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.

Comparison of oncological outcomes for hand-assisted and pure laparoscopic radical nephroureterectomy: results from the Taiwan Upper Tract Urothelial Cancer Collaboration Group.

PURPOSE: Laparoscopic radical nephroureterectomy (LNU) has gradually become the new standard treatment for localized upper tract urothelial cancer (UTUC). With more blunt dissection and tactile sensation, hand-assisted LNU might shorten the operative time compared with the pure laparoscopic approach. However, whether the use of the hand-assisted or the pure laparoscopic approach has an effect on oncological outcomes remains unclear. METHODS: We retrospectively identified 629 patients with non-metastatic UTUC who underwent hand-assisted (n = 515) or pure LNU (n = 114) at 9 hospitals in Taiwan between 2004 and 2019. Overall survival, cancer-specific survival, recurrence-free survival, and bladder recurrence-free survival were compared between these two groups using inverse-probability of treatment weighting (IPTW) derived from the propensity scores for baseline covariate adjustment. RESULTS: The median follow-up period was 32.9 and 28.7 months in the hand-assisted and the pure groups, respectively. IPTW-adjusted Cox proportional hazards models showed that the laparoscopic approach (pure vs. hand-assisted) was not significantly associated with all-cause mortality (HR 0.79, 95% CI 0.49-1.24, p = 0.304), cancer-specific mortality (HR 0.88, 95% CI 0.51-1.51, p = 0.634), or extra-vesical recurrence (HR 0.65, 95% CI 0.41-1.04, p = 0.071). However, the pure laparoscopic approach was significantly associated with lower intra-vescial recurrence (HR 0.64, 95% CI 0.43-0.96, p = 0.029) for patients who underwent LNU. Kaplan-Meier curves also revealed that the pure laparoscopic approach was associated with better bladder recurrence-free survival compared with the hand-assisted laparoscopic approach in both the original cohort and the IPTW-adjusted cohort (log-rank p = 0.042 and 0.027, respectively). CONCLUSIONS: The performance of hand-assisted or pure LNU does not significantly affect the all-cause mortality, cancer-specific mortality, or extra-vesical recurrence for patients with non-metastatic UTUC. However, the hand-assisted laparoscopic approach could increase the risk of intra-vesical recurrence for patients who undergo LNU.

Specific Impacts of Ketamine on Bladder Dysfunction and Associated Histological Alterations in Rats-A Time Course Validation through Transmission Electron Microscopy.

This study explored the specific effects of ketamine on bladder function followed by a sequence of histological changes in a rat bladder at fixed time course intervals. The rats were grouped into normal control and experimental animals, and ketamine (100 mg/kg/day) was administrated to the experimental animals for 2, 4, and 8 weeks, respectively; similarly, the control animals received saline. All animals were evaluated for bladder function and histological responses to the treatment. Ultrastructural changes were observed by transmission electron microscopy (TEM). The results showed progressive bladder dysfunctions with hyperactive bladder conditions according to the time course and frequency of exposure to ketamine. Significantly, decreased inter contraction intervals, residual urine volume, peak micturition pressure, and increased micturition frequency were observed. Bladder histology results revealed substantial inflammation and comprehensive submucosa edema in week 2 and 4 rats along with fibrosis and significant bladder detrusor hypertrophy in week 8 rats. TEM analysis revealed bladder wall thickening, deformed blood vessels, detrusor hypertrophy, wobbled gap junction, and barrier dysfunction at different time course levels in experimental animals. These results provided a profound knowledge about the prognosis and step-by-step pathophysiology of the disease, which might help in developing new therapeutic interventions.

Intracavernous Injection of Platelet-Rich Plasma Therapy Enhances Erectile Function and Decreases the Mortality Rate in Streptozotocin-Induced Diabetic Rats.

Erectile dysfunction (ED) is an agonizing complication of diabetes mellitus (DM) and it is challenging to treat ED in DM patients. Platelet-rich plasma (PRP) is a unique therapeutic strategy comprising intrinsic growth factors. An attempt was made to explore the potentiality of the PRP treatment in DM-induced ED rats in various groups (control, DM-non-ED, DM-ED, and DM-ED treated with PRP). Streptozotocin (STZ) was used to induce DM in rats. The blood glucose levels of the DM rats were maintained at >300 mg/dl. In the 18-week experiment, survival rate, body weight, intracavernous pressure (ICP) variations, and arterial blood pressure were analyzed. The tissue restoration results were validated by histological, immunofluorescence, and transmission electron microscopic analysis. PRP treatment of DM-ED rats significantly increased all parameters of erectile function compared to pre-treatment of PRP and DM-ED treated with vehicle. The histological results revealed that PRP treatment substantially enhanced the regeneration of myelinated nerves and decreased the atrophy of corporal smooth muscle. Notably, the PRP treatment immensely enhanced the survival rate in post-surgery DM-ED rats. These results indicated certain benefits of PRP treatment in delaying damage and preventing post-surgery complications in DM patients. Hence, PRP treatment is a novel multifactorial strategy for DM-ED patients.

Sodium Thiosulfate Ameliorates Renovascular Hypertension-Induced Renal Dysfunction and Injury in Rats.

BACKGROUND/AIMS: Arterial stenosis activates the renin-angiotensin-aldosterone system subsequently resulting in renovascular hypertension (RVHT) and renal oxidative injury. We explored the effect of sodium thiosulfate (STS, Na2S2O3), a developed antioxidant in clinical trial, on RVHT-induced hypertension and renal oxidative injury in rats. METHODS: We induced RVHT in male Wistar rats with bilaterally partial ligation of renal arteries in the 2-kidney 2-clip model. We evaluated the STS effect on RVHT-induced oxidative injury and apoptosis by a chemiluminescence amplification method, Western blot, and immunohistochemistry. RESULTS: We found STS displayed a dose-dependent antioxidant H2O2 activity and adapted the maximal scavenging H2O2 activity of STS at the dosage of 0.1 g/kg intraperitoneally 3 times/week for 4 weeks in RVHT rats. RVHT induced a significant elevation of arterial blood pressure, blood reactive oxygen species amount, neutrophil infiltration, 4-HNE and NADPH oxidase gp91 expression, Bax/Bcl-2/poly(ADP-ribose) polymerase (PARP)-mediated apoptosis formation, blue Masson-stained fibrosis, and urinary protein level. STS treatment significantly reduced hypertension, oxidative stress, neutrophil infiltration, fibrosis, and Bax/Bcl-2/PARP-mediated apoptosis formation and depressed the urinary protein level in the RVHT models. CONCLUSION: Our results suggest that STS treatment could ameliorate RVHT hypertension and renal oxidative injury through antioxidant, antifibrotic, and antiapoptotic mechanisms.

Endometriosis increased the risk of bladder pain syndrome/interstitial cystitis: A population-based study.

OBJECTIVE: Previous studies have suggested an association between bladder pain syndrome/interstitial cystitis (BPS/IC) and endometriosis. However, no nation-wide population study has yet reported an association between them. In this study, we examined the risk of BPS/IC among subjects with endometriosis during a 3-year follow-up in Taiwan using a population-based dataset. STUDY DESIGN: This study comprised 9191 subjects with endometriosis, and 27 573 subjects randomly selected as controls. We individually followed-up each subject (n = 36 764) for a 3-year period to identify subjects subsequently diagnosed with BPS/IC. A Cox proportional hazards regression model was employed to estimate the risk of subsequent BPS/IC following a diagnosis of endometriosis. RESULTS: Incidences of BPS/IC during the 3-year follow-up period was 0.2% and 0.05% for subjects with and without endometriosis, respectively. The hazard ratio for developing BPS/IC over a 3-year period for subjects with endometriosis compared to subjects without endometriosis was 4.43 (95% CI: 2.13-9.23). After adjusting for co-morbidities like diabetes, hypertension, coronary heart disease, obesity, hyperlipidemia, chronic pelvic pain, irritable bowel syndrome, fibromyalgia, chronic fatigue syndrome, depression, panic disorder, migraines, sicca syndrome, allergies, endometriosis, asthma, tobacco use, and alcohol abuse, the Cox proportional hazards regressions revealed that the hazard ratio for BPS/IC among subjects with endometriosis was 3.74 (95% CI = 1.76-7.94, P < 0.001) compared to that in controls. CONCLUSIONS: This study provides epidemiological evidence of an association between endometriosis and a subsequent diagnosis of BPS/IC.

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.

Bladder pain syndrome/interstitial cystitis is associated with asthma: A case-control study.

OBJECTIVE: Although asthma and bladder pain syndrome/interstitial cystitis (BPS/IC) are considered to share similar pathophysiological pathways, the relationship between asthma and BPS/IC is uncertain. This case-control study aimed to investigate the relationship between prior asthma and BPS/IC using a large database in Taiwan. MATERIALS AND METHODS: This study used data from the Taiwan Longitudinal Health Insurance Database 2005. We identified 500 female patients with BPS/IC as cases and 500 propensity score-matched females without BPS/IC as controls. We conducted logistic regressions to estimate the odds ratio (OR) and 95% confidence interval (CI) for prior asthma between cases and controls. RESULTS: Results indicated that 143 (14.30%) of the total sampled patients had received a prior diagnosis of asthma. Moreover, prior asthma was found in 86 (17.20%) cases and 57 (11.40%) controls. The OR of prior asthma for cases was 1.61 (95%CI: 1.13-2.32) compared to propensity score-matched controls. Additionally, the ORs of prior asthma for females with BPS/IC aged 18-59 and ≥60 years were 1.72 (95%CI: 1.11-2.69) and 1.40 (95%CI: 0.74-2.62), respectively, compared to controls. CONCLUSIONS: We concluded that prior asthma was significantly associated with BPS/IC in a female Taiwanese population.

Decreased clinic visits for acute respiratory infections following an adult tonsillectomy: A population-based study.

PURPOSE: This study attempted to investigate the effects of a tonsillectomy on utilization of medical resources for acute respiratory infections by comparing numbers and costs of clinic visits within 1year before and after a tonsillectomy. MATERIALS AND METHODS: Data for this study were retrieved from the Taiwan Longitudinal Health Insurance Database 2005. The study includes 481 patients aged 18-80years who underwent a tonsillectomy and 481 comparison patients. A multivariate regression model employing difference-in-difference was carried out to assess the independent association between a tonsillectomy and the number and costs of clinic visits. RESULTS: We found that for patients who underwent a tonsillectomy, the mean number of clinic visits for acute respiratory care 1year before and after the index date significantly decreased from 7.3 to 4.2 (p<0.001). However, for the comparison group, there was no significant difference in the number (p=0.540) or costs (p=0.221) of clinic visits for acute respiratory care 1year before and after the index date. A multivariate regression model revealed that a tonsillectomy was associated with a reduction of 3.38 in the mean number of clinic visits for acute respiratory care (p<0.001). In other words, a tonsillectomy reduced by 46.3% (3.38/7.3) the number of clinic visits for acute respiratory care after adjusting for sociodemographic characteristics and medical comorbidities compared to comparison patients. CONCLUSIONS: This study demonstrated that a tonsillectomy was of substantial benefit to adult patients in that it provides decreased healthcare utilization for acute respiratory infections.

Increased risk for urological cancer associated with anxiety disorder: a retrospective cohort study.

BACKGROUND: Anxiety disorders (ADs) are common with a high rate of medical comorbidities. Although the association between ADs and the overall cancer risk remains controversial, patients with ADs were found to be more likely to develop specific cancer types. Herein, we estimated the risk of developing urological cancers among patients with ADs in a 5-year follow-up period using a population-based database. METHODS: Two study cohorts were identified from the Taiwan Longitudinal Health Insurance Database 2005: patients with ADs, and comparison subjects selected by one-to-one matching for sex, age, and the year of recruitment. Follow-up was undertaken to determine whether sampled patients and comparison subjects had developed urological cancers in the subsequent 5 years. RESULTS: We found that urological cancers occurred among 0.54% of patients with ADs and 0.13% of comparison subjects. After adjusting for sociodemographic characteristics, medical comorbidities, and alcohol and tobacco use disorder, the stratified Cox proportional hazard regression suggested that patients with ADs were more likely to develop urological cancers relative to comparison subjects (adjusted hazard ratio, 3.67; 95% confidence interval, 2.85 ~ 4.72). The adjusted HR for males with ADs was 3.82 (95% CI: 2.79 ~ 5.23) in comparison to males without ADs. In addition, the adjusted HR for females with ADs was 3.47 (95% CI: 2.26 ~ 5.31) than those females without ADs. CONCLUSIONS: We concluded that during the 5-year follow-up period, there was a significantly increased risk of urological cancers among patients with ADs.

A population-based study on the associations between chronic periodontitis and the risk of cancer.

BACKGROUND: To date, the associations between chronic periodontitis (CP) and cancer lack large-scale population-based epidemiological evidence. This study aimed to investigate the subsequent risk for cancers among subjects with CP. METHODS: This study cohort included 40,140 subjects with CP and 40,140 subjects who were matched for a comparison cohort. We individually tracked each patient for a 5-year period following their index date to identify those who had received a diagnosis of cancer. RESULTS: The incidence rate of cancer during the 5-year follow-up period was 14.80 (95 % CI 14.28-15.34) per 1,000 person-years in subjects with CP. Cox proportional hazards regression revealed that the hazard ratio of cancer during the 5-year follow-up period for subjects with CP was 1.23 (95 % CI 1.20-1.27) compared to that of the comparison cohort. CONCLUSION: We observed an increased risk for the subsequent development of a number of cancers among subjects with CP.

Obstructive sleep apnea and urological comorbidities in males: a population-based study.

PURPOSE: This study aimed to investigate associations between obstructive sleep apnea (OSA) and urological comorbidities using a large population-based dataset. METHODS: This cross-sectional study used the Taiwan Longitudinal Health Insurance Database 2005. We included 1236 males with OSA in the study group and 4944 males without OSA in the comparison group. Conditional logistic regressions were performed to examine relationships between OSA and urological comorbidities. RESULTS: We found that patients with OSA had significantly greater prevalences of hypertrophy of the prostate (15.13 vs. 7.28 %), chronic prostatitis (4.37 vs. 2.16 %,), urinary incontinence (3.32 vs. 0.87 %), nocturia (2.02 vs. 0.61 %), erectile dysfunction (2.91 vs. 0.97 %), urinary calculi (12.06 vs. 6.80 %), and prostate cancer (0.97 vs. 0.40 %) than the comparison group. Additionally, the adjusted odds ratios in males with OSA for hypertrophy of prostate, chronic prostatitis, urinary incontinence, nocturia, erectile dysfunction, urinary calculi, and prostate cancer were 2.54 (95 % confidence interval (CI) 2.05~3.15), 1.95 (95 % CI 1.38~2.74), 4.13 (95 % CI 2.63~6.50), 3.54 (95 % CI 2.03~6.18), 2.95 (95 % CI 1.89~4.61), 1.89 (95 % CI 1.53~2.33), and 2.14 (95 % CI 1.03~4.43) than those without OSA, respectively. CONCLUSIONS: This study concluded that males with OSA had higher odds ratios of hypertrophy of the prostate, chronic prostatitis, urinary incontinence, nocturia, erectile dysfunction, urinary calculi, and prostate cancer than comparison group.

Statin use and thyroid cancer: a population-based case-control study.

OBJECTIVE: Several observational studies raised the possibility that the use of statins may decrease the overall risk of cancer and of specific cancers. This study aimed to evaluate the association of statin use with thyroid cancer based on a population-based data set. DESIGN: The data for this case-control study were sourced from the Taiwan Longitudinal Health Insurance Database 2000. We included 500 subjects with thyroid cancer as cases and 2500 gender- and age-matched subjects without thyroid cancer as controls. We used a conditional logistic regression to calculate the odds ratio (OR) and its corresponding 95% confidence interval (CI) for having previously used statins between cases and controls. RESULTS: The OR of prior statin use for cases was 1.39 (95% CI = 1.08-1.78) compared to controls, and thyroid cancer was significantly associated with previous regular statin use (OR = 1.40, 95% CI = 1.05-1.86). However, thyroid cancer was not significantly associated with previous irregular statin use (OR = 1.35; 95% CI = 0.88-2.07). Furthermore, the significant association between thyroid cancer and previous statin use only existed for females (OR: 1.43; 95% CI: 1.07-1.90) but not for males (OR: 1.28; 95% CI: 0.75-2.17). CONCLUSIONS: We concluded that statin use was associated with thyroid cancer in female patients.

Appendectomy increased the risk of ischemic heart disease.

BACKGROUND: Although the appendix may not be considered vital, recent studies have noted adverse health consequences after appendectomy. This study aimed to use a population-based data set to explore whether appendectomy increases the risk for subsequent ischemic heart disease (IHD) in a 3-y follow-up period. MATERIALS AND METHODS: This study used data from the Longitudinal Health Insurance Database 2000 in Taiwan. The study cohort included 5413 patients who underwent appendectomies. The comparison cohort was selected by randomly recruiting 16,239 enrollees matched with the study group in terms of sex, age, hypertension, hyperlipidemia, and diabetes. Each individual was tracked for 3 y to identify whether he and/or she developed IHD during the follow-up period. Cox proportional hazard regressions were performed for analysis. RESULTS: During a 3-y follow-up, 196 (3.62%) and 375 (2.31%) IHD incidents developed in the study and the comparison cohorts, respectively. For adults aged ≥18 y, experiencing an appendectomy was independently associated with a 1.54-fold increased risk of IHD during the 3 y of follow-up (95% CI = 1.29-1.84). The association persisted in further analyses stratified by age. CONCLUSIONS: There is an increased risk of subsequent IHD within 3 y after appendectomy, and this underscores the need for more serious clinical decision-making in removing the appendix. Regular monitoring for IHDs is also recommended for patients who have undergone an appendectomy.

Increased risk of ischemic stroke among women with bladder pain syndrome/interstitial cystitis: a cohort study from Taiwan.

AIM: Vascular factors are proposed in the etiology of bladder pain syndrome/interstitial cystitis (BPS/IC). In this study, we investigated the risk of stroke among women following a diagnosis of BPS/IC over 3 years of follow-up, compared to controls without a BPS/IC diagnosis. METHODS: This retrospective cohort study used data retrieved from the Taiwan "Longitudinal Health Insurance Database 2000." We identified 847 women who received a diagnosis of BPS/IC between January 1, 2001 and December 31, 2008 (study group) and 4,235 comparison women (women without a BPS/IC diagnosis matched on age and other selected demographic variables. All subjects were tracked for 3 years following the index date to identify those who received a diagnosis of stroke during follow-up. RESULTS: The stroke incidence rate was 20.86 (95% confidence interval (CI): 15.78-27.07) and 11.65 (95% CI: 9.88-13.64) per 1,000 person-years among the study and comparison cohorts, respectively. Cox regression analysis showed a stroke hazard ratio (HR) of 1.52 (95% CI: 1.09-2.14) in the BPS/IC group relative to the comparison group over 3-year follow-up, after adjusting for hypertension, diabetes, coronary heart disease, atrial fibrillation, hyperlipidemia, and chronic kidney disease. The adjusted HR of ischemic stroke was 1.52 (95% CI: 1.02-2.27). However, there was no significant difference between the two groups in hemorrhagic stroke risk. CONCLUSIONS: Our study demonstrates an association between BPS/IC and a subsequent ischemic stroke diagnosis among women in Taiwan.

EGFR mediates docetaxel resistance in human castration-resistant prostate cancer through the Akt-dependent expression of ABCB1 (MDR1).

Recent studies have shown that docetaxel-based chemotherapy confers a survival benefit in patients with castration-resistant prostate cancer (PC). Also epidermal growth factor receptor (EGFR) was found to have multiple roles in prostatic tumorigenesis. However, the EGFR-mediated chemoresistance mechanism in human PC was not well delineated. In this study, we explored the mechanism of EGFR-mediated docetaxel resistance in PC. A series of stable docetaxel-resistant PC/DX sublines were established at our laboratory. The docetaxel IC50s of PC3 and PC/DX25 cells were 0.01 and 1.33 µM, respectively. Cellular resistance to docetaxel was significantly associated with increased EGFR and EGFR activation in PC/DX25. There was a dose-dependent increase in EGFR expression associated with the magnitude of docetaxel resistance. Expression of EGFR in PC/DX25 was higher than that in PC3, RWPE-1 and LNCaP cells. Similar results were also found in human PC tissues by immunohistochemical staining. We showed that docetaxel sensitivity can be stored in PC/DX25 cells by knockdown and inactivation of EGFR expression through EGFR siRNA and specific inhibitors, respectively. Contrarily, overexpression of EGFR or recombinant EGF protein treatment could rescue PC3 cells from docetaxel-mediated cytotoxicity. Gefitninb (ZD1839) significantly inhibited the growth of PC/DX25 cells by MTT in vitro and on xenografted nude mice in vivo. Moreover, EGFR-mediated docetaxel resistance occurred through the Akt-dependent ABCB1 expression in PC cells. These findings demonstrated EGFR played an important role in docetaxel-resistant PC and EGFR inhibition may enhance the therapeutic efficacy of docetaxel-based treatment.

Association between sudden sensorineural hearing loss and anxiety disorder: a population-based study.

Anxiety disorder (AD) is commonly associated with a number of physical illnesses. No previous study has investigated the association between AD and sudden sensorineural hearing loss (SSNHL). In this study, we investigated the association between prior AD and SSNHL using a population-based dataset in Taiwan. Sampled subjects of this case-control study were retrieved from the Taiwan "Longitudinal Health Insurance Database". We identified 3,522 patients who had a diagnosis of SSNHL as cases and 10,566 age- and gender-matched subjects without SSNHL as controls. A conditional logistic regression was used to calculate the odds ratio (OR) for having previously been diagnosed with AD between cases and controls. We found that of 14,088 patients, 13.4% had a prior AD diagnosis, 17.8 and 11.9% for the SSNHL group and controls, respectively. After adjusting for patient socioeconomic characteristics and comorbid medical disorders, SSNHL patients were more likely to have prior AD than the controls (OR 1.49, 95% confidence interval (CI) 1.34-1.66, p < 0.001). Furthermore, we found that the significant relationship between SSNHL and prior AD decreased with age. The relationship was the most pronounced among those aged ≤44 years, with an adjusted OR of 1.86 (95% CI 1.48-2.33, p < 0.001) for cases compared to controls. We concluded that patients with SSNHL had a higher proportion of prior AD than non-SSNHL-diagnosed controls. Further study is needed to confirm our findings and explore the underlying pathomechanisms.

Augmentation enterocystoplasty is effective in relieving refractory ketamine-related bladder pain.

AIMS: To report our early results of augmentation enterocystoplasty (AE) for severe bladder pain associated with chronic ketamine cystitis (KC). METHODS: We performed AE for 14 patients with refractory KC-related bladder pain, which is based on the criteria including severe bladder pain, urgency and frequency and/or upper urinary tract damage such as bilateral hydronephrosis, and contracted bladder. Every patient had been treated conservatively with medication or cystoscopic hydrodistention for at least 1 year before they had received surgical intervention. Video-urodynamic studies were obtained before AE and 3-6 months after surgery. Outcome measurements included visual analogue score (VAS) for pain, cystometric bladder capacity (CBC), maximum urinary flow rate (Qmax), post-void residual, and maximal detrusor pressure (Pdet). The patients' general satisfaction with regard to treatment outcome was also assessed by the Patient Perception of Bladder Condition (PPBC). RESULTS: A total of 4 men and 10 women underwent this procedure as indicated. The mean age was 26.7 (ranged 20-38) years old and the duration of ketamine abuse was 3.82 years (ranged 2-7). Contracted bladder was noted in all patients, hydronephrosis in nine and vesicoureteral reflux (VUR) in eight. At 3-6 months after AE, VAS was remarkably improved from baseline to the end-point (8.29 ± 1.54 vs. 2.14 ± 1.51, P < 0.0001), CBC increased from 50.9 ± 15.7 to 309.2 ± 58.0 ml (P < 0.0001), Qmax increased from 6.94 ± 3.60 to 15.2 ± 5.51 ml/sec (P < 0.0001) and Pdet reduced from 29.7 ± 16.0 to 17.9 ± 8.2 cmH2 O (P = 0.008). All patients reported marked improvement in PPBC from 6.0 to 1.4 ± 0.89 (P < 0.0001). All hydronephrosis disappeared and VUR was resolved in five patients after AE with ureteral reimplantation. CONCLUSIONS: This pilot study demonstrated that AE is effective in relieving refractory ketamine-related bladder pain and lower urinary tract symptoms.

Obstructive sleep apnea increases the risk of bladder pain syndrome/interstitial cystitis: a population-based matched-cohort study.

AIMS: Previous studies indicated a possible association between bladder pain syndrome/interstitial cystitis (BPS/IC) and sleep disorders including sleep abnormalities with delayed onset of sleep, waking up before needed, and snoring. Nevertheless, no previous study has reported the association between obstructive sleep apnea (OSA) and BPS/IC. In this retrospective cohort study, we examined the risk of BPS/IC among subjects with OSA during a 3-year follow-up in Taiwan using a population-based dataset. METHODS: This study comprised 2,940 study subjects with OSA, and 29,400 randomly selected comparison subjects. We individually followed-up each sampled subject (n = 32,340) for a 3-year period to identify those subjects who subsequently received a diagnosis of BPS/IC. A Cox proportional hazards regression model was constructed to estimate the risk of subsequent BPS/IC following a diagnosis of OSA. RESULTS: Incidences of BPS/IC during the 3-year follow-up period were 13.61 (95% confidence interval [CI] = 7.37-23.13) and 3.60 (95% CI = 2.06-4.39) for subjects with and those without OSA, respectively. After adjusting for diabetes, hypertension, coronary heart disease, obesity, hyperlipidemia, chronic pelvic pain, irritable bowel syndrome, fibromyalgia, chronic fatigue syndrome, depression, panic disorder, migraines, sicca syndrome, allergies, endometriosis, asthma, tobacco use disorder, and alcohol abuse, the stratified Cox proportional hazards regressions revealed that the hazard ratio for BPS/IC among subjects with OSA was 3.71 (95% CI = 1.81-7.62, P < 0.001) that of comparison subjects. CONCLUSIONS: This study provides epidemiological evidence of a link between OSA and a subsequent BPS/IC diagnosis. We suggest that clinical practitioners treating subjects with OSA be alert to urinary complaints in this population.