Withdrawal of Long-Term Nucleotide Analog Therapy in Chronic Hepatitis B:Outcomes From the Withdrawal Phase of the HBRN Immune Active Treatment Trial

INTRODUCTION:Withdrawal of nucleos(t)ide analog therapy is increasingly being evaluated in chronic hepatitis B infection as a strategy to induce hepatitis B surface antigen (HBsAg) loss. The Hepatitis B Research Network Immune-Active Trial evaluated treatment with tenofovir (TDF) for 4 years ± an initial 6 months of peginterferon-α (PegIFN) (NCT01369212) after which treatment was withdrawn.METHODS:Eligible participants (hepatitis B e antigen [HBeAg]-/anti-HBe+, hepatitis B virus [HBV] DNA &lt;103IU/mL, no cirrhosis) who discontinued TDF were followed for at least 1 year with optional follow-up thereafter. Retreatment was based on predefined criteria.RESULTS:Among 201 participants who received 4 years of treatment, 97 participants (45 TDF and 52 TDF + PegIFN arm, 79 Asian) discontinued TDF. HBsAg loss occurred in 5 participants, 2 within 25 weeks and 3 within 89-119 weeks postwithdrawal (cumulative rate 4.3% by 2 years). Alanine aminotransferase (ALT) flares (&gt;5× upper limit of normal) after TDF withdrawal occurred in 36 (37.1%) participants and occurred more frequently and earlier in those HBeAg- compared with HBeAg+ at treatment initiation. ALT flares were associated with older age and higher HBV DNA pretreatment and at the visit before the flare. ALT flares were not significantly associated with HBsAg decline or loss but were associated with immune active disease at 1 year (70.6% vs 11.9%, P &lt; 0.0001) and 2 years (66.7% vs 25.9%, P = 0.03) postwithdrawal. Treatment reinitiation was required in 13 (13.4%) participants, and 13 others remained in a sustained inactive carrier state by the end of the study follow-up. No criteria reliably predicted safe treatment withdrawal.DISCUSSION:Results from this trial do not support TDF withdrawal as a therapeutic strategy. HBsAg loss was infrequent within 2 years of stopping long-term TDF. If withdrawal is considered, HBV DNA should be carefully monitored with reinitiation of therapy if levels rise above 4 log10IU/mL to reduce the risk of ALT flares, as they were not associated with subsequent HBsAg decline or loss.</p

Entecavir and Peginterferon Alfaâ 2a in Adults With Hepatitis B e Antigenâ Positive Immuneâ Tolerant Chronic Hepatitis B Virus Infection

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/149552/1/hep30417_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/149552/2/hep30417.pd

First international new intravascular rigid-flex endovascular stent study (FINESS): Clinical and angiographic results after elective and urgent stent implantation

Objectives. The purpose of this study was to determine the feasibility, safety and efficacy of elective and urgent deployment of the new intravascular rigid-flex (NIR) stent in patients with coronary artery disease. Background. Stent implantation has been shown to be effective in the treatment of focal, new coronary stenoses and in restoring coronary flow after coronary dissection and abrupt vessel closure. However, currently available stents either lack flexibility, hindering navigation through tortuous arteries, or lack axial strength, resulting in suboptimal scaffolding of the vessel. The unique transforming multicellular design of the NIR stent appears to provide both longitudinal flexibility and radial strength. Methods. NIR stent implantation was attempted in 255 patients (341 lesions) enrolled prospectively in a multicenter international registry from December 1995 through March 1996. Nine-, 16- and 32-mm long NIR stents were manually crimped onto coronary balloons and deployed in native coronary (94%) and saphenous vein graft (6%) lesions. Seventy-four percent of patients underwent elective stenting for primary or restenotic lesions, 21% for a suboptimal angioplasty result and 5% for threatened or abrupt vessel closure. Fifty-two percent of patients presented with unstable angina, 48% had a previous myocardial infarction, and 45% had multivessel disease. Coronary lesions were frequently complex, occurring in relatively small arteries (mean [±SD] reference diameter 2.8 ± 0.6 mm). Patients were followed up for 6 months for the occurrence of major adverse cardiovascular events. Results. Stent deployment was accomplished in 98% of lesions. Mean minimal lumen diameter increased by 1.51 ± 0.51 mm (from 1.09 ± 0.43 mm before to 2.60 ± 0.50 mm after the procedure). Mean percent diameter stenosis decreased from 61 ± 13% before to 17 ± 7% after intervention. A successful interventional procedure with <50% diameter stenosis of all treatment site lesions and no major adverse cardiac events within 30 days occurred in 95% of patients. Event-free survival at 6 months was 82%. Ninety-four percent of surviving patients were either asymptomatic or had mild stable angina at 6 month follow-up. Conclusions. Despite unfavorable clinical and angiographic characteristics of the majority of patients enrolled, the acute angiographic results and early clinical outcome after NIR stent deployment were very promising. A prospective, randomized trial comparing the NIR stent with other currently available stents appears warranted

Hepatic abnormalities in patients with chronic granulomatous disease

Chronic granulomatous disease (CGD) is a rare congenital disorder characterized by repeated bacterial and fungal infections. Aside from a high incidence of liver abscess, little is known about hepatic involvement in CGD. The aim of this study was to describe the spectrum of liver abnormalities seen in CGD. The charts of 194 patients with CGD followed at the NIH were reviewed, with a focus on liver abnormalities. Liver enzyme elevations occurred on at least one occasion in 73% of patients during a mean of 8.9 years of follow-up. ALT elevations were generally transient. Although transient alkaline phosphatase (ALP) elevations were also common, persistent ALP elevations lasting up to 17.6 years were seen in 25% of patients. Liver abscess occurred in 35% of patients. Drug-induced hepatotoxicity was documented in 15% of patients but likely occurred more frequently. Hepatomegaly was found in 34% and splenomegaly in 56% of patients. Liver histology showed granulomata in 75% and lobular hepatitis in 90% of specimens. Venopathy of the portal vein was common (80%) and associated with splenomegaly. Venopathy of the central vein was also common (63%) and was associated with the number of abscess episodes. Nodular regenerative hyperplasia (NRH) was seen in 9 patients, including 6 of 12 autopsy specimens. CONCLUSION: Liver enzyme abnormalities occur frequently in patients with CGD. In addition to liver abscesses and granulomata, drug hepatotoxicity is likely underappreciated. Vascular lesions such as venopathy and--to a lesser extent--NRH are common. The cause and clinical consequences of venopathy await prospective evaluation

Search for exotic resonances decaying into WZ/ZZ in pp collisions at √s=7 TeV

Journal of High Energy Physics 2013.2 (2013): 036 reproduced by permission of Scuola Internazionale Superiore di Studi Avanzati (SISSA)Artículo escrito por un elevado número de autores, solo se referencian el que aparece en primer lugar, el nombre del grupo de colaboración, si le hubiere, y los autores pertenecientes a la UAMA search for new exotic particles decaying to the VZ final state is performed, where V is either a W or a Z boson decaying into two overlapping jets and the Z decays into a pair of electrons, muons or neutrinos. The analysis uses a data sample of pp collisions corresponding to an integrated luminosity of 5 fb-1 collected by the CMS experiment at the LHC at √s=7 TeV in 2011. No significant excess is observed in the mass distribution of the VZ candidates compared with the background expectation from standard model processes. Model-dependent upper limits at the 95% confidence level are set on the product of the cross section times the branching fraction of hypothetical particles decaying to the VZ final state as a function of mass. Sequential standard model W′ bosons with masses between 700 and 940 GeV are excluded. In the Randall-Sundrum model for graviton resonances with a coupling parameter of 0.05, masses between 750 and 880 GeV are also exclude

Search for stop and higgsino production using diphoton Higgs boson decays

Results are presented of a search for a "natural" supersymmetry scenario with gauge mediated symmetry breaking. It is assumed that only the supersymmetric partners of the top-quark (stop) and the Higgs boson (higgsino) are accessible. Events are examined in which there are two photons forming a Higgs boson candidate, and at least two b-quark jets. In 19.7 inverse femtobarns of proton-proton collision data at sqrt(s) = 8 TeV, recorded in the CMS experiment, no evidence of a signal is found and lower limits at the 95% confidence level are set, excluding the stop mass below 360 to 410 GeV, depending on the higgsino mass

Severe early onset preeclampsia: short and long term clinical, psychosocial and biochemical aspects

Preeclampsia is a pregnancy specific disorder commonly defined as de novo hypertension and proteinuria after 20 weeks gestational age. It occurs in approximately 3-5% of pregnancies and it is still a major cause of both foetal and maternal morbidity and mortality worldwide1. As extensive research has not yet elucidated the aetiology of preeclampsia, there are no rational preventive or therapeutic interventions available. The only rational treatment is delivery, which benefits the mother but is not in the interest of the foetus, if remote from term. Early onset preeclampsia (<32 weeks’ gestational age) occurs in less than 1% of pregnancies. It is, however often associated with maternal morbidity as the risk of progression to severe maternal disease is inversely related with gestational age at onset2. Resulting prematurity is therefore the main cause of neonatal mortality and morbidity in patients with severe preeclampsia3. Although the discussion is ongoing, perinatal survival is suggested to be increased in patients with preterm preeclampsia by expectant, non-interventional management. This temporising treatment option to lengthen pregnancy includes the use of antihypertensive medication to control hypertension, magnesium sulphate to prevent eclampsia and corticosteroids to enhance foetal lung maturity4. With optimal maternal haemodynamic status and reassuring foetal condition this results on average in an extension of 2 weeks. Prolongation of these pregnancies is a great challenge for clinicians to balance between potential maternal risks on one the eve hand and possible foetal benefits on the other. Clinical controversies regarding prolongation of preterm preeclamptic pregnancies still exist – also taking into account that preeclampsia is the leading cause of maternal mortality in the Netherlands5 - a debate which is even more pronounced in very preterm pregnancies with questionable foetal viability6-9. Do maternal risks of prolongation of these very early pregnancies outweigh the chances of neonatal survival? Counselling of women with very early onset preeclampsia not only comprises of knowledge of the outcome of those particular pregnancies, but also knowledge of outcomes of future pregnancies of these women is of major clinical importance. This thesis opens with a review of the literature on identifiable risk factors of preeclampsia