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Monday, December 21st, 2015

By Helen K. Kelley

According to the Centers for Disease Control and Prevention (CDC), more than one-third (34.9 percent) of all adults in the U.S. are obese, and the rate of adult obesity in the U.S. nearly tripled from 1960 to 2010.

Many individuals who fall into the overweight or morbidly obese categories are desperately searching for a “magic” solution that will take away the pounds permanently. Frustrated with diets and pills that often provide only temporary results, thousands of people are lining up for bariatric procedures, which may provide the closest thing to the permanent solution they seek.

According to the American Society for Metabolic and Bariatric Surgery, bariatric surgery has been shown to be the most effective and durable treatment for morbid obesity, and it helps prevent, improve or resolve more than 40 obesity-related diseases or conditions, including type 2 diabetes, heart disease, obstructive sleep apnea and some cancers.

Atlanta Medicine recently spoke with two Atlanta-area bariatric physicians, who shared their knowledge of how the bariatric landscape has changed over the past several years.

Surgical and Non-Surgical Options Improve Patients’ Weight Loss Success

Jean-Pierre Fritz

Jean-Pierre Fritz, M.D

According to Fritz Jean-Pierre, M.D., a bariatric surgeon with WellStar Health System, improvements in both surgical and nonsurgical options over the past 10 years have resulted in both giving patients better weight loss and giving physicians the ability to better predict that weight loss.

He says the most notable change has been an increase in the selection of a more invasive surgery, the gastric sleeve, over the once-popular lap band and other procedures. The gastric sleeve (sleeve gastrectomy) actually removes approximately 80 percent of the stomach, leaving a tubular pouch that resembles a banana. This procedure, which is less complicated than many other types of bariatric surgery, now comprises over 60 percent of all weight loss surgery procedures performed in the U.S.

“There has been a huge switch in choice of surgeries today. We’ve seen a large increase in patients selecting the sleeve gastrectomy in the past five years,” says Dr. Jean-Pierre. “In addition, we are better able to evaluate our patients’ metabolic conditions today, which helps us in making recommendations for the most appropriate weight loss option.”

Dr. Jean-Pierre adds that non-surgical options can also be very good solutions for some patients who desire to lose weight, especially children and adolescents.

“One of the partners in our practice is an obesity specialist who helps patients determine the weight-loss options available to them and which of those options is best suited. Sometimes, diet and exercise are a better approach,” he says. “For young patients, this is often the first and best choice rather than a surgical intervention, which causes lifelong changes.”

For the patient with a very high Body Mass Index (BMI) and/or various comorbidities like diabetes and high blood pressure, Dr. Jean-Pierre says the more aggressive gastric bypass (Roux-en-Y Gastric Bypass) may be the best option.

Christopher J. Hart

Christopher J. Hart, M.D.

“The gastric bypass is still considered the ‘gold standard’ of weight loss surgeries,” he says. “While it’s more invasive, it has a high rate of success for significant long-term weight loss.”

Lifestyle Change is Key Part of Solution

Christopher J. Hart, M.D., chief of staff and medical director of the Atlanta Bariatric Center at Emory Johns Creek Hospital, says that long-term weight loss success depends on the patient’s commitment to making permanent lifestyle changes to ensure that success after surgery.

“Once a person’s BMI rises above the 30-35 percent range, long-term weight loss with just diet and exercise becomes much harder; it becomes about deprivation,” he says. “So the nice thing about bariatric surgery is that it results in the patient being able to eat less and still feel satisfied.”

However, to obtain lasting results, the patient still has to make lifestyle changes after surgery.

“I tell my patients, ‘I can do a technically perfect surgery, but you will still not lose the weight and get healthy unless you hold up your end of the deal – which means good nutrition and exercise,” he says.

Dr. Hart adds that data compiled over the years for different bariatric procedures is an important tool in developing treatments that can help patients achieve permanent weight loss.

“For example, in the early days of the lap band procedure, there was some experimentation – after a patient reached his or her goal weight, the band was removed. The hope was that the patient had made lifestyle changes that would keep the weight off and would no longer need the band for continued support. The data showed that patients regained the weight because their hunger drive returned,” he says. “It’s important to follow our patients throughout the course of their lives so that we can monitor their progress and success as well as compile data that will be helpful in the future. We can use that data to determine success rates and complications, as well as see how we compare against national statistics.”


Spotlight on Hepatitis C

Wednesday, October 29th, 2014

By Helen K. Kelley

From ATLANTA Medicine, Vol. 85, No. 4

Lance Stein, MD

Lance Stein, MD

Hepatitis C, the most common blood-borne infection in the United States today, is considered a public health threat. From new medications just entering the market and clinical trials to educational efforts and a push for identifying those who have the infection, hepatitis C is a hot topic among medical practitioners in Atlanta and elsewhere.

Baby Boomers at risk; new meds have unprecedented success

Hepatitis C is most prevalent in the Baby Boomer generation – those born between 1945 and 1965 – many of whom are asymptomatic and don’t yet know they have the infection. Roughly three-fourths of the current population is now aging and falling into the targeted bracket for having the infection, according to Lance Stein, M.D., a transplant hepatologist at Piedmont Transplant Institute.

“Age is important. If you are infected with hepatitis C, it can do significant damage to the liver … and it actually takes approximately 30 years for that to happen in most patients. So, let’s say if a person was infected in 1970 and is now turning 65, that’s when we’ll begin seeing the problems,” he explains. “Hepatitis C has become a big public health issue. This is why there’s been a huge increase in the establishment of liver cirrhosis clinics and transplant clinics.”

Stein adds that the uptick in patients identified as having hepatitis C just happens, fortunately, to coincide with helpful advances in medicine.

“Hepatitis C has been ‘blowing up’ in terms of new treatment options. These new drugs are much more effective than older treatments like Interferon and Ribavirin, both of which carry significant side effects. But the new treatments are also much more expensive,” he says.

According to Stein, sofosbuvir (Solvadi), which was approved by the FDA in December 2013, is priced at about $84,000 for a three-month treatment. That equates to roughly $1,000 per day. However, the drug has been highly successful to date, with an approximate 89 percent cure rate in people with hepatitis C type 1. Stein says that the high cost upfront may actually end up saving patients and insurers money in the long run.

“The higher cure rate of sofosbuvir, along with fewer side effects than previous treatments, means fewer doctor visits and lab tests than previously required on a regimen like Interferon. It may also prevent the need for a transplant in the future,” he notes. “Some even newer drugs are currently awaiting approval later this year. This is exciting because clinical trials show cure rates for these new treatments are almost 100 percent after a three-month regimen.”

Aasim M. Sheikh, M.D., who specializes in the treatment and management of liver diseases as a gastroenterologist, hepatologist and clinical researcher with GI Specialists of Georgia, agrees that the new drugs hold great promise for people infected with hepatitis C.

Enrique Martinez, MD

Enrique Martinez, MD

“The envelope is being pushed,” he says. “Researchers – big players like Merck, Gilead, Johnson and Abbott – are looking for regimens that combine drugs to result in a minimum number of pills with the fewest side effects and shortest treatment.”

Sheikh adds that there are four different classifications of drugs that are proving to work well in combination.

“These drugs block the hepatitis C virus at different points, shutting down different enzymes that help the virus multiply,” he explains. “Together, they have a synergistic effect in controlling the virus.”

Sheikh states that the most important keys to treating and curing hepatitis C are: identifying people who have the infection; prioritizing and treating those who have the most advanced disease; the development of more effective treatments of shorter duration and fewer side effects; and analyzing the results of various treatment protocols.

“The more people we treat, the more we find out,” he says. “We hope to alter the course of their illness and keep them at a lower risk for further complications.”

Enrique Martinez, M.D., a gastroenterologist and hepatology specialist with Atlanta Gastroenterology Associates, has watched the progression of hepatitis C treatments since he began practicing in 1989.

“This is a very exciting time. It’s amazing when you consider that a disease with only an 8 percent cure rate 25 years ago is now approaching a 100 percent cure rate,” he says. “And it’s interesting that today we consider treatments with a less than 95 percent cure rate to be inferior. Pharmaceutical companies are constantly looking at new combinations of drugs that could result in better and better cure rates for hepatitis C patients.”

Martinez adds that the evolution of drug combinations also holds great promise for special populations with hepatitis C.

“People we previously thought could not be treated for hepatitis C are now being considered possible candidates for the new drug regimens,” he says. “These populations include people with immune disorders such as lupus and rheumatoid arthritis, sickle cell disease or colitis. Even people who must undergo dialysis or who are pre- or post-transplant patients have new hope for treatment.”

Lesley Miller, MD

Lesley Miller, MD

Providing care to an underserved population

The Grady Liver Clinic at Grady Memorial Hospital, established in 2002, is an innovative model for expanding access to hepatitis C care for urban, underserved patients. This population is disproportionately affected by the infection. Dr. Lesley Miller, the clinic’s medical director, says the facility is a unique and revolutionary model because it is run and staffed by general internists (rather than specialists), who work together to provide hepatitis C management – including antiviral treatment – to patients regardless of their insurance status.

“Patients without options for specialty care really benefit from this clinic,” Miller says. “We do a lot of education and counseling, and we provide immunizations against hepatitis A and B, evaluation of liver disease and medical comorbidities, and treatment options. We’re one of the only places [in Atlanta] that can offer these services to people who don’t have health insurance.”

A study of the Liver Clinic’s population for its first five years of operation showed that it was primarily African American (76 percent) and uninsured (59 percent). Patients had difficult-to-treat characteristics, including genotype 1 hepatitis C (90 percent), advanced liver fibrosis (28 percent), and high viral loads. Sixty-seven percent had comorbid medical conditions, and 40 percent had psychiatric disease. Fourteen percent of patients were treated for hepatitis C during the study period.

With those early statistics in mind, Miller is pleased with the medical advances that have made hepatitis C treatment easier for the Clinic’s current patients and is excited about the speed at which new treatment options are progressing.

“It’s unbelievable how fast the research and development in the world of hepatitis C are changing. Things I was doing last month are already different,” she says. “More of our patients are now candidates for treatment than have been in the past, because treatment duration is shorter and the regimens are easier or more relevant for people who have other chronic health problems. It’s gratifying to give patients a regimen that’s not going to make them sick and has a high probability of curing them.”

The stats on hepatitis C

In the National Health and Nutrition Examination Survey (NHANES), conducted between 2003 to 2010, researchers studied people with hepatitis C in order to estimate the prevalence of chronic HCV infection and to identify factors associated with the condition. The survey included interviews and testing of serum samples from participants aged six years and older.

Based on 273 participants who tested positive for HCV RNA:

• The estimated prevalence of HCV infection was 1.0 percent (95 percent CI, 0.8 percent to 1.2 percent), corresponding to 2.7 million chronically infected persons (CI, 2.2 to 3.2 million persons) in the U.S. non-institutionalized civilian population.

• Infected persons were more likely to be aged 40 to 59 years, male, and non-Hispanic black and to have less education and lower family income.

• Factors significantly associated with chronic HCV infection were illicit drug use (including injection drugs) and receipt of a blood transfusion before 1992; 49 percent of persons with HCV infection did not report either risk factor.

Based on the data collected, researchers estimated that approximately 2.7 million U.S. residents in the population sampled by NHANES have chronic HCV infection. The study highlighted the continued urgency of identifying the millions of persons who remain infected and linking them to appropriate care and treatment.

In the news

According to a recent article in The New York Times, “sales of the new hepatitis C drug Sovaldi reached $3.5 billion in the second quarter, a huge figure that puts it on track to become one of the world’s best-selling medicines but could intensify concerns about society’s ability to pay for it.”

The FDA-approved drug, manufactured by Gilead Sciences, is for patients with hepatitis C virus (HCV) genotypes 1, 2, 3 or 4 infection.


Understanding the Immune Response

Tuesday, December 11th, 2012

by Gary E. Myerson, M.D., F.A.C.R.

From ATLANTA Medicine, 2012, Rheumatology, Vol. 83, No. 3

Gary E. Myerson, M.D.

Gary E. Myerson, M.D.

Centuries ago, geography itself served as the primary barrier to disease exposure. But man’s exploration of the planet, enhanced by progressive technological expertise, has permitted both exposure to and expansion of diseases worldwide. However, our increasing knowledge of science overall and the specific components of the immune response has led to numerous diseases either being reduced or eliminated.

The immune response is an ancient system. Certain components, however, have not significantly changed in the millions of years of existence of species with vertebrae. The homo-sapiens and homo-erectus, nearly 250,000 years ago, possessed an immune system similar to ours. Innate immune response has been present throughout this entire period. It has been our “equalizer” in dealing with the microscopic environment that envelops us. We have made” friends” with many microbes, resulting in relationships that are symbiotic, while others are indeed antagonistic or parasitic. It is this inherent, genetically provided, innate response that is our defense against invaders both physically and chemically. The Adaptive or acquired immune response, our body’s ability to develop antibodies, has allowed us to improve or enhance our own innate immune response. Biologic therapy with monoclonal antibodies now allows us to manipulate specific proteins important in the immune response.

Our first line of defense includes the skin and lining surfaces of the internal body organs. There are enzymes in body secretions including lysozymes, phospholipases and defensins, which disrupt cell membranes promoting cell death. Periodically, the anatomical barriers are penetrated and an “acute inflammatory reaction” follows. The release of acute phase reactants: transferrin, CRP, interferon and interleukins, results in the cardinal signs of inflammation: calor/hot, rubor/red, dolor/painful and tumor/swelling.  The phagocytic cells including the neutrophils, macrophages, dendritic cells, natural killer or NK cells and eosinophils are the major players in identifying and responding to microscopic invaders. The phagocytic cells are directed to specific locations via cytokines, protein communicators of inflammation that identify, engulf and destroy pathogens.

These cells are primary players of the innate immune response – the oldest form of the host defense system. The innate immune response is triggered when microbes
(bacteria, virus and fungi) are detected. On or attached to the cell membranes of pathogens are commonly shared patterns (PAMPS). These include lipopolysaccharides(LPS), lipoteichoic acid, flagellin, RNA of viruses, amongst others. These molecules are recognized by receptors on the phagocytic cells called pattern recognition receptors (PRR).

One large group of the PRRs is a specific subgroup entitled Toll-like receptors (TLR). These highly specific receptors, numbered 1 through 13, identify and bind PAMPS, resulting in cytokine production triggering inflammation.

The complement cascade is also a major component of the innate immune response. The Complement system serves as an identifier and clearing house of pathogens by promoting vascular permeability, recruitment of phagocytic cells and ultimately the opsonization of bacteria and immune complexes. Opsonization refers to the coating and subsequent marking of bacteria for future destruction.

A large component of opsonization occurs in the spleen, which is why splenectomized patients particularly need vaccinations. Complement CH50 is a measure of total complement activity. Individuals with active autoimmune disease may have low levels of C3 and C4 due to  overactivity of the complement cascade.  This results in immune complex formation and the consumption of complement.

When the inflammation resolves, complement levels return to the normal range. Therefore, low levels of CH50 and C3 and C4 reflect active autoimmune disease, but higher levels do not.

Innate immune response is a non-antigen specific, immediate reaction. It does not produce immunological memory. For long-term protection, there is our adaptive or acquired immune response. Immunological memory is accomplished by the development of antibodies as our ready reserve defense force. Subsequent encounters with the same organism result in an enhanced response. There is a period of approximately 10-14 days for antigen-specific antibodies to be developed.

All cells of the immune system have their origin in the bone marrow. The myeloid series primarily produces the cells of the innate immune system including the neutrophils, monocytes and dendritic cells.  While the lymphoid series(lymphocytes) produces cells for the acquired or adaptive immune response, the T cells undergo differentiation into their distinct types under the influence of the thymus gland. B cells become mature in the lymph nodes and the spleen.

There is a tremendous amount of interaction between both systems, utilizing the myeloid series innate immune system for stimulation and activation of the acquired immune response. T-cells are involved in the cell-mediated immune response. They have no cytotoxic activity and do not kill infected cells or clear pathogens directly. Instead, they control the immune response by directing other cells to perform these tasks.

The cytokines the T-cells produce are the “protein communicators of inflammation.” Three important cytokines include TNF alpha and interleukins IL-1 and IL-6. These have been identified as primary players in autoimmune diseases including rheumatoid arthritis, psoriasis and psoriatic arthritis, Ankylosing spondylitis and inflammatory bowel disease(specifically Crohn’s disease) as well as Uveitis and Sarcoidosis.The T-cell begins as a “naïve” cell, which requires antigen presentation in order for it to become activated. These antigen-presenting cells (APC) include the macrophage, dendritic cell and the B cell.  The APC presents the antigen to the naive T-cell via its major histocompatibility complex (MHC) T-cell receptor (TCR). Depending on the APC cell type and the predominance of surrounding cytokines, T-cells differentiate in one of four directions:

1. TH 1 cells. APCs include the macrophages and dendritic cells. IL 12 and interferon (INF) gamma are the cytokines that drive differentiation. This type of T-cell usually develops from exposure to intracellular bacteria, fungus or viruses.

2. TH 17 cells. Neutrophils; IL 23, IL-1, IL-6. Usually from exposure of extracellular bacteria and fungi.

3. TH 2 cells. Eosinophils and basophils. IL-4. Usually from exposure to parasites.

4. T reg (regulatory) cells. Response to self-antigens. IL-10 and TGF beta. Down regulates autoimmune response.  There is however cross stimulation and inhibition
depending on which interleukin predominates. For instance, IL6 inhibits TGF beta, therefore driving TH 17 production and reducing T reg production, Alternatively, IL-4 while driving TH2 production inhibits TH 17 production.

Cell membranes of T-cells have cluster differentiation (CD) glycoproteins CD4 and CD8. Cells with the CD4 glycoprotein are referred to as helper cells, and those with
CD8 glycoprotein are referred to as cytotoxic T-cells. CD4 helper cells assist in the maturation of B cells into plasma cells and memory B cells. They also assist in the activation of cytotoxic T-cells and macrophages. Cytotoxic CD8 cells destroy viral-infected and tumor cells and also play a role in transplant rejection.

The humoral immune response is directed by B lymphocytes (B cells) differentiating into plasma cells which produce antibodies. The B cell develops through several stages. A B cell begins as a progenitor cell, then progresses to a pro-B cell and finally a pre-B cell. At this point, it leaves the bone marrow to mature in the lymph nodes and spleen where it becomes exposed to the pathogenic environment. As it matures, it develops three surface receptors – Blys, TACI and the B-cell receptor (BCR). When these receptors are bound, the cell matures and continues to exist. Failure to bind these receptors results in apoptosis or programmed cell death. This has become a recent important discovery since Benlysta, a new drug for the treatment of lupus, works by inhibiting Blys, the cell surface receptor.

These immunoglobulins are a hallmark of our defense system. We’re aware that deficiencies in any one of them or their subtypes results in the development of recurrent infections. Specific types of intravenous and subcutaneous gammaglobulin are available for those deficiency states. Memory B cells are formed from activated B cells that are specific to the antigen encountered during the primary immune response. These cells are capable of living “a long time” and can respond quickly following a second exposure to the same antigen.

B-1 cells and B-2 cells, B-1 cells express high levels of IgM greater than IgG and
are polyspecific – meaning that they have the ability to produce low-level response to many antigens.

Unlike the T cell, the B cell does not need the antigen presented to it. It recognizes the antigen in the blood or lymphatic system and engulfs it. It can then act as an antigen-presenting cell itself by displaying its antigen bound to its unique MHC on the cell surface allowing a T-cell to bind to it. Through a co-stimulatory mechanism necessitating a second binding site to be activated, cytokines can then be released. The cytokines released by that T-cell further propagate the B cell into its mature state, producing plasma cells and more immunoglobulin. Antibodies bind to their specific antigens forming immune-complexes. These complexes are then “cleaved” by the complement system and eliminated through the reticuloendothelial system.

Autoimmune diseases result from aberrant antibody production. These autoantibodies are actually produced on a regular basis by all individuals. Fortunately, more than 90 percent of them undergo spontaneous apoptosis and never progress. Anti-B cell medications predominantly work by interfering with the B cell during its maturation. Examples of these medications are being utilized in both oncology and rheumatology.

A baby’s immune defenses are passively transferred from the mother at birth. The baby’s own immune defenses take approximately three months to begin to function.



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