Prognostic value of myocardial fibrosis on cardiac magnetic resonance imaging in patients with ischemic cardiomyopathy: A systematic review.

The use of cardiac magnetic resonance imaging (c-MRI) in risk stratification for clinical outcomes of patients with ischemic cardiomyopathy (ICM) remains low. This systematic review investigated the prognostic value of myocardial fibrosis as assessed by late gadolinium enhancement (LGE) on c-MRI in patients with ICM for ventricular tachyarrhythmia, sudden cardiac death (SCD), or all-cause mortality. METHODS: We conducted a systematic review of the electronic databases Pubmed and Embase for relevant prospective English-language studies published between January 1990 and February 2019. All included articles were prospective studies that comprised of human participants older than 18 years with ICM and a primary or secondary prevention implantable cardioverter/defibrillator (ICD); had a sample size >30 participants; had at least 6 months of follow-up; and reported on ventricular tachyarrhythmia, SCD, and all-cause mortality. A total of 90 articles related to ICM were identified and were subsequently screened independently by 2 authors. Pooled sensitivity and specificity of LGE were calculated using random-effects model. RESULTS: Eight studies with 1,085 participants were included in the final analysis. The mean age of patients varied from 43 to 83 years, with most patients being men. The most common comorbidities reported included history of diabetes mellitus (22%-62%), hyperlipidemia (40%-86%), and hypertension (35%-88%). The ejection fraction of each study was reported as mean or median and varied from 22% to 35%. During a follow-up that ranged from 8.5 to 65 months, there were 110 ventricular arrhythmic events reported. The pooled sensitivity and specificity of LGE for ICD therapy delivered for ventricular arrhythmias were 0.79 (95% CI: 0.66-0.87) and 0.28 (95% CI: 0.14-0.46), respectively. For all-cause mortality, the pooled sensitivity and specificity of LGE were 0.76 (95% CI: 0.40-0.93) and 0.41 (95% CI: 0.14-0.75), respectively. Although SCD was of significant interest to our review, only 1 of the studies reported on the association between LGE and SCD, leading to the subsequent exclusion of SCD from the end point analysis. CONCLUSIONS: LGE has high prognostic value in predicting adverse outcomes in patients with ICM and may provide helpful information for clinical decision making related to SCD prevention. Our findings illustrate how LGE may improve current risk stratification, prognostication, and selection of patients with ICM for ICD therapy.

Survival after lung transplantation in recipients with alpha-1-antitrypsin deficiency compared to other forms of chronic obstructive pulmonary disease: a national cohort study.

Alpha-1-antitrypsin deficiency (AATD) is grouped with chronic obstructive pulmonary disease (COPD); however, this may not be appropriate. This study assessed whether AATD confers a different prognosis than COPD following lung transplantation. We employed the United Network for Organ Sharing (UNOS) database, grouping patients by diagnoses of AATD or COPD. Kaplan-Meier methods and Cox modeling were performed to determine the association of diagnosis and overall survival. Of 9569 patients, 1394 (14.6%) had a diagnosis of AATD. Patients with AATD who received a single-lung transplant had reduced 1-year survival [adjusted hazard ratio (AHR): 1.68, 95% CI: 1.26, 2.23]. Among patients who received a bilateral lung transplant, there was no significant difference in survival by diagnosis (AHR for AATD as compared to COPD: 0.96, 95% CI: 0.82, 1.12). After the implementation of the lung allocation score (LAS), there was no significant difference in survival among patients who received a single (AHR: 1.15, 95% CI: 0.69, 1.95) or bilateral (AHR: 0.99, 95% CI: 0.73, 1.34) lung transplant by diagnosis. Lung transplantation is increasingly employed in the care of the patient with COPD. Although recipients undergoing LTX for AATD are at increased risk of both acute rejection and airway dehiscence post-transplant, in the post-LAS era, survival rates are similar for recipients with AATD in comparison with COPD.

Antibody depletion strategy for the treatment of suspected antibody-mediated rejection in lung transplant recipients: Does it work?

BACKGROUND: Donor-specific antibodies (DSAs) after lung transplantation correlate with poor outcomes. The ideal treatment strategy for antibody-mediated rejection AMR is not defined. Our institution implemented an aggressive multimodality protocol for the treatment of suspected AMR. METHODS: Lung transplant recipients with suspected AMR were treated with a standardized protocol of plasma exchange, steroids, bortezomib, rituximab, and intravenous immune globulin. Primary outcome was DSA clearance at 6 months in those alive. Secondary endpoints included preserved allograft function at 6 months, survival at 6 and 12 months and complications due to the protocol. RESULTS: Sixteen lung transplant recipients with documented DSA and allograft dysfunction were included in the analysis. Of the 16 patients, 11 survived to 6 months. Three of those 11 patients (27%) cleared all DSAs within 6 months of the protocol. Four of the 11 patients (36%) had preserved allograft function at 6 months. Overall 12-month patient survival was 56%. Complications included thrombocytopenia (50%) and abdominal pain or gastrointestinal discomfort (18.7%). CONCLUSIONS: This multimodality protocol resulted in clearance of DSAs and preserved lung function in a minority of lung transplant recipients with suspected AMR surviving to 6 months after therapy. There were significant side effects of the protocol.

Racial Differences in Presentation and Outcomes After Peripheral Arterial Interventions: Insights From the NCDR-PVI Registry.

BACKGROUND: We assess the rates of device use and outcomes by race among patients undergoing lower extremity peripheral arterial intervention using the American College of Cardiology National Cardiovascular Data Registry-Peripheral Vascular Intervention (PVI) registry. METHODS: Patients who underwent PVI between April 2014 and March 2019 were included. Socioeconomic status was evaluated using the Distressed Community Index score for patients' zip codes. Multivariable logistic regression was used to assess factors associated with utilization of drug-eluting technologies, intravascular imaging, and atherectomy. Among patients with Centers for Medicare and Medicaid Services data, we compared 1-year mortality, rates of amputation, and repeat revascularizations. RESULTS: Of 63 150 study cases, 55 719 (88.2%) were performed in White patients and 7431 (11.8%) in Black patients. Black patients were younger (67.9 versus 70.0 years), had higher rates of hypertension (94.4% versus 89.5%), diabetes (63.0% versus 46.2%), less likely to be able to walk 200 m (29.1% versus 24.8%), and higher Distressed Community Index scores (65.1 versus 50.6). Black patients were provided drug-eluting technologies at a higher rate (adjusted odds ratio, 1.14 [95% CI, 1.06-1.23]) with no difference in atherectomy (adjusted odds ratio, 0.98 [95% CI, 0.91-1.05]) or intravascular imaging (adjusted odds ratio, 1.03 [95% CI, 0.88-1.22]) use. Black patients experienced a lower rate of acute kidney injury (adjusted odds ratio, 0.79 [95% CI, 0.72-0.88]). In Centers for Medicare and Medicaid Services-linked analyses of 7429 cases (11.8%), Black patients were significantly less likely to have surgical (adjusted hazard ratio, 0.40 [95% CI, 0.17-0.96]) or repeat PVI revascularization (adjusted hazard ratio, 0.42 [95% CI, 0.30-0.59]) at 1 year compared with White patients. There was no difference in mortality (adjusted hazard ratio [0.8-1.4]) or major amputation (adjusted hazard ratio, 2.5 [95% CI, 0.8-7.6]) between Black and White patients. CONCLUSIONS: Black patients presenting for PVI were younger, had higher prevalence of comorbidities and lower socioeconomic status. After adjustment, Black patients were less likely to have surgical or repeat PVI revascularization after the index PVI procedure.

Risk stratification using late gadolinium enhancement on cardiac magnetic resonance imaging in patients with hypertrophic cardiomyopathy: A systematic review and meta-analysis.

Background The role of late gadolinium enhancement (LGE) on cardiac magnetic resonance imaging (c-MRI) for predicting outcomes of patients with hypertrophic cardiomyopathy (HCM) has been debated. Methods We searched PubMed and Embase and various published bibliographies for prospective studies published in English between January 1990 and February 2019. Two investigators screened 2646 abstracts and full-text articles for inclusion and relevant outcomes. We then performed a systematic review and meta-analysis to calculate pooled odds ratios for LGE on c-MRI and a pooled sensitivity and specificity analysis. Results Our systematic review included 8 prospective studies and 3808 patients. LGE positivity was associated with higher odds of the endpoint of sudden cardiac death (SCD;OR 1.69, 95%CI 1.03-2.78), aborted SCD or appropriate implantable cardioverter- defibrillator (ICD) discharge (OR 3.27 [1.75-6.10]), SCD or aborted SCD or appropriate ICD discharge (OR 2.32 [1.56-3.43]), and all-cause mortality (OR 2.10 [CI 1.00-4.41]). The pooled sensitivity and specificity of positive LGE on c-MRI for SCD were 65% and 42%, respectively; for aborted SCD or appropriate ICD discharge, 79% and 39%; for SCD or aborted SCD or appropriate ICD discharge, 74% and 39%; and for all-cause mortality, 78% and 39%. Conclusion In patients with HCM, LGE on c-MRI is a strong predictor of arrhythmic outcomes including SCD, aborted SCD, and appropriate ICD therapy. These data support the routine use of LGE on c-MRI as a marker of SCD risk in this population.

Pubic Bone Resection Provides Objective Pain Control in the Prostate Cancer Survivor With Pubic Bone Osteomyelitis With an Associated Urinary Tract to Pubic Symphysis Fistula.

OBJECTIVE: To investigate pain intensity perception in prostate cancer survivors with pubic bone osteomyelitis with an associated urinary tract to pubic symphysis fistula before and after definitive surgical management. MATERIALS AND METHODS: We performed a review of an institutional review board-approved database of prostate cancer survivors with pubic bone osteomyelitis from 2010 to 2015. Demographic and clinical data were extracted. Pain scores were assessed in patients at varying points before and after definitive treatment using an 11-point numeric rating scale. Statistical analysis was performed using a Wilcoxon signed-rank test and NcNemar's test. RESULTS: We identified 16 patients with a median age of 72 who met inclusion criteria. Chronic narcotic use for pain management was noted in 6 of 16 (37.5%) patients preoperatively. No statistical difference was identified between the pain score at the time of diagnosis and after completion of conservative measures (5.5 vs 5.5, P = .76). A statistically significant decrease in median pain score at the first follow-up appointment was seen compared to the preoperative pain score (0 vs. 5.5, P = .0005). At a median follow-up of 9.4 months (interquartile range 3.7-16.5), a sustained decrease in the median pain intensity score was noted in our cohort compared to their preoperative baseline pain score (5.5 vs 0, P = .0005) and pain score at the time of diagnosis (5.5 vs 0, P = .004.) CONCLUSION: Pubic bone resection provides immediate and sustained improvement in pain intensity perception in the prostate cancer survivor with pubic bone osteomyelitis with an associated urinary tract to pubic symphysis fistula.

The association of myosin IB with actin waves in dictyostelium requires both the plasma membrane-binding site and actin-binding region in the myosin tail.

F-actin structures and their distribution are important determinants of the dynamic shapes and functions of eukaryotic cells. Actin waves are F-actin formations that move along the ventral cell membrane driven by actin polymerization. Dictyostelium myosin IB is associated with actin waves but its role in the wave is unknown. Myosin IB is a monomeric, non-filamentous myosin with a globular head that binds to F-actin and has motor activity, and a non-helical tail comprising a basic region, a glycine-proline-glutamine-rich region and an SH3-domain. The basic region binds to acidic phospholipids in the plasma membrane through a short basic-hydrophobic site and the Gly-Pro-Gln region binds F-actin. In the current work we found that both the basic-hydrophobic site in the basic region and the Gly-Pro-Gln region of the tail are required for the association of myosin IB with actin waves. This is the first evidence that the Gly-Pro-Gln region is required for localization of myosin IB to a specific actin structure in situ. The head is not required for myosin IB association with actin waves but binding of the head to F-actin strengthens the association of myosin IB with waves and stabilizes waves. Neither the SH3-domain nor motor activity is required for association of myosin IB with actin waves. We conclude that myosin IB contributes to anchoring actin waves to the plasma membranes by binding of the basic-hydrophobic site to acidic phospholipids in the plasma membrane and binding of the Gly-Pro-Gln region to F-actin in the wave.