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NTRK-rearranged spindle cell neoplasm is a group of tumors characterized by NTRK1/2/3 gene fusion. Recently, tumors with other kinase fusion genes were reported to exhibit similar morphologies. Herein, we discuss an adult-onset soft tissue tumor with similar histologic patterns as kinase gene fusion-related tumors but with BRAF and NRAS mutations. A female in her 40s had a 40 mm tumor with an unclear border in the soft tissue of her foot joint. Short spindle-shaped tumor cell proliferation with abundant capillaries and collagen fiber bundles were observed. The tumor infiltrated the subcutaneous adipose tissue, exhibiting a lipofibromatosis-like pattern. Immunohistochemically, the tumor cells coexpressed CD34, S-100, and BRAF V600E. Whole-exome sequencing revealed BRAF p.V600E and NRAS p.Q61K mutations. Since BRAF activation occurs in BRAF fusion gene tumors and BRAF mutations, they could share a similar mechanism in tumorigenesis. This case suggests the further expansion of kinase-related spindle cell tumors., (© 2024 Japanese Society of Pathology and John Wiley & Sons Australia, Ltd.)

Sleep-related breathing disorder (SRBD) and exercise-induced blood pressure (BP) elevation are known risk factors for hypertension. However, the relation between them remains unknown. This cross-sectional study examined the relationship between SRBD and exercise-induced BP elevation in a Japanese occupational population. Using the 3% oxygen desaturation index (3%ODI) obtained by a portable monitor for overnight saturation of percutaneous oxygen (SpO2), participants were classified into low (0 ≤ 3%ODI < 5), medium (5 ≤ 3%ODI < 15), and high (15 ≤ 3%ODI) 3%ODI groups. We included employees who had undergone an exercise electrocardiogram test after monitoring for overnight SpO2. In total, 928 employees were included. The median age of the participants was 50 years, 96% were male, the mean body mass index was 23.9 ± 3.1 kg/m 2 , and the median 3%ODI was 4.9 (interquartile range: 1.6-6.5). Among them, 30% and 5% were categorized into the medium and high 3%ODI groups, respectively. At a median exercise intensity of 10.1 METs, BP changed from 124 ± 16/76 ± 12 mmHg before to 183 ± 26/85 ± 14 mmHg after exercise, with a mean systolic BP change of +59 ± 23 mmHg (-20 to +128 mmHg). When we defined systolic BP change of +60 mmHg or more as exercise-induced BP elevation, the odds ratio for exercise-induced BP elevation increased significantly with higher 3%ODI levels after multivariate adjustment for parameters including current use of antihypertensive medication and maximal exercise intensity (p for trend = 0.01). Higher 3%ODI was significantly associated with higher prevalence of exercise-induced BP elevation, suggesting sympathetic hyperactivity occurs in SRBD patients. Our results suggest the potential presence of SRBD should be considered in individuals with exercise-induced BP elevation., Competing Interests: Compliance with ethical standards. Conflict of interest: The authors declare no competing interests., (© 2024. The Author(s).)

Purpose: Younger age and steep posterior tibial slope (PTS) have been reported as risk factors for graft failure after anterior cruciate ligament reconstruction (ACLR). Few studies have evaluated these risk factors simultaneously in a large cohort of patients undergoing double-bundle ACLR (DB-ACLR). Therefore, this retrospective study aimed to simultaneously investigate known risk factors such as PTS and age in DB-ACLR, determine their thresholds and calculate odds ratios (ORs)., Methods: We investigated 482 knees that underwent DB-ACLR with a follow-up period of at least 2 years. Receiver operating characteristic analysis determined cut-off values for age and PTS for graft failure. Subsequently, logistic regression analysis was conducted to evaluate the effects of age, sex, height, weight, laterality, surgical waiting period, pre-operative sport type and level, meniscal injury, hyperextension, general joint laxity and PTS on graft failure., Results: Graft failure was observed in 33 out of 482 knees (6.8%). Notably, the graft failure group was significantly younger (18.0 ± 5.0 years [standard deviation] vs. 30.4 ± 13.1 years, p  < 0.01) and had a steeper PTS (11.9 ± 2.3° [standard deviation] vs. 9.6 ± 2.9°, p  < 0.01) than the group with no graft failure. The cut-off values were 20.0 years for age (specificity, 64.6%; sensitivity, 87.9% and area under the curve, 0.808) and 12.0° for PTS (specificity, 70.9%; sensitivity, 69.7% and area under the curve, 0.734). Logistic regression analysis identified an age of <20 years (OR = 10.1; p  < 0.01), PTS of ≥12° (OR = 5.6; p  < 0.01) and pre-operative participation in pivoting sports (OR = 6.0; p  < 0.01) as significant risk factors for graft failure., Conclusion: We identified an age of <20 years, PTS of ≥12° and pre-operative participation in pivoting sports as significant risk factors for graft failure after DB-ACLR., Level of Evidence: Level III., Competing Interests: The authors declare no conflict of interest., (© 2024 The Author(s). Journal of Experimental Orthopaedics published by John Wiley & Sons Ltd on behalf of European Society of Sports Traumatology, Knee Surgery and Arthroscopy.)

Some animals seek information to solve problems when they do not know the answer. Information-seeking behavior has become a key focus in studies of animal metacognition, providing insights into how animals monitor their own knowledge states. This behavior is thought to be a form of metacognitive control. Nevertheless, research on such metacognitive control has been biased toward specific taxa, such as primates, and has not been conducted in rodents, which are the most common experimental animals. This study examined whether mice exhibit information-seeking behavior during two visual discrimination tasks and what factors influence this behavior. We trained mice to discriminate between stimuli differing in luminance or orientation, with more minor differences increasing task difficulty. An information-seeking option was introduced during these tasks, allowing mice to eliminate distractor stimuli and ensure a correct response. The results indicated that mice sought information more frequently during difficult discriminations than easier ones. However, subsequent generalization tests revealed that the mice relied on environmental cues to utilize the information-seeking option. These findings suggest that information-seeking behavior in mice may not solely reflect metacognitive processes, and further investigation is needed to explore alternative explanations., Competing Interests: Declarations. Ethical approval: The study adhered to the Japanese Society of Animal Psychology guidelines and was approved by the Animal Care and Use Committee of Sagami Women’s University (approval number 2019-06). Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Background: Triple-negative breast cancer (TNBC) recurrence and metastasis are the major causes of failure in TNBC therapy. The difficulties in treating TNBCs may be because of increased cancer cell plasticity that involves the fine-tuning of cellular redox homeostasis, mitochondrial bioenergetics, metabolic characteristics, and the development of cancer stem cells (CSCs)., Purpose: To investigate the effects and the underlying mechanisms of the phytosesquiterpene lactone deoxyelephantopin (DET) and its semi-synthesized derivative (DETD-35) in suppressing different phenotypic TNBC cell populations that contribute to tumor metastasis., Methods: A timelapse microfluidic-based system was established to analyze the effects of DETD-35 and DET on cell migration behavior in an oxygen gradient. Seahorse real-time cell metabolic analyzer and gas chromatography/quadrupole-time-of-flight mass spectrometry (GC/Q-TOF MS) were utilized to analyze the effects of the compounds on mitochondrial bioenergetics in TNBC cells. A miRNA knockout technique and miRNA sponges were employed to evaluate the miR-4284 involvement in the anti-TNBC cell effect of either compound., Results: DETD-35 and DET attenuated TNBC cell migration toward hypoxic regions under a 2-19 % oxygen gradient in a timelapse microfluidic-based system. DETD-35 and DET also suppressed CSC-like phenotypes, including the expression of Sox2, Oct4, and CD44 in TNBC cells under hypoxic conditions. DETD-35 and DET affected mitochondrial basal respiration, ATP production, proton leak, and primary metabolism, including glycolysis, the TCA cycle, and amino acid metabolism in the lung-metastatic TNBC cells. Furthermore, the expression of mitophagy markers PARKIN, BNIP3, PINK1, LC3-II, and apoptotic markers Bax, cleaved caspase 7, and cleaved PARP in hypoxic and lung-metastatic TNBC cells was also regulated by treatment with either compound. In miR-4284 knockout cells or miR-4284 inhibitor co-treated TNBC cells, DET- and DETD-35-induced over-expression of mitophagic and apoptotic markers was partially reversed, indicating miR-4284 involved with the compounds caused programmed cell death., Conclusion: This study demonstrated the novel activities of DETD-35 and DET in suppressing CSC-like phenotypes and metastatic TNBC cells through the de-regulation of mitochondrial bioenergetics., Competing Interests: Declaration of competing interest The authors declare no competing interests., (Copyright © 2024 Elsevier GmbH. All rights reserved.)

NRAS Q61 mutations are driver genetic alterations associated with common melanocytic nevi. Herein, we describe a case of NRAS-mutant melanocytic tumor with a blue nevus-like morphology. A 71-year-old Japanese man presented with a 4.6-mm nodule on his back. Histopathological examination revealed a dense distribution of spindle-shaped melanocytes in the upper dermis and a sparse distribution of dendritic melanocytes in the mid-dermis. The vertical periadnexal extension reached the deep dermis at the center of the tumor. A small junctional component, hyperpigmentation, sclerotic stroma, mild nuclear atypia, and a few mitotic figures were observed. Immunohistochemical examination revealed no PRAME expression and preserved p16 expression. Diffuse RASQ61R immunoreactivity was observed in these tumor cells. Nuclear β-catenin expression was not observed. Targeted RNA sequencing revealed two mutations, NRAS c.182A>G (Q61R) and FGFR2 c.-157A>G, but no other pathogenic alterations such as BRAF, GNAQ, GNA11, CTNNB1, PRKAR1A, or IDH1 mutations or kinase gene fusions. The histopathology fits that of compound-type blue nevus, which is called "Kamino nevus"; however, this tumor was genetically considered to be on the spectrum of conventional acquired melanocytic nevi but not on that of blue nevi. Morphologically, NRAS-driven melanocytic nevi resemble blue nevi without IDH1 R132C coexistence., (© 2024 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: Neoadjuvant chemotherapy followed by esophagectomy is the standard treatment for resectable advanced esophageal squamous cell carcinoma (ESCC) in Japan. Triplet chemotherapy is the standard neoadjuvant regimen. Inflammatory markers such as neutrophil-to-lymphocyte ratio (NLR) are well-known prognostic factors for esophageal cancer. However, their usefulness in patients with resectable advanced disease undergoing esophagectomy after neoadjuvant triplet chemotherapy is unknown., Method: We examined 144 ESCC patients who underwent neoadjuvant triplet chemotherapy followed by esophagectomy between January 2015 and December 2020 to investigate the relationship between inflammatory markers and recurrence-free survival (RFS). Optimal marker cutoff values for RFS were determined using receiver operating characteristic curve analysis. Patients were divided into high and low NLR groups (NLR cutoff, 3.0)., Results: NLR was high in 61 patients and low in 83. Univariate analyses demonstrated that low NLR was significantly associated with worse RFS (p = 0.049). Multivariate analyses demonstrated that high NLR was an independent predictor of RFS (odds ratio, 1.911; 95% confidence interval, 1.098-3.327; p = 0.022). RFS significantly differed between the low and high NLR groups. RFS did not significantly differ between the patients when stratified according to the other inflammatory markers., Conclusion: Preoperative NLR is an easily obtained and useful predictor of RFS in patients with resectable advanced ESCC treated with neoadjuvant triplet chemotherapy followed by esophagectomy., (© 2024. The Author(s), under exclusive licence to The Japanese Association for Thoracic Surgery.)

We successfully found that boroxazolidone can dissociate under aqueous conditions, which were applicable to a solution containing proteins. The immobilization of a newly synthesized diarylborinic acid on beads enabled the capture and release of target proteins of bioactive compounds through boroxazolidone formation and dissociation.

Background: Osteonecrosis of the femoral head (ONFH) primarily affects young individuals and is a leading cause of total hip arthroplasty in this population. Joint-preserving regenerative therapies involving core decompression (CD), enhanced with cells, growth factors, and bone substitutes, have been developed but lack extensive validation. Exosomes are emerging as a promising regenerative therapy. Human adipose stem cell (hADSC)-derived exosomes exhibit angiogenic and wound-healing effects on damaged and diseased tissues, suggesting their potential efficacy in treating early-stage ONFH. We aimed to investigate the efficacy of hADSC-derived exosomes based on CD in a medium-sized animal model (rabbit)., Methods: Exosomes were extracted using the ultrafiltration filter technique from the culture supernatants of two types of hADSCs. Characterization of exosomes was performed through nanoparticle tracking analysis, transmission electron microscopy, and the detection of specific biomarkers (CD9, CD63, and CD81) by western blotting. Eighteen rabbits underwent surgical vascular occlusion and intramuscular corticosteroid injections to induce ONFH. Concurrently, CD treatment with local administration of hADSC-derived exosomes (exosome group) or saline (control group) was performed. Femoral heads were harvested at 4, 8, and 12 weeks postoperatively and evaluated using micro-computed tomography and tissue staining to assess the protective effects on osteonecrosis, angiogenesis, and osteogenesis., Results: Exosomes had average particle concentrations of 1.8 × 10 12 or 1.8 × 10 9 particles/mL, with particle size distributions averaging 61.2 ± 14.7 or 123.1 ± 46.3 nm, and were confirmed by specific biomarkers. The exosome group exhibited a significant reduction in the severe progression of ONFH to stages 3 or 4 of the modified Ficat and Arlet classification, compared to the control group, which had four cases of stages 3 or 4. The exosome group showed significantly fewer empty lacunae in the subchondral bone area (p < 0.05) and significantly less articular cartilage injury (p < 0.05) compared to the corresponding in the control group. There were no significant differences in the microvessel number, bone trabecular structure, or volume of new bone in the medial region of the CD., Conclusions: hADSC-derived exosomes can prevent the progression of ONFH by inhibiting osteonecrosis and cartilage damage. The ultrafiltration filter technique is effective for exosome extraction, indicating that exosomes hold potential as a therapeutic agent for ONFH., Competing Interests: Declarations. Ethics approval and consent to participate: The experiments were approved by the Ethics Animal Research Committee at Graduate School of Medicine, Kyoto University, Japan. All procedures were conducted in accordance with the Guidelines for the Care and Use of Laboratory Animals. Consent for publication: None. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Background: It is unclear if shelf acetabuloplasty provides adequate bone coverage when conversion total hip arthroplasty (THA) is required in patients with developmental dysplasia of the hip (DDH). We aimed to investigate the short-term results of conversion THA after shelf acetabuloplasty., Methods: Forty-six patients requiring conversion THAs after a prior shelf acetabuloplasty were matched to THAs for osteoarthritis secondary to Crowe I DDH in a 1:1 ratio. Surgical factors, clinical scores, cup placement, and bone coverage of the cup were evaluated., Results: The preoperative Japanese Orthopaedic Association (JOA) score and flexion range of motion (ROM) were lesser in the shelf group (JOA: 49.2 ± 22.4 vs. 60.1 ± 14.5, p < 0.01, flexion ROM: 69 ± 22.4 vs. 82.1 ± 17.5, p < 0.01). There were no significant differences in JOA (88.7 ± 8.7 vs. 92.1 ± 8.0,p = 0.053) and flexion ROM (93.5 ± 17.3° vs. 99.5 ± 8.0, p = 0.08) after the index THA.All cups in both groups were placed at the anatomical hip centre. The cup centre edge angle (cup CE) was significantly lower in the shelf group (21.3°vs. 28.4, p = 0.0011), and ratio of cup coverage over the cup was lower in the shelf group (77.0% vs. 86.9%, p < 0.0001). There was no significant difference in the number of cases where acetabular bone grafting was performed (87.0% vs. 80.4%, p = 0.46). The operative time tended to be longer in the shelf group (117 ± 30.3 min vs. 106.6 ± 25.3 min, p = 0.06), and there was no significant difference in intraoperative blood loss (294.3 ± 33.8 vs. 313.3 ± 25.9, p = 0.50)., Conclusion: Conversion THA after prior shelf acetabuloplasty provided encouraging short-term results with no major complications. Prior shelf acetabuloplasty did not complicate subsequent THA. Bone coverage of the acetabular component was inadequate in total hip arthroplasty, even with prior shelf acetabuloplasty., Competing Interests: Declarations. Ethics approval and consent to participate: All procedures performed in studies involving human participants were in accordance with the ethical standards of the Kyoto University Graduate School and Faculty of Medicine, Ethic Committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. The study was approved by Kyoto University Graduate School and Faculty of Medicine, Ethic Committee. Consent for publication: Not Applicable. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

We assessed the association between a genome-wide polygenic risk score (PRS) developed for lung adenocarcinoma (LUAD) risk and mutation on the epidermal growth factor receptor (EGFR) gene in 998 East Asian never-smoking female LUAD cases (518 EGFR-positive; 480 EGFR-negative) and 4,544 never-smoking controls using case-case and multinomial regression analyses. We found that the PRS was more strongly associated with EGFR-positive LUAD compared to EGFR-negative LUAD, where the association between the fourth quartile of the PRS and EGFR-positive LUAD (OR=8.63, 95% CI:5.67, 13.14) was significantly higher than the association between the fourth quartile of the PRS with EGFR-negative LUAD (OR=3.50, 95% CI: 2.44, 5.00) (p-heterogeneity=3.66x10 -3 ). Our findings suggest that germline genetic susceptibility may be differentially associated with LUAD in never-smoking female East Asian patients depending on the cancer's mutation status, which may have important public health and clinical implications., (Copyright © 2024. Published by Elsevier Inc.)

Ureters can be visualized on a monitor via fluorescence observation technology and an near-infrared (NIR) fluorescent ureteral catheter (NIRFUC). Eureka, an artificial intelligence (AI) platform, can be used to analyze surgical videos and highlight nerves and loose connective tissue (LCT) in the dissection layer. In this study, we aimed to evaluate the feasibility of using simultaneous NIRFUC and AI assistance for anatomical recognition during laparoscopic surgery. The research target was video recordings of laparoscopic colorectal surgery in which the ureters were visualized using an NIRFUC (n = 56, November 2022 to May 2024). Eureka was used to analyze the nerves and LCTs in these videos. Three physicians reviewed and analyzed the videos, scoring the fluorescence visualization of the ureters and LCT by Eureka, the fluorescence visualization of the ureters and hypogastric nerve by Eureka, and the fluorescence visualization of the ureters and lumbar splanchnic nerves by Eureka, using a Likert scale. The scoring system was as follows: 0, very poor; 1, poor; 2, acceptable; 3, good; and 4, very good. The mean Likert scale score was 3.99 for the ureters and LCT, 3.11 for the ureters and hypogastric nerve, and 3.53 for the ureters and lumbar splanchnic nerves. The training data used for this AI model did not include NIR fluorescence image observations. Anatomical highlighting with AI and fluorescence visualization of the ureters were possible in the images analyzed by Eureka. These findings suggest that both AI and NIR can be used simultaneously for real-time navigation in the future., Competing Interests: Declarations. Ethics Approval: This study was approved by the Research Ethics Committee of the Kawaguchi Municipal Medical Center (Saitama, Japan) (Approval number: 2020-3, 2022-01(2023-11)). Consent to Participate: Written informed consent was obtained from all patients. Consent to Publication: The Author confirms that the work described has not been published previously. Competing Interests: Shunjin Ryu was funded by a cooperative research grant from Anaut Inc. Yuta Imaizumi, Keisuke Goto, M.D., Sotaro Iwauchi, M.D., Takehiro Kobayashi, M.D., Ryusuke Ito, M.D., Ph.D., and Yukio Nakabayashi, M.D., Ph.D., have no conflicts of interest or financial ties to disclose., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: A substantial portion of gastric cancer (GC) is linked to Epstein-Barr virus (EBV) infection. The characteristics of this viral genome, such as specific viral strains and large structural variations, influence the progression of diseases like nasopharyngeal carcinoma and hematological malignancy. However, the EBV genomes from GC have not been thoroughly characterized., Methods: Our study involved 849 consecutive GC patients diagnosed at Nagoya City University Hospital, Japan (NCU cohort). We detected EBV from formalin-fixed, paraffin-embedded sections using a novel direct PCR-based rapid detection method. Additionally, we analyzed 142 EBV whole genomes (125 newly sequenced) from GC, comparing them with 205 genomes from other EBV-associated diseases., Results: We identified 32 (3.8%) patients associated with EBVaGC in the NCU cohort. Moreover, the direct PCR identified several GC specimens containing EBV-infected lymphocytes or their follicles. The dominant viral strain in GC was type 1 EBV, prevalent in most parts of the world, and no GC-specific strain was identified. We found no significant associations between single-nucleotide variants in the viral genome and GC. Structural variations of the EBV genome were infrequent in GC (4 cases, 2.1%), contrasting with EBV-associated hematological malignancy, which frequently carries large deletions., Conclusions: This study is the first to uncover the genomic variations of EBV in GC. While EBV is definitively linked to GC, the characteristics of its genomes do not strongly correlate with disease development or progression. Our findings on viral genomes supplement the current understanding of human genomes in EBVaGC., Competing Interests: Declarations. Conflict of interest: Akira Satou received a research grant from Eisai Company. Other authors declare that they have no conflict of interest., (© 2024. Japanese Society of Gastroenterology.)

Aims: Sebaceous neoplasms constitute a group of adnexal tumours, including sebaceous adenoma, sebaceoma and sebaceous carcinoma. Although mismatch repair deficiency may be observed, the nature of the genetic alterations contributing to the development of most of these tumours is still unknown. In the present study, we describe the clinical, microscopic, and molecular features of eight sebaceomas with GRHL gene rearrangement., Methods and Results: Among these sebaceomas, four occurred in women and four in men; the median age was 63 years (range = 29-89). The tumours were located in the head and neck area in all cases. Microscopic examination revealed a well-demarcated lesion located in the dermis with focal extension into the subcutaneous tissue (three cases). The neoplasms displayed macronodular (eight cases), cribriform (seven cases) and organoid (six cases) growth patterns, occurring in combination. The tumours were mainly composed of immature basophilic cells associated with scattered mature sebocytes. Numerous small infundibular cysts were present in seven cases. Mitotic activity was low (none/one to four mitoses/mm 2 ). Immunohistochemistry showed positivity for androgen receptor and p63. Preserved expression of MLH1, PMS2, MSH2 and MSH6 was observed in all cases. RNA-sequencing revealed RCOR1::GRHL2 (three cases), BCL6::GRHL1 (two cases), a BCOR::GRHL2 (one case), RCOR1::GRHL1 (one case) and TLE1::GRHL1 (one case) fusion transcript. Methylation analysis demonstrated that GRHL-fused sebaceomas form an independent cluster and highlight the proximity of such tumours with poromas with folliculo-sebaceous differentiation., Conclusions: In conclusion, we report recurrent fusions of the GRHL genes in a distinctive subset of sebaceomas harbouring infundibulocystic differentiation, a frequent organoid growth pattern and lack of mismatch repair deficiency., (© 2024 The Author(s). Histopathology published by John Wiley & Sons Ltd.)

Background: Glioblastoma is an aggressive cancer that originates from abnormal cell growth in the brain and requires metabolic reprogramming to support tumor growth. Metabolic reprogramming involves the upregulation of various metabolic pathways. Although the activation of specific metabolic pathways in glioblastoma cell lines has been documented, the comprehensive profile of metabolic reprogramming and the role of each pathway in glioblastoma tissues in patients remain elusive., Methods: We analyzed 38 glioblastoma tissues. As a test set, we examined 20 tissues from Kyushu University Hospital, focusing on proteins related to several metabolic pathways, including glycolysis, the one-carbon cycle, glutaminolysis, and the mitochondrial tricarboxylic acid cycle. Subsequently, we analyzed an additional 18 glioblastoma tissues from Kagoshima University Hospital as a validation set. We also validated our findings using six cell lines, including U87, LN229, U373, T98G, and two patient-derived cells., Results: The levels of mitochondria-related proteins (COX1, COX2, and DRP1) were correlated with each other and with glutaminolysis-related proteins (GLDH and GLS1). Conversely, their expression was inversely correlated with that of glycolytic proteins. Notably, inhibiting the glutaminolysis pathway in cell lines with high GLDH and GLS1 expression proved effective in suppressing tumor growth., Conclusions: Our findings confirm that glioblastoma tissues can be categorized into glycolytic-dominant and mitochondrial-dominant types, as previously reported. The mitochondrial-dominant type is also glutaminolysis-dominant. Therefore, inhibiting the glutaminolysis pathway may be an effective treatment for mitochondrial-dominant glioblastoma., Competing Interests: Declarations Ethics approval and consent to participate The use of glioblastoma tissues for this study was approved by the Ethics Committee of the Graduate School of Medical Sciences, Kyushu University, and Kagoshima University. Written informed consent was obtained by all patients. Consent for publication Not applicable. Competing interests The authors declare no competing interests., (© 2024. The Author(s).)

Background: Atrial fibrillation (AF) is a prevalent multifactorial arrhythmia associated with specific single-nucleotide polymorphisms (SNPs). Pulmonary vein (PV) isolation is an established treatment for AF; however, recurrence risk remains caused by AF triggers beyond the PVs. Understanding the embryological origins of these triggers could improve treatment outcomes., Objectives: This study aimed to investigate the association between embryologically categorized AF triggers, clinical and genetic backgrounds, and postablation prognosis., Methods: In cohort 1, comprising 3,067 patients with AF undergoing PV isolation, the clinical characteristics and outcomes were analyzed. Among them, 815 patients underwent genetic analysis using AF-associated SNPs (cohort 2). Patients were delineated based on the developmental origin of the AF triggers: common PV, sinus venosus (SV), and primitive atrium (PA)., Results: SV-origin extra-PV AF triggers occurred in 20.3% (n = 622) of patients, whereas PA-origin triggers occurred in 11.9% (n = 365) of patients in cohort 1. Multivariate analysis of cohort 2 revealed that female sex, lower body mass index, absence of hypertension, rs2634073 near PITX2, and rs6584555 in NEURL1 were associated with SV-AF, whereas nonparoxysmal AF and rs2634073 near PITX2 were predictors of PA-AF. The PA group had a significantly higher arrhythmia recurrence rate after repeated procedures than the common PV (HR: 1.75; 95% CI: 1.34-2.29; P < 0.001) and SV-AF (HR: 1.31; 95% CI: 1.19-1.45; P < 0.001) groups with more de novo AF triggers. However, the incidence of adverse events did not differ significantly among the 3 groups., Conclusions: SV-derived AF triggers may have hereditary factors with a favorable postablation prognosis, whereas PA-derived triggers are linked to AF persistence and poor ablation response. Variants near PITX2 may play a pivotal role in extra-PV triggers., Competing Interests: Funding Support and Author Disclosures This research received financial support from the Tailor-made Medical Treatment Program (grant number 1K157), Grant-in-Aid (Grant No. 26293052) bestowed by the Ministry of Education, Culture, Sports, Science, and Technology (MEXT) of Japan, and the Practical Research Project for Life-Style Related Diseases Including Cardiovascular Diseases and Diabetes Mellitus, courtesy of the Japan Agency for Medical and Development (AMED) under Project Code 15656344. The authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2024 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Pulmonary pleomorphic carcinoma (PC) is a rare non-small-cell lung carcinoma (NSCLC) with a poor prognosis, characterized by tumor necrosis (TN). NETosis is a form of neutrophil-specific cell death, which is morphologically characterized by prominent neutrophil infiltration and cell detritus in the necrotic foci. Seventy-six patients with pulmonary PC who underwent complete resection were enrolled. Tumor necrosis was evaluated using digitally scanned resected specimens. The regions of NETosis were quantified using citrullinated histone H3 (citH3)- and myeloperoxidase-positive regions. We examined the association between the NETosis area and the prognostic outcomes and assessed the correlation between the NETosis area and systemic inflammation. Tumor necrosis was observed in 70 patients (92%). In all the cases, the TN region was accompanied by a citH3-positive region. The patients with high NETosis area (n = 54) had significantly shorter overall survival than those with low NETosis area (n = 16) (p = 0.013). Furthermore, a high NETosis area was an independent poor prognostic factor in the multivariate analyses. Systemic inflammatory markers, including C-reactive protein (CRP), CRP-to-albumin ratio, and neutrophil-to-lymphocyte ratio, were significantly higher in patients with high NETosis area than in those with low NETosis area. Furthermore, the levels of these inflammatory markers were significantly decreased postsurgery. This study shows that in surgically resected pulmonary PC, patients with high NETosis areas have higher systemic inflammation and worse prognosis., (© 2024 The Author(s). Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.)

Carotenoids are essential components of the photosynthetic apparatus and precursors of plant hormones, such as strigolactones (SLs). SLs are involved in various aspects of plant development and stress-response processes, including the establishment of root and shoot architecture. SL biosynthesis begins with the reversible isomerization of all- trans -carotene into 9- cis -β-carotene, catalysed by DWARF27 β-carotene isomerase (D27). Sequence comparisons have revealed the presence of D27-related proteins in photosynthetic eukaryotes and cyanobacteria lacking SLs. To gain insight into the evolution of SL biosynthesis, we characterized the activity of a cyanobacterial D27 protein ( Ca D27) from Cyanobacterim aponinum , using carotenoid-accumulating Escherichia coli cells and in vitro enzymatic assays. Our results demonstrate that Ca D27 is an all- trans / cis and cis / cis -β-carotene isomerase, with a cis / cis conversion preference. Ca D27 catalysed 13- cis /15- cis- , all- trans /9- cis -β-carotene, and neurosporene isomerization. Compared with plant enzymes, it exhibited a lower 9- cis -/all- trans -β-carotene conversion ratio. A comprehensive genome survey revealed the presence of D27 as a single-copy gene in the genomes of 20 out of 200 cyanobacteria species analysed. Phylogenetic and enzymatic analysis of Ca D27 indicated that cyanobacterial D27 genes form a single orthologous group, which is considered an ancestral type of those found in photosynthetic eukaryotes. This article is part of the theme issue 'The evolution of plant meta‌bolism'.

Progress toward single-molecule electronics relies on a thorough understanding of local physico-chemical processes and development of synthetic routines for controlled hetero-coupling. We demonstrate a structurally unexpected ring closure process for a homo-coupled 4,4'-bipicenyl, realized in on-surface synthesis. An initial covalent C-C coupling of 4-bromopicene locks at lower temperatures the position and geometrically shields part of 4,4'-bipicenyl. Employing this effect of shielding might offer a path toward controlled stepwise hetero-coupling. At higher temperatures, a thermally activated three-dimensional rotation upon hydrogen dissociation, a dehydrogenative roto-cyclization, lifts the surface-dimensionality restriction, and leads to the formation of a perylene. Thereby, the shielded molecular part becomes accessible again., (© 2024 Wiley-VCH GmbH.)

Nivolumab plus ipilimumab (NIVO+IPI) has a long-term response rate of 30% for patients with metastatic renal cell carcinoma (mRCC). However, 20% of patients develop primary resistant disease (PRD) to NIVO+IPI and show poor survival outcomes. In this study, we aimed to evaluate the effect of PRD as a second-line treatment in patients with mRCC. The data used in this multi-institutional, retrospective cohort were collected between August 2015 and January 2023. In total, 189 patients with mRCC were treated with NIVO+IPI and then with a vascular endothelial growth factor receptor-tyrosine kinase inhibitor. Associations between PRD and progression-free survival of second-line treatment (PFS), progression-free survival 2 (PFS2), and overall survival (OS) were analyzed. The median age at NIVO+IPI initiation was 67 years in the male-dominant population (n = 140, 74.1%), and most patients had clear cell histology (n = 140, 74.1%). PRD was recorded in 42 (22.2%) of 189 patients during NIVO+IPI therapy. Patients who experienced PRD showed poor PFS (hazard ratio [HR], 1.788; 95% confidence interval [CI], 1.176-2.718; p = 0.007), PFS2 (HR, 4.127; 95% CI, 2.649-6.431; p < 0.001), and OS (HR, 3.330; 95% CI, 2.040-5.437; p < 0.001). Before starting second-line therapy, patients with PRD tended to have a poor performance status compared with non-PRD patients and a higher IMDC risk. Second-line drug therapy was not associated with treatment outcomes in patients with PRD. PRD in patients with mRCC receiving NIVO+IPI as first-line treatment was associated with poor clinical course, even with second-line therapy., (© 2024 The Author(s). Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.)

Purpose: To evaluate the cerebellar cognitive affective syndrome scale (CCAS-S) in patients with acute cerebellar stroke (ACS) and examine its relationship with the discharge destination., Methods: Patients with first-time ACS admitted to our hospital between April 2021 and April 2023 were included. The CCAS-S, Mini-Mental State Examination (MMSE), and Scale for the Assessment and Rating of Ataxia (SARA) were evaluated 1 week after stroke onset, and Functional Independence Measure (FIM)/Barthel Index (BI) at discharge, duration of hospitalization, and discharge destination were evaluated. The Mann-Whitney U test was used to compare CCAS-S and variables., Results: Thirteen consecutive patients with ACS and age-matched comparison groups were included. The MMSE was within the normal range in all patients; however, patients with stroke had a lower total CCAS-S score (median 72, IQR 66-80) and a higher number of failed tests (median 4, IQR 3-5) than comparison. Significant deficits were observed in semantic fluency ( p  = 0.008), category switching ( p  = 0001), and similarity ( p  = 009). Definite CCAS were diagnosed 10 patients, respectively. Patients discharged home showed better SARA and FIM/BI but similar CCAS-S compared to those discharged to rehabilitation hospitals., Conclusion: In patients with ACS, it is the impairment of motor function, not CCAS, that affects discharge destination.

Generics and biosimilars play an important role in sustaining the universal healthcare insurance systems in Japan. The Pharmaceuticals and Medical Devices Agency (PMDA) reviews the quality, efficacy, and safety of generics and biosimilars for marketing authorization in Japan. Trend analyses of generics and biosimilars in terms of regulatory science have rarely been published. The PMDA and National Institute of Health Sciences websites were verified for generics and biosimilars, and information related to guidelines and notifications and the number of newly approved generics and biosimilars for fiscal year (FY) 2009-2023 were compiled. Approximately 1,900 and 200 generic drug products were approved in Japan in FY 2010 and 2023, respectively. The number of approved generic drug products has gradually decreased to one-tenth in the past 15 years. Overall, 35 biosimilars were approved in FY 2009-2023. The number of approved biosimilars has increased since FY 2017. This article reported a trend analysis of generics and biosimilars in terms of guidelines, notifications, and the number of applied and approved drug products in FY 2009-2023. Our primary goal is to increase patient access to affordable generics and biosimilars with assurance in appropriate quality., Competing Interests: Declarations Disclaimer The views expressed in this article are those of the authors and do not necessarily reflect the official views of the Pharmaceuticals and Medical Devices Agency. Ethics Approval and Consent to Participate Not Applicable. Consent for Publication All authors consent for publication. Conflict of Interest Ryosuke Kuribayash, Kanoko Goto, and Takumi Ogawa declare that they have no conflict of interest that might be relevant to the contents of this article., (© 2024. The Author(s), under exclusive licence to American Association of Pharmaceutical Scientists.)

Background: Some patients with postoperative hip fractures (HF) experience persistent severe pain. In this longitudinal study, we examined the characteristics of patients with persistent pain after HF surgery, and the factors influencing pain intensity., Methods: We conducted an 8-week prospective study in patients with postsurgical HF. Verbal rating scale (VRS), and multifaceted outcomes, including pressure pain threshold (PPT) (affected site and biceps), were evaluated at 2, 4, and 8 weeks postoperatively. Patients were divided into mild (VRS ≤1) and severe (VRS ≥2) groups according to pain intensity at 8 weeks postoperatively. Statistical analyses were performed using two-way ANOVA and decision-tree analysis., Results: VRS, PPT at the affected site and biceps, and physical activity (PA) time were significantly lower in the severe group than in the mild group 2 weeks postoperatively. VRS, PPT at the affected site, pain catastrophizing (PCS)-13, and the Tampa Scale for Kineshiophobia (TSK)-11 did not show significant improvements in the severe group. Decision tree analysis revealed that the VRS and PCS-13 at 4 weeks, PA time at 2 weeks, and TSK-11 change between 4 weeks and 2 weeks were factors influencing severe pain intensity at 8 weeks after HF surgery., Conclusion: Persistent severe pain after HF surgery was characterised by high peripheral and central sensitisation, pain catastrophizing, and reduced PA at 2 weeks after HF surgery. In addition, early pain intensity, pain catastrophizing, and PA may be hierarchically influential factors for persistent pain 8 weeks after HF surgery., Competing Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2024.)

Hypertension and tobacco smoking pose independent risks for cardiovascular diseases, but their association is unclear especially in Japanese. We investigated the impact of smoking status on the risk of new-onset hypertension in male and female Japanese workers. We evaluated 5439 subjects without hypertension who participated in medical check-ups in 2007-2018. The outcome was the development of hypertension (blood pressure ≥140/90 mmHg or initiation of antihypertensive drugs). Cox's proportional hazards models were used to assess the association between smoking status and the hypertension incidence. During the average 6.0-year follow-up, 1395 individuals (25.6%) developed hypertension. The crude incidence rates of hypertension (per 100 person-years) were: current non-smokers (n = 3033), 3.4; quitters (n = 445), 4.2; and sustained smokers (n = 1961), 5.7. The multivariable-adjusted hazard ratio was 1.34 (1.20-1.50) for sustained smokers and 1.03 (0.86-1.24) for quitters compared to current non-smokers (P for trend <0.01). In stratified analyses, the risk of incident hypertension was significantly higher in the sustained smokers with lower blood pressure or without diabetes at baseline versus the current non-smokers. A significant risk reduction of hypertension development due to smoking cessation was revealed in the subjects with higher blood pressure levels at baseline or without body weight gain after smoking cessation. Smoking was an independent risk factor for incident hypertension. Smoking cessation reduced the risk of hypertension development compared to sustained smoking, especially among the subjects with higher blood pressure levels. Maintaining one's body weight after smoking cessation would also help prevent hypertension development., (© 2024. The Author(s), under exclusive licence to The Japanese Society of Hypertension.)

Purpose: Very high-power short-duration (vHPSD) ablation creates shallower lesions, potentially reducing efficacy. This study aims to identify factors leading to insufficient lesions during pulmonary vein antral isolation (PVAI) with vHPSD-ablation and to develop an optimized PVAI strategy using this technology., Methods: PVAI was performed on 41 atrial fibrillation patients using vHPSD-ablation (90 W/4 s). Lesion parameters were recorded and analyzed to identify predictors of insufficient lesions. An optimized PVAI strategy, based on these predictors, was tested in subsequent 42 patients., Results: In total, 3099 RF-applications, including 103(3.3%) insufficient lesions, were analyzed. First-pass PVAI was achieved in 19/40(47.5%) right PVs and 24/41(58.5%) left PVs. Multivariate analysis identified significant predictors of insufficient lesions: local largest bipolar voltage (Bi-V), average contact force, baseline impedance, impedance drop, temperature rise, inter-lesion distance (ILD), and anatomical location (carina or not). An ILD:4-6 mm increased the risk of insufficient lesions 2.2-fold, and lesions at the carina increased it 3.6-fold for both ILD < 4 mm and ILD:4-6 mm. Local largest Bi-V was the strongest predictor for insufficient lesions. The optimized PVAI approach, utilizing vHPSD-ablation with an ILD < 4 mm in non-carinal areas with Bi-V < 4 mV, and high-power ablation-index guided ablation (HPAI, 50 W, ablation-index:450-550) in remaining areas, achieved first-pass PVAI in 92.7% of right PVs and 88.1% of left PVs, using vHPSD-ablation in approximately 65% of total RF-applications. The optimized PVAI achieved significantly higher first-pass PVI rate (p < .0001) with shorter ablation time (p = .04)., Conclusion: Appropriate use of vHPSD and HPAI, based on local largest Bi-V and anatomical information, may achieve high first-pass PVAI rates in shorter ablation time with minimal energy delivery., (© 2024 Wiley Periodicals LLC.)

Polygenic risk scores (PRSs) are promising for risk stratification but have mainly been developed in European populations. This study developed single- and multi-ancestry PRSs for lung adenocarcinoma (LUAD) in East Asian (EAS) never-smokers using genome-wide association study summary statistics from EAS (8,002 cases; 20,782 controls) and European (2,058 cases; 5,575 controls) populations. A multi-ancestry PRS, developed using CT-SLEB, was strongly associated with LUAD risk (odds ratio=1.71, 95% confidence interval (CI):1.61,1.82), with an area under the receiver operating curve value of 0.640 (95% CI:0.629,0.653). Individuals in the highest 20% of the PRS had nearly four times the risk compared to the lowest 20%. Individuals in the 95 th percentile of the PRS had an estimated 6.69% lifetime absolute risk. Notably, this group reached the average population 10-year LUAD risk at age 50 (0.42%) by age 41. Our study underscores the potential of multi-ancestry PRS approaches to enhance LUAD risk stratification in EAS never-smokers.

Competing Interests: Funding Support and Author Disclosures Drs Goto and Miyazaki and their departments were endowed by APEX, Boston Scientific Japan, Japan Lifeline, Medtronic Japan, and WIN International. Dr Miyazaki has received honoraria from Bristol-Meyers Squibb, Boston Scientific Japan, Daiichi Sankyo, Medtronic Japan, and Nippon Boehringer Ingelheim. Dr Sasano has received honoraria from Daiichi Sankyo. Dr Inoue has received honoraria from Bayer Yakuhin, Bristol-Meyers Squibb, Boston Scientific Japan, Daiichi Sankyo, Johnson and Johnson, Medtronic Japan, and Nippon Boehringer Ingelheim. Dr Yamane has received honoraria from BEG Company Ltd, Daiichi Sankto, and Medtronic Japan; and research grants from Nippon Boehringer Ingelheim, Dr Kusano has received honoraria from Biotronik Japan, Bayer Yahukin, Daiichi Sankyo, Medtronic Japan, Nippon Boehringer Ingelheim, and Pfizer Japan; and research grants from Biotronik Japan, HITACHI, JSR, Mebix, and Medtronic Japan. Dr Shimizu has received honoraria from Bristol-Meyers Squibb, Boston Scientific Japan, BY, Daiichi Sankyo. Johnson & Johnson, Medtronic Japan, Nippon Boehringer Ingelheim, Novartis Pharma, and Pfizer Japan; and research grants from Daiichi Sankyo, and Nippon Boehringer Ingelheim; and research grants from Daiichi Sankyo, and Nippon Boehringer Ingelheim.

Background: We aimed to examine the effectiveness of a nurse-led, screening-triggered early specialized palliative care intervention program for patients with advanced lung cancer., Methods: Patients with advanced lung cancer who underwent initial chemotherapy were randomized to intervention and usual care groups between January 2017 and September 2019. The intervention comprised comprehensive needs assessments, counseling, and service coordination by advanced-level nurses. Patients in the usual care group received the usual oncological care. The primary end point was a change in the trial outcome index (TOI) scores from baseline to 12 weeks. The secondary end-points were TOI scores at week 20, depression, anxiety, and survival., Results: In total, 102 patients were assigned to each group. Compared with the usual care group, no significant improvement in TOI scores was observed at 12 weeks in the intervention group (mean group difference: 2.13; 90% confidence interval: -0.70, 4.95; p = 0.107, one-sided), whereas significant improvement was observed at 20 weeks (3.58; 90% confidence interval: 0.15, 7.00; p = 0.043). There were no significant differences in the change from baseline depression and anxiety between the groups from baseline at week 12 and 20 weeks (depression: p = 0.60 and 0.10, anxiety: p = 0.78 and 0.067). Survival did not significantly differ between the groups (median survival time: 12.1 vs. 11.1 months; p = 0.302)., Conclusions: Nurse-led, screening-triggered, early specialized palliative care did not show significant superiority over usual care during the 12-week study period. However, it may have yielded delayed clinical benefits, such as improved quality of life and this feasible model can be acceptable in clinical practice., Trial Registration: The University Hospital Medical Information Network Clinical Trials Registry: UMIN000025491., (© 2024 The Author(s). Cancer Medicine published by John Wiley & Sons Ltd.)

Background/aim: In rectal cancer surgery, anastomotic leakage (AL) is the most important complication and has a reported frequency of 11-15%. The causes of AL leakage are complex, and AL prevention should be performed in multiple directions. Thus, this study examined the usefulness of the comprehensive and multifaceted AL preventive measures., Patients and Methods: In total, 164 rectal surgery patients who had low rectal staple anastomosis below the peritoneal reflection were enrolled. The patients were divided into two groups: (i) the multifaceted AL prevention group (MP group, n=34) and (ii) the insufficient AL prevention group (IP group, n=130). Multifaceted AL prevention was defined as intestinal blood flow evaluated via indocyanine green (ICG)-fluorescence imaging (FI), the use of a single-staple technique (SST) without intersecting stapling lines or "dog ears", the use of transanal suture reinforcement according to the air leakage test, and the use of a transanal tube for anatomical decompression and a diverting stoma for diverting the fecal stream. The AL rates were retrospectively compared between the two groups. The data are expressed as the median and interquartile range., Results: The rate of AL was significantly lower in the MP group (0%) than in the IP group (11.54%) (p=0.0423)., Conclusion: Multifaceted AL prevention, including ICG-FI and SST, achieved a zero incidence of AL. Multifaceted prevention significantly lessened AL more than inadequate prevention did. Therefore, if the weight of each preventive measure cannot be clearly identified, to avoid AL, it is important to take all preventive measures from multiple aspects., (Copyright © 2024, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Introduction: HER2 mutations are reported to occur in 2%-5% of all cases of non-small cell lung cancer (NSCLC). The clinical outcomes in patients with HER2-mutant NSCLC treated with immune checkpoint inhibitors (ICIs) plus platinum-based chemotherapy as 1st line treatment still remain unclear., Methods: Using the large-scale clinico-genomic database of LC-SCRUM-Asia, the clinico-genomic characteristics and therapeutic outcomes of patients with HER2-mutant NSCLC were investigated., Results: Of the 15,251 patients with NSCLC enrolled in the LC-SCRUM-Asia database, tumor HER2 mutations were detected in 402 patients (2.6 %). The most common subtype of HER2 mutations was exon 20 in-frame insertions (79 %), followed in frequency by mutations in the tyrosine kinase domain other than Exon20ins (10 %) and mutations in extracellular domains (7 %). NSCLCs harboring HER2 mutations showed a higher tumor mutation burden (TMB) as compared with NSCLCs harboring EGFR mutations or ALK fusions (median: 4.22 vs. 2.54 and 2.52 mutation per megabase, respectively). Of the 402 patients, 268 patients had received platinum-based chemotherapy with ICIs (Chemo-ICI, n = 95) or without ICI (Chemo-alone, n = 173) as 1st line treatment. The progression-free survival (PFS) was significantly longer in the Chemo-ICI group as compared with the Chemo-alone group (median 8.5 vs. 6.3 months; HR [95 %CI]: 0.66 [0.50-0.88]; P < 0.005). Multivariate analysis identified use of ICIs in addition to platinum-based chemotherapy as an independent favorable prognostic factor for PFS. There was no significant difference in the overall survival between the patients of the Chemo-ICI and Chemo-alone groups (median 31.1 vs. 23.3 months; HR [95 %CI]: 0.80 [0.57-1.12], P = 0.20)., Conclusions: Addition of ICIs to platinum-based chemotherapy in 1st line treatment may improve the PFS in patients with HER2-mutant NSCLC. The relatively high TMB might be involved in the prolongation of the PFS in patients with HER2-mutant NSCLC receiving platinum-based chemotherapy with ICIs., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Hibiki Udagawa reports grants from Takeda Pharmaceutical Co., Ltd., Nippon Boehringer Ingelheim Co., Ltd., Amgen K.K., Taiho Pharmaceutical Co., Ltd. And MSD K.K. and honoraria for lectures from DAIICHI SANKYO COMPANY, LIMITED, CHUGAI PHARMACEUTICAL CO., LTD., Novartis Pharma K.K., Taiho Pharmaceutical Co. Ltd., Taiho Pharmaceutical Co. Ltd., and MSD K.K. outside the current study. Shingo Matsumoto reports grants from Merck, Chugai Pharmaceutical, MSD and Janssen Pharmaceutical and honoraria for lectures from Eli Lilly outside the current study. Hiroki Izumi reports grants from Amgen, Eisai, Takeda Pharmaceutical Co, Bristol-Myers Squibb Japan, Chugai, AstraZeneca, Ono Pharmaceutical Co, MSD and Merck outside the current study. Yuichiro Ohe reports grants from AstraZeneca, Chugai, Eli Lilly, Kirin, Sumitomo, Pfizer, Taiho, Novartis, Takeda, Daiichi-Sankyo and Janssen and honoraria for lectures from AstraZeneca, Chugai, Chugai, ONO, BMS, Boehringer Ingelheim, Bayer, Pfizer, MSD, Taiho, Nippon Kayaku, Kyowa Hakko Kirin, Eisai and Daiichi-Sankyo and payment for expert testimony from AstraZeneca, Chugai, ONO, BMS, Kyorin, Celltrion, Amgen, Nippon Kayaku, Boehringer Ingelheim, AnHeart Therapeutics Inc., PharmaMar outside the current study. Terufumi Kato reports grants from Abbvie, Amgen, Arrivent, AstraZeneca, Bayer, BeiGene, BluePrint, Bristol-Meyers Squibb, Chugai, Daiichi-Sankyo, Eli Lilly, Gilead, GlaxoSmithKline, Haihe, Janssen, Merck KGaA, MSD, Novartis, Pfizer, Regeneron and Takeda and honoraria for lectures from Amgen, AstraZeneca, BeiGene, Boehringer Ingelheim, Bristol-Meyers Squibb, Chugai, Daiichi-Sankyo, Eli Lilly, GlaxoSmithKline, Janssen, Merck KGaA, MSD, Novartis, Ono, Pfizer, Taiho, and Takeda and other from AstraZeneca, BeiGene, Chugai, Daiichi-Sankyo, Janssen, Merck KGaA, MSD, Novartis, Pfizer outside the current study. His spouse is an employer of Eli Lilly. Kazumi Nishino reports grants from ONO PHARMACEUTICAL CO., LTD., TAIHO PHARMACEUTICAL CO., LTD., MSD, AbbVie, DAIICHI SANKYO COMPANY, LIMITED, Amgen, Eisai Co., Ltd., Sanofi K.K., Janssen Pharmaceutical K.K., Novartis Pharmaceuticals, Pfizer, Eli Lilly Japan, Merck Biopharma Co., Ltd., Takeda Pharmaceutical Co.,Ltd., AstraZeneca, Merus NV, Gilead Sciences, CHUGAI PHARMACEUTICAL CO., LTD, Bayer Yakuhin, Ltd and AMGEN and honoraria for lectures from AstraZeneca, Nippon Boehringer Ingelheim, Eli Lilly Japan, MSD, Novartis Pharmaceuticals, Pfizer, Merck Biopharma Co., Ltd., Janssen Pharmaceutical K.K., Bristol Myers Squibb, Nippon Kayaku, ONO PHARMACEUTICAL CO., LTD., Takeda Pharmaceutical Co.,Ltd., CHUGAI PHARMACEUTICAL CO., LTD, AMGEN, DAIICHI SANKYO COMPANY, LIMITED, Nippon Boehringer Ingelheim Co., Ltd. outside the current study. Yuki Sato reports honoraria for lectures from AstraZeneca, MSD, Novartis, Chugai Pharmaceutical, Ono Pharmaceutical, Pfizer, Taiho Pharmaceutical, Nippon Kayaku, Bristol Myers Squibb, Eli Lilly, Takeda, Kyowa Kirin, Daiichi Sankyo and Boehringer Ingelheim outside the current study. Ryo Toyozawa reports grants from Abbvie, Amgen, AnHeart Therapeutics, Daiichi Sankyo, Eli Lilly Japan, MSD, Novartis Pharma, Pfizer Japan and Takeda Pharmaceutical and honoraria for lectures from AstraZeneca, Bristol-Myers Squibb, Chugai Pharmaceutical, Eli Lilly Japan, MSD, Nippon Kayaku, Ono Pharmaceutical, Pfizer Japan, Taiho Pharmaceutical, Takeda Pharmaceutical and Thermo Fisher Scientific outside the current study. Koichi Azuma reports honoraria for lectures from AstraZeneca K.K., Ono Pharmaceutical, Chugai Pharmaceutical, MSD, Bristol-Myers Squibb and Takeda Pharmaceutical outside the current study. Tetsuya Sakai reports grants from Amgen, GlaxoSmithKline K.K, Daiichi Sankyo and NEC and honoraria for lectures from AstraZeneca, Novartis, Thermo Fisher Scientific, Takeda, OLYMPUS, Taiho, Chugai, MSD, Merck, Daiichi Sankyo, RIKEN GENESIS and Amco outside the current study. Yuji Shibata reports grants from MSD, Blueprint Medicines Corporation and Novartis and honoraria for lectures from Pfizer, Bristol-Myers Squibb, AstraZeneca, Ono Pharmaceutical Co., Ltd., Chugai, Takeda, Merck and Eli Lilly Japan outside the current study. Kaname Nosaki reports grants from Takeda, AstraZeneca, MSD K.K, Abbvie, Chugai Pharma, Daiichi Sankyo/UCB Japan and AnHeart Therapeutics and honoraria for lectures from AstraZeneca, Chugai Pharma, Lilly, MSD, Pfizer, Taiho Pharmaceutical, Janssen, Ono Pharmaceutical, Takeda, Novartis and Merck outside the current study. Yoshitaka Zenke reports grants from AstraZeneca, Daiichi-Sankyo, Amgen, GSK, Roche, MSD and Merck and honoraria for lectures from AstraZenca, Lilly, Chugai, Ono, Bristol-Meyers Squibb, Takeda, Boheringer-Ingelheim, Taiho, MSD, Novartis, Pfizer, Nihon Kayaku, Kyowa Kirin and Amgen outside the current study. Shigeki Umemura reports grants from Taiho pharmaceutical, Lilly and MSD and honoraria for lectures from MSD, Chugai Pharmaceutical, Takeda, AstraZeneca and Daiichi sankyo outside the current study. Kiyotaka Yoh reports grants from Abbvie, Amgen, ArriVent Biopharma, AstraZeneca, Boehringer Ingelheim, Chugai Pharma, Daiichi sankyo, Lilly, MSD, Taiho and Takeda and consulting fees from Boehringer Ingelheim and Abbvie and honoraria for lectures from Amgen, AstraZeneca, Bristol-Myers Squibb, Chugai Pharma, Daiichi sankyo, Kyowa kirin, Lilly, MSD, Ono Pharmaceutical and Takeda outside the current study. Masahiro Seike reports grants from Chugai Pharmaceutical, Eli Lilly, Kyowa Hakko Kirin, Taiho Pharmaceutical and Nippon Kayaku and honoraria for lectures from AstraZeneca, Chugai Pharmaceutical, Eli Lilly, Bristol-Myers Squibb, Pfizer, Nippon Kayaku, Daiichi-Sankyo, Merck Biopharma, MSD K.K, Taiho Pharmaceutical, Ono Pharmaceutical, Nippon Boehringer Ingelheim, Takeda Pharmaceutical, Kyowa Hakko Kirin, Novartis and Amgen inc outside the current study. Koichi Goto reports grants from Amgen K.K., Astellas Pharma Inc., AstraZeneca K.K., Nippon Boehringer Ingelheim Co., Ltd., Bristol-Myers Squibb K.K., CHUGAI PHARMACEUTICAL CO., LTD., DAIICHI SANKYO COMPANY, LIMITED, Eisai Co., Ltd., Janssen Pharmaceutical K.K., Kyowa Kirin Co., Ltd., Merck Biopharma Co., Ltd., MEDICAL& BIOLOGICAL LABORATORIES CO., LTD., MSD K.K., Novartis Pharma K.K., ONO PHARMACEUTICAL CO., LTD., Pfizer R&D Japan G.K., Sumitomo Pharma Co., Ltd., Taiho Pharmaceutical Co., Ltd., Eli Lilly Japan K.K., Bayer Yakuhin, Ltd., Merus N.V. and Takeda Pharmaceutical Co., Ltd. for the present manuscript. Koichi Goto also reports grants from Amgen Inc., AbbVie GK, AnHeart Therapeutics Inc., Blueprint Medicines Corporation., Craif Inc., Guardant Health Asia, Middle East & Africa, Inc, Haihe Biopharma Co., Ltd., Ignyta,Inc., Life Technologies Japan Ltd., Loxo Oncology, Inc., Lunit Inc., Precision Medicine Asia Co., Ltd., RIKEN GENESIS CO., LTD., Spectrum Pharmaceuticals, Inc., Sysmex Corporation., Turning Point Therapeutics,Inc. and honoraria for lectures from Amgen K.K., Amoy Diagnosties Co.,Ltd., AstraZeneca K.K., Bayer U.S., Bristol-Myers Squibb K.K., CHUGAI PHARMACEUTICAL CO., LTD., DAIICHI SANKYO COMPANY, LIMITED, Eisai Co., Ltd., Eli Lilly Japan K.K., Guardant Health Japan Corp., iTeos Therapeutics Inc., Janssen Pharmaceutical K.K., Thermo Fisher Scientific K.K., Merck Biopharma Co., Ltd., Nippon Kayaku Co.,Ltd., Novartis Pharma K.K., ONO PHARMACEUTICAL CO., LTD., Pharma Mar, S.A., RIKEN GENESIS CO., LTD., Taiho Pharmaceutical Co., Ltd. And Takeda Pharmaceutical Co., Ltd. And other from Amgen Inc., Amgen K.K., AstraZeneca K.K., Bayer HealthCare Pharmaceuticals Inc., Bristol-Myers Squibb K.K., DAIICHI SANKYO COMPANY, LIMITED, Eli Lilly Japan K.K., GlaxoSmithKline K.K., Haihe Biopharma Co., Ltd., Janssen Pharmaceutical K.K. and SYNEOS HEALTH CLINICAL K.K. Other authors report no potential conflict of interest to disclose.., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Clinicopathological differences exist between ulcerative colitis-associated colorectal cancer (UC-CRC) and sporadic colorectal cancer (S-CRC). However, differences in the prognosis remain controversial, and the reason for these differences remains unclear. We therefore assessed the differences between patients with UC-CRC and S-CRC., Patients and Methods: This was a matched-pair analysis of the clinicopathological characteristics and prognosis of patients with UC-CRC and S-CRC who underwent colorectal resection between January 2000 and December 2021 at two institutions. Patients were matched according to age, sex, date of surgery, tumor location, and Union for International Cancer Control (UICC) stage., Results: A total of 5992 patients underwent surgery for CRC at the two institutions, and 288 patients (48 with UC-CRC and 240 with S-CRC) were matched in this study. Patients with UC-CRC underwent more invasive surgery and had a longer operative time than those with S-CRC, but there was no marked difference in postoperative complications or perioperative mortality. Long-term outcomes showed a similar 5-year overall survival (OS) for UC-CRC and S-CRC (86.5% versus 88.8%, p = 0.742); however, in stage 3 patients, patients with UC-CRC had a poorer 5-year OS than those with S-CRC (51.4% versus 83.8%, p = 0.032). The first recurrence sites in stage 3 UC-CRC were peritoneal dissemination followed by the bones, while those in S-CRC were the liver and pulmonary system., Conclusions: Despite no significant differences in surgical outcomes, patients with UC-CRC had a poorer prognosis than those with S-CRC at stage 3. The recurrence patterns in UC-CRC differed from those in S-CRC, suggesting a possible prognostic difference., (© 2024. Society of Surgical Oncology.)

Among skin epithelial tumors, recurrent mutations in the APC/CTNNB1 genes resulting in activation of the Wnt/β-catenin pathway have been reported predominantly in neoplasms with matrical differentiation. In the present study, we describe the morphologic, immunohistochemical, and genetic features of 16 primary cutaneous carcinomas harboring mutations activating the Wnt/β-catenin pathway without evidence of matrical differentiation, as well as 4 combined tumors in which a similar Wnt/β-catenin-activated carcinoma component was associated with Merkel cell carcinoma (MCC) or pilomatrical carcinoma. Among the pure tumor cases, 6 of 16 patients were women with a median age of 80 years (range, 58-98 years). Tumors were located on the head and neck (n = 7, 44%), upper limb (n = 4, 25%), trunk (n = 3, 18%), and leg (n = 2, 13%). Metastatic spread was observed in 4 cases resulting in death from disease in 1 patient. Microscopically, all cases were poorly differentiated neoplasms infiltrating the dermis and/or subcutaneous tissue. In 13 cases, solid "squamoid" areas were associated with a basophilic component characterized by rosette/pseudoglandular formation resulting in a biphasic appearance. Three specimens consisted only of poorly differentiated carcinoma lacking rosette formation. Immunohistochemical studies showed frequent expression of EMA (100%), BerEP4 (100%), cytokeratin 7 (94%), chromogranin A (44%), synaptophysin (82%), and cytokeratin 20 (69%). Complete loss of Rb expression was observed in all but 1 case. Nuclear β-catenin and CDX2 expressions were detected in all cases. Recurrent pathogenic somatic mutations were observed in APC (60%), CTNNB1 (40%), and RB1 (n = 47%). Global methylation analysis confirmed that cases with rosette formation constituted a homogeneous tumor group distinct from established skin tumor entities (pilomatrical carcinoma, MCC, and squamous cell carcinoma), although the 3 other cases lacking such morphologic features did not. In addition, we identified 4 combined neoplasms in which there was a component showing a similar poorly differentiated rosette-forming carcinoma demonstrating Rb loss and β-catenin activation associated with either MCC (n = 3) or pilomatrical carcinoma (n = 1). In conclusion, we describe a distinctive neoplasm, for which we propose the term "Wnt/β-catenin-activated rosette-forming carcinoma," morphologically characterized by the association of rosette formation, squamous and/or neuroendocrine differentiation, diffuse CDX2 expression, Rb loss, and mutations in CTNNB1/APC genes., (Copyright © 2024 United States & Canadian Academy of Pathology. Published by Elsevier Inc. All rights reserved.)

Introduction: The novel cryoballoon with 28 mm or 31 mm adjustable diameters, aims to achieve a wide antral pulmonary vein isolation (PVI). However, the distribution of antral lesions and their variations based on left atrial (LA) remodeling require further clarification., Methods: We evaluated 22 patients (67 [59.5-74.8] years, 19 males) who underwent PVI of atrial fibrillation (AF) (13 paroxysmal AF [PAF] and 9 non-PAF) using size-adjustable cryoballoons. LA electro-anatomical mapping was performed post-PVI with three-dimensional mapping systems. We assessed the shapes of the LA and pulmonary veins (PVs) and the distribution of isolated areas (IAs), comparing the results between PAF and non-PAF patients., Results: In the left PVs (LPVs), the distance between the PV orifice and IA edge (PVos-IA) was larger on the roof and posterior segments (~15 mm) but relatively smaller on the anterior segment near the PV ridge (<10 mm). For the right PVs (RPVs), it was more extensive in the posterior segment (10-15 mm). Comparing PAF and non-PAF, there were no significant differences in the PVos-IA except for the right posterior-carina segment, antrum IA (LPVs: 5.9 ± 1.6 vs. 5.8 ± 0.8 cm², p = .81; RPVs: 4.8 ± 2.3 vs. 4.8 ± 1.2 cm², p = .81), distances between the right and left IAs on the LA posterior wall (LAPW), and un-isolated LAPW area (9.0 ± 4.9 vs. 9.9 ± 2.5 cm², p = .62). No individual PVIs were observed in either group. Two patients exhibited overlapping IAs on the roof, and one patient who underwent 31 mm balloon applications for all PVs exhibited an LAPW isolation., Conclusion: The size-adjustable cryoballoon achieved a wide antral PVI even in non-PAF patients., (© 2024 Wiley Periodicals LLC.)

There is no study that has investigated the impact of exercise in a combined hypoxic and hot environment on endothelial function. Therefore, we tested whether aerobic exercise in a combined hypoxic and hot conditions induces further enhancement of endothelial function. Twelve healthy males cycled at a constant workload (50% of their maximal oxygen uptake under normoxic/thermoneutral conditions) for 30 min in four different environments: exercise under normoxic condition (NOR: fraction of inspiratory oxygen or FiO 2  = 20.9%, 20°C), exercise under hypoxic condition (HYP: FiO 2  = 14.5%, 20°C), exercise under hot condition (HOT: FiO 2  = 20.9%, 30°C), and exercise under combined hypoxia and hot conditions (HH: FiO 2  = 14.5%, 30°C). Before, during, and after exercise, cardiovascular variables (e.g., heart rate, blood flow, and shear rate), blood variables, and endothelial function evaluated by flow-mediated dilation (FMD) were assessed. Heart rates were significantly higher throughout the HH trial's experimental period than the other trials (p < 0.05). However, in the HH trial, brachial artery blood flow and shear rate did not differ from those in other trials after exercise. Plasma catecholamines (epinephrine, norepinephrine, and dopamine) elevations in response to exercise were significantly higher in the HH trial than in the other three trials (p < 0.05). No considerable differences were observed in FMD responses among trials before and after the exercise. In conclusion, aerobic exercise in a combined hot and hypoxic environment further activated sympathetic nervous activity but did not considerably enhance blood flow, shear rate, or endothelial function., (© 2024 The Author(s). Clinical Physiology and Functional Imaging published by John Wiley & Sons Ltd on behalf of Scandinavian Society of Clinical Physiology and Nuclear Medicine.)

The phenotypes of RP1-related inherited retinal dystrophies (RP1-IRD), causing autosomal dominant (AD) and autosomal recessive (AR) diseases, vary depending on specific RP1 variants. A common nonsense mutation near the C-terminus, c.5797 C > T (p.Arg1933*), is associated with RP1-IRD, but the exact role of this mutation in genotype-phenotype correlation remains unclear. In this study, we retrospectively analyzed patients with RP1-IRD (N = 42) from a single center in Japan. AR RP1-IRD patients with the c.5797 C > T mutation (N = 14) mostly displayed macular dystrophy but rarely retinitis pigmentosa or cone-rod dystrophy. Conversely, AR RP1-IRD patients without the c.5797 C > T mutation, including those with other pathogenic RP1 variants, were mostly diagnosed with severe retinitis pigmentosa. Full-field electroretinograms were significantly better in patients homozygous or compound heterozygous for the c.5797 C > T mutation than in those without this mutation, corresponding to their milder phenotypes. Clinical tests also revealed a slower onset of age and a better mean deviation value with the static visual field in AR RP1-IRD patients with the c.5797 C > T mutation compared to those without. Therefore, the presence of c.5797 C > T may partly account for the phenotypic variety of RP1-IRD and may yield milder phenotypes. These findings may be useful for predicting the prognosis of RP1-IRD patients., (© 2024. The Author(s).)

The present study examined the effects of gastric emptying rate and intestinal cell damage following a single session of endurance exercise under "hypoxic" or "normoxic" conditions at the same relative intensity. Eleven healthy males performed two trials on different days, consisting of a 60 min run on a treadmill at 70% maximal running velocity (vMax) while inspiring hypoxic (F i O 2 : 14.5%; HYP) or normoxic air (F i O 2 : 20.9%; NOR). The average running velocity was 11.4  ±  0.7 km/h in NOR and 10.8  ±  0.5 km/h in HYP, respectively. Venous blood samples were collected to evaluate plasma intestinal fatty acid binding protein (I-FABP) as an indicator of exercise-induced intestinal cell damage. The gastric emptying rate was determined by the 13 C-sodium acetate breath test. Running velocities at 70% vMax and arterial oxygen saturation were significantly lower under HYP than NOR (p < 0.001). Peak heart rate and rating of perceived exertion during exercise did not differ significantly between the trials. Maximum 13 C excretion time (an indication of the gastric emptying rate) was significantly delayed in the HYP (NOR: 38.5  ±  5.0 min, HYP: 45.5  ±  9.6 min; p = 0.010). Furthermore, the score of nausea increased slightly, but increased significantly after exercise only in the HYP (p = 0.04). However, exercise-induced changes in plasma I-FABP, adrenaline, and noradrenaline concentrations did not differ significantly between the two trials. These results suggest that endurance exercise under hypoxic conditions impairs digestive function in the stomach compared to exercise under normoxic conditions performed at the same relative intensity., (© 2024. The Author(s).)

Introduction: Despite the availability of several epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs), most patients with non-small-cell lung cancer (NSCLC) eventually develop resistance to these agents. Notably, EGFR &#95;C797S mutations confer resistance to the third-generation EGFR-TKI osimertinib and no approved post-osimertinib targeted pharmacology options are currently available. BLU-945 is a novel, reversible, and orally available next-generation EGFR-TKI that selectively targets EGFR-activating ( EGFR m) and resistance mutations (including EGFR&#95;C797S) with nanomolar potency while sparing wild-type EGFR in vitro., Methods: In vitro activity of BLU-945 as a single agent and in combination with osimertinib was tested in engineered EGFR -mutant cell lines as well as patient-derived cells and patient-derived organoids. In vivo activity was evaluated in osimertinib-resistant patient-derived xenograft mouse models. Three patient cases from the global, first-in-human, phase I/II SYMPHONY trial (NCT04862780) demonstrating the clinical efficacy of BLU-945 were reported., Results: In vitro BLU-945 demonstrated inhibited cell viability and growth of EGFR -mutant/osimertinib-resistant cell lines. BLU-945 demonstrated in vivo tumor shrinkage in osimertinib-resistant models of NSCLC (osimertinib second line: EGFR &#95;L858R/C797S and third line: EGFR &#95;ex19del/T790M/C797S and L858R/T790M/C797S) both as monotherapy and in combination with osimertinib. BLU-945 also demonstrated tumor shrinkage in patients from the SYMPHONY trial., Conclusion: Our findings demonstrate the preclinical and early clinical activity of BLU-945 in EGFR m NSCLC progressing on previous EGFR-TKIs., Competing Interests: S.M.L. reports grants from AstraZeneca, BeiGene, Bristol Myers Squibb, Boehringer-Ingelheim, Bridge BioTherapeutics, Daichii-Sankyo, Eli Lily, Gilead, GlaxoSmithkline, Jiangsu Hengrui Medicine, J Ints Bio, Oscotec, Roche, Takeda, and Yuhan. S.S.S. is a shareholder of Blueprint Medicines Corporation. C.C. is an employee of and a shareholder of Blueprint Medicines Corporation. Y.A.M. is an employee of and a shareholder of Blueprint Medicines Corporation. R.W. is a shareholder of Blueprint Medicines Corporation. Z.Z. is a shareholder of Blueprint Medicines Corporation. L.E.T.-M. reports work was conducted as an employee of Blueprint Medicines Corporation and is currently a shareholder of Blueprint Medicines Corporation. F.S. is a shareholder of Blueprint Medicines Corporation. F.A. is an employee of and a shareholder of Blueprint Medicines Corporation. T.A.D. is an employee of and a shareholder of Blueprint Medicines Corporation. J.H. is an employee of Blueprint Medicines Corporation and a shareholder of Blueprint Medicines Corporation. A.Z. is a shareholder of Blueprint Medicines Corporation. J.R. reports consulting fees or honoraria from Amgen, AstraZeneca, BioAtla, G1 Therapeutics, Genentech, Guardant Health, Jazz, Janssen, Sanofi-Genzyme, Summit, and Takeda Pharmaceuticals, and has also been contracted for research (institutional) with AstraZeneca, BioAtla, Blueprint Medicines, Enliven, EpimAb Biotherapeutics, LOXO Oncology, ORIC, and Redcloud. D.H.L. reports personal fees from AbbVie, AstraZeneca, BC World Pharm, Boehringer-Ingelheim, Bristol-Myers Squibb, ChongKeunDang, Eli Lilly, Janssen, Merck Sharp & Dohme, Novartis, Ono, Pfizer, Roche, ST Cube, Takeda Oncology, and Yuhan, and non-financial support from Blueprint Medicines Corporation and Takeda Oncology outside the submitted work. B.C.C. reports grants from AbbVie, AstraZeneca, Bayer, Blueprint Medicines Corporation, Champions Oncology, Dizal Pharma, Dong-A ST, Eli Lilly, GI Innovation, Janssen, MedPacto, Merck Sharp & Dohme, MOGAM Institute, Novartis, Ono, Yuhan, and consultancy fees from AstraZeneca, Blueprint Medicines Corporation, Bristol Myers Squibb, Boehringer-Ingelheim, Eli Lilly, Janssen, MedPacto, Merck Sharp & Dohme, Novartis, Ono, Pfizer, Roche, Takeda, and Yuhan and currently owns stock in BridgeBio Therapeutics, Gencurix Inc, KANAPH Therapeutic Inc, TheraCanVac Inc., has served on a scientific advisory board for KANAPH Therapeutic Inc, receives royalties for Champions Oncology and is the founder of Daan Biotherapeutics., (© The Author(s), 2024.)

Background: Very high power and short duration (vHPSD) ablation is recently used for pulmonary vein isolation. However, low first-pass isolation rates have been reported, possibly because of shallow lesion formation, necessitating deeper lesions to improve treatment outcomes., Objective: This study aimed to confirm the safety and efficacy of double radiofrequency applications of vHPSD ablation in an in vivo beating swine heart model., Methods: Eighteen swine were anesthetized and underwent vHPSD ablation using the QDOT-MICRO catheter at 90 W for 4 seconds, targeting a contact force of 10 g. Radiofrequency applications were performed as single application (SA) and double applications (DA) with 4-8 seconds rest intervals. Lesion surface area and volume were measured postablation., Results: A total of 337 atrial lesions and 74 ventricular lesions were created. Both 4-6 seconds DA and 7-8 seconds DA produced significantly larger and deeper lesions than did SA, with atrial surface lengths averaging 9.0 mm for 4-6 seconds DA, 9.2 mm for 7-8 seconds DA, and 8.0 mm for SA. Transmurality was observed at 100% for 4-6 seconds and 7-8 seconds DAs, while it was 94% for SA (P = .002). Ventricular lesion metrics followed similar trends. Except for 1 event of tiny char formation during 4 seconds DA in the ventricle, neither steam pops nor char formation was observed in either the atrium or the ventricle., Conclusion: In an in vivo swine heart model, DA with 4-6 seconds and 7-8 seconds intervals create deeper and wider lesions than does SA, suggesting its potential for clinical application in areas with thicker myocardial walls. However, DA with very short intervals may still pose a risk of excessive tissue heating., Competing Interests: Disclosures Drs Goto, Takigawa, and Miyazaki received endowments from Medtronic Japan, Boston Scientific, Japan Lifeline, and Win International. No other authors have conflict of interest to declare., (Copyright © 2024 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)

Background: We conduct a retrospective analysis of patients with pathological fractures resulting from upper extremity malignancies, focusing on the evaluation of treatment strategies employed., Materials and Methods: We retrospectively studied 10 patients with metastatic bone tumors of the upper extremities. The study variables included tumor site, primary pathology, duration from the first diagnosis of the primary lesion to the occurrence of the pathological fracture, use of bone-modifying drugs, surgical technique, adjuvant therapy, postoperative functional assessment, Katagiri's score, American Society of Anesthesiologists physical status (ASA-PS), outcome, and correlations between the Eastern Cooperative Oncology Group Performance Status (ECOG-PS) and Musculoskeletal Tumor Society (MSTS) score., Results: The sites involved were the humerus and radius in eight and two patients, respectively. Primary pathologies were liver cancer in three patients, lung cancer and renal cancer in two patients each, and one patient each with multiple myeloma, plasmacytoma, and Hodgkin's lymphoma. Nine patients experienced pathological fractures, and one had an impending fracture. The median time from primary tumor diagnosis to fracture was 12.5 months. Bone-modifying drugs were administered in all cases. Surgical procedures included intramedullary nails in seven patients and plate fixation in two. Chemotherapy served as adjuvant therapy in nine cases. The mean MSTS score was 26.5, and Katagiri's score averaged 6. The median ASA-PS stood at 2. Outcomes showed seven patients alive with disease and three dead from disease. A significant association between the ECOG-PS and MSTS score was not observed., Conclusion: Pathological fractures caused by malignant bone tumors of the upper extremity should be treated proactively with surgery regardless of prognosis., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. Animal subjects: All authors have confirmed that this study did not involve animal subjects or tissue. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Hashimoto et al.)

Introduction: SCLC has been treated as a single entity resulting in limited survival improvement. Developing effective tools for guiding appropriate therapeutic strategies is crucial., Methods: A total of 1035 SCLCs were prospectively analyzed by a genomic screening platform: LC-SCRUM-Asia. Fresh frozen tumor samples were subjected to a next-generation sequencing system enabling the integrative analysis of cancer-related genes. A phase 2 trial of gedatolisib for SCLC with PI3K/AKT/mTOR pathway mutations was conducted based on this screening., Results: On the basis of the treatment outcomes and therapeutic targets, the following five distinct genetic subgroups were identified in SCLC: NSCLC-subgroup (genetic alterations associated with NSCLC, 8.5%); Hotspot-subgroup (targetable hotspot mutations common in tumors, 3.0%); PI3K-subgroup (PI3K/AKT/mTOR pathway mutations, 7.4%); MYC-subgroup (MYC family amplifications, 13.0%); and HME-subgroup (mutations in the histone-modifying enzymes, 17.6%). The NSCLC-subgroup (hazard ratio = 1.57; 95% confidence interval: 1.22-2.03) and MYC-subgroup (hazard ratio = 1.56; 95% confidence interval: 1.26-1.93) had significantly shorter progression-free survivals after first-line platinum-based treatment. The Hotspot-subgroup and MYC-subgroup were candidates for novel targeted therapies. The HME-subgroup had a favorable survival in patients who received programmed cell death (ligand) 1 inhibitor-based therapies (p = 0.005, log-rank test) regardless of some overlap with other subgroups. There were 15 patients enrolled into the phase 2 trial of gedatolisib in the PI3K-subgroup, and the overall response rate and the disease control rate were 6.7% and 20%, respectively. The MYC-subgroup or NSCLC-subgroup was associated with unfavorable clinical outcomes in this trial., Conclusions: Molecular classification of SCLC by genetic approach is beneficial for predicting the treatment outcomes and effectively guiding the clinical choices., Competing Interests: Disclosure Dr. Umemura reports receiving grants from Taiho Pharmaceutical and honoraria from Merck Sharp & Dohme and Chugai Pharmaceutical. Dr. Udagawa reports receiving grants from Takeda and Boehringer Ingelheim. Dr. Murakami reports receiving grants from Chugai Pharma, AstraZeneca, Takeda, Daiichi Sankyo, AbbVie, IQVIA, Taiho Pharmaceutical, and Bayer; receiving honoraria from Pfizer, Chugai Pharma, Daiichi Sankyo, AstraZeneca, Takeda, Amgen, Ono Pharmaceutical, Bristol-Myers Squibb Japan, Merck Sharp & Dohme, Novartis, Lilly Japan, Taiho Pharmaceutical, Eisai, and Nihonkayaku; and having participation on a data safety monitoring board or advisory board for Chugai Pharma, GAIA BioMedicine, Daiichi Sankyo, and Amgen. Dr. Daga reports receiving honoraria from AstraZeneca and Chugai Pharmaceutical. Dr. Toyozawa reports receiving grants from Pfizer, AbbVie, Amgen, AnHeart Therapeutics, Daiichi Sankyo, Eli Lilly Japan, Novartis Pharma, and Takeda Pharmaceutical and honoraria from Pfizer, AstraZeneca, Chugai Pharmaceutical, Eli Lilly Japan, Merck Sharp & Dohme, Nippon Boehringer Ingelheim, Novartis Pharma, Ono Pharmaceutical, Taiho Pharmaceutical, and Takeda Pharmaceutical. Dr. Kozuki reports receiving grants from Pfizer, Chugai Pharmaceutical Co., AstraZeneca, Eli Lilly Japan, Taiho Pharmaceutical Co., Bristol-Myers Squibb, Ono Pharmaceutical Co., Merck Sharp & Dohme, Kyowa Hakko Kirin, Merck Biopharma, Daiichi Sankyo, Amgen, AbbVie, Sanofi, Eisai, LabCorp Development Japan, IQVIA Services Japan, Gilead Sciences, and Bayer; consulting fees from Pfizer, Chugai Pharmaceutical Co., AstraZeneca, Ono Pharmaceutical Co., Daiichi Sankyo, Bayer, and AbbVie; and honoraria from Pfizer, Chugai Pharmaceutical Co., AstraZeneca, Eli Lilly Japan, Taiho Pharmaceutical Co., Bristol-Myers Squibb, Ono Pharmaceutical Co., Merck Sharp & Dohme, Kyowa Hakko Kirin, Nippon Boehringer Ingelheim, Merck Biopharma, Nippon Kayaku, Novartis, Daiichi Sankyo, Takeda Pharmaceutical Co., Bayer, Sawai, and Amgen. Dr. Sakakibara-Konishi reports receiving grants from Lilly. Dr. Ohe reports receiving grants from Pfizer, AstraZeneca, Chugai, Lilly, ONO, Bristol-Myers Squibb, Kyorin, Dainippon-Sumitomo, Taiho, Novartis, Takeda, Kissei, Daiichi Sankyo, Janssen, and Loxo; receiving payment for expert testimony from AstraZeneca, Chugai, ONO, Bristol-Myers Squibb, Kyorin, Celltrion, Amgen, Nippon Kayaku, Boehringer Ingelheim, and AnHeart Therapeutics Inc., and having leadership roles with JSMO, JLCS, and JCOG. Dr. Morise reports receiving grants from Boehringer Ingelheim and Eli Lilly; honoraria from Pfizer, Boehringer Ingelheim, Daiichi Sankyo, AstraZeneca, Eli Lilly, Chugai Pharmaceutical, Merck Sharp & Dohme, Ono Pharmaceutical, and Taiho Pharmaceutical; and other financial or nonfinancial interests from Pfizer, Chugai, AstraZeneca, Ono, Merck Serono, Kissei, Taiho, and Novartis. Dr. Kato reports receiving grants from Pfizer, AbbVie, Amgen, AstraZeneca, BeiGene, BluePrint, Chugai, Daiichi Sankyo, Eli Lilly, Haihe, Merck KGaA, Merck Sharp & Dohme, Novartis, Regeneron, Takeda, and TurningPoint; receiving honoraria from Pfizer, Amgen, AstraZeneca, BeiGene, Boehringer Ingelheim, Chugai, Daiichi Sankyo, Eli Lilly, GlaxoSmithKline, Janssen, Merck KGaA, Merck Sharp & Dohme, Novartis, Ono, Taiho, and Takeda; having participation on a data safety monitoring board or advisory board from Pfizer, AstraZeneca, BeiGene, Daiichi Sankyo, Janssen, Merck KGaA, Merck Sharp & Dohme, and Novartis; and receiving other financial or nonfinancial interests for Eli Lilly. Dr. Furuya reports receiving honoraria from Pfizer, Eli Lilly Japan, AstraZeneca, Boehringer Ingelheim Japan, Chugai, Bristol-Myers Squibb, Taiho, and Novartis. Dr. Nakachi reports receiving honoraria from AstraZeneca, Chugai Pharmaceutical, and Novartis Pharma. Dr. Nomura reports receiving grants from AstraZeneca and Amgen and honoraria from AstraZeneca, Chugai, Kyowa Hakko, JMDC, Byer, and Asahi-Kasei Pharma. Dr. Sato reports receiving grants from Taiho Pharmaceutical, Boehringer Ingelheim, Bayer, Chugai Pharma, Eisai, Ono Pharmaceutical, Takeda, Aspyrian Therapeutics, Pentax Medical Devices, and Daiichi Sankyo/UCB Japan. Dr. Ishii reports receiving grants from Daiichi Sankyo, Inc., Ono Pharmaceutical Co., Ltd., Noile-Immune Biotech, Takeda Pharmaceutical Company Limited, Sumitomo Dainippon Pharma Co., Ltd., Nihon Medi-Physics Co., Ltd., Indivumed GmbH, and H.U. Group Research Institute; consulting fees from Takeda Pharmaceutical Company Limited; and honoraria from Roche Diagnostics K.K., Chugai Pharmaceutical Co., Ltd., Novartis International AG, Eli Lilly Japan K.K., Takeda Pharmaceutical Company Limited, AstraZeneca, Riken Genesis Co., Ltd., and Merck Biopharma Japan. Dr. Kirita reports receiving consulting fees from Eli Lilly and honoraria from Pfizer, Merck Sharp & Dohme Oncology, Boehringer Ingelheim, Novartis, Takeda Pharmaceuticals, Boston Scientific, Chugai Pharma, ONO Pharma, Merk BioPharma, Thermo Fisher Scientific, AstraZeneca, Taiho Pharmaceuticals, Amgen, and Bristol-Myers Squibb. Dr. Sakai reports receiving grants from Amgen and Daiichi Sankyo and honoraria from AstraZeneca, Chugai, Novartis, Merck Sharp & Dohme, Thermo Fisher Scientific, and Merck. Dr. Shibata reports receiving grants from Merck Sharp & Dohme and Blueprint Medicines Corporation and honoraria from Pfizer, Chugai, Bristol-Myers Squibb, Takeda, AstraZeneca, Merck, Ono Pharmaceutical Co., Ltd., and Eli Lilly Japan. Dr. Izumi reports receiving grants from AbbVie, AstraZeneca, Amgen, Takeda, Eisai, and Ono Pharmaceutical; receiving honoraria from Takeda, Merck, Ono Pharmaceutical, Merck Sharp & Dohme, Chugai, and Bristol-Myers Squibb Japan; and having participation on a data safety monitoring board or advisory board for Amgen. Dr. Nosaki reports receiving grants from AbbVie, AnHeart Therapeutics, AstraZeneca, Chugai Pharma, Daiichi Sankyo, Merck Sharp & Dohme, and Takeda; receiving honoraria from Pfizer, AstraZeneca, Chugai Pharma, Lilly, Merck Sharp & Dohme, Taiho Pharmaceutical, Yansen Pharma, Ono, Takeda, Novartis, and Merck; and having participation on a data safety monitoring board or advisory board for Daiichi Sankyo/UCB/Japan and AbbVie. Dr. Zenke reports receiving grants from AstraZeneca, Merck Sharp & Dohme, Daiichi Sankyo, Amgen, GlaxoSmithKline, Roche, and Merck and honoraria from Pfizer, AstraZeneca, Lilly, Chugai, Ono, Bristol-Myers Squibb, Takeda, Boehringer Ingelheim, Taiho, Merck Sharp & Dohme, Novartis, Nihon Kayaku, Kyowa Kirin, and Amgen. Dr. Matsumoto reports receiving grants from Chugai Pharma, Janssen Pharmaceutical, and Merck Sharp & Dohme and honoraria from Eli Lilly, Merck Biopharma, Chugai Pharma, Novartis Pharma, Guardant Health, and AstraZeneca. Dr. Yoh reports receiving grants from Pfizer, AbbVie, Amgen, AstraZeneca, Boehringer Ingelheim, Chugai, Daiichi Sankyo, Lilly, Merck Sharp & Dohme, Taiho, and Takeda; receiving honoraria from AbbVie, Amgen, AstraZeneca, Boehringer Ingelheim, Bristol-Myers Squibb, Chugai, Daiichi Sankyo, Janssen, Kyowa Kirin, Lilly, Merck Serono, Novartis, Ono, Otsuka, Taiho, and Takeda; and having participation on a data safety monitoring board or advisory board for Boehringer Ingelheim. Dr. Niho reports receiving grants from Chugai, Eli Lilly, Daiichi Sankyo, Boehringer Ingelheim, GlaxoSmithKline, Kyowa Kirin, Kyorin, Taiho, Nippon Kayaku, and Teijin; receiving consulting fees from Pfizer, AstraZeneca, and Daiichi Sankyo; and receiving honoraria from Pfizer, AstraZeneca, Amgen, Boehringer Ingelheim, Chugai, Daiichi Sankyo, Eisai, Eli Lilly, Kyorin, Kyowa Kirin, Merck Biopharma, Merck Sharp & Dohme, Nippon Kayaku, Novartis, Ono, and Takeda. Dr. Goto reports receiving grants from Pfizer, Amgen Inc., Amgen K.K., Amgen Astellas BioPharma K.K., AstraZeneca K.K., Bayer Yakuhin, Ltd., Boehringer Ingelheim Japan, Inc., Bristol-Myers Squibb K.K., Blueprint Medicines Corporation, Craif Inc., Daiichi Sankyo Co., Ltd., Eisai Co., Ltd., Eli Lilly Japan K.K., Haihe Biopharma Co., Ltd., Ignyta, Inc., Janssen Pharmaceutical K.K., Kissei Pharmaceutical Co., Ltd., Kyowa Kirin Co., Ltd., Life Technologies Japan Ltd., Loxo Oncology, Inc., LSI Medience Corporation, Medical & Biological Laboratories Co., Ltd., Merck Biopharma Co., Ltd., Merus N.V., Merck Sharp & Dohme K.K., Novartis Pharma K.K., Ono Pharmaceutical Co., Ltd., Precision Medicine Asia Co., Ltd., Riken Genesis Co., Ltd., Sumitomo Pharma Co., Ltd., Spectrum Pharmaceuticals, Inc., Sysmex Corporation, Taiho Pharmaceutical Co., Ltd., Takeda Pharmaceutical Co., Ltd., Turning Point Therapeutics, Inc., and Xcoo, Inc.; receiving honoraria from Amgen Inc., Amgen K.K., Amoy Diagnostics Co., Ltd., AstraZeneca K.K., Bayer HealthCare Pharmaceuticals Inc., Bayer Yakuhin, Ltd., Boehringer Ingelheim Japan, Inc., Blueprint Medicines Corporation, Daiichi Sankyo Co., Ltd., Eisai Co., Ltd., Eli Lilly Japan K.K., Guardant Health Inc., Haihe Biopharma Co., Ltd., Janssen Pharmaceutical K.K., Medpace Japan K.K., Merck Biopharma Co., Ltd., Nippon Kayaku Co., Ltd., Novartis Pharma K.K., Ono Pharmaceutical Co., Ltd., Otsuka Pharmaceutical Co., Ltd., Riken Genesis Co., Ltd., Taiho Pharmaceutical Co., Ltd., Takeda Pharmaceutical Co., Ltd., and Xcoo, Inc.; and having participation on a data safety monitoring board or advisory board for Amgen Inc., Amgen K.K., Daiichi Sankyo Co., Ltd., and Eli Lilly Japan K.K. The remaining authors declare no conflict of interest., (Copyright © 2024 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved.)

Purpose: Positive surgical margins (PSM) after robot-assisted radical prostatectomy (RARP) for prostate cancer (PCa) can increase the risk of biochemical recurrence and PCa-specific mortality. We aimed to evaluate the impact of multidisciplinary team meetings (MDTM) on reducing the incidence of PSM following RARP., Methods: We retrospectively collected the clinical data of consecutive patients undergoing RARP at Hiroshima University between February 2017 and October 2023. The MDTM, comprising a radiologist, uropathologist, and urologist, reviewed the preoperative magnetic resonance imaging (MRI) and prostate biopsy results of each patient before RARP and considered the areas requiring attention during RARP. Surgeons were categorized as experienced or non-experienced based on the number of RARP procedures performed., Results: In the pT2 population, the PSM rate was significantly lower in cases evaluated using the MDTM than in those not (11.1% vs. 24.0%; p = 0.0067). Cox regression analysis identified that a PSA level > 7 ng/mL (hazard ratio 2.2799) and nerve-sparing procedures (hazard ratio 2.2619) were independent predictors of increased PSM risk while conducting an MDTM (hazard ratio 0.4773) was an independent predictor of reduced PSM risk in the pT2 population. In the pathological T3 population, there was no significant difference in PSM rates between cases evaluated and not evaluated at an MDTM. In cases evaluated at an MDTM, similar PSM rates were observed regardless of surgeon experience (10.4% for non-experienced and 11.9% for experienced surgeons; p = 0.9999)., Conclusions: An MDTM can improve the PSM rate of pT2 PCa following RARP., (© 2024. The Author(s).)

Purpose: Post-operative meniscal cyst formation occurs following all-inside device meniscal repair. This study aimed to compare the incidence of cysts in patients who underwent meniscal repair with and without all-inside suture devices., Methods: This retrospective study included 227 knees that underwent meniscal repair between 2021 and 2022. The incidence of post-operative meniscal cysts was compared between patients who underwent repair using an all-inside suture anchor device (Group SA) and those who did not use an anchor (Group NA), based on post-operative magnetic resonance imaging (MRI) findings. Risk factors, such as the number of anchors used, were investigated. Using a subgroup analysis, the incidence of meniscal cysts based on the type of device used was investigated., Results: Groups SA and NA comprised 125 and 102 knees, respectively. Group SA had 11 cases of cysts (9% incidence), whereas Group NA had 7 cases (7% incidence), and no statistically significant difference was observed ( p  = 0.63). Symptomatic cysts were observed in two patients (1.6%) in Group SA, whereas none was observed in Group NA (0%); the difference was not significant ( p  = 0.50). Factors such as the number of anchors and sutures used and MRI timing were not identified as risk factors. Cyst incidence varied according to anchor type: Stryker AIR+ (4 out of 55, 7%), Smith & Nephew Fast-Fix 360 (7 out of 56, 13%) and Arthrex Fiber Stitch (0 out of 26, 0%), with no significant difference found ( p  = 0.14)., Conclusion: The incidence of cysts in patients undergoing meniscal repair with an all-inside suture anchor device was 9%, showing no significant difference compared with Group NA. Cyst incidence was not affected by device type., Level of Evidence: Level III, retrospective comparative study., Competing Interests: The authors declare no conflict of interest., (© 2024 The Author(s). Journal of Experimental Orthopaedics published by John Wiley & Sons Ltd on behalf of European Society of Sports Traumatology, Knee Surgery and Arthroscopy.)

A 54-year-old woman developed stage IV breast cancer 8 years prior. Chemotherapy was administered, and she was started on zoledronic acid treatment for her bone metastases. Her chemotherapy regimen was then switched, owing to disease progression. Fifty-seven months after starting treatment with zoledronic acid, the patient suffered an atypical femoral fracture of her right femur, for which she underwent surgery. Twenty months later, she developed another atypical femoral fracture in her left femur and underwent intramedullary nail fixation. Zoledronic acid and denosumab use in patients with metastatic bone tumors caused by breast cancer should be done cautiously, considering atypical femoral fracture risk., (© Japan College of Rheumatology 2024. Published by Oxford University Press. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site–for further information please contact journals.permissions@oup.com.)

Purpose: To ascertain the characteristics of achromatopsia (ACHM) in Japan by analyzing the genetic and phenotypic features of patients with ACHM., Methods: The medical records of 52 patients from 47 Japanese families who were clinically diagnosed with ACHM were reviewed in this retrospective observational study., Results: Thirty-six causative variants of ACHM were identified in 26 families via whole-exome sequencing: PDE6C (12 families), CNGA3 (10 families), CNGB3 (two families), and GNAT2 (two families). However, none of the 6 causative variants that are known to cause ACHM, or the 275 other genes listed in RetNet, were observed in 19 families. A significant trend toward older age and worsening of ellipsoid zone disruption on optical coherence tomography images was observed (P < 0.01). Progressive ellipsoid zone disruptions were observed in 13 eyes of seven patients during the follow-up visits. These patients harbored one or more variants in PDE6C., Conclusion: The ACHM phenotype observed in this study was similar to those observed in previous reports; however, the causative gene variants differed from those in Europe. The low identification ratio of causative genes in whole-exome sequencing suggests the presence of unique hotspots in Japanese patients with ACHM that were not detectable via ordinal whole-exome sequencing.

Hidrocystoma is thought to be a benign retention cyst of sweat ductal units. The lesion is usually located in the periorbital skin; however, lesions with similar histopathological features are rarely observed in extra-facial sites. Herein, we present four cases of hidrocystoma-like tumours in extra-facial skin sites that harboured a RET or ALK rearrangement. This study features a 67-year-old female with a 10 mm-sized digital tumour (Case 1), a 62-year-old male with an 8 mm-sized clavicular tumour (Case 2), a 61-year-old male with a 19 mm-sized digital tumour (Case 3), and an 11-year-old female with a 10 mm-size lower leg tumour (Case 4) as well as five control cases (Cases 5-9) of classical periorbital hidrocystoma. In Cases 1-4, multicystic tumours comprising a two-cell layer of inner cuboidal ductoglandular (p63- and SOX10+/-) and outer flat myoepithelial (p63+ and SOX10+) cells were observed. The inner ductoglandular tumour cells exhibited micropapillary projections and Roman bridging structures. No apparent atypical cells were observed. NCOA4::RET in Cases 1 and 3, CCDC6::RET in Case 2, and SLC12A2::ALK in Case 4 were revealed by next-generation sequencing or Sanger sequencing. In contrast, control cases of classical hidrocystoma (Cases 5-9) did not show intracystic proliferation, abundant cytoplasm, ALK immunoreactivity, or NCOA4::RET detection in the tumour cells. RET/ALK-rearranged hidrocystoma-like tumours are tumour entities that can be distinguished from classical hidrocystoma. This RET/ALK-rearranged neoplasm is benign and is frequently observed in the digits. Future studies will establish the concept, detailed clinicopathological characteristics, and genetic variations of hidrocystoma-like tumours., (Copyright © 2024 Royal College of Pathologists of Australasia. Published by Elsevier B.V. All rights reserved.)

The purpose of our narrative review is to summarize the utilization of social media (SoMe) platforms for research communication within the field of surgery. We searched the PubMed database for articles in the last decade that discuss the utilization of SoMe in surgery and then categorized the diverse purposes of SoMe. SoMe proved to be a powerful tool for disseminating articles. Employing strategic methods like visual abstracts enhances article citation rates, the impact factor, h-index, and Altmetric score (an emerging alternative metric that comprehensively and instantly quantifies the social impact of scientific papers). SoMe also proved valuable for surgical education, with online videos shared widely for surgical training. However, it is essential to acknowledge the associated risk of inconsistency in quality. Moreover, SoMe facilitates discussion on specific topics through hashtags or closed groups and is instrumental in recruiting surgeons, with over half of general surgery residency programs in the US efficiently leveraging these platforms to attract the attention of potential candidates. Thus, there is a wealth of evidence supporting the effective use of SoMe for surgeons. In the contemporary era where SoMe is widely utilized, surgeons should be well-versed in this evidence., (© 2024. The Author(s).)

This observational study evaluated the validity of end-tidal CO 2 (ETCO 2 ) as a surrogate for arterial PCO 2 (PaCO 2 ) in infants on neurally adjusted ventilatory assist (NAVA), particularly considering the influence of variable spontaneous breathing on capnography waveforms. The study involved 16 infants, analyzing 50 paired ETCO 2 and PaCO 2 values. Deming regression analysis highlighted a notably stronger correlation for maximum ETCO 2 (r 2  = 0.6783, p <0.0001) compared to mean ETCO 2 (r 2  = 0.5686, p <0.0001) and demonstrated a significantly weaker association for minimum ETCO 2 (r 2  = 0.1838). These findings emphasize the superior predictive value of maximum ETCO 2 in estimating PaCO 2 , advocating its reliable use in clinical monitoring, especially given the dynamic capnography associated with NAVA's variable pressures. The results suggest ETCO 2 's potential to enhance noninvasive respiratory management, reduce the frequency of blood sampling, and improve overall care for infants requiring mechanical ventilation., (© 2023. The Author(s), under exclusive licence to Dr. K C Chaudhuri Foundation.)

Objectives: This study aimed to elucidate the clinical characteristics and predictors of long-term postoperative urinary incontinence (PUI) after robot-assisted radical prostatectomy (RARP)., Methods: This study included patients who underwent RARP at our institution and were stratified into PUI (≥1 pad/day) and continence (0 pad/day) groups at 60 months after RARP. A propensity score-matched analysis with multiple preoperative urinary status (Expanded Prostate Cancer Index Composite urinary subdomains, total International Prostate Symptom Score (IPSS), and IPSS-quality of life scores) was performed to match preoperative urinary status in these groups. Serial changes in urinary status and treatment satisfaction preoperatively and until 60 months after RARP were compared, and predictors of long-term PUI were assessed using multivariate logistic regression analysis., Results: A total of 228 patients were included in the PUI and continence groups (114 patients each). Although no significant difference in preoperative urinary status was observed between the two groups, the postoperative urinary status significantly worsened overall in the PUI group than in the continence group. Treatment satisfaction was also significantly lower in the PUI group than in the continence group from 12 to 60 months postoperatively. Multivariate logistic regression analysis revealed that age (≥70 years) and biochemical recurrence (BCR) were significant predictors of the long-term PUI group (p < 0.05)., Conclusions: Patients with long-term PUI had poor overall postoperative urinary status and lower treatment satisfaction than the continence group. Considering the age and risk of BCR is important for predicting long-term PUI when performing RARP., (© 2024 The Author(s). International Journal of Urology published by John Wiley & Sons Australia, Ltd on behalf of The Japanese Urological Association.)

Objective: This prospective study compared PIVKA-II and PT-INR levels in infants who received two vitamin K (VK) prophylactic regimens., Methods: A single institution administered 119 healthy newborns 2 mg of VK syrup. Infants were assigned to a 3-time regimen (n = 56) with VK at birth, five days (5D), and 1-month-old (1 M), or a 13-time regimen (n = 63) with VK at birth, 5D, and then weekly for 11 weeks., Results: The 13-time regimen significantly lowered PIVKA-II and reduced PT-INR at 1 M in both breastfed (PIVKA-II: 18-16 mAU/mL, p = 0.02; PT-INR: 1.37-1.13, p < 0.01) and formula-fed infants (PIVKA-II: 18-15 mAU/mL, p = 0.01; PT-INR: 1.54-1.24, p < 0.01), compared to baseline measurements taken at 5D. The 3-time regimen did not significantly alter PIVKA-II levels and only improved PT-INR (2.00-1.50, p < 0.01) in formula-fed infants., Conclusion: The 13-time VK regimen significantly enhanced coagulation profiles more effectively than the 3-time regimen., (© 2024. The Author(s), under exclusive licence to Springer Nature America, Inc.)