Congenic hematopoietic stem cell transplantation promotes survival of heart allografts in murine models of acute and chronic rejection.

The ability to induce tolerance would be a major advance in the field of solid organ transplantation. Here, we investigated whether autologous (congenic) hematopoietic stem cell transplantation (HSCT) could promote tolerance to heart allografts in mice. In an acute rejection model, fully MHC-mismatched BALB/c hearts were heterotopically transplanted into C57BL/6 (CD45.2) mice. One week later, recipient mice were lethally irradiated and reconstituted with congenic B6 CD45.1 Lin-Sca1+ckit+ cells. Recipient mice received a 14-day course of rapamycin both to prevent rejection and to expand regulatory T cells (Tregs). Heart allografts in both untreated and rapamycin-treated recipients that did not undergo HSCT were rejected within 33 days (median survival time = 8 days for untreated recipients, median survival time = 32 days for rapamycin-treated recipients), whereas allografts in HSCT-treated recipients had a median survival time of 55 days (P < 0.001 vs. both untreated and rapamycin-treated recipients). Enhanced allograft survival following HSCT was associated with increased intragraft Foxp3+ Tregs, reduced intragraft B cells, and reduced serum donor-specific antibodies. In a chronic rejection model, Bm12 hearts were transplanted into C57BL/6 (CD45.2) mice, and congenic HSCT was performed two weeks following heart transplantation. HSCT led to enhanced survival of allografts (median survival time = 70 days vs. median survival time = 28 days in untreated recipients, P < 0.01). Increased allograft survival post-HSCT was associated with prevention of autoantibody development and absence of vasculopathy. These data support the concept that autologous HSCT can promote immune tolerance in the setting of allotransplantation. Further studies to optimize HSCT protocols should be performed before this procedure is adopted clinically.

Appropriate utilization of cardiac computed tomography for the assessment of stable coronary artery disease.

BACKGROUND: Appropriate use criteria (AUC) have been developed in response to growth in cardiac imaging utilization and concern regarding associated costs. Cardiac computed tomography angiography (CCTA) has emerged as an important modality in the evaluation of coronary artery disease, however its appropriate utilization in actual practice is uncertain. Our objective was to determine the appropriate utilization of CCTA in a large quaternary care institution and to compare appropriate utilization pre and post publication of the 2013 AUC guidelines. We hypothesized that the proportion of appropriate CCTA utilization will be similar to those of other comparable cardiac imaging modalities and that there would be a significant increase in appropriate use post AUC publication. METHODS: We employed a retrospective cohort study design of 2577 consecutive patients undergoing CCTA between January 1, 2012 and December 30, 2016. An appropriateness category was assigned for each CCTA. Appropriateness classifications were compared pre- and post- AUC publication via the chi-square test. RESULTS: Overall, 83.5% of CCTAs were deemed to be appropriate based on the AUC. Before the AUC publication, 75.0% of CCTAs were classified as appropriate whereas after the AUC publication, 88.0% were classified as appropriate (p < 0.001). The increase in appropriate utilization, when extrapolated to the Medicare population of the United States, was associated with potential cost savings of approximately $57 million per year. CONCLUSIONS: We report a high rate of appropriate use of CCTA and a significant increase in the proportion of CCTAs classified as appropriate after the AUC publication.

Evaluation of a Novel Global Immunity Assay to Predict Infection in Organ Transplant Recipients.

Background: Solid organ transplant recipients (SOTRs) are predisposed to infection due to the need for lifelong immunosuppression, although tools to measure the overall degree of immunosuppression are limited. In this study, we used a novel global cell-mediated immunity (CMI) assay to quantify the degree of immunosuppression and predict subsequent infections. Methods: Consecutive SOTRs were enrolled and provided whole blood to conduct the global CMI assay (QuantiFERON Monitor) at 1, 3, and 6 months posttransplant. The assay measures plasma interferon gamma (IFN-γ) levels after stimulation of whole blood with antigens that stimulate both innate and adaptive immunity. Bacterial, viral, and fungal infections were prospectively recorded. Results: We enrolled 137 patients who provided CMI measurements on at least 1 study timepoint. Median age was 58 years; transplant types were kidney (32.1%), liver (30.7%), and lung (36.5%). At least 1 episode of infection occurred in 32 of 137 (23.4%) patients between 1 and 3 months, 34 of 135 (25.1%) between 3 and 6 months, and 39 of 132 (29.5%) between 6 and 12 months. IFN-γ levels were significantly lower in those with at least 1 episode of infection vs no infection at month 1 (P = .04), month 3 (P = .05), and month 6 (P = .006). Patients who developed opportunistic infections (OIs) also showed a significantly lower CMI than those without OI at months 3 and 6. Using a cutoff value of ≤10 IU/mL of IFN-γ, there was a 2- to 3-fold greater likelihood of subsequent infection in those with lower CMI. Conclusions: We show that a novel global immunity assay is able to quantify the level of immunosuppression and predict the risk of subsequent infection episodes in organ transplant recipients.

Ultrasound utilization for implantation of cardiac implantable electronic devices.

Ultrasound (US) guidance for implantation of cardiac implantable electronic devices (CIED) is currently not routine practice. This article sought to review published data on the use of ultrasound in each of the major surgical steps involved in implantation of CIEDs, including achieving anesthesia, obtaining venous access and implantation of leads. A literature review was performed, revealing a total of 20 peer-reviewed studies that assessed US guidance for CIED implantation; 3 of these were randomized trials while the remainder were mostly feasibility studies. The available data suggest that ultrasound can be useful in guiding implantation of CIEDs, with a trend towards less complication rates; however, more high-quality studies that compare US guidance to traditional techniques in CIED implantation are required.

A Novel Nerve Block Technique for a Patient Undergoing Cardiac Device Implantation.

A woman with type 1 myotonic dystrophy received an implantable cardioverter-defibrillator using a novel combination of ultrasound-guided supraclavicular nerve and pectoral nerve blocks. The entire procedure was completed without any procedural sedation or local anesthetic, and the patient did not experience any pain during or after the procedure. (Level of Difficulty: Advanced.).

Predictive and prognostic values of ERCC1 and XRCC1 in biliary tract cancers.

AIMS: To investigate the predictive and prognostic values of DNA repair genes excision repair cross-complementation group 1 (ERCC1) and X-ray repair cross-complementing group 1 (XRCC1) in tumour samples from patients with a diagnosis of biliary tract cancer (BTC). METHODS: Expressions of ERCC1 and XRCC1 were determined by immunohistochemistry (IHC) for 160 patients with BTC and association with clinicopathological features and patient survival was performed to evaluate their predictive and prognostic values. RESULTS: Neoplastic tissue showed much lower nuclear expression compared with non-neoplastic tissue for ERCC1 (median immunostaining score (IS)=0.7 (95% CI 0.2 to 1.3) vs 8.0 (95% CI 5.5 to 8.0), p<0.001) and XRCC1 (median IS=4.0 (95% CI 3.0 to 5.5) vs 8.0 (95% CI 8.0 to 12.0), p<0.001). High nuclear expression of both proteins was able to predict better overall survival (OS) in patients with gallbladder adenocarcinoma, distal bile duct and perihilar cholangiocarcinoma undergoing gemcitabine as adjuvant therapy (ERCC1: median OS estimate=39.7 vs 22.9 months, p=0.011; XRCC1: median OS estimate=33.8 vs 14.6 months, p=0.005). Intense cytoplasmic expression of XRCC1 was found in 12 patients; these patients had significantly more frequent lymph node metastasis (90.0% vs 48.1%, p=0.017) and worse OS (median estimate=12.6 months vs 25.6 months, p=0.004) and recurrence-free survival (median estimate=5.7 months vs 15.1 months, p=0.011). Vascular invasion was significantly more frequent in patients with low nuclear expression for ERCC1 (58.7% vs 20.9%, p<0.001) and XRCC1 (69.6% vs 30.3%, p=0.001). CONCLUSIONS: IHC expression of ERCC1 and XRCC1 has some predictive and prognostic values in patients with BTC. Nuclear expression of ERCC1 and XRCC1 may be used to predict therapeutic response in patients undergoing gemcitabine monotherapy.