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Background: Hepatocellular carcinoma (HCC) with inferior vena cava (IVC) tumor thrombus is generally considered to be borderline resectable because of its poor prognosis. 1-5 This report describes a patient who underwent multidisciplinary treatment for HCC with massive IVC tumor thrombus., Methods: The 56-year-old woman in this study had diffuse HCC of the medial and anterior segments. She received an explanation of the procedure and provided informed consent. A tumor thrombus was observed in the right atrium through the middle and left hepatic veins and in the anterior branch of the portal vein. The HCC was considered unresectable, and atezolizumab plus bevacizumab combination therapy was initiated. However, the tumor thrombus progressed to the right atrium after two courses. The treatment was changed to hepatic arterial infusion chemotherapy with cisplatin and three-dimensional conformal radiotherapy to the tumor thrombus in the right atrium, followed by systemic lenvatinib., Results: The patient's tumor marker levels decreased significantly, and the tumor thrombus regressed into the IVC. Left hepatic trisegmentectomy and IVC tumor thrombectomy were performed. 6-8 Although Clavien-Dindo IIIa postoperative biliary leakage was observed, the patient was discharged on postoperative day 56. Pathologic findings showed no viable residual tumor cells in either the main tumor or the tumor thrombus, and the patient had a pathologic complete response. At this writing, the patient has been recurrence-free for 19 months since the initial treatment without any adjuvant therapy., Conclusion: This report presents a case of unresectable HCC treated with multimodality therapy followed by salvage surgery. The patient achieved a long-term cancer-free and drug-free status through aggressive treatment. This patient's experience offers hope for aggressive treatment of advanced HCC., Competing Interests: Disclosure: The authors declare that they have no conflicts of interest and received no funding support for this research. Informed consent: The patient received an explanation of the procedure and provided their informed consent., (© 2024. Society of Surgical Oncology.)

Pyruvate is situated at the intersection of oxidative phosphorylation (OXPHOS) and glycolysis, which are the primary energy-producing pathways in cells. Cancer therapies targeting these pathways have been previously documented, indicating that inhibiting one pathway may lead to functional compensation by the other, resulting in an insufficient antitumor effect. Thus, effective cancer treatment necessitates concurrent and comprehensive suppression of both. However, whether a metabolic switch between the metabolic pathways occurs in colorectal and gastric cancer cells and whether blocking it by inhibiting both pathways has an antitumor effect remain to be determined. In the present study, we used two small molecules, namely OXPHOS and glycolysis inhibitors, to target pyruvate metabolic pathways as a cancer treatment in these cancer cells. OXPHOS and glycolysis inhibition each augmented the other metabolic pathway in vitro and in vivo. OXPHOS inhibition alone enhanced glycolysis and showed antitumor effects on colorectal and gastric cancer cells in vitro and in vivo. Moreover, glycolysis inhibition in addition to OXPHOS inhibition blocked the metabolic switch from OXPHOS to glycolysis, causing an energy depletion and deterioration of the tumor microenvironment that synergistically enhanced the antitumor effect of OXPHOS inhibitors. In addition, using hyperpolarized 13C-magnetic resonance spectroscopic imaging (HP-MRSI), which enables real-time and in vivo monitoring of molecules containing 13C, we visualized how the inhibitors shifted the flux of pyruvate and how this dual inhibition in colorectal and gastric cancer mouse models altered the two pathways. Integrating dual inhibition of OXPHOS and glycolysis with HP-MRSI, this therapeutic model shows promise as a future "cancer theranostics" treatment option., Competing Interests: The authors have declared that no competing interests exist., (Copyright: This is an open access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication.)

Work-life balance is often discussed in Japan. Yet surgeons find it challenging to take paternity leave because of their demanding surgical duties and a strong sense of responsibility. One Japanese male surgeon had his first paternity experience as a research fellow in the US. When he returned to Japan, he resumed his surgical training and started a research project to become an academic surgeon. When he and his wife were expecting their second child, they discussed his paternity participation before the delivery and decided on a sustainable paternity participation plan. By coordinating his responsibilities with his co-workers, he limited his attendance at work to daytime hours only for 1 month to manage paternity duties. This adjustment did not affect the number of main and assistant operations conducted that month and effective optimization of workflow processes decreased the extra workload for other team members. His experience suggests that the optimization of workflow processes can enhance personal life, including paternity participation. (150/150)., (© 2024. The Author(s).)

Objectives: To investigate the effect of preoperative muscle quality on functional outcomes after total hip arthroplasty (THA)., Design: Retrospective cohort study., Setting and Participants: We included 426 patients who underwent primary THA between 2015 and 2022 to evaluate the relationship between preoperative muscle quality and 1-year functional outcomes following THA., Methods: The muscle cross-sectional area (CSA) and density at baseline were measured using preoperative computed tomography. The CSA was further divided based on muscle quality into intramuscular adipose tissue (IMAT), normal-density muscle (NDM), and low-density muscle (LDM) based on muscle density thresholds. According to their functional recovery, patients were classified into sufficient functional recovery (Harris hip score [HHS] ≥89) and insufficient functional recovery (HHS <89) groups based on their HHS at 1-year post THA. Propensity score matching was performed to balance the baseline characteristics of the patient groups, including age, sex, body mass index, HHS, University of California, Los Angeles activity scores, and gait speed. The preoperative muscle density, CSA, IMAT, NDM, and LDM of the gluteus maximus, gluteus medius, gluteus minimus, iliopsoas, and rectus femoris muscles were compared between the groups., Results: Ninety matched pairs were analyzed following covariate adjustment using propensity scores. The insufficient group had significantly more IMAT in all muscles preoperatively than did the sufficient group (P < .05). In addition, the muscle density and NDM of the gluteus maximus, gluteus medius, and iliopsoas in the insufficient group were significantly worse than those in the sufficient group (P < .05). Conversely, the 2 groups showed no significant differences in LDM., Conclusions and Implications: Our results revealed that patients with a significantly higher IMAT prevalence and reduced NDM preoperatively were less likely to experience significant improvement after THA. Therefore, we propose that undergoing THA with good muscle quality represents the optimal timing for achieving higher functional recovery., Competing Interests: Disclosure The authors declare no conflicts of interest, (Copyright © 2024. Published by Elsevier Inc.)

Background: The use of life-sustaining treatment (LST) in the final stage of life is a major policy concern due to increased costs, while its intensity does not correlate with quality. Previous reports have shown declining trends in LST use in Japan. However, regional practice variations remain unclear. This study aims to describe regional variations in LST use before death among the oldest old in Japan., Methods: A descriptive study was conducted among patients aged 85 years or older who passed away between April 2013 and March 2014. The study utilized health insurance claims from Japan's National Database (NDB) to examine the use of cardiopulmonary resuscitation (CPR), mechanical ventilation (MV), and admission to the acute care ward (ACW) in the last 7 days of life., Results: Among 224,391 patients, the proportion of patients receiving LST varied by region. CPR ranged from 8.6% (Chubu) to 12.9% (Shikoku), MV ranged from 7.1% (Chubu) to 12.3% (Shikoku), and admission to ACW ranged from 4.5% (Chubu) to 10.1% (Kyushu-Okinawa). The adjusted odds ratios (AOR) for regional variation compared with Kanto were as follows: CPR (in Shikoku, AOR 1.85; 95% confidence interval [CI], 1.73-1.98), MV (in Shikoku, AOR 1.75; 95% CI, 1.63-1.87), and ACW admission (in Kyushu-Okinawa, AOR 1.69; 95% CI, 1.52-1.88)., Conclusion: The study presents descriptive information regarding regional differences in the utilization of LST for the oldest old in Japan. Further research is necessary to identify the factors that contribute to these variations and to address the challenge of improving the quality of end-of-life care.

Background: Postoperative symptom exacerbation after resection of cerebral cavernous malformations (CCMs) is usually due to surgical damage to the eloquent areas or venous outflow obstruction from injury to a developmental venous anomaly (DVA)., Observations: A 21-year-old right-handed female presented with headache, right limb weakness, and aphasia. Magnetic resonance imaging (MRI) revealed a 3.5-cm CCM with significant perilesional edema in the middle frontal gyrus. Despite medical treatment, her weakness worsened, necessitating emergency resection. Imaging revealed no DVA or venous obstructions. Histopathological examination revealed marked neutrophil infiltration, indicating noninfectious inflammation. One week postoperatively, MRI revealed increased edema around the resection site. Although the aphasia improved, paralysis (manual muscle testing grade 3) persisted, prompting betamethasone administration. The symptoms rapidly improved over 10 days, and the patient was discharged symptom free on day 20 with no recurrence thereafter., Lessons: Patients with prolonged postoperative deficits after CCM resection can experience noninfectious inflammation. Anti-inflammatory treatments such as corticosteroids may be necessary in similar cases with poor recovery from edema and symptoms. https://thejns.org/doi/10.3171/CASE24570.

The mammalian striatum is divided into two types of anatomical structures: the island-like, mu opioid receptor (MOR)-rich striosome compartment and the surrounding matrix compartment. Both compartments have two types of spiny projection neurons (SPNs), dopamine receptor D1 (D1R)-expressing direct pathway SPNs (dSPNs) and dopamine receptor D2 (D2R)-expressing indirect pathway SPNs. These compartmentalized structures have distinct roles in the development of movement disorders, although the functional significance of the striosome compartment for motor control and dopamine regulation remains to be elucidated. The aim of this study was to explore the roles of striosome in locomotion and dopamine dynamics in freely moving mice. We targeted striosomal MOR-expressing neurons with male MOR-CreER mice, which express tamoxifen-inducible Cre recombinase under MOR promoter, and Cre-dependent adeno-associated virus vector. The targeted neuronal population consisted mainly of dSPNs. We found that the Gq-coupled designer receptor exclusively activated by designer drugs (DREADD)-based chemogenetic stimulation of striatal MOR-expressing neurons caused a decrease in the number of contralateral rotations and total distance traveled. Wireless fiber photometry with a genetically-encoded dopamine sensor revealed that chemogenetic stimulation of striatal MOR-expressing neurons suppressed dopamine signals in the dorsal striatum of freely moving mice. Furthermore, the decrease in mean dopamine signal and the reduction of transients were associated with ipsilateral rotational shift and decrease of average speed, respectively. Thus, a subset of striosomal dSPNs inhibits contralateral rotation, locomotion, and dopamine release in contrast to the role of pan-dSPNs. Our results suggest that striatal MOR-expressing neurons have distinct roles in motor control and dopamine regulation. Significance of statement The striatum plays a crucial role in motor control, and it consists of two anatomical compartments: mu opioid receptor (MOR)-rich striosomes and the surrounding matrix. The striosome sends efferent inhibitions to midbrain dopaminergic neurons, but it remains unknown whether striosomes are involved in motor control and dopamine regulation in behaving animals. We used MOR-expression based targeting, chemogenetics and wireless fiber photometry with a genetically-encoded dopamine sensor, and we found that chemogenetic stimulation of striosomal MOR-expressing neurons inhibits contralateral rotations, locomotion, and dopamine release in the dorsal striatum. The rotational shift and the locomotion decrease might be differently associated with dopamine dynamics. This study provides compelling evidence that striosomal MOR-expressing neurons inhibit motor behavior and dopamine release in freely moving animals., (Copyright © 2024 the authors.)

Background: Restenosis after carotid artery stenting (CAS) is associated with the risk of developing ischemic stroke. We aimed to evaluate the inhibitory effect of cilostazol addition on in-stent restenosis (ISR) in patients treated with CAS., Methods: In a randomized, open-label, blind-end point trial, patients with symptomatic and asymptomatic carotid artery stenosis and scheduled for CAS were randomly assigned to adding cilostazol (50 or 100 mg, twice per day) on other antiplatelets from 3 days before CAS or not adding cilostazol. Concomitant use of other antiplatelets was unrestricted. ISR was diagnosed by a peak systolic velocity of at least 1.75 m/s on duplex ultrasonography. The primary outcome was incidence of ISR within 2 years after CAS. Secondary outcomes included occurrences of cardiovascular events or any death and hemorrhagic events., Results: Participants were recruited from December 2010 to September 2015. Although the sample size was initially set to be 900 (450 in each group), 631 patients (mean age 69.9 years, 558 men, 325 in the cilostazol, and 306 in the noncilostazol group) were included in the primary analysis. Within 2 years' follow-up, ISR occurred in 31 of 325 patients (cumulative incidence 10.8%) in the cilostazol group and 46 of 306 patients (19.6%) in the noncilostazol group (hazard ratio, 0.64 [95% CI, 0.41-1.0]; P =0.056). In the exploratory analysis, incidence of ISR beyond 30 days after CAS was lower in the cilostazol group than in the noncilostazol group (10.3% versus 19.3%; P =0.040). Incidences of cardiovascular events or any death and hemorrhagic events were similar between the groups (6.2% versus 6.7% and 2.3% versus 1.4%, respectively)., Conclusions: The addition of cilostazol to other antiplatelet agents could contribute to the reduction of ISR in the chronic stage of patients who underwent CAS, the authenticity of which depends on further studies with sufficient statistical power., Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT01261234., Competing Interests: Otsuka Pharmaceutical provided funding for this study to the Translational Research Center for Medical Innovation, but was not involved in the planning, management, or discussion of the results of the study. Dr Yamagami reports a research grant from Bristol-Myers Squibb; lecturer’s fees from Stryker, Medtronic, Johnson & Johnson, Medico’s Hirata, Bristol-Myers Squibb, Diichi-Sankyo, Boston Scientific, and Otsuka Pharmaceutical. Dr Matsumaru reports research grants, travel support, and data and safety monitoring fees from Philips; lecturer’s fees from Diichi-Sankyo, Bayer, Stryker, Jimro, Johnson & Johnson, Terumo, Kaneka, Medtronic, and Philips. Dr Yoshimura reports lecturer’s fees from Idorsia, Bristol-Myers Squibb, Terumo, Daiichi Sankyo, Kaneka, Johnson & Johnson, Bayer, Medtronic, Boehringer Ingelheim and Stryker. Dr Matsumoto reports lecturer’s fees from Kaneka medics, Medico’s Hirata, Fuji systems, GE Healthcare, Otsuka Pharmaceutical, Takeda Pharmaceutical Limited, Medtronic, Century Medical, Stryker, Medtronic and Terumo; and royalties from Sumitomo Bakelite. Dr N. Sakai reports a research grant from Biomedical Solutions, Medtronic, Terumo and TG Medical; lecturer’s fees from Asahi-Intec, Biomedical Solutions, Daiichi Sankyo, Kaneka, Medtronic, Otsuka Pharmaceutical and Terumo; and membership on the advisory boards for Johnson & Johnson, Medtronic, and Terumo outside the submitted work. The other authors report no conflicts.

Background & Aims: This study aimed to clarify the association between physical activity (PA) and physical functions, including both muscle quantity and quality of ankle plantar flexor muscles in patients with knee osteoarthritis (OA)., Methods: A retrospective cohort study was conducted with ninety-two patients with knee OA. PA, leg muscle cross-sectional area (CSA), knee strength, passive knee angle, and knee pain of the affected side were assessed. PA was assessed by the 2011 Knee Society scoring system. CSA of the quadriceps and ankle plantar flexor muscles on the affected side was measured using a computed tomography image. Based on muscle attenuation assessed with Hounsfield units (HU), the muscle quality of targeted muscle was divided into 4 groups as follows: fat tissue (-190 to -30 HU), very low-density muscle (-29 to -1 HU), low-density muscle (0 to 34 HU), and normal-density muscle (NDM, 35 to 100 HU). The CSA was obtained for each of the 4 groups. Univariate and multivariate linear regression analyses were performed to determine the factors associated with PA., Results: The regression analysis revealed that higher PA was independently associated with the NDM CSA of ankle plantar flexor (β = 0.51), higher knee extension strength (β = 0.28), and milder knee pain (β = -0.29) after adjustment with age, sex, height, weight, and body mass index., Conclusion: The present study suggested that NDM CSA of ankle plantar flexor in addition to knee function is one of the factors determining the PA in patients with knee OA., Competing Interests: Declaration of competing interest Some authors (SM, SK, KN) have a financial relationship with Kyocera and Zimmer-Biomet unrelated to this study., (Copyright © 2024 European Society for Clinical Nutrition and Metabolism. Published by Elsevier Ltd. All rights reserved.)

Background: Palonosetron, a second-generation 5-HT 3 receptor antagonist (5-HT 3 RA), is more effective than first-generation 5-HT 3 RA. Several studies have investigated whether dexamethasone (DEX), when combined with palonosetron as a 5-HT 3 RA, can be spared in the delayed phase after moderately emetogenic chemotherapy (MEC). In this systematic review, we aimed to determine which between 1- and 3-day DEX administration, when combined with palonosetron, is more useful in patients receiving MEC., Methods: The PubMed, Cochrane Library, and Ichushi-Web databases were searched for relevant studies published between 1990 and 2020. We included studies that compared the efficacy of 1- and 3-day DEX administration in preventing nausea and vomiting associated with MEC. Outcomes were "prevention of vomiting (complete response rate and no vomiting rate)," "prevention of nausea" (complete control rate, total control rate, no nausea rate, and no clinically significant nausea rate)" in the delayed phase, "prevention of blood glucose level elevation," and "prevention of osteoporosis.", Results: Eight studies were included in this systematic review. The no vomiting rate was significantly higher in the 3-day DEX group than in the 1-day DEX group. However, the other efficacy items did not significantly differ between the two groups. Meanwhile, insufficient evidence was obtained for "prevention of blood glucose level elevation" and "prevention of osteoporosis.", Conclusions: No significant differences in most antiemetic effects were found between 1- and 3-day DEX administration. Thus, DEX administration could be shortened from 3 days to 1 day when used in combination with palonosetron., Competing Interests: Declarations. Conflict of interest: Kazuhisa Nakashima received honoraria from Taiho Pharmaceutical Co., Ltd., Chugai Pharmaceutical Co., Ltd., AstraZeneca K.K., and Eli Lilly Japan K.K. Michiyasu Murakami received honoraria from Taiho Pharmaceutical Co., Ltd. Eriko Satomi received honoraria from Shionogi & Co., Ltd. Masayuki Takeda received honoraria from Chugai Pharmaceutical Co., Ltd., AstraZeneca K.K., Novartis Pharma K.K., Ono Pharmaceutical Co., Ltd., and Bayer. Takako Eguchi Nakajima received research funding from KBBM, Inc. and Takeda Pharmaceutical Co., Ltd. Junichi Nishimura received honoraria from Taiho Pharmaceutical Co., Ltd. Narikazu Boku received honoraria from Ono Pharmaceutical Co., Ltd., Bristol Myers Squibb, Daiichi Sankyo Co., Ltd., Taiho Pharmaceutical Co., Ltd., and Eli Lilly Japan K.K. Koji Matsumoto received honoraria from MSD K.K., Kyowa Kirin Co., Ltd., and Chugai Pharmaceutical Co., Ltd. as well as research funding from Daiichi Sankyo Co., Ltd., MSD K.K., Gilead Sciences, Inc., and Eli Lilly Japan K.K. Nobuyuki Yamamoto received honoraria from MSD K.K., Accuray Japan K.K., AstraZeneca K.K., Abbvie Inc., Amgen Inc., Ono Pharmaceutical Co., Ltd., Guardant Health Japan Corp., Daiichi Sankyo Co., Ltd., Taiho Pharmaceutical Co., Ltd., Takeda Pharmaceutical Co., Ltd., Chugai Pharmaceutical Co., Ltd., Chugai Foundation for Innovative Drug Discovery Science, Lao Tsumura Co., Ltd., Terumo Corporation, Eli Lilly Japan K.K., Nippon Kayaku Co., Ltd., Novartis AG, Pfzer Global Supply Japan Inc., Merck Biopharma Co., Ltd, Pfzer Global Supply Japan Inc., Merck Biopharma Co., Ltd., Janssen Pharmaceutical K.K., and USACO Corporation, as well as legal fees in case of lawsuit from Taiho Pharmaceutical Co., Ltd., Boehringer Ingelheim Japan, Chugai Pharmaceutical Co., Ltd., Kyowa Kirin Co., Ltd., Nippon Kayaku Co., Ltd., Prime Research Institute for Medical RWD, Inc., AstraZeneca K.K., and A2 Healthcare Corporation. Other authors declare that they have no conflict of interest. Ethical approval: Not applicable. Informed consent: Formal consent was not required for this type of study. Consent to participate: Not applicable. Consent for publication: All authors consented to the publication of this study., (© 2024. The Author(s) under exclusive licence to Japan Society of Clinical Oncology.)

Our understanding of neoadjuvant treatment with microtubule inhibitors (MTIs) for triple negative breast cancer (TNBC) remains limited. To advance our understanding of the role of breast cancer driver genes' mutational status with pathological complete response (pCR; ypT0/isypN0) prediction and to identify distinct gene sets for MTIs like eribulin and paclitaxel, we carried out targeted genomic (n = 50) and whole transcriptomic profiling (n = 64) of TNBC tumor samples from the Japan Breast Cancer Research Group 22 (JBCRG-22) clinical trial. Lower PIK3CA, PTEN, and HRAS mutations were found in homologous recombination deficiency (HRD)-high (HRD score ≥ 42) tumors with higher pCR rates. When HRD-high tumors were stratified by tumor BRCA mutation status, the pCR rates in BRCA2-mutated tumors were higher (83% vs. 36%). Transcriptomic profiling of TP53-positive tumors identified downregulation of FGFR2 (false discovery rate p value = 2.07e-7), which was also the only common gene between HRD-high and -low tumors with pCR/quasi-pCR treated with paclitaxel and eribulin combined with carboplatin, respectively. Differential enrichment analysis of the HRD-high group posttreatment tumors revealed significant correlation (p = 0.006) of the glycan degradation pathway. FGFR2 expression and the differentially enriched pathways play a role in the response and resistance to MTIs containing carboplatin treatment in TNBC patients., (© 2024 The Author(s). Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.)

Aims: Despite the reported success of low-carbohydrate diets in improving glycemic control in the Western countries, no studies have investigated the effects of such diets in Asians. We aimed to conduct a systematic review and meta-analysis of randomized controlled trials to examine the effects of low-carbohydrate diets on glycemic control in East Asian adults., Materials and Methods: We systematically searched the PubMed, Cochrane Library, and Embase databases from inception to June 28, 2023, to identify randomized controlled trials examining the efficacy of low-carbohydrate diets in patients with type 2 diabetes (PROSPERO number CRD 42023453007). The primary outcome was the difference in glycated hemoglobin levels between the low-carbohydrate diet and control groups. The secondary outcome was the difference in body mass index, fasting blood glucose level, blood pressure, and lipid profile., Results: Six randomized controlled trials met the eligibility criteria. The study duration ranged from 3 to 18 months, with five studies conducted within 6 months. The results showed that low-carbohydrate diets were more beneficial in lowering glycated hemoglobin levels and body mass index than control diets. The risk of bias for the six studies was minimal for two and moderate for four. The heterogeneity among the studies was low., Conclusions: Low-carbohydrate diets improved glycated hemoglobin levels and body mass index in East Asians compared with control diets. Therefore, carbohydrate restriction may be effective for glycemic management in East Asians with type 2 diabetes for at least 6 months., (© 2024 The Author(s). Journal of Diabetes Investigation published by Asian Association for the Study of Diabetes (AASD) and John Wiley & Sons Australia, Ltd.)

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is a curative treatment for relapsed or refractory non-Hodgkin lymphoma (R/R NHL). Allo-HSCT using post-transplant cyclophosphamide (PTCY-haplo) and umbilical cord blood transplantation (uCBT) are important donor options in the absence of matched related siblings. However, the data comparing these two donor sources in R/R NHL are limited. Using the Japanese nationwide transplantation registry data, we identified 857 patients with R/R NHL, including 169 patients who received PTCY-haplo and 688 who received uCBT for their first allo-HSCT between January 2013 and December 2021; 514 patients (60%) had B-cell lymphoma. More PTCY-haplo recipients received allo-HSCT using a reduced-intensity conditioning regimen in recent years. The 3-year overall survival (OS), progression-free survival (PFS), and graft-versus-host disease (GVHD)-free/relapse-free survival (GRFS) rates in the PTCY-haplo and uCBT groups were 44% versus 39% (P = 0.326), 34% versus 33% (P = 0.660), and 19% versus 23% (P = 0.910), respectively; the adjusted hazard ratios for OS, PFS, and GRFS were 0.89 (95% confidence interval: 0.69-1.15, P = 0.373), 0.98 (0.78-1.22, P = 0.852), and 0.92 (0.83-1.21, P = 0.920), respectively. The PTCY-haplo group showed faster neutrophil and platelet engraftment and a lower incidence of grade III-IV acute GVHD. Thus, PTCY-haplo and uCBT could serve as alternative donor sources in patients with R/R NHL., Competing Interests: Competing interests: The authors declare no competing interests. Ethics approval statement: This study was approved by the Japanese Data Center for Hematopoietic Cell Transplantation (JDCHCT) and Institutional Review Board of Kobe City Medical Center General Hospital and was conducted in accordance with the Declaration of Helsinki (approval number: zn230805). Informed consent: Written informed consent was obtained from all patients prior to TRUMP2 registration., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)

Context: Cultural adaptation is essential for optimizing programs centered around autonomy, such as the Serious Illness Care Program (SICP), especially for populations valuing family-involved decision-making., Objectives: We aimed to evaluate the feasibility and efficacy of a culturally adapted SICP-based nurse-physician collaborative Advance Care Planning (ACP) intervention tailored for patients with advanced cancer who prefer family-involved decision-making., Methods: Oncology nurses, extensively trained and closely collaborating with physicians, conducted structured discussions with patients in the intervention group. The culturally adapted SICP-based ACP intervention was supplemented with trust-building, family involvement, and understanding of patient values. Primary inclusion criteria included patients within six weeks of initiating first-line palliative chemotherapy. Primary endpoints were achieving a 70% completion rate and assessing spiritual well-being (FACIT-Sp) at six months. Secondary endpoints included anxiety (GAD-7), depression (PHQ-9), quality of life (QOL) (CoQoLo), and ACP progress (ACP Engagement Scale) at the same interval., Results: Forty-one patients (67.2%) completed the six-month follow-up, falling short of the targeted completion rate. The least-squares mean change from baseline in spiritual well-being at six months was 3.00 in the intervention group and -2.22 in the standard care group (difference, 5.22 points; 95% confidence interval, 1.38-9.06; P = 0.009). Similar superiority of the intervention was observed in QOL and ACP progress., Conclusion: Despite not meeting the targeted completion rate, the intervention group demonstrated enhanced spiritual well-being, QOL, and ACP progress. Our findings suggest revisions to the intervention manual to improve feasibility and to progress to an efficacy-focused randomized controlled trial., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

This study aims to investigate the effects of neuromuscular electrical stimulation (NMES) in addition to conventional early mobilization in the early postoperative period after living donor liver transplantation (LTx) on body composition and physical function. This was a retrospective single-center cohort study. Adult subjects who were admitted for living donor LTx from 2018 to 2023 were included in the analysis. After April 2020, patients underwent 4 weeks of NMES in addition to conventional rehabilitation. The skeletal muscle mass index, body cell mass, and physical function, including the 6-minute walking distance, were assessed before surgery and at discharge, and changes in these outcomes were compared before and after the introduction of NMES. Sixty-one patients were in the NMES group, and 53 patients before the introduction of NMES were in the control group. ANCOVA with etiology, obstructive ventilatory impairment, Child-Pugh classification, and initial body composition value as covariates demonstrated that there was a significantly smaller decline of body cell mass (-2.9±2.7 kg vs. -4.4±2.7 kg, p = 0.01), as well as of the skeletal muscle mass index (-0.78±0.73 kg/m 2 vs. -1.29±1.21 kg/m 2 , p = 0.04), from baseline to discharge in the NMES group than in the control group; thus, the decline after surgery was suppressed in the NMES group. Four weeks of NMES, in addition to conventional rehabilitation in the early period after LTx, may attenuate the deterioration of muscle mass. It is suggested that NMES is an option for developing optimized rehabilitation programs in the acute postoperative period after LTx., (Copyright © 2024 American Association for the Study of Liver Diseases.)

Patients with Marfan syndrome (MFS) present with various symptoms, such as aortic aneurysm/dissection, tall stature, and lens deviation. Among them, acute aortic dissection is a complication that leads to sudden death. Some individuals with MFS are reluctant to see a cardiologist and discontinue regular checkups until they develop life-threatening complications. We conducted a grounded theory study to investigate how individuals with MFS decided whether to adhere to healthcare recommendations, specifically to attend cardiology appointments. The study recruited individuals with a clinical or genetic diagnosis of MFS from a Japanese university hospital and individuals from a support group. Semi-structured interviews were conducted with 28 consenting participants. In this study, we identified the decision-making processes of individuals with MFS concerning their cardiology visits. We extracted "perception of the gap between their health status and medical recommendations" as the central category. This decision-making process consisted of three parts: (A) the process by which an individual with MFS sees a cardiologist for the first time, (B) the process by which an individual with MFS keeps up with cardiology checkups, and (C) the process by which parents bring their children with MFS to the cardiologist. Individuals who learned of the possibility of MFS decided whether to adhere to medical recommendations depending on how they perceived the gap between their health status and the medical recommendations. In addition to medical information and treatment experience, adaptation to MFS, which changed through interactions with others, influenced the perception of the gap. This study suggests the role of genetic counseling and molecular genetic diagnosis as factors that may facilitate adaptation to MFS. The involvement of genetic counselors is important for helping individuals with MFS keep up with regular checkups while affirming their own experiences. These results provide insight into adherence to medical recommendations for individuals with MFS., (© 2023 National Society of Genetic Counselors.)

Introduction: Tixagevimab and cilgavimab (T/C) are neutralizing antibodies against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that can be used to prevent SARS-CoV-2 infection in solid organ transplant (SOT) recipients. However, their neutralizing activity against recent variants was reduced, raising concerns regarding the emergence of breakthrough coronavirus diseases 2019 (COVID-19). This study aimed to investigate the status of the COVID-19 breakthrough after T/C administration., Methods: We retrospectively investigated breakthrough COVID-19 in SOT recipients administered T/C at Kyoto University Hospital, Japan, from November 2022 to March 2023. Patients were monitored for 6 months after T/C administration. SARS-CoV-2 infection was diagnosed using polymerase chain reaction or antigen tests. The monthly incidence rates of SARS-CoV-2 infection were calculated using the person-time method., Results: T/C were administered to 67 SOT recipients (liver, 16; lung, 36; and kidney, 15), of whom five were infected with SARS-CoV-2. All five cases were classified as mild, and none of these patients required admission to the intensive care unit (ICU) or died. All infected individuals tested positive for SARS-CoV-2 after March 2023, when T/C-resistant subvariant strains became predominant. The monthly incidence rate of SARS-CoV-2 infection, calculated using the person-time method, suggested an increasing trend., Conclusions: During the T/C-resistant variant epidemic, SARS-CoV-2 infections were identified even after T/C administration, suggesting that the prophylactic effects of T/C were invalid. Therefore, emerging variants must be carefully monitored and characterized to determine appropriate antiviral strategies, such as the use of suitable neutralizing antibodies., Competing Interests: Declaration of competing interest We declare that there are no conflicts of interest., (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: Thumb carpometacarpal (CMC) arthritis is a painful and debilitating condition, which in severe cases may be treated by surgery. Previous studies have emphasised the importance of rehabilitation following surgery to achieve optimal results. This study aimed to investigate whether intensive hand therapy is effective in improving hand functions after arthroscopic partial trapeziectomy with suture-button (SB) suspensionplasty in patients with thumb CMC arthritis. Methods: This was a retrospective observational study that used non-randomised historical controls. Patients who underwent arthroscopic partial trapeziectomy with SB suspensionplasty were divided into two groups according to whether they had postoperative hand therapy or not (hand therapy group, n = 12; no hand therapy group, n = 11). CMC joint pain, range of motion (ROM), grip and pinch strength in the operative side and Quick Disability of the Arm, Shoulder and Hand (QuickDASH) score were compared before surgery and at the final follow-up for each group. Results: CMC joint pain, ROM and QuickDASH scores significantly improved following surgery, in both groups. Conversely, postoperative grip and pinch strength only increased significantly in the hand therapy group (grip strength: effect size = 0.36, pinch strength: effect size = 0.44). Conclusions: This study demonstrates that early-stage intensive hand therapy is an effective intervention after arthroscopic partial trapeziectomy with SB suspensionplasty, specifically for improving grip and pinch strength. Level of Evidence: Level III (Therapeutic).

Serum leucine-rich alpha-2 glycoprotein (LRG) can monitor disease activities during biologics treatment in patients with inflammatory bowel disease (IBD). It is unclear whether the pretreatment serum LRG level can predict clinical effectiveness including serum trough levels of ustekinumab in patients with IBD. This multicenter prospective cohort study included 184 patients (Crohn's disease, 104; ulcerative colitis, 80) who received ustekinumab (n = 119) or anti-tumor necrosis factor (n = 65) between January 2019 and March 2023. Multivariate logistic regression analysis revealed serum LRG level at week 0 (0w-LRG, odds ratio 0.12, 95% confidence interval 0.02-0.68) as one of significant factors for clinical remission at week 8. We divided patients into the low- and the high-LRG groups by the median 0w-LRG (18.2 µg/mL) and compared the effectiveness. In patients who received ustekinumab, the proportion of clinical remission at week 8 was significantly different between in the low- (76.9%) and in the high-LRG group (59.3%, P = 0.038), and median serum trough level at week 8 was significantly different between in the low- (10.9 µg/mL, interquartile range 6.7-13.4) and the high-LRG group (5.3 µg/mL, interquartile range 2.4-8.3, P < 0.001). The 0w-LRG can predict the effectiveness including serum trough levels of ustekinumab during induction treatment for patients with IBD., Competing Interests: Declarations. Competing interests: S. Shinzaki received lecture fees from Janssen Pharmaceutical K.K., Mitsubishi Tanabe Pharma Corporation, and lecture fees and grants from AbbVie GK, Sekisui Medical Co., Ltd.; A. Yonezawa: grants from Shimadzu Corporation and Ayumi Pharma Corporation.; H. Iijima: lecture fees from AbbVie GK and Mitsubishi-Tanabe Pharma Corporation; T. Takehara: grants from Mitsubishi-Tanabe Pharma Corporation, and lecture fees and grants from AbbVie GK. None of the aforementioned are related to this study. The remaining authors do not have any conflicts of interest to disclosure. Ethnics approval and consent to participate: This study was carried out in accordance with the Declaration of Helsinki, and approved by the ethics committee of Osaka University Hospital, the ethics committee of National Hospital Organization Osaka National Hospital, the ethics committee of Osaka Rosai Hospital, the ethics committee of Toyonaka Municipal Hospital, the ethics committee of Japan Community Healthcare Organization Osaka Hospital, the ethics committee of Itami City Hospital, the ethics committee of Suita Municipal Hospital, the ethics committee of Ikeda Municipal Hospital, the ethics committee of Otemae Hospital, the ethics committee of Kansai Rosai Hospital, the ethics committee of Higashiosaka City Medical Center, the ethics committee of Osaka General Medical Center, the ethics committee of Osaka Police Hospital, the ethics committee of Yao Municipal Hospital and the ethics committee of Hyogo Prefectural Nishinomiya Hospital. Written informed consent was obtained from all patients., (© 2024. The Author(s).)

Objective: Instrumentation surgery in combination with radiotherapy (RT) is one of the key management strategies for patients with spinal metastases. However, the use of materials can affect the RT dose delivered to the tumor site and surrounding tissues, as well as hinder optimal postoperative tumor evaluation. The association of the preoperative Spine Instability Neoplastic Score (SINS) with the need for spinal stabilization and life expectancy are unclear. This multicenter prospective study aimed to investigate the current situation and make recommendations regarding the choice of surgical procedure based on the preoperative SINS and prospectively collected postoperative patient-reported outcomes (PROs)., Methods: The study prospectively included 317 patients with spinal metastases who underwent palliative surgery and had a minimum follow-up period of 6 months. The survey items included SINS, patient background, and clinical data including surgical procedure, history of RT, prognosis, and PROs (i.e., the visual analog scale score, Faces Scale, Barthel Index, Vitality Index, and 5-level EQ-5D health survey) at baseline, and at 1 and 6 months after surgery. The association of preoperative SINS with life expectancy, PROs, and surgical procedures was examined using statistical analysis., Results: Preoperative SINS (three categories) had no association with life expectancy. All PROs evaluated in the study improved up to 6 months after surgery. Pain categories (visual analog scale score and/or Faces Scale) at baseline were correlated with preoperative SINS. As many as 90.9% of enrolled patients underwent fusion surgery, and even in SINS 0-6 cases, implants were used in 64.3% of patients. Postoperative RT was performed in 42.9% of the patients. However, prospective assessments of PROs showed no significant difference between surgical procedures (with and without fusion) in patients with SINS 0-9. In addition, no cases required conversion from noninstrumentation surgery to fusion surgery., Conclusions: Although the choice of surgical procedure should be made on a case-by-case basis on the NOMS (neurological, oncological, mechanical, and systemic) framework, careful consideration is required to determine whether spinal stabilization is needed in patients with SINS ≤ 9, considering the patient's background and the plan for postoperative adjuvant therapy.

Fibroblastic foci (FF) are considered important findings of usual interstitial pneumonia (UIP); however, they are not specific to UIP but are also observed in various fibrotic interstitial lung diseases (ILDs). Previous studies have reported the significance of FF comparing UIP with nonspecific interstitial pneumonia (NSIP) or with secondary interstitial pneumonia, such as collagen vascular disease-related interstitial lung disease (CVD-ILD) or fibrotic hypersensitivity pneumonitis (FHP). However, only few studies have mentioned its location, and no reports have shown significant results regarding its location. This study aimed to compare the spatial distribution of FF across various forms of ILDs, based on anatomical location. Among patients who underwent lung transplantation at Kyoto University Hospital between April 1, 2008, and March 31, 2023, those diagnosed with idiopathic pulmonary fibrosis (IPF) (n = 24), idiopathic NSIP (n = 11), CVD-ILD (n = 36), and FHP (n = 12) were included, and 744 slides were obtained. FF were classified into four categories: peripheral, such as subpleural/paraseptal (pFF); intralobular, along the alveolar wall (aFF); centrilobular (cFF); and distorted or dense fibrotic lesion (dFF). The number of total and each location's FF/cm 2 were counted, and the percentage of each location's FF was calculated. IPF showed more total FF and pFF than NSIP. FHP had more cFF than CVD (p = 0.026) and NSIP (p = 0.018). The dFF was higher in IPF than that in CVD (p = 0.018) and NSIP (p = 0.039). The aFF/total FF was higher in CVD than that in FHP (p = 0.021) and IPF (p < 0.001). A high cFF/total FF was correlated with FHP vs. IPF (p = 0.032). In conclusion, FF with existing peripheral and distorted/dense fibrosis were more closely related to IPF, whereas centrilobular FF were highly correlated with FHP. Moreover, high aFF/total FF was suggestive of CVD., (Copyright © 2024. Published by Elsevier Inc.)

Background: Although health insurance claims data can address questions that clinical trials cannot answer, the uncertainty of disease names and the absence of stage information hinder their use in gastric cancer (GC) research. This study aimed to develop and validate a claims-based algorithm to identify and determine the progression phases of incident GC cases in Japan., Methods: The gold standard for validation in this retrospective observational study was medical records of patients with incident GC who underwent specific treatments, defined by the claim codes associated with GC treatment. The algorithm was developed and refined using a cohort from two large tertiary care medical centers (April-September 2017 and April-September 2019) and subsequently validated using two independent cohorts: one from different periods (October 2017-March 2019 and October 2019-March 2021) and the other from a different institution (a community hospital). The algorithm identified incident cases based on a combination of the International Classification of Diseases, 10th Revision diagnosis codes for GC (C160-169), and claim codes for specific treatments, classifying them into endoscopic, surgical, and palliative groups. Positive predictive value (PPV), sensitivity of incident case identification, and diagnostic accuracy of progression phase determination were evaluated., Results: The developed algorithm achieved PPVs of 90.0% (1119/1244) and 95.9% (94/98), sensitivities of 98.0% (1119/1142) and 98.9% (94/95) for incident case identification, with diagnostic accuracies of 94.1% (1053/1119) and 93.6% (88/94) for progression phase determination in the two validation cohorts, respectively., Conclusions: This validated claims-based algorithm could advance real-world GC research and assist in decision-making regarding GC treatment., Competing Interests: Declarations. Conflict of interest: Hiroshi Seno is the Editor-in-Chief of the Journal of Gastroenterology. To avoid any potential conflicts of interest, he was not involved in the peer review or decision-making processes of this manuscript. Takeo Nakayama reports the following potential conflicts of interest outside the submitted work: a research grant from NTT DATA and stock options from BonBon, Inc. All the other authors declare no competing interests., (© 2024. The Author(s).)

Regeneration of periodontal tissue, particularly the cementum-periodontal ligament (PDL)-bone complex, has long been challenging because the differentiation kinetics of cells and the molecular pathways contributing to the regeneration process are largely unknown. We aimed to evaluate the cell behavior and molecular pathways that contribute to periodontal tissue regeneration in vivo. We analyzed the process of periodontal tissue regeneration through subrenal capsule transplantation of immediately extracted molars in mice. We showed that the regenerated periodontal tissue in the subrenal capsule was morphologically comparable to the intact periodontal tissue, with increased cellular cementum thickness in the apical region. Cell tracing analysis revealed that the cells comprising the regenerated periodontal tissue were derived from transplanted teeth and were indispensable for periodontal tissue regeneration, whereas recipient mouse-derived cells partly contributed to angiogenesis. Bioinformatics analysis based on the gene expression profile in the transplanted teeth indicated that Wnt/β-catenin signaling is involved in periodontal tissue regeneration, which was further confirmed through β-catenin immunohistochemistry. Moreover, the constitutive activation of β-catenin in the cells of transplanted teeth was found to promote accelerated cellular cementum apposition, while the conditional knockout of β-catenin in the cells of transplanted teeth suppressed cellular cementum apposition. Notably, the manipulation of Wnt/β-catenin signaling did not interfere with the bone-PDL-cementum complex, while endogenous osteoclast activity was affected in bone. Our results demonstrated the essential roles of endogenous PDL cells in periodontal tissue regeneration and that Wnt/β-catenin signaling is involved in this process, particularly cellular cementum apposition. Hence, controlling this pathway could promote cementum regeneration, which is a critical process for the regeneration of the cementum-PDL-bone complex. This study provides novel insights into cell behavior and signaling pathways that will advance practical periodontal tissue regeneration., Competing Interests: Declaration of Conflicting InterestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: The advantage of intensified myeloablative conditioning (MAC) over standard MAC has not been determined in haematopoietic stem cell transplantation (HSCT) for adult acute lymphoblastic leukemia (ALL) patients., Methods: To evaluate heterogeneous effects of intensified MAC among individuals, we analyzed the registry database of adult ALL patients between 2000 and 2021. After propensity score matching, we applied a machine-learning Bayesian causal forest algorithm to develop a prediction model of individualized treatment effect (ITE) of intensified MAC on reduction in overall mortality at 1 year after HSCT., Results: Among 2440 propensity score-matched patients, our model shows heterogeneity in the association between intensified MAC and 1-year overall mortality. Individuals in the high-benefit group (n = 1220), defined as those with ITEs greater than the median, are more likely to be younger, male, and to have higher refined Disease Risk Index (rDRI), T-cell phenotype, and grafts from related donors than those in the low-benefit group (n = 1220). The high-benefit approach (applying intensified MAC to individuals in the high-benefit group) shows the largest reduction in overall mortality at 1 year (risk difference [95% confidence interval], +5.94 percentage points [0.88 to 10.51], p = 0.011). In contrast, the high-risk approach (targeting patients with high or very high rDRI) does not achieve statistical significance (risk difference [95% confidence interval], +3.85 percentage points [-1.11 to 7.90], p = 0.063)., Conclusions: These findings suggest that the high-benefit approach, targeting patients expected to benefit from intensified MAC, has the capacity to maximize HSCT effectiveness using intensified MAC., Competing Interests: Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)