Excisional lipectomy versus liposuction in HIV-associated lipodystrophy

Background Human immunodeficiency virus (HIV)-associated lipodystrophy is a known consequence of long-term highly active antiretroviral therapy (HAART). However, a significant number of patients on HAART therapy were left with the stigmata of complications, including fat redistribution. Few studies have described the successful removal of focal areas of lipohypertrophy with successful outcomes. This manuscript reviews the outcomes of excisional lipectomy versus liposuction for HIV-associated cervicodorsal lipodystrophy.Methods We performed a 15-year retrospective review of HIV-positive patients with lipodystrophy. Patients were identified by query of secure operative logs. Data collected included demographics, medications, comorbidities, duration of HIV, surgical intervention type, pertinent laboratory values, and the amount of tissue removed.Results Nine male patients with HIV-associated lipodystrophy underwent a total of 17 procedures. Of the patients who underwent liposuction initially (n=5), 60% (n=3) experienced a recurrence. There were a total of three cases of primary liposuction followed by excisional lipectomy. One hundred percent of these cases were noted to have a recurrence postoperatively, and there was one case of seroma formation. Of the subjects who underwent excisional lipectomy (n=4), there were no documented recurrences; however, one patient’s postoperative course was complicated by seroma formation.Conclusions HIV-associated lipodystrophy is a disfiguring complication of HAART therapy with significant morbidity. Given the limitations of liposuction alone as the primary intervention, excisional lipectomy is recommended as the primary treatment. Liposuction may be used for better contouring and for subsequent procedures. While there is a slightly higher risk for complications, adjunctive techniques such as quilting sutures and placement of drains may be used in conjunction with excisional lipectomy.

Gestational Potential Space Hypothesis: Evolutionary Explanation of Human Females Body Fat Redistribution

Homo sapiens, as well as other primates, developed the evolutionary advantage of storing excess energy as body fat, primarily in the readily accessible visceral fat compartment when food is plentiful for use during scarcity. However, uniquely to female humans, a second transient dimorphic phenotypic change begins at menarche and is reversed by menopause. It is the diversion of visceral fat stores from the abdominal cavity to the gluteofemoral region. The evolutionary purpose for this remains unclear. The author proposes the gestational potential space (GPS) hypothesis: that such fat diversion is for the reproductive purpose of increasing the potential abdominal space available for gestation and reducing the intraabdominal pressure. This hypothesis is supported by the basic laws of physics and increased rates of maternal and fetal complications experienced by those with visceral adiposity. It is important that the GPS hypothesis and alternative hypotheses are tested by comparing the health (particularly reproductive) outcomes of women with varying fat distributions and their offspring. Lay summary The author proposes that fat shifting from the abdominal cavity to the hips and thighs in women, during the childbearing period, is for beneficial for reducing the intraabdominal contents consequently increasing pregnancy potential space. Secondarily, it prevents intraabdominal pressure elevation and reduces maternal and fetal complications associated with visceral fat in pregnancy.

Cardiovascular Changes in Menopause

: Menopause is associated with changes consistent with cardiovascular aging. The effects on cardiac disease is multifaceted affecting endothelial function, coronary artery physiology and metabolic dysfunction leading to structural changes in the coronary anatomy. A systematic review of literature from 1986 to 2019 was conducted using PubMed and Google Scholar. The search was directed to retrieve papers that addressed the changes in cardiovascular physiology in menopause and the current therapies available to treat cardiovascular manifestations of menopause. The metabolic and clinical factors secondary to menopause such as dyslipidemia, insulin resistance, fat redistribution and systemic hypertension contribute to the accelerated risk for cardiovascular aging and disease. Atherosclerosis appears to be the end result of the interaction between cardiovascular risk factors and their accentuation during the perimenopausal period. Additionally, complex interactions between oxidative stress and levels of L-arginine and ADMA may also influence endothelial dysfunction in menopause. The increased cardiovascular risk in menopause stems from the exaggerated effects of changing physiology on the cardiovascular system affecting peripheral, cardiac and cerebrovascular beds. The differential effects of menopause on cardiovascular disease at the subclinical, biochemical and molecular levels form the highlights of this review.

Relationship of Telomere Length to Fat Redistribution in HIV

Persons with HIV demonstrate increased risk for aging-associated complications and have reduced telomere length (TL) compared with age-matched persons without HIV. Our data show that greater visceral fat is related to reduced TL in HIV, independent of age and smoking. Fat redistribution may be a relevant mediator of TL attrition in HIV.

Metformin alleviates aging-associated cellular senescence of human adipose stem cells and derived adipocytes

SUMMARYAging is associated with central fat redistribution, and insulin resistance. To identify age-related adipose features, we evaluated the senescence and adipogenic potential of adipose-derived-stemcells (ASCs) from abdominal subcutaneous fat obtained from healthy normal-weight young (<25y) or older women (>60y).Aged-donor ASCs showed more intense features of aging (senescence, mitochondrial dysfunction, and oxidative stress) than young-donor ASCs. Oxidative stress and mitochondrial dysfunction occurred earlier in adipocytes derived from aged-donor than from young-donor ASCs, leading to insulin resistance and impaired adipogenesis.When aged-donor ASCs were treated with metformin, senescence, oxidative stress and mitochondrial dysfunction returned to the levels observed in young-donor ASCs. Furthermore, metformin’s prevention of senescence and dysfunction during ASC proliferation restored the cells’ adipogenic capacity and insulin sensitivity. This effect was mediated by the activation of AMP-activated-protein-kinase.We show here that targeting senescent ASCs from aged women with metformin may alleviate age-related dysfunction, insulin resistance, and impaired adipogenesis.

Adrenal incidentaloma: management of patients with functionally autonomous cortisol synthesis

Over recent decades due to improved visualization (ultrasound, computer tomography and magnetic resonance imaging) prevalence of adrenal incidentaloma has increased. The term «adrenal incidentaloma» is generic and includes a group of tumors of various morphology and over 1 cm in diameter accidentally discovered during radiologic investigation. The found tumor can be hormonally inactive or actively releasing different hormones, malignant or benign, and originating from different adrenal zones or having non-specific organ origin. Based on the frequency of revealing and clinical significance the most noteworthy is functionally autonomous cortisol synthesis. It means changes of hypothalamic pituitary adrenal axis without classic clinically prominent signs of cortisol excess such as proximal myopathy, stretch marks, body fat redistribution and other metabolic changes related to cortisol. Currently a large number of recommendations on the management and tactics of treatment of adrenal incidentaloma can be found in the literature. Based on the analysis of these guidelines the conclusions were made about the diagnostic errors and incorrect approaches to the choice of treatment of such patients. Recently a lot of studies have been directed to the early detection of carbohydrate and lipid metabolism disorders, relation with obesity and type 2 diabetes mellitus, arterial hypertension and osteoporosis for preserved quality of life of such patients. Influence of hypercorticism is considered to worsen the course of these conditions but at the moment no effect of adrenalectomy on mortality and life duration was confirmed.

936. Body Fat Redistribution/Accumulation, Pancreatic Disorders, Musculoskeletal Disorders, IRIS, Severe Systemic Rash and Hypersensitivity Reactions Following Initiation of Commonly Prescribed Antiretrovirals

Background Dolutegravir (DTG), elvitegravir (EVG), raltegravir (RAL), and darunavir (DRV) are commonly used for the treatment of HIV. We assessed the frequency of 6 select disorders after prescription of DTG-, EVG-, RAL-, or DRV-based regimens. Methods HIV-positive patients in the OPERA® Observational Database initiating DTG-, EVG-, RAL-, or DRV-containing regimens were included. Disorders of interest were body fat redistribution/accumulation, pancreatic disorders, and musculoskeletal disorders, as defined in Figures 2–3, as well as immune reconstitution inflammatory syndrome (IRIS), severe systemic rash and hypersensitivity reaction (HSR). Baseline patient characteristics and disorder history were described. The proportion of patients with disorders of interest during follow-up were compared between core agents for each disorder. All events occurring during follow-up were considered prevalent, while incident disorders excluded patients with any history of disorder. To account for multiple comparisons, the Sidak Correction was applied (adjusted α level: 0.017). Results Out of 22,674 patients, 7,860 (35%) initiated DTG, 9,738 (43%) EVG, 1,600 (7%) RAL, and 3,477 (15%) DRV. Baseline demographic and clinical characteristics varied by core agent initiated (Figure 1). Compared with DTG, history of body fat redistribution/accumulation was less frequent in patients initiating EVG, and more frequent in patients initiating RAL (Figure 2). EVG users also had a lower prevalence during follow-up than DTG users (Figure 3). However, there was no difference in new onset of body fat redistribution/accumulation between groups (Figure 3). No difference in prevalent or incident pancreatic or musculoskeletal disorders was detected between core agents (Figure 3). IRIS, severe systemic rash, and HSR occurred in no more than 2 patients per core agent group, with no difference detected between groups. Conclusion Incident body fat redistribution/accumulation, pancreatic disorders, musculoskeletal disorders, IRIS, severe systemic rash, and HSR were rare in this large cohort of patients initiating DTG, EVG, RAL, or DRV. Despite some channeling of patients with a disorder history towards DTG and RAL use, the likelihood of new events did not differ by core agent. Disclosures L. Brunet, Epividian, Inc.: Employee, Salary. ViiV Healthcare: ViiV Healthcare has contracted research with my employer, Epividian, Inc., Employer received funding for research. Merck: Merck has contracted research with my employer, Epividian, Inc., Employer received funding for other research. J. Fusco, Epividian, Inc.: Employee, Salary. ViiV Healthcare: Viiv Healthcare contracted research with my employer, Epividian, Inc., Employer received funding for research. Merck & Co.: Merck contracted research with my employer, Epividian, Inc., Employer received funding for research. V. Vannappagari, ViiV HealthCare: Employee, GlaxoSmithKline Company Stock and Salary. L. Ragone, ViiV Healthcare: Employee and Shareholder, restricted shares and Salary. G. Fusco, Epividian, Inc.: Employee, Salary. ViiV Healthcare: Viiv Healthcare contracted research with my employer, Epividian, Inc., Employer received funding for research. Merck & Co.: Merck contracted research with my employer, Epividian, Inc., Employer received funding for research.