What if HIV were unable to develop resistance against a new therapeutic agent?

Background

The HIV integrase inhibitor, Dolutegravir (DTG), was recently approved by the Food and Drug Administration in the United States and is the only HIV drug that has not selected for resistance mutations in the clinic when used as part of first-line therapy. This has led to speculation that DTG might have a higher genetic barrier for the development of drug resistance than the other compounds that are used in therapy.

Discussion

In this Opinion article, we speculate that this is due to greatly diminished replication capacity on the part of viruses that might become resistant to DTG when the drug is used in initial therapy and that DTG might be able to be used in HIV prevention and eradication strategies. We also note that no compensatory mutation that might restore viral replication fitness to HIV in the aftermath of the appearance of a single drug resistance mutation has yet to be observed.

Summary

DTG is a valuable addition to the anti-HIV armamentarium of drugs and its long-term utility may potentially exceed its obvious use in treatment of HIV disease.

     

Predicting survival in newly diagnosed idiopathic pulmonary fibrosis: a 3-year prospective study

The natural history of idiopathic pulmonary fibrosis (IPF) is not well defined and its clinical course is variable. We sought to investigate the survival and incidence of acute exacerbations (AEs) and their significant predictors in newly diagnosed patients. 70 patients newly diagnosed with IPF were prospectively followed for at least 3 yrs. Baseline evaluation included Medical Research Council dyspnoea score (MRCDS), 6-min walk test, pulmonary function tests, all of which were repeated at 6 months, and high-resolution computed tomography. A retrospective cohort of 68 patients was used for confirmation. Mean survival from the time of diagnosis was 30 months, with a 3-yr mortality of 46%. A Risk stratificatiOn ScorE (ROSE) based on MRCDS > 3, 6-min walking distance ≤ 72% predicted and composite physiologic index > 41 predicted 3-yr mortality with high specificity. 6-month progression of ROSE predicted rapid progression. 3-yr incidence of AE was 18.6%, mostly occurring in the first 18 months; risk factors for AE were concomitant emphysema and low diffusing coefficient of the lung for carbon monoxide. Results were confirmed in an independent cohort of patients. In newly diagnosed IPF, advanced disease at presentation, rapid progression and AEs are the determinants of 3-yr survival. The purpose of the multifactorial ROSE is to risk-stratify patients in order to predict survival and detect rapid disease progression.     

Ruthenium on phosphorous-modified alumina as an effective and stable catalyst for catalytic transfer hydrogenation of furfural

Supported ruthenium was used in the liquid phase catalytic transfer hydrogenation of furfural. To improve the stability of Ru against leaching, phosphorous was introduced on a Ru/Al₂O₃ based catalyst upon impregnation with ammonium hypophosphite followed by either reduction or calcination to study the effect of phosphorous on the physico-chemical properties of the active phase. Characterization using X-ray diffraction, solid state ³¹P nuclear magnetic resonance spectroscopy, X-ray absorption spectroscopy, temperature programmed reduction with H₂, infrared spectroscopy of pyridine adsorption from the liquid phase and transmission electron microscopy indicated that phosphorous induces a high dispersion of Ru, promotes Ru reducibility and is responsible for the formation of acid species of Brønsted character. As a result, the phosphorous-based catalyst obtained after reduction was more active for catalytic transfer hydrogenation of furfural and more stable against Ru leaching under these conditions than a benchmark Ru catalyst supported on activated carbon.

Phosphorous induces structural changes in Ru/Al₂O₃ that make it more active and more stable for liquid phase hydrogenation of furfural.     

Routine single-port sleeve gastrectomy: a study of 60 consecutive patients

BackgroundSingle-port surgery has been developed for many digestive procedures, such as cholecystectomy and colectomy. Our objective was to present our preliminary results for laparoscopic single-port sleeve gastrectomy (SPSG), performed in our department for the treatment of morbid obesity, at Antoine Beclere Hospital and Paris XI University.MethodsFrom July 2010 to February 2011, all patients evaluated by our multidisciplinary team for morbid obesity and eligible for sleeve gastrectomy underwent SPSG. The data were collected prospectively.ResultsSixty consecutive patients underwent SPSG. The median age was 40.1 years; 6 patients were men and 48 were white. The median body mass index was 46.5 kg/m². The co-morbidities included diabetes in 12, essential hypertension in 31, sleep apnea in 39, dyslipidemia in 33, and coronary artery disease in 9. Of the 60 patients, 9 had previously undergone laparotomy and 5 had undergone bariatric surgery. The median operating time was 86 minutes. All procedures were achieved laparoscopically, with 10 patients requiring a second trocar and 3 patients 2 additional trocars. No conversion to open surgery was required. One leak was reported, and 1 patient experienced cubital nerve compression. The median hospital stay was 4 days. During a median follow-up of 8 months, most preoperative co-morbidities resolved, and the Bariatric Analysis and Reporting Outcome System score for care efficacy was 6.8 of 9.ConclusionSPSG is feasible in routine bariatric surgery. The results for weight loss and co-morbidity resolution seem to be equivalent to those with “multiple port” laparoscopy. New instruments and specific training are required. We believe that this technique is a natural evolution of minimally invasive surgery requiring additional investigation in prospective studies.     

Évaluation gnoso-praxique linguale des enfants de 4 ans et demi à 9 ans et demi

The study of lingual gnosis and praxis skills of children aged from 4.5 years old to 9.5 years old has been realized on normal children and on children under speech therapy for speech and language disorder. The comparison of normal children between our research and the one of Tardieu shows that today's children aged between 6.5 and 9.5 years have lower gnostic skills than in 1973. We observe a lingual gnostic deficit for children of all ages receiving speech therapy, the gap tending to fade as they get older. It seems appropriate to integrate a speech-language assessment test to better understand the gnostic deficit of children with a verbal orality and/or eating disorder. Such information would help to define the therapeutic approach of the speech therapy and thus promote the education gnoso-oral praxis early.     

Urokinase-type plasminogen activator and plasminogen activator inhibitor type-1 mRNA assessment in breast cancer by means of NASBA: correlation with protein expression

Urokinase plasminogen activator (uPA) and its main inhibitor, plasminogen activator inhibitor type-1 (PAI-1) determined in tumor tissue by means of enzyme-linked immunosorbent assay (ELISA) can discriminate patients with primary breast cancer at high risk vs low risk for recurrence. The aim of this study was to analyze uPA and PAI-1 messenger RNA (mRNA) expression by means of quantitative nucleic acid sequence-based amplification (NASBA) on 77 primary breast tumor samples and to correlate this expression with the uPA and PAI-1 protein content. We observed that the 2 markers were significantly overexpressed (uPA, P < .0001; PAI-1, P = .0042) in mRNA in the ELISA+ group. The receiver operating characteristic (ROC) curves demonstrated high concordance between NASBA and ELISA (area under the ROC curve of 0.84 and 0.70 for uPA and PAI-1, respectively) and showed that uPA and PAI-1 status could be predicted by using the molecular assay with sensitivity and specificity values of 80.8% and 82.4% and sensitivity and specificity values of 66.7% and 74.0%, respectively.