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Toshiyuki Takemori,1 Teruya Kawamoto,1,2 Hitomi Hara,1 Naomasa Fukase,1 Shuichi Fujiwara,1 Kazumichi Kitayama,1 Shunsuke Yahiro,1 Tomohiro Miyamoto,1 Yutaka Mifune,1 Yuichi Hoshino,1 Kenichiro Kakutani,1 Tomoyuki Matsumoto,1 Takehiko Matsushita,1 Takahiro Niikura,1 Ryosuke Kuroda,1 Toshihiro Akisue1,3 1Department of Orthopaedic Surgery, Kobe University Graduate School of Medicine, Kobe, Japan; 2Division of Orthopaedic Surgery, Kobe University Hospital International Clinical Cancer Research Center, Kobe, Japan; 3Department of Rehabilitation Science, Kobe University Graduate School of Health Sciences, Kobe, JapanCorrespondence: Teruya Kawamoto, Department of Orthopaedic Surgery, Kobe University Graduate School of Medicine, 7-5-1, Kusunoki-cho, Chuo-ku, Kobe, 650-0017, Japan, Tel +81-783825985, Fax +81-783516944, Email trykwmt@med.kobe-u.ac.jpPurpose: Soft tissue sarcomas (STSs) constitute a group of rare, heterogeneous tumors representing approximately 1% of all cancers. Owing to the rarity and pathological diversity of the disease, unplanned excision (UE) has often been performed for STS, resulting in an unfavorable prognosis. This study aimed to clarify clinical outcomes and prognostic factors in STS patients who underwent UE.Patients and Methods: In a retrospective review of the medical records of patients with STS who underwent surgery at our institution between 1999 and 2015, patients were enrolled to either a UE group or a planned excision (PE) group. An analysis was then conducted to identify factors associated with prognosis after UE.Results: Of 134 patients undergoing surgery for STS, 110 were enrolled to the PE group and 24 to the UE group. The median size of the primary tumor was significantly smaller, and more lesions were located in the superficial layer in the UE group than in the PE group. In addition, plastic reconstruction after additional radical resection was required significantly more often in the UE group than in the PE group. No significant difference in overall survival, local recurrence-free survival, or disease-free survival (DFS) between the UE and PE groups was observed; however, metastasis-free survival was significantly better in the UE group. In the UE group, poorer DFS was associated with older age (≥ 61 years) and a larger primary tumor (≥ 2.9 cm).Conclusion: A prognosis similar to that in patients undergoing PE could be achieved by appropriate additional surgeries in patients initially undergoing UE. However, UE for STS should be avoided, especially in older patients and those with a larger primary tumor.Keywords: unplanned excision, soft tissue sarcoma, survival, prognostic factor

OBJECTIVE: To investigate the role of transforming growth factor beta (TGFbeta)/bone morphogenetic protein (BMP) superfamily members on accumulation of superficial zone protein (SZP) in articular chondrocytes and synoviocytes. METHODS: Chondrocytes and synoviocytes were isolated from articular cartilage and synovium from calf stifle joints and cultured as monolayers in serum-free chemically defined medium. Articular chondrocytes were isolated from 3 distinct zones of the cartilage: superficial, middle, and deep. Accumulation of SZP in the culture medium in response to various members of the TGFbeta/BMP superfamily was demonstrated by immunoblotting and quantified by enzyme-linked immunosorbent assay. RESULTS: TGFbeta stimulated SZP accumulation in both superficial zone chondrocytes and synoviocytes. The 3 isoforms of TGFbeta elicited a similar dose response. Inhibition of TGFbeta receptor type I kinase by the specific inhibitor SB431542 abolished the TGFbeta-stimulated accumulation of SZP. BMPs up-regulated SZP accumulation in the superficial zone; however, the magnitude of the effects was not as great as was observed with TGFbeta. There was an additive action between TGFbeta and BMP on SZP accumulation. The response of synoviocytes to BMP was stronger than that of superficial zone chondrocytes. Activin up-regulated SZP accumulation in synoviocytes, but not in chondrocytes. CONCLUSION: TGFbeta is a critical regulator of SZP accumulation in both superficial zone articular chondrocytes and synoviocytes. TGFbeta and BMP have an additive effect. Synoviocytes are more sensitive to BMP family members and activins than are superficial zone articular chondrocytes. Thus, regulation of SZP accumulation by TGFbeta /BMP superfamily members is regulated differently in articular chondrocytes and synoviocytes. [ABSTRACT FROM AUTHOR]

BACKGROUND: Substantial bone loss and bone defects increase the amount of allografting required in hip revision surgery. Thus, the use of a synthetic material to limit the amount of allograft tissue required for impaction grafting is desirable. We evaluated the potential of hydroxyapatite (HA) mixtures to provide initial mechanical stability to a polished tapered femoral stem. MATERIAL AND METHODS: We determined the initial stability of a polished tapered femoral stem after reconstructing a cavitary femoral bone defect by impaction bone grafting with cement in Sawbones composite femurs. Three types of graft material were tested for their ability to improve initial rotational stability. The graft materials investigated were pure allograft, a mixture of 50% allograft and 50% hydroxyapatite (HA), and pure HA. RESULTS: We found a statistically significant difference between the three groups as regards torsional micromotion and failure load. INTERPRETATION: Our findings suggest that reconstruction of femoral bone defects with pure HA or a mixture of allograft and HA provides adequate initial stability for femoral revision arthroplasty using impaction grafting. [ABSTRACT FROM AUTHOR]

While it has been reported that familial Alzheimer's disease (FAD)-linked mutants of amyloid precursor protein (APP) and presenilin (PS)2 induce neuronal cytotoxicity in a manner sensitive to antioxidant and pertussis toxin (PTX), little of the mechanism for PS1-mediated neuronal cell death has been characterized. We previously found that multiple mechanisms, different in detail, underlie cytotoxicities by two FAD-linked mutants of APP, using neuronal cells with an ecdysone-controlled expression system. Here we report that this system revealed that (i) low expression of FAD-linked M146L-PS1 caused neuronal cell death, whereas that of wild-type (wt)PS1 did not; (ii) mutation-specific cytotoxicity by M146L-PS1 was sensitive to antioxidant glutathione-ethyl-ester and resistant to Ac-DEVD-CHO; (iii) cytotoxicity by higher expression of wtPS1 was resistant to both; and (iv) cytotoxicity by M146L-PS1 was inhibited by PTX. It was also highly likely that the involved superoxide-generating enzyme was nitric oxide synthase (NOS), and that the PTX-sensitive cytotoxic signal by M146L-PS1 was mediated by none of the G[sub i/o] proteins. We conclude that M146L-PS1 activates a NOS-mediated cytotoxic pathway via a novel PTX target. [ABSTRACT FROM AUTHOR]

Abstract Background Passive immunization with antibodies directed to Aβ decreases brain Aβ/amyloid burden and preserves memory in transgenic mouse models of Alzheimer's disease (AD). This therapeutic strategy is under intense scrutiny in clinical studies, but its application is limited by neuroinflammatory side effects (autoimmune encephalitis and vasogenic edema). Methods We intravenously administered the monoclonal Aβ protofibril antibody PFA1 to aged (22 month) male and female 3 × tg AD mice with intermediate or advanced AD-like neuropathologies, respectively, and measured brain and serum Aβ and CNS cytokine levels. We also examined 17 month old 3 × tg AD female mice with intermediate pathology to determine the effect of amyloid burden on responses to passive immunization. Results The 22 month old male mice immunized with PFA1 had decreased brain Aβ, increased serum Aβ, and no change in CNS cytokine levels. In contrast, 22 month old immunized female mice revealed no change in brain Aβ, decreased serum Aβ, and increased CNS cytokine levels. Identical experiments in younger (17 month old) female 3 × tg AD mice with intermediate AD-like neuropathologies revealed a trend towards decreased brain Aβ and increased serum Aβ accompanied by a decrease in CNS MCP-1. Conclusions These data suggest that passive immunization with PFA1 in 3 × tg AD mice with intermediate disease burden, regardless of sex, is effective in mediating potentially therapeutic effects such as lowering brain Aβ. In contrast, passive immunization of mice with a more advanced amyloid burden may result in potentially adverse effects (encephalitis and vasogenic edema) mediated by certain proinflammatory cytokines.

Background: Passive immunization with antibodies directed to Aβ decreases brain Aβ/amyloid burden and preserves memory in transgenic mouse models of Alzheimer's disease (AD). This therapeutic strategy is under intense scrutiny in clinical studies, but its application is limited by neuroinflammatory side effects (autoimmune encephalitis and vasogenic edema).Methods: We intravenously administered the monoclonal Aβ protofibril antibody PFA1 to aged (22 month) male and female 3 × tg AD mice with intermediate or advanced AD-like neuropathologies, respectively, and measured brain and serum Aβ and CNS cytokine levels. We also examined 17 month old 3 × tg AD female mice with intermediate pathology to determine the effect of amyloid burden on responses to passive immunization.Results: The 22 month old male mice immunized with PFA1 had decreased brain Aβ, increased serum Aβ, and no change in CNS cytokine levels. In contrast, 22 month old immunized female mice revealed no change in brain Aβ, decreased serum Aβ, and increased CNS cytokine levels. Identical experiments in younger (17 month old) female 3 × tg AD mice with intermediate AD-like neuropathologies revealed a trend towards decreased brain Aβ and increased serum Aβ accompanied by a decrease in CNS MCP-1.Conclusions: These data suggest that passive immunization with PFA1 in 3 × tg AD mice with intermediate disease burden, regardless of sex, is effective in mediating potentially therapeutic effects such as lowering brain Aβ. In contrast, passive immunization of mice with a more advanced amyloid burden may result in potentially adverse effects (encephalitis and vasogenic edema) mediated by certain proinflammatory cytokines. [ABSTRACT FROM AUTHOR]

Background: Low-intensity pulsed ultrasound (LIPUS) is a non-invasive therapy that accelerates fracture healing. As a new treatment method for fracture, we recently reported that the transcutaneous application of CO 2 accelerated fracture healing in association with promoting angiogenesis, blood flow, and endochondral ossification. We hypothesized that transcutaneous CO 2 application, combined with LIPUS, would promote bone fracture healing more than the single treatment with either of them., Methods: Femoral shaft fractures were produced in 12-week-old rats. Animals were randomly divided into four groups: the combination of CO 2 and LIPUS, CO 2 , LIPUS, and control groups. As the transcutaneous CO 2 application, the limb was sealed in a CO 2 -filled bag after applying hydrogel that promotes CO 2 absorption. Transcutaneous CO 2 application and LIPUS irradiation were performed for 20 min/day, 5 days/week. At weeks 1, 2, 3, and 4 after the fractures, we assessed the fracture healing process using radiography, histology, immunohistochemistry, real-time PCR, and biomechanical assessment., Results: The fracture healing score using radiographs in the combination group was significantly higher than that in the control group at all time points and those in both the LIPUS and CO 2 groups at weeks 1, 2, and 4. The degree of bone fracture healing in the histological assessment was significantly higher in the combination group than that in the control group at weeks 2, 3, and 4. In the immunohistochemical assessment, the vascular densities of CD31- and endomucin-positive microvessels in the combination group were significantly higher than those in the control and LIPUS groups at week 2. In the gene expression assessment, significant upregulation of runt-related transcription factor 2 (Runx2) and vascular endothelial growth factor (VEGF) was detected in the combination group compared to the LIPUS and CO 2 monotherapy groups. In the biomechanical assessment, the ultimate stress was significantly higher in the combination group than in the LIPUS and CO 2 groups., Conclusion: The combination therapy of transcutaneous CO 2 application and LIPUS had a superior effect in promoting fracture healing through the promotion of angiogenesis and osteoblast differentiation compared to monotherapy., (© 2024. The Author(s).)

BACKGROUND Infection control and reconstruction of bone and soft tissue are essential for treating infected nonunion. Continuous local antibiotic perfusion (CLAP) is a drug delivery system that continuously delivers antibiotics at the required concentration, area, and duration. This case report describes the instance of infected nonunion in which infection eradication and bone union were achieved using CLAP and synthetic bone grafting while retaining the implant. CASE REPORT The case was a 31-year-old woman with an infected nonunion. After she underwent osteosynthesis using nail for open fractures of tibia and fibula, bone union remained unachieved, and she exhibited skin defects and draining of pus. Following the removal of the infected granulation tissue from the bone defects, 2 bone marrow needles, serving as intramedullary antibiotic perfusion (iMAP) pins, were inserted into the medullary cavity tibia. A double-lumen tube was placed in the subcutaneous pocket as the intra-soft tissue antibiotic perfusion (iSAP) tube. No bone mobility was observed around the bone defect and nail, and replacement of the implant was not necessary. Beta-tricalcium phosphate was transplanted to the bone defect, and negative pressure wound therapy was applied. Gentamicin was injected continuously through iMAP and iSAP. Finally, the infection was eradicated, and cortical bone bridging was observed without additional surgery or adverse effects. CONCLUSIONS CLAP emerges as a viable treatment option for infected nonunion, as it enables the delivery of antibiotics at a concentration sufficient for infection control while providing the surgeon with flexibility to design the area, dosage, and duration of antibiotic delivery.

The interconnected structures in a 3D scaffold allows the movement of cells and nutrients. Therefore, this study aimed to investigate the in-vivo bioactivity of 3D-printed β-tricalcium phosphate (β-TCP) and hydroxyapatite (HAP) scaffolds that replicate biological bone. This study included 24-week-old male New Zealand white rabbits. A cylindrical bone defect with a diameter of 4.5 mm and a depth of 8 mm was created in the lateral aspect of the distal femur. A 3D-printed scaffold was implanted in the right femur (experimental side), whereas the left femur was kept free of implantation (control side). Micro-CT analysis and histological observations of the bone defect site were conducted at 4, 8, and 12 weeks postoperatively to track the bone repair progress. No evidence of new bone tissue formation was found in the medullary cavity of the bone defect on the control side. In contrast, on the experimental side, the 3D scaffold demonstrated sufficient bioactivity, leading to the growth of new bone tissue. Over time, new bone tissue gradually extended from the periphery toward the center, a phenomenon evident in both micro-CT images and biopsy staining. In the current study, we observed that the cells involved in bone metabolism adhered, spread, and proliferated on our newly designed 3D-printed scaffold with a bone microstructure. Therefore, it is suggested that this scaffold has sufficient bioactivity to induce new bone formation and could be expected to be a more useful artificial bone than the existing version., (© 2024. The Author(s).)

We previously demonstrated that transcutaneous CO 2 application promotes muscle fiber-type switching, fracture healing, and osteogenesis by increasing blood flow and angiogenesis. Here, we aimed to investigate the preventive effects of transcutaneous CO 2 application on disuse osteoporosis and muscle atrophy in a rat hindlimb suspension model. Eleven-week-old male Sprague-Dawley rats were divided into hindlimb suspension (HS), HS with transcutaneous CO 2 application (HSCO 2 ), and control groups. HSCO 2 rats were administered transcutaneous 100 % CO 2 gas in their bilateral hindlimbs, five times a week for 20 min. After 3 weeks, we harvested the gastrocnemius, femur, and tibia for assessment. Histological analysis revealed a significant decrease in the gastrocnemius myofiber cross-sectional area in HS rats compared to the control rats, whereas HSCO 2 rats exhibited a significant increase compared to HS rats. Micro-computed tomography showed significant bone atrophy in the trabecular and cortical bones of the femur in HS rats compared to those of the control rats, whereas significant improvement was noted in HSCO 2 rats. Histological analysis of the proximal tibia revealed more marrow adipose tissue in the HS rats than in the control rats. However, in the HSCO 2 rats, fewer marrow adipose tissue and osteoclasts were observed. Moreover, HSCO 2 rats had more osteoblasts and higher expression of peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α) and vascular endothelial growth factor (VEGF) than the HS rats. The gastrocnemius and distal femur of HSCO 2 rats also exhibited elevated PGC-1α and VEGF expression and upregulation of the myogenesis markers and osteogenesis markers compared to those of HS rats. This treatment effectively prevented disuse osteoporosis and muscle atrophy by promoting local angiogenesis and blood flow. PGC-1α is crucial for promoting this angiogenic pathway. Transcutaneous CO 2 application may be a novel preventive procedure for disuse osteoporosis and muscle atrophy, complementing medication and rehabilitation., 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 © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Introduction: Serpiginous choroiditis presents with large yellow-white exudative lesions that occur near the optic nerve papillae, that progresses slowly with repeated relapses and cures. Although infection and autoimmunity have been implicated, the cause is unknown., Methods: A man was diagnosed with serpiginous choroiditis on clinical and other examinations. He started treatment with oral corticosteroids, cyclophosphamide, adalimumab, azathioprine, rituximab, and mycophenolate mofetil. Only the steroids and cyclophosphamide had a therapeutic effect. Plasma exchange was initiated, and the lesions quickly resolved., Results: Disease control has been maintained by plasma exchange and cyclophosphamide during flare-ups in the fall and winter, suggesting that plasma exchange is effective in the treatment of serpiginous choroiditis., Conclusion: The reproducible response with each recurrence suggests a strong association between the disease and autoimmunity. Furthermore, that some, as yet unknown, autoantibodies are involved in the pathogenesis of serpiginous choroiditis., (© 2024 International Society for Apheresis and Japanese Society for Apheresis.)

Tau is a microtubule-associated protein that contributes to cytoskeletal stabilization. Aggregation of tau proteins is associated with neurodegenerative disorders such as Alzheimer's disease. Several types of posttranslational modifications that alter the physical properties of tau proteins have been identified. SUMOylation is a reversible modification of lysine residues by a small ubiquitin-like modifier (SUMO). In this study, we examined the enzymes that regulate the SUMOylation and deSUMOylation of tau in an alternatively spliced form, 0N4R-tau. Among SUMO E3 ligases, we found protein inhibitor of activated STAT (PIAS)xα and PIASxβ increase the levels of SUMOylated tau. The deSUMOylation enzymes sentrin-specific protease (SENP)1 and SENP2 reduced the levels of SUMO-conjugated tau. SUMO1 modification increased the level of phosphorylated tau, which was suppressed in the presence of SENP1. Furthermore, we examined the effect of tripartite motif (TRIM)11, which was recently identified as an E3 ligase for SUMO2 modification of tau. We found that TRIM11 increased the modification of both 2N4R- and 0N4R-tau by SUMO1, which was attenuated by mutation of the target lysine residue to arginine. These findings suggest that the expression and activity of SUMOylation regulatory proteins modulate the physical properties of tau proteins and may contribute to the onset and/or progression of tau-associated neurodegenerative disorders., Competing Interests: 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., (© 2024 The Authors.)

We report two cases wherein rotating hinge knee (RHK) arthroplasty was performed for Charcot joints that developed secondary to Charcot-Marie-Tooth disease (CMT).  Case 1 was of a 74-year-old woman with CMT. She presented with muscle weakness and sensory disturbances of the distal lower limbs, deformity, and significant medial instability of the bilateral knees. She was then diagnosed with Charcot joints of the knees secondary to CMT, which were treated with RHK arthroplasty. Five years postoperatively, there was no instability, and she was able to stand unassisted without pain. Case 2 was a 90-year-old woman with CMT who presented with muscle weakness and sensory disturbances of the distal lower limbs, deformity, and significant medial instability of the bilateral knees. She was then diagnosed with Charcot joints of the knees secondary to CMT, which were also treated with RHK arthroplasty. One year postoperatively, there was no instability, and she was able to walk smoothly using a walker. These clinical cases indicate that RHK arthroplasty can be a good therapeutic option for Charcot joints of the knees in patients with CMT., 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, Ehara et al.)

Purpose: In an aging society, fragility fractures of the pelvis (FFP) have increased significantly. However, there is no clear consensus on the timing and criteria for transitioning from conservative treatment to surgery for these fractures. Thus, we aimed to investigate the effects of our treatment protocol for FFP based on conservative treatment., Methods: We conducted a retrospective study including 74 patients with FFP at our institution between 2015 and 2021. All patients were treated conservatively for the first two weeks. During this period, only wheelchair transfer was allowed. If the patient could not walk after this period, surgery was performed. Fracture type (Rommens classification), walking ability, presence of complications after admission, presence of fracture union, and surgical treatment was investigated. Patients were divided into two groups: a stable group (type I/II) and an unstable group (type III/IV)., Results: Fracture union was achieved in all patients. Thirteen patients developed complications after being admitted to our hospital; seven showed decreased walking ability, and six required surgeries. The stable and unstable groups comprised 47 and 27 patients, respectively. There were no statistically significant differences between the groups regarding the percentage of patients who developed complications or experienced decrease in walking ability. The percentage of patients who required surgery was significantly higher in the unstable group (p < 0.05)., Conclusion: Our FFP management protocol was effective regardless of fracture type. It is important to provide a period for careful assessment of instability, and to try to prevent fracture progression., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany.)

Acute kidney injury (AKI) secondary to severe falciparum malaria possesses a high mortality rate; however, a prognostic marker of renal dysfunction has not yet been identified. Thus, we reported a case of a patient with AKI secondary to falciparum malaria who underwent hemodialysis and a renal biopsy due to prolonged renal dysfunction. The male patient, in his 50 s, presented to our hospital with vomiting, diarrhea, fever, and decreased level of consciousness. The Giemsa-stained peripheral blood film revealed approximately 5% parasitemia, and a rapid diagnostic test was positive for Plasmodium falciparum. He was diagnosed with severe falciparum malaria and was started on quinine hydrochloride. Hemodialysis was initiated due to the decreased urine output and fluid retention. Subsequently, he was weaned off hemodialysis. The histopathological analysis of a renal biopsy revealed interstitial fibrosis, tubular atrophy, and chronic inflammatory cell infiltration; thus, malarial nephropathy was diagnosed. Thereafter, his renal function stabilized, and he was discharged from the hospital. The urinary liver-type fatty acid-binding protein (L-FABP) level decreased before renal function improved. Our report highlighted that long-term follow-up is essential for severe AKI secondary to malaria. The urinary L-FABP level may be a useful prognostic indicator of AKI secondary to severe falciparum malaria., (© 2024. The Author(s), under exclusive licence to Japanese Society of Nephrology.)

Aims: Continuous local antibiotic perfusion (CLAP) has recently attracted attention as a new drug delivery system for orthopaedic infections. CLAP is a direct continuous infusion of high-concentration gentamicin (1,200 μg/ml) into the bone marrow. As it is a new system, its influence on the bone marrow is unknown. This study aimed to examine the effects of high-concentration antibiotics on human bone tissue-derived cells., Methods: Cells were isolated from the bone tissue grafts collected from six patients using the Reamer-Irrigator-Aspirator system, and exposed to different gentamicin concentrations. Live cells rate, apoptosis rate, alkaline phosphatase (ALP) activity, expression of osteoblast-related genes, mineralization potential, and restoration of cell viability and ALP activity were examined by in vitro studies., Results: The live cells rate (the ratio of total number of cells in the well plate to the absorbance-measured number of live cells) was significantly decreased at ≥ 500 μg/ml of gentamicin on day 14; apoptosis rate was significantly increased at ≥ 750 μg/ml, and ALP activity was significantly decreased at ≥ 750 μg/ml. Real-time reverse transcription-polymerase chain reaction results showed no significant decrease in the ALP and activating transcription factor 4 transcript levels at ≥ 1,000 μg/ml on day 7. Mineralization potential was significantly decreased at all concentrations. Restoration of cell viability was significantly decreased at 750 and 1,000 μg/ml on day 21 and at 500 μg/ml on day 28, and ALP activity was significantly decreased at 500 μg/ml on day 28., Conclusion: Our findings suggest that the exposure concentration and duration of antibiotic administration during CLAP could affect cell functions. However, further in vivo studies are needed to determine the optimal dose in a clinical setting., Competing Interests: A. Maruo reports royalties from Total Medical Supply Company (Japan) and consulting fees from Cubex Medical Company (Japan), which are unrelated to this study., (© 2024 Oe et al.)

Although mRNA vaccines for COVID-19 are highly beneficial and are recommended for patients with kidney disease, adverse reactions in some patients after vaccination have been problematic. Various vasculitis and renal disorders have been reported after vaccination; however, a causal relationship has not yet been identified. In this report, we describe a case of rapidly progressive glomerulonephritis that developed after SARS-CoV-2 vaccination, in which both anti-glomerular basement membrane (anti-GBM) and myeloperoxidase antineutrophil cytoplasmic antibodies (MPO-ANCA) were present. The patient's renal biopsy showed that of the 48 glomeruli in total, four showed global sclerosis and none showed segmental sclerosis. The biopsy showed 11 cellular glomerular crescents and 5 fibrocellular glomerular crescents. Renal function improved with steroids, rituximab, and plasma exchange. Approximately 9 months later, MPO-ANCA was again elevated, and the pulmonary lesions worsened, again requiring multidisciplinary treatment. This case suggests that caution should be exercised in the development of double-positive disease after vaccination, and that long-term observation may be necessary because of the possibility of relapse., (© 2023. The Author(s) under exclusive licence to The Japan Society of Nephrology.)

In this study, we review the properties of three anionic detergents, sodium dodecyl sulfate (SDS), Sarkosyl, and sodium lauroylglutamate (SLG), as they play a critical role in molecular biology research. SDS is widely used in electrophoresis and cell lysis for proteomics. Sarkosyl and, more frequently, SDS are used for the characterization of neuropathological protein fibrils and the solubilization of proteins. Many amyloid fibrils are resistant to SDS or Sarkosyl to different degrees and, thus, can be readily isolated from detergent-sensitive proteins. SLG is milder than the above two detergents and has been used in the solubilization and refolding of proteins isolated from inclusion bodies. Here, we show that both Sarkosyl and SLG have been used for protein refolding, that the effects of SLG on the native protein structure are weaker for SLG, and that SLG readily dissociates from the native proteins. We propose that SLG may be effective in cell lysis for functional proteomics due to no or weaker binding of SLG to the native proteins.

Background: The relationship between the severity of preoperative varus deformity and the amount of its correction in unicompartmental knee arthroplasty (UKA) as well as the thickness of the insert has not been well known., Methods: One hundred and three patients who underwent medial fixed-bearing UKA with the use of the spacer block method were assessed. After the component gap in extension was measured using a UKA tensor, the pre-osteotomy gap was calculated from the thickness of the bone cuts. The relationship between the preoperative hip-knee-ankle (HKA) angle as well as the pre-osteotomy gap and the amount of change in HKA angle were analysed. Also, preoperative HKA angle and the thickness of the bone cuts were compared among groups by the insert thickness., Results: The mean preoperative HKA angle was 7.7 ± 3.1° varus. Patients with more varus deformity and those with a wider pre-osteotomy gap showed a more valgus change in HKA angle. As for the thickness of the insert, the preoperative HKA angle of the patients with the thinnest insert was significantly smaller (less varus) than that of those with the thicker insert while no statistically significant difference was found among the insert groups regarding the amount of the bone cuts., Conclusions: The severity of the preoperative varus deformity as well as the intraoperative pre-osteotomy gap related to the amount of change in HKA angle. As thick inserts tended to be used in severe varus knees, the tibial bone cut can be reduced in such cases., Competing Interests: Declaration of competing interest The authors declare that they have no conflict of interest., (Copyright © 2022 The Japanese Orthopaedic Association. Published by Elsevier B.V. All rights reserved.)

BACKGROUND Distal femoral and proximal tibial fractures often lead to nonunion and post-traumatic osteoarthritis, and total knee arthroplasty (TKA) has emerged as an effective alternative for older patients. This report includes 3 cases of successful TKA treatment. The cases involve a 42-year-old man and a 62-year-old man with Hoffa coronal fractures of the distal femur, and a 50-year-old man with a proximal tibial fracture. These patients underwent multiple osteosynthesis procedures before receiving TKA. CASE REPORT Case 1: A 42-year-old man with a displaced Hoffa's fracture had persistent knee pain. Nonunion post-initial fixation led to reoperation with iliac bone grafting and plate fixation. TKA using a Posterior Stabilized (PS)-type implant resulted in improved motion and function after 3 years. Case 2: A 62-year-old man suffered lateral condyle and ligament injuries from a displaced Hoffa's fracture. Despite plate fixation, dislocation occurred, requiring conversion. TKA with long-stem hinge-type implant, using augmentation block, led to enhanced stability and outcomes at 2 years. Case 3: A 50-year-old man's tibial nonunion, treated with plate fixation, resulted in infection and bone fusion. TKA using a constrained PS-type implant insert addressed the lateral tibial adhesions via iliotibial band (ITB) release and treated severe tibial plateau damage. Positive results were seen at 1 year. CONCLUSIONS The challenges of pseudarthrosis, like bone defects and compromised tissue, highlight the need for precise implant selection based on evaluations of bone quality, defects, knee stability, and hyperextension, rather than resorting to overly-constrained implants.

Background: Surveillance colonoscopy decreases colorectal cancer mortality; however, lesions are occasionally missed. Although an appropriate surveillance interval is indicated, variations may occur in the methods used, such as scope manipulation or observation. Therefore, individual endoscopists may miss certain areas. This study aimed to verify the effectiveness of performing repeat colonoscopies with a different endoscopist from the initial procedure., Methods: We retrospectively reviewed a database of 8093 consecutive colonoscopies performed in the Omori Red Cross Hospital from January 1st 2018 to June 30th 2021. Data from repeat total colonoscopies performed within three months were collected to assess missed lesions. The patients were divided into two groups according to whether the two examinations were performed by different endoscopists (group D) or the same endoscopist (group S). The primary outcome in both groups was the missed lesion detection rate (MLDR)., Results: Overall, 205 eligible patients were analyzed. In total, 102 and 103 patients were enrolled in groups D and S, respectively. The MLDR was significantly higher in group D (61.8% vs. 31.1%, P < 0.0001). Multivariate logistic regression analysis for the detection of missed lesions identified performance by the different endoscopists (odds ratio, 3.38; 95% CI, 1.81-6.30), and sufficient withdrawal time (> 6 min) (odds ratio, 3.10; 95% CI, 1.12-8.61) as significant variables., Conclusions: Overall, our study showed a significant improvement in the detection of missed lesions when performed by different endoscopists. When performing repeat colonoscopy, it is desirable that a different endoscopist perform the second colonoscopy., Trial Registration: This study was approved by the Institutional Review Board of the Omori Red Cross Hospital on November 28, 2022 (approval number:22-43)., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Background: We previously demonstrated that CD34 + cell transplantation in animals healed intractable fractures via osteogenesis and vasculogenesis; we also demonstrated the safety and efficacy of this cell therapy in an earlier phase I/II clinical trial conducted on seven patients with fracture nonunion. Herein, we present the results of a phase III clinical trial conducted to confirm the results of the previous phase studies using a larger cohort of patients., Methods: CD34 + cells were mobilized via administration of granulocyte colony-stimulating factor, harvested using leukapheresis, and isolated using magnetic cell sorting. Autologous CD34 + cells were transplanted in 15 patients with tibia nonunion and 10 patients with femur nonunion, who were followed up for 52 weeks post transplantation. The main outcome was a reduction in time to heal the tibia in nonunion patients compared with that in historical control patients. We calculated the required number of patients as 15 based on the results of the phase I/II study. An independent data monitoring committee performed the radiographic assessments. Adverse events and medical device failures were recorded., Results: All fractures healed during the study period. The time to radiological fracture healing was 2.8 times shorter in patients with CD34 + cell transplantation than in the historical control group (hazard ratio: 2.81 and 95% confidence interval 1.16-6.85); moreover, no safety concerns were observed., Conclusions: Our findings strongly suggest that autologous CD34 + cell transplantation is a novel treatment option for fracture nonunion., Trial Registration: UMIN-CTR, UMIN000022814. Registered on 22 June 2016., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Introduction:  Kinematically aligned total knee arthroplasty (KA-TKA) has gained interest for achieving more favorable clinical outcomes than mechanically aligned TKA. One of the advantages of KA-TKA is reported to be an easy acquisition of intraoperative soft-tissue balance without excessive medial release for varus osteoarthritis. However, we hypothesized that the prosthesis type affects intraoperative soft-tissue balance even in the KA-TKA. The present study aimed to compare intraoperative soft-tissue balance and clinical outcomes of KA-TKAs using single-radius (SR) or multiradius (MR) prostheses., Materials:  AND METHODS: Consecutive 70 cruciate-retaining modified KA-TKAs (31 SR and 39 MR) were performed in patients with varus-type osteoarthritis using a navigation system. Intraoperative soft-tissue balance including joint component gap and varus/valgus balance was measured with femoral component placement and patellofemoral joint reduction throughout the range of motion using offset-type tensor and compared between the two groups. Two years postoperatively, the range of motion and 2011 Knee Society Scores were compared between the two groups., Results and Conclusion:  Joint component gaps showed no significant differences between the two groups from 0 to 30 degrees of flexion. However, during 60 to 120 degrees of flexion, joint component gaps of SR group showed significantly larger values than those of MR group ( p  < 0.05). There were no significant differences in varus/valgus balance throughout the range of motion between the two groups. The postoperative clinical outcomes showed no significant differences between the two groups., Interpretation:  Despite no difference in clinical outcomes, joint component gap showed different patterns due to the prosthesis type in modified KA-TKAs., Competing Interests: None declared., (Thieme. All rights reserved.)