Perioperative management and early complications after intestinal resection with ileocolonic anastomosis in Crohn’s disease: analysis from the PRACTICROHN study

This study is aimed at describing the prevalence of and risk factors associated with early post-operative complications after Crohn’s disease-related intestinal resection. Methods: This was a retrospective analysis of data from the PRACTICROHN cohort. Adult Crohn’s disease patients who underwent ileocolonic resection with ileocolonic anastomosis between January 2007 and December 2010 were included. The complications evaluated included death, ileus, anastomotic leak, abscess, wound infection, catheter-related infection, digestive bleeding and other extra-abdominal infections that occurred in the 30 days after surgery.Results: A total of 364 patients (median age at surgery 38 years and 50% men) were included. Indication for surgery was: stricturing disease (46.4%), penetrating disease (31.3%), penetrating and stricturing disease (14.0%) or resistance to medical treatment (5.8%). Early complications were recorded in 100 (27.5%) patients, with wound infection, intra-abdominal abscess and anastomotic leakage being the most frequent complications. Median hospitalization duration was 16 days for patients with complications vs. 9 days without complications (P<0.001). Complications were more common among patients with penetrating disease (36/114, 31.6%) and those refractory to treatment (9/21, 42.9%) compared with stricturing disease (45/169, 26.6%) or stricturingþpenetrating disease (6/51, 11.8%) (P¼0.040). The rate of complications was higher among patients with diagnosis made at the time of surgery (15/31, 48.4%) compared with the rest (85/331, 25.7%) (P¼0.013). Medication received at the time of surgery did not affect the rate of complications. Conclusions: Almost a quarter of patients developed early complications after intestinal resection. Penetrating disease and urgent surgery were associated with an increased risk of complicationsThis study was supported by Merck Sharp and Dohme, Spai

Late HIV Diagnosis but Earlier Antiretroviral Treatment Initiation in Northwest Spain: Impact of Current Treatment Guidelines

[Abstract] Background: Current HIV treatment guidelines recommend antiretroviral treatment (ART) initiation for all HIV-infected individuals regardless of CD4 count. This study evaluates the immunological and virological status and the clinical characteristics of patients who have started ART in the last 8 years in the Northwest of Spain. Methods: All HIV-infected patients who have started ART between January 2009 and December 2016 at a reference hospital in the Northwest of Spain were included in this retrospective observational study. Epidemiological, clinical, and immunovirological features and antiretroviral drugs used for initiation were recorded. A statistical analysis was performed using SPSS version 19 software. Categorical and continuous variables were compared by the specific statistical tests, and a logistic regression model was used to identify time associated with Center for Disease Control and Prevention (CDC) categories change. Results: A high proportion of HIV-infected patients (66.7%) had initiated ART with CD4 counts <350 cells/mm3 in the last 8 years. From these, most of them (68.3%) had <350 CD4 counts at first contact with HIV specialist medical team, 12.2% had no indications for ART initiation in the last clinic visit before ART initiation according to the national guidelines at that moment, 11.0% were lost to follow-up because of lack of compliance with scheduled visits and 8.5% of patients refused treatment. A logistic regression model showed that a delay of one month since the first contact with HIV specialist medical team to ART initiation involves a risk of worsening in the CDC clinical category (odds ratio: 1.02 [95% confidence interval: 1.012-1.029]; P < .001). A trend towards an earlier start of ART was observed during 2015 and 2016, likely influenced by the last treatment guidelines recommendations. Conclusion: High proportion of HIV-infected patients (66.7%) had initiated ART with CD4 counts <350 cells/mm3 in the last 8 years. The main reasons for this problem were analyzed and an important rate of late diagnosis was identified. However, a trend towards an earlier start of ART was observed during 2015 and 2016, likely influenced by the last treatment guidelines recommendations. These findings highlight the need to promote and facilitate HIV testing to reduce the late diagnosis as well as counseling on HIV prevention, treatment, and linkage care

Clinical experience with the integrase inhibitors Dolutegravir and Elvitegravir in HIV-infected patients: efficacy, safety and tolerance

[Abstract] Two integrase inhibitors (INSTIs), dolutegravir (DTG) and elvitegravir/cobicistat (EVG/COBI), have joined recently the pharmacotherapy arsenal against HIV. This study evaluated the efficacy and tolerability of these INSTIs in the last two years. A retrospective observational study in patients who started DTG or EVG/COBI from January 2015 to January 2017 at a reference hospital in north-western Spain was done. Epidemiological, clinical and immunovirological data were recorded. A statistical analysis was performed with SPSS software. A total of 542 DTG (n = 275)- or EVG/COBI (n = 267)-based therapies were initiated during the study period. Overall, more than 90% of naïve and pre-treated patients had virological suppression in both groups after 48 weeks of initiation of treatment per-protocol snapshot analysis. During follow-up, 10.2% of patients were treated with DTG and 4.5% of those treated with EVG discontinued due to adverse events (AE). In the case of DTG mainly related to neuropsychiatric disturbances (70.4%) and for EVG/COBI with gastrointestinal discomfort (50%). Female sex [HR 2.255 (95%CI 1.121–4.535), p = 0.023] and DTG treatment [HR 2.453 (95%CI 1.221–4.931), p = 0.012] were associated with AE discontinuations. Specifically for neuropsychiatric events, DTG treatment [HR 5.906 (95%CI 1.954–17.846), p = 0.002] and receiving abacavir/lamivudine/DTG [HR 4.380 (95%CI 1.348–14.233), p = 0.014] were identified as predictive risk factors for treatment discontinuations in two different multivariate analyses. A high percentage of AE discontinuations not previously described in clinical trials has been observed, especially with DTG. Female gender and DTG treatment were identified as risk factors for AE discontinuation. DTG-based therapies, especially in combination with abacavir/lamivudine, were associated with an increased risk of treatment discontinuation due to neuropsychiatric AE.Instituto de Salud Carlos III; CPII14/00014Instituto de Salud Carlos III; PI10/02166Instituto de Salud Carlos III; PI13/02266Instituto de Salud Carlos III; CM13/00328Instituto de Salud Carlos III; CM15/00233Instituto de Salud Carlos III; PI16/0215

Plasma mitochondrial DNA levels are inversely associated with HIV-RNA levels and directly with CD4 counts: potential role as a biomarker of HIV replication

[Abstract] Objectives. To evaluate plasma mitochondrial DNA (mtDNA) levels among HIV-infected patients and its potential role as a biomarker of residual viral replication. Methods. HIV-infected patients on follow-up at a reference hospital in north-west Spain were selected. DNA was isolated from plasma samples and mtDNA levels were assessed using a quantitative real-time PCR assay. HIV-RNA levels and CD4+ cell counts were evaluated in the same blood samples used for plasma mtDNA quantification. Epidemiological and clinical variables were included for the analysis. Results. A total of 235 HIV-infected patients were included. Mean plasma mtDNA levels were 217 ± 656 copies/μL for naive (31.9%) and 364 ± 939 copies/μL for HIV-infected patients receiving ART and with suppressed viraemia (P = 0.043). Among the latter, mean plasma mtDNA levels were 149 ± 440 copies/μL for those with low-level viraemia (LLV; HIV-RNA 20–200 copies/mL), 265 ± 723 copies/μL for those with detected-not-quantified (DNQ) viraemia (HIV-RNA <20 copies/mL) and 644 ± 1310 copies/μL for those with not-detected (ND) viraemia. Of note, a linear trend (P = 0.006) was observed among virologically suppressed (LLV, DNQ and ND) patients. ND patients had higher mtDNA levels compared with LLV patients (P = 0.057). Moreover, mtDNA levels were inversely associated with HIV-RNA levels (Spearman’s rho −0.191, P = 0.003) and directly associated with CD4+ counts (Spearman’s rho 0.131, P = 0.046). Conclusions. Increased plasma mtDNA levels are associated with lower HIV-RNA levels and higher CD4+ cell counts. Among ART-suppressed patients, mtDNA levels were significantly higher in those with complete virological suppression (ND) than in those with LLV. These data suggest that plasma mtDNA levels might serve as a biomarker of residual HIV replication.Instituto de Salud Carlos III; CPII14/00014Instituto de Salud Carlos III; PI10/02166Instituto de Salud Carlos III; PI13/02266Instituto de Salud Carlos III; FI14/00557Instituto de Salud Carlos III; CM15/00233Instituto de Salud Carlos III; PI16/02159Instituto de Salud Carlos III; MV16/02159Instituto de Salud Carlos III; PTA2013-8277-

Management and outcomes of patients with Crohn’s disease with first vs multiple surgeries: results from the PRACTICROHN study

Background: Surgery in Crohn’s disease (CD) may be associated with poor prognosis and clinical and surgical recurrence. The aim of this study was to describe and compare the post-operative management and outcomes of patients with CD who underwent first vs recurrent surgeries. Methods: Observational study that included adult CD patients from 26 Spanish hospitals who underwent ileocolonic resection with ileocolonic anastomosis between January 2007 and December 2010. Data were retrospectively collected from the medical records. Results: Data from 314 patients were analysed, of whom 262 (83%) underwent first surgery and 52 (17%) referred to previous CD surgeries. Baseline characteristics were similar between the two groups except for a higher rate of stricturing behavior at diagnosis among re-operated patients (P¼0.03). After surgery, a higher proportion of re-operated patients received prophylactic treatment with immunomodulators compared with patients with first surgery (P¼0.04). In re-operated patients, time to clinical recurrence was not associated with the fact of receiving or not prophylaxis, whereas, in patients with first surgery, recurrence-free survival was greater when prophylaxis was received (P¼0.03). Conclusions: After surgery, a higher proportion of patients with previous surgeries received prophylactic treatment with immunomodulators compared with patients with first surgery. Although prophylactic treatment was beneficial for preventing clinical recurrence in patients operated on for the first time, it did not significantly reduce the risk of further recurrence in patients with previous surgeries. This suggests that effective prophylactic therapies are still needed in this subset of patientsThis study was funded by Merck Sharp & Dohme of Spain, a subsidiary of Merck & Co., Inc., Kenilworth, New Jersey, US

Late HIV Diagnosis but Earlier Antiretroviral Treatment Initiation in Northwest Spain: Impact of Current Treatment Guidelines.

BACKGROUND: Current HIV treatment guidelines recommend antiretroviral treatment (ART) initiation for all HIV-infected individuals regardless of CD4 count. This study evaluates the immunological and virological status and the clinical characteristics of patients who have started ART in the last 8 years in the Northwest of Spain. METHODS: All HIV-infected patients who have started ART between January 2009 and December 2016 at a reference hospital in the Northwest of Spain were included in this retrospective observational study. Epidemiological, clinical, and immunovirological features and antiretroviral drugs used for initiation were recorded. A statistical analysis was performed using SPSS version 19 software. Categorical and continuous variables were compared by the specific statistical tests, and a logistic regression model was used to identify time associated with Center for Disease Control and Prevention (CDC) categories change. RESULTS: A high proportion of HIV-infected patients (66.7%) had initiated ART with CD4 counts <350 cells/mm(3) in the last 8 years. From these, most of them (68.3%) had <350 CD4 counts at first contact with HIV specialist medical team, 12.2% had no indications for ART initiation in the last clinic visit before ART initiation according to the national guidelines at that moment, 11.0% were lost to follow-up because of lack of compliance with scheduled visits and 8.5% of patients refused treatment. A logistic regression model showed that a delay of one month since the first contact with HIV specialist medical team to ART initiation involves a risk of worsening in the CDC clinical category (odds ratio: 1.02 [95% confidence interval: 1.012-1.029]; P < .001). A trend towards an earlier start of ART was observed during 2015 and 2016, likely influenced by the last treatment guidelines recommendations. CONCLUSION: High proportion of HIV-infected patients (66.7%) had initiated ART with CD4 counts <350 cells/mm(3) in the last 8 years. The main reasons for this problem were analyzed and an important rate of late diagnosis was identified. However, a trend towards an earlier start of ART was observed during 2015 and 2016, likely influenced by the last treatment guidelines recommendations. These findings highlight the need to promote and facilitate HIV testing to reduce the late diagnosis as well as counseling on HIV prevention, treatment, and linkage care

Measurement of the cross-section and charge asymmetry of WW bosons produced in proton-proton collisions at s=8\sqrt{s}=8 TeV with the ATLAS detector

This paper presents measurements of the $W^+ \rightarrow \mu^+\nu$ and $W^- \rightarrow \mu^-\nu$ cross-sections and the associated charge asymmetry as a function of the absolute pseudorapidity of the decay muon. The data were collected in proton--proton collisions at a centre-of-mass energy of 8 TeV with the ATLAS experiment at the LHC and correspond to a total integrated luminosity of 20.2~\mbox{fb^{-1}}. The precision of the cross-section measurements varies between 0.8% to 1.5% as a function of the pseudorapidity, excluding the 1.9% uncertainty on the integrated luminosity. The charge asymmetry is measured with an uncertainty between 0.002 and 0.003. The results are compared with predictions based on next-to-next-to-leading-order calculations with various parton distribution functions and have the sensitivity to discriminate between them.Comment: 38 pages in total, author list starting page 22, 5 figures, 4 tables, submitted to EPJC. All figures including auxiliary figures are available at https://atlas.web.cern.ch/Atlas/GROUPS/PHYSICS/PAPERS/STDM-2017-13

Measurement of the production of a W boson in association with a charm quark in pp collisions at √s = 7 TeV with the ATLAS detector

The production of a W boson in association with a single charm quark is studied using 4.6 fb−1 of pp collision data at s√ = 7 TeV collected with the ATLAS detector at the Large Hadron Collider. In events in which a W boson decays to an electron or muon, the charm quark is tagged either by its semileptonic decay to a muon or by the presence of a charmed meson. The integrated and differential cross sections as a function of the pseudorapidity of the lepton from the W-boson decay are measured. Results are compared to the predictions of next-to-leading-order QCD calculations obtained from various parton distribution function parameterisations. The ratio of the strange-to-down sea-quark distributions is determined to be 0.96+0.26−0.30 at Q 2 = 1.9 GeV2, which supports the hypothesis of an SU(3)-symmetric composition of the light-quark sea. Additionally, the cross-section ratio σ(W + +c¯¯)/σ(W − + c) is compared to the predictions obtained using parton distribution function parameterisations with different assumptions about the s−s¯¯¯ quark asymmetry

Measurements of fiducial and differential cross sections for Higgs boson production in the diphoton decay channel at s√=8 TeV with ATLAS

Measurements of fiducial and differential cross sections are presented for Higgs boson production in proton-proton collisions at a centre-of-mass energy of s√=8 TeV. The analysis is performed in the H → γγ decay channel using 20.3 fb−1 of data recorded by the ATLAS experiment at the CERN Large Hadron Collider. The signal is extracted using a fit to the diphoton invariant mass spectrum assuming that the width of the resonance is much smaller than the experimental resolution. The signal yields are corrected for the effects of detector inefficiency and resolution. The pp → H → γγ fiducial cross section is measured to be 43.2 ±9.4(stat.) − 2.9 + 3.2 (syst.) ±1.2(lumi)fb for a Higgs boson of mass 125.4GeV decaying to two isolated photons that have transverse momentum greater than 35% and 25% of the diphoton invariant mass and each with absolute pseudorapidity less than 2.37. Four additional fiducial cross sections and two cross-section limits are presented in phase space regions that test the theoretical modelling of different Higgs boson production mechanisms, or are sensitive to physics beyond the Standard Model. Differential cross sections are also presented, as a function of variables related to the diphoton kinematics and the jet activity produced in the Higgs boson events. The observed spectra are statistically limited but broadly in line with the theoretical expectations

Search for squarks and gluinos in events with isolated leptons, jets and missing transverse momentum at s√=8 TeV with the ATLAS detector

The results of a search for supersymmetry in final states containing at least one isolated lepton (electron or muon), jets and large missing transverse momentum with the ATLAS detector at the Large Hadron Collider are reported. The search is based on proton-proton collision data at a centre-of-mass energy s√=8 TeV collected in 2012, corresponding to an integrated luminosity of 20 fb−1. No significant excess above the Standard Model expectation is observed. Limits are set on supersymmetric particle masses for various supersymmetric models. Depending on the model, the search excludes gluino masses up to 1.32 TeV and squark masses up to 840 GeV. Limits are also set on the parameters of a minimal universal extra dimension model, excluding a compactification radius of 1/R c = 950 GeV for a cut-off scale times radius (ΛR c) of approximately 30