OBJECTIVE: To determine the current retention rate of mepolizumab (MPZ) and identify factors associated with drug retention in patients with eosinophilic granulomatosis with polyangiitis (EGPA) in the Kansai multicentre cohort (REVEAL cohort).
METHODS: Sixty patients diagnosed with EGPA and treated with MPZ between December 2016 and June 2023 were enrolled. The clinical characteristics, including laboratory data, treatments administered, and disease course outcomes were collected retrospectively. The patients were stratified into MPZ continuation (n=53) and discontinuation (n=7) groups, and drug retention was statistically compared using the log-rank test.
RESULTS: The median age of patients was 54.5 years, with 55% females, and 33% antineutrophil cytoplasmic antibody-positive at disease onset. MPZ exhibited a retention rate of 78.7% after five years. The reasons for discontinuation included treatment of coexisting diseases, inadequate response, and remission. Patient characteristics at disease onset were comparable between the groups. Patients receiving immunosuppressants (IS) before MPZ introduction demonstrated significantly higher retention rates (P = 0.038). During the final observation, the MPZ continuation group had a lower vasculitis damage index score (P = 0.027).
CONCLUSIONS: MPZ exhibited a high 5-year retention rate, particularly in patients requiring IS. This study implies that long-term use of MPZ may mitigate irreversible organ damage.

To establish refined risk prediction models for mortality in patients with microscopic polyangiitis (MPA) by using comprehensive clinical characteristics.
Data from the multicentre Japanese registry of patients with vasculitis (REVEAL cohort) were used in our analysis. In total, 194 patients with newly diagnosed MPA were included, and baseline demographic, clinical, laboratory, and treatment details were collected. Univariate and multivariate analyses were conducted to identify the significant risk factors predictive of mortality.
Over a median follow-up of 202.5 (84-352) weeks, 60 (30.9%) of 194 patients died. The causes of death included MPA-related vasculitis (18.3%), infection (50.0%), and others (31.7%). Deceased patients were older (median age 76.2 years) than survivors (72.3 years) (P < 0.0001). The death group had shorter observation periods (median 128.5 [35.3-248] weeks) than the survivor group (229 [112-392] weeks). Compared to survivors, the death group exhibited a higher smoking index, lower serum albumin levels, higher serum C-reactive protein levels, higher Birmingham Vasculitis Activity Score (BVAS), higher Five-Factor Score, and a more severe European Vasculitis Study Group (EUVAS) categorization system. Multivariate analysis revealed that higher BVAS and severe EUVAS independently predicted mortality. Kaplan-Meier survival curves demonstrated lower survival rates for BVAS ≥20 and severe EUVAS, and a risk prediction model (RPM) based on these stratified patients into low, moderate, and high-risk mortality groups.
The developed RPM is promising to predict mortality in patients with MPA and provides clinicians with a valuable tool for risk assessment and informed clinical decision-making.

Chemotherapy-induced peripheral neuropathy (CIPN) is a debilitating condition impacting 30% of cancer survivors. This study is the first to explore whether a brain-based vulnerability to chronic sensory CIPN exists.
This prospective, multicentre cohort study recruited from three sites across Scotland. Brain functional MRI (fMRI) scans (3 Tesla) were carried out on chemotherapy naïve patients at a single fMRI centre in Edinburgh, Scotland. Nociceptive stimuli (with a 256 mN monofilament) were administered during the fMRI. Development of chronic sensory/painful CIPN (CIPN+) was determined based upon European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Chemotherapy-Induced Peripheral Neuropathy 20 changes conducted 9 months after chemotherapy, and imaging data analysed using standard software.
Of 30 patients recruited (two lung, nine gynaecological, and 19 colorectal malignancies), data from 20 patients at 9 months after chemotherapy was available for analysis. Twelve were classified as CIPN+ (mean age, 63.2[9.6] yr, 9.6; six female), eight as CIPN- (mean age 62.9 [SD 5.5] yr, four female). In response to punctate stimulation, group contrast analysis showed that CIPN+ compared with CIPN- had robust activity in sensory, motor, attentional, and affective brain regions. An a priori chosen region-of-interest analysis focusing on the periaqueductal grey, an area hypothesised as relevant for developing CIPN+, showed significantly increased responses in CIPN- compared with CIPN+ patients. No difference in subcortical volumes between CIPN+ and CIPN- patients was detected.
Before administration of any chemotherapy or appearance of CIPN symptoms, we observed altered patterns of brain activity in response to nociceptive stimulation in patients who later developed chronic sensory CIPN. This suggests the possibility of a pre-existing vulnerability to developing CIPN centred on brainstem regions of the descending pain modulatory system.

OBJECTIVE: To estimate the incidence of dengue infection across geographically distinct areas of Brazil.
METHODS: This prospective, household-based, cohort study enrolled participants in five areas and followed them up for up to 4 years (2014-2018). Dengue seroprevalence was assessed at each scheduled visit. Suspected dengue cases were identified through enhanced passive and active surveillance. Acute symptomatic dengue infection was confirmed through reverse-transcriptase quantitative polymerase chain reaction in combination with an antigenic assay (non-structural protein 1) and serology.
RESULTS: Among 3300 participants enrolled, baseline seroprevalence was 76.2%, although only 23.3% of participants reported a history of dengue. Of 1284 suspected symptomatic dengue cases detected, 50 (3.9%) were laboratory-confirmed. Based on 8166.5 person-years (PY) of follow-up, the incidence of laboratory-confirmed symptomatic infection (primary endpoint) was 6.1 per 1000 PY (95% confidence interval [CI]: 4.5, 8.1). Incidence varied substantially in different years (1.8-7.4 per 1000 PY). The incidence of inapparent primary dengue infection was substantially higher: 41.7 per 1000 PY (95% CI: 31.1, 54.6).
CONCLUSIONS: Our findings, highlighting that the incidence of dengue infection is underestimated in Brazil, will inform the design and implementation of future dengue vaccine trials.
BACKGROUND: NCT01751139.

OBJECTIVE: Some observational studies of the general population showed that resting heart rate was associated with mortality. However, the relationship was unclear in dialysis patients.
METHODS: The study was a multicentre prospective cohort analysis including 1102 patients. Patients were classified into four groups based on resting heart rate just before starting the first dialysis session: <60/min; 60-79/min; 80-100/min; and ≥101/min. All-cause mortality, cardiovascular (CV) related mortality, and incidences of CV events after dialysis initiation were compared using the log-rank test. All-cause mortality rates for patients with heart rates <60, 60-79, and ≥101/min were compared to those for patients with heart rates 80-100/min, using multivariate Cox proportional hazard regression analysis. Moreover, we compared the outcomes among patients without use of β-blocker or heart failure symptom at the first dialysis session.
RESULTS: Significant differences were observed in the all-cause mortality rates among the four groups (P = 0.007). Multivariate analysis revealed that all-cause mortality was significantly higher in patients with heart rate ≥ 101/min than in patients with heart rate 80-100/min (hazard ratio [HR] = 2.30, 95% confidence interval [CI]: 1.25-4.23). Subgroup analysis showed that among patients without use of b-blocker or heart failure symptom, all-cause mortality rates for those with heart rates ≥101/min were significantly higher than in patients with heart rate 80-100/min (HR = 2.98, 95% CI: 1.51-5.88, HR = 3.65, 95% CI: 1.59-8.36, respectively).
CONCLUSIONS: The resting heart rate just before starting the first dialysis session was associated with all-cause mortality after dialysis initiation.