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PURPOSE: PSMA overexpression has been associated with aggressive prostate cancer (PCa). However, PSMA PET imaging has revealed highly variable changes in PSMA expression in response to ADT treatment ranging from increases to moderate decreases. To better understand these PSMA responses and potential relationship to progressive PCa, the PET imaging agent, [(18)F]DCFPyL, was used to assess changes in PSMA expression in response to ADT using genomically characterized LuCaP patient-derived xenograft mouse models (LuCaP-PDXs) which were found to be sensitive to ADT (LuCaP73 and LuCaP136;CS) or resistant (LuCaP167;CR). METHODS: [(18)F]DCFPyL (2-(3-{1-carboxy-5-[(6-[(18)F]fluoro-pyridine-3-carbonyl)-amino]-pentyl}-ureido)-pentanedioic acid) was used to assess PSMA in vitro (saturation assays) in LuCaP tumor membrane homogenates and in vivo (imaging/biodistribution) in LuCaP-PDXs. Control and ADT-treated LuCaPs were imaged before ADT (0 days) and 2-, 7-, 14-, and 21-days post-ADT from which tumor:muscle ratios (T:Ms) were determined and concurrently tumor volumes were measured (caliper). After the 21-day imaging, biodistributions and histologic/genomic (PSMA, AR) analysis were done. RESULTS: [(18)F]DCFPyL exhibited high affinity for PSMA and distinguished different levels of PSMA in LuCaP tumors. Post-ADT CS LuCaP73 and LuCaP136 tumor volumes significantly decreased at day 7 or 14 respectively vs controls, whereas the CR LuCaP167 tumor volumes were minimally changed. [(18)F]DCFPyL imaging T:Ms were increased 3–5-fold in treated LuCaP73 tumors vs controls, while treated LuCaP136 T:Ms remained unchanged which was confirmed by day 21 biodistribution results. For treated LuCaP167, T:Ms were decreased (~ 45 %) vs controls but due to low T:M values (

Aquacultivated sea cucumbers often suffer from SKin Ulceration Diseases (SKUDs). SKUDs have been observed in six holothuroid species from nine countries. All SKUDs present a similar symptom—the skin ulceration—and can be induced by bacteria, viruses, or abiotic factors. We here provide an update on SKUDs in holothuroids and analyse the case of the SKUD observed in Holothuria scabra in Madagascar. Field observations revealed a seasonality of the disease (i.e. wintertime maximum peak). Morphological analyses of integument ulcers showed that sea cucumbers react by forming a collagen fibre plug. Metagenomic analyses revealed a higher proportion of Vibrionaceae (Gammaproteobacteria) in ulcers in comparison to the healthy integument of the same individuals. Experimental infection assays were performed with ulcer crude extracts and bacteria isolated from these extracts (e.g. Vibrio parahaemolyticus) but did not significantly induce skin ulceration. Our results suggest that the disease is not induced by a pathogen or, at the very least, that the pathogen is not found within the ulcers as the disease is not transmissible by contact. An initial cause of the SKUD in Madagascar might be the repeated and prolonged exposures to cold temperatures. Opportunistic bacteria could settle in the dermis of ulcerated individuals and promote the ulcer extension. We propose a general nomenclature for SKUDs based on the acronym of the disease, the affected sea cucumber species (e.g. Hs for Holothuria scabra), the concerned region using an ISO code 3166-2 (e.g. MG for Madagascar), the description date (e.g. 20 for the year 2020), and, when known, the inducing agent (first letter of the general taxon, b for bacteria, v for virus in currently known cases; a a if it is an abiotic inducing parameter; nothing if the inducing cause has not been precisely identified). The disease described in this work will be designated under the name SKUD Hs-MG-20.

Drastic sensitivity enhancement of dynamic nuclear polarization is becoming an increasingly critical methodology to monitor real-time metabolic and physiological information in chemistry, biochemistry, and biomedicine. However, the limited number of available hyperpolarized 13C probes, which can effectively interrogate crucial metabolic activities, remains one of the major bottlenecks in this growing field. Here, we demonstrate [1-13C] N-acetyl cysteine (NAC) as a novel probe for hyperpolarized 13C MRI to monitor glutathione redox chemistry, which plays a central part of metabolic chemistry and strongly influences various therapies. NAC forms a disulfide bond in the presence of reduced glutathione, which generates a spectroscopically detectable product that is separated from the main peak by a 1.5 ppm shift. In vivo hyperpolarized MRI in mice revealed that NAC was broadly distributed throughout the body including the brain. Its biochemical transformation in two human pancreatic tumor cells in vitro and as xenografts differed depending on the individual cellular biochemical profile and microenvironment in vivo. Hyperpolarized NAC can be a promising non-invasive biomarker to monitor in vivo redox status and can be potentially translatable to clinical diagnosis.

Introduction: Per 2018 ACC AHA adult congenital heart disease guidelines, routine transthoracic echocardiography (TTE) is recommended for follow-up in patients with d-transposition of the great arteries (dTGA) after atrial switch operation at least annually. Little data are available to suggest utility in clinical management with frequent surveillance, either with or without symptoms. Hypothesis: We hypothesized that frequent TTEs would not lead to significant clinical changes in management and that TTEs performed for symptoms would lead to more detection of pathology and clinically relevant management decisions. Methods: We conducted a retrospective review of all echocardiograms performed for dTGA patients corrected with the atrial switch procedure at Texas Children’s Hospital from 2000-2009 to obtain baseline TTEs and 2010-2019 to analyze for changes in clinical management, associated with TTE performance. Results: We identified 50 patients with dTGA and atrial switch operation with 54% Mustard operation. A total of 333 echocardiograms were performed (6.7/person), 30% (100) with symptoms. The average age at time of all TTEs was 35 +/- 11 years. Most frequent symptoms were palpitations (n=39), dyspnea (n=30), and fatigue (n=27). Changes in management occurred after 9% of studies (10/100 of symptomatic, 21/233 asymptomatic patients, p = NS). Most of these were medication changes (n=18, 11 asymptomatic) and advanced imaging (n=12, 9 asymptomatic). Invasive management after TTE was rare (1 baffle stenting in asymptomatic patient) but after advanced imaging included 4 baffle stent implantations (3 asymptomatic). The interval between TTEs was 1.2 +/- 0.9 years, regardless of symptoms. Conclusions: In dTGA patients after atrial switch operation, routine screening TTEs and symptomatic TTEs had similar yield in detecting pathology leading to a clinical change in management. TTE and subsequent advanced imaging preceded invasive intervention (baffle stenting) in 10% of patients, mostly asymptomatic. Less frequent surveillance TTEs in asymptomatic and advanced imaging in symptomatic dTGA patients with atrial switch operation is cost-effective and should be considered .

Background Adiposity-related ventilatory constraints in older adults can potentially contribute to greater risk of exercise intolerance and mobility disability. This study investigated whether ventilatory limitation, measured by breathing reserve (BR) at peak exercise, is associated with body composition and physical function in older adults with obesity. Methods This study was a cross-sectional analysis of data from a community-based cohort (N = 177) of older men and women (65–79 years) with obesity (body mass index = 30–45 kg/m2). All participants underwent cardiopulmonary exercise testing on a treadmill, dual-energy X-ray absorptiometry for body composition, and physical function assessments. We examined relationships between BR and body composition and physical function using multiple linear regression and compared a subset with (BR ≤ 30%; BR-low; n = 56) and without (BR ≥ 45%; BR-high, n = 48) ventilatory limitation using unpaired Student’s t test and analysis of covariance. Results BR was inversely related to total body mass, lean mass, fat mass, % body fat, and waist circumference (p < 0.05 for all). BR was positively related to 400 m walk time (p = .006) and inversely related to usual gait speed (p = .05) and VO2peak (p < .0001), indicative of worse physical function. BR-low had greater adiposity, but also greater lean mass, higher VO2peak, and faster 400 m walk time, compared to BR-high (p < .05, for all). Conclusions Older adults with obesity who also have ventilatory limitation have overall higher measures of adiposity, but do not have lower peak exercise capacity or physical function. Thus, ventilatory limitation does not appear to be a contributing factor to obesity-related decrements in exercise tolerance or mobility.

Heart failure (HF) in the adult with congenital heart disease (ACHD) is associated with high morbidity and mortality and has been implicated as the leading cause of death in this patient population. The diagnosis of HF in ACHD involves a combination of clinical suspicion from subjective patient history, anatomic imaging, functional diagnostic studies, and rhythm evaluation. Once diagnosed, the approach to management of HF in this population varies widely and by lesion. Unfortunately, there is a paucity of literature available delineating the optimal management of these patients, making clinical decision-making extremely challenging. In this review, we aim to summarize available evidence to help guide the diagnosis and management of HF in ACHD.

Complete heart block is a common complication for adults with congenital heart disease (CHD). Epicardial pacing is preferred in patients with septal shunting due to risk of thromboembolism. Anatomic changes in complex CHD may preclude surgical epicardial lead placement. Thromboembolism risk reduction in such patients requiring endocardial pacing remains questionable. (Level of Difficulty: Advanced.).

Background Interventional catheterization procedures may be needed for patients with severe renal failure who are dependent on dialysis. To avoid the risk of fluid overload and electrolyte derangement during complex procedures in this oliguric/anuric patient population, we performed intra-procedural dialysis, either continuous renal replacement therapy (CRRT) or continous cycling peritoneal dialysis (CCPD). Methods We performed a retrospective review of a cohort of pediatric patients, ages 0–18 years, with dialysis-dependent renal failure who received CRRT or CCPD during catheterization procedures from January 2013 to March 2016. Results Eight patients underwent a total of nine interventional catheterization procedures while receiving intra-procedural dialysis. Median age was 4.5 years (range 8 months to 17 years) and weight, 11.6 kg (11.2–62.6 kg). Six patients had end-stage renal disease (ESRD) and two patients had acute kidney injury (AKI), one due to hepatorenal syndrome and one due to multifactorial causes associated with congenital heart disease. The most common reason for catheterization was occlusive venous thrombosis requiring recanalization. CRRT was used during five cases and CCPD during four cases. Median procedure time was 337 min (95–651 min) and median contrast dose 4.2 mL kg−1 (1.2–8.2 mL kg−1). Euvolemia was maintained based on pre- and post-catheterizations weights, and no significant electrolyte abnormalities occurred based on lab monitoring during and post-procedure. Conclusions Intra-procedural dialysis using CRRT or CCPD enables even small pediatric patients with severe renal failure to undergo long and complex interventional catheterizations by reducing the risk of fluid overload and electrolyte abnormalities. Collaboration between nephrology, cardiology, and dialysis teams is necessary for successful management of this challenging patient population.

Fontan-associated protein-losing enteropathy is difficult to treat and associated with poor prognosis. Cardiac rehabilitation and exercise are thought to have beneficial effects for patients with Fontan circulation. We report the case of a young adult patient palliated to Fontan circulation, with a decade-long history of symptoms related to protein-losing enteropathy. At age 23 years, he appreciated an improvement in symptoms and laboratory values after cardiac rehabilitation and prescriptive exercise.

Purpose Adults with congenital heart disease (ACHD) are an emerging population. Heart failure (HF) is a major cause of morbidity and mortality for ACHD. Sacubitril/valsartan has been shown to reduce the risk of hospitalizations and death from HF in acquired cardiovascular disease but there is little information available on its effect on HF in ACHD. Methods We retrospectively studied patients with complex congenital heart disease (CHD) who were prescribed sacubitril/valsartan to treat HF. Data collected includes New York Heart Association (NYHA) classification, laboratory data, vital signs, and imaging by echocardiogram. Results Eight ACHD patients with HF with a median age of 40.6 [IQR 33.3-52.8] years were treated with sacubitril/valsartan for a median duration of 269 [IQR 102-473] days. Five (62.5%) had a systemic right ventricle and 3 (37.5%) had single ventricle anatomy. Five (62.5%) had severe systemic systolic ventricular dysfunction. At time of last follow-up, 3 (37.5%) patients at NYHA III had no change in functional class, 4 (50%) patients at NYHA IV improved to NYHA II. One patient has not yet returned for follow-up to evaluate functional status. No patients were noted to have a substantial change in renal function or potassium levels. Median brain natriuretic peptide values pre and post- sacubitril/valsartan were 2517 pg/mL and 1040 pg/mL, respectively. Median mean arterial pressures pre and post-sacubitril/valsartan were 83 mmHg and 77 mmHg, respectively. One (12.5%) patient required dose reduction due to hypotension. At time of last follow-up, 2 (25%) achieved 97 mg/100 mg dose of sacubitril/valsartan. No patients experienced symptoms related to angioedema. Conclusion In a small cohort of adults with complex CHD and HF, sacubitril/valsartan was well-tolerated, with some patients experiencing improvement in NYHA class. More studies and a registry of outcomes of sacubitril/valsartan use in ACHD are needed.

Objective: The goal is to evaluate avelumab, an anti-PD-L1 monoclonal immunoglobulin G antibody labeled with zirconium-89 in human PD-L1-expressing cancer cells and mouse xenografts for clinical translation. Methods: [89Zr]Zr-DFO-PD-L1 monoclonal antibody (mAb) was synthesized using avelumab conjugated to desferrioxamine. In vitro binding studies and biodistribution studies were performed with PD-L1+MDA-MB231 cells and MDA-MB231 xenograft mouse models, respectively. Biodistributions were determined at 1, 2, 3, 5, and 7 days post coinjection of [89Zr]Zr-DFO-PD-L1 mAb without or with unlabeled avelumab (10, 20, 40, and 400 µg). Results: [89Zr]Zr-DFO-PD-L1 mAb exhibited high affinity (Kd ∼ 0.3 nM) and detected moderate PD-L1 expression levels in MDA-MB231 cells. The spleen and lymph nodes exhibited the highest [89Zr]Zr-DFO-PD-L1 mAb uptakes in all time points, while MDA-MB231 tumor uptakes were lower but highly retained. In the unlabeled avelumab dose escalation studies, spleen tissue–muscle ratios decreased in a dose-dependent manner indicating specific [89Zr]Zr-DFO-PD-L1 mAb binding to PD-L1. In contrast, lymph node and tumor tissue–muscle ratios increased 4- to 5-fold at 20 and 40 µg avelumab doses. Conclusions: [89Zr]Zr-DFO-PD-L1 mAb exhibited specific and high affinity for PD-L1 in vitro and had target tissue uptakes correlating with PD-L1 expression levels in vivo. [89Zr]Zr-DFO-PD-L1 mAb uptake in PD-L1+tumors increased with escalating doses of avelumab.

OBJECTIVES This study aims to investigate the impact of respiratory symptoms in current and former smokers with and without obstructive lung disease (OLD) on all-cause mortality. DESIGN Secondary analysis in a prospective cohort (the Health, Aging and Body Composition study). SETTING Memphis, Tennessee, and Pittsburgh, Pennsylvania. PARTICIPANTS Black and white men and women with a history of current and former smoking (N = 596; 63% male and 37% female) aged 70-79 years followed for 13 years. Participants were categorized into 4 mutually exclusive groups based on symptom profile and forced expiratory volume in the 1st second to forced vital capacity ratio. The groups were Less Dyspnea-No OLD (N = 196), More Dyspnea-No OLD (N = 104), Less Dyspnea-With OLD (N = 162), and More Dyspnea-With OLD (N = 134). MEASUREMENTS All-cause mortality. RESULTS Overall, 53% in Less Dyspnea-No OLD, 63% in More Dyspnea-No OLD, 67% in Less Dyspnea-With OLD, and 84% in More Dyspnea-With OLD died within the 13- year follow up period (log-rank χ2 = 44.4, P

Supplemental Material, PDL1_supportingInfo_ejagoda_(1) for Immuno-PET Imaging of the Programmed Cell Death-1 Ligand (PD-L1) Using a Zirconium-89 Labeled Therapeutic Antibody, Avelumab by Elaine M. Jagoda, Olga Vasalatiy, Falguni Basuli, Ana Christina L. Opina, Mark R. Williams, Karen Wong, Kelly C. Lane, Steve Adler, Anita Thein Ton, Lawrence P. Szajek, Biying Xu, Donna Butcher, Elijah F. Edmondson, Rolf E. Swenson, John Greiner, James Gulley, Janet Eary and Peter L. Choyke in Molecular Imaging

Key Points Question Have emergency department clinicians responded to the opioid epidemic through altering opioid prescription rates? Findings In this cross-sectional study of 556 176 emergency department patient encounters and 70 218 opioid prescriptions within a single emergency department, yearly prescriptions decreased by 66.3% between 2013 and 2018. This decrease was associated with a 71.1% reduction in the number of opioid prescriptions for musculoskeletal pain (back, limb, joint, and neck pain) and lesser, but still marked, decreases for fractures and kidney stones. Meaning Reductions in yearly opioid prescriptions across varying indications appear to be aligned with recognition of the opioid crisis in addition to national, state, and departmental education guidelines., Importance Opioid prescriptions for treatment of pain in emergency departments (EDs) are associated with long-term opioid use. The temporal pattern of opioid prescribing in the context of the opioid epidemic remains unknown. Objective To examine the temporal pattern of opioid prescribing within an ED for varying pain conditions between 2009 and 2018. Design, Setting, and Participants A population-based, cross-sectional study was conducted at the ED of an urban academic medical center. All patients treated within that ED between January 1, 2009, and December 31, 2018, were included. Main Outcomes and Measures The proportion of patients prescribed an opioid for treatment of pain in the ED temporally by condition, condition type, patient demographics, and physician prescriber. Results Between 2009 and 2018, 556 176 patient encounters took place in the ED, with 70 218 unique opioid prescriptions ordered. A total of 316 632 patients (55.9%) were female, 45 070 (42.6%) were of white race, and 43 412 (40.6%) were privately insured; the median age group was 41 to 45 years. Yearly opioid prescriptions decreased by 66.3% (from 16.3 to 5.5 opioids per 100 encounters) between 2013 and 2018, with a yearly adjusted odds ratio (aOR) of 0.808 (95% CI, 0.802-0.814) compared with the prior year. In patients with musculoskeletal pain (back, joint, limb, and neck pain), opioid prescribing decreased by 71.1% (from 36.7 to 10.6 opioids per 100 encounters between 2013 and 2018; aOR, 0.758; 95% CI, 0.744-0.773). In patients with musculoskeletal trauma (fracture, sprain, contusion, and injury), opioid prescribing decreased by 58.0% (from 34.2 to 14.8 opioids per 100 encounters; aOR, 0.811; 95% CI, 0.797-0.824). In patients with nonmusculoskeletal pain (abdominal pain, kidney stone, respiratory distress, and pharyngitis) opioid prescribing decreased by 53.7% (from 20.1 to 9.3 opioids per 100 encounters; aOR, 0.850; 95% CI, 0.834-0.868). Between 2009 and 2018, patients who were black (aOR, 0.760; 95% CI, 0.741-0.779) and those who were Asian (aOR, 0.714; 95% CI, 0.665-0.764) had the lowest odds of receiving an opioid compared with other racial/ethnic groups. Conclusions and Relevance There was a substantial temporal decrease in the number of opioid prescriptions within this ED during the study period. This decrease was associated with substantial relative reductions in opioid prescribing for treatment of musculoskeletal pain compared with fractures and kidney stones., This cross-sectional study examines the temporal pattern of opioid prescribing for patients with pain conditions in an urban emergency department over a 10-year period.

Previous studies about long-term survivors of the atrial switch operation for d-transposition of the great arteries (TGA), known as the Mustard or Senning procedure, review complications predominantly in the first 3 decades after palliation. Little is published about very late complications after 30

Complete heart block is commonly seen in adults with congenital heart disease. Pacing therapy can improve outcomes, but anatomy may add complexity and limit treatment options. A 50-year-old woman with unpalliated cyanotic single ventricle heart disease consisting of unbalanced atrioventricular

Before the 1950s, D-transposition of the great arteries was associated with nearly 90% mortality within the first year of life. The Mustard and Senning procedures resulted in a significant increase in the lifespan of these patients but with notable long-term complications, including arrhythmias, sinus node dysfunction, chronotropic incompetence, and right ventricular systolic dysfunction. The arterial switch operation (first described by Adib Jatene) initially resulted in nearly universal death. However, the use of coronary buttons for coronary artery translocation has improved operative survival dramatically. It is now considered the treatment of choice in patients amendable to the arterial switch operation. Considered an anatomic repair, resulting in concordant ventriculoarterial connections and a systemic left ventricle, the arterial switch operation reduces the incidence of ventricular dysfunction. However, it is also associated with long-term complications, including aortic root dilatation, aortic valve regurgitation, right ventricular outflow tract obstructions, coronary artery stenosis/compression, and branch pulmonary artery stenosis.

Promoting lasting weight loss among older adults is an important public health challenge. Participation in physical activity aids in weight loss and is important for the maintenance of physical function and quality of life. However, traditional intensive lifestyle interventions place a focus on discrete bouts of structured activity, leaving much of the remainder of the day for sedentary behavior. Structured exercise and weight loss programs often produce short-term weight loss that is typically followed by weight regain, and older adults are more likely to regain weight as fat mass rather than lean mass. Preliminary evidence suggests a focus on day-long movement intended to minimize time spent sitting produces better short-term weight loss and weight maintenance. Herein we describe the design and methods for a three-arm randomized controlled trial comparing mHealth-supported weight loss (WL) + structured exercise (EX); WL + a novel daily movement intervention (SitLess); and WL + EX + SitLess. Older adults (N = 180) will be randomly assigned to one of the three interventions, each comprised of a 6-month intensive phase; a 3-month transition phase; and a 9-month maintenance phase. The primary aim of the study is to determine whether the addition of SitLess to a traditional intensive lifestyle intervention comprised of dietary weight loss and structured exercise produces a larger 18-month reduction in body weight relative to WL + EX and WL + SitLess.

Objective Studies have shown improvement in lipid levels after institution of lifestyle changes in children enrolled in closely monitored programs. There programs are difficult to mimic in real world clinics. We aim to determine if diet and exercise result in improvement in lipid levels in patients seen in a designated lipid clinic in a real life setting. Design Retrospective review of patients followed for dyslipidemia at the Texas Children's Hospital Lipid Clinic from May 1, 2012 to May 1, 2015. Patients included were seen more than once, had repeat lipid testing, and abnormal baseline lipid levels. Multivariate analysis using mixed models were performed to compare outcomes in patients who did and did not participate in lifestyle change. Results Of the 268 patients seen within the study period, 174 (56% male, 44% female) met inclusion criteria. Median age was 11 years. Compared to patients who did not make lifestyle changes: patients who made only diet changes demonstrated significant improvement in weight only (slope = −1.55, P-value = .014), and those who made only exercise changes demonstrated significant improvements in serum cholesterol (slope = −22.8, P-value = .017) and non-HDL cholesterol (slope = −28.7, P-value =

Preventing asthma exacerbations is a goal of National Asthma Guidelines, but identification of at-risk individuals is difficult, especially in older asthmatics. We aimed to characterize exacerbation-prone asthma in older adults to identify characteristics and predictive biomarkers associated with high-risk phenotypes to facilitate precision medicine approaches. 70 non-smoking subjects ≥60 years old in the Severe Asthma Research Program underwent characterization (comprehensive questionnaires, lung function with bronchodilator reversibility, atopy assessment, biomarker collection). Using patient-reported exacerbations two phenotypes were defined; Exacerbation Prone Asthma (EPA,≥1/past year) and Very Frequent Exacerbations (VFE,≥3/past year). Risk and biomarker associations were assessed with odds ratios (OR) using logistic regression. 44% of older asthmatics had EPA. Healthcare utilization and treatment with higher corticosteroid doses were more frequent in EPA compared to non-exacerbating subjects (p

Inhaled corticosteroids are the mainstay of asthma treatment using a step-up approach with incremental dosing and additional controller medications in order to achieve symptom control and prevent exacerbations. While most patients respond well to this treatment approach, some patients remain refractory despite high doses of inhaled corticosteroids and a long-acting β-agonist. The problem lies in the heterogeneity of severe asthma, which is further supported by the emergence of severe asthma phenotypes. This heterogeneity contributes to the variability in treatment response. Randomized controlled trials involving add-on therapies in poorly controlled asthma have challenged the idea of a "one size fits all" approach targeting specific phenotypes in their subject selection. This review discusses severe asthma phenotypes from unbiased clustering approaches and the most recent scientific evidence on novel treatments to provide a guide in personalizing severe asthma treatment.

Reducing asthma exacerbation frequency is an important criterion for approval of asthma therapies, but the clinical features of exacerbation-prone asthma (EPA) remain incompletely defined.To describe the clinical, physiologic, inflammatory, and comorbidity factors associated with EPA.Baseline data from the NHLBI Severe Asthma Research Program (SARP)-3 were analyzed. An exacerbation was defined as a burst of systemic corticosteroids lasting 3 days or more. Patients were classified by their number of exacerbations in the past year: none, few (one to two), or exacerbation prone (≥3). Replication of a multivariable model was performed with data from the SARP-1 + 2 cohort.Of 709 subjects in the SARP-3 cohort, 294 (41%) had no exacerbations and 173 (24%) were exacerbation prone in the prior year. Several factors normally associated with severity (asthma duration, age, sex, race, and socioeconomic status) did not associate with exacerbation frequency in SARP-3; bronchodilator responsiveness also discriminated exacerbation proneness from asthma severity. In the SARP-3 multivariable model, blood eosinophils, body mass index, and bronchodilator responsiveness were positively associated with exacerbation frequency (rate ratios [95% confidence interval], 1.6 [1.2-2.1] for every log unit of eosinophils, 1.3 [1.1-1.4] for every 10 body mass index units, and 1.2 [1.1-1.4] for every 10% increase in bronchodilatory responsiveness). Chronic sinusitis and gastroesophageal reflux were also associated with exacerbation frequency (1.7 [1.4-2.1] and 1.6 [1.3-2.0]), even after adjustment for multiple factors. These effects were replicated in the SARP-1 + 2 multivariable model.EPA may be a distinct susceptibility phenotype with implications for the targeting of exacerbation prevention strategies. Clinical trial registered with www.clinicaltrials.gov (NCT 01760915).

We evaluated whether ventilatory limitation during peak cardiopulmonary exercise testing is associated with worse body composition and physical function in healthy older adults with obesity but without chronic pulmonary disease. 177 healthy adults, 65–80 years old, with obesity (BMI=30-45kg/m2) underwent cardiopulmonary exercise testing on a treadmill, body composition measurement using DXA, and physical function assessment. Participants were categorized into 4 groups based on the lower 95% confidence limit for mean VO2peak (17.49ml/kg/min) and the median breathing reserve at peak exercise (BRpeak, 37.2). Those with low VO2peak/low BRpeak were considered to have ventilatory limitation (VL,n=33), normal BRpeak/low VO2peak had non-ventilatory limitation (NVL,n=48), low BRpeak/high VO2peak were healthy obese (HOb,n=55), and normal BRpeak/high VO2peak were fit obese (FOb,n=41). VO2peak was lowest in VL (14.7 ± 1.7ml/kg/min vs 15.5 ± 1.7ml/kg/min vs 20.7 ± 2.6ml/kg/min vs 19.9ml/kg/min) and was associated with lower oxygen pulse (10.3 ± 1.5ml/HR vs 10.8 ± 2.2ml/HR vs 13.3 ± 2.5ml/HR vs 13.6 ± 3.1ml/HR) and higher VE/CO2 (34.2 ± 5.2 vs 30.1 ± 3.1 vs 31.7 ± 2.5 vs 28.5 ± 3.1) compared to NVL, HOb, and FOb respectively (p

Laboratory-based CD4 monitoring of HIV patients presents challenges in resource limited settings (RLS) including frequent machine breakdown, poor engineering support and limited cold chain and specimen transport logistics. This study assessed the performance of two CD4 tests designed for use in RLS; the Dynal assay and the Alere PIMA test (PIMA). Accuracy of Dynal and PIMA using venous blood was assessed in a centralised laboratory by comparison to BD FACSCount (BD FACS). Dynal had a mean bias of -50.35 cells/µl (r(2) = 0.973, p

Introduction: Interprofessional education (IPE) has been internationally recognized. In the Philippines, however, there is limited experience with IPE. This paper describes the activities of interprofessional teams and the student participants' perceptions of the pilot implementation of the Family Case Management, an IPE initiative of the University of the Philippines Community Health and Development Program in partnership with the Municipality of San Juan, Batangas. Methods: Five teams composed of medical, nursing, occupational therapy, physical therapy and speech pathology students participated. They provided health services to families with complex health needs in the community. Their activities were: (1) orientation of the team, (2) choosing the patient and family, (3) patient and family engagement, (4) assessment and goal-setting, (5) patient and family intervention, and (6) monitoring of outcomes. Students completed a self-administered questionnaire exploring their (1) overall experience, (2) perceptions of the project's most and least useful aspects, and (3) recommendations for improvement. Quantitative and qualitative data analyses were performed. Results: Data showed high ratings of the experience. Themes on the useful aspect of the project were (1) learning about collaboration, (2) appreciation of roles, (3) holistic care, (4) service to the community, and (5) unique learning experience. Themes on the least useful aspects were (1) coordination requirement, (2) patient management, (3) program structure, and (4) community-setting limitations. Recommendations included improvements in communication, orientation, patient management, available resources and supervision. Discussion: The students' appreciation of the Family Case Management demonstrated the opportunity and challenges for IPE implementation in the Philippines.

Studies have shown improvement in lipid levels after institution of lifestyle changes in children enrolled in closely monitored outpatient settings, but it is difficult to mimic this in real world clinics. We aim to determine if diet and exercise result in improvement in lipid levels in patients

A 62-year-old African American woman presented to her primary care physician with binocular photopsias increasing in frequency over 1 year. Magnetic resonance angiography of the brain revealed bilateral 3-mm internal carotid artery aneurysms. She was referred to vascular medicine for further work-up. Her physical examination was unremarkable except for a right-sided femoral bruit. Specific testing for causes of multiple intracranial aneurysms was unremarkable except for positive rapid plasma reagin titers and fluorescent treponemal antibody absorption staining. She was referred to Infectious Diseases clinic where it was determined that the patient had a history of congenital syphilis that was not adequately treated until almost 20 years after birth. Few case reports illustrate the relationship between syphilis and intracranial aneurysms. The authors present this case to increase awareness of this uncommon presentation.

Liposomes are lipid nanoparticles comprised of phospholipid bilayers with an aqueous interior. They have emerged as promising multi-modality imaging agents and engender significant interest as drug delivery vehicles, e.g. doxorubicin liposomes. Although a number of methods for radiolabeling liposomes with various radionuclides have been developed, 18F is the most useful for PET imaging. In this study, preformed maleimide-PEG functionalized liposomes with a mean diameter of 70 nm were obtained by sonication of a lipid mixture consisting of DPPC, cholesterol, and DSPE-PEG2000-Mal (61:30:9) in acetate buffer (pH 6.5) followed by extrusion. 18F labeled 2-(2-(2-(2-fluoroethoxy)ethoxy)ethoxy)ethanethiol was prepared, followed by conjugation with the maleimide-PEG functionalized liposome in 0.1M acetate buffer (0.1% EDTA), pH 6.5-8.0. Liposome sizes did not differ significantly before and after the 18F labeling. The overall radiochemical yield of the reaction was 10-25% (n= 12, uncorrected) in a 180 minute radiolabeling time. Micro PET imaging of rats was done at various times, up to 4 hrs, following IV injection of the 18F liposomes and their bio-distribution was also investigated. Our imaging studies with 18F liposomes appear comparable to images from previously described labeling methods with 18F liposomes remaining in the blood pool at 4 hrs. Our results indicate that this will allow the ready availability of 18F liposomes for vascular imaging and also potentially for cancer imaging. Research Support: This study was funded by the intramural program of the National Institutes of Health. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr LB-420. doi:1538-7445.AM2012-LB-420