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Adipose-derived stem cell (ASC)-released exosomes (ASCexos) have multiple biological activities. We examined the effect of ASCexos derived from the inguinal adipose tissue of exercise-trained rats (EX-ASCexos) on adipogenic conversion of 3T3-L1 cells and analyzed their microRNA (miRNA) expression profiles. Differentiation of 3T3-L1 cells into adipocytes was performed for 9 d with EX-ASCexos or ASCexos from sedentary control rats (SED-ASCexos), and the expression of proteins and miRNA involved in adipogenic differentiation were determined. EX-ASCexos but not SED-ASCexos attenuated 3T3-L1 adipocyte differentiation with increased phosph-Ser112PPARγ expression, the inactive form of PPARγ. These differentiated adipocytes were also accompanied by increased phosph-Thr202/Tyr204ERK and decreased dual-specificity phosphatase 3 (DUSP3) levels. The exosomal miRNAs miR-323-5p, miR-433-3p, and miR-874-3p were identified specifically in EX-ASCexos. Of these, miR-323-5p mimic replicated the EX-ASCexo-induced suppression of 3T3-L1 adipocyte differentiation and altered adipogenesis-related factor expression. In conclusion, exercise training-driven exosomal miR-323-5p suppressed 3T3-L1 adipogenesis by increasing phosph-Ser112PPARγ expression, while phosph-Thr202/Tyr204ERK accumulation inhibited DUSP3 expression., Competing Interests: Declaration of competing interest There are no conflicts of interest to declare., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Purpose: Postoperative stereotactic radiosurgery to the resection cavity in patients with brain metastases is guideline-recommended therapy. However, Japanese Clinical Oncology Group 0504 study showed that postoperative observation could be a therapeutic option in patients with completed resected brain metastases. We hereby investigated the incidence and risk factors for local recurrence after complete resection without immediate radiotherapy and developed a scoring system for its prediction., Methods: We included 53 patients with 54 brain metastases, who underwent complete resection between January 2016 and December 2021. We identified risk factors for local recurrence and developed a scoring system to predict it using the extracted risk factors, by assigning one point to each risk factor and calculating the total scores for each patient. We evaluated the correlation between the prognostic score and time to local recurrence., Results: Local recurrence occurred in 37 of 54 tumors (68.5%), with a median follow-up duration of 21.0 months. The median time to local recurrence was 5.1 months. Univariate and multivariate analyses revealed that non-lung adenocarcinoma, infratentorial tumors, and no postoperative systemic therapy were identified as risk factors for local recurrence (non-lung adenocarcinoma, p = 0.035; infratentorial tumors, p = 0.044; and no postoperative systemic therapy, p = 0.0069). A score ≥ 2 showed a median time to local recurrence of 2.1 months, starkly contrasting with 30.8 months for a score ≤ 1 (p = 0.0002)., Conclusions: Non-lung adenocarcinoma, infratentorial tumors, and no postoperative systemic therapy were risk factors for local recurrence. Our scoring system can predict local recurrence, thus potentially aiding treatment decisions., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Endocrine cell micronests (ECMs) are aggregates of endocrine cells known as enterochromaffin-like cells, typically measuring approximately 50 μm and usually observed in the mucosal layer of atrophic gastric fundic glands associated with hypergastrinemia. Although there are numerous reports on gastric ECMs, reports on duodenal ECMs are exceedingly rare. We report a rare case of Brunner's gland hyperplasia with increased endocrine cells and ECMs. An approximately 40 mm polyp was found in the duodenal bulb of a 57-year-old Japanese male patient during an upper gastrointestinal endoscopy, and a polypectomy was performed. Microscopic examination revealed hyperplasia of Brunner's glands in the duodenal polyp. Compared to normal Brunner's glands, hyperplastic Brunner's glands exhibited more endocrine cells. Additionally, many ECMs were observed in the fibromuscular connective tissue, comprising smooth muscle cells and myofibroblasts, adjacent to the hyperplastic Brunner's glands. The patient presented with hypergastrinemia (2,500 pg/mL; normal range: 30-140 pg/mL), and the ECMs were considered related to this condition. This case represents the first instance of a benign duodenal lesion with an increase in endocrine cells and the presence of ECMs., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. The Ethics Committee at the Affiliated Hospital of Hamamatsu University School of Medicine issued approval 81-004. 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, Meguro et al.)

Introduction Amid an increasing number of patients with pertrochanteric fractures, early prediction of postoperative gait potential could reduce unnecessary rehabilitation and hospitalization. The relationship between preoperative gluteal muscle condition and postoperative gait outcomes remains unclear. The gluteal muscles are crucial for mobility, and their cross-sectional area (CSA) and fatty infiltration are indicators of physical function. Preoperative computed tomography (CT) provides quantitative data on muscle CSA and density, measured in Hounsfield Units (HU). This study aimed to identify which preoperative muscle index, CSA, BMI-adjusted CSA, or muscle density, best predicts postoperative gait ability. We hypothesized that a higher adjusted CSA and muscle density in the gluteus muscles would be associated with superior gait performance. Materials and methods Preoperative assessments included radiographs and CT scans. Patients under 75, with less than four weeks of follow-up, prior contralateral hip surgery, prefracture immobility, male patients, high-energy trauma, or conditions impairing physical performance were excluded. Gait performance was evaluated four weeks postoperatively, classifying patients into two groups: the 'parallel bar group,' requiring parallel bars, and the 'walker group,' walking independently. Patients underwent CM nailing. Preoperative CT scans measured the CSA and muscle density of the gluteus maximus and medius. Measurements were taken from the non-injured side to avoid interference from the fracture. Muscle borders were manually traced, and the CSA and muscle density in HU were calculated. Results Out of 81 patients, 49 met the inclusion criteria (mean age: 87). The patients were divided into the 'parallel bar group' (n=19) and the 'walker group' (n=30) based on postoperative gait performance. No significant differences in age, weight, height, or fracture laterality were observed between groups. The mean (and standard deviation (SD)) of CSA for the gluteus maximus in the 'parallel bar group'/in the 'walker group' was 2211.8 ± 469.8 mm²/2440.0 ± 586.2 mm², respectively (p=0.15), and for the gluteus medius, it was 1751.7 ± 415.2mm²/1869.1 ± 448.3mm², respectively (p=0.36). The mean (and SD) muscle density for the gluteus maximus in the 'parallel bar group'/in the 'walker group' was 13.6 ± 12.7 HU / 20.6 ± 13.0 HU (p=0.07), and for the gluteus medius, it was 25.2 ± 8.4 HU/31.8 ± 10.1 HU, respectively (p=0.02). The ROC curve identified a 30.9 HU cut-off for gluteus medius density, with sensitivity and specificity of 60.7% and 78.9%. The mean (and SD) of BMI-adjusted CSA for the gluteus maximus in the 'parallel bar group'/ in the 'walker group' was 116.4 ± 26.8 m²/10 6 kg/124.3 ± 29.2 m²/10 6 kg, respectively (p=0.35), and for the gluteus medius, it was 93.3 ± 27.2 m²/10 6 kg/95.4 ± 21.3m²/10 6 kg, respectively (p=0.78). Conclusion This study analyzed preoperative CT images of women aged 75 and older with pertrochanteric fractures, comparing gluteal muscle CSA and density with postoperative walking ability. The gluteus medius density was significantly higher in the superior gait group, with a cut-off value of 30.9 HU. However, no significant differences were found in the gluteus maximus density, CSA, or BMI-adjusted CSA. These findings partially support the hypothesis, emphasizing the importance of muscle evaluation in predicting postoperative gait performance., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. The Nishi Hospital Ethics Committee issued approval 2021-1. 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: 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, Noda et al.)

Background: Anastomosing hemangiomas are benign vascular neoplasms occurring mainly in the genitourinary tract and paraspinal soft tissues. There have been no reported cases of anastomosing hemangiomas occurring in the spinal epidural space; therefore, their clinical and radiological presentations remain unclear., Observations: A 55-year-old man presented with progressive back pain and motor and sensory disturbances in both lower extremities. Magnetic resonance imaging (MRI) revealed an extradural lesion at the T4-6 level that extended into the extraspinal region through the left T5-6 intervertebral foramen. Axial MRI revealed that the tumor encircled the spinal cord, with sharp horn-like ends in the intraspinal canal. The patient underwent complete tumor resection with T4-6 laminectomy and left T5-6 foraminotomy. The histopathological diagnosis was an anastomo-sing hemangioma exhibiting anastomosing proliferation of capillary vessels with hobnailed endothelial cells. His symptoms improved, and tumor control was achieved 4 months after surgery without adjuvant therapy., Lessons: Although rare, anastomosing hemangiomas can occur in the spinal epidural space. Radiologically, the tumors show horn-like projections encircling the spinal cord, which can be diagnostic cues. Anastomosing hemangiomas should be included in the differential diagnosis of spinal epidural tumors, especially when characteristic horn-like projections are present. https://thejns.org/doi/10.3171/CASE24265.

Isocitrate dehydrogenase ( IDH ) wild-type glioblastoma (GBM) is a highly aggressive brain tumor with a high recurrence rate despite adjuvant treatment. This study aimed to evaluate the risk factors for non-local recurrence of GBM. In the present study, we analyzed 104 GBMs with a single lesion (non-multifocal or multicentric). Univariate analysis revealed that subventricular zone (SVZ) involvement was significantly associated with non-local recurrence (hazard ratio [HR]: 2.09 [1.08-4.05]). Tumors in contact with the trigone of the lateral ventricle tended to develop subependymal dissemination ( p = 0.008). Ventricular opening via surgery did not increase the risk of non-local recurrence in patients with SVZ involvement ( p = 0.190). A systematic review was performed to investigate the risk of non-local recurrence, and 21 studies were identified. A meta-analysis of previous studies confirmed SVZ involvement (odds ratio [OR]: 1.30 [1.01-1.67]) and O -6-methylguanine DNA methyltransferase promoter methylation (OR: 1.55 [1.09-2.20]) as significant risk factors for local recurrence. A time-dependent meta-analysis revealed a significant association between SVZ involvement and dissemination (HR: 1.69 [1.09-2.63]), while no significant association was found for distant recurrence (HR: 1.29 [0.74-2.27]). Understanding SVZ involvement and specific tumor locations associated with non-local recurrence provides critical insights for the management of GBM.

Background: Atypical teratoid/rhabdoid tumor (AT/RT) is an uncommon malignant neoplasm and rarely occurs in the spinal space, especially in the cauda equina. Only 8 cases of pediatric AT/RT of the cauda equina have been reported. Therefore, its clinical behavior and optimal treatment remain unclear., Observations: The authors describe the case of a 9-year-old boy who presented with progressive back and left leg pain. Initial magnetic resonance imaging showed an intradural extramedullary lesion at the L3-4 level, which progressed rapidly to the L2-5 level within a month. He underwent partial resection of the tumor with an L2-5 laminectomy. The histopathological diagnosis was AT/RT. He received adjuvant chemotherapy and radiotherapy, and his gait disturbance improved postoperatively. At 6 months' follow-up, disease recurrence was not observed., Lessons: Although extremely rare, AT/RT should be included in the differential diagnosis for prompt therapeutic intervention. Safe resection with minimal functional impairment, followed by postoperative chemoradiation, can lead to tumor control and improve neurological function. https://thejns.org/doi/10.3171/CASE24219.

Background: Intracranial solitary fibrous tumors (SFTs) rarely recur in the spinal space. Only 4 cases of spinal recurrence from intracranial SFT have been reported; therefore, the optimal treatment of recurrent spinal SFT remains unclear., Observations: A 53-year-old woman with a history of resection of a right occipital anaplastic SFT presented with progressive back and side pain. She was diagnosed with an intradural extramedullary tumor ventral to the spinal cord at the T5-7 level. She underwent tumor resection with T5-6 laminectomy and T4 and T7 partial laminectomy. The tumor was completely removed in a piecemeal fashion using an ultrasonic aspirator with careful control of bleeding. Her symptoms quickly improved after the surgery, and she returned to normal life. The tumor was diagnosed as SFT. Pazopanib was administered postoperatively. Despite the recurrence of the intracranial tumor, the patient was alive without recurrence of the spinal tumor 14 months after resection., Lessons: Although rare, intracranial SFTs have a risk of spinal recurrence. Complete resection of a recurrent spinal SFT can be achieved even in the ventral location. Pazopanib could be a possible therapeutic option for preventing local tumor recurrence in the management of recurrent spinal SFT. https://thejns.org/doi/10.3171/CASE24217.

Awake surgery contributes to the maximal safe removal of gliomas by localizing brain function. However, the efficacy and safety thereof as a treatment modality for glioblastomas (GBMs) have not yet been established. In this study, we analyzed the outcomes of awake surgery as a treatment modality for GBMs, response to awake mapping, and the factors correlated with mapping failure. Patients with GBMs who had undergone awake surgery at our hospital between March 2010 and February 2023 were included in this study. Those with recurrence were excluded from this study. The clinical characteristics, response to awake mapping, extent of resection (EOR), postoperative complications, progression-free survival (PFS), overall survival (OS), and factors correlated with mapping failure were retrospectively analyzed. Of the 32 participants included in this study, the median age was 57 years old; 17 (53%) were male. Awake mapping was successfully completed in 28 participants (88%). A positive response to mapping and limited resection were observed in 17 (53%) and 13 participants (41%), respectively. The EOR included gross total, subtotal, and partial resections and biopsies in 19 (59%), 8 (25%), 3 (9%), and 2 cases (6%), respectively. Eight (25%) and three participants (9%) presented with neurological deterioration in the acute postoperative period and at 3 months postoperatively, respectively. The median PFS and OS were 15.7 and 36.9 months, respectively. The time from anesthetic induction to extubation was statistically significantly longer in the mapping failure cohort than that in the mapping success cohort. Functional areas could be detected during awake surgery in participants with GBMs. Thus, awake mapping influences intraoperative discernment, contributes to the preservation of brain function, and improves treatment outcomes.

Amyloid A (AA) amyloidosis is induced by administering amyloid fibrils to animals under inflammatory conditions. Silk fibroin (SF), the main component of silk threads, forms amyloid-like fibrils and has been previously reported to induce AA amyloidosis in mice. In this study, SF was cultured in ethanol solution, and after confirming fibril formation through thioflavin T assay, Congo red assay, and observation under electron microscopy, cultured SF ethanol solutions were administered to mice via various routes to investigate the induction of target organs and amyloidosis. As a result, cultured SF ethanol solutions were confirmed to reach the lungs and spleen, but no amyloid deposition was observed. While SF forms amyloid-like fibril structures through cultivation in ethanol solution, its amyloid-enhancing factor (AEF) activity is considered low in mice., (© 2024 IOP Publishing Ltd.)

To elucidate the correlation between dye solubilization into micelles and their core-shell aggregated structure, the structures of block and random copolymer micelles were characterized. The block copolymer micelles exhibited a higher dye solubilization capacity which correlated with their core volume, clear core-shell contrast and slow solubilization rate.

Introduction: Tick-borne diseases (TBDs) are a growing threat in Japan. However, distribution of ticks and their possession of human pathogens remain poorly understood., Methods: In the present study, we collected 3477 ticks at 6 remote, woodland sites in Ibaraki prefecture between May 23 and November 4, 2021, and investigated the distribution and the possession of spotted fever group Rickettia (SFGR)., Results: The collected ticks included Haemaphysalis flava (78.3 %), Haemaphysalis longicornis (9.0 %), Haemaphysalis hystricis (4.6 %), Ixodes turdus (4.3 %), Amblyomma testudinarium (2.1 %), Haemaphysalis cornigera (0.9 %), Haemaphysalis formosensis (0.9 %), Haemaphysalis megaspinosa (0.2 %), Ixodes ovatus (0.1 %), Ixodes nipponensis (0.09 %), and Ixodes columnae (0.03 %). Of 2160 DNA samples extracted from the ticks, the gltA gene and the 17-kDa antigen gene of SFGR were detected in 67 samples. Among 1682 samples from adult and nymph ticks, the positive rate of SFGR was 2.7 %. Sequence analyses of the partial 17-kDa antigen gene demonstrated that the detected SFGR were classified into 8 groups (G1 to G8). The sequences of G2, G4, G5, G6, and G7 were either identical to or differed by one base pair from those of Rickettsia asiatica, Rickettsia tamurae, Rickettsia monacensis, Rickettsia canadensis, and Rickettsia felis, respectively., Conclusion: The present study revealed a diverse tick fauna in Ibaraki prefecture, including detection of species commonly found in southwestern Japan. Although the prevalence of SFGR in ticks was lower than in previous studies, several SFGR causing human infection may be present., (Copyright © 2024 Japanese Society of Chemotherapy, Japanese Association for Infectious Diseases, and Japanese Society for Infection Prevention and Control. Published by Elsevier Ltd. All rights reserved.)

Background and Objective: The disaccharide loading test is a method to assess gastric mucosal damage. Since Trelan-G75, which is used for the sugar tolerance test, contains disaccharide maltose, if maltose is detected at a high sensitivity in the sample blood used in the sugar tolerance test, screening for upper gastrointestinal mucosal damage can be made simultaneously with the sugar tolerance test for the diagnosis of diabetes., Methods: Glucose-6-phosphate is generated by treating maltose with maltose phosphorylase, β-phosphoglucomutase, and glucose-1,6-bisphosphate. Then, change in the absorbance at 405 nm is measured by the enzymatic cycling method using Thio-NADP, β-NADPH, and Glucose-6-phosphate dehydrogenase. After evaluating the optimal condition for this method, it is mounted on an automatic biochemical analyzer, and samples after the sugar tolerance test were assayed., Results: Regarding the performance of this method, the repeatability was 10-50 μmol/L with a CV of ≤1.1%. Concerning the assay range, a curve passing the origin with a range of linearity up to 120 μmol/L was obtained. No effect of dyes or sugars in the blood was noted. As a result of application to patients with gastric mucosal disorders (those who had a health checkup), significant differences were observed depending on the stage of atrophic gastritis., Discussion: This method has a high sensitivity and a high precision and can be used for high-speed analysis on an automatic analyzer. It has the potential to be used as a screening test for gastric mucosal damage., 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.

Objectives: Black spots (BSs) are lentiginous findings observed in the gastric body and fundus during upper gastrointestinal endoscopy and are predominantly seen in patients undergoing Helicobacter pylori eradication treatment. However, the detailed patient background and exact composition are poorly understood. This study aims to clarify the clinicopathological features of BSs, examine patient demographics, and use the NanoSuit-correlative light and electron microscopy (CLEM) method combined with scanning electron microscopy-energy dispersive X-ray spectroscopy for elemental analysis., Methods: Patients who underwent upper gastrointestinal endoscopy between 2017 and 2022 were included. Data on age, medications, blood tests, and H. pylori infection status were retrospectively gathered from medical records. Univariate analysis was conducted to examine BS presence, with results then used in a multivariate model to identify associated risk factors. Additionally, pathological specimens from patients with BSs were analyzed for elemental composition using the NanoSuit-CLEM method combined with scanning electronmicroscopy-energy dispersive X-ray spectroscopy., Results: An analysis of 6778 cases identified risk factors for BSs, including older age and using proton pump inhibitors, statins, corticosteroids, and antithrombotic drugs. Endoscopically, BSs correlated with higher gastric atrophy and lower active H. pylori infection. Iron deposition at BS sites was specifically identified using NanoSuit-CLEM., Conclusions: BSs on gastrointestinal endoscopy may indicate an absence of active H. pylori inflammation. The discovery of iron deposition within BSs using the NanoSuit-CLEM method has offered new insights into the possible causative factors and advances our understanding of the etiology of BSs, bringing us closer to unraveling the underlying mechanisms of their formation., Competing Interests: None., (© 2024 The Author(s). DEN Open published by John Wiley & Sons Australia, Ltd on behalf of Japan Gastroenterological Endoscopy Society.)

Objective: Glioma and meningioma require vastly different surgical approaches, even if only involving a simple craniotomy procedure. Diffusion weighted imaging (DWI) is useful for the postoperative evaluation of ischemic damage. The present study evaluated the expected but unproven differences in DWI findings., Methods: A total of 41 patients with meningiomas and 63 with gliomas met the inclusion criteria for adult cases with superficial lesions treated through simple supratentorial craniotomy. Postoperative DWI findings of DWI-positive rate, DWI-positive area type, and relationship with neurological deficits were evaluated., Results: The DWI-positive rate (P = 0.01) and the proportion of rim-type lesions (P < 0.01) were significantly more common in gliomas. Patients with meningiomas and DWI-positive areas presented with higher rates of new neurological deficits (P < 0.01), and patients with meningiomas on the left side were more likely to develop new neurological deficits (P = 0.02). Patients with gliomas tended to develop new deficits with larger DWI-positive area volumes (P = 0.04)., Conclusions: Postoperative early DWI-positive rate and rim-type lesions are more common after glioma resection than meningioma resection. Larger volumes of DWI-positive areas may be associated with postoperative neurological symptoms in gliomas. DWI-positive finding is less common after meningioma than glioma resection but more likely to be associated with new neurological symptoms. These differences are important for adequate postoperative DWI evaluation of common supratentorial brain tumors., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background and Aims: Pharmacokinetic parameters, such as drug plasma level at trough, time to maximum plasma concentration (T max ), and coagulation factor Xa (FXa) activity generally predict factors for the anticoagulant effects of direct oral anticoagulants (DOACs). Although GI bleeding is a major adverse event after endoscopic submucosal dissection (ESD), little is known about the association between post-ESD bleeding in patients taking DOACs and the pharmacologic parameters. This study aimed to evaluate pharmacologic risk factors for post-ESD bleeding in patients taking DOACs., Methods: We prospectively evaluated the incidence of post-ESD bleeding in patients taking DOACs between April 2018 and May 2022 at 21 Japanese institutions and investigated the association with post-ESD bleeding and pharmacologic factors, including plasma concentration and FXa activity at trough and T max ., Results: The incidence of post-ESD bleeding was 12.8% (14 of 109; 95% confidence interval [CI], 7.2-20.6). Although plasma DOAC concentration and plasma level/dose ratio at trough and T max varied widely among individuals, a significant correlation with plasma concentration and FXa activity was observed (apixaban: correlation coefficient, -0.893; P < .001). On multivariate analysis, risk factors for post-ESD bleeding in patients taking DOACs were higher age (odds ratio [OR], 1.192; 95% CI, 1.020-1.392; P = .027) and high anticoagulant ability analyzed by FXa activity at trough and T max (OR, 6.056; 95% CI, 1.094-33.529; P = .039)., Conclusions: The incidence of post-ESD bleeding in patients taking DOACs was high, especially in older patients and with high anticoagulant effects of DOACs. Measurement of pharmacokinetic parameters of DOACs may be useful in identifying patients at higher risk of post-ESD bleeding., Competing Interests: Disclosure This study was supported in part by a grant-in-aid from Scientific Research (C) (21K07949) and from the Japanese Gastroenterological Association (2020-1). The following author disclosed financial relationships: S. Suzuki: Honoraria for lectures from Fujifilm Corporation, MC Medical, Inc, Mochida Pharmaceutical Co, Ltd, Olympus Corporation, and Takeda Pharmaceutical Company. All other authors disclosed no financial relationships., (Copyright © 2024 American Society for Gastrointestinal Endoscopy. Published by Elsevier Inc. All rights reserved.)

Introduction: Administration of adipose-derived stem cells (ADSCs) into the joint cavity has been shown to alleviate the symptoms of knee osteoarthritis (OA) by releasing exosomes and anti-inflammatory cytokines. However, the therapeutic effect of these cells is limited by their rapid disappearance after administration. Thus, it is necessary to prolong cell survival in the joint cavity. This study aimed to investigate the potential application of ADSCs adhered to atelocollagen microspheres (AMSs) for cell therapy of knee OA., Methods: ADSCs were cultured for 2, 4, and 7 days in AMS suspension or adherent culture dishes. The supernatants were analyzed for IL-10 and exosome secretion via enzyme-linked immunosorbent assay and Nanosight. The effect of AMS was compared with that of adherent-cultured ADSCs (2D-cultured ADSCs) using transcriptome analysis. Moreover, the solubility of AMS and viability of ADSCs were evaluated using synovial fluid (SF) from patients with knee OA., Results: Compared with 2D-cultured ADSCs, AMS-cultured ADSCs exhibited a significant increase in secretion of exosomes and IL-10, and the expression of several genes involved in extracellular matrix and immune regulation were altered. Furthermore, when AMS-cultured ADSCs were cultured in SF from knee OA patients to mimic the intra-articular environment, the SF dissolved the AMSs and released viable ADSCs. In addition, AMS-cultured ADSCs showed significantly higher long-term cell viability than 2D-cultured ADSCs., Conclusion: Increased survival of AMS-adhered ADSCs was observed in the intra-articular environment, and AMSs were found to gradually dissipate. These results suggest that AMS-adhered ADSCs are promising source for cell therapy of knee OA., Competing Interests: The authors declared that there is no conflict of interest regarding the publication of this paper., (© 2024 The Japanese Society for Regenerative Medicine. Production and hosting by Elsevier B.V.)

Ustekinumab is prescribed for the treatment of patients with steroid-resistant moderate to severe Crohn's disease. We investigated its clinical outcome in patients with small and large intestinal lesions. Patients who were newly administered ustekinumab between March 2014 and December 2020 at Hamamatsu University Hospital were included in the study. The primary endpoint was Crohn's disease activity index score at baseline and weeks 8, 24, and 48 after the initiation of treatment, and secondary endpoints were albumin, hemoglobin, and C-reactive protein at these time points. Ustekinumab treatment retention was examined in both groups; the 2 groups were compared using the Friedman test, Mann-Whitney U test, or Fisher exact test. Overall, Crohn's disease activity index scores improved between baseline and 48 weeks, but the difference was not significant. However, there was a significant improvement between baseline and 48 weeks in patients with lesions in the small intestine only. Overall, patients showed significant improvement in albumin levels between baseline and 48 weeks but not in C-reactive protein or hemoglobin levels. When limited to patients with lesions in the small intestine, albumin and hemoglobin levels showed significant improvement. Both types showed high rates of treatment retention, although there was no significant difference. Ustekinumab appears to be a safe and effective treatment option that may be particularly effective in patients with lesions in the small intestine only., Competing Interests: The authors have no funding and conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

High-intensity interval training (HIIT) reportedly enhances the functional properties of the musculoskeletal system. However, the effects of HIIT on tendons remain unclear. Sixteen male rats were randomly assigned to the control (Con) or HIIT group (n = 8 in each group). Rats in the HIIT group executed the HIIT program consisting of 2.5 min treadmill running and 4.5 min rests between the bouts, 5 days per week for 9 weeks. Running speed, number of sets, and inclination were incrementally increased during the training period. Histological analysis revealed no apparent morphological changes in the extracellular matrix structure or nuclei of tenocytes between the groups. Real-time reverse transcription polymerase chain reaction analysis revealed that Igf1Ea mRNA expression was enhanced in the HIIT group. Furthermore, Igfbp5 mRNA expression tended to be higher in the HIIT group. The 9-week HIIT program enhanced tenogenic Igf1Ea mRNA expression., (© 2024. The Author(s), under exclusive licence to Springer Nature B.V.)

Background: Endoscopic resection is widely accepted as a local treatment for rectal neuroendocrine tumors sized ≤ 10 mm. However, there is no consensus on the best method for the endoscopic resection of rectal neuroendocrine tumors. As a simplified endoscopic procedure, endoscopic submucosal resection with a ligation device (ESMR-L) indicates a histologically complete resection rate comparable to that of endoscopic submucosal dissection (ESD). We hypothesized that ESMR-L than ESD would be preferred for rectal neuroendocrine tumors. Hence, this trial aimed to verify whether ESMR-L is non-inferior to ESD in terms of histologically complete resection rate., Methods: This is a prospective, open-label, multicenter, non-inferiority, randomized controlled trial of two parallel groups, conducted at the Shizuoka Cancer Center and 31 other institutions in Japan. Patients with a lesion endoscopically diagnosed as a rectal neuroendocrine tumor ≤ 10 mm are eligible for inclusion. A total of 266 patients will be recruited and randomized to undergo either ESD or ESMR-L. The primary endpoint is the rate of en bloc resection with histologically tumor-free margins (R0 resection). Secondary endpoints include en bloc resection rate, procedure time, adverse events, hospitalization days, total devices and agents cost, adverse event rate between groups with and without resection site closure, outcomes between expert and non-expert endoscopists, and factors associated with R0 resection failure. The sample size is determined based on the assumption that the R0 resection rate will be 95.2% in the ESD group and 95.3% in the ESMR-L group, with a non-inferiority margin of 8%. With a one-sided significance level of 0.05 and a power of 80%, 226 participants are required. Assuming a dropout rate of 15%, 266 patients will be included in this study., Discussion: This is the first multicenter randomized controlled trial comparing ESD and ESMR-L for the R0 resection of rectal neuroendocrine tumors ≤ 10 mm. This will provide valuable information for standardizing endoscopic resection methods for rectal neuroendocrine tumors., Trial Registration: Japan Registry of Clinical Trials, jRCTs042210124. Registered on Jan 6, 2022., (© 2024. The Author(s).)

Background: Long tubular duplication is a rare congenital intestinal disease, that can lead to emergency situations marked by massive hemorrhage. However, preoperative diagnosis and surgical treatment are challenging. This report presents preoperative images and details a surgical procedure for long tubular intestinal duplications with massive hemorrhage., Case Presentation: A 3-year-old boy presented to the emergency department with melena. Despite undergoing a Tc-99m pertechnetate scintigraphy one year prior, which revealed nonspecific findings with enhancement of some parts of the intestine, enhanced abdominal CT revealed an edematous small intestine with luminal extravasation. The patient received a transfusion of red blood cells; however, his hemoglobin level did not improve. Arterial angiography and double-balloon endoscopy revealed no remarkable findings. Exploratory laparotomy revealed a long tubular duplication in half of the small intestine. Utilizing the Wrenn procedure, we successfully removed all duplicate mucosa. Pathological findings showed that almost all duplications contained gastric mucosa and revealed an ulcer with a ruptured arterial vessel. His symptoms were resolved, and the hemoglobin level stabilized. At 2 months postoperatively, no surgical complications were present., Conclusions: Effective management of long tubular duplications with massive hemorrhage involves timely application of the Wrenn procedure. Recognition of specific imaging findings is crucial to prompt exploratory laparotomy, ensuring optimal outcomes and preventing delays in treatment., (© 2024. The Author(s).)

Anti-tumor necrosis factor (TNF) -α antibodies, including infliximab (IFX), adalimumab (ADA), and golimumab, which were the first biologic therapeutic agents, have a crucial position in advanced therapy for ulcerative colitis (UC). We aimed to investigate serum albumin (Alb) change as a prognostic factor for the therapeutic effect of ADA in UC. Thirty-four patients with UC treated with ADA were enrolled in this study and were divided into failure and non-failure groups. Biological data, such as Alb were compared between the two groups. Thirteen patients showed failure within six months. Examination of the biological data showed a significant difference between the two groups only in the week 2/week 0 Alb ratio. In receiver-operating characteristic (ROC) curve analysis to predict failure, the cut-off value of week 2/week 0 Alb ratio was 1.00, and the area under the curve was 0.868 (95% confidence interval: 0.738-0.999). In addition, in the sub-group analysis of only clinically active patients, the week 2/week 0 Alb ratio of the non-failure group was significantly higher than that of the failure group, and the cut-off-value in ROC analysis was 1.00. Week 2/week 0 Alb ratio ≤ 1 predicts failure within six months of ADA for UC., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Ishida et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Genetic testing has been increasingly used in several fields. In many applications, nucleic acid amplification technology is required. However, current methods to detect nucleic acid amplification require expensive reagents and special equipment or exhibit limited sensitivity, which hinders their use. To address this issue, this study reports an assay method for detecting occurrence of acid amplification in post-amplification samples using pyrophosphate, a highly sensitive byproduct of nucleic acid amplification. The method proposed requires two reagents and an automated analyzer. First, hydrogen peroxide is derived from pyrophosphate, an indicator of nucleic acid amplification, and the oxidizing power of hydrogen peroxide is used to produce Fe (III) from Fe (II). The specific metal chelator 5-Br-PAPS forms a complex with the trivalent iron produced, resulting in a highly sensitive coloration. The within-run reproducibility of our method (n = 20) was less than 3.67% at each concentration tested, and the detection limit was 0.075 μmol/L, sufficient for quantitative analysis. The technique described could detect pyrophosphate in a sample that was amplified using the loop-mediated isothermal amplification method after only 10 min. Therefore, the proposed method has the potential to be a new, rapid, and simple detection technique for amplified nucleic acids., 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 Elsevier Inc. All rights reserved.)

Hydrogel-based wound dressings have been developed for rapid wound healing; however, their adhesive properties have not been adequately investigated. Excessive adhesion to the skin causes wound expansion and pain when hydrogels absorb exudates and swell at wound sites. Herein, we developed a low-adhesion and low-swelling hydrogel dressing using alginate, which is non-adhesive to cells and skin tissue, CaCO 3 , and carbonated water. The alginate/CaCO 3 solution rapidly formed a hydrogel upon the addition of carbonated water, and the CO 2 in the hydrogel diffused into the atmosphere, preventing acidification and obtaining a pH value suitable for wound healing. Remarkably, the skin adhesion and swelling of the hydrogel were 11.9- to 16.5-fold and 1.9-fold lower, respectively, than those of clinical low-adhesion hydrogel dressings. In vivo wound-healing tests in mice demonstrated its therapeutic efficacy, and the prepared hydrogel prevented temporary wound dilation during early healing. These results illustrate the importance of controlling skin adhesion and swelling in wound dressings and demonstrate the potential clinical applications of this wound-friendly hydrogel dressing., 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 Elsevier B.V. All rights reserved.)

Introduction We introduced a novel numerical index known as posterior protrusion measures (PPM), derived from lateral plain radiograph images, which effectively serves to distinguish stable from unstable pertrochanteric fractures. The present study aims to scrutinize PPM values among two classified fracture patterns, stable and unstable, within the three-dimensional (3D) CT classification system, establishing a numeric threshold for PPM to differentiate between these groups; explore the potential relationship between the PPM index and unclassified categories; investigate how groups divided by the PPM threshold value can predict fracture stability based on 3D CT. Materials and methods In this study, three observers were tasked with measuring PPM on a single occasion. The chi-square test assessed the association between each demographic parameter on a categorical scale and stable/unstable groups. Continuous variables were also subject to examination. Receiver operating characteristic (ROC) analysis was employed to determine optimal cut-off points of PPM for predicting the presence of stable versus unstable groups. Additionally, the chi-square test examined the linear relation between separated groups based on the defined threshold PPM value and the stable/unstable groups. Results A total of 106 pertrochanteric fractures were identified using CT scan images and plain radiographs in the 3D CT classification system, revealing the stable group of 35 patients and the unstable group of 71 patients. The PPM values for stable/unstable fractures were, on average (± standard deviation), 0.34±0.25/0.50±0.29 for observer 1, 0.31±0.23/0.57±0.31 for observer 2, and 0.41±0.29/0.57±0.26 for observer 3, respectively (p<0.01). We established 0.3 as the cut-off value for PPM. The average PPM value among three observers represented each patient to assess fracture stability. The group with PPM <0.3 included 27 patients (16 stable and 11 unstable), and the group with PPM ≥0.3 group comprised 79 patients (19 stable and 60 unstable; p<0.005). Conclusion The present study revealed a significant difference in PPM values among stable and unstable 3D CT classification groups. Additionally, a threshold PPM value of 0.3 suggests a pivotal point for differentiating fracture stability. This innovative methodology makes a substantial contribution to clinical endeavors, potentially circumventing the necessity for 3D CT scanning., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2023, Noda et al.)

Background: Although the usefulness of endoscopic scores, such as the Mayo Endoscopic Subscore (MES), Ulcerative Colitis Endoscopic Index of Severity (UCEIS), and Ulcerative Colitis Colonoscopic Index of Severity (UCCIS), and biomarkers such as fecal calprotectin (FC) for predicting relapse in ulcerative colitis (UC) has been reported, few studies have included endoscopic scores for evaluating the entire colon., Aim: To compare the usefulness of FC value and MES, UCEIS, and UCCIS for predicting relapse in patients with UC in clinical remission., Methods: In total, 75 patients with UC in clinical and endoscopic remission who visited our institution between February 2019 and March 2022 were enrolled. The diagnosis of UC was confirmed based on the clinical presentation, endoscopic findings, and histology, according to the current established criteria for UC. Fecal samples were collected the day before or after the colonoscopy for measurement of FC. Endoscopic evaluations were performed using MES, UCEIS, and UCCIS. The primary outcome measure of this study was the assessment of the association between relapse within 12 mo and MES, UCEIS, UCCIS, and FC. The secondary outcome was the comparison between endoscopic scores and biomarkers in enrolled patients with UC with mucosal healing., Results: FC and UCCIS showed a significant correlation with UCEIS ( r = 0.537, P < 0.001 and r = 0.957, P < 0.001, respectively). Receiver-operating characteristic analysis for predicting MES 0 showed that the area under the curve of UCCIS was significantly higher than that of FC ( P < 0.01). During the 1-year observation period, 18 (24%) patients experienced a relapse, and both the FC and UCCIS of the relapse group were significantly higher than that of the remission group. The cut-off values for predicting relapse were set at FC = 323 mg/kg and UCCIS = 10.2. The area under the curve of the receiver-operating characteristic analysis for predicting relapse did not show a significant difference between FC and UCCIS. The accuracy of the endoscopic scores and biomarkers in predicting relapse was 86.7% for UCCIS, 85.3% for UCEIS, 76.0% for FC, and 73.3% for MES., Conclusion: The three endoscopic scores and FC may predict UC relapse during clinical remission. Among these scores, UCEIS may be the most useful in terms of ease of evaluation and accuracy., Competing Interests: Conflict-of-interest statement: The authors have no conflicts of interest related to the manuscript., (©The Author(s) 2023. Published by Baishideng Publishing Group Inc. All rights reserved.)

Background A precise preoperative imaging classification system for pertrochanteric fractures is imperative due to the reported unreliability of the current classification system, which relies solely on plain radiographs. This study aims to achieve two primary objectives: (i) elucidate the reproducibility of pertrochanteric fracture evaluation based on the Revised Arbeitsgemeinschaft für Osteosynthesefragen/Orthopedic Trauma Association (AO/OTA) Classification, comparing plain radiographs and computed tomography (CT) scan images, and (ii) investigate the consistency of fracture classification between both imaging modalities. Methods A total of 523 patients (112 males and 411 females, mean age 85 years) who had both preoperative plain radiographic and three-dimensional CT images were enrolled in this study. Following the Revised AO/OTA Classification, three individual observers initially classified the fractures in plain radiograph images as either Stable (A1) or Unstable (A2). Subsequently, they further categorized them into five sub-categories (A1.1, A1.2, A1.3, A2.2, and A2.3). The same classification system was applied to the CT scan images. Inter-observer agreement and consistency of fracture classification between plain radiographs and CT scan images were assessed. Results The inter-observer agreement for fractures classified as stable or unstable using only plain radiographs was found to be fair among the three observers, with a mean κ of 0.397 (95% CI: 0.316-0.478). However, inter-observer agreement improved significantly when using CT scans, with a mean κ of 0.590 (95% CI: 0.518-0.662). Our results demonstrated a consistency level between two graphical modalities ranging from fair to moderate, with κ values of 0.581, 0.383, and 0.335, respectively. It's worth noting that plain radiographic classification occasionally resulted in underestimations, with each observer identifying 16.1%, 34.0%, and 37.9%, respectively, of cases as A1 in plain radiographs that were classified as A2 in CT scans. Conclusions This study reveals a moderate to substantial level of inter-observer agreement for fracture classification when using CT scan images, in contrast to plain radiographs. Fracture evaluation relying solely on plain radiographs sometimes underestimates fracture classification and exhibits less consistency compared to using CT scan images., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2023, Noda et al.)

Background: Evidence of small-bowel capsule endoscopy (SBCE) for evaluating lesions in Crohn's disease (CD) is lacking. We aimed to clarify the effectiveness and safety of SBCE in a large sample of patients with CD., Methods: This multicenter prospective registration study recorded the clinical information and SBCE results of patients with definitive CD (d-CD) or suspected CD (s-CD). The primary outcomes were the rates of successful assessment of disease activity using SBCE, definitive diagnosis of CD, and adverse events. Secondary outcomes were the assessment of SBCE findings in patients with d-CD and s-CD and factors affecting SBCE incompletion and retention; and tertiary outcomes included the association between clinical disease activity or blood examination, endoscopic disease activity, ileal CD, and the questionnaire assessment of patient acceptance of SBCE., Results: Of 544 patients analyzed, 541 underwent SBCE with 7 (1.3%) retention cases. Of 468 patients with d-CD, 97.6% could be evaluated for endoscopic activity. Of 76 patients with s-CD, 15.8% were diagnosed with 'confirmed CD'. CD lesions were more frequently observed in the ileum and were only seen in the jejunum in 3.4% of the patients. Male sex and stenosis were risk factors for incomplete SBCE, and high C-reactive protein levels and stenosis were risk factors for capsule retention. In L1 (Montreal classification) patients, clinical remission was associated with endoscopic remission but showed low specificity and accuracy. The answers to the acceptability questionnaire showed the minimal invasiveness and tolerability of SBCE., Conclusion: SBCE is practical and safe in patients with CD., (© 2023. The Author(s).)

Although immunohistochemistry (IHC) for mismatch repair (MMR) proteins (MMR IHC) is used to identify DNA MMR status, universal screening of all patients with colorectal cancer (CRC) using a combination of both MMR IHC and genetic testing for the BRAFV600E mutation is limited in Japan. This study aimed to better understand the histopathological characteristics of CRCs, which exhibit both deficient mismatch repair (dMMR) and BRAFV600E mutation. MMR IHC of formalin-fixed paraffin-embedded tissues from tumor areas obtained from 651 patients with CRC who underwent surgical resection at Hamamatsu University Hospital (Hamamatsu, Japan) between August 2016 and March 2022 were used to evaluate MMR status, which was determined by staining for the expression of 4 MMR proteins (MLH1, MSH2, PMS2, and MSH6). All dMMR tumors were additionally evaluated for BRAFV600 mutation status via Sanger sequencing. Patient clinical characteristics (age, sex, tumor location, size, and tumor pathology) were then classified using their dMMR and BRAFV600 mutation statuses. Among the 651 patients with CRC, 58 carried tumors with dMMR, of which 52 were deficiency in MLH1 (dMLH1). Interestingly, all 16 medullary carcinomas that were analyzed showed characteristics corresponding to the presence of both dMLH1 and BRAFV600E mutation (P = .01). These results suggest that colorectal medullary carcinomas can be diagnosed based on their unique characteristics of harboring the BRAFV600E mutation and exhibiting dMLH1 expression., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2023 the Author(s). Published by Wolters Kluwer Health, Inc.)

The realization that soluble factors secreted by heterotypic cells play an importanta role in paracrine signaling, which facilitates intercellular communication, enabled the development of physiologically relevant co-culture models for drug screening and the engineering of tissues, such as hepatic tissues. The most crucial issues confronting the use of conventional membrane inserts in segregated co-culture models that are used to study paracrine signaling between heterotypic cells have been identified as long-term viability and retention of cell-specific functions, especially when isolated primary cells are used. Herein, we present an in vitro segregated co-culture model consisting of a well plate incubated with rat primary hepatocytes and normal human dermal fibroblasts which were segregated using a membrane insert with silica nonwoven fabric (SNF) on it. SNF, which mimics a physiological environment much more effectively than a two-dimensional (2D) one, promotes cell differentiation and resultant paracrine signaling in a manner that is not possible in a conventional 2D culture, owing to high mechanical strength generated by its inorganic materials and interconnected network structure. In segregated co-cultures, SNF clearly enhanced the functions of hepatocytes and fibroblasts, thereby showing its potential as a measure of paracrine signaling. These results may advance the understanding of the role played by paracrine signaling in cell-to-cell communication and provide novel insights into the applications of drug metabolism, tissue repair, and regeneration., (© 2023 The Authors. Biotechnology and Bioengineering published by Wiley Periodicals LLC.)

Background: Trauma is a serious medical and economic burden worldwide, and patients with traumatic injuries have a poor survival rate after cardiac arrest. The authors developed a prediction model specific to prehospital trauma care and used machine learning techniques to increase its accuracy., Methods: This retrospective observational study analyzed data from patients with blunt trauma injuries due to traffic accidents and falls from January 1, 2018, to December 31, 2019. The data were collected from the National Emergency Medical Services Information System, which stores emergency medical service activity records nationwide in the United States. A random forest algorithm was used to develop a machine learning model., Results: The prediction model had an area under the curve of 0.95 and a negative predictive value of 0.99. The feature importance of the predictive model was highest for the AVPU (Alert, Verbal, Pain, Unresponsive) scale, followed by oxygen saturation (SpO 2 ). Among patients who were progressing to cardiac arrest, the cutoff value was 89% for SpO 2 in nonalert patients., Conclusions: The machine learning model was highly accurate in identifying patients who did not develop cardiac arrest.

Immobilization or aging associated with limited physical activity can lead to the functional deterioration of tendons, which has become an important public health concern. Therefore, growing research is focused on the effect of exercise training on preserving tendon function. Exercise training subjects muscles and tendons to repeated mechanical stress, and in vitro studies have revealed that repetitive mechanical loading stimulates tendon cell responses to changes in the extracellular matrix and functional properties of the tendon. However, although several types of exercise training have been shown to be effective in preserving tendon function, no studies have investigated the impact of high-intensity interval training (HIIT), which involves composing short bouts of exercise with high-power output. Here, we determined whether the HIIT program enhanced tenogenic progressions by measuring the mRNA expression in rat Achilles tendons. Sixteen rats were randomly assigned into either a sedentary control group (Con, n = 8) or an HIIT group (n = 8). Rats in the HIIT group performed the program with treadmill running; the training volume was incremental (running speed, number of sets, and inclination), and training was conducted 5 days per week for 9 weeks. The rats in the HIIT group exhibited a marked decrease in the body weight and different types of fat weights, and a marked increase in different types of muscle weights. Real-time reverse transcription polymerase chain reaction analysis revealed that mRNA expressions of tendon-related genes Tnxb, Opn, and Tgfb1 were upregulated in the HIIT group compared to that in the Con group. Cross-links in mRNA expressions of collagen-related Dcn and Fmod in the HIIT group tended to be higher than in those Con group. These results suggest that HIIT induces initiation of tenogenic progression and stimulation of cross-link formation between collagen fibrils in rat Achilles tendons., 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 Elsevier Inc. All rights reserved.)

Vonoprazan (VPZ) inhibits gastric acid secretion more potently than proton pump inhibitors. Recently, attention has been focused on the dual therapy with VPZ and amoxicillin (AMOX) for the eradication of H. pylori. The dual VPZ/AMOX therapy attains the sufficient eradication rate with lowering the risk of adverse events in comparison with the triple therapy and quadruple therapy. Therefore, the dual VPZ/AMOX therapy is considered a useful eradication regimen for H. pylori infection.

The electrode tips of conventional monopolar forceps are relatively blunt, complicating the delicate detachment manipulations required for blepharoptosis repair. This study describes the SK forceps, which is a new monopolar electrosurgical forceps we specifically designed for blepharoptosis surgery. The electrode tips in our design were engineered to be as fine as possible. The SK forceps can cut tissues with the electrode tips in contact in the closed position and coagulate bleeding while clasping the blood vessels. When inactivated, the SK forceps can perform similar manipulations to regular surgical forceps. Surgeons holding the nonactivated SK forceps in one hand and regular forceps in the other benefit from greatly improved maneuverability at every step of the procedure. Incision and dissection procedures performed with the SK forceps result in a surgical field with minimal bleeding because the forceps can simultaneously perform hemostasis and incision, which is a characteristic of a high-frequency electrosurgical unit. However, when unexpected bleeding is encountered in the operative field, the SK forceps can clamp the injured vessels and coagulate the bleeding more rapidly and confidently compared with the needle-type monopolar electrodes without switching instruments. Our design allows surgeons to perform successive procedural steps without switching instruments. This characteristic makes the SK forceps a beneficial instrument for blepharoptosis surgery., (Copyright © 2023 The Authors. Published by Wolters Kluwer Health, Inc. on behalf of The American Society of Plastic Surgeons.)

Introduction In a preliminary study of cephalo-medullary (CM) nailing in patients with femoral intertrochanteric fractures, the authors of this study found a 25% to 30% decrease in muscle strength, especially abduction force, during the postoperative follow-up period. This decline was partially attributed to the entry point for the nail insertion causing damage to the gluteus medius tendon at the junction of the greater trochanter after reaming. Therefore, we assumed that changing the position of nail insertion to a "bald spot (BS)" could mitigate postoperative functional impairment. Automated computed tomography (CT) imaging of skeletal muscle cross-sectional area (CSA) and adipose tissue ratio (ATR) can show pathological changes on the operated side compared with the non-operated side. In this study, the authors quantified the difference in postoperative CSA and ATR of the gluteus medius muscle after bald spot nailing versus nail insertion through the conventional tip of the greater trochanter. It was hypothesized that bald spot nailing could avoid significant injury to the gluteus medius muscle. Materials and methods Patients with femoral intertrochanteric fractures were grouped according to the site of cephalo-medullary nailing: greater trochanteric tip (TIP) in 27 patients (8 men and 19 women, mean age 84.9±5.1 years) and BS in 16 patients (3 men and 13 women, mean age 86.9±6.2 years). The CSA and ATR of the gluteus medius muscles were assessed in three slices (A, B, and C from proximal to distal). Each slice was manually traced and automatically calculated based on its contour. Adipose tissue (-100 to -50 in Hounsfield units) in the designated area was distinguished by a bimodal image histogram resulting from the distribution of CT numbers of adipose tissue and muscle. The body mass index (BMI) was used to correct the CSA in each patient. Results In the TIP group, the mean CSA values (mm 2 ) from the non-operated/operated sides were as follows: slice A, 2180.2 ± 616.5/1976.3 ± 421.2; slice B, 2112.3 ± 535.7/1857.7 ± 386.7; and slice C: 1671.8 ± 460.0/1404.1 ± 404.3 (p<0.01 in slices A, B, and C). In the BS group, slice A was 2044.1 ± 473.0/2016.9 ± 388.4; slice B was 2073.2 ± 540.7/1848.3 ± 411.1; and slice C was 1659.1 ± 477.2/1468.5 ± 341.7 (p=0.34 in slice A, and p<0.05 in slices B and C, respectively). The mean CSA values (mm 2 ) of the non-operated minus operated side between the TIP/BS groups were as follows: slice A, 241.3 ± 424.3/-11.8 ± 285.6; slice B, 290.3 ± 313.0/211.8 ± 333.2; and slice C, 276.4 ± 270.4/162.8 ± 319.3 (p < 0.05 in slice A, 0.45, 0.24 in slices B, C, respectively). The mean adjusted CSA per BMI values (mm 2 ) of the non-operated minus the operated side between the TIP/BS groups were slice A, 10.6 ± 19.7/-0.4 ± 14.8; slice B, 13.3 ± 15.0/10.1 ± 16.3; and slice C, 13.1 ± 13.4/ 8.7 ± 15.3 (p < 0.05 in slice A and 0.54 and 0.36 in slices B and C, respectively). Conclusion Nail insertion at the bald spot resulted in a significantly smaller decrease in the CSA of the gluteus medius muscle compared with the conventional tip entry. In addition, an examination of BMI-adjusted CSA showed that CSA was maintained in some image slices. These results suggest that nailing from the BS of the greater trochanter can reduce damage to the gluteus medius muscle and highlight the importance of imaging beyond the usual assessment of skeletal changes., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2023, Noda et al.)

Background: Anesthetic management of pheochromocytoma and paraganglioma with Fontan circulation is challenging for physicians, with attention to cardiovascular physiology., Case Presentation: We performed anesthetic management for pheochromocytoma and paraganglioma in three patients with Fontan circulation. We maintained intraoperative central venous pressure at preoperative level under fluid infusion and administrating nitric oxide to decrease pulmonary arterial resistance. We administered noradrenaline or vasopressin if low blood pressure was present despite adequate central venous pressure. Although noradrenaline is prevalent for the case of noradrenaline-secreting tumor especially after resection, we could maintain blood pressure to administrate vasopressin without increasing central venous pressure. Retroperitoneal laparoscopic approach which could avoid intra-abdominal adhesions might be selectable as case 3., Conclusions: Sophisticated management is required for pheochromocytoma and paraganglioma with Fontan circulation., (© 2023. The Author(s).)

Anionic polysaccharides, including low-methoxy (LM) pectin, are extensively used in biomaterial applications owing to their safety, biocompatibility, and feasibility in constructing supramolecular assemblies by forming egg-box structures with divalent cations. Mixing an LM pectin solution with CaCO 3 spontaneously forms a hydrogel. The gelation behavior can be controlled by adding an acidic compound to change the solubility of CaCO 3 . CO 2 is used as the acidic agent and can be easily removed after gelation, thereby reducing the acidity of the final hydrogel. However, CO 2 addition has been controlled under varied thermodynamical conditions; therefore, specific CO 2 effects on gelation are not necessarily visualized. To evaluate the CO 2 impact on the final hydrogel, which would be extended to control hydrogel properties further, we utilized carbonated water to supply CO 2 into the gelation mixture without changing its thermodynamic conditions. The addition of the carbonated water accelerated gelation and significantly increased the mechanical strength, promoting cross-linking. However, the CO 2 volatilized into the atmosphere, and the final hydrogel became more alkaline than that without the carbonated water, probably because a considerable amount of the carboxy group was consumed for cross-linking. Moreover, when aerogels were prepared from the hydrogels with carbonated water, they exhibited highly ordered networks of elongated porosity in scanning electron microscopy, proposing an intrinsic structural change by CO 2 in the carbonated water. We also controlled the pH and strength of the final hydrogels by changing the CO 2 amounts in the carbonated water added, thereby validating the significant effect of CO 2 on hydrogel properties and the feasibility of using carbonated water., Competing Interests: The authors declare no competing financial interest., (© 2023 The Authors. Published by American Chemical Society.)

Background: Surgical evacuation of intracranial hematoma, including epidural, subdural, intracerebral, and intraventricular hematoma, is recommended in patients with traumatic brain injury (TBI) for prevention of cerebral herniation and possible saving of life. However, preoperative coagulopathy is a major concern for emergent surgery on patients with severe TBI., Methods: We reviewed 65 consecutive patients with severe TBI who underwent emergency craniotomy for intracranial hematomas., Results: Univariate analysis showed preoperative pupil abnormality, absence of pupil light reflex, respiratory failure, preoperative thrombocytopenia (< 100 × 10 9 /L), increased activated partial thromboplastin time (> 36 s), low fibrinogen (< 150 mg/dL), platelet transfusion, red cell concentrate transfusion, and presence of brain contusion and traumatic subarachnoid hemorrhage (SAH) on computed tomography were correlated with poor outcome (death or vegetative state). Multivariate analysis revealed that pupil abnormality (p = 0.001; odds ratio [OR] 0.064, 95% confidence interval [CI] 0.012-0.344), preoperative thrombocytopenia (p = 0.016; OR 0.101, 95% CI 0.016-0.656), and traumatic SAH (p = 0.021; OR 0.211, 95% CI 0.057-0.791) were significant factors. Investigation of the 14 patients with preoperative thrombocytopenia found the emergency surgery was successful, with no postoperative bleeding during hospitalization. However, half of the patients died, and almost a quarter remained in the vegetative state mainly associated with severe cerebral edema., Conclusions: Emergent craniotomy for patients with severe TBI who have preoperative thrombocytopenia is often successful, but the prognosis is often poor. Emergency medical care teams and neurosurgeons should be aware of this discrepancy between successful surgery and poor prognosis in these patients. Further study may be needed on the cerebral edema regulator function of platelets., (© 2021. Belgian Neurological Society.)

Knee osteoarthritis (Knee OA) is an irreversible condition that causes bone deformity and degeneration of the articular cartilage that comprises the joints, resulting in chronic pain and movement disorders. The administration of cultured adipose-derived stem cells (ADSCs) into the knee joint cavity improves the clinical symptoms of Knee OA; however, the effect of synovial fluid (SF) filling the joint cavity on the injected ADSCs remains unclear. In this study, we investigated the effect of adding SF from Knee OA patients to cultured ADSCs prepared for therapeutic use in an environment that mimics the joint cavity. An increase in the viability of ADSCs was observed following the addition of SF. Gene expression profiling of SF-treated ADSCs using DNA microarrays revealed changes in several genes involved in cell survival. Of these genes, we focused on FOSL1, which is involved in the therapeutic effect of ADSCs and the survival and proliferation of cancer stem cells. We confirmed the upregulation of FOSL1 mRNA and protein expression using RT-PCR and western blot analysis, respectively. Next, we knocked down FOSL1 in ADSCs using siRNA and observed a decrease in cell viability, indicating the involvement of FOSL1 in the survival of ADSCs. Interestingly, in the knockdown cells, ADSC viability was also decreased by SF exposure. These results suggest that SF enhances cell viability by upregulating FOSL1 expression in ADSCs. For therapy using cultured ADSCs, the therapeutic effect of ADSCs may be further enhanced if an environment more conducive to the upregulation of FOSL1 expression in ADSCs can be established.

Introduction A demographic survey of femoral pertrochanteric fractures provides several important information for the healthcare system of a country since this fracture is commonly seen in the elderly and has a poor postoperative functional prognosis that is a burden on society. The importance of accurately classifying pertrochanteric fractures as stable or unstable cannot be understated. However, the use of plain radiograph images alone is known to underestimate fracture severity with low inter- or intra-observer agreement. Computed tomography (CT) images offer information for a more accurate classification of pertrochanteric fractures. With this three-dimensional (3D) CT-based study using the revised Arbeitsgemeinschaft für Osteosynthesefragen/Orthopedic Trauma Association (AO/OTA) classification, the purpose of this study is to elucidate the epidemiological demography of patients with pertrochanteric fractures. Material and methods We retrospectively collected 808 patients from five hospitals, classified into two groups: stable (A1) or unstable (A2). Age, gender, fracture laterality, and surgery timing were identified as epidemiological variables. Patients with both preoperative plain radiographs and 3D CT scans were included in the study. The exclusion criteria were AO/OTA A3 type fractures, pathological fractures, previous ipsilateral surgery, 60 years old or younger, and conservatively treated patients. The primary outcome involved detailing the total number of fractures based on classification (A1 or A2) and variables. The secondary outcome involved a comparison between the A1 and A2 groups. Results The mean age of patients at the time of surgery was 85 years (range: 61-103 years). There were 637 female and 171 male patients. There were 463 left-sided fractures and 345 right-sided fractures. Of the 808 patients, 371 (45.9%) were classified to have A1 fractures, and 437 (54.1%) had A2 fractures. The age at surgery, gender, fracture laterality, and surgery timing between the A1 and A2 groups were compared. The mean and standard deviation of the age at surgery for patients in the A1 and A2 groups were 84.9±7.7 and 86.9±6.8, respectively. The number of patients for each age distribution of 61-69, 70-74, 75-79, 80-84, 85-89, 90-94, and 95 or older for the A1 and A2 groups was 18 and 7, 18 and 12, 43 and 44, 76 and 82, 107 and 132, 79 and 110, and 30 and 50, respectively, showing that the difference in categorial distribution was statistically significant (p=0.002). Overall, 278 females and 93 males were classified to have A1 fractures compared with 359 females and 78 males with A2 fractures (p=0.01). There were 166 right-sided and 205 left-sided stable A1 fractures and 179 right-sided and 258 left-sided A2 fractures (not significant (NS)). Among the total number of A1 and A2 surgeries by month, the most were in December with 77 surgeries (37 and 40, respectively), and the least was in June with 37 (18 and 19, respectively). The seasonal classification for A1 and A2 surgeries is as follows: spring with 172 (74 and 98, respectively), summer with 150 (70 and 80, respectively), autumn with 193 (90 and 103, respectively), and winter with 208 (97 and 111, respectively) (NS). Conclusion In this demographic study of 808 patients with pertrochanteric fractures classified by 3D CT images, 371 had A1 fractures and 437 had A2 fractures. A2 fractures were significantly more in females with an age peak of 85-89 years., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2023, Noda et al.)

Background: Post-endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis (PEP) is one of the most serious complications of ERCP. Various procedures can reduce the incidence of PEP, such as wire-guided cannulation, prophylactic pancreatic stent placement, and pretreatment anal insertion of NSAIDs. Recently, iso-osmolar contrast media (IOCM) have been used for ERCP in several hospitals to reduce the risk of PEP in Japan. However, the effect of IOCM is uncertain because few reports have examined IOCM in relation to PEP., Aim: This study aimed to investigate the relationship between contrast media used and the incidence of PEP., Methods: This retrospective study included all qualifying patients who had undergone ERCP at Hamamatsu University Hospital between January 2012 and January 2020. This study examined whether there was a difference in the onset of PEP between patients administered IOCM and high osmolar contrast medium (HOCM). Propensity score matching was used to analyze patient characteristics and ERCP procedures. Amidotrizoic acid was used as HOCM and iodixanol as IOCM., Results: ERCP was performed on 458 patients, and 830 procedures were conducted. After propensity score matching, 162 patients from the amidotrizoic acid group and 162 patients from the iodixanol group were selected. The incidence of PEP was 10.5% (17) in the amidotrizoic acid group and 9.3% (15) in the iodixanol group (P = 0.71). Changes in serum amylase levels post- and pre-ERCP were 240.6 ± 573.8 U/L and 142.7 ± 382.1 U/L in the amidotrizoic acid and iodixanol groups, respectively (P = 0.072)., Conclusion: Iodixanol had no prophylactic effect on PEP and clinical outcomes., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Matsuura et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Introduction The absence of a precise fracture classification system that classifies pertrochanteric fractures into either stable or unstable contributes to a burden on healthcare and has several major implications. We propose an innovative graphical index, which we refer to as posterior protrusion measures (PPM), using plain lateral view radiograph images for the revised AO Foundation (Arbeitsgemeinschaft für Osteosynthesesfragen)/Orthopedic Trauma Association (AO/OTA) classification system. This study aims to: (i) introduce the use of PPM for classifying fractures into stable or unstable under the revised AO/OTA classification system and set the threshold numeric value, (ii) elucidate the reproducibility of inter and intra-observer agreement, and investigate the consistency of fracture classification using PPM versus computed tomography (CT) scan images. Materials and methods Out of 146 patients identified from the database, a total of 126 patients were enrolled in the study. Pertrochanteric fractures were classified as either stable or unstable. Three surgeons were assigned for PPM determination. Regarding the demographical data, the chi-square test was used to assess the significance of each parameter on a categorical scale between the two groups. The independent sample t-test or the Mann-Whitney U test was used to compare the two independent groups. Interclass correlation coefficient (ICC) values for continuous variables and kappa values (κ) for categorical variables were calculated to assess inter-observer and intra-observer agreement. Receiver-operating characteristic (ROC) analysis was used to determine optimal cut-off points of PPM to predict consistency between separate fracture classification groups, one using PPM values with a threshold derived from plain radiograph images, and the other using CT scan images. Results Among a total of 126 pertrochanteric fractures, the A1 (stable) group consisted of 39 patients (10 males, 29 females), whereas the A2 (unstable) group consisted of 87 patients (14 males, 73 females) (not significant, NS). Intraclass correlation coefficient (ICC) values of PPM for the inter-observer agreement were 0.796 (0.723-0.852), 0.664 (0.554-0.751), and 0.702 (0.601-0.781) at first examination and 0.729 (0.635-0.801) at the second. The intra-observer agreement was 0.869 (0.819-0.906) and 0.603 (0.480-0.703). We examined for consistency of fracture classification group of PPM values with a threshold of 0.4 (A1<0.4, A2=0.4 or more) and CT-based group. For the first examination, there was mostly "moderate" agreement in fracture classification (stable or unstable) between plain radiograph and CT scan images, κ (95%CI): 0.427 (0.266-0.588), 0.493 (0.335-0.651), and 0.359 (0.176-0.544), and for the second, 0.418 (0.251-0.585), and 0.451 (0.284-0.620), respectively. Conclusion We propose a supplementary tool, namely PPM that allows for possible alternative classification of pertrochanteric fractures into A1 (stable) and A2 (unstable) using plain radiograph images under the revised AO/OTA classification system. In this study, a PPM threshold value of 0.4 demonstrated a moderate inter- and intra-observer agreement. It is noteworthy to mention that there was a satisfactory consistency of fracture classification using PPM derived from plain radiograph images when compared to classification using CT scan images. In addition, the PPM method provides a numerical score., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2022, Noda et al.)

Objective: The serrated pathway is a distinct genetic/epigenetic mechanism of the adenoma-carcinoma sequence in colorectal carcinogenesis. Although many groups have reported the genetic-phenotypic correlation of serrated lesions (SLs), previous studies regarding the serrated pathway were conducted on patients with SLs that have different germline and environmental genetic backgrounds. We aimed to compare pure somatic genetic profiles among SLs within identical patient with SPS., Results: We analyzed SLs from one patient with SPS (Case #1) and compared DNA variant profiles using targeted DNA multigene panels via NGS among the patient's hyperplastic polyp (HP), three sessile serrated lesions (SSLs), and one traditional serrated adenoma (TSA), and separately analyzed three SSLs and one tubular adenoma (TA) within another patient with SPS (Case #2). In two patients, known pathogenic variant of BRAF (c.1799 T > A, p.Val600Glu) was observed in one TSA and one SSL in Case #1, and in three SSLs within Case #2. The pure somatic pathogenic variant BRAF (c.1799 T > A, p.Val600Glu) among SLs with identical germline genetic background supports its importance as a strong contributor for SLs., (© 2022. The Author(s).)

Patients with adenomatous polyposis syndromes such as familial adenomatous polyposis are at higher risk of colorectal cancer, hence continuous management is necessary. However, little is known about the etiology of patients with numerous laterally spreading tumors (LSTs), or how genetic alterations uniquely influence LSTs in colorectal carcinogenesis. The present case report investigated a woman with >150 non-granular type LSTs (LST-NG) and one sigmoid colon cancer. After subtotal colectomy via ileorectal anastomosis, genetic and epigenetic analyses were conducted by comparing the profiles of the patient's normal colonic mucosa, four LST-NG lesions and a cancer lesion. Using customized multigene panel testing, no pathogenic germline mutations were detected, including APC regulator of WNT signaling pathway, but identified a somatic pathogenic variant of APC in one LST-NG lesion, and both TP53 and F-box and WD repeat domain containing 7 somatic mutations in the cancer. Comprehensive genome-wide methylation analysis showed that CpG island promoters at zinc finger protein 625, LON peptidase N-terminal domain and ring finger 2, WD repeat domain 17 and syndecan 2 were methylated in both LST-NG and cancer, which may contribute to colorectal tumorigenesis as early as the LST-NG phase., Competing Interests: The authors declare that they have no competing interests., (Copyright: © Iwaizumi et al.)

Objective: Differentiation of suprasellar xanthogranuloma (XG) from adult craniopharyngioma (CP) can be problematic in endoscopic extended transsphenoidal surgery., Methods: We reviewed the clinical data, preoperative imaging, intraoperative endoscopic findings, and intraoperative frozen section pathology in newly diagnosed adult CPs (19 patients) and XGs (6 patients)., Results: Intracystic signal intensity was often high on T1-weighted magnetic resonance images in the XGs but low in the CPs (P = 0.015). Capsular intensity was low on T2-weighted imaging in XGs but iso to high in CPs (P < 0.001). Capsular gadolinium enhancement was often seen in CPs and not in XGs (P < 0.001). CPs often had a solid component with contrast enhancement but none in XGs (P < 0.001). Intraoperative endoscopic observations frequently found a whitish solid component in the CPs but yellow to brown fibrous granulomatous lesions in XGs (P < 0.001). The tumor capsule was dark grayish and soft in CPs, whereas it was fibrously hard in XGs (P = 0.002). Yellowish hemosiderin deposits were seen in all XGs (P = 0.003). Intraoperative pathologic diagnosis of CP was all verified whereas no evidence of tumor was found in XGs (P < 0.001). Partial removal was performed in 4 patients with XGs. No recurrence was observed in these patients during the follow-up period (1.5-8 years)., Conclusions: Careful interpretation of preoperative magnetic resonance imaging, intraoperative endoscopic findings, and intraoperative frozen section diagnosis may be important for the differential diagnosis between XG and CP. In endoscopic-extended transsphenoidal surgery, intentional partial removal can be effective for XG after careful diagnosis., (Copyright © 2022 Elsevier Inc. All rights reserved.)