Conference Schedule

Day1: March 26, 2018

Keynote Forum

Biography

Michael S. Bronze, M.D. was appointed Professor and Chairman, Department
of Medicine, University of Oklahoma Health Sciences Center effective
July 1, 2000. He was named the Stewart G. Wolf Professor in Internal
Medicine in 2004 and David Ross Boyd Professor in 2011. He is board
certified in Internal Medicine and Infectious Diseases. He completed his
medical school training at the University of Tennessee, Memphis in 1982.
His internship and residency were completed at the University of Tennessee,
Memphis and served and additional year as Chief Medical Resident.


Abstract

Hepatitis C (HCV) is a global infection due to Hepacivirus,
a member of the Flaviviridae family. Parenteral routes
including blood transfusion, injecting drug and exposure to
medical procedures usually transmit infection; however, the
virus can be transmitted maternally and in some patients, no
known risk factor is identifiable. Over 170 million persons
worldwide are infected and chronic infection leads to cirrhosis,
hepatocellular carcinoma and increased all-cause mortality. The
majority of infected patients maintain a chronic infection leading
to several hepatic and non-hepatic complications. Linked to
progressive infection is the presence of significant fibrosis
within the liver and several risk factors predict which patients are
likely to develop complications such as cirrhosis, hepatocellular
carcinoma (HCC), and increased all-cause mortality. HCC is the
fifth most common cancer in males, seventh in females and
is a major cause of cancer related death. Eighty-five percent
of cases occur in the developing world and HCV is a leading
predisposition. The pathogenesis of HCV related HCC is complex
and unlike hepatitis B virus, HCV does not integrate into the host
genome. However, HCV does dysregulate cellular proliferation
and differentiation pathways, creates chronic inflammation
and inhibits tumor suppressor gene activity. Our laboratory has
focused on two aspects of HCC carcinogenesis, namely cancer
like stem cells and chronic inflammation. Hepatoma cells
expressing a HCV subgenomic replicon express several cancers
like stem cell markers, especially doublecortin-like kinase
(DCLK1), a microtubule kinase that is a putative marker for
intestinal and pancreatic cancers. Expression of DCLK-1 is linked
to HCV replication and tumorigenesis in xenograft models, and
DCLK-1 is identifiable in tissue and plasma derived from patients
with HCV associated cirrhosis and HCC. SiRNA knockdown of
DCLK-1 inhibits tumor growth in animal models suggesting that
DCKL-1 might be a therapeutic marker. Additionally, total RNA
analysis of FCA4 cells, which also express a HCV subgenomic
replicon, reveals upregulation of DCLK-1 and a number of proinflammatory
markers including S100A9 and SMARCA. These
cells generate tumors in xenograft models that express DCLK-
1, AFP and S100A9 and siRNA knockdown of DCLK-1 abrogates
tumorigenesis and S100A9 expression. Over the last several
years, there has been significant progress in the treatment of
HCV infection. New, pan-genotypic direct antiviral agents (DAA)
have vastly improved our treatment strategies not only achieving
cure in a large percentage of patients, but also showing promise
in reducing the complications of HCV infection.

Biography

Sergey Suchkov graduated from Astrakhan State Medical University and
was awarded with MD and maintained his PhD and Doctor’s degree. He
was working for Helmholtz Eye Research Institute and Moscow Regional
Clinical Research Institute. He was a Secretary-in-Chief of the Editorial
Board, Biomedical Science, an international journal published jointly by
the USSR Academy of Sciences and the Royal Society of Chemistry, UK.
Currently, he is a Director of Center for Personalized Medicine, Sechenov
University; Chair of the Department for Translational Medicine, Moscow
Engineering Physics University and Secretary General of United Cultural
Convention, Cambridge, UK. He is a Member of the New York Academy of
Sciences; American Chemical Society; American Heart Association; AMEE,
Dundee, UK; EPMA, Brussels, EU; PMC, Washington, DC, USA and ISPM,
Tokyo, Japan.


Abstract

A new systems approach to diseased states and wellness
result in a new branch in the healthcare services, namely,
personalized medicine (PM). To achieve the implementa-tion of
PM concept into the daily practice including clinical cardiology,
it is necessary to create a fundamentally new strategy based
upon the subclinical recognition of bioindicators (biopredictors
and biomarkers) of hidden abnormalities long before the
disease clinically manifests itself. Each decision-maker values
the impact of their decision to use PM on their own budget and
well-being, which may not necessarily be optimal for society as a
whole. It would be extremely useful to integrate data harvesting
from different databanks for applications such as prediction
and personalization of further treatment to thus provide more
tailored measures for the patients and persons-at-risk resulting
in improved outcomes whilst securing the healthy state and
wellness, reduced adverse events, and more cost effective
use of health care resources. One of the most advanced
areas in cardiology is atherosclerosis, cardiovascular and
coronary disorders as well as in myocarditis. A lack of medical
guidelines has been identified by the majority of responders as
the predominant barrier for adoption, indicating a need for the
development of best practices and guidelines to support the
implementation of PM into the daily practice of cardiologists!
Implementation of PM requires a lot before the current model
“physician-patient” could be gradually displaced by a new model
“medical advisor-healthy person-at-risk”. This is the reason for
developing global sci-entific, clinical, social, and educational projects
in the area of PM to elicit the content of the new branch.

Tracks

Day2: March 27, 2018

Keynote Forum

Biography

Christopher F Tirotta has been an active Member of Miami Children’s Hospital
medical staff since 1991, practicing with the Department of Anesthesiology;
he has served as the Director of Cardiac Anesthesia since 2002. He has served
as Chief of the Department of Anesthesia since July 2017. He also has a clinical
appointment with the Department of Anesthesiology at The University of
Miami School of Medicine. He received his BA from Cornell University (USA) in
1982 and his MD from New York University School of Medicine (USA) in 1986.
He also received an MBA degree from Columbia University in 1999. He completed
his internship in Internal Medicine at State University of New York, Stony
Brook in 1987. He completed his residency training in Anesthesiology at the
University of Miami/Jackson Memorial Hospital in 1990; he sub-specialized in
pediatric and cardiovascular anesthesia, including heart transplantation.


Abstract

Post-operative pain control continues to be a problem in
surgical patients. A novel formulation of an ultra-long acting
local anesthetic is now available in the US: Exparel or liposomal
bupivacaine. Liposomal bupivacaine is made up of microscopic
polyhedral particles. The liposomes encapsulate the drug,
bupivacaine hydrochloride, without altering molecular structure.
This provides the reliable low dose release of the bupivacaine
over time, providing long-lasting, post-surgical pain relief over
the course of 2-3 days. This eliminates the need for titration of a
single dose or the need for external devices or pumps to prolong
analgesia. Plasma bupivacaine levels may persist for 96 hours after
injection. Peak plasma concentrations are lower in magnitude and
occur later in time than after a similar injection with bupivacaine
HCl. Plasma bupivacaine concentrations are not correlated with
local efficacy. Safety profile was evaluated in 10 clinical trials
in patients undergoing a variety of surgical procedures. Most
common adverse events were nausea, constipation and vomiting.
Exparel demonstrated a favorable cardiac profile. There was no
cardiac toxicity and no QTc prolongation, even a supra-therapeutic
dose. Rate of absorption is dependent on total dose administered,
route of administration and vascularity of the surgical site. Efficacy
has been established. Multiple trials demonstrated a significant
reduction in pain intensity scores and a reduction in overall opioid
consumption as compared to placebo. Liposomal bupivacaine is a
safe and effective novel drug to treat post-surgical pain.
Recent Publications
1. Bramlett K, Onel E, Viscusi E R, Jones K (2012)
A randomized, double-blind, dose-ranging study
comparing wound infiltration of DepoFoam bupivacaine,
an extended-release liposomal bupivacaine, to
bupivacaine HCl for postsurgical analgesia in total knee
arthroplasty. Knee. 19(5):530-536.
2. Bergese S D, Onel E, Morren M, Morganroth J (2012)
Bupivacaine extended-release liposome injection
exhibits a favorable cardiac safety profile. Reg Anesth
Pain Med. 37(2):145-151.
3. Naseem A, Harada T, Wang D, et al. (2012) Bupivacaine
extended release liposome injection does not prolong
QTc interval in a thorough QT/QTc study in healthy
volunteers. J Clin Pharmacol. 52(9):1441-1447.
4. Gorfine S R, Onel E, Patou G, Krivokapic Z V (2011)
Bupivacaine extended-release liposome injection for
prolonged postsurgical analgesia in patients undergoing
hemorrhoidectomy: a multicenter, randomized, doubleblind,
placebo-controlled trial. Dis Colon Rectum.
54(12):1552-1559.
5. Golf M, Daniels S E, Onel E (2011) A phase 3, randomized,
placebo-controlled trial of DepoFoam®bupivacaine
(extended-release bupivacaine local analgesic) in
bunionectomy. Adv Ther. 28(9):776-788.

Biography

My research focuses on the genetic mechanisms and regulatory pathways involved
in pulmonary disease. In my graduate study I had focused on the role of
microRNAs and epigenetic regulators in disease pathology. Specifically, we had
identified alterations in gene regulation that correlates with clinical severity of
disease in IPF. This has allowed us to target potential therapies, some of which
have shown significant promise in our small animal models. While my current
focus is on patients with IPF, these pathways allow diverse application too many
fields of study. We have developed several collaborations with clinicians and researchers
a like examining epigenetic regulation in diseases such as breast cancer,
sepsis and acute respiratory distress syndrome. The central theme of my
research is to identify epigenetic mechanisms by which prolonged macrophage
survival can amplify the immune response and contribute to cancer, metastasis,
Autophagy, chronic lung inflammation in idiopathic pulmonary fibrosis (IPF) and
other inflammatory lung diseases.


Abstract

Background: Sepsis microvascular dysfunction embraces
different cellular components including endothelial cells, in
which it increases its permeability and activation to shed extra
microparticles (MPs) to transport a unique cellular signaling to
the recipient cells. In this study, we observed that microparticles
can retain different epigenetic components as miRNA, mRNA
of DNMTs and HDACs from parent cells that can transfer to
naïve target cells. Importantly, in sepsis, MPs production is
increased. Increased expression of DNMTs results in promoter
hypermethylation which can suppress transcription of not only a
single gene but networks of genes with systemic effects. Sepsis
is an inflammatory insult which can result in vascular dysfunction
leading to systemic shock and eventual death.
Aim: The aim of this study is to distinguish the role of sepsis
microparticles in systemic immunosuppression process and
the impact of these particles upon cellular targets and survival
mechanisms to allow better diagnostic tools and potential novel
therapeutic approach during infection and trauma.
Methodology: Endothelial cells ( HUVEC) and naïve monocytes
treated with MPs from patients with sepsis demonstrated
dramatically reduced of anti-inflammatory genes, TGF-β, TNF-α
expression and some of autophagy molecules (ATG5, ATG7
and LC3) due to hypermethylation of their promoter. These data
demonstrate that mRNAs of epigenetic regulators including
DNMTs are highly expressed in plasma MVs in patients with
sepsis and can be transferred to naïve cells through MVs and
cause pro-inflammatory cytokine gene silencing and autophagy
repression in monocytes. Further, MVs per mL plasma on day 1
alone significantly correlated with death by day 5 (r=0.7125 and
p=0.0042). Using immunostaining techniques and flow cytometer,
we found the major source of plasma MVs in the critically-ill, nonseptic
control patients shifted from monocytes (Mo) to endothelial
cells (EC) in the SS patients (Control: Mo 63.6% and EC 7.4% and
SS: Mo 12% and EC 58.7% qualitatively). Focusing our study on
SS patients who lived and SS patients who died by day 5, our data
shows that while total DNMT mRNA copy numbers per plasma MV
are significantly higher over days 1 and day 3 in those SS patients
who lived, the ratios of DNMT1 (maintenance DNA methylation)
and the combination DNMT3A and DNMT3B (de novo DNA
methylation) are reversed on days 1 and 3 (SS Lived: DNMT3A/3Bto-
DNMT1: day 1=0.68 and day 3=0.87; SS Died: DNMT3A/3B-to-
DNMT1: day 1=2.49 and day 3=2.94). Finally, MV DNMT3A/3B
mRNA from day 1 samples positively correlates with reduced
survival (r=6261 and p=0.0165). Targeting of circulating MVs with
commercially available inhibitors of DNMTs may be a therapeutic
strategy in specific patients with deregulated epigenetic
mechanisms to limit both early and chronic consequences.
Results: We found that MPs from patients with septic shock and
septic had significantly increased mRNA for DNMTs compared
to MPs from patients with critical illness without sepsis and from
normal healthy adults over the course of 5 days. Remarkably,
we noticed that DNMT1 and -3a mRNA has the highest gene
expression in sepsis MPs compared to other DNMTs. Additionally,
naïve monocytes treated with MPs from patients with sepsis
demonstrated increased expression of DNMTs. At the same time
decreased expression at 24 hours.

Tracks