Prevalence of urinary tract cancer in the Spanish cohort of the IDENTIFY study.

INTRODUCTION: Malignant tumors of the urinary tract are associated with high morbidity and mortality, and their prevalence can vary worldwide. Recently, the IDENTIFY study has published results on the prevalence of urinary tract cancer at a global level. This study evaluates the prevalence of cancer within the Spanish cohort of the IDENTIFY study to determine whether the published results can be extrapolated to our population. PATIENTS AND METHODS: An analysis of the data from the Spanish cohort of patients in the IDENTIFY study was performed. This is a prospective cohort of patients referred to secondary care with suspected cancer, predominantly due to hematuria. Patients were recruited between December 2017 and December 2018. RESULTS: A total of 706 patients from 9 Spanish centers were analyzed. Of these, 277 (39.2%) were diagnosed with cancer: 259 (36.7%) bladder cancer, 10 (1.4%) upper tract urothelial carcinoma, 9 (1.2%) renal cancer and 5 (0.7%) prostate cancer. Increasing age (OR 1.05 (95% CI 1.03-1.06; P < 0.001)), visible hematuria (VH) OR 2.19 (95% CI 1.13-4.24; P = 0.02)) and smoking (ex-smokers: OR 2.11(95% CI 1.30-3.40; P = 0.002); smokers: OR 2.36 (95% CI 1.40-3.95; P = 0.001)) were associated with higher probability of bladder cancer. CONCLUSION: This study highlights the risk of bladder cancer in patients with VH and smoking habits. Bladder cancer presented the highest prevalence; higher than the prevalence reported in previous series and presented in the IDENTIFY study. Future work should evaluate other associated factors that allow us to create cancer prediction models to improve the detection of cancer in our patients.

Case of acquired haemophilia a in Southeast Asia following COVID-19 vaccine.

Acquired haemophilia A (AHA) is a rare bleeding disorder with high morbidity and mortality, but it is eminently treatable if diagnosis and treatment are prompt. We report a case of AHA in Southeast Asia following the administration of the Pfizer-BioNTech COVID-19 vaccine. A man in his 80s developed multiple bruises 2 weeks after his first dose of the COVID-19 vaccine. Diagnosis was delayed due to his cognitive impairment and low clinical suspicion. This led to a representation with worsening ecchymosis, a left thigh haematoma and symptomatic anaemia. Laboratory testing was notable for an isolated prolongation of the activated partial thromboplastin time, which remained uncorrected in the mixing test. Further testing confirmed the presence of factor VIII (FVIII) inhibitors and low FVIII titres of 6.7%. He responded to treatment with intravenous methylprednisolone and recombinant activated FVII. Screening for autoimmune diseases and malignancies was negative.

Effects of transplantation-related immunosuppression on co-existent neuroendocrine tumours.

BACKGROUND: Here we detail our experience of managing patients found to have a neuroendocrine neoplasm (NEN) whilst on immunosuppression for a transplanted organ. AIM: We aimed to quantify the behaviour of NENs under solid-organ transplant-related immunosuppression. DESIGN: This was an observational, retrospective case series. METHODS: Ten patients were identified from a prospectively kept database. Three were excluded. RESULTS: Four patients received a liver, two a kidney, and one a heart transplant. All but one received calcineurin-based immunosuppression. NENs were found in five patients post-transplant: one had surgery for transverse colonic neuroendocrine carcinoma NEC (pT4N1M0, Ki67 60%), was cancer-free after four years; one had cold biopsy of duodenal NEN (pT1N0M0, Ki67 2%), cancer-free at four months; one 7 mm pancreatic NEN (pT1N0M0), untreated and stable for seven years; one small-bowel NEN with mesenteric metastasis (pTxNxM1), alive four years after diagnosis; and one untreated small-bowel NEN with mesenteric metastasis, stable at 1 year after liver transplantation. Two NENs were discovered pre-transplant, one pancreatic NEN (pT1N0M0, Ki67 5%), remains untreated and stable at three years. One gastric NEN (type 3, pT1bN0M0, Ki67 2%) remains stable without treatment for two years. CONCLUSIONS: NENs demonstrate indolent behaviour in the presence of transplant-related immunosuppression.

Posterior Reversible Encephalopathy in Undiagnosed Systemic Lupus Erythematosus: A Rare Case Report.

Systemic lupus erythematosus (SLE) is a multisystem autoimmune disorder known to affect the nervous system by direct neuronal damage, vasculitis, or pathologic mechanisms indirectly induced by immune mechanisms related to the production and deposition of immune complexes. SLE has a wide range of clinical manifestations due to the involvement of almost every organ system of the body. SLE presents with serositis, mucositis, arthralgia, glomerulopathy, hematological, cutaneous, and hematological manifestations. Among the neurological manifestations of SLE, posterior reversible encephalopathy is rarely described in the literature. We report a case of posterior reversible encephalopathy in a female patient who presented with seizures, altered mentation, headache, and blurry vision in the setting of undiagnosed SLE.

Well-differentiated gastroenteropancreatic G3 NET: findings from a large single centre cohort.

Neuroendocrine neoplasms are known to have heterogeneous biological behavior. G3 neuroendocrine tumours (NET G3) are characterized by well-differentiated morphology and Ki67 > 20%. The prognosis of this disease is understood to be intermediate between NET G2 and neuroendocrine carcinoma (NEC). Clinical management of NET G3 is challenging due to limited data to inform treatment strategies. We describe clinical characteristics, treatment, and outcomes in a large single centre cohort of patients with gastroenteropancreatic NET G3. Data was reviewed from 26 cases managed at Queen Elizabeth Hospital, Birmingham, UK, from 2012 to 2019. Most commonly the site of the primary tumour was unknown and majority of cases with identifiable primaries originated in the GI tract. Majority of cases demonstrated somatostatin receptor avidity. Median Ki67 was 30%, and most cases had stage IV disease at diagnosis. Treatment options included surgery, somatostatin analogs (SSA), and chemotherapy with either platinum-based or temozolomide-based regimens. Estimated progression free survival was 4 months following initiation of SSA and 3 months following initiation of chemotherapy. Disease control was observed following treatment in 5/11 patients treated with chemotherapy. Estimated median survival was 19 months; estimated 1 year survival was 60% and estimated 2 year survival was 13%. NET G3 is a heterogeneous group of tumours and patients which commonly have advanced disease at presentation. Prognosis is typically poor, though select cases may respond to treatment with SSA and/or chemotherapy. Further study is needed to compare efficacy of different treatment strategies for this disease.

Stem Cell Therapies for Ischemic Stroke: A Systematic Review.

Stroke is one of the leading causes of death and disability worldwide. It is associated with a high economic burden, causing an increasing demand for highly effective, curative, and long-lasting therapies. Stem cells are unique human cells that have the capacity for developing into specialized cell types with the potential for facilitating regeneration and repair of damaged tissues. Therefore, many preclinical studies have shown the feasibility, safety, and efficacy of stem cell-based therapies; however, the evidence is still inadequate for their therapeutic use in humans. We employed a systematic approach to search published data from 2000 to 2020 on five main databases: PubMed, PubMed Central, Google Scholar, ScienceDirect, and Medline. Two research registries were also searched: the Cochrane Registry and clinicaltrial.gov. Data was collected after applying inclusion and exclusion criteria and studies were appraised critically. Both Medical Subject Headings (MeSH) and regular keyword search strategies were employed. The findings of this study are in line with previously reported studies in which stem cell-based therapies were found to be relatively safe, feasible, and effective.

Intraprostatic Cancer Recurrence following Radical Radiotherapy on Transperineal Template Mapping Biopsy: Implications for Focal Ablative Salvage Therapy.

PURPOSE: Men in whom external beam radiotherapy fails are usually placed on delayed hormone therapy. Some of these men have localized recurrence that might be suitable for further local therapy. We describe patterns of recurrence and suitability for focal ablative therapy in those undergoing transperineal template prostate mapping biopsies. MATERIALS AND METHODS: The study included 145 consecutive patients (December 2007 to May 2014) referred with suspicion of recurrence due to rising prostate specific antigen after external beam radiotherapy or brachytherapy who underwent transperineal template prostate mapping biopsies. Suitability for focal ablative therapy required the cancer to be unifocal or unilateral, or bilateral/multifocal with 1 dominant index lesion and secondary lesions with Gleason score 3+3=6 with no more than 3 mm cancer core involvement. RESULTS: Mean patient age was 70.7 (SD 5.8) years. Median prostate specific antigen at time of transperineal template prostate mapping biopsy was 4.5 ng/ml (IQR 2.5-7.7). Overall 75.9% (110) were suitable for a form of focal salvage treatment, 40.7% (59) were suitable for quadrant ablation, 14.5% (21) hemiablation, 14.5% (21) bilateral focal ablation and 6.2% (9) for index lesion ablation. CONCLUSIONS: Three-quarters of patients who have localized radiorecurrent prostate cancer may be suitable for focal ablative therapy to the prostate based on transperineal template prostate mapping biopsies.

Performance characteristics of optical coherence tomography in assessment of Barrett's esophagus and esophageal cancer: systematic review.

Optical coherence tomography (OCT) can generate high-resolution images of the esophagus that allows cross-sectional visualization of esophageal wall layers. We conducted a systematic review to assess the utility of OCT for diagnosing of esophageal intestinal metaplasia (IM; Barrett's esophagus BE)), dysplasia, cancer and staging of early esophageal cancer. English language human observational studies and clinical trials published in PubMed and Embase were included if they assessed any of the following: (i) in-vivo features and accuracy of OCT at diagnosing esophageal IM, sub-squamous intestinal metaplasia (SSIM), dysplasia, or cancer, and (ii) accuracy of OCT in staging esophageal cancer. Twenty-one of the 2,068 retrieved citations met inclusion criteria. In the two prospective studies that assessed accuracy of OCT at identifying IM, sensitivity was 81%-97%, and specificity was 57%-92%. In the two prospective studies that assessed accuracy of OCT at identifying dysplasia and early cancer, sensitivity was 68%-83%, and specificity was 75%-82%. Observational studies described significant variability in the ability of OCT to accurately identify SSIM. Two prospective studies that compared the accuracy of OCT at staging early squamous cell carcinoma to histologic resection specimens reported accuracy of >90%. Risk of bias and applicability concerns was rated as low among the prospective studies using the QUADAS-2 questionnaire. OCT may identify intestinal metaplasia and dysplasia, but its accuracy may not meet recommended thresholds to replace 4-quadrant biopsies in clinical practice. OCT may be more accurate than EUS at staging early esophageal cancer, but randomized trials and cost-effective analyses are lacking.

Validation of MASCC Score for Risk Stratification in Patients of Hematological Disorders with Febrile Neutropenia.

OBJECTIVES: The purpose of this study is to evaluate the association of MASCC score (Multinational Association for Supportive Care in Cancer Score) in patients with febrile neutropenia (as resultant treatment of hematological disorders) for risk assessment of morbidity and mortality. PATIENTS AND METHODS: Patients presenting with Febrile Neutropenia from November 2011 till December 2013 were enrolled in the study. Initially all patients were hospitalized and their MASCC score was calculated, however those with high risk stayed in hospital till full ANC recovery while low risk group was discharged earlier and keenly followed as out-patient while being on prophylactic oral antibiotics. The MASCC risk-index score was calculated and patients with risk score >21 were regarded as low-risk while <21 were labeled as high-risk. RESULTS: On the basis of 226 febrile neutropenia patient 132(58.4 %) were categorized as low risk while 94(41.5 %) as high risk patients according to MASCC risk index score. In low risk group 123(93 %) had uncomplicated infection while 9(7 %) had complicated infections. There was no mortality documented in low risk group while eight patients died in high risk group. CONCLUSION: In this study we correctly predicted outcome of 123(93 %) low risk group patients. The study had positive predictive value of 93 % with both sensitivity and specificity of 65 and 75 % respectively. The MASCC risk score is a valuable tool in determining the outcome in patients with febrile neutropenia.

Role of palliative resection of the primary tumour in advanced pancreatic and small intestinal neuroendocrine tumours: A systematic review and meta-analysis.

PURPOSE: This study aimed to evaluate the impact on overall survival following palliative surgery to remove the primary lesion in unresectable metastatic small intestinal (SI-NET) and pancreatic neuroendocrine tumours (P-NET). METHODS: A systematic review of the literature and meta-analysis was performed. MEDLINE and Embase databases were searched to identify articles comparing patients undergoing palliative primary tumour resection without metastatectomy vs. no resection. Relevant articles were identified in accordance with PRISMA guidelines. The primary outcome was overall survival. Included studies were evaluated for heterogeneity and publication bias. RESULTS: 13 studies met the inclusion criteria, of which 6 presented data suitable for meta-analysis. No randomised controlled trials were identified. Analysis of pooled multivariate hazard ratios demonstrated significantly longer overall survival in patients undergoing resection of both P-NETs (HR 0.43; 95% CI: 0.34-0.57, p < 0.001) and SI-NETs (HR 0.47; 95% CI: 0.35-0.55, p = 0.007). The increase in median survival in patients treated surgically relative to non-surgically ranged from 14 to 46 months in P-NET, and 22-112 months in SI-NET. The number needed to treat in order that one additional patient was alive at five years, ranged from 3.0 to 4.2, and 1.7 to 7.7 respectively. CONCLUSIONS: Meta-analysis demonstrates that palliative resection of primary SI-NETs and P-NETs in the setting of unresectable metastatic disease can increase survival. Although these results should be interpreted with caution due to potential selection and publication bias, the data supports consideration of surgery, particularly in patients with low tumour burdens and good functional status.

A multi-centre cohort study evaluating the role of inflammatory markers in patient's presenting with acute ureteric colic (MIMIC).

BACKGROUND: Spontaneous Stone Passage (SSP) rates in acute ureteric colic range from 47 to 75%. There is conflicting evidence on the role of raised inflammatory markers in acute ureteric colic. The use of an easily applicable biomarker that could predict SSP or need for intervention would improve the management of obstructing ureteric stones. Thus, there is a need to determine in an appropriately powered study, in patients who are initially managed conservatively, which factors at the time of acute admission can predict subsequent patient outcome such as SSP and the need for intervention. Particularly, establishing whether levels of white cell count (WBC) at presentation are associated with likelihood of SSP or intervention may guide clinicians on the management of these patients' stones. DESIGN: Multi-center cohort study disseminated via the UK British Urology Researchers in Surgical Training (BURST) and Australian Young Urology Researchers Organisation (YURO). PRIMARY RESEARCH QUESTION: What is the association between WBC and SSP in patients discharged from emergency department after initial conservative management? PATIENT POPULATION: Patients who have presented with acute renal colic with CT KUB evidence of a solitary ureteric stone. A minimum sample size of 720 patients across 15 centres will be needed. HYPOTHESIS: A raised WBC is associated with decreased odds of spontaneous stone passage. PRIMARY OUTCOME: The occurrence of SSP within six months of presentation with acute ureteric colic (YES/NO). SSP was defined as absence of need for intervention to assist stone passage. STATISTICAL ANALYSIS PLAN: A multivariable logistic regression model will be constructed, where the outcome of interest is SSP using data from patients who do not undergo intervention at presentation. A random effect will be used to account for clustering of patients within hospitals/institutions. The model will include adjustments for gender, age as control variables.

Beam distortion due to gold fiducial markers during salvage high-intensity focused ultrasound in the prostate.

PURPOSE: High intensity focused ultrasound (HIFU) provides a non-invasive salvage treatment option for patients with recurrence after external beam radiation therapy (EBRT). As part of EBRT the prostate is frequently implanted with permanent fiducial markers. To date, the impact of these markers on subsequent HIFU treatment is unknown. The objective of this work was to systematically investigate, using computational simulations, how these fiducial markers affect the delivery of HIFU treatment. METHODS: A series of simulations was performed modelling the propagation of ultrasound pressure waves in the prostate with a single spherical or cylindrical gold marker at different positions and orientations. For each marker configuration, a set of metrics (spatial-peak temporal-average intensity, focus shift, focal volume) was evaluated to quantify the distortion introduced at the focus. An analytical model was also developed describing the marker effect on the intensity at the focus. The model was used to examine the marker's impact in a clinical setting through case studies. RESULTS: The simulations show that the presence of the marker in the pre-focal region causes reflections which induce a decrease in the focal intensity and focal volume, and a shift of the maximum pressure point away from the transducer's focus. These effects depend on the shape and orientation of the marker and become more pronounced as its distance from the transducer's focus decreases, with the distortion introduced by the marker greatly increasing when placed within 5 mm of the focus. The analytical model approximates the marker's effect and can be used as an alternative method to the computationally intensive and time consuming simulations for quickly estimating the intensity at the focus. A retrospective review of a small patient cohort selected for focal HIFU after failed EBRT indicates that the presence of the marker may affect HIFU treatment delivery. CONCLUSIONS: The distortion introduced by the marker to the HIFU beam when positioned close to the focus may result in an undertreated region beyond the marker due to less energy arriving at the focus, and an overtreated region due to reflections. Further work is necessary to investigate whether the results presented here justify the revision of the patient selection criteria or the markers' placement protocol.

Limonene in exhaled breath is elevated in hepatic encephalopathy.

Breath samples were taken from 31 patients with liver disease and 30 controls in a clinical setting and proton transfer reaction quadrupole mass spectrometry (PTR-Quad-MS) used to measure the concentration of volatile organic compounds (VOCs). All patients had cirrhosis of various etiologies, with some also suffering from hepatocellular cancer (HCC) and/or hepatic encephalopathy (HE). Breath limonene was higher in patients with No-HCC than with HCC, median (lower/upper quartile) 14.2 (7.2/60.1) versus 3.6 (2.0/13.7) and 1.5 (1.1/2.3) nmol mol-1 in controls. This may reflect disease severity, as those with No-HCC had significantly higher UKELD (United Kingdom model for End stage Liver Disease) scores. Patients with HE were categorized as having HE symptoms presently, having a history but no current symptoms and having neither history nor current symptoms. Breath limonene in these groups was median (lower/upper quartile) 46.0 (14.0/103), 4.2 (2.6/6.4) and 7.2 (2.0/19.1) nmol mol-1, respectively. The higher concentration of limonene in those with current symptoms of HE than with a history but no current symptoms cannot be explained by disease severity as their UKELD scores were not significantly different. Longitudinal data from two patients admitted to hospital with HE show a large intra-subject variation in breath limonene, median (range) 18 (10-44) and 42 (32-58) nmol mol-1.

Prostate cancer recurrence after Focal Therapy: Treatment options.

Focal therapy is a novel treatment option in localised prostate cancer with or without a visible lesion on MRI. Treatment for low to intermediate risk prostate cancer with focal therapy has demonstrated good short to medium term outcomes with fewer undesirable genitourinary side effects. This has made focal therapy more appealing to men who find the implications of radical treatment unacceptable or are unable to tolerate active surveillance. In this paper we review the literature for treatment options in prostate cancer recurrence post focal therapy. We also cover the different definitions of failure agreed upon in previous consensus meetings, as well as their implications on future management focal therapy patients.

PSA nadir as a predictive factor for biochemical disease-free survival and overall survival following whole-gland salvage HIFU following radiotherapy failure.

BACKGROUND: Treatment options for radio-recurrent prostate cancer are either androgen-deprivation therapy or salvage prostatectomy. Whole-gland high-intensity focussed ultrasound (HIFU) might have a role in this setting. METHODS: An independent HIFU registry collated consecutive cases of HIFU. Between 2005 and 2012, we identified 50 men who underwent whole-gland HIFU following histological confirmation of localised disease following prior external beam radiotherapy (2005-2012). No upper threshold was applied for risk category, PSA or Gleason grade either at presentation or at the time of failure. Progression was defined as a composite with biochemical failure (Phoenix criteria (PSA>nadir+2 ng ml(-1))), start of systemic therapies or metastases. RESULTS: Median age (interquartile range (IQR)), pretreatment PSA (IQR) and Gleason score (range) were 68 years (64-72), 5.9 ng ml(-1) (2.2-11.3) and 7 (6-9), respectively. Median follow-up was 64 months (49-84). In all, 24/50 (48%) avoided androgen-deprivation therapies. Also, a total of 28/50 (56%) achieved a PSA nadir <0.5 ng ml(-1), 15/50 (30%) had a nadir ⩾0.5 ng ml(-1) and 7/50 (14%) did not nadir (PSA non-responders). Actuarial 1, 3 and 5-year progression-free survival (PFS) was 72, 40 and 31%, respectively. Actuarial 1, 3 and 5-year overall survival (OS) was 100, 94 and 87%, respectively. When comparing patients with PSA nadir <0.5 ng ml(-1), nadir ⩾0.5 and non-responders, a statistically significant difference in PFS was seen (P<0.0001). Three-year PFS in each group was 57, 20 and 0%, respectively. Five-year OS was 96, 100 and 38%, respectively. Early in the learning curve, between 2005 and 2007, 3/50 (6%) developed a fistula. Intervention for bladder outlet obstruction was needed in 27/50 (54%). Patient-reported outcome measure questionnaires showed incontinence (any pad-use) as 8/26 (31%). CONCLUSIONS: In our series of high-risk patients, in whom 30-50% may have micro-metastases, disease control rates were promising in PSA responders, however, with significant morbidity. Additionally, post-HIFU PSA nadir appears to be an important predictor for both progression and survival. Further research on focal salvage ablation in order to reduce toxicity while retaining disease control rates is required.

Role of magnetic resonance imaging in the early diagnosis of paratesticular rhabdomyosarcoma.

INTRODUCTION: Paratesticular lesions are common, and one subgroup is paratesticular rhabdomyosarcoma. The latter is a relatively uncommon (but aggressive) tumour that affects children and adolescents predominantly. Ultrasound is the first-line investigation, but can be inconclusive. Magnetic resonance imaging (MRI) can provide useful information, but its role in the diagnosis of rhabdomyosarcoma is not clear. CASE HISTORY: We report a 17-year-old male who presented with a one-month history of a rapidly enlarging, non-tender, lump in the right testicle. Urgent ultrasound of the scrotum revealed a heterogenous paratesticular mass that was hypervascular and showed calcification in the right inguinal area. MRI of the pelvis showed a solid, enhancing lesion of dimension located superior to the upper pole of the right testes and a slightly heterogeneous T2 signal, but was homogenous post-contrast. The patient underwent right radical orchidectomy, and histology results were assessed. He received chemotherapy and is being followed up. CONCLUSIONS: Improvements in imaging in addition to early surgical intervention and chemotherapy treatment are crucial to improve survival chances against rhabdomyosarcoma. Ultrasound findings for benign diseases may mimic those seen in rhabdomyosarcoma. In such cases of diagnostic uncertainty, our surgical team suggest MRI to reduce the risk of a delayed diagnosis and time to treatment.

Development and internal validation of a multivariable prediction model for biochemical failure after whole-gland salvage iodine-125 prostate brachytherapy for recurrent prostate cancer.

BACKGROUND: Localized recurrent prostate cancer after primary radiotherapy can be curatively treated using salvage iodine-125 ((125)I) brachytherapy. Selection is hampered by a lack of predictive factors for cancer control. This study aims to develop and internally validate a prognostic model for biochemical failure (BF) after salvage (125)I brachytherapy. METHODS AND MATERIALS: Whole-gland salvage (125)I brachytherapy patients were treated between 1993 and 2010 in two radiotherapy centers in the Netherlands. Multivariable Cox regression was performed to assess the predictive value of clinical parameters related to BF (Phoenix-definition [prostate-specific antigen [PSA]-nadir + 2.0 ng/mL]). Missing data were handled by multiple imputation. The model's discriminatory ability was assessed with Harrell's C-statistic. Internal validation was performed using bootstrap resampling (2000 data sets). Goodness-of-fit was evaluated with calibration plots. All analyses were performed using the recently published TRIPOD (Transparent reporting of a multivariable prediction model for individual prognosis or diagnosis) statement. RESULTS: After median followup of 74 months (range 5-138), 43 of a total 62 patients developed BF. In multivariable analysis, disease-free survival interval (DFSI) after primary therapy and pre-salvage prostate-specific antigen doubling time (PSADT) were predictors of BF: corrected hazard ratio (HR) 0.99 (95% confidence interval 0.97-0.999; p = 0.04) and 0.94 (95% confidence interval 0.89-0.99; p = 0.03), both for a 1-month increase (optimism-adjusted C-statistic 0.70). Calibration was accurate up to 36 months. Of patients with PSADT >30 months and DFSI >60 months, 36-month biochemical disease-free survival was >75%. Every 12-month increase in DFSI will allow 3-month decrease in PSADT while maintaining the same biochemical recurrence-free rates. CONCLUSIONS: We have presented results from a cohort of patients undergoing salvage (125)I-brachytherapy. Our data show that better selection of patients is possible with the DFSI and PSADT.

Effect of Valvular Surgery in Carcinoid Heart Disease: An Observational Cohort Study.

CONTEXT: Carcinoid heart disease (NET-CHD) is associated with the development of symptom-limited exercise capacity and high rates of morbidity and mortality. OBJECTIVE: This study sought to determine the survival, cardiac function, and functional class following surgery. DESIGN AND SETTING, AND PATIENTS: This was a retrospective observational cohort study between 2005 and 2015 at a European Centre of Excellence for Neuroendocrine Tumours, Queen Elizabeth Hospital Birmingham. England consisting of 62 consecutive patients referred to the NET-Cardiology Service. INTERVENTIONS: Subjects were assessed at referral using transthoracic echocardiography (with saline contrast) and transesophageal echocardiography, and 77% with confirmed NET-CHD underwent cardiovascular magnetic resonance imaging. Symptomatic patients with concomitant severe valvular dysfunction were referred for surgery with stable NET disease. MAIN OUTCOME MEASURE: Survival of patients with proven NET-CHD following medical and surgical treatments was measure. RESULTS: In total, 47/62 patients were diagnosed with NET-CHD. Thirty-two patients (68%) underwent surgery with bioprosthetic valve replacements in all subjects; tricuspid, n = 31; pulmonary, n = 30; mitral, n = 3; and aortic, n = 3. Four patients underwent concomitant coronary artery bypass grafting. There were 4 (13%) early post-operative deaths. One- and 2-y survival rates after surgery were 75 and 69% compared with 45 and 15% in un-operated patients. Post-operatively, functional class was improved (pre-New York Heart Association Classification [NYHA], 2.6 [0.5] vs post-NYHA, 1.7 [1.1]), P < .05, right-ventricular (RV) size was reduced (136 ml/m(2) [25] vs 71 ml/m(2) [7]; P < .01) with preserved RV ejection fraction (61% ± 9 vs 55% ± 10; P = .26). CONCLUSION: Valve surgery improved functional class and resulted in RV reverse remodelling with improved survival rates at 2 y compared with those not proceeding to operation. These data highlight the importance of close collaboration between NET clinicians, cardiology, and cardiothoracic surgery teams. Early referral can improve functional capacity but more research is needed to define the selection of appropriate candidates and randomized data are needed to define the effect of surgery on prognosis.

Examining the potential clinical value of curcumin in the prevention and diagnosis of Alzheimer's disease.

Curcumin derived from turmeric is well documented for its anti-carcinogenic, antioxidant and anti-inflammatory properties. Recent studies show that curcumin also possesses neuroprotective and cognitive-enhancing properties that may help delay or prevent neurodegenerative diseases, including Alzheimer's disease (AD). Currently, clinical diagnosis of AD is onerous, and it is primarily based on the exclusion of other causes of dementia. In addition, phase III clinical trials of potential treatments have mostly failed, leaving disease-modifying interventions elusive. AD can be characterised neuropathologically by the deposition of extracellular ß amyloid (Aß) plaques and intracellular accumulation of tau-containing neurofibrillary tangles. Disruptions in Aß metabolism/clearance contribute to AD pathogenesis. In vitro studies have shown that Aß metabolism is altered by curcumin, and animal studies report that curcumin may influence brain function and the development of dementia, because of its antioxidant and anti-inflammatory properties, as well as its ability to influence Aß metabolism. However, clinical studies of curcumin have revealed limited effects to date, most likely because of curcumin's relatively low solubility and bioavailability, and because of selection of cohorts with diagnosed AD, in whom there is already major neuropathology. However, the fresh approach of targeting early AD pathology (by treating healthy, pre-clinical and mild cognitive impairment-stage cohorts) combined with new curcumin formulations that increase bioavailability is renewing optimism concerning curcumin-based therapy. The aim of this paper is to review the current evidence supporting an association between curcumin and modulation of AD pathology, including in vitro and in vivo studies. We also review the use of curcumin in emerging retinal imaging technology, as a fluorochrome for AD diagnostics.

Effect of Addition of Multiwalled Carbon Nanotubes on the Piezoelectric Properties of Polypropylene Filaments.

The effect of addition of multiwalled carbon nanotubes (CNTs) on the piezoelectric properties of polypropylene (PP) monofilaments has been investigated. Various amounts of CNTs (0%, 0.01%, 0.1% and 1% weight ratios) were melt-blended with PP and the resulting nanocomposites were extruded in a continuous process with simultaneous on-line poling to produce monofilaments. Concurrent stretching at a draw ratio of 5:1 and polarisation at applied electric fields of 15 kV of PP/CNT filaments was observed to enhance the piezoelectric properties. The microstructure and crystallinity of the filaments was analysed using scanning electron microscopy (SEM), differential scanning calorimetric (DSC) and Fourier transform infrared spectroscopy (FTIR) techniques. Voltage generation by the CNT-modified PP filaments was determined by the application of predetermined load impact. The results show that the incorporation of CNTs in the PP fibre structure has a considerable impact on the enhancement of piezoelectric properties of the PP filament obtained that the peak voltage generation was almost four fold (from 0.76 V to 2.92 V) when 0.1 wt% of CNTs added into the polymer. This is owing to the fact that carbon nanotubes act as nucleating agent for enhancing the crystallisation during the melt extrusion process.