Hybrid Local and Charge Transfer Emitters Utilizing Hyperconjugation Effect Towards Solution-Processed Ultra-Deep-Blue OLEDs with External Quantum Efficiency Approaching 12 .

Hybrid local and charge transfer (HLCT) excited state materials, which possess weak donor-acceptor (D-A) pure organic structures, deserve one of the most promising efficient and stable blue emitters. Through high-lying reverse intersystem crossing (hRISC) process, 75 % triplet excitons generated by electrical excitation could be harvested and utilized in organic light-emitting diodes (OLEDs). However, there are still significant challenges to achieve high-efficiency ultra-deep-blue HLCT emitters with low Commission Internationale de l'Eclairage (CIE) 1931 chromaticity coordinate y values. Here, a series of novel blue HLCT emitters based on spiro[1,8-diazafluorene-9,2'-imidazole] structure were designed and synthesized by fine-tuning the spiro[fluorene-9,2'-imidazole] core structure in our previous work through heteroatom substitution and hyperconjugation effect. The target emitters were endowed with excellent photophysical and electrochemical merits, thermal stability and solution processibility. The solution-processed OLED based on 4',5'-bis(4-(9H-carbazol-9-yl)phenyl)spiro[1,8-diazafluorene-9,2'-imidazole] (NFIP-CZ) achieved efficient ultra-deep-blue emission (CIEx,y=0.1581, 0.0422) with the maximum external quantum efficiency (EQEmax), maximum current efficiency (CEmax) and maximum power efficiency (PEmax) of 11.94 %, 4.07 cd ⋅ A-1 and 2.56 lm ⋅ W-1. The record EQE is a breakthrough in both solution-processed and vacuum vapor deposition ultra-deep-blue HLCT OLEDs currently.

Protocol of a parallel, randomized controlled trial on the effects of a novel personalized nutrition approach by artificial intelligence in real world scenario.

BACKGROUND: Nutrition service needs are huge in China. Previous studies indicated that personalized nutrition (PN) interventions were effective. The aim of the present study is to identify the effectiveness and feasibility of a novel PN approach supported by artificial intelligence (AI). METHODS: This study is a two-arm parallel, randomized, controlled trial in real world scenario. The participants will be enrolled among who consume lunch at a staff canteen. In Phase I, a total of 170 eligible participants will be assigned to either intervention or control group on 1:1 ratio. The intervention group will be instructed to use the smartphone applet to record their lunches and reach the real-time AI-based information of dish nutrition evaluation and PN evaluation after meal consumption for 3 months. The control group will receive no nutrition information but be asked to record their lunches though the applet. Dietary pattern, body weight or blood pressure optimizing is expected after the intervention. In phase II, the applet will be free to all the diners (about 800) at the study canteen for another one year. Who use the applet at least 2 days per week will be regarded as the intervention group while the others will be the control group. Body metabolism normalization is expected after this period. Generalized linear mixed models will be used to identify the dietary, anthropometric and metabolic changes. DISCUSSION: This novel approach will provide real-time AI-based dish nutrition evaluation and PN evaluation after meal consumption in order to assist users with nutrition information to make wise food choice. This study is designed under a real-life scenario which facilitates translating the trial intervention into real-world practice. TRIAL REGISTRATION: This trial has been registered with the Chinese Clinical Trial Registry (ChiCTR2100051771; date registered: 03/10/2021).

Brodalumab, an anti-IL17RA monoclonal antibody, in psoriatic arthritis.

BACKGROUND: We assessed the efficacy and safety of brodalumab, a human monoclonal antibody against interleukin-17 receptor A (IL17RA), in a phase 2, randomized, double-blind, placebo-controlled study involving patients with psoriatic arthritis. METHODS: We randomly assigned patients with active psoriatic arthritis to receive brodalumab (140 or 280 mg subcutaneously) or placebo on day 1 and at weeks 1, 2, 4, 6, 8, and 10. At week 12, patients who had not discontinued their participation in the study were offered open-label brodalumab (280 mg) every 2 weeks. The primary end point was 20% improvement in American College of Rheumatology response criteria (ACR 20) at week 12. RESULTS: Of the 168 patients who underwent randomization (57 in the brodalumab 140-mg group, 56 in the brodalumab 280-mg group, and 55 in the placebo group), 159 completed the double-blind phase and 134 completed 40 weeks of the open-label extension. At week 12, the brodalumab 140-mg and 280-mg groups had higher rates of ACR 20 than the placebo group (37% [P=0.03] and 39% [P=0.02], respectively, vs. 18%); they also had higher rates of 50% improvement (ACR 50) (14% [P=0.05] and 14% [P=0.05] vs. 4%). Rates of 70% improvement were not significantly higher in the brodalumab groups. Similar degrees of improvement were noted among patients who had received previous biologic therapy and those who had not received such therapy. At week 24, ACR 20 response rates in the brodalumab 140-mg and 280-mg groups were 51% and 64%, respectively, as compared with 44% among patients who switched from placebo to open-label brodalumab; responses were sustained through week 52. At week 12, serious adverse events had occurred in 3% of patients in the brodalumab groups and in 2% of those in the placebo group. CONCLUSIONS: Brodalumab significantly improved response rates among patients with psoriatic arthritis. Larger studies of longer duration are necessary to assess adverse events. (Funded by Amgen; ClinicalTrials.gov number, NCT01516957 .).

Randomized, double-blind, placebo-controlled study of brodalumab, a human anti-IL-17 receptor monoclonal antibody, in moderate to severe asthma.

RATIONALE: IL-17 signaling has been implicated in development and persistence of asthma. Cytokine-targeted strategies blocking IL-17 receptor signaling may be beneficial in asthma treatment. OBJECTIVES: To determine efficacy and safety of brodalumab, a human anti-IL-17 receptor A monoclonal antibody, in subjects with inadequately controlled moderate to severe asthma taking regular inhaled corticosteroids. METHODS: Three hundred two subjects were randomized to brodalumab (140, 210, or 280 mg) or placebo. Primary endpoint was change in Asthma Control Questionnaire (ACQ) score from baseline to Week 12. Secondary endpoints included FEV1, symptom scores, and symptom-free days. Prespecified subgroup analyses were conducted to identify potential responsive subpopulations. Analyses included randomized subjects receiving one or more doses of investigational product using last-observation-carried-forward imputation. MEASUREMENTS AND MAIN RESULTS: Demographics and baseline characteristics were generally balanced among groups (n = 302; n = 226 brodalumab). For the overall study population, no treatment differences were observed. Nine prespecified subgroups were examined without corrections for multiple testing. In only the high-reversibility subgroup (post-bronchodilator FEV1 improvement ≥ 20%; n = 112) was an ACQ change with nominal significance noted; ACQ responses were nominally significant in the 210-mg group (estimated treatment difference, 0.53) but not significant in the higher 280-mg group (estimated treatment difference, 0.38). Adverse events, generally balanced among groups, were most commonly asthma, upper respiratory tract infection, and injection site reaction. CONCLUSIONS: Inhibition of IL-17 receptor A did not produce a treatment effect in subjects with asthma. The results of the high-reversibility subgroup analysis are of uncertain significance, requiring further study of brodalumab in this asthma subpopulation. Clinical trial registered with www.clinicaltrials.gov (NCT01199289).

Older age at rheumatoid arthritis onset and comorbidities correlate with less Health Assessment Questionnaire-Disability Index and Clinical Disease Activity Index response to etanercept in the RADIUS 2 registry.

BACKGROUND: Controversy exists in understanding the effects of age at onset and comorbidities in predicting rheumatoid arthritis (RA) response to biologic therapy. OBJECTIVE: The objective of this study was to investigate the influence of age at onset and number of comorbidities on Health Assessment Questionnaire-Disability Index (HAQ-DI) and Clinical Disease Activity Index (CDAI) responses in active RA patients after 6 months of treatment with etanercept. METHODS: One thousand eight hundred ninety-nine RA patients were assessed after 6 months of etanercept therapy. Patients met the following inclusion criteria: initiated etanercept, continued therapy for at least 6 months, and were not in CDAI low disease activity (LDA) at baseline (CDAI ≤10.0). Changes in HAQ-DI and CDAI scores over 6 months were analyzed across age of onset quintiles. Multivariate regression models evaluated the independent association between both age at onset and number of comorbidities with change in HAQ-DI/CDAI scores or achieving LDA, while accounting for other covariates. RESULTS: Significant improvements in HAQ-DI and CDAI scores were observed in all age-onset groups, although HAQ-DI improvements were less in older-onset patients. Results of multiple linear regression demonstrated that younger age at onset, higher baseline HAQ-DI/CDAI score, rheumatoid factor positivity, shorter disease duration, and fewer comorbidities at baseline were independently associated with improvement in both HAQ-DI and CDAI scores. Similarly, achieving CDAI LDA after 6 or more months of etanercept was associated with younger age at onset, higher baseline CDAI, shorter disease duration, and fewer comorbidities. CONCLUSIONS: These patients with older-onset RA and more comorbidities clinically improved with etanercept, but had lower odds of achieving CDAI LDA. Age of onset and number of comorbidities may be important in determining RA tumor necrosis factor inhibitor response.

Effects of a Novel Applet-Based Personalized Dietary Intervention on Dietary Intakes: A Randomized Controlled Trial in a Real-World Scenario.

The objective of this study was to assess the feasibility and effectiveness of a novel WeChat applet-based personalized dietary intervention aimed at promoting healthier dietary intakes. A two-arm parallel, randomized, controlled trial was conducted in a real-world scenario and involved a total of 153 participants (the intervention group, n = 76; the control group, n = 77), lasting for 4 months in Shanghai, China. The intervention group had access to visualized nutrition evaluations through the applet during workday lunch time, while the control group received no interventions. A total of 3413 lunch dietary intake records were captured through the applet. Linear mixed models were utilized to assess the intervention effects over time. At baseline, the participants' lunchtime dietary intakes were characterized by insufficient consumption of plant foods (86.9% of the participants) and excessive intake of animal foods (79.7% of the participants). Following the commencement of the intervention, the intervention group showed a significant decrease in the animal/plant food ratio (ß = -0.03/week, p = 0.024) and the consumption of livestock and poultry meat (ß = -1.80 g/week, p = 0.035), as well as a borderline significant increase in the consumption of vegetables and fruits (ß = 3.22 g/week, p = 0.055) and plant foods (ß = 3.26 g/week, p = 0.057) over time at lunch compared to the control group. The applet-based personalized dietary intervention was feasible and effective in improving dietary intakes and, consequently, possibly may manage body weight issues in real-world scenarios.

Differential methylation patterns from clusters associated with glucose metabolism: evidence from a Shanghai twin study.

Aim: To assess the associations between genome-wide DNA methylation (DNAm) and glucose metabolism among a Chinese population, in particular the multisite correlation. Materials & methods: Epigenome-wide associations with fasting plasma glucose (FPG) and hemoglobin A1c (HbA1c) were analyzed among 100 Shanghai monozygotic (MZ) twin pairs using the Infinium HumanMethylationEPIC v2.0 BeadChip. We conducted a Pearson's correlation test, hierarchical cluster and pairwise analysis to examine the differential methylation patterns from clusters. Results: Cg01358804 (TXNIP) was identified as the most significant site associated with FPG and HbA1c. Two clusters with hypermethylated and hypomethylated patterns were observed for both FPG and HbA1c. Conclusion: Differential methylation patterns from clusters may provide new clues for epigenetic changes and biological mechanisms in glucose metabolism.

Skin-interfaced microfluidic biosensors for colorimetric measurements of the concentrations of ketones in sweat.

Ketones, such as beta-hydroxybutyrate (BHB), are important metabolites that can be used to monitor for conditions such as diabetic ketoacidosis (DKA) and ketosis. Compared to conventional approaches that rely on samples of urine or blood evaluated using laboratory techniques, processes for monitoring of ketones in sweat using on-body sensors offer significant advantages. Here, we report a class of soft, skin-interfaced microfluidic devices that can quantify the concentrations of BHB in sweat based on simple and low-cost colorimetric schemes. These devices combine microfluidic structures and enzymatic colorimetric BHB assays for selective and accurate analysis. Human trials demonstrate the broad applicability of this technology in practical scenarios, and they also establish quantitative correlations between the concentration of BHB in sweat and in blood. The results represent a convenient means for managing DKA and aspects of personal nutrition/wellness.

Trapping and proteomic identification of cellular substrates of the ClpP protease in Staphylococcus aureus.

In the important human pathogen Staphylococcus aureus the cytoplasmic ClpP protease is essential for mounting cellular stress responses and for virulence. To directly identify substrates of the ClpP protease, we expressed in vivo a proteolytic inactive form of ClpP (ClpP(trap)) that will retain but not degrade substrates translocated into its proteolytic chamber. Substrates captured inside the proteolytic barrel were co-purified along with the His-tagged ClpP complex and identified by mass spectrometry. In total, approximately 70 proteins were trapped in both of the two S. aureus strains NCTC8325-4 and Newman. About one-third of the trapped proteins are previously shown to be unstable or to be substrates of ClpP in other bacteria, supporting the validity of the ClpP-TRAP. This group of proteins encompassed the transcriptional regulators CtsR and Spx, the ClpC adaptor proteins McsB and MecA, and the cell division protein FtsZ. Newly identified ClpP substrates include the global transcriptional regulators PerR and HrcA, proteins involved in DNA damage repair (RecA, UvrA, UvrB), and proteins essential for protein synthesis (RpoB and Tuf). Our study hence underscores the central role of Clp-proteolysis in a number of pathways that contribute to the success of S. aureus as a human pathogen.

Use of the Asthma Control Questionnaire to predict future risk of asthma exacerbation.

BACKGROUND: Direct correlation of assessments of a validated composite measure such as the Asthma Control Questionnaire (ACQ) and risk of exacerbation has not been previously demonstrated in a randomized controlled trial. OBJECTIVE: To evaluate the ability of the ACQ score over time to predict risk of a future asthma exacerbation. METHODS: This analysis included data from a 12-week placebo-controlled trial (N = 292) of AMG 317, an IL-4 receptor α antagonist, in patients with moderate to severe atopic asthma. At baseline, patients had an ACQ score ≥1.5. Exacerbations were defined as requirement for systemic corticosteroids. A Cox proportional hazards model was used, with ACQ score as the time-dependent covariate. The analysis was repeated for individual components of the ACQ. RESULTS: Each 1-point increase in ACQ was associated with a 50% increased risk of exacerbation (hazard ratio, 1.50; 95% CI, 1.03-2.20) for the following 2-week period. Evaluation of individual ACQ components also demonstrated a similar trend, though each to a lesser degree than the full composite ACQ. CONCLUSION: Although based on a retrospective analysis, with small number of exacerbations, these findings support the utility of the composite ACQ score measurement to predict risk of future exacerbation in clinical trials and clinical practice. The composite ACQ score measurement was found to be a better predictor of future risk than individual ACQ components.

Chitosan Oligosaccharides Alleviate H2O2-stimulated Granulosa Cell Damage via HIF-1α Signaling Pathway.

Oocyte maturation disorder and decreased quality are the main causes of infertility in women, and granulosa cells (GCs) provide the only microenvironment for oocyte maturation through autocrine and paracrine signaling by steroid hormones and growth factors. However, chronic inflammation and oxidative stress caused by ovarian hypoxia are the largest contributors to ovarian aging and GC dysfunction. Therefore, the amelioration of chronic inflammation and oxidative stress is expected to be a pivotal method to improve GC function and oocyte quality. In this study, we detected the protective effect of chitosan oligosaccharides (COS), on hydrogen peroxide- (H2O2-) stimulated oxidative damage in a human ovarian granulosa cell line (KGN). COS significantly increased cell viability, mitochondrial function, and the cellular glutathione (GSH) content and reduced apoptosis, reactive oxygen species (ROS) content, and the levels of 8-hydroxy-2'-deoxyguanosine (8-OHdG), 4-hydroxynonenal (4-HNE), hypoxia-inducible factor-1α (HIF-1α), and vascular endothelial-derived growth factor (VEGF) in H2O2-stimulated KGN cells. COS treatment significantly increased levels of the TGF-ß1 and IL-10 proteins and decreased levels of the IL-6 protein. Compared with H2O2-stimulated KGN cells, COS significantly increased the levels of E2 and P4 and decreased SA-ß-gal protein expression. Furthermore, COS caused significant inactivation of the HIF-1α-VEGF pathway in H2O2-stimulated KGN cells. Moreover, inhibition of this pathway enhanced the inhibitory effects of COS on H2O2-stimulated oxidative injury and apoptosis in GCs. Thus, COS protected GCs from H2O2-stimulated oxidative damage and apoptosis by inactivating the HIF-1α-VEGF signaling pathway. In the future, COS might represent a therapeutic approach for ameliorating disrupted follicle development.

ACE2 decoy receptor generated by high-throughput saturation mutagenesis efficiently neutralizes SARS-CoV-2 and its prevalent variants.

The recent global pandemic was a spillover from the SARS-CoV-2 virus. Viral entry involves the receptor binding domain (RBD) of the viral spike protein interacting with the protease domain (PD) of the cellular receptor, ACE2. We hereby present a comprehensive mutational landscape of the effects of ACE2-PD point mutations on RBD-ACE2 binding using a saturation mutagenesis approach based on microarray-based oligo synthesis and a single-cell screening assay. We observed that changes in glycosylation sites and directly interacting sites of ACE2-PD significantly influenced ACE2-RBD binding. We further engineered an ACE2 decoy receptor with critical point mutations, D30I, L79W, T92N, N322V, and K475F, named C4-1. C4-1 shows a 200-fold increase in neutralization for the SARS-CoV-2 D614G pseudotyped virus compared to wild-type soluble ACE2 and a sevenfold increase in binding affinity to wild-type spike compared to the C-terminal Ig-Fc fused wild-type soluble ACE2. Moreover, C4-1 efficiently neutralized prevalent variants, especially the omicron variant (EC50=16 ng/mL), and rescued monoclonal antibodies, vaccine, and convalescent sera neutralization from viral immune-escaping. We hope to next investigate translating the therapeutic potential of C4-1 for the treatment of SARS-CoV-2.

Dietary Sodium Intake Is Positively Associated with Sugar-Sweetened Beverage Consumption in Chinese Children and Adolescents.

Sugar-sweetened beverage (SSB) consumption among children and adolescents is steadily increasing in China, while the main taste of Chinese food is salty. The present study aimed to determine the relationships between SSB and total fluid consumption and dietary sodium and salt intake among children and adolescents in China. The data were obtained from a cross-sectional investigation in 2015. A total of 3958 participants were included. A 24-h dietary record for three consecutive days was collected to determine the SSB intake and food consumption across school days and rest days. After adjusting for age, sex, yearly household income, maternal education, intentional physical exercise, and instances of eating out in the last week, the dietary sodium intake was positively associated with the SSB consumption (p < 0.05), but salt was not. After stratifying by sex, grades, and puberty status, the associations between dietary sodium intake and SSB consumption were significant in girls, in grades 1-5 and before puberty (p < 0.05). Dietary sodium intake was positively associated with SSB consumption in Chinese children and adolescents, particularly in young children. A reduction of the sodium intake might help reduce SSB consumption among children and adolescents.

Effects of School-Based Interventions on Reducing Sugar-Sweetened Beverage Consumption among Chinese Children and Adolescents.

We set up a series of school-based interventions on the basis of an ecological model targeting sugar-sweetened beverage (SSB) reduction in Chinese elementary and middle schools and evaluated the effects. A total of 1046 students from Chinese elementary and middle schools were randomly recruited in an intervention group, as were 1156 counterparts in a control group. The interventions were conducted in the intervention schools for one year. The participants were orally instructed to answer all the questionnaires by themselves at baseline and after intervention. The difference in difference statistical approach was used to identify the effects exclusively attributable to the interventions. There were differences in grade composition and no difference in sex distribution between the intervention and control groups. After adjusting for age, sex, and group differences at baseline, a significant reduction in SSB intake was found in the intervention group post intervention, with a decrease of 35.0 mL/day (p = 0.034). Additionally, the frequency of SSB consumption decreased by 0.2 times/day (p = 0.071). The students in the elementary schools with interventions significantly reduced their SSB intake by 61.6 mL/day (p = 0.002) and their frequency of SSB consumption by 0.3 times/day (p = 0.017) after the intervention. The boys in the intervention group had an intervention effect of a 50.2 mL/day reduction in their SSB intake (p = 0.036). School-based interventions were effective in reducing SSB consumption, especially among younger ones. The boys were more responsive to the interventions than the girls. (ChiCTR, ChiCTR1900020781.).

Validation and response to treatment of a pruritus self-assessment tool in patients with moderate to severe psoriasis.

BACKGROUND: Pruritus is a common symptom of psoriasis. In many clinical trials of psoriasis treatments, severity of pruritus is a patient-reported outcome. OBJECTIVE: We sought to evaluate a patient-reported pruritus self-assessment tool using data from clinical trials of a tumor necrosis factor blocker. METHODS: The validity of the patient-reported 6-point pruritus assessment tool (0 = none to 5 = severe) was determined using data from a phase III trial of etanercept, a tumor necrosis factor blocker. The performance of the pruritus assessment tool was then evaluated using data from two large etanercept trials. RESULTS: The pruritus assessment tool was validated and deemed to have good test-retest reliability (kappa coefficient = 0.71; 95% confidence interval = 0.62-0.80) and responsiveness (standardized response mean = 1.28; effect size = 1.63, responsiveness statistic = 1.54). Improvements in pruritus scores correlated with improvements in Psoriasis Area and Severity Index after 8 weeks of etanercept therapy in two phase III trials. LIMITATIONS: The pruritus assessment is validated only for patients with moderate to severe plaque psoriasis, and may not be applicable to other patient populations. CONCLUSIONS: The pruritus assessment tool is a valid measurement of pruritus intensity in patients with moderate to severe plaque psoriasis and can discriminate between patients on and off treatment.

Intravascular ultrasound evidence of angiographically silent progression in coronary atherosclerosis predicts long-term morbidity and mortality after cardiac transplantation.

OBJECTIVES: The aim of this study was to determine whether angiographically silent early coronary intimal thickening could predict long-term morbidity and mortality. BACKGROUND: Although intravascular ultrasound (IVUS) is widely used to detect early transplant coronary disease, its prognostic significance has not been well defined. METHODS: The study cohort consisted of 143 patients who underwent early multivessel (2.1 +/- 0.7 arteries/patient) IVUS examination 1.0 +/- 0.5 month and 12.0 +/- 1.0 month after transplantation. The change in intimal thickness was evaluated using paired analysis of 1,069 matched sites. Rapidly progressive vasculopathy was defined as the change in intimal thickness >/=0.5 mm. Patients were followed for a primary end point of all-cause mortality and a secondary composite end point of mortality and nonfatal myocardial infarction (MI). Angiographic disease, defined as any >/=50% diameter stenosis, was assessed in 126 patients. RESULTS: Intravascular ultrasound at one year demonstrated rapid progression in 54 (37%) of 143 patients and new lesions in 67 (47%) of 143 of patients. At a mean clinical follow-up of 5.9 years, more patients with rapidly progressive vasculopathy died, as compared with those without (26% vs. 11%, p = 0.03). Death and MI also occurred more frequently among those with rapid progression than in those without it (51% vs. 16%, p < 0.0001). There was no significant difference in outcome in patients with and without donor-transmitted lesions. Angiographic disease was found in 11 (22%) of 50 patients with and in 2 (2.1%) of 76 patients without (p = 0.003) rapidly progressive vasculopathy. The IVUS-defined rapid progression correlated highly with future development of angiographic disease (p = 0.0005). CONCLUSIONS: Rapidly progressive vasculopathy by IVUS, defined as an increase of >/=0.5 mm in intimal thickness within the first year after transplantation, is a powerful predictor of all-cause mortality, MI, and angiographic abnormalities. Accordingly, such patients may be candidates for more aggressive anti-atherosclerotic and/or immunosuppressive therapy.

Improvement in Psoriasis Signs and Symptoms Assessed by the Psoriasis Symptom Inventory with Brodalumab Treatment in Patients with Psoriatic Arthritis.

OBJECTIVE: To evaluate the effect of brodalumab on psoriasis signs and symptoms assessed by the Psoriasis Symptom Inventory (PSI) in patients with psoriatic arthritis (PsA). METHODS: This prespecified analysis of a phase II study (NCT01516957) evaluated patients with active PsA and psoriasis-affected body surface area ≥ 3%, randomized to brodalumab (140 or 280 mg) or placebo every 2 weeks (Q2W) for 12 weeks with loading dose at Week 1. At Week 12, patients entering an open-label extension received brodalumab 280 mg Q2W. The PSI measures 8 psoriasis signs and symptoms: itch, redness, scaling, burning, stinging, cracking, flaking, and pain. PSI response is defined as total PSI ≤ 8 (range 0-32), each item ≤ 1 (range 0-4). PSI scores were assessed at weeks 12 and 24. RESULTS: There were 107 eligible patients. At Week 12, mean improvement in PSI scores was 7.8, 11.2, and 1.5 in brodalumab 140 mg, 280 mg, and placebo groups, respectively; by Week 24, improvement was 10.2, 12.4, and 11.7. At Week 12, 75.0%, 81.8%, and 16.7% of patients receiving brodalumab 140 mg, 280 mg, and placebo, respectively, achieved PSI response; improvement was sustained through Week 24, when 83.9% of prior placebo recipients achieved response. At Week 12, 25.0%, 36.4%, and 2.8% of patients receiving brodalumab 140 mg, 280 mg, and placebo, respectively, achieved PSI 0. Percentages improved through Week 24: 40.0% brodalumab 140 mg, 42.9% brodalumab 280 mg, and 48.4% placebo. CONCLUSION: Significantly more brodalumab-treated patients with PsA achieved patient-reported improvements in psoriasis signs and symptoms than did those receiving placebo. Improvements were comparable between brodalumab groups.

Predictors of severe right ventricular failure after implantable left ventricular assist device insertion: analysis of 245 patients.

BACKGROUND: Insertion of an implantable left ventricular assist device (LVAD) complicated by early right ventricular (RV) failure has a poor prognosis and is largely unpredictable. Prediction of RV failure after LVAD placement would lead to more precise patient selection and optimal device selection. METHODS AND RESULTS: We reviewed data from 245 patients (mean age, 54+/-11 years; 85% male) with 189 HeartMate (77%) and 56 Novacor (23%) LVADs. Ischemic cardiomyopathy predominated (65%), and 29% had dilated cardiomyopathy. Overall, RV assist device (RVAD) support was required after LVAD insertion for 23 patients (9%). We compared clinical and hemodynamic parameters before LVAD insertion between RVAD (n=23) and No-RVAD patients (n=222) to determine preoperative risk factors for severe RV failure. By univariate analysis, female gender, small body surface area, nonischemic etiology, preoperative mechanical ventilation, circulatory support before LVAD insertion, low mean and diastolic pulmonary artery pressures (PAPs), low RV stroke work (RVSW), and low RVSW index (RVSWI) were significantly associated with RVAD use. Elevated PAP and pulmonary vascular resistance were not risk factors. Risk factors by multivariable logistic regression were preoperative circulatory support (odds ratio [OR], 5.3), female gender (OR, 4.5), and nonischemic etiology (OR, 3.3). CONCLUSIONS: The need for circulatory support, female gender, and nonischemic etiology were the most significant predictors for RVAD use after LVAD insertion. Regarding hemodynamics, low PAP and low RVSWI, reflecting low RV contractility, were important parameters. This information may lead to better patient selection for isolated LVAD implantation.

The effect of combined Angiotensin-converting enzyme inhibition and calcium antagonism on allograft coronary vasculopathy validated by intravascular ultrasound.

BACKGROUND: Hypertension is a potential risk factor for allograft coronary vasculopathy. We evaluated the efficacy of angiotensin-converting enzyme (ACE) inhibitors and calcium antagonists, and their combined use, on the development of coronary vasculopathy in hypertensive heart transplant recipients. METHODS: Eighty-two heart transplant recipients underwent serial intravascular ultrasound (IVUS) analysis at baseline (within 1 month) and at 1 year after transplantation and were evaluated for the development of coronary vasculopathy. Patients were divided into 4 groups. Nineteen normotensive recipients received no treatment, control (Group A). Hypertensive patients were treated with either ACE inhibitors (Group B, n = 37), calcium antagonists (Group C, n = 16), or both (Group D, n = 10). RESULTS: We found a significant reduction in IVUS indices of coronary vasculopathy in heart transplant recipients who used a combination of an ACE inhibitor and a calcium antagonist compared with recipients who used either drug alone (p < 0.05). This synergistic efficacy was independent of the baseline indices evaluated in a multivariate regression analysis model and was noted despite comparable mean arterial pressure among the 3 hypertensive groups at 1 year, thus suggesting the presence of a synergistic anti-proliferative effect beyond the anti-hypertensive efficacy. CONCLUSIONS: The combined use of an ACE inhibitor and a calcium antagonist is more effective than the individual use of either drug alone on the development of coronary vasculopathy in cardiac transplant recipients. Large randomized clinical trials are warranted to evaluate such a synergistic efficacy.