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Objective: The objective of this study was to evaluate the efficacy and safety of dose-dense gemcitabine and cisplatin (ddGC) as neoadjuvant chemotherapy for muscle-invasive bladder cancer (MIBC)., Methods: Patients with locally advanced MIBC (cT2aN0M0-cT4N1M0) who received ddGC between December 2017 and December 2023 were included. Regimens of ddGC with pegfilgrastim were administered every 2 weeks for 4 cycles, followed by radical cystectomy. The pathological complete response (CR) (pT0N0) and objective response (OR) (

Objective: To report the outcomes of repeat biopsies, metastasis and survival in the Prostate Cancer Research International: Active Surveillance (PRIAS)-JAPAN study, a prospective observational study for Japanese patients, initiated in 2010., Patients and Methods: At the beginning, inclusion criteria were initially low-risk patients, prostate-specific antigen (PSA) density (PSAD) <0.2, and ≤2 positive biopsy cores. As from 2014, GS3+4 has also been allowed for patients aged 70 years and over. Since January 2021, the age limit for Gleason score (GS) 3 + 4 cases was removed, and eligibility criteria were expanded to PSA ≤20 ng/mL, PSAD <0.25 nd/mL/cc, unlimited number of positive GS 3 + 3 cores, and positive results for fewer than half of the total number of cores for GS 3 + 4 cases if magnetic resonance imaging fusion biopsy was performed at study enrolment or subsequent follow-up. For patients eligible for active surveillance, PSA tests were performed every 3 months, rectal examination every 6 months, and biopsies at 1, 4, 7 and 10 years, followed by every 5 years thereafter. Patients with confirmed pathological reclassification were recommended for secondary treatments., Results: As of February 2024, 1302 patients were enrolled in AS; 1274 (98%) met the eligibility criteria. The median (interquartile range) age, PSA level, PSAD, and number of positive cores were 69 (64-73) years, 5.3 (4.5-6.6) ng/mL, 0.15 (0.12-0.17) ng/mL, and 1 (1-2), respectively. The clinical stage was T1c in 1089 patients (86%) and T2 in 185 (15%). The rates of acceptance by patients for the first, second, third and fourth re-biopsies were 83%, 64%, 41% and 22%, respectively. The pathological reclassification rates for the first, second, third and fourth re-biopsies were 29%, 30%, 35% and 25%, respectively. The 1-, 5- and 10-year persistence rates were 77%, 45% and 23%, respectively. Six patients developed metastasis, and one patient died from prostate cancer., Conclusion: Pathological reclassification was observed in approximately 30% of the patients during biopsy; however, biopsy acceptance rates decreased over time. Although metastasis occurred in six patients, only one death from prostate cancer was recorded., (© 2024 BJU International.)

Introduction: In certain cases of rectal malignancy in which invasion is confined to the prostate and/or seminal vesicles, bladder-sparing surgery may be chosen instead of total pelvic exenteration. However, even if the bladder is preserved, postoperative urinary dysfunction and vesicourethral anastomotic leakage are concern., Materials and Surgical Technique: We employ various techniques based on robot-assisted radical prostatectomy for reconstructing the urinary tract. These techniques include advanced reconstruction of vesicourethral support, total anatomical reconstruction, and a method called anterior reconstruction. In addition, suture fixation of bladder to the anterior abdominal wall, and re-approximation of bladder by peritoneal suture were done., Discussion: Reliable robot-assisted vesicourethral anastomosis and reinforcement of the anastomotic wall could potentially enhance the self-voiding rate and decrease the risk of anastomotic failure., (© 2024 Asia Endosurgery Task Force and Japan Society of Endoscopic Surgery and John Wiley & Sons Australia, Ltd.)

Background: Active surveillance for prostate cancer was initiated in the early 2000s. We assessed the long-term outcomes of active surveillance in Japan., Methods: This multicenter prospective observational cohort study enrolled men aged 50-80 years with stage cT1cN0M0 prostate cancer in 2002 and 2003. The eligibility criteria included serum prostate-specific antigen level ≤ 20 ng/mL, ≤ 2 positive cores per 6-12 biopsy samples, Gleason score ≤ 6, and cancer involvement < 50% in the positive core. Patients were encouraged to undergo active surveillance. Prostate-specific antigen levels were measured bimonthly for 6 months and every 3 months thereafter. Triggers for recommending treatment were prostate-specific antigen doubling time of < 2 years and pathological progression on repeat biopsy., Results: Among 134 patients, 118 underwent active surveillance. The median age, prostate-specific antigen level at diagnosis, and maximum cancer occupancy were 70 years, 6.5 ng/mL, and 11.2%, respectively. Ninety-one patients had only one positive cancer core. The median observation period was 10.7 years. At 1 year, 65.7% underwent a repeat biopsy, and 37% of patients experienced pathological progression. The active surveillance continuation rates at 5, 10, and 15 years were 28%, 9%, and 4%, respectively. One prostate cancer-related death occurred in a patient who refused treatment despite pathological progression at the one-year repeat biopsy., Conclusion: Active surveillance according to this study protocol was associated with conversion to the next treatment without delay, when indicated, despite the selection criteria and follow-up protocols being less rigorous than those recommended in current international guidelines., (© 2024. The Author(s) under exclusive licence to Japan Society of Clinical Oncology.)

Transurethral procedures such as direct vision internal urethrotomy and urethral dilation have been the traditional treatments for urethral strictures. However, transurethral procedures are associated with high recurrence rates, resulting in many uncured cases and prompting major international urological societies to recommend urethroplasty as the standard treatment owing to its high success rate. In contrast, many Japanese general urologists have little doubts about treating urethral strictures with transurethral treatment. Therefore, urethral stricture treatments in Japan are not in line with those used in other countries. To address this, the Trauma, Emergency Medicine, and Reconstruction Subcommittee of the Japanese Urological Association has developed guidelines to offer standardized treatment protocols for urethral stricture, based on international evidence and tailored to Japan's medical landscape. These guidelines target patients with a clinically suspected urethral stricture and are intended for urologists and general practitioners involved in its diagnosis and treatment. Following the Minds Clinical Practice Guideline Development Manual 2020, the committee identified eight critical clinical issues and formulated eight clinical questions using the "patient, intervention, comparison, and outcome" format. A comprehensive literature search was conducted. For six clinical questions addressed by the existing guidelines or systematic reviews, the level of evidence was determined by qualitative systematic reviews. Quantitative systematic reviews and meta-analyses were performed for the two unique clinical questions. The recommendation grades were determined using the Delphi method and consensus by the committee. These guidelines will be useful to clinicians in daily practice, especially those involved in the care of urethral strictures., (© 2024 The Japanese Urological Association.)

Plastics can contain two types of organic contaminants; absorbed from ambient water, and already contained as additives. To investigate the bioaccumulation of these substances, we conducted two types of exposure experiments using mussels and polyethylene microplastics with absorbed PCBs and containing four types of additives (BDE209, DBDPE, UV327 and UV234). After dietary exposure for 15 days, significantly higher concentrations of total PCBs, UV327 and UV234 were detected in the gonad of exposed groups than in the control groups, respectively. However, no significant differences in BDE209 or DBDPE levels were observed between the control and exposure groups. Although a higher transfer ratio was shown for PCB congeners with octanol-water partition coefficients (logK ow ) below 7, the ratio was lower for higher-hydrophobic PCBs with logK ow above 7. This suggests that higher hydrophobic compounds (not only highly chlorinated PCBs, but also BDE209 and DBDPE) tend not to desorb or leach from plastics., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Background and Purpose: Spread-through air space (STAS) is an unfavorable factor in patients with lung cancer treated with surgery. However, the relationship between the treatment outcomes of stereotactic body radiation therapy (SBRT) for lung cancer and STAS has not been adequately investigated. This study aimed to evaluate the impact of tumor cells in the air space (TCIAS), which show a STAS burden, on treatment outcomes in patients with early-stage lung cancer treated with SBRT., Materials and Methods: Data of patients who underwent SBRT for early-stage lung cancer treated with SBRT were retrospectively reviewed. The influence of the TCIAS status on local progression-free (LPF), regional failure-free (RFF), distant failure-free (DFF), progression-free survival (PFS), and overall survival (OS) rates was assessed using univariate and multivariate analyses., Results: Overall, 68 patients were included. The median follow-up time was 24.3 months. For patients positive/negative for TCIAS, the 2-year LPF, RFF, DFF, PFS, and OS rates were 81.4 %/91.1 %, 73.7 %/96.2 %, 55.9 %/75.3 %, 55.0 %/84.6 %, and 67.8 %/92.2 %, respectively. In the multivariate analysis, TCIAS-positive was a significant unfavorable factor for RFF (hazard ratio [HR]: 4.10; 95 % confidence interval [CI]: 1.04-16.16, p = 0.04), DFF (HR: 2.61, 95 % CI: 1.03-6.57, p = 0.04), and PFS (HR: 2.36; 95 % CI: 1.05-5.30, p = 0.04). By contrast, TCIAS-positive was not a significant risk factor for LPF and OS., Conclusion: TCIAS-positive is an unfavorable factor for regional and distant failure after SBRT. TCIAS status may be useful in predicting the treatment outcome of SBRT for early-stage lung cancer., Competing Interests: Toshiyuki Kozuki received honorarium from MSD, Ono, Kyowa Hakko Kirin, AstraZeneca, Boehringer Ingelheim, Chugai, TAIHO, Eli Lilly, Bristol Myers Squibb, Pfizer, Merck Biopharma, Nippon Kayaku, Novartis, Bayer, Sawai and AMGEN, consulting fee from Chugai, AstraZeneca, Ono, Pfizer, Daiichi-Sankyo, Bayer, and Abbvie, and received research funding MSD, Kyowa Hakko Kirin, AstraZeneca, Eli Lilly, Pfizer, Chugai, TAIHO, Ono, Bristol-Myers, Merck Biopharma, Daiichi-Sankyo, AbbVie, AMGEN, Sanofi, Eisai, Labcorp Development, IQVIA Services, Gilead Sciences, Pfizer, and Bayer. All other authors declare that they have no conflict of interest., (© 2024 The Author(s).)

The relationships between the therapeutic effects of immune checkpoint inhibitors (ICIs) and the intestinal flora have attracted increasing attention. However, the effects of oral probiotics on the efficacies of ICIs used to treat non-small-cell lung cancer (NSCLC) remain unclear. We investigated the effects of probiotics on the efficacies of ICIs in patients treated with and without chemotherapy. We investigated patients with advanced NSCLC on ICI monotherapy or combination ICI and chemotherapy using the Okayama Lung Cancer Study Group Immunotherapy Database (OLCSG-ID) and the Okayama Lung Cancer Study Group Immunochemotherapy Database (OLCSG-ICD). In total, 927 patients (482 on ICI monotherapy, 445 on an ICI + chemotherapy) were enrolled. Most were male, of good performance status, smokers, and without epidermal growth factor receptor (EGFR)/anaplastic lymphoma kinase (ALK) mutations. Probiotics were administered to 19% of patients on ICI monotherapies and 17% of those on ICIs + chemotherapy. Of the former patients, progression-free survival (PFS) and overall survival (OS) were significantly better in the probiotics group (PFS 7.9 vs. 2.9 months, hazard ratio [HR] 0.54, p < .001; OS not attained vs. 13.1 months, HR 0.45, p < .001). Among patients receiving ICI and chemotherapy, there were no significant differences in PFS between those on probiotics and not but OS was significantly better in the probiotics group (PFS 8.8 vs. 8.6 months, HR 0.89, p = .43; OS not attained vs. 22.6 months, HR 0.61, p = .03). Patients on probiotics experienced better outcomes following ICI treatment., (© 2024 UICC.)

Objectives: Immune checkpoint inhibitors and enfortumab vedotin have opened new avenues for sequential treatment strategies for locally advanced/metastatic urothelial carcinoma (la/mUC). In the pre-enfortumab vedotin era, many patients could not receive third-line treatment owing to rapid disease progression and poor general status. This study aimed to analyze real-world sequential treatment practices for la/mUC in Japan, with a focus on patients who do not receive third-line treatment., Methods: We analyzed data for 1023 la/mUC patients diagnosed between January 2020 and December 2021 at 54 institutions from a Japanese nationwide cohort., Results: At the median follow-up of 28.5 months, the median overall survival from first-line initiation for 905 patients who received systemic anticancer treatment was 19.1 months. Among them, 81% and 32% received second- and third-line treatment. Notably, 52% had their treatment terminated before the opportunity for third-line treatment. Multivariate logistic regression analysis revealed that low performance status (≥1), elevated neutrophil-to-lymphocyte ratio (≥3), and low body mass index (<21 kg/m 2 ) at the start of first-line treatment were independent risk factors for not proceeding to third-line treatment (p = 0.0024, 0.0069, and 0.0058, respectively). In this cohort, 33% had one of these factors, 36% had two, and 15% had all three., Conclusions: This study highlights the high frequency of factors associated with poor tolerance to anticancer treatment in la/mUC patients. The findings suggest the need to establish optimal sequential treatment strategies, maximizing efficacy within time and tolerance constraints, while concurrently providing strong supportive care, considering immunological and nutritional aspects., (© 2024 The Authors. International Journal of Urology published by John Wiley & Sons Australia, Ltd on behalf of The Japanese Urological Association.)

Palindromic rheumatism (PR) is a type of cryptogenic paroxysmal arthritis. Several genes may be involved in PR pathogenesis; however, conducting comprehensive case-control genetic studies for PR poses challenges owing to its rarity as a disease. Moreover, case-control studies may overlook rare variants that occur infrequently but play a significant role in pathogenesis. This study aimed to identify disease-related genes in Japanese patients with PR using whole-genome sequencing (WGS) and rare-variant analysis. Genomic DNA was obtained from two familial cases and one sporadic case, and it was subjected to WGS. WGS data of 104 healthy individuals obtained from a public database were used as controls. We performed data analysis for rare variants on detected variants using SKAT-O, KBAC, and SKAT, and subsequently defined significant genes. Significant genes combined with variants shared between the cases were defined as disease-related genes. We also performed pathway analysis for disease-related genes using Reactome. We identified 2,695,244 variants shared between cases; after excluding polymorphisms and noise, 74,640 variants were detected. We identified 540 disease-related genes, including 1,893 variants. Furthermore, we identified 32 significant pathways. Our results indicate that the detected genes and pathways in this study may be involved in PR pathogenesis.

Thermal management is critical in contemporary electronic systems, and integrating diamond with semiconductors offers the most promising solution to improve heat dissipation. However, developing a technique that can fully exploit the high thermal conductivity of diamond, withstand high-temperature annealing processes, and enable mass production is a significant challenge. In this study, the successful transfer of AlGaN/GaN/3C-SiC layers grown on Si to a large-size diamond substrate is demonstrated, followed by the fabrication of GaN high electron mobility transistors (HEMTs) on the diamond. Notably, no exfoliation of 3C-SiC/diamond bonding interfaces is observed even after annealing at 1100 °C, which is essential for high-quality GaN crystal growth on the diamond. The thermal boundary conductance of the 3C-SiC-diamond interface reaches ≈55 MW m -2  K -1 , which is efficient for device cooling. GaN HEMTs fabricated on the diamond substrate exhibit the highest maximum drain current and the lowest surface temperature compared to those on Si and SiC substrates. Furthermore, the device thermal resistance of GaN HEMTs on the diamond substrate is significantly reduced compared to those on SiC substrates. These results indicate that the GaN/3C-SiC on diamond technique has the potential to revolutionize the development of power and radio-frequency electronics with improved thermal management capabilities., (© 2023 Wiley‐VCH GmbH.)

The Japanese Urological Association's guidelines for the treatment of renal trauma were published in 2016. In conjunction with its revision, herein, we present the new guidelines for overall urotrauma. Its purpose is to provide standard diagnostic and treatment recommendations for urotrauma, including iatrogenic trauma, to preserve organ function and minimize complications and fatality. The guidelines committee comprised urologists with experience in urotrauma care, selected by the Trauma and Emergency Medicine Subcommittee of the Specialty Area Committee of the Japanese Urological Association, and specialists recommended by the Japanese Association for the Surgery of Trauma and the Japanese Society of Interventional Radiology. The guidelines committee established the domains of renal and ureteral, bladder, urethral, and genital trauma, and determined the lead person for each domain. A total of 30 clinical questions (CQs) were established for all domains; 15 for renal and ureteral trauma and five each for the other domains. An extensive literature search was conducted for studies published between January 1, 1983 and July 16, 2020, based on the preset keywords for each CQ. Since only few randomized controlled trials or meta-analyses were found on urotrauma clinical practice, conducting a systematic review and summarizing the evidence proved challenging; hence, the grade of recommendation was determined according to the 2007 "Minds Handbook for Clinical Practice Guidelines" based on a consensus reached by the guidelines committee. We hope that these guidelines will be useful for clinicians in their daily practice, especially those involved in urotrauma care., (© 2023 The Japanese Urological Association.)

An 80-year-old woman who had been diagnosed with an endobronchial carcinoid tumor visited our hospital for treatment with an endoscopic technique. However, a bronchoscopic examination at our hospital showed spontaneous regression of the tumor at the orifice of the right middle lobar bronchus. Chest computed tomography five months later revealed no local recurrence. This is the second report of an endobronchial carcinoid tumor vanishing after an endoscopic biopsy.

The environment around deep sea hydrothermal vents is characterized by an abundance of sulfur compounds, including toxic hydrogen sulfide. However, numerous communities of various invertebrates are found in it. It is suggested that invertebrates in the vicinity of hydrothermal vents detoxify sulfur compounds by biosynthesis of taurine-related compounds in the body. On the other hand, the vent endemic polychaete Alvinella pompejana has spherocrystals composed of sulfur and other metals in its digestive tract. It was considered that the spherocrystals contribute to the regulation of sulfur in body fluids. Paralvinella spp. and Polynoidae. gen. sp. live sympatrically and in areas most affected by vent fluid. In this study, we focused on the digestive tract of Paralvinella spp. and Polynoidae. gen. sp. to examine whether they have spherocrystals. We also investigated the possible involvement of bacteria in the digestive tract in spherulization. Examination with a scanning electron microscope (SEM) equipped with Energy Disperse X-ray Spectroscopy (EDS) detected spherocrystals containing sulfur and iron in the digestive tract of Paralvinella spp. In contrast, such spherocrystals were not observed in that of Polynoidae. gen. sp. although sulfur is detected there by inductively coupled plasma-optical emission spectrometry (ICP-OES). Meta-16S rRNA analysis indicated that the floras of the digestive tracts of the two species were very similar, suggesting that enteric bacteria are not responsible for spherocrystal formation. Analysis of taurine-related compounds indicated that the digestive tissues of Polynoidae. gen. sp. contain a higher amount of hypotaurine and thiotaurine than those of Paralvinella spp. Therefore, the two sympatric polychaetes use different strategies for controlling sulfur, i.e., Paralvinella spp. forms spherocrystals containing elemental sulfur and iron in the digestive tract, but Polynoidae. gen. sp. accumulates taurine-related compounds instead of spherocrystals. Such differences may be related to differences in their lifestyles, i.e., burrow-dweller or free-moving, or may have been acquired phylogenetically in the evolutionary process., (© 2023. The Zoological Society of Japan.)

Background: Adding bevacizumab to first-generation epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (TKIs) prolonged the progression-free survival (PFS), but limited data are available for second-generation EGFR-TKIs. AfaBev-CS is a randomized, phase II trial comparing afatinib plus bevacizumab and afatinib alone as first-line treatment., Patients and Methods: Untreated patients with non-squamous non-small cell lung cancer (NSCLC) harboring EGFR mutations (Del19 or L858R) were enrolled and randomly assigned to receive either afatinib (30 mg) plus bevacizumab (AfaBev group) or afatinib (40 mg) monotherapy (Afa group). The primary endpoint was PFS. The power was >50% under the assumptions of a median PFS of 12 months for the Afa group and hazard ratio (HR) of 0.6 for the AfaBev group., Results: Between August 2017 and September 2019, 100 patients were enrolled. There was no significant difference in PFS between the groups. The median PFS was 16.3 and 16.1 months for the AfaBev and Afa groups, respectively, with an HR of 0.865 (95% confidence interval [CI], 0.539 to 1.388; p = 0.55). In terms of overall survival, there was no significant difference between the groups (HR, 0.84; 95% CI, 0.39 to 1.83; p = 0.67). The overall response rate was 82.6% and 76.6% in the AfaBev and Afa groups, respectively (p = 0.61). Grade ≥ 3 diarrhea, hypertension, acneiform rash, paronychia, and stomatitis were frequently observed in the AfaBev group., Conclusions: This study failed to show efficacy of AfaBev over Afa for improving PFS in untreated patients with EGFR-mutated NSCLC., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Dr. Ninomiya reports receiving personal fees from Boehringer Ingelheim, Chugai Pharmaceutical Co., AstraZeneca, Eli Lilly Japan and Eisai. Dr. Ishikawa reports receiving personal fees from Boehringer Ingelheim. Dr. Kozuki reports receiving grants from Chugai Pharmaceutical Co., AstraZeneca, Eli Lilly Japan, Taiho Pharmaceutical Co., Bristol-Myers Squibb, Ono Pharmaceutical Co, MSD, Kyowa Hakko Kirin, Merck Biopharma, Daiichi-Sankyo, AMGEN, Abbvie. Sanofi, Eisai and Labcorp Development Japan; and personal fees from Chugai Pharmaceutical Co., AstraZeneca, Ono Pharmaceutical Co., Pfizer Japan, Daiichi-Sankyo, Bayer, Abbvie, Eli Lilly Japan, Taiho Pharmaceutical Co., Bristol-Myers Squibb, MSD, Kyowa Hakko Kirin, Nippon Boehringer Ingelheim, Merck Biopharma, Nippon Kayaku, Novartis, Takeda Pharmaceutical Co., Bayer, Sawai and AMGEN. Dr. Kuyama reports receiving personal fees from Chugai Pharmaceutical Co., AstraZeneca, Pfizer Japan, Daiichi-Sankyo, Eli Lilly Japan, Taiho Pharmaceutical Co., Bristol-Myers Squibb, MSD, Kyowa Hakko Kirin, Boehringer Ingelheim, Nippon Kayaku, Novartis, Sanofi and Hisamitsu pharmaceutical Co. Inc. Dr. Yokoyama reports receiving grants from MSD, Chugai Pharmaceutical Co. Ltd., Bristol-Myers Squibb Co. Ltd., Boehringer Ingelheim Japan Inc., Takeda Pharmaceutical Co. Ltd., Delta-Fly Pharma and Janssen Pharmaceutical K.K.; and personal fees from AstraZeneca K.K., Chugai Pharmaceutical Co. Ltd., Eli Lilly Japan K.K., Pfizer Japan Inc, Bristol-Myers Squibb Co. Ltd., Ono Pharmaceutical Co. Ltd., Takeda Pharmaceutical Co. Ltd. and Nippon Kayaku Co. Ltd. Dr. Shibayama reports receiving grants from Ono Pharmaceutical Co.; and personal fees from AstraZeneca, Nippon Boehringer Ingelheim and Daiichi-Sankyo. Dr. Aoe reports receiving grants from Ono Pharmaceutical Co., AstraZeneca, Eli Lilly Japan, Bristol-Myers Squibb, MSD, Novartis and Pfizer; and personal fees from Ono Pharmaceutical Co., Bristol-Myers Squibb. Dr. Bessho reports receiving grants from Chugai Pharmaceutical Co., AstraZeneca, MSD, Abbvie and Pfizer; and personal fees from Chugai Pharmaceutical Co., AstraZeneca, Eli Lilly Japan, Taiho Pharmaceutical Co, Bristol-Myers Squibb, Ono Pharmaceutical Co., Nippon Boehringer Ingelheim, Novartis and Pfizer. Dr. Hotta reports receiving grants from Chugai Pharmaceutical Co., AstraZeneca, Eli Lilly Japan, Bristol-Myers Squibb, MSD and Abbvie; and personal fees from Chugai Pharmaceutical Co., AstraZeneca, Eli Lilly Japan, Taiho Pharmaceutical Co., Bristol-Myers Squibb, Ono Pharmaceutical Co., MSD, Pfizer Japan, Takeda Pharmaceutical Co. and Nippon Boehringer Ingelheim. Dr. Kiura reports receiving grants from Chugai Pharmaceutical Co., Taiho Pharmaceutical Co., Ono Pharmaceutical Co., Nippon Boehringer Ingelheim, Nippon Kayaku Co. Ltd., Bristol-Myers Squibb K.K., MSD K.K., Pfizer Japan, TEIJIN Pharma Limited., SHIONOGI Co. Ltd., KYORIN Pharmaceutical Co. Ltd. and Merck Biopharma Co. Ltd. The remaining authors declare no conflict of interest., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Background: Limited information on anticancer therapy for super-elderly patients with non-small-cell lung cancer is available. Immune checkpoint inhibitors offer long-term survival to elderly patients aged ≥65 years with non-small-cell lung cancer. However, the efficacy and safety of immune checkpoint inhibitors in more elderly patients are not well understood., Methods: We retrospectively evaluated the efficacy and safety of immune checkpoint inhibitors in patients aged ≥85 years with advanced non-small-cell lung cancer at nine centers using the Okayama Lung Cancer Study Group-Immunotherapy Database., Results: Among 531 patients who received immune checkpoint inhibitors, 16 were aged ≥85 years (median, 86.5 years; range, 85-93 years). Many had high programmed death-ligand 1 expression and received pembrolizumab as first-line therapy. The objective response rate, median progression-free survival, and median survival time were 25% (95% confidence interval: 1-49), 2.8 months (95% confidence interval: 1.7-4.5), and not reached (95% confidence interval: 4.7-not reached), respectively. Moreover, the 4-year overall survival rate was 60.8% (95% confidence interval: 29.3-81.7), and a long-lasting effect of immune checkpoint inhibitors was observed even in patients aged ≥85 years. The incidence of immune-related and grade ≥3 immune-related adverse events was 32% and 6%, respectively., Conclusions: The effect and toxicity of immune checkpoint inhibitors for patients aged ≥85 years were acceptable. Immune checkpoint inhibitors may be a treatment option for patients aged ≥85 years., Competing Interests: Conflict of Interest T. Kubo received honoraria from Bristol-Myers Squibb, Taiho Pharmaceutical, Kyowa Hakko Kirin, AstraZeneca, Ono Pharmaceutical, Nippon Kayaku, Chugai Pharma, MSD, Pfizer, Lilly, Novartis, Boehringer Ingelheim, and Towa Pharmaceutical; E. Ichihara received honoraria from AstraZeneca K·K., Novartis, Janssen Pharmaceutical K·K., Chugai Pharmaceutical Co. Ltd., Eli Lilly Japan K·K., Pfizer, Bristol-Myers Squibb Co. Ltd., Ono Pharmaceutical Co. Ltd., Takeda Pharmaceutical Co. Ltd., and Boehringer Ingelheim; K. Hotta received research funding from MSD, AstraZeneca K·K., Chugai Pharmaceutical Co. Ltd., Eli Lilly Japan K·K., and Bristol-Myers Squibb Co. Ltd.; Y. Maeda received honoraria from AstraZeneca K·K., Astellas Pharma Inc.Astellas Pharma, Amgen K·K., AbbVie GK, Eisai Co., Ltd, Otsuka Pharmaceutical Co., Ltd., Ono Pharmaceutical Co., Ltd., Kyorin Pharmaceutical Co., Ltd., Kyowa Kirin Co., Ltd., Sanofi K.K., Celgene Corporation, Bristol-Myers Squibb K·K., CSL BehringCSL Behring K·K., Daiichi Sankyo Company, Ltd., Sumitomo Dainippon Pharma Co., Ltd., Takeda Pharmaceutical Company Ltd., Terumo Corporation, Chugai Pharmaceutical Co., Ltd., Nippon Shinyaku Co., Ltd., Novartis Pharma K·K., Pfizer Japan Inc., Mundipharma K·K., Human Life CORD Japan Inc., Meiji Seika Pharma Co., Ltd., Janssen Pharmaceutical K·K., and Yakult Honsha Co., Ltd. and research funding from Chugai Pharmaceutical Co., Ltd., Nippon Shinyaku Co., Ltd., AstraZeneca K·K., Astellas Pharma, Novartis Pharma K·K., Janssen Pharmaceutical K·K., and Mundipharma K.K. and scholarship donations from Astellas Pharma, Asahi Kasei Pharma Corporation, Eisai Co., Ltd., Otsuka Pharmaceutical Co., Ltd., Kyowa Kirin Co., Ltd., TAIHO Pharmaceutical Co., Ltd., Takeda Pharmaceutical Company Ltd., Chugai Pharmaceutical Co., Ltd., Pfizer Japan Inc., Japan Blood Products Organization, and Nippon Shinyaku Co., Ltd.; K. Kiura received consulting fees from Daiichi Sankyo Co., Ltd., Nippon Kayaku Co., Ltd., and Nipro Corporation and honoraria from AstraZeneca K·K., Eli Lilly Japan K·K., Novartis International AG, Taiho Pharmaceutical Co., Ltd., Chugai Pharmaceutical Co., Ltd., Pfizer Japan Inc., Ono Pharmaceutical Co., Ltd. Bristol-Myers Squibb K·K., MSD K·K., Boehringer Ingelheim Co., Ltd. Daiichi Sankyo Co., Ltd., Merck Biopharma Co., Ltd, Nippon Kayaku Co., Ltd., and Takeda Pharmaceutical Co., Ltd. and research funding from Merck Biopharma Co., Ltd, KYORIN Pharmaceutical Co., Ltd., Pfizer Japan Inc., MSD K.K., Boehringer Ingelheim Co., Ltd., Shionogi & Co., Ltd., Nippon Kayaku Co., Ltd., Taiho Pharmaceutical Co., Ltd., Ono Pharmaceutical Co., Ltd., Chugai Pharmaceutical Co., Ltd., TEIJIN Pharma Ltd., Novartis International AG, and Takeda Pharmaceutical Co., Ltd. The other authors have no conflicts of interest., (Copyright © 2023 The Japanese Respiratory Society. Published by Elsevier B.V. All rights reserved.)

Vestimentiferan tubeworms are representative members of deep-sea chemosynthetic ecosystems. In this study, we developed a draft genome and gene models and performed genomic and transcriptomic analyses of Lamellibrachia satsuma, the only vestimentiferan reported from the euphotic zone. The quality of the genome assembly and gene models is comparable to or higher than those of previously reported vestimentiferan tubeworms. Tissue-specific transcriptome sequencing revealed that Toll-like receptor genes and lineage-specific expanded bacteriolytic enzyme genes are highly expressed in the obturacular and vestimental regions, respectively, suggesting the importance of these tissues in defense against pathogens. On the other hand, globin subunit genes are expressed almost exclusively in the trunk region, supporting the hypothesis that the trophosome is the site of haemoglobin biosynthesis. Vestimentiferan-specific expanded gene families included chitinases, ion channels, and C-type lectins, suggesting the importance of these functions for vestimentiferans. C-type lectins in the trunk region, in particular, may be involved in recognition of pathogens, or in interactions between tubeworms and symbiotic bacteria. Our genomic and transcriptomic analyses enhance understanding of molecular mechanisms underlying the unique lifestyle of vestimentiferan tubeworms, particularly their obligate mutualism with chemosynthetic bacteria., (© The Author(s) 2023. Published by Oxford University Press on behalf of Kazusa DNA Research Institute.)

Background: Combination therapy with immune checkpoint inhibitors (ICIs) and chemotherapy (ICI + chemotherapy) has become the standard first line treatment for driver oncogene-negative advanced non-small-cell lung cancer (NSCLC). However, it may be more toxic compared to monotherapy, which limits its use. Moreover, the feasibility of the combination therapy in clinical practice remains unknown., Methods: We conducted a cohort study to determine the implementation rate of ICI + chemotherapy in clinical practice. We retrospectively reviewed clinical data from advanced NSCLC patients who received systemic therapy at 13 institutions between December 2018 and December 2020., Results: After excluding 154 patients with epidermal growth factor receptor (EGFR) or anaplastic lymphoma kinase (ALK) gene alterations, a total of 919 NSCLC patients were included. Among them, 442 were treated with ICI + chemotherapy (48%), whereas 477 were treated with other therapies (52%). Among these 477 patients, 340 did not receive ICI + chemotherapy because of intolerance (71%); thus, more than one-third of the advanced NSCLC patients do not benefit from the combination therapy due to intolerance. Among the 659 NSCLC patients for whom PD-L1 was < 50% or unknown, only 342 received the ICI + chemotherapy combination (52%) even though it is considered preferable to either therapy alone; the remaining 318 patients were treated with other therapies (48%). Among the 318 patients who did not receive ICI + chemotherapy, 274 were intolerant to it (86%)., Conclusion: Our results revealed that a substantial proportion of advanced NSCLC patients did not benefit from ICI + chemotherapy due to intolerance. As treatments for NSCLC are moving toward combinations for greater efficacy, their feasibility in clinical practice must be taken into consideration., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Ramucirumab plus docetaxel combination therapy (DOC/RAM) for advanced non-small cell lung cancer (NSCLC) achieves favorable outcomes; however, efficacy and safety for patients with brain metastases are still unclear., Methods: Eligible patients included those with advanced NSCLC with measurable asymptomatic brain metastases that progressed after chemotherapy. Patients were intravenously administered ramucirumab (10 mg/kg) and docetaxel (60 mg/m2) every 21-day cycle., Results: Due to difficulties in accumulating the planned 65 participants, enrollment was terminated early when 25 patients were enrolled. Primary endpoint: Median progression-free survival (PFS) was 3.9 months (95% CI, 1.8-5.3). Secondary endpoints: Median intracranial progression-free survival was 4.6 months (95% CI, 2.5-5.9); median overall survival was 20.9 months (95% CI, 6.6-not possible to estimate); objective response rate was 20% (95% CI, 6.8-40.7); disease control rate was 68% (95% CI, 46.5-85.1). The most common grade 3 or higher toxicities were neutropenia in 10 patients (40%). Neither intracranial hemorrhage nor grade 5 adverse events were observed. Patients with higher serum soluble vascular endothelial growth factor receptor 2 concentrations at the start of treatment had slightly longer PFS., Conclusion: No clinical concerns were identified with DOC/RAM for NSCLC with brain metastases in this study. Further investigation with a larger sample size is needed to determine the tolerability and safety of these populations (Trial Identifiers: University Hospital Medical Information Network in Japan [UMIN000024551] and Japan Registry of Clinical Trials [jRCTs071180048])., (© The Author(s) 2023. Published by Oxford University Press.)

A pathogen, healthy, latently infected, infectious, and diseased plant (PHLID) model for botanical epidemics was defined for tomato bacterial canker (TBC) caused by the pathogenic plant bacteria, Clavibacter michiganensis subsp. michiganensis ( Cmm ). First, the incubation period had to be defined to develop this type of model. To estimate the parameter of incubation period, inoculation experiments were conducted in which it was assumed that infection is transferred to healthy plants by cutting with contaminated scissors after cutting infected plants with early symptoms or symptomless. The concentration of Cmm was increased over 1 × 10 6 cells/g plant tissue at 20 cm away from the inoculated point on the stem 10 days after inoculation, and then the approximate incubation period of TBC in symptomless infected plants was defined as 10 days. The developed PHLID model showed the dynamics of diseased plants incidence and fitted the curve of the proportion of diseased plants observed in fields well. This model also contains the factors of pathogen and disease control, and it was able to simulate the control effects and combined two different control methods, which were the soil and scissors disinfections to prevent primary and secondary transmissions, respectively. Thus, this PHLID model for TBC can be used to simulate not only the increasing number of diseased plants but also suppressing disease increase.

Microplastic (MP) pollution is a major concern in aquatic environments. Many studies have detected MPs in fishes; however, little is known about differences of microplastic uptake by fish in freshwater (FW) and those in seawater (SW), although physiological conditions of fish differ significantly in the two media. In this study, we exposed larvae (21 days post-hatching) of Oryzias javanicus (euryhaline SW) and Oryzias latipes (euryhaline FW), to 1-µm polystyrene microspheres in SW and FW for 1, 3, or 7 days, after which, microscopic observation was conducted. MPs were detected in the gastrointestinal tracts in both FW and SW groups, and MP numbers were higher in the SW group in both species. Vertical distribution of MPs in the water, and body sizes of both species exhibited no significant difference between SW and FW. Detection of water containing a fluorescent dye revealed that O. javanicus larvae swallowed more water in SW than in FW, as has also been reported for O. latipes. Therefore, MPs are thought to be ingested with water for osmoregulation. These results imply that SW fish ingest more MPs than FW fish when exposed to the same concentration of MPs., (© 2023. The Author(s).)

Scleractinian corals form symbiotic relationships with a variety of microorganisms, including endosymbiotic dinoflagellates of the family Symbiodiniaceae, and with bacteria, which are collectively termed coral holobionts. Interactions between hosts and their symbionts are critical to the physiological status of corals. Coral-microorganism interactions have been studied extensively, but dinoflagellate-bacterial interactions remain largely unexplored. Here, we developed a microbiome manipulation method employing KAS-antibiotic treatment (kanamycin, ampicillin, and streptomycin) to favor pigmented bacteria residing on cultured Cladocopium and Durusdinium , major endosymbionts of corals, and isolated several carotenoid-producing bacteria from cell surfaces of the microalgae. Following KAS-antibiotic treatment of Cladocopium sp. strain NIES-4077, pigmented bacteria increased 8-fold based on colony-forming assays from the parental strain, and 100% of bacterial sequences retrieved through 16S rRNA amplicon sequencing were affiliated with the genus Maribacter . Microbiome manipulation enabled host microalgae to maintain higher maximum quantum yield of photosystem II (variable fluorescence divided by maximum fluorescence [ F v / F m ]) under light-stress conditions, compared to the parental strain. Furthermore, by combining culture-dependent and -independent techniques, we demonstrated that species of the family Symbiodiniaceae and pigmented bacteria form strong interactions. Dinoflagellates protected bacteria from antibiotics, while pigmented bacteria protected microalgal cells from light stress via carotenoid production. Here, we describe for the first time a symbiotic relationship in which dinoflagellates and bacteria mutually reduce environmental stress. Investigations of microalgal-bacterial interactions further document bacterial contributions to coral holobionts and may facilitate development of novel techniques for microbiome-mediated coral reef conservation. IMPORTANCE Coral reefs cover less than 0.1% of the ocean floor, but about 25% of all marine species depend on coral reefs at some point in their life cycles. However, rising ocean temperatures associated with global climate change are a serious threat to coral reefs, causing dysfunction of the photosynthetic apparatus of endosymbiotic microalgae of corals, and overproducing reactive oxygen species harmful to corals. We manipulated the microbiome using an antibiotic treatment to favor pigmented bacteria, enabling their symbiotic microalgal partners to maintain higher photosynthetic function under insolation stress. Furthermore, we investigated mechanisms underlying microalgal-bacterial interactions, describing for the first time a symbiotic relationship in which the two symbionts mutually reduce environmental stress. Our findings extend current insights about microalgal-bacterial interactions, enabling better understanding of bacterial contributions to coral holobionts under stressful conditions and offering hope of reducing the adverse impacts of global warming on coral reefs.

Interstitial oxygen embrittles titanium, particularly at cryogenic temperatures, which necessitates a stringent control of oxygen content in fabricating titanium and its alloys. Here, we propose a structural strategy, via grain refinement, to alleviate this problem. Compared to a coarse-grained counterpart that is extremely brittle at 77 K, the uniform elongation of an ultrafine-grained (UFG) microstructure (grain size ~ 2.0 µm) in Ti-0.3wt.%O is successfully increased by an order of magnitude, maintaining an ultrahigh yield strength inherent to the UFG microstructure. This unique strength-ductility synergy in UFG Ti-0.3wt.%O is achieved via the combined effects of diluted grain boundary segregation of oxygen that helps to improve the grain boundary cohesive energy and enhanced dislocation activities that contribute to the excellent strain hardening ability. The present strategy will not only boost the potential applications of high strength Ti-O alloys at low temperatures, but can also be applied to other alloy systems, where interstitial solution hardening results into an undesirable loss of ductility., (© 2023. The Author(s).)

The patient was a 63-year-old man with biopsy Gleason score of 4＋5 prostate cancer with an initial prostate specific antigen level of (PSA) 51.2ng/ml. On imaging examination, extracapsular invasion, rectal invasion, and pararectal lymph node metastasis were found (cT4N1M0). After 4 years of androgen deprivation therapy, PSA decreased to 0.631ng/ml, and then increased gradually to1.2ng/ml. Computed tomographic scan showed that the primary tumor had shrunk and lymph node metastasis had disappeared; so salvage robot-assisted resection of the prostate (RARP) was performed for non-metastatic castration-resistant prostate cancer (m0CRPC). Since PSA decreased to an undetactable level, hormone therapy was terminated at 1 year. The patient remained recurrence-free for 3 years after surgery. RARP may be effective for m0CRPC, enabling discontinuation of androgen deprivation therapy.

Grapevine crown gall (GCG), which is caused by Allorhizobium vitis (= Rhizobium vitis ) tumorigenic strains, is the most important disease of grapevine around the world. Previously, nonpathogenic A. vitis strains VAR03-1, ARK-1, ARK-2, and ARK-3 were identified as promising biological control agents, but the control effects of each strain were not directly compared and assessed in the field because field trials were conducted in different fields and years. Thus, the results of the control effects obtained from 16 field trials in 12 years from 2006 to 2017 were analyzed and evaluated by a linear mixed model (LMM) and a network meta-analysis (NMA). The results of the LMM strongly indicate that the factor "antagonistic strain" was significantly related to the biological control activity in this study, but the other factors, "concentration of cell suspension", "field", and "year", were not. Then, the results of 16 field trials were combined in an NMA. The estimated relative risk (RR) after treatment with ARK-1, ARK-2, ARK-3, VAR03-1, and K84 were 0.16, 0.20, 0.22, 0.24, and 0.74, respectively. In conclusion, strain ARK-1 was the best antagonist regardless of the concentration of the cell suspension, field, and year differences, and it can be recommended to control GCG., Competing Interests: The authors declare no conflict of interest.

Introduction: In this study, we aimed to assess the impact of perioperative continuation of antithrombotic therapy on bleeding and complications in patients undergoing laparoscopic radical nephrectomy (LRN) and nephroureterectomy (LNU)., Methods: This was a retrospective observational study. Patients who underwent LRN and LNU between January 2017 and July 2019 at our institution were recruited. All patients taking antithrombotic agents continued taking them during the perioperative phase (AA group). Surgical outcomes of patients in the AA group were compared with those of patients who were not taking antithrombotic agents (NA group). The primary outcome was the rate of bleeding complications. Secondary outcomes included intraoperative estimated blood loss, transfusion rate, and complications for up to 90 days., Results: A total of 100 patients were included in the analysis, with 36 and 64 patients assigned to the AA and NA groups, respectively. Patients in the AA group were found to have more severe comorbidities than those in the NA group, with a Charlson Comorbidity Index ≥5, totaling 14 (39%) and 12 (19%), respectively (P = .03). According to surgical outcomes, none of the patients in the AA group required secondary procedures for bleeding complications. Moreover, there were no significant differences between the groups in intraoperative blood loss, hemoglobin deficit, rate of perioperative transfusion, readmission rate, or high-grade complications., Discussion: These results indicate that perioperative use of antithrombotic agents does not increase the risk of bleeding and can be considered safe during LRN and LNU., (© 2022 Asia Endosurgery Task Force and Japan Society of Endoscopic Surgery and John Wiley & Sons Australia, Ltd.)

Background: COVID-19 incidence is high in patients with cancer. The fatality rate was high for the Delta variant, necessitating infection prevention by vaccination. This study evaluated the safety of a SARS-CoV-2 vaccine in patients with advanced lung cancer receiving anticancer therapy., Methods: We prospectively enrolled patients receiving anticancer drugs for advanced lung cancer and planning SARS-CoV-2 vaccination. Early side effects within 7 days of vaccination were evaluated using patient-reported outcome (PRO) surveys. Chi-square test and multivariate logistic regression analyses were used., Results: Post-vaccination PROs were collected from 406 patients (252 were males). The mean age was 72 years. Treatment at the time of initial vaccination included chemotherapy, immune checkpoint inhibitors (ICI), a combination of chemotherapy and ICI, targeted therapy including tyrosine kinase inhibitors, and others in 115, 93, 45, 147, and six cases, respectively. The vaccines administered were BNT162b2 and mRNA273 in 361 and three cases, respectively and unknown in 42 cases. A total of 16.1% of patients developed fever (38°C) after the second mRNA vaccination (95% confidence interval: 12.6%-20.1%). This rate is comparable to data previously reported in 120 patients and slightly higher than that of healthy participants of the BNT162b2 study. Patients receiving treatment with cytotoxic anticancer agents were more likely to have high fever. Multivariate analysis showed no correlation between fever frequency and patient background. No serious initial adverse events due to vaccination were observed., Conclusions: Anti-SARS-CoV-2 mRNA vaccination is safe; however, post-vaccination fever is more common in patients undergoing lung cancer treatment than in healthy individuals., (© 2022 The Authors. Thoracic Cancer published by China Lung Oncology Group and John Wiley & Sons Australia, Ltd.)

Background: The standard of care for unresectable, locally advanced non-small-cell lung cancer (LA-NSCLC) is chemoradiotherapy (CRT) followed by durvalumab, based on the PACIFIC study. Although multiple Japanese phase II studies have shown high efficacy and tolerability of CRT with cisplatin plus S-1 (SP), no prospective study using durvalumab after SP-based CRT has been reported., Objectives: We conducted a multicenter phase II study of this approach, the interim analysis of which showed a high transition rate to durvalumab consolidation therapy. Here, we report the primary analysis results., Design: In treatment-naïve LA-NSCLC, cisplatin (60 mg/m 2 , day 1) and S-1 (80-120 mg/body, days 1-14) were administered with two 4-week cycles with concurrent thoracic radiotherapy (60 Gy) followed by durvalumab (10 mg/kg) every 2 weeks for up to 1 year., Methods: The primary endpoint was 1-year progression-free survival (PFS). The expected 1-year PFS and its lower limit of the 80% confidence interval (CI) were set as 63% and 47%, respectively, based on the results of TORG1018 study., Results: In all, 59 patients were enrolled, with 51 (86.4%) proceeding to durvalumab. The objective response rate throughout the study was 72.9% (95% CI: 59.7-83.6%). After median follow-up of 21.9 months, neither median PFS nor OS was reached. The 1-year PFS was 72.5% (80% CI: 64.2-79.2%, 95% CI: 59.1-82.2%), while the 1-year overall survival was 91.5% (95% CI: 80.8-96.4%). No grade 5 adverse events were observed throughout the study. The most common adverse event during the consolidation phase was pneumonitis (any grade, 78.4%; grade ⩾3, 2.0%). Eventually, 52.5% of patients completed 1-year durvalumab consolidation therapy from CRT initiation., Conclusion: This study of durvalumab after SP-based CRT met its primary endpoint and found a 1-year PFS of 73% from CRT initiation. This study provides the first prospective data on the prognosis and tolerability of durvalumab consolidation from the initiation of CRT., Trial Registration: Japan Registry of Clinical Trials, jRCTs031190127, registered 1 November, 2019, https://jrct.niph.go.jp/latest-detail/jRCTs031190127., Competing Interests: H.T. received personal fees as honoraria from Boehringer Ingelheim, AstraZeneca, Pfizer, Chugai Pharmaceutical, Bristol-Myers Squibb, and Ono Pharmaceutical. S.T. received research funding from AstraZeneca, and personal fees as honoraria from AstraZeneca, Chugai Pharmaceutical, Taiho Pharmaceutical, and Eli Lilly. T.Misu. received personal fees as honoraria from Chugai Pharmaceutical and AstraZeneca. S.K. received personal fees as honoraria from Chugai Pharmaceutical, Bristol-Myers Squibb, Boehringer Ingelheim, AstraZeneca, Pfizer, Eli Lilly, MSD, Taiho Pharmaceutical, Sanofi, Kyowa Kirin, Hisamitsu Pharmaceutical, Daiichi Sankyo, Nippon Kayaku, and Novartis. N.I. received personal fees as honoraria from AstraZeneca. K.Kusa. received personal fees as honoraria from AstraZeneca, Chugai Pharmaceutical, Ono Pharmaceutical, and Nippon Kayaku. N.F. received personal fees as honoraria from Bristol-Myers Squibb, Ono Pharmaceutical, Boehringer Ingelheim, and AstraZeneca. Y.F. received personal fees as honoraria from Bristol-Myers Squibb, Ono Pharmaceutical, Chugai Pharmaceutical, AstraZeneca, Novartis, Merck Biopharma, MSD, Boehringer Ingelheim, Taiho Pharmaceutical, and Daiichi Sankyo. T.T. received personal fees as honoraria from Chugai Pharmaceutical. K.Shib. received personal fees as honoraria from AstraZeneca, Taiho Pharmaceutical, Chugai Pharmaceutical, Bristol-Myers Squibb, and Ono Pharmaceutical. A.B. received research funding from AstraZeneca and personal fees as honoraria from AstraZeneca and Taiho Pharmaceutical. K.Kair. received research funding from AstraZeneca and Nihon Medi-Physics and personal fees as honoraria from Ono Pharmaceutical, Boehringer Ingelheim, Chugai Pharmaceutical, Taiho Pharmaceutical, Eli Lilly, AstraZeneca, and Pfizer. N.S. received research funding from Ono Pharmaceutical, Boehringer Ingelheim, Taiho Pharmaceutical, Chugai Pharmaceutical, Eisai, Daiichi Sankyo, Takeda Pharmaceutical, Shionogi, Nippon Kayaku, and Pfizer, and personal fees as honoraria from Ono Pharmaceutical, Taiho Pharmaceutical, Chugai Pharmaceutical, Eli Lilly, AstraZeneca, Boehringer Ingelheim, MSD, Daiichi Sankyo, Novartis, Bristol-Myers Squibb, Pfizer, Takeda Pharmaceutical, and Nippon Kayaku. No potential conflicts of interest were disclosed by the other authors., (© The Author(s), 2022.)

Objectives: Combined immune checkpoint inhibitor (ICI) therapy and chemotherapy has become the standard treatment for advanced non-small-cell lung cancer (NSCLC). Pleural effusion (PE) is associated with poor outcomes among patients with NSCLC undergoing chemotherapy. However, minimal data exists on PE for patients undergoing combined ICI and chemotherapy. Therefore, we investigated how PE affects survival outcomes in patients with NSCLC undergoing this combined therapy. Methods: We identified patients with advanced NSCLC undergoing chemotherapy and ICI therapy from the Okayama Lung Cancer Study Group−Immune Chemotherapy Database (OLCSG−ICD) between December 2018 and December 2020; the OLCSG−ICD includes the clinical data of patients with advanced NSCLC from 13 institutions. Then, we analyzed the treatment outcomes based on the presence of PE. Results: We identified 478 patients who underwent combined ICI therapy and chemotherapy; 357 patients did not have PE, and 121 patients did have PE. Patients with PE had significantly shorter progression-free survival (PFS) and overall survival (OS) than those without PE (median PFS: 6.2 months versus 9.1 months; p < 0.001; median OS: 16.4 months versus 27.7 months; p < 0.001). The negative effect of PE differed based on the patient’s programmed cell death-ligand 1 (PD-L1) expression status; with the effect being more evident in patients with high PD-L1 expression. In addition, PFS and OS did not differ between patients who did and did not undergo bevacizumab treatment; thus, bevacizumab-containing regimens did not improve the survival outcomes for patients with PE. Conclusion: PE is associated with poor outcomes among patients with NSCLC undergoing combined ICI therapy and chemotherapy.

Spoken dialogue systems must be able to express empathy to achieve natural interaction with human users. However, laughter generation requires a high level of dialogue understanding. Thus, implementing laughter in existing systems, such as in conversational robots, has been challenging. As a first step toward solving this problem, rather than generating laughter from user dialogue, we focus on "shared laughter," where a user laughs using either solo or speech laughs (initial laugh), and the system laughs in turn (response laugh). The proposed system consists of three models: 1) initial laugh detection, 2) shared laughter prediction, and 3) laugh type selection. We trained each model using a human-robot speed dating dialogue corpus. For the first model, a recurrent neural network was applied, and the detection performance achieved an F1 score of 82.6%. The second model used the acoustic and prosodic features of the initial laugh and achieved a prediction accuracy above that of the random prediction. The third model selects the type of system's response laugh as social or mirthful laugh based on the same features of the initial laugh. We then implemented the full shared laughter generation system in an attentive listening dialogue system and conducted a dialogue listening experiment. The proposed system improved the impression of the dialogue system such as empathy perception compared to a naive baseline without laughter and a reactive system that always responded with only social laughs. We propose that our system can be used for situated robot interaction and also emphasize the need for integrating proper empathetic laughs into conversational robots and agents., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Inoue, Lala and Kawahara.)

A healthy, latently infected, diseased (HLD) plant model for botanical epidemics was defined for tomato bacterial canker (TBC) caused by the pathogenic plant bacteria, Clavibacter michiganensis subsp. michiganensis ( Cmm ). To estimate the infection probability parameter, inoculation experiments were conducted in which it was assumed that infection is transferred to healthy plants through contaminated scissors used to cut symptomless infected plants. The approximate concentration of Cmm in symptomless infected plants was 1 × 10 6 cells/mL, and the probability of infection of healthy tomato plants was approximately 0.75 due to cutting with scissors soaked in a cell suspension of Cmm at 1 × 10 6 cells/mL. Three different HLD models were developed by changing some parameters, and the D curve calculated by the developed HLD model A was quite similar to the curve of the proportion of diseased plants observed in fields that had a severe disease incidence. Under a simulation of disease incidence using this model, the basic reproduction number ( R 0 ) was 2.6. However, if the infected scissors were disinfected using ethanol, R 0 was estimated as 0.3. The HLD model for TBC can be used to simulate the increasing number of diseased plants and the term of disease incidence.

Background: Palindromic rheumatism (PR) is an infrequent form of periodic arthritis. Based on the similarity of the pathogenesis of PR to autoinflammatory syndromes, we previously found that the dominant-active splice variant of the inflammasome adaptor protein, apoptosis-associated speck-like protein containing a CARD (ASC), which lacks exon 2 (Δexon2), is expressed in Japanese patients with PR., Objective: Elucidation of the mechanism of Δexon2 ASC production and the effect of IL-1β on splicing., Methods: The genomic DNA of Japanese patients with PR was sequenced. The effect of the observed single nucleotide polymorphisms (SNPs) on ASC splicing was determined via exon trapping using THP-1 cells stimulated with interleukin-1 beta (IL-1β) or ceramide. To investigate the genes that affect alternative splicing via IL-1β, we analyzed the transcriptome of IL-1β-treated THP-1 cells using RNA sequencing., Results: We found the rs8056505 A->G SNP located in the 5'-untranslated region of the genomic ASC gene in patients and that Δexon2 expression was induced by this SNP, whereas it was suppressed by IL-1β or ceramide. We detected 131,426 transcripts and identified 52 differentially expressed genes (DEGs) consisting of 41 downregulated genes and 11 upregulated genes in IL-1β-stimulated THP-1 cells. The splicing-related gene MASCRNA was the most significantly induced gene by IL-1β., Conclusions: We propose a cyclic expression model in which ASC alternates between wild-type and Δexon2 expression regulated by the rs8056505 G allele and splicing factors induced by IL-1β. This cycle may be correlated with the formation of periodic PR pathologies.

Background: The standard of care for unresectable, locally advanced non-small cell lung cancer (LA-NSCLC) is chemoradiotherapy (CRT) followed by durvalumab, based on the PACIFIC trial. Disease progression and pneumonitis were reported as the main reasons to preclude the initiation of durvalumab in multiple retrospective studies. However, the transition rate and the reasons for failure to proceed to consolidation therapy with durvalumab after CRT were not evaluated prospectively. Although phase II studies in Japan have shown high efficacy and tolerability of CRT with cisplatin + S-1 (SP), no prospective study using durvalumab after SP-based CRT has yet been reported. We therefore conducted a phase II study to verify the efficacy and safety of durvalumab following SP-based CRT. In this interim analysis, we report the transition rate and the reasons for its failure., Methods: In treatment-naïve LA-NSCLC, cisplatin (60 mg/m 2 , day 1) and S-1 (80-120 mg/body, days 1-14) were administered with two 4-week cycles with concurrent thoracic radiotherapy (60 Gy) followed by durvalumab every 2 weeks for up to 12 months. The primary endpoint was 12 month progression-free survival rate., Results: Fifty-nine patients were enrolled, of whom 86.4% (51/59) proceeded to durvalumab. All of them initiated durvalumab within 42 days after CRT [median 18 days (range: 3-38)], including 27.5% (14/51) in <14 days. Common reasons for failure to proceed to durvalumab were disease progression (2/59, 3.4%) and adverse events (6/59, 10.2%). Among the latter cases, four resumed treatment and proceeded to durvalumab within 42 days on off-protocol. The objective response rate and the disease control rate were 62.7% and 93.2%, respectively. The incidences of ⩾grade 3 pneumonitis, febrile neutropenia, and esophagitis were 0%, 8.5%, and 3.4%, respectively., Conclusion: Regarding durvalumab after CRT, this interim analysis of the SAMURAI study clarified the high transition rate, early introduction, and reasons for failure to proceed to consolidation therapy, which were not determined in the PACIFIC trial., Trial Registration: Japan Registry of Clinical Trials, jRCTs031190127, registered 1 November, 2019, https://jrct.niph.go.jp/latest-detail/jRCTs031190127., Competing Interests: Competing Interests: ST received research funding from AstraZeneca and personal fees as honoraria from AstraZeneca, Chugai Pharmaceutical, Taiho Pharmaceutical, and Eli Lilly. SK received personal fees as honoraria from Chugai Pharmaceutical, Bristol-Myers Squibb, Boehringer Ingelheim, AstraZeneca, Pfizer, Eli Lilly, MSD, Taiho Pharmaceutical, Sanofi, Kyowa Kirin, Hisamitsu Pharmaceutical, DAIICHI SANKYO, Nippon Kayaku, and Novartis. NI received personal fees as honoraria from AstraZeneca. KK received personal fees as honoraria from AstraZeneca, Chugai Pharmaceutical, Ono Pharmaceutical, and Nippon Kayaku. TY received research funding from Bristol-Myers Squibb, MSD, Chugai Pharmaceutical, Takeda Pharmaceutical, and Delta-Fly Pharma and personal fees as honoraria from Bristol-Myers Squibb, Ono Pharmaceutical, Nippon Kayaku, Chugai Pharmaceutical, Eli Lilly, AstraZeneca, Novartis, and Takeda Pharmaceutical. TT received personal fees as honoraria from Chugai Pharmaceutical. KS received personal fees as honoraria from AstraZeneca, Taiho Pharmaceutical, Chugai Pharmaceutical, Bristol-Myers Squibb, and Ono Pharmaceutical. AB received research funding from AstraZeneca and personal fees as honoraria from AstraZeneca and Taiho Pharmaceutical. KK received research funding from AstraZeneca, and Nihon Medi-Physics and personal fees as honoraria from Ono Pharmaceutical, Boehringer Ingelheim, Chugai Pharmaceutical, Taiho Pharmaceutical, Eli Lilly, AstraZeneca, and Pfizer. TM received personal fees as honoraria from Chugai Pharmaceutical and AstraZeneca. NS received research funding from Ono Pharmaceutical, Boehringer Ingelheim, Taiho Pharmaceutical, Chugai Pharmaceutical, Eisai, DAIICHI SANKYO, Takeda Pharmaceutical, SHIONOGI, Nippon Kayaku, and Pfizer and personal fees as honoraria from Ono Pharmaceutical, Taiho Pharmaceutical, Chugai Pharmaceutical, Eli Lilly, AstraZeneca, Boehringer Ingelheim, MSD, DAIICHI SANKYO, Novartis, Bristol-Myers Squibb, Pfizer, Takeda Pharmaceutical, and Nippon Kayaku. No potential conflicts of interest were disclosed by other authors., (© The Author(s), 2022.)

To evaluate the surgical and functional outcomes between robot-assisted (CRO-RAPN) vs. laparoscopic (CRO-LPN) methods of cortical-renorrhaphy-omitting partial nephrectomy. Between July 2012 and June 2020, patients with localized clinical T1-2 renal masses who underwent CRO-RAPN or CRO-LPN were reviewed. The outcomes of the two groups were compared using propensity-score matching. Trifecta was defined as negative surgical margin, warm ischemic time < 25 min, and absence of complications of Clavien-Dindo grade III or more until three months postoperatively. The preservation rate of the estimated glomerular filtration rate (eGFR) was evaluated at six months postoperatively. Among 291 patients (CRO-RAPN, n = 210; CRO-LPN, n = 81) included in the study, 150 matched pairs of patients were analyzed. Compared to the CRO-LPN group, the CRO-RAPN group was associated with shorter warm ischemic time (13 min vs. 20 min, P < 0.001), shorter total operation time (162 min vs. 212 min, P < 0.001), less estimated blood loss (40 mL vs. 119 mL, P = 0.002), lower incidence of overall complications (3% vs. 16%, P = 0.001), higher preservation rate of eGFR at six months postoperatively (93% vs. 89%, P = 0.003), and higher trifecta achievement rate (84% vs. 64%, P = 0.004). CRO-RAPN contributed to shorter warm ischemic time, less blood loss, fewer complications, and higher preservation of renal function, all of which allowed this technique to achieve a higher rate of trifecta compared to CRO-LPN., (© 2022. The Author(s).)

Background: The role of pembrolizumab in the treatment of poor performance status (PS) patients remains unclear., Patients and Methods: We conducted a phase II trial to investigate the efficacy and safety of pembrolizumab as first-line therapy for non-small-cell lung cancer (NSCLC) patients with PSs of 2-3 and programmed cell death ligand 1 (PD-L1) expression ≥ 50%. The primary endpoint of this study was the objective response rate (ORR)., Results: Fourteen patients treated at eight institutions were enrolled. Most patients had PS 2 (12/14; 86%) and others had PS 3 (2/14; 14%). The ORR was 57.1% (95% confidence interval 28.9-82.3%), which met the primary endpoint. The median progression-free survival (PFS) and 1-year PFS rates were 5.8 months and 20.0%, respectively. At the time of data cut-off, one patient had received treatment for more than 1 year; another patient had received treatment for more than 2 years. Nine patients had improved PS with treatment (Wilcoxon signed-rank test, p = 0.003). Two patients had immune-related adverse events ≥ grade 3: grades 5 and 3 elevation in alanine and aspartate aminotransferases. Two PS 3-stage patients were diagnosed with clinically progressive disease prior to initial computed tomography; both died within 2 months., Conclusion: Pembrolizumab was effective for the treatment of NSCLC patients with a poor PS and PD-L1 level ≥ 50%. However, given the poor outcomes of the PS 3 patients, the drug is not indicated for such patients. Adverse events, including liver dysfunction, should be carefully monitored., Registration Id: UMIN000030955., (© 2022. The Author(s) under exclusive licence to Japan Society of Clinical Oncology.)

Background: Many studies have recently reported the association of concomitant medications with the response and survival in patients with non-small-cell lung cancer (NSCLC) treated with cancer immunotherapy. However, the clinical impact of statin therapy on the outcome of cancer immunotherapy in patients with NSCLC is poorly understood., Methods: In our database, we retrospectively identified and enrolled 390 patients with advanced or recurrent NSCLC who were treated with anti-programmed cell death-1 (PD-1) monotherapy in clinical practice between January 2016 and December 2019 at 3 medical centers in Japan to examine the clinical impact of statin therapy on the survival of patients with NSCLC receiving anti-PD-1 monotherapy. A propensity score-matched analysis was conducted to minimize the bias arising from the patients' backgrounds., Results: The Kaplan-Meier curves of the propensity score-matched cohort showed that the overall survival (OS), but not the progression-free survival (PFS), was significantly longer in patients receiving statin therapy. However, a Cox regression analysis in the propensity score-matched cohort revealed that statin therapy was not an independent favorable prognostic factor, although it tended to be correlated with a favorable outcome., Conclusions: Statin therapy may be a combination tool for cancer immunotherapy in patients with NSCLC. These findings should be validated in further prospective studies with larger sample sizes., (© 2022. The Author(s).)

Cytochrome P450 1a (Cyp1a) is an important enzyme for metabolism of organic pollutants. To understand its reaction to polycyclic aromatic hydrocarbons (PAHs), we knocked out this gene in a marine model fish, Javanese medaka, Oryzias javanicus, using the CRISPR/Cas 9 system. A homozygous mutant (KO) strain with a four-base deletion was established using an environmental DNA (eDNA)-based genotyping technique. Subsequently, KO, heterozygous mutant (HT), and wild-type (WT) fish were exposed to model pollutants, pyrene and phenanthrene, and survivorship and swimming behavior were analyzed. Compared to WT, KO fish were more sensitive to pyrene, suggesting that Cyp1a transforms pyrene into less toxic metabolites. Conversely, WT fish were sensitive to phenanthrene, suggesting that metabolites transformed by Cyp1a are more toxic than the original compound. HT fish showed intermediate results. Thus, comparative use of KO and WT fish can distinguish modes of pollutant toxicity, providing a deeper understanding of fish catabolism of environmental pollutants., (Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Objectives: Since carbonized clots and tissue (debris) tend to adhere firmly to the tip of the endoscopic submucosal dissection (ESD) knife as the procedure proceeds, manual removing the firm debris is often challenging and time-consuming. Recently, effective ultrasonic cleaning for other medical devices has been reported. The aim of the present study was to clarify whether ultrasonic cleaning is effective in removing the debris on the insulation-tipped diathermic (IT) knife-2., Methods: This study was an ex-vivo experimental randomized study. A total of 40 IT knife-2 knives with debris on their tip surfaces were prepared and randomly assigned to two groups (Group A and Group B). The knives in Group A were cleaned using the conventional scrubbing method for 30 s (conventional cleaning method), while those in Group B were cleaned using a combined method of scrubbing for 20 s and ultrasonic cleaning for 10 s (combined ultrasonic cleaning method). The tip electrode of the knife after cleaning was photographed under a microscope (40x). The 40 images of the knives were evaluated by independent three endoscopists and two clinical engineers using the five-step evaluation criteria ranging from cleaning score 1 (dirty) to 5 (clean)., Results: The mean cleaning score of 3.78 (range: 2.33-4.67) in Group B was significantly higher than that of 1.68 (range: 1.00-2.83) in Group A., Conclusions: The combined ultrasonic cleaning method could remove debris adhering to the IT knife-2 more effectively than the conventional cleaning method. Ultrasonic cleaning may be applied for real-world ESD., Competing Interests: The authors declare no conflict of interest., (© 2022 The Authors. DEN Open published by John Wiley & Sons Australia, Ltd on behalf of Japan Gastroenterological Endoscopy Society.)

Background: Palindromic rheumatism (PR) is a rare periodic arthritis characterized by relapsing short episodes of arthritis. Although the pathogenesis of PR is still unclear, the clinical condition is similar to that of autoinflammatory diseases caused by dysregulation of inflammasome-related genes., Objective: We analyzed the inflammasome adapter PYD and CARD domain-containing protein/apoptosis-associated speck-like protein containing a CARD (PYCARD/ASC) in Japanese patients with PR., Methods: Serum interleukin (IL)-1β concentrations in three Japanese patients with PR were measured. We also cloned PYCARD/ASC cDNA variants and expressed them in THP-1 cells to determine their effects on inflammasome activity following stimulation with phorbol 12-myristate 13-acetate and monosodium urate. Lysates of recombinant THP-1 cells were subjected to co-immunoprecipitation assays., Results: Serum IL-1β concentrations were significantly elevated in patients with PR, and a splice variant of PYCARD/ ASC mRNA lacking exon 2 (Δexon2) was dominantly expressed compared with that in controls. Moreover, IL-1β secretion was significantly increased in THP-1 cells expressing Δexon2PYCARD/ASC compared with that in cells expressing the wild-type protein. The amount of NLRP3 bound to Δexon2PYCARD/ASC was increased after stimulation, whereas that bound to the wild-type protein was decreased. There were no differences in caspase-1 binding., Conclusions: Δexon2 PYCARD/ASC was associated with the pathogenesis of PR.

Testicular epidermoid cysts are relatively rare, accounting for about 1% of all testicular tumors, and are often treated by high orchiectomy. We describe here the case of a testicular epidermoid cyst treated by testicle-sparing surgery due to a preoperative diagnosis. A 23-year-old man complained of a painless mass in the right scrotum. Physical examination revealed a firm little fingertip-sized smooth-surfaced mass in the right testis. Ultrasonography showed a hypoechoic lesion with an echogenic rim in the right testis. A T2-weighted magnetic resonance image showed a well-demarcated mass with a low signal outline. On the basis of a preoperative diagnosis of epidermoid cyst, intraoperative testicular frozen section was performed, and the mass was resected surgically while preserving the testis.

Background: Since 2020, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has become prevalent worldwide. In severe cases, the case fatality rate is high, and vaccine prevention is important. This study evaluated the safety of receiving SARS-CoV-2 vaccine in patients with advanced lung cancer receiving anticancer therapy., Methods: We prospectively enrolled patients receiving anticancer drugs for advanced lung cancer who planned to receive SARS-CoV-2 vaccination. Early adverse events within 7 days of vaccine injection were evaluated using patient-reported surveys. The chi-square test and multivariate logistic regression analyses were used., Results: Among 120 patients receiving lung cancer treatment, 73 were men; the mean age of the patients was 73.5 years. The treatments received for lung cancer at the time of the first vaccine injection were chemotherapy, ICIs, combined chemotherapy and ICIs, and targeted therapies, including tyrosine kinase inhibitors, in 30, 28, 17, and 45 patients, respectively. All patients received SARS-CoV-2 messenger RNA (mRNA) vaccine. After the second mRNA vaccine dose, 15.4% of patients had fever of 38°C (95% confidence interval: 9.34%-23.2%); this rate was slightly higher than that for healthy participants at the time of the BNT162b2 trial. Patients treated with cytotoxic anticancer drugs tended to have high fever. In the multivariate analyses, male sex was associated with higher fever frequencies. However, there were no serious early adverse events due to vaccination., Conclusions: Anti-SARS-CoV-2 mRNA vaccination tends to be safe, but fever following vaccination tends to be more common among patients undergoing lung cancer treatment than among healthy individuals., (© 2021 The Authors. Thoracic Cancer published by China Lung Oncology Group and John Wiley & Sons Australia, Ltd.)

Objectives: This study aimed to evaluate how health-related quality of life (HRQOL) is related to repeat protocol biopsy compliance., Materials and Methods: We conducted a retrospective analysis using data from a prospective cohort in the Prostate Cancer Research International: Active Surveillance (PRIAS)-JAPAN study between January 2010 and August 2019. We used the Short Form 8 Health Survey (SF-8), as patient-reported outcomes, to assess HRQOL at AS enrollment and the first year of the protocol. The physical component summary (PCS) and mental component summary (MCS) were calculated from SF-8 questionnaires. The primary outcome was the evaluation of the association of HRQOL at enrollment on the first repeat biopsy compliance. The secondary outcome was the comparison of SF-8 scores during AS, stratified by repeat protocol biopsy compliance., Results: Of 805 patients who proceeded to the first year of the protocol, the non-compliance rate was 15% (121 patients). In the adjusted model, lower MCS at enrollment was significantly associated with the first repeat protocol biopsy non-compliance (odds ratio [OR], 2.134; 95% confidence interval [CI], 1.031-4.42; P = 0.041) but not in lower PCS (OR, 0.667; 95% CI, 0.294-1.514; P = 0.333). All subscales of SF-8 were lower in the non-compliance group than in the compliance group at any point. MCS in the non-compliance group improved over time from the time of AS enrollment (2.34 increased, P = 0.152)., Conclusion: Our data suggest that lower MCS at AS enrollment using patient-reported outcomes was negatively associated with the first repeat protocol biopsy compliance. Our study may support the availability of a simple questionnaire to extract non-compliance., Competing Interests: Conflict of interest None., (Copyright © 2021 Elsevier Inc. All rights reserved.)

A 23-year-old woman was transferred to our hospital due to exacerbating dyspnea with wheeze. After admission, we started mechanical ventilation immediately, and she was diagnosed with status asthmatics. On the following day, she was able to be weaned from the ventilator. However, she required re-intubation because of an unstable respiratory condition just after extubation. Detailed neurological investigations identified blepharoptosis and muscle weakness with easy fatigability. An edrophonium test was positive. Anti-acetylcholine receptor antibody was detected in her serum. She was finally diagnosed with myasthenia gravis and successfully treated with neostigmine and a low-dose corticosteroid.

Objectives: The programmed death-ligand 1 (PD-L1) tumor proportion score (TPS) in tumor tissue samples is an established clinical biomarker for non-small cell lung cancer (NSCLC). However, the significance of PD-L1 expression in other types of samples has not been fully investigated., Patients and Methods: We conducted a multicenter retrospective cohort study of advanced NSCLC patients who received ICI treatment during the clinical course and investigated the effects of ICIs according to PD-L1 expression in cytology samples, including cell block and endobronchial ultrasound-guided (EBUS) transbronchial needle aspiration (TBNA) samples., Results: A total of 264 patients were included in this study: PD-L1 expression was determined in cell block or TBNA specimens in 55 patients, and in tissue samples in 209 patients. Among the former patients, the median progression-free survival (PFS) of those with a TPS for PD-L1 ≥ 50% was significantly longer compared to that of those with a TPS < 50% (6.5 vs. 1.9 months, respectively, p = 0.008). When the cutoff value was set at 1%, the median PFS was 4.2 months in patients with a TPS ≥ 1% and 1.5 months in patients with a TPS < 1% (p < 0.001)., Conclusion: PD-L1 expression determined using cytology specimens predicts the efficacy of ICIs., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Although the risk factors for coronavirus disease 2019 (COVID-19) mortality have been identified, there is limited information about the risk factors for disease progression after hospitalization among Japanese patients with COVID-19 exhibiting no or mild symptoms., Methods: All 302 consecutive patients who were admitted to our institutions and diagnosed with COVID-19 between March and December 2020 were retrospectively assessed. Ultimately, 210 adult patients exhibiting no or mild symptoms on admission were included in the analysis. They were categorized into the stable (no oxygen needed) and worsened (oxygen needed) groups, and their characteristics and laboratory data were compared., Results: Among 210 patients, 49 progressed to a severe disease stage, whereas 161 did not. The mean patient age was 52.14 years, and 126 (60.0%) patients were male. The mean body mass index (BMI) was 23.0 kg/m 2 , and 71 patients were overweight (BMI ≥ 25 kg/m 2 ). Multivariate logistic analysis showed that old age, overweight, diabetes mellitus (DM), and high serum ferritin levels were independent risk factors for disease progression., Conclusions: Clinicians should closely observe patients with COVID-19, especially those with risk factors such as old age, overweight, DM, and high serum ferritin levels, regardless of whether they have no or mild symptoms., (© 2021. The Author(s).)