AACR, Author Interviews, Cancer Research, Lung Cancer, Race/Ethnic Diversity, Surgical Research / 02.05.2016
Segregated Black Patients Less Likely To Receive Lung Cancer Surgery
MedicalResearch.com Interview with:
[caption id="attachment_23958" align="alignleft" width="150"]
Dr. Asal Mohamadi Johnson[/caption]
Asal Mohamadi Johnson, PhD, MPH
Assistant Professor of Epidemiology, Integrative Health Science
Stetson University
DeLand, FL 32723
MedicalResearch.com: What is the background for this study?
Dr. Johnson: Public health research is primarily focused on neighborhood poverty and racial disparities by illustrating differences between white and black individuals or communities. For example, it has been established that African Americans have higher cancer mortality rates and are less likely to receive appropriate treatment that whites. What we wanted to know in this study was the impact of living in segregated areas apart from other area level characteristics such as poverty or education. Instead of solely looking at health disparities between whites and black patients, our study focused on differences in survival among black patients with early stage Non-Small Cell Lung Cancer (NSCLC) living in different levels of neighborhood segregation.
Dr. Asal Mohamadi Johnson[/caption]
Asal Mohamadi Johnson, PhD, MPH
Assistant Professor of Epidemiology, Integrative Health Science
Stetson University
DeLand, FL 32723
MedicalResearch.com: What is the background for this study?
Dr. Johnson: Public health research is primarily focused on neighborhood poverty and racial disparities by illustrating differences between white and black individuals or communities. For example, it has been established that African Americans have higher cancer mortality rates and are less likely to receive appropriate treatment that whites. What we wanted to know in this study was the impact of living in segregated areas apart from other area level characteristics such as poverty or education. Instead of solely looking at health disparities between whites and black patients, our study focused on differences in survival among black patients with early stage Non-Small Cell Lung Cancer (NSCLC) living in different levels of neighborhood segregation.
Dr. Heli Malm[/caption]
Heli Malm, MD, PhD
Specialist in Obstetrics and Gynecology
Teratology Information Service
Helsinki University and Helsinki University Hospital
MedicalResearch.com: What is the background for this study? What are the main findings?
Dr. Malm: Animal studies have demonstrated that exposure to SSRIs during early brain development can result in depression-like behavior in adolescence. Today 6% of pregnant women in the US and 4% in Finland are on selective serotonin reuptake inhibitors (SSRIs) at some stage of pregnancy. SSRIs pass the placenta but no prior studies have followed children beyond childhood to monitor the development of depressive disorders, which typically emerge after puberty onset. Results on autism spectrum disorders (ASD) and attention-deficit/hyperactivity disorders (ADHD) have been conflicting.
The study material is based on national register data from Finland. We investigated offspring psychiatric diagnoses, including depression, anxiety, ASD, and ADHD, of nearly 16,000 mothers who had used SSRIs during pregnancy between 1996 and 2010. Children in this cohort ranged in age from 0 to 15 years old. Because maternal psychiatric illness can affect offspring neurodevelopment in the absence of SSRIs, primary comparisons were made between offspring of the SSRI group and offspring of mothers with a psychiatric disorder diagnosis but no antidepressant use.
Children exposed to SSRIs during gestation were diagnosed with depression at an increasing rate after age 12, reaching a cumulative incidence of 8.2% by age 15, compared to 1.9% in the group of children exposed to maternal psychiatric illness but no antidepressants. Rates of anxiety, autism spectrum disorder (ASD), and attention-deficit/hyperactivity disorder (ADHD) diagnoses did not differ significantly between the two groups.
Dr. Thijs Eijsvogels[/caption]
Thijs M.H. Eijsvogels, PhD
Department of Physiology
Radboud University Medical Center
Nijmegen, The Netherlands
MedicalResearch.com: What is the background for this study?
Dr. Eijsvogels: Regular exercise training is known to reduce the risk for future morbidity and mortality in the general and athletic population. For this purpose, national guidelines recommend to exercise 150 min/week at a moderate intensity or 75 min/week at a high intensity. Recent studies explored the dose-response relationship between weekly exercise volume and cardiovascular health and reported a potential U-shaped association, suggesting that high exercise volumes may attenuate the beneficial health effects.
The aim of the present study was to determine the relationship between lifelong exercise dose and the prevalence of cardiovascular morbidity in a physically active population. Therefore, we collected data in 21,266 participants of the Nijmegen Exercise Study.
Dr. Paul Nghiem[/caption]
Paul Nghiem, MD, PhD
Professor & Head, University of Washington Dermatology
George F. Odland Endowed Chair
Affiliate Investigator, Fred Hutchinson Cancer Research Center
Professor, Adjunct, of Pathology and Oral Health Sciences
Clinical Director, Skin Oncology, Seattle Cancer Care Alliance
UW Medical Center at Lake Union
Seattle WA 98109
MedicalResearch.com: What is the background for this study? What are the main findings?
Dr. Nghiem: Merkel cell carcinoma (MCC) is about 30 times less common than malignant melanoma, but about 3 times more likely to kill a patient than a melanoma. There is no FDA-approved therapy for this cancer & chemotherapy typically only provides about 90 days prior to the cancer progressing. Because of the strong links between MCC and the immune system, including the fact that most MCCs are caused by a virus, there was interest in trying to use immune checkpoint therapy to treat advanced Merkel cell carcinoma. The response to immune stimulation with anti-PD1 therapy was about as frequent as to chemotherapy (56% of patients responded) but importantly, among the responders, 86% remained in ongoing responses at a median of 7.6 months. While still early, this appears to be strikingly more durable than responses to chemotherapy.
Dr. Stephen Freedland[/caption]
Stephen J. Freedland, MD
Associate Director, Faculty Development Samuel Oschin Comprehensive Cancer Institute
Co-Director, Cancer Genetics and Prevention Program
Director, Center for Integrated Research in Cancer and Lifestyle
Professor, Surgery
Warschaw Robertson Law Families Chair in Prostate Cancer
Cedars-Sinai, Los Angeles
MedicalResearch.com: What is the background for this study? What are the main findings?
Dr. Freedland: PSA is a marker of prostate pathology. While often used to screen for prostate cancer, it is not prostate specific and can be elevated due to inflammation or enlarged prostate or other reasons. Whether it predicts the development of urinary symptoms is not clear. Among men with minimal to no urinary symptoms, we found that the higher the PSA, the greater the risk of future development of urinary symptoms.
MedicalResearch.com: What should clinicians and patients take away from your report?
Dr. Freedland: The readers should know that if a man has an elevated PSA and a negative prostate biopsy, the higher the PSA, the greater the risk of future urinary symptoms. These are men who may need closer follow-up.
Dr. Jacqueline French[/caption]
Jacqueline French, MD
Professor, Department of Neurology
Director Translational Research& Clinical Trials Epilepsy
NYU Langone Medical Center
MedicalResearch.com: What is the background for this study?
Dr. French: Tuberous sclerosis complex (TSC) is a disease associated with abnormal cell growth, caused by dysfunction of the TSC1 or TSC2 genes and dysruption of the MTOR pathway, which leads to cortical malformations, neuronal hyperexcitability, and seizures. Seizures in patients with TSC often start within the first year of life, and tend not to respond to traditional treatments. Everolimus is a marketed drug that has been used to treat other manifestations of TSC (including giant cell tumors of the brain, renal angiomyolipomas, and angiofibromas of the skin).
This study was a placebo-controlled add-on study of everolimus for the treatment of refractory seizures in children and adults with epilepsy.Following an 8-week baseline phase, patients aged 2-65 years (stratified by age) with TSC and refractory seizures on 1-3 antiepileptic drugs were randomized to EVE LT or HT Cmin target ranges or placebo, and treated in an 18 week Core Phase (6-wk titration + 12-wk maintenance). Primary endpoints were change from baseline in average weekly frequency of TSC-seizures (seizures not previously shown to be generalized in onset by EEG), expressed as response rate (≥50% reduction [RR]), and percentage reduction.
MedicalResearch.com: What are the main findings?
Dr. French: Overall, 366 patients were randomized to EVE LT (n=117), HT (n=130), or placebo (n=119). The median percentage reduction in TSC-seizures was significantly greater with EVE LT (29.3%, P=0.003) and HT (39.6%, P<0.001) vs placebo (14.9%). RR was also significantly greater with EVE LT (28.2%, P=0.008) and HT (40%, P<0.001) vs placebo (15.1%). The most frequent ≥10% all grade adverse events (AEs) reported with EVE LT/HT vs placebo included stomatitis (28.2%/30.8% vs 3.4%), diarrhea (17.1%/21.5% vs 5%), mouth ulceration (23.9%/21.5% vs 4.2%), nasopharyngitis (13.7%/16.2% vs 16%), upper respiratory tract infection (12.8%/15.4% vs 12.6%), aphthous ulcer (4.3%/14.6% vs 1.7%), and pyrexia (19.7%/13.8% vs 5%). Discontinuations due to AEs (5.1%/3.1% vs 1.7%) were low.
Dr. Alexander Egeberg[/caption]
Alexander Egeberg, MD PhD
National Allergy Research Centre, Departments of Dermato-Allergology and Cardiology
Herlev and Gentofte University Hospital
University of Copenhagen
Hellerup, Denmark
MedicalResearch.com: What is the background for this study? What are the main findings?
Dr. Egeberg: Certain proteins and inflammatory processes have been found in increased levels in the skin of patients with rosacea, and these have also been linked to dementia, in particular Alzheimer's disease. While this may be one potential explanation, we cannot say for sure that this is the cause. Our team have recently shown a link between rosacea and other neurological diseases, and single-case reports have previously described a possible association between rosacea and Alzheimers disease.
However, this is the first comprehensive investigation of Alzheimer's disease in a large population of patients with rosacea. We found a slightly increased risk of dementia, in particular Alzheimer's disease in patients with rosacea.
Dr. Stephen Freedman[/caption]
Stephen B. Freedman MDCM, MSc,
Associate Professor
Department of Paediatrics, Sections of Emergency Medicine and Gastroenterology;
ACHRI Healthy Outcomes Theme Group Leader
Alberta Children’s Hospital, and Alberta Children’s Hospital Research Institute
University of Calgary,
Calgary, Canada
MedicalResearch.com: What is the background for this study?
Dr. Freedman: As a pediatric emergency medicine physician I continue to see large numbers of children who are brought for emergency care because of vomiting and diarrhea. In speaking with their caregivers it is clear that many of them try to administer electrolyte maintenance solutions at home but the children either refuse to drink them or they continue to vomit. As a researcher I have noticed that many children continue to receive intravenous rehydration despite not being significantly dehydrated and it appeared that this was often a physician’s response to a failed oral rehydration challenge in the emergency department, either due to refusal to consume the electrolyte maintenance solution supplied or because the children became more nauseous due to the poor palatability of the solution. It appeared that perhaps a less dogmatic approach aimed at providing fluids that children actually like, might overcome these problems leading to improved outcomes.
MedicalResearch.com: What are the main findings?
Dr. Freedman: Children with mild gastroenteritis and minimal dehydration experienced fewer treatment failures when offered dilute apple juice followed by their preferred fluid choice compared with those instructed to drink electrolyte maintenance solution to replace fluid losses. We found the benefit was greatest in those 24 to 60 months of age. The group provided and instructed to take their preferred fluids were administered intravenous rehydration less frequently.
Dr. Steven Hicks[/caption]
Steven Daniel Hicks, M.D., Ph.D.
Penn State Hershey Medical Group Hope Drive, Pediatrics
Hershey, PA 17033
MedicalResearch.com: What is the background for this study? What are the main findings?
Dr. Hicks: This research was inspired by results of the CHARGE study (examining environmental influences on autism) which showed that specific pesticides (including pyrethroids) increased the risk of autism and developmental delay, particularly when mothers were exposed in the 3rdtrimester.
We recognized that the department of health sprayed pyrethroids from airplanes in a specific area near our regional medical center every summer to combat mosquito borne illnesses. We asked whether children from those areas had increased rates of autism and developmental delay. We found that they were about 25% more likely to be diagnosed with a developmental disorder at our medical center than children from control regions without aerial spraying of pyrethroids.
Dr. J. William Harbour[/caption]
Dr. Lisa Romero[/caption]
Lisa Romero DrPH, MPH
Division of Reproductive Health
National Center for Chronic Disease Prevention and Health Promotion
CDC
MedicalResearch.com: What is the background for this study? What are the main findings?
Dr. Romero: Since 2006, teen birth rates have fallen almost half among Hispanic and black teens; dropping the national teen birth rate to an all-time low. While dramatic declines among Hispanic and black teens have helped reduce gaps, birth rates remain twice as high for these teens nationally compared to white teens, and more than three times as high in some states. Data also highlight the role socioeconomic conditions play, finding that higher unemployment and lower income and education are more common in communities with the highest teen birth rates, regardless of race.
Dr. Keir Menzies[/caption]
Keir Menzies PhD
Assistant Professor
University of Ottawa Brain and Mind Research Institute
University of Ottawa
MedicalResearch.com: What is the background for this study? What are the main findings?
Dr. Menzies: Currently there is significant amount of research identifying the power of stem cells to regenerate damaged or aging tissue. Our research discovered that reduced stem cell health was linked to unusually low levels of a small molecule called NAD, one of the most important cellular molecules to maintain the performance of mitochondria, the engine of the cell. Then by boosting NAD levels, using a special form of vitamin B3 called nicotinamide riboside, stem cells could be rejuvenated during aging by improving mitochondrial function. We then go on to show that by improving stem cell function we could prolong the lifespan of mice, even when the treatment began at a relatively old age.
Dr. Jonathan Slaughter[/caption]
Jonathan Slaughter, MD, MPH
Assistant Professor of Pediatrics
Center for Perinatal Research
Nationwide Children's Hospital/The Ohio State University
Columbus, OH 43205
MedicalResearch.com: What is the background for this study?
Dr. Slaughter: Increasing data has emerged over the last decade showing potential harm following acid suppression use in newborns, older children, and adults. There are virtually no published data that show acid suppression via histamine-2-receptor antagonists (H2RAs) or proton-pump inhibitors (PPIs) is effective for gastroesophageal reflux disease (GERD) treatment or for other indications (stress ulcer prophylaxis, post-operative acid suppression) in healthy or sick newborns. Given the potentially limited effectiveness of these medications and increasing safety concerns following H2RA/PPI use in infants, we wanted to evaluate the frequency and duration of H2RA/PPI use among infants hospitalized within US children's hospital neonatal intensive care units (NICUs) to determine if these drugs appeared to be overused and if use appears to have changed over time. We also evaluated neonatal diagnoses associated with acid suppression to identify targets for future studies that may evaluate the usefulness of acid suppression in neonates following a given diagnosis.
Dr. Ashley Kranjac[/caption]
Ashley Wendell Kranjac, PhD
Department of Sociology and
Kinder Institute for Urban Research
Rice University
Houston, Texas and
[caption id="attachment_23893" align="alignleft" width="125"]
Dr. Robert Wagmiller[/caption]
Robert L. Wagmiller, Jr.
Associate Professor
Department of Sociology
Temple University
Philadelphia, PA 19122
MedicalResearch.com: What is the background for this study? What are the main findings?
Response: The Center for Disease Control recently reported a decline in child obesity amongst 2-to5-year old children between 2003/4 and 2011/12 (see, Ogden et al. 2014). We aimed to identify the sources of this decline because this change occurred in a relatively short period of time. What we found is that the decline in obesity did not occur due to the things that you might expect like changes in physical activity or dietary practices (although there were some differences in these factors across years). But, rather, what we found is that because there were differences in obesity rates for the youngest and oldest children in this age range in 2003/4, but not in 2011/12, that the decline in obesity exists. In other words, because the oldest children in 2003/4 had significantly higher obesity rates than the youngest children in this time period, but this effect is not observable in 2011/12, we see a decline in obesity.
Dr. Shelly B. Flagel[/caption]
Shelly B. Flagel, PhD
Molecular and Behavioral Neuroscience Institute
Department of Psychiatry
University of Michigan, Ann Arbor, MI 48109
MedicalResearch.com: What is the background for this study? What are the main findings?
Dr. Flagel: We used a unique genetic animal model to examine individual differences in addiction liability. This model of selectively bred rat lines allowed us to examine the brains of “addiction-prone” and “addiction-resilient” rats before and after they were exposed to cocaine. I
mportantly, even though all rats were exposed to the same amount of drug, only a certain subset exhibited addiction-like behavior. We focused our neurobiological analyses on two molecules that have been previously implicated in response to drugs of abuse – the dopamine D2 receptor and fibroblast growth factor (FGF2). We examined gene expression and the epigenetic regulation of these molecules and found that low levels of FGF2 in the core of the nucleus accumbens, a brain region known for regulating motivated behavior, may protect individuals from becoming addicted; whereas low levels of D2 in this brain region may predispose individuals to addiction.
Further, this is the first study to show that epigenetic modulation of these molecules may be a predisposing factor and that, the epigenetic regulation of D2 may be especially important in susceptibility to relapse.
Dr. Judith Lechner[/caption]
A.Univ.-Prof. Dr. Judith Lechner
Div. Physiology
Medical University of Innsbruck
Innsbruck Austria
MedicalResearch.com: What is the background for this study? What are the main findings?
Dr. Lechner: Women are not just small men. Sex differences affect most, if not all the organ systems in the body. Over the past decades biomedical researchers have been mainly using male models. Therefore, there is a significant gap in knowledge of female physiology except for organ functions involved in reproduction. While the necessity to fill in these gaps has been advocated, our understanding of sex and gender differences in human physiology and pathophysiology is still limited. This holds especially true for the kidneys, e.g. while international registries show that fewer women than men are in need of renal replacement therapy due to end stage renal disease, the potentially underlying causes are still not known.
The aim of our study was to find out, if hormone changes due to the female menstrual cycle would affect normal renal cells. For this purpose, urinary samples of healthy women of reproductive age were collected daily and analyzed for menstrual cycle-associated changes of marker proteins. Specifically, two enzymes (Fructose-1,6-bisphosphatase, Glutathione-S-transferase alpha) were measured, which are intracellular components of proximal tubular cells, a key population of renal cells. Upon cell damage, these enzymes are released into the urine, qualifying them as clinical markers for early detection of tubular injury. Since even in healthy persons low amounts of these enzymes can be detected in the urine, we used these marker proteins to analyze potential effects of the female hormone cycle on normal functioning of this cell population. As a result, we could detect transient increases of Fructose-1,6-bisphosphatase and Glutathione-S-transferase alpha correlating with specific phases of the female hormone cycle, namely ovulation and menses.
This finding suggests that cyclical changes of female hormones might affect renal cell homeostasis, potentially providing women with an increased resistance against kidney damages. Thus, recurring changes of sex hormone levels, as during the natural menstrual cycle, might be involved in periodic tissue re-modeling not only in reproductive organs, but to a certain extent in the kidneys as well.
Dr. Stacie Dusetzina[/caption]
Stacie B. Dusetzina, PhD
Assistant Professor
Division of Pharmaceutical Outcomes and Policy
Eshelman School of Pharmacy
University of North Carolina at Chapel Hill
Chapel Hill, NC
MedicalResearch.com: What is the background for this study? What are the main findings?
Dr. Dusetzina: Drug prices are of significant policy interest, particularly the prices for so-called “specialty” medications which are used to treat rare and/or complex conditions like cancer. In this study I estimated monthly price for orally-administered cancer treatments that were approved between 2000 and 2014. First I looked at the price of the drug during the year of initial FDA approval and then I looked at annual changes in the price after the year of approval. The main findings are that, even after inflation adjustment, the monthly price paid for orally-administered cancer treatments is increasing rapidly both at the time of approval and in subsequent years.
As an example, if you compare average monthly prices during the first year post-approval for treatments approved between 2000-2010 to those approved after 2010 there was a major increase in launch prices from $5,529 per month to $9,013 per month. Year-to-year changes in price after launch varied a lot by drug ranging from decreases in price of -2.7% per year to increases of 11.4% per year. However, nearly all of the products studied increased in price over time.
Donghao Lu[/caption]
Donghao Lu MD, PhD candidate
Department of Medical Epidemiology & Biostatistics,
Karolinska Institutet
Stockholm
MedicalResearch.com: What is the background for this study? What are the main findings?
Dr. Lu: Psychiatric comorbidities are common among cancer patients. However, whether or not there is already increased risk of psychiatric disorders during the diagnostic workup leading to a cancer diagnosis was largely unknown.
We found that, among cancer patients, the risks for several common and potentially stress-related mental disorders, including depression, anxiety, substance abuse, somatoform/conversion disorder and stress reaction/adjustment disorder started to increase from ten months before cancer diagnosis, peaked during the first week after diagnosis, compared to cancer-free individuals in Sweden.
Dr. Andrew Pecora[/caption]
Andrew L. Pecora, M.D., F.A.C.P., C.P.E.
Dr. Emamifar[/caption]
Dr. Amir Emamifar, MD
Department of Rheumatology
Odense university Hospital
Svendborg Hospital, Denmark
[caption id="attachment_23869" align="alignleft" width="139"]
Dr. Hansen[/caption]
Associate Professor
Dr. Inger Marie Jensen Hansen, PhD, DMsci
Department of Rheumatology
Odense university Hospital
Svendborg Hospital
University of Southern Denmark
MedicalResearch.com: What is the background for this study?
Response: Rheumatoid arthritis is a systemic, inflammatory disease that affects 1% of the general population. Apart from main articular manifestations, rheumatoid arthritis may involve other organs including heart, lung, skin, and eye. The auditory system can be affected during the course of the disease as well; however the association between rheumatoid arthritis and hearing impairment has not been clearly defined. It seems that hearing impairment in rheumatoid arthritis is a multifactorial disease affecting by environmental factors and disease and patient characteristics. We did a comprehensive review of all published data to reveal the potential link between rheumatoid arthritis and hearing impairment.
Dr. Haicong Li[/caption]
Haicong Li
Director and Professor, Department of Geriatrics
China-Japan Friendship Hospital
Beijing, China.
MedicalResearch.com: What is the background for this study? What are the main findings?
Response: Based on our clinical observations over the years, we noticed two common
phenomena:
Dr. Sherry Grace[/caption]
Sherry L. Grace, PhD
Professor, School of Kinesiology and Health Science
York University
Sr. Scientist, Cardiorespiratory Fitness Team
Toronto Rehabilitation Institute, University Health Network
Toronto Western Hospital
Toronto, ON
MedicalResearch.com: What is the background for this study?
Dr. Grace: Cardiac rehabilitation is an outpatient chronic disease management program. It is a standardized model of care, comprised of risk factor assessment and management, exercise training, patient education, as well and dietary and psychosocial counseling. Patients generally attend two times a week for several months.
Participation in cardiac rehab has been shown to reduce death and disability. This is a dose-response association, such that more cardiac rehab participation is associated with even less death, etc. Therefore, it is important that patients adhere to the program, or participate in all the prescribed sessions.
No one has ever reviewed patient adherence to cardiac rehab in a systematic way. It has always been assumed that patients only attend about half of prescribed sessions. Also, many studies have shown that women attend fewer sessions than men. However, this has been known for some time, so we would hope that in the current era, this sex difference would not exist. No study has ever aggregated and analyzed sex differences in program adherence, so we set out to do this.
Evelyn Parr[/caption]
Evelyn Parr
Research Officer / PhD Candidate | Centre for Exercise and Nutrition
Mary MacKillop Institute for Health Research
Australian Catholic University
MedicalResearch.com: What is the background for this study? What are the main findings?
Response: Results from previous investigations suggest that compared to a healthy 'control' diet, increased consumption of dairy foods in an energy restricted diet lead to improved body composition (i.e., a loss of fat mass and the maintenance of lean mass).
We investigated the effects of manipulating the type of dairy foods (i.e., low- or high fat) within high protein, energy restricted diets on body composition and selected health parameters. Eighty-nine middle-aged (35-59 y), male and females who were overweight or obese completed a 16 week intervention comprising 3 d/wk supervised resistance training and 4 d/wk unsupervised aerobic -based exercise (i.e. walking). During this time they consumed a diet that was energy restricted by 250 kcal/d comprising either
1) high protein, moderate carbohydrate (4-5 normal fat dairy product servings),
2) high protein, high carbohydrate (4-5 low-fat, carbohydrate sweetened dairy product servings or
3) a control diet of moderate protein, high carbohydrate diet (1-2 dairy servings).
We found that in the face of energy restriction, when protein intakes were above the recommended daily intakes (>0.8 g/kg body mass) and regular exercise was completed, there was no difference in the loss of fat mass (~8 kg) when participants consumed 4-5 serves of dairy products in either low- or high-fat. Furthermore, participants maintained lean (muscle) mass throughout the energy restricted period.
Prof. Rudi Beyaert[/caption]
Professor Rudi Beyaert
VIB - Inflammation Research Center Ghent University
Department for Biomedical Molecular Biology Unit of Molecular Signal Transduction in Inflammation
Technologiepark Ghent) Belgium
MedicalResearch.com: What is the background for this study? What are the main findings?
Prof. Beyaert: The interest of my laboratory is in understanding the molecular mechanisms that are responsible for the development of inflammatory diseases such as Crohn's disease, multiple sclerosis, rheumatoid arthritis and also psoriasis, which is the topic of the published study. We already know that genetic factors can determine the onset of these inflammatory diseases, but how these genetic factors drive an inflammatory response is still largely unclear. We were specifically interested in the CARD14 gene, because patients with mutations in CARD14 have a very high chance to develop psoriasis. Psoriasis-associated mutations in CARD14 trigger specific skin cells (keratinocytes) to produce and release large amounts of other proteins that recruit and activate specific white blood cells driving an inflammatory response. We now discovered that this effect is dependent on the physical interaction of CARD14 with the protease MALT1 in keratinocytes, leading to the activation of its enzymatic activity and the MALT1-mediated cleavage and inactivation of a number of cellular proteins that normally keep our immune system in check. Treatment of skin cells with small compound MALT1 inhibitors prevents the CARD14-induced production of several pro-inflammatory mediators.
Dr. Babak Hooshmand[/caption]
Babak Hooshmand, MD, PhD, MPH
Center for Alzheimer Research–Aging Research Center
Karolinska Institutet
Stockholm University, Stockholm, Sweden
Department of Neurology, Klinikum Augsburg
Augsburg, Germany
MedicalResearch.com: What is the background for this study? What are the main findings?
Dr. Hooshmand: Low and subnormal levels of vitamin B12 as well as high levels of homocysteine (a vascular risk factor and neurotoxic amino-acid associated with B12 deficiency) are common conditions in the elderly and are associated with a variety of disorders, including cardiovascular and cerebrovascular
conditions. Our study showed that over 6-year of follow-up, both low vitamin B12 status and high homocysteine levels are associated with accelerated brain atrophy in older adults, which precedes clinical dementia.
Prof. Christian Virchow[/caption]
Prof Dr. med. J. Christian Virchow, FRCP, FCCP, FAAAA
University of Rostock, Germany
What is the background for this study? What are the main findings?
Dr. Virchow: House Dust mite related allergic asthma is a very frequent chronic disease. Allergen Immunotherapy (AIT) for this condition in asthma has not been well studied and subcutaneous treatment has been associated with (systemic, potentially serious) side effects. Aim of the study was to investigate, if sublingual AIT can improve a patient relevant endpoint, namely reduce the frequency of exacerbations (primary endpoint: time to first exacerbation compared to placebo) .
Dr. Tanush Gupta[/caption]
Tanush Gupta, MD
Chief Resident & Instructor of Medicine
Department of Medicine
New York Medical College & Westchester Medical Center
Valhalla, NY
MedicalResearch.com: What is the background for this study? What are the main findings?
Dr. Gupta: Cigarette smoking is the leading preventable cause of premature death in the United States (U.S.). Approximately one-third of all coronary artery disease related deaths in the U.S. annually can be attributed to cigarette smoking. However, studies from the pre-thrombolytic and thrombolytic eras have shown that mortality in smokers with ST-segment elevation myocardial infarction (STEMI) may be lower than in nonsmokers, a phenomenon called the “smoker’s paradox.”
The majority of STEMI patients in contemporary practice are treated with primary percutaneous coronary intervention (pPCI). Data on the association of smoking with outcomes in STEMI patients undergoing pPCI are limited and also conflicting as to whether the smoker’s paradox exists in this population. Hence, the purpose of our study was to examine the association of smoking status with in-hospital outcomes in a nationwide cohort of STEMI patients undergoing pPCI, included in the U.S. National Inpatient Sample, over a 10-year time period from 2003 to 2012. Our primary outcome of interest was in-hospital mortality and secondary outcomes were post-procedure hemorrhage, in-hospital cardiac arrest, and average length of stay.
Of 985,174 STEMI patients who underwent pPCI in the U.S. over this time period, 438,954 (44.6%) were smokers. Smokers were on an average 8 years younger than nonsmokers and had lower prevalence of most cardiovascular comorbidities. Smoking status was associated with lower risk-adjusted in-hospital mortality (2.0% vs. 5.9%, adjusted OR 0.60, p<0.001), lower incidence of post-procedure hemorrhage (4.2% vs. 6.1%, adjusted OR 0.81, p<0.001) and in-hospital cardiac arrest (1.3% vs. 2.1%, adjusted OR 0.78, p<0.001), and shorter average length of stay (3.5 days vs. 4.5 days, p<0.001). To assess whether younger age of smokers was influencing the association with in-hospital mortality, we also performed an age-stratified analyses in different age groups. The smoker’s paradox largely persisted in age-stratified analyses suggesting that younger age of smokers was not the sole explanation for this paradox.
We performed additional assessment for confounding to explore whether the paradoxically lower risk-adjusted in-hospital mortality in smokers with STEMI was driven by differences in baseline demographics and comorbidities between hospitalized smokers and nonsmokers in general. To test for such confounding, we examined the association of smoking with in-hospital mortality in 2 conditions in which this association has not been previously studied – hip fractures and severe sepsis – using similar statistical regression models. In both these study populations, smokers were on average younger than nonsmokers and had lower risk-adjusted in-hospital mortality, but, the paradoxical association in both these conditions was weaker in magnitude than in STEMI patients. Since there is no cogent biological hypothesis to explain the lower mortality in smokers with sepsis or hip fractures, it is likely that the smoker’s paradox in STEMI is also at least partly driven by residual confounding due to inadequate adjustment for the biological effects of age. However, as this paradox was stronger in STEMI patients than in patients with hip fractures or severe sepsis, we believe that additional true biological differences between smokers and nonsmokers with STEMI also contribute to the paradoxically lower in-hospital mortality.