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Yuri Iwata,1 Yumiko Iwata,2 Hiroshi Iida,1 Masahiko Inamori,1 Shin Maeda3 1Department of Medical Education, Yokohama City University, Yokohama, Japan; 2Department of English Language, Communication and Cultures, University of the Sacred Heart, Tokyo, Japan; 3Department of Gastroenterology, Yokohama City University, Yokohama, JapanCorrespondence: Yuri Iwata, Department of Medical Education, Yokohama City University, School of Medicine, 3-9 Fukuura, Kanazawa-ku, Yokohama, Kanagawa, 236-0004, Japan, Tel +81-45-787-2626, Fax +81-45-787-2620, Email yuri.sagamed@gmail.comAim: To report on the effects of a smartphone application, among the medical staff and medical students, for learning English as a foreign language.Methods: We conducted an exploratory quasi-experimental study among eight medical staff and 10 medical students in Japan. The participants used an application called ABC Talking (created by ABC Talking Laboratories Inc, currently unavailable due to application renewal), loaded onto their smartphones, to talk with native English speakers from overseas. The participants used the application for five minutes twice a day over five consecutive days as per their convenience. The study collected quantitative and qualitative data using assessments on the participants’ listening and speaking skills and questionnaire. The assessment scores of the first five sessions were compared to those of the last five. Average self-assessment scores and teacher assessment scores were compared using a t-test. A paired t-test was performed on quantitative data of the questionnaire, and content analysis was performed on qualitative data.Results: More than 80% of the calls were made from home and 70% occurred between 9PM and 1AM. The participants’ self-assessment scores on their listening and speaking skills increased significantly from the first five sessions to the last five sessions (14.8– 26.1%). However, there was no significant change in the assessments by the teachers (− 4.5– 2.1%). The self-assessment scores of those with low English proficiency were lower than the teachers’ assessment scores. Improvement of communicative self-confidence and communicative competence, two factors that affect willingness to communicate, were seen from the questionnaire.Conclusion: Using smartphone applications allows on-demand English training, which may be especially useful to medical staff and students who have unpredictable work schedules. Teachers should be aware that learners tend to assess themselves lower than their actual ability so that they can give appropriate feedback to the learners.Keywords: limited English proficiency, communication, medical training, professional competence, language barrier

Kazuhito Misawa,1 Shinji Nakamichi,1 Hiroki Iida,1 Atsuhiro Nagano,1 Erika Mikami,1 Takehiro Tozuka,1 Masaru Matsumoto,1 Akihiko Miyanaga,1 Rintaro Noro,1 Kaoru Kubota,1 Hiroki Yamaguchi,2 Masahiro Seike1 1Department of Pulmonary Medicine and Oncology, Graduate School of Medicine, Nippon Medical School, Tokyo, 113-8603, Japan; 2Department of Hematology, Nippon Medical School, Tokyo, 113-8603, JapanCorrespondence: Shinji Nakamichi, Department of Pulmonary Medicine and Oncology, Graduate School of Medicine, Nippon Medical School, 1-1-5, Sendagi, Bunkyo-ku, Tokyo, 113-8603, Japan, Tel +81-3-3822-2131, Email snakamichi@nms.ac.jpAbstract: Alectinib is a selective anaplastic lymphoma kinase (ALK) tyrosine kinase inhibitor as standard therapy for ALK-rearranged non-small cell lung cancer (NSCLC). Hemolytic anemia is considered as a rare but significant adverse event with alectinib. Here, we report a case of a 73-year-old female with lung adenocarcinoma, harbouring an ALK fusion gene, who received alectinib as second-line therapy and developed gradually progressive grade 4 (6.4 g/dL) drug-induced hemolytic anemia (DIHA) after complete response. We discontinued alectinib and performed a blood transfusion for the severe anemia. The anemia improved with no recurrence of lung adenocarcinoma over 10 months. Regular hematologic monitoring and the possibility of DIHA should be considered in case of progressive hemolytic anemia during alectinib treatment.Keywords: non-small cell lung cancer, ALK, alectinib, drug-induced hemolytic anemia

Toshihiro Saito,1 Shuichi Komatsubara,2 Noboru Hara,3 Tsutomu Nishiyama,3 Akiyoshi Katagiri,4 Fumio Ishizaki,5 Akihiko Hatano,6 Takeshi Komeyama,7 Shugo Hanyu,8 Masahiro Terunuma,9 Tomoyuki Imai,10 Hideto Go,11 Hiroaki Iida,12 Shigenori Kurumada,13 Shunsuke Yamaguchi,4,14 Keisuke Takeda,5,15 Takashi Ando,14,15 Tatsuhiko Hoshii,5 Takashi Kasahara,5 Yoshihiko Tomita5 1Department of Urology, Niigata Cancer Center Hospital, Niigata, Japan; 2Department of Urology, Niigata Minami Hospital, Niigata, Japan; 3Department of Urology, Uonuma Institute of Community Medicine, Niigata University Medical and Dental Hospital, Minamiuonuma, Japan; 4Department of Urology, Niigata Prefectural Central Hospital, Joetsu, Japan; 5Department of Renal and Urinary Pathology, Graduate School of Medical and Dental Sciences, Niigata University, Niigata, Japan; 6Department of Urology, Niigata Prefectural Shibata Hospital, Shibata, Japan; 7Department of Urology, Nagaoka Red Cross Hospital, Nagaoka, Japan; 8Department of Urology, Kashiwazaki General Hospital and Medical Center, Kashiwazaki, Japan; 9Department of Urology, Nagaoka Chuo General Hospital, Nagaoka, Japan; 10Department of Urology, Niigata City General Hospital, Niigata, Japan; 11Department of Urology, Niigata Saiseikai Sanjo Hospital, Sanjo, Japan; 12Department of Urology, Joetsu General Hospital, Joetsu, Japan; 13Department of Urology, Saiseikai Niigata Hospital, Niigata, Japan; 14Department of Urology, Tachikawa General Hospital, Nagaoka, Japan; 15Department of Urology, Murakami General Hospital, Murakami, JapanCorrespondence: Toshihiro SaitoDepartment of Urology, Niigata Cancer Center Hospital, 2-15-3 Kawagishi-cho, Niigata, 951-8566, JapanTel +81-25-266-5111Fax +81-25-233-3849Email urotoshi@niigata-cc.jpPurpose: This study aims to investigate the utility of prostate-specific antigen (PSA) screening by conducting an all-case survey of newly diagnosed prostate cancer patients at Niigata Prefecture, Japan.Patients and Methods: Depending on whether patients were subjected to screening, information was prospectively collected on all prostate cancer patients newly diagnosed between October 1, 2019, and September 30, 2020, at all institutions in Niigata Prefecture where urologists performing prostate biopsy routinely work and differences in clinical parameters were investigated.Results: PSA was measured in 478 out of 1332 patients (35.8%) as part of a community health screening. The rate of metastatic carcinoma (M1) in all patients was 14.9%. When patients were divided into three categories of population-based screening (community health screening and workplace health screening), opportunistic screening (PSA measurements at complete medical check-ups or on patient request), and testing triggered by clinical symptoms or findings, the proportion of metastatic cancer was 4.5%, 3.7%, and 30.6%, respectively, demonstrating that the number of distant metastases was significantly lesser in all patients who underwent screening.Conclusion: The one-year all-case survey of newly diagnosed prostate cancer patients demonstrated that PSA screening significantly contributed to the early diagnosis of current prostate cancer in Japan.Keywords: prostate cancer, PSA screening, population-based screening, opportunistic screening, one-year all-case survey

We report a metal/light-free aerobic oxidative C-C bond formation using sp 3 C-H bond activation of tetrahydroisoquinolines catalyzed by flavin and iodine. The dual catalytic system enabled the oxidative Mannich and aza-Henry reactions by the cross-dehydrogenative coupling between two sp 3 C-H bonds. Furthermore, the flavin-iodine-coupled catalysis was applied to the synthesis of pyrrolo[2,1- a ]isoquinolines through the sequential oxidative 1,3-dipolar cycloaddition and dehydrogenative aromatization. The biomimetic flavin catalysis efficiently activates molecular oxygen; thus the non-metal dual catalytic system enables green oxidative transformation using molecular oxygen as an environmentally friendly terminal oxidant which generates benign water.

We investigated the plasma tumor necrosis factor (TNF)-α levels between patients with schizophrenia remission and healthy controls, and the association between the plasma TNF-α levels and cognitive function and social function. This cross-sectional study included 48 patients with schizophrenia who fulfilled the remission criteria and 20 healthy controls. Plasma TNF-α levels were measured using the enzyme-linked immunosorbent assay, and cognitive function was assessed using the Japanese version of the Brief Assessment of Cognition in Schizophrenia (BACS-J). We measured social function using the Social Functioning Scale (SFS-J). The plasma TNF-α levels were significantly lower in the remission schizophrenia group (31.7 ± 27.4 ng/mL) compared to the heathy control group (55.1 ± 38.5 ng/mL) (P = 0.01). In contrast, no correlation was observed between the plasma levels of TNF-α and all BACS-J scores and all SFS-J scores in either group. This result suggests that plasma TNF-α levels may serve as a clinical biomarker of remission of schizophrenia and that the plasma TNF-α levels bore no association with cognitive function. Thus, TNF-α may have potential as a useful indicator of the therapeutic response in patients with schizophrenia., Competing Interests: Declaration of competing interest None., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Purpose: This study aimed to evaluate a novel technique for cell tracking by visualising the activity of the human sodium/iodide symporter (hNIS) after transplantation of hNIS-expressing multilayered cell sheets in a rat model of chronic myocardial infarction., Methods: Triple-layered cell sheets were generated from mouse embryonic fibroblasts (MEFs) derived from mice overexpressing hNIS (hNIS-Tg). Myocardial infarction was induced by permanent ligation of the left anterior descending coronary artery in F344 athymic rats, and a triple-layered MEFs sheets were transplanted to the infarcted area two weeks after surgery. To validate the temporal tracking and kinetic analysis of the transplanted MEFs sheets, sequential cardiac single-photon emission computed tomography (SPECT) examinations with a 99m TcO 4 - injection were performed. The cell sheets generated using MEFs of wild-type mice (WT) served as controls., Results: A significantly higher amount of 99m TcO 4 - was taken into the hNIS-Tg MEFs than into WT MEFs (146.1 ± 30.9-fold). The obvious accumulation of 99m TcO 4 - was observed in agreement with the region where hNIS-Tg MEFs were transplanted, and these radioactivities peaked 40-60 min after 99m TcO 4 - administration. The volume of distribution of the hNIS-Tg MEF sheets declined gradually after transplantation, implying cellular malfunction and a loss in the number of transplanted cells., Conclusion: The reporter gene imaging with hNIS enables the serial tracking and quantitative kinetic analysis of cell sheets transplanted to infarcted hearts., (© 2024. The Author(s).)

Determining the mechanisms by which plants sense and respond to mechanical stimuli is crucial for unraveling the detailed processes by which plants grow and develop. Mechanosensitive (MS) channels, including MCA1 and its paralog MCA2 in Arabidopsis thaliana, may be essential for these processes. Although significant progress has been made in elucidating the physiological roles of MS channels, comprehensive insights into their expression dynamics remain elusive. Here, we summarize recent advancements and new data on the spatiotemporal expression patterns of the MCA1 and MCA2 genes, revealing their involvement in various developmental processes. Then, we describe findings from our study, in which the expression profiles of MCA1 and MCA2 were characterized in different plant organs at various developmental stages through histochemical analyses and semiquantitative RT‒PCR. Our findings revealed that MCA1 and MCA2 are preferentially expressed in young tissues, suggesting their pivotal roles in processes such as cell division, expansion, and mechanosensing. Lastly, we discuss the differential expression patterns observed in reproductive organs and trichomes, hinting at their specialized functions in response to mechanical cues. Overall, this review provides valuable insights into the dynamic expression patterns of MCA1 and MCA2, paving the way for future research on the precise roles of these genes in planta., (© 2024. The Author(s).)

Aim: To review the indications for rectal mucosal/submucosal biopsy (RMSBx) used for diagnosing Hirschsprung's disease (HD) in pediatric patients. Methods: The medical records of all children between 1 and 15 years old assessed for chronic constipation between 2012 and 2022 were reviewed. Until the end of 2018, enema usage (E+) was a major indication for RMSBx. In 2019, laxative use for 3 months irrespective of enema use was added as an indication (L+). To determine the relevance of enema usage, L+ was subdivided by enema usage into (L+E+) and (L+E-) groups. The effect of changing the indications for RMSBx on the incidence of HD was investigated. Results: Of 562 eligible subjects, E+ = 410, L+ = 152; demographics are similar. RMSBx rate in E+ (E+RMSBx) was 36/410 (8.8%) and in L+ (L+RMSBx) was 42/152 (27.6%;) ( P < .05). For L+RMSBx, 15/42 were L+E+ and 27/42 were L+E-. HD incidence in E+RMSBx was 8/36 (22.2%; E+HD) and in L+RMSBx was 13/42 (31.0%; L+HD) ( p = ns). In L+RMSBx, HD incidence in L+E+ was 5/15 (33.3%; L+E+HD) and in L+E- was 8/27 (29.6%; L+E-HD) ( P = ns). Differences in daily bowel motion frequency 6 months postoperatively were not statistically significant; E+HD (1.75/d) versus L+HD (2.03/d) and L+E+HD (1.60/day) versus L+E-HD (2.31/day). Unassisted voluntary defecation was confirmed 12 months postoperatively in 7/8 (87.5%) E+HD, 11/13 (84.6%) L+HD, 4/5 (80.0%) L+E+HD, and 7/8 (87.5%) L-E-HD; differences were not significant. Laxatives were still required in 2/8 (25.0%) E+HD, 3/13 (23.1%) L+HD, in 1/5 (20.0%) in L+E+HD, and 2/8 (25.0%) L+E-HD; differences were not significant. Conclusion: Incidence of HD was higher in L+HD, but not significantly different suggesting that indications for RMSBx have potential to influence incidence of HD and hint that the incidence of HD could actually be higher. Further assessment of additional indications is warranted to diagnose HD with greater accuracy.

Purpose: It is not uncommon for patients with hip disorders to present with pelvic obliquity (PO), and residual PO after total hip arthroplasty (THA) may not only affect hip joint function but also cause adjacent intervertebral joint disorders. This study aimed to investigate the postoperative PO impact on clinical outcomes and risk factors by comparing patients who had PO after THA to those who did not., Methods: A single-center, retrospective cohort study was conducted. A total of 103 patients who underwent THA were included in this study from 2018 to 2020. Demographics, functional outcomes, and spinopelvic parameters were compared between post-THA PO of less than 2° (NT group, 55 patients) and PO of 2° or more (O group, 48 patients). Multivariate analysis was performed using factors with significant differences in univariate analysis., Results: Postoperative Harris Hip Score Activity was significantly lower in the T group than in the NT group (p = 0.031). Preoperative PO was smaller in the NT group than in the T group (p = 0.001). Preoperative lumbar bending range (LBR) was significantly more flexible in the NT group than in the T group. In the logistic regression analysis, Age (odds ratio 0.957, 95% CI 0.923-0.993, p = 0.020), preoperative PO (odds ratio 1.490, 95% CI 1.100-2.020, p = 0.001), and LBR (odds ratio 0.848, 95% CI 0.756-0.951, p = 0.005) were found to be significant factors., Conclusion: Younger age and large preoperative PO, and poor lumbar spine mobility were identified as risk factors for residual postoperative PO., (© 2024. The Author(s).)

Tourette syndrome (TS) is a developmental neuropsychiatric disorder that is characterized by tic movements. Deep brain stimulation (DBS) may be a treatment option for severe cases refractory to medical and behavioral therapies. In this study, we reviewed the surgical techniques used for DBS in patients with severe TS and its clinical outcomes and sought to determine the optimal surgical procedure and current issues based on our experience and the literature. A total of 14 patients, consisting of 13 men and 1 woman, who underwent centromedian thalamic DBS and were followed up for a mean duration of 2.3 ± 1.0 years, participated in this study. The mean Yale Global Tic Severity Scale severity score significantly improved from 41.4 ± 7.0 at baseline to 19.8 ± 11.4 at 6 months (P = 0.01) and 12.7 ± 6.2 at the last follow-up (P < 0.01). Moreover, the mean Yale Global Tic Severity Scale impairment score significantly improved from 47.1 ± 4.7 at baseline to 23.1 ± 11.1 at 6 months (P < 0.01) and 7.6 ± 2.9 at the last follow-up (P < 0.01). However, there were problems with continuous postoperative monitoring (three cases were lost to follow-up) and surgery-related adverse events, including one case each of lead misplacement and a delayed intracerebral hemorrhage due to severe self-injurious tics. This study aimed to highlight not only the clinical efficacy of DBS for TS but also its challenges. Clinicians should understand the three-dimensional brain anatomy so that they can perform precise surgical procedures, avoid adverse events, and achieve favorable outcomes of DBS for TS.

A 73-year-old man with lung squamous cell carcinoma was administered carboplatin + nab-paclitaxel + pembrolizumab for four cycles. Subsequently, he presented with multiple purpuras on his extremities, joint swelling on his fingers, abdominal pain, and diarrhea, accompanied by acute kidney injury (AKI), increased proteinuria, hematuria, and elevated C-reactive protein levels. Skin biopsy showed leukocytoclastic vasculitis as well as IgA and C3 deposition in the vessel walls. Based on these findings, the patient was diagnosed with IgA vasculitis as an immune-related adverse event (irAE) induced by carboplatin + nab-paclitaxel + pembrolizumab. After discontinuation of pembrolizumab and glucocorticoids, the symptoms immediately resolved. Regular monitoring of skin, blood tests, and urinalysis are necessary, and the possibility of irAE IgA vasculitis should be considered in cases of purpura and AKI during treatment with immune checkpoint inhibitors., Competing Interests: AM has received honoraria from AstraZeneca, Nippon Kayaku, Merck, Kyowa Kirin, and Pfizer. KK has received honoraria Chugai Pharmaceutical, Eli Lilly, and Bristol-Myers Squibb. MS has received grants and contracts from any entity from Taiho Pharmaceutical, Chugai Pharmaceutical, Eli Lilly, Nippon Boehringer Ingelheim, Nippon Kayaku, and Kyowa Hakko Kirin; honoraria from AstraZeneca, MSD K.K, Chugai Pharmaceutical, Taiho Pharmaceutical, Eli Lilly, Ono Pharmaceutical, Bristol-Myers Squibb, Nippon Boehringer Ingelheim, Pfizer, Novartis, Takeda Pharmaceutical, Kyowa Hakko Kirin, Nippon Kayaku, Daiichi-Sankyo Company, Merck Biopharma, and Amgen. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Terashima, Matsumoto, Ozaki, Nakagawa, Nakagome, Terasaki, Iida, Mitsugi, Kuramochi, Okada, Inoue, Matsuki, Kitagawa, Fukuizumi, Onda, Takeuchi, Miyanaga, Kasahara and Seike.)

To effectively treat cerebral arteriovenous malformations (AVMs), peri-nidal flow regulation and metabolic status must be understood. In this study, we used 15 O-oxygen positron emission tomography (PET) post-processing analysis to investigate vascular radioactivity in the nidal region of AVMs. Single-dynamic PET imaging was performed on seven unruptured AVM patients during the sequential inhalation of 15 O 2 and C 15 O 2 . A previously validated dual-tracer basis function method (DBFM) was employed to calculate parametric images. The results of our study were as follows. First, in remote and contralateral AVM regions, DBFM and a previous approach of dual-tracer autoradiography (DARG) showed strong positive correlations in cerebral blood flow ( CBF ), cerebral oxygen metabolism rate ( CMRO 2 ), and oxygen extraction fraction. Second, peri-nidal CBF and CMRO 2 correlation was lower, and overestimation occurred with DARG compared to with DBFM. Third, on comparing DBFM to quantitative 123 I-iodoamphetamine single-photon emission computed tomography (SPECT), CBF correlated significantly. In contrast, the correlation between DARG and quantitative 123 I-iodoamphetamine-SPECT was weaker in the peri-nidal regions. Fourth, analysis of tissue time-activity curves demonstrated good reproducibility using the novel formulation in the control, peri-nidus, and core nidal regions, indicating the adequacy of this approach. Overall, the DBFM approach holds promise for assessing haemodynamic alterations in patients with AVMs., 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.

Purpose: Salivary cortisol (SalC) and low to high pulse ratio (LHR) were used for evaluating perioperative stresses in children., Methods: Children aged 6 months-16 years having elective general (thoracic/abdominal) or minor (open/minimally invasive: MI) procedures underwent pulse monitoring during AM (08:00-12:00) and PM (17:00-21:00) saliva collections from the day before surgery (S-1) to 3 days after surgery (S + 3). SalC/LHR were correlated with age, sex, caregiver attendance, operative time, and surgical site/approach using mixed model analysis and face/numeric pain rating scales (FRS/NRS)., Results: Mean ages (years): minor-open (n = 31) 4.7 ± 2.0, thoracic-open (n = 2) 8.7 ± 4.9, thoracic-MI (n = 6) 9.6 ± 6.1, abdominal-open (n = 14) 4.3 ± 4.1, and abdominal-MI (n = 32) 8.0 ± 5.0. Postoperative SalC increased rapidly and decreased to preoperative levels by S + 3 (p < 0.001). LHR increased slightly without decreasing (p = 0.038). SalC correlated positively with operative time (p = 0.036) and open surgery (p = 0.0057), and negatively with age (p < 0.0001) and caregiver attendance (p < 0.001). SalC correlated positively with FRS (n = 51) at S + 2(PM) (p = 0.023), S + 3(AM) (p < 0.001), S + 3(PM) (p = 0.012) and NRS (n = 34) at S + 1(AM) (p = 0.031), S + 3(AM) (p < 0.044). LHR positively correlated with age (p = 0.0072), female sex (p = 0.0047), and caregiver attendance (p = 0.0026). Postoperative SalC after robotic-assisted MI was significantly lower than after open surgery at S + 2(AM) (p = 0.020)., Conclusions: SalC correlated with pain. Caregiver attendance effectively alleviated stress., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

It is often difficult to achieve adequate bone coverage of the cup in total hip arthroplasty in cases of severe developmental dysplasia of the hip (DDH). This study aimed to evaluate the relationship between subluxation percentage of Crowe classification and cup center-edge (cup-CE) angle to investigate whether subluxation percentage according to the Crowe classification is a useful indicator for cementless cup placement. Cementless cup placement was simulated in 77 women with DDH in 91 hips (Crowe I, 35 hips; Crowe II, 35 hips; and Crowe III, 21 hips) using computed tomography-based computer simulation software. The cups were placed at the anatomic hip center (AHC) and 10-mm high hip center (HHC). The relationship between the subluxation percentage and cup-CE angle was evaluated using Spearman's rank correlation coefficient. In addition, the cutoff values for the subluxation percentage that satisfied a cup-CE angle ≥0° were determined using the receiving operating characteristic curve. The cup-CE angle was negatively correlated with the subluxation percentage in both AHC and 10-mm HHC (correlation coefficient ρ = -0.542 [p < 0.01] and -0.704 [p < 0.01], respectively). The cutoff values for subluxation percentage that satisfied a cup-CE angle ≥0° were 56.1% and 73.6% for AHC and 10-mm HHC, respectively. Cementless cup placement in AHC is difficult in cases with the subluxation percentage ≥56.1%, and HHC reconstruction or femoral structural autograft technique should be considered as an alternative. Moreover, placement at 10 mm above AHC is difficult in cases with subluxation percentage ≥73.6%., (© 2024 Orthopaedic Research Society.)

Poststroke neuroinflammation exacerbates disease progression. [ 11 C]PK11195-positron emission tomography (PET) imaging has been used to visualize neuroinflammation; however, its short half-life of 20 min limits its clinical use. [ 123 I]CLINDE has a longer half-life (13h); therefore, [ 123 I]CLINDE-single-photon emission computed tomography (SPECT) imaging is potentially more practical than [ 11 C]PK11195-PET imaging in clinical settings. The objectives of this study were to 1) validate neuroinflammation imaging using [ 123 I]CLINDE and 2) investigate the mechanisms underlying stroke in association with neuroinflammation using multimodal techniques, including magnetic resonance imaging (MRI), gas-PET, and histological analysis, in a rat model of ischemic stroke, that is, permanent middle cerebral artery occlusion (pMCAo). At 6 days post-pMCAo, [ 123 I]CLINDE-SPECT considerably corresponded to the immunohistochemical images stained with the CD68 antibody (a marker for microglia/microphages), comparable to the level observed in [ 11 C]PK11195-PET images. In addition, the [ 123 I]CLINDE-SPECT images corresponded well with autoradiography images. Rats with severe infarcts, as defined by MRI, exhibited marked neuroinflammation in the peri-infarct area and less neuroinflammation in the ischemic core, accompanied by a substantial reduction in the cerebral metabolic rate of oxygen (CMRO 2 ) in 15 O-gas-PET. Rats with moderate-to-mild infarcts exhibited neuroinflammation in the ischemic core, where CMRO 2 levels were mildly reduced. This study demonstrates that [ 123 I]CLINDE-SPECT imaging is suitable for neuroinflammation imaging and that the distribution of neuroinflammation varies depending on the severity of infarction., Competing Interests: Declaration of competing interest, (Copyright © 2024 Elsevier Inc. All rights reserved.)

Purpose: Hepatocyte mitochondrial morphology and gene expression were compared between biliary atresia (BA), infantile cholestasis (IC), and normal liver (NL) as prognostic indicators., Methods: Specimens of liver at portoenterostomy (PE) for BA, from intrahepatic bile duct paucity patients for IC, and from choledochal cyst or hepatoblastoma patients for NL were collected prospectively (P) beginning in 2021 (P-BA = 11, P-IC = 9, P-NL = 7) and retrospectively (R) from paraffin-embedded tissue going back to 1981 (R-BA = 25, R-IC = 9, R-NL = 4). The P-cohort had transmission electron microscopy (TEM) to image mitochondria, immunoblotting for heat shock protein 60 (HSP60), and quantitative PCR (qPCR) for HSP60 and mitochondrial functional genes. Both cohorts had immunofluorescence for HSP60 quantified as a ratio to albumin-positive hepatocytes (ALB) with HSP60/ALB<1.0 as a cutoff limit using ImageJ., Results: HSP60 was significantly lower in BA/IC than NL on qPCR (BA: p < 0.01, IC: p < 0.05) and lower in BA than IC/NL on immunoblotting (p < 0.05). HSP60/ALB was significantly lower in BA than NL/IC (p < 0.001). Despite BA subjects being matched for types of BA and ages at PE, HSP60/ALB did not correlate with jaundice clearance (JC; T-Bil<1.2 mg/dL) but was significantly higher in native liver survivors (NLS) after PE compared with liver transplant (LTx) cases (p < 0.05) and significantly lower in LTx cases achieving JC than NLS achieving JC (p < 0.05). TEM showed BA had significantly more mitochondrial inclusion bodies (p < 0.05) and significantly larger cristae (p < 0.01) than IC/NL. qPCR in BA showed significant repression of mitochondrial functional genes for mRNA stabilization and energy facilitation., Conclusion: HSP60/ALB correlates with NLS after PE for BA., Level of Evidence: II., Competing Interests: Declaration of competing interest The authors declare that they have no conflicts of interest., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Eccentric rotational acetabular osteotomy is performed to prevent osteoarthritis caused by developmental dysplasia of the hip (DDH). To achieve sufficient acetabular coverage, understanding the characteristics of acetabular coverage in DDH is necessary. However, the features of acetabular coverage in males with DDH remain unclear. We thought that the differences in acetabular coverage between females and males might be associated with the differences in pelvic morphology between the sexes., Questions/purposes: (1) What are the differences in the acetabular coverage between females and males with DDH? (2) What are the differences in the rotations of the ilium and ischium between females and males with DDH? (3) What is the relationship between the rotation of the ilium and ischium and the acetabular coverage at each height in females and males with DDH?, Methods: Between 2016 and 2023, 114 patients (138 hips) underwent eccentric rotational acetabular osteotomy at our hospital. We excluded patients with Tönnis Grade 2 or higher, a lateral center-edge angle of 25º or more, and deformities of the pelvis or femur, resulting in 100 patients (122 hips) being included. For female patients (98 hips), the median (range) age was 40 years (10 to 58), and for the male patients (24 hips), it was 31 years (14 to 53). We used all patients' preoperative AP radiographs and CT data. The crossover sign, posterior wall sign, and pelvic width index were evaluated in AP radiographs. The rotation of the innominate bone in the axial plane was evaluated at two different heights, specifically at the slice passing through the anterior superior iliac spine and the slice through the pubic symphysis and ischial spine in CT data. Furthermore, we evaluated the anterior and posterior acetabular sector angles. Comparisons of variables related to innominate bone measurements and acetabular coverage measurements between females and males in each patient were performed. The correlations between pelvic morphology measurements and acetabular coverage were evaluated separately for females and males, and the results were subsequently compared to identify any sex-specific differences. For continuous variables, we used the Student t-test; for binary variables, we used the Fisher exact test. A p value less than 0.05 was considered statistically significant., Results: In the evaluation of AP radiographs, an indicator of acetabular retroversion-the crossover sign-showed no differences between the sexes, whereas the posterior wall sign (females 46% [45 of 98] hips versus males 75% [18 of 24] hips, OR 3.50 [95% confidence interval (CI) 1.20 to 11.71]; p = 0.01) and pelvic width index less than 56% (females 1% [1 of 98] versus males 17% [4 of 24], OR 18.71 [95% CI 1.74 to 958.90]; p = 0.005) occurred more frequently in males than in females. There were no differences in the iliac rotation parameters, but the ischium showed more external rotation in males (females 30° ± 2° versus males 24° ± 1°; p < 0.001). Regarding acetabular coverage, no differences between females and males were observed in the anterior acetabular sector angles. In contrast, males showed smaller values than females for the posterior acetabular sector angles (85° ± 9° versus 91° ± 7°; p = 0.002). In females, a correlation was observed between iliac rotation and acetabular sector angles (anterior acetabular sector angles: r = -0.35 [95% CI -0.05 to 0.16]; p < 0.001, posterior acetabular sector angles: r = 0.42 [95% CI 0.24 to 0.57]; p < 0.001). Similarly, ischial rotation showed a correlation with both acetabular sector angles (anterior acetabular sector angles: r = -0.34 [95% CI -0.51 to -0.15]; p < 0.001 and posterior acetabular sector angles: r = 0.45 [95% CI 0.27 to 0.59]; p < 0.001). Thus, in females, we observed that external iliac rotation and ischial internal rotation correlated with increased anterior acetabular coverage and reduced posterior coverage. In contrast, although acetabular coverage in males showed a correlation with iliac rotation (anterior acetabular sector angles: r = -0.55 [95% CI -0.78 to -0.18]; p = 0.006 and posterior acetabular sector angles: r = 0.74 [95% CI 0.48 to 0.88]; p < 0.001), no correlation was observed with ischial rotation., Conclusion: In males, acetabular retroversion occurs more commonly than in females and is attributed to their reduced posterior acetabular coverage. In females, an increase in the posterior acetabular coverage was correlated with the external rotation angle of the ischium, whereas in males, no correlation was found between ischial rotation and posterior acetabular coverage. In treating males with DDH via eccentric rotational acetabular osteotomy, it is essential to adjust bone fragments to prevent inadequate posterior acetabular coverage. Future studies might need to investigate the differences in acetabular coverage between males and females in various limb positions and consider the direction of bone fragment rotation., Clinical Relevance: Our findings suggest that males with DDH exhibit acetabular retroversion more frequently than females, which is attributed to the reduced posterior acetabular coverage observed in males. The smaller posterior acetabular coverage in males might be related to differences in ischial morphology between sexes. During eccentric rotational acetabular osteotomy for males with DDH, adequately rotating acetabular bone fragments might be beneficial to compensate for deficient posterior acetabular coverage., Competing Interests: Each author certifies that there are no funding or commercial associations (consultancies, stock ownership, equity interest, patent/licensing arrangements, etc.) that might pose a conflict of interest in connection with the submitted article related to the author or any immediate family members. All ICMJE Conflict of Interest Forms for authors and Clinical Orthopaedics and Related Research® editors and board members are on file with the publication and can be viewed on request., (Copyright © 2024 by the Association of Bone and Joint Surgeons.)

Background: There are no definitive guides to determine the timing of reimplantation in two-stage revision total hip arthroplasties (THA) for periprosthetic joint infection (PJI). This study was to design to support a rational strategy of surgical treatment using serum C-reactive protein (CRP)., Methods: We analyzed a total of 75 hips for PJI in the process of performing two-stage and multiple-stage revision THAs. CRP level was retrospectively evaluated every week and transformed to log2 (CRP) using a logistic regression model. Prosthesis survival from recurrent infection was determined by Kaplan-Meier analysis, using implant removal as the endpoint. Receiver operating characteristic curves were calculated using each log2 (CRP) to assess predictions of recurrent infection., Results: The 10-year survival rates were 85% (95% confidence interval, 76-95) and 100% for two-stage and multiple-stage revision THAs, respectively. Preoperatively, at 1, 2, 3, and 5 weeks, log2 (CRP) was not associated with recurrent infection. In failed two-stage revision THAs, log2 (CRP) at 3 weeks divided by that at 2 weeks showed a significant difference. Failure was associated with a ratio of >4.0 for the CRP level between 3 and 2 weeks., Conclusion: In two-stage revision THA for PJI, patients with CRP elevation from 2 weeks to 3 weeks, especially 4-fold elevation, suggests the need for further debridement and postponement of second-staged reimplantation., Competing Interests: Declaration of competing interest All authors have no conflicts of interest relevant to this article to declare., (Copyright © 2023 The Japanese Orthopaedic Association. Published by Elsevier B.V. All rights reserved.)

Purpose: This study aimed to clarify the factors that cause the lateralization and superiorization of the femoral head after eccentric rotational acetabular osteotomy (ERAO) by examining the three-dimensional morphology of the osteotomy site using computed tomography (CT)., Methods: This study included 52 patients who underwent ERAO for hip dysplasia. Postoperatively, the center of the femoral head was measured for lateralization and superiorization. We defined the iliac and sciatic osteotomy angles in the coronal and axial CT planes, respectively. The surgical factors for lateralization and superiorization were analysed using multiple logistic regression analysis. We also analysed the relationship between the femoral head relocation and clinical outcomes (as assessed using Japanese Orthopaedic Association (JOA) scores)., Results: Thirty-five patients had hips with lateralized femoral heads, and 25 patients' femoral heads were superiorized. Logistic regression analysis revealed that a higher osteotomy angle of the ilium in the coronal plane served as a significant predictor of superiorization of the femoral head. Similarly, a larger osteotomy angle of the ischium in the axial plane and the amount of change in the lateral centre edge angle were identified as predictors of lateralization. A weak negative correlation was observed between the amount of lateralization and the JOA score., Conclusion: Large osteotomy angles in the superior and posterior aspects of the acetabulum carry a risk of superiorization and lateralization of the center of the femoral head. Surgeons should be aware of the need to chisel through the internal plate to achieve the results described in the ERAO theory., Study Design: A single-center, retrospective study., Competing Interests: Declaration of competing interest The authors declare no competing interests., (Copyright © 2023 The Japanese Orthopaedic Association. Published by Elsevier B.V. All rights reserved.)

Purpose: Muscle quality is more important than muscle mass for assessing physical function. Computed tomography (CT) is used to evaluate intramuscular fatty infiltration. The mid-thigh quadriceps CT attenuation values (CTV) expressed in Hounsfield units (HU) negatively correlate with physical function. Patients with hip osteoarthritis (HOA) have lower extremity muscle atrophy, including decreased cross-sectional area (CSA), CTV, and muscle strength. Using preoperative CT images, we investigated the association between mid-thigh quadriceps CSA, CTV, and postoperative outcomes in patients with HOA., Methods: This study included 62 patients who had unilateral HOA (62 hips) and underwent total hip arthroplasty (THA). We investigated the association between preoperative and postoperative Japanese Orthopaedic Association (JOA) hip scores, 12-item Short Form survey (SF-12), mid-thigh quadriceps CSA, and CTV., Results: The mean age was 64.7 ± 10.1 years, with 15 men (24.2%), and the mean body mass index was 24.3 ± 4.3 kg/m 2 . Secondary HOA was present in 79.0% of patients. The mean CSA and CTV of the mid-thigh quadriceps on the operative side were 38.8 ± 9.8 cm 2 and 40.3 ± 7.8 HU, respectively. Multiple regression analyses adjusted for age and sex showed that preoperative mid-thigh quadriceps CSA was not associated with preoperative and postoperative JOA hip scores or SF-12. The preoperative mid-thigh quadriceps CTV was associated with the postoperative JOA hip score in the gait ability domain and SF-12 in the physical component summary domain., Conclusion: Preoperative muscle quality is associated with postoperative outcomes in patients who have HOA regardless of age and sex., (© 2024. The Author(s) under exclusive licence to SICOT aisbl.)

The outcome of total hip arthroplasty (THA) in patients with end-stage arthritis of the hip is associated with preoperative physical status. This study was performed to examine the relationship between the preoperative severity of sarcopenia and clinical outcomes after THA. This retrospective cohort study was performed among 306 consecutive patients (mean age: 63.7 ± 12.9 years, 222 women) undergoing THA at a university hospital. The severity of sarcopenia was determined based on the skeletal muscle mass index (SMI), handgrip strength, and gait speed according to the criteria of the Asian Working Group for Sarcopenia 2019. The severe sarcopenia prevalence rate was 10.6%. Severe sarcopenia was significantly associated with the risk of delayed functional recovery (adjusted odds ratio, 2.82; 95% confidence interval, 1.03-7.72; p = 0.043) compared with the non-sarcopenia group after adjusting for pre-existing risk factors, including preoperative hip function and physical activity. The addition of SMI, handgrip strength, and gait speed to the model for risk of functional recovery delay significantly increased the area under the receiver operating characteristic curve ( p = 0.038). Severe sarcopenia was significantly associated with poorer hip function and patient-reported outcomes at 6 months after surgery compared with the non-sarcopenia group. Severe sarcopenia was adversely associated with postoperative clinical outcomes in patients undergoing THA.

An essential ketone body, β-hydroxybutyrate (BOHB), plays various roles in physiological regulations via protein acylations such as lysine acetylation and β-hydroxybutyrylation. Here, to understand how BOHB systemically regulates acylations from an overarching perspective, we administered a ketogenic diet to mice to increase BOHB concentration and examined acylations. We found that global acetylation and β-hydroxybutyrylation dramatically increase in various organs except for the brains, where the increase was much smaller than in the other organs. Interestingly, we observe no increase in histone acetylation in the organs where significant global protein acetylation occurs despite a substantial rise in histone β-hydroxybutyrylation. Finally, we compared the transcriptome data of the mice's liver after the ketogenic diet to the public databases, showing that upregulated genes are enriched in those related to histone β-hydroxybutyrylation in starvation. Our data indicate that a ketogenic diet induces diverse patterns of acylations depending on organs and protein localizations, suggesting that different mechanisms regulate acylations and that the ketogenic diet is associated with starvation in terms of protein modifications., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Yuya Nishida reports financial support was provided by Japan Society for the Promotion of Science. Hirotaka Watada reports financial support was provided by Japan Society for the Promotion of Science., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Flavin photocatalysis were utilised for an aerobic oxidative reaction between arylamines and o -phenylenediamine. This metal-free reaction proceeded in methanol under visible light irradiation and consumed only atmospheric molecular oxygen, providing a novel eco-friendly method for the synthesis of benzimidazoles.

Background and Objective: Other iatrogenic immunodeficiency-associated lymphoproliferative disorders (OIIA-LPD) are rare but well-known diseases that manifest during or after methotrexate (MTX) administration. Limited information is available on the clinical characteristics of OIIA-LPD of the lung because only a few cases have been reported. Thus, we aimed to assess the incidence and prognosis of patients with OIIA-LPD of the lung., Methods: Patients with OIIA-LPD of the lung treated at our institution between January 2008 and July 2020 were retrospectively analysed., Results: Among the 51 patients with OIIA-LPD, 16 (31.3%, 7 men, 9 women) had OIIA-LPD of the lung (median age, 69 [range, 63-82] years). Peripheral lesions were observed in 10 (62.5%), central lesions in two (12.5%), and both lesions in four (25.0%) patients. Nine of the 16 patients underwent bronchoscopic biopsy, seven were diagnosed (diagnostic yield, 77.8%) and, re-biopsy was performed in 2 patients. Eight (50.0%) patients had LPD and six (37.5%) had diffuse large B-cell lymphoma. In the 14 patients with confirmed treatment efficacy, the overall response rate to MTX withdrawal was 71.4%. However, chemotherapy was required in case of larger lesions (three patients). Death related to OIIA-LPD occurred in only one patient, and 11 of the 14 patients were alive during the study period (median follow-up time, 53.7 [range, 4.3-84.2] months)., Conclusion: The incidence of OIIA-LPD of the lung is 31.3% and higher than that reported previously. The treatment effect of MTX withdrawal seems to be sufficient; however, in some cases, chemotherapy may be required from the beginning., 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 Elsevier Ltd. All rights reserved.)

Evidence is accumulating that osteal macrophages, in addition to bone-resorbing osteoclasts and bone-forming osteoblasts, participate vitally in bone remodeling process. Oncostatin M (OSM), an inflammatory cytokine belonging to interleukin-6 superfamily, is recognized as an essential factor secreted by osteal macrophages to orchestrate bone remodeling. Osteoprotegerin (OPG) produced by osteoblasts regulates osteoclastogenesis. We have reported that bone morphogenetic protein-4 (BMP-4) stimulates OPG synthesis in MC3T3-E1 osteoblast-like cells, and that SMAD1/5/8(9), p38 mitogen-activated protein kinase (MAPK), and p70 S6 kinase are involved in the OPG synthesis. The present study aims to investigate the effect of OSM on the synthesis of OPG stimulated by BMP-4 in osteoblasts. OSM suppressed the release and the mRNA expression of OPG upregulated by BMP-4 in MC3T3-E1 cells. Neither the BMP-4-induced phosphorylation of SMAD1/5/9 nor that of p38 MAPK was affected by OSM. On the other hand, the phosphorylation of p70 S6 kinase stimulated by BMP-4 was considerably suppressed by OSM. These results strongly suggest that OSM suppresses the BMP-4-stimulated OPG synthesis via inhibition of the p70 S6 kinase-mediated pathway in osteoblast-like cells., (© 2024 The Author(s). Cell Biochemistry and Function published by John Wiley & Sons Ltd.)

Aim: Advanced glycation end-products (AGEs) are irreversibly and heterogeneously formed compounds during the non-enzymatic modification of macromolecules, such as proteins. Aging and lifestyle habits, such as high-fat and high-protein diets, and smoking, promote AGEs accumulation. This study aimed to investigate the relationship between fall risk and AGEs in community-dwelling older adults., Methods: This cross-sectional study included patients from the 2022 Yakumo Study who were evaluated for fall risk index 5-items version, locomotive syndrome stage and AGEs. AGEs were evaluated using Skin autofluorescence (SAF) measured by the AGE reader (DiagnOptics Technologies BV, Groningen, the Netherlands). We divided the participants into two groups according to the presence or absence of fall risk (fall risk index 5-items version ≥6 or not), and investigated the factors associated with fall risk., Results: The fall risk group had a higher age and SAF, and a higher proportion of locomotive syndrome stage >2 than the without fall risk group in patients aged ≥65 years (P < 0.01). The multivariate logistic regression analysis after adjustment of age, sex and body mass index showed that locomotive syndrome stage ≥2 and SAF were independent associators of fall risk in older adults (odds ratio 3.26, P < 0.01, odds ratio 2.96, P < 0.05, respectively). The optimal cutoff value of the SAF for fall risk was 2.4 (area under the curve 0.631; 95% CI 0.53-0.733; sensitivity 0.415; specificity 0.814; P < 0.05)., Conclusion: The accumulation of AGEs in skin tissues can be used to screen for fall risk comprehensively. Geriatr Gerontol Int 2024; 24: 517-522., (© 2024 Japan Geriatrics Society.)

Background: Recent studies have indicated the importance of muscle quality in addition to muscle quantity in sarcopenia pathophysiology. Intramuscular adipose tissue (IMAT), which originates from mesenchymal progenitors (MPs) in adult skeletal muscle, is a key factor affecting muscle quality in older adults, suggesting that controlling IMAT formation is a promising therapeutic strategy for sarcopenia. However, the molecular mechanism underlying IMAT formation in older adults has not been clarified. We recently found that the vitamin D receptor (VDR) is highly expressed in MPs in comparison to myotubes (P = 0.028, N = 3), indicating a potential role of vitamin D signalling in MPs. In this study, we aimed to clarify the role of vitamin D signalling in MP kinetics, with a focus on adipogenesis., Methods: MPs isolated from mouse skeletal muscles were subjected to adipogenic differentiation conditions with or without vitamin D (1α,25(OH)2D3, 100 nM) for 7 days, and adipogenicity was evaluated based on adipogenic marker expression. For in vivo analysis, tamoxifen-inducible MP-specific VDR-deficient (Vdr MPcKO ) mice were newly developed to investigate whether lack of vitamin D signalling in MPs is involved in IMAT formation. To induce muscle atrophy, Vdr MPcKO male mice were subjected to tenotomy of the gastrocnemius muscle, and then muscle weight, myofibre cross-sectional area, adipogenic marker expression, and fatty infiltration into the muscle were evaluated at 3 weeks after operation (N = 3-4). In addition, a vitamin D-deficient diet was provided to wild-type male mice (3 and 20 months of age, N = 5) for 3 months to investigate whether vitamin D deficiency causes IMAT formation., Results: Vitamin D treatment nearly completely inhibited adipogenesis of MPs through Runx1-mediated transcriptional modifications of early adipogenic factors such as PPARγ (P = 0.0031) and C/EBPα (P = 0.0027), whereas VDR-deficient MPs derived from Vdr MPcKO mice differentiated into adipocytes even in the presence of vitamin D (P = 0.0044, Oil-Red O + area). In consistency with in-vitro findings, Vdr MPcKO mice and mice fed a vitamin D-deficient diet exhibited fat deposition in atrophied (P = 0.0311) and aged (P = 0.0216) skeletal muscle, respectively., Conclusions: Vitamin D signalling is important to prevent fate decision of MPs towards the adipogenic lineage. As vitamin D levels decline with age, our data indicate that decreased vitamin D levels may be one of the causes of IMAT formation in older adults, and vitamin D signalling may be a novel therapeutic target for sarcopenia., (© 2024 The Authors. Journal of Cachexia, Sarcopenia and Muscle published by Wiley Periodicals LLC.)

Perinatal hypoxic-ischaemic encephalopathy (HIE) is the leading cause of irreversible brain damage resulting in serious neurological dysfunction among neonates. We evaluated the feasibility of positron emission tomography (PET) methodology with 15 O-labelled gases without intravenous or tracheal cannulation for assessing temporal changes in cerebral blood flow ( CBF ) and cerebral metabolic rate for oxygen ( CMRO 2 ) in a neonatal HIE rat model. Sequential PET scans with spontaneous inhalation of 15 O-gases mixed with isoflurane were performed over 14 days after the hypoxic-ischaemic insult in HIE pups and age-matched controls. CBF and CMRO 2 in the injured hemispheres of HIE pups remarkably decreased 2 days after the insult, gradually recovering over 14 days in line with their increase found in healthy controls according to their natural maturation process. The magnitude of hemispheric tissue loss histologically measured after the last PET scan was significantly correlated with the decreases in CBF and CMRO 2. This fully non-invasive imaging strategy may be useful for monitoring damage progression in neonatal HIE and for evaluating potential therapeutic outcomes., 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.

Background: To examine whether the "Effectiveness of Guideline for Dissemination and Education in psychiatric treatment (EGIUDE)" project affects the rate of prescriptions of hypnotic medication and the type of hypnotic medications prescribed among psychiatrists, for schizophrenia and major depressive disorder in Japan., Methods: The EGUIDE project is a nationwide prospective study of evidence-based clinical guidelines for schizophrenia and major depressive disorder in Japan. From 2016 to 2021, clinical and prescribing data from patients discharged from hospitals participating in the EGUIDE project were used to examine hypnotic medication prescriptions The prescribing rate of hypnotics and the prescribing rate of each type of hypnotic (benzodiazepine receptor agonist, nonbenzodiazepine receptor agonist, melatonin receptor agonist, and orexin receptor antagonist) were compared among patients who had been prescribed medication by psychiatrists participating in the EGUIDE project and patients who had been prescribed medication by nonparticipating psychiatrists. Multivariate logistic regression analysis was performed to examine the effect of the EGUIDE project on the prescription of hypnotic medications., Results: A total of 12,161 patients with schizophrenia and 6,167 patients with major depressive disorder were included. Psychiatrists participating in the EGUIDE project significantly reduced the rate of prescribing hypnotic medication and benzodiazepine receptor agonists for both schizophrenia (P < 0.001) and major depressive disorder (P < 0.001) patients., Conclusion: This is the first study to investigate the educational effects of guidelines for the treatment of psychiatric disorders on psychiatrists in terms of prescribing hypnotic medications to patients. The EGUIDE project may play an important role in reducing hypnotic medication prescription rates, particularly with respect to benzodiazepine receptor agonists. The results suggest that the EGUIDE project may result in improved therapeutic behavior., (© 2024. The Author(s).)

Romidepsin is an important therapeutic option for patients with peripheral T-cell lymphoma (PTCL). However, the timing of romidepsin administration remains controversial. The objective of this study was to characterize the safety and efficacy of romidepsin as consolidation therapy after gemcitabine, dexamethasone, and cisplatin (GDP) therapy (GDPR). This study of patients treated between March 2019 and March 2021 was registered with the Japan Registry of Clinical Trials (registration number: jRCT0000000519). If complete response, partial response, or stable disease was confirmed after 2-4 GDP cycles, romidepsin was administered every 4 weeks for 1 year. Seven patients with relapsed/refractory (R/R) PTCL (T-follicular helper phenotype [n = 1] and angioimmunoblastic T-cell lymphoma [n = 6]) were included in this prospective study (PTCL-GDPR). After a median follow-up of 34 months of patients in PTCL-GDPR, the 2-year overall survival rate was 71%, and the overall response rate after treatment was 57%. Common adverse events in patients with PTCL-GDPR included hematological toxicities such as neutropenia, which improved with supportive treatment. There were no treatment-related mortalities. GDPR might be safe and effective in elderly transplant-ineligible patients with R/R PTCL; however, further investigation is required.

Introduction: Early surgery for hip fracture, within 48 hours of hospital admission, is effective in reducing mortality. However, the average preoperative waiting time for hip fractures in Japan is 4.5 days and the 1-year mortality rate after a hip fracture is 10% in Japan. This study aimed to investigate whether early surgery, within 48 hours, could reduce the 1-year mortality rate in patients with hip fractures in Japan., Methods: This cohort study involved 402 consecutive patients with hip fractures who underwent surgical treatment between January 2013 and September 2019. The exclusion criteria were an age of <60 years and in-hospital injury. A total of 389 patients were included in this study. The patients were divided into two groups: those who underwent early surgery within 48 hours of admission (early group) and those who di not undergo early surgery (delayed group). We compared patient characteristics and treatment outcomes between the 2 groups., Results: A comparison of patient characteristics revealed that the early group had lower hemoglobin levels (P=0.046), lower C-reactive protein levels ( P  = 0.031), lower numbers of patients with weekend hospitalization, lower numbers of patients with a history of using medications that may cause bleeding ( P  < 0.01), and who received general anaesthesia ( P  < 0.01). However, there were no significant differences with regard to the other variables between the 2 groups. A treatment outcome analysis showed that the early group had shorter waiting times for surgery ( P  < 0.01) and shorter stays in acute-care wards ( P  < 0.01). However there were no differences in the total hospital stay, Barthel index at discharge, home discharge rates, in-hospital mortality rates, and 1-year mortality., Conclusion: Our findings indicate that early surgery did not reduce the 1-year mortality rate in older patients with hip fractures in Japan., 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.

Advanced glycation end products (AGEs) have been reported to be associated with osteoporosis, aging, sarcopenia, and frailty. This study aimed to investigate the association AGEs with locomotive syndrome (LS). Participants were Japanese individuals aged 39 years or older who participated in the Yakumo Study (n=230). AGEs were measured by skin autofluorescence (SAF) using an AGE reader. We investigated SAF values for each locomotive stage. Multivariate logistic regression models were used to calculate the odds ratios of LS-associated factors. The relationships between SAF and physical performance and bone mineral density (BMD) were investigated. A receiver operating characteristic (ROC) curves were generated to determine the optimal cut-off value of SAF for predicting LS. SAF values tended to increase correspondingly with LS severity. SAF was an independently explanatory factor for LS (odds ratio 2.70; 95% confidence interval [CI] 1.040-6.990). SAF was positively correlated with the 10-m walking speed, The Timed Up and Go test results, and was negatively correlated with BMD. ROC curve represented by SAF for the presence or absence of LS risk had an area under the curve of 0.648 (95% CI: 0.571-0.726). High SAF values were identified as an independent risk factor for LS. AGEs could be a potential screening tool for people for LS., Competing Interests: There are no conflicts of interest among the authors.

Quizartinib is a potent, oral, second-generation, selective type II FMS-like receptor tyrosine kinase 3 (FLT3) inhibitor. It has shown improved overall survival in a randomized, multinational, Phase 3 (QuANTUM-First) study in patients with FLT3-internal tandem duplication (ITD)-positive newly diagnosed acute myeloid leukemia. We conducted 2 Phase 1b studies in Japan and China to evaluate the safety, pharmacokinetics, and efficacy of quizartinib in combination with standard induction and consolidation chemotherapy in patients with newly diagnosed acute myeloid leukemia. Quizartinib was started at a dose level of 20 mg/day and then escalated to 40 mg/day, the dose used in the Phase 3 study. Seven patients were enrolled according to the 3 + 3 dose-escalation method in each study, including 3 patients who were FLT3-ITD positive. No dose-limiting toxicities were observed at dose levels up to 40 mg/day in both studies. Grade 3 or higher, quizartinib-related, treatment-emergent adverse events included febrile neutropenia, hematologic toxicities, and infections. QT prolongation on electrocardiogram was observed in 5 patients. The pharmacokinetics of quizartinib and its metabolite AC886 were similar between the studies and consistent with previous findings in the United States. We confirmed the tolerability of Japanese and Chinese patients to the dose of quizartinib and chemotherapy regimens used in the QuANTUM-First study., (© 2024 Daiichi Sankyo Co., Ltd. Clinical Pharmacology in Drug Development published by Wiley Periodicals LLC on behalf of American College of Clinical Pharmacology.)

Purpose: After cemented total hip arthroplasty, the risk of periprosthetic fracture (PPF) of taper-slip stems is higher than that of composite-beam stems. We aimed to assess the conditions resulting in PPFs of taper-slip stems using a falling weight., Methods: Taper-slip stems were fixed to five types of simulated bone models using bone cement, and the fractures were evaluated by dropping stainless-steel weights from a predetermined height onto the heads. The periprosthetic fracture height in 50% of the bone models (PPFH 50 ) was calculated using the staircase method., Results: For the fixation with 0° of flexion, the values for PPFH 50 were 61 ± 11, 60 ± 13, above 110, 108 ± 49, and 78 ± 12 cm for the cobalt-chromium-molybdenum alloy, stainless steel alloy (SUS), titanium alloy (Ti), smooth surface, and thick cement mantle models, respectively; for the fixation with 10° of flexion (considering flexure), the PPFH 50 values were 77 ± 5, 85 ± 9, 90 ± 2, 89 ± 5, and 81 ± 11 cm, respectively. The fracture rates of the polished-surface stems were 78.6 and 35.7% at the proximal and distal sites, respectively (p < 0.05); the fracture rates of the smooth-surface stems were 14.2 and 100%, respectively (p < 0.05)., Conclusion: The impact tests demonstrated that the conditions that were less likely to cause PPFs were use of Ti, a smooth surface, a thick cement mantle, and probably, use of SUS., (© 2024. The Author(s) under exclusive licence to SICOT aisbl.)

Introduction: There are no widely accepted algorithms for determining optimal treatment for periprosthetic joint infection (PJI). Our study aimed to confirm the validity of a previously published scoring system in a larger number of patients to support a rational surgical treatment strategy for periprosthetic hip infection., Materials and Methods: Between February 2001 and December 2020, we performed 155 consecutive revision total hip arthroplasties (THAs) for PJI, with mean follow-up of 6 years. One-stage revision THA was performed in 56 hips and two-stage revision THA in 99 hips. Prosthesis survival from recurrent infection was determined by Kaplan-Meier analysis, using implant removal as the endpoint. The pre-operative scoring system (full score of 12 points), including 6 essential elements, was retrospectively evaluated., Results: The 10-year survival rates were 98% for one-stage (95% confidence interval [CI], 94-100) and 87% (95% CI, 79-96) for two-stage revision THA. Multivariate Cox regression analysis provided a total preoperative score as an independent risk factor for implant removal (hazard ratio, 0.17; 95% CI, 0.06-0.49; p < 0.001). The sensitivity and specificity at the cut-off of 4 points on the scoring system were 80% and 91%, respectively. The average score for one-stage revision THA in successful and failed cases were 8.9 and 6.0, and for two-stage revision THA were 6.5 and 3.9, respectively. We found significant differences between successful cases in one- and two-stage revision THA (p < 0.05)., Conclusions: The preoperative scoring system was useful for managing PJI. One-stage revision THA is recommended in patients scoring ≥ 9 points, and meticulously performed two-stage revision THA is encouraged for patients scoring ≥ 4 points., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Carotid artery stenosis or occlusion (CASO) is a major cause of vascular cognitive impairment (VCI). There is currently no effective treatment for VCI induced by CASO. Resveratrol, a type of polyphenol, improves cognitive performance in rat CASO models via pleiotropic effects. Furthermore, we previously reported the longevity gene, SIRT1 , which can be activated by resveratrol, improves cognitive and cerebral blood flow impairment in mouse CASO models by activating endothelial nitric oxide synthase. However, clinical evidence remains limited., Methods: The REsveratrol for VAscular cognitive impairment investigating cerebral Metabolism and Perfusion (REVAMP) trial is a randomized, double-blind, placebo-controlled trial involving patients with asymptomatic CASO. Each participant will receive either 150 mg/day of resveratrol or a placebo for 35 weeks. The primary objective is to determine whether resveratrol improves cognitive impairment, as assessed using the Alzheimer's disease Assessment Scale-cognitive subscale 13. One of our secondary objectives is to determine whether resveratrol improves cerebral hemodynamic impairment as assessed via 15 O-gas positron emission tomography. We will recruit 100 patients (50 per group)., Discussion: The REVAMP trial may provide valuable insights into new therapeutic options, as multitarget neuroprotection could potentially improve cognitive function along with enhancements in cerebral hemodynamic status in patients with asymptomatic CASO. Clinical trial registration : The REVAMP trial was prospectively registered in the Japan Registry of Clinical Trials (jRCTs051230013) on April 13, 2023., Competing Interests: YH receives a grant from Nature Holdings Co., Ltd. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Hattori, Minami, Omae, Yoshimoto, Abe, Yamamoto, Iida and Ihara.)

Porphyromonas gingivalis ( Pg ) utilizes FimA fimbriae to colonize the gingival sulcus and evade the host immune system. The biogenesis of all FimA-related components is positively regulated by the FimS-FimR two-component system, making the FimS sensory protein an attractive target for preventing Pg infection. However, the specific environmental signal received by FimS remains unknown. We constructed random Pg mutant libraries to identify critical amino acid residues for signal sensing by FimS. Optimized error-prone polymerase chain reaction (PCR) was used to introduce a limited number of random mutations in the periplasmic-domain-coding sequence of fimS , and expression vectors carrying various mutants were generated by inverse PCR. More than 500 transformants were obtained from the fimS -knockout Pg strain using the Escherichia coli - Pg conjugal transfer system, whereas only ~100 transformants were obtained using electroporation. Four and six transformant strains showed increased and decreased fimA expression, respectively. Six strains had single amino acid substitutions in the periplasmic domain, indicating critical residues for signal sensing by FimS. This newly developed strategy should be generally applicable and contribute to molecular genetics studies of Pg , including the elucidation of structure-function relationships of proteins of interest.

Aims: Retroperitoneoscopic simple nondismembered pyeloplasty (SNDP) with da Vinci Si assistance was developed because of a possible risk for alignment shift after retroperitoneoscopic diamond-shaped bypass pyeloplasty (Diamond-Bypass; DP). Outcomes of SNDP and DP were compared. Materials and Methods: For SNDP, a small longitudinal incision is made on the border of the dilated pelvis and narrowed ureter at the ureteropelvic junction (UPJ). Extending this incision toward the pelvis allows identification of mucosa while maintaining the integrity of surrounding tissues that are so thin and fragile that they will not influence lumen alignment. Data for DP were obtained from a previously published article. Results: For SNDP ( n  = 3), mean age at surgery was 2.67 years (range: 1-4), mean operative time was 176 minutes. Mean postoperative Society of Fetal Urology (SFU) grades for hydronephrosis were 1.2, 0.7, and 0.6, 1, 2, and 3 months after stent removal, respectively. Postoperative diethylenetriaminepentaacetic acid (DTPA) was normal ( n  = 3). For DP ( n  = 5) mean age at surgery was 4.3 years (range: 1-14), mean operative time was 189 minutes. Mean postoperative SFU grades were 2.8, 2.2, and 1.6, respectively. Postoperative DTPA was normal ( n  = 4) and delayed ( n  = 1). All SNDP and DP were asymptomatic by 3 months after stent removal. Conclusion: Both SNDP and DP have favorable outcomes. If the UPJ is located at the lowest end of the renal pelvis, SNDP may improve hydronephrosis more quickly.

Background: The Nuss procedure is currently the mainstream of pectus excavatum (PE) surgery; however, it is considered to be more difficult for asymmetric cases than for symmetric ones. Sternocostal elevation (SCE), which was performed at our hospital, is a surgical method that determines the extent of resection of the costal cartilage while comparing the left and right balance during surgery; thus, it is highly useful for correcting rib cage with strong asymmetry., Methods: Of the 256 patients who underwent SCE at our hospital between July 2014 and July 2022, 58 (22.7%) with asymmetric PE were retrospectively examined. However, patients with advanced scoliosis having a Cobb angle of 25° or higher were excluded; therefore, 51 (19.9%) patients were analyzed. Two indices and other measurements were evaluated to determine the success of correction for asymmetry using computed tomography (CT)., Results: The difference between the left and right thoraxes, the Haller index, and the sternal torsion angle significantly improved. Furthermore, we herein set a new numerical index as an indicator of asymmetry improvement and to be used for a more standard thorax morphology; the difference between the left and right thoraxes/the average of the left and right thoraxes. That new index also significantly improved., Conclusions: SCE is considered a highly useful surgical method for asymmetric PE., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://jtd.amegroups.com/article/view/10.21037/jtd-23-1824/coif). The authors have no conflicts of interest to declare., (2024 Journal of Thoracic Disease. All rights reserved.)

Context: Studies on human renal metabolism are scanty. Nowadays, functional imaging allows the characterization of renal metabolism in a noninvasive manner. We have recently demonstrated that fluorodeoxyglucose F18 (18F FDG) positron emission tomography can be used to analyze renal glucose uptake (GU) rates, and that the renal cortex is an insulin-sensitive tissue., Objective: To confirm that renal GU is decreased in people with obesity and to test whether circulating metabolites are related to renal GU., Design, Setting and Participants: Eighteen people with obesity and 18 nonobese controls were studied with [18F]FDG positron emission tomography during insulin clamp. Renal scans were obtained ∼60 minutes after [18F]FDG injection. Renal GU was measured using fractional uptake rate and after correcting for residual intratubular [18F]FDG. Circulating metabolites were measured using high-throughput proton nuclear magnetic resonance metabolomics., Results: Cortical GU was higher in healthy nonobese controls compared with people with obesity (4.7 [3.4-5.6] vs 3.1 [2.2-4.3], P = .004, respectively), and it associated positively with the degree of insulin sensitivity (M value) (r = 0.42, P = .01). Moreover, cortical GU was inversely associated with circulating β-OH-butyrate (r = -0.58, P = .009), acetoacetate (r = -0.48, P = .008), citrate (r = -0.44, P = .01), and free fatty acids (r = -0.68, P < .0001), even when accounting for the M value. On the contrary, medullary GU was not associated with any clinical parameters., Conclusion: These data confirm differences in renal cortical GU between people with obesity and healthy nonobese controls. Moreover, the negative correlations between renal cortex GU and free fatty acids, ketone bodies, and citrate are suggestive of substrate competition in the renal cortex., (© The Author(s) 2023. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: In some cases, patients feel a perceived leg length discrepancy (P-LLD) despite no radiographic leg length discrepancy (R-LLD) after total hip arthroplasty (THA). We aimed to investigate the rate of postoperative P-LLD and the factors that cause postoperative P-LLD., Methods: A retrospective study was conducted on 100 patients with R-LLD ≤5 mm after THA. Patients were classified into two groups based on P-LLD post-THA: group P (with P-LLD) and group E (without P-LLD). Relevant data on the general characteristics and radiological findings between the two groups were compared., Results: We observed that 25 & 75% of patients belonged to group P and group E, respectively, with no significant difference in patient background. Postoperative Japanese Orthopedic Association (JOA) classification of pain and activities of daily living scores were significantly lower in group P than in group E (37.2 ± 3.9 vs. 39.1 ± 2.2, respectively; P = 0.013, and 16.2 ± 4.2 vs. 18.2 ± 2.2, respectively; P = 0.011). The preoperative pelvic oblique angle (POA) was significantly larger in group P than in group E (3.3 ± 2.3° vs. -0.2 ± 2.1°; respectively; P < 0.01). The pelvis tilted toward the surgical side was significantly higher in group P than in group E(88% vs 57%; respectively; P = 0.013). The preoperative C7 coronal vertical axis (C7 CVA) was significantly larger in group P than in group E (6.7 ± 14.7 mm vs. -0.2 ± 10.3 mm; respectively; P = 0.028). Multivariate logistic analysis revealed that preoperative POA (OR, 3.71; 95% CI: 1.86-8.12; P < 0.01) and the pelvis tilted toward the surgical side (OR, 4.14; 95% CI: 2.07-9.71; P = 0.022) were independent risk factors for P-LLD after THA., Conclusion: Even though there was no postoperative R-LLD, 25% of patients had P-LLD. A large preoperative POA and the pelvis tilted toward the surgical side were independent risk factors for P-LLD after THA., Competing Interests: Declaration of competing interest All authors declare that they have no conflict of interest., (Copyright © 2023 The Japanese Orthopaedic Association. Published by Elsevier B.V. All rights reserved.)

The synthesis of a chiral supramolecular organogel via the hierarchical helical self-assembly of optically active riboflavin and melamine derivatives is described herein. Owing to the photocatalysis of riboflavin and the supramolecular chirality induced in the helically stacked riboflavin/melamine complex, the gel is observed to act as a light-stimulated chiral sensor of optically active alcohols by detecting the change in color from yellow to green. The gel also served as an efficient chiral adsorbent, enabling optical resolution of a racemic compound with high chiral recognition ability., (© 2023 Wiley-VCH GmbH.)

The specification of the embryonic central nervous system (CNS) into future brain (forebrain, midbrain, or hindbrain) and spinal cord (SC) regions is a critical step of CNS development. A previous chicken embryo study indicated that anterior epiblast cells marked by Sox2 N2 enhancer activity are specified to the respective brain regions during the transition phase of the epiblast to the neural plate-forming neural primordium. The present study showed that the SC precursors positioned posterior to the hindbrain precursors in the anterior epiblast migrated posteriorly in contrast to the anterior migration of brain precursors. The anteroposterior specification of the CNS precursors occurs at an analogous time (∼E7.5) in mouse embryos, in which an anterior-to-posterior incremental gradient of Wnt signal strength was observed. To examine the possible Wnt signal contribution to the anteroposterior CNS primordium specification, we utilized mouse epiblast stem cell (EpiSC)-derived neurogenesis in culture. EpiSCs maintained in an activin- and FGF2-containing medium start neural development after the removal of activin, following a day in a transitory state. We placed activin-free EpiSCs in EGF- and FGF2-containing medium to arrest neural development and expand the cells into neural stem cells (NSCs). Simultaneously, a Wnt antagonist or agonist was added to the culture, with the anticipation that different levels of Wnt signals would act on the transitory cells to specify CNS regionality; then, the Wnt-treated cells were expanded as NSCs. Gene expression profiles of six NSC lines were analyzed using microarrays and single-cell RNA-seq. The NSC lines demonstrated anteroposterior regional specification in response to increasing Wnt signal input levels: forebrain-midbrain-, hindbrain-, cervical SC-, and thoracic SC-like lines. The regional coverage of these NSC lines had a range; for instance, the XN1 line expressed Otx2 and En2, indicating midbrain characteristics, but additionally expressed the SC-characteristic Hoxa5. The ranges in the anteroposterior specification of neural primordia may be narrowed as neural development proceeds. The thoracic SC is presumably the posterior limit of the contribution by anterior epiblast-derived neural progenitors, as the characteristics of more posterior SC regions were not displayed., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Nakamura, Watanabe, Boitet, Satake, Iida, Yoshihi, Ishii, Kato and Kondoh.)

Objective: Minimal residual disease assessment of BCR-ABL messenger ribonucleic acid levels is crucial in Philadelphia chromosome-positive acute lymphoblastic leukemia for prognosis and treatment planning. However, accurately quantifying minor BCR-ABL transcripts, which comprise 70% of Philadelphia chromosome-positive acute lymphoblastic leukemia cases, lacks a national-approved method., Methods: We developed the "Otsuka" minor BCR-ABLmessenger ribonucleic acid assay kit with exceptional precision (0.00151%). Minor BCR-ABL messenger ribonucleic acid levels were analyzed in 175 adults, 36 children with acute lymphoblastic leukemia and 25 healthy individuals to evaluate the kit's performance., Results: The "Otsuka" kit showed high concordance with a commonly used chimeric gene screening method, indicating reliable detection of positive cases. Quantitative results demonstrated a robust correlation with both a laboratory-developed test and a diagnostic research product. The "Otsuka" kit performs comparably or even surpass to conventional products, providing valuable insights into Philadelphia chromosome-positive acute lymphoblastic leukemia pathology., Conclusions: The 'Otsuka" minor BCR-ABL messenger ribonucleic acid assay kit exhibits excellent performance in quantifying minor BCR-ABL transcripts in Philadelphia chromosome-positive acute lymphoblastic leukemia patients. Our results align well with established screening methods and show a strong correlation with laboratory-developed tests and diagnostic research products. The "Otsuka" kit holds great promise as a valuable tool for understanding Philadelphia chromosome-positive acute lymphoblastic leukemia pathology and guiding effective treatment strategies., (© The Author(s) 2023. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permission@oup.com.)

Background: Collapse cessation is of utmost importance following a long period of collapse due to osteonecrosis of the femoral head (ONFH). This study investigated the relationship between collapse cessation and the extent of the necrotic regions of ONFH., Methods: Overall, 74 patients who had symptomatic ONFH (collapse < 3 mm) at the first visit with a minimum follow-up of 3 years were included in this study. Patients were categorized based on collapse progression or cessation into the progression and stable groups. The extent of the antero-posterior (AP) and medio-lateral necrotic regions between the groups was assessed using sagittal and coronal sections of T1-magnetic resonance imaging. Additionally, the most effective cutoff value was determined from the receiving operating characteristic curve where collapse cessation could be obtained, while the survival rates were determined with collapse progression as the endpoints were evaluated., Results: Overall, 45 and 29 patients were in the progression and stable groups, respectively. The AP and medio-lateral necrotic regions were significantly different (P < .01 and P < .01, respectively) between the progression and stable groups. A cutoff value of 62.1% of the AP necrotic regions was determined from the receiving operating characteristic curve analysis. The 5-year survival rates with collapse progression as the endpoints were 5.4 and 77.8% in the AP necrotic regions of ≥62.1 and <62.1%, respectively (P < .01)., Conclusions: Cases with AP necrotic regions of ≤62.1% can be expected to have collapse cessation, which could be a useful index for ONFH treatment strategies., Level of Evidence: Level IV., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: Liver resection offers substantial advantages over open liver resection (OLR) for patients with hepatocellular carcinoma (HCC) in terms of reduced intraoperative blood loss and morbidity. However, there is limited evidence comparing the indications and perioperative outcomes with the open versus laparoscopic approach for resection. This study aimed to compare postoperative outcomes between patients undergoing laparoscopic liver resection (LLR) and OLR for HCC with clinically significant portal hypertension (CSPH)., Methods: A total of 316 HCC patients with CSPH (the presence of gastroesophageal varices or platelet count < 100,000/ml and spleen diameter > 12 cm) undergoing minor liver resection at eight centers were included in this study. To adjust for confounding factors between the LLR and OLR groups, an inverse probability weighting method analysis was performed., Results: Overall, 193 patients underwent LLR and 123 underwent OLR. After weighting, LLR was associated with a lower volume of intraoperative blood loss and the incidence of postoperative complications (including pulmonary complications, incisional surgical site infection, and paralytic ileus) compared to the OLR group. The 3-, 5-, and 7-year postoperative recurrence-free survival rates were 39%, 26%, and 22% in the LLR group and 49%, 18%, and 18% in the OLR group, respectively (p = 0.18). And, the 3-, 5-, and 7-year postoperative overall survival rates were 71%, 56%, and 44% in the LLR group and 76%, 51%, 44% in the OLR group, respectively (p = 0.87)., Conclusions: LLR for HCC patients with CSPH is clinically advantageous by lowering the volume of intraoperative blood loss and incidence of postoperative complications, thereby offering feasible long-term survival., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)