An exploration of testicular cancer survivors' experience of ejaculatory dysfunction following retroperitoneal lymph node dissection-a sub-study of the PREPARE clinical trial.

PURPOSE: Ejaculatory dysfunction secondary to retrograde ejaculation or anejaculation is a complication of retroperitoneal lymph node dissection (RPLND) for survivors of testicular cancer. We explored survivors' experiences of ejaculatory dysfunction following RPLND. METHODS: In a sub-study of a single-arm phase 2 clinical trial (ACTRN12622000537752/12622000542796), participants reporting ejaculatory dysfunction ≥ 6 months following RPLND were invited to complete semi-structured interviews. Purposive sampling was used. Interviews continued until thematic saturation occurred, and codebook thematic analysis of interviews was performed. RESULTS: Of 58 individuals recruited to the trial, 33 (57%) reported ejaculatory dysfunction. Of these, 32 (97%) agreed to interview and 15 participated. Participants interviewed had median age 34 years (range 24-66), 12 (80%) in a long-term relationship with median time from surgery 36 months (range 11-112). Three overarching themes were identified. The first reflected the value of RPLND despite ejaculatory dysfunction. The second illuminated the impact(s) of ejaculatory dysfunction closely mapped to life stage, with flow-on impacts to fertility, sex, psychological wellbeing and communication. The third reflected information needs. Fertility was a substantial source of concern for some participants. Ejaculatory dysfunction had no effect on sex for some, whilst for others, sex was less pleasurable. Some reported benefits. Few reported ejaculatory dysfunction challenged masculinity, confidence, or self-esteem. CONCLUSIONS: Future research should examine interventions to reduce distress related to fertility, challenged masculinity and body image. IMPLICATIONS FOR CANCER SURVIVORS: Whilst most participants considered ejaculatory dysfunction to have little impact on their sexual function and relationships, some reported significant difficulties varying by life stage and relationship status.

Dapansutrile ameliorated chondrocyte inflammation and osteoarthritis through suppression of MAPK signaling pathway.

INTRODUCTION: Osteoarthritis (OA) is one of the most common joint diseases in the elderly population. Proinflammatory cytokines, such as Interleukin-1ß (IL-1ß), play an important role in the development and progression of OA. Dapansutrile is a specific inhibitor of the NOD-like receptor protein 3 (NLRP3) inflammasome and exhibits anti-inflammatory properties. METHODS: In this study, we investigated the protective effect and the underlying mechanism of dapansutrile on cartilage degeneration in vitro and in vivo. In the present study, chondrocytes were isolated from rats and then were treated with dapansutrile. After that, the expression of (Cox-2, inducible nitric oxide synthase (iNOS), Mmp-3, Mmp-9, Mmp-13 and IL-10) were evaluated at RNA level, then the expression of (COX-2, MMP-3, MMP-9, MMP-13, SOX-9 and COL2) were evaluated at protein level. Subsequently, the activation of the mitogen-activated protein kinase (MAPK) pathway was tested using western blotting (WB). Additionally, the rat OA model was developed to evaluate the protective effects of dapansutrile in vivo. RESULTS: The results showed that dapansutrile had no obvious cytotoxicity on rat chondrocytes at 24 h (0, 1, 2, 5 and 10 µM). Dapansutrile significantly decreased IL-1ß-induced upregulation of COX2, iNOS, matrix metalloproteinase 3 (MMP3), 9 (MMP9) and 13 (MMP13), and reversed IL-1ß-induced the downregulation of IL-10, SOX9 and COL2. Dapansutrile also inhibited IL-1ß-induced upregulation of the MAPK signaling pathway by downregulating the expression levels of phospho-ERK, and phospho-P38 in a concentration dependent manner. In addition, dapansutrile exhibited protective effects in rat OA model with lower Mankin's score and Osteoarthritis Research Society International (OARSI) score. CONCLUSION: Our study suggested that dapansutrile effectively inhibited chondrocyte inflammation by suppressing MAPK signaling pathway in vitro, and ameliorated cartilage degeneration in vivo, indicating an anti-inflammatory effect in OA treatment.

Cellulose-Derived Supercapacitors from the Carbonisation of Filter Paper.

Advanced carbon materials are important for the next-generation of energy storage apparatus, such as electrochemical capacitors. Here, the physical and electrochemical properties of carbonised filter paper (FP) were investigated. FP is comprised of pure cellulose and is a standardised material. After carbonisation at temperatures ranging from 600 to 1700 °C, FP was contaminant-free, containing only carbon and some oxygenated species, and its primary fibre structure was retained (diameter ≈20-40 µm). The observed enhancement in conductivity of the carbonised FP was correlated with the carbonisation temperature. Electrochemical capacitance in the range of ≈1.8-117 F g(-1) was achieved, with FP carbonised at 1500 °C showing the best performance. This high capacitance was stable with >87 % retained after 3000 charge-discharge cycles. These results show that carbonised FP, without the addition of composite materials, exhibits good supercapacitance performance, which competes well with existing electrodes made of carbon-based materials. Furthermore, given the lower cost and renewable source, cellulose-based materials are the more eco-friendly option for energy storage applications.

In vitro assessment of the gastrointestinal tolerance and immunomodulatory function of Bacillus methylotrophicus isolated from a traditional Korean fermented soybean food.

AIMS: This study aimed to investigate the potential of Bacillus methylotrophicus as a probiotic. METHODS AND RESULTS: A Bacillus isolate designated strain C14 was isolated from Korean traditional fermented soybean paste (doenjang). The strain was identified, and its physiological and biochemical properties were characterized. The gastrointestinal tolerance and immunomodulatory function of strain C14 were also investigated. Strain C14 was identified as B. methylotrophicus by analysis of its biochemical properties using the API 50CHB system and by phylogenetic analysis of the 16S rDNA sequence. Strain C14 showed >80% and >75% of survival for artificial gastric juices (pH 2.5 and 1% pepsin) and 0.5% (w/v) bile salt, respectively. Heat-killed B. methylotrophicus C14 inhibited the adhesion of various pathogens and enhanced the adhesion of probiotic bacteria to Caco-2 cells. The heat-killed cells also induced high levels of immune cell proliferation compared with the control and stimulated interleukin-6 and tumour necrosis factor-α production in mouse macrophages. CONCLUSIONS: Bacillus methylotrophicus C14 could be used as a probiotic. SIGNIFICANCE AND IMPACT OF THE STUDY: Recently identified B. methylotrophicus is a new potential probiotic with high gastrointestinal tolerance.

Parathyromatosis following spontaneous rupture of a parathyroid adenoma: natural history and the challenge of management.

Parathyromatosis, the presence of small nodules of hyper-functioning parathyroid tissue scattered throughout the soft tissues of the neck and superior mediastinum, is a rare cause of persistent primary hyperparathyroidism. We report the first case of parathyromatosis secondary to spontaneous rupture of a parathyroid adenoma. Despite running an indolent course, this case highlights the potential challenges of management of parathyromatosis and the value of calcimimetic therapy as an adjunct to surgery for disease control.

Removing the need for crossmatched blood in elective EVAR.

OBJECTIVES: The unit cost for crossmatching blood is £137.22 (€158.94). A maximum surgical blood order schedule for elective EVAR does not exist. We studied the crossmatch to transfusion ratio in our series to establish this recommendation. MATERIALS AND METHODS: A single centre retrospective study of consecutive EVAR cases between October 2001 and December 2010. Blood loss, units transfused and indication for transfusion per case were analysed. RESULTS: 203 elective EVAR cases were studied. Median blood loss was 200 ml with a mean of 288 ml (range 50-8400 ml). A total of twelve patients (6%) required blood transfusion. Six cases (3%) for postoperative Hb <8 g/dL and three patients (1.5%) for medical complications. Three patients required a massive transfusion; two had peri-procedural haemorrhage and one patient developed a large groin haematoma. The crossmatch to transfusion ratio was 11.1. CONCLUSIONS: The maximum surgical blood order for elective EVAR should be a group and save (type and screen) sample because of the high crossmatch to transfusion ratio. Intraoperative transfusion is rarely required (<1%) but often necessitates large transfusion quantities. In this circumstance each hospital is required to have an emergency protocol to manage massive blood loss. Applying these principles across all surgical specialities may lead to significant financial savings, improve efficiency and reduce wastage.

Salvaging the limb salvage: management of complications following endoprosthetic reconstruction for tumours around the knee.

INTRODUCTION: Limb-salvage surgery, including endoprosthetic reconstruction after tumour resection, has become the standard management for local control of tumours around the knee. As the nature of surgery is technically complex and demanding, there is potential for significant morbidity arising from complications. This study describes our experience with complications following endoprosthetic reconstruction around the knee. METHODS: Retrospective analysis of consecutive resections and endoprosthetic reconstructions for tumours around the knee between 1996 and September 2005 performed at St Vincent's Hospital, Melbourne. RESULTS: Fifty consecutive cases were reviewed, with a median follow-up of 24.5 (range, 2-124) months. Median age was 41 (range, 13-79) years. Tumour types included 38 primary musculoskeletal malignancies, 8 metastatic tumours, 2 bony lymphomas and 2 benign lesions. There were eight deaths, nine cases of subsequent metastatic spread and no local recurrences. There were six cases of deep infection, two each of non-resolving nerve palsy, fracture and mechanical wear, and one each of symptomatic patellofemoral impingement, aseptic loosening and intraoperative popliteal artery trauma. Five patients required endoprosthetic revision, and three subsequent amputations were described. Excellent functional outcome and emotional acceptance was observed amongst patients that underwent revision. CONCLUSION: Resection and endoprosthetic reconstruction of tumours around the knee is both technically challenging and resource-intensive. It is imperative that morbidity from complications is limited through the minimisation of their incidence and the provision of optimal management. This series demonstrates that good patient outcomes can be achieved in specialist centres with experienced surgeons and adoption of a multidisciplinary approach.

Anatomy and anaesthesia of the lumbar somatic plexus.

Cadaveric dissection demonstrated the lumbar plexus to lie within the substance of psoas major, with the major branches of the lumbar plexus emerging into the psoas compartment adjacent to the L5 vertebra. Within psoas major, the lateral femoral cutaneous and femoral nerves were separated from the obturator nerve by a muscular fold in 36 of 60 plexuses. Anatomical variations were common, with the accessory obturator nerve being identified in 12 per cent of plexuses. All previously described lumbar plexus block approaches positioned the needle within close proximity to the lumbar plexus. Modifications to these approaches may increase efficacy and reduce complication rates.

Clinical decision support systems for the practice of evidence-based medicine.

BACKGROUND: The use of clinical decision support systems to facilitate the practice of evidence-based medicine promises to substantially improve health care quality. OBJECTIVE: To describe, on the basis of the proceedings of the Evidence and Decision Support track at the 2000 AMIA Spring Symposium, the research and policy challenges for capturing research and practice-based evidence in machine-interpretable repositories, and to present recommendations for accelerating the development and adoption of clinical decision support systems for evidence-based medicine. RESULTS: The recommendations fall into five broad areas--capture literature-based and practice-based evidence in machine--interpretable knowledge bases; develop maintainable technical and methodological foundations for computer-based decision support; evaluate the clinical effects and costs of clinical decision support systems and the ways clinical decision support systems affect and are affected by professional and organizational practices; identify and disseminate best practices for work flow-sensitive implementations of clinical decision support systems; and establish public policies that provide incentives for implementing clinical decision support systems to improve health care quality. CONCLUSIONS: Although the promise of clinical decision support system-facilitated evidence-based medicine is strong, substantial work remains to be done to realize the potential benefits.

Electronic trial banks: a complementary method for reporting randomized trials.

BACKGROUND: Randomized clinical trial (RCT) results are often difficult to find, interpret, or apply to clinical care. The authors propose that RCTs be reported into electronic knowledge bases-trial banks-in addition to being reported in text. What information should these trial-bank reports contain? METHODS: Using the competency decomposition method, the authors specified the ideal trial-bank contents as the information necessary and sufficient for completing the task of systematic reviewing. RESULTS: They decomposed the systematic reviewing task into four top-level tasks and 62 subtasks. 162 types of trial information were necessary and sufficient for completing these subtasks. These items relate to a trial's design, execution, administration, and results. CONCLUSION: Trial-bank publishing of these 162 items would capture into computer-understandable form all the trial information needed for critically appraising and synthesizing trial results. Decision-support systems that access shared, up-to-date trial banks could help clinicians manage, synthesize, and apply RCT evidence more effectively.

Observations on multiple sperm granulomas in the rat epididymis following vasectomy.

Seven epididymides of long-term vasectomized rats showing multiple sperm granulomas were studied in serial histological sections. Despite the presence of the multiple granulomas, only two rats showed continuity of the epididymal duct with the central sperm mass of a granuloma. A further three specimens showed breaks in the epididymal epithelium at sites of local distension in the epididymal tail. Granulomas in the epididymal body seem to receive spermatozoa only transiently. The spermatozoa at the center of granulomas in continuity with the epididymal duct showed evenly distributed sperm heads. A number of others showed clumping of spermatozoa, attributed to stagnation of flow and fluid resorption. In many granulomas, folds in the macrophage layer with a connective tissue core rich in lymphocytes and plasma cells projected into the central sperm mass. We conclude that the sperm granuloma is a dynamic structure that shows changes with age and that the sperm granuloma closest to the testis must not be assumed to be the one that is draining the spermatozoa.

Polyurethane: material for the next generation of heart valve prostheses?

OBJECTIVES: The prospects for a durable, athrombogenic, synthetic, flexible leaflet heart valve are enhanced by the recent availability of novel, biostable polyurethanes. As a forerunner to evaluation of such biostable valves, a prototype trileaflet polyurethane valve (utilising conventional material of known in vitro behaviour) was compared with mechanical and bioprosthetic valves for assessment of in vivo function, durability, thromboembolic potential and calcification. METHODS: Polyurethane (PU), ATS bileaflet mechanical, and Carpentier-Edwards porcine (CE) valves were implanted in the mitral position of growing sheep. Counting of high-intensity transient signals (HITS) in the carotid arteries, echocardiographic assessment of valve function, and examination of blood smears for platelet aggregates were undertaken during the 6-month anticoagulant-free survival period. Valve structure and hydrodynamic performance were assessed following elective sacrifice. RESULTS: Twenty-eight animals survived surgery (ten ATS; ten CE; eight PU). At 6 months the mechanical valve group (n=9) showed highest numbers of HITS (mean 40/h, P=0.01 cf. porcine valves), and platelet aggregates (mean 62.22/standard field), but no thromboembolism, and no structural or functional change. The bioprosthetic group (n=6) showed low HITS (1/h) and fewer aggregates (41.67, P=1.00, not significant), calcification and severe pannus overgrowth with progressive stenosis. The PU valves (n=8) showed a small degree of fibrin attachment to leaflet surfaces, no pannus overgrowth, little change in haemodynamic performance, low levels of HITS (5/h) and platelet aggregates (17.50, P<0.01 cf. mechanical valves, P=0.23 cf. porcine valves), and no evidence of thromboembolism. CONCLUSIONS: In the absence of valve-related death and morbidity, and retention of good haemodynamic function, the PU valve was superior to the bioprosthesis; lower HITS and aggregate counts in the PU valve imply lower thrombogenicity compared with the mechanical valve. A biostable polyurethane valve could offer clinical advantage with the promise of improved durability (cf. bioprostheses) and low thrombogenicity (cf. mechanical valves).

Platelet aggregation and high-intensity transient signals (HITS) in a sheep model of mitral valve replacement.

BACKGROUND AND AIMS OF THE STUDY: The composition of microemboli detected as high-intensity transient signals (HITS) by Doppler ultrasound in patients with prosthetic heart valves is still debated. Here, platelet aggregation and HITS were investigated in a sheep model. METHODS: Insonation of the carotid artery was performed in 20 sheep with either a mechanical or a biological mitral valve prosthesis in place. The effect of ICI 170809, a 5HT2a antagonist, on the frequency of HITS and on platelet aggregates, counted in arterial blood smears per nine high-power fields, was assessed at three and six months after valve implantation. The mitral transvalvular gradient was measured by transthoracic echocardiography at three and six months. RESULTS: Data are expressed as median and interquartile range. At three months, there were 36 (20-114) HITS/h in the mechanical group, and 0 (0-15) HITS/h in the biological group. At six months, there were 21 (0-82) and 0 (0-2) HITS/h, respectively. The occurrence of HITS was unaffected by either ICI 170809, or by duration of implant in either group. Platelet aggregate counts were higher with the mechanical than with the biological valve at three months, but not at six months. ICI 170809 reduced platelet aggregate counts in both valve types; the reduction was not significant in the bioprosthetic valve group. The pressure gradient across the bioprosthesis increased during the study from 2 (2-3) mmHg to 7.5 (6-10) mmHg, but was unchanged in the mechanical valve. CONCLUSIONS: (i) It was confirmed that the frequency of HITS is higher with the mechanical prosthesis than the bioprosthesis; (ii) circulating platelet aggregates in the bioprosthetic valve group tended to increase as structural valve deterioration occurred; (iii) the frequency of HITS was not influenced by either an increase or a decrease in circulating platelet aggregates; and (iv) HITS detected in patients with prosthetic valves are unlikely to be due to circulating platelet aggregates.

Quantitative overview of randomized trials of amiodarone to prevent sudden cardiac death.

BACKGROUND: Some randomized clinical trials of amiodarone therapy to prevent sudden cardiac death have had positive results and others have had negative results, but all were relatively small. This meta-analysis aimed to pool all trials to assess the effect of amiodarone on mortality and the impact of differences in patient population and study design on trial outcomes. METHODS AND RESULTS: Fifteen randomized trials were identified, and outcome measures were combined by use of a random effects model. The effect of patient population and study design on total mortality was assessed by use of a hierarchical Bayes model. Amiodarone reduced total mortality by 19% (confidence limits, 6% to 31%; P<.01), with somewhat greater reductions in cardiac mortality (23%, P<.001) and sudden death (30%, P<.001). Mortality reductions were similar in trials enrolling patients after myocardial infarction (21%), with left ventricular dysfunction (22%), and after cardiac arrest (25%). There was a trend toward greater risk reduction in trials requiring evidence of ventricular ectopy (25%) than in the remaining trials (10%). The trials using placebo controls had considerably less risk reduction (10%) than trials with active controls (27%) or usual care controls (42%, posterior odds <0.02). CONCLUSIONS: Amiodarone reduced total mortality by 10% to 19% in patients at risk of sudden cardiac death. Amiodarone reduced risk similarly in patients after myocardial infarction, with heart failure, or with clinically evident arrhythmia. The apparent inconsistencies among results of randomized trials appear to be due to small sample sizes and the type of control group used, not the type of patient enrolled.

A meta-analysis of randomized trials comparing coronary artery bypass grafting with percutaneous transluminal coronary angioplasty in multivessel coronary artery disease.

We performed a meta-analysis of randomized trials that compared percutaneous transluminal coronary angioplasty (PTCA) with coronary artery bypass graft (CABG) surgery in patients with multivessel coronary artery disease. The outcomes of death, combined death, and nonfatal myocardial infarction (MI), repeat revascularization, and freedom from angina were analyzed. The overall risk of death and nonfatal MI was not different over a follow-up of 1 to 3 years (CABG:PTCA odds ratio [OR] 1.03, 95% confidence interval 0.81 to 1.32, p = 0.81). Patients randomized to CABG tended to have a higher risk of death or MI in the early, periprocedural period (OR 1.33, p = 0.091), but a lower risk in subsequent follow-up (OR 0.74, p = 0.093). CABG patients were much less likely to undergo another revascularization procedure (p < 0.00001), and were more likely to be angina free (OR 1.57, p < 0.00001). Thus, CABG and PTCA patients have similar overall risks of death and nonfatal MI at 1 to 3 years of follow-up, but relative risk differences in mortality of up to 25% cannot be excluded. CABG patients have significantly less angina and less repeat revascularization than PTCA patients.