Effect of F11 Receptor/Junctional Adhesion Molecule-A-derived Peptide on Neointimal Hyperplasia in a Murine Model.

PURPOSE: To determine whether inhibition of the F11 receptor/JAM-A (F11R) using F11R-specific antagonist peptide 4D results in inhibition of smooth muscle cell (SMC) proliferation and migration in vivo, known as neointimal hyperplasia (NIH), using a mouse focal carotid artery stenosis model (FCASM). MATERIALS AND METHODS: The mouse FCASM was chosen to test the hypothesis because the dominant cell type at the site of stenosis is SMC, similar to that in vascular access stenosis. Fourteen C57BL/6 mice underwent left carotid artery (LCA) partial ligation to induce stenosis, followed by daily injection of peptide 4D in 7 mice and saline in the remaining 7 mice, and these mice were observed for 21 days and then euthanized. Bilateral carotid arteries were excised for histologic analysis of the intima and media areas. RESULTS: The mean intimal area was significantly larger in control mice compared with peptide 4D-treated mice (0.031 mm2 [SD ± 0.024] vs 0.0082 mm2 [SD ± 0.0103]; P = .011). The mean intima-to-intima + media area ratio was significantly larger in control mice compared with peptide 4D-treated mice (0.27 [SD ± 0.13] vs 0.089 [SD ± 0.081]; P = .0079). NIH was not observed in the right carotid arteries in both groups. CONCLUSIONS: Peptide 4D, an F11R antagonist, significantly inhibited NIH in C57BL/6 mice in a FCASM.

Triple negative breast cancer metastasis is hindered by a peptide antagonist of F11R/JAM­A protein.

BACKGROUND: The F11R/JAM-A cell adhesion protein was examined as the therapeutic target in triple negative breast cancer (TNBC) with the use of the peptide antagonist to F11R/JAM-A, that previously inhibited the early stages of breast cancer metastasis in vitro. METHODS: The online in silico analysis was performed by TNMPlot, UALCAN, and KM plotter. The in vitro experiments were performed to verify the effect of peptide 4D (P4D) on human endothelial cell lines EA.hy926 and HMEC-1 as well as on human TNBC cell line MDA-MB-231. The cell morphology upon P4D treatment was verified by light microscopy, while the cell functions were assessed by colony forming assay, MTT cell viability assay, BrdU cell proliferation assay, and Transepithelial/Endothelial Electrical Resistance measurements. The in vivo experiments on 4T1 murine breast cancer model were followed by histopathological analysis and a series of quantitative analyses of murine tissues. RESULTS: By in silico analysis we have found the elevated gene expression in breast cancer with particular emphasis on TNBC. The elevated F11R expression in TNBC was related with poorer survival prognosis. Peptide 4D has altered the morphology and increased the permeability of endothelial monolayers. The colony formation, viability, and proliferation of MDA-MB-231 cells were decreased. P4D inhibited the metastasis in 4T1 breast cancer murine model in a statistically significant manner that was demonstrated by the resampling bootstrap technique. CONCLUSIONS: The P4D peptide antagonist to F11R/JAM-A is able to hinder the metastasis in TNBC. This assumption needs to be confirmed by additional 4T1 mouse model study performed on larger group size, before making the decision on human clinical trials.

Impact of diabetes on COVID-19 patient health outcomes in a vulnerable racial minority community.

BACKGROUND: Diabetes is a growing health concern in the United States and especially New York City. New York City subsequently became an epicenter for the coronavirus pandemic in the Spring of 2020. Previous studies suggest that diabetes is a risk factor for adverse outcomes in COVID-19. OBJECTIVE: To investigate the association between diabetes and COVID-19 outcomes as well as assess other covariates that may impact health outcomes. DESIGN: Retrospective cohort study of COVID-19 hospitalized patients from March to May, 2020. PARTICIPANTS: In total, 1805 patients were tested for COVID-19 and 778 tested positive for COVID-19. Patients were categorized into 2 groups: diabetes (measured by an Hba1c >6.5 or had a history of diabetes) and those without diabetes. RESULTS: After controlling for other comorbidities, diabetes was associated with increased risk of mortality (aRR = 1.28, 95% CI 1.03-1.57, p = 0.0231) and discharge to tertiary care centers (aRR = 1.69, 95% CI 1.04-2.77, p = 0.036). compared to non-diabetes. Age and coronary artery disease (CAD) increased the risk of mortality among diabetic patients compared to patients with diabetes alone without CAD or advanced age. The diabetes cohort had more patients with resolving acute respiratory failure (62.2%), acute kidney injury secondary to COVID-19 (49.0%) and sepsis secondary to COVID-19 (30.1%). CONCLUSION: This investigation found that COVID-19 patients with diabetes had increased mortality, multiple complications at discharge, and increased rates of admission to a tertiary care center than those without diabetes suggesting a more severe and complicated disease course that required additional services at time of discharge.

Determination of unacceptable antigens by summation of anti-HLA eplet antibody strength (MFI) based on single antigen bead assays: Excellent correlation with negative cell based cross matches.

The reliability of single antigen bead (SAB) assays and their use in predicting a negative cell based cross match (CBXM) is essential in the era of expanded organ sharing. A wide range of accuracy (80-95%) in predicting negative CBXM has been reported. We hypothesized that in SAB assays an antibody against an HLA eplet that was common among a number of different HLA alleles would be distributed among all of the shared eplet positive SABs. This would reduce binding to the donor specific SAB resulting in an under-estimate of antibody strength. We tested this proposal in adsorption studies using, instead of lymphocytes, a novel reagent, single-SAB (sSAB). Properties of SAB assays were examined that provided a basis for conducting adsorption - elution experiments with the sSABs. We found that incubation of sera with sA*02:01 or sB*42:01 not only depleted reactivity to these alleles but also depleted reactivity to beads that shared the reactive eplet. Anti-eplet strength from SAB data (sum of the MFI of eplet positive SABs (MFI-s) was compared with CBXM out comes in two case studies and with 99 proficiency testing sera. In these validation studies, an MFI-s above 11,000 was associated with a positive FCXM. This approach was placed into clinical practice for listing unacceptable antigens that shared a common eplet. CDCXMs (n = 3261) and FCXMs (n = 1012) were performed on patients listed in UNOS for deceased donor kidneys. All CDCXMs were negative and all FCXMs except one were negative. We conclude that summation of eplet strength provides a highly reliable method of predicting prospective negative CBXMs resulting in substantial savings of time and effort. Based on shared eplet summation data, CMS/NYSDOH has accepted our bead based XM (BBXM) method (aka, virtual XM) performed prior to transplant as fulfilling the regulation that XM results be available before kidney transplantation.

HIV Testing Correlates: U.S. and Foreign Born High-Risk Black Heterosexual Men.

In the U.S., Black men are disproportionately affected by HIV, with some of the highest HIV incidence rates and lowest rates of HIV testing. We examined correlates of HIV testing and knowledge among participants of the Barbershop Talk with Brothers (BTWB) project, an HIV prevention program targeting high-risk sexual behaviors among Black heterosexual men in Brooklyn, New York. Specifically, we examined differences between U.S. vs. foreign-born status and HIV testing rates, HIV knowledge, and socio-demographic factors. Of the 855 men included, the mean age was 33 years and 35.0% were foreign-born. Lifetime HIV testing was reported at 84%, with greater proportion of U.S. vs foreign-born men reporting lifetime (88.6% vs. 75.0%) and recent testing (68.6% vs. 51.0%), p < 0.001. Among foreign-born men, recent HIV testing was associated with lower stigma and greater HIV transmission knowledge than those un-tested. The authors recommend tailored approaches to increasing HIV testing in Black communities, based on nativity and social factors.

Association of Physical Function and Survival in Older-Adult Renal Transplant Recipients.

There is an increase in older-adult renal transplant recipients in United States. The objective of this study was to assess the association between physical function (PF) and patient survival in renal transplant recipients who are aged 65 years or older. Using United Network for Organ Sharing (UNOS) data from 2007 to 2016, renal transplant recipients aged 65 years or older were included. Multivariable Cox regression was used to assess associations between survival and functional status adjusted for age, sex, race, donor quality, diabetes, and dialysis vintage. The study identified 26,721 patients. Patient survival was significantly higher in recipients who needed no assistance and lowest in patients in need of total assistance (P < .0001). In deceased donor (DD) transplants, the relative risk for mortality was 2.06 (1.74-2.43) for total assistance and 1.17 (1.08-1.28) for moderate assistance compared to no assistance (P < .0001). In living donor (LD) transplants, the relative risk of mortality was 1.38 (0.78-2.42) for patients needing total assistance and 1.37 (1.14-1.65) for patients needing moderate assistance compared to patients who did not need assistance (0.003). PF is an independent predictor of post-transplant mortality. Assessment of older potential renal transplant recipients should include assessment and standardization of functional status to counsel about post-transplant survival.

Anti-N-methyl-d-aspartate Receptor Encephalitis Related Sinus Node Dysfunction and the Lock-Step Phenomenon.

Described in 2007, anti-N-methyl-d-aspartate receptor encephalitis (ANMDARE) is a rare autoimmune limbic encephalitis affecting young adults (predominantly women of reproductive age) and is a paraneoplastic manifestation of ovarian teratoma in about half of the cases. ANMDARE is characterized by psychiatric changes, neurological changes, autonomic instability and cardiac dysrhythmias. In this report, we present a 36-year-old woman who was 16 weeks pregnant and brought to the hospital with confusion and subsequently had a seizure with Electroencephalography (EEG) demonstrated an extreme delta brush pattern consistent with ANMDARE. Patient developed sinus nodal dysfunction and was also found to have ovarian teratoma, a rather typical presentation for ANMDARE, that is considered a paraneoplastic syndrome for ovarian teratoma. In this report, we highlight the cardiac manifestation of ANMDARE, the pathophysiology associated with autonomic instability, and management strategies of this rare, and largely devastating illness.

In vivo data: treatment with the F11R/JAM-A peptide 4D decreases mortality and reduces the generation of atherosclerotic plaques in ApoE-deficient mice.

The data in this article focus on the F11 Receptor (F11R/JAM-A; Junctional Adhesion Molecule-A; JAM-A, F11R), a cell adhesion protein constitutively expressed on the membrane surface of circulating platelets and localized within the tight junctions of healthy endothelial cells (ECs). Previous reports have shown that F11R/JAM-A plays a critical role in the adhesion of platelets to an inflamed endothelium due to its' pathological expression on the luminal surface of the cytokine-inflamed endothelium. Since platelet adhesion to an inflamed endothelium is an early step in the development of atherosclerotic plaque formation, and with time, resulting in heart attacks and stroke, we conducted a long-term, study utilizing the atherosclerosis-prone ApoE -/- mice to attempt a blockade of the formation of atherosclerotic plaques by preventing the adhesion of platelets to the inflamed vasculature in vivo. Utilizing a nonhydrolyzable peptide derived from an amino acid sequence of F11R/JAM-A, peptide 4D, we have shown in culture that the adhesion of platelets to the inflamed endothelial cells could be blocked by peptide 4D. The present data demonstrate the positive health benefits of chronic peptide 4D administration to the atherosclerosis-prone ApoE-/- mice, and provides new information for potential use of this F11R derived peptide in the prevention of atherosclerosis. The data presented in this article provide further experimental support for the study presented in Babinska et al., Atherosclerosis 284 (2019) 92-101.

Early Experience With Methylprednisolone on SARS-CoV-2 Infection in the African American Population, a Retrospective Analysis.

BACKGROUND: Coronavirus disease-19 (COVID-19) is associated with acute kidney injury (AKI) and acute respiratory distress syndrome (ARDS) with high mortality rates. In African American (AA) populations, COVID-19 presentations and outcomes are more severe. NIH and Interim WHO guidelines had suggested against the use of corticosteroids unless in clinical trials until the recent publication of the RECOVERY trial. Here, we analyzed the treatment effect of methylprednisolone on patients with AKI and ARDS during the initial 2 months of COVID-19 and detail the learning effect within our institution. METHODS: Between March 1 and April 30, 2020, 75 AA patients met our inclusion criteria for ARDS and AKI, of which 37 had received corticosteroids. Twenty-eight-day mortality, improvement in PaO2/FiO2 ratio, and renal function were analyzed. The impact of methylprednisolone treatment was assessed with multivariable methods. RESULTS: Survival in the methylprednisolone group reached 51% at 21 days compared to 29% in the non-corticosteroid group (P < .001). Methylprednisolone improved the likelihood of renal function improvement. PaO2/FiO2 ratio in the methylprednisolone group improved by 73% compared to 45% in the non-corticosteroid group (P = .01). Age, gender, BMI, preexisting conditions, and other treatment factors did not show any impact on renal or PaO2/FiO2 ratio improvement. The use of anticoagulants, the month of treatment, and AKI during hospitalization also influenced outcomes. CONCLUSION: In AA COVID-19 positive patients with ARDS and AKI, IV methylprednisolone lowered the incidence of mortality and improved the likelihood of renal and lung function recovery. Further investigation with a randomized control trial of corticosteroids is warranted.

Functional inhibition of F11 receptor (F11R/junctional adhesion molecule-A/JAM-A) activity by a F11R-derived peptide in breast cancer and its microenvironment.

PURPOSE: To examine the involvement of the F11R/JAM-A protein in breast cancer metastasis, we utilized the F11R/JAM-A antagonistic peptide 4D (P4D) in experiments of transendothelial migration (TEM) of breast cancer cells. METHODS: Experiments were conducted in the mouse 4T1 breast cancer model utilizing the human mammary epithelial cell and endothelial cell lines. The levels of soluble F11R/JAM-A (sJAM-A) in the murine plasmas were measured by ELISA. Levels of F11R/JAM-A mRNA and protein in cell lines were assessed by qRT-PCR and Western blot, respectively. Cell surface expression of F11R/JAM-A was demonstrated by flow cytometry. Functional tests included the TEM of breast cancer cells and adhesion of breast cancer cells to the endothelium. The endothelial permeability was studied by fluorescent tracer assay and by the Real-Time Cell Analysis (RTCA). RESULTS: The tumor inducers Tß4 and TGF-ß1 reduced the levels of sJAM-A in murine plasma, and reduced the F11R/JAM-A protein levels in the human microvascular endothelial cell line HMEC-1. The adhesion and TEM measured between breast cancer cells and inflamed or Tß4-treated endothelium were inhibited by P4D. The presence of P4D did not destabilize the pre-existing tight junctions in the endothelial monolayer. The barrier-protecting effect of P4D was stronger than that of forskolin, when a booster dose of P4D was applied to the inflamed endothelium. CONCLUSIONS: F11R/JAM-A protein can be considered as a novel target in the treatment of breast cancer metastasis. In vivo and clinical studies are needed to further investigate the effectiveness of F11R/JAM-A-derived peptide as a possible anti-metastatic drug.

A peptide antagonist of F11R/JAM-A reduces plaque formation and prolongs survival in an animal model of atherosclerosis.

BACKGROUND AND AIMS: The F11 Receptor (F11R), AKA Junctional Adhesion Molecule-A (JAM-A) (F11R/JAM-A), is an adhesion protein constitutively expressed on the membrane surface of circulating platelets and the luminal surface of inflamed endothelial cells (EC). Platelet adhesion to an inflamed endothelium is one of the early steps of atherosclerotic plaque formation. Our previous studies, conducted with cultured EC in vitro, have demonstrated the expression of F11R/JAM-A on the luminal surface of inflamed EC, platelet adhesion to inflamed EC through F11R/JAM-A interactions, and inhibition of this interaction by the presence of F11R/JAM-A antagonistic peptide (F11Rpeptide 4D). In the present study, we examined in vivo the overall health-benefits and cardiovascular effects of long-term treatment of animals prone to atherosclerosis, ApoE-/- mice, with F11R-peptide 4D. METHODS: Twenty ApoE-/- mice were assigned to daily treatment with peptide 4D and compared to their counterparts control untreated mice. Mice were observed for wellness and survival. Plaque size in the aorta and heart was measured using histological analysis. Effects of peptide 4D (or scramble control) on platelet adhesion to inflamed endothelium were measured using intravital microscopy. RESULTS: Significant reductions in atherosclerotic plaques number and size, an overall robust health with longer survival were found in the peptide 4D treated group of ApoE-/- mice. Intravital microscopic studies conducted in exposed vessels of ApoE-/- mice demonstrated significant inhibition by peptide 4D of platelet adhesion to the cytokine-inflamed endothelium. CONCLUSIONS: Our results demonstrate that peptide 4D significantly reduces atherosclerotic plaque formation in ApoE-/- mice and inhibits platelet adhesion to the inflamed arterial endothelium.

Trends and outcomes in dual kidney transplantation- A narrative review.

Dual kidney transplantation (DKT) is a viable option to increase the donor pool and improve access equity to kidney transplantation. Dual kidneys are procured from carefully selected marginal donors that are not generally acceptable to most transplant centers. This is a narrative review of literature focusing on donor kidney allocation systems and selection of the ideal recipient for DKT. We also discussed surgical approaches for DKTs as well as patient and allograft outcomes. We found that most studies to date showed that DKTs has similar graft survival and delayed graft function rates when compared to single kidney transplants (SKTs). DKT is technically feasible with outcomes that are comparable to expanded criteria donor kidneys (ECD); and has substantial potential in expanding the donor pool. For allograft survival, most studies with strict allocation criteria showed that graft survival was similar in DKT as compared to SKT - ECD transplants.. Our review may encourage transplant centers to review their policies for donor and recipient selection leading to increase in DKT.

Mortality in Living Kidney Donors With ESRD: A Propensity Score Analysis Using the United States Renal Data System.

INTRODUCTION: In recent years, data have emerged on the outcomes of living kidney donors who develop end-stage renal disease (ESRD). We aimed to evaluate mortality rates in kidney donors who had initiated dialysis compared with a propensity-matched cohort of dialysis patients without previous kidney donation. METHODS: We used the United States Renal Data System (USRDS) and abstracted 274 previous living kidney donors between 1995 and 2009. There were 609,398 individuals on dialysis without kidney donation. We used propensity score matching to identify 258 donors and 258 nondonors. The time-dependent Cox proportional hazards model was used to compare survival between the 2 matched cohorts. RESULTS: In the propensity score-matched cohort, mortality was lower in donors compared with nondonors (19% vs. 49%; P < 0.0001). The time-dependent Cox proportional hazards model demonstrated that donors had significantly lower mortality compared with nondonors 0 to 5 years since start of dialysis (hazard ratio [HR]: 0.17; 95% confidence interval [CI] 0.11-0.27; P < 0.0001) and with nondonors 5 to 10 years on dialysis (HR: 0.34; 95% CI: 0.19-0.63; P < 0.001). We were unable to estimate the difference between the 2 groups after 10 years on dialysis with any precision (HR: 0.51; 95% CI: 0.18-1.42; P = 0.20) due to the small sample size. CONCLUSION: We observed a lower mortality rate in living kidney donors with ESRD compared with matched nondonors. This data should guide clinicians in the informed consent process with prospective donors.

Statins and New-Onset Diabetes in Cardiovascular and Kidney Disease Cohorts: A Meta-Analysis.

BACKGROUND: Statins have long been prescribed for the primary and secondary prevention of cardiovascular disease (CVD) and kidney disease. Their benefits and efficacy are widely accepted in current clinical practice, but like any other therapeutic agents, they have adverse effects. One of the emerging concerns with statin therapy is the development of new-onset diabetes mellitus (NODM), a dreaded risk factor for CVD and kidney disease and widely viewed as CVD equivalent. Accumulating evidence indicates that NODM is a consequence of statin use. METHODS: We conducted a meta-analysis of studies reporting on associations between NODM and statin use. Based on strict exclusion criteria, a total of 11 studies were selected. Their data were analyzed using Comprehensive Meta-Analysis® statistical software and reported as odds ratios (OR) with 95% confidence intervals (CI). RESULTS: The cumulative fixed effect for use of statin therapy and incident NODM was an OR of 1.61 (95% CI 1.55-1.68, p < 0.001). Our results suggest that statin therapy is associated with NODM, such that there is a small but significant risk of NODM among patients receiving statin for CVD prevention therapy. However, this high-risk population also has other diabetes risk factors (such as obesity and hypertension) contributing to the development of NODM. CONCLUSIONS: It is imperative that patients on statin therapy be monitored carefully for NODM. However, it can be argued that the risk of statin therapy is offset by the multitude of cardiovascular and kidney-protective effects provided by such an important and highly effective therapeutic agent.

Gender disparity in fistula use at initiation of hemodialysis varies markedly across ESRD networks-Analysis of USRDS data.

BACKGROUND: Gender disparities had been noted in the care of women with end stage renal disease (ESRD) in the early 2000's, including less frequent initiation of hemodialysis utilizing a fistula but more recent data have not been examined and underlying factors have not been extensively studied. STUDY DESIGN: Data from the United States Renal Data System (USRDS) were examined, including 202,999 hemodialysis patients. Only those who had received prior nephrology care were included. Multiple logistic regression was used, adjusted for possible confounders, including age, race, cause of ESRD, BMI, height, history of alcohol or drug abuse, medical comorbidities, ability to ambulate, time of nephrology care, type of insurance, and ESRD network. RESULTS: The odds of arteriovenous fistula (AVF) use at initiation of hemodialysis were significantly lower in women compared to men (OR = 0.69, 95% CI 0.67-0.71, P < 0.0001). The gender gap in AVF use at initiation was highest in New York and the upper Midwest (networks 2 and12) and smallest for Southern California and the Pacific Northwest and Alaska (18 and 16). Gender disparity was more pronounced for black women, with odds ratios for AVF use at initiation of dialysis (OR = 0.66, 95% CI 0.62-0.69), P < 0.0001 as compared to non-black (OR 0.70, 95% CI 0.68-0.73), P ≤ 0.0001. LIMITATIONS: Limitations include use of USRDS data. Data misclassification or errors in data reporting may exist and certain comorbid conditions may be underreported. Data regarding rate of primary fistula non-function are also not available. CONCLUSION: Adjusted odds ratio for AVF use was significantly lower in women compared to men, independent of time of nephrology care and other predictors. The gender disparity was most pronounced for black women and also varied from 20% to 46% lower odds for AVF use in women for different ESRD networks, after controlling for possible confounding variables, suggesting that practice based factors may be of importance in explaining this important finding.

Lessons Learned from the Implementation of a Shared Community-Academic HIV Prevention Intervention.

BACKGROUND: Community-based participatory research (CBPR) is used to guide the design and evaluation of programs aimed at addressing complex health issues. Effective administrative management of CBPR projects is essential to ensuring the success and fidelity of these programs. OBJECTIVE: We identify an administrative framework to support the implementation and management of a community- academic CBPR initiative. METHODS: The Barbershop Talk with Brothers (BTWB) project was a cluster randomized CBPR intervention designed to reduce HIV among high-risk heterosexual men. Eight-hundred sixty men, representing 53 barbershops, participated in the project. RESULTS: The 3Ps framework is defined by 1) partnership, 2) product, and 3) process. We describe the implementation of the 3Ps through applied examples including partnership management strategies, planning of shared resources, and flexible budgeting that can support the unique infrastructure of a shared community-academic project. CONCLUSIONS: The 3Ps are a translatable framework for comparable shared community-academic research projects to adopt.

Association of restless legs syndrome and mortality in end-stage renal disease: an analysis of the United States Renal Data System (USRDS).

BACKGROUND: Objective of the study is to assess prevalence and survival among end stage renal disease patients with restless legs syndrome (RLS) within a national database (USRDS). METHODS: A case-control, retrospective analysis was performed. Differences in characteristics between the groups, RLS and those with no sleep disorder (NSD), were determined using χ2 tests. Cox proportional hazard regression was used to assess survival between those with RLS and propensity score matched controls. RESULTS: Cases of restless legs syndrome were defined as patients that had received an ICD-9 code of 333.94 at any point during their treatment (n = 372). RLS group demonstrated a significantly higher proportion of patients with major depressive disorder, dysthymic disorder, anxiety, depression, minor depressive disorder, and psychological disorder. The difference between the survival was not statistically significant in those without sleep disorder as compared to those with RLS (HR =1.16±0.14, p = 0.3). CONCLUSIONS: True prevalence of RLS in dialysis patients can only be estimated if knowledge gap for care providers in diagnosis of RLS is addressed. RLS patients also have increased incidence of certain psychological disorders which needs to be addressed.

Dialysis in the Elderly and Impact of Institutionalization in the United States Renal Data System.

BACKGROUND: We hypothesized that in the very elderly dialysis patients in the United States, institutionalization in nursing homes would increase mortality in addition to age alone. METHODS: Incident dialysis patients from 2001 to 2008 above the age of 70 were included. Patients above 70 were categorized into 4 groups according to age as 70-75, 76-80, 81-85, and >85 years and further divided into institutionalized and noninstitutionalized. Kaplan-Meier survival curves were plotted to assess patient survival. RESULTS: A total of 349,440 patients were identified above the age of 70 at the time of initiation of dialysis. For institutionalized patients, the mean survival was significantly lower, 1.71 ± 0.03 years for those in the age range 70-75, 1.44 ± 0.02 years for those in the age range 76-80, 1.25 ± 0.02 years for those in the age range 81-85, and 1.04 ± 0.02 for those in the >85 years age group (p = 0.0001). The hazard ratio for mortality in institutionalized elderly patients on dialysis was 1.80 ([95% CI 1.77-1.83]; p = 0.0001). After adjustment for other variables (multivariate Cox regression), to be institutionalized was still an independent risk factor for mortality (adjusted hazard ratio = 1.57 [95% CI 1.54-1.60]; p = 0.0001). CONCLUSION: There was increased mortality in institutionalized elderly patients as compared to noninstutionalized elderly patients in the same age group. In accordance with the increased frailty and decreased benefits of therapies in the very elderly, especially in those with additional co-morbidities besides age, palliative and end-of-life care should be considered.

Obesity, Cardiovascular Disease and Sleep Disorders: Insights into the Rising Epidemic.

Cardiovascular disease (CVD) is the main cause of death among adult men and women in the USA and impacts millions around the globe. Traditional risk factors for CVD include obesity, diabetes, hypertension and dyslipidemia. The modern-day epidemic of obesity not only increased the rate of CVD but also ushered in an additional CVD risk factor to be added to the list; that is obstructive sleep apnea (OSA). In this review, we discuss the growing epidemic of obesity and OSA, highlighting the common pathogenic hypotheses linking these risk factors to CVD. We will also highlight the therapeutic rationale of OSA as a way to reduce CVD risk.

Mortality after Renal Allograft Failure and Return to Dialysis.

INTRODUCTION: The outcomes of patients who fail their kidney transplant and return to dialysis (RTD) has not been investigated in a nationally representative sample. We hypothesized that variations in management of transplant chronic kidney disease stage 5 leading to kidney allograft failure (KAF) and RTD, such as access, nutrition, timing of dialysis, and anemia management predict long-term survival. METHODS: We used an incident cohort of patients from the United States Renal Data System who initiated hemodialysis between January 1, 2003 and December 31, 2008, after KAF. We used Cox regression analysis for statistical associations, with mortality as the primary outcome. RESULTS: We identified 5,077 RTD patients and followed them for a mean of 30.9 ± 22.6 months. Adjusting for all possible confounders at the time of RTD, the adjusted hazards ratio (AHR) for death was increased with lack of arteriovenous fistula at initiation of dialysis (AHR 1.22, 95% CI 1.02-1.46, p = 0.03), albumin <3.5 g/dL (AHR 1.33, 95% CI 1.18-1.49, p = 0.0001), and being underweight (AHR 1.30, 95% CI 1.07-1.58, p = 0.006). Hemoglobin <10 g/dL (AHR 0.96, 95% CI 0.86-1.06, p = 0.46), type of insurance, and zip code-based median household income were not associated with higher mortality. Glomerular filtration rate <10 mL/min/1.73 m2 at time of dialysis initiation (AHR 0.83, 95% CI 0.75-0.93, p = 0.001) was associated with reduction in mortality. CONCLUSIONS: Excess mortality risk observed in patients starting dialysis after KAF is multifactorial, including nutritional issues and vascular access. Adequate preparation of patients with failing kidney transplants prior to resuming dialysis may improve outcomes.