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Background: Patiromer and sodium polystyrene sulfonate (SPS) are cation-exchangers approved for the treatment of chronic hyperkalemia. Data regarding their efficacy acutely is lacking. Despite this, both drugs are frequently used in the emergent setting. Objective: The purpose of this study was to compare the potassium reduction of patiromer to SPS within 6 to 24 hours following a single dose. Methods: This retrospective quality improvement project included hyperkalemic patients receiving 1 dose of patiromer or SPS and had a second potassium level drawn in 6 to 24 hours. Doses of 8.4 g of patiromer and 15 g of SPS were considered “low dose” while 16.8 g of patiromer and 30 g of SPS were considered “high dose.” The presence of a dose-response relationship was assessed through a linear regression analysis. Results: Mean (SD) potassium reduction was higher in SPS than patiromer [0.76 (0.63) mEq/L vs 0.32 (0.65) mEq/L, ( P = .001)]. A dose response relationship was not demonstrated in low versus high dose groups [−0.21 (0.14), P = .13] and CKD, ESRD, and renal transplant patients when compared to patients with normal renal function [0.11 (0.17), P = .51, −0.07 (0.19), P = −0.07 (0.19), P = .73, and −0.10 (0.22), P = .65]. Conclusions: This study suggests a clinically significant reduction in potassium with SPS compared to patiromer. Although SPS was successful in demonstrating this outcome, due to well-documented adverse reactions in the literature and a time to onset of 6 hours, it cannot be recommended for use in acute hyperkalemia either.

Background We aimed to study organizational aspects, case mix, and practices in Indian intensive care units (ICUs) from 2018 to 2019, following the Indian Intensive Care Case Mix and Practice Patterns Study (INDICAPS) of 2010–2011. Methods An observational, 4-day point prevalence study was performed between 2018 and 2019. ICU, patient characteristics, and interventions were recorded for 24 hours, and ICU outcomes till 30 days after the study day. Adherence to selected compliance measures was determined. Data were analyzed for 4,669 adult patients from 132 ICUs. Results On the study day, mean age, acute physiology and chronic health evaluation (APACHE II), and sequential organ failure assessment (SOFA) scores were 56.9 ± 17.41 years, 16.7 ± 9.8, and 4.4 ± 3.6, respectively. Moreover, 24% and 22.2% of patients received mechanical ventilation (MV) and vasopressors or inotropes (VIs), respectively. On the study days, 1,195 patients (25.6%) were infected and 1,368 patients (29.3%) had sepsis during their ICU stay. ICU mortality was 1,092 out of 4,669 (23.4%), including 737 deaths and 355 terminal discharges (TDs) from ICU. Compliance for process measures related to MV ranged between 62.7 and 85.3%, 11.2 and 47.4% for monitoring delirium, sedation, and analgesia, and 7.7 and 25.3% for inappropriate transfusion of blood products. Only 34.8% of ICUs routinely used capnography. Large hospitals with ≥500 beds, closed ICUs, the APACHE II and SOFA scores, medical admissions, the presence of cancer or cirrhosis of the liver, the presence of infection on the study day, and the need for MV or VIs were independent predictors of mortality. Conclusions Hospital size and closed ICUs are independently associated with worse outcomes. The proportion of TDs remains high. There is a scope for improvements in processes of care. Registered at clinicaltrials.gov (NCT03631927). How to cite this article Divatia JV, Mehta Y, Govil D, Zirpe K, Amin PR, Ramakrishnan N, et al. Intensive Care in India in 2018–2019: The Second Indian Intensive Care Case Mix and Practice Patterns Study. Indian J Crit Care Med 2021;25(10):1093–1107.

Epidemiological and clinical studies have demonstrated a consistent relationship between increased systemic inflammation and increased risk of cardiovascular events. In chronic inflammatory states, traditional risk factors only partially account for the development of coronary artery disease (CAD) but underestimate total cardiovascular risk likely due to the residual risk of inflammation. Computed coronary tomography angiography (CCTA) may aid in risk stratification by noninvasively capturing early CAD, identifying high risk plaque morphology and quantifying plaque at baseline and in response to treatment. In this review, we focus on reviewing studies on subclinical atherosclerosis by CCTA in individuals with chronic inflammatory conditions including rheumatoid arthritis (RA), systemic lupus erythematous (SLE), human immunodeficiency virus (HIV) infection and psoriasis. We start with a brief review on the role of inflammation in atherosclerosis, highlight the utility of using CCTA to delineate vessel wall and plaque characteristics and discuss combining CCTA with laboratory studies and emerging technologies to complement traditional risk stratification in chronic inflammatory states.

Background and aims Psoriasis is an immune-mediated inflammatory disease with increased risk of myocardial infarction. Preclinical studies in psoriasis models show an association between chronic inflammation and immune cell proliferation in the spleen and bone marrow (BM). We sought to test the hypothesis that splenic and BM 18F-fluorodeoxyglucose (18F-FDG) uptake is heightened in psoriasis and that higher uptake associates with systemic inflammation and subclinical atherosclerotic disease measures in this cohort. Methods Multimodality imaging and biomarker assays were performed in 240 participants (210 with psoriasis and 30 healthy). Splenic and BM uptake was obtained using 18F-FDG positron emission tomography/computed tomography (PET/CT). Coronary artery plaque characteristics including non-calcified burden (NCB) and lipid rich necrotic core (LRNC) were quantified using a dedicated software for CT angiography. All analyses were performed with StataIC 16 (Stata Corp., College Station, TX, USA). Results Splenic and BM 18F-FDG uptake was increased in psoriasis (vs. healthy volunteers) and significantly associated with proatherogenic lipids, immune cells and systemic inflammation. Higher splenic 18F-FDG uptake associated with higher total coronary burden (β = 0.37; p Conclusions Heightened splenic and BM uptake of 18F-FDG is associated with proatherogenic lipids, immune cells, inflammatory markers and coronary artery disease. These findings provide insights into atherogenic mechanisms in psoriasis and suggest that immune cell proliferation in the spleen and BM is associated with subclinical atherosclerosis.

The molecular mechanisms governing orderly shutdown and retraction of CD4+ type 1 helper T (TH1) cell responses remain poorly understood. Here we show that complement triggers contraction of TH1 responses by inducing intrinsic expression of the vitamin D (VitD) receptor and the VitD-activating enzyme CYP27B1, permitting T cells to both activate and respond to VitD. VitD then initiated the transition from pro-inflammatory interferon-γ+ TH1 cells to suppressive interleukin-10+ cells. This process was primed by dynamic changes in the epigenetic landscape of CD4+ T cells, generating super-enhancers and recruiting several transcription factors, notably c-JUN, STAT3 and BACH2, which together with VitD receptor shaped the transcriptional response to VitD. Accordingly, VitD did not induce interleukin-10 expression in cells with dysfunctional BACH2 or STAT3. Bronchoalveolar lavage fluid CD4+ T cells of patients with COVID-19 were TH1-skewed and showed de-repression of genes downregulated by VitD, from either lack of substrate (VitD deficiency) and/or abnormal regulation of this system. During homeostasis TH1 cells activate a cell-intrinsic inflammatory shutdown program and shift to IL-10 production. Chauss et al. find that this TH1 homeostatic program is dependent on vitamin D signaling and is disrupted in severe COVID-19.

OBJECTIVE Advances in diabetes technology have transformed the treatment paradigm for type 1 diabetes, yet the burden of disease is significant. We report on a pivotal safety study of the first tubeless, on-body automated insulin delivery system with customizable glycemic targets. RESEARCH DESIGN AND METHODS This single-arm, multicenter, prospective study enrolled 112 children (age 6–13.9 years) and 129 adults (age 14–70 years). A 2-week standard therapy phase (usual insulin regimen) was followed by 3 months of automated insulin delivery. Primary safety outcomes were incidence of severe hypoglycemia and diabetic ketoacidosis. Primary effectiveness outcomes were change in HbA1c and percent time in sensor glucose range 70–180 mg/dL (“time in range”). RESULTS A total of 235 participants (98% of enrolled, including 111 children and 124 adults) completed the study. HbA1c was significantly reduced in children by 0.71% (7.8 mmol/mol) (mean ± SD: 7.67 ± 0.95% to 6.99 ± 0.63% [60 ± 10.4 mmol/mol to 53 ± 6.9 mmol/mol], P < 0.0001) and in adults by 0.38% (4.2 mmol/mol) (7.16 ± 0.86% to 6.78 ± 0.68% [55 ± 9.4 mmol/mol to 51 ± 7.4 mmol/mol], P < 0.0001). Time in range was improved from standard therapy by 15.6 ± 11.5% or 3.7 h/day in children and 9.3 ± 11.8% or 2.2 h/day in adults (both P < 0.0001). This was accomplished with a reduction in time in hypoglycemia CONCLUSIONS This tubeless automated insulin delivery system was safe and allowed participants to significantly improve HbA1c levels and time in target glucose range with a very low occurrence of hypoglycemia.

Inflammation in the form of elevated high-sensitivity c-reactive protein (hs-CRP) has been shown to be critical in the development of atherothrombosis. Psoriasis, a chronic inflammatory skin disease, is associated with high systemic-inflammation, elevated neutrophil-to-lymphocyte ratio (NLR) and accelerated non-calcified coronary artery burden (NCB) by coronary computed tomography angiography (CCTA). We hypothesized that NLR would associate with early, rupture-prone atherosclerosis assessed as NCB independent of hs-CRP.316 consecutive psoriasis participants were recruited with 233 having one-year follow-up as part of a prospective, observational cohort study design. CCTA scans were performed to assess NCB in all three major epicardial coronary arteries.Patients with above average NLR (mean: 2.29 ​± ​1.21) were older (mean ​± ​SD; 52.0 ​± ​12.8 vs. 47.9 ​± ​12.6, p ​= ​0.002), had higher hs-CRP (med. IQR: 2.3 (0.9-7.3) vs. 1.4 (0.7-3.2), p ​= ​0.001) and had higher NCB (mean ​± ​SD; 1.21 ​± ​0.58 vs. 1.13 ​± ​0.49, p ​= ​0.018) when compared to patients with below average NLR. NLR associated with psoriasis area severity index score (β ​= ​0.14, p ​= ​0.017), hs-CRP (β ​= ​0.16, p ​= ​0.005), as well as NCB independent of traditional risk factors, body mass index, statin use and hs-CRP (β ​= ​0.08, p ​= ​0.009). One year of biologic therapy for psoriasis was associated with a reduction in NLR (-14.5%, p ​ ​0.001), and this change in NLR associated with change in NCB in fully adjusted models and beyond hs-CRP (β ​= ​0.17, p ​= ​0.002).NLR associated with psoriasis severity, hs-CRP and NCB at baseline. Biologic therapy reduced NLR over time and this change in NLR associated with the change in NCB at one-year. Taken together, these findings suggest that NLR may capture psoriasis patients at higher risk of NCB due to residual inflammation not fully captured by hs-CRP.

Psoriasis is a common chronic inflammatory condition associated with a higher risk of cardiovascular disease. Psoriasis confers a dose-dependent increase in risk for the metabolic syndrome and its components. The metabolic syndrome and its components have been associated with higher coronary atherosclerosis in psoriasis and cardiovascular events in the general population. In this review, we discuss the role of inflammation and psoriasis in cardiometabolic diseases with a focus on the metabolic syndrome and its components. We highlight the relationship between psoriasis and important cardiovascular risk factors encompassed by obesity, dyslipidemia, insulin resistance and hypertension. Furthermore, we briefly highlight literature on anti-inflammatory therapies and their impact on the components of the metabolic syndrome as well as directly quantified coronary atherosclerosis burden.

Psoriasis and type 2 diabetes (T2D) are complex conditions with significant impact on health. Psoriasis patients have higher risk of type 2 diabetes (~1.5 Odds Ratio) and vice versa, controlling for body mass index (BMI), yet there has been limited study comparing their genetic architecture. We hypothesized there are shared genetic components between psoriasis and T2D. Trans-disease meta-analysis (TDMA) was applied to 8,016,731 well-imputed genetic markers from large-scale meta-analyses of psoriasis (11,024 cases and 16,336 controls) and T2D adjusted for BMI (74,124 cases and 824,006 controls). We confirmed our findings in a hospital-based study (42,112 patients) and tested for causal relationships with multi-variable Mendelian randomization. Mendelian randomization identified a causal relationship between psoriasis and T2D (p=1.6x10(−4), OR=1.01), and highlighted the impact of BMI. TDMA further revealed 4 genome-wide significant loci (p

Objective Patients with rheumatoid arthritis (RA) are 1.5 times more likely to develop cardiovascular disease (CVD) attributed to chronic inflammation. A decrease in inflammation in patients with RA is associated with increased low-density lipoprotein (LDL) cholesterol. This study was undertaken to prospectively evaluate the changes in lipid levels among RA patients experiencing changes in inflammation and determine the association with concomitant temporal patterns in markers of myocardial injury. Methods A total of 196 patients were evaluated in a longitudinal RA cohort, with blood samples and high-sensitivity C-reactive protein (hsCRP) levels measured annually. Patients were stratified based on whether they experienced either a significant increase in inflammation (an increase in hsCRP of ≥10 mg/liter between any 2 time points 1 year apart; designated the increased inflammation cohort [n = 103]) or decrease in inflammation (a decrease in hsCRP of ≥10 mg/liter between any 2 time points 1 year apart; designated the decreased inflammation cohort [n = 93]). Routine and advanced lipids, markers of inflammation (interleukin-6, hsCRP, soluble tumor necrosis factor receptor II), and markers of subclinical myocardial injury (high-sensitivity cardiac troponin T [hs-cTnT], N-terminal pro-brain natriuretic peptide) were measured. Results Among the patients in the increased inflammation cohort, the mean age was 59 years, 81% were women, and the mean RA disease duration was 17.9 years. The average increase in hsCRP levels was 36 mg/liter, and this increase was associated with significant reductions in LDL cholesterol, triglycerides, total cholesterol, apolipoprotein (Apo B), and Apo A-I levels. In the increased inflammation cohort at baseline, 45.6% of patients (47 of 103) had detectable circulating hs-cTnT, which further increased during inflammation (P = 0.02). In the decreased inflammation cohort, hs-cTnT levels remained stable despite a reduction in inflammation over follow-up. In both cohorts, hs-cTnT levels were associated with the overall estimated risk of CVD. Conclusion Among RA patients who experienced an increase in inflammation, a significant decrease in routinely measured lipids, including LDL cholesterol, and an increase in markers of subclinical myocardial injury were observed. These findings highlight the divergence in biomarkers of CVD risk and suggest a role in future studies examining the benefit of including hs-cTnT for CVD risk stratification in RA.

We present a 45-year-old woman with complex gastrointestinal anatomy leading to short gut syndrome and chronic diarrhea who was admitted with symptomatic severe hypophosphatemia attributed to renal phosphate wasting induced by intravenous iron preparation ferric carboxymaltose. She was maintained on intravenous phosphate replacements. The treatment course was complicated by respiratory illness leading to volume depletion, acute kidney injury, and phosphate nephropathy. She developed chronic kidney disease and underwent kidney transplant. Our case report aims to increase awareness of hypophosphatemia related to ferric carboxymaltose.

Background: Psoriasis is associated with accelerated non-calcified coronary burden (NCB) by coronary computed tomography angiography (CCTA). Machine learning (ML) algorithms have been shown to effectively identify cardiometabolic variables with NCB in cross-sectional analysis. Objective: To use ML methods to characterize important predictors of change in NCB by CCTA in psoriasis over 1-year of observation. Methods: The analysis included 182 consecutive patients with 80 available variables from the Psoriasis Atherosclerosis Cardiometabolic Initiative, a prospective, observational cohort study at baseline and 1-year using the random forest regression algorithm. NCB was assessed at baseline and 1-year from CCTA. Results: Using ML, we identified variables of high importance in the context of predicting changes in NCB. For the cohort that improved NCB (n = 102), top baseline variables were cholesterol (total and HDL), white blood cell count, psoriasis area severity index score, and diastolic blood pressure. Top predictors of 1-year change were change in visceral adiposity, white blood cell count, total cholesterol, c-reactive protein, and absolute lymphocyte count. For the cohort that worsened NCB (n = 80), the top baseline variables were HDL cholesterol related including apolipoprotein A1, basophil count, and psoriasis area severity index score, and top predictors of 1-year change were change in apoA, apoB, and systolic blood pressure. Conclusion: ML methods ranked predictors of progression and regression of NCB in psoriasis over 1 year providing strong evidence to focus on treating LDL, blood pressure, and obesity; as well as the importance of controlling cutaneous disease in psoriasis.

Intermittent fasting blunts inflammation in asthma1 and rheumatoid arthritis2, suggesting that fasting may be exploited as an immune-modulatory intervention. However, mechanisms underpinning anti-inflammatory effects of fasting remain poorly characterized3, 4, 5. Here, we show that fasting in humans is sufficient to blunt CD4+ T helper cell responsiveness. RNA-seq and flow cytometric immunophenotyping of peripheral blood mononuclear cells (PBMCs) from volunteers subjected to overnight or 24-hour fasting, and 3-hours of refeeding implicate that fasting blunts CD4+ T helper cell activation and differentiation. Transcriptomic analysis reveal that the longer fast-duration has a more robust effect on CD4+ T cell biology. Through bioinformatic analyses, we identify the transcription factor FOXO4 and its canonical target FKBP5 as a potential fasting-responsive regulatory axis. Genetic gain- or loss-of-function of FOXO4 and FKBP5 is sufficient to modulate Th1 and Th17 cytokine production. Moreover, we find that fasting-induced or genetic overexpression of FOXO4 and FKBP5 is sufficient to downregulate mTORC1 signaling and suppress STAT1/3 activation. Our results identify FOXO4-FKBP5 as a novel fasting-induced, STAT-mediated, regulatory pathway to blunt human CD4+ T helper cell responsiveness., Summary: How fasting limits inflammation is poorly understood. RNA-seq analysis identified induction of the FOXO4-FKBP5 axis by fasting. Gain and loss of function studies in CD4+ T cells shows that FOXO4 and FKBP5 levels mediate T helper cell responsiveness, in part, by reducing mTORC1 and STAT1/3 signaling.

Psoriasis is a chronic, inflammatory, multisystem disease that affects up to 3.2% of the United States population. This guideline addresses important clinical questions that arise in psoriasis management and care and provides recommendations based on the available evidence. The treatment of psoriasis with topical agents and with alternative medicine will be reviewed, emphasizing treatment recommendations and the role of dermatologists in monitoring and educating patients regarding benefits as well as risks that may be associated. This guideline will also address the severity assessment methods of psoriasis in adults.

Aims The neutrophil–lymphocyte ratio (NLR) is a readily available inflammatory biomarker that may associate with atherosclerosis and predict cardiovascular (CV) events. The aims of this study are to determine whether the NLR predicts incident major adverse cardiovascular events (MACE) and is modified by anti-inflammatory therapy. Methods and results Baseline and on-treatment NLRs were calculated from complete blood counts among 60 087 participants randomized in the CANTOS, JUPITER, SPIRE-1, SPIRE-2, and CIRT trials to receive placebo or canakinumab, rosuvastatin, bococizumab, or methotrexate, respectively, and followed up for MACE. All analyses were performed first in CANTOS, and then externally validated in the other four trials. For the five trials, hazard ratios for major CV events and mortality comparing NLR quartiles were computed using Cox proportional hazards models, and the effect of each randomized intervention on the NLR was evaluated in comparison to placebo. The NLR modestly correlated with interleukin-6, C-reactive protein, and fibrinogen levels but minimally with lipids. In all five randomized trials, baseline NLR predicted incident CV events and death; the per-quartile increase in risk of MACE was 20% in CANTOS [95% confidence interval (CI) 14–25%, P Conclusion The NLR, an easily obtained inflammatory biomarker, independently predicts CV risk and all-cause mortality, and is reduced by interleukin-1β blockade with canakinumab.

Objective We aimed to evaluate and compare the effectiveness of physical and yoga therapies as an adjuvant therapy along with standard pharmacologic treatment in patients with migraine. Materials and Methods A total of 61 consenting patients diagnosed to have migraine were randomized into three groups to receive either standard treatment alone, physical therapy along with standard treatment, or yoga therapy along with standard treatment. The respective adjuvant intervention was taught to the respective group of patients and they were advised to perform it daily for 3 months with weekly telephonic reminders and review of their activity logs. Outcome measures assessed were headache frequency, Short-Form McGill Pain Questionnaire (SF-MPQ), and Headache Impact Test-6 (HIT-6) at recruitment and once every month for 3 months. Statistical Analysis Statistical analysis of the study was done by using Stata 14.1 software. All the descriptive statistics, paired t-test was used to compare the difference between pre and postintervention values of headache frequency, SF-MPQ, and HIT-6 score within all the three groups. Analysis of variance test and post hoc test were used to compare the differences between all groups for outcome measures (p < 0.05). Results Headache frequency and the visual analog scale before intervention compared during each month intervals for 3 months in all the three groups were significantly decreased in all the three groups (p < 0.005). Yoga or physical therapy as an adjuvant to standard treatment leads to a higher reduction in headache frequency and severity. Sensory and affective pain ratings of SF-MPQ and HIT-6 also showed a significant improvement at 1 to 3 months of treatment compared with baseline in all the three groups. Conclusion Either physical or yoga therapy as an adjuvant to standard pharmacologic treatment may further improve the quality of life and reduce headache frequency in patients with migraine.

Background Psoriasis is associated with elevated risk of heart attack and increased accumulation of subclinical noncalcified coronary burden by coronary computed tomography angiography (CCTA). Machine learning algorithms have been shown to effectively analyze well-characterized data sets. Objective In this study, we used machine learning algorithms to determine the top predictors of noncalcified coronary burden by CCTA in psoriasis. Methods The analysis included 263 consecutive patients with 63 available variables from the Psoriasis Atherosclerosis Cardiometabolic Initiative. The random forest algorithm was used to determine the top predictors of noncalcified coronary burden by CCTA. We evaluated our results using linear regression models. Results Using the random forest algorithm, we found that the top 10 predictors of noncalcified coronary burden were body mass index, visceral adiposity, total adiposity, apolipoprotein A1, high-density lipoprotein, erythrocyte sedimentation rate, subcutaneous adiposity, small low-density lipoprotein particle, cholesterol efflux capacity and the absolute granulocyte count. Linear regression of noncalcified coronary burden yielded results consistent with our machine learning output. Limitation We were unable to provide external validation and did not study cardiovascular events. Conclusion Machine learning methods identified the top predictors of noncalcified coronary burden in psoriasis. These factors were related to obesity, dyslipidemia, and inflammation, showing that these are important targets when treating comorbidities in psoriasis.

Chronic inflammatory diseases including human immunodeficiency virus infection, psoriasis, rheumatoid arthritis, and systemic lupus erythematosus predispose to atherosclerotic cardiovascular disease (ASCVD). Inflammatory bowel disease (IBD) is a common chronic inflammatory condition, and the United States has the highest prevalence worldwide. IBD has so far been overlooked as a contributor to the burden of ASCVD among young and middle-age adults, but meta-analyses of cohort studies suggest that IBD is an independent risk factor for ASCVD. This review discusses the epidemiological links between IBD and ASCVD and potential mechanisms underlying these associations. ASCVD risk management of patients with IBD is challenging because of their young age and the inability of current risk scores to fully capture their increased risk. The role of IBD in current primary prevention guidelines is evaluated, and strategies for enhanced ASCVD risk reduction in patients with IBD are outlined. Finally, the authors discuss knowledge gaps and future research directions in this innovative field.

To determine whether a simulated low-dose metal artifact reduction (MAR) CT technique is comparable with a clinical dose MAR technique for shoulder arthroplasty evaluation. Two shoulder arthroplasties in cadavers and 25 shoulder arthroplasties in patients were scanned using a clinical dose (140 kVp, 300 qrmAs); cadavers were also scanned at half dose (140 kVp, 150 qrmAs). Images were reconstructed using a MAR CT algorithm at full dose and a noise-insertion algorithm simulating 50% dose reduction. For the actual and simulated half-dose cadaver scans, differences in SD for regions of interest were assessed, and streak artifact near the arthroplasty was graded by 3 blinded readers. Simulated half-dose scans were compared with full-dose scans in patients by measuring differences in implant position and by comparing readers’ grades of periprosthetic osteolysis and muscle atrophy. The mean difference in SD between actual and simulated half-dose methods was 2.42 HU (95% CI [1.4, 3.4]). No differences in streak artifact grades were seen in 13/18 (72.2%) comparisons in cadavers. In patients, differences in implant position measurements were within 1° or 1 mm in 149/150 (99.3%) measurements. The inter-reader agreement rates were nearly identical when readers were using full-dose (77.3% [232/300] for osteolysis and 76.9% [173/225] for muscle atrophy) and simulated half-dose (76.7% [920/1200] for osteolysis and 74.0% [666/900] for muscle atrophy) scans. A simulated half-dose MAR CT technique is comparable both quantitatively and qualitatively with a standard-dose technique for shoulder arthroplasty evaluation, demonstrating that this technique could be used to reduce dose in arthroplasty imaging.

BACKGROUND AND AIMS: Amygdalar 18F-fluorodeoxyglucose (FDG) uptake represents chronic stress-related neural activity and associates with coronary artery disease by coronary computed tomography angiography (CCTA). Allostatic load score is a multidimensional measure related to chronic physiological stress which incorporates cardiovascular, metabolic and inflammatory indices. To better understand the relationship between chronic stress-related neural activity, physiological dysregulation and coronary artery disease, we studied the association between amygdalar FDG uptake, allostatic load score and subclinical non-calcified coronary artery burden (NCB) in psoriasis. METHODS: Consecutive psoriasis patients (n=275 at baseline and n=205 at one-year follow-up) underwent CCTA for assessment of NCB (QAngio, Medis). Amygdalar FDG uptake and allostatic load score were determined using established methods. RESULTS: Psoriasis patients were middle-aged, predominantly male and white, with low cardiovascular risk by Framingham risk score and moderate-severe psoriasis severity. Allostatic load score associated with psoriasis severity (β=0.17, p=0.01), GlycA (a systemic marker of inflammation, β=0.49, p

Evaluation of coronary artery disease (CAD) using coronary computed tomography angiography (CCTA) has seen a paradigm shift in the last decade. Evidence increasingly supports the clinical utility of CCTA across various stages of CAD, from the detection of early subclinical disease to the assessment of acute chest pain. Additionally, CCTA can be used to noninvasively quantify plaque burden and identify high-risk plaque, aiding in diagnosis, prognosis, and treatment. This is especially important in the evaluation of CAD in immune-driven conditions with increased cardiovascular disease prevalence. Emerging applications of CCTA based on hemodynamic indices and plaque characterization may provide personalized risk assessment, affect disease detection, and further guide therapy. This review provides an update on the evidence, clinical applications, and emerging technologies surrounding CCTA as highlighted at the 2019 National Heart, Lung and Blood Institute CCTA Summit.

Background: Psoriasis is a chronic immune-mediated inflammatory skin disease associated with increased development of metabolic abnormalities including obesity and dyslipidemia, as well as increased cardiovascular disease (CVD) risk. Shared pathophysiological mechanisms linking psoriasis to CVD include altered immune activation, elevated chronic systemic inflammation, and lipoprotein dysfunction characterized by oxidative damage to lipids and apolipoproteins. Objective: This review aims to provide evidence-based proof for existing relationships between psoriatic inflammation, lipid oxidation, and increased CVD risk. Methods: We included review articles and original research papers, published between 1980 and 2020, using the following key words: psoriasis, oxidized lipids, oxidation, dyslipidemia, and inflammation. Results: Systemic inflammation underlying psoriasis leads to increased skin accumulation of pro-inflammatory oxidized lipids, derived from the omega-6 fatty acids, along with counteracting anti-inflammatory lipid mediators, products of the omega-3 polyunsaturated fatty acids. Imbalance in these metabolites culminates in impaired inflammation resolution and results in multisystemic biological alterations. Sustained systemic inflammation results in excessive lipid oxidation, generating proatherogenic oxidized low- and high-density lipoproteins. Together, these pathophysiological mechanisms contribute to increased CVD risk associated with psoriasis disease. Conclusion: Available anti-inflammatory treatment showed promising clinical results in treating psoriasis, although further research is warranted on managing associated dyslipidemia and establishing novel cardiometabolic markers specific for both skin and vascular pathology.

Background Niacin has modest but overall favorable effects on plasma lipids by increasing high density lipoprotein cholesterol (HDL-C) and lowering triglycerides. Clinical trials, however, evaluating niacin therapy for prevention of cardiovascular outcomes have returned mixed results. Recent evidence suggests that the HDL proteome may be a better indicator of HDL’s cardioprotective function than HDL-C. The objective of this study was to evaluate the effect of niacin monotherapy on HDL protein composition and function. Methods A 20-week investigational study was performed with 11 participants receiving extended-release niacin (target dose = 2 g/day) for 16-weeks followed by a 4-week washout period. HDL was isolated from participants at weeks: 0, 16, and 20. The HDL proteome was analyzed at each time point by mass spectrometry and relative protein quantification was performed by label-free precursor ion intensity measurement. Results In this cohort, niacin therapy had typical effects on routine clinical lipids (HDL-C + 16%, q Conclusion Extended-release niacin therapy, in the absence of other lipid-modifying medications, can increase HDL-associated SAA, an acute phase protein associated with HDL dysfunction.

Psoriasis is a chronic inflammatory disease involving multiple organ systems and affecting approximately 2% of the world's population. In this guideline, we focus the discussion on systemic, nonbiologic medications for the treatment of this disease. We provide detailed discussion of efficacy and safety for the most commonly used medications, including methotrexate, cyclosporine, and acitretin, and provide recommendations to assist prescribers in initiating and managing patients on these treatments. Additionally, we discuss newer therapies, including tofacitinib and apremilast, and briefly touch on a number of other medications, including fumaric acid esters (used outside the United States) and therapies that are no longer widely used for the treatment of psoriasis (ie, hydroxyurea, leflunomide, mycophenolate mofetil, thioguanine, and tacrolimus).

The T1D Exchange established a learning platform by evaluating the current state of care and engaging 10 diabetes clinics in collaborative quality improvement (QI) activities. Participating clinics are sharing data and best practices to improve care delivery for people with type 1 diabetes. This article describes the design and initial implementation of this platform, known as the T1D Exchange Quality Improvement Collaborative. This effort has laid a foundation for learning from variation in type 1 diabetes care delivery via QI methodology and has demonstrated success in improving processes through iterative testing cycles and transparent sharing of data.

Fluorodeoxyglucose-PET/computed tomography combines the high sensitivity of PET with the excellent spatial resolution provided by computed tomography, making it a potentially powerful tool for capturing and quantifying early vascular diseases. Patients with chronic inflammatory states have an increased risk of cardiovascular events; there is also increased vascular fluorodeoxyglucose uptake seen compared with healthy controls. This review examines the use of fluorodeoxyglucose-PET/computed tomography in assessing low-grade vascular inflammation in chronic inflammation and then reviews fluorodeoxyglucose-PET/computed tomography as a tool in monitoring the efficacy of various treatments known to modulate cardiovascular disease.

Psoriasis is associated with a higher risk of liver diseases. We investigated the impact of hepatic steatosis (European cohort) and hepatic inflammation (United States cohort) on subclinical atherosclerosis. In the European cohort (n = 76 psoriasis participants and 76 controls), nonalcoholic fatty liver disease, assessed by the sonographic hepatorenal index, was more prevalent in psoriasis than in controls (61% vs. 45%; P = 0.04). Participants with psoriasis with nonalcoholic fatty liver disease had a higher prevalence of subclinical atherosclerosis (ultrasonographic presence of plaque in femoral or carotid arteries) than participants with psoriasis without nonalcoholic fatty liver disease (61% vs. 23%; P = 0.006) and controls with nonalcoholic fatty liver disease (61% vs. 32%; P < 0.05). Sonographic hepatorenal index was a determinant of subclinical atherosclerosis in psoriasis (OR = 3.5; P = 0.01). In the United States cohort (n = 162 participants with psoriasis who underwent positron emission tomography and coronary computed tomography angiography), those with high hepatic 2-[fluorine-18]fluoro-2-deoxy-D-glucose uptake had higher noncalcified (1.3 [0.49 mm2] vs. 1.0 [0.40 mm2]), fibrofatty (0.23 [0.15 mm2] vs. 0.11 [0.087 mm2]), and lipid-rich necrotic core (4.3 [2.3 mm2] vs. 3.0 [1.7 mm2]) coronary burden (all P < 0.001). Hepatic 2-[fluorine-18]fluoro-2-deoxy-D-glucose uptake associated with noncalcified (β = 0.28; P < 0.001), fibrofatty (β = 0.49; P < 0.001), and lipid-rich necrotic core (β = 0.28; P = 0.003) burden. These results show the downstream cardiovascular effects of subclinical liver disease in psoriasis. pre-print 723 KB

The traditional intravitreal injection delivery of anti-vascular endothelial growth factor (anti-VEGF) to the posterior segment of the eye for treatment of retinal diseases is invasive and associated with sight-threatening complications. To avoid such complications, there has been significant interest in developing polymers for topical drug delivery to the retina. This study reports a nanomicelle drug delivery system made of a co-polymer EPC (nEPCs), which is capable of delivering aflibercept to the posterior segment topically through corneal-scleral routes. EPC is comprised of polyethylene glycol (PEG), polypropylglycol (PPG) and polycaprolactone (PCL) segments. In this study, aflibercept-loaded nEPCs (nEPCs+A) is capable of penetrating the cornea in ex-vivo porcine eye models and deliver a clinically significant amount of aflibercept to the retina of laser-induced choroidal neovascularisation (CNV) murine models, causing CNV regression. nEPCs+A also demonstrates biocompatibility in-vitro and in-vivo. Interestingly, this study also suggests that nEPCs have intrinsic anti-angiogenic properties. The ability to deliver anti-VEGF drugs and the intrinsic anti-angiogenic properties of nEPCs may result in synergistic effects which can be harnessed for effective therapeutics. nEPCs may be a promising topical anti-VEGF delivery platform for the treatment of retinal diseases. This article is protected by copyright. All rights reserved.

Background/Introduction Psoriasis is a chronic inflammatory condition associated with adipose dysfunction and high-risk coronary artery disease features, including non-calcified coronary burden (NCB) and lipid-rich necrotic core (LRNC). Visceral adipose tissue (VAT) is a metabolically-active depot that secretes inflammatory and proatherogenic factors, and is associated with increased NCB. Additionally, an atherogenic myeloid score (AMS) comprised of classical monocytes, low-density granulocytes, and platelets was shown to associate with psoriasis severity and NCB. Purpose To investigate the relationship between VAT and high-risk plaque features and test whether this relationship was potentially mediated by myeloid cells. Methods A cohort of 131 psoriasis patients were included in this study. Atherogenic myeloid score components were calculated using complete blood count data (platelets) and by flow cytometry (monocytes, LDGs). Coronary NCB and LRNC were quantified using QAngio and vascuCAP respectively. VAT was defined as intra-abdominal fat and was quantified using an automated contouring software with abdominal CT scans. Statistical analyses were performed using STATA 12. Results The cohort was middle-aged 50 (42–61) (median (IQR)), and predominantly male (61%). High VAT vs low VAT groups differed significantly in their NCB ((0.910±0.279) vs (1.431±0.517)); p Conclusions VAT associated with LRNC, and this relationship was partially mediated by the atherogenic myeloid score. These findings suggest that bioactive VAT may impart risk on coronary artery disease in part through myeloid cells. Funding Acknowledgement Type of funding sources: Public grant(s) – National budget only. Main funding source(s): National Heart, Lung, and Blood Institute Intramural Research Program in Bethesda, Maryland Figure 1. Log-transformed atherogenic myeloid score partially mediates the relationship between VAT and log-transformed LRNC. Adjusted by Framingham Risk Score, PASI score, biologic therapy, statin therapy, type 2 diabetes, hyperlipidemia, and subcutaneous adipose tissue volume. Red arrow: represents indirect effect; Beta: standard regression coefficient.

Background Psoriasis is a common chronic inflammatory condition associated with an increased risk of obesity and higher coronary atherosclerosis burden by coronary computed tomography angiography (CCTA). Prior studies have shown that the ability to expand subcutaneous adipose tissue (SAT) may serve to identify individuals at a lower risk of atherosclerotic cardiovascular disease. However, the relationship between abdominal SAT and high-risk subclinical coronary artery disease requires exploration. Purpose To characterize the relationship between abdominal SAT volume measured on low-dose computed tomography, and coronary artery disease assessed as noncalcified and lipid-rich necrotic core burden by CCTA in psoriasis. Methods We performed a cross-sectional study of 232 participants with psoriasis and without known cardiovascular disease. All participants underwent CCTA to characterize coronary artery disease burden and low dose abdominal computed tomography to quantify subcutaneous adipose tissue volumes. Fat depot volumes were first adjusted in a sex specific manner for each participant's body mass index in a linear regression model. The residual values from the sex stratified linear regression models were used for analyses. Coronary artery disease burden was quantified in the three main coronary arteries (QAngio, Medis, The Netherlands) and averaged. Analyses were performed with StataIC 16 (Stata Corp., College Station, TX, USA). Results Of the 232 participants, 92 (40%) were women and the average age was 50 years. In women, there was a positive correlation between abdominal SAT and systemic inflammation as assessed by hs-CRP (r=0.30; p=0.004) and GlycA (r=0.29; p=0.007) as well as total cholesterol (r=0.24; p=0.02) and LDL cholesterol (r=0.22; p=0.04). In men, abdominal SAT correlated with hs-CRP (r=0.18; p=0.04) and insulin resistance as assessed by the homeostatic model for insulin resistance (r=0.17; p=0.04). In models fully adjusted for traditional cardiovascular risk factors, abdominal SAT volume negatively associated with noncalcified and lipid-rich necrotic core burden in men (β=−0.17; p=0.03, β=−0.21; p=0.02, respectively), but not women (β=−0.04; p=0.72, β=0.05; p=0.68, respectively) with psoriasis (Table). Conclusions In psoriasis, for a given body mass index, abdominal SAT negatively associated with coronary atherosclerosis burden in men. The observed sex-specific effects on subclinical coronary artery disease warrant further study of abdominal SAT in states of chronic inflammation. Funding Acknowledgement Type of funding sources: Public grant(s) – National budget only. Main funding source(s): National Heart, Lung and Blood Institute Intramural Research Program in Bethesda, Maryland

However, eye cancer may be the rare disease that matches malignancy; it is the most prevalent form of cancer. It is curable in many of the circumstances, equivalent to the alternative types of cancer, if correctly diagnosed, but the diagnosis approach is very complex and the most troubling difficulty for eye cancer care. This document introduces an automated technique for the identification of the skin of the eye, using a neural convolution network (CNN) with a grey victimisation conversion to top picture resolution. 200 samples pre-diagnosed square measurement based on the traditional data, resized and median filtered for low resolution batter image and ultimately supplied to the Convolution Neural Network specification. Although the planned technology requires a broad calculation, a accurate high rate of 92.5% is getting to exceed careful victimisation Convolution Neural Network classifier for classification of features and the extraction of the neural network can be used to extract options from the image..

Context Cardiovascular disease (CVD) is a major cause of mortality in adults with type 1 diabetes. Objective We prospectively evaluated CVD risk factors in a large, contemporary cohort of adults with type 1 diabetes living in the United States. Design Observational study of CVD and CVD risk factors over a median of 5.3 years. Setting The T1D Exchange clinic network. Patients Adults (age ≥ 18 years) with type 1 diabetes and without known CVD diagnosed before or at enrollment. Main Outcome Measure Associations between CVD risk factors and incident CVD were assessed by multivariable logistic regression. Results The study included 8,727 participants (53% female, 88% non-Hispanic white, median age 33 years [interquartile ratio {IQR} = 21, 48], type 1 diabetes duration 16 years [IQR = 9, 26]). At enrollment, median HbA1c was 7.6% (66 mmol/mol) (IQR = 6.9 [52], 8.6 [70]), 33% used a statin, and 37% used blood pressure medication. Over a mean follow-up of 4.6 years, 325 (3.7%) participants developed incident CVD. Ischemic heart disease was the most common CVD event. Increasing age, body mass index, HbA1c, presence of hypertension and dyslipidemia, increasing duration of diabetes, and diabetic nephropathy were associated with increased risk for CVD. There were no significant gender differences in CVD risk. Conclusion HbA1c, hypertension, dyslipidemia and diabetic nephropathy are important risk factors for CVD in adults with type 1 diabetes. A longer follow-up is likely required to assess the impact of other traditional CVD risk factors on incident CVD in the current era.

Psoriasis is a chronic, multisystem, inflammatory disease that affects approximately 1% of children, with onset most common during adolescence. This guideline addresses important clinical questions that arise in psoriasis management and provides evidence-based recommendations. Attention will be given to pediatric patients with psoriasis, recognizing the unique physiology, pharmacokinetics, and patient-parent-provider interactions of patients younger than 18 years old. The topics reviewed here mirror those discussed in the adult guideline sections, excluding those topics that are irrelevant to, or lack sufficient information for, pediatric patients.

Background: There is limited literature on the occurrence and management of psoriasis involving the ear. Objective: To better understand psoriasis of the ear and current approaches for management. Methods: The Medical Board of the National Psoriasis Foundation was surveyed on the frequency and presentation of psoriasis of the ear, the types of examinations performed, and the rationale for choice of treatment. Results: In this survey, the observed frequency of ear psoriasis was wide (10%-70%). The scalp was the most common concurrent site of extra-auricular psoriasis. Inspection of the ear was commonly reported; however, 75% of respondents report not inspecting the canal. Topical corticosteroids were the most commonly used treatment. Systemic and biologic therapies are infrequently used. Limitations: This study is limited by the sample size of respondents. Not every question of the survey was answered by all those surveyed. Conclusions: Results from our survey suggest that the evaluation of psoriasis of the ear is often not complete. Inspection of the ear, including the canal, is recommended, especially if the scalp is involved. Routine inspection of the ear is recommended both to evaluate treatment response and for potential adverse side effects. In the setting of persistent ear disease, collaboration between dermatologists and otolaryngologists is encouraged.

Background There are limited data about the impact of narrowband ultraviolet B phototherapy on patient-reported measures of health-related quality of life. Objective To evaluate the impact of adalimumab and phototherapy on health-related quality of life. Methods We examined patient-reported outcomes from a multicenter, randomized, placebo-controlled trial ( ClinicalTrials.gov no. NCT01553058 ). The Dermatology Life Quality Index and EQ-5D-3L were evaluated every 4 weeks. Results We enrolled 97 patients: 30.9% were female, mean age was 43.5 years (standard deviation, 14.0), and median Psoriasis Area and Severity Index score was 16.7 (interquartile range, 13.9-21.6). At week 12, patients being treated with adalimumab (odds ratio [OR], 2.88; 95% confidence interval [CI], 1.02-8.17) and phototherapy (OR, 8.83; 95% CI, 2.47-31.57) were more likely to achieve the minimal clinically important difference in the Dermatology Life Quality Index compared with those receiving placebo. There were higher odds of achieving the minimal clinically important difference for the EQ-5D-3L Index score when comparing phototherapy versus placebo (OR, 9.78; 95% CI, 2.99-31.95) and phototherapy versus adalimumab (OR, 4.07; 95% CI, 1.42-11.70). Limitations Small sample size, secondary analysis, generalizability. Conclusion Phototherapy and adalimumab both improve skin-related quality of life and overall health-related quality of life compared with placebo in patients with psoriasis; however, patients treated with phototherapy achieved more improvement in overall health-related quality of life compared with patients treated with adalimumab.

Psoriasis is a chronic inflammatory disease involving multiple organ systems and affecting approximately 3.2% of the world's population. In this section of the guidelines of care for psoriasis, we will focus the discussion on ultraviolet (UV) light-based therapies, which include narrowband and broadband UVB, UVA in conjunction with photosensitizing agents, targeted UVB treatments such as with an excimer laser, and several other modalities and variations of these core phototherapies, including newer applications of pulsed dye lasers, intense pulse light, and light-emitting electrodes. We will provide an in-depth, evidence-based discussion of efficacy and safety for each treatment modality and provide recommendations and guidance for the use of these therapies alone or in conjunction with other topical and/or systemic psoriasis treatments.

Backgound and aims The low-density lipoprotein receptor-deficient (Ldlr−/−) mouse has been utilized by cardiovascular researchers for more than two decades to study atherosclerosis. However, there has not yet been a systematic effort to document the ultrastructural changes that accompany the progression of atherosclerotic plaque in this model. Methods Employing several different staining and microscopic techniques, including immunohistochemistry, as well as electron and polarized microscopy, we analyzed atherosclerotic lesion development in Ldlr−/− mice fed an atherogenic diet over time. Results Lipid-like deposits occurred in the subendothelial space after only one week of atherogenic diet. At two weeks, cholesterol crystals (CC) formed and increased thereafter. Lipid, CC, vascular smooth muscles cells, and collagen progressively increased over time, while after 4 weeks, relative macrophage content decreased. Accelerated accumulation of plate- and needle-shaped CC accompanied plaque core necrosis. Lastly, CC were surrounded by cholesterol microdomains, which co-localized with CC through all stages of atherosclerosis, indicating that the cholesterol microdomains may be a source of CC. Conclusions Here, we have documented, for the first time in a comprehensive way, atherosclerotic plaque morphology and composition from early to advanced stages in the Ldlr−/− mouse, one of the most commonly used animal models utilized in atherosclerosis research.

Background Patients with type 1 diabetes (T1DM) typically have normal or even elevated plasma high density lipoprotein (HDL) cholesterol concentrations; however, HDL protein composition can be altered without a change in cholesterol content. Alteration of the HDL proteome can result in dysfunctional HDL particles with reduced ability to protect against cardiovascular disease (CVD). The objective of this study was to compare the HDL proteomes of youth with T1DM and healthy controls (HC) and to evaluate the influence of glycemic control on HDL protein composition. Methods This was a cross-sectional case–control study. Blood samples were obtained from patients with T1DM and HC. HDL was isolated from plasma by size-exclusion chromatography and further purified using a lipid binding resin. The HDL proteome was analyzed by mass spectrometry using label-free SWATH peptide quantification. Results Samples from 26 patients with T1DM and 13 HC were analyzed and 78 HDL-bound proteins were measured. Youth with T1DM had significantly increased amounts of complement factor H related protein 2 (FHR2; adjusted P Conclusions Youth with T1DM have proteomic alterations of their HDL compared to HC, despite similar concentration of HDL cholesterol. The influence of these compositional changes on HDL function are not yet known. Future efforts should focus on investigating the role of these HDL associated proteins in regard to HDL function and their role in CVD risk in patients with T1DM. Trial registration NCT02275091

Visual Abstract, Highlights • LDGs are a subset of neutrophils that were elevated in psoriasis and associated with the severity of disease. • In psoriasis, LDGs associated with noncalcified coronary plaque burden beyond cardiovascular risk factors and in vitro, induced endothelial cell damage. • Compared to normal-density granulocyte neutrophils, platelet-associated biological pathways were upregulated in LDGs, suggesting enhanced platelet adherence to the LDG surface. • LDGs co-localized with platelets in circulation, and the LDG-platelet interaction associated more strongly with non-calcified coronary burden by coronary CTA compared to LDGs alone., Summary Psoriasis is an inflammatory skin disease associated with increased cardiovascular risk and serves as a reliable model to study inflammatory atherogenesis. Because neutrophils are implicated in atherosclerosis development, this study reports that the interaction among low-density granulocytes, a subset of neutrophils, and platelets is associated with a noncalcified coronary plaque burden assessed by coronary computed tomography angiography. Because early atherosclerotic noncalcified burden can lead to fatal myocardial infarction, the low-density granulocyte−platelet interaction may play a crucial target for clinical intervention.

Patients with type 2 diabetes have a significantly increased risk of cardiovascular disease (CVD) compared to the general population-with CVD accounting for two out of every three deaths in patients with diabetes. In 2008, the FDA suggested that CVD risk should be evaluated for any new antidiabetic therapy, leading to a multitude of large CVD outcome trials to assess CVD risk from these medications. Interestingly, several of these outcome trials with new novel antidiabetic therapies have demonstrated a clear and definite CVD advantage at mid-term follow up in high-risk patients with T2DM. In this review, we discuss two relatively new classes of diabetic drugs, sodium-glucose cotransporter 2 inhibitors and glucagon-like peptide 1 agonists, and their efficacy in improving cardiovascular outcomes.

Background A major issue with the current management of psoriasis is our inability to predict treatment response. Objective Our aim was to evaluate the ability to use baseline molecular expression profiling to assess treatment outcome for patients with psoriasis. Methods We conducted a longitudinal study of 46 patients with chronic plaque psoriasis treated with anti-TNF agent etanercept, and molecular profiles were assessed in more than 200 RNA-seq samples. Results We demonstrated correlation between clinical response and molecular changes during the course of the treatment, particularly for genes responding to IL-17A/TNF in keratinocytes. Intriguingly, baseline gene expressions in nonlesional, but not lesional, skin were the best marker of treatment response at week 12. We identified USP18, a known regulator of IFN responses, as positively correlated with Psoriasis Area and Severity Index (PASI) improvement (P = 9.8 × 10−4) and demonstrate its role in regulating IFN/TNF responses in keratinocytes. Consistently, cytokine gene signatures enriched in baseline nonlesional skin expression profiles had strong correlations with PASI improvement. Using this information, we developed a statistical model for predicting PASI75 (ie, 75% of PASI improvement) at week 12, achieving area under the receiver-operating characteristic curve value of 0.75 and up to 80% accurate PASI75 prediction among the top predicted responders. Conclusions Our results illustrate feasibility of assessing drug response in psoriasis using nonlesional skin and implicate involvement of IFN regulators in anti-TNF responses.

Background Youth with type 1 diabetes (T1D) have normal or elevated High‐Density Lipoprotein Cholesterol (HDL‐C), however, the function of HDL, partly mediated by the HDL proteome, may be impaired. Metformin can be used as an adjunct therapy in youth with T1D, but its effects on the HDL proteome are unknown. Objective To determine the effect of metformin on the HDL proteome. Subjects Youth (12–20 years old) with T1D who had a BMI > 90th percentile, HbA1c > 8.0% and Tanner stage 5. Methods Double‐blinded, placebo‐controlled randomized sub‐study. We examined the effects of metformin (n = 25) or placebo (n = 10) after 6 months on HDL proteome. Changes in HDL proteins were measured by data‐independent acquisition (DIA) mass spectrometry and compared between treatment groups. As a secondary outcome, associations between proteins of interest and the most studied function of HDL, the cholesterol efflux capacity (CEC), was examined. Results The relative abundance of 84 HDL‐associated proteins were measured. Two proteins were significantly affected by metformin treatment, peptidoglycan recognition protein 2 (PGRP2; +23.4%, p = .0058) and alpha‐2‐macroglobulin (A2MG; +29.8%, p = .049). Metformin did not significantly affect CEC. Changes in affected HDL proteins did not correlate with CEC. Conclusions Despite having little effect on HDL‐C, metformin increased PGRP2 and A2MG protein on HDL in youth with T1D, but had no significant effect on CEC. Further studies are needed to understand the impact of PGRP2 and A2MG on other HDL functions., We hypothesized that metformin could change the protein cargo on HDL and subsequently improve HDL function in youth with T1D. We analysed samples from a large RCT metformin‐placebo trial and we found that despite having little effect on HDL‐C, metformin increased PGRP2 and A2MG protein on HDL in youth with T1D, but had no significant effect on cholesterol efflux. Further studies are needed to understand the impact of PGRP2 and A2MG on other HDL functions.

Aim: Overnight insulin dosing relies on glucose level and evening food intake, although PA also impacts glycemic levels. We assessed associations between antecedent energy expenditure (EE) from PA and nocturnal glycemia in youth with T1D. Methods: Youth completed 3-day PA logs (PA type, duration, intensity) and wore 3-day masked CGM (iPro™) quarterly for 18 months. We assigned a MET value to PA and calculated EE (kcal/day), using only complete 24-hour days. CGM metrics were calculated for days (6 AM-11:59 PM) and nights (12 AM-5:59 AM) when ≥50% of CGM data were available. Results: Youth (N=136, 48% male) were ages 8-17 years (M±SD 12.8±2.5), with T1D duration 5.9±3.1 years and daily insulin dose 0.9±0.3 U/kg; 73% used insulin pumps. Median (IQR) PA duration and EE were 60 (10-120) minutes/day and 287 (0-695) kcal/day, respectively. CGM metrics by day/night appear in Table. In partial correlations adjusted for multiple observations/person, higher EE was associated with lower mean glucose (r=-.12, p=.0001), more %time 180 (r=-.09, p=.006) that night. Time in range was unchanged. When youth EE was 180 (p=.03) that night. Conclusion: In youth with T1D, PA can reduce nocturnal hyperglycemia and increase nocturnal hypoglycemia. These findings can help tailor automated insulin delivery algorithms according to PA. Disclosure R. O. La banca: None. L. K. Volkening: None. K. Milaszewski: Consultant; Self; Lilly USA, LLC. E. Dassau: Consultant; Self; Eli Lilly and Company, Employee; Self; Eli Lilly and Company, Research Support; Self; Dexcom, Inc., Tandem Diabetes Care, Speaker’s Bureau; Self; Dexcom, Inc., Roche Diabetes Care, Stock/Shareholder; Self; Eli Lilly and Company. S. N. Mehta: None. L. M. Laffel: Consultant; Self; AstraZeneca, Boehringer Ingelheim International GmbH, Dexcom, Inc., Dompe, Insulogic LLC, Janssen Pharmaceuticals, Inc., Laxmi Therapeutic Devices, LifeScan, Lilly Diabetes, Medtronic, Provention Bio, Inc. Funding National Institutes of Health (K12DK094721, P30DK036836); Iacocca Family Foundation

Aim: PA is an important part of diabetes management. ADA recommends that youth with T1D participate daily in ≥60 minutes of moderate to vigorous PA. We prospectively assessed daily PA in youth with T1D and compared demographic and diabetes variables according to frequency of PA ≥60 minutes/day. Methods: Youth (N=125, ages 8-17) with T1D completed 3-day PA records every 3 months for 18 months. Diabetes treatment data and A1c were collected at the same time. For each youth, we calculated the % of days with ≥60 minutes PA and compared those with ≥60 minutes PA on Results: Youth (50% male, 90% white, 74% pump-treated) had a mean±SD age 12.8±2.5 years, T1D duration 6.0±3.2 years, and A1c 8.2±0.9%. Youth had a median of 16 (IQR 12-17) PA record days. The % of days with ≥60 minutes PA ranged from 0 to 100% (median 53% [IQR 35-71%]), with 59% of youth reporting ≥60 minutes PA on ≥50% of days. Youth with ≥60 minutes PA on ≥50% of days were younger (12.4 vs. 13.5 years, p=.02), had shorter T1D duration (5.2 vs. 7.0 years, p=.002), lower daily insulin dose (0.86 vs. 1.00 u/kg, p=.002), and lower A1c (8.1 vs. 8.4%, p=.03) than youth with ≥60 minutes PA on Conclusion: A substantial proportion of youth with T1D do not exercise per recommendations. Given associations of PA with lower A1c, additional efforts to support exercise management in T1D are needed along with support for PA throughout the year. Disclosure R. O. La banca: None. L. K. Volkening: None. H. Desrochers: None. E. Dassau: Consultant; Self; Eli Lilly and Company, Employee; Self; Eli Lilly and Company, Research Support; Self; Dexcom, Inc., Tandem Diabetes Care, Speaker’s Bureau; Self; Dexcom, Inc., Roche Diabetes Care, Stock/Shareholder; Self; Eli Lilly and Company. S. N. Mehta: None. L. M. Laffel: Consultant; Self; AstraZeneca, Boehringer Ingelheim International GmbH, Dexcom, Inc., Dompe, Insulogic LLC, Janssen Pharmaceuticals, Inc., Laxmi Therapeutic Devices, LifeScan, Lilly Diabetes, Medtronic, Provention Bio, Inc. Funding National Institutes of Health (K12DK094721, P30DK036836); Iacocca Family Foundation

Background: While Medicare Advantage (MA) is projected to be the most common Medicare plan by 2030, little is known regarding differential diabetes care quality delivered under MA vs. traditional Fee-for-Service (FFS). Methods: Among 345,911 adults >65y with T2D enrolled in the Diabetes Collaborative Registry (2014-2017), 229,598 (66%) were enrolled in FFS and 116,313 (34%) in MA plans (for ≥1 month). Quality measures, intermediate outcomes, and prescription patterns were compared, adjusted for sociodemographic and clinical factors. Results: Mean age was 75±7y, 48% were women, and 51% had CAD in both plans. MA beneficiaries were more likely to receive ACEi/ARBs for CAD, have tobacco cessation counseling, and screening for retinopathy, foot care, and nephropathy (adj P≤0.001). However, MA beneficiaries had higher SBP (+0.2mmHg), LDL-c (+1.0mg/dL), and HbA1c (+0.1%) (adj P Conclusion: While MA plans enable greater access to preventative care, this may not translate to improved intermediate health outcomes nor access to newer antihyperglycemic therapies with proven outcome benefits. Long-term outcomes under various Medicare plans require surveillance. Disclosure U. Essien: None. Y. Tang: None. T. Litam: None. R. Patel: None. R. K. Wadhera: None. N. Desai: Research Support; Self; Amgen Inc., AstraZeneca, Boehringer Ingelheim International GmbH, Cytokinetics Inc., MyoKardia, Novartis Pharmaceuticals Corporation. S. N. Mehta: None. M. N. Kosiborod: Consultant; Self; Amgen Inc., Applied Therapeutics, AstraZeneca, Bayer AG, Boehringer Ingelheim International GmbH, Eli Lilly and Company, Janssen Scientific Affairs, LLC., Merck & Co., Inc., Novo Nordisk, Sanofi, Vifor Pharma Management Ltd., Research Support; Self; AstraZeneca, Boehringer Ingelheim International GmbH. M. Vaduganathan: Advisory Panel; Self; American Regent, Inc., Amgen Inc., AstraZeneca, Bayer AG, Boehringer Ingelheim Pharmaceuticals, Inc., Cytokinetics Inc., Relypsa Inc., Speaker’s Bureau; Self; Novartis AG. Funding American College of Cardiology