During meiotic recombination, homologue-templated repair of programmed DNA double-strand breaks (DSBs) produces relatively few crossovers and many difficult-to-detect non-crossovers. By intercrossing two diverged mouse subspecies over five generations and deep-sequencing 119 offspring, we detect thousands of crossover and non-crossover events genome-wide with unprecedented power and spatial resolution. We find that both crossovers and non-crossovers are strongly depleted at DSB hotspots where the DSB-positioning protein PRDM9 fails to bind to the unbroken homologous chromosome, revealing that PRDM9 also functions to promote homologue-templated repair. Our results show that complex non-crossovers are much rarer in mice than humans, consistent with complex events arising from accumulated non-programmed DNA damage. Unexpectedly, we also find that GC-biased gene conversion is restricted to non-crossover tracts containing only one mismatch. These results demonstrate that local genetic diversity profoundly alters meiotic repair pathway decisions via at least two distinct mechanisms, impacting genome evolution and Prdm9-related hybrid infertility.

Background

The prognostic meaning of an undetectable ultrasensitive prostate-specific antigen (USPSA) level after prostatectomy remains unclear.

Objective

To determine whether an undetectable USPSA level obtained after surgery is a predictor of biochemical recurrence (BCR)-free survival.

Design, setting, and participants

From the Urologic Oncology Database at the University of California San Francisco, 525 men were identified who had a USPSA measurement 1-3 mo postoperatively with at least 2 yr of follow-up. All preoperative and pathologic criteria were recorded.

Measurements

Patients were stratified based on their initial USPSA level. We defined an undetectable USPSA level at ≤0.05 ng/ml. Recurrence was defined as two consecutive prostate-specific antigen (PSA) levels ≥0.2 ng/ml or secondary treatment.

Results and limitations

We found that 456 patients (87%) had undetectable USPSA and 69 patients (13%) had detectable USPSA immediately postprostatectomy. A 5-yr recurrence-free rate of 86% was found in the undetectable USPSA group compared with 67% in the detectable USPSA group (p<0.01). For patients with pT3 disease, men with an undetectable USPSA had a 5-yr BCR-free survival rate of 78% compared with 40% for men with a detectable USPSA (p<0.01). A multivariable analysis confirmed that patients with an undetectable USPSA were 67% less likely to recur (hazard ratio: 0.33; 95% confidence interval: 0.20-0.55). As the detection level of PSA is lowered, the false-positive rate of BCR necessarily increases. A limitation of the study is its retrospective nature.

Conclusions

An undetectable USPSA after radical prostatectomy is a prognostic indicator of BCR-free survival at 5 yr and may aid in predicting outcome in higher risk patients.

Purpose

A randomized, placebo controlled clinical trial of folic acid supplementation for the chemoprevention of colorectal adenoma revealed an increased incidence of prostate cancer in the treatment group. Limited data exist on postdiagnostic folate/folic acid intake and the risk of prostate cancer progression. We prospectively examined the association between postdiagnostic folate consumption and the risk of prostate cancer recurrence after radical prostatectomy, external beam radiation therapy and brachytherapy.

Materials and methods

This study was done in 1,153 men treated with radical prostatectomy, external beam radiation therapy and brachytherapy who had clinical stage T1-T2c prostate adenocarcinoma and participated in the CaPSURE Diet and Lifestyle substudy by completing the semiquantitative Food Frequency Questionnaire in 2004 to 2005. We used Cox proportional hazards regression to analyze the association between folate intake and prostate cancer progression.

Results

Prostate cancer progressed in 101 men (8.76%) during a mean 34-month followup. After multivariate adjustment we observed no evidence of an association of the intake of total folate, dietary folate or dietary folate equivalents with prostate cancer recurrence. On secondary analysis by treatment after radical prostatectomy patients in the lowest decile of dietary folate intake had a 2.6-fold increase in the risk of recurrence (HR 2.56, 95% CI 1.23-5.29, p = 0.01). In patients treated with external beam radiation and brachytherapy we observed no evidence of an association between prostate cancer progression and increased folate intake.

Conclusions

Results suggest that the consumption of foods and multivitamins that contain folate is not associated with prostate cancer progression after definitive treatment.

Study design

Systematic review. Surgical decompression for degenerative cervical myelopathy (DCM) is associated with perioperative complications, including difficulty or discomfort with swallowing (dysphagia) as well as changes in sound production (dysphonia). This systematic review aims to (1) outline how dysphagia and dysphonia are defined in the literature and (2) assess the quality of definitions using a novel 4-point rating system.

Methods

An electronic database search was conducted for studies that reported on dysphagia, dysphonia or other related complications of DCM surgery. Data extracted included study design, surgical details, as well as definitions and rates of surgical complications. A 4-point rating scale was developed to assess the quality of definitions for each complication.

Results

Our search yielded 2,673 unique citations, 11 of which met eligibility criteria and were summarized in this review. Defined complications included odynophagia (n = 1), dysphagia (n = 11), dysphonia (n = 2), perioperative swelling complications (n = 2), and soft tissue swelling (n = 3). Rates of dysphagia varied substantially (0.0%-50.0%) depending on whether this complication was patient-reported (4.4%); patient-reported using a modified Swallowing Quality of Life questionnaire (43.1%) or the Bazaz criteria (8.8%-50.0%); or diagnosed using an extensive protocol consisting of clinical assessment, a bedside swallowing test, evaluation by a speech and language pathologist and a modified barium swallowing test/fiberoptic endoscopy (42.9%). The reported incidences of dysphonia also ranged significantly from 0.6% to 38.0%.

Conclusion

There is substantial variability in reported rates of dysphagia and dysphonia due to differences in data collection methods, diagnostic strategies, and definitions. Consolidation of nomenclature will improve evaluation of the overall safety of surgery.

Objective

To assess provider and practice characteristics that drive opioid prescription behavior using the American Urological Association census data.

Methods

Stratified weighted analysis using 1,157 census samples was performed to represent 12,660 urologists who practiced in the United States in 2018. We compared urologists according to their opioid prescription patterns to evaluate factors and motivations behind opioid use in the post-operative setting.

Results

Overall, 11,205 (88.5%) urologists prescribe opioids in the post-operative setting. The presence of procedure-specific institutional prescribing guidelines was associated with a greater tendency to prescribe ≤10 pills, and lesser tendency to prescribe 11 to 49 and ≥50 tablets following open abdominal (P = .003), laparoscopic (P < .001), scrotal (P < .001), and endoscopic surgeries (P < .001). The presence of institutional prescribing guidelines was associated with decreasing opioid prescriptions over a three-year period whereas not having guidelines was associated with an unchanged prescription practice over time. Basing current prescriptions on what was given to prior patients was reported by 85% and was more likely to result in an unchanged amount of prescriptions over time (29.2% vs 13.3%, P = .007). Motivations to avoid patient phone calls were reported by 23.8% and were more likely to increase the opioids provided within the next 3 years (3.2% vs 0.1%, P < .001).

Conclusion

Practitioners who endorsed using institutional guidelines prescribed fewer opioids following all types of surgery and were more likely to decrease their prescription behavior over time. This data supports continued efforts to provide urologists with more evidence-based guidance on best practice opioid prescribing in the future.

STUDY DESIGN: Systematic review update. OBJECTIVES: Interventions that aim to optimize spinal cord perfusion are thought to play an important role in minimizing secondary ischemic damage and improving outcomes in patients with acute traumatic spinal cord injuries (SCIs). However, exactly how to optimize spinal cord perfusion and enhance neurologic recovery remains controversial. We performed an update of a recent systematic review (Evaniew et al, J. Neurotrauma 2020) to evaluate the effects of Mean Arterial Pressure (MAP) support or Spinal Cord Perfusion Pressure (SCPP) support on neurological recovery and rates of adverse events among patients with acute traumatic SCI. METHODS: We searched PubMed/MEDLINE, EMBASE and ClinicalTrials.gov for new published reports. Two reviewers independently screened articles, extracted data, and evaluated risk of bias. We implemented the Grades of Recommendation, Assessment, Development, and Evaluation (GRADE) approach to rate confidence in the quality of the evidence. RESULTS: From 569 potentially relevant new citations since 2019, we identified 9 new studies for inclusion, which were combined with 19 studies from a prior review to give a total of 28 studies. According to low or very low quality evidence, the effect of MAP support on neurological recovery is uncertain, and increased SCPP may be associated with improved neurological recovery. Both approaches may involve risks for specific adverse events, but the importance of these adverse events to patients remains unclear. Very low quality evidence failed to yield reliable guidance about particular monitoring techniques, perfusion ranges, pharmacological agents, or durations of treatment. CONCLUSIONS: This update provides an evidence base to support the development of a new clinical practice guideline for the hemodynamic management of patients with acute traumatic SCI. While avoidance of hypotension and maintenance of spinal cord perfusion are important principles in the management of an acute SCI, the literature does not provide high quality evidence in support of a particular protocol. Further prospective, controlled research studies with objective validated outcome assessments are required to examine interventions to optimize spinal cord perfusion in this setting.

Study design

Narrative Review.

Objectives

The objective of this review is to provide a stepwise approach to the assessment of patients with potential symptoms of degenerative cervical myelopathy (DCM).

Methods

N/A.

Results

DCM is an overarching term used to describe progressive compression of the cervical spinal cord by age-related changes to the spinal axis. These alterations to normal anatomy narrow the spinal canal, reduce the space available for the spinal cord, and may ultimately compress the ascending and descending neural tracts. Patients with DCM present with a wide range of symptoms that can significantly impact quality of life, including bilateral hand numbness and paresthesia, gait impairment, motor weakness of the upper and lower extremities, and bladder and bowel dysfunction. Unfortunately, DCM is often misdiagnosed, resulting in delayed assessment and management by the appropriate specialist. The proper evaluation of a patient with suspected DCM includes obtaining a detailed patient history, conducting a comprehensive neurological examination, and ordering appropriate tests to rule in or out other diagnoses.

Conclusion

This review summarizes a stepwise approach to the diagnosis of patients with DCM.

Study design

Narrative review.

Objective

The current review aimed to describe the role of existing techniques and emerging methods of imaging and electrophysiology for the management of degenerative cervical myelopathy (DCM), a common and often progressive condition that causes spinal cord dysfunction and significant morbidity globally.

Methods

A narrative review was conducted to summarize the existing literature and highlight future directions.

Results

Anatomical magnetic resonance imaging (MRI) is well established in the literature as the key imaging tool to identify spinal cord compression, disc herniation/bulging, and inbuckling of the ligamentum flavum, thus facilitating surgical planning, while radiographs and computed tomography (CT) provide complimentary information. Electrophysiology techniques are primarily used to rule out competing diagnoses. However, signal change and measures of cord compression on conventional MRI have limited utility to characterize the degree of tissue injury, which may be helpful for diagnosis, prognostication, and repeated assessments to identify deterioration. Early translational studies of quantitative imaging and electrophysiology techniques show potential of these methods to more accurately reflect changes in spinal cord microstructure and function.

Conclusion

Currently, clinical management of DCM relies heavily on anatomical MRI, with additional contributions from radiographs, CT, and electrophysiology. Novel quantitative assessments of microstructure, perfusion, and function have the potential to transform clinical practice, but require robust validation, automation, and standardization prior to uptake.

Objective

To characterise the use of social media among members of the American Urological Association (AUA), as the use of social media in medicine has greatly expanded in recent years.

Subjects and methods

In December 2012 to January 2013, the AUA e-mailed a survey with 34 questions on social media use to 2000 randomly selected urologists and 2047 resident/fellow members. Additional data was collected from Symplur analytics on social media use surrounding the AUA Annual Meeting in May 2013.

Results

In all, 382 (9.4%) surveys were completed, indicating 74% of responders had an online social media account. The most commonly used social media platforms were Facebook (93%), followed in descending order by LinkedIn (46%), Twitter (36%) and Google+ (26%). Being aged <40 years was an important predictor of social media use (83% vs 56%), with greater uptake among residents/fellows compared with attendings (86% vs 66%). Only 28% of respondents used social media partly or entirely for professional purposes. During the 2013 AUA Annual Meeting, there were >5000 tweets from >600 distinct contributors.

Conclusion

As of early 2013, among respondents to an e-mail survey, most urologists and urology trainees used some form of social media, and its use in urology conferences has greatly expanded.