Pre-transplant CD69+ extracellular vesicles are negatively correlated with active ATLG serum levels and associate with the onset of GVHD in allogeneic HSCT patients

Graft versus host disease (GVHD) is a major complication of allogeneic hematopoietic stem cell transplantation (HSCT). Rabbit anti-T lymphocyte globulin (ATLG) in addition to calcineurin inhibitors and antimetabolites is a suitable strategy to prevent GVHD in several transplant settings. Randomized studies already demonstrated its efficacy in terms of GVHD prevention, although the effect on relapse remains the major concern for a wider use. Tailoring of ATLG dose on host characteristics is expected to minimize its side effects (immunological reconstitution, relapse, and infections). Here, day -6 to day +15 pharmacokinetics of active ATLG serum level was first assayed in an explorative cohort of 23 patients by testing the ability of the polyclonal serum to bind antigens on human leukocytes. Significantly lower levels of serum active ATLG were found in the patients who developed GVHD (ATLG_AUC(CD45): 241.52 +/- 152.16 vs. 766.63 +/- 283.52 (mu g*day)/ml, p = 1.46e(-5)). Consistent results were obtained when the ATLG binding capacity was assessed on CD3+ and CD3+/CD4+ T lymphocytes (ATLG_AUC(CD3): 335.83 +/- 208.15 vs. 903.54 +/- 378.78 (mu g*day)/ml, p = 1.92e(-4); ATLG_AUC(CD4): 317.75 +/- 170.70 vs. 910.54 +/- 353.35 (mu g*day)/ml, p = 3.78e(-5). Concomitantly, at pre-infusion time points, increased concentrations of CD69+ extracellular vesicles (EVs) were found in patients who developed GVHD (mean fold 9.01 +/- 1.33; p = 2.12e(-5)). Consistent results were obtained in a validation cohort of 12 additional ATLG-treated HSCT patients. Serum CD69+ EVs were mainly represented in the nano (i.e. 100 nm in diameter) EV compartment and expressed the leukocyte marker CD45, the EV markers CD9 and CD63, and CD103, a marker of tissue-resident memory T cells. The latter are expected to set up a host pro-inflammatory cell compartment that can survive in the recipient for years after conditioning regimen and contribute to GVHD pathogenesis. In summary, high levels of CD69+ EVs are significantly correlated with an increased risk of GVHD, and they may be proposed as a tool to tailor ATLG dose for personalized GVHD prevention

Kinetics of cytomegalovirus and Epstein-Barr virus DNA in whole blood and plasma of kidney transplant recipients: Implications on management strategies

This retrospective multicenter cohort study investigated the kinetics (ascending and descending phases) of cytomegalovirus (CMV) and Epstein-Barr virus (EBV)-DNA in whole blood (WB) and plasma samples collected from adult kidney transplant (KT) recipients. CMV-DNA kinetics according to antiviral therapy were investigated. Three hundred twenty-eight paired samples from 42 episodes of CMV infection and 157 paired samples from 26 episodes of EBV infection were analyzed by a single commercial molecular method approved by regulatory agencies for both matrices. CMV-DNAemia followed different kinetics in WB and plasma. In the descending phase of infection, a slower decay of viral load and a higher percentage of CMV-DNA positive samples were observed in plasma versus WB. In the 72.4% of patients receiving antiviral therapy, monitoring with plasma CMV-DNAemia versus WB CMV-DNAemia could delay treatment interruption by 7-14 days. Discontinuation of therapy based on WB monitoring did not result in relapsed infection in any patients. Highly different EBV-DNA kinetics in WB and plasma were observed due to lower positivity in plasma; EBV positive samples with a quantitative result in both blood compartments were observed in only 11.5% of cases. Our results emphasize the potential role of WB as specimen type for post-KT surveillance of both infections for disease prevention and management

Clinical characteristics of very old patients hospitalized in internal medicine wards for heart failure: a sub-analysis of the FADOI-CONFINE Study Group

The incidence and prevalence of chronic heart failure are increasing worldwide, as is the number of very old patients (>85 years) affected by this disease. The aim of this sub-analysis of the multicenter, observational CONFINE study was to detect clinical and therapeutic peculiarities in patients with chronic heart failure aged >85 years. We recruited patients admitted with a diagnosis of chronic heart failure and present in the hospital in five index days, in 91 Units of Internal Medicine. The patients' clinical characteristics, functional and cognitive status, and the management of the heart failure were analyzed. A total of 1444 subjects were evaluated, of whom 329 (23.1%) were over 85 years old. Signs and symptoms of chronic heart failure were more common in very old patients, as were severe renal insufficiency, anemia, disability and cognitive impairment. The present survey found important age-related differences (concomitant diseases, cognitive status) among patients with chronic heart failure, as well as different therapeutic strategies and clinical outcome for patients over 85 years old. Since these patients are usually excluded from clinical trials and their management remains empirical, specific studies focused on the treatment of very old patients with chronic heart failure are needed

Complexity of patients with chronic obstructive pulmonary disease hospitalized in internal medicine: a survey by FADOI

Chronic obstructive pulmonary disease (COPD) is one of the most frequent pathologies among patients hospitalized in Internal Medicine (IM) Departments. COPD is frequently associated with concomitant diseases, which represent major causes of death, and affect disease management. Objectives of our study are to assess the prevalence of COPD patients in IM, to evaluate their comorbidity status, and to describe their complexity, by means of the validated multidimensional prognostic index (MPI) score. COMPLEXICO is an observational, prospective, multicenter study, enrolling consecutive patients hospitalized for any cause in IM, with diagnosis of COPD documented by spirometry. A total of 1002 patients in 43 IM Units in Italy were enrolled. The prevalence of COPD in IM was found to be 18.1%, and 72.8% of patients had at least three chronic diseases other than COPD. The mean MPI was 0.43±0.15, and according to a stratification algorithm 31.8% of patients were classified as having low-risk, 58.9% moderate-risk and 9.3% severe-risk of adverse outcome. More than two-thirds of COPD patients in our study present moderate to severe risk of poor outcome according to the MPI stratification

SIAMOC position paper on gait analysis in clinical practice: General requirements, methods and appropriateness. Results of an Italian consensus conference

Gait analysis is recognized as a useful assessment tool in the field of human movement research. However, doubts remain on its real effectiveness as a clinical tool, i.e. on its capability to change the diagnostic-therapeutic practice. In particular, the conditions in which evidence of a favorable cost-benefit ratio is found and the methodology for properly conducting and interpreting the exam are not identified clearly. To provide guidelines for the use of Gait Analysis in the context of rehabilitation medicine, SIAMOC (the Italian Society of Clinical Movement Analysis) promoted a National Consensus Conference which was held in Bologna on September 14th, 2013. The resulting recommendations were the result of a three-stage process entailing i) the preparation of working documents on specific open issues, ii) the holding of the consensus meeting, and iii) the drafting of consensus statements by an external Jury. The statements were formulated based on scientific evidence or experts' opinion, when the quality/quantity of the relevant literature was deemed insufficient. The aim of this work is to disseminate the consensus statements. These are divided into 13 questions grouped in three areas of interest: 1) General requirements and management, 2) Methodological and instrumental issues, and 3) Scientific evidence and clinical appropriateness. SIAMOC hopes that this document will contribute to improve clinical practice and help promoting further research in the field

Differential cross section measurements for the production of a W boson in association with jets in proton–proton collisions at √s = 7 TeV

Measurements are reported of differential cross sections for the production of a W boson, which decays into a muon and a neutrino, in association with jets, as a function of several variables, including the transverse momenta (pT) and pseudorapidities of the four leading jets, the scalar sum of jet transverse momenta (HT), and the difference in azimuthal angle between the directions of each jet and the muon. The data sample of pp collisions at a centre-of-mass energy of 7 TeV was collected with the CMS detector at the LHC and corresponds to an integrated luminosity of 5.0 fb[superscript −1]. The measured cross sections are compared to predictions from Monte Carlo generators, MadGraph + pythia and sherpa, and to next-to-leading-order calculations from BlackHat + sherpa. The differential cross sections are found to be in agreement with the predictions, apart from the pT distributions of the leading jets at high pT values, the distributions of the HT at high-HT and low jet multiplicity, and the distribution of the difference in azimuthal angle between the leading jet and the muon at low values.United States. Dept. of EnergyNational Science Foundation (U.S.)Alfred P. Sloan Foundatio

Penilaian Kinerja Keuangan Koperasi di Kabupaten Pelalawan

This paper describe development and financial performance of cooperative in District Pelalawan among 2007 - 2008. Studies on primary and secondary cooperative in 12 sub-districts. Method in this stady use performance measuring of productivity, efficiency, growth, liquidity, and solvability of cooperative. Productivity of cooperative in Pelalawan was highly but efficiency still low. Profit and income were highly, even liquidity of cooperative very high, and solvability was good

Optimasi Portofolio Resiko Menggunakan Model Markowitz MVO Dikaitkan dengan Keterbatasan Manusia dalam Memprediksi Masa Depan dalam Perspektif Al-Qur`an

Risk portfolio on modern finance has become increasingly technical, requiring the use of sophisticated mathematical tools in both research and practice. Since companies cannot insure themselves completely against risk, as human incompetence in predicting the future precisely that written in Al-Quran surah Luqman verse 34, they have to manage it to yield an optimal portfolio. The objective here is to minimize the variance among all portfolios, or alternatively, to maximize expected return among all portfolios that has at least a certain expected return. Furthermore, this study focuses on optimizing risk portfolio so called Markowitz MVO (Mean-Variance Optimization). Some theoretical frameworks for analysis are arithmetic mean, geometric mean, variance, covariance, linear programming, and quadratic programming. Moreover, finding a minimum variance portfolio produces a convex quadratic programming, that is minimizing the objective function ðð¥with constraintsð ð 𥠥 ðandð´ð¥ = ð. The outcome of this research is the solution of optimal risk portofolio in some investments that could be finished smoothly using MATLAB R2007b software together with its graphic analysis