Prognostic Value of Left and right ventricular deformation strain analysis on Acute Cellular rejection in Heart Transplant recipients: A 6-year outcome study.

PURPOSE: Two-dimensional (2D) strain analysis is a sensitive method for detecting myocardial dysfunction in acute cellular rejection (ACR) from post-transplant complications. This study aims to evaluate the utility of novel left (LV) and right ventricular (RV) strain parameters for prognostic risk stratification associated with ACR burden at 1-year post transplantation. METHODS: 128 Heart transplant patients, assessed between 2012 and 2018, underwent transthoracic echocardiography and endomyocardial biopsy. 2D strain analysis was performed and history of rejection burden was assessed and grouped according to ACR burden at 1-year post transplantation. The primary endpoint was all-cause mortality at 6-years follow up. RESULTS: 21 patients met primary the endpoint. Multivariate analysis of 6-year all-cause mortality showed LV global longitudinal strain (LV GLS) (Hazard Ratio [HR] = 1.21, CI = 1.06-1.49), LV early diastolic strain rate (LV ESr) (HR = 1.31, CI = 1.12-1.54), RV GLS (HR = 1.12, CI = 1.02-1.25) and RV ESr (HR = 1.26, CI = 1.12-1.47) were significant predictors of outcome. Univariate analysis also showed LV GLS, LV ESr, RV GLS and RV ESr were significant predictors of outcome. Optimal cut-off for predicting 6-year mortality for LV GLS by receive operator characteristic was 15.5% (sensitivity: 92%, specificity: 79%). Significant reductions (p < 0.05) in LV GLS, RV GLS and LV and RV ESr between rejection groups were seen. CONCLUSIONS: Non-invasive LV and RV strain parameters are predictors of mortality in post-transplant patient with ACR. LV GLS and LV ESr are superior to other strain and conventional echo parameters.

Impact of inter-vendor variability on evaluation of left ventricular mechanical dispersion.

PURPOSE: Left ventricular mechanical dispersion (LVMD) is a novel speckle tracking parameter for prognostic assessment of arrhythmic risk prediction. There is growing evidence to support its use in a variety of cardiomyopathic processes. There is paucity of data addressing any presence of inter-vendor discrepancies for LVMD. The aim of this study was to assess inter-vendor variability of LVMD in vendor specific software (VSS) and vendor independent software (VIS) in subjects with preserved and reduced left ventricular function. METHODS: Fifty-nine subjects (14 normal subjects and 45 subjects with cardiac disease) were recruited and 2D speckle tracking echocardiographic images were acquired on two different ultrasound machines (GE and Philips). LVMD was measured by two different VSS (EchoPac GE and QLAB Philips) and one VIS (TomTec Arena). RESULTS: There was significant bias and wide limits of agreement (LOA) in the overall cohort observed between two different VSS (17.6 ms; LOA: -29.6 to 64.8; r: .47). There was acceptable bias and narrower LOA with good agreement for LVMD between images obtained on different vendors when performed on VIS (-3.1 ms; LOA: -27.6 to 21.4; r: .75). QLAB LVMD was consistently higher than GE LVMD and TomTec LVMD in both preserved and reduced left ventricular function. LVMD measurements have high intra-vendor reproducibility with excellent inter and intra-observer agreement. CONCLUSIONS: There was acceptable bias and narrower LOA for LVMD assessment on a VIS. Inter-vendor variability exists for LVMD assessment between VSS. Serial measurements of LVMD should be performed using a single vendor for consistent and reliable results.

Novel left and right ventricular strain analysis to detect subclinical myocardial dysfunction in cardiac allograft rejection.

Early detection of acute cellular rejection (ACR) by echocardiography shows potential clinical benefit as ACR remains a significant contributor to morbidity and mortality. This retrospective, longitudinal study sought to investigate the use of novel left (LV) and right ventricular (RV) strain analysis to detect biopsy proven ACR. 46 heart transplant patients (Mean age 46 ± 16 years) with biopsy proven ACR were grouped according to biopsy results: 1R-ACR (n = 36) and 2R-ACR (n = 10). Serial two-dimensional transthoracic echocardiography with strain analysis was performed. Echocardiographic parameters were serially measured: (1) rejection free period (0R-ACR); (2) pre-ACR period (pre-ACR); (3) during ACR (1R-ACR or 2R-ACR) and (4) post-ACR (Post-ACR). Significant reductions for LV Global Longitudinal Strain (LV GLS) and LV Early diastolic Strain rate (LV ESr) were observed between 0R-ACR and pre-ACR (LV GLS 0R-ACR: 17.3% vs Pre-2R ACR: 15.4%, p = 0.016; LV ESr 0R-ACR: 1.00/s vs Pre-2R ACR: 0.74/s, p = 0.007) with LV ESr demonstrating the highest sensitivity (92%) and specificity (81%) to predict ACR. LV ESr and the E/LV ESr ratio were significantly different (p = 0.0001; p = 0.016) during pre-1R ACR period vs 0R whereas LV GLS showed no significant differences for grade 1R-ACR. Diastolic mechanical dispersion showed significant increases in dispersion during ACR for the 1R-ACR group and early significant increases pre-2R ACR. Systolic and diastolic RV strain parameters showed a similar trend for both ACR groups. Systolic and diastolic strain parameters can detect myocardial dysfunction before biopsy confirmed 2R-ACR. Early diastolic strain rate parameters are most sensitive detecting subclinical myocardial dysfunction pre-ACR. Novel strain parameters are potentially useful clinical tool for prediction of early ACR in heart transplant.

Advantage and validation of vendor-independent software for myocardial strain analysis compared to vendor-specific software.

INTRODUCTION: One of the main limitations incorporating strain imaging into widespread clinical practice is inter-vendor incompatibility. This poses a problem when serial strain measurements are required in a multi-vendor echocardiography laboratory. METHODS: This study sought to compare the variability of two-dimensional speckle-tracking global and regional longitudinal strain using vendor-specific software and vendor-independent software from images acquired by two different commercially available ultrasound systems. Forty subjects underwent two sequential echocardiographic acquisitions using different ultrasound systems (GE Vivid E9 and Philips iE33). Global longitudinal strain and regional peak longitudinal strain were derived using vendor-specific software (EchoPAC BT 13 v201 and QLAB version 10.3) and vendor-independent software (TomTec Image Arena version 4.6). Agreement and reproducibility of global and regional strain between vendor-specific and vendor-independent software were assessed by independent blinded observers. RESULTS: Global longitudinal strain derived from vendor-independent software was comparable to global longitudinal strain derived from vendor-specific software, whilst regional strain was lower in agreement compared to global longitudinal strain. There was good overall agreement and high inter- and intra-observer reproducibility using vendor-independent software for global longitudinal strain and regional strain. CONCLUSIONS: Vendor-independent software provides good agreement with vendor-specific software for global longitudinal strain. However, minor variability exists for regional strain measurements between vendor-independent and vendor-specific software. Good agreement of strain measurements derived by vendor-independent software suggests vendor-independent software could potentially be useful for serial follow-up of global longitudinal strain.

Myocardial work and left ventricular contractile reserve during stress echocardiography: An angiographic validation.

OBJECTIVE: This study sought to determine the contractile reserve (CR) response to exercise stress echocardiography (ESE) quantified by the novel parameter, non-invasive myocardial work (MW), in subjects with angiographically proven coronary artery disease (CAD). METHODS: CR was measured by the relative change in ejection fraction (EF), global longitudinal strain (GLS) and MW indices from rest to peak exercise in 304 patients referred for clinically indicated ESE. Positive ESE patients proceeded to coronary angiography and further risk stratified based on either percutaneous or surgical intervention. RESULTS: CRGLS and global work index (CRGWI ) significantly decreased with exercise induced ischemia and angiographically proven significant CAD (CRGLS -1.6±3.5%; CRGWI -8.6±511 mm Hg% decrement, p < 0.001) compared to non-ischemic patients (CRGLS 1.4±2.2%; CRGWI 398±404 mm Hg% improvement). Global constructive work (CRGCW ) was significantly higher (p < 0.0001) in non-ischemic (818±457 mm Hg%) and blunted in ischemic patients (208±550 mm Hg%). CRGCW (AUC .81; 95%CI:.75-.86) demonstrated the most association for inducible ischemia followed by CRGLS (AUC .75; 95%CI:.69-.80), CRGWI (AUC .73, 95%CI:.67-.79) and CREF (AUC .71; 95%CI:.65-.77, p < 0.001). Subgroup analysis showed patients requiring surgical revascularization demonstrated a significantly lower CRGWE (-11.5±7.6%, p < 0.05) as a result of reduced CRGCW (281±573 mm Hg%, p < 0.05) and increased global wasted work (CRGWW , 289±151 mm Hg%, p = 0.09). CONCLUSION: Multivessel disease requiring surgical revascularization have the greatest reduction in CR. MW may potentially improve detection of ischemia and further risk stratification during ESE to maximize the benefits of revascularization.

Mentoring in Global Cancer Research Training.

This manuscript illustrates general concepts of mentoring in low- and middle-income countries (LMICs). The focus of this manuscript is on public health research based on our experiences with the Cancer Epidemiology Education in Special Populations (CEESP) Program which is further illustrated in this Supplement. While the CEESP Program provides research training in global and US minority settings, this manuscript is focused on the global aspects of the program. We describe the process of selecting students into the CEESP Program, the process of mentoring them, and the preparation of the mentoring sites. We emphasize the review of the CEESP mentors in LMICs and put forward recommendations for enhancing their mentoring skills and disseminating the experience to other US and global institutions interested in global cancer education.

Lessons learned, Summary, Challenges, and Recommendations.

In this final section, we summarize the different manuscripts included in his Supplement and outline the lessons learned. We also elaborate on the common educational challenges reported in the included articles and the possible recommendations for future global cancer education.

Developing and Maintaining a Global Research Training Infrastructure for Cancer Education.

This manuscript illustrates the 20-year process of establishing research sites that have been developed and maintained by the authors in collaboration with oncology colleagues at institutions in low- and middle-income countries. This infrastructure has been created for research training of US public health graduate students over the past 20 years for the Cancer Epidemiology Education in Special Populations (CEESP) Program funded by the US National Cancer Institute (R25 CA112383). We describe the history and resources that were utilized for developing and maintaining the research training infrastructure. We then define the elements needed for selecting and nurturing these global sites for education and research training of students. The elements include data and field resources, patient population, facilities for cancer management, laboratory resources, academic collaborators, and population parameters and cultural characteristics. These elements have also been essential in our US domestic training sites. We then emphasize the strengths and limitations of our global sites. Finally, we elaborate on our learning experience over the past 20 years. We believe that the material provided in this manuscript will serve as a useful toolkit for faculty, mentors, students, and trainees interested developing and/or utilizing research sites for cancer epidemiology and cancer prevention and control research training programs in global settings.

Needs for Cancer Education In Oman Based on the Breast Cancer Screening Program.

Most breast cancers in Oman are diagnosed at advanced stages and therefore early detection is important. The Oman Cancer Association (OCA) initiated a mobile mammography program in 2009, but no studies have evaluated its impact. This study aimed at estimating the proportion and predictors of OCA-screened women who had repeated mammography (adherence) and the sensitivity and specificity of the program. Demographic, screening, diagnosis, and treatment data of 13,079 women screened in the OCA mammography clinic from 2009 to 2016, and medical records of all breast cancer patients seen at Royal and Sultan Qaboos University hospitals during the same period were retrieved. Logistic regression analysis was conducted to identify predictors of adherence. A total of 8278 screened women over age 42 years (median age of 50 ± 8 years) were included in the study. Only 18% of initially negative screened women were compliant with recommended subsequent screening. Predictors of adherence included age (50-69 years), family history of cancer, family history of breast cancer, and breast self-examination. The overall cancer detection rate was 4.1/1000 screened women. Positive predictive value of screening was 4.7% with a sensitivity rate of 53% and specificity of 92%. This study showed a low mammography adherence among previously screened women. The study revealed low sensitivity, high specificity, and an acceptable cancer detection rate. Future programs should focus on improving data collection of screened women, maintaining the linkage of databases of screening and treatment clinics, and developing guidelines for breast cancer screening in Oman. The recommendations based on the study results should be incorporated into future professional, patient, and public cancer education programs.

Global Aspects of the Cancer Epidemiology Education in Special Populations (CEESP) Program.

This manuscript provides a brief overview of the global aspects of the Cancer Epidemiology Education in Special Populations (CEESP) Program. The overview illustrates program history, aims, progress, evaluation, and dissemination. This manuscript sets the stage for the CEESP manuscripts included in this supplement that illustrate in the program infrastructure, mentoring, the student experiences, and unique features of students for achieving success. In this manuscript, we briefly outline some of the dissemination examples that resulted from utilizing the CEESP infrastructure, as outlined in some of the articles reporting on global research training sites from Egypt, Morocco, Oman, and Tanzania.

Field Research Experience of Medical Students: Learning and Translation from Global to Underserved US Settings.

While most medical schools in the USA provide opportunities for global health experiences, global health education is not included consistently or emphasized adequately in many medical school curricula. The City University of New York Medical School (CSOM) has a mission to educate and train students who are traditionally underrepresented in medicine to practice primary care in medically underserved communities in New York. This manuscript documents the experience of the CSOM in expanding global health education by introducing a new global health cancer training program, partnering with clinicians at the Ocean Road Cancer Institute (ORCI) in Tanzania. This manuscript illustrates the following points: (1) the CSOM curriculum that focuses on community health and social medicine; (2) the process by which students learn by developing research proposals for global cancer; (3) the field research experience and lessons learned; (4) learning about cancer and medicine in a developing country; and (5) lessons learned for translation from global to domestic underserved populations. We also suggest a checklist for future students interested in pursuing global cancer education and research, and recommendations for maximizing learning and career development of students interested in global cancer research and its application to underserved populations in the USA.

Resting global myocardial work can improve interpretation of exercise stress echocardiography.

Sensitivity and specificity of ESE to determine hemodynamically significant coronary artery disease (CAD) is limited by subjective qualitative interpretation resulting in false-positive results. The objective of this study was to determine whether resting myocardial work estimated from non-invasive left ventricular pressure-strain loops can help improve the interpretation of exercise stress echocardiography (ESE). Resting global myocardial work was performed on 288 patients referred for clinically indicated ESE with no resting regional wall motion abnormalities and normal ejection fraction (≥ 55%). Coronary angiography was used to validate the presence of significant CAD in those with a positive ESE. Resting global myocardial work index (GWI) was significantly reduced (p < 0.001) in patients with true-positive (1544 ± 354 mmHg%) compared to negative (1819 ± 317 mmHg%) and false-positive (1857 ± 344 mmHg%) ESE. A GWI of ≤ 1391 mmHg (AUC 0.73; sensitivity 94%; specificity 73%) predicted true-positive ESE. Predictors of a true-positive ESE were (1) lower myocardial work efficiency (odds ratio 0.731, 95% CI 0.58-0.92, p = 0.007), (2) lower GWI (odds ratio 0.997, 95% CI 0.996-0.999, p = 0.006) (3) male gender (odds ratio 5.47, 95% CI 1.84-16.31, p = 0.002) and (4) E/e' ratio (odds ratio 1.15, CI 1.01-1.31, p = 0.032). Myocardial work is a potentially valuable quantitative parameter that provides incremental value over qualitative ESE interpretation and improves appropriate patient selection for coronary angiography.

Higher comorbidities and early death in hospitalized African-American patients with Covid-19.

BACKGROUND: African-Americans/Blacks have suffered higher morbidity and mortality from COVID-19 than all other racial groups. This study aims to identify the causes of this health disparity, determine prognostic indicators, and assess efficacy of treatment interventions. METHODS: We performed a retrospective cohort study of clinical features and laboratory data of COVID-19 patients admitted over a 52-day period at the height of the pandemic in the United States. This study was performed at an urban academic medical center in New York City, declared a COVID-only facility, serving a majority Black population. RESULTS: Of the 1103 consecutive patients who tested positive for COVID-19, 529 required hospitalization and were included in the study. 88% of patients were Black; and a majority (52%) were 61-80 years old with a mean body mass index in the "obese" range. 98% had one or more comorbidities. Hypertension was the most common (79%) pre-existing condition followed by diabetes mellitus (56%) and chronic kidney disease (17%). Patients with chronic kidney disease who received hemodialysis were found to have lower mortality, than those who did not receive it, suggesting benefit from hemodialysis Age > 60 years and coronary artery disease were independent predictors of mortality in multivariate analysis. Cox proportional hazards modeling for time to death demonstrated a significantly high ratio for COPD/Asthma, and favorable effects on outcomes for pre-admission ACE inhibitors and ARBs. CRP (180, 283 mg/L), LDH (551, 638 U/L), glucose (182, 163 mg/dL), procalcitonin (1.03, 1.68 ng/mL), and neutrophil:lymphocyte ratio (8.3:10.0) were predictive of mortality on admission and at 48-96 h. Of the 529 inpatients 48% died, and one third of them died within the first 3 days of admission. 159/529patients received invasive mechanical ventilation, of which 86% died and of the remaining 370 patients, 30% died. CONCLUSIONS: COVID-19 patients in our predominantly Black neighborhood had higher in-hospital mortality, likely due to higher prevalence of comorbidities. Early dialysis and pre-admission intake of ACE inhibitors/ARBs improved patient outcomes. Early escalation of care based on comorbidities and key laboratory indicators is critical for improving outcomes in African-American patients.

Using Key Informants to Evaluate Barriers to Education and Acceptability of the HPV Vaccine in Tanzania: Implications for Cancer Education.

Cervical cancer is the third most common cancer globally, with high mortality when left untreated. In sub-Saharan Africa, Tanzania shows higher incidence rates of cervical cancer at 59.1 per 100,000 compared with the global average of 13.1 per 100,000. The HPV vaccine has been shown to successfully reduce HPV infection and is recommended for school-age girls and boys in the USA. Understanding the acceptability of the HPV vaccine and the barriers to vaccination is important for ensuring that HPV vaccination programs are successful. In 2016, Tanzania began school-based HPV vaccination programs in cities and towns surrounding Dar es Salaam, the largest city in Tanzania. Successful implementation of HPV vaccination programs in Dar es Salaam relies on overcoming barriers to vaccination. This study focused on primary school teachers as key informants to assess these barriers. Participants were given a short survey and then asked to participate in focus group sessions. Overall, knowledge of HPV was low, with only 37% of participants having heard of the HPV and only 28.6% having heard of the HPV vaccine. Teachers had a very positive response to the HPV educational sessions. Of the teachers who completed the questionnaires, 100% of them were willing to speak with their school parents about the HPV vaccine and 99% would recommend this vaccine to parents. This study has significant implications for national cancer prevention vaccination programs, not only in Tanzania, but also in other countries starting HPV vaccination as teachers are potentially important advocates for immunization and other childhood health initiatives.

Experiential Learning in Career Development.

This manuscript demonstrates the learning experiences of graduate public health students through mentored field research in cancer epidemiology and cancer prevention over the past 13 years. The program has been funded through an R25 grant from the National Cancer Institute (NCI) since 2006 and has supported nearly 200 students from different universities in the USA. Included are data on student recruitment, selection, mentorship, and evaluation of research training in US minority settings as well as foreign countries. Examples of students' learning experiences and life-long skills that shaped students' careers are presented. The insights that fostered the experiential learning idea among key leaders at the NCI Cancer training branch have proven to be sound.

Quantifying the under-estimation of cervical Cancer in remote regions of Tanzania.

BACKGROUND: Cervical cancer is the most common cancer among women in Sub-Saharan countries, including Tanzania. While early detection and diagnosis are available in some parts of this large country, radiotherapy has been only available at the Ocean Road Cancer Institute (ORCI), in the capital city of Dar es Salaam and is just starting in a few regions. METHODS: The objective of this study was to compare the observed incidence of cervical cancer for the two remote regions of Mwanza in western Tanzania and Mbeya in southern Tanzania, based on their patients treated at the ORCI from 2011 to 2014. RESULTS: The number patients referred and treated at ORCI were (120 from Mwanza, and 171 from Mbeya, representing 24.6 and 32.8% of the patients histopathologically confirmed in the two sites, respectively. The results showed significant underestimation of cervical cancer in the two regions. The vast majority of patients who were histopathologically-confirmed in their local regions (73.92% from Mwanza and 65.1% from Mbeya), but did not receive the needed radiotherapy treatment at the ORCI. The estimated incidence for the two regions based on the number of patients treated at the ORCI were underestimated by 53.9% for Mwanza and 68.9% for Mbeya. CONCLUSIONS: Local establishment of radiotherapy treatment facilities in remote regions in Tanzania and similar other low-income countries is essential for providing effective treatment and improving survival of diagnosed cervical cancer patients. Linkage between the records of local remote hospitals and the main cancer treatment center in the capital city can also help support the emerging the population-based cancer registry at ORCI.

Findings, Phenotypes, Diagnostic Accuracy, and Treatment in Freeman-Burian Syndrome.

Freeman-Burian syndrome (FBS) is a rare congenital myopathic craniofacial syndrome. Since publication of the genotype-correlated clinical diagnostic criteria, no complete survey of the literature has been accomplished. As part of the clinical practice guideline development, we evaluate diagnostic accuracy for FBS from 1938 to 2019 and range of findings, complications, treatments, and outcomes. Published manuscripts in PubMed, Google Scholar, and OMIM describing cases with a reported diagnosis of FBS, Sheldon-Hall syndrome, and distal arthrogryposes type 1 and 3 are initially included. Articles with sufficient case-level data for diagnosis verification are analyzed further. Of 724 unique papers considered, 188 papers describing 304 unique patients are included; 101 papers and 119 patients reflect an FBS diagnosis, with 80 patients meeting the full diagnostic criteria. Most cases are re-screened as distal arthrogryposis type 1. Among all cases re-screened as FBS, the presence of FBS pathognomonic craniofacial findings is not correlated with other physical findings. There are no significant differences between patients meeting the full diagnostic criteria and those not, but both are distinct from other diagnoses. Plastic surgery demonstrates the highest cumulative diagnostic accuracy for FBS overall (86.66%), while orthopedic surgery shows the lowest (44.83%). No statistically usable treatment-related or psychosocial data are available. Quality of case reports and patient data vary widely, reducing the statistical strength and significance. Major knowledge gaps exist in treatment, psychosocial, and longitudinal outcomes. At this point, it is impossible to derive clinical practice guidelines exclusively from the literature.