Adipose Tissue Inflammation and Cardiovascular Disease: An Update.

PURPOSE OF REVIEW: The obesity epidemic is on the rise, and while it is well known that obesity is associated with an increase in cardiovascular risk factors such as type 2 diabetes mellitus, hypertension, and obstructive sleep apnea, recent data has highlighted that the degree and type of fat distribution may play a bigger role in the pathogenesis of cardiovascular disease (CVD) than body mass index (BMI) alone. We aim to review updated data on adipose tissue inflammation and distribution and CVD. RECENT FINDINGS: We review the pathophysiology of inflammation secondary to adipose tissue, the association of obesity-related adipokines and CVD, and the differences and significance of brown versus white adipose tissue. We delve into the clinical manifestations of obesity-related inflammation in CVD. We discuss the available data on heterogeneity of adipose tissue-related inflammation with a focus on subcutaneous versus visceral adipose tissue, the differential pathophysiology, and clinical CVD manifestations of adipose tissue across sex, race, and ethnicity. Finally, we present the available data on lifestyle modification, medical, and surgical therapeutics on reduction of obesity-related inflammation. Obesity leads to a state of chronic inflammation which significantly increases the risk for CVD. More research is needed to develop non-invasive VAT quantification indices such as risk calculators which include variables such as sex, age, race, ethnicity, and VAT concentration, along with other well-known CVD risk factors in order to comprehensively determine risk of CVD in obese patients. Finally, pre-clinical biomarkers such as pro-inflammatory adipokines should be validated to estimate risk of CVD in obese patients.

Population-based analysis of non-operative management and treatment patterns in older women with estrogen receptor-positive breast cancer.

PURPOSE: To examine the proportion of older women with ER + HER2- breast cancer receiving non-operative management versus surgery, and to evaluate the use of axillary staging and adjuvant radiation in this population. METHODS: We queried the SEER database to identify all women aged 70 years or older with stage I-III ER + HER2- invasive breast cancer diagnosed between 2010 and 2016. We evaluated trends in non-operative management, breast surgery, axillary staging, and adjuvant radiation according to age at diagnosis. RESULTS: We identified 57,351 older women with ER + HER2- disease. Overall, 3538 (6.2%) of the cohort underwent non-operative management, 38,452 (67.0%) underwent breast-conserving surgery (BCS), and 15,361 (26.8%) underwent mastectomy. The proportion of patients undergoing non-operative management increased from 2.8% among 70-74-year-old women to 30.1% in those ≥ 90 years old (p < 0.001). In 53,813 women who underwent surgery, 36,850 (68.5%) underwent sentinel lymph node biopsy, while 10,861 (20.2%) underwent axillary lymph node dissection. Subgroup analysis of 29,032 older women undergoing BCS for stage I ER + HER2- breast cancer revealed a 14.2% rate of omission of axillary staging, increasing from 5.3% in those 70-74 years to 67.6% in those ≥ 90 years old (p < 0.001). Receipt of adjuvant radiation occurred in 63.3% of older women following BCS and 18% post-mastectomy, with similar trends towards omission in older age groups. CONCLUSION: Primary breast surgery remains the dominant management strategy for the majority of older women with ER + HER2- breast cancer. Omission of axillary staging and adjuvant radiation are used in a minority of eligible women undergoing breast conservation for early-stage disease.

Knowledge and attitude regarding Ebola virus disease among medical students of Rawalpindi: A preventable threat not yet confronted.

OBJECTIVE: To assess the knowledge and attitude regarding Ebola virus disease (EVD) among medical students of Rawalpindi. METHODS: A descriptive cross sectional study was carried out in a medical college of Rawalpindi from September 2014-November 2014. About 400 students were inducted with 77% (n=308) response rate. After taking informed verbal consent from students and administration, a pre-designed and pre-tested questionnaire was circulated among students of third, fourth and final year MBBS as well as third and fourth year BDS. The data collected was entered and analyzed using SPSS 20. RESULTS: The response rate was 77% (308/400). About 244 (79.2%) of students had heard about EVD before. One hundred and sixty four (53.2%) of the students correctly identified that no treatment is available for EVD as yet. Also 163 (52.9%) said that no vaccine was available against the virus either. Washing hands every time after touching a patient in clinics/wards was important for 151 (49.0%) while 223 (72.4%) claimed to use proper techniques to dispose off used injections. CONCLUSION: Students have basic knowledge regarding EVD. However, there is deficient information regarding the diagnosis and precautionary measures required to control it.

Association Between Sociodemographic Factors and Vision Difficulty in the National Health Interview Survey: A Population-Based Analysis.

PURPOSE: To investigate the relationship between social determinants of health with self-reported vision difficulty. DESIGN: Cross-sectional, population-based analysis. METHODS: The National Health Interview Survey (NHIS) is an annual survey based on the U.S. population ≥18 years of age. It provides self-reported data on demographic characteristics, socioeconomic factors, health status, and health care access. The 2021 NHIS database was used in this study. Adult participants of the NHIS who responded to the vision difficulty question "Do you have difficulty seeing, even when wearing glasses or contact lenses?" were included in this analysis. The outcome of interest was self-reported vision difficulty by participants. Analysis was done through univariable and multivariable logistic regression. RESULTS: Overall, there were 29,464 participants included in the analysis. Univariable logistic regression showed an increased odds of self-reported vision difficulty among female (odds ratio [OR] 1.28 [95% confidence interval {CI} 1.20-1.38]; P < .001), gay, lesbian, or bisexual participants (OR 1.24 [95% CI 1.04-1.49]; P = .02), those who possessed public compared with private insurance (OR 1.83 [95% CI 1.69-1.99]; P < .001), those with less than a high school education (OR 1.88 [95% CI 1.67-2.13]; P < .001), and those with an income below the poverty threshold (OR 2.22 [95% CI 1.96-2.51]; P < .001). Multivariable analysis revealed an increased risk of vision difficulty reported amongst non-Hispanic Black participants (OR 1.65 [95% CI 1.21-2.25]; P = .002). CONCLUSIONS: A multitude of sociodemographic factors are associated with self-reported vision difficulty in the U.S. POPULATION: Our findings emphasize the importance of considering factors of social determinants of health in clinical practice and policymaking for patients with vision loss.

A Case of Burnt-Out Cardiac Sarcoidosis Presenting With Sustained Ventricular Tachycardia.

Cardiac sarcoidosis is a challenging clinical entity in terms of diagnosis and management. Cardiac involvement is the most common cause of death in patients with sarcoidosis. Recently, there have been new advancements in the imaging modalities that aid in the diagnosis of this condition, including cardiac MRI and PET scan. These tools can help identify and determine the extent of the progression of sarcoidosis, which can have diagnostic and therapeutic implications. In this report, we present the case of a 74-year-old man with no history of sarcoidosis who presented with sustained ventricular tachycardia (VT) and was subsequently found to have findings consistent with burnt-out sarcoidosis on imaging. This case highlights the differences in the management of various stages of cardiac sarcoid involvement to reduce adverse outcomes.

Machine Learning Estimation of Low-Density Lipoprotein Cholesterol in Women With and Without HIV.

INTRODUCTION: Low-density lipoprotein cholesterol (LDL-C) is typically estimated from total cholesterol, high-density lipoprotein cholesterol, and triglycerides. The Friedewald, Martin-Hopkins, and National Institutes of Health equations are widely used but may estimate LDL-C inaccurately in certain patient populations, such as those with HIV. We sought to investigate the utility of machine learning for LDL-C estimation in a large cohort of women with and without HIV. METHODS: We identified 7397 direct LDL-C measurements (5219 from HIV-infected individuals, 2127 from uninfected controls, and 51 from seroconvertors) from 2414 participants (age 39.4 ± 9.3 years) in the Women's Interagency HIV Study and estimated LDL-C using the Friedewald, Martin-Hopkins, and National Institutes of Health equations. We also optimized 5 machine learning methods [linear regression, random forest, gradient boosting, support vector machine (SVM), and neural network] using 80% of the data (training set). We compared the performance of each method using root mean square error, mean absolute error, and coefficient of determination (R2) in the holdout (20%) set. RESULTS: SVM outperformed all 3 existing equations and other machine learning methods, achieving the lowest root mean square error and mean absolute error, and the highest R2 (11.79 and 7.98 mg/dL, 0.87, respectively, compared with those obtained using the Friedewald equation: 12.45 and 9.14 mg/dL, 0.87). SVM performance remained superior in subgroups with and without HIV, with nonfasting measurements, in LDL <70 mg/dL and triglycerides > 400 mg/dL. CONCLUSIONS: In this proof-of-concept study, SVM is a robust method that predicts directly measured LDL-C more accurately than clinically used methods in women with and without HIV. Further studies should explore the utility in broader populations.

Anisocytosis is associated with myocardial fibrosis and exercise capacity in heart failure with preserved ejection fraction.

BACKGROUND: Red Blood Cell Distribution Width (RDW), a measure of variability in size of circulating red blood cells and is a marker of inflammation. OBJECTIVES: We sought to test the hypothesis that RDW reflects an inflammatory milieu permissive for cardiac fibrosis in those with Heart Failure and preserved ejection fraction (HFpEF). METHODS: We analyzed the association between RDW and fibrosis in two separate cohorts. Cohort 1 (n = 200) was a retrospective analysis of blood biomarkers measured in the RELAX trial (Clinicaltrials.gov NCT00763867) and Cohort 2 (n = 160) included a single center cohort of patients with preserved ventricular function referred for cardiac magnetic resonance imaging (cMRI). Linear regression was used to adjust for potential confounders, and a mediation analysis used to explore relationships with exercise intolerance (peak VO2 max). RESULTS: Within Cohort 1, anisocytosis (RDW > 14.5) was prevalent (49.5%) and was associated with greater baseline clinical comorbidities, a lower Peak VO2 and more frequent heart failure hospitalizations. The RDW was associated with biomarkers of inflammation and cardiac fibrosis. In Cohort 2, RDW was associated with cMRI myocardial fibrosis (extracellular volume; Spearman's rho=0.38, P<0.001) which was independent of age, sex, LV ejection fraction, and hematocrit (P = 0.026). Individuals with both anisocytosis and myocardial fibrosis identified a subgroup of at high risk for 2-year mortality (HR 16.28 [4.30-61.66], P<0.001). CONCLUSIONS: In two independent cohorts of patients with HFpEF, elevated RDW is associated reduced exercise capacity and greater fibrosis as measured by serum biomarkers and cMRI. Additional studies are needed to validate this novel relationship.

Takotsubo cardiomyopathy in orthotopic liver transplant recipients: A cohort study using multi-center pooled electronic health record data.

BACKGROUND: Takotsubo cardiomyopathy (TCM), or stress-induced cardiomyopathy, is associated with adverse prognosis. Limited data suggest that TCM occurring in orthotopic liver transplant (OLT) recipients is associated with elevated peri-operative risk. AIM: To characterize the predictors of TCM in OLT recipients, using a large, multi-center pooled electronic health database. METHODS: A multi-institutional database (Explorys Inc, Cleveland, OH, USA), an aggregate of de-identified electronic health record data from 26 United States healthcare systems was surveyed. A cohort of patients with a Systematized Nomenclature of Medicine-Clinical Terms of "liver transplant" between 09/2015 and 09/2020 was identified. Subsequently, individuals who developed a new diagnosis of TCM following OLT were identified. Furthermore, the risk associations with TCM among this patient population were characterized using linear regression. RESULTS: Between 09/2015 and 09/2020, of 37718540 patients in the database, 38740 (0.10%) had a history of OLT (60.6% had an age between 18-65 years, 58.1% female). A new diagnosis of TCM was identified in 0.3% of OLT recipients (45.5% had an age between 18-65 years, 72.7% female), compared to 0.04% in non-OLT patients [odds ratio (OR): 7.98, 95% confidence intervals: 6.62-9.63, (P < 0.0001)]. OLT recipients who developed TCM, compared to those who did not, were more likely to be greater than 65 years of age, Caucasian, and female (P < 0.05). There was also a significant association with cardiac arrhythmias, especially ventricular arrhythmias (P < 0.0001). CONCLUSION: TCM was significantly more likely to occur in LT recipients vs non-recipients. Older age, Caucasian ethnicity, female gender, and presence of arrhythmias were significantly associated with TCM in LT recipients.

Lessons Learned From a Patient-Centered, Team-Based Intervention for Patients With Type 2 Diabetes at High Cardiovascular Risk: Year 1 Results From the CINEMA Program.

Background The care for patients with type 2 diabetes necessitates a multidisciplinary team approach to reduce cardiovascular risk, but implementation of effective integrated strategies has been limited. Methods and Results We conceptualized and initiated a patient-centered, team-based intervention called Center for Integrated and Novel Approaches in Vascular-Metabolic Disease (CINEMA) at University Hospitals Cleveland Medical Center. Patients with type 2 diabetes at high risk for cardiovascular events, including those with established atherosclerotic cardiovascular disease, elevated coronary artery calcium score >100, chronic heart failure with reduced ejection fraction, and/or chronic kidney disease stages 2 to 4 were included. Herein, we present the year 1 results for the program. From May 2020 through August 2021, there were 417 referrals. Among 206 eligible patients, 113 (55%) completed a baseline and ≥1 follow-up visit through December 2021, with mean (SD) time of 105 (34) days between baseline and first follow-up visits. Mean age was 59 years, with 49% women and 37% Black patients. Patients had significant reductions from baseline in glycosylated hemoglobin (-10.8%), total cholesterol (-7.9%), low-density lipoprotein cholesterol (-13.5%), systolic blood pressure (-4.0%), and body mass index (-2.7%) (P≤0.001 for all). In addition, among the 129 (63%) eligible patients not on sodium-glucose cotransporter 2 inhibitor or glucagon-like peptide-1 receptor agonist at baseline, 81% were prescribed evidence-based therapy with sodium-glucose cotransporter 2 inhibitor (n=66 [51%]) and/or glucagon-like peptide-1 receptor agonist (n=67 [52%]) to reduce the risk of cardiovascular disease in the initial 3-month follow-up period. Conclusions A team-based, patient-centered approach to high-risk disease management appears to be a promising paradigm for care delivery associated with greater use of evidence-based therapies and improved control of multiple cardiovascular risk factors.

Prevalence and manifestations of diagnosed fibromuscular dysplasia by sex and race: Analysis of >4500 FMD cases in the United States.

OBJECTIVE: Fibromuscular Dysplasia (FMD) is a rare non-atherosclerotic non-inflammatory vascular disease associated with arterial aneurysms and dissections. The epidemiology of FMD is not well understood. We sought to characterize the epidemiology of FMD utilizing a large aggregated electronic medical record database. METHODS: We used a commercial database (Explorys, IBM Watson), which aggregates data from electronic health records from 26 major integrated healthcare systems in the United States. Fibromuscular dysplasia cases were identified using a unique systemized nomenclature of medical terminology (SNOMED CT) term. We calculated the overall and age-, race-, and sex-based prevalence of FMD, and evaluated sex and race-specific differences in manifestations. RESULTS: A total of 40,566,670 individuals were active in the database from January 2015 to January 2020. Of these, 4860 had a diagnosis of FMD with an overall prevalence of 12.0 cases per 100,000 individuals. The majority of patients with FMD were female (n=4130, 85.0%), Caucasian (n=3960, 80.5%) and adults aged 18 to 65 years (n=2610, 53.7%). FMD was more common in women (prevalence 18.4 per 100,000) than men (4.0 per 100,000) and among Caucasians (15.8 per 100,000) than African Americans (11.2 per 100,000). Men and African Americans with FMD were more likely to have traditional atherosclerotic risk factors (hypertension, diabetes mellitus type 2, smoking, obesity, hyperlipidemia, chronic kidney disease), and vascular manifestations (stroke, renal infarction, claudication), compared with women and Caucasians. Men with FMD were more likely to have dissection of aorta and renal artery as well as aneurysm of vertebral artery, coronary artery, aorta and iliac artery. African-Americans were more likely to have ruptured aortic aneurysms than Caucasians. CONCLUSIONS: The overall prevalence of FMD in this large aggregated electronic medical record study is estimated at 12.0 per 100,000 persons. FMD is more common in women and Caucasians, with variable characteristics and manifestations.

Performance of Methods to Estimate Low-Density Lipoprotein Cholesterol in Women With and Without HIV Infection.

BACKGROUND: Low-density lipoprotein cholesterol (LDL-C) is estimated from total cholesterol, high-density lipoprotein cholesterol and triglycerides using predefined equations which assume fixed or varying relationships between these parameters and may underestimate or overestimate LDL-C. Data on the performance of these equations in persons with HIV are limited. We sought to investigate the utility of the 3 most widely used methods (Friedewald, Hopkins, and the recently proposed NIH equation) to predict LDL-C in persons with HIV. METHODS: We identified 7397 direct LDL-C (5219 HIV, 2127 uninfected controls, 51 seroconvertors) measurements in the Women's Interagency HIV Study, and used the 3 equations (Friedewald, Hopkins, and NIH) to calculate LDL-C. We compared the performance of the 3 equations using root mean square error and coefficient of determination (R2). RESULTS: Overall, the Friedewald equation had the best performance characteristics, outperforming Hopkins and NIH methods with lower root mean square error and higher R2 at lower triglyceride levels. However, this association did not hold true at higher triglyceride levels (quartiles 3 and 4), whereas the Hopkins equation had better performance characteristics in quartile 3, none of the 3 equations were optimal in quartile 4. After adjusting for fasting status and triglycerides levels, HIV+ had larger mean difference compared with directly measured LDL using all 3 methods. CONCLUSIONS: All 3 methods have lower accuracy in HIV+ vs HIV- women, even after adjusting for triglyceride levels and fasting status. Further research should focus on identifying methods to estimate LDL-C in HIV.

Risk of Venous Thromboembolism in Acute Necrotizing Pancreatitis: A Large Database Study.

OBJECTIVES: Studies on the incidence of venous thromboembolism (VTE) in acute pancreatitis (AP) are scarce. We conducted a large database study to evaluate this relationship. METHODS: Data were extracted from a large electronic health record (Explorys; IBM Watson Health, Armonk, NY). We identified patients with AP in 2018 and 2019, analyzing VTE incidence at 30 days after diagnosis of AP. Univariate and multivariate analyses were performed to identify risk factors associated with VTE. RESULTS: A total of 25,620 cases of acute necrotizing pancreatitis (ANP) and 155,800 cases of acute nonnecrotizing pancreatitis (ANNP) were identified. The incidence of VTE was 7.1% for ANP, compared with 2.8% in ANNP (P < 0.001). On multivariate analysis, ANP conferred significantly greater odds of VTE (adjusted odds ratio, 2.78; 95% confidence interval, 2.73-2.84; P < 0.001), independent of other variables. In those with ANP, the presence of VTE was associated with a significantly higher mortality (23.5% vs 15.9%, P < 0.001). CONCLUSIONS: Acute necrotizing pancreatitis carries near 2.5-fold risk of VTE, and a 3-fold risk of PE, compared with those with ANNP. Venous thromboembolism development in ANP is associated with higher mortality.

Health Related Quality of Life in Patients with Single Lower Limb Amputation.

OBJECTIVE: To determine the effects of age, cause of amputation, and anatomic level of amputation on the health related quality of life (HRQOL) in individuals with unilateral lower limb amputation. STUDY DESIGN: Across-sectional survey. PLACE AND DURATION OF STUDY: The Armed Forces Institute of Rehabilitation Medicine, from August 2014 to February 2015. METHODOLOGY: Short Form-36 (SF-36) health related quality of life (HRQOL). Survey questionnaire was used to collect data. The responses were scored by using the quality metric health outcomes™ scoring software 4.5. The scores were entered and analysed in SPSS version 21. RESULTS: Atotal of 52 patients were inducted with mean age of 30.71 ±7.50 years. Mean physical component summary (PCS) was lower than mental component summary (MCS) (38.7 vs. 44.8). RP and RE scores were found to be significantly associated with gender (p=0.024 and p=0.003, respectively). Age group was also significantly associated with RP(p=0.037) and SF (p=0.041). When SF-36 domains were compared with level of amputation (i.e. trans-tibial and transfemoral), none of the domains showed any statistically significant results. CONCLUSION: Age and indication affect different aspects of quality of life but level of amputation did not. If these are known and anticipated before any type of rehabilitation, this could help in anticipation of health consequences and prevention accordingly.

Colonoscopic perforation leading to a diagnosis of Ehlers Danlos syndrome type IV: a case report and review of the literature.

INTRODUCTION: Colonoscopic perforation is a rare but serious complication of colonoscopy. Factors known to increase the risk of perforation include colonic strictures, extensive diverticulosis, and friable tissues. We describe the case of a man who was found to have perforation of the sigmoid colon secondary to an undiagnosed connective tissue disorder (Ehlers-Danlos syndrome type IV) while undergoing surveillance for hereditary non-polyposis colorectal cancer. CASE PRESENTATION: A 33-year-old Caucasian man presented to our hospital with an acute abdomen following a colonoscopy five days earlier as part of hereditary non-polyposis colorectal cancer screening. His medical history included bilateral clubfoot. His physical examination findings suggested left iliac fossa peritonitis. A computed tomographic scan revealed perforation of the sigmoid colon and incidentally a right common iliac artery aneurysm as well. Hartmann's procedure was performed during laparotomy. The patient recovered well post-operatively and was discharged. Reversal of the Hartmann's procedure was performed six months later. This procedure was challenging because of dense adhesions and friable bowel. The histology of bowel specimens from this surgery revealed thinning and fibrosis of the muscularis externa. The patient was subsequently noted to have transparency of truncal skin with easily visible vessels. An underlying collagen vascular disorder was suspected, and genetic testing revealed a mutation in the collagen type III, α1 (COL3A1) gene, which is consistent with a diagnosis of Ehlers-Danlos syndrome type IV. CONCLUSIONS: Ehlers-Danlos syndrome type IV, the vascular type, is a rare disorder caused by mutations in the COL3A1 gene on chromosome 2q31. It is characterized by translucent skin, clubfoot, and the potentially fatal complications of spontaneous large vessel rupture, although spontaneous uterine and colonic perforations have also been reported in the literature. The present case presentation describes the identification of Ehlers-Danlos syndrome type IV in a patient with a non-spontaneous colonic perforation secondary to an invasive investigation for another hereditary disorder pre-disposing him to colorectal cancer. Invasive procedures such as arteriograms and endoscopies are relatively contra-indicated in Ehlers-Danlos syndrome type IV. Alternatives with a lower risk of perforation, such as computed tomographic colonography, need to be considered for patients requiring ongoing colorectal cancer surveillance. Furthermore, management of vascular aneurysms in patients with Ehlers-Danlos syndrome type IV requires consideration of the risks of endovascular stenting, as opposed to open surgical intervention, because of tissue friability. Genetic and reproductive counseling should be offered to affected individuals and their families.

Laparoscopic skills suffer on the first shift of sequential night shifts: program directors beware and residents prepare.

OBJECTIVE: Research evaluating fatigue-induced skills decline has focused on acute sleep deprivation rather than the effects of circadian desynchronization associated with multiple shifts. As a result, the number of consecutive night shifts that residents can safely be on duty without detrimental effects to their technical skills remains unknown. A prospective observational cohort study was conducted to assess the impact of 7 successive night shifts on the technical surgical performance of junior residents. METHODS: The interventional strategy included training 21 residents from surgery and allied disciplines on a virtual reality surgical simulator, towards the achievement of preset benchmark scores, followed by 294 technical skills assessments conducted over 1764 manpower night shift hours. Primary outcomes comprised serial technical skills assessments on 2 tasks of a virtual reality surgical simulator. Secondary outcomes included assessments of introspective fatigue, duration of sleep, and prospective recordings of activity (number of "calls" received, steps walked, and patients evaluated). RESULTS: Maximal deterioration in performance was observed following the first night shift. Residents took significantly longer to complete the first (P = 0.002) and second tasks (P = 0.005) compared with baseline. They also committed significantly greater numbers of errors (P = 0.025) on the first task assessed. Improved performance was observed across subsequent shifts towards baseline levels. CONCLUSIONS: Newly acquired technical surgical skills deteriorate maximally after the first night shift, emphasizing the importance of adequate preparation for night rotas. Performance improvements across successive shifts may be due to ongoing learning or adaptation to chronic fatigue. Further research should focus on assessments of both technical procedural skills and cognitive abilities to determine the rotas that best minimize errors and maximize patient safety.