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OBJECTIVE New-onset diabetes after kidney transplantation (NODAT) has adverse clinical and economic implications. A risk score for NODAT could help identify research subjects for intervention studies. RESEARCH DESIGN AND METHODS We conducted a single-center retrospective cohort study using pretransplant clinical and laboratory measurements to construct a risk score for NODAT. NODAT was defined by hemoglobin A1c (HbA1c) ≥6.5%, fasting serum glucose ≥126 mg/dL, or prescribed therapy for diabetes within 1 year posttransplant. Three multivariate logistic regression models were constructed: 1) standard model, with both continuous and discrete variables; 2) dichotomous model, with continuous variables dichotomized at clinically relevant cut points; and 3) summary score defined as the sum of the points accrued using the terms from the dichotomous model. RESULTS A total of 316 subjects had seven pretransplant variables with P < 0.10 in univariate logistic regression analyses (age, planned corticosteroid therapy posttransplant, prescription for gout medicine, BMI, fasting glucose and triglycerides, and family history of type 2 diabetes) that were selected for multivariate models. Areas under receiver operating curves for all three models were similar (0.72, 0.71, and 0.70). A simple risk score calculated as the sum of points from the seven variables performed as well as the other two models in identifying risk of NODAT. CONCLUSIONS A risk score computed from seven simple pretransplant variables can identify risk of NODAT.

Object The authors sought to identify the presence of a “July effect,” a transient increase in adverse outcomes during July, among a cohort of spontaneous subarachnoid hemorrhage (SAH) admissions recorded in the National Inpatient Sample (NIS). Methods The discharge status, admission month, patient demographics, treatment parameters, and hospital characteristics among spontaneous SAH admissions were extracted from the 2001–2008 NIS. Multivariate regression was used to determine whether an unfavorable discharge status and/or in-hospital mortality significantly increased in summer months in a pattern suggestive of a July effect. Additional models were generated to assess the impact of hospital teaching status on these outcomes. Results Among 57,663,486 hospital admissions from the 2001–2008 NIS, 52,879 cases of spontaneous SAH (ICD-9-CM 430) were treated at teaching (36,914 cases [70%]) and nonteaching (15,965 cases [30%]) facilities. Regression models failed to reveal a July effect for in-hospital mortality (χ2 = 0.75, p = 1.000) or unfavorable discharges (χ2 = 1.69, p = 0.999) among monthly SAH admissions, although they did suggest a significant reduction in these outcomes (in-hospital mortality, OR = 0.89, p < 0.001; unfavorable discharges, OR = 0.88, p < 0.001) among teaching hospitals as compared with nonteaching hospitals after adjustment for disparities in demographic, treatment, and hospital characteristics. Conclusions The discharge disposition among SAH admissions within the NIS was not suggestive of a July effect but did reveal that teaching institutions have significantly lower rates of adverse outcomes when compared with nonteaching hospitals. Note, however, that the origins of this difference related to teaching status remain unclear.

Abstract Background Accelerated recovery pathways may reduce length of hospital stay after surgery but there are few data on minimally invasive colorectal operations. Methods An enhanced recovery pathway (ERP) was instituted, including preoperative analgesia, limited intravenous fluids and opiates, and early feeding. Intrathecal analgesia was administered as needed, but epidural analgesia was not used. The first 66 patients subjected to the ERP were case-matched by surgeon, procedure and age (within 5 years) with patients treated previously in a fast-track pathway (FTP). Short-term and postoperative outcomes to 30 days were compared. Results Hospital stay was shorter with the ERP than the FTP: median (interquartile range, i.q.r.) 3 (2–3) versus 3 (3–5) days (P &lt; 0·001). A 2-day hospital stay was achieved in 44 and 8 per cent of patients respectively (P &lt; 0·001). Patients in the ERP had a shorter time to recovery of bowel function: median (i.q.r.) 1 (1–2) versus 2 (2–3) days (P &lt; 0·001). Thirty-day complication rates were similar (32 per cent ERP, 27 per cent FTP; P = 0·570). Readmissions within 30 days were more common with ERP, but the difference was not statistically significant (10 versus 5 patients; P = 0·170). Total hospital stay for those readmitted was shorter in the ERP group (18 versus 23 days). Conclusion ERP decreased the length of hospital stay after minimally invasive colorectal surgery. Copyright © 2011 British Journal of Surgery Society Ltd. Published by John Wiley & Sons, Ltd.

Ano1 is a recently discovered Ca2+-activated Cl− channel expressed on interstitial cells of Cajal (ICC) that has been implicated in slow-wave activity in the gut. However, Ano1 is expressed on all classes of ICC, even those that do not contribute to generation of the slow wave, suggesting that Ano1 may have an alternate function in these cells. Ano1 is also highly expressed in gastrointestinal stromal tumors. Mice lacking Ano1 had fewer proliferating ICC in whole mount preparations and in culture, raising the possibility that Ano1 is involved in proliferation. Cl− channel blockers decreased proliferation in cells expressing Ano1, including primary cultures of ICC and in the pancreatic cancer-derived cell line, CFPAC-1. Cl− channel blockers had a reduced effect on Ano1(−/−) cultures, confirming that the blockers are acting on Ano1. Ki67 immunoreactivity, 5-ethynyl-2′-deoxyuridine incorporation, and cell-cycle analysis of cells grown in low-Cl− media showed fewer proliferating cells than in cultures grown in regular medium. We confirmed that mice lacking Ano1 had less phosphorylated retinoblastoma protein compared with controls. These data led us to conclude that Ano1 regulates proliferation at the G1/S transition of the cell cycle and may play a role in tumorigenesis.

Background and Purpose— Ischemic stroke has a strong familial component to risk. The Siblings With Ischemic Stroke Study (SWISS) is a genome-wide, family-based analysis that included use of imputed genotypes. The Siblings With Ischemic Stroke Study was conducted to examine the associations between single-nucleotide polymorphisms (SNPs) and risk of stroke and stroke subtypes within pairs. Methods— The Siblings With Ischemic Stroke Study enrolled 312 probands with ischemic stroke from 70 US and Canadian centers. Affected siblings were ascertained by centers and confirmed by central record review; unaffected siblings were ascertained by telephone contact. Ischemic stroke was subtyped according to Trial of Org 10172 in Acute Stroke Treatment criteria. Genotyping was performed with an Illumina 610 quad array (probands) and an Illumina linkage V array (affected siblings). SNPs were imputed by using 1000 Genomes Project data and MACH software. Family-based association analyses were conducted by using the sibling transmission-disequilibrium test. Results— For all pairs, the correlation of age at stroke within pairs of affected siblings was r =0.83 (95% CI, 0.78–0.86; P <2.2×10 −16 ). The correlation did not differ substantially by subtype. The concordance of stroke subtypes among affected pairs was 33.8% (kappa=0.13; P =5.06×10 −4 ) and did not differ by age at stroke in the proband. Although no SNP achieved genome-wide significance for risk of ischemic stroke, there was clustering of the most associated SNPs on chromosomes 3p and 6p. Conclusions— Stroke subtype and age at stroke in affected sibling pairs exhibit significant clustering. No individual SNP reached genome-wide significance. However, 2 promising candidate loci were, although these risk loci warrant further examination in larger sample collections.

Employing general strain theory, the authors examine gender differences in the dynamic strain-and-coping relations between GPA, depression, and drinking. Using longitudinal high school data from the Youth Development Study, the authors test five hypotheses. GPA negatively affects drinking (confirming Hypothesis 1), but without consistent gender differences (Hypothesis 1a). GPA also negatively affects depression (Hypothesis 2), and more strongly for girls (Hypothesis 2a). Depression's positive effect on drinking supports Hypothesis 3, but gender comparisons refute Hypothesis 3a. Conversely, drinking positively affects lagged depression (Hypothesis 4), and more strongly for girls (Hypothesis 4a). Finally, drinking's largely absent effect on GPA rejects Hypothesis 5a, whereas depression's negative effect on lagged GPA, stronger among girls, supports Hypothesis 5b and Hypothesis 5c. A deleterious chain of effects occurs across high school, but mostly for girls only, possibly implicating gendered behavioral norms and socialization. This study informs general strain theory by suggesting that alcohol may provide divergent behavioral and emotional coping functions, respectively, for boys and girls.

The pathogenesis of multiple sclerosis (MS) remains elusive. Recent reports advocate greater involvement of B cells and immunoglobulins in the initiation and propagation of MS lesions at different stages of their ontogeny. The key role of B cells and immunoglobulins in pathogenesis was initially identified by studies in which patients whose fulminant attacks of demyelination did not respond to steroids experienced remarkable functional improvement following plasma exchange. The positive response to Rituximab in Phase II clinical trials of relapsing-remitting MS confirms the role of B cells. The critical question is how B cells contribute to MS. In this paper, we discuss both the deleterious and the beneficial roles of B cells and immunoglobulins in MS lesions. We provide alternative hypotheses to explain both damaging and protective antibody responses.

Background— Operative mortality after left ventricular assist device (LVAD) implantation is heavily influenced by patient selection and the technical difficulty of surgery. However, how we treat our patients and LVAD setting may affect the patient outcome beyond this period. We postulated that the presence of echocardiographic variables 1 month after surgery suggesting appropriate degree of LV unloading and an adequate forward flow would be important in determining clinical outcomes after the initial successful LVAD implantation. Methods and Results— We retrospectively analyzed various variables in echocardiographic examinations performed 30 days after LVAD implant in 76 consecutive patients receiving continuous flow device for their association with a compound end point (90-day mortality, readmission for heart failure, or New York Heart Association class III or higher at the end of the 90-day period). The echocardiographic associations examined included estimated LVAD flow, with and without native LV contribution, interventricular septal position, the status of aortic valve opening, an estimated left atrial pressure (ELAP), the mitral flow E-wave deceleration time, and the ratio of deceleration time to E-wave velocity (mitral deceleration index [MDI]). Four patients died during the 30- to 90-day period, 6 patients were readmitted for heart failure, and 25 patients were considered to have New York Heart Association class III or higher at the end of the 90-day period. Variables associated with adverse outcome included increased ELAP (odds ratio, 1.30 [1.16–1.48]; P <0.0001), MDI <2 ms/[cm/s] (odds ratio, 4.4 implantation [1.22–18]; P =0.02) and decreased tricuspid lateral annulus velocity (odds ratio, 0.70 implantation [0.48–0.95]; P =0.02). A leftward deviation of interventricular septum was associated with a worse outcome (odds ratio, 3.03 implantation [1.21–13.3]; P =0.01). Conclusions— Mortality and heart failure after LVAD surgery appear to be predominantly determined by echocardiographic evidence of inefficient unloading of the left ventricle and persistence of right ventricular dysfunction. Increased estimated LA pressure and short MDI are associated with worse mid term outcome. Leftward deviation of the septum is associated with worse outcome as well.