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During the unprecedented COVID-19 outbreak, new-onset or relapsing glomerulonephritis, such as ANCA-associated glomerulonephritis and Immunoglobulin A (IgA) nephropathy, following COVID-19 has been reported. However, to date, the association of COVID-19 with preexistent IgA vasculitis (IgAV) remains unclear. Here, we present the case of a 20-something old Japanese woman with preexistent IgAV who newly developed glomerulonephritis following COVID-19. At the diagnosis of IgAV, she had cutaneous purpura, joint pains, and gastrointestinal symptoms, but no signs of kidney involvement. Three months ago, she was tested positive for COVID-19 and subsequently developed hematuria and proteinuria. She was then admitted to our hospital and renal biopsy showed glomerular mesangial expansion and hypercellularity and cellular and fibrocellular crescents, accompanied by diffuse IgA and C3 deposits. With the diagnosis of de novo IgAV nephritis, the patient was treated with intravenous methylprednisolone followed by oral prednisolone. She had favorable responses to this treatment and has achieved and maintained the remission of hematuria and proteinuria after initiation of glucocorticoid therapy. Our case highlights that immune response to SARS-CoV-2 infection could trigger the onset of glomerulonephritis in the IgAV patients who have no renal involvement., (© 2024. The Author(s), under exclusive licence to Japanese Society of Nephrology.)

Background: This study aimed to assess the feasibility and safety of a problem-solving exercise program based on the items in the short physical performance battery (SPPB) for older patients with chronic respiratory diseases (CRDs) to inform future randomized controlled trials., Methods: This was a multicenter, prospective, non-randomized feasibility study. Participants with CRD received an enhancement program based on the SPPB decline items (balance, walk, and/or chair stand) for 4 weeks. The feasibility, safety, and efficacy of the problem-solving exercise program in improving the SPPB score, physical function, and step count (measured using a pedometer) were assessed., Results: Overall, 36 patients were enrolled in this study, and adherence to the exercise program was high (100%). No exercise program-related adverse events were observed. The implementation of the exercise program ranged from 70 to 100%. The mean daily step count increased from 2152 ± 1498 steps during the first week to 2899 ± 1865 steps in the last week (p<0.01). Additionally, the SPPB total score increased from 8.9 ± 1.8 points to 10.7 ± 1.3 points at the end of the program (p<0.001)., Conclusions: The problem-solving exercise program based on SPPB is feasible and safe for older patients with CRDs. However, the effectiveness of this exercise program should be validated in large-scale, randomized-controlled trials in the future., Trial Registration: University Hospital Medical Information Network Center (UMIN-CTR) UMIN: approval number: UMIN000048761., Competing Interests: Declaration of competing interest The authors have no conflicts of interest., (Copyright © 2024. Published by Elsevier B.V.)

Background: Recovery of walking independence in critically ill patients is required for safe discharge home. However, the pre-admission predictors affecting this outcome in this patient group are unknown. This study aimed to identify these predictors., Methods: We included subjects who required mechanical ventilation for at least 48 h and could walk before admission. We investigated frailty, cognitive impairment, and malnutrition risk according to the pre-admission health status. Walking independence was defined as the ability to walk for at least 45 m on level ground. The primary outcome was the association between the time to event from an ICU discharge to walking independence, and pre-admission predictors were analyzed using a Fine-Gray proportional hazards regression., Results: The rate of walking independence was 38.0 (100 cases/person-month; sample N = 144). In the proportional hazards regression model, adjusted for covariates, frailty (hazard ratio [HR] 0.08 [95% CI 0.01-0.67]), pre-frailty (HR 0.37 [95% CI 0.14-0.99]), cognitive impairment (HR 0.21 [95% CI 0.05-0.90]), and malnutrition risk (HR 0.20 [95% CI 0.07-0.58]) were associated with walking independence., Conclusions: Pre-admission frailty or pre-frailty, cognitive impairment, and malnutrition risk can help predict walking independence in critically ill patients who require mechanical ventilation., Competing Interests: The authors have disclosed no conflicts of interest., (Copyright © 2024 by Daedalus Enterprises.)

The coronavirus disease (COVID-19) pandemic negatively affected the diagnosis and treatment of several cancer types. However, this pandemic's exact impact and extent on bone and soft tissue sarcomas need to be clarified. We aimed to investigate the effect of the COVID-19 pandemic and emergency declaration by the local government on consultation behavior and clinical stage at diagnosis of bone and soft tissue sarcoma. A total of 403 patients diagnosed with bone and soft tissue sarcoma who initially visited three sarcoma treatment hospitals between January 2018 and December 2021 were included. The monthly number of newly diagnosed soft tissue sarcoma patients was reduced by 25%, and the proportion of soft tissue patients with stage IV disease at diagnosis significantly increased by 9% during the COVID-19 pandemic compared to before the COVID-19 pandemic. Furthermore, the monthly number of new primary bone and soft tissue sarcoma patients significantly decreased by 43% during the state of emergency declaration. The COVID-19 pandemic had a negative impact on soft tissue sarcoma patients' consultation behavior and increased the proportion of advanced-stage patients at initial diagnosis. An emergency declaration by the local government also negatively affected primary bone and soft tissue sarcoma patients' consultation behavior., (© 2024. The Author(s).)

Purpose: Patient sedation and analgesia are vital for safety and comfort during extracorporeal membrane oxygenation (ECMO). However, adsorption by the circuit may alter drug pharmaco-kinetics and remains poorly characterized. This study is the first to examine the concentrations of DEX and MDZ in the presence of drug-drug interactions using an in vitro extracorporeal circuit system that incorporates a polymer-coated polyvinyl chloride tube, but not a membrane oxygenator., Methods and Results: Nine in vitro extracorporeal circuits were prepared using polymer-coated PVC tubing. Once the circuits were primed and running, either a single drug or two drugs were injected as boluses into the circuit with three circuits per drug. Drug samples were drawn following injection at 2, 5, 15, 30, 60, and 120 min and at 4, 12, and 24 h. They were then analyzed using high-performance liquid chromatography with mass spectrometry. When compared with an injection of DEX alone, the combination of DEX and MDZ is highly changed, with DEX and MDZ affecting the availability of free drugs in the circuit., Conclusions: The change of DEX and MDZ concentrations was confirmed by a combination of both drugs as compared with either single-infusion DEX or MDZ in an in vitro extracorporeal circuit. Drug-drug interactions developed between DEX and MDZ through albumin in an extracorporeal circuit; as a result, the unbounded drugs might change in the circuit., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Onychomycosis is a chronic and intractable disease whose prevalence increases during aging. In elderly patients, if onychomycosis is left untreated and progresses to a severe stage it may cause functional decline of the lower limbs due to foot pain. This could lead to a decline in activities of daily living and secondary impairment such as cognitive decline. Thus, the treatment of onychomycosis in elderly patients is important. We have previously shown that fosravuconazole is relatively safe and effective for onychomycosis in elderly patients. In the present study, we continued the follow-up study and investigated the efficacy of re-administration of fosravuconazole in patients with recurrent onychomycosis. One hundred and twenty-five patients aged ≥65 years who had been initially diagnosed with onychomycosis at our hospital's dermatology department, and who had responded well to fosravuconazole at 48 weeks after the initial treatment, were followed up until 144 weeks after the start of the initial treatment. Patients who experienced a recurrence within 24 weeks after the start of the follow-up were assigned to the short-term recurrence group, and those who experienced a recurrence after 24 weeks were assigned to the long-term recurrence group. All patients in both groups were re-treated with fosravuconazole to evaluate its efficacy. The short-term and long-term recurrence groups consisted of 17 (14.3%) and 10 (8.4%) patients, respectively. There were no significant differences in mean age and sex ratio between the two groups. There were no serious adverse effects in either group, and the toenail opacity ratio was significantly reduced after 12 weeks of re-treatment in both groups. The short-term and long-term recurrence groups were significantly more likely to have wedge-shaped onychomycosis and total dystrophic onychomycosis, respectively. The results suggest that re-administration of fosravuconazole is safe and as effective as the first administration for elderly patients with recurrent onychomycosis. This study was registered at UMIN-CTR (UMIN000053516)., (© 2024 Japanese Dermatological Association.)

TGF-β is an immunosuppressive cytokine and plays a key role in progression of cancer by inducing immunosuppression in tumor microenvironment. Therefore, inhibition of TGF-β signaling pathway may provide a potential therapeutic intervention in treating cancers. Herein, we report the discovery of a series of novel thiazole derivatives as potent inhibitors of ALK5, a serine-threonine kinase which is responsible for TGF-β signal transduction. Compound 29b was identified as a potent inhibitor of ALK5 with an IC 50 value of 3.7 nM with an excellent kinase selectivity., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Masaaki Sawa is a Chief Scientific Officer of Carna Biosciences, Inc. and owns stocks of Carna Biosciences, Inc. Kazuhito Naka receives research funding from Carna Biosciences, Inc. All the other authors were full time employees of Carna Biosciences, Inc. and have no competing/conflict of interest., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Introduction: In total knee arthroplasty (TKA), the implant positions and knee kinematics, as well as the manifestation of medial pivot motion, play pivotal roles in determining postoperative clinical outcomes. The purpose of the current study was to analyze the correlation between knee kinematics, which was measured during TKA and implant positions derived using computed tomography (CT) examination after TKA., Methods: This study comprised 64 patients (76 knees) who underwent primary TKA between 2015 and 2022. A navigation system was used in TKA procedures, and intraoperative knee kinematics were automatically calculated with it. Utilizing three-dimensional evaluation software, positioning of implants was quantified with CT images taken pre- and post-operatively. Multiple regression analyses were employed to explore the impact of femoral component position (FP) and tibial component position (TP) on knee kinematics, focusing on the extent of tibial rotational motion (TRM) during passive knee motion., Results: FP affected TRM between knee extension and 90° flexion ( p  = 0.003, 95 % confidence interval [CI]: 0.315-1.384) and between knee extension and full flexion ( p  = 0.0002, 95 % CI: 0.654-1.844) after TKA. FP in internal rotation positively affected internal TRM after TKA. TP was not associated with TRM., Conclusions: Findings of the current study suggest that FP in internal rotation positively impacts knee kinematics after TKA., Competing Interests: All authors declare that they have no conflict of interest., (© 2024 Professor P K Surendran Memorial Education Foundation. Published by Elsevier B.V. All rights are reserved, including those for text and data mining, AI training, and similar technologies.)

Although Oxford unicompartmental knee arthroplasty is often used to successfully treat patients with knee osteoarthritis isolated at the medial compartment, we present a case of fracture just below the tibial keel caused by either a shift in medial loading position or an increased amount of tibial osteotomy. Finite element analysis was used to determine which factor was more important. First, a 3D-surface model of the patient's tibia and the implant shape were created using computed tomography-Digital Imaging and Communications in Medicine (CT-DICOM) data taken preoperatively. The finite element analysis found that following unicompartmental knee arthroplasty, the cortical stress (normal, 5.8 MPa) on the medial tibial metaphyseal cortex increased as the load point moved medially (3 and 12 mm medially: 7.0 and 10.7 MPa, respectively) but was mild with increased tibial bone resection (2 and 6 mm lower: 6.1 and 6.5 MPa, respectively). Implanting the femoral component more medially than the preoperative plan increases stresses in the medial cortex of the tibia and may cause fractures., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Imada et al.)

Objectives: Locomotive syndrome stage 3 (LS3), which has been established recently, may imply a greater need for care than LS stage 0 (LS0), LS stage 1 (LS1), and LS stage 2 (LS2). The relationship between LS3 and long-term care in Japan is unclear. Therefore, this study aimed to examine this relationship., Methods: A total of 531 patients (314 women and 217 men; mean age, 75 years) who were not classified as requiring long-term care and underwent musculoskeletal examinations in 2012 were grouped according to their LS stage. Group L comprised patients with LS3 and Group N comprised those with LS0, LS1, and LS2. We compared these groups according to their epidemiology results and long-term care requirements from 2013 to 2018., Results: Fifty-nine patients (11.1%) were diagnosed with LS3. Group L comprised more patients (50.8%) who required long-term care than Group N (17.8%) (P < 0.001). Group L also comprised more patients with vertebral fractures and knee osteoarthritis than Group N (33.9% vs 19.5% [P = 0.011] and 78% vs 56.4% [P < 0.001], respectively). A Cox proportional hazards model and Kaplan-Meier analysis revealed a significant difference in the need for nursing care between Groups L and N (log-rank test, P < 0.001; hazard ratio, 2.236; 95% confidence interval, 1.451-3.447)., Conclusions: Between 2012 and 2018, 50% of patients with LS3 required nursing care. Therefore, LS3 is a high-risk condition that necessitates interventions. Approaches to vertebral fractures and osteoarthritis of the knee could be key., (© 2024 The Korean Society of Osteoporosis. Publishing services by Elsevier B.V.)

Eelgrass meadows have attracted much attention not only for their ability to maintain marine ecosystems as feeding grounds for marine organisms but also for their potential to store atmospheric and dissolved CO 2 as blue carbon. This study comprehensively evaluated the bacterial and chemical data obtained from eelgrass sediments of different scales along the Japanese coast to investigate the effect on the acclimatization of eelgrass. Regardless of the eelgrass habitat, approximately 1% Anaerolineales , Babeliales , Cytophagales , and Phycisphaerales was present in the bottom sediment. Sulfate-reducing bacteria (SRB) were present at 3.69% in eelgrass sediment compared to 1.70% in bare sediment. Sulfur-oxidizing bacteria (SOB) were present at 2.81% and 1.10% in the eelgrass and bare sediment, respectively. Bacterial composition analysis and linear discriminant analysis revealed that SOB detoxified H 2 S in the eelgrass meadows and that the larger-scale eelgrass meadows had a higher diversity of SOB. Our result indicated that there were regional differences in the system that detoxifies H 2 S in eelgrass meadows, either microbial oxidation mediated by SOB or O 2 permeation via the physical diffusion of benthos. However, since bacterial flora and phylogenetic analyses cannot show bias and/or causality due to PCR, future kinetic studies on microbial metabolism are expected.

Introduction: We evaluated whether the clinical outcomes, including postoperative knee range of motion (ROM), after unicompartmental knee arthroplasty (UKA) were associated with the sagittal spinopelvic parameters and coronal alignment of the full lower extremity., Methods: Forty-two patients (50 knees: six men, seven knees; 36 women, 43 knees) who underwent medial UKA between April 2015 and December 2022 were included. Preoperative radiographic examinations of the index for sagittal spinopelvic alignment included the sagittal vertical axis (SVA), lumbar lordosis, sacral slope (SS), pelvic tilt (PT), and pelvic incidence. The anteroposterior hip-knee-ankle angle (HKAA) was calculated. The relationship of clinical outcomes and the risk of knee flexion angle ≤125° and knee flexion contracture ≥10° 1-year post-UKA with radiographic parameters were evaluated., Results: Preoperative HKA angle affected postoperative knee flexion angle ≤125° ( p  = 0.017, 95% confidence interval [CI]: 0.473-0.930) in logistic regression analysis. Patients with a knee flexion angle ≤125° had a higher preoperative HKAA (9.8 ± 3.0°), higher SVA (83.8 ± 37.0 mm), and lower SS (23.7 ± 9.0°) than those with a flexion angle >125° (preoperative HKAA: 6.6 ± 4.0°, SVA: 40.3 ± 46.5 mm, SS: 32.0 ± 6.3°) ( p  = 0.029, 0.012, and 0.004, respectively). PT related to postoperative knee flexion contracture ≥10° ( p  = 0.010, 95% CI: 0.770-0.965) in the logistic regression analysis. Patients with flexion contracture ≥10° had higher PT (35.0 ± 6.6°) and SVA (82.2 ± 40.5 mm) than those with flexion contracture <10° (PT, 19.3 ± 9.0°; SVA, 42.4 ± 46.5 mm) ( p  = 0.001 and 0.028, respectively). The postoperative clinical outcome was correlated with the postoperative knee flexion angle and SVA ( p  = 0.036 and 0.020, respectively)., Conclusions: The preoperative HKAA affected postoperative knee flexion angle, and the knee flexion contracture and clinical outcomes post-UKA were associated with PT and SVA, respectively. To predict outcomes for knee ROM and clinical scores after UKA, radiographic examination, including the sagittal spinopelvic parameters and the coronal view of the full lower extremity, is essential., Competing Interests: All authors declare that they have no conflict of interest., (© 2024 Professor P K Surendran Memorial Education Foundation. Published by Elsevier B.V. All rights reserved.)

This retrospective observational study aimed to assess the clinical characteristics of platypnea-orthodeoxia syndrome in patients with coronavirus disease 2019 (COVID-19) treated using mechanical ventilation or high-flow nasal canula. We analyzed 42 consecutive patients with COVID-19 from January 2020 to March 2022. The primary outcomes were the incidence of platypnea-orthodeoxia syndrome, the time with required long-term oxygen therapy, and short-term prognosis. Additionally, we examined the relationships between platypnea-orthodeoxia syndrome and COVID-19 severity, the time with long-term oxygen therapy, and short-term prognosis. Of the 42 included patients, 15 (35.7 %) had platypnea-orthodeoxia syndrome. Although mortality was not significantly different between both groups, the oxygen withdrawal rate in the platypnea-orthodeoxia syndrome group was significantly lower than that in the group without this syndrome. Clinical staff should be aware of the possibility of platypnea-orthodeoxia syndrome during positional changes in patients with COVID-19. Recognizing POS can improve early detection, countermeasures, and safety during physiotherapy., Competing Interests: Declaration of competing interest Tetsuya Hara reports lecture fees from Ono Pharmaceutical Co., Ltd., and grants from Ono Pharmaceutical Co., Ltd., Edwards Lifesciences Co., Ltd., and Asahi Kasei Pharma Co., Ltd., outside of the submitted work. Masatoshi Hanada, Yuji Ishimatsu, Noriho Sakamoto, Nobuyuki Ashizawa, Hirotomo Yamanashi, Motohiro Sekino, Koichi Izumikawa, Hiroshi Mukae, Koya Ariyoshi, Takahiro Maeda, Shuntaro Sato, and Ryo Kozu have no conflict of interest., (Copyright © 2024 The Japanese Respiratory Society. Published by Elsevier B.V. All rights reserved.)

Purpose: Functional magnetic resonance imaging (fMRI) visualizes hemodynamic responses associated with brain and spinal cord activation. Various types of pain have been objectively assessed using fMRI as considerable brain activations. This study aimed to develop a pain model in cynomolgus macaques undergoing knee surgery and confirm brain activation due to resting pain after knee surgery., Methods: An osteochondral graft surgery on the femoral condyle in the unilateral knee was performed on four cynomolgus macaques ( Macaca fascicularis ). Resting pain was evaluated as changes in brain fMRI findings with a 3.0-T MRI scanner preoperatively, postoperatively, and after postoperative administration of morphine. In the fMRI analysis, Z-values >1.96 were considered statistically significant., Results: Brain activation without stimulation after surgery in the cingulate cortex (3.09) and insular cortex (3.06) on the opposite side of the surgery was significantly greater than that before surgery (1.05 and 1.03, respectively) according to fMRI. After the administration of morphine, activation due to resting pain decreased in the cingulate cortex (1.38) and insular cortex (1.21)., Conclusion: Osteochondral graft surgery on the femoral condyle can lead to postoperative resting pain. fMRI can reveal activation in pain-related brain areas and evaluate resting pain due to knee surgery., Competing Interests: The authors declare no conflict of interest., (© 2024 Professor P K Surendran Memorial Education Foundation. Published by Elsevier B.V. All rights reserved.)

Abstract: Klippel-Trenaunay syndrome (KTS) is characterized by port-wine stains, mixed vascular malformations, and soft tissue and bone hypertrophy. Klippel-Trenaunay syndrome is occasionally complicated by chyluria, for which there is no effective treatment currently. We report a case of KTS complicated by intractable chyluria and hematuria due to a lymphatic-ureteral fistula. The patient was successfully treated with multiple lymphaticovenular anastomoses (LVAs).A 66-year-old woman with an enlarged left lower extremity since childhood was diagnosed with KTS. At 60 years of age, she developed chyluria (urine albumin, 2224 μg/mL) and hematuria. Lymphoscintigraphy showed a lymphatic-ureteral fistula near the ureterovesical junction. Conservative treatment was ineffective. She also developed left lower extremity lymphedema, which gradually worsened. Leg cellulitis and purulent pericarditis developed because of hypoalbuminemia (minimum serum albumin level, 1.3 g/dL).We performed 14 LVAs in 2 surgeries to reduce lymphatic fluid flow through the lymphatic-ureteral fistula. The chyluria and hematuria resolved soon after the second operation, and the urine albumin level decreased (3 μg/mL). After 28 months, she had no chyluria or hematuria recurrence and her serum albumin level improved (3.9 g/dL). Multiple LVAs can definitively treat chyluria caused by a lymphatic-ureteral fistula in patients with KTS., Competing Interests: Conflicts of interest and sources of funding: The authors received no grants for the research, authorship, and/or publication of this article., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Early pregnancy detection in alpacas, whose breeding season is limited to the rainy season and has a long gestation period, is important for reproductive management. Conventional detection methods such as ultrasonography cannot be used to detect pregnancy before 30 days after mating. In this study, we examined the feasibility of using fecal steroid hormones as an early detection method in pregnant and non-pregnant alpacas. Fecal and blood samples were collected from pregnant and non-pregnant alpacas after mating. Progesterone (P4) and estradiol 17-β were extracted and quantified from blood and fecal samples. A positive correlation exists between the steroid hormones in serum and feces, indicating that serum steroid hormone concentrations can be estimated from fecal steroid hormones. Within 10 days after mating, both pregnant and non-pregnant alpacas had fecal P4 concentrations greater than 1.0 ng/mg dry matter (DM), but by 15 days after mating, fecal P4 concentrations decreased to the pre-mating concentration in non-pregnant alpacas. From 15 days after mating, non-pregnant alpacas had a low fecal P4 concentration (< 1 ng/mg DM), whereas a high fecal P4 concentration indicated the possibility of pregnancy, suggesting that this test is clinically beneficial as a supportive test for pregnancy detection., (© 2024 Japanese Society of Animal Science.)