From the Director
Time keeps flying by! We capped off the week with an outstanding Grand Rounds by VA Chief Jason Webb, and were able to honor some of our residents and faculty with end of the year awards. Congratulations to our nominees and winners:
- 2013 Eugene Stead Award: Michael Blazing and Tom Holland
- VA Faculty Teaching Award: Kenneth Lyles
- Lecocq Award for Outstanding Senior Resident Talk: Scott Westphal, Dustin Norton, Megan Diehl
- Bruce Dixon Award: Zach Healy
role next year. As his final act as GME rep, Phil has scouted out the DMP call room...not too shabby!
Keep Calm and Maestro On!
Aimee
QI Corner:
Quality Improvement and Patient Safety Noon Conference Thank you to Dr. Zubin Eapen from the Duke Heart Center and his discussion of the management of CHF and the Same Day Access Heart Failure Clinic. And please join us for our next QI & PS conference on Wed, June 19. Dr. Bimal Shah will be discussing the Department of Medicine Quality Structure Quality Champion, May 2013 Congratulation to Dr. Matt Hitchcock, our Quality Champ for May 2013. Dr. Hitchcock was chosen based on his efforts to improve patient safety by participation in hospital medicine M&M. Thank you to Matt for providing high quality and safe patient care. If you would like to nominate someone for Quality Champ, please contact George Cheely, Ryan Schulteis, Joel Boggan, or Jon Bae [box]What Did I Read This Week
(submitted by David Butterly, MD)
Terminal Complement Inhibitor Eculizumab in Atypical Hemolytic-Uremic Syndrome NEJM , June 6 2013, 368: 2169-2181
[/box] This paper was published in this past weeks NEJM. We discussed this in Neprhrology Journal Club and one of the
authors, Larry Greenbaum from Emory, gave Nephrology Grand Rounds this past week, which gave me the opportunity to hear the findings and learn more about the disease process.
The Hemolytic-Uremic Syndrome is characterized by non-immune anemia, thrombocytopenia, and renal impairment. The disorder occurs most frequently in children and is generally heralded by diarrhea which is often bloody. Most cases are secondary to infection with E Coli which produce the Shiga-like toxin and can be seen with several other bacterial infections including Streptococcus pneumonia.
Approximately 10% of cases are classified as atypical since they are not associated with Stx-producing bacteria. Atypical HUS (a-HUS) has a poor prognosis with high mortality and progression to ESRD. Research has linked a-HUS to uncontrolled activation of the complement system. Genetic studies have linked a-HUS to a variety of abnormalities including complement factor H (CFH) deficiency, CFH point mutations, Autoantibodies against CFH, Abnormalities in Membrane Cofactor protein, and CFI, among others. Mutations in the complement system confer a predisposition for a-HUS and penetrance is in the 40-60% range, so that not all patients with the gene develop disease. Short-term and long-term outcomes vary according to the underlying genetic defect and complement abnormality. Roughly 60-70% of patients with CFH, CFI, or C3 mutations will lose renal function or die during the initial episode or develop ESRD after relapses of their disease. Kidney transplantation in these patients can also be problematic with very high recurrence rates ranging from 60-90%. Combined Kidney and Liver transplant may normalize complement abnormalities but is also associated with a high morbidity and mortality.
The present study reports the results of Phase I and II trials in patients with atypical HUS who were treated with Eculizumab. Eculizumab is a humanized monoclonal antibody which binds with high affinity to the C5 complement protein, preventing the generation of pro-inflammatory C5a and C5-9. It is currently FDA approved for the treatment of PNH and prior case reports have shown efficacy in atypical-HUS.
This is a multicenter, open labeled, study and reports on the outcomes in 37 patients (17 in Trial 1 and 20 in Trial 2) who received Eculizumab for a median of 64 and 62 weeks. The patients were enrolled at 27 centers across Europe and North America. The primary end points for the trial included a change in platelet count and thrombotic angiopathy event free status along with renal function and need for dialysis. Figure 1 (pg 2171) shows study design for the 2 Trials. ADAMTS13 activity less than 5% or evidence of Shiga toxin-producing E Coli infection were key exclusion criteria for the trials.
Demographics of the groups are shown in Table 1 (pgs 2174-75). Median age was 28 with ranges 13-68. Median time from diagnosis was 9.7 months in Trial 1 and 48 months in Trial 2. Patients were all receiving Plasma exchange at the time of enrollment. Median number of treatments was 17 (Trial 1) and 62 in Trial 2. The degree of renal insufficiency was significant (Creatinine 2.6-2.9) with median GFR 19 (Trial 1) and 28 ml/min (Trial II). 35% in Group I and 10% in Trial 2 were on dialysis at time of enrollment.
Primary endpoints for the studies are shown in Table 2 and Figure 2 (pages 2176-2178). Normalization or hematologic values (Platelet Count and LDH) occurred in 88% of patients in Trial 1 and 90% in Trial 2. In trial 1, 15 of 17 patients had Thrombotic Microangiopathy event free status and required no further Plasma Exchange.
Renal outcomes were similarly good with improved GFR in both trials. In trial 1, dialysis was discontinued in 80% of patients requiring HD prior to Eculizumab. Not surprisingly, earlier initiation of Eculizumab led to greater improvements in GFR.
The drug proved safe and was well tolerated in the groups. Of note, administration of Eculizumab has been associated with Meningococcal infections and all patients received vaccination and prophylaxis prior to enrollment. This study highlights the importance of complement dysregulation in the pathophysiology of atypical HUS. Terminal complement inhibition with Eculizumab was associated with improved hematologic parameters and renal function. For those wanting to learn more about the disease. I would also suggest the excellent review in the NEJM in 2009 by Norris and Remuzzi.
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From the Chief Residents
Grand Rounds
Date Chief Resident Grand Rounds June 21 Jeffrey Clarke, MDNoon Conference
| Date | Topic | Lecturer | Vendor |
| 6/17 | Renal Tubular Disorders | Dr. Greenberg | The Pita Pit |
| 6/18 | Med-Peds Conference: Young Adult Vaccinations | Sue Woods | Sushi |
| 6/19 | QI Patient Safety Conference | Jon Bae/Bimal | Saladelia |
| 6/20 | CCNC: innovative model of care management | Dr. Greenblatt | Moe's |
| 6/21 | Chair's Conference | Chiefs | Chic-fil-A |
Maestro Care - How to Make it Work For You
(submitted by Clay Musser, MD and Brian Griffith, MD)
[/box] Maestro "hot topics" will be continuing this week as shown below. Maestro Noon Conference Presentations- June 14th – Insulin Orders/Ordersets
- June 19th – Core Notes / Smartphrases
- June 20th – Core Ordersets
- June 21st - Cutover/Go-LIVE
- June 17th 5-6:30pm
- June 18th 4-5:30pm
From the Residency Office
Now Accepting Applications for Global Health Elective Rotations
The Hubert-Yeargan Center for Global Health (HYC) is now accepting applications for Global Health Elective Rotations for July 2014 and March 2015.
Application is open to residents from the Departments of Medicine and Pediatrics: Internal Medicine (PGY 2); Med-Peds (PGY 3); Med-Psych (PGY 4); Pediatrics (PGY 2).
The application and FAQ sheet are attached and available at http://dukeglobalhealth.org/education-and-training/global-health-elective-rotation.
Interviews will be held in late September/early October. For more information about this opportunity, contact Tara Pemble, Program Coordinator at tara.pemble@duke.edu or 668-8352.
Application Deadline: September 17, 2013
2013_GH_Rotations_Application
Addendum_GH_Rotation_Application
Kempner Society's Donation to Lincoln Community Health Center
The Kempner Society recently donated the proceeds from the Annual Stead Tread ($6,750) to the Lincoln Community Health Center. Pictured here are representatives of the group with Philip Harewood (Lincoln CEO) and Howard Eisenson (CMO). the residents present are Kevin, Marianna, and Meredith. Submitted by Matt Crowley, MD, Kempner Stead Group Leader
Contact Information/Opportunities
Upcoming Dates and Events
- June 20: Kerby Society Durham Bulls Outing
- June 21: Chief Grand Rounds - Jeffrey Clarke, MD
Useful links
- 2013 Life Support Offerings - January - June
- http://duke.exitcareoncall.com/.
- Main Internal Medicine Residency website
- Main Curriculum website
- Ambulatory curriculum wiki
- Confidential Comment Line Note: ALL submissions are strictly confidential unless you chose to complete the optional section requesting a response.
- Department of Medicine