Why does diabetic retinopathy happen, and how can we stop it?

Diabetic retinopathy (DR) is a complication of diabetes. We can prevent DR both by preventing diabetes (primary prevention) and by improving the management of diabetes to slow down the onset, and reduce the severity, of DR (secondary prevention)

Diabetic macular oedema: the role of steroids and VEGF

Despite advances in controlling diabetes, diabetic macular oedema remains the leading cause of blind registration in the working population in England and Wales. The only proven effective treatment for diabetic macular oedema is laser photocoagulation. However this treatment has limited benefits since it reduces the chance of moderate visual loss by approximately 50% and is unlikely to improve visual acuity. Intravitreal steroids have been used in the treatment for diabetic macular oedema. Initial pilot studies suggest it can decrease retinal thickening and increase visual acuity in the long-term. Vascular endothelial growth factor is thought to play a critical role during the pathogenesis of diabetic macular oedema. The mechanism of action of both steroids and vascular endothelial growth factor on permeability has still to be fully elucidated. The aims of this thesis were to establish a reliable model of retinal microvascular endothelial cells and to characterise cellular changes following exposure to corticosteroids or vascular endothelial growth factor. Separate clinical work was aimed at evaluating the benefits of steroid treatment alone or combined with pars plana vitrectomy as a treatment of diabetic macular oedema. We also aimed to identify any prognostic indicators for treatment by both examining the morphological features of diabetic macular oedema observed on optical coherence tomography and by assaying the vascular endothelial growth factor concentration in the ocular fluids of eyes with diabetic macular oedema. Our results show that our retinal and brain microvascular endothelial cells were morphologically very similar; in particular with respect to the spatial localization of junctional proteins. Vascular endothelial growth factor led to an increase in the permeability and a decrease in the staining of the junctional proteins. By using signal transduction inhibitors, we showed that vascular endothelial growth factor-induced permeability and vascular endothelial growth factor-induced zonula occludens-1 loss occurred via different pathways suggesting that zonula occludens-1 loss was unlikely to be the downstream effector of vascular endothelial growth factor-induced permeability. Hydrocortisone leads to a decrease in permeability and an increase in the junctional expression of a number of tight junctional proteins. Both hydrocortisone and triamcinolone were able to inhibit vascular endothelial growth factor but not lysophosphatidic acid induced permeability suggesting that steroids are able to counteract the effects of certain but all vasoactive compounds. Overall our results suggested that steroids and VEGF lead to opposing effects on microvascular endothelial cells. Our randomized controlled trial showed that intravitreal triamcinolone was no more beneficial than laser photocoagulation for persistent diabetic macular oedema. A retrospective analysis of the morphological characteristics observed on Optical coherence tomography did not provide any characteristic that was prognostic of the outcome of intervention. Additionally, an exploratory case series of pars plana vitrectomy with 4 mg intravitreal triamcinolone was unable to show that combined treatment was of benefit in the long-term. Lastly the intraocular concentration of vascular endothelial growth factor was not predictive of the outcome of treatment

A pilot study to measure dynamic elasticity of the bladder during urodynamics

AIMS: Previous studies using isolated strips of human detrusor muscle identified adjustable preload tension, a novel mechanism that acutely regulates detrusor wall tension. The purpose of this investigation was to develop a method to identify a correlate measure of adjustable preload tension during urodynamics. METHODS: Patients reporting urgency most or all of the time based on ICIq-OAB survey scores were prospectively enrolled in an extended repeat fill-and-empty urodynamics study designed to identify a correlate of adjustable preload tension which we now call dynamic elasticity. Cystometric capacity was determined during initial fill. Repeat fills to defined percentages of capacity with passive emptying (via syringe aspiration) were performed to strain soften the bladder. A complete fill with active voiding was included to determine whether human bladder exhibits reversible strain softening. RESULTS: Five patients completed the extended urodynamics study. Intravesical pressure (p(ves)) decreased with subsequent fills and was significantly lower during Fill 3 compared to Fill 1 (P=0.008), demonstrating strain softening. Active voiding after Fill 3 caused strain softening reversal, with p(ves) in Fill 4 returning to the baseline measured during Fill 1 (P=0.29). Dynamic elasticity, the urodynamic correlate of adjustable preload tension, was calculated as the amount of strain softening (or its reversal) per %capacity (average p(ves) between fills/%capacity). Dynamic elasticity was lost via repeat passive filling and emptying (strain softening) and regained after active voiding regulated the process (strain softening reversal). CONCLUSIONS: Improved understanding of dynamic elasticity in the human bladder could lead to both improved sub-typing and novel treatments of overactive bladder

The impact of age, gender and severity of overactive bladder wet on quality of life, productivity, treatment patterns and satisfaction

Objective: The objective of this article is to determine the impact of idiopathic overactive bladder wet (OAB wet) severity, age and gender on health-related quality of life (HRQoL), productivity, treatment patterns and treatment satisfaction. Materials and methods: A prospective, cross-sectional online survey of adults in the United Kingdom was performed to screen for self-reported symptoms of OAB wet. Respondents completed the King’s Health Questionnaire or the Incontinence Quality of Life, as well as the Euroqol 5D, and the Work Productivity and Activity Impairment Specific Health Problem questionnaire, and questions pertaining to distress, treatment and treatment satisfaction. Results: A total of 249 of 1126 respondents (22.1%) met the criteria for OAB wet. Respondents with moderate/severe OAB wet and all women experienced significantly worse HRQoL and work productivity than those with mild symptoms and all men, respectively. Among all OAB wet responders, 62.7% were receiving treatment for their condition, predominantly pads (40.2%); only 1.6% were receiving specialised treatment. Nearly one-half (44.6%) were somewhat or completely dissatisfied with their current treatment. Conclusion: In individuals with OAB wet, severity and gender negatively impact HRQoL and work productivity. A substantial proportion of OAB wet individuals were untreated, and low treatment satisfaction was reported in those receiving treatment. Treatment was generally conservative

Therapy Insight: Parenteral Estrogen treatment for Prostate Cancer—a new dawn for an old therapy

Oral estrogens were the treatment of choice for carcinoma of the prostate for over four decades, but were abandoned because of an excess of cardiovascular and thromboembolic toxicity. It is now recognized that most of this toxicity is related to the first pass portal circulation, which upregulates the hepatic metabolism of hormones, lipids and coagulation proteins. Most of this toxicity can be avoided by parenteral (intramuscular or transdermal) estrogen administration, which avoids hepatic enzyme induction. It also seems that a short-term but modest increase in cardiovascular morbidity (but not mortality) is compensated for by a long-term cardioprotective benefit, which accrues progressively as vascular remodeling develops over time. Parenteral estrogen therapy has the advantage of giving protection against the effects of andropause (similar to the female menopause), which are induced by conventional androgen suppression and include osteoporotic fracture, hot flashes, asthenia and cognitive dysfunction. In addition, parenteral estrogen therapy is significantly cheaper than contemporary endocrine therapy, with substantive economic implications for health providers

Impact of anaemia at discharge following colorectal cancer surgery

Objectives: Preoperative anaemia is common in patients with colorectal cancer and increasingly optimised prior to surgery. Comparably little attention is given to the prevalence and consequences of postoperative anaemia. We aimed to investigate the frequency and short- or long-term impact of anaemia at discharge following colorectal cancer resection. Methods: A dedicated, prospectively populated database of elective laparoscopic colorectal cancer procedures undertaken with curative intent within a fully implemented ERAS protocol was utilised. The primary endpoint was anaemia at time of discharge (haemoglobin (Hb) < 120 g/L for women and < 135 g/L for men). Patient demographics, tumour characteristics, operative details and postoperative outcomes were captured. Median follow-up was 61 months with overall survival calculated with the Kaplan-Meier log rank method and Cox proportional hazard regression based on anaemia at time of hospital discharge. Results: A total of 532 patients with median 61-month follow-up were included. 46.4% were anaemic preoperatively (cohort mean Hb 129.4 g/L ± 18.7). Median surgical blood loss was 100 mL (IQR 0–200 mL). Upon discharge, most patients were anaemic (76.6%, Hb 116.3 g/L ± 14, mean 19 g/L ± 11 below lower limit of normal, p < 0.001). 16.7% experienced postoperative complications which were associated with lower discharge Hb (112 g/L ± 12 vs. 117 g/L ± 14, p = 0.001). Patients discharged anaemic had longer hospital stays (7 [5–11] vs. 6 [5–8], p = 0.037). Anaemia at discharge was independently associated with reduced overall survival (82% vs. 70%, p = 0.018; HR 1.6 (95% CI 1.04–2.5), p = 0.034). Conclusion: Anaemia at time of discharge following elective laparoscopic colorectal cancer surgery and ERAS care is common with associated negative impacts upon short-term clinical outcomes and long-term overall survival

Operative time and outcome of enhanced recovery after surgery after laparoscopic colorectal surgery

Background and Objectives: Combining laparoscopy and enhanced recovery provides benefit to short-term outcomes after colorectal surgery. Advances in training and techniques have allowed surgeons to operate on cases that are technically challenging and associated with prolonged operative time. Laparoscopic techniques improve the outcome of enhanced recovery after colorectal surgery; however, there are no specifications on the effect of prolonged operations on the outcome. The objective was to elucidate the impact of prolonged surgery and blood loss on the outcome of enhanced recovery after surgery after laparoscopic colorectal surgery. Methods: Four-hundred patients who underwent elective colorectal resection on enhanced recovery after surgery in Yeovil District Hospital between 2002 and 2009 were retrospectively reviewed. Delayed discharge was defined as a prolonged length of stay beyond the mean in this series (≥8 days). Results: Three-hundred eighty-five patients were included. Median operative time was 180 minutes with a median blood loss of 100 mL. Conversion was not associated with a prolonged length of stay. Operative time and blood loss correlated with length of stay in a stepwise fashion. There were 2 cutoff points of operative time at 160 minutes and 300 minutes (5 hours), where risk of prolonged stay increased significantly (odds ratio [OR] = 2.02; 95% confidence interval [CI], 1.05-3.90; P= 027), and blood loss of >500 mL (OR = 3.114; 95% CI, 1.501-6.462, P =.002). Conclusions: Total operative timing impacts negatively on the outcome of enhanced recovery after laparoscopic colorectal resections with increased risk of delayed discharge seen after ~2.5 hours and 5-hour duration. © 2014 by JSLS, Journal of the Society of Laparoendoscopic Surgeons