Evidence-Based Criteria for Determining Peripapillary OCT Reliability.

PURPOSE: To assess the impact of OCT signal strength (SS) and artifact on retinal nerve fiber layer (RNFL) measurement reliability and to understand whether glaucoma severity modifies this relationship. DESIGN: Retrospective, longitudinal cohort study. PARTICIPANTS: Two thousand nine hundred ninety-two OCT scans from 474 eyes of 241 patients with glaucoma or glaucoma suspect status. METHODS: We extracted mean RNFL thickness and SS and manually graded scans for artifact. To analyze the effect of SS and artifact on OCT reliability, we (1) created a multilevel linear model using measured RNFL thickness values and demographic and clinical data to estimate the true (predicted) RNFL thickness, (2) calculated model residuals (ΔRNFL) as our reliability measure, and (3) created a second multilevel linear model with splines and interaction terms that modeled overall and quadrant specific reliability (ΔRNFL) as the outcome, using SS and artifact as predictors. MAIN OUTCOME MEASURES: Impact of SS and artifact on ΔRNFL. RESULTS: For SS between 10 and 3, the impact of decreases in SS on OCT reliability is modest (-0.67 to -1.25 ΔRNFL per 1-point decrease in SS; P < 0.05). But at less than 3, changes in SS have a large impact on reliability (-15.70 to -16.34 ΔRNFL per 1-point decrease in SS; P < 0.05). At SS between 10 and 3, decreases in SS tend to have a larger impact on reliability in eyes with severe glaucoma (-1.25 per 1-point decrease in SS; P < 0.05) compared with eyes with mild or moderate glaucoma (-0.67 to -0.75 per 1-point decrease in SS; P < 0.05). The presence of artifact has a significant impact on OCT reliability independent of the effects of SS (-4.76 ΔRNFL; P < 0.05). Artifact affects reliability solely in the quadrant in which it occurs, with artifact in one quadrant showing no impact on ΔRNFL in the opposite quadrant (P > 0.05). CONCLUSIONS: Signal strength decreases down to 3 have relatively mild impacts on OCT reliability. At less than 3, the impact of further decreases in SS on reliability are substantial. The effect of SS on reliability is greater in severe glaucoma. Artifacts result in a decrease in reliability independent of the effect of SS. We propose evidence-based guidelines to guide physicians on whether to trust the results of an OCT scan.

Selecting Patients with Small Renal Masses for Active Surveillance: A Domain Based Score from a Prospective Cohort Study.

PURPOSE: We sought to identify predictors of active surveillance in a prospective cohort study of patients with a small renal mass demonstrating favorable outcomes. We generated a summary score to discriminate patients selected for active surveillance or primary intervention. MATERIALS AND METHODS: We analyzed the records of 751 patients from 2009 to 2018 who were enrolled in the DISSRM (Delayed Intervention and Surveillance for Small Renal Masses) Registry to compare active surveillance and primary intervention in the domains of demographics, tumor characteristics, comorbidity and patient reported quality of life. Regression models were created to assess univariable and multivariable model discrimination by the AUC and quality by the AIC (Akaike information criterion). The DISSRM score was based on the most predictive combination of variables and validated for its association with overall survival by Kaplan-Meier survival curves and a Cox proportional hazards regression model. RESULTS: Of the patients 410 (55%) elected active surveillance and 341 (45%) elected primary intervention. Of the domains patient age, the Charlson comorbidity index, tumor diameter and the SF-12® Physical Component Score had the greatest discrimination for clinical selection into active surveillance. These domains made up the DISSRM score (AUC 0.801). The maximum DISSRM score was 7. The average score for active surveillance was 4.19 (median 4, IQR 2-6) and 72% of scores were 4 or greater. The average score for primary intervention was 3.03 (median 3, IQR 1-5) and 63% of scores were 3 or less. A higher DISSRM score was associated with worse overall survival, for example a score of 6-7 had a HR of 10.45 (95% CI 1.25-87.49, p = 0.03). CONCLUSIONS: The DISSRM score represents a measure of oncologic and competing risks of death in various important domains in patients with a small renal mass. It could be used to guide the management selection. Patients with intermediate scores that express illness uncertainty may require additional workup, such as confirmatory biopsy, to reach a treatment decision.

Ascorbate starvation alters endoplasmic reticulum-resident enzymes in cardiac fibroblasts, priming them for increased procollagen secretion.

Since ascorbate is unnecessary for cell growth and survival, cardiac fibroblasts are routinely cultured without it. However, ascorbate is necessary for optimal collagen synthesis, so we hypothesized that its presence would influence cell phenotype. Cardiac fibroblasts cultured without ascorbate had increased intracellular levels of procollagens, with procollagen α1(III) showing the largest accumulation. Endoplasmic reticulum (ER)-resident proteins that are known to bind single-stranded procollagens were also elevated. These included the catalytic prolyl 4-hydroxylase subunits, lysyl hydroxylases, and hydroxylysyl galactosyltransferases, with prolyl 4-hydroxylase α1 and α2 (P4HA1 and P4HA2) demonstrating the largest increases. There were no differences in the levels of protein disulfide isomerase (P4HB/PDI) or the triple-helical procollagen chaperone, HSP47, with or without ascorbate. Results were similar with mouse and rat cardiac fibroblasts, suggesting a conserved response. Ascorbate-replete cells that were subsequently deprived of the vitamin lost the ability to secrete intact procollagen α1(I) within ~3days, approximately when intracellular procollagen α1(III) and P4HA1 levels began to rise. Upon ascorbate re-addition, starved fibroblasts initially secreted high levels of procollagen that gradually declined over ~4days, a pattern that was not universal as extra domain A (EDA)-fibronectin secretion was unchanged. Despite the necessity of the P4HA enzymes for triple-helical procollagen formation, they were not responsible for early increased secretion. However, in the absence of ascorbate, P4HA2 overexpression increased intracellular turnover of procollagens, suggesting that it may help clear accumulating procollagens from the ER. Cardiac fibroblasts change in the absence of ascorbate to cope with increased intracellular levels of procollagens. These changes occur slowly and can render the cells phenotypically altered for several days after ascorbate re-addition. These findings have direct implications for the study of cardiac fibroblasts in culture, and may help our understanding of the response of these cells to fluctuating nutrient levels in ischemic myocardium.

A novel class of negative allosteric modulators of NMDA receptor function.

NMDA receptors mediate a slow Ca(2+)-permeable component of excitatory synaptic transmission, and are involved in numerous normal brain functions including learning and memory. NMDA receptor over-activation can lead to cell death and abnormal excitation in ischemia associated with stroke, traumatic brain injury, and epilepsy. We have explored a series of novel noncompetitive allosteric modulators of NMDA receptor function characterized by an iminothiazolidinone ring. Saturating concentrations of these compounds inhibit NMDA receptors to varying maximal extents, raising the possibility that they may attenuate over-activation in pathological situations while preserving some minimal receptor function, which may limit side-effects. The best in class compounds have sub-micromolar IC50 values and show modest preference for GluN2C- and GluN2D-containing receptors.

Medical management of benign prostatic hyperplasia.

Medical management of benign prostatic hyperplasia (BPH) has progressed gradually in recent years and remains the starting point for most symptomatic patients seeking treatment. Beyond well-known alpha-blockers and 5-alpha reductase inhibitors, there is growing evidence for the use of phosphodiesterase-5 inhibitors and beta-3 agonists in managing the condition, which may afford additional relief of "bothersome" symptoms in some patients. This review details contemporary medical management of BPH with an emphasis on the indications for certain classes of pharmacotherapy and their relative benefits and side effects. Surgical and procedural treatment of BPH is covered in a separate review.

Contemporary surgical and procedural management of benign prostatic hyperplasia.

Interventions for benign prostatic hyperplasia have evolved from transurethral resection of the prostate and simple prostatectomy to a myriad of office-based and operating-room procedures. The contemporary approach involves matching the right procedure to the right patient, choosing on the basis of prostate characteristics, patient preference, and urologist expertise. This review details currently available and guideline-backed surgical and procedural treatments.

Reliability of Several Glaucoma Tests in Patients With Boston Type 1 Keratoprosthesis.

PURPOSE: Managing glaucoma after Boston type 1 keratoprosthesis (KPro) surgery remains challenging. We herein assessed the fitness of commonly used clinical tests to evaluate glaucoma in KPro eyes versus eyes with penetrating keratoplasty (PK) as controls. METHODS: Sixteen patients with KPro and 14 patients with PK tested in an identical manner. After the 10-2 visual field with size V stimulus, intraocular pressure (IOP) was estimated with palpation by the first observer. Then, retinal nerve fiber layer (RNFL) thickness analysis was performed twice using optical coherence tomography by an ophthalmic photographer, before and after a short break. After the second observer estimated the IOP, the visual field was repeated. Finally, color photographs of the optic disk were captured by an ophthalmic photographer. The cup-to-disk ratio was assessed by 2 masked observers, at 2 different time points, in a random manner. Agreements between and within observers and reliability of repeated measurements were evaluated using the intraclass correlation coefficient (ICC) and Bland-Altman plots. RESULTS: Inter-rater agreement of palpation IOP estimate was moderate for eyes with KPro (ICC = 0.47) and fair for eyes with PK (ICC = 0.27). Visual field and RNFL thickness showed high test-retest reliability in both KPro and PK eyes (ICC > 0.80 for both). Inter-rater agreement of cup-to-disk ratio assessments was substantial in eyes with both KPro (ICC = 0.62) and PK (ICC = 0.70). CONCLUSIONS: The 10-2 visual field and RNFL thickness seem sufficiently repeatable and might allow the detection of glaucoma progression in KPro eyes. Such testing is important, given limited inter-rater agreement regarding the palpation IOP estimate.

External validation of the priapism impact profile in a Jamaican cohort of patients with sickle cell disease.

BACKGROUND: Priapism impairs quality of life and has a predilection for males with sickle cell disease (SCD). The Priapism Impact Profile (PIP) is a novel 12-item instrument designed to measure general health-related impact of priapism. The aim of the study was to evaluate the validity and reliability of the PIP in a Jamaican cohort of SCD patients experiencing priapism. METHODS: One hundred SCD patients with a history of priapism were recruited from a sickle cell clinic in Kingston, Jamaica and administered the PIP questionnaire. Patients rated each item of the PIP for clarity and importance. Statistical testing was employed to evaluate the psychometric performance of the PIP. Content validation was assessed based on patient descriptive rating of the items based on clarity, and importance and criterion-oriented validity were assessed by evaluating the PIP's ability to distinguish between patient subgroups. Test-retest repeatability was assessed in 20 of the 100 patients. RESULTS: Patients were stratified into active (54) and remission (46) priapism groups based on their experience of priapism within the past year. Patients in the active priapism group were younger (p = 0.011), had a shorter duration of disease (p = 0.023), and had more frequent priapism episodes (p = 0.036) than the remission group. PIP questionnaire scores differed significantly with respect to priapism activity (p < 0.001) and prevalence of erectile dysfunction (p < 0.05) but not by priapism severity (p = 0.62). The PIP questionnaire had good content validity, with questions rated as having medium or high clarity and importance by an average of 82.8% and 69.2% of patients, respectively. CONCLUSION: The PIP questionnaire was successfully validated in a Jamaican cohort of SCD patients and adequately discriminated patients with active priapism from those in remission. The instrument may be utilized in routine clinical management of patients with SCD-associated priapism. Further clinical investigations are warranted in other populations.

Penile Prosthesis Implantation in an Exstrophy-Epispadias Complex Patient: A Case Report.

Penile prosthesis implantation (PPI) is a definitive treatment option for patients with medically refractory erectile dysfunction (ED). It is a safe, reliable operation with high patient satisfaction and few complications. We report a novel case of an adult patient with exstrophy-epispadias complex who underwent PPI for ED and discuss the surgical challenges presented by the unique anatomic constraints of this condition. Sotimehin AE, Burnett AL. Penile Prosthesis Implantation in an Exstrophy-Epispadias Complex Patient: A Case Report. Sex Med 2019;7:540-542.

Measuring Disability in Glaucoma.

BACKGROUND: Glaucomatous visual field loss can have far-reaching and debilitating consequences on an individual, affecting one's ability to perform many important tasks. Although assessment of glaucoma-related disability constitutes an important part of clinical care, there remains a lack of organized, detailed information on the most suitable methods to capture disability in glaucoma. PURPOSE: This review details the available methods to measure glaucoma-related disability and highlights important findings from studies utilizing these various methods. METHODS: The literature was reviewed to identify papers evaluating disability in glaucoma and findings were summarized by research methodology used and area of impairment. RESULTS: Identified methods for capturing glaucoma-related disability included qualitative descriptions, glaucoma-specific quality of life questionnaires, vision-specific questionnaires, general health questionnaires, functional domain-specific questionnaires, evaluation of task performance, event assessment (ie, falls and motor vehicle accidents), and real-world behavior (ie, daily physical activity). Findings using these methods show a strong relationship between glaucoma and/or glaucoma severity and difficulties with reading, driving, mobility, and other tasks such as prehension and facial recognition. In addition, glaucoma has financial and psychological implications on the patient, and can affect caregivers in some cases as well. CONCLUSIONS: A wide variety of research tools have been used to characterize the disability resulting from glaucoma. Together, these tools show that glaucoma affects many abilities which are important for independent living. Strengths and limitations of the various research techniques are discussed so that future studies may use the method(s) most suitable for answering the research question posed.

Locations, Circumstances, and Outcomes of Falls in Patients With Glaucoma.

PURPOSE: To characterize the locations, circumstances, and outcomes of falls in patients with varying degrees of glaucoma. DESIGN: Prospective cohort study. METHODS: Patients with suspected or diagnosed glaucoma completed monthly calendars reporting falls. After each fall, a 30-item questionnaire was administered to determine fall location, circumstances, and injury. Mean deviation on visual field (VF) testing was used to categorize glaucoma severity. Main outcome measures were fall locations, circumstances, and outcomes. RESULTS: One-hundred forty-two patients experienced 330 falls. Falls were most likely to occur in/around the home (71%), and this likelihood did not vary significantly with severity of VF damage (P > .2). The most commonly cited fall circumstances were tripping (43.6%), slipping (31.3%), uneven flooring (23.5%), and poor vision (15.9%). The circumstances related to falls did not vary by severity of VF damage (P > .2), except for poor vision, which was more frequently cited in individuals with more advanced VF damage (P = .001). Forty-three percent of falls resulted in some injury; and the likelihood of injury did not vary by severity of VF loss (P = .60) or any other factor except floor type and number of comorbidities (P < .05 for all). Falls in persons with more severe glaucoma were more likely to result in a fracture (9.4%) or an emergency room visit (18.8%), though these associations did not persist in multivariable models (P > .5 for all). CONCLUSIONS: Glaucoma patients fall mostly in/around the home and demonstrate similar fall circumstances across the spectrum of disease severity, suggesting that current fall prevention interventions, particularly those emphasizing home modification, may be an adequate starting point to prevent falls in this high-risk-group.