tbuckley/cabot-search huggingface dataset:
Abstract MP47: Maternal Trimethylamine-n-oxide Is Associated With Risk Of Gestational Diabetes Mellitus In A Low-income, Urban, Multi-ethnic Population
Authors: Kristen L McArthur, Mingyu Zhang, Xiumei Hong, Guoying Wang, Xiaobin Wang, Noel T Mueller
Journal: Circulation (2021)

Introduction: Trimethylamine-N-oxide (TMAO) is a metabolite influenced by gut microbiota composition and diet (e.g. eggs and red meat). While TMAO has been associated with type 2 diabetes in adults, it is still unclear whether TMAO is associated with risk of gestational diabetes (GDM). Results from the two case-control studies conducted on this topic in China were mixed, with one showing a U-shaped association and the other showing a linear association between TMAO and GDM. There is need to examine this association in a distinct population, in which the sources of TMAO may vary. Hypothesis: We hypothesized that higher TMAO concentration in both maternal and umbilical cord blood plasma (collected within 24-72 hours of birth) is associated with higher odds of GDM. Methods: We used data from the women in the Boston Birth Cohort (enrolled from 1998 to 2013) and fitted logistic regression models to examine the association of maternal and cord blood TMAO concentration with odds of GDM. TMAO was inversely normalized and was modeled in tertiles and as a continuous variable. GDM was diagnosed by a physician; women with pre-pregnancy diabetes were excluded from analyses. Final models were adjusted for covariates (see Table footnote). Results: Among our analytic sample (n=1405 participants), 1248 contributed maternal blood and 865 contributed cord blood. A total of 123 women developed GDM. Before and after adjustment for covariates, higher concentration of TMAO in maternal blood was associated with higher odds of GDM. After adjustment for potential confounders, the highest vs. lowest tertile of TMAO was associated with 1.75 times (95% CI 1.04, 2.96) the odds of GDM (Table). We found no association between cord blood TMAO and GDM (Table). Conclusion: In a population of predominantly low-income, urban mothers, higher maternal TMAO concentration measured in maternal blood (but not cord), was associated with higher odds of GDM. Our findings need to be replicated in prospective cohort studies that measure TMAO in early pregnancy.
Abstract 13193: Association of Abnormal P-wave Indices With Brain MRI Infarcts: The Atherosclerosis Risk in Communities Neurocognitive Study (ARIC-NCS)
Authors: Jorge L Reyes, Faye L Norby, Wendy Wang, Romil Parikh, Niki C Oldenburg, Pamela L Lutsey, Clifford R Jack, Michelle C Johansen, Rebecca F Gottesman, Elsayed Z Soliman, Alvaro Alonso, Lin Y Chen
Journal: Circulation (2020)

Introduction: We recently reported that abnormal P-wave indices (PWI)—ECG markers of atrial cardiomyopathy (AC)—are associated with an increased risk of dementia, independent of atrial fibrillation (AF) and clinical ischemic stroke. The mechanisms, however, remain unclear, but may include silent ischemia. Hypothesis: Abnormal PWI are associated with higher prevalence of cortical infarcts on MRI, suggesting cardioembolism as a potential mechanism. Methods: ARIC-NCS participants (mean age, 72.2±5.3 years; 60% women; 29% black) who underwent 3T brain MRI scans in 2011-2013 were included. Abnormal PWI included P-wave terminal force in lead V1 [(PTFV1) defined as ≥4000 μV*ms] and P-wave duration [(PWD) defined as &gt;120 ms], which were measured from standard 12-lead ECGs. Brain MRI outcomes included cortical infarcts, cerebral microbleeds (CMB), and markers of small vessel disease [white matter hyperintensities (WMH) and lacunar infarcts]. We used weighted multivariable logistic and linear regression analyses. Results: Of the 1,850 participants, 464 had abnormal PTFV1 and 415 had prolonged PWD. After multivariable adjustment including AF, abnormal PTFV1 and PWD were significantly associated with 26-44% increased odds of cortical and lacunar infarcts (Table) . Although PWD was associated with CMB in Model 1, the association was no longer significant after multivariable adjustment. Finally, abnormal PWIs were not associated with WMH after adjusting for stroke and AF (P &gt;0.5). Conclusions: Abnormal PWI are associated with higher prevalence of cortical infarcts, suggesting cardioembolism with silent ischemia as a possible mechanism underlying the association of AC with dementia. More research is needed to evaluate other mechanisms such as cerebral small vessel disease.
Reliability of Serial Prostate Magnetic Resonance Imaging to Detect Prostate Cancer Progression During Active Surveillance: A Systematic Review and Meta-analysis
Authors: Pawel Rajwa, Benjamin Pradere, Fahad Quhal, Keiichiro Mori, Ekaterina Laukhtina, Nicolai A. Huebner, David D’Andrea, Aleksandra Krzywon, Sung Ryul Shim, Pascal A. Baltzer, Raphaële Renard-Penna, Michael S. Leapman, Shahrokh F. Shariat, Guillaume Ploussard
Journal: European Urology (2021)

Although magnetic resonance imaging (MRI) is broadly implemented into active surveillance (AS) protocols, data on the reliability of serial MRI in order to help guide follow-up biopsy are inconclusive.To assess the diagnostic estimates of serial prostate MRI for prostate cancer (PCa) progression during AS.We systematically searched PubMed, Scopus, and Web of Science databases to select studies analyzing the association between changes on serial prostate MRI and PCa progression during AS. We included studies that provided data for MRI progression, which allowed us to calculate diagnostic estimates. We compared Prostate Cancer Radiological Estimation of Change in Sequential Evaluation (PRECISE) accuracy with institution-specific definitions.We included 15 studies with 2240 patients. Six used PRECISE criteria and nine institution-specific definitions of MRI progression. The pooled PCa progression rate, which included histological progression to Gleason grade ≥2, was 27%. The pooled sensitivity and specificity were 0.59 (95% confidence interval [CI] 0.44-0.73) and 0.75 (95% CI 0.66-0.84) respectively. There was significant heterogeneity between included studies. Depending on PCa progression prevalence, the pooled negative predictive value for serial prostate MRI ranged from 0.81 (95% CI 0.73-0.88) to 0.88 (95% CI 0.83-0.93) and the pooled positive predictive value ranged from 0.37 (95% CI 0.24-0.54) to 0.50 (95% CI 0.36-0.66). There were no significant differences in the pooled sensitivity (p = 0.37) and specificity (p = 0.74) of PRECISE and institution-specific schemes.Serial MRI still should not be considered a sole factor for excluding PCa progression during AS, and changes on MRI are not accurate enough to indicate PCa progression. There was a nonsignificant trend toward improved diagnostic estimates of PRECISE recommendations. These findings highlight the need to further define the optimal triggers and timing of biopsy during AS, as well as the need for optimizing the quality, interpretation, and reporting of serial prostate MRI.Our study suggests that serial prostate magnetic resonance imaging (MRI) alone in patients on active surveillance is not accurate enough to reliably rule out or rule in prostate cancer progression. Other clinical factors and biomarkers along with serial MRI are required to safely tailor the intensity of follow-up biopsies.
Single-Cell Joint Methylomics and Transcriptomics Define the Epigenetic Evolution and Lineage Histories of Chronic Lymphocytic Leukemia
Authors: Ronan Chaligne, Federico Gaiti, Steven Kothen-Hill, Hongcang Gu, Kevin Huang, Rafael Schulman, Kye-Tae Kim, Evan Biederstedt, Lili Wang, Martin J. Aryee, Andreas Gnirke, Catherine J. Wu, Alexander Meissner, Dan A. Landau
Journal: Blood (2017)
Response to ‘A call to standardize the BCC:SCC ratio’
Authors: B.C. Ma, V.N. Sahni, L.D. Edwards, D.R. Sahni, A.M. Secrest
Journal: British Journal of Dermatology (2021)

Linked Article: Jiyad et al. Br J Dermatol 2021; 184:545. The peer review history for this article is available at https://publons.com/publon/10.1111/bjd.20486.
Abstract 16822: Growth Curves Describing a Single Ventricle Population After Fontan Procedure
Authors: Bethany Runkel, Vincent Staggs, Chelsea Hosey Cojocari, Jonathan B Wagner
Journal: Circulation (2020)

Introduction: Complex single ventricle congenital heart disease (CHD) patients are subject to multiple stressors early in life that affect somatic growth. Pre-Fontan growth patterns are well-described, but post-Fontan growth has not been extensively studied in the current era. We sought to describe post-Fontan growth patterns by creating sex-specific body mass index (BMI)-for-age curves. Hypothesis: There is no difference in the growth of post-Fontan pediatric patients when compared to published normative data. Methods: A single-center, preexisting database was retrospectively queried for all patients who underwent Fontan procedure between 2006 and 2018. Patients with a genetic syndrome, a primary endocrine disorder, or significant prematurity were excluded. BMI-for-age curves were created for both male and female patients using anthropometric data extracted from the electronic medical record. Curves were then visually compared with Centers for Disease Control and Prevention (CDC) growth charts. Results: Of 227 patients who underwent primary Fontan operation, 37 were excluded. Of the remaining 190 patients, 59% were male. All had an extracardiac conduit, half had right-ventricular dominant CHD, and 15% had a Fontan fenestration. Median age and weight at surgery were 3.9 years and 15 kilograms, respectively. BMI curves were similar in appearance to CDC BMI-for-age growth charts, with adiposity rebound at age 6. BMI increased more rapidly in teen boys compared with girls, and a total of five patients (2.6%) had BMI values greater than 25 kg/m 2 at 16 years of age. Conclusion: Post-Fontan patients at our institution demonstrate BMI-for-age patterns similar to those of the general population during childhood and early adolescence, with adiposity rebound occurring at a typical age. Though excess weight gain does not completely spare patients with single ventricle CHD, overweight status appears to be less common than in the general pediatric population.
Abstract 15754: Coronary Calcification is Associated With Prior GnRH Agonist Therapy in Men With Recurrent Prostate Cancer Undergoing PET/CT Imaging
Authors: Avira Som, Preet Ayoub Shaikh, Daniel Lenihan, Melissa Reimers, Brian Baumann, Kathleen W Zhang
Journal: Circulation (2020)

Background: Gonadotropin releasing hormone (GnRH) agonist therapy is associated with major adverse cardiovascular (CV) events in men with prostate cancer. The effect of GnRH agonists on vascular calcification is not known. Methods: Consecutive patients who underwent 18F-fluciclovine positron emission tomography (PET) /computed tomography (CT) at our institution for recurrent prostate cancer were retrospectively identified. Clinical and demographic data were obtained from the medical record. Patients without available data on prior prostate cancer therapies received were excluded (n=25). Coronary calcification was qualitatively assessed on non-gated CT scans using a published scoring system. The association of prior GnRH agonist therapy with coronary calcification was evaluated using stratified odds ratio (OR) analysis in a 2x2 contingency table. Results: Among 186 men included, median age was 69.0 years (IQR 64.3, 74.5) and CV comorbidities were common (72% hypertension, 68% hyperlipidemia, 43% current or former smoking, and 21% diabetes mellitus). 55 patients (30%) received prior hormone therapy, 50 of whom received a GnRH agonist either as single- or multi-agent therapy. Men with prior GnRH agonists were older than those without prior GnRH agonists (71.4 vs. 68.4 years, p=0.025). There were no significant differences in prevalence of CV comorbidities between the two groups. Men with at least mild coronary calcification were more likely to have received prior GnRH agonist therapy (OR=3.0, 95% CI 1.2-7.1, p=0.015 by Fisher’s exact test), with a stronger association seen in younger men (OR=3.9, age &lt;69 years) than in older men (OR=1.8, age ≥69). Conclusions: Coronary calcification is associated with prior GnRH agonist therapy in men with recurrent prostate cancer undergoing PET/CT imaging. The utility of vascular protective therapies including aspirin and statin to mitigate the adverse CV effects of GnRH agonists requires further study.
Reduced levels of the adenomatous polyposis coli (APC) protein are associated with ceramide-induced apoptosis of colon cancer cells
Authors: Satya Narayan, Aruna S. Jaiswal
Journal: Cancer Research (2004)

3902   Colorectal cancer is the second most common cause of cancer-related death in both men and women in the Western world. Although surgery is the most effective treatment, approximately 50% of the people presumably cured by resection develop recurrent symptoms. Therefore, the development of strategies that would reduce the incidence of this malignancy would be particularly beneficial. One such strategy that has shown considerable promise is chemoprevention; in particular, chemoprevention that is based on the use of dietary factors. The natural chemopreventive agent, C 2 -ceramide, is regarded as a second-lipid messenger that can be released from sphingomyelin in response to extracellular and intracellular stimuli. It is well established that CF1 mice fed with a diet supplemented with C 2 -ceramide or other sphingomyelins exhibit a significantly lower incidence of colon cancers in response to the carcinogen 1,2-dimethylhydrazine (DMH) than mice fed a normal diet. However, the mechanism(s) by which C 2 -ceramide inhibits colon cancer growth is not well understood. Since mutations of the  adenomatous polyposis coli  ( APC ) and  p53  genes are commonly found in colorectal cancers and they are involved in cell cycle arrest and apoptosis, we analyzed the relative roles of APC and p53 in the induction of apoptosis of different colon cancer cell lines with and without wild-type  p53  and  APC  genes on proliferation and/or apoptosis and determined the role of p53 and APC proteins in these processes. The protein and mRNA levels in these cell lines with and without treatments were determined by Western and Northern blot analysis, respectively. The cell cycle and apoptosis profiles were determined by FACS analysis. Our findings indicate that C 2 -ceramide can induce apoptosis independently of the p53/p21(Waf-1/Cip-1) pathway. Also, the C 2 -ceramide induction of apoptosis showed a correlation with a reduction in the levels of the APC protein and mRNA. Moreover, the C 2 -ceramide-induced apoptosis was blocked by pretreatment with ZnCl 2 , which stabilized the levels of the APC protein. These results suggest that the treatment with C 2 -ceramide reduces the levels of APC protein and that the reduction in the levels of this protein plays a key role in the ability of C 2 -ceramide to induce apoptosis of colon cancer cells.
Abstract 15257: Epicardial and Peri-atrial Fat Attenuation Predict Recurrence in Patients Undergoing Repeat Catheter Ablation for Refractory Atrial Fibrillation
Authors: Mark S Brahier, Fengwei Zou, Frank Migliarese, Milos Tomovic, Alexandra Taylor, Veit Sandfort, Athanasios Thomaides, Peter Bergquist, Monvadi B Srichai, Jose D Vargas
Journal: Circulation (2020)

Background: Identifying factors predictive of atrial fibrillation (AF) recurrence after catheter ablation (CA) can improve patient selection. It has been hypothesized that inflammatory paracrine signaling by metabolically active adipose tissue induces pathologic changes in surrounding cardiovascular tissue. In fact, fat attenuation on CT has been previously associated with AF recurrence after de novo CA. The purpose of this study was to investigate the predictive qualities of epicardial and peri-atrial adipose tissue in a population undergoing repeat CA. We hypothesized that higher epicardial and left peri-atrial fat attenuation would predict recurrence as markers of increased localized inflammation. Methods: The study population consisted of 84 patients with symptomatic, drug and ablation-refractory AF undergoing repeat CA. All patients had a pre-ablation, contrast-enhanced cardiac CT, which was analyzed for mean fat attenuation in Hounsfield units (HU) and left atrial volume using the post-processing program 3D Slicer. Patients were followed for recurrence of atrial tachyarrhythmias after a 3-month blanking period. We performed logistic regression to adjust for age, sex, BMI, hypertension, smoking history, diabetes, obstructive sleep apnea, and left atrial volume index. Results: Repeat CA patients with recurrence (n=52) had a higher epicardial fat attenuation (-84.8 ±5.6 vs -88.1 ±5.2 HU; p=0.009) and peri-atrial fat attenuation (-81.0 ±4.7 vs -83.2 ±4.3 HU; p=0.036) than those without recurrence (n=32) at a mean follow-up period of 26 ±18 months. Logistic regression analysis showed that epicardial fat attenuation (OR 1.21; p=0.005) and peri-atrial fat attenuation (OR 1.27; p=0.007) are predictive of AF recurrence independent of traditional risk factors. Conclusions: Epicardial and left peri-atrial adipose attenuation are predictive of recurrence in patients undergoing repeat CA for AF.
Abstract 15575: The Clonal Hematopoiesis Mutation <i>Jak2</i> <sup>V617F</sup> Aggravates NETosis and Endothelial Injury in Mouse Arteries With Erosion-like Intimas
Authors: Roberto Molinaro, Rob S Sellar, Grasiele Sausen, Amelie Vromman, Eduardo Folco, Galina K Sukhova, Benjamin Ebert, Peter Libby
Journal: Circulation (2020)

Introduction: In the current era of intense LDL lowering, superficial erosion may be on the rise as a cause of ACS (25-30%). Experimental data on human atheromata support a role for neutrophils and the formation of neutrophil extracellular traps (NETs) in the pathogenesis of superficial erosion and subsequent thrombosis. The common mutation of Janus kinase 2 ( Jak2 V617F ) borne by clones of leukocytes derived from bone marrow stem cells sensitizes neutrophils to undergo NETosis and linked NET formation to increased thrombosis. Jak2 V617F associates with accelerated atherosclerosis and venous thrombosis in patients with myeloproliferative neoplasms (MPN) and in individuals harboring this mutation but without a demonstrable MPN. Hypothesis We hypothesized that i) the Jak2 V617F associated with clonal hematopoiesis and increased atherosclerotic and thrombotic risk in humans, predisposes to NETosis and subsequent endothelial injury and thrombosis at sites of flow disturbance in arteries with erosion-like intimas; and ii) the clinically approved Jak-1,2 inhibitor, ruxolitinib (Rux), can preserve endothelial integrity and reduce thrombosis in mice with myeloid Jak2 V617F . Methods: We generated cohorts of mice harboring Jak2 V617F or wild-type Jak2 . We used a surgical preparation recapitulating features of superficial erosion and assessed endothelial integrity, thrombosis, and NET formation in relation to genotype and in vivo Rux treatment. Results and Conclusions: Evans blue extravasation following introduction of flow disturbance at sites of erosion-prone intimas showed significant impairment of endothelial barrier in the group of mice bearing the Jak2 V617F mutation compared to control (WT) mice ( ** p&lt;0.005). We further observed more thrombosis in mice bearing the Jak2 V617F mutation. Immunohistochemical evaluation of the regions of experimental superficial erosion revealed reduced endothelial continuity and increased NET accumulation in Jak2 V617F vs. WT mice. Rux treatment mitigated the adverse effects of Jak2 V617F on both NET accumulation and endothelial integrity, supporting the translational potential of these observations in individuals with clonal hematopoiesis due to Jak2 V617F and acute coronary syndromes.
Abstract 259: The Contribution of Endothelial Derived Hyperpolarizing Factor and Nitric Oxide to Vasodilator tone in Hypercholesterolemia
Authors: Muhiddin Ozkor, Abdul Sheikh, Nino Kavtaradze, Jesse Jorgensen, Khan Pohlel, Salman Sher, Amita Manatunga, Arshed A Quyyumi
Journal: Circulation (2007)

Vasodilator tone in humans is modulated by a variety of endothelium-derived factors including nitric oxide (NO) and endothelium-derived hyperpolarizing factor (EDHF). EDHF contributes to vasodilati...
Are sugar-sweetened beverages contributing to the rising occurrence of colorectal cancer in young adults?
Authors: Neil Murphy, Peter T Campbell, Marc J Gunter
Journal: Gut (2021)

In contrast to falling or stabilising rates in older adults, the incidence of colorectal cancer in young adults (diagnosed prior to age 50 years; ‘early-onset colorectal cancer’) has increased over recent decades in many countries.1 2 In the USA and several other high-income countries, the incidence rates for early-onset colorectal cancer have risen across successive birth cohorts since the 1960s.3 This birth cohort effect suggests that secular changes in exposure to putative risk factors since this period may be driving the higher rates of colorectal cancer in younger adults.

Candidate risk factors that meet this criterion include the adoption of unhealthy dietary habits, such as higher consumption of sugar-sweetened beverages and soft drinks. In the USA, sugar-sweetened beverage consumption rose markedly for all ages between 1977 and 1996, including 70% and 83% increases for the 2–18 years old and 19–39 years old age groups, respectively.4 Previous epidemiological studies have generally found no evidence of an association between sugar-sweetened beverage intake and colorectal cancer. For example, a pooled analysis of 13 prospective cohort studies that examined the association between sugar-sweetened carbonated soft drink consumption and colon cancer, reported a relative risk of 0.94 (95% CI 0.66 to 1.32) …
Abstract 15616: Virtual Care: Empowering Patients and Providers
Authors: Kaavya Paruchuri, Romit Bhattacharya, Jaclyn Pagliaro, Ami Bhatt
Journal: Circulation (2020)

Introduction: The COVID-19 pandemic has catalyzed widespread usage of telemedicine due to the unprecedented need for remote patient care. Scaling virtual visits from occasional occurrences to standard of care is not without hurdles. Here we describe operationalizing virtual cardiovascular clinic in one large academic teaching hospital. Methods: To avoid implicit bias in perceived comfort with technology, virtual video (VV) visits were offered to all patients whose in-person office visit was cancelled. Those who declined were subsequently offered phone appointments. Patients who agreed to VV were called prior to their appointment time by staff to guide them through setup. Providers were given written, illustrated instructions on setup augmented with short how-to video demonstrations. They each completed a practice session with a staff member acting as a “test patient” to demonstrate basic functions within Zoom including use of chat, virtual waiting room, screen share and inviting additional participants (such as family, staff or interpreters). Providers were trained on workflows to allow seamless transitions across multidisciplinary team members involved in patient care. Results: Prior to the pandemic, there were mean (SD) 12.6 (2.8) VV appointments per month. Telemedicine adoption rose rapidly across provider types after travel restrictions were enacted, with the majority of visits initially occurring telephonically (Figure 1A and 1B). VV visits were also noted to increase swiftly with 3,164 VV visits in April 2020 and 5,452 in May 2020. After training sessions, providers felt comfortable using integrated virtual care tools (Figure 1C). Conclusions: Virtual clinic can be rapidly implemented and scaled within a healthcare system. Training materials and support for both patients and providers are key to increasing adoption of new technology. Hybrid systems will be needed to harmonize synchronous in-person and asynchronous virtual care in the longer term.