IL-23 is a heterodimeric cytokine composed of the IL-12p40 “soluble receptor” subunit and a novel cytokine-like subunit related to IL-12p35, termed p19. Human and mouse IL-23 exhibit some activities similar to IL-12, but differ in their capacities to stimulate particular populations of memory T cells. Like IL-12, IL-23 binds to the IL-12R subunit IL-12Rβ1. However, it does not use IL-12Rβ2. In this study, we identify a novel member of the hemopoietin receptor family as a subunit of the receptor for IL-23, “IL-23R.” IL-23R pairs with IL-12Rβ1 to confer IL-23 responsiveness on cells expressing both subunits. Human IL-23, but not IL-12, exhibits detectable affinity for human IL-23R. Anti-IL-12Rβ1 and anti-IL-23R Abs block IL-23 responses of an NK cell line and Ba/F3 cells expressing the two receptor chains. IL-23 activates the same Jak-stat signaling molecules as IL-12: Jak2, Tyk2, and stat1, -3, -4, and -5, but stat4 activation is substantially weaker and different DNA-binding stat complexes form in response to IL-23 compared with IL-12. IL-23R associates constitutively with Jak2 and in a ligand-dependent manner with stat3. The ability of cells to respond to IL-23 or IL-12 correlates with expression of IL-23R or IL-12Rβ2, respectively. The human IL-23R gene is on human chromosome 1 within 150 kb of IL-12Rβ2.

Little is known about survival and hospitalization among alternative-regimen hemodialysis (HD) users compared to thrice-weekly conventional HD patients who have similar characteristics and medical histories. We conducted a cohort study of alternative-regimen HD users and propensity score (PS)-matched controls. Collaborating clinicians identified 101 patients in their programs who used nocturnal HD (NHD) and 44 patients who used short daily HD (SDHD) for 60 days or more. Ten PS-matched control patients for each NHD and SDHD patient were identified from the United States Renal Data System database. Primary outcomes were risk for all-cause mortality and risk for the composite outcome of mortality or major morbid event (AMI or stroke), investigated in Cox proportional hazards models. Risks for all-cause, cardiovascular-related, infection-related, and vascular access-related hospital admissions were also explored. NHD was associated with reduced mortality risk (HR 0.34; 95% CI, 0.21-0.58; P < 0.0001) and with reduced risk for mortality or major morbid event (HR 0.49; 95% CI, 0.31-0.78; P = 0.003) compared to controls. There was a reduced but non-significant risk of death for patients using SDHD compared to controls (HR 0.61; 95% CI, 0.30-1.24; P = 0.17). All-cause and specific hospitalizations did not differ significantly between NHD and SDHD patients and their matched control cohorts. This study provides additional evidence that NHD may improve patient survival.

Smoking, one marker of priority placed on health status, and intrusiveness/control issues should be addressed in intervention efforts to improve compliance in patients treated by HD and PD.

Background Slow walk (gait) speed predicts functional decline, institutionalization and mortality risks in the geriatric population. A gait speed evidence base for dialysis patient outcomes is needed. Study Design Prospective cohort study. Setting & Participants 752 prevalent hemodialysis (HD) patients aged 20–92 evaluated 2009–2012 in 7 Atlanta and 7 San Francisco clinics in a USRDS special study. Predictor Usual walk speed in meters per second, categorized as 0.6 m/s or faster (baseline n=575), <0.6 m/s (baseline n=94), and unable to perform walk test (baseline n=83). Outcomes Survival; hospitalization; Activities of Daily Living (ADL) difficulty; SF-36 physical function (PF). Measurements Cox proportional hazards models investigated gait speed and mortality over a median follow-up of 703 days. Multivariable logistic or linear regression models estimated associations of baseline gait speed with hospitalization, need for ADL assistance, and SF-36 PF score after 12-months. Results Participants who walked 0.6 m/s or faster had 53 (9%) deaths, those who walked <0.6 m/s had 19 (20%) deaths, and those unable to walk had 37 (44%) deaths. Adjusted mortality hazard ratios were 2.17 (95% CI, 1.19–3.98) for participants who walked <0.6 m/s and 6.93 (95% CI, 4.01–11.96) for those unable to walk, compared with participants walking 0.6 m/s or faster. After 12 months, compared with baseline walk speed 1.0 m/s or faster (n=169 participants), baseline walk speed 0.6 to <0.8 m/s (n=116) was associated with increased odds of hospitalization (OR, 2.04; 95% CI, 1.19–3.49) and ADL difficulty (OR, 3.88; 95% CI, 1.46–10.33) and with a −8.20 (95% CI, −13.57 to −2.82) estimated change in SF-36 PF score. Limitations Cohort not highly representative of overall US in-center HD population. Conclusions: Because walking challenges the heart, lungs, circulatory, nervous, and musculoskeletal systems, gait speed provides an informative marker of health status. The association of gait speed with HD patients’ risk for functional decline warrants continued study.

The purpose of this study was to identify early patterns of care for Alzheimer's disease (AD) in a cohort of African-American patients and their caregivers presenting at an inner city clinic and a suburban memory assessment clinic. Caregivers (N=79) of patients diagnosed with probable AD were interviewed. Data were collected about the delay from noticing first AD signs until recognition that a problem existed and delay from problem recognition until first physician consultation. Patients and caregivers had lower educational status, and patients had been diagnosed more recently at the inner city clinic than at the suburban clinic, although MMSE scores of patients at the two clinics did not differ; median delays in caregivers' recognizing a problem and in consulting a physician were also similar across clinics. Delay was as long as 7 years between noticing symptoms and problem recognition and between problem recognition and physician consultation. Although patients attending the suburban clinic were more likely to have previously seen a physician than those attending the inner city clinic, they were no more likely to have received a prior diagnosis of AD. Lack of physician contact is likely to be widespread in families caring for African Americans with AD. Physician consultation is more characteristic of more highly educated families but may not yield a correct diagnosis for the patient. Intensive efforts are needed to connect African-American families with physicians and to achieve more timely diagnosis of AD to enable families to understand the illness, plan for patient safety, and make long-term plans.

Belatacept, a T cell costimulation-blocker demonstrated superior renal function, lower cardiovascular risk, and improved graft/patient survival in renal transplant recipients. Despite the potential benefits, adoption of belatacept has been limited in part due to concerns regarding higher rates and grades of acute rejection in clinical trials. Since July 2011 we have utilized belatacept-based immunosuppression regimens in clinical practice. In this retrospective analysis of 745 patients undergoing renal transplantation at our center, we compared patients treated with belatacept (n=535) to a historical cohort receiving a tacrolimus-based protocol (n=205). Patient and graft survival were equivalent between all groups. An increased rate of acute rejection was observed in an initial cohort treated with a protocol similar to the low-intensity regimen from the BENEFIT trial vs the historical tacrolimus group (50.5% vs 20.5%). The addition of a transient course tacrolimus reduced rejection rates to acceptable levels (16%). Treatment with belatacept was associated with superior eGFR (belatacept 63.8ml/min vs tacrolimus 46.2ml/min at 4 years, p<0.0001). There were no differences in serious infections including rates of CMV or BK viremia. We describe the development of a costimulatory blockade-based strategy that ultimately allows renal transplant recipients to achieve CNI-free immunosuppression.

SummaryBackground and objectives The extent to which racial and socioeconomic disparities in access to kidney transplantation are related to not being assessed for transplant suitability before or shortly after the time of initiation of dialysis is not known. The aims of this study were to determine whether there were disparities based on race, ethnicity, or type of insurance in delayed assessment for transplantation and whether delayed assessment was associated with lower likelihood of waitlisting and kidney transplantation. Results Overall, 12.5% of patients had reportedly not been assessed for transplantation. Patients without private insurance were more likely to be reported as not assessed (multivariable adjusted odds ratio=1.33, 95% confidence interval=1.28-1.40 for Medicaid), with a pronounced racial disparity but no ethnic disparity among patients aged 18 to ,35 years (odds ratio=1.27, 95% confidence interval=1.13-1.43; P,0.001 for interaction with age). Not being assessed for transplant around the time of dialysis initiation was associated with lower likelihood of waitlisting in multivariable analysis (hazard ratio=0.59, 95% confidence interval=0.57-0.62 in the first year) and transplantation (hazard ratio=0.46, 95% confidence interval=0.41-0.51 in the first year), especially within the first 2 years.Conclusions Racial and insurance-related disparities in transplant assessment potentially delay transplantation, particularly among younger patients.

Robotic-assisted therapy may be an effective alternative or adjunct to the delivery of intensive task practice interventions to enhance hand function recovery in patients with stroke.