Searching for Preclinical Models of Acute Decompensated Heart Failure: a Concise Narrative Overview and a Novel Swine Model

Cardiovascular Drugs and Therapy - Available animal models of acute heart failure (AHF) and their limitations are discussed herein. A novel and preclinically relevant porcine model of decompensated...     

Inhibitors of the Hepatitis C Virus Polymerase; Mode of Action and Resistance

The hepatitis C virus (HCV) is a pandemic human pathogen posing a substantial health and economic burden in both developing and developed countries. Controlling the spread of HCV through behavioural prevention strategies has met with limited success and vaccine development remains slow. The development of antiviral therapeutic agents has also been challenging, primarily due to the lack of efficient cell culture and animal models for all HCV genotypes, as well as the large genetic diversity between HCV strains. On the other hand, the use of interferon-α-based treatments in combination with the guanosine analogue, ribavirin, achieved limited success, and widespread use of these therapies has been hampered by prevalent side effects. For more than a decade, the HCV RNA-dependent RNA polymerase (RdRp) has been targeted for antiviral development. Direct acting antivirals (DAA) have been identified which bind to one of at least six RdRp inhibitor-binding sites, and are now becoming a mainstay of highly effective and well tolerated antiviral treatment for HCV infection. Here we review the different classes of RdRp inhibitors and their mode of action against HCV. Furthermore, the mechanism of antiviral resistance to each class is described, including naturally occurring resistance-associated variants (RAVs) in different viral strains and genotypes. Finally, we review the impact of these RAVs on treatment outcomes with the newly developed regimens.     

18F-FDG PET/CT as predictive and prognostic factor in esophageal cancer treated with combined modality treatment

Annals of Nuclear Medicine - [18F] fluorodeoxyglucose positron emission tomography/computed tomography ([18F] FDG-PET/CT) is used for diagnosis, staging, response assessment and prognosis...     

Double Inversion Recovery MR Sequence for the Detection of Subacute Subarachnoid Hemorrhage

BACKGROUND AND PURPOSE:The diagnosis of subacute subarachnoid hemorrhage is important because rebleeding may occur with subsequent life-threatening hemorrhage. Our aim was to determine the sensitivity of the 3D double inversion recovery sequence compared with CT, 2D and 3D FLAIR, 2D T2*, and 3D SWI sequences for the detection of subacute SAH.MATERIALS AND METHODS:This prospective study included 25 patients with a CT-proved acute SAH. Brain imaging was repeated between days 14 and 16 (mean, 14.75 days) after clinical onset and included MR imaging (2D and 3D FLAIR, 2D T2*, SWI, and 3D double inversion recovery) after CT (median delay, 3 hours; range, 2–5 hours). A control group of 20 healthy volunteers was used for comparison. MR images and CT scans were analyzed independently in a randomized order by 3 blinded readers. For each subject, the presence or absence of hemorrhage was assessed in 4 subarachnoid areas (basal cisterns, Sylvian fissures, interhemispheric fissure, and convexity) and in brain ventricles. The diagnosis of subacute SAH was defined by the presence of at least 1 subarachnoid area with hemorrhage.RESULTS:For the diagnosis of subacute SAH, the double inversion recovery sequence had a higher sensitivity compared with CT (P < .001), 2D FLAIR (P = .005), T2* (P = .02), SWI, and 3D FLAIR (P = .03) sequences. Hemorrhage was present for all patients in the interhemispheric fissure on double inversion recovery images, while no signal abnormality was noted in healthy volunteers. Interobserver agreement was excellent with double inversion recovery.CONCLUSIONS:Our study showed that the double inversion recovery sequence has a higher sensitivity for the detection of subacute SAH than CT, 2D or 3D FLAIR, 2D T2*, and SWI.

Nontraumatic subarachnoid hemorrhage accounts for 3% of all strokes, and 85% are related to a ruptured intracranial aneurysm.¹ CT is highly sensitive for the diagnosis of SAH at the acute stage.² However, clinical symptoms may be atypical and result in delayed admission. In such patients, the diagnosis of subacute SAH is important because rebleeding may occur with subsequent life-threatening intracranial hemorrhage.³When performed several days after symptom onset, CT does not appear reliable for the diagnosis of SAH^4,5 and is outperformed by brain MR imaging in this setting.⁶ Indeed, FLAIR MR imaging is more sensitive than CT for SAH detection at both acute^7–9 and subacute¹⁰ stages. 3D FLAIR is even more specific than 2D FLAIR by reducing flow-related artifacts, which are known to provide false-positive findings on 2D FLAIR.¹¹ Nevertheless, SAH can still be misdiagnosed by using FLAIR imaging due to the time interval after onset¹² or artifacts.^13,14 T2* gradient-echo sequences are useful for subacute or chronic SAH depiction.^6,15,16 Susceptibility-weighted imaging uses tissue magnetic-susceptibility differences to generate a unique contrast, based on a 3D flow-compensated gradient-echo sequence.¹⁷ Previous studies have suggested that SWI could accurately detect small amounts of SAH and intraventricular hemorrhage (IVH).^18–20 A recent study focusing on the detection of microbleeds also demonstrated that SWI had a greater sensitivity for blood products than the conventional T2* sequence.²¹ However, no study available compares the diagnostic performance of T2* and SWI for the detection of spontaneous SAH, to our knowledge.Double inversion recovery (DIR) MR imaging is useful for the detection of cortical lesions.^22–24 This technique is based on a 3D turbo spin-echo acquisition with variable refocusing flip angles (BrainView, Philips Healthcare, Best, the Netherlands; Cube, GE Healthcare, Milwaukee, Wisconsin; SPACE, Siemens, Erlangen, Germany). DIR includes 2 inversion recovery pulses designed for the suppression of both CSF and normal white matter.²⁴ Data are still not available on the value of 3D DIR for the detection of SAH. The purpose of our study was to determine the sensitivity of the 3D DIR sequence compared with CT, 2D and 3D FLAIR, 2D T2*, and 3D SWI sequences for the detection of subacute SAH.