Impact of antiviral therapy on short- and long-term outcomes of patients with chronic obstructive pulmonary disease after influenza infection.

Background: Respiratory complications often accompany influenza in patients with chronic obstructive pulmonary disease (COPD). In this retrospective study, we quantified the impact of antiviral therapy on exacerbations, healthcare resource utilization (HRU), and costs in patients with COPD across 5 influenza seasons.

Methods: Using claims data from US MarketScan® databases, we identified patients with COPD who had an influenza diagnosis during the 2012-2016 influenza seasons.

Outcomes of antiviral treatment for influenza in type 2 diabetes.

Objectives: To evaluate the long-term effects of antiviral treatment on influenza-related health care resource utilization (HCRU) and costs in patients with type 2 diabetes (T2D) and a diagnosis of influenza.

Study Design: Retrospective cohort study.

Methods: Claims data from the IBM MarketScan Commercial Claims Database were used to identify patients with T2D and a diagnosis of influenza between October 1, 2016, and April 30, 2017.

Impact of influenza infection on the short- and long-term health of patients with chronic obstructive pulmonary disease.

Background: Influenza is a common cause of acute respiratory infection that leads to exacerbation of underlying chronic obstructive pulmonary disease (COPD). To elucidate the short- and long-term effects of influenza in patients with COPD, we examined health care resource utilization (HRU) and costs up to 13 months following influenza infection.

Methods: We conducted a retrospective cohort study using U.

Direct plasmonic detection of circulating RAS mutated DNA in colorectal cancer patients.

RAS mutations in the blood of colorectal cancer (CRC) patients are emerging as biomarkers of acquired resistance to Epidermal Growth Factor Receptor therapy. Unfortunately, reliable assays granting fast, real-time monitoring of treatment response, capable of refining retrospective, tissue-based analysis, are still needed. Recently, several methods for detecting blood RAS mutations have been proposed, generally relying on multi-step and PCR-based, time-consuming and cost-ineffective procedures.

Prospective, Single-Arm, Longitudinal Study of Biomarkers in Real-World Patients with Severe Asthma.

Background: ARIETTA was a prospective, single-arm, noninterventional, multicenter study in patients with severe asthma.

Objective: To examine the predictive and prognostic abilities of type 2 biomarkers for severe asthma outcomes.

Methods: Adult patients with severe asthma receiving daily inhaled corticosteroids (fluticasone propionate ≥500 μg or equivalent) and ≥1 second controller medication were enrolled.

Selective Functionalization with PNA of Silicon Nanowires on Silicon Oxide Substrates.

Silicon nanowire chips can function as sensors for cancer DNA detection, whereby selective functionalization of the Si sensing areas over the surrounding silicon oxide would prevent loss of analyte and thus increase the sensitivity. The thermal hydrosilylation of unsaturated carbon-carbon bonds onto H-terminated Si has been studied here to selectively functionalize the Si nanowires with a monolayer of 1,8-nonadiyne. The silicon oxide areas, however, appeared to be functionalized as well.

Attachment of a Ru Complex to a Self-Folding Hexaamide Deep Cavitand.

We report the design, synthesis and characterization of a new Ru metallocavitand that is catalytically active in alkene epoxidation reactions. The elaboration of the resorcin[4]arene's aromatic cavity produced a self-folding, deep hexaamide cavitand featuring a single diverging terpyridine (tpy) group installed at its upper rim. The construction of the metallocavitand involved the initial chelation of a Ru chloride complex by the tpy ligand followed by the incorporation of 2-(phenylazo)pyridine (azpy) as an ancillary ligand.

Revisiting Type 2-high and Type 2-low airway inflammation in asthma: current knowledge and therapeutic implications.

Asthma is a complex respiratory disorder characterized by marked heterogeneity in individual patient disease triggers and response to therapy. Several asthma phenotypes have now been identified, each defined by a unique interaction between genetic and environmental factors, including inflammatory, clinical and trigger-related phenotypes. Endotypes further describe the functional or pathophysiologic mechanisms underlying the patient's disease.

Assessing biomarkers in a real-world severe asthma study (ARIETTA).

The prognostic value of asthma biomarkers in routine clinical practice is not fully understood. ARIETTA (NCT02537691) is an ongoing, prospective, longitudinal, international, multicentre real-world study designed to assess the relationship between asthma biomarkers and disease-related health outcomes. The trial aims to enrol and follow for 52 weeks approximately 1200 severe asthma patients from approximately 160 sites in more than 20 countries.

Molecular Motion and Conformational Interconversion of Ir(I)·COD Included in Rebek's Self-Folding Octaamide Cavitand.

We report experimental and theoretical evidence of restrained axial rotation for heteroleptic L2·Ir(I)·1,5-cyclooctadiene (COD) complexes included in the aromatic cavity of Rebek's self-folding octaamide cavitand. At 298 K, the axial spinning motion of the included organometallic guests was slow on the (1)H NMR time scale and produced a proton spectrum for the bound host indicative of C2 symmetry. Signals corresponding to aromatic protons of the bound host coalesced at 323 K, indicating that the spinning process of the included guest became fast on the (1)H NMR time scale and that the complex approached C4 symmetry.

Field-scale relationships among soil properties and shallow groundwater quality.

It is important to understand the link between land surface/soil properties and shallow groundwater quality. To that end, soil properties and near-water-table groundwater chemistry of a shallow, unconfined aquifer were measured on a 100-m grid on a 64-ha irrigated field in southeastern North Dakota. Soil properties and hydrochemistry were compared via multivariate analysis that included product-moment correlations and factor analysis/principal component analysis.

Dipeptidyl peptidase IV (DPPIV/CD26) inhibition does not improve engraftment of unfractionated syngeneic or allogeneic bone marrow after nonmyeloablative conditioning.

In order to develop minimally toxic bone marrow transplantation (BMT) protocols suitable for use in a wider range of indications, it is important to identify ways to enhance BM engraftment at a given level of recipient conditioning. CXCL12/stromal cell-derived factor-1α plays a crucial physiological role in homing of hematopoietic stem cells to BM. It is regulated by the ectopeptidase dipeptidyl peptidase IV (DPPIV; DPP4) known as CD26, which cleaves dipeptides from the N-terminus of polypeptide chains.

The effect of low-dose Continuous Erythropoietin receptor activator in an experimental model of acute Cyclosporine A induced renal injury.

The use of Cyclosporine A (CsA) as rejection prophylaxis following organ transplantation is limited by its nephrotoxicity. CsA induces renal damage that is associated with tubulo-interstitial injury and parenchymal sequestration of macrophages, perpetuating pro-inflammatory processes. Furthermore, CsA exerts a diabetogenic effect by damaging pancreatic islet cell integrity.

An experimental approach toward chronic pulmonary allograft rejection: Orthotopic lung versus heterotopic tracheal segment transplantation in rats.

Background: Despite the impact of chronic rejection (CR) on long-term outcomes, clinically relevant experimental models are sparse, often including a design of subcutaneous implantation of tracheal segments. However, this latter site lacks anatomic correlation, adequate perfusion, and ventilatory function. In this study, we compared the spatial and sequential course of CR in models of orthotopic single lung transplantation (LT) versus heterotopically implanted tracheal segments in rats.

Inhibition of CD26/DPP IV attenuates ischemia/reperfusion injury in orthotopic mouse lung transplants: the pivotal role of vasoactive intestinal peptide.

The T cell activation Ag CD26/dipeptidylpeptidase IV (DPP IV) combines co-stimulatory and enzymatic properties. Catalytically, it functions as an exopeptidase, modulating biological activity of key chemokines and peptides. Here we investigated the effect of organ-specific inhibition of DPP IV catalytic activity on ischemia/reperfusion injury after extended ischemia in the mouse model of orthotopic single lung transplantation.

Increased T-bet to GATA-3 ratio during acute allograft rejection in the rat lung.

Acute allograft rejection (AR) remains a major problem in solid organ transplantation. The pivotal mechanism hinges on alloantigen recognition by recipient T helper (T(h)) cells that differentiate into T(h)1 and T(h)2. This study investigated the association of mRNA levels of the transcription factors T-box expressed in T cells and GATA-binding protein 3 with the development of T(h)1/T(h)2-directed immune responses.

A model of chronic lung allograft rejection in the rat.

Bronchiolitis obliterans, the pathological hallmark of chronic pulmonary rejection, severely impacts long-term survival following lung transplantation. However, experimental reproduction of this pathophysiological phenomenon has not been achieved with contemporary in vivo models. Here, a model of chronic rejection is described, with sensitised recipients receiving unilateral orthotopic rat lung transplants.

The effect of organ-specific CD26/DPP IV enzymatic activity inhibitor-preconditioning on acute pulmonary allograft rejection.

Background: Systemic inhibition of serum CD26/dipeptidylpeptidase (DPP IV) enzymatic activity abrogated acute rejection of pulmonary allografts, whereas organ-specific inhibition ameliorated ischemia/reperfusion injury in syngeneic transplants. Here, we analyze the effect of allograft-specific inhibitor preconditioning on acute rejection in the presence of cyclosporine-based immunosuppressive therapy.

Methods: Orthotopic left single lung transplantation (Tx) in rats (LBNF1 to LEWIS).

Distribution of macrophages and T cells in syngrafts and allografts after experimental rat lung transplantation.

Macrophages and T cells have a pivotal role in orchestrating the acute lung allograft rejection response. We investigated the spatial and temporal distribution of these immune cells and the synthesis patterns of the T(h)1- and T(h)2-cytokine IL-12 and IL-10 during the early course after transplantation (Tx). Orthotopic single-lung Tx was performed in Lewis to Lewis (syngrafts) and Brown Norway/Lewis F(1) hybrid to Lewis (allografts).

Primary graft dysfunction in lung transplantation: the role of CD26/dipeptidylpeptidase IV and vasoactive intestinal peptide.

Background: Enzymatic activity inhibition of CD26/dipeptidylpeptidase IV (CD26/DPP IV) attenuated short-term post-Tx (transplantation) ischemia-reperfusion injury after 18-hr-ischemia. Here, we investigated the effect of intragraft CD26/DPP IV catalytic inhibition on primary graft dysfunction during 7 day post-Tx, following extended ischemia.

Methods: A syngeneic rat (LEW [Lewis abstract]) orthotopic lung Tx model was used, grafts exposed to 18 hr cold ischemia before Tx.

Immunosuppressive therapy in lung transplantation: state of the art.

The coming of age of lung transplantation is accompanied by an immunosuppressive armamentarium that has been brought forward from other transplant indications. Widely employed on the basis of few small randomized studies, and mostly single-center experience or empirical expert knowledge, anti-rejection therapeutic strategies in pulmonary transplantation have hardly been rigorously evaluated in large-scale prospective international trials. This review compiles the available findings on the use of current immunosuppressants in clinical lung transplantation, accentuating high level-of-evidence study results.

A mouse model of orthotopic, single-lung transplantation.

Objectives: Progress in studying acute and chronic pulmonary allograft rejection has been hampered by the lack of feasible experimental animal transplantation models. Contemporary approaches are limited by anatomic applicability (heterotopic tracheal implantation) and lack of genetic variability (rat model). To utilize the breadth of available genetic modifications in a physiologic setup, we optimized and validated a procedure of orthotopically transplanted, perfused, and ventilated single pulmonary transplantation in mice.

Airway complications after lung transplantation: risk factors, prevention and outcome.

Purpose: Anastomotic complications following lung transplantation (LuTx) have been described in up to 15% of patients. Challenging to treat, they are associated with high morbidity and a mortality rate of 2-5%. The aim of this study was to analyze the incidence of complications in a consecutive series of bronchial anastomosis after LuTx at our center and to delineate the potential risk factors.

A multicenter, randomized, double-blind trial of everolimus versus azathioprine and placebo to maintain steroid-induced remission in patients with moderate-to-severe active Crohn's disease.

Objectives: A prospective study was undertaken to compare the efficacy of everolimus versus azathioprine or placebo in maintaining steroid-induced remission in active Crohn's disease (CD) and assess the safety and pharmacokinetics of everolimus.

Methods: This was a randomized, double-blind, placebo-controlled, proof-of-concept study in adults with moderate-to-severe active CD. The patients received oral steroids for a rapid induction of remission plus everolimus 6 mg/day, azathioprine 2.