Development of the UroARC Surgical Calculator: A Novel Risk Calculator for Older Adults Undergoing Surgery for Bladder Outlet Obstruction.

PURPOSE: Bladder outlet obstruction (BOO) is common in older adults. Many older adults who pursue surgery have additional vulnerabilities affecting surgical risk, including frailty. A clinical tool that builds on frailty to predict surgical outcomes for the spectrum of BOO procedures would be helpful to aid in surgical decision-making but does not currently exist. MATERIALS AND METHODS: Medicare beneficiaries undergoing BOO surgery from 2014 to 2016 were identified and analyzed using the Medicare MedPAR, Outpatient, and Carrier files. Eight different BOO surgery categories were created. Baseline frailty was calculated for each beneficiary using the Claims-Based Frailty Index (CFI). All 93 variables in the CFI and the 17 variables in the Charlson Comorbidity Index were individually entered into stepwise logistic regression models to determine variables most highly predictive of complications. Similar and duplicative variables were combined into categories. Calibration curves and tests of model fit, including C statistics, Brier scores, and Spiegelhalter P values, were calculated to ensure the prognostic accuracy for postoperative complications. RESULTS: In total, 212,543 beneficiaries were identified. Approximately 42.5% were prefrail (0.15 ≤ CFI < 0.25), 8.7% were mildly frail (0.25 ≤ CFI < 0.35), and 1.2% were moderately-to-severely frail (CFI ≥0.35). Using stepwise logistic regression, 13 distinct prognostic variable categories were identified as the most reliable predictors of postoperative outcomes. Most models demonstrated excellent model discrimination and calibration with high C statistic and Spiegelhalter P values, respectively, and high accuracy with low Brier scores. Calibration curves for each outcome demonstrated excellent model fit. CONCLUSIONS: This novel risk assessment tool may help guide surgical prognostication among this vulnerable population.

High risk of complications after a "low risk" procedure: A national study of nursing home residents and older adults undergoing haemorrhoid surgery.

AIM: To evaluate 30-day complications and 1-year mortality for older adults undergoing haemorrhoid surgery. METHOD: This retrospective cohort study evaluated older adults (age 66+) undergoing haemorrhoid surgery using Medicare claims and the minimum data set (MDS). Long-stay nursing home residents were identified, and propensity score matched to community-dwelling older adults. Generalized estimating equation models were created to determine the adjusted relative risk of 30-day complications, length of stay (LOS), and 1-year mortality. Among nursing home residents, functional and cognitive status were evaluated using the MDS-activities of daily living (ADL) score and the Brief Instrument of Mental Status. Faecal continence status was evaluated among a subset of nursing home residents. RESULTS: A total of 3664 subjects underwent haemorrhoid surgery and were included in the analyses. Nursing home residents were at significantly higher risk for 30-day complications (52.3% vs. 32.9%, aRR 1.6 [95% CI: 1.5-1.7], p < 0.001), and 1-year mortality (24.9% vs. 16.1%, aRR 1.6 [95% CI: 1.3-1.8], p < 0.001). Functional and mental status showed an inflection point of decline around the time of the procedure, which did not recover to the baseline trajectory in the following year. Additionally, a subset of nursing home residents demonstrated worsening faecal incontinence. CONCLUSION: This study demonstrated high rates of 30-day complications and 1-year mortality among all older adults (yet significantly worse among nursing home residents). Ultimately, primary care providers and surgeons should carefully weigh the potential harms of haemorrhoid surgery in older adults living in a nursing home.

A High-Certainty Visual Servo Control Method for a Space Manipulator with Flexible Joints.

This paper introduces a novel high-certainty visual servo algorithm for a space manipulator with flexible joints, which consists of a kinematic motion planner and a Lyapunov dynamics model reference adaptive controller. To enhance kinematic certainty, a three-stage motion planner is proposed in Cartesian space to control the intermediate states and minimize the relative position error between the manipulator and the target. Moreover, a planner in joint space based on the fast gradient descent algorithm is proposed to optimize the joint's deviation from the centrality. To improve dynamic certainty, an adaptive control algorithm based on Lyapunov stability analysis is used to enhance the system's anti-disturbance capability. As to the basic PBVS (position-based visual servo methods) algorithm, the proposed method aims to increase the certainty of the intermediate states to avoid collision. A physical experiment is designed to validate the effectiveness of the algorithm. The experiment shows that the visual servo motion state in Cartesian space is basically consistent with the planned three-stage motion state, the average joint deviation index from the centrality is less than 40%, and the motion trajectory consistency exceeds 90% under different inertial load disturbances. Overall, this method reduces the risk of collision by enhancing the certainty of the basic PBVS algorithm.

Frailty Is Associated with an Increased Risk of Complications and Need for Repeat Procedures after Sling Surgery in Older Adults.

PURPOSE: Sling surgery is the gold standard treatment for stress urinary incontinence in women. While data support the use of sling surgery in younger and middle-aged women, outcomes in older, frail women are largely unknown. MATERIALS AND METHODS: Data were examined for all Medicare beneficiaries ≥65 years old who underwent sling surgery with or without concomitant prolapse repair from 2014 to 2016. Beneficiaries were stratified using the Claims-Based Frailty Index (CFI) into 4 categories: not frail (CFI <0.15), prefrail (0.15 ≤CFI <0.25), mildly frail (0.25 ≤CFI <0.35) and moderately to severely frail (CFI ≥0.35). Outcomes included rates and relative risk of 30-day complications, 1-year mortality and repeat procedures for persistent incontinence or obstructed voiding at 1 year. RESULTS: A total of 54,112 women underwent sling surgery during the study period, 5.2% of whom were mildly to moderately to severely frail. Compared to the not frail group, moderately to severely frail beneficiaries demonstrated an increased adjusted relative risk (aRR) of 30-day complications (56.5%; aRR 2.5, 95% CI: 2.2-2.9) and 1-year mortality (10.5%; aRR 6.7, 95% CI: 4.0-11.2). Additionally, there were higher rates of repeat procedures in mildly to severely frail beneficiaries (6.6%; aRR 1.4, 95% CI: 1.2-1.6) compared to beneficiaries who were not frail. CONCLUSIONS: As frailty increased, there was an increased relative risk of 30-day complications, 1-year mortality and need for repeat procedures for persistent incontinence or obstructed voiding at 1 year. While there were fewer sling surgeries in performed frail women, the observed increase in complication rates was significant. Frailty should be strongly considered before pursuing sling surgery in older women.

Androgen Deprivation Therapy and the Risk of Dementia after Treatment for Prostate Cancer.

PURPOSE: The association between androgen deprivation therapy (ADT) and dementia in men with prostate cancer remains inconclusive. We assessed the association between cumulative ADT exposure and the onset of dementia in a nationwide longitudinal registry of men with prostate cancer. MATERIALS AND METHODS: A retrospective analysis of men aged ≥50 years from the CaPSURE (Cancer of the Prostate Strategic Urologic Research Endeavor) registry was performed. The primary outcome was onset of dementia after primary treatment. ADT exposure was expressed as a time-varying independent variable of total ADT exposure. The probability of receiving ADT was estimated using a propensity score. Cox proportional hazards regression was performed to determine the association between ADT exposure and dementia with competing risk of death, adjusted for propensity score and clinical covariates among men receiving various treatments. RESULTS: Of 13,570 men 317 (2.3%) were diagnosed with dementia after a median of 7.0 years (IQR 3.0-12.0) of followup. Cumulative ADT use was significantly associated with dementia (HR 2.02; 95% CI 1.40-2.91; p <0.01) after adjustment. In a subset of 8,506 men, where propensity score matched by whether or not they received ADT, there was also an association between ADT use and dementia (HR 1.59; 95% CI 1.03-2.44; p=0.04). There was no association between primary treatment type and onset of dementia in the 8,489 men in the cohort who did not receive ADT. CONCLUSIONS: Cumulative ADT exposure was associated with dementia. This increased risk should be accompanied by a careful discussion of the needs and benefits of ADT in those being considered for treatment.

Emulation of a target trial with sustained treatment strategies: an application to prostate cancer using both inverse probability weighting and the g-formula.

As with many chronic illnesses, recurrent prostate cancer generally requires sustained treatment to prolong survival. However, initiating treatment immediately after recurrence may negatively impact quality of life without any survival gains. Therefore, we consider sustained strategies for initiating treatment based on specific characteristics of prostate-specific antigen (PSA), which can indicate disease progression. We define the protocol for a target trial comparing treatment strategies based on PSA doubling time, in which androgen deprivation therapy is initiated only after doubling time decreases below a certain threshold. Such a treatment strategy means the timing of treatment initiation (if ever) is not known at baseline, and the target trial protocol must explicitly specify the frequency of PSA monitoring until the threshold is met, as well as the duration of treatment. We describe these and other components of a target trial that need to be specified in order for such a trial to be emulated in observational data. We then use the parametric g-formula and inverse-probability weighted dynamic marginal structural models to emulate our target trial in a cohort of prostate cancer patients from clinics across the United States.

Comparative Outcomes for Pelvic Organ Prolapse Surgery among Nursing Home Residents and Matched Community Dwelling Older Adults.

PURPOSE: We compared short and long-term outcomes between nursing home residents and matched community dwelling older adults undergoing surgery for pelvic organ prolapse. MATERIALS AND METHODS: This retrospective cohort study evaluates women 65 years old or older undergoing different types of pelvic organ prolapse repairs (anterior/posterior, apical and colpocleisis) between 2007 and 2012 using Medicare claims and the Minimum Data Set for Nursing Home Residents. Long-stay nursing home residents were identified and propensity score matched (1:2) to community dwelling older individuals based on procedure type, age, race and Charlson score. Generalized estimating equation models were created to determine the relative risk of hospital length of stay 3 or more days, 30-day complications and 1-year mortality between the 2 groups. Kaplan-Meier curves were created comparing 1-year mortality between groups. RESULTS: There were 799 nursing home residents and 1,598 matched community dwelling older adults who underwent pelvic organ prolapse surgery and were included in our analyses. Nursing home residents demonstrated statistically significant increased risk for hospital length of stay 3 or more days (38.9% vs 18.6%, adjusted RR 2.1, 95% CI 1.8-2.4), 30-day complications (15.1% vs 3.8%, aRR 3.9, 95% CI 2.9-5.3) and 1-year mortality (11.1% vs 3.2%, aRR 3.5, 95% CI 2.5-4.8) compared to community dwelling older adults. Kaplan-Meier curves illustrated similar survival findings at 1 year (11.1%, 95% CI 9.0-13.3 vs 3.2%, 95% CI 2.3-4.1, p <0.0001). CONCLUSIONS: Despite matching on several characteristics, nursing home residents demonstrated worse short and long-term outcomes compared to community dwelling older adults, suggesting other key vulnerabilities exist that contribute additional surgical risk in this population.

LINC00324 accelerates the proliferation and migration of osteosarcoma through regulating WDR66.

Osteosarcoma (OS) is a type of malignancy featured with high morbidity and easy metastasis. Although past years have witnessed the great improvement in the treatments of OS, there remains a long way to go. Therefore, further research on the underlying molecular mechanism of OS progression is in imminent need. Long noncoding RNAs (lncRNA) are recognized as a cluster of transcripts over 200 bases. Increasing studies have unveiled their significant regulatory roles in cancers, including in osteosarcoma. Long intergenic non-protein coding RNA 324 (LINC00324) is a newly identified lncRNA exerting oncogenic functions in several cancers, but its role in OS is yet to be uncovered. Therefore, the present study planned to explore the role of LINC00324 in osteosarcoma. We first validated the upregulation of LINC00324 in OS tissues and cell lines and established its correlation with OS tumor progression and metastasis. Importantly, the prognostic significance of LINC00324 was identified in patients with OS. Gain- and loss-of-function assays revealed that LINC00324 accelerated cell proliferation and migration in OS. Mechanistically, we revealed that LINC00324 stabilized WD repeat-containing protein 66 (WDR66) messenger RNA through interacting with Hu antigen R. Rescue assays verified that WDR66 was required for the regulation of LINC00324 in promoting proliferation and migration of OS cells. In conclusion, the present study proved that LINC00324 accelerated the proliferation and migration of osteosarcoma cells through regulating WDR66, providing a new prognostic target for osteosarcoma.

Association of Lower Urinary Tract Symptom Severity with Kidney Function among Community Dwelling Older Men.

PURPOSE: Most international practice guidelines recommend screening for chronic kidney disease among older men with lower urinary tract symptoms. However, prior studies supporting these guidelines are insufficient due to incomplete assessments of kidney function and inadequate adjustment for confounding factors. MATERIALS AND METHODS: We conducted a cross-sectional study among 5,530 American men older than 65 years in the multicenter Osteoporotic Fractures in Men Study. Chronic kidney disease was defined per international guidelines as estimated glomerular filtration rate less than 60 ml/minute/1.73 m2 based on serum creatinine or cystatin C, or urinary albumin-to-creatinine ratio 30 mg/gm or greater. Lower urinary tract symptoms were assessed with the American Urological Association Symptom Index. Associations were estimated using multivariable linear and modified Poisson regression models. RESULTS: Chronic kidney disease prevalence was 16% among 5,530 men with serum creatinine, 24% among 1,504 men with serum cystatin C and 14% among 1,487 men with urinary albumin-to-creatinine measurements. Lower urinary tract symptoms were not associated with lower estimated glomerular filtration rate based on serum creatinine or cystatin C. Although symptom severity was modestly associated with a higher prevalence of chronic kidney disease in age/site adjusted analyses, confidence intervals were wide and associations using all 3 definitions were not statistically significant after adjustment for important confounders, including cardiovascular disease and analgesic use. CONCLUSIONS: Lower urinary tract symptoms are not independently associated with multiple measures of kidney dysfunction or prevalence of chronic kidney disease among older community dwelling men. Our results do not support recommendations for kidney function testing among older men with lower urinary tract symptoms.

Risk Factors for Biopsy Reclassification over Time in Men on Active Surveillance for Early Stage Prostate Cancer.

PURPOSE: Few validated clinical tools currently exist to standardize the frequency of biopsies for men on active surveillance for low risk prostate cancer. We determined predictors of biopsy reclassification at specific time points after enrollment on active surveillance. MATERIALS AND METHODS: We identified men with clinically low risk prostate cancer prospectively enrolled on active surveillance at the University of California, San Francisco between 2000 and 2016. Biopsy reclassification was defined as Gleason Grade Group 2 or greater on subsequent biopsy. Multivariable Cox proportional hazards regression models were used to identify factors associated with risk of biopsy reclassification at first surveillance biopsy and 1 to 3, 3 to 5 and 5 to 10 years after enrollment, adjusting for clinicodemographic factors, PI-RADS® (Prostate Imaging Reporting and Data System) score and genomic testing. RESULTS: A total of 1,031 men were included in the study. On multivariable analysis biopsy reclassification was associated with prostate specific antigen density 0.15 or greater (HR 3.37, 95% CI 1.83-6.21), percentage biopsy cores positive (HR 1.27, 95% CI 1.05-1.54) and high genomic score (HR 2.81, 95% CI 1.21-6.52) at first surveillance biopsy and also at 1 to 3 years, after adjustment. Prostate specific antigen density 0.15 or greater (HR 2.36, 95% CI 1.56-3.56) and prostate specific antigen kinetics (HR 2.19, 95% CI 1.43-3.34) were associated with reclassification at 3 to 5 years. A PI-RADS 4-5 score was not associated with biopsy reclassification at any time point. CONCLUSIONS: High genomic score, prostate specific antigen kinetics and prostate specific antigen density 0.15 or greater were associated with reclassification within 3 years of commencing active surveillance, and prostate specific antigen kinetics and prostate specific antigen density 0.15 or greater remained associated with reclassification at 5 years after diagnosis.