Hepatitis D virus and liver transplantation: Indications and outcomes

Hepatitis D virus(HDV) is a dependent virus that relies on hepatitis B virus for its replication and transmission. Chronic hepatitis D is a severe form of viral hepatitis that can result in end stage liver disease. Currently, pegylated interferon alpha is the only approved therapy for chronic HDV infection and is associated with significant side effects. Liver transplantation(LT) is the only treatment option for patients with end-stage liver disease, hepatocellular carcinoma, or fulminant hepatitis due to coinfection with HDV. As LT for HDV and hepatitis B virus coinfection is uncommon in the United States, most data on the long-term impact of LT on HDV are from international centers. In this review, we discuss the indications and results of LT with treatment options in HDV patients.     

Layered activation of epicardial scar in arrhythmogenic right ventricular dysplasia: possible substrate for confined epicardial circuits

Background- Ventricular tachycardia ablation in arrhythmogenic right ventricular dysplasia (ARVD) is more successful when including epicardial ablation. Scarring may cause independent, layered epicardial activation and promote epicardially confined ventricular tachycardia circuits. We aimed to characterize transmural right ventricular activation in ARVD patients and to compare this with reference patients without structural heart disease. Methods and Results- Eighteen ARVD patients underwent detailed endocardial and epicardial sinus rhythm electroanatomic mapping. Bipolar activation was annotated at the sharpest intrinsic deflection including late potentials and compared with 6 patients with normal hearts. Total scar area was larger on the epicardium (97±78 cm(2)) than the endocardium (57±44 cm(2); P=0.04), with significantly more isolated potentials. Total epicardial activation time was longer than endocardial (172±54 versus 99±27 ms; P<0.01), and both were longer than in reference patients. Earliest endocardial site was the right ventricular anteroseptum in 17 of 18 ARVD patients versus 5 of 6 controls (P=0.446), and latest endocardial site was in the outflow tract in 13 of 18 ARVD patients versus 4 of 6 controls and tricuspid annulus in 5 of 18 ARVD patients versus 2 of 6 controls (P=1.00). In reference patients, epicardial activation directly opposite endocardial sites occurred in 5.2±1.9 ms, suggesting direct transmural activation. In contrast, ARVD patients had major activation delay to the epicardium with laminar central scar activation from the scar border, not by direct transmural spread from the endocardium. Conclusions- Transmural right ventricular activation is modified by ARVD scarring with a delayed epicardial activation sequence suggestive of independent rather than direct transmural activation. This may predispose ventricular tachycardia circuits contained entirely within the epicardium in ARVD and explains observations on the need for direct epicardial ablation to eliminate ventricular tachycardia.     

Radiofrequency catheter ablation for ventricular tachycardia

The management of ventricular tachycardia (VT) has evolved considerably in recent times. The majority of patients with VT have structural heart disease and often implantable defibrillators. Implantable defibrillators can terminate ventricular arrhythmias and prevent sudden death but do not prevent these arrhythmias from occurring. Ventricular tachycardia may also occur in patients without structural heart disease and although these patients generally have a benign prognosis, the symptoms can be significant. Radiofrequency catheter ablation has a definite role as an alternative to anti-arrhythmic therapy in both groups of patients. This review outlines the indications, techniques and outcomes of catheter ablation in the management of patients with ventricular tachycardia.     

Induced pluripotent stem cell model recapitulates pathologic hallmarks of Gaucher disease

Gaucher disease (GD) is an autosomal recessive disorder caused by mutations in the acid β-glucocerebrosidase gene. To model GD, we generated human induced pluripotent stem cells (hiPSC), by reprogramming skin fibroblasts from patients with type 1 (N370S/N370S), type 2 (L444P/RecNciI), and type 3 (L444P/L444P) GD. Pluripotency was demonstrated by the ability of GD hiPSC to differentiate to all three germ layers and to form teratomas in vivo. GD hiPSC differentiated efficiently to the cell types most affected in GD, i.e., macrophages and neuronal cells. GD hiPSC-macrophages expressed macrophage-specific markers, were phagocytic, and were capable of releasing inflammatory mediators in response to LPS. Moreover, GD hiPSC-macrophages recapitulated the phenotypic hallmarks of the disease. They exhibited low glucocerebrosidase (GC) enzymatic activity and accumulated sphingolipids, and their lysosomal functions were severely compromised. GD hiPSC-macrophages had a defect in their ability to clear phagocytosed RBC, a phenotype of tissue-infiltrating GD macrophages. The kinetics of RBC clearance by types 1, 2, and 3 GD hiPSC-macrophages correlated with the severity of the mutations. Incubation with recombinant GC completely reversed the delay in RBC clearance from all three types of GD hiPSC-macrophages, indicating that their functional defects were indeed caused by GC deficiency. However, treatment of induced macrophages with the chaperone isofagomine restored phagocytosed RBC clearance only partially, regardless of genotype. These findings are consistent with the known clinical efficacies of recombinant GC and isofagomine. We conclude that cell types derived from GD hiPSC can effectively recapitulate pathologic hallmarks of the disease.     

Phylogenies reveal predictive power of traditional medicine in bioprospecting

There is controversy about whether traditional medicine can guide drug discovery, and investment in bioprospecting informed by ethnobotanical data has fluctuated. One view is that traditionally used medicinal plants are not necessarily efficacious and there are no robust methods for distinguishing those which are most likely to be bioactive when selecting species for further testing. Here, we reconstruct a genus-level molecular phylogenetic tree representing the 20,000 species found in the floras of three disparate biodiversity hotspots: Nepal, New Zealand, and the Cape of South Africa. Borrowing phylogenetic methods from community ecology, we reveal significant clustering of the 1,500 traditionally used species, and provide a direct measure of the relatedness of the three medicinal floras. We demonstrate shared phylogenetic patterns across the floras: related plants from these regions are used to treat medical conditions in the same therapeutic areas. This finding strongly indicates independent discovery of plant efficacy, an interpretation corroborated by the presence of a significantly greater proportion of known bioactive species in these plant groups than in random samples. We conclude that phylogenetic cross-cultural comparisons can focus screening efforts on a subset of traditionally used plants that are richer in bioactive compounds, and could revitalize the use of traditional knowledge in bioprospecting.     

Extended-release Niacin Acutely Suppresses Postprandial Triglyceridemia

ObjectivePostprandial triglyceridemia predicts cardiovascular events. Niacin might lower postprandial triglycerides by restricting free fatty acids. Immediate-release niacin reduced postprandial triglycerides, but extended-release niacin failed to do so when dosed the night before a fat challenge. The study aims were to determine whether extended-release niacin dosed before a fat challenge suppresses postprandial triglycerides and whether postprandial triglycerides are related to free fatty acid restriction.MethodsA double-blinded, placebo-controlled, random-order crossover experiment was performed, in which healthy volunteers took 2 g extended-release niacin or placebo 1 hour before heavy cream. We sampled blood over 12 hours and report triglycerides and free fatty acid as means ± standard deviation for incremental area under the curve (AUC) and nadir.ResultsBy combining 43 fat challenges from 22 subjects, postprandial triglycerides incremental AUC was +312 ± 200 mg/dL*h on placebo versus +199 ± 200 mg/dL*h on extended-release niacin (33% decrease, P = .02). The incremental nadir for free fatty acid was ?0.07 ± 0.15 mmol/L on placebo versus ?0.27 ± 0.13 mmol/L on extended-release niacin (P < .0001), and free fatty acid incremental AUC decreased from +2.9 ± 1.5 mmol/L*h to +1.5 ± 1.5 mmol/L*h on extended-release niacin (20% decrease, P = .0015). The incremental AUC for triglycerides was strongly related to the post-dose decrease in free fatty acid (r = +0.58, P = .0007).ConclusionsGiven right before a fat meal, even a single dose of extended-release niacin suppresses postprandial triglyceridemia. This establishes that postprandial triglycerides suppression is an acute pharmacodynamic effect of extended-release niacin, probably the result of marked free fatty acid restriction. Further study is warranted to determine whether mealtime dosing would augment the clinical efficacy of extended-release niacin therapy.     

Catheter‐based anatomic and functional assessment of coronary arteries in anomalous aortic origin of a coronary artery,myocardial bridges and Kawasaki disease

Most diagnostic testing in patients with anomalous aortic origins of coronary arteries, myocardial bridges, and coronary artery changes after Kawasaki disease are performed with the use of noninvasive techniques. In some cases, however, further diagnostic information is needed to guide the clinician in treating these patients. In such instances, cardiac catheterization with invasive anatomic and functional testing is an invaluable tool. Moreover, interventional treatment in the cardiac catheterization laboratory may be performed in a small subset of these patients. As the diagnosis of these conditions is now becoming more common, it is important for pediatric interventional cardiologists to be familiar with these techniques. In this article, the role of angiography, intravascular ultrasound, fractional flow reserve, and optical coherence tomography in these patients is reviewed.     

Association between serotonin denervation and resting‐state functional connectivity in mild cognitive impairment

Resting‐state functional connectivity alterations have been demonstrated in Alzheimer's disease (AD) and mild cognitive impairment (MCI) before the observation of AD neuropathology, but mechanisms driving these changes are not well understood. Serotonin neurodegeneration has been observed in MCI and AD and is associated with cognitive deficits and neuropsychiatric symptoms, but the role of the serotonin system in relation to brain network dysfunction has not been a major focus of investigation. The current study investigated the relationship between serotonin transporter availability (SERT; measured using positron emission tomography) and brain network functional connectivity (measured using resting‐state functional MRI) in 20 participants with MCI and 21 healthy controls. Two SERT regions of interest were selected for the analysis: the Dorsal Raphe Nuclei (DRN) and the precuneus which represent the cell bodies of origin and a cortical target of projections of the serotonin system, respectively. Both regions show decreased SERT in MCI compared to controls and are the site of early AD pathology. Average resting‐state functional connectivity did not differ between MCI and controls. Decreased SERT in DRN was associated with lower hippocampal resting‐state connectivity in MCI participants compared to controls. Decreased SERT in the right precuneus was also associated with lower resting‐state connectivity of the retrosplenial cortex to the dorsal lateral prefrontal cortex and higher resting‐state connectivity of the retrosplenial cortex to the posterior cingulate and in patients with MCI but not in controls. These results suggest that a serotonergic mechanism may underlie changes in brain functional connectivity in MCI. Hum Brain Mapp 38:3391–3401, 2017. © 2017 Wiley Periodicals, Inc.     

Extracranial meningioma: an unusual presentation of a mass over inner canthus of left eye

Meningiomas are commonly encountered as intracranial brain tumours, but extracranial meningiomas do occur although seen rarely. Here we present a case of extracranial meningioma presenting as a mass over the medial canthus of left eye and the glabella with extension into the left ethmoid sinuses, without any neurological symptoms or signs. The patient underwent surgical excision, plastic surgical reconstruction and adjuvant radiotherapy after 3-dimensional conformal treatment planning.     

Functional evaluation after primary flexor tendon repair in zone II

The purpose of this prospective study was to evaluate the results of primary treatment of flexor tendon laceration in zone II according to Verdan's zone system. Special emphasis was given to the postoperative rehabilitation program. Nineteen patients (23 fingers) with laceration of the flexor tendons in zone II were treated operatively. Twelve males and seven females were included in the study. Their mean age was 28 years (range, 16 to 50 years). In 12 cases a concomitant laceration of the digital nerve was present. In all cases primary repair of all injured tendons and nerves was performed and a dorsal splint was applied. On the third to fifth postoperative day an exercise program commenced involving passive flexion-active extension of the injured fingers. Eighteen (22 fingers) of 19 patients completed the follow-up. The results were evaluated according to Strickland's original classification system. The result was excellent in 15 cases, good in five and fair in two. After primary repair of injured flexor tendons, a program of close follow-up, early protected motion and unrestricted motion of the interphalangeal joints offers the best chance of restoring optimal function to the hand.