Quantification of epi- and pericardial adipose tissue deposits between males and females during cardiac CT may potentially help categorize coronary artery disease risk with thoracic circumference.

INTRODUCTION: This study aims to investigate the association between epi- and pericardial adipose tissue deposits around the heart against patient body habitus when using cardiac computed tomography (CT). METHODS: Ninety-two consecutive patients with suspected coronary artery disease underwent coronary CT angiography with quantitative cardiac and adipose tissue volume measurements. Body mass index (BMI), body surface area (BSA), thoracic circumference, anteroposterior diameter, cardiac and adipose tissue volumes were compared between genders by employing Pearson's correlation and results were considered statistically significant if p ≤ 0.05. RESULTS: Statistically significant differences between genders were observed with males having a greater height (males 1.72 ± 0.11), BMI (30.76 ± 7.87 kg/m2), BSA (2.06 ± 0.21 m2), thoracic circumference (1022.12 ± 97.90 mm2), and pericardial adipose tissue volume (46.72 ± 36.62 mm3) (p < 0.05). For men, for Group 1 (BMI ≤ 27) each of the measured volumes showed moderate correlation between pericardial adipose tissue and AP chest-diameter (r = 0.429, p <0.05), whereas in Group 2 (27 < BMI ≤ 31.1), coronary artery volume had a strong association with the AP chest-diameter (r = 0.453, p < 0.05). CONCLUSION: BMI and thoracic circumference are closely related to variable epi- and pericardial adipose tissue volumes in both males and females during cardiac CT. IMPLICATIONS FOR PRACTICE: Quantification of epi- and pericardial adipose tissue deposits between males and females during cardiac CT may help further categorise coronary artery disease risk when including BMI and thoracic circumference for males and females.

State of the art of coronary computed tomography angiography.

OBJECTIVES: The aim of this paper is to evaluate contrast media (CM) bolus geometry and opacification patterns in the coronary arteries with particular focus on patient, scanner and safety considerations during coronary computed tomography angiography (CCTA). KEY FINDINGS: The rapid evolution of computed tomography (CT) technology has seen this imaging modality challenge conventional coronary angiography in the evaluation of coronary artery disease. Increases in spatial and temporal resolutions have enabled CCTA to become the modality of choice when evaluating the coronary vascular tree as an alternative in the diagnostic algorithm for acute chest pain. However, these new technologic improvements in scanner technology have imposed new challenges for the optimisation of CM delivery and image acquisition strategies. CONCLUSION: Understanding basic CM-imaging principles is essential for designing optimal injection protocols according to each specific clinical scenario, independently of scanner technology. IMPLICATIONS FOR PRACTICE: With rapid advances in CT scanner technology including faster scan acquisitions, the risk of poor opacification of coronary vasculature increases significantly. Therefore, awareness of CM delivery protocols is paramount to consistently provide optimal image quality at a low radiation dose.

Gadolinium and Multiple Sclerosis: Vessels, Barriers of the Brain, and Glymphatics.

The pathogenesis of multiple sclerosis is characterized by a cascade of pathobiologic events, ranging from focal lymphocytic infiltration and microglia activation to demyelination and axonal degeneration. MS has several of the hallmarks of an inflammatory autoimmune disorder, including breakdown of the BBB. Gadolinium-enhanced MR imaging is currently the reference standard to detect active inflammatory lesions in MS. Knowledge of the patterns and mechanisms of contrast enhancement is vital to limit the radiologic differential diagnosis in the staging and evaluation of MS lesion activity. The aim of this review was the following: 1) to outline the pathophysiology of the effect of lymphocyte-driven inflammation in MS, 2) to describe the effects of gadolinium on the BBB and glymphatic system, and 3) to describe gadolinium enhancement patterns and artifacts that can mimic lesions in MS.

p62/SQSTM1 upregulation constitutes a survival mechanism that occurs during granulocytic differentiation of acute myeloid leukemia cells.

The p62/SQSTM1 adapter protein has an important role in the regulation of several key signaling pathways and helps transport ubiquitinated proteins to the autophagosomes and proteasome for degradation. Here, we investigate the regulation and roles of p62/SQSTM1 during acute myeloid leukemia (AML) cell maturation into granulocytes. Levels of p62/SQSTM1 mRNA and protein were both significantly increased during all-trans retinoic acid (ATRA)-induced differentiation of AML cells through a mechanism that depends on NF-κB activation. We show that this response constitutes a survival mechanism that prolongs the life span of mature AML cells and mitigates the effects of accumulation of aggregated proteins that occurs during granulocytic differentiation. Interestingly, ATRA-induced p62/SQSTM1 upregulation was impaired in maturation-resistant AML cells but was reactivated when differentiation was restored in these cells. Primary blast cells of AML patients and CD34(+) progenitors exhibited significantly lower p62/SQSTM1 mRNA levels than did mature granulocytes from healthy donors. Our results demonstrate that p62/SQSTM1 expression is upregulated in mature compared with immature myeloid cells and reveal a pro-survival function of the NF-κB/SQSTM1 signaling axis during granulocytic differentiation of AML cells. These findings may help our understanding of neutrophil/granulocyte development and will guide the development of novel therapeutic strategies for refractory and relapsed AML patients with previous exposure to ATRA.

Primary effusion lymphoma in an elderly patient effectively treated by lenalidomide: case report and review of literature.

Primary effusion lymphoma (PEL) is a rare aggressive subset of non-Hodgkin B-cell lymphoma. It is caused by Kaposi sarcoma-associated herpesvirus/human herpesvirus type 8 (KSHV/HHV8). It occurs mainly, but not exclusively, in HIV-positive patients. PEL predominantly develops in serous cavities and occasionally in extracavitary regions. PEL carries a very poor prognosis with a median survival time of <6 months. Indeed, currently used treatment modalities such as CHOP chemotherapy are far from achieving complete and sustainable remission. Therefore, there is no clear standard of care established in the treatment of PEL patients, stressing the need for novel-targeted approaches. Here, we have attempted a comprehensive assessment of the treatment of PEL, discussed avant-garde therapies and updated the state of preclinical research with promising clinical applications in the field. These include inhibitors of viral replication, modulators of cell signaling and inflammation, nuclear factor kappa B (NF-κB) and histone deacetylase inhibitors, and recently the combination of arsenic trioxide and interferon-alpha. Some of these targeted therapies have not yet reached clinical studies, although others were used in a few individual case reports with low numbers of patients. We also describe the first case of a 77-year-old, HIV-negative, HHV8-positive patient diagnosed with PEL limited to the pleural and peritoneal cavities. He received lenalidomide 25 mg/day for 21 days every 28 days. Treatment was well tolerated with no side effects. He rapidly improved after 1 month of treatment and progressively achieved complete remission persistent after 18 months of therapy. We believe that this review will bridge an important gap between classical chemotherapy and modern approaches of targeted therapy. Finally, our findings warrant further evaluation of lenalidomide in future prospective clinical studies.

Mechanistic insights into the antileukemic activity of hyperforin.

Hyperforin is a prenylated phloroglucinol present in the medicinal plant St John's wort (Hypericum perforatum). The compound has many biological properties, including antidepressant, anti-inflammatory, antibacterial and antitumor activities. This review focuses on the in vitro antileukemic effects of purified hyperforin and related mechanisms in chronic lymphoid leukemia (CLL) and acute myeloid leukemia (AML) - conditions that are known for their resistance to chemotherapy. Hyperforin induces apoptosis in both CLL and AML cells. In AML cell lines and primary AML cells, hyperforin directly inhibits the kinase activity of the serine/threonine protein kinase B/AKT1, leading to activation of the pro-apoptotic Bcl-2 family protein Bad through its non-phosphorylation by AKT1. In primary CLL cells, hyperforin acts by stimulating the expression of the pro-apoptotic Bcl-2 family member Noxa (possibly through the inhibition of proteasome activity). Other hyperforin targets include matrix metalloproteinase-2 in AML cells and vascular endothelial growth factor and matrix metalloproteinase-9 in CLL cells - two mediators of cell migration and angiogenesis. In summary, hyperforin targets molecules involved in signaling pathways that control leukemic cell proliferation, survival, apoptosis, migration and angiogenesis. Hyperforin also downregulates the expression of P-glycoprotein, a protein that is involved in the resistance of leukemia cells to chemotherapeutic agents. Lastly, native hyperforin and its stable derivatives show interesting in vivo properties in animal models. In view of their low toxicity, hyperforin and its derivatives are promising antileukemic agents and deserve further investigation in vivo.

Magnetic resonance imaging of the gallbladder: spectrum of abnormalities.

Various pathologies involving the gallbladder can manifest clinically, producing nonspecific clinical symptoms and making diagnosis difficult and challenging. Real-time sonography is the most widely used diagnostic study for the gallbladder and the primary screening examination of choice. With increasing use of magnetic resonance imaging (MRI) and MR cholangiopancreatography (MRCP), gallbladder pathology is frequently seen. Understanding the basic patterns of various disease manifestations and appearance on MRI is the key to making an accurate diagnosis. Given its inherent tissue contrast and contrast sensitivity, MRI in conjunction with MRCP can be a very valuable test in evaluating gallbladder pathology. Gallbladder pathology can be classified into congenital (such as absence), inflammatory (acute, hemorrhagic, and chronic cholecystitis), traumatic, benign (polyps) and malignant tumors (gallbladder carcinoma and lymphoma), and other disease processes can be seen in cholelithiasis, cholesterosis, thickened gallbladder wall, and Mirrizzi syndrome.