4th World Congress on Rare Diseases and Orphan Drugs June 11-12, 2018 Dublin, Ireland

Pulmonary arterial hypertension (PAH) and idiopathic pulmonary fibrosis (IPF) are two progressive, debilitating, and fatal lung diseases. Both diseases are limited in treatment options and have no cure. Pulmonary hypertension, inflammation, and structural remodeling, all with varying degrees of severity, are the most common and significant underlying pathophysiologic factors associated with these conditions. Although the pathogenesis is not clearly understood, increased levels of inflammatory cytokines, including growth factors and dysfunctional endothelial vasoactive mediators (e.g., serotonin, 5-HT; endothelin, ET; nitric oxide, NO; and prostacyclin, PGI2), are found in the lungs of PAH and IPF patients. The 5-HT receptor signaling pathway appears to play a central role in the pathobiology of both conditions. RP5063, a new chemical entity, is a potent modulator of 5-HT signaling that involves specifically the 5-HT2A/2B/7 receptors within the lung. The signal transduction pathways involving these 5-HT receptors mediate significant underlying pathophysiology (vasoconstriction, and vascular/alveolar inflammation, fibrosis, and proliferation) for PAH and IPF. RP5063 has demonstrated proof of concept in translational animal models that emulate IPF and PAH in humans. The U.S. FDA has granted an Orphan Drug Designation to RP5063 for the treatment of PAH and IPF, in which clinical phase 2 studies are planned to start soon. This presentation will briefly review approved therapies and unmet medical needs for PAH and IPF. It will segue to the current understanding of 5-HT receptor signaling pathways in the pathobiology of these two diseases, and will then discuss RP5063 pharmacology and preclinical efficacy for PAH and IPF. It will close by delineating the clinical pharmacokinetic/ pharmacodynamic and safety profiles of this compound

Gianluca Colella is specialized works in Orthopaedics and Traumatology at University Federico II – Napoli, Fellow at Spine Surgery Division - Istituto Ortopedico Rizzoli.He has done his Master Degree in Medicine and Surgery at University Federico II Naples, with a discussion “Trattamento chirurgico e tecniche ricostruttive dei tumori del femore prossimale: limb salvage surgery", and also Abilitation to Medical and Surgical Profession. . He is also responsible for a specialized clinic dedicated to the study and treatment of severe spinal deformities associated with rare diseases at the Rizzoli Orthopedic Institute

Background: Kyphoscoliosis is the most common and rapidly  evolving spinal deformity in rare syndromes. Early Onset and  Congenital deformities, often associated with a lot of malformation, are difficult to manage. The aim of the study is to describe an approach to spinal deformities in rare syndromes and assess the effectiveness of growing systems.

Methods: We report 11 cases of pediatric patients with scoliosis (7 males, 4 females) : 2 NF1, 2 arthrogryposis, 1 Spondylo-rib dysplasia, 1 trisomy 8, 1 syringomyelia, 1 Arnold Chiari type I, 1 Prader Willi, 1 Kabuki syndrome, 1 Escobar. This is a retrospective study from 2006 to 2011. The inclusion criteria were 1) EOS or congenital scoliosis in rare disease, 2) Growing rod system, 3) followup 24 months (12-36) . Surgery was performed using VEPTR in 4 patients (Mean age 1st visit: 3 yy (1-7) at surgery: 5 yy (3-9), GROWING ROD in 7 patient (Mean age 1st visit: 6 yy (3-10) at surgery: 9 yy (5-12)

 

Results: The patients were clinically and radiologically reviewed at a mean follow-up of 11 months. We made 11 first surgery and 15 lengthening procedures. The thoracic curve correction was of 50% ( from 65° to 39°). Children are grown on average of 2,5 cm/ each follow up year, results so similar to the phisiological growth. We had 8 postoperative mechanical complications on 26 surgeries: 4 screws loosening, 3 broken rods, 1 rib-hook loosening; 6 cases were treated during the planned lenghthening and 2 with revision

surgery not originally planned.

 

Deputy Chairman, Intensive Care Department, Consultant, Pulmonary and Critical Care Medicine, Professor, King Saud Bin Abdulaziz University for Health Sciences,Riyadh, Kingdom of Saudi Arabia, Dr. AlDawood graduate from College of Medicine in Kingdom of Saudi Arabia. Then he completed the Residency in Internal Medicine Program in McMaster University in Canada He obtained Critical Care and Respirology Fellowship Program in McMaster University, Canada (Jul 97-Jun 00). In July 2000, he joined King Abdulaziz Medical City, Riyadh, Saudi Arabia as a Consultant in Critical Care and Pulmonary Medicine up to the present. He is currently the Deputy Chairman of the Intensive Care Department and Professor in King Saud Bin Abdulaziz University for Health Sciences. In addition, he has more than 40 publications including articles in the New England Journal of Medicine (NEJM), JAMA, American Journal of Respiratory Critical Care Medicine, BMC Anesthesiology, and Critical Care Medicine

Background: Since September 2012, 170 confirmed infections with Middle East respiratory syndrome coronavirus (MERS-CoV) havebeen reported to the World Health Organization, including 72 deaths. Data on critically ill patients with MERS-CoV infection are limited.

Objective: To describe the critical illness associated with MERS-CoV.

Design: Case series.

Setting: 3 intensive care units (ICUs) at 2 tertiary care hospitals in

Saudi Arabia.

Patients: 12 patients with confirmed or probable MERS-CoV infection.

Measurements: Presenting symptoms, comorbid conditions, pulmonary and extrapulmonary manifestations, measures of severity

of illness and organ failure, ICU course, and outcome are described, as are the results of surveillance of health care workers (HCWs) and patients with potential exposure.

Results: Between December 2012 and August 2013, 114 patients were tested for suspected MERS-CoV; of these, 11 ICU patients (10%) met the definition of confirmed or probable cases. Three of these patients were part of a health care–associated cluster that also

included 3 HCWs. One HCW became critically ill and was the 12th patient in this case series. Median Acute Physiology and Chronic Health Evaluation II score was 28 (range, 16 to 36). All 12 patients had underlying comorbid conditions and presented with acute severe hypoxemic respiratory failure. Most patients (92%) had extrapulmonary manifestations, including shock, acute kidney injury,

and thrombocytopenia. Five (42%) were alive at day 90. Of the 520 exposed HCWs, only 4 (1%) were positive.

Limitation: The sample size was small.

Conclusion: MERS-CoV causes severe acute hypoxemic respiratory failure and considerable extra pulmonary organ dysfunction and is associated with high mortality. Community-acquired and health care–associated MERS-CoV infection occurs in patients with chronic comorbid conditions. The health care–associated cluster suggests that human-to-human transmission does occur with unprotected exposure.