Kidney transplant program waitlisting rate as a metric to assess transplant access

Kidney transplant program performance in the United States is commonly measured by posttransplant outcomes. Inclusion of pretransplant measures could provide a more comprehensive assessment of transplant program performance and necessary information for patient decision-making. In this study, we propose a new metric, the waitlisting rate, defined as the ratio of patients who are waitlisted in a center relative to the person-years referred for evaluation to a program. Furthermore, we standardize the waitlisting rate relative to the state average in Georgia, North Carolina, and South Carolina. The new metric was used as a proof-of-concept to assess transplant-program access compared to the existing transplant rate metric. The study cohorts were defined by linking 2017 United States Renal Data System (USRDS) data with transplant-program referral data from the Southeastern United States between January 1, 2012 and December 31, 2016. Waitlisting rate varied across the 9 Southeastern transplant programs, ranging from 10 to 22 events per 100 patient-years, whereas the program-specific waitlisting rate ratio ranged between 0.76 and 1.33. Program-specific waitlisting rate ratio was uncorrelated with the transplant rate ratio (r = −.15, 95% CI, −0.83 to 0.57). Findings warrant collection of national data on early transplant steps, such as referral, for a more comprehensive assessment of transplant program performance and pretransplant access.     

Racial and Ethnic Disparities in Genetic Testing at a Hereditary Breast and Ovarian Cancer Center

BackgroundPrior studies suggest that referral to genetic counseling and completion of genetic testing vary by race/ethnicity; however, the data are limited.ObjectiveWe sought to evaluate patterns of genetic testing and clinical outcomes across race/ethnicity at a hereditary breast and ovarian cancer center.DesignThe medical records for all patients undergoing genetic assessment at a hereditary breast and ovarian cancer center were reviewed and stratified by self-reported race/ethnicity (non-Hispanic White, Hispanic, non-Hispanic Black, and Asian).ParticipantsA total of 1666 patients met inclusion criteria (non-Hispanic Whites, 1367; Hispanics, 85, non-Hispanic Blacks, 101; Asians, 113).Main MeasuresDemographics, patient characteristics, and referral patterns for patients who underwent genetic testing were analyzed using Kruskal-Wallis tests, chi-square test, or Fisher’s exact tests, stratifying by self-reported race/ethnicity. Pathogenic mutations and variants of unknown significance (VUS) were reviewed. Outcomes of patients with genetic mutations and personal history of breast and/or gynecologic malignancies were compared.Key ResultsNon-Hispanic Whites were more likely to be referred due to family cancer history compared to all other ethnicities while Non-Hispanic Blacks, Hispanics, and Asians were more likely to be referred due to personal history of cancer (p < 0.001). Non-Hispanic Blacks and Hispanics were more likely to have advanced-stage cancer at the time of genetic testing (p < 0.02). Rates of mutations did not differ by race/ethnicity when Ashkenazi Jewish patients were excluded (p = 0.08). Among patients found to have a BRCA1/2 mutation, Non-Hispanic Whites were more likely to undergo cancer screening and risk-reducing surgery compared with all other ethnicities (p = 0.04).ConclusionsMinority patients were more likely to utilize genetic services following a cancer diagnosis and less likely due to family cancer history, suggesting a missed opportunity for mutation detection and cancer prevention in this population. Efforts to eradicate racial/ethnic disparities in early access to genetic testing and guided cancer prevention strategies are essential.Electronic supplementary materialThe online version of this article (10.1007/s11606-020-06064-x) contains supplementary material, which is available to authorized users.     

Increased levels of interleukin-10 and IgG3 are hallmarks of Indian post-kala-azar dermal leishmaniasis

BACKGROUND: Post-kala-azar dermal leishmaniasis (PKDL), an established sequela of visceral leishmaniasis (VL), is proposed to facilitate anthroponotic transmission of VL, especially during interepidemic periods. Immunopathological mechanisms responsible for Indian PKDL are still poorly defined. METHODS: Our study attempted to characterize the immune profiles of patients with PKDL or VL relative to that of healthy control subjects by immunophenotyping, intracellular cytokine staining of peripheral blood mononuclear cells, and enzyme-linked immunosorbent assay for serum cytokines and immunoglobulin G (IgG) subclasses. RESULTS: Patients with PKDL had significantly raised percentages of peripheral CD3+CD8+ cells compared with control subjects, a difference that persisted after cure. Patients with PKDL showed an intact response to phytohemagglutinin, with the percentages of lymphocytes expressing interferon (IFN)-gamma, interleukin (IL)-2, IL-4, and IL-10 being comparable to those in control subjects. Patients with VL had decreased IFN-gamma and IL-2 expression, which was restored after cure, and increased IL-10 expression, which persisted after cure. In their response to Leishmania donovani antigen, patients with PKDL showed a 9.6-fold increase in the percentage of IL-10-expressing CD3+CD8+ lymphocytes compared with control subjects, and this percentage decreased with treatment. Patients with PKDL had raised levels of IgG3 and IgG1 (surrogate markers for IL-10), concomitant with increased serum levels of IL-10. CONCLUSIONS: IL-10-producing CD3+CD8+ lymphocytes are important protagonists in the immunopathogenesis of Indian PKDL.     

Mechanistic insight into the improved Li ion conductivity of solid polymer electrolytes

Polymer based solid electrolytes (SEs) are envisaged as futuristic components of safer solid state energy devices. But the semi-crystalline nature and slow dynamics of the host polymer matrix are found to hamper the ion transport through the solid polymer network and hence solid state devices are still far beyond the scope of practical application. In this study, we unravel the synergistic roles of Li salt (LiClO₄) and two different polymers – polyethylene oxide (PEO) and polydimethyl siloxane (PDMS), in the Li ion transport through their solid blend based electrolyte. A detailed study using dielectric spectroscopy and thermo-mechanical analysis is conducted to understand the tunability of the PEO chain dynamics with LiClO₄ and the mechanism of hopping of Li ions by forming ion pairs with oxygen dipoles on the PEO backbone is established. Despite the lack of PDMS''s capability to solvate ions and promote ion transport directly, its proper mixing within the PEO host matrix is demonstrated to enhance ion transport due to the influence of PDMS on the segmental dynamics of PEO. A detailed molecular dynamics study supported by experimental validation suggests that even inert polymers can affect the dynamics of the active host matrix and increase ion transport, leading to next generation high ionic conductivity solid matrices, and opens new avenues in designing polymer based transparent electrolytes.

The studies shown here prove that both the Li salt and ‘inert-polymer’ mixing have paramount importance in the tunability of Li ion conductivity in solid electrolytes for batteries.     

The relative distribution of membranous and cytoplasmic met is a prognostic indicator in stage I and II colon cancer

PURPOSE: The association hepatocyte growth factor receptor (Met) tyrosine kinase with prognosis and survival in colon cancer is unclear, due in part to the limitation of detection methods used. In particular, conventional chromagenic immunohistochemistry (IHC) has several limitations including the inability to separate compartmental measurements. Measurement of membrane, cytoplasm, and nuclear levels of Met could offer a superior approach to traditional IHC. EXPERIMENTAL DESIGN: Fluorescent-based IHC for Met was done in 583 colon cancer patients in a tissue microarray format. Using curvature and intensity-based image analysis, the membrane, nuclear, and cytoplasm were segmented. Probability distributions of Met within each compartment were determined, and an automated scoring algorithm was generated. An optimal score cutpoint was calculated using 500-fold crossvalidation of a training and test data set. For comparison with conventional IHC, a second array from the same tissue microarray block was 3,3'-diaminobenzidine immunostained for Met. RESULTS: In crossvalidated and univariate Cox analysis, the membrane relative to cytoplasm Met score was a significant predictor of survival in stage I (hazard ratio, 0.16; P = 0.006) and in stage II patients (hazard ratio, 0.34; P < or = 0.0005). Similar results were found with multivariate analysis. Met in the membrane alone was not a significant predictor of outcome in all patients or within stage. In the 3,3'-diaminobenzidine-stained array, no associations were found with Met expression and survival. CONCLUSIONS: These data indicate that the relative subcellular distribution of Met, as measured by novel automated image analysis, may be a valuable biomarker for estimating colon cancer prognosis.     

Variation in Fourier transform infrared spectra of some homeopathic potencies and their diluent media

OBJECTIVE: The aim of this study was to determine whether potentized homeopathic drugs and their diluent media differ from each other with respect to their Fourier transform infrared (FTIR) spectra. DESIGN: FTIR spectra of Nux vomica 30C, Lycopodium 30C, Santonin 30C, Cina 30C, Cina 206C, Cina 1006C, and their diluent media 90% ethanol and Ethanol 30C were obtained in the wave number range of 2000-1000 cm1 at 20 degrees C. Potassium bromide powder soaked with the potencies, pressed into pellets, and air dried were used to measure the spectra. Because water structures in homeopathic potencies are thought to carry specific information on drug molecules and because O-H bending vibrational band (v2) exclusively belongs to water, the study was restricted to the bands in that wave number region. Alcohol has no absorption in the O-H bending region. RESULTS: The potencies were found to differ from each other and their diluent media in the number of v2 bands, their wave number (cm1), shape, and half-width (cm1) of the bands. CONCLUSIONS: The number and other characteristics of the v2 band represent the number of hydrogen-bonded water species and their hydrogen-bonding strength, respectively. The potencies and their diluent media therefore differ from each other in the number of hydrogen-bonded water species and their hydrogen-bonding strength. The observation that KBr pellets soaked with a potentized drug retains its specific spectral absorption properties simply confirms that medicated sucrose globules, used in homeopathic dispensing, are capable of retaining the therapeutic properties of the drug.