Day 2 :
Keynote Forum
Daqing Ma
Imperial College London, Chelsea and Westminster Hospital, UK
Keynote: The role of necroptosis in the pathogenesis of lung injury following kidney transplant and beyond
Time : 09:30-10:05
Biography:
Daqing Ma is a Reader and Head of Anaesthesia Research of the Section of Anaesthetics, Pain Medicine & Intensive Care, Department of Surgery & Cancer, Faculty of Medicine, Imperial College London, and Chelsea and Westminster Hospital, London, UK. He has more than 150 publications of original articles being published in the English peer reviewed journals (e.g. PNAS, Annals of Neurology, Annals of Surgery, BMJ, JASN, Kidney International, The FASEB Journal, Critical Care Medicine, Anesthesiology and etc.) covering research fields of Anesthesiology, Pharmacology, Neuroscience, Neurology and Nephrology. He is a fellow elect of Royal College of Anaesthetists (UK). He is a Board Member of British Journal of Anaesthesia and a council member of Anaesthetic Research Society (UK). He is an Academic Editor of PLoS One and an Associate Editor of Journal Alzheimer Disease and Editorial Board Member of other 5 journals.
Abstract:
Necroptosis is a type of regulated cell death dependent on the activity of receptor-interacting serine/threonine-protein (RIP) kinases. However, unlike apoptosis, it is caspase-independent. Increasing evidence has implicated necroptosis in the pathogenesis of disease, including ischemic injury, neurodegeneration, viral infection and many others. Key players of the necroptosis signalling pathway are now widely recognized as therapeutic targets. Necrostatins may be developed as potent inhibitors of necroptosis, targeting the activity of RIP1. Necrostatin-1, the first generation of necrostatins, has been shown to confer potent protective effects in different animal models. This lecture covers the role of necroptosis in the pathogenesis of lung injury after kidney transplant and other solid organ injury following ischaemia/reperfusion.
Keynote Forum
Du Toit Loots
North-West University, South Africa
Keynote: “TB or not TB†that is the question – Understanding and diagnosing TB using metabolomics
Time : 10:05-10:40
Biography:
Du Toit Loots currently heads the “Infectious and Acquired Disease Metabolomics” unit at NWU, with a focus on new biomarker discovery for better characterizing and diagnosing diseases, TB in particular. He has, to date, contributed to a total of 68 publications: 60 of which are peer reviewed scientific manuscripts in top international journals, 4 chapters in books and 4 publications in non-peer reviewed popular magazines. He is currently International Editor for Journal of Cell and Tissue Research and has additionally registered 1 full patent, with application to TB diagnostics, and published a new synthesis method for NaFe(III)EDTA, a highly bioavailable form of iron for combating anaemia. In recognition of these efforts, he received a number of awards including the: International Nestle Nutrition Institute for Africa Research Award; Janssen-Cilag Award, International ARP Walker Research Award and International Scripps Centre for Integrative Medicine\\\\\\\'s Research Award.
Abstract:
Despite the fervent genomic and proteomic based research efforts to date, since its discovery in 1882, TB is still a major global problem, and hence new approaches are necessary to better characterize and diagnose this disease. Using a variety of LC-MS, GC-MS and NMR metabolomics based methodologies, we have investigated tuberculosis from a variety of different perspectives, for the purpose of identifying new biomarkers which better explain the mechanisms related to drug resistance, virulence, growth and host-microbe interactions/adaptations. Furthermore, these biomarkers are also showing promise for the development of improved diagnostic approaches, not only for identifying TB complex, but also for detecting drug resistant strains, distinguishing various Mycobacterium species, and predicting treatment outcome.
- Pulmonary Disease: Tuberculosis
Pulmonary Disease: Pneumonia
Lung Cancer and Treatment Strategies
Session Introduction
Shashank Gupta
Johns Hopkins University, USA
Title: Efflux inhibition during tuberculosis treatment
Time : 11:20-11:50
Biography:
Shashank Gupta completed his graduate studies from ICGEB, New Delhi, India in 2009 and moved to Johns Hopkins University as a Postdoctoral fellow in early 2010. Currently, he is a Research Associate with HHMI and working on tuberculosis field at Johns Hopkins University. His studies with Mycobacterium tuberculosis will help understand the underlying mechanisms of host-pathogen interaction with special focus on mycobacterial pathogenesis and the other pathways involved in tuberculosis. His recent studies with efflux pump inhibitors have shown that verapamil can be used to accelerate both the bactericidal and the sterilizing activity of standard tuberculosis treatment.
Abstract:
Drug resistance during tuberculosis treatment is a major health concern today in the developing countries. One of the mechanisms contributing to the resistance is the efflux of the tuberculosis drugs out of the cell through a variety of pumps. Efflux pump inhibitors such as verapamil may help overcome this tolerance and resistance mechanism and enhance the activity of tuberculosis drugs. Verapamil is an FDA approved drug used to treat heart disease and hypertension. We have recently found that adding verapamil to standard chemotherapy reduced the time required to successful treatment from standard six months to four months, but also significantly decreased the risk of relapse. Another drug that has been recently approved by FDA for tuberculosis treatment is bedaquiline, also known as TMC-207. We found that co-administration of verapamil with sub-inhibitory doses of bedaquiline gave the same bactericidal effect in mice as full bedaquiline dose. In addition to, we also found that adding verapamil to bedaquiline monotherapy protected from development of resistant mutants in vivo. Thus, use of verapamil with bedaquiline may enable use of lower doses of bedaquiline, thereby reducing its dose-related toxicities in tuberculosis patients.
Orna Yariv
University of Tel-Aviv, Israel
Title: EASY AIR - Pulmonary rehabilitation telemedicine
Time : 11:50-12:20
Biography:
Orna Yariv is working as a Physiotherapist in Pulmonary rehabilitation at Laniado Hospital. He served as Medical trainer-A.C.S.M. from 1989- 1998 at Physiotherapy Clinic in Tel Aviv , Israel He also worked as Manager - Telemedicine Pulmonary Rehabilitation in a reputed organization and also serving as Volunteering manager -respiratory Q&A forum since 2012.
Abstract:
Daily treatments and support of patients with lung diseases include drainage, training and education towards physical activity. The overall goal of these treatments is to improve the quality of life of these chronic patients. A primary challenge in the treatment of these patients is the difficulty in achieving an efficient guidance of the patients that will improve the efficacy of their treatment. In the coming lecture I will present my experience in expanding the role of the care-giver using pulmonary rehabilitation telemedicine. I use telemedicine to treat patients in a variety conditions, times and places: at home, while hospitalized, and even while on vacation or at work. Moreover, we use telemedicine specifically for patients leaving in rural areas and for housebound patients. Preliminary communication media are the e-mail and Facebook that are followed by scheduled Skype appointments. Skype-appointments are used (a) to track medical history, (b) to find primary problems that the patient is occupied with, and (c) to understand their level of functionality. This information is used to build a patient-tailored rehabilitation program that is based on traditional Pulmonary Rehabilitation. Following appointments are used to combine education and to demonstrate needed exercises. My patients improve their walking distance and amount of upclimbing stairs. Tele-rehabilitation therapy does not replace traditional pulmonary rehabilitation but rather enhances it by providing an additional way to treat and to ease patients’ life.
Du Toit Loots
North-West University, South Africa
Title: Tuberculosis: Adaptations of man and microbe in order to outcompete and survive
Time : 12:20-12:50
Biography:
Du Toit Loots currently Heads the “Infectious and Acquired Disease Metabolomics” unit at NWU with a focus on new biomarker discovery for better characterizing and diagnosing diseases, TB in particular. He has to date contributed to a total of 68 publications: 60 of which are peer reviewed scientific manuscripts in top international journals, 4 chapters in books and 4 publications in non-peer reviewed popular magazines. He is currently International Editor for Journal of Cell and Tissue Research and has additionally registered 1 full patent with application to TB diagnostics and published a new synthesis method for NaFe (III) EDTA, a highly bio-available form of iron for combating anaemia. In recognition of these efforts, he received a number of awards including the: International Nestle Nutrition Institute for Africa Research Award; Janssen-Cilag Award, International ARP Walker Research Award and International Scripps Centre for Integrative Medicine's Research Award.
Abstract:
Tuberculosis (TB) caused by the organism Mycobacterium tuberculosis is a deadly bacterial disease infecting approximately one-third of the world’s population. The most recent World Health Organization (WHO) report indicates 1.5 million deaths and 9 million newly reported TB cases per annum, 95% of which are in developing countries. Despite the fervent genomic and proteomic based research efforts to date, since its discovery in 1882, TB is still a major global problem and hence new approaches are necessary to better characterize this disease especially the adaptations of the host and microbe/host-microbe interactions as they compete to survive. Using GCxGC-TOFMS metabolomics, we have to date identified 31 new sputum and 12 new urinary metabolite markers never before associated with TB providing new insights into the adaptations of the host and microbe metabolome during active TB. The most significant of these are the TB-induced abnormal metabolites resulting from changes to host fatty acid and amino acid metabolism in particular to that of tryptophan, phenylalanine and tyrosine mediated through INF-γ and possibly also reduced insulin. Additionally, an alternative mechanism by which the host produces hydrogen peroxide via glucose oxidation in order to more efficiently eliminate the bacterial threat is proposed. Through these altered metabolic pathways elevated concentrations of various neurotransmitters and other abnormal toxic metabolites related to some of the symptoms associated with TB were identified, subsequently providing clues to better treatment approaches. Adaptations of the microbe during active TB includes the use of a rather unique citramalic acid cycle in conjunction with an up-regulated glyoxylate cycle accompanied by a greater dependence on fatty acids and glutamate as alternative carbon sources.
Grace Kaguthi
Kenya Medical Research Institute, Kenya
Title: Chest radiographs for pediatric TB diagnosis: Inter-rater agreement and utility
Time : 12:50-13:20
Biography:
Grace Kaguthi is a Medical Doctor and Clinical Trialist with the Centre for Respiratory Diseases Research (KEMRI). She is currently pursuing her PhD in Tuberculosis epidemiology at the University of Amsterdam. She is a lead investigator in phase II and phase III trials of novel tuberculosis vaccines, treatments for sickle cell disease, malaria and tuberculosis treatment trials. She is a Member of the Ethics Review Unit at the Kenya Medical Research Institute which reviews and approves research protocols.
Abstract:
The chest radiograph (CXR) is considered a key diagnostic tool for pediatric tuberculosis (TB) in clinical management and endpoint determination in TB vaccine trials. We set out to compare inter-rater agreement for TB diagnosis in western Kenya. A pediatric pulmonologist and radiologist (experts), a medical officer (M.O), and four clinical officers (C.Os) with basic training in pediatric CXR reading blindly assessed CXRs of infants who were TB suspects in a cohort study. C.Os had access to clinical findings for patient management. Weighted kappa scores summarized inter-rater agreement on lymphadenopathy and abnormalities consistent with TB. Sensitivity and specificity of raters were determined using microbiologically confirmed TB as the gold standard (n=8). A total of 691 radiographs were reviewed. Agreement on abnormalities consistent with TB was poor; k=0.14 (95% CI: 0.10–0.18) and on lymphadenopathy moderate k=0.26 (95% CI: 0.18–0.36). M.O [75% (95% CI: 34.9%–96.8%)] and C.Os [63% (95% CI: 24.5%–91.5%)] had high sensitivity for culture confirmed TB. TB vaccine trials utilizing expert agreement on CXR as a non-microbiologically confirmed endpoint will have reduced specificity and will underestimate vaccine efficacy. C.Os detected many of the bacteriologically confirmed cases; however, this must be interpreted cautiously as they were un-blinded to clinical features.
Abdulhadi Almutairi
King Fahad Specialist Hospital, Saudi Arabia
Title: Extended resections for lung cancer: Can they be justified
Time : 14:10-14:40
Biography:
Abdulhadi Almutairi has graduated from College of Medicine, King Saud University, Saudi Arabia in 2000. He completed his Surgical Residency at King Faisal Specialist Hospital, Saudi Arabia. His passion for thoracic surgery has led him to join a Clinical Thoracic Surgery Fellowship in a world-renowned thoracic surgery program at McMaster University, Hamilton, Ontario. Throughout his career, he has developed a strong interest in thoracic oncology in general and lung cancer specifically. Beside lung cancer surgery, he is also interested in tracheal surgery, mediastinal surgery and chest wall primary tumors. He is an active Member of the Society of Thoracic Surgeons (STS), International Thymic Malignancy Interest group (ITMIG) and Chest Wall International group (CWIG). He has over 20 publications and currently working on Editing a Surgery Textbook. He is a strong Advocate of Quality in Surgical Education and is the Program Director of Surgery Residency training program.
Abstract:
Surgical resection remains a critical component of multidisciplinary therapy for locally advanced lung cancers. However, extended resection for treating locally advanced lung cancer is surrounded by intense debate. The advancements in novel chemotherapy and targeted therapy have influent our decisions on treating these cases by radical surgical intervention that carries a significant morbidity and mortality. Long-term survival is limited to retrospective and anecdotal data. Moreover, in the era of patient-centered care, the patient decision to go for neoadjuvant or definitive systemic therapy remains critical and may alter the landscape of surgical scene. Historically, racialists (thoracic surgeons with enormous surgical experience) have fought locally advanced lung cancer with extended resection that entails lobectomy or pneumonectomy en bloc with adjacent involved structure in order to achieve complete surgical resection and negative margins. This may on itself and by itself improve survival in highly selected patients. The magnitude of this benefit is very difficult to quantify largely because the data is limited to small patient sample and high volume centers. Never the less, this improvement, albeit modest cannot be ignored or rejected. In this talk, we aim to dissect the current literature regarding this important matter and shed some light on the techniques that have been refined over the years in order to serve a well defined subsets of patients with locally advanced lung cancer who may be offered this type of radical surgery knowing the amount of risk taking is massive and the expected results remain a matter of speculation.
Videlis Nduba
Kenya Medical Research Institute, Kenya
Title: Incidence of tuberculosis and cohort retention among adolescents in Western Kenya
Time : 14:40-15:10
Biography:
Videlis Nduba is a Senior Research Officer at the Center for Respiratory Diseases Research, Kenya Medical Research Institute. He is a Medical Officer and Epidemiologist with experience leading several clinical trials. He previously conducted epidemiological trials in infants and adolescents to determine the incidence of tuberculosis in Western Kenya. He is currently involved with TB vaccine and drug trials.
Abstract:
Setting: Karemo division, Siaya County, Western Kenya, with the highest TB notification rates in Kenya (400/100,000). Objective: To determine the incidence of tuberculosis and one year cohort retention in 12–18 year adolescents, in preparation for Phase III TB vaccine trials. Design: Adolescents were enrolled and followed up for 1-2 years to determine TB incidence. Adolescents who had a positive tuberculin skin test, history of cohabitation with a TB case within the previous 2 years, or at least one TB symptom received clinical examination, sputum examination, and a chest X-ray. TB cases were defined as definite if bacteriologically confirmed and clinical if diagnosed by a clinician based on a suggestive chest X-ray scored using Chest Radiograph Review System (CRRS) and having at least one clinical symptom. Risk factors were explored using Poisson regression. Results: Among 4965 adolescents without TB at baseline, 26 TB cases were found during follow up with a corresponding incidence density of 4.4 (95% CI, 3.0-6.4) events per 1000 person years of observation. Tuberculin skin test (TST) conversion (RR=3.5; CI 1.5, 7.7) and history of previous tuberculosis (RR=12.5; CI 1.8, 100) were the strongest predictors of incident TB. Overall (4086/4957) 82.4% of adolescents were retained in the study after 1 year of follow up. Being female, older, out of school and being orphaned were significant risk factors for lower retention rates. Conclusion: Given the high incidence of tuberculosis and good cohort retention, this setting is suitable for TB vaccine trials targeting adolescents.
- Young Researcher Forum
Session Introduction
Nancy Gupta
University of Alberta, Canada
Title: A novel mucosal lipopeptide based vaccine against mycobacteria
Time : 15:45-16:05
Biography:
Nancy Gupta completed her PhD and is working in Laboratory Medicine and Pathology under Dr. Rakesh Kumar, Dr. Dennis Kunimoto University of Alberta Edmonton,Canada.
Abstract:
Tuberculosis (TB) is a major global health threat to humans, with 9.3 million new cases and 2 million deaths annually from Mycobacterium tuberculosis infection. BCG is the only available vaccine which is only 0-80% effective. Development of vaccine against mycobacteria is challenging and several experimental vaccine candidates did not demonstrate sufficient efficacy in clinical trials. Early secreted antigenic target 6-kDa (ESAT-6) has been suggested to be an important antigen for protective immunity and BCG lacks ESAT-6. In this study, we aimed to examine the immune responses generated upon immunization with lipopeptides of ESAT-6 and their protective efficacy in a mouse modal of Mycobacterium tuberculosis infection. Our results demonstrated that intranasal immunization with lipopeptides of ESAT-6 antigen is capable of stimulating potent and multifunctional antigen specific T cell responses in spleen and lead to substantial infiltration of immune cells in the Bronchio Alveolar Lavage (BAL). Subcutaneous immunization also induced immune responses in spleen comparable to that obtained from intranasal route but failed to recruit immune cells in the BAL. Pre-immunization of mice with lipopeptides of ESAT-6intranasallyled to a significant reduction in Mycobacterium tuberculosis (H37Ra) loads in lungs, liver and spleen compared to subcutaneous vaccination. Our study revealed the potential of lipidated peptides of ESAT-6 antigen as a promising mucosal vaccine against tuberculosis.
Saurabh Garg
University of Alberta, Canada
Title: Investigation of novel alkynyl and alkynyloxy pyrimidine nucleoside analogs as antimycobacterial agents
Time : 16:05-16:25
Biography:
Saurabh Garg completed his PhD and is working at Laboratory Medicine and Pathology under Dr. Rakesh Kumar, Dr. Robert Rennie University of Alberta Edmonton,Canada.
Abstract:
A rapid increase of the antibiotic resistance against microbial pathogens over the past several decades has become one of the most serious medical challenges to the world. Tuberculosis (TB) caused by Mycobacterium tuberculosis is the second leading cause of infectious deaths globally. In 2013, an estimated 9 million people developed tuberculosis and 1.4 million died from this disease. The resurgence of TB cases and the emergence of drug-resistant strains of mycobacteria necessitate the search for new antimycobacterial agents that are non toxic and distinct from the current drugs. We have designed, synthesized and evaluated novel pyrimidine nucleosides (1-20) for their antimycobacterial activities in vitro. The 3-N- and or 5-O-propynyl pyrimidine nucleosides (1-14) were synthesized by reacting 5-hydroxy and 5-hydroxymethyl pyrimidine nucleosides with propargyl bromide. 5-Acetylenic nucleosides (15-20) were prepared by coupling 5-iodo pyrimidine nucleosides with trimethylsilyl acetylene followed by de-protection with sodium methoxide. The antimycobacterial activity of compounds 1-20 alone and in combination with first line antituberculosis drug isoniazid was evaluated against Mycobacterium tuberculosis (Mtb), Mycobacterium bovis (M. bovis) and Mycobacterium avium (M. avium) using microplate alamar blue assay. Among alkynyl compounds 5-(2-propynyloxy) uridine (4) and N-3-propynylnucleoside analogs (5 and 12-14) exhibited modest activity against Mtb (H37Ra) and M. bovis with EC50=160-180 μg/mL, however, they demonstrated strong synergistic interactions with isoniazid. C-5 Ethynyl substituted pyrimidine nucleosides analogs (15-20) were found to be inactive as antimycobacterial agents. Compounds 1-20 did not show cytotoxicity up to the highest concentration tested (CC50>200 μg/mL).
Jomo Osborne
The Brooklyn Hospital Center, USA
Title: Catheter-directed thrombolysis in patients with Acute pulmonary thromboembolism - A case series at The Brooklyn Hospital Center
Time : 16:25-16:45
Biography:
Dr. Jomo Osborne earned his medical degree in his native country Guyana and later completed a Masters of Health Science degree in Cuernavaca, Mexico. He has presented at many international conferences and co-authored several peer review articles and conference abstracts. He is currently a surgical resident at The Brooklyn Hospital Centre. His research interest includes sub-massive pulmonary embolism, minimally invasive surgery and surgical quality improvement.
Abstract:
Pharmacomechanical catheter-directed thrombolysis in patients with acute pulmonary thromboembolism (PE) is a proven safe and effective method of preventing complications such as right ventricular collapse, cardiogenic shock and death. Three patients with massive or sub-massive pulmonary embolism presented to the Emergency Department at our institution with shortness of breath and were diagnosed with acute PE using computed tomography pulmonary angiogram (CTA). The patients were: A 57 year-old woman with a history of hypertension and previous thyroid cancer which was treated with thyroidectomy presented with a pulmonary arterial saddle embolus and right cardiac dysfunction; a 55 year-old woman on chemotherapy with a history of deep vein thrombosis (DVT), previous tumor-debulking and extended right hemicolectomy for metastatic leiomyosarcoma presented with a large central pulmonary embolus in the right main pulmonary artery without right ventricular strain; a 54 year-old man with a history of lower extremity DVT with a right main pulmonary artery embolus and right ventricular strain. Based on the clot location in each patient, an EKOS catheter was placed in the main pulmonary artery or its branches and alteplase was infused at a rate of 1mg per hour over 10-24 hours. Simultaneously, the patients were anticoagulated with heparin. The patient’s hemodynamic status, coagulation profile and fibrinogen levels were continuously monitored for clinical improvement. The follow-up CTA showed 75% to 100% clot reduction in each patient. Complications included a right-sided groin hematoma at the catheter-insertion site in one patient which required temporary discontinuation of thrombolytic and anti-coagulation therapy. Our observations of these three patients show that this method of treatment is a safe and effective initial measure to restore pulmonary artery blood flow in patients diagnosed with acute PE. However, it is still associated with the risk of complications.
Suhaj A
Manipal University, India
Title: Impact of patient education on health related quality of life of COPD patients- A randomized controlled study
Time : 16:45-17:05
Biography:
Suhaj A is Assistant Professor-Senior Scale in the Department of Pharmacy Practice at MCOPS. Areas of Interest, Expertise and Research: Pharmaceutical Care, Drug Safety and Pharmacoeconomics, Clinical Pharmacy and Pharmaco therapeutics, Pharmaceutical Care in COPD patients PROFESSIONAL AFFILIATIONS AND CONTRIBUTIONS: He is member of ISPOR.
Abstract:
Background: Chronic Obstructive Pulmonary Disease (COPD) comprises a group of diseases associated with airflow obstruction and breathing-related problems. COPD cannot be cured but adherence to the therapy can improve management of symptoms and delay disease progression. Patients’ knowledge and awareness about the disease are important in improving quality of life. Aim: Our study was aimed to assess the impact of patient education on Health Related Quality of Life (HRQoL) of COPD patients. Method: An open label randomized controlled study was conducted among 206 COPD patients who were admitted in the university hospital after obtaining the ethical clearance. HRQoL of the patients in the control and intervention group at baseline and follow-up visits were measured using St. George Respiratory Questionnaire. Patients were followed up at 6 months during a scheduled visit. Statistical analyses were performed using SPSS® version 20. Result: Mean age of the study population (n=206) was 58.42±9.72. 93.5% were males. There is no significant difference in overall HRQoL between control (45.2%) and intervention group (44.8%) at baseline. After intervention, overall HRQoL was improved in intervention group (P < 0.05) compared to control group (P>0.05) at follow-up. Study population in the intervention group (at follow-up) has reported better HRQoL compared to the intervention group (at baseline), control group (at baseline) and control group (at follow-up). Conclusion: The results of the study suggest that the clinical pharmacist can play a major role in improving patient knowledge and thereby improve medication adherence and health related quality of life.