bluuebunny/crossref_metadata_2025_split huggingface dataset:
322 Efficacy and safety of lebrikizumab in moderate-to-severe atopic dermatitis: 52-week results of two randomized, double-blinded, placebo-controlled phase 3 trials (ADvocate1 and ADvocate2)
Authors: Blauvelt Andrew , Thyssen Jacob P , Guttman-Yassky Emma  , Bieber Thomas , Carrascosa Jose Manuel , Simpson Eric , Rosmarin David  , Elmaraghy Hany , Meskimen Eric , Natalie Chitra R , Liu Zhuqing , Xu Chenjia , Pierce Evangeline , Morgan-Cox MaryAnn , Silverberg Jonathan I 
Published: January 2023

Abstract
Lebrikizumab (LEB) is a novel, high-affinity monoclonal antibody that selectively binds to interleukin (IL)-13. To evaluate the efficacy and safety of LEB monotherapy in patients with moderate-to-severe atopic dermatitis (AD) in two identical phase 3 trials ADvocate1 (ADv1) and ADvocate2 (ADv2). Patients who responded to LEB 250 mg every 2 weeks (LEB Q2W) at the end of the 16-week induction period were re-randomized in a 2 : 2 : 1 ratio to receive LEB Q2W, LEB 250 mg every 4 weeks (LEB Q4W) or placebo (LEB withdrawal) for an additional 36 weeks. Response, at week 16, was defined as achieving an IGA (0, 1) with a ≥2-point improvement or EASI75 and no use of rescue medication. Efficacy outcomes reported at week 52 included IGA (0, 1), EASI 75, ≥4-point reduction in Pruritis Numeric Rating Scale (NRS), EASI 90 and DLQI ≥4-point. Safety analysis was conducted on all patients who received ≥1 dose of LEB. Patients maintained IGA (0, 1) in LEB Q2W (ADv1, 75.8%; ADv2, 64.6%), LEB Q4W (ADv1, 74.2%; ADv2, 80.6%) and LEB withdrawal (ADv1, 46.5%; ADv2, 49.8%). Maintenance of EASI75 was, in LEB Q2W (ADv1, 79.2%; ADv2, 77.4%), LEB Q4W (ADv1, 79.2%; ADv2, 84.7%) and LEB withdrawal (ADv1, 61.3%; ADv2, 72.0%). For Pruritus NRS ≥4-point improvement from baseline, patients-maintained improvement in the LEB Q2W (ADv1, 81.2%; ADv2, 90.3%), LEB Q4W (ADv1, 80.4%; ADv2, 88.1%) and LEB withdrawal (ADv1, 65.4%; ADv2, 67.6%). Maintenance of EASI90 was, in LEB Q2W (ADv1, 66.1%; ADv2, 61.5%), LEB Q4W (ADv1, 66.6%; ADv2, 67.4%) and LEB withdrawal (ADv1, 45.5%; ADv2, 36.9%). DLQI ≥4-point improvement from baseline was LEB Q2W (ADv1, 64.0%; ADv2, 59.0%), LEB Q4W (ADv1, 62.7%; ADv2, 73.0%) and LEB withdrawal (ADv1, 57.7%; ADv2, 45.5%). TEAEs were reported by 58.1% (ADv1) and 67.8% (ADv2) LEB-treated patients at week 52. Serious adverse events were reported by 3.3% of ADv1 patients and 2.7% of ADv2 patients. In ADv1 and ADv2, 2.3% and 3.9% of patients reported an adverse event leading to treatment discontinuation, respectively. Both LEB Q2W and LEB Q4W maintained improvement in all reported outcomes for the treatment of moderate-to-severe AD through 52 weeks. The safety profile was consistent with previously published data.
337 Dupilumab treatment is not associated with an increased overall risk of infections in patients aged 6 months to 5 years with moderate-to-severe atopic dermatitis
Authors: Siegfried Elaine C , Cork Michael J , Arkwright Peter D , Wollenberg Andreas , Eichenfield Lawrence F , Ramien Michele , Khokhar Faisal A , Chen Zhen , Zhang Annie , Cyr Sonya L 
Published: January 2023

Abstract
Patients with atopic dermatitis (AD) have an increased risk of infection, including skin infections. Previous studies in children aged 6–11 years and adolescents showed that dupilumab is not associated with an increased risk of overall infections and is associated with a lower incidence of skin infections compared with a placebo. This post-hoc analysis reports the impact of dupilumab treatment on infections, including skin infections, in children aged 6 months to 5 years with moderate-to-severe AD. In LIBERTY AD PRESCHOOL, a double-blind, placebo-controlled trial (NCT03346434, part B), children aged 6 months to 5 years with moderate-to-severe AD (Investigator’s Global Assessment score ≥3) were randomized 1 : 1 to subcutaneous dupilumab every 4 weeks (200 mg if baseline weight was ≥5 to &lt;15 kg, 300 mg if weight was ≥15 to &lt;30 kg) or placebo with concomitant low-potency topical corticosteroids for 16 weeks. Exposure-adjusted rates (patients with ≥1 event per 100 patient-years [nP/100 PY]) and systemic anti-infective medication use (nP/100PY) were used to compare treatment groups. 162 patients were randomized to dupilumab (n = 83) or placebo (n = 79). During the 16-week treatment period, total infections rates were numerically lower in the dupilumab-treated group (nP/100PY: 185.2) compared with the placebo-treated group (nP/100PY: 245.7). Fewer infections of skin-structure and soft tissues were reported in the dupilumab group (nP/100PY: 24.7) compared with the placebo group (nP/100PY: 40.2). Dupilumab-treated patients had significantly lower rates of non-herpetic skin infections (nP/100PY: 42.7) than placebo-treated patients (nP/100PY: 92.7; P &lt; 0.05 vs. placebo). There was no significant difference in rates of herpetic skin infections between the dupilumab (nP/100PY: 20.0) and placebo groups (nP/100PY: 17.1; P = 0.817 vs. placebo). No helminthic infections were reported in either group. Systemic anti-infective medication use was significantly less frequent in the dupilumab group (nP/100PY: 104.7) compared with placebo (nP/100PY: 203.0; P &lt; 0.05 vs. placebo). The overall safety of dupilumab was consistent with the known safety profile. Dupilumab treatment is associated with lower overall infections and significantly lower non-herpetic skin infections than placebo in children aged 6 months to 5 years with moderate-to-severe AD.
341 Dupilumab improves itch and skin lesions in adults with prurigo nodularis regardless of prior use of immunosuppressants or phototherapy: post-hoc results from PRIME and PRIME2 clinical trials
Authors: Kwatra Shawn G , Yosipovitch Gil , Ständer Sonja  , Kim Brian S , Msihid Jérôme , Bansal Ashish , Martinčová Renata , Wiggins Simmi  , Levit Noah A , Thomas Ryan B , Bahloul Donia 
Published: January 2023

Abstract
Dupilumab is the only FDA-approved systemic therapy for prurigo nodularis (PN), however, immunosuppressants (IS) and phototherapy have been used off-label for the treatment of this condition. Patients with prior IS/phototherapy treatment may represent a more severe and/or treatment-refractory population of patients with PN. Report post-hoc efficacy of dupilumab in patients with PN, with or without prior use of IS or phototherapy for PN. LIBERTY-PN PRIME and PRIME2 (NCT04183335 and NCT04202679) are randomized, 24-week, phase 3 studies in adults with PN that is inadequately controlled by topical prescription therapies or for whom those therapies are not advisable. Primary outcomes included a ≥4-point improvement in the weekly average of Worst Itch Numerical Rating Scale (WI-NRS) from baseline to week 24, and an Investigator’s Global Assessment for PN stage (IGA PN-S) score of 0/1 (clear/almost clear) at week 24. Safety outcomes included the incidence of treatment-emergent adverse events (TEAEs). Among patients with PN, 8.0% reported prior use of phototherapy, and 36.7% reported prior use of IS; overall, 126 (dupilumab group, n = 62; placebo group, n = 64) patients with and 185 (dupilumab, n = 91; placebo, n = 94) patients without prior IS/phototherapy use were included. A larger proportion of patients with prior treatment vs. patients without prior treatment had severe disease, as measured by IGA PN-S (40.5% vs. 29.0%). The baseline WI-NRS score (SD) for overall patients with prior treatment was 8.6 (1.0) and for patients without prior treatment was 8.4 (1.0). At week 24, 67.7% vs. 15.6% of patients in the dupilumab vs. placebo groups with prior treatment (odds ratio [95% confidence interval]: 13.6 [3.7–49.7]; P &lt; 0.0001), and 52.7% vs. 21.3% of patients without prior treatment (5.8 [2.4–14.0]; P &lt; 0.0001) achieved improvement in WI-NRS. Similarly, 35.5% vs. 10.9% (3.1 [1.2–8.4]; P = 0.0162) of patients with and 53.8% vs. 21.3% (5.0 [2.3–10.8]; P &lt; 0.0001) of those without prior treatment achieved IGA PN-S score of 0/1, respectively. TEAEs were reported by 43 (69.4%) vs. 34 (53.1%) patients (dupilumab vs. placebo groups) with and 54 (60.0%) vs. 55 (59.1%) without prior treatment, respectively. Patients treated with dupilumab experienced a greater and clinically meaningful improvement in itch and achieved skin that was clear/almost clear of nodules at week 24, regardless of prior use of IS/phototherapy for the treatment of PN. The incidence of TEAEs was generally consistent among patients with and without prior IS/phototherapy.
Blood–brain barrier opening of the default mode network in Alzheimer’s disease with magnetic resonance-guided focused ultrasound
Authors: Meng Ying , Goubran Maged , Rabin Jennifer S , McSweeney Melissa , Ottoy Julie , Pople Christopher B , Huang Yuexi , Storace Alexandra , Ozzoude Miracle , Bethune Allison , Lam Benjamin , Swardfager Walter , Heyn Chinthaka , Abrahao Agessandro , Davidson Benjamin , Hamani Clement , Aubert Isabelle , Zetterberg Henrik , Ashton Nicholas J , Karikari Thomas K , Blennow Kaj , Black Sandra E , Hynynen Kullervo , Lipsman Nir 
Published: January 2023

Abstract
The blood–brain barrier (BBB) protects the brain but is also an important obstacle for the effective delivery of therapeutics in Alzheimer’s disease and other neurodegenerative disorders. Transcranial magnetic resonance-guided focused ultrasound (MRgFUS) has been shown to reversibly disrupt the BBB. However, treatment of diffuse regions across the brain along with the effect on Alzheimer’s disease relevant pathology need to be better characterized. This study is an open-labelled single-arm trial (NCT03739905) to investigate the feasibility of modulating BBB permeability in the default mode network and the impact on cognition, amyloid and tau pathology as well as BBB integrity. Nine participants [mean age 70.2 ± 7.2 years, mean Mini-Mental State Examination (MMSE) 21.9] underwent three biweekly procedures with follow-up visits up to 6 months. The BBB permeability of the bilateral hippocampi, anterior cingulate cortex and precuneus was transiently increased without grade 3 or higher adverse events. Participants did not experience worsening trajectory of cognitive decline (ADAS-cog11, MMSE). Whole brain vertex-based analysis of the 18F-florbetaben PET imaging demonstrated clusters of modest SUVR reduction in the right parahippocampal and inferior temporal lobe. However, CSF and blood biomarkers did not demonstrate any amelioration of Alzheimer’s disease pathology (P-tau181, amyloid-β42/40 ratio), nor did it show persistent BBB dysfunction (plasma PDGFRbeta and CSF-to-plasma albumin ratio). This study provides neuroimaging and fluid biomarker data to characterize the safety profile of MRgFUS BBB modulation in neurodegeneration as a potential strategy for enhanced therapeutic delivery.
Coordinating efforts to optimize next-generation kidney replacement therapies: the European Kidney Health Alliance Work Group ‘Breakthrough Innovation’
Authors: Wieringa Fokko , Søndergaard Henning , Ortiz Alberto 
Published: January 2023

ABSTRACT
Chronic kidney disease (CKD) is one of the fastest growing health problems, set to become the fifth global death cause by 2040. Factors contributing to this fast growth include increased survival from other diseases (cancer, cardiovascular disease, diabetes, etc.), population aging, lack of early CKD diagnosis tools, insufficient CKD awareness within healthcare systems, limited therapeutic armamentarium to prevent CKD progression and limitations of currently available kidney replacement therapies (KRTs). The European Kidney Health Alliance (EKHA) and the American Association of Kidney Patients joined forces within the Decade of the KidneyTM framework to address these issues. We report on the rationale and vision of the EKHA Work Group ‘Breakthrough Innovation’ which aims to disrupt the existing innovation paradox on KRT. We discuss how the concepts of international technological roadmapping and coopetition may leverage breakthrough KRT technologies, and present a map of the kidney innovation playing field, driven by patient advocacy groups.
Nationwide trends of gatekeeper to invasive coronary angiography in suspected coronary artery disease
Authors: Cho I , Cha M J , Kim W D , Hong S J , Hong G R 
Published: January 2023

Abstract

Funding Acknowledgements
Type of funding sources: None.

Background and Objectives
Real-world trends in the utility and type of gatekeeping studies in invasive coronary angiography (ICA) requires further investigation.

Methods
We identified outpatients who underwent noninvasive cardiac tests or directly ICA for suspected coronary artery disease (CAD) from the nationwide Korea Health Insurance Review and Assessment Service-National Patient Sample database between 2012 and 2018.

Results
Among 71,401 patients, the percentage of patients who were evaluated for suspected CAD was 34.7% for treadmill test (TMT), 4.2% for single-photon emission computed tomography (SPECT), 24.2% for coronary computed tomography angiography (CCTA), 1.6% for multiple gatekeepers, and 32.3% for directly ICA without noninvasive studies (Figure 1). The proportion of CCTA as a gatekeeper showed linear increase, (18.6% in 2012 and 28.8% in 2018; p &lt; 0.001), while those of TMT, SPECT, and direct ICA have decreased (p &lt; 0.001, p = 0.03, and p &lt; 0.001, respectively). The overall incidence of downstream ICA after gatekeeper was 13.8% (6,662/48,346), and SPECT showed higher ICA rate in pairwise comparison with TMT and CCTA (p &lt; 0.001). Patients who performed gatekeepers before ICA showed higher rate of subsequent PCI (34.7% vs. 32.3%; p &lt; 0.001) and CABG (3.5% vs. 1.0%; p &lt; 0.001), compared to those who directly underwent ICA, and CCTA was associated with higher revascularization rate after ICA in pairwise comparison with TMT and SPECT (p &lt; 0.001).

Conclusion
Nationwide database demonstrated that CCTA is utilized increasingly as a gatekeeper for ICA and is associated with high revascularization rate after ICA in outpatients with suspected CAD.
Change in minimum indexed left atrial volume predicts incident heart failure: the multi-ethnic study of atherosclerosis
Authors: Lim D , Varadarajan V , Quinaglia T , Pezel T , Wu C , Noda C , Heckbert S , Bluemke D , Ambale-Venkatesh B , Lima J 
Published: January 2023

Abstract

Funding Acknowledgements
Type of funding sources: None.

Background and Purpose
Longitudinal change in the left atrium prior to the onset of heart failure has not been as well studied as left atrial (LA) dysfunction in pre-existing heart failure. This study used cardiac magnetic resonance (CMR) imaging to investigate the relationship between longitudinal change in LA volume and function and incident heart failure (HF), in a multi-ethnic population free of known cardiovascular disease at baseline.

Methods and Results
In the Multi-Ethnic Study of Atherosclerosis (MESA), 2470 participants (60±9 years, 47% males), free at baseline of clinically recognized cardiovascular disease, had LA volume, emptying fractions and peak longitudinal strain assessed with Multimodality Tissue Tracking (MTT; version 6.0 Toshiba, Japan) on CMR imaging at baseline (2000-02) and at follow-up 9.4±0.6 years later. Seventy three (3%) participants subsequently developed incident HF 7.1±2.1 years after the follow-up CMR exam. In cox regression models, an annualized change in all LA parameters were significantly associated with an increased risk of incident HF. An annual increase of 1ml/m2 in minimum indexed LA volumes (∆LAVimin) was most strongly associated with the risk of incident HF (Hazard Ratio(HR)=1.85, 95% confidence interval(CI) [1.49-2.29], P&lt;0.001) and improved model reclassification and discrimination in predicting incident HF (c-statistic=0.80, 95%CI [0.75-0.86]; NRI=0.13, P=0.04; IDI=0.04, P=0.01; x2=6.52, P=0.69) adjusting for known risk factors (age, gender, systolic blood pressure, anti-hypertensive medication use, smoking status, diabetes mellitus, total cholesterol, previous atrial fibrillation) and baseline LA parameters.

Conclusion
In this multi-ethnic population free of clinical cardiovascular disease at baseline, ∆LAVimin was most strongly associated with, and incrementally predictive of incident HF, after adjusting for known risk factors and baseline LA measures.
Seven-day holter monitoring detects more significant arrhythmias than 24-hour and 3-day monitoring
Authors: Lim Y L , Mond H , Michael R , Liew T S , Chu E , Health P , Visagathilagar T , Basioni N , Chia J , Bharatula S 
Published: January 2023

Abstract

Funding Acknowledgements
Type of funding sources: None.

Background/Introduction
24-hour Holter monitors have been used widely to assess patients with suspected and known arrhythmias. Recent studies have shown increased yield of arrhythmia detection with longer durations of Holter monitoring.

Purpose
The aim of the study was to evaluate the incremental yield in significant arrhythmias detected using a 7-day continuous Holter monitor, as compared to what can be achieved within a 24-hour and 48 to 72 hours study.

Methods
A retrospective study of patients from 72 sites in two geographical locations, A and B, who completed a continuous 7-days patch monitor study was performed. 801 of these studies detected significant arrhythmias; pauses 3 seconds or more (PA), ventricular tachycardia of 6 beats or more (VT), and paroxysmal atrial fibrillation (PAF). The day of the first occurrence of a significant arrhythmia was noted and tallied to determine the incremental yield of a multiday Holter monitoring.

Results
Of 801 total cases detected with significant arrhythmia, only 278 (35%) were detected in the first 24hours, while 523 (65%) cases were detected after Day 1. 331 (41%) had first significant arrhythmia detected after the 3rd day of monitoring, with 68 (44%) being PA, 125 (40%) PAF, and 138 (41%) VT. Notably, in Group A, 31 (72%) of total VT detected and 35 (72%) of total PAF detected were first picked up after Day 1, 21 (49%) of total VT were first detected only after the 3rd day of monitoring.

Conclusions
1-day (24-hour) monitoring period fails to detect a significant number of potentially serious cardiac arrhythmias. Extended continuous Holter monitoring increases the yield of detection, with a substantial fraction (40-49%) detected after the 3rd day of monitoring. No difference in results obtained between two geographical locations demonstrates strong evidence that findings are consistent across different sites. Review of current practice and guidelines is necessary to further expand usage of multiday Holter monitoring, thus increasing benefits to patients.
Catheter ablation vs medical therapy for treatment of atrial fibrillation patients with heart failure with preserved ejection fraction: a systematic review and meta-analysis
Authors: Jiang H , Su H Y , Tan V H , Yeo C 
Published: January 2023

Abstract

Funding Acknowledgements
Type of funding sources: None.

Introduction
Catheter ablation (CA) is used as a treatment option in selected patients with atrial fibrillation (AF) and heart failure with reduced ejection fraction (HFrEF) as studies have shown that it reduces heart failure (HF) hospitalization, improves survival, and reduces rates of AF recurrence when compared to medical therapy. However, it is not known whether this benefit persists in patients with heart failure with preserved ejection fraction (HFpEF).

Purpose
The aim of this meta-analysis is to compare CA versus medical therapy in patients with AF and HFpEF

Methods
MEDLINE, EMBASE, and Cochrane Central Register of Controlled Trials were searched from August 2012 to August 2022. All randomized controlled trials (RCTs), propensity score matched (PSM) studies, and observational studies including conference abstracts providing outcomes in patients with HFpEF and AF after CA were included. Outcomes examined include all-cause mortality, HF hospitalizations, and AF recurrence. A random-effects model using R statistical software was used to calculate odds ratios (OR) and 95% confidence intervals (CI).

Results
Of 3151 studies screened, 8 studies (1 RCT, 4 PSM, 3 observational) were included with a pooled population of 2171 and 24087 patients with AF and HFpEF who underwent CA and medical therapy respectively. There were no significant differences in baseline age (70.6 vs 70.7, p = 0.16), proportion of hypertension (85.0% vs 86.4%, p = 0.58), diabetes (33.8% vs 35.8%, p = 0.39), coronary artery disease (40.2% vs 41.8%, p = 0.06), or men (42.3 vs 36.6%, p = 0.42). After a mean weighted follow-up of 9.45 months, there was no significant difference in all-cause mortality (OR 0.77 [0.47-1.26], p = 0.07), HF hospitalizations (OR 0.44 [0.18-1.08], p = 0.22), but a significantly lower rate of AF recurrence (OR 0.22 [0.09-0.54], p = 0.001) associated with CA.

Conclusion
In patient with HFpEF, CA significantly reduced AF recurrence compared with medical therapy but with no difference in mortality or HF hospitalization. CA continues to have an important role to play in treatment of AF even in HFpEF patients.
Voltage/mass ratio (VMR) prognosis value in heart failure (HF) patients with transthyretin cardiac amyloidosis (ATTR-CA)
Authors: Costa J , Pierre M , Nazeyrollas P 
Published: January 2023

Abstract

Funding Acknowledgements
Type of funding sources: None.

Introduction
Transthyretin cardiac amyloidosis (ATTR-CA) is an emerging cause of heart failure (HF) and is associated with cardiac mass hypertrophy and voltage impairment, but little is known on how theses markers interplay with survival.

Objective
To evaluate if cardiac voltage/mass ratio (VMR) is associated with prognosis in HF patients involving ATTR-CA.

Methods
Patients with confirmed mutated (m) or wild-type (wt) ATTR-CA addressed in a single cardiology center underwent retrospective ECG and echocardiographic study to define voltage with Sokolow indice (SV1+RV5, in mV) and left ventricular mass (LVM, g/m²) according to ASE definition. Two groups of patients were defined according to the median cardiac voltage/mass ratio (VMR in µV/g/m²) : Low (VMR &lt; 6.1) or normal (VMR ≥ 6.1). Tc99m-HDP myocardial uptake (MU) on bone scintigraphy (BS) was described according to Perugini (P) classification : PI (MU &lt; chest bones), PII (MU = chest bones) and PIII (MU &gt; bones). Main end-point was overall mortality.

Results
Among the 74 patients included, mean age was 82±7 years, 80% were males (Graph 1) and 25 (34%) were classified as ATTRwt-CA, 3 (4%) as ATTRm-CA, and 46 (62%) had ongoing genetic exploration. Mean follow-up was 543±332 days. Overall mortality was 21%. On BS, 6 patients (8%) were ranked as PI, 30 (42%) PII and 36 (50%) PIII, with no difference on mortality rates. After ANOVA, mean VMRi significantly decreased with intensity of Tc99m-HDP myocardial uptake on BS (p=0.033, Graph 2A). After log-rank test, survival was impaired in the low VMR group (p=0.034, Graph 2B). After Cox regression, low voltage/masse ratio remained associated with increased risk of mortality (HR 4.6, 95% CI [1.1–18.6], p=0.03), after adjusting on age, sex, left ventricle ejection fraction and log(NT-proBNP).

Conclusion
VMR is a simple index to collect and significantly associated with impaired survival in HF patients with ATTR-CA. Further studies are needed to confirm these results.