AOSD. Blood tests revealed leukocytosis with neutrophilia, high C-reactive protein (CRP), and liver dysfunction. Her anti-ds-DNA antibody titer and serum complement titer were at the same level as before and remained stable. We suspected AOSD based on the high serum ferritin level but hesitated to diagnose AOSD because of the patient's SLE history. We measured serum interleukin (IL)-18; it was extremely high at 161,221 pg/mL, which was strongly suggestive of AOSD. We thus diagnosed AOSD complicated during the course of treatment for SLE. The patient's arthralgia and high CRP level persisted after we increased her oral prednisolone dose and added oral methotrexate, but her symptoms eventually improved with the addition of intravenous tocilizumab. We note that the presence of autoantibodies or other rheumatic diseases cannot be absolutely ruled out in the diagnosis of AOSD. Although high serum IL-18 levels are not specific for AOSD, the measurement of serum IL-18 may aid in the diagnosis of AOSD in similar rare cases.

Optimizing the corticosteroid dose in steroid-sensitive nephrotic syndrome.

The use of corticosteroids in the treatment of steroid-sensitive nephrotic (SSNS) syndrome in children has evolved surprisingly slowly since the ISKDC consensus over 50 years ago. From a move towards longer courses of corticosteroid to treat the first episode in the 1990s and 2000s, more recent large, well-designed randomized controlled trials (RCTs) have unequivocally shown no benefit from an extended course, although doubt remains whether this applies across all age groups. With regard to prevention of relapses, daily ultra-low-dose prednisolone has recently been shown to be more effective than low-dose alternate-day prednisolone. Daily low-dose prednisolone for a week at the time of acute viral infection seems to be effective in the prevention of relapses but the results of a larger RCT are awaited. Recently, corticosteroid dosing to treat relapses has been questioned, with data suggesting lower doses may be as effective. The need for large RCTs to address the question of whether corticosteroid doses can be reduced was the conclusion of the authors of the recent corticosteroid therapy for nephrotic syndrome in children Cochrane update. This review summarizes development in thinking on corticosteroid use in SSNS and makes suggestions for areas that merit further scrutiny.

Changes in oral corticosteroid use in asthma treatment-A 20-year Danish nationwide drug utilisation study.

Oral corticosteroids (OCS) are used in asthma management but can cause serious adverse effects. We aimed to investigate the usage trends in a nationwide asthma cohort in Denmark from 1999 to 2018. Using national registers, we identified young adults (18-45 years) with two or more asthma drug collections within 12 months since the age of 15 years as indicative of active asthma. OCS exposure level was stratified as high use (≥5 mg prednisolone/day/year) and low use (<5 mg/day/year). Lorenz curves were computed to illustrate potential skewness of consumption among the OCS users. We identified 318 950 individuals with a median age of 29 years (IQR 20-38 years) whereof 57% were women. The 1-year prevalence of OCS users was stable at 4.8% (median, IQR 4.7%-4.8%), but with nearly 40% decrease in high-users from 0.54% in 1999 to 0.33% in 2018. The median annual exposure decreased from 500 mg/year (1999) to 250 mg/year (2018). We found a substantial skewness in the distribution of OCS usage with 10% of users accounting for almost 50% of all OCS use. The prevalence of OCS users among young adults with active asthma has been relatively stable from 1999 to 2018, but with a decreasing prevalence of high-users and annual consumption.

Risk factors for failure of ileal pouch-anal anastomosis in patients with refractory ulcerative colitis.

BACKGROUND: Proctocolectomy with ileal pouch-anal anastomosis is the standard surgical procedure for ulcerative colitis refractory to medical treatment. In a few cases, ileal pouch-anal anastomosis cannot be completed due to intraoperative technical problems. The aim of this single-center study was to identify risk factors for a technically failed ileal pouch-anal anastomosis. METHODS: In total, 391 patients with ulcerative colitis who received ileal pouch-anal anastomosis were identified. Clinical and perioperative data from patients with successful ileal pouch-anal anastomosis (IPAA+) were compared to data from failed ileal pouch-anal anastomosis (IPAA-). Definition of failed ileal pouch-anal anastomosis was intraoperative failure to perform ileal pouch-anal anastomosis. Risk factors for failed ileal pouch-anal anastomosis were assessed by logistic regression. Cut-off values were calculated on the basis of receiver operating characteristic curves and the Youden Index. RESULTS: The rate of failed ileal pouch-anal anastomosis was 26 of 391 (6.6%). In 22 of 26 cases (84.6%), there was an insufficient length of the small intestinal mesentery. Patients with failed ileal pouch-anal anastomosis were more often male (80.8% vs 54.5%, P = .009), older (47.1 ± 14.1 vs 39.2 ± 12.8 years, P = .007), had a higher body mass index 27.2 ± 4.5 vs 23.7 ± 4.3 kg/m2, P < .001), and had extraintestinal manifestations more frequently (65.4% vs 26.3%, P < .001). Further risk factors for failed ileal pouch-anal anastomosis were hypertension and Cushing's syndrome. CONCLUSION: Technical failure of ileal pouch-anal anastomosis is elevated in patients with higher body mass index, with refractory ulcerative colitis, and/or extended immunosuppressive medication. Three-staged ileal pouch-anal anastomosis and optimizing preoperative conditions may help to elevate the rate of successful ileoanal pouch construction in these patients.

Potential benefits of precise corticosteroid therapy for critical COVID-19.

This study was aimed to explore the precise dose of corticosteroid therapy in critical COVID-19. A total of forty-five critical COVID-19 patients were enrolled. The process of critical COVID-19 was divided into alveolitis and fibrosis stages. Most nonsurvivors died in fibrosis phase. Nonsurvivors had more dyspnea symptoms, fewer days of hospitalization, shorter duration of alveolitis and fibrosis. High-dose daily corticosteroid therapy (≥150 mg/d) was associated with shorter survival time and lower lymphocyte count in fibrosis phase. Moreover, a high cumulative dose (≥604 mg) was tied to longer duration of virus shedding, lower oxygenation index (OI), higher incidence of tracheal intubation, fewer lymphocytes and higher levels of C-reactive protein (CRP) and lactate dehydrogenase (LDH). In alveolitis phase, the low-to-moderate-dose daily corticosteroid therapy and a small cumulative dose reduced lymphocytes. In conclusion, low-to-moderate dose corticosteroids may be beneficial in the fibrosis phase. High-dose corticosteroid therapy in the fibrosis phase aggravates the severity of critical COVID-19.

Abiraterone acetate and prednisolone with or without enzalutamide for high-risk non-metastatic prostate cancer: a meta-analysis of primary results from two randomised controlled phase 3 trials of the STAMPEDE platform protocol.

BACKGROUND: Men with high-risk non-metastatic prostate cancer are treated with androgen-deprivation therapy (ADT) for 3 years, often combined with radiotherapy. We analysed new data from two randomised controlled phase 3 trials done in a multiarm, multistage platform protocol to assess the efficacy of adding abiraterone and prednisolone alone or with enzalutamide to ADT in this patient population. METHODS: These open-label, phase 3 trials were done at 113 sites in the UK and Switzerland. Eligible patients (no age restrictions) had high-risk (defined as node positive or, if node negative, having at least two of the following: tumour stage T3 or T4, Gleason sum score of 8-10, and prostate-specific antigen [PSA] concentration ≥40 ng/mL) or relapsing with high-risk features (≤12 months of total ADT with an interval of ≥12 months without treatment and PSA concentration ≥4 ng/mL with a doubling time of <6 months, or a PSA concentration ≥20 ng/mL, or nodal relapse) non-metastatic prostate cancer, and a WHO performance status of 0-2. Local radiotherapy (as per local guidelines, 74 Gy in 37 fractions to the prostate and seminal vesicles or the equivalent using hypofractionated schedules) was mandated for node negative and encouraged for node positive disease. In both trials, patients were randomly assigned (1:1), by use of a computerised algorithm, to ADT alone (control group), which could include surgery and luteinising-hormone-releasing hormone agonists and antagonists, or with oral abiraterone acetate (1000 mg daily) and oral prednisolone (5 mg daily; combination-therapy group). In the second trial with no overlapping controls, the combination-therapy group also received enzalutamide (160 mg daily orally). ADT was given for 3 years and combination therapy for 2 years, except if local radiotherapy was omitted when treatment could be delivered until progression. In this primary analysis, we used meta-analysis methods to pool events from both trials. The primary endpoint of this meta-analysis was metastasis-free survival. Secondary endpoints were overall survival, prostate cancer-specific survival, biochemical failure-free survival, progression-free survival, and toxicity and adverse events. For 90% power and a one-sided type 1 error rate set to 1·25% to detect a target hazard ratio for improvement in metastasis-free survival of 0·75, approximately 315 metastasis-free survival events in the control groups was required. Efficacy was assessed in the intention-to-treat population and safety according to the treatment started within randomised allocation. STAMPEDE is registered with ClinicalTrials.gov, NCT00268476, and with the ISRCTN registry, ISRCTN78818544. FINDINGS: Between Nov 15, 2011, and March 31, 2016, 1974 patients were randomly assigned to treatment. The first trial allocated 455 to the control group and 459 to combination therapy, and the second trial, which included enzalutamide, allocated 533 to the control group and 527 to combination therapy. Median age across all groups was 68 years (IQR 63-73) and median PSA 34 ng/ml (14·7-47); 774 (39%) of 1974 patients were node positive, and 1684 (85%) were planned to receive radiotherapy. With median follow-up of 72 months (60-84), there were 180 metastasis-free survival events in the combination-therapy groups and 306 in the control groups. Metastasis-free survival was significantly longer in the combination-therapy groups (median not reached, IQR not evaluable [NE]-NE) than in the control groups (not reached, 97-NE; hazard ratio [HR] 0·53, 95% CI 0·44-0·64, p<0·0001). 6-year metastasis-free survival was 82% (95% CI 79-85) in the combination-therapy group and 69% (66-72) in the control group. There was no evidence of a difference in metatasis-free survival when enzalutamide and abiraterone acetate were administered concurrently compared with abiraterone acetate alone (interaction HR 1·02, 0·70-1·50, p=0·91) and no evidence of between-trial heterogeneity (I2 p=0·90). Overall survival (median not reached [IQR NE-NE] in the combination-therapy groups vs not reached [103-NE] in the control groups; HR 0·60, 95% CI 0·48-0·73, p<0·0001), prostate cancer-specific survival (not reached [NE-NE] vs not reached [NE-NE]; 0·49, 0·37-0·65, p<0·0001), biochemical failure-free-survival (not reached [NE-NE] vs 86 months [83-NE]; 0·39, 0·33-0·47, p<0·0001), and progression-free-survival (not reached [NE-NE] vs not reached [103-NE]; 0·44, 0·36-0·54, p<0·0001) were also significantly longer in the combination-therapy groups than in the control groups. Adverse events grade 3 or higher during the first 24 months were, respectively, reported in 169 (37%) of 451 patients and 130 (29%) of 455 patients in the combination-therapy and control groups of the abiraterone trial, respectively, and 298 (58%) of 513 patients and 172 (32%) of 533 patients of the combination-therapy and control groups of the abiraterone and enzalutamide trial, respectively. The two most common events more frequent in the combination-therapy groups were hypertension (abiraterone trial: 23 (5%) in the combination-therapy group and six (1%) in control group; abiraterone and enzalutamide trial: 73 (14%) and eight (2%), respectively) and alanine transaminitis (abiraterone trial: 25 (6%) in the combination-therapy group and one (<1%) in control group; abiraterone and enzalutamide trial: 69 (13%) and four (1%), respectively). Seven grade 5 adverse events were reported: none in the control groups, three in the abiraterone acetate and prednisolone group (one event each of rectal adenocarcinoma, pulmonary haemorrhage, and a respiratory disorder), and four in the abiraterone acetate and prednisolone with enzalutamide group (two events each of septic shock and sudden death). INTERPRETATION: Among men with high-risk non-metastatic prostate cancer, combination therapy is associated with significantly higher rates of metastasis-free survival compared with ADT alone. Abiraterone acetate with prednisolone should be considered a new standard treatment for this population. FUNDING: Cancer Research UK, UK Medical Research Council, Swiss Group for Clinical Cancer Research, Janssen, and Astellas.

Outcome of low-dose prednisolone use for the induction of remission in lupus nephritis patients.

OBJECTIVES: This study aimed to compare the efficacy of low-dose prednisolone with conventional high-dose regimen in proliferative lupus nephritis (LN) for remission. METHODS: This open-label randomized clinical trial was conducted in the Department of Rheumatology, Bangabandhu Sheikh Mujib Medical University (BSMMU), Dhaka, Bangladesh. A total of 32 LN patients were randomized into low-dose (experimental) and high-dose (control) groups. All subjects received standard dose of intravenous (I/V) methylprednisolone and pulse I/V cyclophosphamide. Oral prednisolone, 0.5 mg/kg/d and 1 mg/kg/d were given to experimental and control groups respectively for initially 4 weeks then tapered. The patients were followed for 24 weeks. The rates of renal remission (complete and partial) were assessed at 24 weeks. The disease activity, biochemical markers, and quality of life were evaluated at baseline and at 24 weeks. RESULTS: Complete renal remission was achieved by 66.7% of patients in each group (P = .99). Renal remission (partial/complete) was achieved by 86.7% and 83.3% of patients in the prednisolone low-dose group and high-dose group respectively (P = .99). In between groups, no significant difference was observed in the improvement of active urinary sediments, serum creatinine level, anti-double-stranded DNA level, complements level, disease activity and Short Form-12 score. The prednisolone dose-related adverse events like cushingoid facies, abdominal stria, infections and serious adverse events like death occurred more in the high-dose prednisolone group. CONCLUSIONS: It has been observed that low-dose prednisolone regimen may be effective in LN. Steroid dose-related side effects and rate of infections were lower in this group.

New-onset Evans syndrome associated with systemic lupus erythematosus after BNT162b2 mRNA COVID-19 vaccination.

Evans syndrome presents as concurrent autoimmune hemolytic anemia (AIHA) and immune thrombocytopenia (ITP). Systemic lupus erythematosus (SLE) is the most frequent autoimmune disorder associated with Evans syndrome. We herein report a case of new-onset Evans syndrome associated with SLE after BNT162b2 mRNA coronavirus disease 2019 (COVID-19) vaccination in a 53-year-old woman. Blood examination at diagnosis showed hemolytic anemia with a positive Coombs test and thrombocytopenia. Hypocomplementemia and the presence of lupus anticoagulant indicated a strong association with SLE. Prednisolone administration rapidly restored hemoglobin level and platelet count. This case suggests that mRNA COVID-19 vaccination may cause an autoimmune disorder. Physicians should be aware of this adverse reaction by mRNA COVID-19 vaccination and should consider the benefits and risks of vaccination for each recipient.

Successful rituximab treatment of an elderly Japanese patient with HHV8-positive, HIV-negative multicentric Castleman disease.

Human herpesvirus-8 (HHV8)-positive, human immunodeficiency virus (HIV)-negative multicentric Castleman disease (MCD) is a rare and age-related lymphoproliferative disorder caused by cytokine storm. Rituximab treatment is currently recommended because B-cell depletion eliminates the primary reservoir for HHV8. We report the first case of effective rituximab treatment of a Japanese patient (an 87-year-old woman) with this disorder. Her inflammatory symptoms and lymphadenopathy improved after medium-dose steroid therapy, but these symptoms recurred during steroid tapering. After one course of rituximab therapy, she achieved sustained remission. HHV8-associated MCD should be considered as a possible diagnosis in HIV-negative patients with inflammatory symptoms and lymphadenopathy.