Impact of Treatment with Human Immunodeficiency Virus (HIV) Protease Inhibitors on Hepatitis C Viremia in Patients Coinfected with HIV

The impact of human immunodeficiency virus (HIV) protease inhibitors on hepatitis C (HCV) viremia was assessed in 19 patients infected with both HIV and HCV. HIV and HCV RNA levels were measured before and during treatment with protease inhibitors. before treatment, mean levels of HCV RNA were 5.3 log for HCV RNA and 5.0 log for HIV RNA. CD4 lymphocyte counts were 63/mm3. after 6 weeks of treatment, a mean reduction of 2.1 log10 in HIV RNA (P < .001) and a mean (±SE) increase of 73 (±21) CD4 and 296 (±70) CD8 cells were observed (P < .05). In contrast, both HCV viremia (+0.4 log ± 0.1) and alanine aminotransferase increased (P < .04). HCV RNA levels returned to baseline after 17 and 32 weeks of treatment. Thus, potent anti-HIV regimens with protease inhibitors may temporarily worsen HCV status despite improvement of HIV parameter

STRATEGIC-1: A multiple-lines, randomized, open-label GERCOR phase III study in patients with unresectable wild-type RAS metastatic colorectal cancer.

BACKGROUND: The management of unresectable metastatic colorectal cancer (mCRC) is a comprehensive treatment strategy involving several lines of therapy, maintenance, salvage surgery, and treatment-free intervals. Besides chemotherapy (fluoropyrimidine, oxaliplatin, irinotecan), molecular-targeted agents such as anti-angiogenic agents (bevacizumab, aflibercept, regorafenib) and anti-epidermal growth factor receptor agents (cetuximab, panitumumab) have become available. Ultimately, given the increasing cost of new active compounds, new strategy trials are needed to define the optimal use and the best sequencing of these agents. Such new clinical trials require alternative endpoints that can capture the effect of several treatment lines and be measured earlier than overall survival to help shorten the duration and reduce the size and cost of trials. METHODS/DESIGN: STRATEGIC-1 is an international, open-label, randomized, multicenter phase III trial designed to determine an optimally personalized treatment sequence of the available treatment modalities in patients with unresectable RAS wild-type mCRC. Two standard treatment strategies are compared: first-line FOLFIRI-cetuximab, followed by oxaliplatin-based second-line chemotherapy with bevacizumab (Arm A) vs. first-line OPTIMOX-bevacizumab, followed by irinotecan-based second-line chemotherapy with bevacizumab, and by an anti-epidermal growth factor receptor monoclonal antibody with or without irinotecan as third-line treatment (Arm B). The primary endpoint is duration of disease control. A total of 500 patients will be randomized in a 1:1 ratio to one of the two treatment strategies. DISCUSSION: The STRATEGIC-1 trial is designed to give global information on the therapeutic sequences in patients with unresectable RAS wild-type mCRC that in turn is likely to have a significant impact on the management of this patient population. The trial is open for inclusion since August 2013. TRIAL REGISTRATION: STRATEGIC-1 is registered at Clinicaltrials.gov: NCT01910610, 23 July, 2013. STRATEGIC-1 is registered at EudraCT-No.: 2013-001928-19, 25 April, 2013

A novel hepatitis C virus (HCV) subtype from Somalia and its classification into HCV clade 3.

Hepatitis C virus (HCV) sequences from throughout the world have been grouped into six clades, based on recently proposed criteria. Here, the partial sequences and clade assignment are reported for three HCV isolates from chronic hepatitis C patients from Somalia, for whom conventional assays failed to identify the genotype. Phylogenetic analysis of the sequences of the core, envelope 1 and part of the non- structural 5b regions suggests that all three isolates belong to a distinct HCV genetic group, tentatively classified as subtype 3h. This novel HCV subtype shows the highest sequence similarity with HCV isolates from Indonesia. Despite the fact that these patients were infected with HCV clade 3, none of them responded to standard interferon treatment

Etiology, management, and outcome of the Budd-Chiari syndrome

Background: The Budd-Chiari syndrome (BCS) is hepatic venous outflow obstruction. What is known about the syndrome is based on small studies of prevalent cases. Objective: To characterize the causes and treatment of incident BCS. Design: Consecutive case series of patients with incident BCS, enrolled from October 2003 to October 2005 and followed until May 2006. Setting: Academic and nonacademic hospitals in France, Spain, Italy, Great Britain, Germany, Belgium, the Netherlands, Portugal, and Switzerland. Patients: Persons older than 16 years with definite hepatic outflow obstruction diagnosed by imaging. Persons with hepatic outflow obstruction due to heart failure, sinusoidal obstruction syndrome, cancer, or liver transplantation were excluded. Measurements: Signs and symptoms; laboratory and imaging findings; diagnosis; treatment; and overall, transplantation-free, and intervention-free survival. Results: 163 incident cases of BCS were identified. Median follow-up was 17 months (range, 0.1 to 31 months). Most patients (84%) had at least 1 thrombotic risk factor, and many (46%) had more than 1; the most common was myeloproliferative disorders (49% of 103 tested patients). Patients were mainly treated with anticoagulation (140 patients [86%]), transjugular intrahepatic portosystemic shunting (56 patients [34%]), or liver transplantation (20 patients [12%]), and 80 patients (49%) were managed noninvasively. Only 3 patients underwent surgical shunting. The survival rate was 87% (95% CI, 82% to 93%) at 1 year and 82% (CI, 75% to 88%) at 2 years. Limitation: Treatment was not standardized across all centers, and data on important clinical variables were missing for some patients. Conclusion: Most patients with BCS have at least 1 thrombotic risk factor, and many have more than 1; myeloproliferative disorders are most common. One- and 2-year survival rates are good with contemporary management, which includes noninvasive therapies (anticoagulation and diuretics) and invasive techniques. Transjugular intrahepatic portosystemic shunting seems to have replaced surgical shunting as the most common invasive therapeutic procedure. Primary Funding Source: Fifth Framework Programme of the European Commission

Tracker Operation and Performance at the Magnet Test and Cosmic Challenge

During summer 2006 a fraction of the CMS silicon strip tracker was operated in a comprehensive slice test called the Magnet Test and Cosmic Challenge (MTCC). At the MTCC, cosmic rays detected in the muon chambers were used to trigger the readout of all CMS sub-detectors in the general data acquisition system and in the presence of the 4 T magnetic field produced by the CMS superconducting solenoid. This document describes the operation of the Tracker hardware and software prior, during and after data taking. The performance of the detector as resulting from the MTCC data analysis is also presented

Performance and dynamics of active greywater heat recovery in buildings

In the effort to de-carbonize the building stock, heat pumps are increasingly utilized in Switzerland, with 70% of the fast-growing heat pump market using ambient air as heat source. Inexpensive and easy to implement, these heat pumps are, however, less efficient than their ground- or water-source counterparts. In this modeling study, we aim at increasing the efficiency of air-source heat pumps using domestic greywater-contained heat. We assess the performance improvement relative to standard heat pump configurations across various climates, seasons, building envelopes, and domestic hot water consumption patterns. The results show that the annually-averaged coefficient of performance improves by 4.1% on average – ranging from 0.6% to 7.5%. This efficiency gain translates on average to 1.8 kWh/week of compressor electricity savings. Although attractive due to its simplicity, the proposed open-loop configuration – preheating of an external heat source – only leads to moderate performance improvement of air-source heat pumps. Based on these results, we extensively discuss and compare alternative system configurations and identify several fundamental differences in the heat recovery dynamics of each configuration. We show that closed-loop systems – using greywater as direct heat source – show the largest performance improvement potential, although being more expensive and complex to implement

Tracker Operation and Performance at the Magnet Test and Cosmic Challenge

During summer 2006 a fraction of the CMS silicon strip tracker was operated in a comprehensive slice test called the Magnet Test and Cosmic Challenge (MTCC). At the MTCC, cosmic rays detected in the muon chambers were used to trigger the readout of all CMS sub-detectors in the general data acquisition system and in the presence of the 4 T magnetic field produced by the CMS superconducting solenoid. This document describes the operation of the Tracker hardware and software prior, during and after data taking. The performance of the detector as resulting from the MTCC data analysis is also presented