The influence of risk factors, biomarkers and care settings on SUDEP counseling.

Although sudden unexpected death in epilepsy (SUDEP) is the most feared epilepsy outcome, there is a dearth of SUDEP counseling provided by neurologists. This may reflect limited time, as well as the lack of guidance on the timing and structure for counseling. We evaluated records from SUDEP cases to examine frequency of inpatient and outpatient SUDEP counseling, and whether counseling practices were influenced by risk factors and biomarkers, such as post-ictal generalized EEG suppression (PGES). We found a striking lack of SUDEP counseling despite modifiable SUDEP risk factors; counseling was limited to outpatients despite many patients having inpatient visits within a year of SUDEP. PGES was inconsistently documented and was never included in counseling. There is an opportunity to greatly improve SUDEP counseling by utilizing inpatient settings and prompting algorithms incorporating risk factors and biomarkers.

Serotonin receptor expression in hippocampus and temporal cortex of temporal lobe epilepsy patients by postictal generalized electroencephalographic suppression duration.

OBJECTIVE: Prolonged postictal generalized electroencephalographic suppression (PGES) is a potential biomarker for sudden unexpected death in epilepsy (SUDEP), which may be associated with dysfunctional autonomic responses and serotonin signaling. To better understand molecular mechanisms, PGES duration was correlated to 5HT1A and 5HT2A receptor protein expression and RNAseq from resected hippocampus and temporal cortex of temporal lobe epilepsy patients with seizures recorded in preoperative evaluation. METHODS: Analyses included 36 cases (age = 14-64 years, age at epilepsy onset = 0-51 years, epilepsy duration = 2-53 years, PGES duration = 0-93 s), with 13 cases in all hippocampal analyses. 5HT1A and 5HT2A protein was evaluated by Western blot and histologically in hippocampus (n = 16) and temporal cortex (n = 9). We correlated PGES duration to our previous RNAseq dataset for serotonin receptor expression and signaling pathways, as well as weighted gene correlation network analysis (WGCNA) to identify correlated gene clusters. RESULTS: In hippocampus, 5HT2A protein by Western blot positively correlated with PGES duration (p = .0024, R2  = .52), but 5HT1A did not (p = .87, R2  = .0020). In temporal cortex, 5HT1A and 5HT2A had lower expression and did not correlate with PGES duration. Histologically, PGES duration did not correlate with 5HT1A or 5HT2A expression in hippocampal CA4, dentate gyrus, or temporal cortex. RNAseq identified two serotonin receptors with expression that correlated with PGES duration in an exploratory analysis: HTR3B negatively correlated (p = .043, R2  = .26) and HTR4 positively correlated (p = .049, R2  = .25). WGCNA identified four modules correlated with PGES duration, including positive correlation with synaptic transcripts (p = .040, Pearson correlation r = .52), particularly potassium channels (KCNA4, KCNC4, KCNH1, KCNIP4, KCNJ3, KCNJ6, KCNK1). No modules were associated with serotonin receptor signaling. SIGNIFICANCE: Higher hippocampal 5HT2A receptor protein and potassium channel transcripts may reflect underlying mechanisms contributing to or resulting from prolonged PGES. Future studies with larger cohorts should assess functional analyses and additional brain regions to elucidate mechanisms underlying PGES and SUDEP risk.

SUDEP education among U.S. and international neurology trainees.

We evaluated baseline sudden unexpected death in epilepsy (SUDEP) knowledge and counseling practices among national and international adult neurology trainees with a 12-question online survey. The survey was emailed to all 169 U.S. neurology residency program directors and select international neurology/epilepsy program leaders. Program leaders were asked to distribute the survey link to adult neurology trainees. There were 161 respondents in the U.S. and 171 respondents outside the U.S. The latter were from 25 Latin American, European, Asian, and African countries. More than 90% of all trainees reported familiarity with SUDEP definition. Familiarity with SUDEP risk factors and mitigation measures ranged from 56% to 67% across these groups, with international trainees slightly more familiar with risk factors (67% vs. 61% in U.S.) but less familiar with mitigation measures (56% vs. 63% in U.S.). Approximately half of national (49%) and international (54%) trainees rarely or never counseled patients on SUDEP. Less than half of national (44%) and international (41%) trainees were educated about SUDEP. Many U.S. and adult neurology trainees remain unfamiliar with SUDEP risk factors and mitigation measures. Sudden unexpected death in epilepsy counseling falls below recommended standards. We suggest that worldwide neurology training programs' leaderships consider improving SUDEP education targeted at adult neurology trainees.

SUDEP classification: Discordances between forensic investigators and epileptologists.

We compared sudden unexpected death in epilepsy (SUDEP) diagnosis rates between North American SUDEP Registry (NASR) epileptologists and original death investigators, to determine degree and causes of discordance. In 220 SUDEP cases with post-mortem examination, we recorded the epileptologist adjudications and medical examiner- and coroner- (ME/C) listed causes of death (CODs). COD diagnosis concordance decreased with NASR's uncertainty in the SUDEP diagnosis: highest for Definite SUDEP (84%, n = 158), lower in Definite Plus (50%, n = 36), and lowest in Possible (0%, n = 18). Rates of psychiatric comorbidity, substance abuse, and toxicology findings for drugs of abuse were all higher in discordant cases than concordant cases. Possible SUDEP cases, an understudied group, were significantly older, and had higher rates of cardiac, drug, or toxicology findings than more certain SUDEP cases. With a potentially contributing or competing COD, ME/Cs favored non-epilepsy-related diagnoses, suggesting a bias toward listing CODs with structural or toxicological findings; SUDEP has no pathognomonic features. A history of epilepsy should always be listed on death certificates and autopsy reports. Even without an alternate COD, ME/Cs infrequently classified COD as "SUDEP." Improved collaboration and communication between epilepsy and ME/C communities improve diagnostic accuracy, as well as bereavement and research opportunities.

Radical prostatectomy improves and prevents age dependent progression of lower urinary tract symptoms.

PURPOSE: The prevalence of lower urinary tract symptoms increases with age and impairs quality of life. Radical prostatectomy has been shown to relieve lower urinary tract symptoms at short-term followup but the long-term effect of radical prostatectomy on lower urinary tract symptoms is unclear. MATERIALS AND METHODS: We performed a prospective cohort study of 1,788 men undergoing radical prostatectomy. The progression of scores from the self-administered AUASS (American Urological Association symptom score) preoperatively, and at 3, 6, 12, 24, 48, 60, 84, 96 and 120 months was analyzed using models controlling for preoperative AUASS, age, prostate specific antigen, pathological Gleason score and stage, nerve sparing, race and marital status. This model was also applied to patients stratified by baseline clinically significant (AUASS greater than 7) and insignificant (AUASS 7 or less) lower urinary tract symptoms. RESULTS: Men exhibited an immediate worsening of lower urinary tract symptoms that improved between 3 months and 2 years after radical prostatectomy. Overall the difference between mean AUASS at baseline and at 10 years was not statistically or clinically significant. Men with baseline clinically significant lower urinary tract symptoms experienced immediate improvements in lower urinary tract symptoms that lasted until 10 years after radical prostatectomy (13.5 vs 8.81, p <0.001). Men with baseline clinically insignificant lower urinary tract symptoms experienced a statistically significant but clinically insignificant increase in mean AUASS after 10 years (3.09 to 4.94, p <0.001). The percentage of men with clinically significant lower urinary tract symptoms decreased from baseline to 10 years after radical prostatectomy (p = 0.02). CONCLUSIONS: Radical prostatectomy is the only treatment for prostate cancer shown to improve and prevent the development of lower urinary tract symptoms at long-term followup. This previously unrecognized long-term benefit argues in favor of the prostate as the primary contributor to male lower urinary tract symptoms.

Hypothalamic-Pituitary-Adrenal Axis Dysfunction Elevates SUDEP Risk in a Sex-Specific Manner.

Epilepsy is often comorbid with psychiatric illnesses, including anxiety and depression. Despite the high incidence of psychiatric comorbidities in people with epilepsy, few studies address the underlying mechanisms. Stress can trigger epilepsy and depression. Evidence from human and animal studies supports that hypothalamic-pituitary-adrenal (HPA) axis dysfunction may contribute to both disorders and their comorbidity ( Kanner, 2003). Here, we investigate if HPA axis dysfunction may influence epilepsy outcomes and psychiatric comorbidities. We generated a novel mouse model (Kcc2/Crh KO mice) lacking the K+/Cl- cotransporter, KCC2, in corticotropin-releasing hormone (CRH) neurons, which exhibit stress- and seizure-induced HPA axis hyperactivation ( Melon et al., 2018). We used the Kcc2/Crh KO mice to examine the impact on epilepsy outcomes, including seizure frequency/burden, comorbid behavioral deficits, and sudden unexpected death in epilepsy (SUDEP) risk. We found sex differences in HPA axis dysfunction's effect on chronically epileptic KCC2/Crh KO mice seizure burden, vulnerability to comorbid behavioral deficits, and SUDEP. Suppressing HPA axis hyperexcitability in this model using pharmacological or chemogenetic approaches decreased SUDEP incidence, suggesting that HPA axis dysfunction may contribute to SUDEP. Altered neuroendocrine markers were present in SUDEP cases compared with people with epilepsy or individuals without epilepsy. Together, these findings implicate HPA axis dysfunction in the pathophysiological mechanisms contributing to psychiatric comorbidities in epilepsy and SUDEP.

Long-term satisfaction and predictors of use of intracorporeal injections for post-prostatectomy erectile dysfunction.

PURPOSE: Intracorporeal injections have low use rates and high discontinuation rates. We examined factors associated with intracorporeal injection use, long-term satisfaction with intracorporeal injection and reasons for discontinuation in men treated with radical prostatectomy. MATERIALS AND METHODS: Between October 2000 and September 2003, 731 men who underwent open radical retropubic prostatectomy were enrolled in a prospective outcomes study. The 8-year followup evaluation included the UCLA-PCI, and a survey capturing intracorporeal injection use, satisfaction and reasons for discontinuation. Logistic regression was used to determine associations between intracorporeal injection use and preoperative variables. RESULTS: The 8-year self-assessment was completed by 368 (50.4%) men. Of these men 140 (38%) indicated prior or current intracorporeal injection use, with only 34 using intracorporeal injection at 8 years. Overall, 44% of the men were satisfied with intracorporeal injections. Reasons for discontinuation included dislike (47%), pain (33%), return of erection (19%), inefficacy (14%) and no partner (6%). Men trying intracorporeal injections had greater preoperative UCLA-PCI sexual function scores (75.2 vs 65.62, p = 0.00005) as well as greater decreases in this score at 3 months (p = 0.0002) and 2 years (p = 0.003). Higher preoperative sexual function scores were independently associated with the use of intracorporeal injections in a model adjusted for age, marital status, nerve sparing status and body mass index (OR 1.021, 95% CI 1.008-1.035). CONCLUSIONS: Men pursuing intracorporeal injections have better baseline erectile function and experience greater deterioration in erectile function during the early postoperative period. Despite the high efficacy of injections, many men discontinue intracorporeal injections due to dislike or discomfort. Satisfaction rates for intracorporeal injections indicate their long-term role in restoring sexual function in men with post-prostatectomy erectile dysfunction.

Correlation between benign prostatic hyperplasia and inflammation.

PURPOSE OF REVIEW: This review aims to evaluate the available evidence on the role of prostatic inflammation in the pathogenesis and progression of benign prostatic hyperplasia (BPH). RECENT FINDINGS: Although there is still no evidence of a causal relation, accumulating evidence suggests that inflammation may contribute to the development of BPH and lower urinary tract symptoms (LUTS). Inflammatory infiltrates are frequently observed in prostate tissue specimens from men with BPH and the presence or degree of inflammation has been found to be correlated with prostate volume and weight. The inflammatory injury may contribute to cytokine production by inflammatory cells driving local growth factor production and angiogenesis in the prostatic tissue. This proinflammatory microenvironment is closely related to BPH stromal hyperproliferation and tissue remodeling with a local hypoxia induced by increased oxygen demands by proliferating cells which supports chronic inflammation as a source of oxidative stress leading to tissue injury in infiltrating area. SUMMARY: Although the pathogenesis of BPH is not yet fully understood and several mechanisms seem to be involved in the development and progression, recent studies strongly suggest that BPH is an immune inflammatory disease. The T-cell activity and associated autoimmune reaction seem to induce epithelial and stromal cell proliferation. Further understanding of the role of inflammation in BPH and clinical detection of this inflammation will expand the understanding of BPH pathogenesis and its histologic and clinical progression, allow risk stratification for patients presenting with BPH-related LUTS, and suggest novel treatment strategies.

Risk of sudden unexpected death in epilepsy (SUDEP) with lamotrigine and other sodium channel-modulating antiseizure medications.

OBJECTIVE: In vitro data prompted U.S Food and Drug Administration warnings that lamotrigine, a common sodium channel modulating anti-seizure medication (NaM-ASM), could increase the risk of sudden death in patients with structural or ischaemic cardiac disease, however, its implications for Sudden Unexpected Death in Epilepsy (SUDEP) are unclear. METHODS: This retrospective, nested case-control study identified 101 sudden unexpected death in epilepsy (SUDEP) cases and 199 living epilepsy controls from Epilepsy Monitoring Units (EMUs) in Australia and the USA. Differences in proportions of lamotrigine and NaM-ASM use were compared between cases and controls at the time of admission, and survival analyses from the time of admission up to 16 years were conducted. Multivariable logistic regression and survival analyses compared each ASM subgroup adjusting for SUDEP risk factors. RESULTS: Proportions of cases and controls prescribed lamotrigine (P = 0.166), one NaM-ASM (P = 0.80), or ≥2NaM-ASMs (P = 0.447) at EMU admission were not significantly different. Patients taking lamotrigine (adjusted hazard ratio [aHR] = 0.56; P = 0.054), one NaM-ASM (aHR = 0.8; P = 0.588) or ≥2 NaM-ASMs (aHR = 0.49; P = 0.139) at EMU admission were not at increased SUDEP risk up to 16 years following admission. Active tonic-clonic seizures at EMU admission associated with >2-fold SUDEP risk, irrespective of lamotrigine (aHR = 2.24; P = 0.031) or NaM-ASM use (aHR = 2.25; P = 0.029). Sensitivity analyses accounting for incomplete ASM data at follow-up suggest undetected changes to ASM use are unlikely to alter our results. SIGNIFICANCE: This study provides additional evidence that lamotrigine and other NaM-ASMs are unlikely to be associated with an increased long-term risk of SUDEP, up to 16 years post-EMU admission.

Association between postictal EEG suppression, postictal autonomic dysfunction, and sudden unexpected death in epilepsy: Evidence from intracranial EEG.

OBJECTIVE: The association between postictal electroencephalogram (EEG) suppression (PES), autonomic dysfunction, and Sudden Unexpected Death in Epilepsy (SUDEP) remains poorly understood. We compared PES on simultaneous intracranial and scalp-EEG and evaluated the association of PES with postictal heart rate variability (HRV) and SUDEP outcome. METHODS: Convulsive seizures were analyzed in patients with drug-resistant epilepsy at 5 centers. Intracranial PES was quantified using the Hilbert transform. HRV was quantified using root mean square of successive differences of interbeat intervals, low-frequency to high-frequency power ratio, and RR-intervals. RESULTS: There were 64 seizures from 63 patients without SUDEP and 11 seizures from 6 SUDEP patients. PES occurred in 99% and 87% of seizures on intracranial-EEG and scalp-EEG, respectively. Mean PES duration in intracranial and scalp-EEG was similar. Intracranial PES was regional (<90% of channels) in 46% of seizures; scalp PES was generalized in all seizures. Generalized PES showed greater decrease in postictal parasympathetic activity than regional PES. PES duration and extent were similar between patients with and without SUDEP. CONCLUSIONS: Regional intracranial PES can be present despite scalp-EEG demonstrating generalized or no PES. Postictal autonomic dysfunction correlates with the extent of PES. SIGNIFICANCE: Intracranial-EEG demonstrates changes in autonomic regulatory networks not seen on scalp-EEG.

Ictal ECG-based assessment of sudden unexpected death in epilepsy.

Introduction: Previous case-control studies of sudden unexpected death in epilepsy (SUDEP) patients failed to identify ECG features (peri-ictal heart rate, heart rate variability, corrected QT interval, postictal heart rate recovery, and cardiac rhythm) predictive of SUDEP risk. This implied a need to derive novel metrics to assess SUDEP risk from ECG. Methods: We applied Single Spectrum Analysis and Independent Component Analysis (SSA-ICA) to remove artifact from ECG recordings. Then cross-frequency phase-phase coupling (PPC) was applied to a 20-s mid-seizure window and a contour of -3 dB coupling strength was determined. The contour centroid polar coordinates, amplitude (alpha) and angle (theta), were calculated. Association of alpha and theta with SUDEP was assessed and a logistic classifier for alpha was constructed. Results: Alpha was higher in SUDEP patients, compared to non-SUDEP patients (p < 0.001). Theta showed no significant difference between patient populations. The receiver operating characteristic (ROC) of a logistic classifier for alpha resulted in an area under the ROC curve (AUC) of 94% and correctly classified two test SUDEP patients. Discussion: This study develops a novel metric alpha, which highlights non-linear interactions between two rhythms in the ECG, and is predictive of SUDEP risk.

Preoperative statin therapy is not associated with biochemical recurrence after radical prostatectomy: our experience and meta-analysis.

PURPOSE: The effect of statins on prostate cancer recurrence has been investigated in several studies with inconsistent results. We investigated whether statins were associated with biochemical recurrence in a large cohort of men after radical prostatectomy. We also performed a meta-analysis of existing studies. MATERIALS AND METHODS: A total of 1,446 patients who underwent radical prostatectomy at New York University were followed a median of 57 months for biochemical recurrence events. Baseline demographic and clinical characteristics were compared between 437 statin users and 1,009 nonusers. Kaplan-Meier curves and Cox models were used to examine biochemical recurrence-free survival by statin use. A meta-analysis was performed with data from our cohort and 5 published studies using the random effects model. RESULTS: Statin users were slightly older and more likely to have diabetes (p <0.01). They were similar to nonusers in race and body mass index. Although preoperative prostate specific antigen and tumor stage were similar between the 2 groups, the proportion of patients with pathological Gleason score 7-10 tumors was slightly higher among statin users (p = 0.03). The biochemical recurrence-free survival rate was 87.4% and 89.0% for statin users and nonusers, respectively, at the end of followup (log rank p = 0.26). Overall biochemical recurrence was not associated with statin use (HR 1.15, 95% CI 0.82-1.61). Results were similar when patients were stratified by D'Amico low and intermediate or high risk groups. Meta-analysis revealed no overall association between statins and biochemical recurrence (pooled HR 1.00, 95% CI 0.80-1.19). CONCLUSIONS: Our findings are consistent with the results of the meta-analysis, which indicated that preoperative statin use does not impact the overall risk of biochemical recurrence.

The effect of surgical intervention for stress urinary incontinence (UI) on post-prostatectomy UI during sexual activity.

OBJECTIVE: To determine the impact of anti-incontinence surgical procedures (artificial urinary sphincter [AUS] or male sling) on bother due to urinary incontinence (UI) during sexual activity after radical prostatectomy (RP). PATIENTS AND METHODS: Between October 2000 and December 2007, 27 men in a large single-surgeon RP series underwent anti-incontinence surgery with an AUS or male sling. In all, 16 of these 27 men completed a questionnaire retrospectively capturing bother attributable to UI during arousal and orgasm and the impact of the AUS/male sling on UI and sexual quality of life (QoL). RESULTS: In all, 15 men were evaluable. Of these, 11 were sexually active; four and seven men underwent AUS and sling placement, respectively. All 11 men had a marked improvement in stress UI symptoms, which was the primary indication for surgery. All men undergoing AUS had an improvement in their sexual QoL, and most (three of four men) indicated marked improvement. Slightly more than half of men undergoing the sling procedure reported marked improvement in sexual QoL. CONCLUSIONS: Our study shows a beneficial effect of anti-incontinence surgery on UI during sexual activity. Whether these surgical approaches would benefit men with significant bother due to UI limited to sexual activity warrants further investigation.

Comparison of health-related quality-of-life outcomes for African-American and Caucasian-American men after radical prostatectomy.

UNLABELLED: What's known on the subject? and What does the study add? In addition to a higher prevalence and biological aggressiveness of prostate cancer, African-Americans tend towards narrower pelvises than Caucasians resulting in a potentially more difficult surgical dissection doing radical prostatectomy and increased positive surgical margins. In this study, there was no difference in urinary or sexual HRQL or overall satisfaction between African-Americans and Caucasians 2 years after radical prostatectomy, suggesting that the potential technical challenges of a narrower pelvis do not translate into poorer outcomes for African-Americans. OBJECTIVE: To determine if any differences exist in postoperative health-related quality-of-life (HRQL) outcomes, e.g. erectile function and continence, after radical prostatectomy (RP) in African-American (AA) vs Caucasian-American (CA) men. PATIENTS AND METHODS: Between October 2000 and July 2008, 1338 CA and 56 AA men underwent open RP by a single surgeon and signed informed consent to participate in a prospective longitudinal outcomes study. The American Urological Association Symptom Score (AUA-SS) and University of California, Los Angeles, Prostate Cancer Index (UCLA-PCI) and a global assessment of satisfaction were self-administered at baseline and after RP 24 months. Urinary, sexual, and satisfaction outcomes were compared at 24 months. RESULTS: AA men had significantly higher rates of hypertension and diabetes. There were no other significant baseline differences in age, co-morbidities, body mass index, phosphodiesterase type 5 inhibitor use, preoperative prostate-specific antigen level, AUA-SS, and UCLA-PCI scores. There were no differences in the percentage of men undergoing nerve-sparing procedures, estimated blood loss, transfusion rates, or complication rates between the groups. At 24 months after RP the mean UCLA-PCI urinary and sexual function and bother scores and global satisfaction scores were similar between the groups. CONCLUSION: AA and CA men experience no significant differences in urinary and sexual HRQL or overall satisfaction after open RP when performed by a single experienced surgeon.

Blood loss during radical prostatectomy: impact on clinical, oncological and functional outcomes and complication rates.

UNLABELLED: Study Type - Outcomes (cohort) Level of Evidence 2b What's known on the subject? and What does the study add? It is generally accepted in the medical community that total and intra-operative blood loss after RALP is significantly lower in comparison with ORRP. This has led to speculation that less bleeding results in better visualization of the operative field resulting in superior potency and continence. Blood loss (BL) during ORRP does not adversely impact clinical and functional outcomes irrespective of how BL is defined. Thus, the lower BL associated with RALP would not be expected to improve functional or oncological outcomes. OBJECTIVE: To determine the short- and long-term impact of blood loss (BL) on clinical, oncological and functional outcomes as well as complication rates after an open radical retropubic prostatectomy (ORRP). PATIENTS AND METHODS: Between 2000 and 2008, 1567 men who underwent an ORRP participated in our prospective longitudinal outcomes study. Haematocrit (Hct) levels, transfusion rates, BL and complications were recorded prospectively. Validated, self-administered quality-of-life (QoL) questionnaires were completed at baseline, 3, 6 and 12 months and yearly thereafter. Urinary function and erectile dysfunction were assessed using AUA Symptom Score and the UCLA Prostate Cancer Index and analysis of variance (anova)/chi-square tests were used to compare clinical, BL, biochemical recurrence (BCR) and QoL outcomes amongst the three groups for continuous/categorical variables. RESULTS: The mean estimated BL was 742.7 (45 to 3500) mL and 5.4% and 3.8% received an autologous (AU) or allogeneic (AL) blood transfusions, respectively. The average baseline, induction, postoperative and discharge Hct was 43.8%, 48.3%, 35.7% and 34.1%, respectively. The estimated BL and the rate of change of Hct correlated moderately (r=0.41, P<0.0001). Tertiles of BL were based on the difference between induction and discharge Hct (Delta 1) and the average Delta 1 for Groups 1, 2 and 3 were 7.9%, 12.7% and 17.2%, respectively. Intra-operative, early/delayed complications, length of hospital stay (LoS), SM surgical margins status, anastomotic stricture and BCR were not statistically different (P<0.001) and the mean AUASS, UCLA Prostate Cancer urinary bother scores, urinary function scores, sexual bother/function scores at 24 months were similar amongst all tertiles (P>0.05). CONCLUSIONS: BL during ORRP does not adversely impact clinical and functional outcomes irrespective of how BL is defined. Thus, the lower BL associated with robotic-assisted laparoscopic prostatectomy (RALP) in and of itself would not be expected to improve functional or oncological outcomes.

Clinical evaluation of a novel method for the measurement of prostate-specific antigen, AccuPSA(TM) , as a predictor of 5-year biochemical recurrence-free survival after radical prostatectomy: results of a pilot study.

Study Type - Diagnostic (validating cohort) Level of Evidence 1b What's known on the subject? and What does the study add? Nadir Ultrasensitive PSA levels has some value for predicting BCR following RD. AccuPSA assays lower limit of PSA quantification of <0.01 pg/ml greatly enhances sensitivity and specificity of nadir PSA to predict BCR following RP. Our pilot study shows an AccuPSA of 3 pg/ml has a sensitory and specificity of 100% and 75% respectively for predicting 5 year BCR following RP. OBJECTIVES • To conduct a proof of concept study to evaluate a novel digital single molecule immunoassay (AccuPSA(TM) ) that detects prostate-specific antigen (PSA) a thousandfold more sensitively than current PSA detection methods. • To determine the ability of the AccuPSA(TM) assay to predict 5-year biochemical recurrence (BCR)-free survival after radical prostatectomy (RP). PATIENTS AND METHODS • A total of 31 frozen serum specimens were obtained from specimen logs maintained at New York University Langone Medical Center and the Johns Hopkins University School of Medicine on men who had undergone RP. Those men without evidence of BCR had a minimum of 5 years' PSA follow-up. • In all cases, preoperative and pathological information were available, as was a serum specimen 3-6 months after RP, with a PSA level of <0.1 ng/mL measured by conventional PSA methods at the time of serum collection. • Specimens were tested using the AccuPSA(TM) method. • A Cox proportional hazard model and Kaplan-Meier analysis were used to determine whether AccuPSA(TM) predicted the risk of BCR. RESULTS • Overall, 11/31 (35.5%) men developed BCR. • Mean AccuPSA(TM) nadir levels were significantly different (P < 0.001) between the non-BCR group (2.27 pg/mL) and the BCR group (46.99 pg/mL). • Using a multivariate Cox proportional hazard model, AccuPSA(TM) nadir level was a significant predictor of BCR-free survival (P < 0.01). • Kaplan-Meier analysis of up to 5 years follow-up showed that 100% of men with AccuPSA(TM) nadir values <3 pg/mL did not develop BCR, whereas 62.5% of men with values >3 pg/mL developed BCR (P= 0.00024). • The sensitivity, specificity, positive predictive value and negative predictive value of the AccuPSA(TM) method was 100%, 75%, 69% and 100%, respectively. CONCLUSIONS • AccuPSA(TM) assay predicts 5-year BCR- free survival after RP. • Identifying a reliable predictor of BCR soon after RP has important implications for frequency of PSA testing, selection of candidates for adjuvant therapy, and reassuring a large subset of men that they are not at risk of recurrence. • Larger studies are needed to validate these findings.

Dietary Transitions and Health Outcomes in Four Populations - Systematic Review.

IMPORTANCE: Non-communicable chronic diseases (NCDs) such as obesity, type 2 diabetes, heart disease, and cancer were rare among non-western populations with traditional diets and lifestyles. As populations transitioned toward industrialized diets and lifestyles, NCDs developed. OBJECTIVE: We performed a systematic literature review to examine the effects of diet and lifestyle transitions on NCDs. EVIDENCE REVIEW: We identified 22 populations that underwent a nutrition transition, eleven of which had sufficient data. Of these, we chose four populations with diverse geographies, diets and lifestyles who underwent a dietary and lifestyle transition and explored the relationship between dietary changes and health outcomes. We excluded populations with features overlapping with selected populations or with complicating factors such as inadequate data, subgroups, and different study methodologies over different periods. The selected populations were Yemenite Jews, Tokelauans, Tanushimaru Japanese, and Maasai. We also review transition data from seven excluded populations (Pima, Navajo, Aboriginal Australians, South African Natal Indians and Zulu speakers, Inuit, and Hadza) to assess for bias. FINDINGS: The three groups that replaced saturated fats (SFA) from animal (Yemenite Jews, Maasai) or plants (Tokelau) with refined carbohydrates had negative health outcomes (e.g., increased obesity, diabetes, heart disease). Yemenites reduced SFA consumption by >40% post-transition but men's BMI increased 19% and diabetes increased ~40-fold. Tokelauans reduced fat, dramatically reduced SFA, and increased sugar intake: obesity and diabetes rose. The Tanushimaruans transitioned to more fats and less carbohydrates and used more anti-hypertensive medications; stroke and breast cancer declined while heart disease was stable. The Maasai transitioned to lower fat, SFA and higher carbohydrates and had increased BMI and diabetes. Similar patterns were observed in the seven other populations. CONCLUSION: The nutrient category most strongly associated with negative health outcomes - especially obesity and diabetes - was sugar (increased 600-650% in Yemenite Jews and Tokelauans) and refined carbohydrates (among Maasai, total carbohydrates increased 39% in men and 362% in women), while increased calories was less strongly associated with these disorders. Across 11 populations, NCDs were associated with increased refined carbohydrates more than increased calories, reduced activity or other factors, but cannot be attributed to SFA or total fat consumption.

Interictal EEG and ECG for SUDEP Risk Assessment: A Retrospective Multicenter Cohort Study.

Objective: Sudden unexpected death in epilepsy (SUDEP) is the leading cause of epilepsy-related mortality. Although lots of effort has been made in identifying clinical risk factors for SUDEP in the literature, there are few validated methods to predict individual SUDEP risk. Prolonged postictal EEG suppression (PGES) is a potential SUDEP biomarker, but its occurrence is infrequent and requires epilepsy monitoring unit admission. We use machine learning methods to examine SUDEP risk using interictal EEG and ECG recordings from SUDEP cases and matched living epilepsy controls. Methods: This multicenter, retrospective, cohort study examined interictal EEG and ECG recordings from 30 SUDEP cases and 58 age-matched living epilepsy patient controls. We trained machine learning models with interictal EEG and ECG features to predict the retrospective SUDEP risk for each patient. We assessed cross-validated classification accuracy and the area under the receiver operating characteristic (AUC) curve. Results: The logistic regression (LR) classifier produced the overall best performance, outperforming the support vector machine (SVM), random forest (RF), and convolutional neural network (CNN). Among the 30 patients with SUDEP [14 females; mean age (SD), 31 (8.47) years] and 58 living epilepsy controls [26 females (43%); mean age (SD) 31 (8.5) years], the LR model achieved the median AUC of 0.77 [interquartile range (IQR), 0.73-0.80] in five-fold cross-validation using interictal alpha and low gamma power ratio of the EEG and heart rate variability (HRV) features extracted from the ECG. The LR model achieved the mean AUC of 0.79 in leave-one-center-out prediction. Conclusions: Our results support that machine learning-driven models may quantify SUDEP risk for epilepsy patients, future refinements in our model may help predict individualized SUDEP risk and help clinicians correlate predictive scores with the clinical data. Low-cost and noninvasive interictal biomarkers of SUDEP risk may help clinicians to identify high-risk patients and initiate preventive strategies.

Post-prostatectomy incontinence during sexual activity: a single center prevalence study.

PURPOSE: The prevalence and mechanism of incontinence during sexual activity after radical prostatectomy has not been well described. We determined the prevalence and severity of incontinence during sexual activity with time and the relationship between incontinence during sexual activity and stress urinary incontinence in the absence of sexual activity. MATERIALS AND METHODS: A total of 1,459 men with prostate cancer underwent radical prostatectomy between October 2000 and December 2007, as performed by 1 surgeon. Patients completed UCLA-PCI preoperatively, and 3, 6, 12 and 24 months postoperatively. We analyzed the frequency distribution of incontinence during sexual activity and stress urinary incontinence with time. We also examined the relationship between incontinence during sexual activity and stress urinary incontinence by chi-square analysis. RESULTS: The percent of patients who reported any bother from incontinence during sexual activity was 44.4% at 3 months, which decreased to 36.1% at 24 months. The percent of patients reporting major bother from incontinence during sexual activity was 22.4% and 12.1% at 3 and 24 months, respectively. Bother from incontinence during sexual activity and from stress urinary incontinence were strongly associated at all times (p<0.001). More than half of the men with major bother due to incontinence during sexual activity also reported bother from stress urinary incontinence. However, more than 10% of those with no stress urinary incontinence problem reported major bother from incontinence during sexual activity. CONCLUSIONS: Incontinence during sexual activity is a persistent problem for some men after radical prostatectomy. Significant incontinence during sexual activity may occur in the absence of stress urinary incontinence during nonsexual activities. Effective management of this problem requires further investigation.

The short-term use of erythropoetin-stimulating agents: impact on the biochemical recurrence of prostate cancer.

OBJECTIVE: To examine the impact of short-term preoperative utilization of erythropoietin-stimulating agents (ESAs) on biochemical recurrence (BCR)-free survival rates after open radical retropubic prostatectomy (ORRP) in light of the fact that the risk/benefit of ESAs has recently been questioned by the Food and Drug Administration (FDA) after reports showing a decreased survival. PATIENTS AND METHODS: From 2000 to 2008, 1567 patients underwent ORRP and 97.5% of these signed informed consent to participate in the New York University Prospective and Longitudinal Outcomes Study. Of the remaining 1528 patients, 1317 (86%) received preoperative ESA (group 1) and 211 (14%) did not (group 2). Patients were also classified as having low-, intermediate- or high-risk disease based on D'Amico risk categories. Kaplan-Meier survival curves and Cox's proportional hazard models were used to estimate BCR-free survival by ESA treatment. RESULTS: A significant difference was observed for BCR-free survival between the low- and intermediate/high-risk groups. There were no statistically significant differences between groups 1 and 2 for BCR-free survival in the entire study populations and within risk groups. In addition, Cox regression models showed no statistically significant differences in BCR-free survival according to preoperative ESA administration in the entire cohort as well as among the low- and intermediate/high-risk groups. CONCLUSIONS: The short-term use of ESAs as a preoperative blood management strategy for patients undergoing ORRP has no clinically relevant adverse effects on the biology of prostate cancer. The present study supports the use of these agents before the procedure in patients undergoing surgery for localized disease.