A systematic review and meta-analysis of radiotherapy and particle beam therapy for skull base chondrosarcoma: TRP-chondrosarcoma 2024.

Introduction: Chondrosarcoma is a rare malignant bone tumor. Particle beam therapy (PT) can concentrate doses to targets while reducing adverse events. A meta-analysis based on a literature review was performed to examine the efficacy of PT and photon radiotherapy for skull base chondrosarcoma. Methods: The meta-analysis was conducted using 21 articles published from 1990 to 2022. Results: After PT, the 3- and 5-year overall survival (OS) rates were 94.1% (95% confidence interval [CI]: 91.0-96.2%) and 93.9% (95% CI: 90.6-96.1%), respectively, and the 3- and 5-year local control rates were 95.4% (95% CI: 92.0-97.4%) and 90.1% (95% CI: 76.8-96.0%), respectively. Meta-regression analysis revealed a significant association of PT with a superior 5-year OS rate compared to three-dimensional conformal radiotherapy (p < 0.001). In the studies used in the meta-analysis, the major adverse event of grade 2 or higher was temporal lobe necrosis (incidence 1-18%, median 7%). Conclusion: PT for skull base chondrosarcoma had a good outcome and may be a valuable option among radiotherapy modalities. However, high-dose postoperative irradiation of skull base chondrosarcoma can cause adverse events such as temporal lobe necrosis.

A novel predictive formula for highly accurate discrimination between truly Helicobacter pylori-uninfected and currently infected/spontaneously eradicated individuals for gastric cancer screening.

The ABC classification, which categorizes gastric cancer risk based on serum Helicobacter pylori (H pylori) antibody and pepsinogen levels, has a limitation of potentially misclassifying high-risk individuals as low risk. To overcome the problem, we previously developed a 4-parameter predictive formula (age, serum H pylori antibody, PGI, and PGII) using logistic regression analysis to accurately identify low-risk truly H pylori-uninfected status. Our predictive formula demonstrated superior sensitivity and specificity in distinguishing between low-risk truly uninfected individuals and high-risk currently/spontaneously eradicated status individuals, compared to the modified ABC classification based on latex immunoassay kits (traditional 3-parameter model). This study aimed to revalidate the diagnostic accuracy of the predictive formula in a new and different study population. We applied the predictive formula to the target population and compared the sensitivity and specificity with those of the traditional 3-parameter model. A total of 788 enrollees were analyzed: 703 were classified as truly uninfected, 45 as currently infected, and 40 as spontaneously eradicated according to the results of stool antigen testing and endoscopic findings. The sensitivities and specificities of the predictive formula and the traditional 3-parameter model were 89.5% and 87.1% versus 89.8% and 80.0%, respectively. The specificity of the predictive formula was superior in the 70 to 89 age range and H pylori antibody < 3 U/mL groups. The predictive formula had higher specificity than the traditional 3-parameter model. The results should contribute to efficient gastric cancer screening by predicting H pylori infection status.

Effects of Radio-Taiso on Health-Related Quality of Life in Older Adults with Frailty: A Randomized Controlled Trial.

BACKGROUND: Radio-Taiso could be a sustainable public health strategy for maintaining quality of life (QoL) in older adults with frailty. This study aimed to investigate whether Radio-Taiso provided greater benefits for health-related quality of life (HR-QoL) and to identify the mechanisms underlying the effectiveness in this population. METHODS: A 12-week randomized controlled trial enrolled 226 older Japanese adults with pre-frailty or frailty, assessed using the modified frailty phenotype. Participants were randomly allocated to the intervention (Radio-Taiso + nutrition program) or control (nutrition program) groups. The Radio-Taiso program comprised five 60-min group sessions and daily practice at the participants' homes. The primary outcome was the change in the mental domain of HR-QoL, assessed using the SF-36®. The secondary outcomes included six physical fitness items and exercise self-efficacy. RESULTS: Overall, 104 and 105 participants in the intervention and control groups, respectively, were analyzed based on the intention-to-treat principle. The median (interquartile range) daily practice rate of Radio-Taiso was 94.1% (73.2-98.8%). Although general linear models adjusted for baseline values and allocation stratification factors showed that the intervention group obtained greater benefits (adjusted mean differences [95% confidence intervals]) in the up-and-go (0.3 [0.1, 0.6] s), 2-min step-in-place (-3.2 [-6.2, -0.2] steps) tests, and exercise self-efficacy scale (-1.4 [-2.6, -0.1] points) than the control group, there were no group differences in changes in the mental domain score of HR-QoL. CONCLUSIONS: Radio-Taiso provided greater benefits for agility/dynamic balance, aerobic endurance, and exercise self-efficacy in older adults with frailty; however, these changes do not improve HR-QoL.

An analysis of muscle growth after proton beam therapy for pediatric cancer.

Retardation of growth and development is a well-known late effect after radiotherapy for pediatric patients. The goal of the study was to examine the effect of proton beam therapy (PBT) on the growth of muscles included in the irradiated area. The subjects were 17 pediatric patients (age ≤ 5 years) who received PBT with a treatment field including a muscle on only one side out of a pair of symmetrical bilateral muscles and had imaging evaluations for at least 1 year after PBT. The thicknesses of the irradiated and non-irradiated (contralateral) muscles were measured retrospectively on CT or MRI axial images collected before and after PBT. The change of thickness divided by the period (years) for each muscle was compared between the irradiated and contralateral sides. Correlations of muscle growth with irradiation dose and age at the start of treatment were also evaluated. The median observation period was 39.2 months. The measurement sites included the erector spinae (n = 9), gluteus maximus (n = 5) and rhomboids + trapezius (n = 3) muscles. The average changes in muscle thickness were 0.24 mm/year on the irradiated side and 1.19 mm/year on the contralateral side, showing significantly reduced growth on the irradiated side (P = 0.001). Younger patients had greater muscle growth. Irradiation dose was not significant, but muscle growth tended to decrease as the dose increased, and muscles irradiated at >50 Gy (RBE) showed little growth. These results show that muscle growth is affected by PBT and that long-term follow-up is needed to evaluate muscle growth retardation.

Tumor Response on Diagnostic Imaging after Proton Beam Therapy for Hepatocellular Carcinoma.

BACKGROUND: Follow-up after treatment for hepatocellular carcinoma (HCC) can be mostly performed using dynamic CT or MRI, but there is no common evaluation method after radiation therapy. The purpose of this study is to examine factors involved in tumor reduction and local recurrence in patients with HCC treated with proton beam therapy (PBT) and to evaluate HCC shrinkage after PBT. METHODS: Cases with only one irradiated lesion or those with two lesions irradiated simultaneously were included in this study. Pre- and post-treatment lesions were evaluated using Response Evaluation Criteria in Solid Tumors (RECIST) by measuring the largest diameter. RESULTS: The 6-, 12-, and 24-month CR + PR rates after PBT were 33.1%, 57.5%, and 76.9%, respectively, and the reduction rates were 25.1% in the first 6 months, 23.3% at 6-12 months, and 14.5% at 13-24 months. Cases that reached CR/PR at 6 and 12 months had improved OS compared to non-CR/non-PR cases. CONCLUSIONS: It is possible that a lesion that reached SD may subsequently transition to PR; it is reasonable to monitor progress with periodic imaging evaluations even after 1 year of treatment.

Multivariate generalized mixed-effects models for screening multiple adverse drug reactions in spontaneous reporting systems.

Introduction: For assessing drug safety using spontaneous reporting system databases, quantitative measurements, such as proportional reporting rate (PRR) and reporting odds ratio (ROR), are widely employed to assess the relationship between a drug and a suspected adverse drug reaction (ADR). The databases contain numerous ADRs, and the quantitative measurements need to be calculated by performing the analysis multiple times for each ADR. We proposed a novel, simple, and easy-to-implement method to estimate the PRR and ROR of multiple ADRs in a single analysis using a generalized mixed-effects model for signal detection. Methods: The proposed method simultaneously analyzed the association between any drug and numerous ADRs, as well as estimated the PRR and ROR for a specific combination of drugs and suspected ADRs. Furthermore, the proposed method was applied to detect drug-drug interactions associated with the concurrent use of two or more drugs. Results and discussion: In our simulation studies, the false-positive rate and sensitivity of the proposed method were similar to those of the traditional PRR and ROR. The proposed method detected known ADRs when applied to the Food and Drug Administration Adverse Event Reporting System database. As an important advantage, the proposed method allowed the simultaneous evaluation of several ADRs using multiple drugs.

Proton Beam Therapy for Hepatocellular Carcinoma: Multicenter Prospective Registry Study in Japan.

PURPOSE: A prospective multicenter registry study was started May 2016 in Japan to evaluate the efficacy and safety of proton beam therapy (PBT) for hepatocellular carcinoma (HCC). METHODS AND MATERIALS: Patients who received PBT for HCC from May 2016 to June 2018 were registered in the database of the Particle Beam Therapy Committee and Subcommittee of the Japanese Society for Radiation Oncology. Overall survival (OS), progression-free survival (PFS), and local recurrence were evaluated. RESULTS: Of the 755 registered patients, 576 with initial PBT and no duplicate cancer were evaluated. At final follow-up, 322 patients were alive and 254 had died. The median follow-up period for survivors was 39 months (0-58 months). The median OS time of the 576 patients was 48.8 months (95% CI, 42.0-55.6 months) and the 1-, 2-, 3-, and 4-year OS rates were 83.8% (95% CI, 80.5%-86.6%), 68.5% (64.5%-72.2%), 58.2% (53.9%-62.2%), and 50.1% (44.9%-55.0%), respectively. Recurrence was observed in 332 patients, including local recurrence in 45 patients. The median PFS time was 14.7 months (95% CI, 12.4-17.0 months) and the 1-, 2-, 3-, and 4-year PFS rates were 55.2% (95% CI, 51.0%-59.2%), 37.5% (33.5%-41.5%), 30.2% (26.3%-34.2%), and 22.8% (18.5%-27.4%), respectively. The 1-, 2-, 3-, and 4-year OS rates were significantly higher for tumor size <5 versus 5 to 10 cm (P < .001) and <5 versus ≥10 cm (P < .001); Child-Pugh score A/B versus C (P < .001); and distance of the tumor from the gastrointestinal tract <1 versus 1 to 2 cm (P < .008) and <1 versus >2 cm (P < .001). At final follow-up, 27 patients (4.7%) had late adverse events of grade 3 or higher, with liver failure (n = 7), and dermatitis (n = 7) being most common. CONCLUSIONS: This multicenter prospective data registry indicated that PBT for HCC gives good therapeutic effects (3-year local control rate of 90%) with a low risk of severe late adverse events.

Three-dimensional analysis reveals a high incidence of lung adenocarcinoma in the upper region.

PURPOSE: The lung is a unique organ with a ventilation-perfusion mismatch, which can cause inhomogeneous incidence rates of lung cancer depending on the location in the lung. We aimed to evaluate the incidence of lung adenocarcinoma in each lobe by analyzing the incidence per unit volume, to evaluate the incidence without being affected by differences in the size of each lobe or in the size of the lungs between individuals. METHODS: The number of adenocarcinomas in each lobe was counted. Lung volumes were measured using a three-dimensional computer workstation. The tumor incidence per unit volume was analyzed based on the number of tumors in each lobe. RESULTS: The number of tumors per unit volume was 0.467 in the right upper lobe (RUL), 0.182 in the right middle lobe, 0.209 in the right lower lobe, 0.306 in the left upper segment (LUS), 0.083 in the left lingular segment, and 0.169 in the left lower lobe. The tumor incidence rate of RUL + LUS was 2.269 times that of the other lobes, a value that was significantly higher when using the bootstrap method (p < 0.001). CONCLUSIONS: The incidence of adenocarcinoma per unit volume in both upper lobes was higher than that in other lobes.

Risk Factors for Radiation Necrosis and Local Recurrence after Proton Beam Therapy for Skull Base Chordoma or Chondrosarcoma.

[Proposal] Here, we retrospectively evaluate risk factors for radiation necrosis and local recurrence after PBT for skull base chordoma or chondrosarcoma. [Patients and Methods] We analyzed 101 patients who received PBT for skull base chordomas and chondrosarcomas from January 1989 to February 2021. Multivariable logistic regression models were applied for local recurrence, temporal lobe radiation necrosis rates, and temporal lobe radiation necrosis. [Results] In multivariate analysis, chordoma and large tumor size were independent significant factors for local recurrence. The 1-, 2-, 3-, 4- and 5-year local recurrence rates were 3.9%, 16.9%, 20.3%, 28.5% and 44.0% for chordoma and 0%, 0%, 0%, 0% and 7.1% for chondrosarcoma, respectively. The local recurrence rates of small tumors (<30 mm) were 4.3%, 14.7%, 17.7%, 17.7% and 25.9%, and those for large tumors were 3.6%, 15.1%, 19.2%, 32.7% and 59.6%, respectively. In multivariate analysis, BED Gy10 and total dose were risk factors for radiation necrosis. [Conclusions] For skull base chordoma and chondrosarcoma, the risk factors of local recurrence were chordoma and large tumor size, and those of radiation necrosis were BED Gy10 and total dose, respectively. DVH analysis is needed to investigate the risk factors for brain necrosis in more detail.

A genome-wide association study for allergen component sensitizations identifies allergen component-specific and allergen protein group-specific associations.

Background: Allergic diseases are some of the most common diseases worldwide. Genome-wide association studies (GWASs) have been conducted to elucidate the genetic factors of allergic diseases. However, no GWASs for allergen component sensitization have been performed. Objective: We sought to detect genetic variants associated with differences in immune responsiveness against allergen components. Methods: The participants of the present study were recruited from the Tokyo Children's Health, Illness, and Development study, and allergen component-specific IgE level at age 9 years was measured by means of allergen microarray immunoassays. We performed GWASs for allergen component sensitization against each allergen (single allergen component sensitization, number of allergen components analyzed, n = 31), as well as against allergen protein families (allergen protein group sensitization, number of protein groups analyzed, n = 16). Results: We performed GWAS on 564 participants of the Tokyo Children's Health, Illness, and Development study and found associations between Amb a 1 sensitization and the immunoglobulin heavy-chain variable gene on chromosome 14 and between Phl p 1 sensitization and the HLA class II region on chromosome 6 (P < 5.0 × 10-8). A GWAS-significant association was also observed between the HLA class II region and profilin sensitization (P < 5.0 × 10-8). Conclusions: Our data provide the first demonstration of genetic risk for allergen component sensitization and show that this genetic risk is related to immune response genes including immunoglobulin heavy-chain variable gene and HLA.

Proton Beam Therapy versus Radiofrequency Ablation for Patients with Treatment-Naïve Single Hepatocellular Carcinoma: A Propensity Score Analysis.

Introduction: Proton beam therapy (PBT) is known to be an effective locoregional treatment for hepatocellular carcinoma (HCC). However, few comparative studies in treatment-naïve cases have been reported. The aim of this study was to compare the survival outcomes of PBT with those of radiofrequency ablation (RFA) in patients with treatment-naïve solitary HCC. Methods: Ninety-five consecutive patients with treatment-naïve HCC, a single nodule measuring ≤5 cm in diameter, and a Child-Pugh score of ≤8 who were treated with PBT at the University of Tsukuba Hospital between 2001 and 2013 were enrolled in the study. In addition, 836 patients with treatment-naïve HCC treated by RFA at the University of Tokyo Hospital during the same period were analyzed as controls. Recurrence-free survival (RFS) and overall survival (OS) were compared in 83 patient pairs after propensity score matching. Results: The 1-year, 3-year, and 5-year RFS rates were 86.6%, 49.5%, and 35.5%, respectively, in the PBT group and 59.5%, 34.0%, and 20.9% in the RFA group (p = 0.058); the respective OS rates were 97.6%, 77.8%, and 57.1% in the PBT group and 95.1%, 81.7%, and 67.7% in the RFA group (p = 0.16). Regarding adverse effects, no grade 3 or higher adverse events were noted in the PBT; however, two grade 3 adverse events occurred within 30 days of RFA in the RFA group: one hemoperitoneum and one hemothorax. Discussion: After propensity score matching, PBT showed no significant difference in RFS and OS compared to RFA. PBT can be an alternative for patients with solitary treatment-naïve HCC.

Correlation of motor-auditory cross-modal and auditory unimodal N1 and mismatch responses of schizophrenic patients and normal subjects: an MEG study.

Introduction: It has been suggested that the positive symptoms of schizophrenic patients (hallucinations, delusions, and passivity experience) are caused by dysfunction of their internal and external sensory prediction errors. This is often discussed as related to dysfunction of the forward model that executes self-monitoring. Several reports have suggested that dysfunction of the forward model in schizophrenia causes misattributions of self-generated thoughts and actions to external sources. There is some evidence that the forward model can be measured using the electroencephalography (EEG) and magnetoencephalography (MEG) components such as N1 (m) and mismatch negativity (MMN) (m). The objective in this MEG study is to investigate differences in the N1m and MMNm-like activity generated in motor-auditory cross-modal tasks in normal control (NC) subjects and schizophrenic (SC) patients, and compared that activity with N1m and MMNm in the auditory unimodal task. Methods: The N1m and MMNm/MMNm-like activity were recorded in 15 SC patients and 12 matched NC subjects. The N1m-attenuation effects and peak amplitude of MMNm/MMNm-like activity of the NC and SC groups were compared. Additionally, correlations between MEG measures (N1m suppression rate, MMNm, and MMNm-like activity) and clinical variables (Positive and Negative Syndrome Scale (PANSS) scores and antipsychotic drug (APD) dosages) in SC patients were investigated. Results: It was found that (i) there was no significant difference in N1m-attenuation for the NC and SC groups, and that (ii) MMNm in the unimodal task in the SC group was significantly smaller than that in the NC group. Further, the MMNm-like activity in the cross-modal task was smaller than that of the MMNm in the unimodal task in the NC group, but there was no significant difference in the SC group. The PANSS positive symptoms and general psychopathology score were moderately negatively correlated with the amplitudes of the MMNm-like activity, and the APD dosage was moderately negatively correlated with the N1m suppression rate. However, none of these correlations reached statistical significance. Discussion: The findings suggest that schizophrenic patients perform altered predictive processes differently from healthy subjects in latencies reflecting MMNm, depending on whether they are under forward model generation or not. This may support the hypothesis that schizophrenic patients tend to misattribute their inner experience to external agents, thus leading to the characteristic schizophrenia symptoms.

Retrospective Analysis of the Areas Responsible for Light Flash and Odor During Proton Beam Therapy and Photon Therapy.

Background Abnormal sensations were frequently experienced by patients who received irradiation of the brain or head and neck region. We have previously suggested correlations with irradiation of the nasal cavity and retina. Purpose We performed a retrospective dose-volume histogram analysis focused on the brain and head and neck tumor to examine the relationship between these abnormal sensations and the details of irradiation. Methods Multivariate logistic regression models were applied for the presence or absence of light flash and odor. Gender, age, radiotherapy method (proton beam therapy vs. photon radiotherapy), dose of retina, optic nerve, chiasmatic gland, pituitary, nasal cavity, oral cavity, frontal lobe, parietal lobe, occipital lobe, temporal lobe, amygdala, and hippocampus were set as candidates of explanatory variables. Results Light flash and odor during radiotherapy have been suggested to be associated with younger age and retina and nasal cavity irradiation. Multivariate analyses including dose-volume histograms indicated that light flash was related to age, chiasmatic gland irradiation, and pituitary dose, and odor was related to age and nasal cavity irradiation. Conclusion Our results indicate that light flash during radiotherapy is caused by irradiation of the visual pathway and that odor is caused by irradiation of the nasal cavity or olfactory bulb.

Development and validation of a prediction model for rehospitalization among people with schizophrenia discharged from acute inpatient care.

Objective: Relapses and rehospitalization prevent the recovery of individuals with schizophrenia or related psychoses. We aimed to build a model to predict the risk of rehospitalization among people with schizophrenia or related psychoses, including those with multiple episodes. Methods: This retrospective cohort study included individuals aged 18 years or older, with schizophrenia or related psychoses, and discharged between January 2014 and December 2018 from one of three Japanese psychiatric hospital acute inpatient care ward. We collected nine predictors at the time of recruitment, followed up with the participants for 12 months, and observed whether psychotic relapse had occurred. Next, we applied the Cox regression model and used an elastic net to avoid overfitting. Then, we examined discrimination using bootstrapping, Steyerberg's method, and "leave-one-hospital-out" cross-validation. We also constructed a bias-corrected calibration plot. Results: Data from a total of 805 individuals were analyzed. The significant predictors were the number of previous hospitalizations (HR 1.42, 95% CI 1.22-1.64) and the current length of stay in days (HR 1.31, 95% CI 1.04-1.64). In model development for relapse, Harrell's c-index was 0.59 (95% CI 0.55-0.63). The internal and internal-external validation for rehospitalization showed Harrell's c-index to be 0.64 (95% CI 0.59-0.69) and 0.66 (95% CI 0.57-0.74), respectively. The calibration plot was found to be adequate. Conclusion: The model showed moderate discrimination of readmission after discharge. Carefully defining a research question by seeking needs among the population with chronic schizophrenia with multiple episodes may be key to building a useful model.

Safety of romiplostim administered immediately after cord-blood transplantation: a phase 1 trial.

Graft failure and delayed hematopoietic recovery are the major limitations of cord-blood transplantation (CBT). Romiplostim, a thrombopoietin-receptor agonist, promotes megakaryopoiesis and multilineage hematopoiesis in aplastic anemia. The decreased number of hematopoietic stem cells in the early phase after CBT and aplastic anemia share certain characteristics. Therefore, we hypothesized that romiplostim administration immediately after CBT may promote multilineage hematopoietic recovery. We investigated the safety and preliminary efficacy of administering romiplostim a day after CBT. This phase 1 dose-escalation study included six adults with hematologic malignancies in remission. Romiplostim was administered subcutaneously within 7 days after single-unit CBT, initially at doses of 5 µg/kg or 10 µg/kg in three patients, then once a week for 14 weeks or until platelet recovery. The maximum dose was 20 µg/kg. The median number of romiplostim administrations was 6 (range, 3-15). Romiplostim-related adverse events included bone pain (3/6) and injection site reaction (1/6). Non-hematological grade ≥ 3 toxicities were observed in four patients; febrile neutropenia was the most common (4/6). All patients achieved neutrophil engraftment and the median time was 14 days (range, 12-32). Platelet counts ≥ 50 × 109 /L were recorded in all patients except for one who died on day 48; the median time was 34 days (range, 29-98). No relapse, thrombosis, or bone marrow fibrosis was observed during a median follow-up of 34 months. Romiplostim may be safely administered in the early phase of CBT. Further phase 2 trial is warranted for its efficacy evaluation. Trial registration number: UMIN000033799, August 18, 2018.

Efficacy of Low-Dose Isoproterenol Infusion for the Exclusion of a Left Atrial Appendage Thrombus in Patients With Dense Spontaneous Echo Contrast Caused by Atrial Fibrillation.

BACKGROUND: In patients with atrial fibrillation (AF) and severe blood stasis in the left atrial appendage (LAA), dense spontaneous echo contrast (SEC) disturbs the distinct visualization of the LAA interior, thus making thrombus diagnosis inconclusive. We aimed to prospectively assess the efficacy and safety of a protocol for a low-dose isoproterenol (ISP) infusion to reduce SEC to exclude an LAA thrombus.Methods and Results: We enrolled 17 patients with AF and dense SEC (Grade 4 or sludge). ISP was infused with gradually increasing doses of 0.01, 0.02, and 0.03 µg/kg/min at 3-min intervals. After increasing the dose to 0.03 µg/kg/min for 3 min, or when the LAA interior was visible, the infusion was terminated. We reassessed the SEC grade, presence of an LAA thrombus, LAA function, and left ventricular ejection fraction (LVEF) within 1 min of ISP termination. Compared with baseline, ISP significantly increased LAA flow velocity, the LAA emptying fraction, LAA wall velocities, and LVEF (all P<0.01). ISP administration significantly reduced the SEC grade (median) from 4 to 1 (P<0.001). The SEC grade decreased to ≤2 in 15 (88%) patients, and the LAA thrombus was excluded. There were no adverse events. CONCLUSIONS: Low-dose ISP infusion may be effective and safe to reduce SEC and exclude an LAA thrombus by improving LAA function and LVEF.

[Relationship between low back pain and physical activity and sitting time among community-dwelling older adults: A cross-sectional study].

Objectives　Japan has a high prevalence of low back pain among older adults requiring long-term care, which results in increasing expenses; therefore, prevention measures are necessary. This study aimed to examine the relationship between low back pain and physical activity and sitting time according to sex and age (65-74 years [young-old adults]; ≥75 years [old-old adults]) who had not received long-term care certification.Methods　A self-administered survey was mailed to 7,080 adults >65 years of age residing in Tsuru City (Yamanashi Prefecture, Japan) from January to February 2018, and had not received long-term care certification. Demographic information, health status (body mass index and medical history), lifestyle (dietary habits, alcohol consumption, and smoking), presence of low back pain, physical activity, sitting time, and social participation were measured. Low back pain was evaluated by asking, "Did you experience pain in parts of the body other than the knees for the past month?" Those who answered, "experienced low back pain" were categorized as "with low back pain". The short form of the International Physical Activity Questionnaire was used to assess physical activity, which was categorized into three groups: <150, 150-299, and ≥300 min/week. Sitting time was divided into two groups: <480 and ≥480 min/day. Multiple logistic regression analysis was used to determine the association between low back pain and physical activity and sitting time, according to sex and age.Results　Of the 7,080 individuals surveyed, 4,877 responded (2,217 male, 2,660 female), corresponding to a response rate of 68.9%. The number of older adults with low back pain was 1,542 (31.6%) including 673 (30.4%) males and 869 (32.7%) females. The rate of low back pain in young-old adults was 29.8% and 33.6% in old-old adults. There was no significant relationship between lower back pain and physical activity among the young-old adults. In the old-old adults, there was a significant relationship in the male ≥300 min group (odds ratio [OR] 0.66 [95%CI 0.48-0.89]), and in both female 150-299 (OR 0.69 [95%CI 0.48-0.99]) and ≥300 (OR 0.59 [95%CI 0.44-0.80]) min/week groups.Conclusion　The complaint rate for low back pain was approximately 30%, regardless of sex or age. These results suggest that interventions to prevent low back pain are necessary. Moreover, physical activity, but not sitting time, was associated with low back pain in both males and females among the old-old adults.

Efficacy and Safety of Bladder Preservation Therapy in Combination with Atezolizumab and Radiation Therapy (BPT-ART) for Invasive Bladder Cancer: Interim Analysis from a Multicenter, Open-label, Prospective Phase 2 Trial.

PURPOSE: To evaluate the safety and pathologic complete response (pCR) rate of radiation therapy with atezolizumab as bladder-preserving therapy for invasive bladder cancer. METHODS AND MATERIALS: A multicenter, phase 2 study was conducted with patients with clinically T2-3 or very-high-risk T1 bladder cancer who were poor candidates for or refused radical cystectomy. The interim analysis of pCR is reported as a key secondary endpoint ahead of the progression-free survival rate primary endpoint. Radiation therapy (41.4 Gy to the small pelvic field and 16.2 Gy to the whole bladder) was given in addition to 1200 mg intravenous atezolizumab every 3 weeks. After 24 treatment weeks, response was assessed after transurethral resection, and tumor programmed cell death ligand-1 (PD-L1) expression was assessed using tumor-infiltrating immune cell scores. RESULTS: Forty-five patients enrolled from January 2019 to May 2021 were analyzed. The most common clinical T stage was T2 (73.3%), followed by T1 (15.6%) and T3 (11.1%). Most tumors were solitary (77.8%), small (<3 cm) (57.8%), and without concurrent carcinoma in situ (88.9%). Thirty-eight patients (84.4%) achieved pCR. High pCR rates were achieved in older patients (90.9%) and in patients with high PD-L1-expressing tumors (95.8% vs 71.4%). Adverse events (AEs) occurred in 93.3% of patients, with diarrhea being the most common (55.6%), followed by frequent urination (42.2%) and dysuria (20.0%). The frequency of grade 3 AEs was 13.3%, whereas no grade 4 AEs were observed. CONCLUSIONS: Combination therapy with radiation therapy and atezolizumab provided high pCR rates and acceptable toxicity, indicating it could be a promising option for bladder preservation therapy.

Proton beam therapy for muscle-invasive bladder cancer: A systematic review and analysis with Proton-Net, a multicenter prospective patient registry database.

To assess the safety and efficacy of proton beam therapy (PBT) for muscle-invasive bladder cancer (MIBC), we examined the outcomes of 36 patients with MIBC (cT2-4aN0M0) who were enrolled in the Proton-Net prospective registry study and received PBT with concurrent chemotherapy from May 2016 to June 2018. PBT was also compared with X-ray chemoradiotherapy in a systematic review (X-ray (photon) radiotherapy). The radiotherapy consisted of 40-41.4 Gy (relative biological effectiveness (RBE) delivered in 20-23 fractions to the pelvic cavity or the entire bladder using X-rays or proton beams, followed by a boost of 19.8-36.3 Gy (RBE) delivered in 10-14 fractions to all tumor sites in the bladder. Concurrently, radiotherapy was given with intra-arterial or systemic chemotherapy of cisplatin alone or in combination with methotrexate or gemcitabine. Overall survival (OS), progression-free survival (PFS) and local control (LC) rates were 90.8, 71.4 and 84.6%, respectively, after 3 years. Only one case (2.8%) experienced a treatment-related late adverse event of Grade 3 urinary tract obstruction, and no severe gastrointestinal adverse events occurred. According to the findings of the systematic review, the 3-year outcomes of XRT were 57-84.8% in OS, 39-78% in PFS and 51-68% in LC. The weighted mean frequency of adverse events of Grade 3 or higher in the gastrointestinal and genitourinary systems was 6.2 and 2.2%, respectively. More data from long-term follow-up will provide us with the appropriate use of PBT and validate its efficacy for MIBC.

Antigen-specific T cell balance reveals Why patients with atopic dermatitis fail to achieve immune tolerance.

The number of regulatory T cells (Tregs) and how they behave in the pathogenesis of atopic dermatitis (AD) are still controversial. We identified and quantified Tregs, mite-specific Tregs, and mite-specific effector T cells (Teffs) in patients with AD and healthy controls (HCs). We collected peripheral blood and analyzed the cells using flow cytometry after stimulation with mite antigens. Mite-specific Tregs and mite-specific Teffs were recognized by the expression of CD137 and CD154, respectively. Patients with AD had more Tregs than HCs; however, when focusing on a single antigen, the ratio of mite-specific Tregs/Teffs was lower in patients with AD than in HCs. Furthermore, the mite-specific Teffs in patients with AD were more likely to produce proinflammatory cytokines interleukin (IL)-4 and IL-13. This Teff-dominant imbalance is thought to be the cause of development of atopic status in patients with AD without immune tolerance.