Prediction of clinically significant prostate cancer through urine metabolomic signatures: A large-scale validated study.

PURPOSE: Currently, there are no accurate markers for predicting potentially lethal prostate cancer (PC) before biopsy. This study aimed to develop urine tests to predict clinically significant PC (sPC) in men at risk. METHODS: Urine samples from 928 men, namely, 660 PC patients and 268 benign subjects, were analyzed by gas chromatography/quadrupole time-of-flight mass spectrophotometry (GC/Q-TOF MS) metabolomic profiling to construct four predictive models. Model I discriminated between PC and benign cases. Models II, III, and GS, respectively, predicted sPC in those classified as having favorable intermediate risk or higher, unfavorable intermediate risk or higher (according to the National Comprehensive Cancer Network risk groupings), and a Gleason sum (GS) of ≥ 7. Multivariable logistic regression was used to evaluate the area under the receiver operating characteristic curves (AUC). RESULTS: In Models I, II, III, and GS, the best AUCs (0.94, 0.85, 0.82, and 0.80, respectively; training cohort, N = 603) involved 26, 24, 26, and 22 metabolites, respectively. The addition of five clinical risk factors (serum prostate-specific antigen, patient age, previous negative biopsy, digital rectal examination, and family history) significantly improved the AUCs of the models (0.95, 0.92, 0.92, and 0.87, respectively). At 90% sensitivity, 48%, 47%, 50%, and 36% of unnecessary biopsies could be avoided. These models were successfully validated against an independent validation cohort (N = 325). Decision curve analysis showed a significant clinical net benefit with each combined model at low threshold probabilities. Models II and III were more robust and clinically relevant than Model GS. CONCLUSION: This urine test, which combines urine metabolic markers and clinical factors, may be used to predict sPC and thereby inform the necessity of biopsy in men with an elevated PC risk.

Repeated vertebral compression fractures in young adult may imply functional adrenal tumor.

BACKGROUND: Patients with adrenal Cushing's syndrome (ACS) typically present with central obesity, hirsutism, hypertension, or glucose intolerance, which can be easily identified by a clinical physician. However, recognizing those with subclinical CS or those with less common symptoms and signs is challenging to the subspecialist, which can lead to delayed diagnosis and treatment. We report a case who presented with repeated vertebral fractures in 6 months. Typical physical appearance of CS was not shown so that suspicions were not raised until severe osteoporosis was demonstrated from bone marrow density study. From our case report, endocrine tests and image survey should always be considered in young patients with repeat vertebral fractures. CASE PRESENTATION: A 48-year-old man presented with severe back pain for 3 months. Second and fifth lumbar spine (L2 and L5) vertebral compression fractures were noted from X-ray and magnetic resonance imaging (MRI), and vertebroplasty was performed by orthopedic surgeons. After 1 month, a newly developed compression fracture of the ninth to twelfth thoracic spine and L4-L5 were noted. Severe osteoporosis was noted from the hip bone mineral density test, and he was referred to an endocrinologist for analysis. Serial endocrine tests confirmed hypercortisolism, and subsequent abdomen MRI showed a left adrenal tumor. ACS was diagnosed. Left laparoscopic adrenalectomy was performed, and the patient received cortisol supplement for 12 months. Thereafter, no new fractures were identified. CONCLUSIONS: ACS should be considered and carefully verified in middle-aged adults who present with severe osteoporosis and repeated vertebral compression fracture.

I-Tiao-Gung extract through its active component daidzin improves cyclophosphamide-induced bladder dysfunction in rat model.

AIMS: We explored the therapeutic potential of intragastric administration traditional Chinese medicine Glycine tomentella Hayata (I-Tiao-Gung, ITG) extract and its active component Daidzin on cyclophosphamide (CYP)-induced cystitis and bladder hyperactivity in rats. METHODS: Female Wistar rats were divided into control, CYP (200 mg/kg), CYP + ITG (1.17 g/kg/day), CYP + Daidzin (12.5 mg/kg/day), and 1 week of ITG preconditioning with CYP (ITG + CYP) groups. We determined the trans cystometrogram associated with external urethral sphincter electromyogram, and the expression of M2 and M3 muscarinic and P2 × 2 and P2 × 3 purinergic receptors by Western blot in these animals. RESULTS: ITG extract contains 1.07% of Daidzin and 0.77% of Daidzein by high-performance liquid chromatography. Daidzin was more efficient than Daidzein in scavenging H2 O2 activity by a chemiluminescence analyzer. CYP induced higher frequency, shorter intercontraction interval, lower maximal voiding pressure, lower threshold pressure, and Phase-2 emptying contraction with a depressed external urethral sphincter electromyogram activity, and hemorrhagic cystitis in the bladders. The altered parameters by CYP were significantly improved in CYP + ITG, CYP + Daidzin, and ITG + CYP groups. The P2 × 2 and P2 × 3 expressions were significantly upregulated in CYP group, but were depressed in CYP + ITG, CYP + Daidzin, and ITG + CYP groups. The M2 expression was not significantly different among these five groups. The M3 expression was significantly upregulated in CYP group, but was significantly depressed in CYP + ITG, CYP + Daidzin, and ITG + CYP groups. CONCLUSIONS: These data suggest that ITG extract through its active component Daidzin effectively improved CYP-induced cystitis by the action of restoring Phase 2 activity and inhibiting the expressions of P2 × 2, P2 × 3, and M3 receptors.

Incremental Healthcare Service Utilization for Open-angle Glaucoma: A Population-Based Study.

PURPOSE: To investigate differences in the utilization of healthcare services between subjects with open-angle glaucoma (OAG) and comparison subjects without OAG using Taiwan's National Health Insurance population-based database. PATIENTS AND METHODS: The study comprised 2204 subjects with OAG and 2204 sex-matched and age-matched subjects without OAG. We individually followed each subject for a 1-year period to evaluate their healthcare resource utilization. Outcome variables of the healthcare resource utilization were as follows: numbers of outpatient visits and inpatient days and the mean costs of outpatient and inpatient treatment. In addition, we divided healthcare resource utilization into ophthalmologic and nonophthalmologic services. RESULTS: As for the utilization of ophthalmologic services, OAG subjects had significantly more outpatient visits (7.4 vs. 1.3, P<0.001) and significantly higher outpatient costs (US$272 vs. US$39, P<0.001) than comparison subjects. For nonophthalmologic services, OAG subjects also had significantly more outpatient visits (29.4 vs. 21.8, P<0.001) and significantly higher outpatient costs (US$1263 vs. US$847, P<0.001) than comparison subjects. Furthermore, OAG subjects incurred significantly higher inpatient costs compared with comparison subjects (US$434 vs. US$234, P<0.001). For all healthcare services, OAG subjects had significantly more outpatient visits (36.8 vs. 23.1, P<0.001) and significantly higher outpatient (US$1535 vs. US$887, P<0.001) and total (US$2245 vs. US$1122, P<0.001) costs than comparison subjects. In other words, the total cost was about 2-fold greater for OAG subjects than comparison subjects. CONCLUSIONS: We concluded that subjects with OAG had significantly higher utilization of all healthcare services than comparison subjects.

Laparoendoscopic single-site (LESS) retroperitoneal partial adrenalectomy using a custom-made single-access platform and standard laparoscopic instruments: technical considerations and surgical outcomes.

BACKGROUND: We previously reported our initial experience with laparoendoscopic single-site (LESS) retroperitoneal partial adrenalectomy using a custom-made single-port device and conventional straight laparoscopic instruments. METHODS: Between December 2010 and February 2012, LESS retroperitoneal partial adrenalectomies were performed in 11 patients. Six patients had aldosterone-producing adenomas (APAs) and five patients had nonfunctioning tumors. A single-port access was created with an Alexis wound retractor (Applied Medical, Rancho Santa Margarita, CA, USA) through an incision of 2-3 cm beneath the tip of the 12th rib. All procedures were performed with straight laparoscopic instruments. RESULTS: All LESS procedures were successfully completed without conversion to traditional laparoscopic conversion. The tumors ranged from 1 cm to 4.7 cm (mean, 2.3 cm). The operative time was 71-257 minutes (mean, 121 minutes). Most patients (n = 8) had minimal blood loss; the other three patients had a blood loss of 150 mL, 100 mL, and 100 mL. The mean hospital stay was 3 days (range, 1-6 days). There were no perioperative or postoperative complications. Pathological examinations revealed negative surgical margins in all specimens. All patients with Conn's syndrome had an improvement in blood pressure and normalization of plasma renin activity and serum aldosterone levels; all patients were free of potassium supplementation. CONCLUSION: Our results clearly demonstrate that LESS retroperitoneal partial adrenalectomy can be performed safely and effectively using a custom-made single-access platform and standard laparoscopic instruments.

Dementia is associated with iron-deficiency anemia in females: a population-based study.

Cognitive derangement and neurological symptoms are observed in patients with anemia. Although it is still controversial, a few studies suggested that anemia may increase the risk of dementia. This study aimed to explore the association between iron-deficiency anemia (IDA) and dementia in a population-based case-control study. We retrieved our study sample from the Taiwan Longitudinal Health Insurance Database 2000. We extracted 8300 subjects with a diagnosis of dementia and 8300 age- and gender-matched controls. The results showed that there was a significant difference in the prevalence of prior IDA between cases and controls (6.0% vs. 3.8%, p<0.001). The conditional logistic regression analysis suggested that the odds ratio (OR) of prior IDA for cases was 1.36 (95% CI: 1.07-1.74) compared to controls after adjusting for subjects' monthly income, geographic location, urbanization level, hyperlipidemia, diabetes, hypertension, and alcohol abuse. Among female subjects, the adjusted OR of prior IDA for cases was as high as 2.00 (95% CI: 1.42-2.80) compared to controls. However, in men-no increased odds of prior IDA were observed, compared to controls. We concluded that women with dementia had a higher prevalence of prior IDA, compared to controls.

CKD as a risk factor for bladder recurrence after nephroureterectomy for upper urinary tract urothelial carcinoma.

BACKGROUND: The aim of this study is to examine chronic kidney disease (CKD) as a risk factor for bladder recurrence and cancer-specific and total mortality in a cohort of patients with upper urinary tract (UUT) urothelial carcinoma (UC) treated by means of nephroureterectomy. STUDY DESIGN: Cohort study. SETTINGS & PARTICIPANTS: 150 patients with primary UC of the ureter or renal pelvis treated by means of nephroureterectomy at a single center. PREDICTOR: Presence and severity of CKD according to preoperative markers of kidney damage, estimated glomerular filtration rate calculated using the Modification of Diet in Renal Disease Study equation, and other covariates. OUTCOMES & MEASUREMENTS: Subsequent bladder recurrences, cancer-specific survival, and overall survival. RESULTS: Of 150 patients, 37 (25%) had no CKD, 71 patients (47%) had CKD stages 1 to 4, and 42 patients (28%) had CKD stage 5. 41 (27%) and 31 patients (21%) reported exposure to herbal medicine or tobacco use, respectively. During a mean follow-up of 4 years, 53 patients (35%) developed bladder recurrence and 27 (18%) died, of whom 14 (9.3%) died of cancer. Overall 5-year bladder recurrence-free and cancer-specific survival rates were 62% and 89%, respectively (n = 150). Risks of bladder recurrence were 2.43 (95% confidence interval, 1.00 to 5.93) and 3.95 (95% confidence interval, 1.59 to 9.80), greater in patients with CKD stages 1 to 4 and CKD stage 5 compared with patients without CKD, respectively. Ureteral involvement of the primary tumor (hazard ratio, 1.97; 95% confidence interval, 1.12 to 3.48) also was associated significantly with an increased rate of bladder recurrence. The risk of death from all causes or UC was not significantly greater in patients with CKD stages 1 to 4 or CKD stage 5 compared with those without CKD. Higher tumor stage (pT2 to 4) was associated significantly with overall death (hazard ratio, 5.15; 95% confidence interval, 1.84 to 14.48). LIMITATIONS: A retrospective study in an area of high incidence of both UUT-UC and CKD. CONCLUSIONS: Advancing CKD stage of patients and positive ureteral involvement of the primary tumor (especially in the lower ureter) are associated with greater risk of subsequent bladder recurrence in patients with UUT-UC treated by means of radical surgery.