Scientific opportunities in resilience research for cardiovascular health and wellness. Report from a National Heart, Lung, and Blood Institute workshop.

Exposure of biological systems to acute or chronic insults triggers a host of molecular and physiological responses to either tolerate, adapt, or fully restore homeostasis; these responses constitute the hallmarks of resilience. Given the many facets, dimensions, and discipline-specific focus, gaining a shared understanding of "resilience" has been identified as a priority for supporting advances in cardiovascular health. This report is based on the working definition: "Resilience is the ability of living systems to successfully maintain or return to homeostasis in response to physical, molecular, individual, social, societal, or environmental stressors or challenges," developed after considering many factors contributing to cardiovascular resilience through deliberations of multidisciplinary experts convened by the National Heart, Lung, and Blood Institute during a workshop entitled: "Enhancing Resilience for Cardiovascular Health and Wellness." Some of the main emerging themes that support the possibility of enhancing resilience for cardiovascular health include optimal energy management and substrate diversity, a robust immune system that safeguards tissue homeostasis, and social and community support. The report also highlights existing research challenges, along with immediate and long-term opportunities for resilience research. Certain immediate opportunities identified are based on leveraging existing high-dimensional data from longitudinal clinical studies to identify vascular resilience measures, create a 'resilience index,' and adopt a life-course approach. Long-term opportunities include developing quantitative cell/organ/system/community models to identify resilience factors and mechanisms at these various levels, designing experimental and clinical interventions that specifically assess resilience, adopting global sharing of resilience-related data, and cross-domain training of next-generation researchers in this field.

Eosinophils in lichen sclerosus et atrophicus.

BACKGROUND: The classic histopathologic features of lichen sclerosus et atrophicus (LS) include lymphoplasmacytic inflammation below a zone of dermal edema and sclerosis. The presence of eosinophils in LS has received little attention, but the finding of tissue eosinophils, particularly eosinophilic spongiosis in LS, has been suggested as a marker for the coexistence of autoimmune bullous disease or allergic contact dermatitis (or both). We sought to determine whether the histopathologic presence of dermal eosinophils or eosinophilic spongiosis (or both) in biopsies from patients with LS is associated with autoimmune bullous disease, autoimmune connective tissue disease or allergic contact dermatitis. METHODS: A retrospective review of the histopathology and medical records of 235 patients with LS who were evaluated from June 1992 to June 2012 was performed. RESULTS: Sixty-nine patients (29%) had eosinophils on histopathology. Among patients with associated diseases, a statistically significant association between the eosinophil cohort and the cohort without eosinophils was not detected. CONCLUSIONS: The importance of eosinophils is uncertain, but our data suggest that the finding of tissue eosinophils alone is not sufficient to prompt an extensive workup for additional diagnoses.

Prevalence of Airflow Obstruction in U.S. Adults Aged 40-79 Years: NHANES Data 1988-1994 and 2007-2010.

BACKGROUND: The study evaluated the change in the prevalence of airflow obstruction in the U.S. population 40-79 years of age from years 1988-1994 to 2007-2010. METHODS: Spirometry data from two representative samples of the U.S. population, the National Health and Nutrition Examination Surveys (NHANES) conducted in 1988-1994 and 2007-2010, were used. The American Thoracic Society/European Respiratory Society (ATS/ERS) criteria were used to define airflow obstruction. RESULTS: Based on ATS/ERS criteria, the overall age-adjusted prevalence of airflow obstruction among adults aged 40-79 years decreased from 16.6% to 14.5% (p < 0.05). Significant decreases were observed for the older age category 60-69 years (20.2% vs. 15.4%; p < 0.01), for males (19.0% vs. 15.4%; p < 0.01), and for Mexican American adults (12.7% vs. 8.4%; p < 0.001). The prevalence of moderate and more severe airflow obstruction decreased also (6.4% vs. 4.4%; p < 0.01). Based on ATS/ERS criteria, during 2007-2010, an estimated 18.3 million U.S. adults 40-79 years had airflow obstruction, 5.6 million had moderate or severe airflow obstruction and 1.4 million had severe airflow obstruction. CONCLUSIONS: The overall age-adjusted prevalence of airflow obstruction among U.S. adults aged 40-79 years decreased from 1988-1994 to 2007-2010, especially among older adults, Mexican Americans, and males.

Ultrasound and fine-needle aspiration in dermatology, underuse of minimally invasive, efficient diagnostic tools.

BACKGROUND: Ultrasound imaging and ultrasound-guided fine-needle aspiration (FNA) are common procedures used to evaluate and sample cutaneous and subcutaneous tissue. Although ultrasound and FNA have been explored for individual neoplasms, lymph node involvement, and metastases, their use in day-to-day dermatology is not well defined. OBJECTIVE: To investigate the use and utility of ultrasound and FNA in the dermatologic surgery division of a large academic institution. METHODS: Retrospective case review of all ultrasound and FNA procedures ordered by a dermatologic surgeon over a 3-year period. RESULTS: Metastatic disease was suspected in 11 of 21 (52.4%) cases. Cytology confirmed the presence of metastatic disease in two of the 11 cases, and metastatic disease was identified in one additional case in which the diagnosis was not suspected at clinical presentation. Cytology revealed leukemia or lymphoma in three (14.3%) cases, two of which were new diagnoses. Sonographic imaging and cytology revealed a benign diagnosis in 16 (76.2%) cases, five of which were reactive lymph nodes. CONCLUSIONS: The results suggest that ultrasound and FNA are underused techniques that may play an important role in dermatology diagnostics and have the potential for expansion in day-to-day clinical practice.

Reticulated acanthoma with sebaceous differentiation: another sebaceous neoplasm associated with Muir-Torre syndrome?

Reticulated acanthoma with sebaceous differentiation (RASD) represents a rare benign cutaneous epithelial neoplasm with sebaceous differentiation. There has been much speculation about the relationship between RASD and Muir-Torre syndrome (MTS). We report a 53 year-old man who presented with RASD in addition to a prior history of sebaceous adenomas. Immunohistochemically, the tumour cells in the RASD and sebaceous adenomas showed a significantly reduced MSH6 protein expression, whereas there was no loss of MLH1, MSH2 and PMS2. This benign neoplasm, which can be mistaken for various other cutaneous lesions with sebaceous differentiation, deserves wider recognition for its possible association with MTS.

Pemphigus vegetans variant of IgA pemphigus, a variant of IgA pemphigus and other autoimmune blistering disorders.

Pyodermatitis-pyostomatitis vegetans (PPV) constitutes an inflammatory mucocutaneous dermatosis that is associated with inflammatory bowel disease. Clinically, PPV appears as pustules on mucosal surfaces and as vegetating exudative plaques on intertriginous surfaces. It is typically a clinical diagnosis supported by histological findings. Microscopic findings include epidermal hyperplasia, focal acantholysis, and a dense mixed inflammatory infiltrate with intraepithelial and subepithelial eosinophilic microabscesses. In the recent literature, immunofluorescence has been thought to be negative in PPV or, if positive, an aberrant finding. Herein, we report 2 cases of PPV associated with inflammatory bowel disease, which display intercellular IgA deposits. Although these cases may represent isolated epiphenomena, it is possible that the paucity of PPV cases with immunofluorescent studies hitherto has led to an oversight of an interesting association between intercellular IgA and PPV.

Comparing Blood Pressure Values Obtained by Two Different Protocols: National Health and Nutrition Examination Survey, 2017-2018.

Objectives Blood pressure (BP) is traditionally measured using a mercury sphygmomanometer. Given environmental concerns about mercury, clinical and survey settingsare moving to automated devices with an oscillometric protocol to obtain BP. This report compares BP measurement using the mercury and oscillometric protocols.

Clinicopathologic features of IgG/IgA pemphigus in comparison with classic (IgG) and IgA pemphigus.

BACKGROUND: The pemphigus group is characterized by the presence of circulating immunoglobulins against desmosomes. IgG/IgA pemphigus is defined by the presence of IgG and IgA cell surface deposits upon direct immunofluorescence (DIF) and/or circulating IgG and IgA autoantibodies upon indirect immunofluorescence. Previous reports of patients with IgG/IgA pemphigus are sparse. Whether IgG/IgA pemphigus is best classified as a subtype of IgG (classic) pemphigus or IgA pemphigus, or as a distinct entity, has yet to be determined. OBJECTIVES: We compared the features of patients with IgG/IgA pemphigus to those of IgG pemphigus and IgA pemphigus. METHODS: Retrospective clinicopathologic study of patients with IgG, IgG/IgA, and IgA pemphigus evaluated at our clinic (1993-2013). RESULTS: We included 26, 13, and seven patients with IgG, IgG/IgA, and IgA pemphigus, respectively. Patients with IgG/IgA pemphigus did not differ significantly from patients with IgG pemphigus in terms of clinical and microscopic features, DIF findings, anti-desmoglein antibody values, and treatments required. However, patients with IgG/IgA pemphigus were significantly different from patients with IgA pemphigus regarding intertriginous distribution (P = 0.038) and pustular lesions (P < 0.001), acantholysis (P = 0.043), and presence of intercellular C3 deposits on DIF (P < 0.001). CONCLUSION: Comparative clinicopathologic data imply that IgG/IgA pemphigus may best be regarded as a variant of IgG pemphigus and distinct from IgA pemphigus.

Trends in serum lipids and lipoproteins of adults, 1960-2002.

CONTEXT: Serum total and low-density lipoprotein (LDL) cholesterol contribute significantly to atherosclerosis and its clinical sequelae. Previous analyses of data from the National Health and Nutrition Examination Surveys (NHANES) showed that mean levels of total cholesterol of US adults had declined from 1960-1962 to 1988-1994, and mean levels of LDL cholesterol (available beginning in 1976) had declined between 1976-1980 and 1988-1994. OBJECTIVE: To examine trends in serum lipid levels among US adults between 1960 and 2002, with a particular focus on changes since the 1988-1994 NHANES survey. DESIGN, SETTING, AND PARTICIPANTS: Blood lipid measurements taken from 6098 to 15 719 adults who were examined in 5 distinct cross-sectional surveys of the US population during 1960-1962, 1971-1974, 1976-1980, 1988-1994, and 1999-2002. MAIN OUTCOME MEASURES: Mean serum total cholesterol, LDL cholesterol, high-density lipoprotein (HDL) cholesterol, and geometric mean serum triglyceride levels, and the percentage of adults with a serum total cholesterol level of at least 240 mg/dL (> or =6.22 mmol/L). RESULTS: Between 1988-1994 and 1999-2002, total serum cholesterol level of adults aged 20 years or older decreased from 206 mg/dL (5.34 mmol/L) to 203 mg/dL (5.26 mmol/L) (P=.009) and LDL cholesterol levels decreased from 129 mg/dL (3.34 mmol/L) to 123 mg/dL (3.19 mmol/L) (P<.001). Greater and significant decreases were observed in men 60 years or older and in women 50 years or older. The percentage of adults with a total cholesterol level of at least 240 mg/dL (> or =6.22 mmol/L) decreased from 20% during 1988-1994 to 17% during 1999-2002 (P<.001). There was no change in mean HDL cholesterol levels and a nonsignificant increase in geometric mean serum triglyceride levels (P = .06). CONCLUSIONS: The decrease in total cholesterol level observed during 1960-1994 and LDL cholesterol level observed during 1976-1994 has continued during 1999-2002 in men 60 to 74 years and women 50 to 74 years. The target value of no more than 17% of US adults with a total cholesterol level of at least 240 mg/dL (> or =6.22 mmol/L), an objective of Healthy People 2010, has been attained. The increase in the proportion of adults using lipid-lowering medication, particularly in older age groups, likely contributed to the decreases in total and LDL cholesterol levels observed. The increased prevalence of obesity in the US population may have contributed to the increase in mean serum triglyceride levels.

Prevalence of lower-extremity disease in the US adult population >=40 years of age with and without diabetes: 1999-2000 national health and nutrition examination survey.

OBJECTIVE: Although lower-extremity disease (LED), which includes lower-extremity peripheral arterial disease (PAD) and peripheral neuropathy (PN), is disabling and costly, no nationally representative estimates of its prevalence exist. The aim of this study was to examine the prevalence of lower-extremity PAD, PN, and overall LED in the overall U.S. population and among those with and without diagnosed diabetes. RESEARCH DESIGN AND METHODS: The analysis consisted of data for 2873 men and women aged >or=40 years, including 419 with diagnosed diabetes, from the 1999-2000 National Health and Nutrition Examination Survey. The main outcome measures consisted of the prevalence of lower-extremity PAD (defined as ankle-brachial index <0.9), PN (defined as >or=1 insensate area based on monofilament testing), and of any LED (defined as either PAD, PN, or history of foot ulcer or lower-extremity amputations). RESULTS: Of the U.S. population aged >or=40 years, 4.5% (95% CI 3.4-5.6) have lower-extremity PAD, 14.8% (12.8-16.8) have PN, and 18.7% (15.9-21.4) have any LED. Prevalence of PAD, PN, and overall LED increases steeply with age and is higher (P < 0.05) in non-Hispanic blacks and Mexican Americans than non-Hispanic whites. The prevalence of LEDs is approximately twice as high for individuals with diagnosed diabetes (PAD 9.5% [5.5-13.4]; PN 28.5% [22.0-35.1]; any LED 30.2% [22.1-38.3]) as the overall population. CONCLUSIONS: LED is common in the U.S. and twice as high among individuals with diagnosed diabetes. These conditions disproportionately affect the elderly, non-Hispanic blacks, and Mexican Americans.

Human herpesviruses 6, 7, and 8 from a dermatologic perspective.

Human herpesviruses (HHVs) have frequently been suspected as etiologic agents or cofactors in cutaneous disease. However, clearly established associations are rare. Investigations into an etiologic association between HHVs and cutaneous disease are complicated by the ubiquity and nearly universal prevalence of some herpesviruses. This article summarizes the associations between cutaneous disease and HHV-6, HHV-7, and HHV-8. In addition to a personal library of references, the PubMed database of biomedical literature was searched using the following Medical Subject Heading terms: HHV-6, HHV-7, and HHV-8, each in conjunction with cutaneous manifestations, virology, epidemiology, dermatopathology, and therapeutics, between 1998 and March 2011. Free-text searches with known or suspected disease associations were added for broader coverage. The results have been summarized to provide a practical review for the physician likely to encounter cutaneous diseases.