Whole-genome sequencing predicting phenotypic antitubercular drug resistance: meta-analysis.

BACKGROUND: For simultaneous prediction of phenotypic drug susceptibility test (pDST) for multiple anti-tuberculosis drugs, the whole genome sequencing (WGS) data can be analyzed using either catalogue-based approach, wherein one causative mutation suggests resistance, (e.g., WHO catalog) or non-catalogue-based approach using complicated algorithm (e.g., TB-profiler, machine learning). The aim was to estimate the predictive ability of WGS-based tests with pDST as the reference, and to compare the two approaches. METHODS: Following the systematic literature search, the diagnostic test accuracies for 14 drugs were pooled using a random-effect bivariate model. RESULTS: Out of 779 articles, 44 articles with 16,821 specimens for meta-analysis and 13 articles not for meta-analysis were adopted. The areas under summary receiver operating characteristic curve suggested "excellent" (0.97-1.00) for 2 drugs (isoniazid 0.975, rifampicin 0.975), "very good" (0.93-0.97) for 8 drugs (pyrazinamide 0.946, streptomycin 0.952, amikacin 0.968, kanamycin 0.963, capreomycin 0.965, para-aminosalicylic acid 0.959, levofloxacin 0.960, ofloxacin 0.958), and "good" (0.75-0.93) for 4 drugs (ethambutol 0.926, moxifloxacin 0.896, ethionamide 0.878, prothionamide 0.908). The non-catalogue-based and catalogue-based approaches had similar ability for all drugs. CONCLUSION: WGS accurately identifies isoniazid and rifampicin resistance. For most drugs, positive WGS results reliably predict pDST positive. The two approaches had similar ability.

Urinary pentosidine level is associated with the risk of fracture in community-dwelling older adults: a prospective observational study.

A history of fracture in adulthood and urinary pentosidine levels were independently and significantly associated with fracture occurrence in this prospective observational study of community-dwelling older adults. PURPOSE: This prospective observational study aimed to determine the factors associated with fragility fractures in community-dwelling older adults. METHODS: Overall, 254 older adults who were participants of the Good Aging and Intervention Against Nursing Care and Activity Decline study in 2016 were included in this study. Grip strength, muscle mass, gait speed, calcaneal bone density, and the levels of parathyroid hormone, osteocalcin, 25-hydroxyvitamin D, total procollagen type I N-terminal propeptide, insulin-like growth factor-1 (IGF-1), tartrate-resistant acid phosphatase-5b, and urinary pentosidine were measured at baseline. Participants were classified as fracture ( +) or fracture (-) based on the data collected during a 5-year follow-up period. RESULTS: Excluding those who were lost to follow-up during the observation period, 182 participants (64 men and 118 women, mean age: 74.2 years, range: 47-99 years) were included in the analysis. During the observation period, 23 patients experienced 24 new fractures. In univariate analysis, sex, height, weight, history of fracture in adulthood, baseline grip strength, muscle mass, bone density, and the levels of urinary pentosidine and IGF-1 at baseline were significantly different between patients who developed a fracture during follow-up and those who did not. In multivariate analysis, a history of fracture in adulthood and urinary pentosidine levels were independently and significantly associated with fracture occurrence. CONCLUSION: High urine pentosidine levels and a history of fracture in adulthood are independent risk factors for fracture occurrence in community-dwelling older adults.

Urinary pentosidine level is associated with grip strength and gait speed in community-dwelling adults: a cross-sectional study.

BACKGROUND: Muscle and bone interactions might be associated with osteoporosis and sarcopenia. Urinary pentosidine and serum 25-hydroxyvitamin D (25(OH)D) might affect muscle and bone interactions. It is unclear whether these biomarkers are affected by age and sex or play a role in muscle and physical functions. We aimed to investigate the association between urinary pentosidine and serum 25(OH)D levels with muscle mass, muscle strength, and physical performance in community-dwelling adults. METHODS: Two-hundred and fifty-four middle-aged and elderly adults were enrolled. There was no significant difference in age between 97 men (75.0 ± 8.9 years) and 157 women (73.6 ± 8.1 years). The skeletal muscle mass index (SMI), grip strength, and gait speed were assessed. The urinary pentosidine level was measured. We evaluated the association of urinary pentosidine and serum 25(OH)D levels with age and sex (student's t-test) and correlations between biomarker and each variable (Pearson's correlation coefficients). Multiple regression analysis was performed with grip strength and gait speed as dependent variables and with age, height, weight, body mass index (BMI), speed of sound (SOS), SMI, glycated hemoglobin (HbA1c), estimated glomerular filtration rate (eGFR), 25(OH)D, and pentosidine as independent variables using the stepwise method. RESULTS: The urinary pentosidine level was negatively correlated with grip strength, gait speed, eGFR, and insulin-like growth factor-1 (IGF-1) in men and with SOS, grip strength, and gait speed in women. The serum 25(OH)D level was positively correlated with IGF-1 in women and grip strength in men. Grip strength was associated with age, height, and pentosidine in men and height and pentosidine in women. Gait speed was associated with age, BMI, and pentosidine in men and age, height, and pentosidine in women. CONCLUSION: Urinary pentosidine levels are significantly associated with grip strength and gait speed and may serve as a biomarker of muscle and bone interactions.

Age-related changes in muscle elasticity around the shoulder joint in young male baseball players: A prospective longitudinal study.

BACKGROUND: Longitudinal changes of elasticity in the muscle tissues around the shoulder joint during the growth period have not been assessed using shear wave elastography. METHODS: This study enrolled male students aged 13-18 years who played baseball or rubber baseball as an extra-curricular activity during junior high or high school or on a baseball team outside of school. The exclusion criterion was a history of surgery for athletic injury. One hundred and twenty-one boys were included in the study. The elasticity of the superior part of the trapezius, the supraspinatus, and the infraspinatus were measured by ultrasound. The shear elastic modulus (SEM), which is the ratio of the strain ratio (SR) in the acoustic coupler to the SR of each muscle, was calculated as a representative value. Six months after the baseline assessment, subjects were evaluated regarding any newly developed pain in the joint of the throwing shoulder, and categorized into either the non-pain group or the pain group. RESULTS: Although all muscle SEMs tended to increase in both the throwing and non-throwing shoulders, no significant difference was observed in the prevalence of shoulder joint pain between ages (p = 0.541). The results of a binominal logistic regression analysis, adjusted for age, body mass index, playing position in baseball, frequency of baseball practice, shoulder range of motion, and muscle strength showed that a decrease in SEM values of the supraspinatus was a risk factor for the development of new pain (odds ratio: 0.056; 95% confidence interval 0.011-0.299; p = 0.001). CONCLUSIONS: The elasticity of muscle tissues around the throwing shoulder increased with age, and low tissue elasticity of the supraspinatus of the throwing shoulder was a factor that triggered pain during throwing motions.

Customized exercise programs implemented by physical therapists improve exercise-related self-efficacy and promote behavioral changes in elderly individuals without regular exercise: a randomized controlled trial.

BACKGROUND: Specialized, individualized exercise programs that increase self-efficacy (SE) are essential for the development and maintenance of regular exercise. The objective of this study is to examine the effect of customized exercise programs (CEPs) implemented by physical therapists in improving exercise-related SE and promoting behavioral changes among elderly individuals who do not exercise regularly compared with commonly prescribed exercises. METHODS: In this randomized controlled study, the sampling frame consisted of participants in an annual town-sponsored medical check-up. The inclusion criteria were no regular exercise and age of 65-74 years at enrollment. The subjects in the intervention group (CEP group) were instructed to perform individualized exercises prescribed based on an original algorithm. Data collection was performed at baseline and 3, 6, 9, and 12 months after exercise instruction. The primary outcome was SE for exercise at the last time point. Secondary outcomes were SE for exercise, stage of change in exercise behavior, knee pain, and low back pain at each evaluation time point. RESULTS: Fifty subjects (CEP group n = 26; control group n = 24) were randomized. In the CEP group, 25 of 26 subjects were analyzed at 3 months, 26 of 26 subjects were analyzed at 6 and 9 months, and 25 of 26 subjects were analyzed at 12 months. In the control group, 23 of 24 subjects were analyzed at 3, 6, 9, and 12 months. SE for exercise improved 24.0% (CEP group 30.8%; control group 16.7%) compared to baseline. No significant differences were observed in the primary outcome. SE for exercise was significantly lower at 9 and 12 months compared with baseline in the control group. Stage of change for exercise behavior was significantly higher at 3 months compared with baseline in the CEP group and at 6 months in the control group. Knee pain was worse at 3 months compared with baseline in the control group. CONCLUSIONS: This study suggested that exercise instruction with CEPs contributes to the maintenance of SE for exercise and is useful for changing exercise behavior in elderly individuals who do not regularly exercise. TRIAL REGISTRATION: UMIN000027240 , registered on 03/05/2017.

Association of serum bone- and muscle-derived factors with age, sex, body composition, and physical function in community-dwelling middle-aged and elderly adults: a cross-sectional study.

BACKGROUND: Understanding interactions between bone and muscle based on endocrine factors may help elucidate the relationship between osteoporosis and sarcopenia. However, whether the abundance or activity of these endocrine factors is affected by age and sex or whether these factors play a causal role in bone and muscle formation and function is unclear. We aimed to evaluate the association of serum bone- and muscle-derived factors with age, sex, body composition, and physical function in community-dwelling middle-aged and elderly adults. METHODS: In all, 254 residents (97 men, 157 women) participated in this cross-sectional study conducted in Japan. The calcaneal speed of sound (SOS) was evaluated by quantitative ultrasound examination. Skeletal muscle mass index (SMI) was calculated by bioelectrical impedance analysis. Grip strength was measured using a dynamometer. Gait speed was measured by optical-sensitive gait analysis. Serum sclerostin, osteocalcin (OC), insulin-like growth factor-1 (IGF-1), myostatin, and tartrate-resistant acid phosphatase-5b (TRACP-5b) concentrations were measured simultaneously. The difference by sex was determined using t test. Correlations between serum bone- and muscle-derived factors and age, BMI, SOS, SMI, grip strength, gait speed, and TRACP-5b in men and women were determined based on Pearson's correlation coefficients. Multiple regression analysis was performed using the stepwise method. RESULTS: There was no significant difference with regard to age between men (75.0 ± 8.9 years) and women (73.6 ± 8.1 years). Sclerostin was significantly higher in men than in women and tended to increase with age in men; it was significantly associated with SOS and TRACP-5b levels. OC was significantly higher in women than in men and was significantly associated with TRACP-5b levels and age. IGF-1 tended to decrease with age in both sexes and was significantly associated with SOS and body mass index. Myostatin did not correlate with any assessed variables. CONCLUSIONS: Sclerostin was significantly associated with sex, age, and bone metabolism, although there was no discernable relationship between serum sclerostin levels and muscle function. There was no obvious relationship between OC and muscle parameters. This study suggests that IGF-1 is an important modulator of muscle mass and function and bone metabolism in community-dwelling middle-aged and elderly adults.

Association between speed of sound of calcaneal bone assessed by quantitative ultrasound and sarcopenia in a general older adult population: A cross-sectional study.

BACKGROUND: Lower calcaneal speed of sound may be related to sarcopenia because sarcopenia and osteopenia/osteoporosis show a linked relationship in older adults. The purpose of this study is to clarify whether the speed of sound of calcaneal bone assessed by quantitative ultrasound is associated with sarcopenia in a community-dwelling older adult population. METHODS: This was a cross-sectional observational study. The participants in the study were recruited from a group of individuals who had registered for an annual town-sponsored medical check-up. The inclusion criteria for participation in the study were (1) aged older than 40 years, (2) living independently, and (3) able to walk without assistance. Those who had nursing care insurance were excluded. Four hundred sixty-seven residents (182 men, 285 women) were registered in the study. Demographic information, fall history, muscle mass index, grip strength, and gait speed were assessed. The speed of sound through the calcaneal bone was evaluated using a CM-200 sonometer. The assessment for sarcopenia is based on the recommendations of the Asian Working Group for Sarcopenia. RESULTS: Speed of sound was positively correlated with muscle mass index and gait speed in men, and was positively correlated with grip strength and gait speed in women, when adjusted for age and body mass index. In a multivariate logistic regression analysis adjusted for age and sex and other confounders, speed of sound was independently related with lower gait speed and sarcopenia in women. Speed of sound under 1470.5 m/sec had discriminated for sarcopenia in females. CONCLUSION: We propose that the speed of sound of calcaneal bone may be used to screen for sarcopenia in women. Sarcopenia should be considered if the speed of sound value is less than 1470.5 m/s in older women.

Self-care agency, lifestyle, and physical condition predict future frailty in community-dwelling older people.

The purpose of this 2 year longitudinal study was to identify the relationship between self-care agency, lifestyle, physical condition, and frailty among community-dwelling older people in a rural area of Japan. The participants were 133 older individuals aged 65 years or above. Data collection was conducted via face-to-face interviews using self-administered questionnaires. Background information, such as age, sex, current employment status, family structure, medication use, comorbidities, and knee and lower back pain, were assessed. The definition of frailty was based on the Frailty Checklist. Self-care agency, lifestyle habits, and locomotive syndrome were assessed using specific assessment scores. Logistic regression analysis showed that locomotive syndrome, knee and lower back pain, and stroke are risk factors for frailty. Among the factors associated with frailty, current employment, regular exercise, and self-care agency were recognized as preventive factors of depression, decreased cognitive function, and being housebound. Our findings suggest that enhancing self-care agency, regular exercise, and self-management skills for chronic illness and disability may decrease the progression of frailty among older people.

Association between sarcopenia and low back pain in local residents prospective cohort study from the GAINA study.

BACKGROUND: Low back pain (LBP) is one of the most common ailments that people experience in their lifetime. On the other hands, Sarcopenia also leads to several physical symptoms and contributes to reducing the quality of life of elderly people.The purpose of this study is to investigate the association between sarcopenia and low back pain among the general population. METHODS: The subjects included 216 adults (79 men and 137 women; mean age, 73.5 years) undergoing a general medical examination in Hino, Japan. Skeletal muscle index (SMI), The percentage of young adults' mean (%YAM) of the calcaneal bone mass using with quantitative ultrasound (QUS) method and walking speed were measured, and subjects who met the criteria of the Asian Working Group for Sarcopenia were assigned to the sarcopenia group. Subjects with decreased muscle mass only were assigned to the pre-sarcopenia group, and all other subjects were assigned to the normal group. Then, we compared the correlations with low back pain physical finding. The Oswestry Disability Index (ODI) and the low back pain visual analogue scale (VAS) were used as indices of low back pain. Statistical analysis was performed among three groups with respect their characteristic, demographics, data of sarcopenia determining factor, VAS and ODI. We also analysed prevalence of LBP and sarcopenia. We investigated the correlations between ODI and the sarcopenia-determining factors of walking speed, muscle mass and grip strength. RESULTS: Sarcopenia was noted in 12 subjects (5.5%). The pre-sarcopenia group included 38 subjects (17.6%), and the normal group included 166 subjects (76.9%). The mean ODI score was significantly higher in the sarcopenia group (25.2% ± 12.3%; P < 0.05) than in the pre-sarcopenia group (11.2% ± 10.0%) and the normal group (11.9% ± 12.3%). %YAM and BMI were significantly lower in the sarcopenia group than in other groups (P < 0.05). A negative correlation existed between walking speed and ODI (r = -0.32, P < 0.001). CONCLUSIONS: The results of this study suggested that decreased physical ability due to quality of life in residents with LBP may be related to sarcopenia.

Gait variability analysed using an accelerometer is associated with locomotive syndrome among the general elderly population: The GAINA study.

BACKGROUND: Gait variability analysed using an accelerometer provides a unique measurement of locomotive dysfunction in patients with musculoskeletal disease or in frail elderly subjects. Therefore, assessing gait variability may become a clinical screening method for the locomotive syndrome. The purpose of this study was to investigate whether gait variability analysed using an accelerometer was associated with locomotive syndrome in the general elderly population. METHODS: A total of 273 residents were screened after a yearly medical check-up, and of these, 223 subjects (mean age, 73.6 ± 8.3 years) met the eligibility criteria. Demographic information, body function and structure measurements (bone mass, grip strength, muscle mass, and postural alignment), and gait parameters were assessed. Gait variability analysis was based on acceleration using a wireless tri-axial accelerometer attached to the 3rd lumbar vertebra process by a trunk belt. Autocorrelation coefficients were used to represent gait variability in three directions: vertical, mediolateral, and anteroposterior. The subjects were classified as either having or not having the locomotive syndrome based on the 5-question Geriatric Locomotive Function Scale. RESULTS: Of the 223 subjects, 41 (18.3%) had the locomotive syndrome. Autocorrelation coefficients in three directions were lower in the subjects with locomotive syndrome. Using multivariate logistic regression analysis with adjustment factors, of the autocorrelation coefficients only gait variability in the vertical axis remained a significant independent associated with the locomotive syndrome. CONCLUSION: This finding suggested that gait variability based on evaluation of autocorrelation coefficients in the vertical axis measured using an accelerometer has the potential to become a screening method for the locomotive syndrome in the general elderly population.

Automated stride assistance device improved the gait parameters and energy cost during walking of healthy middle-aged females but not those of young controls.

[Purpose] The aim of this study was to clarify the effects of an automated stride assistance device on gait parameters and energy cost during walking performed by healthy middle-aged and young females. [Subjects and Methods] Ten middle-aged females and 10 young females were recruited as case and control participants, respectively. The participants walked for 3 minutes continuously under two different experimental conditions: with the device and without the device. Walking distance, mean walking speed, mean step length, cadence, walk ratio and the physiological cost index during the 3-minutes walk were measured. [Results] When walking with the stride assistance device, the step length and walk ratio of the middle-aged group were significantly higher than without it. Also, during walking without assistance from the device, the physiological cost index of the middle-aged group significantly increased; whereas during walking with assistance, there was no change. The intergroup comparison in the middle-aged group showed the physiological cost index was lower under the experimental condition with assistance provided, as opposed to the condition without the provision of assistance. [Conclusion] The results of this study show that the stride assistance device improved the gait parameters of the middle-aged group but not those of young controls.

Geographic and economic influences on benralizumab prescribing for severe asthma in Japan.

Benralizumab, a monoclonal antibody targeting IL-5 receptors, reduces exacerbations and oral corticosteroid requirements for severe, uncontrolled eosinophilic asthma. In Japan, geographic disparities in asthma outcomes suggest differential prescribing and access. This study aimed to quantify regional prescribing variations for benralizumab nationwide. Using Japan's National Database (NDB) of insurance claims (2009-2019), benralizumab standardized claim ratios (SCRs) were calculated for 47 prefectures. Correlations between SCRs and other biologics' SCRs, economic variables like average income, and physician densities were evaluated through univariate analysis and multivariate regressions. Income-related barriers to optimal prescribing were examined. Wide variation emerged in benralizumab SCRs, from 40.1 to 184.2 across prefectures. SCRs strongly correlated with omalizumab (r = 0.61, p < 0.00001) and mepolizumab (r = 0.43, p = 0.0024). Average monthly income also positively correlated with benralizumab SCRs (r = 0.45, p = 0.0016), whereas lifestyle factors were insignificant. Respiratory specialist density modestly correlated with SCRs (r = 0.29, p = 0.047). In multivariate regressions, average income remained the most robust predictor (B = 0.74, p = 0.022). Benralizumab SCRs strongly associate with income metrics more than healthcare infrastructure/population factors. Many regions show low SCRs, constituting apparent prescribing gaps. Access barriers for advanced asthma therapies remain inequitable among Japan's income strata. Addressing affordability alongside specialist allocation can achieve better prescribing quality and asthma outcomes.

High red blood cell distribution width attenuates the effectiveness of Immune checkpoint inhibitor therapy: An exploratory study using a clinical data warehouse.

BACKGROUND: Immune checkpoint inhibitors (ICIs) have improved outcomes in cancer treatment but are also associated with adverse events and financial burdens. Identifying accurate biomarkers is crucial for determining which patients are likely to benefit from ICIs. Current markers, such as PD-L1 expression and tumor mutation burden, exhibit limited predictive accuracy. This study utilizes a Clinical Data Warehouse (CDW) to explore the prognostic significance of novel blood-based factors, such as the neutrophil-to-lymphocyte ratio and red cell distribution width (RDW), to enhance the prediction of ICI therapy benefit. METHODS: This retrospective study utilized an exploratory cohort from the CDW that included a variety of cancers to explore factors associated with pembrolizumab treatment duration, validated in a non-small cell lung cancer (NSCLC) patient cohort from electronic medical records (EMR) and CDW. The CDW contained anonymized data on demographics, diagnoses, medications, and tests for cancer patients treated with ICIs between 2017-2022. Logistic regression identified factors predicting ≤2 or ≥5 pembrolizumab doses as proxies for progression-free survival (PFS), and Receiver Operating Characteristic analysis was used to examine their predictive ability. These factors were validated by correlating doses with PFS in the EMR cohort and re-testing their significance in the CDW cohort with other ICIs. This dual approach utilized the CDW for discovery and EMR/CDW cohorts for validating prognostic biomarkers before ICI treatment. RESULTS: A total of 609 cases (428 in the exploratory cohort and 181 in the validation cohort) from CDW and 44 cases from EMR were selected for study. CDW analysis revealed that elevated red cell distribution width (RDW) correlated with receiving ≤2 pembrolizumab doses (p = 0.0008), with an AUC of 0.60 for predicting treatment duration. RDW's correlation with PFS (r = 0.80, p<0.0001) and its weak association with RDW (r = -0.30, p = 0.049) were confirmed in the EMR cohort. RDW also remained significant in predicting short treatment duration across various ICIs (p = 0.0081). This dual methodology verified pretreatment RDW elevation as a prognostic biomarker for shortened ICI therapy. CONCLUSION: This study suggests the utility of CDWs in identifying prognostic biomarkers for ICI therapy in cancer treatment. Elevated RDW before treatment initiation emerged as a potential biomarker of shorter therapy duration.

Real-world evidence of efficacy of pembrolizumab plus chemotherapy and nivolumab plus ipilimumab plus chemotherapy as initial treatment for advanced non-small cell lung cancer.

BACKGROUND: For advanced non-small cell lung cancer (NSCLC), combination therapies including a PD-1 inhibitor plus chemotherapy or a PD-1 inhibitor, CTLA-4 inhibitor, and chemotherapy are standard first-line options. However, data directly comparing these regimens are lacking. This study compared the efficacy of pembrolizumab plus chemotherapy (CP) against nivolumab plus ipilimumab and chemotherapy (CNI) in a real-world setting. METHODS: In this multicenter retrospective study, we compared the efficacy and safety of CP and CNI as first-line therapies in 182 patients with stage IIIB-IV NSCLC. Primary outcomes were overall survival (OS) and progression-free survival (PFS), while secondary outcomes included the response rate (RR) and safety profiles. Kaplan-Meier survival curves and Cox proportional hazards models were utilized for data analysis, adjusting for confounding factors such as age, gender, and PD-L1 expression. RESULTS: In this study, 160 patients received CP, while 22 received CNI. The CP group was associated with significantly better PFS than the CNI group (median 11.7 vs. 6.6 months, HR 0.56, p = 0.03). This PFS advantage persisted after propensity score matching to adjust for imbalances. No significant OS differences were observed. Grade 3-4 adverse events occurred comparably, but immune-related adverse events were numerically more frequent in the CNI group. CONCLUSIONS: In real-world practice, CP demonstrated superior PFS compared with CNI. These findings can inform treatment selection in advanced NSCLC.

HLA-DQA1*01:03 and DQB1*06:01 are risk factors for severe COVID-19 pneumonia.

The clinical spectrum of COVID-19 includes a wide range of manifestations, from mild symptoms to severe pneumonia. HLA system plays a pivotal role in immune responses to infectious diseases. The purpose of our study was to investigate the association between HLA and COVID-19 severity in a Japanese population. The study included 209 Japanese COVID-19 patients aged ≥20 years. Saliva samples were collected and used to determine the HLA genotype by HLA imputation through genome-wide association analyses. The association between HLA genotype and COVID-19 severity was then evaluated. The allele frequency was compared between patients with respiratory failure (severe group: 91 cases) and those without respiratory failure (non-severe group: 118 cases), categorising the data into three time periods: pre-Omicron epidemic period, Omicron epidemic period, and total period of this study (from January 2021 to May 2023). In comparing the severe and non-severe groups, the frequencies of the HLA-DQA1*01:03 (35.1% vs. 10.5%, odds ratio [OR] = 4.57, corrected p [pc] = 0.041) and -DQB1*06:01 (32.4% vs. 7.9%, OR = 5.54, pc = 0.030) alleles were significantly higher in the severe group during the pre-Omicron epidemic period. During the Omicron epidemic period, HLA-DQB1*06 (32.4% vs. 7.9%, OR = 5.54, pc = 0.030) was significantly higher in the severe group. During total period of this study, HLA-DQA1*01:03 (30.2% vs. 14.4%, OR = 2.57, corrected pc = 0.0013) and -DQB1*06:01 (44.5% vs. 26.7%, OR = 2.20, pc = 0.013) alleles were significantly higher in the severe group. HLA-DQB1*06:01 and -DQA1*01:03 were in strong linkage disequilibrium with each other (r2 = 0.91) during total period of this study, indicating that these two alleles form a haplotype. The frequency of the HLA-DQA1*01:03-DQB1*06:01 in the severe group was significantly higher than in the non-severe group during pre-Omicron epidemic period (32.4% vs. 7.9%, OR = 5.59, pc = 0.00072), and total period of this study (28.6% vs. 13.1%, OR = 2.63, pc = 0.0013). During Omicron epidemic period, the haplotype did not demonstrate statistical significance, although the odds ratio indicated a value greater 1. Frequencies of the HLA-DQA1*01:03 and -DQB1*06:01 alleles were significantly higher in severe COVID-19 patients, suggesting that these alleles are risk factors for severe COVID-19 pneumonia in the Japanese population.

Efficacy and safety of benralizumab in elderly patients with severe eosinophilic asthma.

Background: Biologics are the important drugs for severe asthma, but clinical trials included few elderly patients. Data on the safety and efficacy of benralizumab in elderly asthma patients are limited. Methods: This clinical study was a multicentre, retrospective, observational study at two hospitals. Patients aged ≥18 years diagnosed with severe asthma treated with benralizumab were included. Elderly patients were defined as those aged 70 years or older. Efficacy and safety were then analyzed in elderly and non-elderly patients. The primary endpoints were the annual number of asthma exacerbations for efficacy and the discontinuation rate due to adverse events for safety. Results: Between August 2016 and October 2022, 61 patients were enrolled; 10 patients were excluded, and 51 (22 elderly, 29 non-elderly) patients were analyzed. In elderly patients, the annual number of asthma exacerbations before treatment with benralizumab (pre-benralizumab) was 3.78, and the number during treatment with benralizumab was 1.26, a decrease of 2.52 (95% confidence interval [CI], 1.3 to 3.74, p < 0.001). In non-elderly patients, the annual number of asthma exacerbation in the pre-benralizumab period was 3.24, and during treatment with benralizumab it was 0.68, a decrease of 2.56 (95% CI, 1.3 to 3.82, p < 0.001). There was no significant difference in discontinuation due to treatment-related adverse events (elderly vs non-elderly, 2 (9%) vs 0 (0%), p = 0.18). Conclusion: Benralizumab reduced the annual number of asthma exacerbations and was well tolerated in elderly patients.

Improved diagnostic accuracy with three lung tumor markers compared to six-marker panel.

Background: Combining multiple tumor markers increases sensitivity for lung cancer diagnosis in the cost of false positive. However, some would like to check as many as tumor markers in the fear of missing cancer. We though to propose a panel of fewer tumor markers for lung cancer diagnosis. Methods: Patients with suspected lung cancer who simultaneously underwent all six tests [carcinoembryonic antigen (CEA), cytokeratin-19 fragment (CYFRA), squamous cell carcinoma-associated antigen (SCC), neuron-specific enolase (NSE), pro-gastrin-releasing peptide (ProGRP), and sialyl Lewis-X antigen (SLX)] were included. Tumor markers with significant impact on the lung cancer in a logistic regression model were included in our panel. Area under the curve (AUC) was compared between our panel and the panel of all six. Results: We included 1,733 [median 72 years, 1,128 men, 605 women, 779 (45%) confirmed lung cancer]. Logistic regression analysis suggested CEA, CYFRA, and NSE were independently associated with the lung cancer diagnosis. The panel of these three tumor markers [AUC =0.656, 95% confidence interval (CI): 0.630-0.682, sensitivity 0.650, specificity 0.662] had better (P<0.001) diagnostic performance than six tumor markers (AUC =0.575, 95% CI: 0.548-0.602, sensitivity 0.829, specificity 0.321). Conclusions: Compared to applying all six markers (at least one marker above the upper limit of normal), the panel with three markers (at least one marker above the upper limit of normal) led to a better predictive value by lowering the risk of false positives.

Relationship Between Preoperative Psoas Major Muscle Quality and Forgotten Joint Score-12 in Patients After Total Hip Arthroplasty.

Background: There are limited reports on the factors affecting the Forgotten Joint Score-12 (FJS-12) in patients after total hip arthroplasty (THA). Therefore, this study aimed to determine whether the quantity and quality of the preoperative psoas muscle are related to the FJS-12 in post-THA patients. Methods: This retrospective cohort study used mailed questionnaires and medical records. Questionnaires containing the FJS-12 were mailed to 752 patients who underwent THA at our hospital between April 2015 and August 2020. The quantity and quality of the psoas major muscle were measured by computed tomography. The association between FJS-12 and the quantity and quality of the psoas major muscle was assessed by logistic regression analysis adjusted for potentially relevant factors. Results: In total, 484 patients were included in the analysis. The FJS-12 score of the analyzed subjects was 75 points. Poor psoas major muscle quality was associated with a poor group of patients scoring <50 on the FJS-12. This association was independent of the adjustment factors. However, the quantity of psoas muscle was not associated. Conclusions: The quality of the psoas major muscle is associated with FJS-12. In the rehabilitation of patients undergoing THA, focusing on the quality of the psoas major muscle may help achieve the ultimate goal.

Relationship among Osteoporosis, Sarcopenia, Locomotive Syndrome, and Spinal Kyphosis in Older Individuals Living in a Local Mountain Area.

STUDY DESIGN: Cross-sectional cohort study. PURPOSE: This study investigated the relationship among osteoporosis, sarcopenia, locomotive syndrome, and spinal kyphosis in older individuals living in a mountain area. OVERVIEW OF LITERATURE: Kyphosis greatly reduces the quality of life of older individuals. Osteoporosis and sarcopenia are kyphosiscausing factors. METHODS: This cross-sectional study included 361 individuals aged ≥65 years (mean age, 75.0 years) living in a local mountain area and underwent medical check-ups from 2014 to 2018. The survey items included kyphosis index, body mass index, back pain prevalence, back pain Visual Analog Scale score, Oswestry Disability Index, walking speed, grip strength, skeletal mass index, osteoporosis (% young adult mean [YAM]), LOCOMO 5 score, and presence of sarcopenia (Asian Working Group for Sarcopenia). The participants were divided into the N (kyphosis index: <12; n=229, 63.4%), M (kyphosis index: 12-15; n=99, 27.4%), and K (kyphosis index: ≥15; n=33, 9.2%) groups. p -values of <0.05 were considered statistically significant. An association factor of kyphosis (kyphosis index: ≥15) was investigated with logistic regression analysis. RESULTS: Age and LOCOMO 5 scores were significantly higher (p <0.05) and %YAM and walking speed were significantly lower (p <0.05) in the K group than in the M and N groups. Other survey items showed significant differences. Only %YAM (odds ratio, 0.20; 95% confidence interval, 0.04-0.96) was an independent factor associated with a kyphosis index of ≥15. CONCLUSIONS: Decreased muscle mass and muscle strength would be related to kyphosis; however, no such relations were noted. Bone loss was significantly related to kyphosis. Osteoporosis-induced decrease in vertebral body height is present in the background. Sarcopenia and locomotive syndrome were not related to kyphosis, whereas decreased bone density was independently associated with kyphosis in older individuals living in a mountain area.

Atezolizumab addition to platinum doublet: evaluating survival outcomes for patients with extensive disease small cell lung cancer.

BACKGROUND: The efficacy of adding atezolizumab to the platinum doublet regimen for extensive disease small cell lung cancer (ED-SCLC) remains marginally limited. METHODS: We retrospectively assessed the real-world efficacy and safety of atezolizumab in addition to carboplatin and etoposide (EP + A), versus carboplatin and etoposide (EP) alone in previously untreated ED-SCLC patients. RESULTS: From a total of 99 patients, 46 were assigned to the EP + A group, and 53 to the EP group. No significant difference was observed in progression-free survival between the groups. However, the overall survival (OS) was significantly longer in the EP + A group (20.8 vs 12.1 months; HR: 0.52; p = 0.0127). Patients older than 70 years, male, with performance status 0-1, without liver metastasis, and low levels of C-reactive protein and neutrophil-lymphocyte ratio, experienced longer OS in the EP + A group compared to the EP group. CONCLUSION: The addition of atezolizumab to the platinum doublet regimen significantly extended OS in ED-SCLC patients, particularly among certain subgroups, suggesting its potential value in personalized treatment strategies. Further investigation is warranted to validate these findings.