Search

Copyright of Canadian Journal of Anaesthesia / Journal Canadien d'Anesthésie is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Abstract Neuropathic pain is a debilitating pain condition that occurs after nerve damage. Such pain is considered to be a reflection of the aberrant excitability of dorsal horn neurons. Emerging lines of evidence indicate that spinal microglia play a crucial role in neuronal excitability and the pathogenesis of neuropathic pain, but the mechanisms underlying neuron-microglia communications in the dorsal horn remain to be fully elucidated. A recent study has demonstrated that platelet-derived growth factor (PDGF) expressed in dorsal horn neurons contributes to neuropathic pain after nerve injury, yet how PDGF produces pain hypersensitivity remains unknown. Here we report an involvement of spinal microglia in PDGF-induced tactile allodynia. A single intrathecal delivery of PDGF B-chain homodimer (PDGF-BB) to naive rats produced a robust and long-lasting decrease in paw withdrawal threshold in a dose-dependent manner. Following PDGF administration, the immunofluorescence for phosphorylated PDGF β-receptor (p-PDGFRβ), an activated form, was markedly increased in the spinal dorsal horn. Interestingly, almost all p-PDGFRβ-positive cells were double-labeled with an antibody for the microglia marker OX-42, but not with antibodies for other markers of neurons, astrocytes and oligodendrocytes. PDGF-stimulated microglia in vivo transformed into a modest activated state in terms of their cell number and morphology. Furthermore, PDGF-BB-induced tactile allodynia was prevented by a daily intrathecal administration of minocycline, which is known to inhibit microglia activation. Moreover, in rats with an injury to the fifth lumbar spinal nerve (an animal model of neuropathic pain), the immunofluorescence for p-PDGFRβ was markedly enhanced exclusively in microglia in the ipsilateral dorsal horn. Together, our findings suggest that spinal microglia critically contribute to PDGF-induced tactile allodynia, and it is also assumed that microglial PDGF signaling may have a role in the pathogenesis of neuropathic pain.

Abstract: We have reported in the past that female rats fed a powdered diet showed better spatial learning and memory functions than female rats a fed pelleted diet. In the present study, we examined the effects of feeding with powdered diet on acetylcholine release in the hippocampus in both sexes of rats. After weaning (3 weeks of age), rats were fed either standard pelleted diet or powdered diet, and after maturation (9–12 weeks of age), they were used in an in vivo microdialysis study, in which no eserine (a cholinesterase inhibitor) was added to the perfusate. The dialysate was collected from the dorsal hippocampus at 20-min intervals under freely moving conditions for more than 24 h. Acetylcholine in the dialysate was measured by high performance liquid chromatography. As we reported previously, the acetylcholine release showed a clear daily rhythm in both sexes, and males showed significantly greater acetylcholine release in the hippocampus than females in rats fed pelleted diet. Conversely, in rats fed powdered diet, no sex difference in the acetylcholine release was observed, since feeding with powdered diet significantly increased the acetylcholine release only in females. To further examine the number of cholinergic neurons in the medial septum and horizontal limb of the diagonal band of Broca, immunocytochemistry for choline acetyltransferase was performed in both sexes of rats fed either standard pelleted diet or powdered diet. However, neither sex nor feeding conditions affect the number of choline acetyltransferase immunoreactive cells in the areas. These results suggest that powdered diet after weaning enhances spontaneous acetylcholine release in the hippocampus in female rats without changes in the number of cholinergic neurons in the areas. It is possible that this effect of feeding contributes to improve the performance in spatial learning and memory functions in female rats fed powdered diet. [Copyright &y& Elsevier]

Background: Neoadjuvant pembrolizumab plus chemotherapy and adjuvant pembrolizumab have been established as the optimal systemic therapies for patients with early stage triple-negative breast cancer (TNBC); however, their efficacy and feasibility in the Japanese population remain unexplored., Methods: This study included patients with early stage TNBC or low estrogen receptor (ER) positivity (1-9%) with human epidermal growth factor receptor type 2- (HER2-) negative breast cancer who received neoadjuvant pembrolizumab plus chemotherapy from October 2022 at Cancer Institute Hospital of Japanese Foundation for Cancer Research. Information regarding clinicopathological features, systemic therapy, treatment outcomes, and adverse events of patients who underwent surgery by February 2024 was retrospectively collected., Results: Overall, 69 patients received neoadjuvant pembrolizumab plus carboplatin and paclitaxel therapy, and 46 underwent surgery by February 2024. The median age of the patients was 53.5 years, and 80.4% and 19.6% had stage II and III disease, respectively. TNBC and ER-low HER2-negative breast cancer accounted for 82.6% and 17.4% cases, respectively. Overall pathological complete response rate was 56.5%, with 87.5% in patients with ER-low HER2-negative tumors. The completion rates for neoadjuvant pembrolizumab, chemotherapy, and pembrolizumab plus chemotherapy were 65.2%, 56.5%, and 52.2%, respectively. Furthermore, 80.4% and 15.2% of patients experienced grade 3 or higher treatment-related adverse events and immune-related adverse events, respectively, and 34% experienced unexpected hospitalization during neoadjuvant treatment., Conclusions: The efficacy and safety profiles of neoadjuvant pembrolizumab plus chemotherapy in the Japanese population are consistent with previous reports. This regimen may have therapeutic potential against ER-low HER2-negative tumors and TNBC., Competing Interests: Declarations. Conflict of interest: Yosuke Aoyama has received honoraria for lectures from TAIHO, MSD, Pfizer, Eli Lilly, and Daiichi Sankyo. Yukinori Ozaki has received honoraria from Pfizer, Kyowa Kirin, Eli Lilly, and Daiichi Sankyo. Meiko Nishimura has received honoraria for lectures from Pfizer, Kyowa Kirin, Eli Lilly, Chugai, and Eizai. Fumikata Hara has received honoraria from Pfizer, Kyowa Kirin, Eli Lilly, Chugai, Daiichi Sankyo, and MSD. Toshimi Takano has received honoraria for lectures from Chugai, Daiichi-Sankyo, and Eli Lilly. Takayuki Ueno has received payments to his institution from Eli Lilly and payments from Chugai, Eisai, AstraZeneca, and Novartis. The other authors did not report any conflicts of interest. Ethical approval: All procedures involving human participants were performed in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. Informed consent was obtained from all individual participants included in the study., (© 2024. The Author(s), under exclusive licence to The Japanese Breast Cancer Society.)

Background: With advent of newer treatments for psoriasis, real-world use of biologics in Japan is evolving., Methods: This retrospective study utilized data from patients with ≥1 psoriasis-related biologic claims record between January 2016 and December 2020 in Japan to evaluate treatment patterns, healthcare resource utilization (HCRU), and associated costs. Data were analyzed using descriptive statistics., Results: Of 1,614 eligible patients, 72.5% were male, 29.2% had comorbid hypertension and 26.6% had comorbid cardiovascular disease. Interleukin (IL)-17 and tumor necrosis factor alpha (TNFα) inhibitors were commonly prescribed across lines of treatment, while IL-23 inhibitors were most considered for switches (92% of switches were from IL-12/23/IL-17/TNFα inhibitors). The overall mean adherence rate for all classes was 80.1%, but adherence varied across biologics. Infliximab and IL-23 inhibitor users exhibited optimal medical possession ratios, reflecting the best adherence rates. Overall HCRU (visits/patient-year) was 9.05 for outpatient visits, 0.09 for inpatient hospitalization, and 0.5 for psoriasis-related phototherapy. HCRU associated with hospitalization was slightly higher for bio-experienced patients and so was the overall costs per patient-year relative to bio-naïve patients., Conclusion: Variable adherence rates observed suggest the need for improvement in treatment management with different biologics. Bio-experienced patients burdened by disease progression and treatment switches may result in increased HCRU.

Utilizing the unique properties of fluorine substitution is an effective strategy for constructing highly functional materials. Here, we synthesized a novel copolymer composed of [1.1.1]propellane and perfluoro(propyl vinyl ether) (PPVE), rich in alternating sequences. The spin-coated copolymer film was amorphous, and its surface exhibited an extremely low surface free energy (γ). The γ value was lower than that of polytetrafluoroethylene despite containing only 40 mol % PPVE units. This can be attributed to the cancellation of the C-F dipole moments by the entirely random orientation of the fluorine units.

Introduction: Poor persistence to biologics can result in suboptimal health outcomes and increased economic burden for chronic conditions, including psoriasis (PsO). In Japan, studies evaluating factors responsible for biologic treatment persistence in patients with PsO are limited. We assessed biologic treatment persistence (median treatment duration and overall treatment survival) and associated factors in patients with PsO in a real-world setting., Methods: This retrospective analysis of insurance claims records from the Japan Medical Data Center (JMDC) database included patients with PsO [International Classification of Diseases (ICD) code: L40.x] ≥ 18 years of age who had received biologic treatment. Treatment persistence was analyzed using data from 2016 to 2020 by biologic class and by individual biologics (infliximab, adalimumab, ustekinumab, guselkumab, secukinumab, ixekizumab, and brodalumab) in bio-naïve (who initiate first biologic at index) and bio-experienced patients. Kaplan-Meier survival (treatment persistence), and multivariate Cox proportional hazard regression (predictive factors) analyses were used., Results: Overall, 1528 patients with PsO were included (mean age 47.4 years). Infliximab had the longest median treatment duration (33.6 months), while brodalumab had the shortest (9.7 months) among biologics evaluated. Of the biologics evaluated, 1-year treatment survival was highest with guselkumab (83%), and lowest with brodalumab (45%). Bio-experienced patients showed slightly longer median treatment duration than bio-naïve patients (22.8 versus 18.1 months). Factors predictive of treatment persistence were sex [male; hazard ratio (HR) 0.84, p = 0.016] and specific PsO diagnostic codes, such as L40.0 (PsO vulgaris; HR 0.69; p = 0.006), L40.1 (generalized pustular PsO; HR 0.75; p = 0.034), and L40.9 (PsO unspecified; HR 0.72; p = 0.001). Meanwhile, age and Charlson Comorbidity Index score were significantly associated with adalimumab and infliximab treatment persistence, respectively., Conclusion: Among biologics evaluated, infliximab had the longest median treatment duration, and guselkumab had the highest 1-year treatment survival. Sex and specific PsO diagnostic codes influenced overall treatment persistence. These findings could inform long-term treatment plans for PsO in real-world clinical settings., Competing Interests: Declarations Conflict of Interest Celine Miyazaki, Junya Masuda, and Phiona I-Ching Tsai are employees of Janssen Pharmaceutical K.K., Japan and may own stock in Johnson & Johnson. Hidehisa Saeki has received lecture fees from Mitsubishi Tanabe Pharma Corporation, Taiho Pharmaceutical Co., Ltd., Torii Pharmaceutical Co. Ltd., Maruho Co., Ltd., Kyowa Kirin Co., Ltd., AbbVie GK, Novartis Pharma K.K., Eli Lilly Japan K.K., LEO Pharma K.K., Celgene Corp., Janssen Pharmaceutical K.K., and UCB Japan Co. Ltd. and/or research costs from Maruho Co., Ltd, AbbVie GK, and LEO Pharma K.K; and/or scholarship donations from Taiho Pharmaceutical Co., Ltd., Maruho Co., Ltd., Eisai Co., Ltd., and Sun Pharma Japan Ltd. Ethical Approval All required approvals and permissions for data extraction from the JMDC database and performing pre-specified analyses were obtained. The study used de-identified patient data and was conducted in compliance with all laws and regulations, national guidelines, and other standards regarding the handling of personal information. Informed consent and ethics committee approval were not applicable based on the Ethical Guidelines for Epidemiological Research issued by the Japanese Ministry of Health, Welfare and Labor., (© 2024. The Author(s).)

Objectives: Our objective was to assess the efficacy of golimumab (GLM) in patients with poor prognostic factors (PPFs)., Methods: This is a post hoc analysis of GO-FORTH Phase 2/3 study. Cluster analysis was used to determine a patient population with high-risk patterns based on seven PPFs suggested by the European Alliance of Associations for Rheumatology recommendations and limited physical function. Radiographic progression, disease activity, and physical function and associated factors were evaluated over 52 weeks., Results: Overall, 261 rheumatoid arthritis patients were classified into three clusters characterised by high disease activity, high C-reactive protein levels, and limited physical function at baseline. GLM showed suppression of progressive modified total sharp score and decreases in Disease Activity Score 28-joint counts with erythrocyte sedimentation rate and Health Assessment Questionnaire - Disease Index, in all the clusters. In Cluster C that showed almost all the PPF characteristics, a higher rate of change in modified total sharp score ≤0 was observed in GLM 100 mg group than in GLM 50 mg group (63.9% versus 46.5%). C-reactive protein concentration and physical limitation were associated with radiographic progression of Cluster C in GLM treatment., Conclusions: GLM was effective in rheumatoid arthritis patients in a subpopulation at high risk of PPF in GO-FORTH study. A dose of 100 mg may be more beneficial in preventing radiographic progression in this population., (© Japan College of Rheumatology 2024. Published by Oxford University Press.)

Introduction : Soluble C-type lectin-like receptor -2 (sCLEC-2) has been recognized as a marker of platelet activation, and attention has been drawn to formulas combining sCLEC-2 levels with platelet count and D-dimer levels. Methods : In this study, sCLEC-2 levels, as well as sCLEC-2/platelet count (sCLEC-2/PLT), sCLEC-2 × D-dimer (sCLEC-2xDD), and sCLEc-2xDD/PLT formulas were used to detect thrombotic diseases, including microvascular thrombosis (MVT), arterial thromboembolism (ATE), and venous thromboembolism (VTE), with the aim of evaluating the ability of the three parameters combined in these formulas to diagnose thrombotic diseases. Results : The plasma sCLEC-2 levels were significantly higher in patients with infectious or thrombotic diseases than in those with neither thrombosis nor infection; however, there was no significant difference among patients with infection, ATE, VTE, and MVT; the correlations among sCLEC-2, platelet count, and D-dimer level were poor. The sCLEC-2/PLT ratio was the highest in patients with MVT, and the sCLEC-2 × D-dimer value was higher in patients with MVT and VTE than in those with neither thrombosis nor infection. Although receiver operating characteristic (ROC) analysis shows the differential diagnosis of thrombotic diseases from non-thrombosis without infection, the sCLEC-2 × D-dimer/platelet count was useful for differential diagnosis among MVT and infection or non-thrombotic diseases. Conclusions : sCLEC-2 is useful for the diagnosis of thrombosis, and the formulas of sCLEC-2 with platelet count or D-dimer are useful for the diagnosis of thrombosis using ROC analyses for the thrombosis group vs. the non-thrombosis group without infection.

Long-term monitoring and treatment of landfill leachate (LFL) and landfill gas (LFG) is required until landfilled municipal solid waste (MSW) is sufficiently stabilized and post-closure care can be terminated. Monitoring data of methane (CH 4 ) emissions in LFG from a marine landfill over 30 years were compared with the IPCC first order decay (FOD) model estimates. The observed changes in CH 4 showed a similar attenuation trend to the estimates, but the observed CH 4 emissions were only about 30% of the estimate over 30 years; LFL is considered to be another pathway for organic carbon to be released to the environment, but the total organic carbon in discharged LFL was only about 0.2% of CH 4 carbon in LFG emission over the same period. The increase in the CO 2 /CH 4 ratio in LFG over time suggests that the discrepancy between estimated and observed emissions is due to methane oxidation in the overlying soil, in addition to the high coefficient values used in the FOD model. Total organic carbon (TOC) in LFL discharged as effluent reached a maximum value in the early stages of the landfill and gradually decreased, but only to about one-third of the maximum value after more than 30 years and a decrease in the amount of effluent. As incineration of MSW is expected to reduce organic carbon and nitrogen, the CH 4 reduction effect of incineration of business and household waste and sewage sludge was investigated using FOD model estimates.

Background: Reports on treatment patterns of biologic disease-modifying antirheumatic drugs (bDMARDs)/Janus kinase inhibitors (JAKi) for rheumatoid arthritis (RA) in clinical practice are still sparse in Japan, especially in combination with conventional synthetic DMARDs (csDMARDs)., Objectives: The aim of this study was to investigate treatment patterns of bDMARD/JAKi in the treatment of RA in real-world clinical practice in Japan., Method: A retrospective cohort study was conducted using the Japanese Medical Data Vision health claims database. The inclusion criteria required a recorded diagnosis of RA, defined by ICD-10 codes, in patients aged 18 years and older on the index date. We analyzed 39,903 RA patients treated with DMARDs from 2008 to 2020., Results: Among analyzed subjects, 10,196 patients (25.6%) were prescribed bDMARDs/JAKi in combination with csDMARDs, and 3067 patients (7.7%) were prescribed these drugs without csDMARDs. Among the bDMARDs/JAKi, tumor necrosis factor inhibitors (TNFi) were the most commonly prescribed DMARD overall, and also the most common first-line therapy, accounting for 60.0% or 45.5% of patients prescribed these drugs in combination with or without csDMARDs, respectively. Switching, temporary discontinuation (restarting with the same agents), and discontinuation of bDMARDs/JAKi were observed in 3150 (30.9%), 1379 (13.5%), and 2025 (19.9%) patients with csDMARDs, and in 849 (27.7%), 513 (16.7%), and 833 (27.2%) patients without csDMARDs, respectively., Conclusions: Real-world treatment trajectories of bDMARDs/JAKi with and without csDMARDs was analyzed in RA patients in Japan between 2008 and 2020. TNFi were the predominant first-line therapy, and likely to be switched to different classes. Understanding the current treatment patterns, including discontinuation, is important to find an optimal treatment strategy for RA patients., (© 2024. The Author(s).)

A 52-week postmarketing surveillance study was initiated to evaluate the safety and effectiveness of guselkumab, a human anti-interleukin 23 subunit p19 monoclonal antibody, in Japanese patients with psoriasis vulgaris, psoriatic arthritis, generalized pustular psoriasis, and erythrodermic psoriasis in real-world practice. Here, we report results of the 20-week interim analysis of the ongoing postmarketing surveillance study. Patients who received guselkumab between May 2018 (the date of commercial launch in Japan) and October 2020 were registered in this study. In total, 411 and 245 patients were included in the safety and effectiveness analysis sets, respectively. Adverse drug reactions (ADRs) occurred in 6.6% (27 of 411) and serious ADRs in 2.2% (nine of 411) of patients. The most frequent ADRs by System Organ Class were "Infections and infestations" (2.4%), with nasopharyngitis being the most frequently observed ADR (0.7%). The mean Psoriasis Area Severity Index score decreased from 11.6 at baseline to 6.5 at week 4 and 2.2 at week 20, with improvements achieving statistical significance at each time point. Clinical Global Impression, Dermatology Life Quality Index, and Nail Psoriasis Severity Index outcomesalso showed substantial improvements. Our findings demonstrate that guselkumab is well tolerated and effective in Japanese patients with psoriasis through 20 weeks of treatment in real-world clinical practice, showing significant effectiveness observed as early as 4 weeks. The study was officially registered with the University Hospital Medical Information Network Clinical Trials Registry with the identifier UMIN000032969., (© 2024 Janssen Pharmaceutical K.K. The Journal of Dermatology published by John Wiley & Sons Australia, Ltd on behalf of Japanese Dermatological Association.)

Ciguatera poisoning (CP) is the most common type of marine biotoxin food poisoning worldwide, and it is caused by ciguatoxins (CTXs), thermostable polyether toxins produced by dinoflagellate Gambierdiscus and Fukuyoa spp. It is typically caused by the consumption of large fish high on the food chain that have accumulated CTXs in their flesh. CTXs in trace amounts are found in natural samples, and they mainly induce neurotoxic effects in consumers at concentrations as low as 0.2 µg/kg. The U.S. Food and Drug Administration has established CTX maximum permitted levels of 0.01 µg/kg for CTX1B and 0.1 µg/kg for C-CTX1 based on toxicological data. More than 20 variants of the CTX1B and CTX3C series have been identified, and the simultaneous detection of trace amounts of CTX analogs has recently been required. Previously published works using LC-MS/MS achieved the safety levels by monitoring the sodium adduct ions of CTXs ([M+Na] + > [M+Na] + ). In this study, we optimized a highly sensitive method for the detection of CTXs using the sodium or lithium adducts, [M+Na] + or [M+Li] + , by adding alkali metals such as Na + or Li + to the mobile phase. This work demonstrates that CTXs can be successfully detected at the low concentrations recommended by the FDA with good chromatographic separation using LC-MS/MS. It also reports on the method's new analytical conditions and accuracy using [M+Li] + .

We evaluated the suitability of supercritical fluid chromatography (SFC) for oligonucleotide analysis using 4-mer oligonucleotides with various phosphorothioate (PS) contents as model compounds. Column screening showed that the diol-modified column was able to separate sequences with different PS contents. Optimization of the column body and additives allowed us to analyze polar oligonucleotides using SFC. Various sequences were also analyzed using the optimized method. A good peak shape was obtained when the guanine plus cytosine content of the analyte was two or less in the 4-mer oligonucleotides. Furthermore, we found that the retention times of the selected sequences were positively correlated with polar surface areas, indicating that oligonucleotides interact with polar stationary phases. In contrast, more hydrophobic full PS sequences were retained more strongly in the diol column than the full phosphodiester (PO) sequences. This suggests that the diol column has unique selectivity for PO and PS linkages. These results indicate that SFC is potentially applicable to oligonucleotide analysis with a separation mechanism that is different from that of ion-pair reversed-phase liquid chromatography., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier B.V.)

Background: Hormone receptor (HR)-positive breast cancer is a disease for which no immune checkpoint inhibitors have shown promise as effective therapies. Cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitors synergistically increased the effectiveness of antiprogrammed cell death protein-1 (anti-PD-1)/programmed death-ligand 1 (PD-L1) antibodies in preclinical studies., Methods: This non-randomized, multicohort, phase II study evaluated the efficacy and safety of the anti-PD-1 antibody nivolumab 240 mg administered every 2 weeks in combination with the CDK4/6 inhibitor abemaciclib 150 mg twice daily and either fulvestrant (FUL) or letrozole (LET) as a first-line or second-line treatment for HR-positive HER2-negative metastatic breast cancer. The primary end point was the objective response rate (ORR), and secondary end points were toxicity, progression-free survival, and overall survival. Blood, tissue, and fecal samples were collected at multiple points for correlative studies to evaluate immunity biomarkers., Results: From June 2019 to early study termination due to safety concerns on July 2020, 17 patients were enrolled (FUL: n=12, LET: n=5). One patient with a prior treatment history in the FUL cohort was excluded. ORRs were 54.5% (6/11) and 40.0% (2/5) in the FUL and LET cohorts, respectively. Treatment-emergent (TE) adverse events (AEs) of grade ≥3 occurred in 11 (92%) and 5 (100%) patients in the FUL and LET cohorts, respectively. The most common grade ≥3 TEAEs were neutropenia (7 (58.3%) and 3 (60.0%) in the FUL and LET cohorts, respectively), followed by alanine aminotransferase elevation (5 (41.6%) and 4 (80.0%)). One treatment-related death from interstitial lung disease occurred in the LET cohort. Ten patients developed liver-related grade ≥3 AEs. Liver biopsy specimens from 3 patients showed hepatitis characterized by focal necrosis with predominant CD8+ lymphocyte infiltration. Marked elevation of tumor necrosis factor-related cytokines and interleukin-11, and a decrease in peripheral regulatory T cells (Tregs), were observed in patients with hepatotoxicity. These findings suggest that treatment-related toxicities were immune-related AEs likely caused by proinflammatory cytokine production and suppression of Treg proliferation due to the addition of abemaciclib to nivolumab therapy., Conclusions: Although the combination of nivolumab and abemaciclib was active, it caused severe and prolonged immune-related AEs., Trial Registration Number: JapicCTI-194782, jRCT2080224706, UMIN000036970., Competing Interests: Competing interests: HS reports grants from Eisai and lecture fees from Daiichi Sankyo and Eisai to her institution outside the submitted work. JT reports grants from Daiichi Sankyo, Eli Lilly, and FSJD to his institution outside the submitted work; consulting fees, support for attending a meeting, and fees for an advisory board from Daiichi Sankyo; lecture fee from Eli Lilly; and payments for an advisory board from AstraZeneca. YT reports grants from Ono Pharmaceuticals, Taiho, Eli Lilly, Daiichi Sankyo, and MSD. NM reports grants from Chugai, Eli Lilly, AstraZeneca, Daiichi Sankyo, MSD, Eisai, Novartis Pharma, Sanofi, Kyowa-Kirin, and Nippon-Kayaku to his institution outside the submitted work; and lecture fees from Chugai, Pfizer, AstraZeneca, and Eli Lilly. MT reports lecture fees from AstraZeneca, Daiichi Sankyo, Eisai, and Eli Lilly, and MSD. KM reports contracts from MSD, Chugai, Eisai, Daiichi Sankyo, Eli Lilly, and ICON Japan to his institution; lecture fees from Daiichi Sankyo, Chugai, Kyowa-Kirin, and MSD; and fees for an advisory board from Daiichi Sankyo. KA reports grants from Chugai, Eisai, and Takeda Pharmaceutical; lecture fees from AstraZeneca, Daiichi Sankyo, Taiho, Pfizer, Novartis Pharma, Eli Lilly, and Chugai. HI reports grants from Chugai, Eli Lilly, Nihon Kayaku, Daiichi Sankyo, AstraZeneca, Taiho, Pfizer, MSD, Sanofi, Novartis, Bayer, and Boehringer Ingelheim to his institution outside submitted work; consulting fees from Chugai, Kyowa Kirin, AstraZeneca, Eli Lilly, Pfizer, and Daiichi Sankyo; and lecture fees from Chugai, AstraZeneca, Eli Lilly, Pfizer, Taiho, Daiichi Sankyo, Eisai, and Kyowa Kirin. TM reports grants from Sysmex, Eisai, MSD, Pfizer, Novartis Pharma, Sanofi, Chugai, AstraZeneca, and Ono Pharmaceuticals outside submitted work; lecture fees from Eisai, Pfizer, Novartis Pharma, Chugai, Eli Lilly, AstraZeneca, Kyowa-Kirin, and Taiho. KIY reports lecture fees from Chugai and Bristol Myers Squibb outside the submitted work. CKI reports research funding from Otsuka Pharmaceutical and Eli Lilly outside the submitted work; lecture fees from Taiho. HK reports grants from Chugai, Taiho, and Mochida Pharmaceutical; lecture fees from AstraZeneca, Daiichi Sankyo, Taiho, Pfizer, and Novartis. KEY reports a grant from Boehringer Ingelheim; lecture fees from Chugai, Eli Lilly, AstraZeneca, Pfizer, and Boehringer Ingelheim. TT reports lecture fees from Chugai, Daiichi Sankyo, Eisai, Eli Lilly, and Celltrion Healthcare. All other authors declare no competing interests., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

This paper situates a ten-year period of political upheaval in addressing the problem of Single Room Occupancy (SRO) housing in Vancouver, Canada, within an epistemic transformation of public health. Until 1970, the Vancouver Health Department exemplified a colonial history of public health in establishing the city's skid road as a cordon sanitaire . But the 1970s saw a sudden fading of the Department's authority just as a more collaborative approach to housing policy was emerging. The sunsetting of sanitary enforcement was driven in part by the arrival of a "new public health" that became primarily concerned with defining public health problems and solutions through the regulation of racialized bodies and behaviors-a cordon thérapeutique . By the 1980s, this shift constituted an epistemic and regulatory abandonment of SRO housing, leading to the accelerated deterioration of the entire housing stock and costing incalculable human suffering and the loss of lives., Competing Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2021.)

Introduction: The persistence of golimumab (GLM) treatment in Japanese patients with rheumatoid arthritis (RA) has been evaluated previously, but evidence of long-term real-world use is lacking. This study assessed the long-term persistence of GLM use, its influencing factors, and impact of prior medications in patients with RA in actual clinical practice in Japan., Methods: This is a retrospective cohort study of patients with RA using data from a hospital insurance claims database in Japan. The identified patients were stratified as only GLM treatment (naïve), had one biological disease-modifying anti-rheumatic drug (bDMARD)/Janus kinase (JAK) inhibitor treatment prior to GLM [switch (1)] and had at least two bDMARDs/JAK prior to GLM treatment [switch (≥ 2)]. Patient characteristics were evaluated using descriptive statistics. Kaplan-Meier survival and Cox regression methods were used to analyze GLM persistence at 1, 3, 5, and 7 years and the associated factors. Treatment differences were compared using a log-rank test., Results: GLM persistence rate in the naïve group was 58.8%, 32.1%, 21.4%, and 11.4% at 1, 3, 5, and 7 years, respectively. Overall persistence rates in the naïve group were higher than in switch groups. Higher GLM persistence was observed among patients aged 61-75 years and those concomitantly using methotrexate (MTX). Also, women were less likely to discontinue treatment compared to men. Higher Charlson Comorbidity Index score, initial GLM dose of 100 mg, and switch from bDMARDs/JAK inhibitor were related to a lower persistence rate. As a prior medication, infliximab showed the longest persistence for subsequent GLM, and using this as a reference, tocilizumab, sarilumab, and tofacitinib subgroups had significantly shorter persistence, respectively (p = 0.001, 0.025, 0.041)., Conclusion: This study presents the long-term real-world results for persistence of GLM and its potential determinants. These most recent and long-term observations demonstrated that GLM and other bDMARDs continue to benefit patients with RA in Japan., (© 2023. The Author(s).)

Background: The simple risk index recorded in the emergency room (ER-SRI), which is calculated using the formula (heart rate × [age / 10] 2 ) / systolic blood pressure, was shown to be able to stratify the prognosis in ST-elevation myocardial infarction (STEMI) patients. However, the prognostic impact of the prehospital simple risk index (Pre-SRI) remains unknown., Methods and results: This study enrolled 2,047 STEMI patients from the Mie Acute Coronary Syndrome (ACS) registry. Pre-SRI was calculated using prehospital data and ER-SRI was calculated using emergency room data. The primary endpoint was 30-day all-cause mortality. The cut-off values of Pre-SRI and ER-SRI for predicting 30-day mortality were 34.8 and 34.1, with accuracies of 0.816 and 0.826 based on receiver operating characteristic analyses (P<0.001 for both). There was no difference in the accuracy of the 2 indices. Multivariate Cox regression analysis demonstrated that a High Pre-SRI (≥34) was a significant independent predictor of 30-day mortality. With combined Pre-SRI and ER-SRI assessment, patients with High Pre-SRI/High ER-SRI showed significantly higher mortality than those with High Pre-SRI/Low ER-SRI, Low Pre-SRI/High ER-SRI, and Low Pre-SRI/Low ER-SRI (P<0.001). The addition of High Pre-SRI to High ER-SRI showed incremental prognostic value of the Pre-SRI., Conclusions: Pre-SRI can identify high-risk STEMI patients at an early stage and combined assessment with Pre-SRI and ER-SRI could be of incremental prognostic value for risk stratification in STEMI patients.

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., (© 2023. The Author(s).)

Background: The efficacy and safety of golimumab in elderly patients with renal dysfunction are not well evaluated due to the exclusion criteria of clinical trials., Objective: To assess the persistence and safety of golimumab in elderly rheumatoid arthritis patients with renal dysfunction., Patients and Methods: In this retrospective observational study, we used Japan's nationwide electronic medical records and claims database to identify patients aged 65 years and older who were newly prescribed golimumab for rheumatoid arthritis between July 2011 and June 2018. Patients were divided into three groups according to estimated glomerular filtration rate (eGFR; high, ≥ 90; moderate, ≥ 60, < 90; low, ≥ 30, < 60), and the persistence of golimumab and adverse events were compared between the groups., Results: A total of 423 patients met the eligibility criteria. At 6 months, the persistence rates of golimumab were 62.4%, 63.7% and 67.0% in the high, moderate and low eGFR groups, respectively. In Cox proportional hazards regression analysis, baseline eGFR was not associated with golimumab persistence or adverse events, but concomitant methotrexate and low baseline C-reactive protein (CRP) were associated with longer golimumab persistence., Conclusion: Reduced renal function was not associated with continuation of golimumab or incidence of adverse events, suggesting that the persistence of golimumab therapy in patients with rheumatoid arthritis is independent of the baseline level of renal function. On the other hand, concomitant use of methotrexate and low baseline CRP levels were suggested as factors that may affect the persistence of golimumab treatment., (© 2022. The Author(s).)

Background: Higher body mass index (BMI) is associated with worse prognosis in pre- and postmenopausal patients with breast cancer (BC). However, there is insufficient evidence regarding the optimal adjuvant endocrine therapy for obese premenopausal women with hormone receptor (HR)-positive BC., Aim: To evaluate the impact of obesity and adjuvant endocrine therapy on prognosis in premenopausal patients with BC., Methods and Results: We retrospectively reviewed the medical record of premenopausal women who received curative surgery for clinical stage I-III HR-positive BC from 2007 to 2017. Patients were classified into five groups according to BMI: underweight (UW), normal weight (NW), obese 1 degree (OB1), obese 2 degree (OB2), and obese 3 degree (OB3) categories. The primary analysis was a comparison of BC-specific survival (BCSS) according to BMI (UW/NW vs. OB1-3) and adjuvant endocrine therapy (with or without ovarian function suppression [OFS]). Of 13 021 patients, the data of 3380 patients were analyzed. BCSS in OB1-3 patients was significantly worse than that in patients with UW/NW (hazard ratio [HR] 2.37; 95% confidence interval [CI], 1.40-4.02: p = .0009). In OB1-3 patients who received tamoxifen (TAM), BCSS was significantly worse than that in UW/NW patients (p = .0086); however, a significant difference was not shown in patients who received TAM and OFS (p = .0921)., Conclusion: High BMI was associated with worse prognosis in premenopausal patients with HR-positive BC who received adjuvant TAM. The role of OFS as adjuvant endocrine therapy remains unclear, and further studies are required to explore the adequate management of obese premenopausal patients., (© 2022 The Authors. Cancer Reports published by Wiley Periodicals LLC.)

Purpose: This study investigated the clinical impact of pretreatment neutrophil-to-lymphocyte ratio (NLR) on survival in patients with oligometastatic breast cancer., Patients and Methods: We collected data from 397 patients who underwent primary breast surgery from 2004 to 2015 and developed recurrence during the follow-up. We reviewed the images and clinical information and defined OMD according to the European Society for Medical Oncology advanced breast cancer guidelines. The NLR was calculated using pretreatment data of primary breast cancer. The cutoff value of the NLR was determined by receiver operating characteristic curve with Youden Index., Results: Among 397 patients, 131 had OMD at recurrence. The low-NLR group included patients of significantly older age at primary cancer than those in the high-NLR group. A low NLR indicated a better overall survival (p = 0.023) after adjusting for relevant factors, including estrogen receptor status, surgical resection of metastatic disease, metastatic organ number, disease-free interval, and liver metastasis than did the high-NLR group. We developed prognostic models for OMD using six independent prognostic factors, including the NLR. The number of factors was associated with overall survival; patients with all six favorable factors showed a good overall survival of 90.9% at 8 years and those with four or more factors showed 70.4%., Conclusions: The NLR was an independent prognostic factor for overall survival in OMD. The number of favorable prognostic factors was associated with overall survival. A prognostic model, including the NLR, will help identify patients with a favorable prognosis., (© 2022. The Author(s).)

Background: Aortic valve stenosis (AS) leads to increased cardiovascular mortality and morbidity, and recent studies reported that even mild-to-moderate AS was associated with poor prognosis in the general population. This study investigated the prognostic impact of mild or moderate AS, defined as 2.0 m/s ≤ peak aortic jet velocity (Vmax) ≤3.9 m/s using echocardiography in acute myocardial infarction (AMI) patients., Methods and results: This study enrolled 3,049 AMI patients using data from the Mie ACS registry. Patients were divided into 2 groups according to Vmax: Group 1: Vmax <2.0 m/s and/or visually intact aortic valve in which all 3 leaflets are fully and evenly open; Group 2: 2.0 m/s ≤ Vmax ≤ 3.9 m/s. There were 2,976 patients in Group 1and 73 patients in Group 2. The Group 2 patients were older, had a higher percentage of males and had lower body mass index and Killip ≥2 than the Group 1 patients. Angiographic data, door-to-balloon time, and mechanical support were not different between the 2 groups. The Group 2 patients demonstrated a significantly higher all-cause mortality rate (P<0.01) and composite of cardiovascular death and heart failure hospitalization (P<0.01), and Kaplan-Meier analysis showed the same tendency in propensity score-matched patients., Conclusions: The present study revealed that mild or moderate AS based on Vmax is associated with poor prognosis following AMI.

Secondary lymphoid tissues, such as the spleen and lymph nodes (LNs), contribute to breast cancer development and metastasis in both anti- and pro-tumoral directions. Although secondary lymphoid tissues have been extensively studied, very little is known about the immune conversion in mesenteric LNs (mLNs) during breast cancer development. Here, we demonstrate inflammatory immune conversion of mLNs in a metastatic 4T1 breast cancer model. Splenic T cells were significantly decreased and continuously suppressed IFN-γ production during tumor development, while myeloid-derived suppressor cells (MDSCs) were dramatically enriched. However, T cell numbers in the mLN did not decrease, and the MDSCs only moderately increased. T cells in the mLN exhibited conversion from a pro-inflammatory state with high IFN-γ expression to an anti-inflammatory state with high expression of IL-4 and IL-10 in early- to late-stages of breast cancer development. Interestingly, increased migration of CD103 + CD11b + dendritic cells (DCs) into the mLN, along with increased (1→3)-β-D-glucan levels in serum, was observed even in late-stage breast cancer. This suggests that CD103 + CD11b + DCs could prime cancer-reactive T cells. Together, the data indicate that the mLN is an important lymphoid tissue contributing to breast cancer development.

Background: Although serum uric acid (UA) is considered as a risk factor for cardiovascular disease, few data exist regarding the relationship between hyperuricemia, coronary blood flow, and subsequent outcome in patients with acute myocardial infarction (AMI). The purpose of our study is to assess whether hyperuricemia is associated with suboptimal coronary flow and increased risk of mortality in patients with AMI after percutaneous coronary intervention (PCI)., Methods: Using the Rural AMI registry data, 989 consecutive patients with AMI who underwent emergent PCI and had UA measurement at admission were analyzed. We defined hyperuricemia as serum UA ≥7.0 mg/dL in men and ≥ 6.0 mg/dL in women. The primary endpoint was suboptimal coronary flow, defined as post PCI Thrombosis In Myocardial Infarction flow grade ≤ 2. The secondary outcome was in-hospital mortality., Results: Hyperuricemia was found in 249 (25.2%) patients. Patients with hyperuricemia were more often complicated with cardiogenic shock compared with those without (16.9% vs. 7.4%, p < 0.001). In addition, the median high-sensitivity C-reactive protein was significantly higher in patients with hyperuricemia (0.18 mg/dL; IQR, 0.09-0.71 mg/dL) than in those without (0.14 mg/dL; IQR, 0.07-0.41 mg/dL, p < 0.05). Under these conditions, the prevalence of suboptimal coronary flow after PCI (17.3% vs. 10.1%, p < 0.05) and in-hospital mortality (10.8% vs. 3.6%, p < 0.001) were significantly higher in patients with hyperuricemia compared with those without. Multivariable logistic regression analysis revealed that hyperuricemia was significantly associated with suboptimal coronary flow [odds ratio (OR), 1.60; 95% confidence interval (CI), 1.02-2.49; p < 0.05] and in-hospital mortality (OR, 2.08; 95% CI, 1.05-4.12; p < 0.05)., Conclusions: Assessment of serum UA upon admission provides useful information for predicting suboptimal coronary flow and in-hospital mortality in patients with AMI undergoing PCI., Competing Interests: Declaration of competing interest The authors declare that there is no conflict of interest., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Background: Even though hospital admissions for acute myocardial infarction (AMI) decreased globally during the COVID-19 pandemic in early 2020, limited information is available on subsequent demographic trends in the number of cases and management of AMI through the first 12 months of the COVID-19 pandemic. Methods and Results: We assessed demographic trends, patient characteristics, and AMI outcomes (n=730) during the first 12 months of the COVID-19 pandemic and compared them with corresponding months during the control period (February 2016-January 2020; n=2,742) using data from the Mie ACS Registry. Although a 25.8% reduction in hospitalizations for AMI was observed in the 3 months following the declaration of a state of emergency (47.7 vs. 64.3/month; P=0.002), the total number of AMI patients was similar between the 12-month COVID-19 and control periods (60.8 vs. 57.2/month; P=0.58). The number of patients requiring direct ambulance transport was lower in the first half of the COVID-19 than control period (44.4% vs. 51.5; P=0.028). In-hospital mortality was higher in the second half of the COVID-19 than control period (8.9% vs. 5.8%; P=0.032). Conclusions: Through the first 12 months of the COVID-19 pandemic, the number of AMI cases was similar to that in previous years. The COVID-19 pandemic changed the behavior of AMI patients and both pre- and in-hospital medical management, which significantly affected the severity and prognosis of AMI., Competing Interests: K.D. received departmental research grant support from Otsuka Pharmaceutical Co., Ltd., DAIICHI SANKYO Co., Ltd., Novartis Pharma K.K., AstraZeneca K.K., Kowa Co., Ltd., Bayer Co., Ltd., and Nippon Boehringer Ingelheim Co., Ltd. in 2021; lecture fees from Otsuka Pharma Inc. and departmental research grant support from Otsuka Pharmaceutical Co., Ltd. in 2020; and lecture fees from Otsuka Pharmaceutical Co., Ltd. in 2019. The remaining authors have no conflicts of interest to disclose., (Copyright © 2022, THE JAPANESE CIRCULATION SOCIETY.)

Newly developed anti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) drugs are being rapidly approved in countries worldwide. These new drugs are being approved after testing with a limited number of cases, and in real-world clinical practice, unknown and potentially serious adverse events that could not be detected in clinical trials may emerge. Accordingly, in the event of an adverse drug reaction for which a causal relationship with these new drugs cannot be ruled out, it is vital to promptly report the details of the case to the regulatory authorities. To date, through close cooperation between physicians and pharmacists, we have reported four cases of adverse drug reactions for which a causal relationship to anti-SARS-CoV-2 drugs cannot be ruled out. Herein, we introduce safety measures taken by pharmacists when using these new drugs in the hospital, and a system for reporting to the regulatory authorities when adverse events occur., Competing Interests: The authors have no conflicts of interest to disclose., (2022, National Center for Global Health and Medicine.)

Background: The diagnostic criteria for disseminated intravascular coagulation (DIC) vary and are complicated and the cut-off values are different. Simple and quick diagnostic criteria for DIC are required in physicians for critical care., Material and Methods: Platelet counts, prothrombin time-international normalized ratio (PT-INR) and D-dimer levels were examined in 1293 critical ill patients. Adequate cut-off values of these parameters were determined and a quick DIC score using these biomarkers was proposed. The quick DIC score was evaluated using a receiver operating characteristic (ROC) analysis., Results: Using the Japanese Ministry of Health, Labor and Welfare diagnostic criteria, 70 and 109 patients were diagnosed with DIC and pre-DIC, respectively. The ROC analysis of factors difference between DIC and non-DIC, revealed the following cut-off values: PT-INR, 1.20; platelet count, 12.0 × 10 10 /L and D-dimer, 10.0 μg/mL. Based on the above results, the quick DIC score system was proposed. All patients with DIC had a quick DIC score of 3, 4 or 5, and 85.3% of the patients with pre-DIC had a quick DIC score of ≥3 points. All patients with pre-DIC had a score of ≥2 points. In the ROC analysis, the area under the curve was 0.997 for DIC vs. non-DIC, and 0.984 for pre-DIC + DIC vs. non-DIC, and the cut-off value was 3 points for DIC and 2 points for DIC + pre-DIC. The quick DIC scores of non-survivors were significantly higher than those of survivors., Conclusions: The Quick DIC score system is a simple and useful tool that can be used for the diagnosis of DIC and pre-DIC. Further evaluation of the quick DIC score system in a large-scale study is required.