Compositional Variations between Adult and Infant Skin Microbiome: An Update.

Human skin and its commensal microbiome form the first layer of protection to the outside world. A dynamic microbial ecosystem of bacteria, fungi and viruses, with the potential to respond to external insult, the skin microbiome has been shown to evolve over the life course with an alteration in taxonomic composition responding to altered microenvironmental conditions on human skin. This work sought to investigate the taxonomic, diversity and functional differences between infant and adult leg skin microbiomes. A 16S rRNA gene-based metataxonomic analysis revealed significant differences between the infant and adult skin groups, highlighting differential microbiome profiles at both the genus and species level. Diversity analysis reveals differences in the overall community structure and associated differential predicted functional profiles between the infant and adult skin microbiome suggest differing metabolic processes are present between the groups. These data add to the available information on the dynamic nature of skin microbiome during the life course and highlight the predicted differential microbial metabolic process that exists on infant and adult skin, which may have an impact on the future design and use of cosmetic products that are produced to work in consort with the skin microbiome.

Multi-disciplinary community respiratory team management of patients with chronic respiratory illness during the COVID-19 pandemic.

The Greater Glasgow & Clyde NHS Trust Community Respiratory Response Team was established to manage patients with chronic respiratory disease at home during the COVID-19 pandemic. The team aimed to avert hospital admission while maximally utilising remote consultations. This observational study analysed outcomes of the triage pathway used, use of remote consultations, hospital admissions and mortality among patients managed by the team. Patients' electronic health records were retrospectively reviewed. Rates of emergency department attendance, hospital admission and death within 28 days of referral were compared across triage pathways. Segmented linear regression was carried out for emergency admissions in Greater Glasgow and Clyde pre- and post- Community Respiratory Response Team implementation, using emergency admissions for chronic obstructive pulmonary disease in the rest of Scotland as control and adjusting for all-cause emergency admissions. The triage category correlated with hospital admission and death. The red pathway had the highest proportion attending the emergency department (21%), significantly higher than the amber and green pathways (p = 0.03 and p = 0.004, respectively). The highest number of deaths were in the blue "end-of-life" pathway (p < 0.001). 87% of interactions were undertaken remotely. Triage severity appropriately led to targeted home visits. No nosocomial COVID-19 infections occurred among patients or staff. The Community Respiratory Response Team was associated with a significant decrease in emergency admissions (RR = 0.96 for each additional month under the Poisson model) compared to the counterfactual if the service had not been in place, suggesting a benefit in reducing secondary care pressures. The Community Respiratory Response Team effectively managed patients with chronic respiratory disease in the community, with an associated reduction in secondary care pressures during the COVID-19 pandemic.

Alteration of barrier properties, stratum corneum ceramides and microbiome composition in response to lotion application on cosmetic dry skin.

Xerosis, commonly referred to as dry skin, is a common dermatological condition affecting almost a third of the population. Successful treatment of the condition traditionally involves the application of cosmetic products facilitating the moisturisation of the skin with a range of ingredients including glycerol and fatty acids. While the effectiveness of these treatments is not in question, limited information exists on the impact on the skin microbiome following use of these products and the improvement in skin hydration. Here, we describe improvements in skin barrier properties together with increased levels of cholesterol, ceramides and long-chain fatty acids following application of Body Lotion. Concomitant alterations in the skin microbiome are also seen via 16S rRNA metataxonomics, in combination with both traditional and novel informatics analysis. Following 5 weeks of lotion use, beneficial skin bacteria are increased, with improvements in microbiome functional potential, and increases in pathways associated with biosynthesis of multiple long chain fatty acids.

Effect of the PIVO Device on the Procedure of Phlebotomy from Peripheral IV Catheters.

Short peripheral catheters (SPC) are an existing conduit into many patients' veins and line draws from SPC are a desired method of routine blood collection especially in difficult venous access patients. The PIVO device facilitates blood collection through SPC and is being used clinically in a number of hospitals. This study aimed to determine the appropriate wait time following a flush and the minimum waste volume required to obtain an undiluted blood sample when using the PIVO device and how that differed from current guidelines from SPC line draws. A clinical study was conducted examining the analyte results of samples drawn with PIVO through a SPC at varying wait times following a saline flush. Both an initial waste volume and a postwaste sample were compared to a venipuncture control. The resulting samples showed no saline dilution as measured by sodium and creatinine results at all studied wait times. These findings suggest that blood collections using the PIVO device can produce a clinically valid sample with a 30-second wait following a SPC flush and no waste volume prior to sample collection.

PA32540 for the secondary prevention of cardiovascular disease in patients at risk for aspirin-associated gastric ulcers.

Prescribed in patients with a history of myocardial infarction, stroke, transient ischemic attack, coronary intervention or bypass surgery, aspirin is one of the medications most commonly used in the secondary prevention of cardiovascular diseases. It has become a mainstay of therapy after years of solid evidence supporting its efficacy in clinical trials. However, a number of risks and side effects accompany its benefits, including the notable risk of bleeding and gastrointestinal side effects. Numerous mechanisms have been proposed to attenuate these effects to promote adherence and to expand the population for which aspirin is a reasonable treatment option. A polypill or combination formulation that includes a proton pump inhibitor, a drug commonly prescribed alongside aspirin, is one potential avenue of therapy. One such combination pill, PA32540, has undergone Phase I and Phase III trials and shows promising safety and efficacy results in these preliminary trials.

Saphenous vein graft disease: review of pathophysiology, prevention, and treatment.

Saphenous vein graft (SVG) disease after coronary artery bypass grafting (CABG) occurs in three phases: thrombosis, intimal hyperplasia, and atherosclerosis. Within the first month, thrombosis plays a major role. From month 1 to month 12, intimal hyperplasia occurs. Beyond 12 months, atherosclerosis becomes the primary cause for late graft failure. Endothelial damage has been shown to be the major underlying pathophysiology of SVG disease. Many factors contribute to endothelial damage from the moment the vein is harvested to when the vein is grafted into an arterial environment. To address this disease process, various therapeutic modalities, from surgical methods to medical treatment, have been evaluated. Surgically, the technical method of harvesting the vein has been shown to affect SVG patency. From a pharmacologic perspective, only two guideline class I recommended medications, aspirin and statins, have been shown to improve short- and long-term SVG patency after CABG. Despite these surgical and medical advances, SVG disease remains a significant problem with 1-year patency rates of 89% dropping to 61% after 10 years. This review discusses the pathogenesis of SVG disease, predictors of SVG failure, and current surgical and pharmacologic therapies to address SVG disease, including possible future treatment.

Heart failure patient adherence: epidemiology, cause, and treatment.

Poor adherence to therapeutic regimens is a significant impediment to improving clinical outcomes in the HF population. Typical rates of adherence to prescribed medications, low-sodium diets, and aerobic exercise programs remain lower than that needed to decrease morbidity and mortality associated with HF. Factors contributing to poor adherence include multiple comorbidities, clinical depression, and decreased cognitive functioning. HF education and programs to enhance self-management skills have improved patient quality of life but have yet to decrease mortality or rehospitalization rates significantly. Telemonitoring to improve adherence behaviors and self-management interventions within broader HF management programs have demonstrated significant clinical improvements in this population.

Safety, effectiveness, and outcomes of cardiac catheterization in nonagenarians.

With an aging population, nonagenarians (≥90 years of age) are increasingly being considered for cardiac catheterization. Because of the paucity of outcomes data in this population, we sought to evaluate the acute and intermediate outcomes of nonagenarians undergoing cardiac catheterization. A retrospective cohort of 44 nonagenarians undergoing 53 cardiac catheterizations from 2002 to 2010 was identified. Mean age was 91 years (range 90 to 96) with 57% of patients being women. Thirteen percent presented with ST-segment elevation myocardial infarction, 32% with non-ST-segment elevation myocardial infarction, 14% with unstable angina, 25% with chronic angina, and 16% with aortic stenosis. Eighteen percent had left main coronary artery disease and 73% had multivessel coronary disease. Complications occurred in 6 of 44 patients (3 with acute kidney injury, 2 with atrial fibrillation, 1 with femoral artery pseudoaneurysm). Twenty patients were treated with medical management, 1 patient underwent coronary artery bypass surgery, and 2 patients underwent aortic valve replacement. Twenty-one patients underwent percutaneous coronary intervention in 27 different vessels. There was procedural success in 93% of these patients. There were no major adverse cardiac events. Five complications occurred after the intervention (4 atrial fibrillations, 1 femoral artery pseudoaneurysm). Cumulative mortalities at 1 month and 6 and 12 months were 0%, 9%, and 20% respectively. In patients who underwent percutaneous coronary intervention or surgery, mortalities were 0%, 0%, and 13% at 1 month and 6 and 12 months, respectively.

Change in intrathoracic impedance measures during acute decompensated heart failure admission: results from the Diagnostic Data for Discharge in Heart Failure Patients (3D-HF) Pilot Study.

BACKGROUND: Despite the high number of admissions for acute decompensated heart failure (ADHF), there are no specific criteria for discharge readiness. A number of patients have implantable devices that might provide data to assist in determining readiness for discharge. METHODS AND RESULTS: The 3D-HF (Diagnostic Data for Discharge in Heart Failure Patients) study was a prospective observational pilot study enrolling HF patients with Optivol-capable cardiac devices within 48 hours of a hospital admission characterized by worsening HF symptoms. The primary end point was the difference in times from admission to 50% improvement in impedance and to when patient was medically ready for discharge. The nonparametric sign test was used to determine if the difference was significant. A total of 20 subjects were enrolled over a 24-month period. The median ADHF length of stay was 7 days. Of the 20 subjects, 18 achieved the intrathoracic impedance improvement threshold before discharge. The time to reach the threshold for improvement was 2.5 days (interquartile range 2.0-6.0). The difference between days to 50% impedance and days to provider's discharge decision was 3.0 (P = .0072). CONCLUSIONS: Intrathoracic impedance changes were evident over a short duration in the majority of patients admitted for ADHF and may be a potential criterion for discharge readiness.

Safety of iodinated intravenous contrast medium administration in sickle cell disease.

BACKGROUND: Increased sickling of erythrocytes following intravenous iodinated contrast has been described in patients with sickle cell disease. In vitro, the effect is correlated with the tonicity, viscosity, acidity, and ionic nature of contrast media. Less erythrocyte sickling is observed in vitro with second-generation low- and iso-osmolar contrast agents. Clinical impact of these newer intravenous contrast agents has not been investigated. PURPOSE: To review adverse outcomes following contrast administration in a cohort of patients with sickle cell disease. METHODS: Inpatients with sickle cell disease who received iodinated intravenous were identified. Medical records were reviewed for evidence of worsening crisis and occurrence of adverse events within 48 hours of contrast administration. Data points were further analyzed with the goal of identifying predictors of adverse outcome. RESULTS: There were 132 imaging studies that met inclusion criteria in 79 patients, mostly with homozygous hemoglobin S. The low-osmolar contrast Optiray (Coviden Imaging Inc., Hazelwood, Mo) was used in 45%. Administration of fluids, Mucomyst (Bristol-Myers Squibb, New York, NY), oxygen, or blood transfusion preceded 58% of studies. Minor adverse events followed 16% of studies, with new or worsening pain being most common (12%). Contrast-induced nephropathy occurred in 1.5%, resolving in all cases. Prehydration was associated with a decreased incidence of adverse events (P=.02). CONCLUSION: Adverse events related to intravenous contrast occur in sickle cell disease patients at a rate similar to the general population, without an increase in contrast-induced nephropathy. Subjective reports of new or worsening pain crisis do not translate to objective findings. Beneficial diagnostic imaging can be performed without increased risk of serious complication in this population.

Reporting of clinical trials: publication, authorship, and trial registration.

Transparency is the foundation on which all of research integrity rests. The public trust from patients, providers, and policy makers depends on fidelity to the mandates of accountability and access. Two important foundational practices for maintaining transparency in research and the reporting of clinical trials discussed in this review concern manuscript authorship and clinical trial registry, recognizing recent controversies regarding honorary and ghost authorship in the publication of industry-sponsored studies.

Review of advanced heart failure device diagnostics examined in clinical trials and the potential benefit from monitoring capabilities.

Over the past decade, emerging clinical trial data supported the usefulness of implanted therapeutic cardiac devices (pacemakers and defibrillators) for the treatment of heart failure (HF). Interest has now developed in evaluating the potential of device diagnostics to identify HF patients at risk for clinical events and to be used in the management of HF patients. Initial studies have provided inconsistent results. A number of trial design elements have likely played a role in the lack of positive results, including cohort risk determination, intensity of usual care, intensity of the intervention, and selection of end points for the study. These issues will be important to understand when evaluating future clinical trial results and developing new studies, particularly in other HF patient cohorts such as HF with preserved left ventricular function.

Peroxisome proliferator-activated receptor delta agonists inhibit T helper type 1 (Th1) and Th17 responses in experimental allergic encephalomyelitis.

Multiple sclerosis (MS) is a neurological disorder that affects more than a million people world-wide. The aetiology of MS is not known and there is no medical treatment available that can cure MS. Experimental autoimmune encephalomyelitis (EAE) is a T-cell-mediated autoimmune disease model of MS. The pathogenesis of EAE/MS is a complex process involving activation of immune cells, secretion of inflammatory cytokines and destruction of myelin sheath in the central nervous system (CNS). Peroxisome proliferator-activated receptors (PPARs) are nuclear hormone receptor transcription factors that regulate cell growth, differentiation and homeostasis. PPAR agonists have been used in the treatment of obesity, diabetes, cancer and inflammation. We and others have shown that PPARgamma, alpha and delta agonists inhibit CNS inflammation and demyelination in the EAE model of MS. In this study we show that the PPARdelta agonists GW501516 and L165041 ameliorate MOGp35-55-induced EAE in C57BL/6 mice by blocking interferon (IFN)-gamma and interleukin (IL)-17 production by T helper type 1 (Th1) and Th17 cells. The inhibition of EAE by PPARdelta agonists was also associated with a decrease in IL-12 and IL-23 and an increase in IL-4 and IL-10 expression in the CNS and lymphoid organs. These findings indicate that PPARdelta agonists modulate Th1 and Th17 responses in EAE and suggest their use in the treatment of MS and other autoimmune diseases.

Sleep-disordered breathing and heart failure: focus on obstructive sleep apnea and treatment with continuous positive airway pressure.

BACKGROUND: Among patients with heart failure, sleep-disordered breathing is a common problem, with a prevalence ranging from 24% to 76%. Encompassed within the general category of sleep-disordered breathing are 2 types of sleep apnea: obstructive sleep apnea (OSA) occurs when the oropharyngeal musculature relaxes, causing a collapse of the upper airway, and central sleep apnea occurs when the brain stem fails to stimulate breathing. METHODS AND RESULTS: This article focuses on the relationship between heart failure and OSA, the treatment of OSA with continuous positive airway pressure (CPAP), and the role of CPAP in improving such effects of heart failure as ejection fraction, blood pressure, sympathetic activity, sleepiness, heart rate, and mortality. CONCLUSIONS: It is important to distinguish the type of sleep-disordered breathing a patient may have. Further studies are needed to elucidate the effects of CPAP and other therapies.

Aspirin and clopidogrel use in the early postoperative period following on-pump and off-pump coronary artery bypass grafting.

OBJECTIVE: Preoperative use of clopidogrel increases the risk of bleeding, but its postoperative use has not been studied. We studied early postoperative clopidogrel use in on-pump and off-pump coronary artery bypass grafting. METHODS: Data were obtained from the University HealthSystem Consortium database. We conducted a retrospective analysis of data of 15,067 adults who had coronary artery bypass grafting between 2003 and 2006 and received perioperative aspirin alone or in combination with clopidogrel, with the latter administered within 2 days after coronary artery bypass grafting. Logistic regression was used to analyze in-hospital mortality, 30-day readmission, ischemic or thrombotic events, and bleeding events, with propensity score adjustment for clopidogrel treatment. RESULTS: Combined aspirin and clopidogrel were used in 3268 patients (22%). Compared with aspirin alone, aspirin plus clopidogrel was associated with reductions of in-hospital mortality (0.95% vs 1.78%; adjusted odds ratio: 0.50; 95% confidence interval: 0.25, 0.99) and bleeding events (4.19% vs 5.17%; adjusted odds ratio: 0.70; 95% confidence interval: 0.51, 0.97). Ischemic or thrombotic events were not significantly different (1.29% vs 1.53%; adjusted odds ratio, 0.99; 95% confidence interval: 0.59, 1.64). The relative effect of combined treatment did not differ between on-pump and off-pump coronary artery bypass grafting. CONCLUSIONS: Early postoperative clopidogrel combined with aspirin may be safe and beneficial compared with perioperative aspirin treatment alone, in both on-pump and off-pump coronary artery bypass grafting. However, a possibility of selection bias calls for randomized controlled trials to confirm our findings.

Lifestyle risk factors and utilization of preventive services in disabled elderly adults in the community.

Lifestyle risk factor counseling and preventive health services are important to disabled elderly adults to prevent adverse health outcomes. We aimed to examine the prevalence of lifestyle risk factors and utilization of preventive health services in community-dwelling 2,982 adults, aged 60 years or older, with or without disability, in Southeastern Pennsylvania in 2004. The severity of disability was classified as no [independent activities of daily living (ADL) and instrumental activities of daily living (IADL)], some (independent ADL, dependent IADL), and severe limitation (dependent ADL). The prevalence of lifestyle risk factors (cigarette smoking, obesity, binge alcohol use, unhealthy diet, and physical inactivity) and utilization rate of a comprehensive list of preventive health services (risk factor counseling, disease management, vaccination, and cancer screening) were measured, across the disability categories. The prevalence of disability was 14.6% for some limitation and 10.3% for severe limitation. As disability increases, participants with unhealthy diet, physical inactivity, and obesity became more prevalent (8.8, 15.7, and 25.2% for no, some, and severe limitation, respectively) and fewer osteoporosis screenings were performed (51.5, 38.8, and 37.8%). Utilization of other services did not vary significantly across the disability categories, but participants with some or severe limitation were less likely than those without to receive needed health services overall (19.3% or 16.2 vs. 24.2%; P for trend = .047). In conclusion, disabled elderly adults have more undesirable lifestyle risk factors, but are less likely to receive needed health services than nondisabled counterparts. More attention is needed to this vulnerable population.

Prevalence of hypovitaminosis D in cardiovascular diseases (from the National Health and Nutrition Examination Survey 2001 to 2004).

This cross-sectional study examined the burden of cardiovascular diseases (CVDs) using serum 25-hydroxyvitamin D (25[OH]D) and prevalence of hypovitaminosis D in adults with CVDs using data from NHANES 2001 to 2004. Serum 25(OH)D levels were divided into 3 categories (> or =30, 20 to 29, and <20 ng/ml), and hypovitaminosis D was defined as vitamin D <30 ng/ml. Of 8,351 adults who had 25(OH)D measured, mean 25(OH)D was 24.3 ng/ml, and the prevalence of hypovitaminosis D was 74%. The burden of CVDs increased with lower 25(OH)D categories, with 5.3%, 6.7%, and 7.3% coronary heart disease; 1.5%, 2.4%, and 3.2% heart failure; 2.5%, 2.0%, and 3.2% stroke; and 3.6%, 5.0%, and 7.7% peripheral arterial disease. Across all CVDs, hypovitaminosis D was more common in blacks than Hispanics or whites. Compared with persons at low risk for CVDs (68%), it was more prevalent in those at high risk (75%; odds ratio [OR] 1.32, 95% confidence interval [CI] 1.05 to 1.67), with coronary heart disease (77%; OR 1.48, 95% CI 1.14 to 1.91), and both coronary heart disease and heart failure (89%; OR 3.52, 95% CI 1.58 to 7.84) after controlling for age, race, and gender. In conclusion, hypovitaminosis D was highly prevalent in US adults with CVDs, particularly those with both coronary heart disease and heart failure.

Stat4 isoforms differentially regulate inflammation and demyelination in experimental allergic encephalomyelitis.

Experimental allergic encephalomyelitis (EAE) is a T cell-mediated autoimmune disease model of multiple sclerosis. Signal transducer and activator of transcription 4 (Stat4) is a transcription factor activated by IL-12 and IL-23, two cytokines known to play important roles in the pathogenesis of EAE by inducing T cells to secrete IFN-gamma and IL-17, respectively. We and others have previously shown that therapeutic intervention or targeted disruption of Stat4 was effective in ameliorating EAE. Recently, a splice variant of Stat4 termed Stat4beta has been characterized that lacks 44 amino acids at the C terminus of the full-length Stat4alpha. In this study we examined whether T cells expressing either isoform could affect the pathogenesis of EAE. We found that transgenic mice expressing Stat4beta on a Stat4-deficient background develop an exacerbated EAE compared with wild-type mice following immunization with myelin oligodendrocyte glycoprotein peptide 35-55, while Stat4alpha transgenic mice have greatly attenuated disease. The differential development of EAE in transgenic mice correlates with increased IFN-gamma and IL-17 in Stat4beta-expressing cells in situ, contrasting increased IL-10 production by Stat4alpha-expressing cells. This study demonstrates that Stat4 isoforms differentially regulate inflammatory cytokines in association with distinct effects on the onset and severity of EAE.

Racial disparity in the relationship between hospital volume and mortality among patients undergoing coronary artery bypass grafting.

OBJECTIVE: To examine whether the volume-mortality relationship in coronary artery bypass grafting (CABG) differs by race and operative risk. SUMMARY BACKGROUND DATA: In-hospital mortality after CABG is inversely associated with hospital volume. Racial disparities exist in the outcomes of CABG, possibly due to blacks' high operative risk. METHODS: We analyzed 71,949 CABG procedures performed between 2002 and 2005 at 93 academic medical centers participating in the University HealthSystem Consortium. In-hospital mortality was examined across hospital volume categories (very low, <100/yr; low, 100-299/yr; medium, 300-499/yr; and high, > or =500/yr) via logistic regression. RESULTS: In-hospital mortality was 2.0% in whites and 2.8% in blacks. Controlling for patient risk, geographic region, and proportion of African American patients treated at the hospital, the benefit of higher volume was substantial for blacks but only modest for whites (race-by-volume interaction; P = 0.033). Odds ratios of mortality for increasing volume categories (compared with very low volume) were 0.46, 0.37, and 0.47 among blacks but only 0.85, 0.77, and 0.75 among whites. Racial disparities in mortality existed mostly in very low-volume hospitals. The differential volume effect across the 2 racial groups seemed to be primarily driven by regional patterns, as the volume effect was much more pronounced in the South and the Midwest (region by volume interaction; P = 0.033). CONCLUSIONS: Blacks have greater reduction in mortality than whites by undergoing CABG at higher-volume hospitals, regardless of operative risk. Because of limited generalizability, these findings should be confirmed using more representative database.

Modifiable cardiovascular risk factors among individuals in low socioeconomic communities and homeless shelters.

To understand cardiovascular health in low socioeconomic populations, we analyzed the data from 426 low socioeconomic community-dwelling males and females and 287 homeless males in Philadelphia. Despite higher prevalence of smoking and hypertension, the proportion of homeless participants at increased risk for coronary heart disease was comparable with that of low socioeconomic community-dwelling participants. Among various characteristics, emotional stress was significantly associated with coronary heart disease risk in low socioeconomic community-dwelling participants only, suggestive of a differential psychosocial effect of stress. Our findings suggest that low socioeconomic populations are heterogeneous with respect to their risk factors and needs for interventions.