Citations

AbstractThe histopathology of cardiac xenograft rejection has evolved over the last 20 yr with the development of new modalities for limiting antibody‐mediated injury, advancing regimens for immune suppression, and an ever‐widening variety of new donor genetics. These new technologies have helped us progress from what was once an overwhelming anti‐Gal‐mediated hyperacute rejection to a more protracted anti‐Gal‐mediated vascular rejection to what is now a more complex manifestation of non‐Gal humoral rejection and coagulation dysregulation. This review summarizes the changing histopathology of Gal‐ and non‐Gal‐mediated cardiac xenograft rejection and discusses the contributions of immune‐mediated injury, species‐specific immune‐independent factors, transplant and therapeutic procedures, and donor genetics to the overall mechanism(s) of cardiac xenograft rejection.

ABSTRACT The detection of pathogens associated with gastrointestinal disease may be important in certain patient populations, such as immunocompromised hosts, the critically ill, or individuals with prolonged disease that is refractory to treatment. In this study, we evaluated two commercially available multiplex panels (the FilmArray gastrointestinal [GI] panel [BioFire Diagnostics, Salt Lake City, UT] and the Luminex xTag gastrointestinal pathogen panel [GPP] [Luminex Corporation, Toronto, Canada]) using Cary-Blair stool samples ( n = 500) submitted to our laboratory for routine GI testing (e.g., culture, antigen testing, microscopy, and individual real-time PCR). At the time of this study, the prototype (non-FDA-cleared) FilmArray GI panel targeted 23 pathogens (14 bacterial, 5 viral, and 4 parasitic), and testing of 200 μl of Cary-Blair stool was recommended. In contrast, the Luminex GPP assay was FDA cleared for the detection of 11 pathogens (7 bacterial, 2 viral, and 2 parasitic), but had the capacity to identify 4 additional pathogens using a research-use-only protocol. Importantly, the Luminex assay was FDA cleared for 100 μl raw stool; however, 100 μl Cary-Blair stool was tested by the Luminex assay in this study. Among 230 prospectively collected samples, routine testing was positive for one or more GI pathogens in 19 (8.3%) samples, compared to 76 (33.0%) by the FilmArray and 69 (30.3%) by the Luminex assay. Clostridium difficile (12.6 to 13.9% prevalence) and norovirus genogroup I (GI)/GII (5.7 to 13.9% prevalence) were two of the pathogens most commonly detected by both assays among prospective samples. Sapovirus was also commonly detected (5.7% positive rate) by the FilmArray assay. Among 270 additional previously characterized samples, both multiplex panels demonstrated high sensitivity (>90%) for the majority of targets, with the exception of several pathogens, notably Aeromonas sp. (23.8%) by FilmArray and Yersinia enterocolitica (48.1%) by the Luminex assay. Interestingly, the FilmArray and Luminex panels identified mixed infections in 21.1% and 13.0% of positive prospective samples, respectively, compared to only 8.3% by routine methods.

Objectives. We examined whether a proactive care smoking cessation intervention designed to overcome barriers to treatment would be especially effective at increasing cessation among African Americans receiving care in the Veterans Health Administration. Methods. We analyzed data from a randomized controlled trial, the Veterans Victory over Tobacco study, involving a population-based electronic registry of current smokers (702 African Americans, 1569 Whites) and assessed 6-month prolonged smoking abstinence at 1 year via a follow-up survey of all current smokers. We also examined candidate risk adjustors for the race effect on smoking abstinence. Results. The interaction between patient race and intervention condition (proactive care vs usual care) was not significant. Overall, African Americans had higher quit rates than Whites (13% vs 9%; P < .006) regardless of condition. Conclusions. African Americans quit at higher rates than Whites. These findings may be a result of the large number of veterans receiving smoking cessation services and the lack of racial differences in receipt of these services as well as racial differences in smoking history, self-efficacy, and motivation to quit that favor African Americans.

Abstract Recent studies provide a functional link between kallikrein 6 (Klk6) and the development and progression of disease in patients with multiple sclerosis (MS) and in its murine models. To evaluate the involvement of additional kallikrein family members, we compared Klk6 expression with four other kallikreins (Klk1, Klk7, Klk8, and Klk10) in the brain and spinal cord of mice infected with Theiler’s murine encephalomyelitis virus, an experimental model of progressive MS. The robust upregulation of Klk6 and Klk8 in the brain during the acute phase of viral encephalitis and in the spinal cord during disease development and progression points to their participation in inflammation, demyelination, and progressive axon degeneration. More limited changes in Klk1, Klk7, and Klk10 were also observed. In addition, Klk1, Klk6, and Klk10 were dynamically regulated in T cells in vitro as a recall response to viral antigen and in activated monocytes, pointing to their activities in the development of adaptive and innate immune function. Together, these results point to overlapping and unique roles for multiple kallikreins in the development and progression of virus-mediated central nervous system inflammatory demyelinating disease, including activities in the development of the adaptive and innate immune response, in demyelination, and in progressive axon degeneration.

Background Cardiac allograft vasculopathy is the leading cause of graft failure and death in heart transplant ( HT x) recipients; however, the association between the etiology of heart failure (ischemic cardiomyopathy [ ICM ] or non‐ ICM ) that led to HT x and progression of c ardiac allograft vasculopathy , and adverse events after HT x has not been explored. Methods and Results We retrospectively included 165 HT x patients, who were followed‐up with at least 2 virtual histology–intravascular ultrasound examinations after HT x, and grouped them as ICM (n=46) or non‐ ICM (n=119). Coronary artery plaque volume was analyzed using virtual histology–intravascular ultrasound, and cardiovascular event data—a composite of myocardial infarction, hospitalization for heart failure and arrhythmia, revascularization, retransplantation, and death including cardiovascular death—were collected from the medical records of all study subjects. ICM patients had significantly higher plaque volume at both first ( P =0.040) and follow‐up ( P =0.015) intravascular ultrasound examinations. After multivariate adjustment for traditional coronary risk factors, ICM was significantly associated with plaque progression (odds ratio 3.10; CI 1.17 to 9.36; P =0.023). Ten‐year cardiovascular event‐free survival was 50% in ICM patients compared with 84% in non‐ ICM patients (log‐rank test P =0.003). In multivariate Cox proportional hazard analysis, ICM was significantly associated with a higher event rate after HT x (hazard ratio 2.02; 95% CI 1.01 to 4.00; P =0.048). Conclusion Our study demonstrates that ischemic etiology of cardiomyopathy prior to HT x may be independently associated with plaque progression and higher event rate after HT x.

Study Design Case report. Objective Multifocal epithelioid hemangioendothelioma (EHE) of the spine is a rare disorder. We describe a novel, multimodal treatment of a painful osteolytic lumbar lesion secondary to EHE. The minimally invasive treatment results in an excellent patient outcome with decreased morbidity compared to traditional techniques. Methods A previously healthy young adult presented with a painful osteolytic lesion at the L2 vertebrae. Imaging revealed multifocal spinal lesions consistent with a history of EHE. Core needle biopsy confirmed the diagnosis. Preoperative cryoablation of L2 was followed by a staged surgery, which included a partial L2 corpectomy, tumor resection, bone grafting, and vertebral reconstruction using a minimally invasive technique. This treatment was followed by prolonged therapy with interferon and bisphosphonate. Results At 3.5 years’ follow-up, the patient has maintained his vertebral body height, has not required a fusion, and has had no recurrence of disease. Conclusion Multimodal treatment consisting of tumor cryoablation, partial corpectomy, allograft reconstruction of the vertebrae, and adjuvant interferon and bisphosphonate can result in good outcomes for well-contained EHE tumors of the spine.

Background: More stringent accuracy guidelines for hospital-use glucose meters have recently been published, but it remains unclear whether glucose meters can meet these accuracy guidelines when measurement is performed on critically ill patients with fresh whole blood samples. Materials and Methods: We performed a retrospective evaluation of a conventional (Roche Diagnostics [Indianapolis, IN] AccuChek ® Inform) and a newer-generation (Nova Biomedical [Waltham, MA] StatStrip ® ) glucose system by comparing paired (drawn within 5 min of each other) whole blood glucose meter and laboratory serum glucose values obtained from intensive care unit (ICU) patients. We also performed a prospective evaluation of the accuracy of the Nova StatStrip. Results: The median (interquartile range) bias between Roche AccuChek Inform and serum laboratory glucose measurements was 11 (6–18) mg/dL, compared with a median bias between the Nova StatStrip and serum glucose measurements of 1 (−5 to 5) mg/dL. StatStrip met International Organization for Standardization 15197 and Clinical and Laboratory Standards Institute (CLSI) POCT12-A3 accuracy guidelines using both retrospective and prospective datasets. Conclusions: The newer-generation (StatStrip) glucose meter met more stringent CLSI POCT12-A3 accuracy criteria because of reduced bias compared with the previous-generation device. Reduced glucose meter bias led to fewer insulin dosing discrepancies when the insulin dose determined from serum glucose was compared with that determined from the glucose meter value using the institutional glycemic control protocol.

The Sleeping Beauty (SB) transposon system has been shown to mediate new gene sequence integration resulting in long-term expression. Here the effectiveness of hyperactive SB100X transposase was tested, and we found that hydrodynamic co-delivery of a firefly luciferase transposon (pT2/CaL) along with SB100X transposase (pCMV-SB100X) resulted in remarkably sustained, high levels of luciferase expression. However, after 4 weeks there was a rapid, animal-by-animal loss of luciferase expression that was not observed in immunodeficient mice. We hypothesized that this sustained, high-level luciferase expression achieved using the SB100X transposase elicits an immune response in pT2/CaL co-administered mice, which was supported by the rapid loss of luciferase expression upon challenge of previously treated animals and in naive animals adoptively transferred with splenocytes from previously treated animals. Specificity of the immune response to luciferase was demonstrated by increased cytokine expression in splenocytes after exposure to luciferase peptide in parallel with MHC I–luciferase peptide tetramer binding. This anti-luciferase immune response observed following continuous, high-level luciferase expression in vivo clearly impacts its use as an in vivo reporter. As both an immunogen and an extremely sensitive reporter, luciferase is also a useful model system for the study of immune responses following in vivo gene transfer and expression.