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Purpose: Resuscitative endovascular balloon occlusion of the aorta (REBOA) is now a feasible and less invasive resuscitation procedure. This study aimed to compare the clinical course of trauma and non-trauma patients undergoing REBOA.Methods: Patient demographics, etiology, bleeding sites, hemodynamic response, length of critical care, and cause of death were recorded. Characteristics and outcomes were compared between non-trauma and trauma patients. Kaplan-Meier survival analysis was then conducted.Results: Between August 2011 and December 2015, 142 (36 non-trauma; 106 trauma) cases were analyzed. Non-traumatic etiologies included gastrointestinal bleeding, obstetrics and gynecology-derived events, visceral aneurysm, abdominal aortic aneurysm, and post-abdominal surgery. The abdomen was a common bleeding site (69%), followed by the pelvis or extra-pelvic retroperitoneum. None of the non-trauma patients had multiple bleeding sites, whereas 45% of trauma patients did (P < 0.001). No non-trauma patients required resuscitative thoracotomy compared with 28% of the trauma patients (P < 0.001). Non-trauma patients presented a lower 24-h mortality than trauma patients (19 vs. 51%, P = 0.001). The non-trauma cases demonstrated a gradual but prolonged increased mortality, whereas survival in trauma cases rapidly declined (P = 0.009) with similar hospital mortality (68 vs. 64%). Non-trauma patients who survived for 24 h had 0 ventilator-free days and 0 ICU-free days vs. a median of 19 and 12, respectively, for trauma patients (P = 0.33 and 0.39, respectively). Non-hemorrhagic death was more common in non-trauma vs. trauma patients (83 vs. 33%, P < 0.001).Conclusions: Non-traumatic hemorrhagic shock often resulted from a single bleeding site, and resulted in better 24-h survival than traumatic hemorrhage among Japanese patients who underwent REBOA. However, hospital mortality increased steadily in non-trauma patients affected by non-hemorrhagic causes after a longer period of critical care. [ABSTRACT FROM AUTHOR]

Background: The role of adult weight change in breast cancer (BC) risk is unclear in Japanese women.Methods: A total of 10,106 postmenopausal women aged 40-64 years (the Miyagi Cohort) were followed from 1990 to 2003, and 108 BC cases were identified. Hazard ratios (HRs) were estimated according to body mass index (BMI) at the current age and at the of age 20 years, and weight change since age 20 years.Results: Higher current BMI was associated with an increased risk of BC (P for trend=0.02), whereas higher BMI at the age 20 years was inversely associated with this risk (P for trend=0.002). There was a significant association between weight change since age 20 years and BC risk (P for trend=0.0086). Compared with stable weight, HR was 0.35 for weight loss of 5 kg or more (P for weight loss trend=0.04) and 1.55 for weight gain of 12 kg or more (P for weight gain trend=0.05).Conclusion: Adiposity at younger and current age has differential effects on BC risk among postmenopausal women; weight gain in adulthood being associated with an increased, and weight loss with a decreased risk. [ABSTRACT FROM AUTHOR]

We established the distribution of amino acid alterations in quinolone resistance-determining regions (QRDRs) of Streptococcus pneumoniae isolates in Japan and described the correlation of these alterations with serotypes determined by multilocus sequencing typing. Among 141 S. pneumoniae isolates, five levofloxacin-resistant isolates harbored mutations in both gyrA and parC and/or parE and were clonally unrelated. Among 136 levofloxacin-susceptible isolates, one isolate (MIC = 2 mg/l) had a first-step parC mutation at Asp78. Twenty isolates had Lys137Asp in parC and Ile460Val in parE and contained nine serotypes and eight clonal complexes (CCs), including all eight Colombia23F-26 (CC138) isolates. Eighty-one isolates had Ile460Val in parE alone and contained 14 serotypes and 16 CCs, including 36 of 37 Netherlands3-31 (CC180) isolates and all 22 Taiwan19F-14 (CC271) isolates. In contrast, seven of ten Taiwan23F-15 (CC242) isolates were wild-type. Although each QRDR genotype contained various serotypes and CCs, prevalent clones were mostly associated with a single QRDR genotype. [ABSTRACT FROM AUTHOR]

For geographical information systems (GIS) to be useful in the management of Japanese paddy fields, it is vital to be able to prepare base maps that define sections of field. We attempted to prepare a base map by detecting the edges of submerged paddy fields from a SPOT image with the use of multi-resolution wavelet transform. The raw image of SPOT band 3 was decomposed into a low frequency approximation image and a set of high frequency detailed images to five levels, and then reconstructed. The reconstructed image at the fifth level was obtained from all of the high frequency images except for the low frequency approximation image. The image reconstructed up to full scale was then applied to a zero-crossing scheme and three post-processings-line thinning, removal of isolated pixels, and connection of pixels with their neighbours-in order to obtain clear edges. The spatial features of the image indicating the edges obtained by multi-resolution wavelet transform were compared quantitatively with those obtained by using a difference of Gaussian (DOG) filter. The multi-resolution wavelet transform was better than the DOG filter in that the base map obtained by the wavelet transform method represented a 'field block', which is typically composed of 10 holdings of paddy field, more precisely than with the DOG filter, and in that the number of open polygons on this map was smaller, indicating that the wavelet transform method is more suitable for producing the base map in GIS for the management of paddy fields. [ABSTRACT FROM AUTHOR]

Abstract In a family study of a Japanese propositus with the D-- phenotype, the serological data of her D--phenotype and those of her parents were discrepant. Gene analysis of the propositus showed a gross deletion of the RHCE gene and a new rearrangement of RHCE to yield the CE-D-CE hybrid. It was demonstrated that the hybrid CE-D-CE gene consisted of exon 1 from the RHCE gene, followed by exons 3 to 7 from the RHD gene and exons 8 to 10 from the RHCE gene. However, whether or not exon 2 of the RHD or the RHCE gene was contained in the CE-D-CE gene remained unclear. Moreover, spacer analysis between both RH genes and the family study suggested that the D-- gene complex from the paternal and maternal sides consisted of only the CE-D-CE hybrid gene and a single RHD gene, respectively. For the purpose of confirming the parent-child relationship, a paternity test using DNA fingerprint and polymerase chain reaction (PCR) analysis at the D1S80 locus were performed. DNA fingerprints with two kinds of DNA minisatellite probes (33.15 and 33.6) confirmed that the parent-child relationship in the D-propositus was compatible. However, in the present case, at the D1S80 locus, the PCR product derived from the mother was lacking, thereby negating a parent-child relationship. It is probable that the RH genes and D1S80 locus exist in close proximity, because they are situated in chromosomes 1p 34.3-36.1 and 1p 36.1-36.3, respectively. These data suggested that at the stage of gametogenesis, both the RHCE gene and the D1S80 locus from the maternal side may have been deleted, thereby producing the D-- gene complex. [ABSTRACT FROM AUTHOR]

In Japan, it has recently been decided to grow crops other than paddy rice in the paddy fields, since the demand for rice has decreased. This study was carried out in order to obtain information about this decision. Since soil organic matter is important for soil fertilities, detailed descriptions of the spatial variability of soil organic matter, therefore are desirable in this decision. The spatial variability in the Aidu Basin, northern Japan, was predicted using disjunctive cokriging. The disjunctive cokriging estimator used soil sample data as the variate, and as covariate, estimates of soil organic matter obtained from Landsat Thematic Mapper images of submerged paddies. The disjunctive cokriging estimator provided a better estimate than a traditional regression analysis. However, we should pay attention in using the estimate. Since soil organic matter content might not be directly linked to crop production for some soils, we should make these decisions by comparing the estimate with conventional soil maps. This paper also investigated relations between the spatial structure of soil components, which have a major influence on soil colour, such as organic matter and that of each TM band data, using semivariograms. The nested structures of semivariograms for soil colour components could be found in semivariograms from TM Bands 1-3. The nugget variance and range in the band data were influenced by spatial patterns of soil colour components. [ABSTRACT FROM AUTHOR]

A 66-year-old Japanese man had a positive fecal occult blood test at a regular check-up, and a large polypoid mass was detected in the cecum by barium enema study. Colonoscopy showed a submucosal tumor with ulcer protruding into the cecal lumen. A large-forceps biopsy specimen was taken from the bottom of the ulcer. With the tentative diagnosis of neurogenic tumor, ileocecal resection was performed. The tumor showed spindle-cell proliferation in a concentric or fascicular pattern. Immunohistochemically, the tumor cells were diffusely positive for S-100 protein, and they had intracytoplasmic periodic acid Schiff (PAS)-positive crystalloids. The mitosis count was low (about 1 per 20 high-power fields). The pathological diagnosis of this tumor was benign gastrointestinal schwannoma. A large number of schwannoma cases have been reported since 1910 when Verocay reported it as a true tumor that stemmed from Schwann cells and did not contain neuroganglion cells. However, gastrointestinal schwannomas are rare, and schwannomas of the large intestine are extremely rare. We reviewed 40 cases already reported in Japan and this present case in order to clarify the clinicopathological features of this tumor. [ABSTRACT FROM AUTHOR]

Toxoplasma gondii infection was studied in 41 Japanese serows (Capricornis crispus), a goat-antelope in mainland Japan. Blood and muscle specimens were collected from 41 subjects between 2006 and 2010. Presence of antibodies to T. gondii in the sera was examined by using the latex agglutination test (cutoff titer 1:32); 10 of 41 (24.4%) were seropositive. Toxoplasma gondii DNA was detected in muscle tissue of 1 seropositive serow using a semi-nested PCR assay for the B1 gene. A partial nucleotide sequence (220 bp) corresponding to the B1 gene of T. gondii was obtained by direct sequencing; the sequence was 99.1% identical to that of the RH strain. This study is the first report to show direct evidence for the T. gondii infection in Japanese serows [ABSTRACT FROM AUTHOR]

Clin Microbiol Infect 2011; 17: 1409-1414 Abstract Streptococcus pneumoniae resides on mucosal surfaces in the nasopharynx, where selection for horizontal transfer of antimicrobial resistance genes and virulence factors may provide a survival advantage. We investigated the distribution of genes for pneumococcal cell surface proteins and their correlations with multilocus sequence typing (MLST), Pneumococcal Molecular Epidemiology Network (PMEN) clones and antimicrobial resistance, to identify pneumococcal virulence factors predicting prevalent clones from 156 pneumococcal isolates recovered from adult patients with community-acquired pneumonia in Japan. Pneumococcal eno, pavA, piuA, cbpA and cbpG were present in all isolates, and hyl and piaA were distributed among the clinical isolates. In contrast, pneumococcal rlrA, pclA, psrP, nanC and pspA family 1-type genes were variably distributed and significantly associated with MLST (Wallace coefficients (W) were over 84%). Serotype was a weaker predictor of sequence type (W, 0.75) than vice versa (W, 0.97). A multiple logistic regression analysis adjusted to the presence of virulence genes, pspA family 1 genes and carriage serotypes revealed that pclA and rlrA correlated with PMEN clones and antimicrobial resistance, and are likely to contribute to the selection of prevalent clones. [ABSTRACT FROM AUTHOR]

A total of 141 Streptococcus pneumoniae isolates from patients with community-acquired pneumonia were collected from May 2003 through October 2004. The strains were tested for antimicrobial agent susceptibility, serotype and genotype by multilocus sequence typing (MLST) and the presence of the pilus rlrA islet. MLST analysis identified 49 sequence types (STs), of which 19 were novel. eBURST analysis using the MLST database (3773 STs) grouped the isolates into 27 clonal complexes and three singletons. A total of 92 (65.2%) isolates were related to ten of the 43 international Pneumococcal Molecular Epidemiology Network (PMEN) clones; major clones found were multidrug-resistant Netherlands3-31 [clonal complex (CC) 180], Taiwan19F-14 (CC271), Taiwan23F-15 (CC242), and Colombia23F-26 (CC138) (the latter new to Asia). We adopted univariate and multiple logistic regression models to identify factors associated with PMEN CCs. Multivariate analysis showed that multidrug resistance (OR 6.3; 95% CI 2.0–22.9), carriage serogroups (OR 7.2; 95% CI 2.5–23.7), prevalence of rlrA (OR 12.6; 95% CI 3.6–59.7) and central nervous system-related disorders (OR 7.7; 95% CI 1.8–48.4) were independently associated with PMEN CCs. Our data indicate that multidrug-resistant PMEN clones are highly prevalent, contributing to the high frequency of resistance to antimicrobial agents in Japan, and suggest that certain predisposing factors in patients contribute to the high frequency of these clones. [ABSTRACT FROM AUTHOR]

Lactic acid bacteria (LAB) play important roles in acid production and flavor formation in fermented dairy products. Lactic acid bacteria strains with distinct characteristics confer unique features to products. Diverse LAB have been identified in raw milk and traditional fermented milk prepared from raw milk. However, little is known about LAB in raw milk in Japan. To preserve diverse LAB as potential starters or probiotics for future use, we have isolated and identified various kinds of LAB from raw milk produced in Japan. In this study, we focused on Lactobacillus delbrueckii , one of the most important species in the dairy industry. We identified L. delbrueckii subspecies isolated from raw milk in Hokkaido, Japan, by analyzing intraspecific diversity using 4 distinct methods, hsp60 cluster analysis, multilocus sequence analysis, core-genome analysis, and whole-genome analysis based on average nucleotide identity. The subspecies distribution and a new dominant subset of L. delbrueckii from raw milk in Japan were revealed. The discovery of new strains with different genotypes is important for understanding the geographic distribution and characteristics of the bacteria and further their use as a microbial resource with the potential to express unconventional flavors and functionalities. The strains identified in this study may have practical applications in the development of fermented dairy products. [ABSTRACT FROM AUTHOR]

Abstract: The second GeV bremsstrahlung photon beamline has been constructed for meson photo-production experiments at Research Center for Electron Photon Science, Tohoku University, where a 1200MeV electron synchrotron called STretcher Booster (STB) has been in operation primarily for Quark Nuclear Physics. An internal radiator is employed to produce the bremsstrahlung photon beam out of circulating electrons in the STB ring. A photon tagging system is placed inside one of the bending magnets of the ring. The tagged energy of the photon beam ranges from 740 to 1150MeV for 1200MeV operation of the STB synchrotron. The details of the tagging system and the characteristics of the photon beam are described. [Copyright &y& Elsevier]

This is an annual report by the Japanese Breast Cancer Society, which provides statistics on the clinical data on breast cancer in Japan, extracted from the National Clinical Database-Breast Cancer Registry (NCD-BCR). This report includes an update of 102,453 breast cancer cases at 1339 institutions registered in the NCD-BCR in 2022. Among the 101,793 female patients, the median age at cancer diagnosis was 62 years (interquartile range, 50-73 years), and 29.4% of the patients were premenopausal. Of these patients, 15,437 (15.2%) and 42,936 (42.2%) were diagnosed with stage 0 and I disease, respectively. Estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2 (HER2) were positive in 78.7%, 69.4%, and 12.8% of the patients, respectively. Of the 97,154 patients without distant metastasis, 40,521 (41.7%) underwent breast-conserving surgery, and 5780 (5.9%) patients underwent some form of breast reconstruction procedures at the time of mastectomy. A total of 66,894 (68.9%) patients were treated with sentinel lymph node biopsy and 7155 (7.4%) patients were treated with sentinel lymph node biopsy followed by axillary node dissection. In the group of patients treated with breast-conserving surgery (n = 40,521), 29,500 (72.8%) received whole-breast irradiation. In the group of patients who underwent mastectomy (n = 54,476), 6226 (11.4%) received radiation therapy to the chest wall. Of the 13,950 patients receiving preoperative chemotherapy with or without molecular targeted therapy, 4308 (30.9%) achieved a pathological complete response, with the highest rate of 60.5% in patients with the hormone receptor-negative/HER2-positive subtype., Competing Interests: Declarations. Conflicts of interest: Grants or contracts from any entity–MK: Nippon Kayaku, Kyowa Kirin, Advalife Science, Guardant Health AMEA, Shimadzu and GL Sciences; S Sasada: Daiichi Sankyo, Chugai, Eli Lilly, Gilead Sciences, and Nipro; S Saji: Taiho, Eisai, Chugai, Takeda, MSD, Astra Zeneca, Daiichi Sankyo, Gilead, Eli Lilly, and Sanofi; NN: Chugai, Pfizer, Eisai, Mochida, Daiichi Sankyo, and Novartis. Consulting fees–HK: EPS corporation; MY: Roche Japan. Payment or honoraria for lectures—MN: AstraZeneca, Chugai, Daiichi Sankyo, Denka, Eisai, Eli Lilly, Kyowa-Kirin, MSD, Novartis, Pfizer, and Taiho; HK: Novartis; MK: Guardant Health AMEA, Chugai, Daiichi Sankyo, Pfizer Japan, Eisai, Taiho Pharmaceutical, and Devicor Medical Japan; YS: Pfizer, Astra Zeneca, Daiichi Sankyo, Eisai, Eli Lily, Chugai, MSD, Nippon Kayaku, Kyowa Kirin, Sysmex, Celltrion, and Healthcare Japan; S Saji: Chugai, Kyowa Kirin, MSD, Novartis, Eisai, Takeda, Daiichi Sankyo, Eli Lilly, Astra Zeneca, Pfizer, Taiho, Ono, Nipponkayaku, Gilead, and Exact Sciences; NN: Chugai, Eli Lilly, MSD, Daiichi-Sankyo, AstraZeneca, and Pfizer; MM: Chugai, AstraZeneca, Eli Lilly, Pfizer, MSD, Taiho, Daiichi Sankyo, and Eisai; MY: Roche Japan, Agilent Technologies, Chugai pharma, Ono Yakuhin, MSD, and Daiichi Sankyo. Participation on a Data Safety Monitoring Board or Advisory Board–S Saji: Chugai/Roche, Astra Zeneca, Eli Lilly, Pfizer, Kyowa Kirin, Daiichi Sankyo, MSD; MY: Daiichi Sankyo. Leadership or fiduciary role–S Saji: JBCRG, JBCS, JSMO, and BIG. Other financial or non-financial interests–HK and NK: affiliation with a social collaboration department at the University of Tokyo supported by the National Clinical Database, Johnson & Johnson K.K., Nipro corporation, and Intuitive Surgical Sarl. MK: participation in the clinical trials led by JBCRG, Roche, Eli Lilly, and Merck. Ethical approval: This article does not contain any studies with animals performed by any of the authors. All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards., (© 2025. The Author(s).)

Large-scale population cohort studies that collect genomic information are tasked with returning an assessment of genetic risk for hereditary cancers to participants. While several studies have applied to return identified genetic risks to participants, comprehensive surveys of participants' understanding, feelings, and behaviors toward cancer risk remain to be conducted. Here, we report our experience and surveys of returning genetic risks to 100 carriers of pathogenic variants for hereditary cancers identified through whole genome sequencing of 50 000 individuals from the Tohoku Medical Megabank project, a population cohort study. The participants were carriers of pathogenic variants associated with either hereditary breast and ovarian cancer (n = 79, median age=41) or Lynch syndrome (n = 21, median age=62). Of these, 28% and 38% had a history of cancer, respectively. We provided information on cancer risk, heritability, and clinical actionability to the participants in person. The comprehension assessment revealed that the information was better understood by younger (under 60 years) females than by older males. Scores on the cancer worry scale were positively related to cancer experiences and general psychological distress. Seventy-one participants were followed up at Tohoku University Hospital; six females underwent risk-reducing surgery triggered by study participation and three were newly diagnosed with cancer during surveillance. Among first-degree relatives of hereditary breast and ovarian cancer carriers, participants most commonly shared the information with daughters. This study showed the benefits of returning genetic risks to the general population and will provide insights into returning genetic risks to asymptomatic pathogenic variant carriers in both clinical and research settings., Competing Interests: Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)

Background: Crohn's disease (CD) is an incurable inflammatory condition that often requires multiple surgeries, negatively impacting quality of life. As such, treatment strategies that aim to prevent damage to the bowel and reduce the burden of surgeries for patients with CD are important. This retrospective, long-term, observational study investigated whether tumor necrosis factor inhibitor (TNFi) treatment was associated with decreased rates of abdominal surgery in Japanese patients with CD., Methods: Patients were divided into two groups based on prior TNFi therapy (TNFi-treated and TNFi-untreated). Outcomes assessed included surgery rate, cumulative surgery-free survival rate, and time to surgery. For surgery rate, treatment groups were compared through estimation of an odds ratio (OR) with 95% confidence intervals (CIs). Cumulative surgery-free survival rate and time to surgery was calculated using Kaplan-Meier methodology and compared using log-rank tests. The primary analysis compared outcomes between the TNFi-treated and TNFi-untreated groups. Subgroup analyses compared outcomes between two subgroups of the TNFi-treated group (infliximab-treated vs. adalimumab-treated) and the TNFi-untreated group., Results: Overall, 124 patients with CD were included in the analysis (TNFi-treated: N = 86; TNFi-untreated: N = 38). Of those patients who received TNFi treatment, 62 received infliximab and 24 received adalimumab. The median (range) observation period in the TNFi-treated and TNFi-untreated groups was 4.62 (0.41-13.75) years and 8.13 (0.08-30.25) years, respectively. Median time to surgery was 3 years in the TNFi-untreated group and 6.58 years in the TNFi-treated group. A significantly lower proportion of patients in the TNFi-treated group required surgery (3/86) compared with those in the TNFi-untreated group (17/38; OR [CI]: 0.0446 [0.0120-0.1667]; P < 0.0001). Cumulative surgery-free survival rates were significantly higher in the TNFi-treated group versus the TNFi-untreated group (P < 0.0001). Compared with the TNFi-untreated group, the proportion of patients who required surgery was significantly lower with both infliximab (1/62; OR [CI]: 0.0203 [0.0025-0.1616]; P = 0.0002) and adalimumab (2/24; OR [CI]: 0.1123 [0.0231-0.5466]; P = 0.0068). Cumulative surgery-free survival rates were significantly higher in the infliximab-treated group versus the TNFi-untreated group (P < 0.0001)., Conclusions: Introduction of TNFis for the treatment of CD may lead to a reduction in surgery rates and prolong time to surgery., Competing Interests: Declarations. Ethical approval: All patients provided written, informed consent. This study was conducted in accordance with the Declaration of Helsinki; however, given it is a retrospective observational study, formal ethical approval from the Oita Red Cross hospital ethics committee was not required. Written approval to use the data included in the current study was obtained from Dr Fukuwaza, Director of the Oita Red Cross hospital. Patient consent to participate: Consent obtained. Consent for publication: Not applicable. Competing interests: The author declares no competing interests., (© 2024. The Author(s).)

Road traffic accidents are a global health concern. K-car vehicles, also known as "mini vehicles," are defined as those having an engine displacement <660 cc, vehicle length <3.4 m, width <1.48 m, and height <2.0 m. K-cars have become increasing popular not only in Japan but also in other countries. Compared with standard vehicles, the occupant space of a K-car vehicle is considerably smaller; thus, passengers may be more vulnerable to the external forces generated in a collision, which in turn can lead to deformation of the occupant space and less protection against injuries. However, data are scarce regarding whether K-car vehicles are related to poorer survival outcomes and severe trauma. We conducted a retrospective cohort study involving patients who were injured in four-wheeled vehicle accidents between 2002 and 2023 and admitted to a community teaching hospital in Japan. The vehicle configuration was divided into standard and K-car vehicles. The primary endpoint was in-hospital mortality. Other outcomes included severe trauma, defined as Injury Severity Score (ISS) >15, and anatomically specific severe injury of the head and neck, chest, abdomen, pelvis, and extremities, defined as Abbreviated Injury Scale score ≥3. Of 5331 eligible patients, 2384 (44.7%) were K-car vehicle occupants. In propensity score-matched analysis with 1947 pairs, we observed an increase for in-hospital mortality in the K-car vehicle group (2.6% vs. 4.0%, odds ratio 1.53, 95% confidence interval 1.07-2.19). Compared with standard vehicles, K-car vehicles were associated with a greater risk of severe trauma and serious injuries of the head and neck, chest, abdomen, pelvis, and extremities. These study data should be used to encourage vehicle occupants and automobile manufacturers to consider objective facts regarding the safety of vehicles in a traffic accident., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2025 Ono et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

We characterized the safety and efficacy of the bispecific antibody teclistamab in Japanese patients with relapsed/refractory multiple myeloma (RRMM). Patients were pretreated with a proteasome inhibitor (PI), immunomodulatory drug (IMiD), and anti-CD38 monoclonal antibody (mAb). The primary endpoint was frequency and type of treatment-emergent adverse events (TEAEs) in phase 1, and overall response rate (ORR; ≥ partial response [PR]) in phase 2. In phase 1, 14 patients received once-weekly (QW) subcutaneous teclistamab (0.72 mg/kg [n = 5]; 1.5 mg/kg [n = 5]; 3 mg/kg [n = 4]). No dose-limiting toxicities were observed. As of April 2024, 26 phase-2 patients received the recommended phase-2 dose (QW) (RP2D: 1.5 mg/kg) of teclistamab. Biweekly (Q2W) dosing was allowed after maintaining response for ≥ 6 months. At a median follow-up of 14.32 months, ORR was 76.9% (≥ very good PR: 76.9%; ≥ complete response: 65.4%). Median duration of response, progression-free survival, and overall survival were not reached. Common TEAEs included CRS (grade ≤ 2), neutropenia, and infections. No patient had immune effector cell-associated neurotoxicity syndrome (ICANS) and dose reductions. Teclistamab demonstrated deep and durable responses in Japanese patients with RRMM, consistent with the global pivotal MajesTEC-1 study, supporting the potential for a new standard of care for Japanese RRMM patients., Competing Interests: Declaration. Conflict of interest: Tadao Ishida: Research funding received from Alexion pharma, BMS, GSK, Janssen, Pfizer, Prothena, Sanofi, and Takeda. Honoraria received from BMS, CSL Behring, Janssen, Ono, Pfizer, Sanofi, and Takeda. Yoshiaki Kuroda: Payment or honoraria received from Amgen, Asahi Kasei Pharma, Astrazeneca, BMS, Janssen, Ono, Sanofi, SymBio Pharmaceuticals, and Takeda Pharmaceuticals. Kosei Matsue: Grants or contract received from Astrazeneca. Takuya Komeno: Grants or contracts received from Abbvie, BMS, Janssen Pharmaceutical K.K., and Sanofi. Takuro Ishiguro: Payment or honoraria received from Janssen Pharmaceutical K.K., Sanofi, BMS, Ono Pharmaceutical, Takeda Pharmaceutical Company Limited, and Novartis. Jun Ishikawa: None. Toshiro Ito: None. Hiroshi Kosugi: Payment or honoraria received from Abbvie G.K., Asahi Kasei Pharma, Astrazeneca K.K., Beckton Dickinson K.K., BMS K.K., Chugai, GSK K.K., Janssen Pharmaceutical K.K., Japan Blood Products Organization, Kyowa Kirin, Kissei Pharmaceutical, Nippon Shinyaku, Novartis Pharma K.K., Novo Nordisk Pharma Japan, Ono, Sanofi K.K., and Takeda. Kazutaka Sunami: Research funding received from: Abbvie, Beigene, BMS, Chugai, GSK, Incyte, Janssen, Kyowa Kirin, Mitsubishi Tanabe, Novartis, Ono, Otsuka, Pfizer, and Sanofi. Honoraria received from BMS, Janssen, and Sanofi. Kazuko Nishikawa: Employee of Janssen Pharmaceutical K.K. Kazuhiro Shibayama: Employee of Janssen Pharmaceutical K.K., and own stock or stock options in Johnson & Johnson. Kensuke Aida: Employee of Janssen Pharmaceutical K.K. Hiroshi Yamazaki: Employee of Janssen Pharmaceutical K.K., own stocks or stock options in Kameya Shoji Co., Ltd. Mitsuo Inagaki: Employee of Janssen Pharmaceutical K.K., and own stocks or stock options in Johnson & Johnson. Hisanori Kobayashi: Employee of Janssen Pharmaceutical K.K., and own stocks or stock options in Johnson and Johnson. Shinsuke Iida: All support for the present manuscript received from Janssen. Grants received from Abbvie, Amgen, BMS, Daiichi Sankyo, GSK, Janssen, Novartis, Ono, Otsuka, Pfizer Sanofi, Shionogi, and Takeda. Consulting fees received from Abbvie, Astrazeneca, BMS, GSK, Janssen, Novartis, Otsuka, Pfizer, and Sanofi. Payment or honoraria received from Astrazeneca, BMS, Janssen, Ono, Pfizer, Sanofi, and Takeda. Other financial or non-financial interests received from Chugai. Ethical approval: The study protocol and associated study documents were approved by the Institutional Review Board. Good Clinical Practice (GCP) guidelines, established by the International Council for Harmonization (ICH), and all relevant regulatory requirements were followed during the conduct of this study., (© 2024. The Author(s).)

Background: We conducted a randomize phase II study to evaluate the efficacy and safety of topoisomerase II inhibitor amrubicin plus topoisomerase I inhibitor irinotecan (AI) compared with cisplatin plus irinotecan (PI) as first-line therapy in patients with extensive-disease (ED) small-cell lung cancer (SCLC)., Patients and Methods: Chemo-naïve patients with pathologically proven ED-SCLC (including limited disease (LD) SCLC with malignant effusion) were enrolled. Patients were randomized 1:1 to receive either AI (amrubicin 90mg/m 2 on day 1 and irinotecan 50mg/m 2 on days 1 and 8 of a 21-day cycle) or PI (cisplatin 60mg/m 2 on day 1 and irinotecan 60mg/m 2 on days 1, 8 and 15 of a 28-day cycle). The primary endpoint was overall survival proportion at 1 year., Results: A total of 100 patients were randomly assigned to AI (n = 50) or to PI (n = 50). The 1-year overall survival proportions were 68.0% (95% confidence interval (CI): 56.2-82.2%) for AI and 59.2% (46.9-74.7%) for PI (1-sided P = .18). Median survival time was 14.8 months for AI and 13.5 months for PI with a hazard ratio (HR) of 0.618 (0.398-0.961, stratified log-rank test P = .031). Median progression-free survival time was 4.8 months for AI and 5.4 months for PI (stratified log-rank test, P = .54). Objective response rate was 70.0% (55.4-82.1%) for AI and 55.1% (40.2-69.3%) for PI (Fisher exact test, P = .15). There was no significant difference in hematological toxicity, whereas rates of vomiting, loss of appetite, diarrhea, and elevated serum creatinine are more frequent in PI. Interstitial lung disease (Grade 2 or 3) developed in 5 patients in AI and in 1 patient in PI. There was no treatment-related death., Conclusion: Although the study did not meet its primary endpoint, AI showed promising efficacy and good tolerability in chemo-naïve patients with ED-SCLC., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Legionella pneumonia is one of the major causes of severe pneumonia, in which treatment delay might lead to a poor prognosis. Therefore, as far as possible, early diagnosis and treatment of Legionella pneumonia is essential. Regarding the antimicrobials for Legionella pneumonia, fluoroquinolones, such as levofloxacin, or macrolides, such as azithromycin (AZM), are recommended in Japan and other countries. Lascufloxacin (LSFX), the newest fluoroquinolone developed in Japan, has been in use in daily clinical practice since January 2020. However, there are only few reports of Legionella pneumonia cases treated with LSFX. Here, we report three cases of hospitalized Legionella pneumonia patients that were successfully treated using LSFX. All three patients were admitted to the medical ward on admission, although one patient was subsequently transferred to the ICU for mechanical ventilatory management due to worsening of the pneumonia on day 3. All patients improved and were discharged following LSFX treatment (the patient admitted to the ICU was treated using LSFX + AZM combination therapy) without any severe adverse events. LSFX might be considered to be the first antibiotic choice for Legionella pneumonia, similar to levofloxacin. However, further data regarding the treatment of Legionella pneumonia cases using LSFX are needed to evaluate its efficacy and safety., Competing Interests: Declaration of competing interest None., (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.)

This rapid communication highlights the correlation between protein kinase B alpha (AKT1)-phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha (PIK3CA)- phosphatase and tensin homolog (PTEN) alterations and clinicopathological factors in Japanese patients with metastatic recurrent breast cancer (mBC). This study analyzed 1967 patients with luminal-type breast cancer who underwent cancer gene panel testing. The results demonstrated that AKT pathway alterations, including PI3K/AKT/PTEN, occurred in 1038 (52.8%) cases. Patients with AKT pathway mutations were older (p = 0.002) and had a higher rate of invasive lobular carcinoma (ILC) histology (p = 0.001), progesterone receptor (PgR) positivity (p = 0.006), and bone metastases (p = 0.001), and a lower rate of germline BRCA2 (p < 0.001). Comprehensive genomic profile results demonstrated a higher tumor mutational burden (TMB) (< 0.001) and lower tumor BRCA1/2 expression (< 0.001) in patients with mutations in the AKT pathway. These results are crucial for characterizing candidates for AKT pathway-targeted molecular therapies and conceptualizing optimal treatment strategies. Clinical trial registration: This study is an observational study and is therefore not registered with the clinical trials registration., Competing Interests: Declarations. Conflict of interest: Payment or honoraria for lectures—HT: Chugai, Daiichi Sankyo, Pfizer, Eli Lilly, Eisai AstraZeneca, MSD, Takeda, and Kyowa Kirin; MM: Chugai, Pfizer, Eli Lilly, MSD, Eisai, Taiho and AstraZeneca; NH: Chugai, Daiichi Sankyo, Pfizer, Eli Lilly, Takeda, Novartis, Eisai, AstraZeneca, MSD and Kyowa Kirin; AE: Kyowa Kirin; TI: Chugai, Daiichi Sankyo, Pfizer, Eli Lilly; YH, MS, TM, MY, TK and AS have no conflicts of interest to declare. Ethical approval: All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards., (© 2024. The Author(s).)

A combination of nivolumab and ipilimumab (NIVO + IPI) is the only approved combination of two immune checkpoint inhibitors for metastatic or advanced renal cell carcinoma (mRCC). Inadequate evidence of treatment with NIVO + IPI has been reported in Japanese cohorts. We evaluated the clinical efficacy of NIVO + IPI treatment. Patients with mRCC who received NIVO + IPI at nine Japanese facilities between August 2018 and March 2023 were enrolled in this study. The primary endpoint in this study was the assessment of oncological outcomes in patients with mRCC who received NIVO + IPI. Eighty-four patients with mRCC were enrolled. The median follow-up period was 18.3 months, and median progression-free and overall survival were 13.3 and 50.9 months, respectively. The objective response rate was 47.6%, and the disease control rate was 78.6%. To our knowledge, this is the largest study that evaluates Japanese patients with mRCC receiving NIVO + IPI treatment. In this study, the real-world oncological outcomes after NIVO + IPI treatment were comparable to those in the CheckMate 214 study.

Superoxide dismutase (SOD) catalyzes the highly reactive superoxide anion to form hydrogen peroxide, which facilitates cell proliferation and death. We investigated whether red cell SOD (R-SOD) activity is associated with an increased risk of cancer in a Japanese general population. We prospectively analyzed data from 1,921 participants (800 men and 1,121 women; age, 58.7 ± 14.7 years) in a Hidaka cohort study. After a median follow-up period of 10.9 years, 160 participants had developed cancer. The Cox proportional hazards model was used to estimate quartile-specific HRs and 95% confidential intervals (CI) for cancer risk. After adjustment for potential cancer risk factors including age, sex, current smoking habit, alcohol use, physical activities, body mass index, plasma immunoreactive insulin, and non-high-density lipoprotein cholesterol levels, we found a significant association between R-SOD activity and an increased risk of cancer (HR, 1.61; 95% CI, 1.03-2.52; P = 0.037). In analyses conducted separately by sex, a significant association was found in men (HR, 2.49; 95% CI, 1.35-4.59; P = 0.003) but not women (HR, 1.46; 95% CI, 0.70-3.05; P = 0.320). After excluding participants who developed cancer within 5 years of the baseline survey, the association was more evident in men (HR, 4.64; 95% CI, 1.88-11.45; P = 0.001). We found no association with cancer risk in women (HR, 1.01; 95% CI, 0.39-2.65; P = 0.983). Increased R-SOD activities were associated with an increased risk of cancer, particularly in men in this population., Significance: Our study is the first to show that increased R-SOD activity is associated with a significantly higher cancer risk in men but not in women. Antioxidative enzymes such as SOD are essential for maintaining cellular redox balance. Their roles in cancer development and prevention are yet to be fully elucidated., (©2024 The Authors; Published by the American Association for Cancer Research.)

Background: Sacituzumab govitecan (SG) is a Trop-2-directed antibody-drug conjugate approved outside Japan for second-line and later metastatic triple-negative breast cancer (mTNBC), based on the ASCENT study (NCT02574455). We report SG safety and efficacy in an open-label, phase 1/2 bridging study in Japanese patients with advanced solid tumors (ASCENT-J02; NCT05101096; jRCT2031210346)., Methods: Phase 1 was a standard 3 + 3 design. Patients received intravenous SG 6 mg/kg, escalating to 10 mg/kg, on Days 1 and 8 per 21-day cycle; primary endpoints were safety, incidence of dose-limiting toxicity/toxicities (DLTs), and determination of the recommended phase 2 dose (RP2D). In the multicohort phase 2 study, patients in the mTNBC cohort with previously treated disease received SG at the RP2D; primary endpoint was independent review committee (IRC)-assessed objective response rate (ORR; RECIST v1.1). Safety was a secondary endpoint., Results: In phase 1 (N = 15), one DLT (grade 3 elevated transaminases) occurred with SG 10 mg/kg; RP2D was SG 10 mg/kg regardless of UGT1A1 status. In phase 2, 36 patients with mTNBC received SG 10 mg/kg. At median follow-up of 6.1 months, IRC-assessed ORR was 25.0% (95% CI 12.1-42.2; P = 0.0077). Median progression-free survival was 5.6 months (95% CI 3.9-not reached [NR]); median overall survival was NR. No treatment-emergent adverse events led to discontinuation or death., Conclusions: SG RP2D was established as 10 mg/kg in Japanese patients. SG showed efficacy in Japanese patients with previously treated mTNBC, a manageable safety profile, and no new safety signals, consistent with the previous ASCENT study., (© 2024. The Author(s).)

Background: Proton-based, definitive chemoradiotherapy (P-CRT) for esophageal squamous cell carcinoma (ESCC) previously showed comparable survival outcomes with the surgery-based therapy, i.e., neoadjuvant chemotherapy followed by esophagectomy (NAC-S), in a single-institutional study. This study aimed to validate this message in a Japanese multicenter study., Methods: Eleven Japanese esophageal cancer specialty hospitals have participated. A total of 518 cases with clinical Stage I-IVA ESCC between 2010 and 2019, including 168 P-CRT and 350 NAC-S patients, were enrolled and long-term outcomes were evaluated. Propensity-score weighting analyses with overlap weighting for confounding adjustment were used., Results: The 3-year overall survival (OS) of the P-CRT group was equivalent to the NAC-S group (74.8% vs. 72.7%, hazard ratio [HR]: 0.87, 95% confidence interval [CI]: 0.61-1.25). Although, the 3-year P-CRT group progression-free survival (PFS) was inferior to the NAC-S group (51.4% vs. 59.6%, HR 1.39, 95% CI 1.04-1.85), the progression P-CRT group cases showed better survival than the NAC-S group (HR 0.58, 95% CI 0.38-0.88), largely because of salvage surgery or endoscopic submucosal dissection for local progression. The survival advantage of P-CRT over NAC-S was more pronounced in the cT1-2 (HR 0.61, 95% CI 0.29-1.26) and cStage I-II (HR 0.50, 95% CI 0.24-1.07) subgroups, although this trend was not evident in other populations, such as cT3-4 and cStage III-IVA., Conclusions: Proton-based CRT for ESCC showed equivalent OS to surgery-based therapy. Especially for patients with cT1-2 and cStage I-II disease, proton-based CRT has the potential to serve as a first-line treatment., (© 2024. The Author(s), under exclusive licence to The Author(s) under exclusive licence to The Japan Esophageal Society.)

Purpose: Proton beam therapy (PBT) has recently been included in Japan's health insurance benefit package for certain cancer types. This study aimed to determine the cost-effectiveness of PBT as a replacement for conventional three-dimensional conformal radiotherapy (3D-CRT) for locally advanced esophageal cancer (LAEC) that is not covered by social insurance., Methods: We estimated the incremental cost-effectiveness ratio (ICER) of PBT as a replacement for 3D-CRT, using clinical evidence from the literature and expert opinions. We used an economic model, decision tree, and Markov model to illustrate the courses followed by patients with LAEC. Effectiveness was estimated as quality-adjusted life years (QALY) using utility weights for the health state. Social insurance fees were calculated as costs. We assumed two base cases depending on the two existing levels of fees for PBT in social insurance: 2,735,000 Japanese yen (US$20,652) or 1,600,000 yen (US$13,913). The stability of the ICER against these assumptions was appraised using sensitivity analysis., Results: The effectiveness of PBT and 3D-CRT was 2.62 and 2.51 QALY, respectively. The estimated ICER was 14,025,268 yen (US$121,958) per QALY for the higher fee level and 7,026,402 yen (US$61,099) for the lower fee level. According to the Japanese threshold for cost-effectiveness of anticancer therapy of 7,500,000 yen (US$65,217) per QALY gain, the inclusion of PBT for LAEC in the benefit package of social insurance is cost-effective if a lower fee is applied., Conclusion: PBT is a cost-effective alternative to 3D-CRT for LAEC and making it available to patients under social insurance could be justifiable., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Sawada et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Despite advances, most patients with multiple myeloma (MM) experience relapse and repeat multiple treatment lines, highlighting an unmet need for patients with relapsed or refractory MM (RRMM). Bispecific antibodies are a new option, but their efficacy and safety in Japanese patients are unknown., Methods: This was an analysis of Japanese patients receiving elranatamab monotherapy in MagnetisMM-2 (NCT04798586) and MagnetisMM-3 (NCT04649359). Both studies evaluated a priming dose regimen of elranatamab followed by weekly subcutaneous doses, in patients with disease progression while receiving or who were intolerant to ≥3 prior therapies (≥1 proteasome inhibitor, ≥1 immunomodulatory drug and ≥1 anti-CD38 monoclonal antibody). The primary endpoints were dose limiting toxicities (DLTs) in MagnetisMM-2 and confirmed objective response rate (ORR) in MagnetisMM-3. In both, key secondary endpoints included safety, tolerability, duration of response, time to response, progression-free survival and overall survival., Results: In MagnetisMM-2 (N = 4) and MagnetisMM-3 (n = 12), median ages were 68.5 and 66.5 years, respectively. No DLTs were observed in MagnetisMM-2. ORRs were 50.0% (95% CI, 6.8-93.2) and 58.3% (95% CI, 27.7-84.8) in MagnetisMM-2 and MagnetisMM-3, respectively. All patients experienced treatment-emergent adverse events in MagnetisMM-2 (grade 3/4: 75.0%) and MagnetisMM-3 (grade 3/4: 100%); cytokine release syndrome occurred in 100% (grade 3/4: 25.0%) and 58.3% (no grade 3/4) of patients, respectively. Neither study reported immune effector cell-associated neurotoxicity syndrome., Conclusions: No new safety signals were observed, and ORRs were similar to that of the overall MagnetisMM-3 trial population, supporting further studies of elranatamab in Japanese patients with RRMM. ClinicalTrials.gov identifier: NCT04798586 (MagnetisMM-2), NCT04649359 (MagnetisMM-3)., (© The Author(s) 2024. Published by Oxford University Press.)

The 88 th Annual Scientific Meeting of the Japanese Circulation Society (JCS2024) was held from Friday, March 8 th to Sunday, March 10 th in Kobe, Japan. The main theme of this 3-day meeting was "The Future of Cardiology: Challenges in Overcoming Cardiovascular Disease". As COVID-19 has been finally conquered, with revision of its categorization under the Infectious Disease Control Law and relaxation of infection prevention measures, it was once again possible to have face-to-face presentations and lively discussion. JCS2024 was a major success, with 19,209 participants and attendees, thanks to the greatly appreciated cooperation and support from all affiliates.

Background and Objectives : Minimally invasive trauma management, including interventional radiology and non-operative approaches, has proven effective. Consequently, our hospital established a trauma IVR protocol called "Ohta Nishinouchi Hospital trauma protocol (ONH trauma protocol) in 2013, mainly for trunk trauma. However, the efficacy of the ONH trauma protocol has remained unverified. We aimed to assess the protocol's impact using interrupted time-series analysis (ITSA). Materials and Methods : This retrospective cohort study was conducted at Ohta Nishinouchi hospital, a tertiary emergency hospital, from January 2004 to December 2019. We included patients aged ≥ 18 years who presented to our institution due to severe trauma characterized by an Abbreviated Injury Scale of ≥3 in any region. The primary outcome was the incidence of in-hospital deaths per 100 transported patients with trauma. Multivariable logistic regression analysis was conducted with in-hospital mortality as the outcome, with no exposure before protocol implementation and with exposure after protocol implementation. Results : Overall, 4558 patients were included in the analysis. The ITSA showed no significant change in in-hospital deaths after protocol induction (level change -1.49, 95% confidence interval (CI) -4.82 to 1.84, p = 0.39; trend change -0.044, 95% CI -0.22 to 0.14, p = 0.63). However, the logistic regression analysis revealed a reduced mortality effect following protocol induction (odds ratio: 0.50, 95% CI: 0.37 to 0.66, p < 0.01, average marginal effects: -3.2%, 95% CI: -4.5 to -2.0, p < 0.01). Conclusions : The ITSA showed no association between the protocol and mortality. However, before-and-after testing revealed a positive impact on mortality. A comprehensive analysis, including ITSA, is recommended over before-and-after comparisons to assess the impact of the protocol.

Objectives: Early gastric cancer endoscopic resection (ER) is prominent in Japan. However, evidence regarding ER of gastric submucosal tumors (SMT) is limited. This prospective multicenter phase II study investigated the efficacy and safety of endoscopic full-thickness resection (EFTR) for gastric SMT., Methods: Endoscopic full-thickness resection indication for gastric SMT was 11-30 mm, histologically proven or clinically suspicious (irregular margin, increasing size, or internal heterogeneity) gastrointestinal stromal tumors (GIST), with no ulceration and intraluminal growth type. The primary end-point was the complete ER (ER0) rate, with a sample size of 42., Results: We enrolled 46 patients with 46 lesions between September 2020 and May 2023 at seven Japanese institutions. The mean ± SD (range) endoscopic tumor size was 18.8 ± 4.5 (11-28) mm. The tumor resection and defect closure times were 54 ± 26 (22-125) min and 33 ± 28 (12-186) min, respectively. A 100% ER0 was achieved in all 46 patients. The EFTR procedure was accomplished in all patients without surgical intervention. One patient had delayed perforation and was managed endoscopically. GIST accounted for 76% (n = 35) of the cases. R0, R1, and RX rates were 33 (77%), 3 (6.5%), and 7 (15%), respectively., Conclusion: Endoscopic full-thickness resection for gastric SMT of 11-30 mm is efficacious. It warrants further validation in a large-scale cohort study to determine the long-term outcome of this treatment for patients with gastric GIST., (© 2023 Japan Gastroenterological Endoscopy Society.)

Background: Safinamide is an effective adjunctive therapy for wearing-off in Parkinson's disease (PD); however, evidence is lacking in older patients and those in the early stages of wearing-off. This study evaluated the efficacy and safety of safinamide as adjunctive therapy in patients with PD treated with levodopa monotherapy in clinical practice., Methods: This multicentre, open-label observational study was conducted at five sites in Japan. Patients diagnosed with PD and wearing-off initiated safinamide as adjunctive therapy with levodopa monotherapy. Efficacy endpoints were mean changes in Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Part I, III, and IV scores; daily ON-time without dyskinesia using 24-h patient symptom diaries; and 39-item Parkinson's Disease Questionnaire (PDQ-39) scores at 18 weeks of treatment., Results: In total, 24 patients initiated safinamide (66.7% were aged ≥75 years); the mean duration of wearing-off was 1.2 years. MDS-UPDRS Part III total score, Part IV total score, and PDQ-39 summary index decreased significantly from baseline (mean change -7.0 [p = 0.012], -2.4 [p = 0.007] and - 5.3 [p = 0.012], respectively). There was a non-statistically significant increase of 1.55 h in mean daily ON-time without dyskinesia. Numerical Rating Scale total score for pain (p = 0.015), and scores for OFF-period pain (p = 0.012) and nocturnal pain (p = 0.021) subdomains were significantly improved in the subgroup with pain. Most reported adverse events were classified as mild., Conclusion: Safinamide improved motor and non-motor symptoms and quality of life-related measures in older patients with PD in the early stages of wearing-off without new safety concerns., Study Registration: University Hospital Medical Information Network in Japan; study ID: UMIN000044341., Competing Interests: Declaration of competing interest N.N., S.S. and W.S. report honoraria and consultation fees from Eisai Co., Ltd. during the conduct of the study. T.H., K.N., R.N., A.Y., Y.S. and H.S. report honoraria from Eisai Co., Ltd. during the conduct of the study. S.-I.U., T.O. and Y.F. have no competing interests to declare. T.K. and T.I. are employees of Eisai Co. Ltd. N.H. reports honoraria, consultation fees and grants from Eisai Co., Ltd. during the conduct of the study., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Encephalopathy is the most severe complication of various common infections, including influenza and herpes, and it often results in death or severe neurological disability. The risk factors for viral encephalopathy include non-steroidal anti-inflammatory drug (NSAID) use; however, studies on NSAID-related encephalopathy are limited. In this study, we aimed to investigate the characteristics of NSAID-related encephalopathy. We investigated the incidence of NSAID-related encephalopathy using data from the United States Food and Drug Administration Adverse Event Reporting System (FAERS) and Japanese Adverse Drug Event Report (JADER) databases containing reports on spontaneous adverse effects (AEs) published by the Pharmaceuticals and Medical Devices Agency. We used these databases to detect AEs based on reported odds ratios. By separating suspicious drugs, concomitant drugs, and drug interactions involving NSAIDs, we investigated the relationship between encephalopathy pathology and AEs of NSAIDs. Significant encephalopathy signals were detected for loxoprofen and etodolac in the FAERS database and loxoprofen in the JADER database. In the JADER database, significant encephalopathy signals in loxoprofen-treated patients were detected in 70-79-year-old, ≥80-year-old, influenza viral infection, and herpes virus infection groups. Significant encephalopathy signals in patients with herpes virus infection were detected in the ≥80-year-old and loxoprofen-treated groups. Regarding the involvement of loxoprofen in the development of encephalopathy, the JADER database listed loxoprofen as a suspect drug, without indicating any concomitant drug interactions. In conclusion, our findings suggest that loxoprofen and etodolac may be associated with viral encephalopathy. Accordingly, prudence is recommended when using loxoprofen in older individuals with viral infections.

Hyperglycemic emergencies frequently lead to acute kidney injury (AKI) and require treatment with large amount of intravenous fluids. However, the effects of chloride loading on this population have not yet been investigated. We conducted a multicenter, retrospective, cohort study in 21 acute-care hospitals in Japan. The study included hospitalized adult patients with diabetic ketoacidosis (DKA) and hyperosmolar hyperglycemic syndrome (HHS) who had AKI upon arrival. The patients were classified into high and low chloride groups based on the amount of chloride administered within the first 48 h of their arrival. The primary outcome was recovery from AKI; secondary outcome was major adverse kidney events within 30 days (MAKE30), including mortality and prolonged renal failure. A total of 390 patients with AKI, including 268 (69%) with DKA and 122 (31%) with HHS, were included in the study. Using the criteria of Kidney Disease Improving Global Outcomes, the severity of AKI in the patients was Stage 1 (n = 159, 41%), Stage 2 (n = 121, 31%), and Stage 3 (n = 110, 28%). The analysis showed no significant difference between the two groups in recovery from AKI (adjusted hazard ratio, 0.96; 95% CI 0.72-1.28; P = 0.78) and in MAKE30 (adjusted odds ratio, 0.91; 95% CI 0.45-1.76; P = 0.80). Chloride loading with fluid administration had no significant impact on recovery from AKI in patients with hyperglycemic emergencies.Trial Registration This study was registered in the UMIN clinical trial registration system (UMIN000025393, registered December 23, 2016)., (© 2024. The Author(s), under exclusive licence to Società Italiana di Medicina Interna (SIMI).)

Allogeneic haematopoietic stem cell transplantation (allo-HSCT) is the only curative therapy for adult T-cell leukaemia/lymphoma (ATL). Specific HLAs are associated with outcomes of immunotherapy and allo-HSCT. We hypothesised that individual HLAs would affect the clinical outcomes of ATL patients after allo-HSCT. Using data from a Japanese registry, we retrospectively analysed 829 patients with ATL who received transplants from HLA-identical sibling donors or HLA-A, -B, -C or -DRB1 allele-matched unrelated donors between 1996 and 2015. We evaluated the overall mortality risk of HLA-A, -B and -DR antigens with frequencies exceeding 3%. Outcomes were compared between transplants with or without specific HLA antigens. Of the 25 HLAs, two candidates were identified but showed no statistically significant differences by multiple comparison. HLA-B62 was associated with a lower risk of mortality (hazard ratio [HR], 0.68; 95% confidence interval [CI]: 0.51-0.90; p = 0.008), whereas HLA-B60 was associated with a higher risk of mortality (HR, 1.64; 95% CI: 1.19-2.27; p = 0.003). In addition, HLA-B62 was associated with a lower risk of transplant-related mortality (TRM) (HR, 0.52; 95% CI: 0.32-0.85, p = 0.009), whereas HLA-B60 was associated with a higher risk of grades III-IV acute graft-versus-host disease (HR, 2.63; 95% CI: 1.62-4.27; p < 0.001). Neither HLA influenced relapse. The higher risk of acute GVHD in HLA-B60-positive patients and the lower risk of TRM in HLA-B62-positive patients were consistent with previously obtained results from patients with other haematological malignancies. Consideration of HLA in ATL patients may help to predict risk and outcomes after allo-HSCT., (© 2024 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Aims: We investigated the characteristics of infection and the utility of inflammatory markers in diabetic ketoacidosis (DKA) and hyperosmolar hyperglycemic syndrome (HHS)., Methods: A multicenter, retrospective observational study in 21 acute-care hospitals was conducted in Japan. This study included adult hospitalized patients with DKA and HHS. We analyzed the diagnostic accuracy of markers including C-reactive protein (CRP) and procalcitonin (PCT) for bacteremia. Multiple regression models were created for estimating bacteremia risk factors., Results: A total of 771 patients, including 545 patients with DKA and 226 patients with HHS, were analyzed. The mean age was 58.2 (SD, 19.3) years. Of these, 70 tested positive for blood culture. The mortality rates of those with and without bacteremia were 14 % and 3.3 % (P-value < 0.001). The area under the curve (AUC) of CRP and PCT for diagnosis of bacteremia was 0.85 (95 %CI, 0.81-0.89) and 0.76 (95 %CI, 0.60-0.92), respectively. Logistic regression models identified older age, altered level of consciousness, hypotension, and higher CRP as risk factors for bacteremia., Conclusions: The mortality rate was higher in patients with bacteremia than patients without it. CRP, rather than PCT, may be valid for diagnosing bacteremia in hyperglycemic emergencies., Trial Registration: This study is registered in the UMIN clinical trial registration system (UMIN000025393, Registered December 23, 2016)., 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 B.V. All rights reserved.)

The emergence of novel drugs has significantly improved outcomes of patients with plasma cell neoplasms (PCN). The Japanese Society of Hematology conducted a prospective observational study in newly diagnosed PCN patients between 2016 and 2021. The analysis focused on 1385 patients diagnosed with symptomatic PCN between 2016 and 2018. The primary endpoint was the 3-year overall survival (OS) rate among patients requiring treatment (n = 1284), which was 70.0% (95%CI 67.4-72.6%). Approximately 94% of these patients received novel drugs as frontline therapy. The 3-year OS rate was 90.3% (95%CI 86.6-93.1%) in the 25% of patients who received upfront autologous stem cell transplantation (ASCT), versus just 61.4% (95%CI 58.0-64.6%) in those who did not receive upfront ASCT. The only unfavorable prognostic factor that affected OS in ASCT recipients was an age of 65 or higher. For patients who did not receive ASCT, independent unfavorable prognostic factors included frontline treatment with conventional chemotherapies, international staging system score of 2/3, extramedullary tumors, and Freiberg comorbidity index of 2/3. This study unequivocally demonstrates that use of novel drugs improved OS in Japanese myeloma patients, and underscores the continued importance of upfront ASCT as the standard of care in the era of novel drugs., (© 2024. The Author(s).)

Background: Although the therapeutic relationship (or 'alliance') is well known to be a key component of psychiatric treatment, there has been no simple way to objectively measure the patient-therapist relationship. Here, we measured the psychological distance between patients and their therapists by using the Pictorial Representation of Illness and Self Measure (PRISM)., Patients and Methods: We analyzed the patient-therapist relationship of 112 patients from two hospitals in Japan (54 males, 57 females, 1 unknown; age 46.20 ± 15.03 years [mean ± SD]) who completed the PRISM and self report questionnaires (LSNS-6, K6, and BASIS-32) about their social network, psychological distress, and outcomes of mental health treatment., Results: PRISM measurements were available for all patients who consented to participate. In the comparison by disease category, schizophrenia recorded the closest distance to the psychiatrist in charge, followed by bipolar disorder, depression, and neurotic disorder. Regarding the distance to the psychiatrist in charge, PRISM showed a weak negative correlation (r = -0.23, p < 0.05) with age, indicating that with increasing age, the therapeutic rela tionship was more important to the patients., Conclusion: Our findings indicate the possibility of implementing PRISM to assess the impact of the therapeutic relationship in patients with a wide range of psychiatric disorders, and they suggest that PRISM holds great potential for clinical application.

Objectives: Endoscopic submucosal dissection (ESD) for superficial esophageal squamous cell carcinoma (ESCC) is performed for the treatment of lesions with varied backgrounds and factors. However, the predictive factors associated with the technical difficulty of ESD remain unknown in patients with varied lesions. Therefore, this study aimed to identify the predictive factors associated with the technical difficulty of ESD for ESCC using a retrospective cohort., Methods: This multicenter, retrospective study was conducted in 10 hospitals in Japan. Consecutive patients who underwent esophageal ESD between January 2013 and December 2019 were enrolled. Lesions of subepithelial tumors, adenocarcinoma, and adenoma were excluded. Difficult lesions were defined as ESD requiring a long procedure time (≥120 min), perforation development, piecemeal resection, or discontinued ESD. In the present study, the clinical factors were assessed to identify the technical difficulty of ESD using univariate and multivariate analyses., Results: Among 1708 lesions treated with esophageal ESD, eight subepithelial tumors, 44 adenocarcinomas, and two adenomas were excluded. Finally, 1505 patients with 1654 lesions were analyzed, and 217 patients with 217 lesions (13.1%) were classified as patients with difficult lesions. In multivariate analysis, the predictive factors associated with the technical difficulty of ESD were as follows: tumors with varices, tumors with diverticulum, antiplatelet use (discontinued), circumference of tumor (≥1/2), preoperative tumor size ≥30 mm, trainee, and nonhigh-volume center., Conclusion: This multicenter retrospective study identified the predictive factors associated with the technical difficulty of ESD for ESCC with varied backgrounds and factors., (© 2023 Japan Gastroenterological Endoscopy Society.)

Introduction: EndoTrac is a line-attached sheath-type traction device that enables us to control the direction and the force of traction during endoscopic submucosal dissection (ESD). The efficacy of EndoTrac for gastric ESD has not been fully verified., Methods and Analysis: The G-Trac study is a multicentre (nine general hospitals and two university hospitals in Japan) collaborative trial assessing the efficacy of EndoTrac for gastric ESDs. Patients with superficial gastric neoplasms will be enrolled and randomly assigned to undergo either conventional ESD or EndoTrac ESD. Allocation will be stratified according to tumour location, operator experience and tumour diameter at an allocation rate of 1:1. The type of endoknife used will be confirmed before randomisation. The primary outcome, procedure time, will be compared between the groups in both intention-to-treat and per-protocol analyses using the Wilcoxon rank sum test. The efficacy-related, safety-related and device-related outcomes will be assessed in the secondary analysis. The planned sample size of the 142 patients in the two groups will enable us to detect a difference with a power of 80% by using the Wilcoxon rank sum test, assuming an effect size of 0.54, asymptotic relative efficiency of 0.864 and a two-sided type 1 error rate of 5%., Ethics and Dissemination: This trial was approved by the certified review board of Kobe University (22 December 2022). The results from this trial will be disseminated through peer-review journals, presentations at national and international conferences, and data sharing with other researchers., Trial Registration Number: jRCT1052220166., Competing Interests: Competing interests: Takashi Toyonaga has received royalties from Top for the development of the EndoTrac. The other authors declare no conflicts of interest regarding this article., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Real-world studies permit inclusion of a more diverse patient population and provide more information on the effectiveness of treatments used in routine clinical practice. This prospective, multicenter, observational study investigated the effectiveness and safety of ixazomib plus lenalidomide and dexamethasone (IRd) in 295 patients with relapsed/refractory multiple myeloma (RRMM) in routine clinical practice in Japan. Patients had a median age of 74 years, 80.0% were aged ≥ 65 years, 42.0% had received ≥ 3 lines of prior treatment, and 28.5% were "frail" according to the International Myeloma Working Group frailty score. After a median follow-up of 25.0 months, median progression-free survival (PFS) was 15.3 (95% CI 12.4-19.5) months, while median overall survival was not reached. The overall response rate was 53.9%, and 31.5% of patients had a very good partial response or better. In the subgroup analysis, median PFS was better in patients with 1 versus 2 or ≥ 3 lines of prior treatment (29.0 vs 19.2 or 6.9 months) and paraprotein versus clinical relapse (16.0 vs 7.9 months), but median PFS was not notably affected by frailty score or age group. Dose adjustment was more frequent among patients aged > 75 years, especially early after IRd treatment initiation. Treatment-emergent adverse events (TEAEs) of any grade occurred in 84.4% of patients and 24.7% of patients discontinued treatment due to TEAEs; no new safety concerns were found. These findings suggest that oral IRd triplet regimen is an effective and tolerable treatment option for RRMM patients in real-world settings outside of clinical trials.ClinicalTrials.gov identifier: NCT03433001; Date of registration: 14 February 2018., (© 2023. The Author(s).)

Suicide is an increasingly important public healthcare concern worldwide. Studies examining the effect of attempted suicide on clinical outcomes among patients with trauma are scarce. We conducted a retrospective cohort study at a community emergency department in Japan. We included all severely injured patients with an Injury Severity Score > 15 from January 2002 to December 2021. The primary outcome measure was in-hospital mortality. The other outcome of interest was hospital length of stay. One-to-one propensity score matching was performed to compare these outcomes between suicide attempt and no suicide attempt groups. Of the 2714 eligible patients, 183 (6.7%) had trauma caused by a suicide attempt. In the propensity score-matched analysis with 139 pairs, the suicide attempt group showed a significant increase in-hospital mortality (20.9% vs. 37.4%; odds ratio 2.27; 95% confidence intervals 1.33-3.87) compared with the no suicide attempt group. Among survivors, the median hospital length of stay was significantly longer in the suicide attempt group than that in the no suicide attempt group (9 days vs. 12 days, p = 0.0076). Because of the unfavorable consequences and potential need for additional healthcare, increased attention should be paid to patients with trauma caused by a suicide attempt., Competing Interests: The authors have no conflicts of interest to declare.

Introduction: Diabetic ketoacidosis (DKA) and hyperglycemic hyperosmolar syndrome (HHS) are life-threatening complications of diabetes mellitus. Their clinical profiles have not been fully investigated., Methods: A multicenter retrospective cohort study was conducted in 21 acute care hospitals in Japan. Patients included were adults aged 18 or older who had been hospitalized from January 1, 2012, to December 31, 2016 due to DKA or HHS. The data were extracted from patient medical records. A four-group comparison (mild DKA, moderate DKA, severe DKA, and HHS) was performed to evaluate outcomes., Results: A total of 771 patients including 545 patients with DKA and 226 patients with HHS were identified during the study period. The major precipitating factors of disease episodes were poor medication compliance, infectious diseases, and excessive drinking of sugar-sweetened beverages. The median hospital stay was 16 days [IQR 10-26 days]. The intensive care unit (ICU) admission rate was 44.4% (mean) and the rate at each hospital ranged from 0 to 100%. The in-hospital mortality rate was 2.8% in patients with DKA and 7.1% in the HHS group. No significant difference in mortality was seen among the three DKA groups., Conclusions: The mortality rate of patients with DKA in Japan is similar to other studies, while that of HHS was lower. The ICU admission rate varied among institutions. There was no significant association between the severity of DKA and mortality in the study population., Trial Registration: This study is registered in the UMIN clinical Trial Registration System (UMIN000025393, Registered 23th December 2016)., (© 2023. Springer-Verlag Italia S.r.l., part of Springer Nature.)

Background: No multidomain intervention trials have been designed for the prevention of cognitive decline in older adults with type 2 diabetes., Objectives: To investigate the efficacy of a multidomain intervention in preventing cognitive decline in older adults with type 2 diabetes and cognitive impairment., Design: Eighteen-month, multi-centered, randomized controlled trial., Setting: Twelve hospitals in Japan., Participants: Outpatients with type 2 diabetes aged 70-85 years with cognitive impairment., Intervention: The multidomain intervention program includes management of metabolic and vascular risk factors, exercise, nutritional counseling, and promotion of social participation. Participants in the control group received usual care and treatment for type 2 diabetes., Measurements: The primary outcome was the change in a composite score combining several neuropsychological tests from baseline to the 18-month follow-up. To assess the differences in cognitive changes between the intervention and control groups, a mixed-effects model for repeated measures was used., Results: Between March 13, 2019, and May 8, 2020, 361 participants were screened, and 154 were randomly assigned to either the intervention group (n = 81) or the control group (n = 73). Finally, 110 participants completed the trial. The between-group difference in the composite score changes was 0.068 (95% confidence interval, -0.091 to 0.226). Analyses for secondary outcomes indicated a positive impact of the intervention on memory and indicated that the intervention led to changes in dietary habits with increased intakes of niacin and meat, along with weight reduction compared to the control group., Conclusion: The multidomain intervention did not demonstrate efficacy in preventing cognitive decline. However, this trial provided proof-of-concept evidence that multidomain interventions may offer cognitive benefits and contribute to changes in dietary behavior and weight reduction in older adults with type 2 diabetes and cognitive impairment. These findings should be confirmed in future studies., Competing Interests: TSu declares a research fellowship from the Manpei Suzuki Diabetes Foundation and a grant from the Keiko-Yamasaki Memorial Funds. AA declares honoraria from Novo Nordisk Pharma Ltd, Sumitomo Parma Co. Ltd., and Ono pharmaceutical Co. Ltd. NI declares research grants and contracts from Terumo Co., Drawbridge Inc., Asken Inc., Daiichi-Sankyo Co. Ltd., Mitsubishi Tanabe Pharma Corp., Takeda Pharmaceutical Co. Ltd., Japan Tobacco Inc., Kyowa Kirin Co. Ltd., Sumitomo Dainippon Pharma Co. Ltd., MSD K.K., Ono Pharmaceutical Co. Ltd., Nippon Boehringer Ingelheim Co. Ltd., LifeScan Japan K.K., and Kowa Co. Ltd.; honoraria for lectures from Novo Nordisk Pharma Ltd., Nippon Boehringer Ingelheim Co. Ltd., Mitsubishi Tanabe Pharma Corp., Sumitomo Dainippon Pharma Co., Ltd., Sanofi K.K., Eli Lilly Japan K.K., and Kyowa Kirin Co. Ltd. MOg declares honoraria for lectures from AstraZeneca K.K., Ono Pharmaceutical Co. Ltd., Kyowa Kirin Co. Ltd., Kowa Co. Ltd., Sanofi K.K., Sumitomo Dainippon Pharma Co. Ltd., Daiichi-Sankyo Co. Ltd., Taisho Pharmaceutical Holdings Co. Ltd., Mitsubishi Tanabe Pharma Corp., Teijin Pharma Ltd., Terumo Co., Eli Lilly Japan K.K., Nippon Boehringer Ingelheim Co. Ltd., Novartis Pharma K.K., and Novo Nordisk Pharma Ltd. Other authors declare no conflicts of interest.

We retrospectively gathered data of 21 patients (13 male and 8 female; median age 65 years) diagnosed with immunoglobulin M (IgM)-related light-chain (AL) amyloidosis in Japan to investigate characteristics of IgM-AL amyloidosis and its optimal treatment strategy. Median IgM and difference free light chain (FLC) at diagnosis were 1257 mg/dl and 34.3 mg/l, respectively. Organ involvement was observed in the heart in 7 patients (33%), kidneys in 15 (71%), and lymph nodes in 5 (24%). Initial treatments were melphalan/dexamethasone in 7 patients, bortezomib/cyclophosphamide/dexamethasone in 3, autologous stem cell transplantation in 3, rituximab/bendamustine in 1, other in 3, and none in 4. Hematological responses among 15 evaluable patients were as follows: 3 reached complete response (CR), 4 partial response (PR), and 1 very good PR (VGPR), making the overall response rate of PR or better 40%. Median overall survival (OS) was 14.0 months and 1-year OS was 71.4%. Prognosis was significantly poorer in patients with cardiac involvement than those with non-cardiac involvement (1-year OS 27.8% vs. 85.7%, p = 0.0468). The involved FLC value was low in several patients and therapeutic response was difficult to assess. Further study is necessary to determine the optimal treatment for IgM-AL amyloidosis., (© 2023. Japanese Society of Hematology.)

Multiple myeloma therapy has made remarkable progress with the advent of new drugs. We explored the treatment pattern and outcomes in Japanese patients with multiple myeloma using the Medical Data Vision database. Patients were categorized as per the initial diagnosis period (2003-2015 and 2016-2020), considering the adoption of these new agents and then based on stem cell transplantation. Overall, 6438 patient data were extracted as eligible for data analysis, and the median age at the index diagnosis date was 72.0 years. Bortezomib/dexamethasone was the most common regimen for induction therapy in patients requiring stem cell transplantation from 2003-2015, and the use of bortezomib/lenalidomide/dexamethasone increased from 2016-2020. Lenalidomide/dexamethasone was the most commonly used post-transplant therapy. In the non-stem cell transplantation group, bortezomib/dexamethasone was mainly used for both periods, while lenalidomide/dexamethasone was primarily used from 2016-2020. There was a trend toward shorter first-line treatment duration and a shift to additional treatment patterns with new drugs at the following lines. The time to inpatient death period suggested an improvement between the two periods. Thus, this study revealed that recent diversification of treatment options is preferred and contributes to improved outcomes in the clinical practice of multiple myeloma in Japan., Competing Interests: I have read the journal’s policy and the authors of this manuscript have the following competing interests. HH received consulting fees and honoraria from Janssen, Ono, and Takeda; grants from Takeda, Kyowa Kirin, and BMS. TI received consulting fees and honoraria from Ono, Takeda, BMS, Janssen, and Sanofi; research fundings support from Takeda, Janssen, Pfizer, and BMS. SO has nothing to declare. AM is an employee of Janssen Pharmaceutical K.K. KK was an employee of Janssen Pharmaceutical K.K and is currently affiliated with Kite Japan Gilead Sciences, Tokyo, Japan, and have share in Gilead Science. SI is the current editor in Cancer Science journal and received consulting fees and honoraria from BMS, Janssen, Takeda, Ono, Sanofi, and Pfizer; research funding support from BMS, Janssen, Daiichi Sankyo, Amgen, Ono, AbbVie GK, GSK, Eli Lilly, Caelum Biosciences, Inc., Pfizer, Takeda, and Sanofi; grants from Chugai, Takeda, Ono, and Sanofi., (Copyright: © 2023 Handa et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)