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Many patients with impaired renal function have concurrent indications for anticoagulant therapy, including atrial fibrillation and venous thromboembolism. For mild chronic kidney disease, data from clinical trials and existing guidelines can be applied to clinical management. The benefits and harms of anticoagulation therapy in patients with more advanced renal impairment are nuanced, as both thrombotic and bleeding risk are increased. Until recently, data regarding anticoagulants in severe renal impairment were primarily observational, but emerging evidence includes a few small clinical trials and the emergence of novel agents hypothesized to have improved efficacy and safety in this population. In this review, we summarize existing data on anticoagulation in patients with chronic kidney disease. We suggest a framework for anticoagulation decision-making in the burgeoning worldwide population of patients with chronic kidney disease.
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Objectives: Falls are common in adults aged 65 years and older and are the leading cause of traumatic brain injuries in this age group. Alcohol use may increase the risk of falls as well as the severity of resultant injuries. The aim of this study was to examine the association between self-reported alcohol use and the prevalence of intracranial hemorrhage (ICH) in this patient group. Methods: This was a secondary analysis of the Geriatric Head Trauma Short Term Outcomes Project (GREAT STOP), a study of older adults with blunt head trauma from a fall. We determined the characteristics of every fall event, including patient demographics and medical history, and clinical signs and symptoms related to head trauma. Self-reported alcohol use was categorized as none, occasionally, weekly, or daily. We defined ICH as any acute ICH detected by computed tomography scan. We evaluated the association between alcohol use frequency and ICH, adjusted for patient factors and head injury risk factors. Results: Of 3128 study participants, 18.2% (n = 567) reported alcohol use: 10.3% with occasional use, 1.9% with weekly use, and 6.0% with daily use. ICH was more common in patients who used alcohol (20.5%, 22.0%, and 25.1% for occasional, weekly, and daily alcohol users, respectively, vs. 12.0% for non-users, p < 0.001). The frequency of alcohol use was independently associated with ICH, adjusted for patient and head injury risk factors. The adjusted odds ratios (with 95% confidence intervals) for occasional, weekly, and daily alcohol users increased from 2.0 (1.5â2.8) to 2.1 (1.1â4.1) and 2.5 (1.7â3.6), respectively, and showed the characteristics of doseâresponse effect. Conclusions: Alcohol use in older adult emergency department patients with head trauma is relatively common. Self-reported alcohol use appears to be associated with a higher risk of ICH in a dose-dependent fashion. Fall prevention strategies may need to consider alcohol mitigation as a modifiable risk factor.
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High-risk human papillomavirus (hrHPV) is an emerging risk factor for sinonasal squamous cell carcinoma (SNSCC). The goal of this study was to assess the prevalence of hrHPV and subtype distribution in SNSCC and correlation with patient and clinical characteristics. This retrospective cohort study included 43 cases diagnosed with incident primary SNSCC at the University of Cincinnati Medical Center from 2010 to 2015. The prevalence of hrHPV was interrogated using a multi-assay approach that included p16 immunohistochemistry (IHC), RNA in-situ hybridization (ISH), and hrHPV DNA sequencing. The association of hrHPV with 5-year overall survival (OS) and 2-year disease-free survival (DFS) was assessed. Fourteen cases (32.6â¯%) were classified as hrHPV positive, based on the a priori definition of having either a positive RNAScope™ ISH test or hrHPV DNA and p16-positive IHC; 9 cases (20.9â¯%) were positive for all three tests. All cases that arose from an inverted sinonasal papilloma (ex-ISP) were negative for hrHPV. HPV16 was the most common subtype among hrHPV positive cases (58.8â¯%), followed by HPV18 (17.6â¯%). No significant association was observed between hrHPV and OS or DFS after adjusting for potential confounding. hrHPV is prevalent in a sizable fraction of SNSCC. Additional studies are needed to better elucidate the relationship with patient survival outcomes and determine the optimal testing modality for prognostication.
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BACKGROUND: Eosinophil accumulation is a main feature of Eosinophilic Gastritis (EoG) and is associated with its histological diagnosis and pathology. However, multiple clinical trials demonstrate that EoG endoscopic, non-eosinophil histological and clinical features remain persistent despite complete eosinophil depletion. OBJECTIVE: To examine gastric T cell composition and associated cytokine levels following benralizumab-induced eosinophil depletion compared to placebo-treated EoG patients. METHODS: A cohort of subjects with EoG was treated for 12 weeks, with 3 administrations of benralizumab (anti-IL-5 receptor α antibody, n = 5) or placebo (n = 4) from a subset of subjects who participated in a recent phase 2 benralizumab trial. Single-cell suspensions of gastric biopsies were stimulated with phorbol 12,13-dibutyrate (PDBU) and ionomycin in the presence of brefeldin A and monensin. Harvested cells were fixed, stained, and analyzed by flow cytometry to examine T cell populations and associated cytokines. RESULTS: Following benralizumab treatment but not placebo, blood and gastric eosinophil levels decreased 16-fold and 10-fold, respectively. While histologic score and features were significantly decreased, no change was observed in endoscopic score and features. Following complete eosinophil depletion with benralizumab, gastric T helper type 2 (Th2) cells were higher by 3-fold, and their associated type 2 cytokine production of IL-4, IL-5, and IL-13 were higher by 4-fold, 5.5-fold, and 2.5-fold, respectively, compared to EoG patients who were administered with a placebo. CONCLUSION: We have identified a putative positive feedback loop whereby eosinophil depletion results in a paradoxical increase of Th2 cells and derived cytokines; this finding suggests an explanation for the limited success of eosinophil depletion as monotherapy in eosinophil-associated gastrointestinal disorders (EGID).
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BACKGROUND AND AIMS: Inflammatory cells within atherosclerotic lesions secrete proteolytic enzymes that contribute to lesion progression and destabilization, increasing the risk for an acute cardiovascular event. Elastase is a serine protease, secreted by macrophages and neutrophils, that may contribute to the development of unstable plaque. We previously reported interaction of endogenous protease-inhibitor proteins with high-density lipoprotein (HDL), including alpha-1-antitrypsin, an inhibitor of elastase. These findings support a potential role for HDL as a modulator of protease activity. In this study, we test the hypothesis that enhancement of HDL-associated elastase inhibitor activity is protective against atherosclerotic lesion progression. METHODS: We designed an HDL-targeting protease inhibitor (HTPI) that binds to HDL and confers elastase inhibitor activity. Lipoprotein binding and the impact of HTPI on atherosclerosis were examined using mouse models. Histology and immunofluorescence staining of aortic root sections were used to examine the impact of HTPI on lesion morphology and inflammatory features. RESULTS: HTPI is a small (1.6 kDa) peptide with an elastase inhibitor domain, a soluble linker, and an HDL-targeting domain. When incubated with human plasma ex vivo, HTPI predominantly binds to HDL. Intravenous administration of HTPI to mice resulted in its binding to plasma HDL and increased elastase inhibitor activity on isolated HDL. Accumulation of HTPI within plaque was observed after administration to Apoe-/- mice. To examine the effect of HTPI treatment on atherosclerosis, prevention and progression studies were performed using Ldlr-/- mice fed Western diet. In both study designs, HTPI-treated mice had reduced lipid deposition in plaque. CONCLUSIONS: These data support the hypothesis that HDL-associated anti-elastase activity can improve the atheroprotective potential of HDL and highlight the potential utility of HDL enrichment with anti-protease activity as an approach for stabilization of atherosclerotic lesions.
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To assess the value of deep learning in selecting the optimal embryo for in vitro fertilization, a multicenter, randomized, double-blind, noninferiority parallel-group trial was conducted across 14 in vitro fertilization clinics in Australia and Europe. Women under 42 years of age with at least two early-stage blastocysts on day 5 were randomized to either the control arm, using standard morphological assessment, or the study arm, employing a deep learning algorithm, intelligent Data Analysis Score (iDAScore), for embryo selection. The primary endpoint was a clinical pregnancy rate with a noninferiority margin of 5%. The trial included 1,066 patients (533 in the iDAScore group and 533 in the morphology group). The iDAScore group exhibited a clinical pregnancy rate of 46.5% (248 of 533 patients), compared to 48.2% (257 of 533 patients) in the morphology arm (risk difference -1.7%; 95% confidence interval -7.7, 4.3; P = 0.62). This study was not able to demonstrate noninferiority of deep learning for clinical pregnancy rate when compared to standard morphology and a predefined prioritization scheme. Australian New Zealand Clinical Trials Registry (ANZCTR) registration: 379161 .
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Temperature is a primary factor influencing organismal development, and the fluctuating daily and seasonal thermal regimes of temperate climates may challenge the ability of viviparous reptiles to optimize body temperatures during gestation. Testing how viviparous reptiles navigate highly variable thermal conditions (e.g., relatively cold nights and/or highly fluctuating temperatures) is a powerful way to understand how they use microhabitats for thermoregulatory benefits. We assessed the thermal ecology of pregnant and non-pregnant female Prairie Rattlesnakes (Crotalus viridis) inhabiting a high-elevation, montane shrubland in northwest Colorado throughout their short summer active season, addressing the thermal consequences of microhabitat selection with a focus on thermoregulation of pregnant females at communal rookery sites. We deployed operative temperature models to collect data on the thermal quality of microhabitats used by the snakes, and calculated thermoregulatory accuracy of the snakes by comparing their field-active body temperatures with preferred body temperatures of snakes placed in a thermal gradient. Pregnant females inhabited rocky, hilltop rookeries that had higher thermal quality due to higher and less variable nighttime temperatures compared to microhabitats in the surrounding prairie. Pregnant females therefore thermoregulated more accurately than non-pregnant females. The difference was most pronounced during the night, when pregnant females at rookeries maintained higher body temperatures than non-pregnant snakes in the prairie. Our results support the hypothesis that one major reason female rattlesnakes at high latitudes and/or high elevations forgo migration and gestate at communal, rocky, hilltop rookeries is that, relative to prairie microhabitats, they provide better conditions for thermoregulation during pregnancy.
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Diffuse intrinsic pontine glioma (DIPG) is a rare childhood malignancy with poor prognosis. There are no effective treatment options other than external beam therapy. We conducted a pilot, first-in-human study using 124I-omburtamab imaging and theranostics as a therapeutic approach using a localized convection-enhanced delivery (CED) technique for administering radiolabeled antibody. We report the detailed pharmacokinetics and dosimetry results of intratumoral delivery of 124I-omburtamab. Methods: Forty-five DIPG patients who received 9.0-370.7 MBq of 124I-omburtamab intratumorally via CED underwent serial brain and whole-body PET/CT imaging at 3-5 time points after injection within 4, 24-48, 72-96, 120-144, and 168-240 h from the end of infusion. Serial blood samples were obtained for kinetic analysis. Whole-body, blood, lesion, and normal-tissue activities were measured, kinetic parameters (uptake and clearance half-life times) estimated, and radiation-absorbed doses calculated using the OLINDA software program. Results: All patients showed prominent activity within the lesion that was retained over several days and was detectable up to the last time point of imaging, with a mean 124I residence time in the lesion of 24.9 h and dose equivalent of 353 ± 181 mSv/MBq. Whole-body doses were low, with a dose equivalent of 0.69 ± 0.28 mSv/MBq. Systemic distribution and activities in normal organs and blood were low. Radiation dose to blood was very low, with a mean value of 0.27 ± 0.21 mGy/MBq. Whole-body clearance was monoexponential with a mean biologic half-life of 62.7 h and an effective half-life of 37.9 h. Blood clearance was biexponential, with a mean biologic half-life of 22.2 h for the rapid α phase and 155 h for the slower ß phase. Conclusion: Intratumoral CED of 124I-omburtamab is a novel theranostics approach in DIPG. It allows for delivery of high radiation doses to the DIPG lesions, with high lesion activities and low systemic activities and high tumor-to-normal-tissue ratios and achieving a wide safety margin. Imaging of the actual therapeutic administration of 124I-omburtamab allows for direct estimation of the therapeutic lesion and normal-tissue-absorbed doses.
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BACKGROUND: Postoperative stress urinary incontinence (SUI) after Holmium Laser Enucleation of the Prostate (HoLEP) has improved with the early apical release (EAR) technique. However, some patients develop SUI despite using EAR HoLEP. The aim of this study is to investigate whether a novel classification of the external sphincter is correlated with postoperative SUI. METHODS: The data of 98 patients who underwent EAR HoLEP for benign prostatic hyperplasia were prospectively analyzed. We propose a novel endoscopic classification of external sphincter appearance after HoLEP graded from 0 (best preserved) to 3 (most degraded). Patients were followed for 6 months postoperatively and administered validated questionnaires. A logistic regression was performed to compare moderate SUI rates at sphincter grade 3, controlling for age, obesity, catheter dependency and grams resected at 6 weeks and 3 months. RESULTS: The sphincter grades included 6 grade 0, 47 grade 1, 30 grade 2, and 15 grade 3. Patients were divided into a group without SUI (n= 51), and a group with SUI (n=47) at 6 weeks postoperatively by International Consultation on Incontinence Questionnaire (ICIQ). Patients with reported SUI on ICIQ were more likely to have sphincter grades > 2 at 6 weeks (p= 0.001) and 3 months (p< 0.0001). At 6 months, persistent SUI was associated with sphincter grade 3 (p< 0.0001). Logistic regression demonstrated that sphincter grade 3 was associated with clinically significant SUI at 3 months (p <0.01) Conclusions: Lower sphincter grades are associated with improved return of continence after EAR HoLEP.
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CLINICAL IMPLICATIONS: Tezepelumab use for asthma successfully induced and sustained eosinophilic esophagitis remission and reversed its pathologic transcriptome. This case provides insight into the mechanistic underpinnings of type 2 inflammation in EoE and the clinical utility of targeting these pathways for treatment.
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Hispanic Immigrants (HI) have lower vaccination rates than their non-Hispanic white counterparts. Culturally appropriate interventions are more influential in evoking change among viewers; therefore, it is important to understand the cultural factors of specific ethnic groups. In this study, we identify cultural barriers to vaccination of Hispanic Immigrants. An electronic survey was administered among HI parents living in the United States. Using structural equation modeling, we found that high religious practice and positive religious beliefs towards vaccination correspond with positive vaccine attitudes (+0.20 and +0.587, respectively). Trust in institutions is strongly correlated with strong positive vaccine attitudes (+0.734). While trusting one's folk practitioner more than a medical doctor leads to negative vaccine attitudes (-0.596), the use of home remedies is associated with positive vaccine attitudes (+0.486). The cultural competence of a medical practitioner, especially regarding folk medicine, is essential to lower cultural barriers HI patients face in vaccination.
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I.Protein misfolding is a widespread phenomenon that can result in the formation of protein aggregates, which are markers of various disease states, including Alzheimer's disease (AD). In AD, amyloid beta (Aß) peptides, particularly Aß40 and Aß42, are key players in the disease's progression, as they aggregate to form amyloid plaques and contribute to neuronal toxicity. Recent research has shifted attention from solely Aß fibrils to also include Aß protofibrils and oligomers as potentially critical pathogenic agents. Particularly, oligomers demonstrate greater toxicity compared to other Aß specie. Hence, there is an increased interest in studying the correlation between toxicity and their structure and aggregation pathway. The present study investigates the aggregation of a 150 kDa Aß42 oligomer that does not lead to fibril formation over time. Using negative stain transmission electron microscopy (TEM), size exclusion chromatography (SEC), dynamic light scattering (DLS), and cryo-electron microscopy (cryo-EM), we demonstrate that 150 kDa Aß42 oligomers form higher-order string-like assemblies over time. The strings are unique from the classical Aß fibril structures. The significance of our work lies in elucidating molecular behavior of a novel non-fibrillar form of Aß42 aggregate.
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In cryogenic electron microscopy (cryo-EM), specimen preparation remains a bottleneck despite recent advancements. Classical plunge freezing methods often result in issues like aggregation and preferred orientations at the air/water interface. Many alternative methods have been proposed, but there remains a lack a universal solution, and multiple techniques are often required for challenging samples. Here, we demonstrate the use of lipid nanotubes with nickel NTA headgroups as a platform for cryo-EM sample preparation. His-tagged specimens of interest are added to the tubules, and they can be frozen by conventional plunge freezing. We show that the nanotubes protect samples from the air/water interface and promote a wider range of orientations. The reconstruction of average subtracted tubular regions (RASTR) method allows for the removal of the nanotubule signal from the cryo-EM images resulting in isolated images of specimens of interest. Testing with ß-galactosidase validates the method's ability to capture particles at lower concentrations, overcome preferred orientations, and achieve near-atomic resolution reconstructions. Since the nanotubules can be identified and targeted automatically at low magnification, the method enables fully automated data collection. Furthermore, the particles on the tubes can be automatically identified and centered using 2D classification enabling particle picking without requiring prior information. Altogether, our approach that we call specimen preparation on a tube RASTR holds promise for overcoming air-water interface and preferred orientation challenges and offers the potential for fully automated cryo-EM data collection and structure determination.
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PURPOSE: To estimate incidence rates of suicidal ideation and behavior following treatment initiation with gabapentinoids or dopamine agonists (DAs) in patients with newly diagnosed early-onset idiopathic restless legs syndrome (RLS) and to examine suicidal behavior risk, comparing between those receiving gabapentinoids and DAs. METHODS: A new user retrospective cohort study using MarketScan claims data from 2012 to 2019 was conducted. Exposures were monotherapy gabapentinoids or DAs initiated within 60 days of new RLS diagnosis. Three varying outcome measures of suicidality were examined and incidence rates were calculated for each. A log-binomial regression model the estimated relative risk (RR) of the outcomes with gabapentinoids. Propensity score weighting adjusted for baseline covariates, including age, substance use disorders, hyperlipidemia, antipsychotic use, hypnotic/sedative use, and mood stabilizer use, which were most imbalanced before weighting. RESULTS: The cohort included 6672 patients, with 4986 (74.7%) initiating a DA and 1686 (25.3%) initiating a gabapentinoid. Incidence rates for all outcome measures were higher in the gabapentinoid group (suicidality: 21.6 vs. 10.7 per 1000 person-years; suicidality with self-harm: 23.0 vs. 11.1 per 1000 person-years; overdose- and suicide-related events: 30.0 vs. 15.5 person-years). Associated risk of suicidality (adjusted RR, 1.27 [95% CI, 0.86-1.88]); suicidality with self-harm (adjusted RR, 1.30 [95% CI, 0.89-1.90]); or overdose- and suicide-related events (adjusted RR, 1.30 [95% CI, 0.93-1.80]) was not significant with gabapentinoids. CONCLUSIONS: Incidence rates for suicidal ideation and behavior were higher among the gabapentinoid group, although increased risk was not detected after adjustment. A possible signal cannot be ruled out given limitations of the data and rarity of the outcome.
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Gabapentina , Síndrome das Pernas Inquietas , Ideação Suicida , Humanos , Feminino , Masculino , Estudos Retrospectivos , Síndrome das Pernas Inquietas/epidemiologia , Síndrome das Pernas Inquietas/tratamento farmacológico , Adulto , Pessoa de Meia-Idade , Gabapentina/efeitos adversos , Incidência , Agonistas de Dopamina/efeitos adversos , Agonistas de Dopamina/uso terapêutico , Adulto Jovem , Estudos de Coortes , Idoso , Adolescente , Fatores de RiscoRESUMO
Hepatic sinusoids are highly specialized microcirculatory conduits within the hepatic lobules that facilitate liver functions. The sinusoids can be affected by various disorders, including sinusoidal dilatation, sinusoidal obstruction syndrome (SOS), sinusoidal cellular infiltration, perisinusoidal infiltration, and endothelial neoplasms, such as hemangioendothelioma and angiosarcoma. While these disorders, particularly SOS and neoplasms, can be life threatening, their clinical manifestation is often nonspecific. Patients may present with right upper quadrant pain, jaundice, hepatomegaly, ascites, splenomegaly, and unexplained weight gain, although the exact manifestation depends on the cause, severity, and duration of the disease. Ultimately, invasive tests may be necessary to establish the diagnosis. A comprehensive understanding of imaging manifestations of various sinusoidal disorders contributes to early diagnosis and can help radiologists detect subclinical disease. Additionally, specific imaging features may assist in identifying the cause of the disorder, leading to a more focused and quicker workup. For example, a mosaic pattern of enhancement of the liver parenchyma is suggestive of sinusoidal dilatation; peripheral and patchy reticular hypointensity of the liver parenchyma on hepatobiliary MR images is characteristic of SOS; and associated diffuse multiple hyperintensities on diffusion-weighted images may be specific for malignant sinusoidal cellular infiltration. The authors provide an overview of the pathogenesis, clinical features, and imaging appearances of various hepatic sinusoidal disorders, with a special emphasis on SOS. ©RSNA, 2024 Supplemental material is available for this article.
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Hepatopatia Veno-Oclusiva , Humanos , Hepatopatia Veno-Oclusiva/diagnóstico por imagem , Neoplasias Hepáticas/diagnóstico por imagem , Diagnóstico DiferencialRESUMO
The emergence of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) and onset of the coronavirus disease-19 (COVID-19) pandemic led to an immediate need for therapeutic treatment options. Therapeutic antibodies were developed to fill a gap when traditional antivirals were not available. In late 2020, the United States Government undertook an effort to compare candidate therapeutic antibodies in virus neutralization assays and in the hamster model of SARS-CoV-2 infection. With the emergence of SARS-CoV-2 variants, the effort expanded to evaluate the efficacy of nearly 50 products against major variants. A subset of products was further evaluated for therapeutic efficacy in hamsters. Here we report results of the hamster studies, including pathogenicity with multiple variants, neutralization capacity of products, and efficacy testing of products against Delta and Omicron variants. These studies demonstrate the loss of efficacy of early products with variant emergence and support the use of the hamster model for evaluating therapeutics.
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Importance: Polygenic risk scores (PRSs) for coronary artery disease (CAD) are a growing clinical and commercial reality. Whether existing scores provide similar individual-level assessments of disease liability is a critical consideration for clinical implementation that remains uncharacterized. Objective: Characterize the reliability of CAD PRSs that perform equivalently at the population level at predicting individual-level risk. Design: Cross-sectional Study. Setting: All of Us Research Program (AOU), Penn Medicine Biobank (PMBB), and UCLA ATLAS Precision Health Biobank. Participants: Volunteers of diverse genetic backgrounds enrolled in AOU, PMBB, and UCLA with available electronic health record and genotyping data. Exposures: Polygenic risk for CAD from previously published PRSs and new PRSs developed separately from the testing cohorts. Main Outcomes and Measures: Sets of CAD PRSs that perform population prediction equivalently were identified by comparing calibration and discrimination (Brier score and AUROC) of generalized linear models of prevalent CAD using Bayesian analysis of variance. Among equivalently performing scores, individual-level agreement between risk estimates was tested with intraclass correlation (ICC) and Light's Kappa, measures of inter-rater reliability. Results: 50 PRSs were calculated for 171,095 AOU participants. When included in a model of prevalent CAD, 48 scores had practically equivalent Brier scores and AUROCs (region of practical equivalence = 0.02). Across these scores, 84% of participants had at least one score in both the top and bottom risk quintile. Continuous agreement of individual risk predictions from the 48 scores was poor, with an ICC of 0.351 (95% CI; 0.349, 0.352). Agreement between two statistically equivalent scores was moderate, with an ICC of 0.649 (95% CI; 0.646, 0.652). Light's Kappa, used to evaluate consistency of assignment to high-risk thresholds, did not exceed 0.56 (interpreted as 'fair') across statistically and practically equivalent scores. Repeating the analysis among 41,193 PMBB and 50,748 UCLA participants yielded different sets of statistically and practically equivalent scores which also lacked strong individual agreement. Conclusions and Relevance: Across three diverse biobanks, CAD PRSs that performed equivalently at the population level produced unreliable individual risk estimates. Approaches to clinical implementation of CAD PRSs must consider the potential for discordant individual risk estimates from otherwise indistinguishable scores.
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Treatment of rare/ultra-rare tumors is an unmet need due to a lack of standardized therapies and clinical trials. We developed the Molecular Tumor Board (MTB), a multidisciplinary team that integrates molecular profiling to generate personalized, N-of-One treatments for advanced cancers. This study evaluates 112 patients with rare/ultra-rare tumors who presented to the MTB and were evaluable for clinical therapeutic outcome. Overall, 46/112 patients (41%) received a treatment regimen with a high degree of matching between tumor molecular alterations and drugs given (reflected by a high Matching Score (≥50%)). Patients with a high versus low Matching Score experienced significantly longer progression-free survival (p = 0.005) and overall survival (p = 0.047), and higher rates of clinical benefit (stable disease ≥6 months, partial response, or complete response) (54% vs. 32% p = 0.027). The MTB facilitated personalized N-of-One matching of drugs to tumor molecular alterations, which was associated with improved clinical outcomes in patients with rare/ultra-rare cancers.
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Heart failure (HF) is one of the most common, complex, heterogeneous diseases in the world, with over 1-3% of the global population living with the condition. Progression of HF can be tracked via MRI measures of structural and functional changes to the heart, namely left ventricle (LV), including ejection fraction, mass, end-diastolic volume, and LV end-systolic volume. Moreover, while genome-wide association studies (GWAS) have been a useful tool to identify candidate variants involved in HF risk, they lack crucial tissue-specific and mechanistic information which can be gained from incorporating additional data modalities. This study addresses this gap by incorporating transcriptome-wide and proteome-wide association studies (TWAS and PWAS) to gain insights into genetically-regulated changes in gene expression and protein abundance in precursors to HF measured using MRI-derived cardiac measures as well as full-stage all-cause HF. We identified several gene and protein overlaps between LV ejection fraction and end-systolic volume measures. Many of the overlaps identified in MRI-derived measurements through TWAS and PWAS appear to be shared with all-cause HF. We implicate many putative pathways relevant in HF associated with these genes and proteins via gene-set enrichment and protein-protein interaction network approaches. The results of this study (1) highlight the benefit of using multi-omics to better understand genetics and (2) provide novel insights as to how changes in heart structure and function may relate to HF.