Effectiveness and safety of rituximab in severely relapsed antineutrophil cytoplasmic antibody-associated vasculitis: a retrospective analysis of a Japanese multicentre cohort from the J-CANVAS.

We aimed to clarify the long-term safety and efficacy of rituximab (RTX) as a remission induction therapy following severe relapse in patients with antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV). We retrospectively collected the data of patients with severely relapsed AAV from a Japanese multicentre cohort. The primary exposure was RTX use; the primary outcome was complete remission (CR) proportions at week 24. Baseline characteristics were compared between the RTX and non-RTX groups. We performed multivariate logistic regression analysis and one-to-one propensity score matching analysis as a sensitivity analysis. Totally, 100 patients were enrolled: 52 in the RTX group and 48 in the non-RTX group. Baseline characteristics were comparable between the two groups, except for age, AAV subtype and ANCA serotype. The median age was 71 vs. 75 years, and the PR3-ANCA positivity rate was 44.2% vs. 18.8% in the RTX and non-RTX groups, respectively. No significant difference was observed in CR proportions at week 24 between the two groups (79.2% vs. 68.1%, p = 0.321), with an adjusted odds ratio of 1.27 (95% confidence interval [CI] 0.47-3.51). At week 48, CR proportions were significantly higher in the RTX group (91.7% vs. 64.9%, p = 0.005), with an adjusted odds ratio of 2.95 (95% CI 0.97-9.91). Serious infection rates were lower in the RTX group than in the non-RTX group, with no statistically significant difference. RTX was not superior to conventional immunosuppressive therapies at week 24 but showed significantly favourable results at week 48 for severely relapsed AAV.

Combinational manipulation of transcription factors, CreA and ClbR, is a viable strategy to improve cellulolytic enzyme production in Aspergillus aculeatus.

The production of cellulolytic enzymes in response to inducible carbon sources is mainly regulated at the transcriptional level in filamentous fungi. We have identified a cellobiose-response regulator (ClbR) controlling the expression of cellulolytic enzyme-encoding genes in Aspergillus aculeatus. However, the engineering potential of combining the deletion of transcriptional repressors with the overexpression of transcriptional activators to enhance enzyme production has not been analyzed. Here, we investigated the effect of the deletion of the transcriptional repressor creA and the overexpression of the transcriptional activator clbR in enzyme production in A. aculeatus. Here, we verified that a combination of creA deletion and clbR overexpression (Δc&OE) improved cellulase, ß-1,4-xylanase, and ß-glucosidase production. Cellulase and ß-1,4-xylanase production increased 3.4- and 8.0-fold in Δc&OE compared with the host strain (MR12) at 96-h incubation, respectively. ß-Glucosidase production in ΔcreA and Δc&OE increased approximately 5.0-fold compared with that in MR12 at 240-h incubation. Transcriptional analysis revealed that the increase in enzyme production was due to increased expression of cellobiohydrolase, endo-ß-1,4-glucanase, ß-1,4-xylanase, and ß-glucosidase 1 (bgl1). Interestingly, bgl1 expression in ΔcreA increased in a dose-dependent manner in response to glucose. Thus, combinational manipulation of transcription factors improved cellulase, xylanase, and ß-glucosidase production in A. aculeatus.

Two-fractionated stereotactic magnetic resonance-guided adaptive radiation therapy for patients with prostate cancer (SMART PRO trial): protocol for a confirmatory clinical trial.

INTRODUCTION: In an MRI-guided linear accelerator (MR-LINAC) system, the planned doses for organs at risk and for tumours are assessed by MR imaging and re-contouring at every treatment. This allows treatment to be safer and more precise by ensuring that it is suitable for the state of the patient's organs on that day, as well as by allowing images to be acquired during radiation therapy to prevent radiation while organs are in motion.Here, we will conduct a confirmatory study of two-fractionated stereotactic magnetic resonance-guided adaptive radiation therapy for patients with localised prostate cancer. METHODS AND ANALYSIS: This will be a single-arm study to demonstrate the safety and efficacy of ultra-hypofractionated radiation (26 Gy/2 Fr) using an MR-LINAC system in patients with very low-intermediate risk prostate cancer.The primary endpoint will be the incidence of grade ≥2 acute urinary tract adverse events occurring within 90 days of the start of radiation therapy.The sample size has been determined to be 58. ETHICS AND DISSEMINATION: This study is performed in accordance with Ethical Guidelines for Medical and Health Research Involving Human Subjects, published by Japan's Ministry of Education, Science and Technology and the Ministry of Health, Labour and Welfare and the modified act on the Protection of Personal Information as well as the Declaration of Helsinki. This study was approved by the institutional ethics committee of the National Cancer Center on 20 November 2021.The findings of this trial will be submitted to an international peer-reviewed journal and the key findings will be presented at an international scientific conference.Authorship will be ascribed in accordance with the International Committee of Medical Journal Editors guidance. TRIAL REGISTRATION NUMBER: UMIN000049746.

Effectiveness of intravenous methylprednisolone pulse in patients with severe microscopic polyangiitis and granulomatosis with polyangiitis.

OBJECTIVES: To evaluate the effectiveness and safety of two different intravenous methylprednisolone (IVMP) pulse doses in patients with severe microscopic polyangiitis (MPA) and granulomatosis with polyangiitis (GPA). METHODS: We emulated a target trial using observational data from the nationwide registry in Japan. Patients with severe glomerulonephritis or diffuse alveolar haemorrhage were selected and pseudo-randomised into three groups using propensity score-based overlap weighting as follows: non-IVMP, IVMP 0.5 g/day, and IVMP 1.0 g/day. The primary outcome was all-cause death, and the secondary outcomes were composite all-cause death and kidney failure, severe relapse, and serious infection from 2 to 48 weeks after treatment initiation. To estimate the treatment effects, the Cox proportional hazard model and Fine-Gray subdistribution hazard model were used. RESULTS: In this emulated target trial, of 201 eligible patients (MPA, 175; GPA, 26), 6 (2.8%) died, 4 (2.0%) had kidney failure, 11 (5.3%) had severe relapse, and 40 (19.8%) had severe infections. Hazard ratios (HR) for IVMP 0.5 g/day and IVMP 1.0 g/day pulse groups compared with non-IVMP pulse were as follows: all-cause death = 0.46 (95% confidence interval [95%CI]: 0.07-2.81) and 0.07 (95%CI: 0.01-0.41); all-cause death/kidney failure = 1.18 (95%CI: 0.26-5.31) and 0.59 (95%CI: 0.08-4.52); subdistribution HRs for severe relapse = 1.26 (95%CI: 0.12-13.70) and 3.36 (95%CI: 0.49-23.29); and serious infection = 1.88 (95%CI: 0.76-4.65) and 0.94 (95%CI: 0.28-3.13). CONCLUSIONS: IVMP 1.0 g/day pulse may improve 48-week mortality in patients with severe MPA/GPA.

How to select and understand guidelines for patient-reported outcomes: a scoping review of existing guidance.

BACKGROUND: Over the past few decades, patient-reported outcomes (PROs) have been used to understand patient health conditions better. Therefore, numerous PRO measures (questionnaires) and guidelines or guidance have been developed. However, it is challenging to select target guidance from among the many available guidance and to understand the chosen guidance. This study comprehensively collected the existing PRO guidance for clinical trials or studies and practices to support novice PRO users in academia, industry, clinical practice, and regulatory and reimbursement decision-making. METHODS: For the scoping review, we searched the MEDLINE, Embase, Google Books, WorldCat, and the National Library of Medicine (NLM) Bookshelf databases from 2009 to 2023. The eligibility criteria were PRO guidance for clinical trials, clinical practice, or application such as health technology assessment. Those guidance cover aspects such as quality of life (QOL), PRO, health-related QOL, health state utilities, psychometric requirements, implementation methods, analysis and interpretation, or clinical practice applications. After the systematic search, three researchers individually reviewed the collected data, and the reviewed articles and books were scrutinized using the same criteria. RESULTS: We collected the PRO guidance published in articles and books between 2009 and 2023. From the database searches, 1,455 articles and 387 books were identified, of which one book and 33 articles were finally selected. The collected PRO guidance was categorized into the adoption of PRO measures, design and reporting of trials or studies using PROs, implementation of PRO evaluation in clinical trials or studies or clinical practice, analysis and interpretation of PROs, and application of PRO evaluation. Based on this categorization, we suggest the following for novices: When selecting guidance, novices should clarify the "place" and "purpose" where the guidance will be used. Additionally, they should know that the terminology related to PRO and the scope and expectations of PROs vary by "places" and "purposes". CONCLUSIONS: From this scoping review of existing PRO guidance, we provided summaries and caveats to assist novices in selecting guidance that fits their purpose and understanding it.

Cycloheximide in the nanomolar range inhibits seed germination of Orobanche minor.

From the 992 samples of culture extracts of microorganisms isolated from soil in Japan, we found that the extract of Streptomyces sp. no. 226 inhibited Orobanche minor seed germination without significantly affecting the seed germination of Trifolium pratense and the growth of Aspergillus oryzae and Escherichia coli. Using ESI-MS, 1H-NMR, and 13C-NMR, we identified the active compound as cycloheximide. Cycloheximide had half-maximum inhibitory concentrations of 2.6 ng/mL for the inhibition of seed germination of O. minor and 2.5 µg/mL for that of the conidial germination of A. oryzae. Since cycloheximide is known to inhibit translation by interacting with ribosomal protein L28 (RPL28) in yeast, we investigated whether RPL protein of O. minor plays a critical role in the inhibition of O. minor seed germination. Our data suggested that O. minor RPL27A was not sensitive to cycloheximide by comparing it to the strain expressing S. cerevisiae RPL28. These findings suggest the presence of an unidentified mechanism by which cycloheximide hinders O. minor seed germination.

Perceptions regarding the concept and definition of patient-reported outcomes among healthcare stakeholders in Japan with relation to quality of life: a cross-sectional study.

Patient-reported outcomes (PROs) are frequently used in a variety of settings, including clinical trials and clinical practice. The definition of PRO and quality of life (QOL) and their relationship have been concluded through discussions among experts that has been the premise of PRO guidelines are not clearly stated in the guidelines. Therefore, the definition of PRO, especially in relation to QOL, is sometimes explained simply, as "PRO includes QOL," but this complicated matters. This study investigated the perceptions of PRO among various stakeholders (including patients and their families, the industry, clinicians, regulatory or health technology assessment personnel, and academic researchers) in Japan to clarify its definitions and that of QOL, including their relationship.We conducted a two-step survey: a qualitative interview survey and a web-based survey to ensure the validity of the survey. During the interviews, eight stakeholders described their perceptions and thoughts on PRO and its relationship to QOL, and their experience of using PRO. Overall 253 clinicians, 249 company employees, and 494 patients participated in the web survey to confirm how the findings of the interview survey supported the results.In the interview survey, patient advocates described various perspectives of PRO and QOL, including unexpected dynamic relationships, while the most other stakeholders explained PRO and QOL with the language used in the guidelines, but their responses were split. The web-based survey revealed that all stakeholders had a lower awareness of PRO than QOL. The most common perception of PRO, especially in the relationship to QOL, was "they did not fully overlap." Although there were differences in perceptions of the relationship between PRO and QOL among clinicians, company employees, and patients, all perceived PRO as a tool to facilitate communication in clinical practice.The present results are inconsistent with the simplified explanation of PRO, but consistent with the original PRO guideline definitions, which also considered the role of PRO in clinical practice. To make PRO a more potent tool, all stakeholders using PRO should confirm its definition and how it differs from QOL, have a unified recognition in each PRO use, and avoid miscommunication.

Psychological Barriers to the Use of Opioid Analgesics for Treating Pain in Patients With Advanced Recurrent Cancer: A Multicenter Cohort Study.

Background: We aimed to gain insight into psychological barriers toward initiation of strong opioid analgesic use in patients with advanced recurrent cancer. Methods: This study included 46 patients who were prescribed with opioid analgesics for advanced recurrent cancer. The primary outcome was psychological barriers assessed using the Japanese version of the Barriers Questionnaire-II (JBQ-II). The secondary outcomes were psychological changes and pain relief one week after the induction of strong opioid analgesics. Results: The mean age of participants was 63.6 years. Furthermore, 26.1% had an Eastern Cooperative Oncology Group (ECOG) performance status of ≥3. The mean JBQ-II total score was 1.97 (95% confidence interval: 1.75-2.19). At the initiation of opioid therapy, there was no difference in the total scores between the baseline and one week later. Nevertheless, there was a significant difference in the subscale "disease progression" score (mean 2.97 vs. 2.59, difference in means 0.38, standard error 0.16, p = 0.026). Personalized Pain Goal (PPG) was achieved in about half of the participants, and a trend toward a higher score in the subscale "harmful effects" (concern about adverse events) was observed in those who did not achieve PPG. Conclusion: This study showed that patients with advanced recurrent cancer have psychological barriers to opioid induction. The relationship between the presence of psychological barriers before and after induction of opioid analgesics and the speed of pain improvement was determined. The results may provide fundamental information for prospective intervention studies to develop individualized education programs for patients with psychological barriers to opioids.Clinical Trial Registration Number UMIN000042443.

C-terminus of serine-arginine protein kinase-like protein, SrpkF, is involved in conidiophore formation and hyphal growth under salt stress in Aspergillus aculeatus.

The serine-arginine protein kinase-like protein, SrpkF, was identified as a regulator for the cellulose-responsive induction of cellulase genes in Aspergillus aculeatus. To analyze various aspects of SrpkF function, we examined the growth of the control strain (MR12); C-terminus deletion mutant, which produced SrpkF1-327 (ΔCsrpkF); whole gene-deletion mutant of srpkF (ΔsrpkF), srpkF overexpressing strain (OEsprkF); and the complemented strain (srpkF+) under various stress conditions. All test strains grew normally on minimal medium under control, high salt (1.5 M KCl), and high osmolality (2.0 M sorbitol and 1.0 M sucrose). However, only ΔCsrpkF showed reduced conidiation on 1.0 M NaCl media. Conidiation of ΔCsrpkF on 1.0 M NaCl media was reduced to 12% compared with that of srpkF+. Further, when OEsprkF and ΔCsrpkF were pre-cultured under salt stress conditions, germination under salt stress conditions was enhanced in both strains. By contrast, deletion of srpkF did not affect hyphal growth and conidiation under the same conditions. We then quantified the transcripts of the regulators involved in the central asexual conidiation pathway in A. aculeatus. The findings revealed that the expression of brlA, abaA, wetA, and vosA was reduced in ΔCsrpkF under salt stress. These data suggest that in A. aculeatus, SrpkF regulates conidiophore development. The C-terminus of SrpkF seems to be important for regulating SrpkF function in response to culture conditions such as salt stress.

A multicenter phase II trial of the triplet antiemetic therapy with palonosetron, aprepitant, and olanzapine for a cisplatin-containing regimen. - PATROL-I.

Dexamethasone is one of the key antiemetic agents and is widely used even now. However, dexamethasone has been associated with several adverse reactions even after short-term administration. Therefore, developing a steroid-free antiemetic regimen is an important issue to consider. Thus, the purpose of this study was to investigate the efficacy and safety of palonosetron, aprepitant, and olanzapine in a multi-institutional phase II study. Chemotherapy-naive patients scheduled to receive cisplatin were enrolled and evaluated for the occurrence of chemotherapy-induced nausea and vomiting during 120 h after chemotherapy. The primary endpoint of the study was total control (TC) in the overall phase. The key secondary endpoint was complete response (CR), which was assessed in the acute, delayed, and overall phase, respectively. Adverse events were evaluated according to the Common Terminology Criteria for Adverse Events. Eighty-five patients were enrolled from 8 centers in Japan, of which 83 were evaluable for analyses. The percentage of patients who achieved TC during the overall phase was 31.3%. CR was achieved in 61.4%, 84.3%, and 65.1% of patients during the overall, acute, and delayed phases, respectively. The most frequently reported adverse event was anorexia. The primary endpoint was below the threshold and we could not find benefit in the dexamethasone-free regimen, but CR during the overall phase was similar to that of the conventional three-drug regimen. This antiemetic regimen without dexamethasone might be an option for patients for whom corticosteroids should not be an active application.

Dexamethasone-sparing on days 2-4 with combined palonosetron, neurokinin-1 receptor antagonist, and olanzapine in cisplatin: a randomized phase III trial (SPARED Trial).

BACKGROUND: This study evaluated the non-inferiority of dexamethasone (DEX) on day 1, with sparing on days 2-4 in cisplatin-based chemotherapy. METHODS: Patients with malignant solid tumors who were treated with cisplatin (≥50 mg/m²) were randomly assigned (1:1) to receive either DEX on days 1-4 (Arm D4) or DEX on day 1 (Arm D1) plus palonosetron, NK-1 RA, and olanzapine (5 mg). The primary endpoint was complete response (CR) during the delayed (24-120 h) phase. The non-inferiority margin was set at -15%. RESULTS: A total of 281 patients were enrolled, 278 of whom were randomly assigned to Arm D4 (n = 139) or Arm D1 (n = 139). In 274 patients were included in the efficacy analysis, the rates of delayed CR in Arms D4 and D1 were 79.7% and 75.0%, respectively (risk difference -4.1%; 95% CI -14.1%-6.0%, P = 0.023). However, patients in Arm D1 had significantly lower total control rates during the delayed and overall phases, and more frequent nausea and appetite loss. There were no significant between-arm differences in the quality of life. CONCLUSION: DEX-sparing is an alternative option for patients receiving cisplatin; however, this revised administration schedule should be applied on an individual basis after a comprehensive evaluation. CLINICAL TRIALS REGISTRY NUMBER: UMIN000032269.

Independent, cooperative regulation of cellulolytic genes by paralogous transcription factors ClbR and ClbR2 in Aspergillus aculeatus.

The cellobiose-responsive regulator ClbR, a Zn(II)2Cys6 binuclear-cluster transcription factor, is a positive regulator of carbohydrate-active enzyme (CAZyme) genes responsive to cellulose in Aspergillus aculeatus. Because Zn(II)2Cys6 transcription factors tend to dimerize with proteins of the same family, we searched for a counterpart of ClbR and identified ClbR2, which is 42% identical to ClbR, as an interacting partner of ClbR by yeast two-hybrid screening. Genetic analyses suggested that ClbR and ClbR2 cooperatively regulate the expression of CAZyme genes in response to cellulose and 1,4-ß-mannobiose in A. aculeatus. CAZyme genes under the control of the transcription factor ManR were regulated by ClbR and ClbR2, whereas those controlled by the transcription factor XlnR were regulated by ClbR, but not ClbR2. These findings suggest that ClbR participates in multiple regulatory pathways in A. aculeatus by altering an interacting factor.

Registry study of immune-related adverse events using electronic patient-reported outcome in patients with cancer receiving immune checkpoint inhibitors: protocol for a multicentre cohort study.

INTRODUCTION: The use of immune checkpoint inhibitors (ICIs) is rapidly expanding in cancer treatment. ICIs have a unique safety profile, characterised by immune-related adverse events (irAEs). The safety profile of ICIs lacks patient experience and perspectives. This study primarily aims to obtain a database for descriptive research on the status of irAEs using the Patient-Reported Outcomes version of the Common Terminology Criteria (PRO-CTCAE) in patients with gastrointestinal cancer, lung cancer and malignant pleural mesothelioma treated with regimens containing ICIs. METHODS AND ANALYSIS: This is an ongoing, multicentre, observational study in Japan. Eligible patients must be at least 20 years old and have been diagnosed with lung cancer, malignant pleural mesothelioma or gastrointestinal cancer and plan to use ICIs. Participants will install the electronic PRO (ePRO) application and report adverse events via ePRO using PRO-CTCAE once weekly for up to 48 weeks. A registry will be established using background information obtained from medical records. The sample size is determined by 1 year projection without using statistical methods. Statistical analyses will include point estimates and 95% CIs for the incidence of each adverse event by cancer type and regimen at each time point. ETHICS AND DISSEMINATION: This research will be conducted per the Declaration of Helsinki, the Ethical Guidelines for Life Science and Medical Research Involving Human Subjects issued by the Ministry of Education, Culture, Sports, Science and Technology and the Ministry of Health, Labor and Welfare, and the revised Personal Information Protection Law. The study protocol was approved by the Ethics Committee (approval ID T2021-0180) of Tokyo Medical University Hospital on 15 October 2021. REGISTRATION DETAILS: The study began enrolling patients in December 2021. The target enrolment is 260; as of October 2022, 141 have been enrolled, and the enrolment is scheduled to end on 30 June 2023. TRIAL REGISTRATION NUMBER: UMIN000046418.

Optimal Dose of Intravenous Cyclophosphamide during remission induction therapy in ANCA-associated vasculitis: a retrospective cohort study of J-CANVAS.

OBJECTIVES: To identify the optimal dose of intravenous cyclophosphamide (IVCY) for induction therapy for anti-neutrophil cytoplasmic antibody-associated vasculitis (AAV). METHODS: We retrospectively assessed patients with AAV who received IVCY every 2-3 weeks during the remission induction phase. The associations of the IVCY dose with infection-free survival and relapse-free survival were analysed using a Cox regression model. We compared patients in three categories: very low-dose (VLD), low-dose (LD), and conventional dose (CD) (<7.5 mg/kg, 7.5-12.5 mg/kg, and >12.5 mg/kg, respectively). The non-linear association between IVCY dose and the outcomes were also evaluated. RESULTS: Of the 80 patients (median age 72 years), 12, 42, and 26 underwent the VLD, LD, and CD regimens, respectively, of whom 4, 3, and 7 developed infection or died. The adjusted hazard ratios for infection or death were 4.3 (95% confidence interval (CI) 0.94-19.8) for VLD and 5.1 (95% CI 1.21-21.3) for CD, compared with LD. We found the hazard ratio for infection or death increased when the initial IVCY dose exceeded 9 mg/kg. Relapse-free survival did not differ clearly. CONCLUSION: Low-dose IVCY (7.5-12.5 mg/kg) may result in fewer infections and similar relapse rates compared with the conventional regimen (>12.5 mg/kg).

Protocol for the ASTRO study (SSOP-01): a multicentre prospective cohort study investigating adverse events based on electronic patient-reported outcomes in patients with breast cancer after adjuvant chemotherapy.

INTRODUCTION: Symptom-related adverse events associated with perioperative chemotherapy in patients with breast cancer include short-term adverse events such as nausea and vomiting. However, changes in the severity and duration of prolonged symptom-related adverse events have not been fully investigated. We present a protocol of a study that aims to clarify the prevalence of symptom-related adverse events in patients with breast cancer 1 year after neoadjuvant or adjuvant chemotherapy using an electronic patient-reported outcomes (ePRO) system. METHODS AND ANALYSIS: This multicentre prospective observational cohort study will include patients with breast cancer who have received preoperative or postoperative adjuvant chemotherapy. The final injection date of the cytotoxic agent will be the study initiation date. Patients will report every 2 weeks from the initiation date to 12 weeks and every 4 weeks from 12 weeks to 1 year, and they can enter this information into the ePRO system from anywhere. The primary outcome will be the prevalence of symptom-related adverse events according to the ePRO system 1 year after the date of the last injection of the cytotoxic drug used in neoadjuvant or adjuvant chemotherapy for breast cancer. To increase multi-institutional enrolment, two cohorts will be included. Cohort 1 will comprise patients with acquisition of baseline patient information regarding preoperative chemotherapy and presurgery characteristics. Cohort 2 will comprise patients without acquisition of baseline patient information. The target sample size is ≥250 per year. ETHICS AND DISSEMINATION: The study protocol has been approved by the ethics committee at each participating institution. The results will be presented at major national and international conferences and submitted to peer-reviewed journals. TRIAL STATUS: Registration was started in October 2021. By August 2022, a total of 132 participants were enrolled. Follow-up will be continued through December 2024. TRIAL REGISTRATION NUMBER: UMIN000045422.

Seasonal Influence on Development of Antineutrophil Cytoplasmic Antibody-Associated Vasculitis: A Retrospective Cohort Study Conducted at Multiple Institutions in Japan (J-CANVAS).

OBJECTIVE: To clarify seasonal and other environmental effects on the onset of antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV). METHODS: We enrolled patients with new-onset eosinophilic granulomatosis with polyangiitis (EGPA), microscopic polyangiitis (MPA), and granulomatosis with polyangiitis (GPA) registered in the database of a Japanese multicenter cohort study. We investigated the relationship between environmental factors and clinical characteristics. Seasons were divided into 4 (spring, summer, autumn, and winter), and the seasonal differences in AAV onset were analyzed using Pearson chi-square test, with an expected probability of 25% for each season. RESULTS: A total of 454 patients were enrolled, with a mean age of 70.9 years and a female proportion of 55.5%. Overall, 74, 291, and 89 patients were classified as having EGPA, MPA, and GPA, respectively. Positivity for myeloperoxidase (MPO)-ANCA and proteinase 3 (PR3)-ANCA was observed in 355 and 46 patients, respectively. Overall, the seasonality of AAV onset significantly deviated from the expected 25% for each season (P = 0.001), and its onset was less frequently observed in autumn. In ANCA serotypes, seasonality was significant in patients with MPO-ANCA (P < 0.001), but not in those with PR3-ANCA (P = 0.97). Additionally, rural residency of patients with AAV was associated with PR3-ANCA positivity and biopsy-proven pulmonary vasculitis. CONCLUSION: The onset of AAV was influenced by seasonal variations and was less frequently observed in autumn. In contrast, the occurrence of PR3-ANCA was triggered, not by season, but by rural residency.

Adherence to anti-retroviral therapy, decisional conflicts, and health-related quality of life among treatment-naïve individuals living with HIV: a DEARS-J observational study.

BACKGROUND: Supporting people living with HIV using anti-retroviral therapy (ART) is important due to the requirement for strict medication adherence. To date, no data from longitudinal studies evaluating adherence by treatment-naïve people living with HIV are currently available. We investigated the adherence of treatment-naïve people living with HIV over time and examined the relationships among decisional conflicts, adherence, and health-related quality of life (HRQL). METHODS: The survey items included adherence (visual analogue scale [VAS]), decisional conflict (decisional conflict scale [DCS]), and HRQL (Medical Outcomes Study HIV Health Survey [MOS-HIV]). The DCS and MOS-HIV scores and the VAS and MOS scores were collected electronically at the ART initiation time point and at 4-, 24-, and 48-week post-treatment time points. RESULTS: A total of 215 participants were enrolled. The mean DCS score was 27.3 (SD, 0.9); 23.3% of participants were in the high-score and 36.7% in the low-score groups. The mean adherence rates at 4, 24, and 48 weeks were 99.2% (standard error [SE], 0.2), 98.4% (SE, 0.4), and 96.0% (SE, 1.2), respectively. The least-square means of the MOS-HIV for the DCS (high vs. low scores) were 64.4 vs. 69.2 for general health perceptions and 57.7 vs. 64.0 for HRQL, respectively. CONCLUSION: Adherence among treatment-naïve people living with HIV was maintained at a higher level, and HRQL tended to improve with ART. People with high levels of decisional conflict tended to have lower HRQL scores. Support for people living with HIV during ART initiation may be related to HRQL.

Association between hypogammaglobulinaemia and severe infections during induction therapy in ANCA-associated vasculitis: from J-CANVAS study.

OBJECTIVES: To investigate the association between decreased serum IgG levels caused by remission-induction immunosuppressive therapy of antineutrophil cytoplasmic antibody-associated vasculitis (AAV) and the development of severe infections. METHODS: We conducted a retrospective cohort study of patients with new-onset or severe relapsing AAV enrolled in the J-CANVAS registry, which was established at 24 referral sites in Japan. The minimum serum IgG levels up to 24 weeks and the incidence of severe infection up to 48 weeks after treatment initiation were evaluated. After multiple imputations for all explanatory variables, we performed the multivariate analysis using a Fine-Gray model to assess the association between low IgG (the minimum IgG levels <500 mg/dl) and severe infections. In addition, the association was expressed as a restricted cubic spline (RCS) and analysed by treatment subgroups. RESULTS: Of 657 included patients (microscopic polyangiitis, 392; granulomatosis with polyangiitis, 139; eosinophilic granulomatosis with polyangiitis, 126), 111 (16.9%) developed severe infections. The minimum serum IgG levels were measured in 510 patients, of whom 77 (15.1%) had low IgG. After multiple imputations, the confounder-adjusted hazard ratio of low IgG for the incidence of severe infections was 1.75 (95% confidence interval: 1.03-3.00). The RCS revealed a U-shaped association between serum IgG levels and the incidence of severe infection with serum IgG 946 mg/dl as the lowest point. Subgroup analysis showed no obvious heterogeneity between treatment regimens. CONCLUSION: Regardless of treatment regimens, low IgG after remission-induction treatment was associated with the development of severe infections up to 48 weeks after treatment initiation.

Protocol for a confirmatory trial of the effectiveness and safety of palliative arterial embolization for painful bone metastases.

BACKGROUND: Transcatheter arterial embolization (TAE) has long been used for hemostasis of traumatic or postoperative hemorrhage and embolization of tumors. Previous retrospective studies of TAE for painful bone metastases showed 60%-80% pain reduction with a median time to response of 1-2 days. Compared with radiotherapy and bisphosphonates, time to response appeared earlier than that of radiotherapy or bone-modifying agents. However, few prospective studies have examined TAE for this indication. Here, we describe the protocol for a confirmatory study designed to clarify the efficacy and safety profile of TAE. METHODS: This study will be a multicenter, single-arm confirmatory study (phase 2-3 design). Patients with painful bone metastases from any primary tumor are eligible for enrollment. TAE will be the main intervention. Following puncture of the femoral artery under local anesthesia and insertion of an angiographic sheath, angiography will confirm that the injected region includes tumor vasculature. Catheter position will be adjusted so that the embolization range does not include non-target tissues. Spherical embolic material will then be slowly injected into the artery to embolize it. The primary endpoint (efficacy) is the proportion of subjects with pain relief at 72 h after TAE and the secondary endpoint (safety) is the incidence of all NCI Common Terminology Criteria for Adverse Events version 5.0 Grade 4 adverse events and Grade ≥ 3 necrosis of the central nervous system. DISCUSSION: If the primary and secondary endpoints are met, TAE can be a treatment choice for painful bone metastases. Trial registry number is UMIN-CTR ID: UMIN000040794. TRIAL REGISTRATION: The study is ongoing, and patients are currently being enrolled. Enrollment started in March 2021. A total of 36 patients have participated as of Aug 2022. PROTOCOL VERSION: Ver1.4, 13/07/2022.