CD69+ resident memory T cells are associated with graft-versus-host disease in intestinal transplantation.

Graft-versus-host disease (GvHD) is a common, morbid complication after intestinal transplantation (ITx) with poorly understood pathophysiology. Resident memory T cells (TRM ) are a recently described CD69+ memory T cell subset localizing to peripheral tissue. We observed that T effector memory cells (TEM ) in the blood increase during GvHD and hypothesized that they derive from donor graft CD69+TRM migrating into host blood and tissue. To probe this hypothesis, graft and blood lymphocytes from 10 ITx patients with overt GvHD and 34 without were longitudinally analyzed using flow cytometry. As hypothesized, CD4+ and CD8+CD69+TRM were significantly increased in blood and grafts of GvHD patients, alongside higher cytokine and activation marker expression. The majority of CD69+TRM were donor derived as determined by multiplex immunostaining. Notably, CD8/PD-1 was significantly elevated in blood prior to transplantation in patients who later had GvHD, and percentages of HLA-DR, CD57, PD-1, and naïve T cells differed significantly between GvHD patients who died vs. those who survived. Overall, we demonstrate that (1) there were significant increases in TEM at the time of GvHD, possibly of donor derivation; (2) donor TRM in the graft are a possible source; and (3) potential biomarkers for the development and prognosis of GvHD exist.

SCAI shock classification in acute myocardial infarction: Insights from the National Cardiogenic Shock Initiative.

OBJECTIVES: We applied the cardiovascular angiography and interventions (SCAI) shock staging system to patients presenting with acute myocardial infarction and cardiogenic shock (AMI-CS) who were enrolled in the National Cardiogenic Shock Initiative (NCSI). BACKGROUND: The SCAI shock staging system provides a framework for evaluation of patients with CS based on clinical and hemodynamic parameters, but has not been validated in patients with AMI-CS managed with a contemporary treatment algorithm that incorporates early use of Impella. METHODS: Consecutive patients enrolled in NCSI were identified, all of whom were managed with invasive hemodynamic guidance and supported with Impella. Patients were retrospectively categorized into appropriate SCAI shock stages, and outcomes were assessed accordingly. RESULTS: A total of 300 patients were included in the analysis; 182 patients (61%) presented in Stage C shock, 25 (8%) in Stage D, and 93 (31%) in Stage E. Survival to hospital discharge was 76, 76, and 58%, respectively (p = .006). Survival was <20% among patients in Stage E at 24 hr, regardless of baseline stage. There was near perfect agreement in shock staging between two independent clinicians at baseline (kappa = 0.975, 95% CI, 0.95-1.00, p < .001) and at 24 hr (kappa = 0.985, 95% CI, 0.77-1.00, p < .001). CONCLUSION: In patients with AMI-CS enrolled in NCSI, SCAI Shock classification was reproducible, and predicted survival when applied at presentation and at 24 hr.

Factors Associated With 5- and 10-Year Survival After Intestinal Transplantation in Infants and Children.

OBJECTIVES: Intestinal transplantation is an option for permanent intestinal failure with parenteral nutrition intolerance. We sought to determine long-term intestinal graft survival in pediatric patients at our center and to identify factors influencing survival. METHODS: Retrospective chart review of 86 patients transplanted between 2003 and 2013, targeting potential explanatory variables related to demographics, perioperative factors, and postoperative complications. RESULTS: Intestinal graft survival was 71% and 65% after 5 and 10 years, respectively. Five-year graft survival was attained in 79% of patients with a history of anatomic intestinal failure compared with 45% with functional intestinal failure (P = 0.0055). Compared with nonsurvival, 5-year graft survival was also associated with reduced incidences of graft-versus-host disease (2% vs 16%, P = 0.0237), post-transplant lymphoproliferative disorder (3% vs 24%, P = 0.0067), and de novo donor-specific antibodies (19% vs 57%, P = 0.0451) plus a lower donor-recipient weight ratio (median 0.727 vs 0.923, P = 0.0316). Factors not associated with 5-year intestinal graft survival included graft rejection of any severity and inclusion of a liver graft. Factors associated with graft survival at 10 years were similar to those at 5 years. CONCLUSIONS: In our experience, outcomes in pediatric intestinal transplantation have improved substantially for anatomic but not functional intestinal failure. Graft survival depends on avoidance of severe infectious and immunological complications including GVHD, whereas inclusion of a liver graft provides no obvious survival benefit. Reduced success with functional intestinal failure may reflect inherently increased susceptibility to complications in this group.

Metabolomic Analysis of Liver Tissues for Characterization of Hepatocellular Carcinoma.

Hepatocellular carcinoma (HCC) causes more than half a million annual deaths worldwide. Understanding the mechanisms contributing to HCC development is highly desirable for improved surveillance, diagnosis, and treatment. Liver tissue metabolomics has the potential to reflect the physiological changes behind HCC development. Also, it allows identification of biomarker candidates for future evaluation in biofluids and investigation of racial disparities in HCC. Tumor and nontumor tissues from 40 patients were analyzed by both gas chromatography-mass spectrometry (GC-MS) and liquid chromatography-mass spectrometry (LC-MS) platforms to increase the metabolome coverage. The levels of the metabolites extracted from solid liver tissue of the HCC area and adjacent non-HCC area were compared. Among the analytes detected by GC-MS and LC-MS with significant alterations, 18 were selected based on biological relevance and confirmed metabolite identification. These metabolites belong to TCA cycle, glycolysis, purines, and lipid metabolism and have been previously reported in liver metabolomic studies where high correlation with HCC progression is implied. We demonstrated that metabolites related to HCC pathogenesis can be identified through liver tissue metabolomic analysis. Additionally, this study has enabled us to identify race-specific metabolites associated with HCC.

Thresholds for interpreting the fragility index derived from sample of randomised controlled trials in cardiology: a meta-epidemiologic study.

The fragility index (FI) was proposed as a simplified way to communicate robustness of statistically significant results and their susceptibility to a change of a handful number of events. While this index is intuitive, it is not anchored by a cut-off or a guide for interpretation. We identified cardiovascular trials published in six high impact journals from 2007 to 2021 (500 or more participants and a dichotomous statistically significant primary outcome). We estimated area under curve (AUC) to determine FI value that best predicts whether the treatment effect was precise, defined as adequately powered for a plausible relative risk reduction (RRR) of 25% or 30% or having a CI that is sufficiently narrow to exclude a risk reduction that is too small (close to the null, <0.05). The median FI of 201 included cardiovascular trials was 13 (range 1-172). FI exceeded the number of patients lost to follow-up in 46/201 (22.89%) trials. FI values of 19 and 22 predicted that trials would be precise (powered for RRR of 30% and 25%; respectively, combined with CI that excluded risk reduction <0.05). AUC for meeting these precision criteria was 0.90 (0.86-0.94). In conclusion, FI values that range 19-22 may meet various definitions of precision and can be used as a rule of thumb to suggest that a treatment effect is likely precise and less susceptible to random error. The number of patients lost to follow-up should be presented alongside FI to better illustrate fragility.

Invasive electrophysiological testing to predict and guide permanent pacemaker implantation after transcatheter aortic valve implantation: A meta-analysis.

Background: Atrioventricular conduction abnormalities after transcatheter aortic valve implantation (TAVI) are common. The value of electrophysiological study (EPS) for risk stratification of high-grade atrioventricular block (HG-AVB) and guidance of permanent pacemaker (PPM) implantation is poorly defined. Objective: The purpose of this study was to identify EPS parameters associated with HG-AVB and determine the value of EPS-guided PPM implantation after TAVI. Methods: We performed a systematic review and meta-analysis of studies investigating the value of EPS parameters for risk stratification of TAVI-related HG-AVB and for guidance of PPM implantation among patients with equivocal PPM indications after TAVI. Results: Eighteen studies (1230 patients) were eligible. In 7 studies, EPS was performed only after TAVI, whereas in 11 studies EPS was performed both before and after TAVI. Overall PPM implantation rate for HG-AVB was 16%. AV conduction intervals prolonged after TAVI, with the AH and HV intervals showing the largest magnitude of changes. Pre-TAVI HV >70 ms and the absolute value of the post-TAVI HV interval were associated with subsequent HG-AVB and PPM implantation with odds ratios of 2.53 (95% confidence interval [CI] 1.11-5.81; P = .04) and 1.10 (95% CI 1.03-1.17; P = .02; per 1-ms increase), respectively. In 10 studies, PPM was also implanted due to abnormal EPS findings in patients with equivocal PPM indications post-TAVI (typically new left bundle branch block or transient HG-AVB). Among them, the rate of long-term PPM dependency was 57%. Conclusion: Selective EPS testing may assist in the risk stratification of post-TAVI HG-AVB and in the guidance of PPM implantation, especially in patients with equivocal PPM indications post-TAVI.

Diagnostic accuracy of neuroimaging in emergency department patients with acute vertigo or dizziness: A systematic review and meta-analysis for the guidelines for reasonable and appropriate care in the emergency department.

BACKGROUND: Patients presenting to the emergency department (ED) with acute vertigo or dizziness represent a diagnostic challenge. Neuroimaging has variable indications and yield. We aimed to conduct a systematic review and meta-analysis of the diagnostic test accuracy of neuroimaging for patients presenting with acute vertigo or dizziness. METHODS: An electronic search was designed following patient-intervention-control-outcome (PICO) question-(P) adult patients with acute vertigo or dizziness presenting to the ED; (I) neuroimaging including computed tomography (CT), CT angiography (CTA), magnetic resonance imaging (MRI), magnetic resonance angiography (MRA), and ultrasound (US); (C) MRI/clinical criterion standard; and (O) central causes (stroke, hemorrhage, tumor, others) versus peripheral causes of symptoms. Articles were assessed in duplicate. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were followed. Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) was used to assess certainty of evidence in pooled estimates. RESULTS: We included studies that reported diagnostic test accuracy. From 6309 titles, 460 articles were retrieved, and 12 were included: noncontrast CT scan-six studies, 771 patients, pooled sensitivity 28.5% (95% confidence interval [CI] 14.4%-48.5%, moderate certainty) and specificity 98.9% (95% CI 93.4%-99.8%, moderate certainty); MRI-five studies, 943 patients, sensitivity 79.8% (95% CI 71.4%-86.2%, high certainty) and specificity 98.8% (95% CI 96.2%-100%, high certainty); CTA-one study, 153 patients, sensitivity 14.3% (95% CI 1.8%-42.8%) and specificity 97.7% (95% CI 93.8%-99.6%), CT had higher sensitivity than CTA (21.4% and 14.3%) for central etiology; MRA-one study, 24 patients, sensitivity 60.0% (95% CI 26.2%-87.8%) and specificity 92.9% (95% CI 66.1%-99.8%); US-three studies, 258 patients, sensitivity ranged from 30% to 53.6%, specificity from 94.9% to 100%. CONCLUSIONS: Noncontrast CT has very low sensitivity and MRI will miss approximately one in five patients with stroke if imaging is obtained early after symptom onset. The evidence does not support neuroimaging as the only tool for ruling out stroke and other central causes in patients with acute dizziness or vertigo presenting to the ED.

Persistence of left atrial thrombus in patients with hypertrophic cardiomyopathy and atrial fibrillation.

BACKGROUND: We recently demonstrated that patients with atrial fibrillation (AF) and hypertrophic cardiomyopathy (HCM) have an increased risk of left atrial (LA) thrombus. In this study, we aimed to evaluate thrombus management, thrombus persistence, and thromboembolic events for HCM and non-HCM patients with AF and LA thrombus. METHODS: From a cohort of 2,155 AF patients undergoing transesophageal echocardiography (TEE) for any indication, this study included 122 patients with LA thrombus (64 HCM patients and 58 non-HCM controls). RESULTS: There was no difference in mean CHA2DS2-VASc scores between HCM and control patients (3.9 ± 2.2 vs 3.8 ± 2.0, p = 0.88). Ten (16%) and 4 (7%) patients in the HCM and control groups, respectively, were in sinus rhythm at the time of TEE identifying the LA thrombus (p = 0.13). In all patients, the anticoagulation strategy was modified after the LA thrombus diagnosis. A total of 36 (56%) HCM patients and 34 (59%) control patients had follow-up TEE at median 90 and 62 days, respectively, after index TEE. The HCM group had significantly higher 90-day rates of persistent LA thrombus compared to the control group (88% vs 29%; p < 0.001). In adjusted models, HCM was independently associated with LA thrombus persistence. Among patients with LA thrombus, the 5-year cumulative incidence of thromboembolic events was 11% and 2% in HCM and control groups, respectively (p = 0.22). CONCLUSIONS: Among patients with AF with LA thrombus identified by TEE, those with HCM appear to have a higher risk of LA thrombus persistence than non-HCM patients despite anticoagulation.