Effect of Inflammation on the Relationship of Pulse Pressure and Mortality in Haemodialysis

The effect of hypertension on mortality in haemodialysis patients is controversial and can be confounded by non-traditional risk factors like systemic inflammation. This study examined the effect of systolic blood pressure (SBP), diastolic blood pressure (DBP), and pulse pressure (PP) on mortality in haemodialysis patients, separately with and without markers of systemic inflammation

Blood pressure and long-term mortality in United States hemodialysis patients: USRDS Waves 3 and 4 Study11The data reported here were supplied by the United States Renal Data System. Interpretation of these data is the responsibility of the authors, and in no way should be seen as an official policy or interpretation of the U.S. government.

Blood pressure and long-term mortality in United States hemodialysis patients: USRDS Waves 3 and 4 Study.BackgroundThe long-term prognostic associations of pre- and post-dialysis blood pressures, interdialytic weight gain, and antihypertensive use in hemodialysis patients are unclear.MethodsThe United States Renal Data System (USRDS) Dialysis Morbidity and Mortality Waves 3 and 4 Study, a randomly generated sample of 11,142 subjects receiving hemodialysis on December 31, 1993, was examined, with vital status followed until May 2000.ResultsPre- and post-dialysis blood pressure values, interdialytic weight gain and number of antihypertensives averaged 151.8/79.7, 137.0/74, 3.6% and 0.76, respectively. Prognostic discrimination was maximized by considering pre- and post-systolic and diastolic blood pressure values simultaneously, in a pattern suggesting that wide pulse pressures were associated with mortality (P < 0.0001). Comorbidity adjustment markedly affected associations, with low pre-dialysis diastolic (P < 0.05), low post-dialysis dialysis diastolic pressure (P < 0.05), high post-dialysis dialysis systolic pressure (P < 0.05), and high interdialytic weight gains (P = 0.005) associated with mortality. Each class of antihypertensive drug, except angiotensin-converting enzyme (ACE)-inhibitors, was associated with lower mortality in unadjusted models, an effect most pronounced for beta-blockers (hazards ratio 0.72, 95% CI 0.66 to 0.79, P < 0.0001). Comorbidity adjustment eliminated survival associations for each antihypertensive class except beta-blockers.ConclusionsPre- and post-dialysis blood pressure values have independent associations with mortality, in a way that implicates wide pulse pressures. Much of the adverse prognosis of wide pulse pressures probably reflects older age and cardiovascular comorbidity. Large interdialytic weight gains are associated with shorter survival when comorbidity is taken into account. Beta-blocker use shows a robust association with survival, and may be protective

Betti numbers for numerical semigroup rings

We survey results related to the magnitude of the Betti numbers of numerical semigroup rings and of their tangent cones.Comment: 22 pages; v2: updated references. To appear in Multigraded Algebra and Applications (V. Ene, E. Miller Eds.

A fundamental bimodal role for neuropeptide Y1 receptor in the immune system

Psychological conditions, including stress, compromise immune defenses. Although this concept is not novel, the molecular mechanism behind it remains unclear. Neuropeptide Y (NPY) in the central nervous system is a major regulator of numerous physiological functions, including stress. Postganglionic sympathetic nerves innervating lymphoid organs release NPY, which together with other peptides activate five Y receptors (Y1, Y2, Y4, Y5, and y6). Using Y1-deficient (Y1−/−) mice, we showed that Y1−/− T cells are hyperresponsive to activation and trigger severe colitis after transfer into lymphopenic mice. Thus, signaling through Y1 receptor on T cells inhibits T cell activation and controls the magnitude of T cell responses. Paradoxically, Y1−/− mice were resistant to T helper type 1 (Th1) cell–mediated inflammatory responses and showed reduced levels of the Th1 cell–promoting cytokine interleukin 12 and reduced interferon γ production. This defect was due to functionally impaired antigen-presenting cells (APCs), and consequently, Y1−/− mice had reduced numbers of effector T cells. These results demonstrate a fundamental bimodal role for the Y1 receptor in the immune system, serving as a strong negative regulator on T cells as well as a key activator of APC function. Our findings uncover a sophisticated molecular mechanism regulating immune cell functions that can lead to stress-induced immunosuppression

Brane/flux annihilation transitions and nonperturbative moduli stabilization

By extending the calculation of Kahler moduli stabilization to account for an embiggened antibrane, we reevaluate brane/flux annihilation in a warped throat with one stabilized Kahler modulus. We find that depending on the relative size of various fluxes three things can occur: the decay process proceeds unhindered, the anti-D3-branes are forbidden to decay classically, or the entire space decompactifies. Additionally, we show that the Kahler modulus receives a contribution from the collective 3-brane tension. This allows for a significant change in compactified volume during the transition and possibly mitigates some fine tuning otherwise required to achieve large volume.Comment: 25 pages, 6 figures, LaTeX. v2: references adde

Gut microbiota induce IGF-1 and promote bone formation and growth

New interventions are needed to improve bone health and reduce the risk for osteoporosis and fracture. Dysbiosis is increasingly linked to metabolic abnormalities, although the effect of the microbiota on skeletal health is poorly understood. Previous studies suggest microbiota are detrimental to bone by increasing resorption. In this report, we show that the gut resident microbiota promote bone formation, as well as resorption, with long-term exposure to microbiota resulting in net skeletal growth. Microbiota induce the hormone insulin-like growth factor 1 (IGF-1), which promotes bone growth and remodeling. Short-chain fatty acids (SCFAs), produced when microbiota ferment fiber, also induce IGF-1, suggesting a mechanism by which microbiota affect bone health. Manipulating the microbiome or its metabolites may afford opportunities to optimize bone health and growth

Cardiovascular outcomes reported in hemodialysis trials

Patients on long-term hemodialysis are at very high risk for cardiovascular disease but are usually excluded from clinical trials conducted in the general population or in at-risk populations. There are no universally agreed cardiovascular outcomes for trials conducted specifically in the hemodialysis population. In this review, we highlight that trials reporting cardiovascular outcomes in hemodialysis patients are usually of short duration (median 3 to 6 months) and are small (59% of trials have \u3c100 participants). Overall, the cardiovascular outcomes are very heterogeneous and may not reflect outcomes that are meaningful to patients and clinicians in supporting decision making, as they are often surrogates of uncertain clinical importance. Composite outcomes used in different trials rarely share the same components. In a field in which a single trial is often insufficiently powered to fully assess the clinical and economic impact of interventions, differences in outcome reporting across trials make the task of meta-analysis and interpretation of all the available evidence challenging. Core outcome sets are now being established across many specialties in health care to prevent these problems. Through the global Standardized Outcomes in Nephrology-Hemodialysis initiative, cardiovascular disease was identified as a critically important core domain to be reported in all trials in hemodialysis. Informed by the current state of reporting of cardiovascular outcomes, a core outcome measure for cardiovascular disease is currently being established with involvement of patients, caregivers, and health professionals. Consistent reporting of cardiovascular outcomes that are critically important to hemodialysis patients and clinicians will strengthen the evidence base to inform care in this very high-risk population

Outcomes of surgical mitral and aortic valve replacements among kidney transplant candidates: implications for valve selection

Background: Limited literature exists that evaluated outcomes of kidney transplant–eligible patients who are having dialysis and who are undergoing valve replacement. Our main objective in this study was to compare mortality, reoperation, and bleeding episodes between bioprosthetic and mechanical valve procedures among kidney transplant–eligible patients who are having dialysis. Methods and Results: We studied 887 and 1925 dialysis patients from the United States Renal Data System, who underwent mitral valve replacement and aortic valve replacement (AVR) after being waitlisted for a kidney transplant (2000–2015), respectively. Time to death, time to reoperation, and time to bleeding requiring hospitalizations were compared separately for AVR and mitral valve replacement. Kaplan–Meier survival curves, Cox proportional hazards model for time to death, accelerated time to event model for time to reoperation, and counting process model for time to recurrent bleeding were used. There were no differences in mortality (hazard ratio [HR], 0.92; 95% CI, 0.77–1.09) or risk of reoperation or risk of significant bleeding events between bioprosthetic and mechanical mitral valve replacement. However, mechanical AVR was associated with a modestly significant less hazard of death (HR, 0.83; 95% CI, 0.74–0.94) compared with bioprosthetic AVR. There were no differences in time to reoperation, or time to significant bleeding events between bioprosthetic and mechanical AVR. Conclusions: For kidney transplant waitlisted patients who are on dialysis and who are undergoing surgical valve replacement, bioprosthetic and mechanical valves have comparable survival, reoperation rates, and bleeding episodes requiring hospitalizations at both mitral and aortic locations. These findings emphasize that an individualized informed decision is recommended when choosing the type of valve for this special group of patients having dialysis