Insulin and GH Signaling in Human Skeletal Muscle In Vivo following Exogenous GH Exposure: Impact of an Oral Glucose Load

GH induces acute insulin resistance in skeletal muscle in vivo, which in rodent models has been attributed to crosstalk between GH and insulin signaling pathways. Our objective was to characterize time course changes in signaling pathways for GH and insulin in human skeletal muscle in vivo following GH exposure in the presence and absence of an oral glucose load.Eight young men were studied in a single-blinded randomized crossover design on 3 occasions: 1) after an intravenous GH bolus 2) after an intravenous GH bolus plus an oral glucose load (OGTT), and 3) after intravenous saline plus OGTT. Muscle biopsies were taken at t = 0, 30, 60, and 120. Blood was sampled at frequent intervals for assessment of GH, insulin, glucose, and free fatty acids (FFA).GH increased AUC(glucose) after an OGTT (p<0.05) without significant changes in serum insulin levels. GH induced phosphorylation of STAT5 independently of the OGTT. Conversely, the OGTT induced acute phosphorylation of the insulin signaling proteins Akt (ser(473) and thr(308)), and AS160.The combination of OGTT and GH suppressed Akt activation, whereas the downstream expression of AS160 was amplified by GH. WE CONCLUDED THE FOLLOWING: 1) A physiological GH bolus activates STAT5 signaling pathways in skeletal muscle irrespective of ambient glucose and insulin levels 2) Insulin resistance induced by GH occurs without a distinct suppression of insulin signaling proteins 3) The accentuation of the glucose-stimulated activation of AS 160 by GH does however indicate a potential crosstalk between insulin and GH.ClinicalTrials.gov NCT00477997

Effectiveness of a national quality improvement programme to improve survival after emergency abdominal surgery (EPOCH): a stepped-wedge cluster-randomised trial

Background: Emergency abdominal surgery is associated with poor patient outcomes. We studied the effectiveness of a national quality improvement (QI) programme to implement a care pathway to improve survival for these patients. Methods: We did a stepped-wedge cluster-randomised trial of patients aged 40 years or older undergoing emergency open major abdominal surgery. Eligible UK National Health Service (NHS) hospitals (those that had an emergency general surgical service, a substantial volume of emergency abdominal surgery cases, and contributed data to the National Emergency Laparotomy Audit) were organised into 15 geographical clusters and commenced the QI programme in a random order, based on a computer-generated random sequence, over an 85-week period with one geographical cluster commencing the intervention every 5 weeks from the second to the 16th time period. Patients were masked to the study group, but it was not possible to mask hospital staff or investigators. The primary outcome measure was mortality within 90 days of surgery. Analyses were done on an intention-to-treat basis. This study is registered with the ISRCTN registry, number ISRCTN80682973. Findings: Treatment took place between March 3, 2014, and Oct 19, 2015. 22 754 patients were assessed for elegibility. Of 15 873 eligible patients from 93 NHS hospitals, primary outcome data were analysed for 8482 patients in the usual care group and 7374 in the QI group. Eight patients in the usual care group and nine patients in the QI group were not included in the analysis because of missing primary outcome data. The primary outcome of 90-day mortality occurred in 1210 (16%) patients in the QI group compared with 1393 (16%) patients in the usual care group (HR 1·11, 0·96–1·28). Interpretation: No survival benefit was observed from this QI programme to implement a care pathway for patients undergoing emergency abdominal surgery. Future QI programmes should ensure that teams have both the time and resources needed to improve patient care. Funding: National Institute for Health Research Health Services and Delivery Research Programme

Effectiveness of a national quality improvement programme to improve survival after emergency abdominal surgery (EPOCH): a stepped-wedge cluster-randomised trial

BACKGROUND: Emergency abdominal surgery is associated with poor patient outcomes. We studied the effectiveness of a national quality improvement (QI) programme to implement a care pathway to improve survival for these patients. METHODS: We did a stepped-wedge cluster-randomised trial of patients aged 40 years or older undergoing emergency open major abdominal surgery. Eligible UK National Health Service (NHS) hospitals (those that had an emergency general surgical service, a substantial volume of emergency abdominal surgery cases, and contributed data to the National Emergency Laparotomy Audit) were organised into 15 geographical clusters and commenced the QI programme in a random order, based on a computer-generated random sequence, over an 85-week period with one geographical cluster commencing the intervention every 5 weeks from the second to the 16th time period. Patients were masked to the study group, but it was not possible to mask hospital staff or investigators. The primary outcome measure was mortality within 90 days of surgery. Analyses were done on an intention-to-treat basis. This study is registered with the ISRCTN registry, number ISRCTN80682973. FINDINGS: Treatment took place between March 3, 2014, and Oct 19, 2015. 22 754 patients were assessed for elegibility. Of 15 873 eligible patients from 93 NHS hospitals, primary outcome data were analysed for 8482 patients in the usual care group and 7374 in the QI group. Eight patients in the usual care group and nine patients in the QI group were not included in the analysis because of missing primary outcome data. The primary outcome of 90-day mortality occurred in 1210 (16%) patients in the QI group compared with 1393 (16%) patients in the usual care group (HR 1·11, 0·96-1·28). INTERPRETATION: No survival benefit was observed from this QI programme to implement a care pathway for patients undergoing emergency abdominal surgery. Future QI programmes should ensure that teams have both the time and resources needed to improve patient care. FUNDING: National Institute for Health Research Health Services and Delivery Research Programme

The great debate: varicocele treatment and impact on fertility

OBJECTIVE: To evaluate the current literature on the impact and potential mechanisms of varicocele repair on male fertility. DESIGN: Pertinent articles were identified through computer PubMed search on varicocele repair and male infertility. References of selected articles were hand searched for additional citations. CONCLUSIONS: Varicocele repair has been shown to reverse a spectrum of effects contributing to men with impaired fertility. Clinical studies on the intervention have illustrated variable effects on postoperative sperm parameters and pregnancy rates. Studies with conflicting results suffer from a significant number of confounding variables, such variable repair technique or lack of controls. Further studies are warranted on the role of modern microsurgical varicocelectomy given the improvements in assisted reproductive technologies

Measurement of sexual functioning after spinal cord injury: preferred instruments

BACKGROUND/OBJECTIVE: To determine the utility of certain instruments to assess sexuality and fertility after SCI, an expert panel identified key areas to study and evaluated available instruments. These were rated according to certain predefined criteria. METHODS: The authors divided sexual issues into male and female sexual function, male reproductive function, and female reproductive function. The instruments that have been used most frequently to measure these aspects of sexual function over the past 5 years were identified by expert consensus. Finally, these instruments were subjected to a critical review. RESULTS: The Female Sexual Function Index (FSFI), measurement of vaginal pulse amplitude (VPA), the International Index of Erectile Function (IIEF), and the measurement of ejaculatory function and semen quality were considered appropriate measures to assess sexual responses and reproductive function after SCI. There were no measures identified to assess female reproductive function. CONCLUSIONS: For clinical trials aiming to improve sexual function after SCI, the FSFI or the IIEF is currently preferred. Although VPA is an appropriate means to assess female sexual responses, it is only useful for laboratory studies and is too invasive for use in clinical trials. For assessment of male fertility potential, assessment of ejaculatory capacity and semen analysis are recommended

Quality of Information in YouTube Videos on Erectile Dysfunction

INTRODUCTION: Many patients seek information online including on social media. AIM: To assess the quality of information regarding erectile dysfunction (ED) in YouTube videos. METHODS: We searched "erectile dysfunction" on YouTube in October 2019 and evaluated the first 100 videos in English sorted by relevance. MAIN OUTCOME MEASURE: We recorded the user engagement, video producer, intended audience, and content. Videos containing medical information were evaluated using the Patient Education Materials Assessment Tool (PEMAT) and the DISCERN quality criteria for consumer health information. The PEMAT evaluates the understandability and actionability of materials as a percentage. The DISCERN assesses the quality of information by a scale from 1 (serious or extensive shortcomings) to 5 (minimal shortcomings). RESULTS: The median number of total views was 22,450 (range 591-20,255,133) and the median number of views/month was 654 (range 9-723,398). 42 percent of the videos were posted by professional medical institutions, and 21% were posted by individual medical professionals. Most videos were aimed at the general public or patients suffering from ED. The median PEMAT understandability and actionability scores were both 100% (range 50-100% and 33-100%, respectively). The median DISCERN score was 2 (range 1-5) with 80.4% receiving a score of ≤3. Overall, 28% of the videos contained direct misinformation. DISCERN scores were higher in videos produced by medical institutions (P = .0104), not selling specific products (P = .007) and not promoting alternative medicine (P = .0002). The number of subscribers was an independent predictor of views/month (P < .0001). CONCLUSION: Patients may be exposed to videos of poor quality when searching for information about ED on YouTube. The medical community needs to adapt a strategy to improve the quality of online medical information. Fode M, Nolsøe AB, Jacobsen FM, et al. Quality of Information in YouTube Videos on Erectile Dysfunction. J Sex Med 2020;8:408-413.status: publishe

Structured Population-based Prostate-specific Antigen Screening for Prostate Cancer: The European Association of Urology Position in 2019

Prostate cancer (PCa) is one of the first three causes of cancer mortality in Europe. Screening in asymptomatic men (aged 55-69yr) using prostate-specific antigen (PSA) is associated with a migration toward lower staged disease and a reduction in cancer-specific mortality. By 20yr after testing, around 100 men need to be screened to prevent one PCa death. While this ratio is smaller than for breast and colon cancer, the long natural history of PCa means many men die from other causes. As such, the nonselective use of PSA testing and radical treatments can lead to overdiagnosis and overtreatment. The European Association of Urology (EAU) supports measures to encourage appropriate PCa detection through PSA testing, while reducing overdiagnosis and overtreatment. These goals may be achieved using personalized risk-stratified approaches. For diagnosis, the greatest benefit from early detection is likely to come in men assessed using baseline PSA levels at the age of 45yr to individualize screening intervals. Multiparametric magnetic resonance imaging as well as risk calculators based on family history, ethnicity, digital rectal examination, and prostate volume should be considered to triage the need for biopsy, thus reducing the risk of overdiagnosis. For treatment, the EAU advocates balancing patient's life expectancy and cancer's mortality risk when deciding an approach. Active surveillance is encouraged in well-informed patients with low-risk and some intermediate-risk cancers, as it decreases the risks of overtreatment without compromising oncological outcomes. Conversely, the EAU advocates radical treatment in suitable men with more aggressive PCa. Multimodal treatment should be considered in locally advanced or high-grade cancers. PATIENT SUMMARY: Implementation of prostate-specific antigen (PSA)-based screening should be considered at a population level. Men at risk of prostate cancer should have a baseline PSA blood test (eg, at 45yr). The level of this test, combined with family history, ethnicity, and other factors, can be used to determine subsequent follow-up. Magnetic resonance imaging scans and novel biomarkers should be used to determine which men need biopsy and how any cancers should be treated.status: publishe