Low grade papillary transitional cell carcinoma pelvic recurrence masquerading as high grade invasive carcinoma, ten years after radical cystectomy

BACKGROUND: Tumor recurrence following radical cystectomy for a low-grade superficial transitional cell carcinoma (TCC) is exceedingly uncommon and has not been reported previously. CASE PRESENTATION: We describe a case of a young male presenting with anorexia, weight loss and a large, painful locally destructive pelvic recurrence, ten years after radical cystoprostatectomy. The pathology was consistent with a low-grade urothelial carcinoma. After an unsuccessful treatment with cisplatin-based chemotherapy, the patient underwent a curative intent hemipelvectomy with complete excision of tumor and is disease free at one year follow-up. CONCLUSION: A literature review related to this unusual presentation is reported and a surgical solutions over chemotherapy and radiotherapy is proposed

A Phase II Basket Trial of Dual Anti-CTLA-4 and Anti-PD-1 Blockade in Rare Tumors (DART SWOG 1609) in Patients with Nonpancreatic Neuroendocrine Tumors.

PurposeImmune checkpoint blockade has improved outcomes across tumor types; little is known about the efficacy of these agents in rare tumors. We report the results of the (nonpancreatic) neuroendocrine neoplasm cohort of SWOG S1609 dual anti-CTLA-4 and anti-PD-1 blockade in rare tumors (DART).Patients and methodsWe performed a prospective, open-label, multicenter phase II clinical trial of ipilimumab plus nivolumab across multiple rare tumor cohorts, with the (nonpancreatic) neuroendocrine cohort reported here. Response assessment by grade was not prespecified. The primary endpoint was overall response rate [ORR; RECIST v1.1; complete response (CR) and partial response (PR)]; secondary endpoints included progression-free survival (PFS), overall survival (OS), stable disease >6 months, and toxicity.ResultsThirty-two eligible patients received therapy; 18 (56%) had high-grade disease. Most common primary sites were gastrointestinal (47%; N = 15) and lung (19%; N = 6). The overall ORR was 25% [95% confidence interval (CI) 13-64%; CR, 3%, N = 1; PR, 22%, N = 7]. Patients with high-grade neuroendocrine carcinoma had an ORR of 44% (8/18 patients) versus 0% in low/intermediate grade tumors (0/14 patients; P = 0.004). The 6-month PFS was 31% (95% CI, 19%-52%); median OS was 11 months (95% CI, 6-∞). The most common toxicities were hypothyroidism (31%), fatigue (28%), and nausea (28%), with alanine aminotransferase elevation (9%) as the most common grade 3/4 immune-related adverse event, and no grade 5 events.ConclusionsIpilimumab plus nivolumab demonstrated a 44% ORR in patients with nonpancreatic high-grade neuroendocrine carcinoma, with 0% ORR in low/intermediate grade disease

Significant Role of the Cardiopostural Interaction in Blood Pressure Regulation During Standing

Cardiovascular and postural control systems have been studied independently despite the increasing evidence showing the importance of cardio-postural interaction in blood pressure regulation. In this study, we aimed to assess the role of cardio-postural interaction in relation to cardiac baroreflex in blood pressure regulation under orthostatic stress before and after mild exercise. Physiological variables representing cardiovascular control (heart rate and systolic blood pressure), lower limb muscle activation (electromyography), and postural sway (center of pressure derived from force and moment data during sway) were measured from 17 healthy participants (25±2 years; 8 females) during a sit-to stand test before and after sub-maximal exercise. The cardio-postural control (characterized by baroreflex-mediated muscle-pump effect in response to blood pressure changes, i.e., muscle-pump baroreflex) was assessed using wavelet transform coherence and causality analyses in relation to the baroreflex control of heart rate. Significant cardio-postural blood pressure control was evident counting for almost half of the interaction time with blood pressure changes that observed in the cardiac baroreflex (36.6-72.5% pre-exercise and 34.7-53.9% post-exercise). Thus, cardio-postural input to blood pressure regulation should be considered when investigating orthostatic intolerance. A reduction of both cardiac and muscle-pump baroreflexes in blood pressure regulation was observed post-exercise and was likely due to the absence of excessive venous pooling and a less stressed system after mild exercise. With further studies using more effective protocols evoking venous pooling and muscle-pump activity, the cardio-postural interaction could improve our understanding of the autonomic control system and ultimately lead to a more accurate diagnosis of cardio-postural dysfunctions

Holographic Duals of Quark Gluon Plasmas with Unquenched Flavors

We review the construction of gravitational solutions holographically dual to N=1 quiver gauge theories with dynamical flavor multiplets. We focus on the D3-D7 construction and consider the finite temperature, finite quark chemical potential case where there is a charged black hole in the dual solution. Discussed physical outputs of the model include its thermodynamics (with susceptibilities) and general hydrodynamic properties.Comment: Lecture presented at the Workshop "AdS/CFT and Novel Approaches to Hadron and Heavy Ion Physics", Kavli Institute of Theoretical Physics (KITPC), Beijing, China, 13 October 2010. Review article to be published in Communications in Theoretical Physics. 27 pages, 2 figure

D3-D7 Quark-Gluon Plasmas at Finite Baryon Density

We present the string dual to SU(Nc) N=4 SYM, coupled to Nf massless fundamental flavors, at finite temperature and baryon density. The solution is determined by two dimensionless parameters, both depending on the 't Hooft coupling $\lambda_h$ at the scale set by the temperature T: $\epsilon_h\sim\lambda_h Nf/Nc$, weighting the backreaction of the flavor fields and $\tilde\delta\sim\lambda_h^{-1/2}nb/(Nf T^3)$, where $nb$ is the baryon density. For small values of these two parameters the solution is given analytically up to second order. We study the thermodynamics of the system in the canonical and grand-canonical ensembles. We then analyze the energy loss of partons moving through the plasma, computing the jet quenching parameter and studying its dependence on the baryon density. Finally, we analyze certain "optical" properties of the plasma. The whole setup is generalized to non abelian strongly coupled plasmas engineered on D3-D7 systems with D3-branes placed at the tip of a generic singular Calabi-Yau cone. In all the cases, fundamental matter fields are introduced by means of homogeneously smeared D7-branes and the flavor symmetry group is thus a product of abelian factors.Comment: 27 pages; v2: 29 pages, 1 (new) figure, new section 4.4 on optical properties, references, comments added; v3: eq. (3.19), comments and a reference adde

Classifying supersymmetric solutions in 3D maximal supergravity

The work of MS was supported in part by Grant-in-Aid for Young Scientists (B) 24740159 from the Japan Society for the Promotion of Science (JSPS) 10.13039/501100001691. This work is part of the research programme of the Foundation for Fundamental Research on Matter (FOM) 10.13039/ 501100003404, which is part of the Netherlands Organization for Scientific Research (NWO).The work of MS was supported in part by Grant-in-Aid for Young Scientists (B) 24740159 from the Japan Society for the Promotion of Science (JSPS) 10.13039/501100001691. This work is part of the research programme of the Foundation for Fundamental Research on Matter (FOM) 10.13039/ 501100003404, which is part of the Netherlands Organization for Scientific Research (NWO).The work of MS was supported in part by Grant-in-Aid for Young Scientists (B) 24740159 from the Japan Society for the Promotion of Science (JSPS) 10.13039/501100001691. This work is part of the research programme of the Foundation for Fundamental Research on Matter (FOM) 10.13039/ 501100003404, which is part of the Netherlands Organization for Scientific Research (NWO

Inter-observer reproducibility of measurements of range of motion in patients with shoulder pain using a digital inclinometer

BACKGROUND: Reproducible measurements of the range of motion are an important prerequisite for the interpretation of study results. The digital inclinometer is considered to be a useful instrument because it is inexpensive and easy to use. No previous study assessed inter-observer reproducibility of range of motion measurements with a digital inclinometer by physical therapists in a large sample of patients. METHODS: Two physical therapists independently measured the passive range of motion of the glenohumeral abduction and the external rotation in 155 patients with shoulder pain. Agreement was quantified by calculation of the mean differences between the observers and the standard deviation (SD) of this difference and the limits of agreement, defined as the mean difference ± 1.96*SD of this difference. Reliability was quantified by means of the intraclass correlation coefficient (ICC). RESULTS: The limits of agreement were 0.8 ± 19.6 for glenohumeral abduction and -4.6 ± 18.8 for external rotation (affected side) and quite similar for the contralateral side and the differences between sides. The percentage agreement within 10° for these measurements were 72% and 70% respectively. The ICC ranged from 0.28 to 0.90 (0.83 and 0.90 for the affected side). CONCLUSIONS: The inter-observer agreement was found to be poor. If individual patients are assessed by two different observers, differences in range of motion of less than 20–25 degrees can not be distuinguished from measurement error. In contrast, acceptable reliability was found for the inclinometric measurements of the affected side and the differences between the sides, indicating that the inclimeter can be used in studies in which groups are compared

Insulin Resistance Is Not Conserved in Myotubes Established from Women with PCOS

Polycystic ovary syndrome (PCOS) is the most common endocrine disorder among premenopausal women, who often develop insulin resistance. We tested the hypothesis that insulin resistance in skeletal muscle of patients with polycystic ovary syndrome (PCOS) is an intrinsic defect, by investigating the metabolic characteristics and gene expression of in vitro differentiated myotubes established from well characterized PCOS subjects.Using radiotracer techniques, RT-PCR and enzyme kinetic analysis we examined myotubes established from PCOS subjects with or without pioglitazone treatment, versus healthy control subjects who had been extensively metabolically characterized in vivo. Results. Myotubes established from PCOS and matched control subjects comprehensively expressed all insulin-sensitive biomarkers; glucose uptake and oxidation, glycogen synthesis and lipid uptake. There were no significant differences between groups either at baseline or during acute insulin stimulation, although in vivo skeletal muscle was insulin resistant. In particular, we found no evidence for defects in insulin-stimulated glycogen synthase activity between groups. Myotubes established from PCOS patients with or without pioglitazone treatment also showed no significant differences between groups, neither at baseline nor during acute insulin stimulation, although in vivo pioglitazone treatment significantly improved insulin sensitivity. Consistently, the myotube cultures failed to show differences in mRNA levels of genes previously demonstrated to differ in PCOS patients with or without pioglitazone treatment (PLEK, SLC22A16, and TTBK).These results suggest that the mechanisms governing insulin resistance in skeletal muscle of PCOS patients in vivo are not primary, but rather adaptive.ClinicalTrials.gov NCT00145340

Insulin resistance, lipotoxicity, type 2 diabetes and atherosclerosis: the missing links. The Claude Bernard Lecture 2009

Insulin resistance is a hallmark of type 2 diabetes mellitus and is associated with a metabolic and cardiovascular cluster of disorders (dyslipidaemia, hypertension, obesity [especially visceral], glucose intolerance, endothelial dysfunction), each of which is an independent risk factor for cardiovascular disease (CVD). Multiple prospective studies have documented an association between insulin resistance and accelerated CVD in patients with type 2 diabetes, as well as in non-diabetic individuals. The molecular causes of insulin resistance, i.e. impaired insulin signalling through the phosphoinositol-3 kinase pathway with intact signalling through the mitogen-activated protein kinase pathway, are responsible for the impairment in insulin-stimulated glucose metabolism and contribute to the accelerated rate of CVD in type 2 diabetes patients. The current epidemic of diabetes is being driven by the obesity epidemic, which represents a state of tissue fat overload. Accumulation of toxic lipid metabolites (fatty acyl CoA, diacylglycerol, ceramide) in muscle, liver, adipocytes, beta cells and arterial tissues contributes to insulin resistance, beta cell dysfunction and accelerated atherosclerosis, respectively, in type 2 diabetes. Treatment with thiazolidinediones mobilises fat out of tissues, leading to enhanced insulin sensitivity, improved beta cell function and decreased atherogenesis. Insulin resistance and lipotoxicity represent the missing links (beyond the classical cardiovascular risk factors) that help explain the accelerated rate of CVD in type 2 diabetic patients