Progress in Targeting the TGFβ Pathway

Signaling by the transforming growth factor-β (TGF-β) superfamily is important in the regulation of hematopoiesis and is dysregulated in myelodysplastic syndromes (MDS), contributing to ineffective hematopoiesis and clinical cytopenias. TGF-β, activins and growth differentiation factors exert inhibitory effects on red cell formation by activating canonical SMAD2/3 pathway signaling. SMAD2/3 overactivation is seen in numerous subtypes of MDS. Furthermore, reduced levels of inhibitory SMAD7 are

References

• 1.Valcarcel D, Verma A, Platzbecker U, et al. Phase 2 Study of Monotherapy Galunisertib (LY2157299 Monohydrate) in Very Low-, Low-, and Intermediate-Risk Patients with Myelodysplastic Syndromes. Blood. 2015;126:1669.
• 2.Suragani RN, Cawley SM, Li R, Wallner S, et al. Modified activin receptor IIB ligand trap mitigates ineffective erythropoiesis and disease complications in murine β-thalassemia. Blood. 2014 Jun 19;123(25):3864-72.
• 3.Dussiot M, Maciel TT, Fricot A, et al. Nat Med. 2014 Apr;20(4):398-407.
• 4.

     

Health-Related Quality of Life in KEYNOTE-010: a Phase II/III Study of Pembrolizumab Versus Docetaxel in Patients With Previously Treated Advanced,Programmed Death Ligand 1–Expressing NSCLC

Introduction

In the phase II/III KEYNOTE-010 study (ClinicalTrials.gov, NCT01905657), pembrolizumab significantly prolonged overall survival over docetaxel in patients with previously treated, programmed death ligand 1–expressing (tumor proportion score ≥ 1%), advanced NSCLC. Health-related quality of life (HRQoL) results are reported here.

The Relationship Between Air Pollution and Lung Cancer in Nonsmokers in Taiwan

Introduction

For never-smokers (smoked <100 lifetime cigarettes), lung cancer (LC) has emerged as an important issue. We aimed to investigate the effects of prevalence changes in tobacco smoking and particulate matter (PM) 2.5 (PM_2.5) levels on LC in Taiwan, in relation to contrasting PM_2.5 levels, between Northern Taiwan (NT) and Southern Taiwan (ST).

Midazolam exposure in the paediatric intensive care unit predicts acute post-traumatic stress symptoms in children

BackgroundClinically significant post-traumatic stress symptoms (PTSS) have been reported in up to a quarter of paediatric intensive care unit (PICU) survivors. Ongoing PTSS negatively impacts children's psychological development and physical recovery. However, few data regarding associations between potentially modifiable PICU treatment factors, such as analgosedatives and invasive procedures, and children's PTSS have been reported.ObjectivesWe sought to investigate the medical treatment factors associated with children's PTSS after PICU discharge.MethodsA prospective longitudinal cohort study was conducted in two Australian tertiary referral PICUs. Children aged 2-16 y admitted to the PICU between June 2008 and January 2011 for >8 h and <28 d were eligible for participation. Biometric and clinical data were obtained from medical records. Parents reported their child's PTSS using the Trauma Symptom Checklist for Young Children at 1, 3, 6, and 12 months after discharge. Logistic regression was used to assess potential associations between medical treatment and PTSS.ResultsA total of 265 children and their parents participated in the study. In the 12-month period following PICU discharge, 24% of children exhibited clinically elevated PTSS. Median risk of death (Paediatric Index of Mortality 2 [PIM2]) score was significantly higher in the PTSS group (0.31 [IQR 0.14–1.09] v 0.67 [IQR 0.20–1.18]; p = 0.014). Intubation and PICU and hospital length of stay were also significantly associated with PTSS at 1 month, as were midazolam, propofol, and morphine. After controlling for gender, reason for admission, and PIM2 score, only midazolam was significantly and independently associated with PTSS and only at 1 month (adjusted odds ration (aOR) 3.63, 95% CI 1.18, 11.12, p = 0.024). No significant relationship was observed between the use of medications and PTSS after 1 month.ConclusionsElevated PTSS were evident in one quarter (24%) of children during the 12 months after PICU discharge. One month after discharge, elevated PTSS were most likely to occur in children who had received midazolam therapy.     

EARLY COPD: determinantes de la aparición y progresión de la enfermedad pulmonar obstructiva crónica en adultos jóvenes. Protocolo de un estudio caso-control con seguimiento

Introduction and objectivesDeterminants of chronic obstructive pulmonary disease (COPD) in the early stages of its natural history are not well known. Improving our knowledge of these factors will help to design interventions that can modify prognosis.Study objectives are: a) to characterize a COPD population of young adults aged 35-50 years from a multidimensional point of view; b) to compare these patients with smokers with normal lung function; and c) to create a cohort of young adults aged 35-50 years (smokers or former smokers), with and without COPD, who will be followed in the future to improve understanding of the natural history of the disease.Participants and methodThis is a case-control multicenter study aimed at establishing a well-characterized cohort of young adults, smokers or former-smokers, with and without COPD, for subsequent follow-up.A total of 311 participants (101 cases and 210 controls) were selected from approximately 30 primary care settings and 12 hospitals in 8 Spanish regions. Subjects were smokers or former smokers (> 10 pack-years) aged 35-50 years. Diagnosis of COPD was based on a post-bronchodilator result of FEV1/FVC < 70%.The main study variables were: questionnaires on health, symptoms, exacerbations and daily physical activity, lung function tests, blood and sputum samples, and low-dose computed tomography. In the statistical analysis, COPD patient characteristics will be described and compared with control subjects using a logistic regression analysis.     

How accurate is atherosclerosis imaging by coronary computed tomography angiography?

Invasive coronary plaque imaging such as intravascular ultrasound and optical coherence tomography has been widely used to observe culprit or non-culprit coronary atherosclerosis, as well as optimize stent sizing, apposition and deployment. Coronary computed tomographic angiography (CTA) is non-invasively available to assess coronary artery disease (CAD) and has become an appropriate strategy to evaluate patients with suspected CAD. Given recent technologies, semi-automated plaque software is available to identify coronary plaque stenosis, volume and characteristics and potentially allows to be used for the assessment of more details of plaque information, progression and future risk as a surrogate tool of the invasive imaging modalities. This review article aims to focus on various evidence in coronary plaque imaging by coronary CTA and describes how accurate coronary CTA can classify coronary atherosclerosis.