Phase Ib trial of inhaled iloprost for the prevention of lung cancer with predictive and response biomarker assessment.

Introduction: Iloprost, a prostacyclin analog, has lung cancerpreventive activity in preclinical models and improved dysplasia in former smokers in a phase IIb trial. Oral iloprost is currently unavailable. We performed a phase Ib trial of inhaled iloprost in former smokers to assess tolerance and compliance. Methods: Participants self-administered nebulized iloprost (5ug) or placebo four (QID) or two (BID) times daily. As QID dose was well tolerated and due to expiration of the placebo, the BID dosing and placebo were eliminated early on in the trial. Bronchoscopy with biopsyat six standard sites was performed at treatment initiation and two months post-iloprost, with exploratory histological analysis. Bulk RNA sequencing, single cell RNA sequencing and an in vitro assay of epithelial progenitor cell iloprost response were performed on a subset of biopsies in an exploratory investigation of response mechanisms and predictive biomarkers. Results and discussion: Thirty-four of a planned 48 participants were recruited to the trial.Inhaled iloprost was well tolerated with no adverse events > grade 2. Compliance was 67% in the QID group. The trial was not powered to detect histologic response and none was found. Bulk RNA sequencing of biopsies pre/post iloprost suggest that iloprost is immunomodulatory and downregulates cell proliferation pathways. Single cell RNA sequencing showed an increase in CD8-positive T cells with upregulation of genes in interferon γ signaling. In vitro iloprost response by epithelial progenitor cells correlated with histologic response with kappa coefficient of 0.81 (95% CI 0.47, 1.0). Inhaled iloprost was well tolerated with suboptimal compliance. Molecular analysis suggested that iloprosthas immunomodulatory and antiproliferative effects.The progenitor cell iloprost response assay may be a promising avenue to develop predictive biomarkers. Clinical trial registration: https://clinicaltrials.gov/study/NCT02237183, identifier NCT02237183.

Assessment of myocardial function in late preterm and term infants with transient tachypnea of the newborn using tissue Doppler imaging - a pilot observational study.

The aim of this study was to compare conventional and tissue Doppler echocardiography parameters between transient tachypnea of the newborn (TTN) and healthy control infants. This cross sectional pilot observational study was conducted in a level 3 neonatal care unit of India. Consecutively born late preterm and term infants (LPTI) with TTN were eligible for enrollment. Control group was selected from healthy LPTI. Conventional and tissue Doppler (myocardial velocities, myocardial performance index (MPI)) echocardiography was done within first 12 h (D1) and 48-72 h (D3) of life. Conventional echocardiography parameters were fractional shortening (FS), ejection fraction (EF), ventricular output, E/A ratio, fractional area change (FAC), tricuspid annular plane systolic excursion (TAPSE), pulmonary artery systolic pressure (PASP), and pulmonary artery acceleration to ejection time ratio (PATET). Baseline characteristics and echocardiography images were compared between TTN and control groups. Out of 60 infants enrolled, 34 from TTN and 20 from control group were finally analyzed. Mean (SD) gestational age and birth weight of the study population was 366/7(1.8) weeks and 2398(376) g respectively. Left ventricular (LV) parameters were similar between both groups. On D1, right ventricular (RV)e' was smaller (6.42(1) cm/s vs. 7.68(1.68) cm/s, p 0.022), and E/e' (7.79(1.51) vs. 6.08(2.59), p 0.037) was larger in TTN group, indicating RV diastolic dysfunction. RV MPI (0.61(0.11) vs. 0.44(0.12), p < 0.001) was also larger, signifying RV global myocardial dysfunction. Similar findings were observed on D3. PATET was lower in TTN group on both D1 (0.34 (0.05) vs. 0.42 (0.05), p < 0.001) and D3 (0.38 (0.05) vs. 0.43 (0.02), p 0.004) suggesting persistently raised pulmonary arterial pressure, although only 2 infants developed pulmonary hypertension identified by standard echocardiography.   Conclusion: Myocardial tissue Doppler imaging of TTN infants revealed occult right ventricular diastolic dysfunction secondary to persistently raised pulmonary arterial pressure. What is Known: •Transient tachypnea of the newborn may be associated with pulmonary arterial hypertension. What is New: •Tissue Doppler imaging in infants with transient tachypnea of the newborn revealed occult right ventricular diastolic dysfunction secondary to raised pulmonary arterial pressure, not detected by standard echocardiography.

Efficacy and Toxicity Assessment of Different Antibody Based Antiangiogenic Drugs by Computational Docking Method.

Bevacizumab and trastuzumab are two antibody based antiangiogenic drugs that are in clinical practice for the treatment of different cancers. Presently applications of these drugs are based on the empirical choice of clinical experts that follow towards population based clinical trials and, hence, their molecular efficacies in terms of quantitative estimates are not being explored. Moreover, different clinical trials with these drugs showed different toxicity symptoms in patients. Here, using molecular docking study, we made an attempt to reveal the molecular rationale regarding their efficacy and off-target toxicity. Though our study reinforces their antiangiogenic potentiality and, among the two, trastuzumab has much higher efficacy; however, this study also reveals that compared to bevacizumab, trastuzumab has higher toxicity effect, specially on the cardiovascular system. This study also reveals the molecular rationale of ocular dysfunction by antiangiogenic drugs. The molecular rationale of toxicity as revealed in this study may help in the judicious choice as well as therapeutic scheduling of these drugs in different cancers.

Adolescents speak: why do we smoke?

OBJECTIVES: To assess the role of different factors that are associated with initiation and continuation of adolescent smoking. MATERIALS AND METHODS: A total of 2535 students (1465 males and 1070 females) between the age groups of 14 and 19 years were selected from four schools and two colleges of the city by two-stage cluster sampling design for this cross-sectional study. RESULTS: The prevalence of cigarette smoking was 21.58%. Smoking was found to be considerably influenced with having seen best friend, father, sibling and favorite movie star smoke and also with receiving pocket money. CONCLUSION: Experimentation of substance use, motivated by family members, peer groups and the surrounding environment is common among adolescents and starts early in life. Therefore, it is necessary to come up with health promotion programs directed toward students which encourage attitude shaping among them toward self-confidence and healthy life style.