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Rituximab (RTX) has been reported to effectively maintain remission in anti-neutrophil cytoplasmic antibody-associated vasculitis (AAV). In this multicenter study involving 57 patients who achieved remission after 24 weeks, we evaluated the effectiveness of RTX in maintaining remission in patients with AAV. Patients were divided into three groups based on RTX administration: continuous, induction phase-only, and maintenance phase-only groups. The continuous group had a remission maintenance rate after 48 weeks of treatment compared with the induction phase-only group (100% vs. 88.2%, p = 0.29). More patients in the continuous group received three or more RTX doses during the induction period (82.4% vs. 52.9%, p = 0.06), and this group had a lower incidence of infection (5.9% vs. 29.4%, p = 0.08). Compared with the maintenance-only group, the continuous group had a numerically higher proportion of patients in remission after 48 weeks of treatment (100% vs. 83.3%, p = 0.26) and a lower incidence of infection (5.9% vs. 50%, p = 0.04); however, the N in the maintenance phase was small and suspected to have low power. Regardless of the method of RTX administration (induction phase-only or continuous), administering RTX during the induction phase may be crucial for achieving remission.

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is a hereditary cerebral small vessel disease caused by mutations in NOTCH3. CADASIL patients experienced recurrent strokes in middle age, resulting in development of dementia. To prevent disease progression, avoidance of recurrent subcortical stroke is crucial in managing CADASIL. However, CADASIL is resistant to antiplatelet therapy used in stroke prevention and no effective treatment strategies have yet to be established.Lomerizine hydrochloride is a calcium channel blocker that selectively inhibits cerebral vasoconstriction and is approved for prevention of migraine in Japan. We reported a CADASIL case in which cognitive impairment and cerebral hypoperfusion improved during lomerizine administration1). Furthermore, we demonstrated that lomerizine may provide significant benefits in stroke prevention in a single center observational study of 30 CADASIL subjects, particularly in those who have had ischemic stroke in the 2 years prior to taking the drug2).We are currently conducting the LOMCAD trial (jRCTs051220072), a multicenter, prospective, single-arm clinical trial designed to evaluate the efficacy of lomerizine in preventing recurrent ischemic events in CADASIL subjects who had at least two cerebral ischemic events within the past two years, compared to historical controls. The target number of enrolled cases is 20 (single group) and the enrollment period is from August 2022 to November 2023. The study treatment period is 24 months. The primary endpoint is symptomatic cerebral ischemic events during the 24 months after the start of study treatment. Secondary endpoints are ① Number of symptomatic cerebral ischemic events, ② All cerebral ischemic events, ③Changes in modified Rankin.Our previous observational study showed that of the subjects who had 2 episodes of symptomatic cerebral infarction, transient ischemic attack, or asymptomatic acute ischemic foci during the 2 years without lomerizine hydrochloride, symptomatic cerebral ischemic events were observed in the 64%. In the analysis the prior distribution was set to Beta (2.5, 1.5). In this clinical study, a Bayesian sample size design based on a prior predictive distribution was used. Seventeen cases are needed to achieve a probability of effectiveness if the treatment is determined as effective.

Abstract Background This study investigated the characteristics of hypertrophic pachymeningitis (HP) in antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV), using information from a multicenter study in Japan. Methods We analyzed the clinical information of 663 Asian patients with AAV (total AAV), including 558 patients with newly diagnosed AAV and 105 with relapsed AAV. Clinical findings were compared between patients with and without HP. To elucidate the relevant manifestations for HP development, multivariable logistic regression analyses were additionally performed. Results Of the patients with AAV (mean age, 70.2 ± 13.5 years), HP was noted in 30 (4.52%), including 20 (3.58%) with newly diagnosed AAV and 10 (9.52%) with relapsed AAV. Granulomatosis with polyangiitis (GPA) was classified in 50% of patients with HP. A higher prevalence of GPA was significantly observed in patients with HP than in those without HP in total AAV and newly diagnosed AAV (p < 0.001). In newly diagnosed AAV, serum proteinase 3 (PR3)-ANCA positivity was significantly higher in patients with HP than in those without HP (p = 0.030). Patients with HP significantly had ear, nose, and throat (ENT) (odds ratio [OR] 1.48, 95% confidence interval [CI] 1.03–2.14, p = 0.033) and mucous membrane/eye manifestations (OR 5.99, 95% CI 2.59–13.86, p < 0.0001) in total AAV. Moreover, they significantly had conductive hearing loss (OR 11.6, 95% CI 4.51–29.57, p < 0.0001) and sudden visual loss (OR 20.9, 95% CI 5.24–85.03, p < 0.0001). Conclusion GPA was predominantly observed in patients with HP. Furthermore, in newly diagnosed AAV, patients with HP showed significantly higher PR3-ANCA positivity than those without HP. The ear and eye manifestations may be implicated in HP development.

Background: Anti-neutrophil cytoplasm antibody-associated vasculitis is a multisystem, autoimmune disease that causes organ failure and death. Physical removal of pathogenic autoantibodies by plasma exchange is recommended for severe presentations, along with high-dose glucocorticoids, but glucocorticoid toxicity contributes to morbidity and mortality. The lack of a robust evidence base to guide the use of plasma exchange and glucocorticoid dosing contributes to variation in practice and suboptimal outcomes. Objectives: We aimed to determine the clinical efficacy of plasma exchange in addition to immunosuppressive therapy and glucocorticoids with respect to death and end-stage renal disease in patients with severe anti-neutrophil cytoplasm antibody-associated vasculitis. We also aimed to determine whether or not a reduced-dose glucocorticoid regimen was non-inferior to a standard-dose regimen with respect to death and end-stage renal disease. Design: This was an international, multicentre, open-label, randomised controlled trial. Patients were randomised in a two-by-two factorial design to receive either adjunctive plasma exchange or no plasma exchange, and either a reduced or a standard glucocorticoid dosing regimen. All patients received immunosuppressive induction therapy with cyclophosphamide or rituximab. Setting: Ninety-five hospitals in Europe, North America, Australia/New Zealand and Japan participated. Participants: Participants were aged ≥ 16 years with a diagnosis of granulomatosis with polyangiitis or microscopic polyangiitis, and either proteinase 3 anti-neutrophil cytoplasm antibody or myeloperoxidase anti-neutrophil cytoplasm antibody positivity, and a glomerular filtration rate of

Background:. Although traditional wound dressings such as collagen scaffolds promote granulation tissue formation, the efficacy of these dressings in chronic wounds is limited because of high susceptibility to bacterial growth. Biomaterials that can be applied to chronic wounds should have an anti-bacterial function. We previously reported that administering a silk-elastin solution that forms moisturizing hydrogels to wound surfaces of diabetic mice reduced bacterial growth and promoted granulation tissue formation compared with control or carboxymethyl cellulose hydrogels. We hypothesized that silk-elastin promotes wound healing in human chronic wounds by suppressing bacterial growth. Methods:. An open-label, clinical case series was conducted with a prospective, single-arm design at Kyoto University Hospital in Kyoto, Japan. In this study, 6 patients with chronic skin ulcers of any origin (2 < ulcer area (cm2) < 25) on their lower extremities were included; patients with critical ischemia were excluded. Silk-elastin sponges were applied and covered with a polyurethane film without changing the dressing for 14 days. Inflammation triggered treatment discontinuation due to fear of infection. The primary study endpoint was adverse events, including inflammation and infection. Results:. Poor hydrogel formation, possibly due to continuous exudation, was observed. No serious adverse events were noted. Two patients discontinued treatment on day 6 and day 7, respectively, due to inflammation, but they were not infected. The other 4 patients completed the 14-day silk-elastin sponge treatment without infection. Conclusion:. Silk-elastin sponge is safe for chronic skin ulcers, and its ability to promote wound healing should be determined by confirmatory clinical trials.

Critical limb ischemia (CLI) is a potentially life-threatening condition that involves severely reduced blood flow to the peripheral arteries due to arteriosclerosis obliterans (ASO) of the limbs or a similar condition. CLI patients must undergo revascularization to avoid amputation of the lower limbs and improve their survival prognosis. However, the outcomes of conventional surgical revascularization or endovascular therapy are inadequate; therefore, establishing further effective treatment methods is an urgent task. We perform therapeutic angiogenesis using autologous bone marrow-derived mononuclear cells in clinical practice and demonstrated its safety and efficacy for CLI patients for whom conventional treatments failed or are not indicated. Exercise therapies must be devised for CLI patients who have undergone therapeutic angiogenesis to save their limbs and improve survival. Because evidence regarding the efficacy and safety of exercise therapy for CLI patients is lacking, we plan to perform a prospective trial of the efficacy and safety of optimal exercise therapy following therapeutic angiogenesis for CLI patients.The trial will enroll 30 patients between 20 and 79 years with Rutherford category 4 or 5 CLI caused by ASO who will undergo therapeutic angiogenesis. Participants will be randomly allocated to receive either optimal exercise therapy or fixed exercise therapy. Those receiving optimal exercise therapy will undergo tissue muscle oxygen saturation monitoring using near-infrared spectroscopy while performing exercises and will be prescribed optimal exercise therapy. The optimal amount of exercise will be determined on day 8, 31, 61, 91 and 181 after therapeutic angiogenesis. Ethics and dissemination: This protocol was approved by the Institutional Review Boards of Kyoto Prefectural University of Medicine. In accordance with the Helsinki Declaration, written informed consent has been obtained from all participants prior to enrollment. The results of this trial will be disseminated by publication in a peer-reviewed journal. Trial registration: This trial is registered at http://www.umin.ac.jp/ctr/index.htm (identifier: UMIN000035288). Keywords: Critical limb ischemia, Arteriosclerosis obliterans, Therapeutic angiogenesis, Optimal exercise therapy, Tissue muscle oxygen saturation, Near-infrared spectroscopy