Conjugation of bone grafts with NO-delivery dinitrosyl iron complexes promotes synergistic osteogenesis and angiogenesis in rat calvaria bone defects.

Craniofacial/jawbone deformities remain a significant clinical challenge in restoring facial/dental functions and esthetics. Despite the reported therapeutics for clinical bone tissue regeneration, the bioavailability issue of autografts and limited regeneration efficacy of xenografts/synthetic bone substitutes, however, inspire continued efforts towards functional conjugation and improvement of bioactive bone graft materials. Regarding the potential of nitric oxide (NO) in tissue engineering, herein, functional conjugation of NO-delivery dinitrosyl iron complex (DNIC) and osteoconductive bone graft materials was performed to optimize the spatiotemporal control over the delivery of NO and to activate synergistic osteogenesis and angiogenesis in rat calvaria bone defects. Among three types of biomimetic DNICs, [Fe2(µ-SCH2CH2COOH)2(NO)4] (DNIC-COOH) features a steady kinetics for cellular uptake by MC3T3-E1 osteoblast cells followed by intracellular assembly of protein-bound DNICs and release of NO. This steady kinetics for intracellular delivery of NO by DNIC-COOH rationalizes its biocompatibility and wide-spectrum cell proliferation effects on MC3T3-E1 osteoblast cells and human umbilical vein endothelial cells (HUVECs). Moreover, the bridging [SCH2CH2COOH]- thiolate ligands in DNIC-COOH facilitate its chemisorption to deproteinized bovine bone mineral (DBBM) and physisorption onto TCP (ß-tricalcium phosphate), respectively, which provides a mechanism to control the kinetics for the local release of loaded DNIC-COOH. Using rats with calvaria bone defects as an in vivo model, DNIC-DBBM/DNIC-TCP promotes the osteogenic and angiogenic activity ascribed to functional conjugation of osteoconductive bone graft materials and NO-delivery DNIC-COOH. Of importance, the therapeutic efficacy of DNIC-DBBM/DNIC-TCP on enhanced compact bone formation after treatment for 4 and 12 weeks supports the potential for clinical application to regenerative medicine.

Sustained Releasable Copper and Zinc Biogenic Ions Co-Assembled in Metal-Organic Frameworks Reinforced Bacterial Eradication and Wound Mitigation in Diabetic Mice.

The employment of metal-organic framework (MOF)-based nanomaterials has been rapidly increasing in bioapplications owing to their biocompatibility, drug degradation, tunable porosity, and intrinsic biodegradability. This evidence suggests that the multifunctional bimetallic ions can behave as remarkable candidates for infection control and wound healing. In this study, bimetallic MOFs (Zn-HKUST-1 and FolA-Zn-HKUST-1) embedded with and without folic acid were synthesized and used for tissue sealing and repairing incisional wound sites in mice models. For comparison, HKUST-1 and FolA-HKUST-1 were also synthesized. The Brunauer-Emmett-Teller (BET) surface area measured for HKUST-1, FolA-HKUST-1, Zn-HKUST-1, and FolA-Zn-HKUST-1 from N2 isotherms was found to be 1868, 1392, 1706, and 1179 m2/g, respectively. The measurements of contact angle values for Zn-HKUST-1, FolA-HKUST-1, and Zn-FolA-HKUST-1 were identified as 4.95 ± 0.8, 43.6 ± 3.4, and 60.62 ± 2.0°, respectively. For topical application in wound healing, they display a wide range of healing characteristics, including antibacterial and enhanced wound healing rates. In addition, in vitro cell migration and tubulogenic potentials were evaluated. The significant reduction in the wound gap and increased expression levels for CD31, eNOS, VEGF-A, and Ki67 were observed from immunohistological analyses to predict the angiogenesis behavior at the incision wound site. The wound healing rate was analyzed in the excisional dermal wounds of diabetic mice model in vivo. On account of antibacterial potentials and tissue-repairing characteristics of Cu2+ and Zn2+ ions, designing an innovative mixed metal ion-based biomaterial has wide applicability and is expected to modulate the growth of various gradient tissues.

Radiologically guided percutaneous aspiration and sclerotherapy of symptomatic simple renal cysts: a systematic review of outcomes.

Simple renal cysts are common benign lesions of the kidney with up to 4% of patients developing symptoms necessitating intervention including pain and haematuria. We conducted a systematic review of the literature to determine the efficacy and safety of aspiration-sclerotherapy of symptomatic simple renal cysts. A systematic review using Cochrane guidelines was conducted on published literature from 1990 to 2020. RCTs, cohort studies and case series meeting the inclusion criteria were reviewed and cumulative analysis of outcomes was performed. A total of 4071 patients from 57 studies underwent aspiration ± sclerotherapy for their simple renal cysts. 87.7% of patients who had aspiration with sclerotherapy demonstrated 'treatment success' with a >50% reduction in cyst size and complete resolution of symptoms. 453 minor, transient complications occurred (11.2%) whilst a major complication rate of less than 0.1% (4 patients) was reported. Pooled analysis of all available current literature demonstrates that aspiration-sclerotherapy is a safe and effective first-line therapy for symptomatic simple renal cysts. Although we are unable to compare those undergoing aspiration alone to aspiration-sclerotherapy, it is evident the use of a sclerosing agent is integral to treatment success; however, the optimum agent, volume, injection frequency, and dwelling time are yet to be defined. Cyst size should be considered when discussing treatment options; however, we conclude it reasonable for aspiration-sclerotherapy to be used in the first instance in all cases of symptomatic simple renal cysts. Furthermore, we propose definitions of treatment outcome measures in order to allow direct comparative analysis across future studies.

The "Is mpMRI Enough" or IMRIE Study: A Multicentre Evaluation of Prebiopsy Multiparametric Magnetic Resonance Imaging Compared with Biopsy.

BACKGROUND: Multiparametric magnetic resonance imaging (mpMRI) is now recommended prebiopsy in numerous healthcare regions based on the findings of high-quality studies from expert centres. Concern remains about reproducibility of mpMRI to rule out clinically significant prostate cancer (csPCa) in real-world settings. OBJECTIVE: To assess the diagnostic performance of mpMRI for csPCa in a real-world setting. DESIGN, SETTING, AND PARTICIPANTS: A multicentre, retrospective cohort study, including men referred with raised prostate-specific antigen (PSA) or an abnormal digital rectal examination who had undergone mpMRI followed by transrectal or transperineal biopsy, was conducted. Patients could be biopsy naïve or have had previous negative biopsies. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The primary definition for csPCa was International Society of Urological Pathology (ISUP) grade group (GG) ≥2 (any Gleason ≥7); the accuracy for other definitions was also evaluated. RESULTS AND LIMITATIONS: Across ten sites, 2642 men were included (January 2011-November 2018). Mean age and PSA were 65.3yr (standard deviation [SD] 7.8yr) and 7.5ng/ml (SD 3.3ng/ml), respectively. Of the patients, 35.9% had "negative MRI" (scores 1-2); 51.9% underwent transrectal biopsy and 48.1% had transperineal biopsy, with 43.4% diagnosed with csPCa overall. The sensitivity and negative predictive value (NPV) for ISUP GG≥2 were 87.3% and 87.5%, respectively. The NPVs were 87.4% and 88.1% for men undergoing transrectal and transperineal biopsy, respectively. Specificity and positive predictive value of MRI were 49.8% and 49.2%, respectively. The sensitivity and NPV increased to 96.6% and 90.6%, respectively, when a PSA density threshold of 0.15ng/ml/ml was used in MRI scores 1-2; these metrics increased to 97.5% and 91.2%, respectively, for PSA density 0.12ng/ml/ml. ISUP GG≥3 (Gleason ≥4+3) was found in 2.4% (15/617) of men with MRI scores 1-2. They key limitations of this study are the heterogeneity and retrospective nature of the data. CONCLUSIONS: Multiparametric MRI when used in real-world settings is able to rule out csPCa accurately, suggesting that about one-third of men might avoid an immediate biopsy. Men should be counselled about the risk of missing some significant cancers. PATIENT SUMMARY: Multiparametric magnetic resonance imaging (MRI) is a useful tool for ruling out prostate cancer, especially when combined with prostate-specific antigen density (PSAD). Previous results published from specialist centres can be reproduced at smaller institutions. However, patients and their clinicians must be aware that an early diagnosis of clinically significant prostate cancer could be missed in nearly 10% of patients by relying on MRI and PSAD alone.

Melanotan-induced priapism: a hard-earned tan.

Melanocortin analogues, such as melanotan, are illegally used for artificial tanning. They have also been suggested as possible therapeutic agents in the treatment of erectile dysfunction. This case study presents a patient attending the accident and emergency department, in a tertiary urology centre, with acute priapism after abdominal subcutaneous injection of melanotan. The priapism was diagnosed as 'low-flow' and managed with cavernosal aspiration, irrigation and subsequent intracavernosal injection of phenylephrine. The patient avoided requiring surgical shunting but had not yet recovered erectile function at 4-week follow-up. Acute priapism is an unreported side effect of melanocortin analogue use and this case report presents a patient managed without surgical intervention. Future therapeutic application of these agents will need to take this potential life altering complication into consideration.

What Is the Role of α-Blockers for Medical Expulsive Therapy? Results From a Meta-analysis of 60 Randomized Trials and Over 9500 Patients.

Use of α-blockers for medical expulsive therapy (MET) has been the subject of huge debate in urology. Moreover, there have been a number of randomized controlled trials with differing results. We conducted a systematic review and meta-analysis of randomized controlled trials investigating the efficacy of α-blockers for MET. This review confirms there is a role for α-blockers in MET for ureteric stones specifically in stones >5 mm and distal ureteric stones, which is associated with improved stone expulsion. However, there is a slight increase in risk of nonsignificant side effects.

Malignant ureteric obstruction decompression: how much gain for how much pain? A narrative review.

Over the last thirty years, the management of Malignant Ureteric Obstruction (MUO) has evolved from a single disciplinary decision to a multi-disciplinary approach. Careful consideration must be given to the risks and benefits of decompression of hydronephrosis for an individual patient. There is a lack of consensus of opinion as well as strong evidence to support the decision process. Outcomes that were identified amongst patients undergoing treatment for MUO included prognosis, quality of life (QOL), complications, morbidity and prognostication tools. A total of 63 papers were included. Median survival was 6.4 months in the 53 papers that stated this outcome. Significant predictors to poor outcomes included low serum albumin, hyponatremia, the number of malignancy related events, and performance status of 2 or worse on the European cooperative cancer group. We propose a multi-centre review of outcomes to enable evidence-based consultations for patients and their families.

Natural History of Conservatively Managed Ureteral Stones: Analysis of 6600 Patients.

INTRODUCTION: Ureteral colic has a lifetime prevalence of 10%-15% and is one of the most common emergency urologic presentations. Current European Association of Urology recommends conservative management for "small" (<6 mm) ureteral stones if active removal is not indicated. It is important to understand the natural history of ureteral stone disease to help counsel patients with regard to their likelihood of stone passage and anticipated time frame with which they could be safely observed. We aimed to conduct a systematic review to better establish the natural history of stone expulsion. METHODOLOGY: Literature search was performed using Cochrane and PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-analyses) guidelines. Outcome measures were patient and stone demographics, expulsion rates, expulsion times, and side effect of the medication. A cumulative analysis, with subgroup analysis, was performed on stone location and size. The results were depicted as percentages and an intention-to-treat basis was used. RESULTS: The literature search identified 70 studies and a total of 6642 patients, with a median age of 46 and range of 18-74 years. Overall, 64% of patients successfully passed their stones spontaneously. About 49% of upper ureteral stones, 58% of midureteral stones, and 68% of distal ureteral stones passed spontaneously. Almost 75% of stones <5 mm and 62% of stones ≥5 mm passed spontaneously. The average time to stone expulsion was about 17 days (range 6-29 days). Nearly 5% of participants required rehospitalization due to a deterioration of their condition and only about 1% of patients experienced side effects from analgesia provided. CONCLUSION: We believe this current review is the largest study for the evaluation of natural history of ureteral stones. The evidence suggests that ureteral stones will pass without intervention in 64% of patients, however, this varies from nearly 50%-75% depending on the size and location, in the span of 1-4 weeks.

Medical expulsive therapy for ureteric stones: Analysing the evidence from systematic reviews and meta-analysis of powered double-blinded randomised controlled trials.

OBJECTIVE: To conduct a systematic review and meta-analysis investigating the efficacy and safety of medical expulsive therapy (MET) in low risk of bias (RoB) randomised controlled trials (RCTs). METHODS: A Cochrane style systematic review was conducted on published literature from 1990 to 2016, to include low RoB and a power calculation. A pooled meta-analysis was conducted. RESULTS: The MET group included 1387 vs 1381 patients in the control group. The analysis reveals α-blockers increased stone expulsion rates (78% vs 74%) (P < 0.001), whilst calcium channel blockers (CCBs) had no effect compared to controls (79% vs 75%) (P = 0.38). In the subgroup analysis, α-blockers had a shorter time to stone expulsion vs the control group (P < 0.001). There were no significant differences in expulsion rates between the treatment groups and control group for stones <5 mm in size (P = 0.48), proximal or mid-ureteric stones (P = 0.63 and P = 0.22, respectively). However, α-blockers increased stone expulsion in stones >5 mm (P = 0.02), as well as distal ureteric stones (P < 0.001). The α-blocker group developed more side-effects (6.6% of patients; P < 0.001). The numbers needed to treat for α-blockers was one in 14, for stones >5 mm one in eight, and for distal stones one in 10. CONCLUSION: The primary findings show a small overall benefit for α-blockers as MET for ureteric stones but no benefit with CCBs. α-blockers show a greater benefit for large (>5 mm) ureteric stones and those located in the distal ureter, but no benefit for smaller or more proximal stones. α-blockers are associated with a greater risk of side-effects compared to placebo or CCBs.

Laparoscopic vs robotic nephroureterectomy: Is it time to re-establish the standard? Evidence from a systematic review.

OBJECTIVE: To conduct a systematic review of comparative studies of laparoscopic nephroureterectomy (LNU), the standard management for upper urothelial tumours, and robot-assisted NU (RANU) that has emerged as a viable alternative. METHODS: MEDLINE, EMBASE and the Cochrane Library were searched according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines to identify all studies reporting on both LNU and RANU for upper urothelial tract tumours. RESULTS: In all, 1630 patients were included, of which 838 underwent LNU and 792 RANU. Three studies reported on mean operative time and found it to be less in LNU, with two reporting this to be significant (RANU 298 vs LNU 251 min, P = 0.03; 306 vs 234 min, respectively, P < 0.001). Both studies reporting on median node count found this to be higher in the robotic groups: RANU 5.5 vs LNU 1.0 and RANU 21 vs LNU 11. Positive surgical margins (RANU 1.69% vs LNU 7.06%, P = 0.18), bladder recurrence (24.6% vs 36.89%, P = 0.09), and distant metastases (27.50% vs 17.50%, P = 0.29) were not significantly different between the two techniques. Disease-specific mortality did not differ between the two techniques (RANU 7.5% vs LNU 12.5%, P = 0.46), but postoperative mortality was reduced in RANU (0.14% vs 1.32%, P = 0.03). Overall complication rates were statistically lower in RANU, at 12.5% vs 18.8% (P < 0.001). CONCLUSIONS: This review suggests these techniques are equivalent in terms of perioperative and oncological performance. Furthermore, there may be a lower overall complication rate, as well as postoperative mortality in the robotic group. Further research in the form of a randomised controlled trial is warranted.

Ureteroscopy in Patients with Bleeding Diatheses, Anticoagulated, and on Anti-Platelet Agents: A Systematic Review and Meta-Analysis of the Literature.

INTRODUCTION: Ureteroscopy (URS) is the most common surgical treatment of urolithiasis and can be problematic in patients with a bleeding diathesis. The intent of this review is to systematically review the literature to assess the safety and efficacy of ureteroscopic procedures in these groups of patients. METHODS: The systematic review was performed according to the Cochrane diagnostic accuracy review guidelines. The search strategy was conducted to perform a comprehensive database search (1990-2017). A cumulative analysis was done and where applicable a comparative analysis between bleeding diathesis patients and those without. RESULTS: Eight studies included were all published between 1998 and 2016 with the total number of participants with bleeding diatheses being 1109 with an age range of 18-97. Overall stone-free rate across the studies was 90.8% vs 86.2% in the control group. There was no significant difference in complications between the bleeding diathesis group and control group (N = 12,757, p = 0.07, 95% confidence interval [CI] 0.92, 6.02, I2 = 78%). Pooled analysis for bleeding-related complications shows a statistically significant difference favoring the control arm (N = 12,757, p ≤ 0.0001, 95% CI 1.81, 5.73, I2 = 0%). Pooled analysis for thrombosis shows no statistically significant difference between the bleeding diathesis group and the control arm (N = 118, p = 0.67, 95% CI 0.23, 9.86, I2 = 48%). CONCLUSION: The use of URS with or without the holmium laser is a safe and efficient modality for treating patients with urolithiasis who also have a bleeding diathesis or are anticoagulated or on antiplatelet agents. However, this review would suggest that the increased risk of procedure related bleeding is not insignificant and a patient-centered approach should be taken with regards to continuing these agents or not correcting bleeding diatheses.

Contemporary outcomes and prediction of adherent perinephric fat at partial nephrectomy: a systematic review.

OBJECTIVE: Current guidelines recommend partial nephrectomy for the management of T1a tumours. Adherent perinephric fat (APF) has been recognized as a complicating feature of such surgery. The objective of this article was to present a systematic review of the published literature investigating APF aetiology, risk factors and outcomes. MATERIALS AND METHODS: To identify relevant studies, the PubMed, MEDLINE, Web of Science and Google Scholar databases were searched from 1990 to 2017. RESULTS: Eight studies studying APF were identified. The aetiology of APF appears to be multifactorial, but is thought to be associated with a systemic, chronic inflammatory state secondary to metabolic syndrome. Several risk factors have been identified. Clinically, APF is more prevalent in ageing and male populations, particularly those with high body mass index and waist measurements. Radiological risk factors for APF include increased perinephric fat thickness and stranding, which can be combined to produce the Mayo Adhesive Probability (MAP) score, a predictive index that has been validated in small, external cohorts. The presence of APF at partial nephrectomy is associated with increased operative time and estimated blood loss. However, there is no documented increase in warm ischaemia time or perioperative complications in patients with APF. CONCLUSIONS: More studies are required to identify outcomes and risk factors for APF. Early identification of patients with APF can allow surgeons to guide preoperative planning and patient assessment.

Analgesia for patients undergoing shockwave lithotripsy for urinary stones – a systematic review and meta-analysis

ABSTRACT Background Shock wave lithotripsy (SWL) is the first line treatment modality for a significant proportion of patients with upper urinary tracts stones. Simple analgesics, opioids and non-steroidal anti-inflammatory drugs (NSAIDs) are all suitable agents but the relative efficacy and tolerability of these agents is uncertain. Objectives To determine the efficacy of the different types of analgesics used for the control of pain during SWL for urinary stones. Materials and Methods We searched the Cochrane Renal Group’s Specialised Register, MEDLINE, EMBASE and also hand-searched reference lists of relevant articles (Figure-1). Randomised controlled trials (RCT’s) comparing the use of any opioid, simple analgesic or NSAID during SWL were included. These were compared with themselves, each-other or placebo. We included any route or form of administration (bolus, PCA). We excluded agents that were used for their sedative qualities. Data were extracted and assessed for quality independently by three reviewers. Meta-analyses have been performed where possible. When not possible, descriptive analyses of variables were performed. Dichotomous outcomes are reported as relative risk (RR) and measurements on continuous scales are reported as weighted mean differences (WMD) with 95% confidence intervals. Results Overall, we included 9 RCTs (539 participants from 6 countries). Trial agents included 7 types of NSAIDs, 1 simple analgesic and 4 types of opioids. There were no significant differences in clinical efficacy or tolerability between a simple analgesic (paracetamol) and an NSAID (lornoxicam). When comparing the same simple analgesic with an opioid (tramadol), both agents provided safe and effective analgesia for the purpose of SWL with no significant differences. There were no significant differences in pain scores between NSAIDs or opioids in three studies. Adequate analgesia could be achieved more often for opioids than for NSAIDs (RR 0.358; 95% CI 043 to 0.77, P=0.0002) but consumed doses of rescue analgesia were similar between NSAIDs and opioids in two studies (P=0.58, >0.05). In terms of tolerability, there is no difference in post-operative nausea and vomiting (PONV) between the groups (RR 0.72, 95% CI 0.24 to 2.17, P=0.55). One study compared outcomes between two types of NSAIDs (diclofenac versus dexketoprofen). There were no significant differences in any of our pre-defined outcomes measures. Conclusion Simple analgesics, NSAIDs and opioids can all reduce the pain associated with shock wave lithotripsy to a level where the procedure is tolerated. Whilst there are no compelling differences in safety or efficacy of simple analgesics and NSAIDs, analgesia is described as adequate more often for opioids than NSAIDs.

Medical Expulsive Therapy: Is It Time to SUSPEND Judgement?

Medical expulsive therapy (MET) has been a matter of debate for many years. A number of randomised controlled trials (RCTs) and meta-analyses have been conducted, but outcomes have been varied. This makes it challenging to determine the benefit of using MET as an adjunct in patients with expectantly managed ureteric stones. This article aimed to summarize both the historic and the more contemporary literature in this area by focusing on published meta-analyses and recent RCTs. Studies of interest were those comparing either an α-blocker or a calcium channel blocker with a control. Outcome measures of interest were expulsion rates, expulsion times, and medication-related side effects. All systematic reviews included are in favour of MET versus controls. However, many of the component RCTs had limitations such as a high risk of bias, incomplete blinding and heterogeneous inclusion criteria. A recent well-powered RCT found no benefit of MET for the purpose of conservatively managed ureteric stones. This study had some limitations that stimulated further research in the area, adding to the uncertainty. The most recent RCT and meta-analysis indicates MET is more beneficial in both larger (>5 mm) and distal stones. Uncertainty remains in this arena, and there is a need for a robust multi-institution study to assess MET in a cohort of patients who are expectantly managed with ureteric stones. This should serve to counter the marked heterogeneity and limitations of existing trials and meta-analyses.

Analgesia for patients undergoing shockwave lithotripsy for urinary stones - a systematic review and meta-analysis.

BACKGROUND: Shock wave lithotripsy (SWL) is the first line treatment modality for a significant proportion of patients with upper urinary tracts stones. Simple analgesics, opioids and non-steroidal anti-inflammatory drugs (NSAIDs) are all suitable agents but the relative efficacy and tolerability of these agents is uncertain. OBJECTIVES: To determine the efficacy of the different types of analgesics used for the control of pain during SWL for urinary stones. MATERIALS AND METHODS: We searched the Cochrane Renal Group's Specialised Register, MEDLINE, EMBASE and also hand-searched reference lists of relevant articles (Figure-1). Randomised controlled trials (RCT's) comparing the use of any opioid, simple analgesic or NSAID during SWL were included. These were compared with themselves, each-other or placebo. We included any route or form of administration (bolus, PCA). We excluded agents that were used for their sedative qualities. Data were extracted and assessed for quality independently by three reviewers. Meta-analyses have been performed where possible. When not possible, descriptive analyses of variables were performed. Dichotomous outcomes are reported as relative risk (RR) and measurements on continuous scales are reported as weighted mean differences (WMD) with 95% confidence intervals. RESULTS: Overall, we included 9 RCTs (539 participants from 6 countries). Trial agents included 7 types of NSAIDs, 1 simple analgesic and 4 types of opioids. There were no significant differences in clinical efficacy or tolerability between a simple analgesic (paracetamol) and an NSAID (lornoxicam). When comparing the same simple analgesic with an opioid (tramadol), both agents provided safe and effective analgesia for the purpose of SWL with no significant differences. There were no significant differences in pain scores between NSAIDs or opioids in three studies. Adequate analgesia could be achieved more often for opioids than for NSAIDs (RR 0.358; 95% CI 043 to 0.77, P=0.0002) but consumed doses of rescue analgesia were similar between NSAIDs and opioids in two studies (P=0.58, >0.05). In terms of tolerability, there is no difference in post-operative nausea and vomiting (PONV) between the groups (RR 0.72, 95% CI 0.24 to 2.17, P=0.55). One study compared outcomes between two types of NSAIDs (diclofenac versus dexketoprofen). There were no significant differences in any of our pre-defined outcomes measures. CONCLUSION: Simple analgesics, NSAIDs and opioids can all reduce the pain associated with shock wave lithotripsy to a level where the procedure is tolerated. Whilst there are no compelling differences in safety or efficacy of simple analgesics and NSAIDs, analgesia is described as adequate more often for opioids than NSAIDs.

Penile Fracture: A Meta-Analysis.

OBJECTIVES: To review the causes and management of penile fracture and to compare between surgical and conservative management as well as immediate and delayed interventions in terms of overall and specific complications. METHODS: A search of all reported literature was conducted for all articles reporting on the management and outcomes of penile fractures. Full texts of relevant articles were obtained and screened according to the inclusion criteria. Outcomes measures were numbers of patients receiving surgical or conservative management, aetiology of fracture, length of admission, complications as well as the specifics of diagnostic approaches and operative management. Data was collated and where possible meta-analysed using Revman software. RESULTS: A total of 58 relevant studies involving 3,213 patients demonstrated that intercourse accounts for only 48% of cases with masturbation and forced flexion accounting for 39%. Meta-analysis shows that surgical intervention was associated with significantly fewer complications vs. conservative management (p < 0.000001). Surgical intervention results in significantly less erectile dysfunction (ED), curvature and painful erection than conservative management. There was no significant difference in the number of patients developing plaques/nodules (p = 0.94). Meta-analysis shows that overall early surgery is preferable to delayed surgery but that rates of ED are not significantly different. DISCUSSION: Early surgical intervention is associated with significantly fewer complications than conservative management or delayed surgery. The combined outcome of rapid diagnosis by history and clinical examination and swift surgical intervention is key for reconstruction with minimal long-term complications.

Laparoscopic nephrectomy - Pfannenstiel or expanded port site specimen extraction: a systematic review and meta-analysis.

INTRODUCTION: To anaylse the current evidence regarding the safety, feasibility and advantages of intact specimen extraction via various extraction sites after conventional laparoscopic nephrectomy (LN). MATERIAL AND METHODS: A comprehensive literature search was performed identifying studies evaluating outcomes from Pfannenstiel (PFN) versus extended port site (EPS) extraction sites, after conventional laparoscopic nephrectomy/nephroureterectomy (LRN/LNU) and donor nephrectomy (LDN). Outcome measures included procedure duration, incision length, duration of inpatient stay, analgesic requirements, complications and warm ischemia time (for donor nephrectomy cases). RESULTS: This systematic review of five comparative studies found no significant difference in morbidity, wound length, wound complications or opioid consumption across all studies. Inpatient stay (p = 0.03) and estimated blood loss (p = 0.03) were significantly less in favour of a PFN extraction site. When comparing radical nephrectomy cases alone, the PFN group had a shorter procedure time (NS), less estimated blood loss (p = 0.04), shorter inpatient stay (p <0.05), significantly less morphine use (p <0.006) and fewer wound complications. CONCLUSIONS: This review demonstrates the viability of retrieving a nephrectomy specimen/graft through a PFN incision in relation to the benefits of cosmesis and reduced pain. As reported in several trials, morbidity is not significantly increased and key outcome measures, such as duration of inpatient stay, pain scores, complications, analgesic requirements and time taken to return to normal activities, remain non-inferior. This study is limited by the small number of generally low quality studies available for analysis. Further well-constructed randomised controlled trials are needed to shed more light on this subject area.

Intracranial metastasis of adenocarcinoma of the prostate presenting with symptoms of spinal cord compression.

Spinal cord compression is a not uncommon complication of metastatic prostate cancer. Intracranial metastasis of prostatic adenocarcinoma is however unusual. We report a case of a 67-year-old man with metastatic prostate carcinoma, who presented with a 3-day history of lower limb weakness and collapse. Neurological assessment demonstrated increased tone and reduced power in both legs. As he had typical signs and symptoms of spinal cord compression, an MRI of the spine was performed; this demonstrated no evidence of cord compression. A subsequent CT of the brain demonstrated an extensive parafalcine metastasis. This revealed an extensive enhancing mass extending bilaterally along almost the entire length of the falx cerebri, measuring up to 3 cm in width and associated with marked white matter oedema in the adjacent brain bilaterally. Unfortunately, this man succumbed to his illness a few days later. The imaging findings are presented and highlight the importance of brain imaging in patients presenting with suspected cord compression due to prostatic metastatic disease when MR of the spine shows no evidence of cord compression.

Complete renal artery embolization in a comorbid patient with an arteriovenous malformation.

Renal arteriovenous malformations are uncommon and are rarely a cause for presentation. However, they can occasionally pose life-threatening problems. We present a case of an elderly female who underwent a complete left renal artery embolization, following a difficult presentation complicated by advanced dementia and multiple comorbidities. This is the first documented case of complete renal artery embolisation used to treat a renal AVM.

Managing patient pathways to achieve lung cancer waiting time targets: mixed methods study.

OBJECTIVES: England's National Health Service (NHS) introduced a 62-day target, from referral to treatment, to make lung cancer patient pathways more efficient. This study aims to understand pathway delays that lead to breaches of the target when patients need care in both secondary and tertiary setting, so more than one institution is involved. DESIGN: Mixed methods cross case analysis. SETTING: Two tertiary referral hospitals in London. PARTICIPANTS: Database records of 53 patients were analysed. Nineteen sets of patient notes were used for pathway mapping. Seventeen doctors, four nurses, eight managers and administrators were interviewed. MAIN OUTCOME MEASURES: Qualitative methods include pathway mapping and semi-structured interviews. Quantitative analysis of patient pathway times from cancer services records. RESULTS: The majority of the patient pathway (68.4%) is spent in secondary centres. There is more variability in the processes of secondary centres but tertiary centres do not have perfect processes either. Three themes emerged from discussions: information flows, pathway performance and the role of the multidisciplinary approach. CONCLUSIONS: The actions of secondary centres have a greater influence on whether a patient breaches the 62-day target, compared with tertiary centres. Nevertheless variability exists in both, with potential for improvement.