From the Director

What Did I Read This Week?
Submitted by: Coral Giovacchini, MD
Soyka, MB, et al. Scientific foundations of allergen-specific immunotherapy for allergic disease. Chest. 2014 Nov 1;146(5):1347-57
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Why Did I Read This: Allergy and Immunology is a very interesting field within internal medicine to which we often get very little exposure. This review article provides an excellent summary into the background and application of immunotherapy for allergic disease. Background: Allergic disease is among the most common diseases worldwide, with an exponentially rising prevalence. Symptoms can involve a wide array of organ systems (ENT, skin, upper/lower airways, GI tract, etc.), and patients may present not only to their primary physician, but also to a number of subspecialists with allergic symptoms. Broken down into the basics, allergens comprised of proteins are inhaled, ingested, or otherwise taken up leading to an IgE-mediated local or systemic inflammatory response. In thinking of immune tolerance, this is basically an adaptation of the immune system to external antigens/allergens. Somewhat paradoxically, it is an active immune response to a specific epitope/antigen that leads to clinical allergen tolerance; thus the ultimate goal for allergy therapy is to promote a change in the immune response for tolerance to a specific antigen. Generally physicians prescribe medications for symptom management including antihistamines, topical/systemic corticosteroids, leukotriene antagonists, and many others; however the only therapy for disease modification remains allergen-specific immunotherapy (AIT). Despite the fact that we have been using AIT for the last century, the exact mechanisms in the efficacy of AIT remain somewhat unclear. What We Know - Mechanisms of Allergic Inflammation: During sensitization, allergens are presented by dendritic cells to naïve T cells, resulting in a Th2 switch and derivation of a clonal allergen-specific T-cell population. Depending on the nature of the allergen and the host microenvironment, either immune tolerance develops, OR IgE sensitization cascades. In the setting of allergic sensitization, once a dendritic cell sees an allergic antigen, it will migrate to lymphoid tissues to activate T-cell maturation and mediate cytokine release. These activated Th2 cells will then drive naïve B cells to class switch to IgE. Specific IgE antibodies will engage their receptors on mast cells and basophils, prompting these cells to degranulate once exposed to the same allergen again. In this setting, degranulation releases the vasoactive amines and cytokines responsible for the ensuing type 1 hypersensitivity reaction, furthered by an attraction of eosinophils to the area driving a late-phase reaction in the affected tissues. What We’re Figuring Out – Immune Tolerance: Immune tolerance can be thought of as an adaptation to allergen exposure that down-regulates the allergic inflammation response and thus promotes a “tolerance” to exposure. There are two broad populations of T-regulator cells (native and inducible) and B-regulator cells that produce suppressive factors, such as IL-10 (acts as a immune response suppressor) and up-regulation of IgG4 (which competes with allergen-specific IgE binding sites to prevent the vasoactive degranulation of mast cells and basophils). Interestingly, IgG4 has evolved only in primates as likely an adaptive tolerogenic antibody. A normal human immune response to high dose allergen exposure is induction of immune tolerance. For example a beekeeper with a bee venom tolerance who experiences numerous beestings during a season will still mount an elevated IgE level, but will also have an elevated IgG4:IgE ratio (on the order of thousands!) than an individual with a bee venom allergy. The loss of an immune tolerance (i.e. development of an allergic response to an allergen to which one was previously tolerant), involves several mediators and is an active area of research currently given that there are likely numerous targets for AIT. Clinical Use of AIT: Currently AIT is utilized to ameliorate all symptoms of allergic disorders (including rhinitis, asthma, atopic dermatitis), and has been shown to restore immune tolerance, as well as inhibit development of new sensitizations in the future. Patients are selected via molecular diagnostics demonstrating sensitization to specific allergens. Immunotherapy vaccines are targeted with a mixture of allergen components with the goal of driving an elevated immune response. Current delivery options include the subcutaneous and sublingual routes, and both have favorable efficacy and safety profiles across broad patient populations including children and the elderly. Though there have not been any large head-to-head trials, SLIT may have a lower side-effect profile, and SCIT may be more beneficial for grass pollen AIT, per meta-analysis review. Conventional dosing regimens include treatments every 1-2 weeks with final therapies concluding after a period of several months. There are shorter course regimens and “rush”/”ultra rush” protocols which have been shown to provide safe and efficient results in the appropriate patient populations. Severe and/or uncontrolled asthma is an absolute contraindication to AIT and an FEV1 >70% should be demonstrated in any patient prior to starting therapy. If appropriate asthma control cannot be achieved with standard medication regimens, systemic anti-IgE immunomodulators (i.e. omalizumab) may be initiated as an adjunct to AIT in a carefully selected asthma population. In children with allergic asthma, concurrent AIT has demonstrated improvement in objective parameters in some small trials (i.e. decreased exhaled NOS, improved peak expiratory flow measures, and decreased frequency of asthma exacerbations); however more research is needed in these areas to show definitive results. Interestingly performing AIT in children with allergic rhinosinusitis, despite the high upfront cost, has been proven cost-effective by reducing and eliminating additional allergy and asthma drug cost long term. The Future Of AIT: Currently safety and appropriate patient selection for AIT remains a challenge. Some of the more significant side effects of AIT remain to be local inflammation and wheal formation in up to 50% of patients, which while perhaps not so much of a problem for SCIT, can be a larger issue for SLIT where oral pruritis and swelling can occur in up to 80% of patients. There are current approaches looking into novel route administration (such as intra-lymph node approaches) as well as physical coupling of allergens to immunomodulators, as an attempt to decrease the initial local and systemic inflammatory responses during AIT, respectively. Additionally, there is an active need for identification and validation of specific biomarkers that would predict a clinical response to AIT in patients with an allergic phenotype. In conclusion there are many opportunities for exciting research in the field of allergy and immunology with novel approaches evolving for AIT as a cure for a very widespread disease with global impact.[divider]
Clinic Corner
We welcome Christine Locklay our new Coumadin nurse and Laura Ferrell as our new LPN/triage.

- Forms: as courtesy to each other, please fill out the forms to the best of your knowledge (when reviewing chart). The worst case is to find a form in the resident mailbox that needed to be filled out 3 months earlier.
- Rooming patients on time: we are getting more staff but if there are times when it is busy, Its OK to room your own patients. remember to place a green dot next to pt name (that way we know the patient has been brought back).
- Switching patients: please let your attending know first. If your rooming nurse can switch the patients in epic, that would be great. Please do not go to the front desk to have this changed. Go to Nicole or Sharee first. Remember the allotted slots are different intern, jar and sar. if we switch a 1pm SAR pt to a 1:00pm intern, this creates 2 slots one at 1pm and does not fill the 1:20pm slot so the intern could have 6 patients scheduled.
- Mini Cex: we are doing great! Please make sure you pick one or two patients as one could no show. We are not limited to 3, we can do more. Observation helps with our professionalism and looks for areas of improvement. You need 3 for intern to see patients alone, 3 for JAR and SAR for multiple sign out.
- Its OK to ask for help! I know its against the Duke Culture to be quite and take the work. If you are overwhelmed, talk to your attending who can help redistribute patients or block slots.
- Due to printer problems in the room, all AVS are printing in the resident room.
QI Corner
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From the Chief Residents
Grand Rounds
Fri., Nov. 21: Rheumatology, Dr. Nancy Allen
Noon Conference
Date | Topic | Lecturer | Time | Vendor |
11/17/14 | Interview Day | Lunch w/ applicants | 12:00/MedRes | Picnic Basket |
11/18/14 | MED PEDS INTERVIEW | Lunch w/ applicants | 12:00/MedRes | |
11/19/14 | Resident M&M | Qi Team | 12:00/Room 2002 | Dominos |
11/20/14 | HVCC High Value Screening | Joel Boggan and Aaron Mitchell | 12:00/Room 2001 | Cosmic Cantina |
11/21/14 | Interview Day | Lunch w/ applicants | 12:00/MedRes |
From the Residency Office
Annual Thanksgiving Food Drive
On behalf of the Warren Society and the Residency Council, we are pleased to announce the start of the Annual Internal Medicine Residency Thanksgiving Food Drive! We will be collecting monetary donations via the PayPal link below, in cash (which we can collect in the MedRes office during normal office ours) or in check form, made payable to Duke University. In addition, we are happy to collect any canned or non-perishable food donations which can be delivered to the MedRes office or the ACR offices at Duke, the VA or DRH.All monetary donations will be used to purchased gift cards to local grocery stores and those, along with the food donations, will be delivered to the social workers at the DOC and VA clinics on November 21, 2014.Your generosity in the past has been inspiring and as we remain committed to supporting our local community, please help us provide for those families who may otherwise go without this holiday season.Many, many thanks!https://www.paypal.com/cgi-bin/webscr?cmd=_s-xclick&hosted_button_id=YN4YAUPCVJRYQABIM Summer 2015 Examination Dates
Please see the attached flyer for information on dates and registration!Stead Research Grant RFA
On behalf of the Stead Scholarship Committee, we would like to announce a Request for Applications for a clinical or translational research project involving a team of Internal Medicine, Med-Peds, and/or Med-Psych residents under the leadership of a faculty mentor in the Department of Medicine. The RFA is attached. We are grateful to the leadership of the Stead Scholarship Committee (Chris Woods, Karen Alexander and Ravi Karra) for this generous initiative to promote and support team-research by our residents. Best regards to all, Murat and AimeeChronic Hepatitis C Infection: Making the Decision to Treat
Join Andrew Muir, MD and Susanna Naggie, MD, MHS for a free live workshop for clinicians and patientsACP Abstracts Due!
Please find attached the information to submit abstracts by December 12, 2014 of your scholarly activities (case reports, research, QI projects) American College of Physicians NC Chapter Meeting Date: Feb 13,14 2015 Where: Sheraton RTP Submissions for abstracts due 12/12/14 http://www.acponline.org/about_acp/chapters/nc/abstract_comp.htm Wishing you all success with your projects ! Murat and AimeePartners In Health and BWH Hospitalist Program
PIH is currently seeking excellent physicians in Internal Medicine (or Internal Medicine/Pediatrics) to join our teams in Rwanda, Haiti, and Malawi for the 2015-2016 academic year . This full-time position provides an opportunity to serve as both a clinician educator at a PIH field site and as an academic hospitalist at Brigham & Women’s Hospital in Boston. Candidates interested in this exciting opportunity should submit an application at http://www.pih.org/pages/employment before December 1, 2014, or can contact Dr. Neil Gupta at ngupta@pih.org. Partners In Health and BWH Hospitalist Program Background: Partners In Health (PIH) is a health and social justice organization with a mission to build high quality, comprehensive public health systems around the world. PIH has partnered with local communities and governments over the past 25 years to provide high-quality health care to the poorest of the poor and train the next generation of physicians, nurses and public health professionals in countries around the world. General Description: We are currently seeking excellent physicians in Internal Medicine (or Internal Medicine/Pediatrics) with strong interest in global health and medical education to join our teams in Rwanda, Haiti, and Malawi. This full-time position provides an opportunity to serve as both a clinician educator at a PIH field site and as an academic hospitalist at Brigham & Women’s Hospital in Boston. Specific Responsibilities: Internists at PIH field sites serve as clinician educators, working with local medical staff and trainees on inpatient medical wards and outpatient clinics in rural districts hospitals and health centers as well as academic teaching centers. These clinician educators are faced with a vast diversity of diseases, including but not limited to, HIV, tuberculosis, malaria, non-communicable diseases, oncology, and other tropical infectious diseases. They also supervise international trainees and students rotating from Brigham & Women’s Hospital and other international institutions, engage in quality improvement and research activities, and help to develop and implement innovative programs to strengthen health delivery. Financial Support: The Brigham and Women’s/Faulkner hospitalist program provides hospitalist salary support and full benefits package, including malpractice insurance and health insurance. PIH provides international airfare as well as full accommodations while at PIH sites. Successful candidates will also have the opportunity for academic appointment at Brigham and Women’s Hospital and a diversity of professional development opportunities. Qualifications:- ABIM board-certification or board-eligibility in internal medicine or internal medicine / pediatrics; candidates with sub-specialty interests are welcome to apply
- Board-eligible graduating senior medical residents are eligible to apply
- A desire to gain experience with health care delivery in sub-Saharan Africa
- A talent for teaching and an interest in medical education and quality improvement
- Flexibility, humility, creativity and enthusiasm
- A two-year commitment is encouraged but not required
Information/Opportunities
Sign up to receive a complimentary e-subscription to The American Journal of Medicine in 2015! All you have to do is to complete the online form by December 8, 2014. The subscription starts in January. Internal Medicine Opportunities MD Fellowship Flyer V5 Financial Planning Webinar for New Physicians - CST Des Moines IM Opportunities STL_NocturnistFlyer STL__GenInternalMedicineFlyerUpcoming Dates and Events
November 27, 2014 - Turkey Bowl
December 3, 2014 - SAR Match Party
December 13, 2014 - DoM Holiday Party
February 18, 2015 - Duke vs UNC @ Tyler's Tap Room
February 27, 2015 - Charity Auction
March 3, 2015 - Duke vs UNC
Useful links
- https://intranet.dm.duke.edu/influenza/SitePages/Home.aspx
- http://duke.exitcareoncall.com/.
- Main Internal Medicine Residency website
- Main Curriculum website
- Ambulatory curriculum wiki
- Department of Medicine
- Confidential Comment Line Note: ALL submissions are strictly confidential unless you chose to complete the optional section requesting a response