Search

Variation in the linear energy transfer (LET) profiles of carbon ion radiotherapy (CIRT) plans among cases, even when using the same dose, can influence the antitumor effect; however, there is no biological basis for predicting the antitumor effects of CIRT in relation to LET. Our recent studies suggest that induction of clusters of double-strand breaks (DSBs) in close proximity to each other is a potential mechanism underlying cell killing by high-LET carbon ions. This study aimed to test the hypothesis that the cell killing effect of clinically-used mixed-LET carbon ions can be predicted by the degree of DSB clustering using super-resolution microscopy technologies. A549 lung cancer cells were irradiated with monoenergetic carbon ion beams (LET13–100 keV/µm; 1 Gy) and subjected to immunofluorescence staining to detect γH2AX, a marker of DSBs. Signals from γH2AX foci were detected by DeltaVision OMX, a super-resolution microscope, followed by three-dimensional volume rendering using Imaris software. For each LET, the probability density of γH2AX foci volumes was approximated using the Gaussian function, from which an induction probability (p) of γH2AX foci ≥ v µm3 (0.1–2.0 µm3; 0.1 µm3 increments) was calculated. Cell survival at corresponding irradiation settings was examined in clonogenic assays, from which the cell killing effect (k) was calculated as 1 - the surviving fraction. The correlation between p and k for monoenergetic beams was examined by Spearman's correlation test. The LET profiles of spread-out Bragg peak (SOBP) beams (width, 3–12 cm, 1 cm increments; 1 Gy) was estimated by Monte Carlo simulation using a simulation toolkit, from which the dose-averaged LET was calculated. The relationship between p and k in SOBP beams was analyzed by substituting dose-averaged LET into the formula. Volumes were obtained for 3317 γH2AX foci. For monoenergetic beams, p and k showed the greatest correlation (r = 0.98) at v = 0.7; the difference between the two parameters across LETs was 6.3% ± 5.5%. For SOBP beams, p and k showed the greatest correlation (r = 1) at v = 0.7, with a difference between the two parameters across an SOBP width of 1.6% ± 1.2%. The cell killing effect of clinically-used mixed-LET carbon ions can be predicted from an induction probability of γH2AX foci ≥ 0.7 μm3. These findings provide a biological basis for LET painting in future CIRT planning. [ABSTRACT FROM AUTHOR]

Purpose: Nonsmokers account for 10% to 13% of all lung cancer cases in the United States. Etiology is attributed to multiple risk factors including exposure to secondhand smoking, asbestos, environmental pollution, and radon, but these exposures are not within the current eligibility criteria for early lung cancer screening by low-dose CT (LDCT)., Experimental Design: Urine samples were collected from two independent cohorts comprising 846 participants (exploratory cohort) and 505 participants (validation cohort). The cancer urinary biomarkers, creatine riboside (CR) and N-acetylneuraminic acid (NANA), were analyzed and quantified using liquid chromatography-mass spectrometry to determine if nonsmoker cases can be distinguished from sex and age-matched controls in comparison with tobacco smoker cases and controls, potentially leading to more precise eligibility criteria for LDCT screening., Results: Urinary levels of CR and NANA were significantly higher and comparable in nonsmokers and tobacco smoker cases than population controls in both cohorts. Receiver operating characteristic analysis for combined CR and NANA levels in nonsmokers of the exploratory cohort resulted in better predictive performance with the AUC of 0.94, whereas the validation cohort nonsmokers had an AUC of 0.80. Kaplan-Meier survival curves showed that high levels of CR and NANA were associated with increased cancer-specific death in nonsmokers as well as tobacco smoker cases in both cohorts., Conclusions: Measuring CR and NANA in urine liquid biopsies could identify nonsmokers at high risk for lung cancer as candidates for LDCT screening and warrant prospective studies of these biomarkers., (©2024 The Authors; Published by the American Association for Cancer Research.)

Background and Study Aims: The infliximab biosimilar CT-P13 was the first biosimilar drug targeting tumor necrosis factor-α. However, its efficacy and safety in real-world clinical situations have remained insufficient. Therefore, we aimed to verify the efficacy and safety of CT-P13 in bio-naïve patients with Crohn's disease., Patients and Methods: This retrospective multicenter study compared the remission rate at week 54 between patients with Crohn's disease who were treated with originator infliximab or CT-P13. Endoscopic and laboratory findings were assessed in both groups. A total of 184 (156 originator and 28 CT-P13) patients were analyzed. Of these, 138 originator users and 19 biosimilar users completed 54-week administration., Results: The clinical remission rates in patients taking originator infliximab of CT-P13 at week 54 were 92.5 % and 100 %, respectively. The endoscopic scores of each group significantly decreased from baseline at week 54 in both groups, and the mucosal healing rate at week 54 was 53 % and 64 %, respectively. Laboratory data including C-reactive protein, serum albumin, and hemoglobin significantly improved from baseline to week 14 and 54 in both groups. Adverse events were observed more frequently in the CT-P13 group (25 % vs. 4.5 %, p = 0.0015), but severe adverse events were rare in both groups., Conclusion: The efficacy and safety of CT-P13 were comparable with those of originator infliximab in bio-naïve patients with Crohn's disease evaluated by clinical, endoscopic, and laboratory findings. This study establishes the needed groundwork for the development of a strategy for treatment with biologics in patients with Crohn's disease., Competing Interests: Declaration of 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., (Copyright © 2024 Pan-Arab Association of Gastroenterology. Published by Elsevier B.V. All rights reserved.)

Background: Shoulder and elbow pain are the common complaints associated with throwing injuries in baseball players. Prospective studies evaluating the effectiveness of stretching in increasing posterior shoulder flexibility or strengthening the external rotator muscles as preventive strategies for throwing injuries in baseball players have been published. However, there are limited reviews highlighting the role of preventive interventions for throwing injuries in baseball players. Therefore, this scoping review aimed to summarize the existing literature on preventive interventions for throwing injuries in baseball players., Methods: We searched the Cochrane Central Register of Controlled Trials, MEDLINE, and Scopus databases on 3 March 2023. Two independent reviewers screened the studies based on the eligibility criteria. We extracted existing literature on preventive interventions and effectiveness for throwing injuries in baseball players, and participants' characteristics and results were extracted from the studies. This scoping review was performed in accordance with the Extended Preferred Reporting Items for Systematic Reviews and Meta-Analyses Statement for Scoping Reviews., Results: The initial database search yielded 1170 articles, four of which met the eligibility criteria. Of the included studies, two were randomized controlled trials, and the remaining two were prospective cohort studies. Eligible studies targeted youth-to high school-level players and focused on preventive programs for throwing injuries that manifest in the upper extremities of baseball players. The outcome measure most commonly used to quantify the effectiveness of prevention programs was the incidence of shoulder and elbow injuries, although the definitions vary among studies. The prevention program included sleeper stretching, shoulder external rotation strengthening exercises, and comprehensive prevention programs (focusing on improving the elbow, shoulder, and hip range of motion; rotator cuff and periscapular muscle strength; posture; and lower extremity balance). Each prevention program was reported to have the potential to reduce the incidence of throwing injuries in baseball players, and two studies suggested that high compliance with the program led to a lower injury risk., Conclusion: This scoping review confirmed the presence of studies that examined preventive interventions for throwing injuries in baseball players. Preventive interventions that may reduce throwing injuries in baseball players include sleeper stretching, shoulder external rotation strengthening exercises, and comprehensive prevention programs. However, the characteristics of participants (eg, age, sports level, and position) and the definition of injury varied among previous studies. Injury profiles and prevention strategies may differ according to age, sport level, and position of players, and more studies are needed to prove this issue., (Copyright © 2024 Journal of Shoulder and Elbow Surgery Board of Trustees. Published by Elsevier Inc. All rights reserved.)

Background: Mesonephric adenocarcinoma is an extremely rare subtype of uterine cervical cancer that is associated with a poor prognosis and for which a standardized treatment protocol has not been established. Carbon ion radiotherapy (CIRT) is an emerging radiotherapy modality that has been shown to have a favorable anti-tumor effect, even for tumors resistant to conventional photon radiotherapy or chemotherapy. However, there is no report on CIRT outcomes for mesonephric adenocarcinoma of the uterine cervix., Case Presentation: We treated a 47-year-old Japanese woman with mesonephric adenocarcinoma of the uterine cervix (T2bN0M0 and stage IIB according to the 7th edition of the Union for International Cancer Control and International Federation of Gynecology and Obstetrics, respectively) with CIRT combined with brachytherapy and concurrent chemotherapy. CIRT consisted of whole pelvic irradiation and boost irradiation to the gross tumor; 36.0 Gy (relative biological effectiveness [RBE]) in 12 fractions and 19.2 Gy (RBE) in 4 fractions, respectively, performed once a day, four times per week. Computed tomography-based image-guided adaptive brachytherapy was performed after completion of CIRT, for which the D 90 (i.e., the dose prescribed to 90% of the target volume) for the high-risk clinical target volume was 20.4 Gy in a total of 3 sessions in 2 weeks. A weekly cisplatin (40 mg/m 2 ) dose was administered concomitantly with the radiotherapy for a total of five courses. From 4 months post-CIRT, the patient developed metastasis of the lung, with a total of 10 lung metastases over 70 months; these lesions were treated on each occasion by photon stereotactic body radiotherapy and/or systemic therapy. At 8 years from initial treatment (i.e., 2 years after the last treatment), the patient is alive without any evidence of recurrence and maintains a high quality of life., Conclusions: This is the first report of CIRT for treatment of mesonephric adenocarcinoma of the uterine cervix. The present case indicates the potential efficacy of CIRT in combination with brachytherapy for treatment of this disease., (© 2024. The Author(s).)

Objective: To evaluate the prognostic effect of tumor volume at diagnosis, tumor reduction ratio during external beam radiotherapy (EBRT) with central-shielding method, and cumulative minimal dose to 90% of the high-risk clinical target volume (CTV HR D 90 ) on combined EBRT and image-guided adaptive brachytherapy (IGABT) for cervical cancer., Methods: Consecutive patients who underwent definitive radiotherapy or concurrent chemoradiotherapy for cervical cancer at Gunma University Hospital between January 2010 and December 2019 were retrospectively reviewed. Tumor volume at diagnosis and reduction ratio were calculated using magnetic resonance imaging at diagnosis and before the first IGABT session. The cumulative dose of EBRT and IGABT was calculated as an equivalent dose in 2 Gy fractions (EQD2). Optimal cutoff values were determined according to a receiver operating characteristic curve. Treatment outcomes were evaluated using the Kaplan-Meier method and compared using the log-rank test and Cox proportional hazards regression., Results: A total of 254 patients were included in the analysis. The median follow-up for all patients was 57 (2-134) months. The 5-year overall survival (OS) was 81.9%, progression-free survival (PFS) was 71.3%, and local control (LC) was 94.5%. The patients were divided into four groups according to tumor volume at diagnosis and reduction ratio. The group with tumor volume at diagnosis ≥ 34.1 cm 3 and reduction ratio < 68.8% showed significantly worse OS, PFS, and LC than the other three groups (All p < 0.05). In this group, the patients with a cumulative CTV HR D 90 < 69.6 Gy EQD2 showed significantly worse PFS and LC ( p = 0.042 and p = 0.027, respectively). In the multivariate analysis of OS, adenocarcinoma/adenosquamous carcinoma, International Federation of Gynecology and Obstetrics 2009 stage III/IV, and a reduction ratio of < 68.8% were independent significant poor prognostic factors ( p = 0.045, p = 0.009 and p = 0.001, respectively). In the univariate analysis of LC, a reduction ratio of < 68.8% was the only poor prognostic factor ( p = 0.041)., Conclusion: The patients with large and poorly responding tumors had significantly worse prognoses in terms of OS, PFS, and LC, suggesting that dose escalation should be considered for such tumors., 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 © 2024 Ohtaka, Ando, Oike, Noda, Kaminuma, Murata and Ohno.)

Background and Purpose: Ionizing radiation (IR) induces DNA double-strand breaks (DSBs), leading to micronuclei formation, which has emerged as a key mediator of inflammatory responses after IR. This study aimed to investigate the signaling cascade in inflammatory gene expression using fibroblasts harboring DNA damage response deficiency after exposure to IR., Materials and Methods: Micronuclei formation was examined in human dermal fibroblasts derived from patients with deficiencies in ATM, ATR, MRE11, XLF, Artemis, or BRCA2 after IR. RNA-sequencing analysis was performed to assess gene expression, pathway mapping, and the balance of transcriptional activity using the transcription factor-based downstream gene expression mapping (TDEM) method developed in this study., Results: Deficiencies in ATM, ATR, or MRE11 led to increased micronuclei formation after IR compared to normal cells. RNA-seq analysis revealed significant upregulation of inflammatory expression in cells deficient in ATM, ATR, or MRE11 following IR. Pathway mapping analysis identified the upregulation of RIG-I, MDA-5, IRF7, IL6, and interferon stimulated gene expression after IR. These changes were pronounced in cells deficient in ATM, ATR, or MRE11. TDEM analysis suggested the differential activation of STAT1/3-pathway between ATM and ATR deficiency., Conclusion: Enhanced micronuclei formation upon ATM, ATR, or MRE11 deficiency activated the cGAS/STING, RIG-I-MDA-5-IRF7-IL6 pathway, resulting in its downstream interferon stimulated gene expression following exposure to IR. Our study provides comprehensive information regarding the status of inflammation-related gene expression under DSB repair deficiency after IR. The generated dataset may be useful in developing functional biomarkers to accurately identify patients sensitive to radiotherapy., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Purpose: Recent radiation therapy (RT), such as intensity modulated radiation therapy and particle RT, has improved the concentration of the radiation field targeting tumors. However, severe adverse effects still occur, possibly due to genetic factors in patients. We aimed to investigate the mechanism of exacerbated inflammation during RT., Methods and Materials: Dermal fibroblasts derived from a patient with severe inflammatory adverse effects during RT were compared with 2 normal human dermal fibroblasts. Micronuclei formation, G2/M-checkpoint arrest, DNA damage signaling and repair, and inflammatory gene expression were comprehensively examined., Results: We found greater micronuclei formation in radiation-sensitive fibroblasts (RS-Fs) after ionizing radiation (IR). RS-Fs exhibited premature G2/M-checkpoint release after IR, which triggers micronuclei formation because RS-Fs undergo mitosis with unrepaired DNA double-strand breaks (DSBs). Additionally, we found that DSB end-resection and activation of the ATR-Chk1 pathway were impaired in RS-Fs after IR. Consistent with the increase in the formation of micronuclei, which can deliver cytosolic nucleic acids resulting in an innate immune response, the expression of genes associated with inflammatory responses was highly upregulated in RS-Fs after IR., Conclusions: Although this is a single case of RT-dependent adverse effect, our findings suggest that impaired G2/M-checkpoint arrest due to the lack of DSB end-resection and activation of the ATR-Chk1 pathway causes exacerbated inflammation during RT; therefore, genes involved in G2/M-checkpoint arrest may be a predictive marker for unexpected inflammatory responses in RT., 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 Published by Elsevier Inc. on behalf of American Society for Radiation Oncology.)

Human leukocyte antigen class I (HLA-I) is considered a genetic pathogen for ulcerative colitis (UC). This study aimed to investigate the significance of DNA damage and HLA-I expression in infiltrating immune cells and immune checkpoint protein PD-L1 expression in dysplasia/colitic cancer (CC) and sporadic colorectal cancer (SCRC). We performed immunohistochemical staining for HLA-I, PD-L1, γH2AX (DNA damage marker), and immune cell markers such as CD8, FOXP3, CD68, and CD163 (in surgically resected specimens from 17 SCRC patients with 12 adjacent normal mucosa (NM) and 9 UC patients with 18 dysplasia/CC tumors. The ratio of membrane HLA-I-positive epithelial cells in UC and dysplasia/CC tissues was significantly higher than that in NM and SCRC. High HLA-I expression in dysplasia/CC was associated with high positivity of γH2AX and PD-L1 expression compared to SCRC. The infiltration of CD8-positive T cells and CD68-positive macrophages in HLA-I-high dysplasia/CC was significantly higher than in UC and SCRC. Dysplasia/CC specimens with DNA damage exhibited high levels of HLA-I-positive epithelial cells with high CD8- and CD68-positive immune cell infiltration compared to UC and SCRC specimens. Targeting DNA damage in UC may regulate immune cell infiltration, immune checkpoint proteins, and carcinogenesis by modulating DNA damage-induced HLA-I antigen presentation.

Background: A supervised physiotherapy program (SPP) is a standard regimen after surgical rotator cuff repair (RCR); however, the effect of a home-based exercise program (HEP), as an alternative, on postoperative functional recovery remains unclear. Therefore, the purpose of this meta-analysis was to compare the functional effects of SPP and HEP after RCR., Methods: We searched electronic databases including Central, Medline, and Embase in April 2022. The primary outcomes included the Constant score, American Shoulder and Elbow Surgeons score, University of California Los Angeles shoulder score, and pain score. Secondary outcomes included range of motion, muscle strength, retear rate, and patient satisfaction rate. A meta-analysis using random-effects models was performed on the pooled results to determine the significance., Results: The initial database search yielded 848 records, five of which met our criteria. Variables at 3 months after surgery were successfully analyzed, including the Constant score (mean difference, -8.51 points; 95% confidence interval [CI], -32.72 to 15.69; P=0.49) and pain score (mean difference, 0.02 cm; 95% CI, -2.29 to 2.33; P=0.99). There were no significant differences between the SPP and HEP. Other variables were not analyzed owing to the lack of data., Conclusions: Our data showed no significant differences between SSP and HEP with regard to the Constant and pain scores at 3 months after RCR. These results suggest that HEP may be an alternative regimen after RCR. Level of evidence: I.

Context: Wheelchair basketball athletes have increased upper limb stress, which frequently leads to shoulder pain., Objective: The purpose of this scoping review was to summarize the existing literature on shoulder pain in wheelchair basketball athletes., Methods: We searched PubMed, Cochrane Library, Scopus, and PEDro databases for studies performed between January 1990 and February 2021. Two independent reviewers screened the studies according to the inclusion and exclusion criteria. Participants' characteristics and results were extracted from the study., Results: The initial database search yielded 2455 articles, 11 of which met the inclusion criteria. This review included seven studies in its final analysis; among them, seven determined the prevalence and incidence of shoulder pain, five investigated the factors and mechanisms contributing to shoulder pain, and two reported the treatment and preventive measures. The prevalence of shoulder pain in wheelchair basketball players ranged from 38%-75%, and the incidence of shoulder pain was 14%. Factors/mechanisms included overuse, decreased trunk control, and driving posture. Treatment/preventive measures consisted of shoulder and scapular muscle strengthening and stretching exercises. However, the literature on treatment/prevention was scarce, and its effectiveness was unclear., Conclusion: This scoping review confirmed the high prevalence of shoulder pain in wheelchair basketball players; despite this, studies regarding treatment or preventive measures remain lacking. Further studies investigating the mechanism of onset of shoulder pain and the effectiveness of therapeutic and preventive measures are needed in the future.

Background/aim: This study aimed to develop an improved algorithm for linear energy transfer (LET) estimation in carbon ion radiotherapy (CIRT) using relative biological effectiveness (RBE) and to establish a clinical pipeline for LET assessment., Materials and Methods: New approximation functions for LET versus RBE were developed for the overkill region. LET estimation performance was examined at two facilities (A and B) using archival- and Monte Carlo simulation-derived LET data, respectively, as a reference. A clinical pipeline for LET assessment was developed using Python and treatment planning systems (TPS)., Results: In dataset A, LET estimation accuracy in the overkill region was improved by 80.0%. In dataset B, estimation accuracy was 2.3%±0.67% across 5 data points examined. LET distribution and LET-volume histograms were visualized for multiple CIRT plans., Conclusion: The new algorithm showed a greater LET estimation performance at multiple facilities using the same TPS. A clinical pipeline for LET assessment was established., (Copyright © 2023 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

This pilot study aimed primarily to evaluate plasma levels of a novel metabolite, creatine riboside, in patients with cervical cancer (discovery and validation cohorts, n  = 11 for each) compared with non-cancer subjects (controls, n  = 30). We found that the pre-treatment plasma creatine riboside level was significantly higher in the discovery cohort than in controls. The cut-off value determined from the discovery cohort distinguished 90.9% of the patients in the validation cohort from controls. Unbiased principal component analysis of plasma metabolites in high-creatine riboside samples demonstrated enrichment of pathways involved in arginine and creatine metabolism. These data indicate the potential utility of plasma creatine riboside as a biomarker of cervical cancer., 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, (© 2023 The Authors.)

The Short Physical Performance Battery (SPPB) is a well-established tool to assess the lower extremity physical performance status. The purpose of this study is to examine the impact of brain natriuretic peptide (BNP) levels and SPPB scores on short-term readmission in older patients with heart failure (HF). This prospective cohort study enrolled 325 patients with HF who were hospitalized for acute decompensated HF between November 2017 and December 2021. Variables were analyzed using the Cox proportional hazards model, receiver operating characteristic (ROC) curve, and Kaplan-Meier analysis. The 107 patients who met the inclusion criteria were divided into readmission (within 90 days of discharge; n = 25) and non-readmission (n = 82) groups. Multivariate analysis revealed that BNP level and SPPB score were independent risk factors for readmission within 90 days after discharge. Patients were classified into three groups according to the BNP and SPPB cutoff values calculated using ROC curves. The risk of readmission was significantly higher in Group 3 (BNP ≥ 384 pg/mL and SPPB ≤ 7 points) than in Group 1 (BNP < 384 pg/mL and SPPB > 7 points; hazard ratio: 27.68, 95% confidence interval: 3.672 - 208.700, P = 0.0012). Our study showed that HF patients with high BNP levels and low SPPB scores have a dramatically increased risk of readmission within 90 days of discharge., (© 2022. Springer Japan KK, part of Springer Nature.)

The strong cell killing effect of high linear energy transfer (LET) carbon ions is dependent on lethal DNA damage. Our recent studies suggest that induction of clusters of double-strand breaks (DSBs) in close proximity is one of the potential mechanisms. However, the relationship between LET, the degree of DSB clustering and the cell killing effect of carbon ions remains unclear. Here, we used high-resolution imaging technology to analyze the volume of γH2AX foci induced by monoenergetic carbon ions with a clinically-relevant range of LET (13-100 keV/μm). We obtained data from 3317 γH2AX foci and used a gaussian function to approximate the probability (p) that 1 Gy-carbon ions induce γH2AX foci of a given volume (vth) or greater per nucleus. Cell killing effects were assessed in clonogenic assays. The cell killing effect showed high concordance with p at vth = 0.7 μm3 across various LET values; the difference between the two was 4.7% ± 2.2%. This relationship was also true for clinical carbon ion beams harboring a mixed LET profile throughout a spread-out Bragg peak width (30-120 mm), with the difference at vth = 0.7 μm3 being 1.6% ± 1.2% when a Monte Carlo simulation-derived dose-averaged LET was used to calculate p. These data indicate that the cell killing effect of carbon ions is predictable by the ability of carbon ions to induce γH2AX foci containing clustered DSBs, which is linked to LET, providing the biological basis for LET modulation in the planning of carbon ion radiotherapy., (© The Author(s) 2023. Published by Oxford University Press on behalf of The Japanese Radiation Research Society and Japanese Society for Radiation Oncology.)

Background: Tumor mutational burden (TMB) and stromal CD8-positive tumor-infiltrating lymphocytes (CD8 + TILs) serve important roles in antitumor immune responses to radiotherapy. This study aimed to elucidate the association between TMB, CD8 + TILs, and clinical factors in patients with cervical cancer treated with radiotherapy., Methods: Patients with squamous cell carcinoma of the uterine cervix treated with definitive radiotherapy, and with available somatic mutation data and immunohistochemical staining data from identical tumor tissues, were enrolled retrospectively. The association between TMB and/or CD8 + TIL density and patient characteristics, mutation profiles, and treatment outcome was analyzed., Results: The study analyzed 44 patients (median follow-up period, 61 months). There was no significant correlation between TMB and CD8 + TIL density, or between TMB or CD8 + TIL density and patient characteristics. TMB-high or CD8 + TIL density-low status was associated with worse overall survival and distant metastasis-free survival; the predictive value of these factors became greater when used in combination. TMB-high or CD8 + TIL density-high status was associated with ARID1A mutations., Conclusions: These data indicate independence of TMB and CD8 + TIL density and the involvement of ARID1A alterations in antitumor immune responses in patients with cervical cancers treated with radiotherapy, warranting further mechanistic research and prospective validation.

Objective: We aimed to examine the relationship between physical performance and readmission among older patients with heart failure (HF) over the past year., Methods: This retrospective cohort study included 325 patients with HF who were aged ≥65 years and were hospitalized for acute exacerbation between November 2017 and December 2021. We investigated age, sex, body mass index, length of hospital stay, initiation of rehabilitation, New York Heart Association (NYHA) class, Charlson comorbidity index (CCI) score, medications, cardiac/renal function, nutrition, maximal quadriceps isometric strength, grip strength, and Short Physical Performance Battery (SPPB) score. Data were analyzed using the χ 2 test, Mann-Whitney U test, and logistic regression analysis., Results: Altogether, 108 patients met the inclusion criteria and were divided into the non-readmission (n = 76) and readmission (n = 32) groups. The readmission group exhibited longer hospital stay, more severe NYHA class, higher CCI score, higher brain natriuretic peptide (BNP) levels, lower muscle strength, and lower SPPB score compared to the non-readmission group. In the logistic regression model, BNP level and SPPB score were independent factors associated with readmission., Conclusion: BNP level and SPPB score were associated with readmission in patients with HF within the past year., Competing Interests: The authors report no conflicts of interest., (©2023 Japanese Society of Physical Therapy.)