Citations

Abstract Objective To evaluate unmet needs among individuals with episodic migraine (EM) in the United States (US). Background Data are limited on the impact of headache frequency (HF) and preventive treatment failure (TF) on the burden of migraine in the US. Methods A retrospective, cross‐sectional analysis of 2019 National Health and Wellness Survey (NHWS) data was conducted from an opt‐in online survey that identified respondents (aged ≥18 years) in the US with self‐reported physician‐diagnosed migraine. Participants were stratified by HF (low: 0–3 days/month; moderate‐to‐high: 4–14 days/month) and prior preventive TF (preventive naive; 0–1 TF; ≥2 TFs). Comparisons were conducted between preventive TF groups using multivariable regression models controlling for patient demographic and health characteristics. Results Among individuals with moderate‐to‐high frequency EM, the NHWS identified 397 with ≥2 TFs, 334 with 0–1 TF, and 356 as preventive naive. The 36‐item Short‐Form Health Survey (version 2) Physical Component Summary scores were significantly lower among those with ≥2 TFs, at a mean (standard error [SE]) of 41.4 [0.8] versus the preventive‐naive 46.8 [0.9] and 0–1 TF 44.5 [0.9] groups; p < 0.001 for both). Migraine Disability Assessment Scale scores were significantly higher in the ≥2 TFs, at a mean (SE) of 37.7 (3.9) versus preventive‐naive 26.8 (2.9) ( p < 0.001) and 0–1 TF 30.1 (3.3) ( p = 0.011) groups. The percentages of time that respondents experienced absenteeism (mean [SE] 21.6% [5.5%] vs. 13.4% [3.6%]; p = 0.022), presenteeism (mean [SE] 55.0% [8.3%] vs. 40.8% [6.5%]; p = 0.015), overall work impairment (mean [SE] 59.4% [5.6%] vs. 45.0% [4.4%]; p < 0.001), and activity impairment (mean [SE] 56.8% [1.0%] vs. 44.4% [0.9%]; p < 0.001) were significantly higher in the ≥2 TFs versus preventive‐naive group. Emergency department visits (preventive‐naive, p = 0.006; 0–1 TF, p = 0.008) and hospitalizations ( p < 0.001 both) in the past 6 months were significantly higher in the ≥2 TFs group. Direct and indirect costs were significantly higher in the ≥2 TFs (mean [SE] $24,026 [3460]; $22,074 [20]) versus 0–1 TF ($10,897 [1636]; $17,965 [17]) and preventive‐naive ($11,497 [1715]; $17,167 [17]) groups ( p < 0.001 for all). Results were similar in the low‐frequency EM group. Conclusions In this NHWS analysis, individuals with more prior preventive TFs experienced significantly higher humanistic and economic burden regardless of HF.

AbstractVascularity plays a pivotal role in the progression of breast lesions and may be associated with their aggressiveness and likelihood of being malignant. Contrast-enhanced imaging techniques are necessary to evaluate vascularity due to the limited sensitivity of conventional color Doppler techniques, in which motion artifacts are eliminated using wall filters. However, in this process, low-flow signals from small vessels also get removed unintentionally. Advancements in technology have revolutionized the way ultrasound images are generated, resulting in tremendous improvements in Doppler imaging techniques. The new, ultrasound-based noncontrast microvascular imaging techniques overcome the limitations of conventional Doppler, and are highly sensitive for detecting microvessels and low flow. The resultant high Doppler sensitivity leads to detection of vascularity in more breast lesions. It is important for radiologists to understand the imaging principles and the clinical implications of the new techniques, to optimally utilize them and aid correct diagnosis. Angio-PLUS is one such recent advancement, which uses unfocused or plane waves and three-dimensional wall filtering to analyze tissue motion in time, space, and amplitude domains that effectively distinguish between blood flow and tissue. The information is beneficial for assessing the lesion vascularity without using contrast. This article aims to explain the Doppler imaging techniques, their clinical applications, scanning methods, and review the common Doppler-based diagnostic criteria used in the evaluation of breast lesions.

Abstract Objectives The objective of this study was to explore the prevalence, characteristics and risk factors of COVID-19 breakthrough infections (BIs) in idiopathic inflammatory myopathies (IIMs) using data from the COVID-19 Vaccination in Autoimmune Diseases (COVAD) study. Methods A validated patient self-reporting e-survey was circulated by the COVAD study group to collect data on COVID-19 infection and vaccination in 2022. BIs were defined as COVID-19 occurring ≥14 days after two vaccine doses. We compared BI characteristics and severity among patients with IIMs, patients with other autoimmune rheumatic and non-rheumatic diseases (AIRD, nrAID), and healthy controls (HCs). Multivariable Cox regression models were used to assess the risk factors for BI, severe BI ,and hospitalizations among patients with IIMs. Results Among the 9449 included responses, BIs occurred in 1447 respondents (15.3%). The median age was 44 years [interquartile range (IQR) 21], 77.4% were female, and 182 BIs (12.9%) occurred among the 1406 patients with IIMs. Multivariable Cox regression among the data for patients with IIMs showed increasing age to be a protective factor for BIs [hazard ratio (HR) = 0.98, 95% CI = 0.97–0.99], and HCQ and SSZ use were risk factors (HR = 1.81, 95% CI = 1.24–2.64, and HR = 3.79, 95% CI = 1.69–8.42, respectively). Glucocorticoid use was a risk factor for a severe BI (HR = 3.61, 95% CI = 1.09–11.8). Non-white ethnicity (HR = 2.61, 95% CI = 1.03–6.59) was a risk factor for hospitalization. Compared with other groups, patients with IIMs required more supplemental oxygen therapy (IIMs = 6.0% vs AIRDs = 1.8%, nrAIDs = 2.2% and HCs = 0.9%), intensive care unit admission (IIMs = 2.2% vs AIRDs = 0.6%, nrAIDs and HCs = 0%), advanced treatment with antiviral or monoclonal antibodies (IIMs = 34.1% vs AIRDs = 25.8%, nrAIDs = 14.6% and HCs = 12.8%) and had more hospitalization (IIMs = 7.7% vs AIRDs = 4.6%, nrAIDs = 1.1% and HCs = 1.5%). Conclusion Patients with IIMs are susceptible to severe COVID-19 BIs. Age and immunosuppressive treatments were related to the risk of BIs.

Abstract Objectives To investigate health-related quality of life in patients with idiopathic inflammatory myopathies (IIMs) compared with those with non-IIM autoimmune rheumatic diseases (AIRDs), non-rheumatic autoimmune diseases (nrAIDs) and without autoimmune diseases (controls) using Patient-Reported Outcome Measurement Information System (PROMIS) instrument data obtained from the second COVID-19 vaccination in autoimmune disease (COVAD-2) e-survey database. Methods Demographics, diagnosis, comorbidities, disease activity, treatments and PROMIS instrument data were analysed. Primary outcomes were PROMIS Global Physical Health (GPH) and Global Mental Health (GMH) scores. Factors affecting GPH and GMH scores in IIMs were identified using multivariable regression analysis. Results We analysed responses from 1582 IIM, 4700 non-IIM AIRD and 545 nrAID patients and 3675 controls gathered through 23 May 2022. The median GPH scores were the lowest in IIM and non-IIM AIRD patients {13 [interquartile range (IQR) 10–15] IIMs vs 13 [11–15] non-IIM AIRDs vs 15 [13–17] nrAIDs vs 17 [15–18] controls, P &lt; 0.001}. The median GMH scores in IIM patients were also significantly lower compared with those without autoimmune diseases [13 (IQR 10–15) IIMs vs 15 (13–17) controls, P &lt; 0.001]. Inclusion body myositis, comorbidities, active disease and glucocorticoid use were the determinants of lower GPH scores, whereas overlap myositis, interstitial lung disease, depression, active disease, lower PROMIS Physical Function 10a and higher PROMIS Fatigue 4a scores were associated with lower GMH scores in IIM patients. Conclusion Both physical and mental health are significantly impaired in IIM patients, particularly in those with comorbidities and increased fatigue, emphasizing the importance of patient-reported experiences and optimized multidisciplinary care to enhance well-being in people with IIMs.

Background Comparative evaluations of preventive migraine treatments can help inform clinical decision making for managing migraine in clinical practice. Methods An anchored matching-adjusted indirect comparison analysis was conducted using pooled participant-level data from two phase 3 atogepant trials (ADVANCE and PROGRESS) and one phase 2/3 rimegepant trial (BHV3000-305) to evaluate the relative efficacy and safety/tolerability of atogepant and rimegepant as preventive migraine treatments. Participants receiving atogepant 60 mg once daily, rimegepant orally disintegrating tablet 75 mg once every other day, and placebo were included. Only participants meeting the BHV3000-305 inclusion/exclusion criteria were analyzed: ≥6 monthly migraine days and ≤18 monthly headache days at baseline. The primary efficacy assessment of interest was change in monthly migraine days across weeks 1–12. Results There were 252 participants in the atogepant group and 348 in the rimegepant group. Across weeks 1–12, atogepant 60 mg demonstrated a significantly greater reduction in mean monthly migraine days compared with rimegepant 75 mg (mean difference [95% CI]: −1.65 [−2.49, −0.81]; p < 0.001). Both atogepant and rimegepant demonstrated similar safety/tolerability profiles. Conclusion In this matching-adjusted indirect comparison analysis, oral atogepant 60 mg once daily demonstrated a significantly greater reduction in monthly migraine days compared with rimegepant 75 mg orally disintegrating tablet once every other day.

216 Background: PCa harbors recurrent FOXA1 alterations, yet distinct alteration types may drive divergent consequences. Here, we established several classes of FOXA1 alterations and evaluated their clinical outcomes, molecular correlates, and immunologic landscape in a large cohort of primary and metastatic PCa samples from Caris Life Sciences. Methods: We interrogated the Caris DNA (592-gene/whole exome) and RNA (whole transcriptome) NGS databases. FOXA1 alterations were annotated based on amino acid (a.a.) location and prior functional studies (Table). Real-world overall survival (OS) was determined from insurance claims data using Kaplan-Meier estimates. Gene set enrichment analyses (GSEA) was used to estimate signaling pathway activity. Immune-cell fractions were inferred from bulk RNA-seq using quanTIseq. All comparisons are made relative to FOXA1 WT cases. Results: The overall prevalence of FOXA1 alterations was 16%, with no enrichment in metastatic PCa samples (15.5%). Class 2 mutations were enriched in histologic NEPC, were associated with a classical NEPC mRNA signature, and showed poor survival with ADT (HR 5.6, 95% CI: 2.5–12.5, p<0.001). Conversely, metastatic PCa patients with Class 1B mutations had numerically improved survival with ADT (HR 0.76, 95% CI: 0.50–1.14, p=0.18). All FOXA1 alterations (except Class 2) resulted in increased FOXA1 transcripts, with 1B and 1C having the greatest effects (q<0.0001). Class 0 and 3 alterations had 2–5 fold higher frequency of TMB-high and MSI-high status (q<0.05). Conversely, Class 1B exhibited lower TMB and markedly fewer TP53 mutations (35.7% vs 20.3%, q<0.001) and TMPRSS2-ERG fusions (34.5% vs 4.6%, q<0.001). Class 1B was depleted of AR transcriptional signatures (q=0.01) but enriched of MYC signaling in GSEA analysis (FDR<0.001), and showed reduced expression of B7-H3. On immune-cell deconvolution analysis, Class 1B showed reduced dendritic cells, but increased B cells and neutrophils (DC: 1.96% vs 0.01%, B cell: 4.27% vs 5.29%, neutrophils: 5.05% vs 8.00%, each q<0.001). Conclusions: Different FOXA1 alterations exhibit divergent molecular and clinical features, and should not be interpreted in aggregate. In particular, Class 1B mutations are associated with a unique molecular and immunological landscape with potentially better outcomes to ADT, while Class 2 mutations are associated with NEPC phenotype with inferior ADT sensitivity. [Table: see text]

AbstractThalassemias are a group of inherited monogenic disorders characterized by defects in the synthesis of one or more of the globin chain subunits of the hemoglobin tetramer. Delta‐beta (δβ‐) thalassemia has large deletions in the β globin gene cluster involving δ‐ and β‐globin genes, leading to absent or reduced synthesis of both δ‐ and β‐globin chains. Here, we used direct globin‐chain analysis using tandem mass spectrometry for the diagnosis of δβ‐thalassemia. Two cases from unrelated families were recruited for the study based on clinical and hematological evaluation. Peptides obtained after trypsin digestion of proteins extracted from red blood cell pellets from two affected individuals and their parents were analyzed using liquid chromatography‐tandem mass spectrometry (LC‐MS/MS). Mass spectrometric analysis revealed a severe reduction in δ, β, and Aγ globin proteins with increased Gγ globin protein in the affected individuals. The diagnosis of Gγ(Aγδβ)0 ‐thalassemia in the homozygous state in the affected individuals and in the heterozygous state in the parents was made from our results. The diagnosis was confirmed at the genetic level using multiplex ligation‐dependent probe amplification (MLPA). Our findings demonstrate the utility of direct globin protein quantitation using LC‐MS/MS to quantify individual globin proteins reflecting changes in globin production. This approach can be utilized for accurate and timely diagnosis of hemoglobinopathies, including rare variants, where existing diagnostic methods provide inconclusive results.

To evaluate deep learning-based calcium segmentation and quantification on ECG-gated cardiac CT scans compared with manual evaluation. Automated calcium quantification was performed using a neural network based on mask regions with convolutional neural networks (R-CNNs) for multi-organ segmentation. Manual evaluation of calcium was carried out using proprietary software. This is a retrospective study of archived data. This study used 40 patients to train the segmentation model and 110 patients were used for the validation of the algorithm. The Pearson correlation coefficient between the reference actual and the computed predictive scores shows high level of correlation (0.84; P < .001) and high limits of agreement (±1.96 SD; −2000, 2000) in Bland–Altman plot analysis. The proposed method correctly classifies the risk group in 75.2% and classifies the subjects in the same group. In total, 81% of the predictive scores lie in the same categories and only seven patients out of 110 were more than one category off. For the presence/absence of coronary artery calcifications, the deep learning model achieved a sensitivity of 90% and a specificity of 94%. Fully automated model shows good correlation compared with reference standards. Automating process reduces evaluation time and optimizes clinical calcium scoring without additional resources.