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Complete RNAseq data set.

A significant increase in cyclooxygenase 2 (COX2) gene expression has been shown to promote cylcooxygenase-dependent colon cancer development. Controversy associated with the role of COX2 inhibitors indicates that additional work is needed to elucidate the effects of arachidonic acid (AA)-derived (cyclooxygenase and lipoxygenase) eicosanoids in cancer initiation, progression, and metastasis. We have recently developed a novel Fads1 knockout mouse model that allows for the investigation of AA-dependent eicosanoid deficiency without the complication of essential fatty acid deficiency. Interestingly, the survival rate of Fads1-null mice is severely compromised after 2 months on a semi-purified AA-free diet, which precludes long-term chemoprevention studies. Therefore, in this study, dietary AA levels were titrated to determine the minimal level required for survival, while maintaining a distinct AA-deficient phenotype. Null mice supplemented with AA (0.1%, 0.4%, 0.6%, 2.0%, w/w) in the diet exhibited a dose-dependent increase (P < 0.05) in AA, PGE2, 6-keto PGF1α, TXB2, and EdU-positive proliferative cells in the colon. In subsequent experiments, null mice supplemented with 0.6% AA diet were injected with a colon-specific carcinogen (azoxymethane) in order to assess cancer susceptibility. Null mice exhibited significantly (P < 0.05) reduced levels/multiplicity of aberrant crypt foci (ACF) as compared with wild-type sibling littermate control mice. These data indicate that (i) basal/minimal dietary AA supplementation (0.6%) expands the utility of the Fads1-null mouse model for long-term cancer prevention studies and (ii) that AA content in the colonic epithelium modulates colon cancer risk. Cancer Prev Res; 9(9); 750–7. ©2016 AACR.

Mononuclear cells were isolated from pooled spleens, mesenteric and inguinal lymph nodes. CD3+ T cell population was further analyzed by flow cytometry. Data are reported as percentage of CD3+ T cells in the mononuclear cells. (mean {plus minus} SE, n=4-6). Bars not sharing the same letter indicate significant differences (P < 0.05).

A. Three key criteria to define aberrant crypt include: (1) the area occupied by the crypt and its pericryptal zone is greater than the surrounding normal crypts; (2) irregular shape of the luminal opening; and (3) the epithelial lining is thicker and darker than that of the surrounding crypt. B. Images of ACF with various aberrant crypts/focus (40x magnification).

Fads1 Null mice exhibited low viability when fed a basal AA-free (10% SAF) diet. Dietary supplementation with AA (0.1, 0.4, 0.6 and 2.0%, w/w) dose-dependently reversed the Fads1 Null mouse phenotype (n=3-5).

Detail dietary FA composition.

Data were analyzed using IPA. Selected networks with a Z score < -2.0, and p-value of overlap < 0.001 are reported.

Fear of acquiring severe acute respiratory syndrome coronavirus-2 infection is a major contributor to underutilization of the health care system during the current pandemic. In this report, we describe 4 cases of unexpected deaths that occurred within a short time period in patients with adult congenital heart disease without warning symptoms. (Level of Difficulty: Intermediate.)

As a rare complication after lung transplant, cardiac constriction should not be missed. Physical exam, echocardiography, and catheterization are essential for diagnosis A 65-year-old man with previous coronary artery disease and idiopathic pulmonary fibrosis underwent bilateral lung transplant and subsequently presented for progressive dyspnea and volume overload. Cardiac imaging and cardiac catheterization confirmed constriction, and complete pericardiectomy was performed. The patient had rapid resolution of heart failure symptoms. Pericardial constriction is a rare complication following lung transplant, and we provide a review of the literature and discussion of potential contributing factors. (Level of Difficulty: Intermediate.), Graphical abstract, As a rare complication after lung transplant, cardiac constriction should not be missed. Physical exam, echocardiography, and catheterization are…

A man aged 53 years presented to the emergency department with several hours of substernal chest pain radiating to his left arm. He had multiple myeloma treated with bortezomib, lenalidomide and dexamethasone. ECG showed inferior ST segment elevations. Troponin I was >73 ng/mL on hypersensitive troponin assay. Cardiac catheterisation was performed without obstructive coronary disease. Transthoracic echocardiogram showed normal left ventricular ejection fraction with abnormal global longitudinal strain of −10%. The patient developed ventricular tachycardia requiring electrical cardioversion. Repeat echocardiogram 48 hours later showed …

Cardiac tamponade is a challenging diagnosis in the unstable patient requiring extracorporeal membrane oxygenation. We present a case of cardiac tamponade secondary to hemorrhagic pericardial effusion that developed in the setting of cardiopulmonary resuscitation and venoarterial extracorporeal membrane oxygenation. Specifically, we aim to discuss the pertinent diagnostic challenges in confirming this diagnosis.

Concerns over radiation exposure are ubiquitous to all interventional cardiologists; however, fear of exposure during childbearing years disproportionately deters women from entering the field. This review summarizes the available data on occupational radiation exposure during pregnancy with an emphasis on radiation quantification, the impact of exposure at various stages of fetal development, societal recommendations for safe levels of exposure during gestation, threshold levels necessary to induce fetal harm, and safe practices for the pregnant interventionalist. Reconciling the available information, we conclude that pregnancy in the cardiac catheterization laboratory is both safe and feasible. This review also highlights new technologies that may augment standard radiation safety techniques and are of particular interest to the pregnant interventional cardiologist. Finally, we propose steps to improve female representation in this field, underscoring the importance of a sex-balanced workforce.

Cardiac sarcoidosis is a component of an often multiorgan granulomatous disease of still uncertain cause. It is being recognized with increasing frequency, mainly as the result of heightened awareness and new diagnostic tests, specifically cardiac magnetic resonance imaging and18F-fluorodeoxyglucose positron emission tomography scans. The purpose of this case-based review is to highlight the potentially life-saving importance of making the early diagnosis of cardiac sarcoidosis using these new tools and to provide a framework for the optimal care of patients with this disease. We will review disease mechanisms as currently understood, associated arrhythmias including conduction abnormalities, and atrial and ventricular tachyarrhythmias, guideline-directed diagnostic criteria, screening of patients with extracardiac sarcoidosis, and the use of pacemakers and defibrillators in this setting. Treatment options, including those related to heart failure, and those which may help clarify disease mechanisms are included.

Lead barriers to reduce operator radiation exposure in the catheterization laboratory are effective. This study of a novel vertical radiation shield suggests significant reduction in operator radiation exposure when used in addition to standard protection methods. Although additional barriers may help reduce radiation exposure, further education and training of operators in radiation safety may be as effective and perhaps more effective than additional barriers.

Cancer and cardiovascular disease are the leading causes of mortality in the USA. In this review, we highlight these shared disease pathways and provide a framework for a systems-based approach to reduce overall risk burden. From traditional risk factors such as age and tobacco use to more recently recognized entities including clonal hematopoiesis, we are gaining insights into shared mechanisms. Because of these overlapping risks, providers on each level of patient care (primary care providers, cardiologists, oncologists) need to recognize and reduce these underlying risk factors. There is significant overlap in the epidemiology and risk factors for the development of cardiovascular disease and cancer, providing opportunities for joint risk factor modification.

A significant increase in cyclooxygenase 2 (COX2) gene expression has been shown to promote cylcooxygenase-dependent colon cancer development. Controversy associated with the role of COX2 inhibitors indicates that additional work is needed to elucidate the effects of arachidonic acid (AA)-derived (cyclooxygenase and lipoxygenase) eicosanoids in cancer initiation, progression, and metastasis. We have recently developed a novel Fads1 knockout mouse model that allows for the investigation of AA-dependent eicosanoid deficiency without the complication of essential fatty acid deficiency. Interestingly, the survival rate of Fads1-null mice is severely compromised after 2 months on a semi-purified AA-free diet, which precludes long-term chemoprevention studies. Therefore, in this study, dietary AA levels were titrated to determine the minimal level required for survival, while maintaining a distinct AA-deficient phenotype. Null mice supplemented with AA (0.1%, 0.4%, 0.6%, 2.0%, w/w) in the diet exhibited a dose-dependent increase (P < 0.05) in AA, PGE2, 6-keto PGF1α, TXB2, and EdU-positive proliferative cells in the colon. In subsequent experiments, null mice supplemented with 0.6% AA diet were injected with a colon-specific carcinogen (azoxymethane) in order to assess cancer susceptibility. Null mice exhibited significantly (P < 0.05) reduced levels/multiplicity of aberrant crypt foci (ACF) as compared with wild-type sibling littermate control mice. These data indicate that (i) basal/minimal dietary AA supplementation (0.6%) expands the utility of the Fads1-null mouse model for long-term cancer prevention studies and (ii) that AA content in the colonic epithelium modulates colon cancer risk. Cancer Prev Res; 9(9); 750–7. ©2016 AACR.

Pheochromocytoma is an under-recognized, catecholamine-producing tumor arising from adrenal medullary chromaffin cells. Takotsubo cardiomyopathy is a rare complication of pheochromocytoma. Compared to primary Takotsubo cardiomyopathy, heart failure and cardiogenic shock may be more common in cases

Venoarterial extracorporeal membrane oxygenation (VA-ECMO) is an increasingly utilized treatment for refractory cardiogenic shock. Despite advances in ECMO technology, however, complication rates and mortality remain high. Risk scores have been developed in an attempt to improve outcomes. It remains

Infective endocarditis remains a highly mortal disease, yet the diagnosis often is missed or made only late in the disease course. The spectrum of patients presenting with endocarditis is shifting with different risk factors, predisposing patient characteristics, and treatment recommendations than in the past. This review addresses changes in the epidemiology of infective endocarditis, along with current diagnostic imaging modalities, treatment recommendations, and mortality trends. Risk factors for endocarditis now include the growing population of adults with congenital heart disease and patients with frequent healthcare contact for other comorbidities, as well as patients who are hemodialysed and immunocompromised or use intravenous drugs. Although transthoracic and transesophageal echocardiography are essential for diagnosis, additional testing (nuclear, computed tomographic, and magnetic resonance imaging) is helpful in selected patients. Early surgical management, even in high-risk patients, has a mortality benefit because eradication of infection with antibiotics alone is difficult and because valve destruction often results in hemodynamic compromise. As part of a broad differential diagnosis, clinicians should consider the diagnosis of endocarditis in patients with risk factors, even when the clinical presentation is nonspecific. Blood cultures and echocardiography are the first steps for diagnosis. Other imaging modalities can enhance diagnosis, particularly in patients with intracardiac devices or prosthetic material. Evidence from observational studies support early surgical intervention to reduce morbidity and mortality from this lethal condition.

Vascular plugs are increasingly used for paravalvular leak (PVL) and ventricular pseudoaneurysm. Management of plug embolization is challenging. A 31-year-old man with Klippel-Trenaunay syndrome presented with palpitations. He had prior endocarditis and mechanical MV replacement with anterolateral

There are rare reports in the literature of bortezomib induced cardiotoxicity. We report a presentation of fulminant myocarditis due to bortezomib. A 53 year old male with recent diagnosis of multiple myeloma, on lenalidomide, bortezomib, and dexamethasone, presents to the ER with chest pain. ECG

Arachidonic acid (20:4(Δ5,8,11,14), AA)-derived eicosanoids regulate inflammation and promote cancer development. Previous studies have targeted prostaglandin enzymes in an attempt to modulate AA metabolism. However, due to safety concerns surrounding the use of pharmaceutical agents designed to target Ptgs2 (cyclooxygenase 2) and its downstream targets, it is important to identify new targets upstream of Ptgs2. Therefore, we determined the utility of antagonizing tissue AA levels as a novel approach to suppressing AA-derived eicosanoids. Systemic disruption of the Fads1 (Δ5 desaturase) gene reciprocally altered the levels of dihomo-γ-linolenic acid (20:3(Δ8,11,14), DGLA) and AA in mouse tissues, resulting in a profound increase in 1-series-derived and a concurrent decrease in 2-series-derived prostaglandins. The lack of AA-derived eicosanoids, e.g., PGE₂ was associated with perturbed intestinal crypt proliferation, immune cell homeostasis, and a heightened sensitivity to acute inflammatory challenge. In addition, null mice failed to thrive, dying off by 12 weeks of age. Dietary supplementation with AA extended the longevity of null mice to levels comparable to wild-type mice. We propose that this new mouse model will expand our understanding of how AA and its metabolites mediate inflammation and promote malignant transformation, with the eventual goal of identifying new drug targets upstream of Ptgs2.

A 59-year-old diabetic, obese, male smoker was on neoadjuvant chemotherapy for stage IV rectal cancer with liver metastasis. He presented with perineal pain and a foul smell. The patient had a 20×10 cm necrotic wound extending from the posterior scrotum to the anal verge that was tender, malodorous and draining dishwater fluid (figure 1). Urgent debridement of his Fournier's gangrene …

Research suggests that discrepant cognitive abilities are more common in children with autism spectrum disorder (ASD) and may indicate an important ASD endophenotype. The current study examined the frequency of IQ discrepancy profiles (nonverbal IQ > verbal IQ [NVIQ > VIQ], verbal IQ > nonverbal IQ [VIQ > NVIQ], and no split) and the relationship of gender, age, and ASD symptomatology to IQ discrepancy profile in a large sample of children with ASD. The NVIQ > VIQ profile occurred at a higher frequency than expected, had more young males, and showed more autism symptoms than the other groups. Results suggest that the NVIQ > VIQ profile may be less likely to represent a subtype of ASD, but rather a common developmental pathway for children with ASD and other disorders.