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Background Valvuloarterial impedance (Zva) was introduced as a prognostic measure in patients with aortic stenosis (AS). However, it is unclear whether Zva has a prognostic impact on survival after surgical aortic valve replacement (AVR) in patients with severe AS with preserved ejection fraction (EF). Methods We retrospectively reviewed 929 consecutive patients who had AVR. We investigated 170 elderly patients (age >65 years, mean 76 years) who had AVR secondary to severe AS (mean gradient ≥40 mm Hg; aortic valve area ≤1 cm2; peak velocity ≥4 m/s). Patients with EF <50%, greater than moderate aortic regurgitation, prior heart surgery and concomitant mitral or tricuspid valve surgery were excluded. Zva was calculated and the patients were divided into two groups; low Zva, Zva <4.3 (n=82) and high Zva, Zva ≥4.3 (n=88). The end point was all-cause of death. Survival curves were calculated according to Kaplan-Meier method. Results Age, prevalence of hypertension, diabetes, chronic kidney disease (CKD), atrial fibrillation, symptoms, EF, E/e′ and concomitant coronary artery bypass graft were not different between the groups. Survival was not different between the groups at 5 years (70% in low Zva and 81% in high Zva; p=0.21) and for the entire follow-up period (p=0.23). Only age was a significant factor in predicting survival by multivariate analyses in Cox proportional hazards model after adjusting for Zva, CKD, atrial fibrillation and hypertension. Conclusions Our results suggest that preoperative Zva does not have a prognostic impact on postoperative survival in elderly patients with severe AS with preserved EF. Further investigation is needed to elucidate the controversial results.

Objective To evaluate the outcome of patients after surgical resection of isolated retroperitoneal lymph node ( RPLN ) recurrence of renal cell carcinoma ( RCC ) using a multicentre international cohort. Patients and Methods In all, 50 patients were identified who underwent resection of isolated RPLN recurrence of RCC at four institutions after nephrectomy for pT any N any M0 disease. Progression‐free ( PFS ) and cancer‐specific survival ( CSS ) were estimated using the Kaplan–Meier method. Cox proportional hazards regression models were used to assess the association of clinicopathological characteristics with disease progression. Results The median (interquartile range, IQR ) age at resection was 57.0 (50.0–62.5) years. The median ( IQR ) time to RPLN recurrence after nephrectomy was 12.6 (6.9–39.5) months, with no significant difference in median time to RPLN recurrence between patients with N+ disease at nephrectomy (10.7 [6.5–24.6] months) and those with Nx/pN0 disease at nephrectomy (13.7 [8.7–44.2] months) ( P = 0.66). The median ( IQR ) size of the RPLN recurrence before resection was 2.6 (1.9–5) cm. The most common site for RPLN recurrence was within the interaortocaval region (34%). The median ( IQR ) follow‐up after RPLN resection for patients alive at last follow‐up was 28.0 (13.7–51.2) months. During follow‐up, 26 patients developed RCC recurrence, at a median ( IQR ) of 9.9 (4.0–18.5) months after RPLN resection. Of those who developed a secondary recurrence, disease was again isolated to the retroperitoneum in seven patients. In all, 11 patients subsequently died, including 10 who died from disease. The median PFS after RPLN resection was 19.5 months, with a 3‐ and 5‐year PFS of 40.5% and 35.4%, respectively. We also found that RPLN recurrence at ≤12 months after nephrectomy was associated with a significantly inferior median PFS (12.3 months) compared with RPLN recurrence at >12 months after nephrectomy (47.6 months; P = 0.003). Moreover, on multivariate analysis, a shorter time to recurrence remained associated with a significantly increased risk for subsequent disease progression (hazard ratio 3.51; P = 0.005). Conclusion Surgical resection of isolated RPLN recurrence from RCC may result in durable cancer control in appropriately selected patients. Recurrence at ≤12 months after nephrectomy was associated with a significantly increased risk of progression after resection, underscoring the importance of this variable for risk stratification. Thus, we recommend that, in the setting of isolated RPLN recurrence of RCC (in patients without precluding comorbidities), careful consideration with the patients and medical oncology colleagues be undertaken about the relative and individualised benefits of surgical resection, systemic therapy, and surveillance.

In preparation for the implementation of the Next Accreditation System in Child Neurology, the authors organized the first meeting of child neurology program coordinators in October 2014. A workforce and program-readiness survey was conducted initially. Coordinator job titles varied widely. Most respondents (65%) managed 1 or more fellowships plus child neurology residency. Most had worked in graduate medical education less than 5 years (53%), with no career path (88%), supervised by someone without graduate medical education experience (85%), in divisions where faculty knowledge was judged inadequate (72%). A small proportion of programs had established clinical competency committee policies (28%) and was ready to implement milestone-based evaluations (56%). A post-conference survey demonstrated substantial improvements in relevant skills. The complexity of residency program management in the Next Accreditation System era supports substantive modifications to the program coordinator role. Such changes should include defined career pathway, managerial classification, administrative support, and continuing education.

Creatinine is produced in muscle metabolism as the end-product of creatine phosphate and is subsequently excreted principally by way of the kidneys, predominantly by glomerular filtration. Blood creatinine assays constitute the most common clinically relevant measure of renal function. The use of individual patient-level real-time serum creatinine trajectories provides a very attractive and tantalizing methodology in nephrology practice. Topics covered in this review include acute kidney injury (AKI) with its multifarious rainbow spectrum of renal outcomes; the stimulating vicissitudes of the diverse patterns of chronic kidney disease (CKD) to end-stage renal disease (ESRD) progression, including the syndrome of rapid onset end stage renal disease (SORO-ESRD); the syndrome of late onset renal failure from angiotensin blockade (LORFFAB); and post-operative AKI linked with the role of intra-operative hypotension in patients with diabetes mellitus and suspected diabetic nephropathy with CKD. We conclude that the study of individual patient-level serum creatinine trajectories, albeit a neglected and forgotten diagnostic methodology for diabetic CKD prognostication and prediction, is a most useful diagnostic tool, both in the short-term and in the long-term practice of nephrology. The analysis of serum creatinine trajectories, both in real time and retrospectively, indeed provides supplementary superior diagnostic and prognostic insights in the management of the nephrology patient.

ObjectiveExamine the effects of obesity and metabolic syndrome on outcome in bipolar disorder.MethodThe Comparative Effectiveness of a Second Generation Antipsychotic Mood Stabilizer and a Classic Mood Stabilizer for Bipolar Disorder (Bipolar CHOICE) study randomized 482 participants with bipolar disorder in a 6‐month trial comparing lithium‐ and quetiapine‐based treatment. Baseline variables were compared between groups with and without obesity, with and without abdominal obesity, and with and without metabolic syndrome respectively. The effects of baseline obesity, abdominal obesity, and metabolic syndrome on outcomes were examined using mixed effects linear regression models.ResultsAt baseline, 44.4% of participants had obesity, 48.0% had abdominal obesity, and 27.3% had metabolic syndrome; neither obesity, nor abdominal obesity, nor metabolic syndrome were associated with increased global severity, mood symptoms, or suicidality, or with poorer functioning or life satisfaction. Treatment groups did not differ on prevalence of obesity, abdominal obesity, or metabolic syndrome. By contrast, among the entire cohort, obesity was associated with less global improvement and less improvement in total mood and depressive symptoms, suicidality, functioning, and life satisfaction after 6 months of treatment. Abdominal obesity was associated with similar findings. Metabolic syndrome had no effect on outcome.ConclusionObesity and abdominal obesity, but not metabolic syndrome, were associated with less improvement after 6 months of lithium‐ or quetiapine‐based treatment.

AbstractIn this study, we tested the hypothesis that reduced bioavailability of tetrahydrobiopterin (BH4) is a major mechanism responsible for pathogenesis of endothelial dysfunction in cerebral microvessels of transgenic mice expressing the Swedish double mutation of human amyloid precursor protein (APP) (Tg2576 mice). Endothelial nitric oxide synthase (eNOS) protein expression was significantly increased in cerebral vasculature of Tg2576 mice. In contrast, bioavailability of BH4 was significantly reduced (p < 0.05). Moreover, superoxide anion production was increased in cerebral microvessels of Tg2576 mice (p < 0.05). Incubation with NOS inhibitor, Nω‐nitro‐L‐arginine methyl ester, decreased superoxide anion indicating that uncoupled eNOS is most likely the source of superoxide anion. Increasing BH4 bioavailability either exogenously by BH4 supplementation or endogenously by treatment with the selective peroxisome proliferator‐activated receptor – delta activator GW501516 (2 mg/kg/day, 14 days) attenuated eNOS uncoupling and decreased superoxide anion production in cerebral microvessels of Tg2576 mice (p < 0.05). Treatment with GW501516 restored the biological activity of endothelial nitric oxide in cerebral microvessels of Tg2576 mice, as indicated by the increased nitrite/nitrate content and 3,5‐cyclic guanosine monophosphate levels (p < 0.05). Our studies indicate that sub‐optimal BH4 bioavailability in cerebral vasculature is an important contributor to oxidant stress and endothelial dysfunction in Tg2576 mouse model of Alzheimer's disease. imageExisting evidence suggests that Aβ peptides‐induced up‐regulation of expression and activity of NADPH oxidase causes increased production of superoxide anion (.O2−). .O2− can also be converted to hydrogen peroxide (H2O2) by enzymatic activity of superoxide dismutase (SOD) or spontaneous dismutation. Elevation of .O2− and H2O2 might cause oxidation of tetrahydrobiopterin (BH4) to dihydrobiopterin (BH2) and subsequent uncoupling of endothelial nitric oxide synthase (eNOS) (a) thus reducing levels of nitric oxide (NO) and 3′,5′‐cyclic guanosine monophosphate (cGMP). Supplementation of BH4 or activation of PPARδ prevents detrimental effects of eNOS uncoupling by restoring bioavailability of BH4 and scavenging of .O2−, respectively (b). Activation of PPARδ also increases expression of catalase thereby inactivating H2O2. Generation of H2O2 by uncoupled eNOS in cerebral microvessels of Tg2576 mice is hypothetical.