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Background: Few studies have investigated fracture risk and mortality in a Japanese chronic kidney disease (CKD) stages G3–5 population using a large-scale clinical database. Methods: This retrospective cohort study extracted data from 1 April 2008 to 30 April 2023. A single age–sex-matched control without CKD was matched with each non-dialysis CKD (estimated glomerular filtration rate < 60 mL/min/1.73 m2) patient. The incidences of all and hip fractures and all-cause mortality after the index date were calculated. Results: Among 76,598 (38,299 per group) individuals matched, the incidence of all fractures did not differ between the CKD and control groups (5.7% vs 5.8%; hazard ratio [HR] 1.022 [95% confidence interval CI 0.952–1.098], P = 0.542). The CKD group had higher risk of hip fracture than the control group (incidence of hip fracture, 1.7% vs 1.3%; HR 1.415 [95% CI 1.234–1.622], P < 0.001). Multivariable regression analysis showed an increased risk for hip fracture in the CKD vs control groups, and a greater difference in this risk was observed with younger age. Osteoporosis treatment and bone mineral density (BMD) measurements were 10.0% and 5.3% in the CKD group and 4.4% and 4.4% in the control group, respectively. Mortality was also higher in the CKD group (HR 1.413 [95% CI 1.330–1.501], P < 0.001). Conclusions: Japanese patients with CKD had higher risk of hip fracture than those without. Treatment and BMD measurement for fracture are insufficient in Japanese patients with CKD, and more adequate management of fracture risk is needed. [ABSTRACT FROM AUTHOR]

Objective This study aimed to establish a screening model for differentiating anti-synthetase syndrome (ASS) from other ANA-associated rheumatic diseases (AARDs) using a combination of cytoplasmic and non-cytoplasmic ANA (ncANA) patterns. Methods : This retrospective observational study included patients with AARDs such as SLE, SSc, SS, MCTD and PM/DM who underwent ANA screening between April 2012 and December 2021. Variables included age, sex, ANA patterns (Cytoplasmic and ncANA) and titres. Logistic regression analysis of Cytoplasmic and ncANA patterns was performed to differentiate ASS from other AARDs. Result : The 981 diagnosed cases of AARDs consisted of SS (n  = 451), SSc (n  = 264), SLE (n  = 201), PM/DM (n  = 104), MCTD (n  = 52) and ASS, including PM/DM (n  = 64). Of these, 155 patients had ≥2 overlapping diseases; however, there was no overlap between AARDs and ASS. ASS is more likely to occur when the cytoplasmic titre is positive and the ncANA <320. Receiver operating characteristic analysis of the Cytoplasmic and ncANA range revealed an area under the receiver operating characteristic curve of 0.885 (95% CI: 0.844–0.927). Conclusion : It is important to detect cytoplasmic patterns as an ANA screening test for ASS diagnosis, even if the titre is low. Additionally, combining the cytoplasmic and ncANA patterns yields more accurate ASS screening results. [ABSTRACT FROM AUTHOR]

Background: Coronavirus disease 2019 (COVID‐19)‐associated pulmonary aspergillosis (CAPA) is one of the noticeable complications of COVID‐19 and its incidence varies widely. In Japan, research on the incidence, risk factors and mortality associated with CAPA is limited. Objectives: This study aimed to explore the incidence and potential risk factors for CAPA in patients with severe or critical COVID‐19 and evaluate the relationship between CAPA and mortality of patients with severe or critical COVID‐19. Methods: We investigated the incidence of CAPA in patients with severe and critical COVID‐19 using administrative claims data from acute care hospitals in Japan. We employed multivariable regression models to explore potential risk factors for CAPA and their contribution to mortality in patients with severe and critical COVID‐19. Results: The incidence of CAPA was 0.4%–2.7% in 33,136 patients with severe to critical COVID‐19. Age, male sex, chronic lung disease, steroids, immunosuppressants, intensive care unit admission, blood transfusion and dialysis were potential risk factors for CAPA in patients with severe to critical COVID‐19. CAPA was an independent factor associated with mortality. Conclusions: CAPA is a serious complication in patients with severe and critical COVID‐19 and may increase mortality. [ABSTRACT FROM AUTHOR]

Blood vessels are comprised of endothelial and smooth muscle cells. Obtaining both types of cells from vessels of living donors is not possible without invasive surgery. To address this, we have devised a strategy whereby human endothelial and smooth muscle cells derived from blood progenitors from the same donor could be cultured with autologous leukocytes to generate a same donor "vessel in a dish" bioassay. Autologous sets of blood outgrowth endothelial cells (BOECs), smooth muscle cells (BO‐SMCs), and leukocytes were obtained from four donors. Cells were treated in monoculture and cumulative coculture conditions. The endothelial specific mediator endothelin‐1 along with interleukin (IL)‐6, IL‐8, tumor necrosis factor α, and interferon gamma‐induced protein 10 were measured under control culture conditions and after stimulation with cytokines. Cocultures remained viable throughout. The profile of individual mediators released from cells was consistent with what we know of endothelial and smooth muscle cells cultured from blood vessels. For the first time, we report a proof of concept study where autologous blood outgrowth "vascular" cells and leukocytes were studied alone and in coculture. This novel bioassay has usefulness in vascular biology research, patient phenotyping, drug testing, and tissue engineering. [ABSTRACT FROM AUTHOR]

• Conditioned taste aversion was utilized to characterize taste perception in chickens. • Chickens avoided L-Arg and could learn to avoid L-Val, L-His, and L-Lys. • Chickens were highly sensitive to L-Lys, a crucial limiting amino acid in feeds. • Chickens were sensitive to some sugars despite lacking a sweet taste receptor gene. • The present study provided basic evidence on oral nutrient sensing in chickens. Taste plays an essential role in regulating the feeding behaviors of animals. The present study aimed to characterize the taste sensory profiles of amino acids and sugars in chickens. To achieve this, we employed a conditioned taste aversion learning method, which is characterized by a specific pairing of gastrointestinal malaise and taste perception. Our findings revealed that chickens were able to learn to avoid L-Val, L-Lys, and L-His through conditioned taste aversion learning, and exhibited a strong aversion to L-Arg. These results suggest that chickens are primarily sensitive to basic amino acids, including L-Lys, which is a crucial limiting amino acid in feeds. Interstingly, this sensitivity to basic amino acids in chickens contrasts with humans, who are mainly sensitive to acidic amino acids as umami taste. Furthermore, despite the absence of a mammalian sweet taste receptor gene in the chicken genome, we demonstrated that chickens learned to avoid glucose, galactose, sucrose, and maltose by conditioned taste aversion learning. Taken together, the present study provides the idea that chickens possess a gustatory perception toward specific amino acids and sugars for the detection of beneficial nutrients in their feeds. [ABSTRACT FROM AUTHOR]

To develop a rat T-cell-dependent antibody response (TDAR) model evaluating both primary and secondary antibody responses, keyhole limpet hemocyanin (KLH) was used to immunize rats twice during a 14-day course of study, a pattern closely linked to that of a short-term general toxicity study. Female rats of four representative strains (e.g., Sprague-Dawley, Wistar, Fischer, and Lewis) were immunized twice with intravenous administrations of KLH (300 µg/rat) on Days 5 and 9 during a 14-day treatment regimen with cyclophosphamide (CPA) at 1, 3, or 6 mg/kg/day. The primary and secondary immunizations of KLH markedly elevated serum anti-KLH IgM and IgG levels in all strains on Days 9 and 15. Remarkable higher levels of anti-KLH IgG (≈ 1000 µg/ml) were noted in all strains, which were more than 4-times compared with those of anti-KLH IgM levels at Day 9, indicating that predominant IgG reactions were induced by the dual immunizations. A large inter-individual variability in KLH-specific IgM and IgG production was observed in all strains. However, levels of the KLH-specific antibodies were considered sufficient for the evaluation, even in Sprague-Dawley and Wistar rats reported as strains with a wide range of variability since immunosuppression of CPA on responses in both anti-KLH IgM and IgG were observed in all strains to the same extent. In addition, the sensitivity of the KLH-ELISA assay system detecting the immunosuppressive effects of CPA was comparable to other assay systems with PFC assay or ELISA using SRBC. The results here demonstrated that these experimental designs could provide valuable information about the influence on both the primary and secondary humoral immune responses in rats when exposed to potential immunomodulatory drugs. Furthermore, the design of the presented TDAR study would support comprehensive evaluation together with the outcome of the conventional general toxicity study. [ABSTRACT FROM AUTHOR]

Autoimmune blistering diseases (AIBDs), including pemphigoid and pemphigus, are intractable dermatological disorders clinically characterized by blistering and erosion affecting mucosal membranes and the skin. Due to their rarity and the limited coverage for less severe cases under Japanese medical subsidies, comprehensive epidemiological analyses encompassing less severe cases have not been conducted in Japan. In this study, we analyzed the epidemiology of AIBDs in Japan, utilizing data from a Japanese nationwide database. We identified 9796 cases of bullous pemphigoid (BP), 62 cases of epidermolysis bullosa acquisita (EBA), 871 cases of pemphigus vulgaris (PV), and 578 cases of pemphigus foliaceous (PF). BP patients exhibited an older age distribution compared to EBA, PV, and PF, with median ages of 81, 72, 65, and 70 years, respectively. Higher rates of comorbidities such as Alzheimer's disease, spondylopathies, and extrapyramidal and movement disorders were observed only in BP cases, while other neurodegenerative disorders such as polyneuropathies, unspecified dementia, and schizophrenia were frequent in both BP and EBA. Dipeptidyl peptidase-4 inhibitors were more commonly prescribed before the onset of BP and EBA compared to PV and PF. Treatment patterns indicated that PV patients were more frequently administered higher doses of oral corticosteroids compared to other AIBDs. Additionally, aggressive therapies, including steroid pulse, intravenous immunoglobulin, and plasmapheresis therapies, were more frequently applied in PV cases. In-hospital mortality rates were higher in BP and EBA at 8.0% and 11.3%, respectively, compared to PV and PF at 2.8% and 5.9%, respectively. Kaplan-Meier analysis indicated that BP and EBA reached a 5-year in-hospital mortality rate of approximately 0.21 and 0.34, while PV and PF rates were approximately 0.07 and 0.11, respectively. The Cox hazard model revealed that higher age is the risk factor for in-hospital mortality in all diseases. Kaplan-Meier analysis indicated a cumulative steroid cessation probability of 0.25 at 3 years for BP, and at 6 and 5 years for PV and PF, respectively. The Cox hazard model revealed that higher age and lower maximum corticosteroid dose contribute to the steroid cessation probability in BP, PV, and PF. This study provides insights into the epidemiology, treatment patterns, comorbidities, and outcomes of AIBDs in Japan., (© 2024 Japanese Dermatological Association.)

Background Patients with chronic kidney disease (CKD) were excluded in most trials that investigated the effects of urate-lowering agents, such as febuxostat and allopurinol, in hyperuricemic patients. This exclusion leads to uncertainty regarding the efficacy of febuxostat in patients with CKD. Due to the high prevalence of hyperuricemia in patients with CKD, we aimed to assess the effect of febuxostat on improving patient outcomes concerning cardiovascular events and survival compared with those treated with allopurinol among patients with CKD. Methods We conducted a retrospective cohort study using Japanese nationwide administrative data from Jan 1, 2013, to Sep 30, 2020. Patients aged over 60 years diagnosed with CKD were included in this study if they were prescribed either febuxostat or allopurinol. The primary outcome was the occurrence of cardiovascular events including myocardial infarction, stroke, unstable angina requiring urgent revascularization, and all-cause deaths. We estimated hazard ratios (HR) and 95% CI using a Cox proportional hazard regression model adjusted for comorbidities, medications, and laboratory data. We also assessed defined starting kidney replacement therapy as a secondary endpoint treating death as a competing risk using the Fine & Gray regression model. Results A total of 21,015 patients included those with febuxostat (n=17,796) and those with allopurinol (n=3,219). The association between the type of drug and the occurrence of cardiovascular events did not show a significant difference (0.107 vs. 0.116 events per patient-year; adjusted HR 0.953, 95% CI: 0.854 to 1.062, P=0.381). Similar results were seen for all-cause deaths (0.060 vs. 0.068 events per patient-year; adjusted HR 0.877, 95% CI: 0.760 to 1.012, P=0.073). Regarding the secondary endpoint, the association between the type of drug and the timing of starting kidney replacement therapy did not show a significant difference (0.118 vs. 0.097 events per patient-year; adjusted HR 0.953, 95% CI: 0.854 to 1.062, P=0.425). Conclusion The use of febuxostat was neither associated with a decreased risk of cardiovascular events or deaths nor with the timing of starting kidney replacement therapy compared to the use of allopurinol in patients with CKD., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. Animal subjects: All authors have confirmed that this study did not involve animal subjects or tissue. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: Ayumi Shintani is compensated by Kyowa Kirin, and the payment is made to the institution. Financial relationships: Ayumi Shintani declare(s) personal fees from Daiichi Sankyo. Payment was made to her. Ayumi Shintani declare(s) personal fees from Eisai. Payment was made to her. Ayumi Shintani declare(s) personal fees from Maruho. Payment was made to her. Ayumi Shintani declare(s) personal fees from Novo Nordisk Pharma. Payment was made to her. Ayumi Shintani declare(s) personal fees from Pfizer. Payment was made to her. Ayumi Shintani declare(s) personal fees from Taisho Pharmaceutical. Payment was made to her. Ayumi Shintani declare(s) personal fees from Torii Pharmaceutical. Payment was made to her. Ayumi Shintani declare(s) personal fees from Janssen Pharmaceutical. Payment was made to her. Ayumi Shintani declare(s) personal fees from Kisei Pharmaceutical. Payment was made to her. Ayumi Shintani declare(s) personal fees from Mallinckrodt Pharmaceuticals. Payment was made to her. Ayumi Shintani declare(s) personal fees from Mitsubishi Tanabe Pharma Corporation. Payment was made to her. Ayumi Shintani declare(s) personal fees from Nippon Shinyaku. Payment was made to her. Ayumi Shintani declare(s) personal fees from Ono Pharmaceutical Company Limited. Payment was made to her. Ayumi Shintani declare(s) personal fees from Takeda Pharmaceutical Company Limited. Payment was made to her. Ayumi Shintani declare(s) personal fees from Taisho Pharmaceutical. Payment was made to her. Ayumi Shintani declare(s) personal fees from Kyowa Kirin. Payment was made to her. Ayumi Shintani declare(s) personal fees from Merck Biopharma. Payment was made to her. Ayumi Shintani declare(s) personal fees from Nipro Corporation. Payment was made to her. Yuta Nonomiya declare(s) a grant from Osaka Metropolitan University. An annual fellowship of 3.9 million yen is paid to the author. Yasutaka Ihara declare(s) employment from Daiichi Sankyo. Yasutaka Ihara is an employee of Daiichi Sankyo. Kazuhiko Tsuruya declare(s) a grant from Teijin. Kazuhiko Tsuruya declare(s) a grant from Mochida. Kazuhiko Tsuruya declare(s) personal fees from Teijin. Kazuhiko Tsuruya declare(s) personal fees from Mochida. Kazuhiko Tsuruya declare(s) personal fees from Sanwa Chemical. Kazuhiko Tsuruya declare(s) personal fees from Fuji. Ayumi Shintani declare(s) personal fees from Chugai Pharmaceutical. Payment was made to the institution. Ayumi Shintani declare(s) personal fees from Daiichi Sankyo. Payment was made to the institution. Ayumi Shintani declare(s) personal fees from Kyowa Kirin. Payment was made to the institution and to her. Ayumi Shintani declare(s) personal fees from Takeda Pharmaceutical Company Limited. Payment was made to the institution. Ayumi Shintani declare(s) personal fees from Shionogi Pharma. Payment was made to her. Ayumi Shintani declare(s) personal fees from Abbvie. Payment was made to her. Ayumi Shintani declare(s) personal fees from Asahi Kasei Corporation. Payment was made to her. Ayumi Shintani declare(s) personal fees from AstraZeneca plc. Payment was made to her. Ayumi Shintani declare(s) personal fees from Astellas Pharma. Payment was made to her. Ayumi Shintani declare(s) personal fees from Bayer Yakuhin. Payment was made to her. Ayumi Shintani declare(s) personal fees from Bristol Myers Squibb. Payment was made to her. Ayumi Shintani declare(s) personal fees from Chugai Pharmaceutical. Payment was made to her. Ayumi Shintani declare(s) personal fees from Sanofi K.K. Payment was made to her. Ayumi Shintani declare(s) personal fees from Nippon Kayaku. Payment was made to her. Ayumi Shintani declare(s) personal fees from JCR Pharmaceuticals Co. Payment was made to her. Ayumi Shintani declare(s) personal fees from MSD. Payment was made to her. Hisako Yoshida declare(s) personal fees from Organization for Clinical Medicine Promotion. Other relationships: Febuxostat is sold by the following companies, which I declared in the COI: Teijin, DAIICHI SANKYO ESPHA CO., LTD., and NIPRO CORPORATION. Allopurinol is sold by the following companies, which I declared in the COI: NIPRO ES PHARMA and Shionogi Pharma Co. ., (Copyright © 2024, Otani et al.)

Objectives: Excisional hemorrhoidectomy (EH) is sometimes same-day surgery under local anesthesia (LA); however, the LA injection can be painful. We conducted an open-label, crossover, randomised controlled trial to evaluate the efficacy and safety of pre-cooling in reducing pain associated with LA injection., Methods: Patients aged ≥ 20 years undergoing bilateral EH were randomly assigned to 1 of 2 pre-cooling sequences: a cooling-first sequence and a cooling-second sequence. In the first intervention phase, 2 minutes of pre-cooling was applied before LA injection in patients randomized to the cooling-first sequence; patients in the cooling-second sequence were asked to wait for 2 minutes (without pre-cooling) before LA injection. The pre-cooling sequences and the perianal sides targeted for injection were reversed in the second intervention phase. The primary outcome was the visual analogue scale (VAS) rating for pain from LA injection, which was obtained twice for each patient. Adverse events due to pre-cooling (e.g., skin disorders) were documented., Results: Of 114 screened patients, 51 were randomized to the cooling-first (n = 26; analyzed: n = 26) or cooling-second sequence (n = 25; analyzed: n = 25). The 2-minute pre-cooling was completed by 48 patients (94%). VAS scores for LA injection pain decreased significantly with pre-cooling compared to without (difference estimate, -1.71; 95% confidence interval, -2.12 to -1.31; p< 0.001). No adverse events were reported., Conclusions: Two minutes of skin pre-cooling effectively and safely reduces LA injection pain in patients undergoing EH., Competing Interests: Conflicts of Interest There are no conflicts of interest., (Copyright © 2024 The Japan Society of Coloproctology.)