Liver enzyme elevation after lamivudine withdrawal in HIV-hepatitis B virus co-infected patients: the Swiss HIV Cohort Study

Background The principal causes of liver enzyme elevation among HIV-hepatitis B virus (HBV) co-infected patients are the hepatotoxic effects of antiretroviral therapy (ART), alcohol abuse, ART-induced immune reconstitution and the exacerbation of chronic HBV infection. Objectives To investigate the incidence and severity of liver enzyme elevation, liver failure and death following lamivudine (3TC) withdrawal in HIV-HBV co-infected patients. Methods Retrospective analysis of the Swiss HIV Cohort Study database to assess the clinical and biological consequences of the discontinuation of 3TC. Variables considered for analysis included liver enzyme, HIV virological and immunological parameters, and medication prescribed during a 6-month period following 3TC withdrawal. Results 3TC was discontinued in 255 patients on 363 occasions. On 147 occasions (109 patients), a follow-up visit within 6 months following 3TC withdrawal was recorded. Among these patients, liver enzyme elevation occurred on 42 occasions (29%), three of them (2%) with severity grade III and five of them (3.4%) with severity grade IV elevations (as defined by the AIDS Clinical Trials Group). Three patients presented with fulminant hepatitis. One death (0.7%) was recorded. Conclusions HBV reactivation leading to liver dysfunction may be an under-reported consequence of 3TC withdrawal in HIV-HBV co-infected patients. Regular monitoring of HBV markers is warranted if active therapy against HBV is discontinued.

Valve reconstruction or replacement for long-term biopsy-induced tricuspid regurgitation following heart transplantation

Tricuspid regurgitation following heart transplantation can become a severe problem in a subset of patients, where medical therapy fails. Operative findings are described and results of subsequent results with surgical intervention including repair and replacement are analysed. Although follow-up is short, tricuspid replacement seems superior to reconstruction following heart transplantation. Best results are obtained, if replacement is performed, before right ventricular function deteriorates.

Long-term outcome of ablative therapy of postoperative supraventricular tachycardias in patients with univentricular heart: a European multicenter study

BACKGROUND: Catheter ablation has evolved as a possible curative treatment modality for supraventricular tachycardias (SVT) in patients with univentricular heart. However, the long-term outcome of ablation procedures is unknown. We evaluated the procedural and long-term outcome of ablative therapy of late postoperative SVT in patients with univentricular heart. METHODS AND RESULTS: Patients with univentricular heart (n=19, 11 male; age, 29+/-9 years) referred for ablation of SVT were studied. Ablation was guided by 3D electroanatomic mapping in all but 2 procedures. A total of 41 SVT were diagnosed as intra-atrial reentrant tachycardia (n=30; cycle length, 310+/-68 ms), typical atrial flutter (n=4; cycle length, 288+/-42 ms), focal atrial tachycardia (n=6; cycle length, 400+/-60 ms), and atrial fibrillation (n=1). Ablation was successful in 73% of intra-atrial reentrant tachycardia, 75% of atrial flutter, and all focal atrial tachycardia and focal atrial fibrillation. During the follow-up period of 53+/-34 months, 2 patients were lost to follow-up, 3 died of heart failure, 2 underwent heart transplantation, and 1 underwent conduit replacement. Of the remaining group, 8 had sinus rhythm and 3 had SVT. CONCLUSIONS: Focal and reentrant mechanisms underlie postoperative SVT in patients with univentricular heart. Successive SVT developing over time may be caused by different mechanisms. Ablative therapy is potentially curative, with a procedural success rate of 78%. In patients who had multiple ablation procedures, the SVT originated from different atrial sites, suggesting that these new SVT were caused by progressive atrial disease. Despite recurrent SVT, sinus rhythm at the end of the follow-up period was achieved in 72%.

Transcatheter aortic valve replacement in Europe: adoption trends and factors influencing device utilization

OBJECTIVES The authors sought to examine the adoption of transcatheter aortic valve replacement (TAVR) in Western Europe and investigate factors that may influence the heterogeneous use of this therapy. BACKGROUND Since its commercialization in 2007, the number of TAVR procedures has grown exponentially. METHODS The adoption of TAVR was investigated in 11 European countries: Germany, France, Italy, United Kingdom, Spain, the Netherlands, Switzerland, Belgium, Portugal, Denmark, and Ireland. Data were collected from 2 sources: 1) lead physicians submitted nation-specific registry data; and 2) an implantation-based TAVR market tracker. Economic indexes such as healthcare expenditure per capita, sources of healthcare funding, and reimbursement strategies were correlated to TAVR use. Furthermore, we assessed the extent to which TAVR has penetrated its potential patient population. RESULTS Between 2007 and 2011, 34,317 patients underwent TAVR. Considerable variation in TAVR use existed across nations. In 2011, the number of TAVR implants per million individuals ranged from 6.1 in Portugal to 88.7 in Germany (33 ± 25). The annual number of TAVR implants performed per center across nations also varied widely (range 10 to 89). The weighted average TAVR penetration rate was low: 17.9%. Significant correlation was found between TAVR use and healthcare spending per capita (r = 0.80; p = 0.005). TAVR-specific reimbursement systems were associated with higher TAVR use than restricted systems (698 ± 232 vs. 213 ± 112 implants/million individuals ≥ 75 years; p = 0.002). CONCLUSIONS The authors' findings indicate that TAVR is underutilized in high and prohibitive surgical risk patients with severe aortic stenosis. National economic indexes and reimbursement strategies are closely linked with TAVR use and help explain the inequitable adoption of this therapy.

Papain-induced in vitro disc degeneration model for the study of injectable nucleus pulposus therapy

BACKGROUND CONTEXT Proteolytic enzyme digestion of the intervertebral disc (IVD) offers a method to simulate a condition of disc degeneration for the study of cell-scaffold constructs in the degenerated disc. PURPOSE To characterize an in vitro disc degeneration model (DDM) of different severities of glycosaminoglycans (GAG) and water loss by using papain, and to determine the initial response of the human mesenchymal stem cells (MSCs) introduced into this DDM. STUDY DESIGN Disc degeneration model of a bovine disc explant with an end plate was induced by the injection of papain at various concentrations. Labeled MSCs were later introduced in this model. METHODS Phosphate-buffered saline (PBS control) or papain in various concentrations (3, 15, 30, 60, and 150 U/mL) were injected into the bovine caudal IVD explants. Ten days after the injection, GAG content of the discs was evaluated by dimethylmethylene blue assay and cell viability was determined by live/dead staining together with confocal microscopy. Overall matrix composition was evaluated by histology, and water content was visualized by magnetic resonance imaging. Compressive and torsional stiffness of the DDM were also recorded. In the second part, MSCs were labeled with a fluorescence cell membrane tracker and injected into the nucleus of the DDM or a PBS control. Mesenchymal stem cell viability and distribution were evaluated by confocal microscopy. RESULTS A large drop of GAG and water content of the bovine disc were obtained by injecting >30 U/mL papain. Magnetic resonance imaging showed Grade II, III, and IV disc degeneration by injecting 30, 60, and 150 U/mL papain. A cavity in the center of the disc could facilitate later injection of the nucleus pulposus tissue engineering construct while retaining an intact annulus fibrosus. The remaining disc cell viability was not affected. Mesenchymal stem cells injected into the protease-treated DDM disc showed significantly higher cell viability than when injected into the PBS-injected control disc. CONCLUSIONS By varying the concentration of papain for injection, an increasing amount of GAG and water loss could be induced to simulate the different severities of disc degeneration. MSC suspension introduced into the disc has a very low short-term survival. However, it should be clear that this bovine IVD DDM does not reflect a clinical situation but offers exciting possibilities to test novel tissue engineering protocols.

In pneumococcal meningitis a novel water-soluble inhibitor of matrix metalloproteinases and TNF-alpha converting enzyme attenuates seizures and injury of the cerebral cortex

Matrix metalloproteinases (MMPs) and TNF-alpha converting enzyme (TACE) contribute to the pathophysiology of bacterial meningitis. To date, MMP-inhibitors studied in models of meningitis were compromised by their hydrophobic nature. We investigated the pharmacokinetics and the effect of TNF484, a water-soluble hydroxamate-based inhibitor of MMP and TACE, on disease parameters and brain damage in a neonatal rat model of pneumococcal meningitis. At 1 mg/kg q6h TNF484 reduced soluble TNF-alpha and the collagen degradation product hydroxyproline in the cerebrospinal fluid. Clinically, TNF484 attenuated the incidence of seizures and was neuroprotective in the cortex. Water-soluble MMP-inhibitors may hold promise in the therapy of bacterial meningitis.

Mechanical versus biological aortic valve replacement strategies.

Aortic valve replacement (AVR) is the most frequently performed procedure in valve surgery. The controversy about the optimal choice of the prosthetic valve is as old as the technique itself. Currently there is no perfect valve substitute available. The main challenge is to choose between mechanical and biological prosthetic valves. Biological valves include pericardial (bovine, porcine or equine) and native porcine bioprostheses designed in stented or stentless versions. Homografts and pulmonary autografts are reserved for special indications and will not be discussed in detail in this review. We will focus on the decision making between artificial biological and mechanical prostheses, respectively. The first part of this article reviews guideline recommendations concerning the choice of aortic prostheses in different clinical situations while the second part is focused on novel strategies in the treatment of patients with aortic valve pathology.

The future of transcatheter mitral valve interventions: competitive or complementary role of repair vs. replacement?

Transcatheter mitral interventions has been developed to address an unmet clinical need and may be an alternative therapeutic option to surgery with the intent to provide symptomatic and prognostic benefit. Beyond MitraClip therapy, alternative repair technologies are being developed to expand the transcatheter intervention armamentarium. Recently, the feasibility of transcatheter mitral valve implantation in native non-calcified valves has been reported in very high-risk patients. Acknowledging the lack of scientific evidence to date, it is difficult to predict what the ultimate future role of transcatheter mitral valve interventions will be. The purpose of the present report is to review the current state-of-the-art of mitral valve intervention, and to identify the potential future scenarios, which might benefit most from the transcatheter repair and replacement devices under development.