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Purpose: Doublet chemotherapy with fluoropyrimidine (FP) and oxaliplatin (OX) plus bevacizumab (BEV) is a standard regimen for unresectable metastatic colorectal cancer (MCRC). However, the efficacy of adding OX to FP plus BEV (FP + BEV) remains unclear for older patients, a population for whom FP + BEV is standard. We aimed to confirm the superiority of adding OX to FP + BEV for this population., Methods: This open-label, randomized, phase III trial was conducted at 42 institutions in Japan. Patients with unresectable MCRC age 70-74 years with Eastern Cooperative Oncology Group performance status (ECOG-PS) 2 and those 75 years and older with ECOG-PS 0-2 were randomly assigned (1:1) to an FP + BEV arm or an OX addition (FP + BEV + OX) arm. Fluorouracil plus levofolinate calcium or capecitabine was declared before enrollment. The primary end point was progression-free survival (PFS). The study was registered in the Japan Registry of Clinical Trials (identifier: jRCTs031180145)., Results: Between September 2012 and March 2019, 251 patients were randomly assigned to the FP + BEV arm (n = 125) and the FP + BEV + OX arm (n = 126). The median age was 80 and 79 years in the respective arm. The median PFS was 9.4 months (95% CI, 8.3 to 10.3) in the FP + BEV arm and 10.0 months (9.0 to 11.2) in the FP + BEV + OX arm (hazard ratio [HR], 0.84 [90.5% CI, 0.67 to 1.04]; one-sided P = .086). The median overall survival was 21.3 months (18.7 to 24.3) in the FP + BEV arm and 19.7 months (15.5 to 25.5) in the FP + BEV + OX arm (HR, 1.05 [0.81 to 1.37]). The proportion of any grade ≥3 adverse events was higher in the FP + BEV + OX arm (52% v 69%). There was one treatment-related death in the FP + BEV arm and three in the FP + BEV + OX arm., Conclusion: No benefit of adding OX to FP + BEV as first-line treatment was demonstrated in older patients with MCRC. FP + BEV is recommended for this population.

Rare-earth-transition-metal (RE-TM) ferrimagnets are excellent materials for spin encode/decode operations via spin transport in nonmagnetic regions. This superior performance stems from two key factors. First, the antiferromagnetic coupling between RE4f and TM3d sublattices reduces both the spin-transfer-torque switching time and inter-device magnetic-coupling. Second, the RE-TM ferrimagnets function as spin injectors/ejectors, with the TM3d sublattice solely responsible for carrier spin polarization (p), similar to conventional ferromagnetic metals. We performed spin transport experiments using the sign change of p in RE-TM, which exhibits a positive value above the magnetization compensation temperature and a negative value below it. We measured temperature dependencies of the transverse resistances (RT) of electron-hole compensated metal YH 2 under out-of-plane spin-polarized current injection/ejection from GdFeCo (Gd:Fe:Co=25:66:9). The abrupt change in loop polarity of the out-of-plane field dependence of RT in YH 2 between 290 and 300 K, which aligns with the out-of-field curve of the polar Kerr rotation in GdFeCo electrodes, strongly suggests that the observed RT results from the inverse spin Hall effect (ISHE) in YH 2 . We analytically formulated ISHE in terms of the electron and hole spin currents injected from the spin sources, enabling regression analysis to assess the spin transport characteristics of a GdFeCo/YH2/GdFeCo magnetic double heterostructure. To explain the observed Hall voltages, enhancements in both the spin diffusion length of YH 2 and the spin injection efficiency are necessary.&#xD., (© 2024 IOP Publishing Ltd. All rights, including for text and data mining, AI training, and similar technologies, are reserved.)

Two new structural motifs within the class of heteroleptic Pd n A n B n assemblies, namely syn-cis-Pd 3 A 3 B 3 bowls and bowl- (syn) or saddle- (anti) shaped cis-Pd 4 A 4 B 4 rings are introduced. All of the ten examples share a common longer fluorenone-based bis-monodentate ligand, equipped with meta-pyridine donor groups. The ring size (3- vs. 4-membered) and conformational preference (bowl vs. saddle) are controlled by the choice of the shorter ligand. These carry para-pyridine donors, different aromatic backbones (benzene, thiophene or selenophene) and either no or small or bulky endohedral substituents, serving to control the nuclearity of the heteroleptic rings through different effects (ligand angle, charge distribution or backbone bulk). Moreover, the luminescence of the fluorenone ligand is conserved in the formed architectures. Emission intensity as well as host-guest properties vary depending on the inward-pointing functions. All Pd 3 A 3 B 3 assemblies are shown to bind chiral guest BINOL bis-sulfonate which imparts its chirality to the entire host-guest complex. This results in a guest-induced circular dichroism (CD) and circularly polarized luminescence (CPL) with dissymmetry factor g lum up to 10 -3 ., (© 2024 The Authors. Angewandte Chemie International Edition published by Wiley-VCH GmbH.)

Background/aim: Although the frequency of small bowel obstructions after liver surgery is generally considered low, previous studies have followed-up patients for less than a year, thus the incidence of small bowel obstructions several years after surgery is unknown. Furthermore, the rise in laparoscopic surgeries and the use of adhesion prevention materials may influence the occurrence of small bowel obstructions. This  study aimed to assess the incidence of small bowel obstructions within a five-year period following liver surgery and identify the associated risk factors., Patients and Methods: This case series analysis analyzed patients who underwent liver surgery between April 2012 and March 2014 from 32 participating hospitals. Multivariate analysis was conducted to examine risk factors for small bowel obstructions., Results: A total of 953 patients were included in the analysis, and the incidence of small bowel obstructions was 1.6%. The incidence was significantly higher at 3.4% for surgeries related to metastatic liver cancer compared to other types of surgeries. Laparoscopic surgery had no significant effect on the incidence of SBO (p=0.72). There was no significant difference in the incidence of small bowel obstructions between surgeries that employed adhesion prevention materials and those that did not. Multivariable analysis revealed that longer surgical time and re-operation were independent risk factors for small bowel obstructions., Conclusion: The incidence of small bowel obstructions following surgery for metastatic liver cancer is significantly higher compared to other liver surgeries. Neither laparoscopic surgery nor adhesion prevention materials reduce its occurrence. Longer surgical time and re-operation are independent risk factors for small bowel obstructions., Competing Interests: The Authors have no conflicts of interest to disclose in relation to this study., (©2024 The Author(s). Published by the International Institute of Anticancer Research.)

The usefulness and effectiveness of telepractice have been reported in recent years. Treatment of cleft palate patients with compensatory articulation is based on perceptual identification. Telepractice using videoconferencing platforms causes voice signal distortion and impacts auditory-perceptual perception. This study aimed acoustically examine voice signal distortion and determine the optimal videoconferencing platforms, in addition to the phonemes that can be discriminated with the same quality as in face-to-face interactions. ATR503 with 50 phoneme-balanced Japanese speech sentences was used as a reference corpus. Four videoconferencing platforms, -Zoom, Cisco Webex, Skype, and Google Meet, -and five devices, -iPhone, Android, iPad Air, Windows, and MacBook Pro were used as transmission conditions to examine voice signal distortions with the objective measure log-spectral distortion (LSD). Tukey's test was conducted to evaluate the degree of consonant distortion related to voicings (voiceless and voiced), places of articulation (bilabial, alveolar, alveolo-palatal, palatal, velar, labial-velar, and glottal), and manners of articulation (plosive, fricative, affricate, tap or flap, nasal, and approximant). With statistically significant differences, voiced, bilabial, labial-velar, nasal, and plosive consonants exhibited smaller distortions. In contrast, voiceless, alveolo-palatal, fricative, and affricate consonants exhibited larger distortions. Google Meet exhibited the lowest distortion among videoconferencing platforms and MacBook exhibited the lowest distortion among devices. This study provides significant insights into the telepractice strategies with the appropriate videoconferencing platform and device, and useful settings for cleft palate patients with compensatory articulations with respect to acoustics., (© 2024 The Author(s). Congenital Anomalies published by John Wiley & Sons Australia, Ltd on behalf of Japanese Teratology Society.)

Background: In clinical practice, peritoneal dissemination after curative-intent surgery for pleural mesothelioma occasionally recurs. This study investigated the risk factors and prognosis associated with post-pleurectomy/decortication peritoneal dissemination in pleural mesothelioma, which are rarely reported., Methods: This retrospective review included 160 patients who experienced recurrence after pleurectomy/decortication for pleural mesothelioma between January 2011 and December 2021. Patients with recurrence were classified according to the initial recurrence pattern. The P group experienced recurrence with peritoneal dissemination, and the non-P group experienced recurrence without peritoneal dissemination. The analysis determined the risk factors for peritoneal dissemination using multivariable logistic regression analysis. Survival was analyzed using the Kaplan-Meier method and the log-rank test., Results: Of the 160 patients, 20 (12.5%) exhibited peritoneal dissemination and were assigned to the P group, whereas 140 (87.5%) had recurrence without peritoneal dissemination and were assigned to the non-P group. Multivariable logistic regression analysis showed that diaphragm reconstruction (odds ratio [OR], 2.8; 95% confidence interval [CI], 1.0-8.0; p = 0.048) and female sex (OR, 3.7; 95% CI 1.26-10.8; p = 0.017) were associated with the P group. Post-recurrence survival was worse in the P group than in the non-P group (1-year post-recurrence survival: 22.2% vs. 65.3%; median: 6.7 months vs. 19.4 months; p = 0.0013)., Conclusions: Peritoneal dissemination occurred in approximately one of every eight patients with recurrence after pleurectomy/decortication for pleural mesothelioma, and the incidence was significantly higher among females and patients undergoing diaphragm reconstruction. Moreover, postoperative recurrence of peritoneal dissemination was associated with a poor prognosis., (© 2024. Society of Surgical Oncology.)

We investigated whether soticlestat (TAK-935), a newly discovered cholesterol 24-hydroxylase (CH24H) inhibitor now in phase 3 clinical trials for Dravet and Lennox-Gastaut syndromes, has effects on neurodegeneration in both chronic and acute animal models associated with glutamate hyperexcitation. Soticlestat was administered at doses that approximately halve 24S-hydroxycholesterol in both experiments. In the kainic acid (KA)-induced acute hippocampal degeneration model, soticlestat ameliorated inflammatory cytokine expression, hippocampal degeneration, and memory impairment. We ruled out the possibility that soticlestat directly interferes with KA binding to the KA receptor, or that 24S-hydroxycholesterol modulates KA receptor signaling, by conducting receptor binding and cell death assays. In the PS19 chronic degeneration model of tauopathy, treatment effects were observed in neurodegeneration markers. Notably, there was a significant correlation between the levels of brain 24S-hydroxycholesterol and a proinflammatory cytokine, tumor necrosis factor-α, which is implicated in cognitive decline and lowering of seizure threshold. This is the first study demonstrating that CH24H inhibition can alleviate neurodegeneration concomitant with neuroinflammation. Herein, we discuss the interplay among 24S-hydroxycholesterol production, neuroinflammation, and excitotoxicity. Effects on neurodegeneration and neuroinflammation demonstrated in two preclinical models suggest that soticlestat is effective in ameliorating seizures and addressing cognitive dysfunction in seizure disorders., Competing Interests: Declaration of Competing Interest All authors were employees of Takeda Pharmaceutical Company Limited, Fujisawa, Japan at the time of the study., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: Intraductal papillary mucinous neoplasm is occasionally detected in the preoperative images of patients with gastrointestinal malignancies. Despite numerous studies examining the incidence of extrapancreatic malignancies in patients with intraductal papillary mucinous neoplasm, limited data exist on the prevalence of intraductal papillary mucinous neoplasm in those with gastrointestinal malignancies. Given that intraductal papillary mucinous neoplasm is a known risk factor for pancreatic cancer, this study aimed to evaluate the prevalence of intraductal papillary mucinous neoplasm in patients who underwent radical surgery for extrapancreatic gastrointestinal malignancies and its impact on pancreatic cancer development., Methods: We retrospectively reviewed the preoperative computed tomography images of patients who underwent radical surgery for gastrointestinal malignancies between January 2017 and December 2021 for the presence of intraductal papillary mucinous neoplasm. Patients were divided into intraductal papillary mucinous neoplasm and non-intraductal papillary mucinous neoplasm groups, and clinicopathologic features and long-term outcomes, including pancreatic cancer development, were compared between groups., Results: A total of 814 patients who underwent radical surgery for extrapancreatic gastrointestinal malignancies were included. Among them, 81 patients (10.0%) had intraductal papillary mucinous neoplasm. The median observation period was 39 (0-79) months. Notably, pancreatic cancer developed in 5 patients with intraductal papillary mucinous neoplasm and 1 without. The 5-year cumulative incidences of pancreatic cancer were 8.8% and 0.2% in the intraductal papillary mucinous neoplasm and non-intraductal papillary mucinous neoplasm groups, respectively (P < .001)., Conclusion: Intraductal papillary mucinous neoplasm is frequently detected in the preoperative images of patients with gastrointestinal malignancies and is associated with a significantly higher risk of developing pancreatic cancer. Consequently, long-term surveillance for pancreatic cancer is crucial in patients with intraductal papillary mucinous neoplasm, particularly those with extrapancreatic gastrointestinal malignancies., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Competing Interests: Funding Support and Author Disclosures Drs Higuchi, Yagishita, and Shoda belong to the same endowed department established by contributions from Medtronic Japan, Boston Scientific, Biotronik Japan, and Abbott Medical. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.

Background and Objectives: The impact of preinjury anticoagulation on coagulation parameters over time after traumatic brain injury (TBI) has remained unclear. Based on the hypothesis that preinjury anticoagulation significantly influences the progression and persistence of TBI-induced coagulopathy, we retrospectively examined the association of preinjury anticoagulation with various coagulation parameters during the first 24 hours postinjury in 5 periods., Methods: Data from the Japanese registry of patients with TBI aged ≥65 years admitted between 2019 and 2021 were used. Time since injury was classified into 5 categories through a graphical analysis of coagulation parameters. We examined the association between preinjury anticoagulation and the platelet count, prothrombin time-international normalized ratio (PT-INR), activated partial thromboplastin time (APTT), D-dimer level, and fibrinogen level during each period by analysis of covariance using 10 clinical factors as confounding factors., Results: Data from 545 patients and 795 blood tests were analyzed. The patients' mean age was 78.9 years, and 87 (16%) received anticoagulation therapy. The preinjury anticoagulation group had significantly greater Rotterdam computed tomography scores and poorer outcomes at discharge than the control group, with significantly lower D-dimer levels and higher fibrinogen levels. Analysis of covariance revealed significant associations between the D-dimer level and preinjury anticoagulation within 2 to 24 hours postinjury, APTT and preinjury anticoagulation within 1 to 24 hours, and PT-INR and preinjury anticoagulation throughout all periods up to 24 hours postinjury., Conclusion: Despite more severe TBI signs and poorer outcomes, the preinjury anticoagulation group had significantly lower D-dimer levels, especially within 2 to 24 hours postinjury. Thus, D-dimer levels during this period may not reliably represent TBI severity in patients receiving anticoagulation therapy before injury. Preinjury anticoagulation was also associated with an elevated PT-INR and prolonged APTT from early to 24 hours postinjury, highlighting the importance of aggressive anticoagulant reversal early after injury., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the Congress of Neurological Surgeons.)

Thallium bromide (TlBr) semiconductor detectors are being developed as promising candidates for high-detection-efficiency, high-energy-resolution, and room-temperature gamma-ray spectrometers. This study presents methods for evaluating TlBr crystal quality and carrier transport characteristics using neutron Bragg-dip imaging and the time-of-flight method for pulsed-laser-induced carriers, respectively. Neutron Bragg-dip imaging effectively determines the crystal orientation distribution, revealing crystal imperfections and grain boundaries. Time-of-flight measurements provide a spatial distribution of carrier mobility. In this study, two samples obtained from both the upstream and downstream region in the crystal ingot were evaluated. Although both samples show similar crystal quality, the upstream sample showed high carrier mobility across all areas, whereas the downstream sample exhibits low mobility in some areas. These findings suggest that, at least within the range of carrier mobility currently obtained, the effect of crystal integrity on carrier mobility is less significant than that of impurities. In conclusion, combining neutron Bragg-dip imaging with carrier mobility measurements offers a comprehensive approach to evaluating and improving TlBr detectors., (© 2024. The Author(s).)

Background/Objectives: Endoscopic ultrasound-guided hepaticogastrostomy (EUS-HGS) often requires fistula dilation owing to the placement of a large diameter of the delivery stent. The recently developed delivery devices, which are as thin as 5.9/6.0 Fr, may save the need for fistula dilation. Therefore, we investigated whether large fistula dilation would be required or not in the case of this newly developed thin-diameter delivery stents. Methods: We conducted a retrospective study involving 33 patients implemented with a self-expandable metal stent (SEMS) during EUS-HGS. The patients were categorized based on the delivery device diameter into thin (n = 13; delivery device diameter: 5.9/6.0 Fr) and thick (n = 20; delivery device diameter: 8.5 Fr) groups. We compared the initial rate of success, technical success, and clinical success between the thin and thick groups. The initial rate of success was defined as successful stent placement without a balloon or large diameter mechanical dilation. Results: The rate of the initial stenting success was significantly higher in the thin group (100% [13/13]) compared with that in the thick group (65.0% [13/20]) ( p = 0.027). In the thick group, seven cases with technical difficulty in terms of stent placement could be successfully completed with additional fistula dilation with a 9 Fr bougie dilator or 4 mm balloon dilator; this resulted in a technical success of 100% in both groups ultimately. The rate of clinical success was 100% and 95.0% in the thin and thick groups, respectively ( p = 1.00). Conclusions: Thin delivery stents may facilitate stent placement without the need for a balloon fistula or large-diameter mechanical dilation.

Purpose: Although guidelines recommend adjunctive rifampin and gentamicin use for patients with staphylococcal prosthetic valve endocarditis (PVE), evidence behind the recommendation is limited and conflicting., Methods: We performed a retrospective cohort study of all patients with staphylococcal PVE within the Veterans Health Administration during 2003-2021. Patients were identified with diagnostic codes for prosthetic valves and positive blood cultures for Staphylococcus species and confirmed via manual chart reviews. The primary outcome was the composite of all-cause mortality or recurrence of staphylococcal PVE within one year from diagnosis. Inverse probability of treatment weighting (IPTW) was used to estimate the probability of individuals receiving rifampin using propensity scores. IPTW-adjusted multivariable Cox regression analysis was used to compare outcomes between patients who received rifampin and gentamicin, and those did not., Results: Among 373 patients with staphylococcal PVE, 275 (73.7%) and 225 (60.3%) received at least one dose of rifampin and gentamicin, respectively. The incidence of staphylococcal PVE increased from 0.47 (2003-11) to 0.77 (2012-21) per 10,000 hospitalizations. Gentamicin use declined over time (70.1% in 2003-2011 to 54.8% in 2012-2021, p = 0.04) while rifampin use did not change significantly (76.1% in 2003-2011 to 72.4% in 2012-2021, p = 0.43). The composite outcome was observed in 209 (56.0%). Neither rifampin use (adjusted hazard ratio [HR] 0.77, 95% CI 0.48-1.24) and gentamicin use (adjusted HR 1.11, 95% CI 0.71-1.74) was associated with the composite outcome., Conclusion: No significant association was observed between adjunctive rifampin or gentamicin use and improved outcomes., (© 2024. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

Background: Pleural mesothelioma (PM) is a cancer with usually a dismal prognosis. However, long-term survivors do exist. Herein, we analyzed long-term survivors (>5 years after surgery) from high-volume centres around the world., Methods: This is a multicenter retrospective descriptive analysis of long-term survivors (overall survival ≥ 5 years from surgery) treated within a multimodality therapy approach including macroscopic complete resection. Overall survival was calculated with Kaplan Meier analysis and cases were matched by center and surgery year and compared with a control group of short-term survivors (<2 years) in a conditional logistic regression analysis., Results: There were 276 long-term survivors, most were male (n=166, 63%) with a median age of 59 (range 21-83) years at time of diagnosis. The histology for 246 was epithelioid and non-epithelioid for 30 patients. The disease was on the right side in 58% of the patients. As of this analysis, 148 patients were dead, 104 were alive and 10 were lost to follow-up. Pathological tumor stages were: pT1 (n=50), pT2 (n=63), pT3 (n=90) or pT4 (n=16), pN0 (n=150), pN1 (n=20) and pN2 (n=39). The matched control dataset included 333 patients, 95 cases and 238 controls. Comparing short- with long-term survivors, there was moderate evidence that a low white blood cell (WBC) count before surgery was more often observed in long-term survivors., Conclusions: The data show that long-term survival in PM is possible in a subgroup of surgically treated patients; histological subtype and WBC count seem to be prognosticators for longer survival., (Copyright © 2024. Published by Elsevier Inc.)

Objective: To investigate the incidence of male sexual dysfunction (SD) including erectile dysfunction (ErD) and ejaculatory dysfunction (EjD) after minimally invasive rectal cancer surgery., Background: Male SD significantly affects post-rectal cancer surgery quality of life (QOL). Current assessments using the International Index of Erectile Function-5 are unsuitable for patients with reduced postoperative sexual activity, because it assumes sexual intercourse. This study addresses this gap using the Erection Hardness Score (EHS) and custom ejaculatory questionnaires., Methods: This prospective multicenter open-label phase II trial enrolled 399 patients who underwent laparoscopic (Lap), robotic (Ro), or transanal (Ta) rectal cancer surgery. EHS and custom ejaculatory questionnaires assessed ErD, EjD, and potency impairment at 3, 6, and 12 months postoperatively. The rates were assessed in the full analysis set and compared between the Lap and Ro groups after propensity score matching., Results: At 12 months, the overall incidences of ErD and EjD were 34.7% and 29.8%, respectively. The Ro group showed a significantly lower EjD rate (25.0%) than the Lap group (40.9%), with no significant difference in ErD. Potency impairment was lower in the Ro group at 6 months (32.7% vs. 22.3%) and 12 months (29.0% vs. 17.8%) postoperatively. The Ta group showed relatively high ErD and EjD at 3 months, with some recovery at 12 months., Conclusions: Minimally invasive rectal cancer surgery commonly results in ErD, EjD, and potency impairment. Robotic surgery provides lower EjD rates and less potency impairment. Comprehensive sexual function assessments are essential to inform patients and improve QOL outcomes., Competing Interests: Conflicts of Interest and source of funding: The authors declare no conflicts of interest directly relevant to the content of this article. The authors declare that no funding was received in support of this study., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.)

Determining a novel etiology and mechanism of human cancer requires extraction of characteristic mutational signatures derived from chemical substances. This study explored the mutational signatures of N -nitroso bile acid conjugates using Salmonella strains. Exposing S. typhimurium TA1535 to N -nitroso-glycine/taurine bile acid conjugates induced a predominance of C:G to T:A transitions. Two mutational signatures, B1 and B2, were extracted. Signature B1 is associated with N -nitroso-glycine bile acid conjugates, while Signature B2 is linked to N -nitroso-taurine bile acid conjugates. Signature B1 revealed a strong transcribed strand bias with GCC and GCT contexts, and the mutation pattern of N -nitroso-glycine bile acid conjugates in YG7108, which lacks O 6 -methylguanine DNA methyltransferases, matched that of the wild-type strain TA1535, suggesting that O 6 -methyl-deoxyguanosine contributes to mutations in the relevant regions. COSMIC database-based similarity analysis revealed that Signature B1 closely resembled SBS42, which is associated with occupational cholangiocarcinoma caused by overexposure to 1,2-dichlolopropane (1,2-DCP) and/or dichloromethane (DCM). Moreover, the inflammatory response pathway was induced by 1,2-DCP exposure in a human cholangiocyte cell line, and iNOS expression was positive in occupational cholangiocarcinomas. These results suggest that 1,2-DCP triggers an inflammatory response in biliary epithelial cells by upregulating iNOS and N -nitroso-glycine bile acid conjugate production, resulting in cholangiocarcinoma via DNA adduct formation.

Cold shock proteins (Csps), of around 70 amino acids, share a protein fold for the cold shock domain (CSD) that contains RNA binding motifs, RNP1 and RNP2, and constitute one family of bacterial RNA-binding proteins. Despite similar amino acid composition, Csps have been shown to individually possess inherent specific functions. Here we identify the molecular differences in Csps that allow selective recognition of RNA targets. Using chimeras and mutants of Escherichia coli CspD and CspA, we demonstrate that Lys43-Ala44 in an internal loop of CspD and the N-terminal portion with Lys4 of CspA are important for determining their target specificities. Pull-down assays suggest these distinct specificities reflect differences in the ability to act on the target RNAs rather than differences in binding to the RNA targets. A phylogenetic tree constructed from 1,573 Csps reveals that the Csps containing Lys-Ala in the loop form a monophyletic clade, and the members in this clade are shown to have target specificities similar to E. coli CspD. The phylogenetic tree also finds a small cluster of Csps containing Lys-Glu in the loop, and these exhibit different specificity than E. coli CspD. Examination of this difference suggests a role of the loop of CspD type proteins in recognition of specific targets. Additionally, each identified type of Csp shows a different distribution pattern among bacteria. Our findings provide a basis for subclassification of Csps based on target RNA specificity, which will be useful for understanding of the functional specialization of Csps., (Published by Cold Spring Harbor Laboratory Press for the RNA Society.)

Objectives: This retrospective study aimed to compare treatment outcomes and postoperative courses, including the incidence of esophageal cancer (EC), according to disease types, in 450 achalasia patients who underwent peroral endoscopic myotomy (POEM)., Methods: Data from consecutive POEM procedures performed from September 2011 to January 2023 at a single institution were reviewed. Achalasia was classified into straight (St), sigmoid (S1), and advanced sigmoid (S2) types using esophagography findings. Regarding efficacy, POEM was considered successful if the Eckardt score was ≤3. A statistical examination of the incidence and trend of EC occurrence across the disease type of achalasia was conducted using propensity score matching., Results: Of the 450 patients, 349 were diagnosed with St, 80 with S1, and 21 with S2. POEM efficacy was 97.9% at 1 year and 94.2% at 2 years postprocedure, with no statistical difference between disease types. Using propensity score matching, the incidence of EC in each disease type was as follows: St, 1% (1/98); S1, 2.5% (2/77); S2, 10% (2/18). While no statistical significance was observed between St (1.0%: 1/98) and all sigmoid types (4.0%, 4/95; P = 0.3686). However, a trend test revealed a tendency for EC to occur more frequently in the order of S2, S1, and St type with a statistically significant difference (P = 0.0413)., Conclusions: Outcomes of POEM are favorable for all disease types. After POEM, it is important not only to monitor the improvement of achalasia symptoms but also to pay attention to the occurrence of EC, especially in patients with sigmoid-type achalasia., (© 2024 Japan Gastroenterological Endoscopy Society.)

Background Therapeutic drug monitoring (TDM) is an effective approach to improving the efficacy of drugs with a narrow therapeutic index and high toxicity. TDM-guided dosing of 5-fluorouracil (5-FU) has been shown to result in superior efficacy and fewer adverse events compared to body surface area (BSA)-based dosing. Therefore, accurate measurement of plasma 5-FU concentrations after capecitabine administration is necessary. Capecitabine is a prodrug of 5-FU and is metabolized to 5-FU in multiple steps in the gastrointestinal tract, liver, and within tumors. To solve the problem of frequent blood draws for TDM, we reduced the number of blood draws to two and examined whether changes in 5-FU concentration correlated with adverse events. Methods This study investigated the relationship between the changes in plasma 5-FU concentrations after one and two hours of capecitabine administration in 36 patients and adverse events based on drug concentrations determined after adding 5-NU to the plasma samples. Concentration gradients and adverse events were estimated using the Mann-Whitney test. Results The median one- and two-hour plasma 5-FU concentrations were 67.5 (range 5-307) and 85.5 (range 19-246) ng/mL, respectively. The plasma 5-FU concentration gradient, defined as the difference between the one- and two-hour concentrations, was significantly higher in patients with diarrhea and nausea (p = 0.0234 and p = 0.0409, respectively). Conclusion The high plasma 5-FU concentration gradient suggests rapid degradation of 5-FU into its metabolites, which may lead to predict intestinal mucosal damage, diarrhea, and nausea., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. The institutional review board of Fukuoka University Hospital issued approval 16.10.02. The institutional review board of Fukuoka University Hospital, Fukuoka, Japan issued approval 16.10.02. . 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: This work was supported in part by funding from Fukuoka University (grant no. GR2315). . 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.)

Background: The clinical significance of the lymph node ratio (LNR), the number of metastatic lymph nodes per dissected lymph node, has not been sufficiently clarified in ampullary cancer., Methods: Among patients diagnosed histopathologically with ampullary cancer between 1980 and 2018, the study included 106 who underwent pathological radical resection by pancreaticoduodenectomy. The relationships between the LNR and metastatic lymph node sites and prognosis were examined., Results: Multivariate analysis revealed that sex and lymph node metastasis were independent prognostic factors. In the 46 patients (43%) with metastatic lymph nodes, the LNR in the recurrence group was significantly higher than that in the non-recurrence group (0.15 ± 0.11 vs. 0.089 ± 0.071, p = 0.025). The receiver operating characteristic curve demonstrated that the LNR cut-off value, 0.07 (area under the curve = 0.70, sensitivity 81%, specificity 56%), was a significant indicator for recurrence (22% vs. 61%, p = 0.016) and prognosis (5-year survival: 48% vs. 83%, p = 0.028). Among the metastatic lymph node sites in the 46 positive cases, lymph node metastases developed from the peripancreatic head region (80%, 37/46) to the superior mesenteric artery (33%, 15/46) and para-aortic (11%, 5/46) regions., Conclusion: Lymph node metastasis is an independent prognostic factor, and the LNR is a significant indicator for recurrence and prognosis in patients with ampullary cancer., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background/Objectives : The usefulness of dual-energy computed tomography (DECT) for low absorption in the parenchymal phase and contrast effects in the delayed phase for pancreatic cancer is not clear. Therefore, the diagnostic capability of low-KeV images obtained using DECT for pancreatic cancer in the pancreatic parenchymal and delayed phases was evaluated quantitatively and qualitatively. Methods : Twenty-five patients with pancreatic cancer who underwent contrast-enhanced DECT were included. A total of 50 and 70 KeV CT images, classified as low-keV and conventional CT-equivalent images, were produced, respectively. The tumor-to-pancreas contrast (Hounsfield units [HU]) in the pancreatic parenchymal and delayed phases was calculated by subtracting the CT value of the pancreatic tumor from that of normal parenchyma. Results : The median tumor-to-pancreas contrast on 50 KeV CT in the pancreatic parenchymal phase (133 HU) was higher than that on conventional CT (68 HU) ( p < 0.001). The median tumor-to-pancreas contrast in the delayed phase was -28 HU for 50 KeV CT and -9 HU for conventional CT ( p = 0.545). For tumors < 20 mm, the tumor-to-pancreas contrast of 50 KeV CT (-39 HU) had a significantly clearer contrast effect than that of conventional CT (-16.5 HU), even in the delayed phase ( p = 0.034). Conclusions : These 50 KeV CT images may clarify the low-absorption areas of pancreatic cancer in the pancreatic parenchymal phase. A good contrast effect was observed in small pancreatic cancers on 50 KeV delayed-phase images, suggesting that DECT is useful for the visualization of early pancreatic cancer with a small tumor diameter.

Background: Central sensitization has a significant effect on pain after osteotomy around the knee (OAK). The central sensitization inventory (CSI) score is considered disease specific, and the appropriate cut-off values for OAK are unclear. The purpose of this study was to establish the optimal CSI cut-off value affecting the postoperative outcomes of OAK based on the postoperative knee injury and osteoarthritis outcome score (KOOS)., Methods: Patients who underwent OAK for medial compartment knee osteoarthritis were included. The postoperative KOOS symptoms, pain, and activities of daily living (ADL) were categorized into two groups (score ≥80 each for symptoms, pain, and ADL, and score <80 for any of the three) and were used as factors to calculate receiver operating characteristic curves and the area under the curve with the CSI score. Cut-off values were calculated using the Youden index and the threshold value closest to the upper left corner. Subsequently, logistic multivariate analysis was performed using the KOOS and the obtained CSI cut-off values and other variables., Results: A total of 173 patients were included in this study. The area under the curve of the model was 0.801 (95 % confidence interval, 0.74-0.87), and a CSI score of 12 was determined as the cut-off value. Logistic multivariate analysis based on the cut-off value showed that only the CSI score (odds ratio, 9.79; 95 % CI, 4.47-21.4; P < 0.01) was significant., Conclusions: The optimal CSI cut-off value affecting the postoperative outcomes of OAK calculated using the postoperative KOOS was 12, which was supported by multivariate analysis results. Central sensitization assessment with an appropriate cut-off value would allow a more personalized treatment approach and may contribute to a better postoperative outcome., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

Background: Nontraumatic shoulder pain is a prevalent issue among male high school volleyball players, but its comprehensive assessment has been lacking in prior research, which often isolated specific aspects of shoulder function. This study aimed to identify contributing factors to shoulder pain in this population., Hypothesis: The hypothesis posited that limited shoulder internal rotation (IR) range of motion (ROM), imbalance in rotator cuff muscle strength, intrinsic sensory disturbance, and joint stability are associated with shoulder pain in male high school volleyball players. Additionally, there was an anticipation that a substantial proportion of players would experience shoulder pain but refrain from reporting it to coaches., Methods: Forty-nine male volleyball players aged 15-17 years were evaluated between February and June 2023. Questionnaires assessed the prevalence of shoulder pain during spiking and/or serving, as well as the frequency of reporting this pain to coaches. Various factors, including acromio-humeral distance, shoulder ROM, isometric strength, proprioception, joint stability (Upper Quarter Y-Balance Test), joint position sense, and upper extremity power (Seated Medicine Ball Throw Test; SMBT), were quantified. Logistic regression analyses was conducted to explore potential connections between these variables and shoulder pain., Results: Shoulder pain was reported by 39% of participants, but it was rarely communicated to coaches (95%). Jump serves (odds ratio 1.84, p=0.02) and reduced shoulder IR ROM (odds ratio 0.94, p=0.03) were associated with shoulder pain., Conclusion: This study provides crucial insights into the prevalence, severity, and associated factors of shoulder pain among male high school volleyball players. The findings underscore the importance of improving athlete-coach communication to facilitate early intervention and preventive measures. Significant associations were observed between the use of jump serves, reduced shoulder internal rotation range of motion, and shoulder pain, highlighting the relevance of specific volleyball techniques in injury prevention. These findings offer valuable guidance to coaches and trainers in developing interventions aimed at mitigating the risk of shoulder pain and enhancing player performance., (Copyright © 2024. Published by Elsevier Inc.)

Background: We have previously reported a saline-linked bipolar clamp-crush technique as a novel robotic liver resection method. Herein, we present the surgical techniques and outcomes of robotic left hepatectomy using the Glissonean approach and our liver transection technique., Methods: The key procedures included the following: (1) encircling the left Glissonean pedicle using the Tip-Up fenestrated grasper, (2) dissecting the liver parenchyma using the saline-linked bipolar clamp-crush technique, (3) moving the endoscope one trocar to the right to facilitate visualisation of the liver transection plane, and (4) stapling the left pedicle and left hepatic vein. Seven robotic left hepatectomies were performed., Results: The median operative time and estimated blood loss were 395 min and 50 mL, respectively. The median length of postoperative hospital stay was 9 days. Pneumothorax was the only severe postoperative complication., Conclusions: Robotics left hepatectomy using the Glissonean approach and the saline-linked bipolar clamp-crush technique appears safe and feasible., (© 2024 John Wiley & Sons Ltd.)

Aim: Interprofessional collaboration between medical professionals is an essential aspect of caring for Japan's super-aging population, but studies on the subject have been geographically limited in scope. Therefore, we aimed to determine the factors necessary for pharmacists to achieve interprofessional collaboration in home-based care in Japan., Methods: Our online questionnaire survey was conducted from February 1, 2023 to February 15, 2023. The Japan Pharmaceutical Association introduced this survey to their membership, and survey letters were sent to hospitals and community pharmacies that were not included in this association., Results: The study involved 1156 and 36 participants working in a community pharmacy and a hospital, respectively. These participants were divided into the collaboration group and the non-collaboration group. Enough time for visiting patients and for preparing the first visiting plan was important to achieve interprofessional collaboration in home-based care for a hospital pharmacist. More than 5 years of experience working in home-based care and participation in pre-visit conferences, discharge conferences, meetings with persons in charge of services were independent factors in collaborating with other medical staff for a community pharmacist., Conclusion: Hospital pharmacists with enough time to prepare and visit for home-based care and community pharmacists working in home-based care for more than 5 years and who share information on home-based care with medical staff achieved interprofessional collaboration in home-based care. Geriatr Gerontol Int 2024; 24: 1008-1014., (© 2024 Japan Geriatrics Society.)

With the declining birth rates and aging societies in developed countries, the average age of the working population is increasing. Older people tend to get tired more easily, so prevention of fatigue is important to improve the quality of life for older workers. This study aimed to assess the mechanism of fatigue in older people, especially focused on relation between dysfunction of erythrocyte and fatigue. Total power (TP), which is the value of autonomic nerve activity, was measured as a value of fatigue and significantly decreased in workers with aging. As properties of senescent erythrocytes, the erythrocyte sedimentation rate and damaged erythrocytes population increased with aging and correlated with TP. These results suggested that the accumulation of damaged erythrocytes contributes to fatigue. Recent studies revealed that senescence-associated secretory phenotype (SASP), a phenomenon in which senescent cells secrete a variety of cytokines, affected hematopoiesis in bone marrow. We analyzed the effects of SASP factors on erythropoiesis and found that Interleukin -1α (IL-1α) suppressed erythrocyte differentiation of hematopoietic stem cells in vitro. We also showed that IL-1α levels in human blood and saliva increase with aging, suggesting the possibility that IL-1α level in saliva can be used to predict the decline in hematopoietic function., (© 2024. The Author(s), under exclusive licence to Springer Nature B.V.)

Background: Identifying patients who can be spared nonbeneficial surgery is crucial, as pancreatic cancer surgery is highly invasive, with substantial negative effects on quality of life. The study objective was to investigate a useful indicator of patients who do not gain prognostic benefit from radical surgery after neoadjuvant therapy for resectable and borderline resectable pancreatic cancer., Method: We compared factors among 609 patients with resectable or borderline resectable pancreatic cancer receiving neoadjuvant therapy during 2005-2019. Patients were divided into a poor-prognosis group (no surgery or postresection recurrence within a year) and a good-prognosis group (no recurrence or recurrence >1 year after resection)., Results: Patients who experience a recurrence within a year of resection (poor-prognosis group) did no better than patients who received neoadjuvant therapy and progressed but never made it to surgery. The value of carbohydrate antigen 19-9 after neoadjuvant therapy was the most significant indicator to predict the poor prognosis group and the elevation of carbohydrate antigen 19-9 (>200 U/mL) identified only poor prognosis group with high specificity of 96.6%. The overall survival of patients with more than 200 of carbohydrate antigen 19-9 after neoadjuvant therapy was significantly very poor and their 2-year survival rate was only 41.4%., Conclusion: A striking elevation of carbohydrate antigen 19-9 after neoadjuvant therapy for resectable or borderline resectable pancreatic cancer is a good indicator of poor prognosis. Patients with carbohydrate antigen 19-9 >200 U/mL after neoadjuvant therapy should not undergo radical surgery., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Alarmins resulting from cell death or oxidative stress are involved in the development of Kawasaki disease (KD) vasculitis. In a previous study, we demonstrated the potential role of interleukin (IL)-33 as an alarmin in the development of KD vasculitis. Although edematous dissociation (necrotic change) of the tunica media is thought to be a major source of IL-33 in KD vasculitis, it has not yet been elucidated., Methods and Results: We investigated the impact of IL-33 released from necrotic human coronary artery smooth muscle cells (HCASMCs) on human coronary artery endothelial cells (HCAECs) using a coculture assay. Subsequently, we evaluated the anti-inflammatory effects of anti-IL-33 and anti-suppression of tumorigenicity 2 (ST2) antibodies compared with conventional therapies of KD, such as high-dose IgG or anti-tumor necrosis factor (TNF)-α antibody. Primary necrosis of HCASMCs induced significant release of IL-33. In cocultures of necrotic HCASMCs with HCAECs, the necrotic HCASMCs significantly induced the production of various proinflammatory cytokines in the HCAECs. Anti-IL-33 and anti-ST2 antibodies exhibited unique inhibitory effects on the production of platelet-derived growth factor-BB or IL-12(p70) in HCAECs., Conclusions: There is potential involvement of edematous dissociation of the tunica media in the development of KD vasculitis. Furthermore, the distinctive anti-inflammatory effects of the anti-IL-33/ST2 axis drugs suggest novel therapeutic options for patients with refractory KD.

Adrenocorticotropic hormone (ACTH) therapy is effective for infantile epileptic spasms syndrome (IESS) but can induce immunosuppression. In Japan, Bacille Calmette-Guérin (BCG) vaccination, modified in 2013 to reduce osteitis/osteomyelitis risk, coincides with the peak onset age of IESS. This raises concerns about infection risks when administering ACTH therapy post-vaccination. To evaluate the impact of BCG vaccination timing on treatment decisions, we retrospectively reviewed the medical records of 86 IESS patients at our hospital (1996-2020). Infants who received ACTH therapy within eight weeks of BCG vaccination experienced no serious adverse events. Four patients deferred or opted out of ACTH therapy, with seizure remission taking 2-15 weeks. The overlap between IESS onset and BCG vaccination period presents clinical challenges in determining the appropriate timing for ACTH therapy. Further epidemiological and immunological research is needed to clarify the relationship between ACTH therapy and BCG-associated adverse events and to optimize treatment strategies and vaccination schedules., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)

Objectives: Comparative effectiveness of 13-valent pneumococcal conjugate vaccine (PCV13), 23-valent polysaccharide vaccine (PPSV23), and their combinations for adults in preventing invasive pneumococcal disease (IPD) has yet to be thoroughly investigated. We aimed to estimate the comparative effectiveness of preventing IPD, using population-based data from the Veterans Health Administration (VHA) in the United States., Methods: We included all patients who were between 65 and 74 years, had established primary care within VHA between 2005 and 2021, and had not received any prior pneumococcal vaccination. We measured time-to-event from cohort enrolment to the onset of IPD, considering death a competing risk event, and used Cox regression models to estimate cause-specific hazards. PCV13 only, PPSV23 only, PCV13 after PPSV23, and PPSV23 after PCV13 were incorporated into models as time-dependent covariates. Patient demographics and comorbidities were also included in the model., Results: A total of 3 044 067 patients were enrolled in the cohort, with 863 958 deaths (28.4%) and 1731 cases of IPD (0.06%) during the study period. The overall incidence rate of IPD in this population was 5.36 per 100 000 patient-years. A total of 921 070 patients (30.3%) received at least one dose of effective pneumococcal vaccine. In multivariate analysis adjusted for comorbidities, PCV13 alone was not associated with the reduced risk of IPD, whereas PPSV23 had protective association with IPD incidence (adjusted hazard ratio [aHR], 0.70; 95% CI, 0.59-0.83). When combined, PCV13 followed by PPSV23 had a stronger protective association (aHR, 0.54; [0.36-0.83]) compared with PPSV23 followed by PCV13 (aHR, 0.73; [0.58-0.91])., Discussion: In this large cohort study at the VHA, the combination of PCV13 and PPSV23, particularly PCV13 followed by PPSV23, was associated with a lower risk of IPD, indicating additional benefits in combined vaccinations with potential importance in vaccination order. Further studies are needed to evaluate the effect of newer pneumococcal vaccines., (Copyright © 2024 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

A 74-year-old woman was diagnosed with invasive breast ductal carcinoma, cT2N0M1 (PUL), stage Ⅳ, and treated with abemaciclib and letrozole. The day after drug administration, the patient developed a fever of 38℃ and dyspnea upon exertion, and was diagnosed with drug-induced pneumonia. Steroid pulse therapy was administered during hospitalization, and the patient was discharged after the dose of prednisolone was gradually reduced. This case shows that, when abemaciclib is administered, drug-induced lung injury can occur within 1 week.

Purpose: To compare surgical results between ab-externo microshunt surgery and trabeculectomy, focusing on postoperative corneal astigmatism., Study Design: Retrospective study., Methods: Subjects were patients with glaucoma who underwent either standalone ab-externo microshunt surgery or trabeculectomy. Data on ophthalmic examinations obtained preoperatively and 1, 3, and 5 months postoperatively were analyzed. To assess corneal astigmatism, two separate data sets measured by anterior segment optical coherence tomography and autorefractometer were evaluated. Multivariate linear mixed model analyses were conducted to identify factors associated with the astigmatism changes., Results: Sixty eyes were examined: 13 eyes underwent microshunt surgery, and 47 eyes underwent trabeculectomy. The total corneal astigmatism measurements by anterior segment optical coherence tomography (AS-OCT) were: - 1.15 ± 0.85 D and - 1.17 ± 0.81 D for the microshunt and trabeculectomy groups, respectively, preoperatively. At five months postoperatively they were - 0.92 ± 0.47 D and - 1.61 ± 0.83 D, respectively (P = 0.807 for the microshunt group and P = 0.005 for the trabeculectomy group: Wilcoxon signed-rank test). AS-OCT also indicated similar results for posterior corneal astigmatism. Autorefractometry also found the total corneal astigmatism was significantly changed only in the trabeculectomy group. The linear mixed model analysis revealed that trabeculectomy (P = 0.001), older age (P = 0.004), and longer postoperative period (P = 0.015) were correlated with greater astigmatism changes. The intraocular pressures significantly decreased following both surgical treatments., Conclusions: Standalone ab-externo microshunt surgery has less effect on corneal astigmatism during a 5 month period than trabeculectomy. Both surgical procedures significantly reduced intraocular pressure., (© 2024. Japanese Ophthalmological Society.)

Purpose: To assess the safety and efficacy of ripasudil for retinopathy of prematurity (ROP)., Study Design: Phase 1/2, multicenter, open-label, single-arm, 12-week clinical trial., Methods: Infants born with gestational age (GA) of ≤ 32 weeks or weight of ≤ 1500 g with zone I or II, ≥ stage 1, ROP in both eyes were enrolled. Ripasudil eye drops were administered to patients in both eyes. Phase 1 was a dose-escalation study (once daily for 1 week, then twice daily for 2 weeks); an additional dosing up to 9 weeks was allowed if no safety issues occurred. In phase 2, ripasudil was administered twice daily for up to 12 weeks. Adverse events were assessed. The proportion of patients with type 1 ROP progression, number of days for type 1 ROP progression, and progression to the most advanced ROP stage were estimated., Results: Twenty-four infants were enrolled (phase 1, n = 3; phase 2, n = 21). Nineteen and four patients experienced systemic and ocular adverse events, respectively. Efficacy endpoints were not different between the ripasudil and historical control groups. However, in the GA ≤ 27 weeks subgroup, fewer patients progressed to type 1 ROP in the ripasudil than in the historical control group (P = 0.09). In the GA ≤ 27 weeks subgroups, the 25th percentile for the number of days for type 1 ROP progression was 22 days in the historical control group and 44 days in the ripasudil group., Conclusion: Ripasudil was safe and inhibited/delayed type 1 ROP progression, especially in infants with short GA., (© 2024. Japanese Ophthalmological Society.)

Background and Objectives: This study aimed to evaluate the prognostic value of aberrant right hepatic artery (A-RHA) involvement in patients with pancreatic cancer (PC)., Methods: This study enrolled 474 patients who underwent upfront pancreatectomy or neoadjuvant treatment for resectable (R) or borderline resectable (BR) PC from four institutions. The patients were divided into three groups: A-RHA involvement group (n = 12), patients who had sole A-RHA involvement without major arterial involvement; BR-A group (n = 104), patients who had major arterial involvement; R/BR-PV group (n = 358), others., Results: All patients in the A-RHA involvement group underwent margin-negative resection. The median overall survival of the entire cohort in the A-RHA involvement, R/BR-PV, and BR-A groups was 41.2, 33.5, and 25.2 months, respectively. Although survival in the R/BR-PV group was significantly more favorable than that in the BR-A group (p = 0.0003), no significant difference was observed between the A-RHA involvement group and the R/BR-PV (p = 0.7332) and BR-A (p = 0.1485) groups., Conclusions: The prognosis of patients with PC and sole A-RHA involvement was comparable to that of patients with R/BR-PV., (© 2024 Wiley Periodicals LLC.)

Background & Aims: This study aimed to investigate the temporal changes in body composition following esophagectomy in patients with esophageal cancer using bioelectrical impedance analysis and to assess the prognostic implications of these changes., Methods: Our study included 528 patients who underwent esophagectomy and preoperative body composition measurements between January 2013 and June 2020. Postoperative body composition was measured in 493 patients at discharge as follows: 184 at 1 month, 144 at 2 months, 143 at 3 months, 103 at 6 months, 58 at 9 months, and 78 at 12 months., Results: Body weight (BW) continuously decreased until the 6 postoperative months (POMs), reaching -11.5% compared with preoperative levels. Subsequently, almost no change was observed at 12 POMs. Skeletal muscle mass (SMM) decreased until 3 POMs but gradually recovered after 3 POMs. Conversely, body fat mass (BFM) consistently decreased over time post-esophagectomy. The patients were categorized into moderate (>-10%) and severe (≤-10%) groups based on % BW, % SMM, and % BFM losses at 3 POMs. Severe SMM loss at 3 POMs correlated with reduced overall survival (OS) (3-year OS: 85.9% in moderate vs. 75.1% in severe, p = 0.035). BFM loss was associated with reduced recurrence-free survival (3-year RFS: 83.3% in moderate vs. 62.0% in severe, p = 0.011). Multivariate analysis identified pStages Ⅲ and Ⅳ, % SMM loss ≤ -10%, and % BFM loss ≤ -10% as independent factors for worse OS., Conclusion: Post-esophagectomy, distinct temporal changes in BW, SMM, and BFM are observed. Significant reductions in SMM and BFM 3 POMs indicate a poor long-term prognosis., Competing Interests: Conflict of interest Authors declare no conflict of interests for this article., (Copyright © 2024. Published by Elsevier Ltd.)

Pembrolizumab plus chemotherapy has been indicated as the first-line treatment for metastatic or unresectable locally advanced esophageal cancer. However, pretreatment biomarkers for predicting clinical outcomes remain unclear. We investigated the predictive value of inflammation-based prognostic scores in patients treated with pembrolizumab and chemotherapy. The Prognostic Nutritional Index (PNI), C-reactive protein/albumin ratio (CAR), neutrophil-to-lymphocyte ratio (NLR), and platelet-to-lymphocyte ratio (PLR) were calculated before initial treatment in 65 eligible patients with metastatic or unresectable locally advanced esophageal cancer receiving pembrolizumab plus CF therapy, and the relationship between these biomarkers and clinical outcomes was analyzed. The objective response rate (ORR) and progression disease (PD) were observed in 51% and 21% of all patients. Patients with PNI<39 have significantly worse treatment responses than those with PNI≥39 (ORR; 28% vs. 60%, PD; 44% vs. 13%, P =0.020). Progression-free survival (PFS) is significantly associated with the PNI and CAR ( P <0.001 and P =0.004, respectively). Overall survival (OS) is associated with PNI, CAR, and PLR ( P <0.001, P =0.008, and P =0.018, respectively). The PNI cutoff value of 39 is identified as an independent factor for PFS (odds ratio=0.27, 95% CI: 0.18-0.81, P =0.012) and OS (odds ratio=0.22, 95% CI: 0.08-0.59, P =0.003). Patients with PNI<39 have significantly worse 6-month PFS and 1-year OS than those with PNI≥39 (27.8% vs. 66.7%, 27.2% vs. 81.1%, respectively). In conclusion, inflammation-based prognostic scores are associated with survival in patients treated with pembrolizumab plus CF therapy. Pretreatment PNI is a promising candidate for predicting treatment response and survival., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Japan is one of the world's most aging societies and the number of elderly patients taking antithrombotic drugs is increasing. In recent years, dual antiplatelet therapy (DAPT), in which two antiplatelet drugs are administered, has become common in anticipation of its high therapeutic efficacy. However, there are concerns about increased bleeding complications in use of DAPT. Therefore, the goal of this study was to investigate the effects of DAPT in patients with traumatic brain injury (TBI). A prospective, multicenter, observational study was conducted from December 2019 to May 2021 to examine the effects of antithrombotic drugs and reversal drugs in 721 elderly patients with TBI. In the current study, the effect of DAPT on TBI was examined in a secondary analysis. Among the registered patients, 132 patients taking antiplatelet drugs only were divided into those treated with single antiplatelet therapy (SAPT) (n=106) and those treated with DAPT (n=26) prior to TBI. Glasgow Coma Scale (GCS) on admission, pupillary findings, course during hospitalization, and outcome were compared in the two groups. A similar analysis was performed in patients with a mild GCS of 13-15 (n=95) and a moderate to severe GCS of 3-12 (n=37) on admission. The DAPT group had significantly more males (67.0 % vs. 96.2 %), a higher severity of illness on admission, and a higher frequency of brain herniation findings on head CT (21.7 % vs. 46.2 %), resulting in significantly higher mortality (12.3 % vs. 30.8 %). The only significant factor for mortality was severity on admission. The rate of DAPT was significantly higher in patients with a moderate to severe GCS on admission, and DAPT was the only significant factor related to severity on admission. These findings suggest that the severity of injury on admission influences the outcome six months after injury, and that patients with more severe TBI on admission are more likely to have been treated with DAPT compared to SAPT., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Rotavirus (RV) vaccines were first introduced in 2011 and adopted for universal vaccination in 2020 in Japan. However, the effectiveness of RV vaccines after being adopted for universal vaccination in 2020 has not been reported. Because of the easy accessibility of clinics in Japan, many children are not usually hospitalized for RV gastroenteritis (RVGE). Therefore, in order to evaluate the impact of the RV vaccine since 2008, we investigated the incidence of hospitalization for RVGE as well as the frequency of children aged < 5 years who received medical treatment for severe RVGE at clinics in Shibata City, Japan. The RV vaccine coverage rate was 94.0% (1,046/1,113) in Shibata City after universal vaccination in 2020; this was a significant increase from previous rates. The incidence per 1000 person - years for RVGE hospitalization and severe RVGE at clinics were significantly higher among children aged < 3 years than in previous time periods. The incidence in children with all acute gastroenteritis (AGE) decreased significantly after universal vaccination during the COVID-19 pandemic. The proportion of severe RVGE among all AGE cases also decreased significantly after universal vaccination among children aged < 3 years (0.0%) and those aged 3-4 years (0.6%). There were significant differences in the distribution of RV genotypes isolated from the feces of children with RVGE between different eras divided by RV vaccination rates, especially G1P[8], which was the major genotype before it recently almost disappeared. Further studies are warranted to assess the impact of the COVID-19 pandemic.

Competing Interests: The authors declare that they have no conflict of interest.

The aim of this study is to estimate eye lens exposure dose when handling radiopharmaceuticals and interacting with patients receiving radiopharmaceuticals, and to verify the usefulness of X-ray protective goggles in mitigating such radiation exposure using phantoms. To evaluate radiation exposure during the handling of radiopharmaceuticals, we employed a fluorescent glass dosimeter to measure the radiation doses associated with 99m Tc, 123 I, 131 I, 111 In, and 18 F at distances of 30 cm and 60 cm, followed by calculation of the 3 mm dose equivalent rate (3DER). We then estimated the dose reduction rates for various scenarios, including the use of syringe shields and X-ray protective goggles with lead equivalences of 0.07, 0.15, 0.75, and 0.88 mmPb, as well as their combined application. X-ray protective goggles with lead equivalence of 0.75 mmPb outperformed those with 0.07 mmPb and 0.15 mmPb, for all radionuclides and at both source distances. X-ray protective goggles with 0.88 mmPb outperformed those with 0.75 mmPb during handling of 131 I and 111 In at a distance of 30 cm. In the remaining scenarios, X-ray protective goggles with 0.88 mmPb resulted in marginal reductions or no discernible additional effects. The overall shielding effect of X-ray protective goggles was less pronounced for 131I and 18F, but the combined use of a syringe shield with X-ray protective goggles with 0.75 or 0.88 mmPb improved the dose reduction rate for all scenarios. In simulating patient care, X-ray protective goggles with 0.88 mmPb demonstrated a dose reduction effect of approximately 50% or more. X-ray protective goggles could reduce the 3DER for the eye lens, and were more effective when combined with a syringe shield. It is valid to use a lead equivalence of 0.88 mmPb to fully harness the protective capabilities of X-ray shielding goggles when dealing with all five types of nuclides in clinical settings., Competing Interests: The authors have no conflicts of interest to disclose., (2024, National Center for Global Health and Medicine.)

Background: Delayed anterior cruciate ligament (ACL) reconstruction often causes residual anterolateral rotatory instability (ALRI) and consequent knee osteoarthritis, warranting the recommendation of early ACL reconstruction within 6 months after injury. Nonetheless, some cases show notable instability, even shortly after injury. The purpose of this study was to identify risk factors for an increase in quantitatively measured pivot shift in patients with ACL-deficient knees within 6 months after injury., Methods: Patients with primary ACL reconstruction within 6 months after injury and quantitative triaxial accelerometer measurements of preoperative pivot shift were included. Descriptive statistics were calculated for 11 independent variables (age, gender, time from injury to surgery, KT-1000, knee extension angle, lateral and medial posterior tibial slope angle, medial and lateral meniscus tears, ramp lesion and Tegner active scale). A single regression analysis was performed on the 11 items and acceleration during the pivot shift, and a multiple regression analysis was performed for items with p value less than 0.1., Results: Overall, 111 patients met the inclusion criteria. Single regression analysis showed that medial posterior tibial slope angle, medial meniscus tear and ramp lesion were significantly correlated with acceleration during the pivot shift ( p  < 0.001, p  = 0.04 and p  = 0.001). Multiple regression analysis identified medial posterior tibial slope angles and ramp lesions as independent factors for increased preoperative pivot shift ( p  = 0.005 and 0.01)., Conclusion: A steep medial posterior tibial slope angle and ramp lesion were independent risk factors for increased quantitatively measured pivot shift in patients with ACL-deficient knees., Level of Evidence: Level IV, case series 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.)

We report a case of rectosigmoid cancer complicated by pyogenic spondylitis. The patient was a 71-year-old man who had anemia and back pain. Endoscopy revealed a rectosigmoid tumor, confirmed to be well-differentiated adenocarcinoma. Imaging indicated rectosigmoid cancer with pyogenic spondylitis at the L1 vertebra. We performed radical resection (robotic-assisted Hartmann's procedure) after controlling the inflammation caused by pyogenic spondylitis. Colon cancer complicated by pyogenic spondylitis is rare. Here, we describe the mechanisms of this infection and treatment strategies along with a review of the literature., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. 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, Tanaka et al.)

The right gastroepiploic artery (RGEA) is frequently used in coronary artery bypass grafting (CABG) for right coronary artery bypass requiring long-term patency. We experienced a case of upper-third advanced gastric cancer after CABG using RGEA. The absence of enlarged lymph nodes (LNs) or distant metastasis was confirmed through computed tomography (CT), and the RGEA graft remained patent according to coronary CT angiography. Based on these findings, the patient underwent robotic total gastrectomy while preserving the RGEA graft without infra-pyloric LN dissection. We suggested that caution should be exercised to avoid injury to the graft during gastrectomy, and robotic surgery could contribute to safely preserving the RGEA. We should consider the decision to dissect the infra-pyloric LN for the patient's safety and curability., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. 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, Yamana et al.)

Introduction: Intrauterine herpes simplex virus (HSV) infection is uncommon and challenging to diagnose, requiring detection of HSV in skin lesions within 48 h post-birth., Case Presentation: A preterm female infant presented with the typical triad of blisters, microcephaly, and chorioretinitis, but the initial diagnostic approach was elusive due to negative results for TORCH pathogens from vesicles/serum. Referred at 7 months for developmental delay and epilepsy, her brain imaging showed calcification and cortical dysplasia. Polymerase chain reaction (PCR) of her preserved dried umbilical cord detected HSV-2 DNA, diagnosing intrauterine HSV infection. HSV-2 was later found in relapsed blisters at 8 months but not in cerebrospinal fluid or brain tissue. A literature review identified 104 congenital/intrauterine HSV cases; 28.8% presented the typical triad, and 50% were diagnosed using specimens collected 48 h post-birth., Conclusion: This case marks the first retrospective diagnosis of intrauterine HSV infection via PCR on preserved umbilical cord, underscoring its diagnostic value., (© 2024 S. Karger AG, Basel.)

Organelle stress exacerbates podocyte injury, contributing to perturbed lipid metabolism. Simultaneous organelle stresses can occur in the kidney in the diseased state; therefore, a thorough analysis of organelle communication is crucial for understanding the progression of kidney diseases. Although organelles closely interact with one another at membrane contact sites, limited studies have explored their involvement in kidney homeostasis. The endoplasmic reticulum (ER) protein, PDZ domain-containing 8 (PDZD8), is implicated in multiple-organelle-tethering processes and cellular lipid homeostasis. In this study, we aimed to elucidate the role of organelle communication in podocyte injury using podocyte-specific Pdzd8-knockout mice. Our findings demonstrated that Pdzd8 deletion exacerbated podocyte injury in an accelerated obesity-related kidney disease model. Proteomic analysis of isolated glomeruli revealed that Pdzd8 deletion exacerbated mitochondrial and endosomal dysfunction during podocyte lipotoxicity. Additionally, electron microscopy revealed the accumulation of abnormal, fatty endosomes in Pdzd8-deficient podocytes during obesity-related kidney diseases. Lipidomic analysis indicated that glucosylceramide accumulated in Pdzd8-deficient podocytes, owing to accelerated production and decelerated degradation. Thus, the organelle-tethering factor, PDZD8, plays a crucial role in maintaining mitochondrial and endosomal homeostasis during podocyte lipotoxicity. Collectively, our findings highlight the importance of organelle communication at the 3-way junction among the ER, mitochondria, and endosomes in preserving podocyte homeostasis.

Plasmonic substrates have been extensively investigated due to their potential applications in fluorescence microscopy, chemical sensing, and photochemical reactions. The optical properties of the substrate depend on the spatial and temporal features of the plasmon excited. Hence, the ability to directly visualize plasmon dynamics is crucial. In this study, we investigated the spatial and temporal properties of plasmon excitation in a plasmonic nanobowl substrate consisting of a periodic hexagonal array of nanoscale bowl-like structures developed with self-assembly. Near-field transmission imaging revealed that multiple plasmon resonance bands are observed from visible to near-infrared spectral region, and the optical contrast of the image is dependent on the observed band. Near-field two-photon photoluminescence microscopy revealed that the probability of excitation inside each nanoscale bowl-like structure is greater than that in the surrounding area. Near-field time-resolved imaging revealed that the nanobowl substrate exhibited a substantially long plasmon dephasing time, exceeding 12 fs. Based on the spectral features of the near-field and far-field spectra, we found that optically dark plasmon mode is excited by the near-field illumination and only partly contributes to the long dephasing time observed. This fact indicates that the dephasing time is extended by some other mechanism in the periodic substrate. We revealed from this study that the enhanced optical fields induced in the nanobowl structure originate from the photosynergetic effect of the cavity mode and plasmon mode excited., (© 2024 Author(s). Published under an exclusive license by AIP Publishing.)

This study aimed to develop a method to evaluate the quality of bovine in vitro fertilized (IVF) embryos based on gene expression profiling via whole-transcriptome amplification. The expression of 11 developmentally important genes in individual bovine in vivo-derived (IVD) and IVF embryos were examined. Gene expression profiling was conducted by classifying the expression level of each gene in individual embryos as low, medium, or high. The IVF group had a higher (P < 0.01) proportion of embryos with low expression of SOX2, NANOG, and FGF4. In addition, a correlation analysis between the expression levels of each gene in individual embryos demonstrated that the relationship between gene expression differed with respect to IVD and IVF embryos. Our results suggest that the expression profiling of developmentally important genes using IVD embryos as normal controls could be a useful indicator for evaluating the quality of bovine IVF embryos.

Objective: The association between sarcopenia and prognosis in patients with platinum-resistant recurrent ovarian cancer remains unclear. This study investigated whether sarcopenia is a prognostic factor in patients with platinum-resistant recurrent ovarian cancer., Methods: A total of 52 patients diagnosed with platinum-resistant recurrent ovarian cancer who had undergone non-platinum chemotherapy at our institution formed our study population. Body composition and clinicopathological data of these patients were collected retrospectively. Abdominal computed tomography (CT) scans obtained at the time of platinum-resistant recurrent ovarian cancer diagnosis were used to measure the cross-sectional area of skeletal muscles at L3 level. These values were corrected for height to calculate the skeletal muscle index, and accordingly sarcopenia was defined. Overall survival was defined as the primary outcome of the study. The impact of sarcopenia on overall survival was assessed using Cox proportional hazards regression models with inverse probability weighting of treatment based on propensity scores and log-rank tests., Results: The median patient age was 63 years (IQR: 53-71). The most common International Federation of Gynecology and Obstetrics (FIGO) 2018 stage was stage III (50%) and the most common histology was serous or adenocarcinoma (67.3%). The optimal cut-off value of skeletal muscle index was 35.6 cm 2 /m 2 , which was calculated using the data of 21 patients with sarcopenia and 31 without sarcopenia. Sarcopenia was significantly associated with shorter overall survival (HR 1.93; 95% CI 1.06-3.49; p=0.03). Subgroup analysis based on patient attributes and prognostic factors suggested a consistent prognostic impact of sarcopenia. Sarcopenia was identified as a significant risk factor, particularly in patients who had higher CA125 levels (HR, 2.47; 95% CI, 1.07 to 5.69; p=0.034) and a higher neutrophil-to-lymphocyte ratio (HR, 2.92; 95% CI, 1.02 to 8.31; p=0.045)., Conclusion: Sarcopenia significantly shortened the overall survival of patients with platinum-resistant recurrent ovarian cancer., Competing Interests: Competing interests: None declared., (© IGCS and ESGO 2024. Re-use permitted under CC BY-NC. No commercial re-use. Published by BMJ.)