Fluoroquinolone resistance and clinical characteristics of acute bacterial prostatitis in Japan: A multicenter study by the Japanese research group for urinary tract infection.

OBJECTIVE: This multicenter study aimed to analyze the risk factors for fluoroquinolone (FQ) resistance and to clarify the clinical characteristics of acute bacterial prostatitis (ABP) in Japan. METHODS: A total of 124 patients clinically diagnosed with ABP at 13 medical institutions participating in the Japanese Research Group for Urinary Tract Infection between January and December 2017 were retrospectively reviewed. RESULTS: Of the 124 patients included in this study, 37 were outpatients, and 87 were inpatients. The main underlying medical conditions before the onset of ABP were severe dysuria, urinary retention, transurethral manipulation, indwelling urinary catheter, and transrectal prostate biopsy (TRBx). The main symptoms were fever (≥37.5 °C), prostate tenderness, dysuria, micturition pain, urinary retention, and macrohematuria. Bacteremia was observed in 14 patients. Prostatic abscess was observed in three patients. Escherichia coli was the predominant organism, accounting for 48 % (51/106). FQ-resistant E. coli was detected in 33 % (17/51), and extended-spectrum beta-lactamase-producing E. coli in 12 % (6/51). TRBx (odds ratio [OR] = 48.60, 95 % confidence interval [CI]: 5.49-430.00, p < 0.001) and inpatient status (OR = 29.00, 95 % CI: 1.95-430.00, p = 0.014) were risk factors for the detection of FQ-resistant bacteria. CONCLUSIONS: The detection rate of FQ-resistant bacteria was significantly higher with TRBx ABP and inpatient status. These findings have important implications for the management of ABP and antimicrobial treatment, especially for TRBx ABP, which should be considered a separate category.

Association of conventional cigarette smoking, heated tobacco product use and dual use with hypertension.

BACKGROUND: Heated tobacco products (HTPs) have emerged as alternatives to conventional cigarettes. However, their health effects remain largely unknown. This study aimed to prospectively explore the association between the use of cigarettes and HTPs and the risk of hypertension. METHODS: This cohort study analysed data from 30 152 workers (82.0% men, mean age 42.9 ± 11.0 years) who were initially free of hypertension, participating in the Japan Epidemiology Collaboration on Occupational Health Study. Participants were categorized into five groups based on their self-reported tobacco product use: never smokers, past smokers, exclusive cigarette smokers, exclusive HTP users and dual users of cigarettes and HTPs. Hypertension cases were identified using three data points from annual health checkup data collected between 2019 and 2021. Cox proportional hazards regression models were used to investigate the association between tobacco product use and hypertension. RESULTS: During a mean follow-up of 2.6 years (range: 0.1-4.0 years), 3656 new cases of hypertension were identified. Compared with never smokers, the risk of hypertension was higher among exclusive cigarette smokers [hazard ratio (HR) 1.26, 95% confidence interval (CI) 1.13-1.41] and exclusive HTP users (HR 1.19, 95% CI 1.06-1.34). There was also a suggestion of increased risk of hypertension among dual users (HR 1.16, 95% CI 0.98-1.38). Furthermore, the risk of hypertension increased with the intensity of cigarette/HTP use in all tobacco product users. CONCLUSIONS: Similarly, both cigarette smoking and HTP use elevate the risk of hypertension. HTPs should not be regarded as less harmful alternatives to traditional cigarettes for preventing hypertension.

Comparison of oncological outcomes of upfront androgen receptor signaling inhibitors and combined androgen blockade in Japanese patients with metastatic castration-sensitive prostate cancer.

In recent years, randomized controlled trials have demonstrated that upfront androgen receptor signaling inhibitors (ARSIs) prolong overall survival (OS) compared with androgen deprivation therapy (ADT) alone or combined androgen blockade (CAB) in patients with metastatic castration-sensitive prostate cancer (mCSPC). However, it remains unclear whether upfront ARSI is superior to CAB in Asian populations, among which the efficacy of ADT/CAB is considered relatively high. In this study, we compared the oncological outcomes of upfront ARSI and CAB in Japanese patients with mCSPC. Patients with mCSPC who underwent systemic therapy between May 2009 and October 2023 were enrolled retrospectively. Propensity score matching (PSM) was performed to compare the castration-resistant prostate cancer-free survival (CRPC-FS), cancer-specific survival (CSS), and OS between patients treated with upfront ARSI (ARSI group) and those treated with CAB (CAB group). In total, 30 and 142 patients were enrolled in the ARSI and CAB groups, respectively. After PSM (25 patients in each group), CRPC-FS was significantly longer in the ARSI group than in the CAB group (median: 36.7 vs. 12.3 months, hazard ratio: 0.44, 95% confidence interval: 0.20-0.97, p = 0.035). No significant differences were observed in CSS or OS between the two groups. In conclusion, when compared to CAB, upfront ARSI might have the potential to extend CRPC-FS among individuals in the Japanese population.

Myelodysplastic syndrome occurring after enfortumab vedotin treatment for metastatic urothelial carcinoma.

Introduction: Enfortumab vedotin is an antibody-drug conjugate targeting Nectin-4 for the treatment of advanced urothelial carcinoma in patients previously treated with platinum-containing chemotherapy and immune checkpoint inhibitors. Common adverse events include rashes, peripheral neuropathy, and hyperglycemia. However, there are no reports on the development of myelodysplastic syndrome during enfortumab vedotin therapy in clinical settings. Case presentation: A 72-year-old male patient experienced prolonged and severe thrombocytopenia 18 weeks after the start of enfortumab vedotin therapy for metastatic urothelial carcinoma, requiring daily platelet transfusions. Bone marrow examination and chromosomal analysis confirmed the diagnosis of myelodysplastic syndrome. Treatment with eltrombopag proved to be effective. Conclusion: This is the first report of the development of myelodysplastic syndrome during enfortumab vedotin therapy in a clinical setting. Although rare, myelodysplastic syndrome can occur during enfortumab vedotin therapy.

The Effects of Vibegron Add-on Therapy on Alpha 1-Blocker Therapy for Sexual Function and Overactive Bladder Symptoms in Benign Prostatic Hyperplasia: A Prospective, Open-Label Study.

Background: The effect of combining an α1-adrenergic receptor blocker (α1-blocker) and the ß3-adrenoceptor agonist vibegron for treating persistent overactive bladder (OAB) symptoms associated with benign prostatic hyperplasia (BPH) on sexual function remains uncertain. Therefore, we aimed to evaluate the effects of vibegron as an add-on to α1-blocker therapy on both OAB and sexual function. Methods: Forty-three patients with BPH in whom OAB symptoms were inadequately controlled by α1-blocker treatment were included in this prospective open-label study. The OAB Symptom Score (OABSS), International Prostate Symptom Score (IPSS), 15-item International Index of Erectile Function (IIEF-15), and Erection Hardness Score (EHS), as well as the residual urine volume and serum-free testosterone (FT) and C-reactive protein (CRP) levels, were evaluated before and 8 weeks after the daily administration of 50 mg vibegron/α1-blocker combination therapy. Results: Vibegron/α1-blocker combination therapy significantly improved the OABSS (from 6.9 ± 2.6 to 5.1 ± 2.9, p < 0.0001) and IIEF intercourse satisfaction domain (from 1.1 ± 2.3 to 1.9 ± 2.6, p = 0.02). No significant differences were observed for the IPSS, EHS, total IIEF-15 score, residual urine volume, and serum FT and CRP levels. Conclusions: The study findings suggest that vibegron/α1-blocker combination therapy improves OAB and sexual satisfaction.

Integrated impact of multiple body composition parameters on overall survival in gastrointestinal or genitourinary cancers: A descriptive cohort study.

BACKGROUND: This study aimed to evaluate if combining low muscle mass with additional body composition abnormalities, such as myosteatosis or adiposity, could improve survival prediction accuracy in a large cohort of gastrointestinal and genitourinary malignancies. METHODS: In total, 2015 patients with surgically-treated gastrointestinal or genitourinary cancer were retrospectively analyzed. Skeletal muscle index, skeletal muscle radiodensity, and visceral/subcutaneous adipose tissue index were determined. The primary outcome was overall survival determined by hospital records. Multivariate Cox hazard models were used to identify independent predictors for poor survival. C-statistics were assessed to quantify the prognostic capability of the models with or without incorporating body composition parameters. RESULTS: Survival curves were significantly demarcated by all 4 measures. Skeletal muscle radiodensity was associated with non-cancer-related deaths but not with cancer-specific survival. The survival outcome of patients with low skeletal muscle index was poor (5-year OS; 65.2%), especially when present in combination with low skeletal muscle radiodensity (5-year overall survival; 50.2%). All examined body composition parameters were independent predictors of lower overall survival. The model for predicting overall survival without incorporating body composition parameters had a c-index of 0.68 but increased to 0.71 with the inclusion of low skeletal muscle index and 0.72 when incorporating both low skeletal muscle index and low skeletal muscle radiodensity/visceral adipose tissue index/subcutaneous adipose tissue index. CONCLUSION: Patients exhibiting both low skeletal muscle index and other body composition abnormalities, particularly low skeletal muscle radiodensity, had poorer overall survival. Models incorporating multiple body composition prove valuable for mortality prediction in oncology settings.

Aberrant cell adhesiveness due to DNA hypermethylation of KLF11 in papillary urothelial carcinomas.

PURPOSE: The aim of this study was to clarify DNA methylation profiles determining the clinicopathological diversity of urothelial carcinomas. METHODS: Genome-wide DNA methylation analysis was performed using the Infinium HumanMethylation450 BeadChip in 46 paired samples of non-cancerous urothelium (N) and corresponding cancerous tissue (T), and 26 samples of normal control urothelium obtained from patients without urothelial carcinomas (C). For genes of interest, correlation between DNA methylation and mRNA expression was examined using the Cancer Genome Atlas database. In addition, the role of a selected target for cancer-relevant endpoints was further examined in urothelial carcinoma cell lines. RESULTS: The genes showing significant differences in DNA methylation levels between papillary carcinomas and more aggressive non-papillary (nodular) carcinomas were accumulated in signaling pathways participating in cell adhesion and cytoskeletal remodeling. Five hundred ninety-six methylation sites showed differences in DNA methylation levels between papillary and nodular carcinomas. Of those sites, that were located in CpG-islands around transcription start site, 5'-untranslated region or 1st exon, 16 genes exhibited inverse correlations between DNA methylation and mRNA expression levels. Among the latter, only the KLF11 gene showed papillary T sample-specific DNA hypermethylation in comparison to C and N samples. The DNA methylation levels of KLF11 were not significantly different between T samples and N samples or T samples and C samples for patients with papillo-nodular or nodular carcinomas. Knockdown experiments using the urothelial carcinoma cell lines HT1376 and 5637, which are considered models for papillary carcinoma, revealed that KLF11 participates in altering the adhesiveness of cells to laminin-coated dishes, although cell growth was not affected. CONCLUSION: These data indicate that DNA hypermethylation of KLF11 may participate in the generation of papillary urothelial carcinomas through induction of aberrant cancer cell adhesion to the basement membrane.

Changes in the trends of initial treatment for newly diagnosed prostate cancer in Japan: a nationwide multi-institutional study.

BACKGROUND: In previous large-scale studies conducted through 2010, androgen deprivation therapy (ADT) was the most common initial treatment for prostate cancer patients in Japan. However, recent advancements in treatment technologies have significantly affected the management of prostate cancer in Japan. This study analyzed the trends in initial treatments for prostate cancer based on two nationwide surveys. METHODS: Two Japan-wide multi-institutional surveys, J-CaP2010 and J-CaP2016, were conducted to enroll patients newly histologically diagnosed with prostate cancer in 2010 and 2016-18, respectively. Both surveys included age at diagnosis, initial PSA level, ISUP Grade Group, TNM classification, and initial treatment for prostate cancer. RESULTS: J-CaP2010 included data from 8192 patients across 140 institutions, whereas J-CaP2016 included data from 21 841 patients across 186 institutions. In J-CaP2016, the proportion of radical prostatectomy (RP) and radiation therapy (RT) in the initial treatment increased (from 32% to 36% and 21% to 26%, respectively), whereas the proportion of ADT decreased (from 40% to 29%) compared with those in J-CaP2010. The increase in RP or RT was noticeable in patients aged 75 years and older (from 20% to 38%) and those with high-risk localized cancer (from 58% to 74%) or locally advanced cancer (from 38% to 56%). The proportion of active surveillance or watchful waiting increased in patients with low-risk localized cancer (from 21% to 41%). The proportion of robot-assisted RP within all RPs and the proportion of intensity-modulated RT within all RTs increased remarkably (from 2.3% to 78% and 20% to 50%, respectively). CONCLUSIONS: In Japan, RP and RT have increased as initial treatments for prostate cancer, whereas ADT has decreased. Consequently, RP has emerged as the most commonly selected initial treatment, replacing ADT.

Association of conventional cigarette smoking, heated tobacco product use, and dual use with hearing loss: A working population-based study.

INTRODUCTION: Although conventional cigarette smoking has been linked to an increased risk of hearing loss, the association between heated tobacco products (HTPs) and hearing loss is unknown. The objective of this study was to investigate the association between cigarette and HTP use and hearing loss. METHODS: This cross-sectional study examined the data of 7769 employees from five companies (Study I) and 34404 employees from a large company (Study II), all participants in the Japan Epidemiology Collaboration on Occupational Health Study. The participants were categorized into five groups based on their self-reported tobacco use: never smokers, former smokers, exclusive cigarette smokers, exclusive users of HTPs, and those who used both cigarettes and HTPs. Hearing levels were measured using pure-tone audiometry at 1 and 4 kHz frequencies. Separate analyses were carried out for each study, and the results were then combined using fixed-effect models to pool the estimates. RESULTS: The analysis included 42173 participants, with a prevalence of 12.9% for exclusive cigarette smoking, 9.8% for exclusive HTP use, and 5.5% for dual use. The pooled adjusted odds ratios with 95% confidence intervals for unilateral hearing loss at 4 kHz were 1.21 (95% CI: 1.10-1.33) for former smokers, 1.83 (95% CI: 1.64-2.05) for exclusive cigarette smokers,1.46 (95% CI: 1.28-1.67) for exclusive HTP users, and 1.66 (95% CI: 1.41-1.96) for dual users, compared to never smokers. Additionally, the adjusted odds ratios for hearing loss at 4 kHz among exclusive cigarette smokers, exclusive HTP users, and dual users increased with the intensity of cigarette/HTP consumption (all p for trend <0.001). No significant associations were found between exclusive HTP use, dual use, and hearing loss at 1 kHz, apart from exclusive cigarette smoking. CONCLUSIONS: In this cross-sectional study, associations were found between exclusive cigarette smoking, exclusive HTP use, dual use, and hearing loss, particularly at 4 kHz. Further research is needed to confirm these findings.

Association between Fish Intake and Serum Testosterone Levels in Older Males: The Hitachi Health Study II.

Background: Fish are rich in omega-3 polyunsaturated fatty acids and vitamin D, which can promote testosterone synthesis and secretion. However, some contaminants present in fish may disrupt testosterone production. Objective: This study aimed to investigate the association between fish intake (total, fatty, and lean fish) and serum testosterone levels in older males. Methods: This cross-sectional study included 1545 Japanese males aged 60-69 y who participated in the baseline survey of the Hitachi Health Study II. Fish intake was estimated using a validated brief-type self-administered diet history questionnaire. Total testosterone levels were measured by chemiluminescence immunoassay. Multivariable linear regression analysis was used to analyze the association between fish intake and serum testosterone levels. Results: Higher total fish intake was associated with higher levels of serum testosterone, with an adjusted mean [95% confidence interval (CI) of 5.63 (5.43, 5.83) and 5.99 (5.78, 6.20)] ng/mL for the 1st and 4th quartiles of total fish intake, respectively (P for trend = 0.06). When analyzing fatty and lean fish separately, higher intake of lean fish, but not fatty fish, was associated with higher levels of serum testosterone: adjusted mean (95% CI): 5.63 (5.43, 5.82) and 6.00 (5.79, 6.20) ng/mL for the 1st and 4th quartiles of lean fish intake, respectively (P for trend = 0.01). Conclusions: Among older males, higher intake of total fish, particularly lean fish, was associated with higher serum testosterone levels. Curr Dev Nutr 20xx;x:xx.

Dimension reduction of microbiome data linked Bifidobacterium and Prevotella to allergic rhinitis.

Dimension reduction has been used to visualise the distribution of multidimensional microbiome data, but the composite variables calculated by the dimension reduction methods have not been widely used to investigate the relationship of the human gut microbiome with lifestyle and disease. In the present study, we applied several dimension reduction methods, including principal component analysis, principal coordinate analysis (PCoA), non-metric multidimensional scaling (NMDS), and non-negative matrix factorization, to a microbiome dataset from 186 subjects with symptoms of  allergic rhinitis (AR) and 106 controls. All the dimension reduction methods supported that the distribution of microbial data points appeared to be continuous rather than discrete. Comparison of the composite variables calculated from the different dimension reduction methods showed that the characteristics of the composite variables differed depending on the distance matrices and the dimension reduction methods. The first composite variables calculated from PCoA and NMDS with the UniFrac distance were strongly associated with AR (FDR adjusted P = 2.4 × 10-4 for PCoA and P = 2.8 × 10-4 for NMDS), and also with the relative abundance of Bifidobacterium and Prevotella. The abundance of Bifidobacterium was also linked to intake of several nutrients, including carbohydrate, saturated fat, and alcohol via composite variables. Notably, the association between the composite variables and AR was much stronger than the association between the relative abundance of individual genera and AR. Our results highlight the usefulness of the dimension reduction methods for investigating the association of microbial composition with lifestyle and disease in clinical research.

Blood pressure classification using the Japanese Society of Hypertension Guidelines for the Management of Hypertension and cardiovascular events among young to middle-aged working adults.

The Japanese Society of Hypertension updated guidelines for hypertension management (JSH2019), changing the blood pressure (BP) classification. However, evidence is sparse regarding the association of the classification with cardiovascular disease (CVD) events among young to middle-aged workers in Japan. We examined this issue using longitudinal data from Japan Epidemiology Collaboration on Occupational Health Study with a prospective cohort design. Participants were 81,876 workers (aged 20-64 years) without taking antihypertensive medication at baseline. BP in 2011 or 2010 was used as exposure. CVD events that occurred from 2012 to 2021 were retrieved from a within-study registry. Cox regression was used to calculate multivariable-adjusted hazard ratios of CVD events. During 0.5 million person-years of follow-up, 334 cardiovascular events, 75 cardiovascular deaths, and 322 all-cause deaths were documented. Compared with normal BP (systolic BP [SBP] < 120 mmHg and diastolic BP [DBP] < 80 mmHg), multivariable-adjusted hazard ratios (95% confidence intervals) of cardiovascular events were 1.98 (1.49-2.65), 2.10 (1.58-2.77), 3.48 (2.33-5.19), 4.12 (2.22-7.64), and 7.81 (3.99-15.30) for high normal BP (SBP120-129 mmHg and DBP < 80 mmHg), elevated BP (SBP130-139 mmHg and/or DBP80-89 mmHg), stage 1 hypertension (SBP140-159 mmHg and DBP90-99 mmHg), stage 2 hypertension (SBP160-179 mmHg and/or DBP100-109 mmHg), and stage 3 hypertension (SBP ≥ 180 mmHg and/or DBP ≥ 110 mmHg), respectively. The highest population attributable fraction was observed in elevated BP (17.8%), followed by stage 1 hypertension (14.1%). The present data suggest that JSH2019 may help identify Japanese workers at a higher cardiovascular risk.

Fourth national Japanese antimicrobial susceptibility pattern surveillance program: Bacterial isolates from patients with complicated urinary tract infections.

INTRODUCTION: Antimicrobial susceptibility patterns of bacterial pathogens isolated from patients with complicated urinary tract infections were analyzed using the national surveillance data, comprising 793 bacterial strains from eight clinically relevant species. MATERIALS AND METHODS: Data were collected for the fourth national surveillance project from July 2020 to December 2021 by the Japanese Society of Chemotherapy, the Japanese Association for Infectious Disease, and the Japanese Society of Clinical Microbiology. Surveillance was supervised with the cooperation of 43 medical institutions throughout Japan. RESULTS: Fluoroquinolone required a minimum inhibitory concentration (MIC) of 2-64 mg/L to inhibit the 330 tested Escherichia coli strains. The proportion of levofloxacin-resistant E. coli strains increased from 28.6% in 2008 to 29.6% in 2011, 38.5% in 2015, and 44.5% in 2021. The proportion of levofloxacin-resistant strains of Pseudomonas aeruginosa also increased from previous survey results, showing a continuing downward trend. Conversely, the proportion of levofloxacin-resistant strains of Enterococcus faecalis decreased relative to previous reports. Neither multidrug-resistant P. aeruginosa nor carbapenem-resistant Enterobacteriaceae were detected. For methicillin-resistant Staphylococcus aureus (MRSA), the proportion of vancomycin-susceptible strains (MIC of 2 µg/mL) decreased from 14.7% to 7.7%. DISCUSSION: Bacterial strains that produced extended-spectrum ß-lactamase included E. coli (82/330 strains, 24.8%), Klebsiella pneumoniae (11/68 strains, 16.2%), and Proteus mirabilis (4/26 strains, 15.4%). As compared to previous surveillance reports, these strains showed an increase in proportion over the years.

Development of risk-score model in patients with negative surgical margin after robot-assisted radical prostatectomy.

A total of 739 patients underwent RARP as initial treatment for PCa from November 2011 to October 2018. Data on BCR status, clinical and pathological parameters were collected from the clinical records. After excluding cases with neoadjuvant and/or adjuvant therapies, presence of lymph node or distant metastasis, and positive SM, a total of 537 cases were eligible for the final analysis. The median follow-up of experimental cohort was 28.0 (interquartile: 18.0-43.0) months. We identified the presence of International Society of Urological Pathology grade group (ISUP-GG) ≥ 4 (Hazard ratio (HR) 3.20, 95% Confidence Interval (95% CI) 1.70-6.03, P < 0.001), lymphovascular invasion (HR 2.03, 95% CI 1.00-4.12, P = 0.049), perineural invasion (HR 10.7, 95% CI 1.45-79.9, P = 0.020), and maximum tumor diameter (MTD) > 20 mm (HR 1.9, 95% CI 1.01-3.70, P = 0.047) as significant factors of BCR in the multivariate analysis. We further developed a risk model according to these factors. Based on this model, 1-year, 3-year, and 5-year BCR-free survival were 100%, 98.9%, 98.9% in the low-risk group; 99.1%, 94.1%, 86.5% in the intermediate-risk group; 93.9%, 84.6%, 58.1% in the high-risk group. Internal validation using the bootstrap method showed a c-index of 0.742 and an optimism-corrected c-index level of 0.731. External validation was also carried out using an integrated database derived from 3 other independent institutions including a total of 387 patients for the final analysis. External validation showed a c-index of 0.655. In conclusion, we identified risk factors of biochemical failure in patients showing negative surgical margin after RARP and further developed a risk model using these risk factors.

Lower pretreatment serum testosterone level predicts poor prognosis in the patients with metastatic hormone-sensitive prostate cancer undergoing androgen deprivation therapy.

OBJECTIVE: This study aimed to reveal the association between pretreatment serum testosterone levels and prognosis in patients with metastatic hormone-sensitive prostate cancer treated with androgen deprivation therapy. METHODS: A total of 91 patients were included in this retrospective study. Clinical data were obtained through chart review. Multivariate cox proportional hazards analyses addressed the impact of variables on castration-resistant prostate cancer-free and overall survivals. RESULTS: During a median follow-up of 41.7 months, 61 (67%) and 49 (54%) patients developed castration-resistant prostate cancer and died, respectively. The median castration-resistant prostate cancer-free and overall survivals were 15.5 and 59.9 months, respectively. The cutoff value for discriminating between low- and high-testosterone levels was determined as 450 ng/dl by calculating the receiver operating characteristic curve. Patients in the low-testosterone group (n = 37) had a significantly higher body mass index, worse comorbidities represented by the higher Charlson comorbidity index and higher serum lactate dehydrogenase levels, than those in the high-testosterone group (n = 54). Castration-resistant prostate cancer free and overall survivals were significantly shorter in the low-testosterone group than in the high-testosterone group (P = 0.021 and P < 0.001, respectively). Multivariate analysis identified testosterone level of <450 ng/dl as an independent factor predicting development of castration-resistant prostate cancer (hazard ratio 2.28, P = 0.007), along with high-volume disease and Gleason score 9-10. Similarly, testosterone level of <450 ng/dl was independently associated with shorter overall survival (hazard ratio 2.84, P = 0.006), along with higher Charlson comorbidity index, visceral metastasis and higher alkaline phosphatase level. CONCLUSIONS: Lower baseline serum testosterone levels predict poor prognosis in patients with metastatic hormone-sensitive prostate cancer.

Should insulin resistance (HOMA-IR), insulin secretion (HOMA-ß), and visceral fat area be considered for improving the performance of diabetes risk prediction models.

INTRODUCTION: Insulin resistance and defects in pancreatic beta cells are the two major pathophysiologic abnormalities that underlie type 2 diabetes. In addition, visceral fat area (VFA) is reported to be a stronger predictor for diabetes than body mass index (BMI). Here, we tested whether the performance of diabetes prediction models could be improved by adding HOMA-IR and HOMA-ß and replacing BMI with VFA. RESEARCH DESIGN AND METHODS: We developed five prediction models using data from a cohort study (5578 individuals, of whom 94.7% were male, and 943 had incident diabetes). We conducted a baseline model (model 1) including age, sex, BMI, smoking, dyslipidemia, hypertension, and HbA1c. Subsequently, we developed another four models: model 2, predictors in model 1 plus fasting plasma glucose (FPG); model 3, predictors in model 1 plus HOMA-IR and HOMA-ß; model 4, predictors in model 1 plus FPG, HOMA-IR, and HOMA-ß; model 5, replaced BMI with VFA in model 2. We assessed model discrimination and calibration for the first 10 years of follow-up. RESULTS: The addition of FPG to model 1 obviously increased the value of the area under the receiver operating characteristic curve from 0.79 (95% CI 0.78, 0.81) to 0.84 (0.83, 0.85). Compared with model 1, model 2 also significantly improved the risk reclassification and discrimination, with a continuous net reclassification improvement index of 0.61 (0.56, 0.70) and an integrated discrimination improvement index of 0.09 (0.08, 0.10). Adding HOMA-IR and HOMA-ß (models 3 and 4) or replacing BMI with VFA (model 5) did not further materially improve the performance. CONCLUSIONS: This cohort study, primarily composed of male workers, suggests that a model with BMI, FPG, and HbA1c effectively identifies those at high diabetes risk. However, adding HOMA-IR, HOMA-ß, or replacing BMI with VFA does not significantly improve the model. Further studies are needed to confirm our findings.

Six-year outcomes of robot-assisted radical prostatectomy versus volumetric modulated arc therapy for localized prostate cancer: A propensity score-matched analysis.

BACKGROUND: Although robot-assisted radical prostatectomy (RARP) and intensity-modulated radiotherapy are the leading respective techniques of prostatectomy and radiotherapy for localized prostate cancer, almost no study has directly compared their outcomes; none have compared mortality outcomes. METHODS: We compared 6­year outcomes of RARP (n = 500) and volumetric modulated arc therapy (VMAT, a rotational intensity-modulated radiotherapy, n = 360) in patients with cT1-4N0M0 prostate cancer. We assessed oncological outcomes, namely overall survival (OS), cancer-specific survival (CSS), radiological recurrence-free survival (rRFS), and biochemical recurrence-free survival (bRFS), using propensity score matching (PSM). We also assessed treatment-related complication outcomes of prostatectomy and radiotherapy. RESULTS: The median follow-up duration was 79 months (> 6 years). PSM generated a matched cohort of 260 patients (130 per treatment group). In the matched cohort, RARP and VMAT showed equivalent results for OS, CSS, and rRFS: both achieved excellent 6­year outcomes for OS (> 96%), CSS (> 98%), and rRFS (> 91%). VMAT had significantly longer bRFS than RARP, albeit based on different definitions of biochemical recurrence. Regarding complication outcomes, patients who underwent RARP had minimal (2.6%) severe perioperative complications and achieved excellent continence recovery (91.6 and 68.8% of the patients achieved ≤ 1 pad/day and pad-free, respectively). Patients who underwent VMAT had an acceptable rate (20.0%) of grade ≥ 2 genitourinary complications and a very low rate (4.4%) of grade ≥ 2 gastrointestinal complications. CONCLUSION: On the basis of PSM after a 6-year follow-up, RARP and VMAT showed equivalent and excellent oncological outcomes, as well as acceptable complication profiles.

Latest evidence on clinical outcomes and prognostic factors of advanced urothelial carcinoma in the era of immune checkpoint inhibitors: a narrative review.

The management of advanced (locally advanced or metastatic) urothelial carcinoma has been revolutionized since pembrolizumab was introduced in 2017. Several prognostic factors for advanced urothelial carcinoma treated with pembrolizumab have been reported, including conventional parameters such as performance status and visceral (especially liver) metastasis, laboratory markers such as the neutrophil-to-lymphocyte ratio, sarcopenia, histological/genomic markers such as programmed cell death ligand 1 immunohistochemistry and tumor mutational burden, variant histology, immune-related adverse events, concomitant medications in relation to the gut microbiome, primary tumor site (bladder cancer versus upper tract urothelial carcinoma) and history/combination of radiotherapy. The survival time of advanced urothelial carcinoma has been significantly prolonged (or 'doubled' from 1 to 2 years) after the advent of pembrolizumab, which will be further improved with novel agents such as avelumab and enfortumab vedotin. This review summarizes the latest evidence on clinical outcomes and prognostic factors of advanced urothelial carcinoma in the contemporary era of immune checkpoint inhibitors.

Prostate-specific antigen doubling time predicts the efficacy of site-directed therapy for oligoprogressive castration-resistant prostate cancer.

Background: In recent years, site-directed therapies (SDTs) targeting progressive lesions in patients with oligometastatic prostate cancer have attracted attention. However, whether they effectively treat oligoprogressive castration-resistant prostate cancer (CRPC) remains unclear. Here, we investigated the efficacy of SDT in patients with oligoprogressive CRPC and identified prognostic factors. Methods: We reviewed 59 patients with oligoprogressive CRPC who underwent SDT targeting prostate or metastatic lesions between April 2014 and March 2022. We evaluated the associations between several pretreatment clinical variables and treatment procedures and a >50% prostate-specific antigen (PSA) response, progression-free survival (PFS), and time to next treatment (TTNT). Results: A PSA response of >50% was observed in 66% of patients. The median PFS and TTNT were 8.3 months and 9.9 months, respectively. Patients with PSA doubling time ≥6 months showed a higher >50% PSA response rate (87% vs. 45%; P < 0.001), longer PFS (median, 15.0 vs. 5.0 months; P < 0.001), and longer TTNT (median, 16.3 vs. 5.9 months; P < 0.001) than patients with PSA doubling time <6 months. In multivariate analyses, a PSA doubling time of ≥6 months independently predicted a >50% PSA response, favorable PFS, and TTNT (P = 0.037, 0.025, and 0.017, respectively). Conclusion: PSA doubling time of ≥6 months may be a key indicator of the favorable efficacy of SDT for oligoprogressive CRPC.