Clinical and Health Affairs
2010 American College of Physicians Poster Competition Winners
Each year, the state chapters of the American College of Physicians invite medical students, residents, and fellows to take part in a scientific poster competition. Residents and students submitted more than 170 posters for consideration at the Minnesota chapter’s annual meeting in Minneapolis last November. Each of the internal medicine training programs (Abbott Northwestern Hospital, Hennepin County Medical Center, Mayo Clinic, and the University of Minnesota) was well-represented with submissions in the clinical vignette, research, and quality improvement categories.
Posters were judged by practicing internists as well as internists from the state’s academic medical centers. Each judge conducted “Poster Rounds,” which allowed the judge as well as the presenter’s peers the opportunity to view the poster being presented. Criteria used by judges included clinical relevance, originality, and written and visual presentation.
The Minnesota chapter will sponsor the winners in presenting their posters at the American College of Physicians’ annual meeting in San Diego in April. Congratulations to all of the participants on their excellent work.
Clinical Vignette Winner
Gout Encephalopathy: An Under-Recognized Complication of Crystalline Arthritis?
By Michael Wilson, M.D., Arthur Beyder, M.D., Ph.D., and Thomas Beckman, M.D., Department of Internal Medicine, Mayo Clinic
Rheumatological disorders are not frequently considered in the differential diagnosis of patients with delirium and fever. Previous studies have described patients with delirium secondary to calcium pyrophosphate deposition disease. However, we could find only one case report of a patient with delirium attributed to gout.
Case: A 72-year-old woman with a history of gout and mild cognitive impairment was admitted to the hospital after five days of confusion, functional decline, and knee pain. On presentation, her temperature was 38.3 degrees C, and she was oriented to name only. Physical examination revealed synovitis, erythema, warmth, and tenderness of the left knee and bilateral MCP, PIP, and DIP joints in her hands. Her white blood cell count was 19,000/mm3. Extensive testing for infection including chest X-ray, urinalysis, blood cultures, stool studies, cerebrospinal fluid analysis (with PCR for herpes, varicella, and West Nile Virus), computed tomography of the head and abdomen, and abdominal ultrasound was unremarkable. Arthrocentesis of her left knee revealed intracellular urate crystals with a negative gram stain and culture. The patient completed 48 hours of empiric intravenous antibiotics. Even after antibiotics were stopped after no infectious etiology was identified, the patient had continued delirium, fever, and leukocytosis. She was diagnosed with acute polyarticular gout and was subsequently treated with oral colchicine. Twenty-four hours after initiation of colchicine treatment, the patient’s delirium, fever, and leukocytosis completely resolved. At one- and three-month follow-up visits, the patient had continued baseline mental status.
Discussion: Up to 50% of patients with polyarticular gout present with systemic fever and leukocytosis. Monosodium urate crystals trigger the release of cytokines. Fever indicates that cytokines have crossed the blood brain barrier and reached the hypothalamus. Cytokines exert other effects on the central nervous system that have been implicated in the pathogenesis of delirium: decreased acetylcholine release, increased dopamine release, increased sleepiness, increased non-rapid eye movement sleep, increased slow-wave activity on EEG, neuronal injury, and seizures. Colchicine is a potent inhibitor of cytokines and, thus, may improve delirium associated with gout-induced cytokine release.
Conclusion: Acute polyarticular gout can present with delirium in addition to fever and leukocytosis. This case illustrates the challenge of evaluating a patient with altered mental status and highlights the importance of considering crystal deposition arthropathies in the differential diagnosis. Prompt diagnosis and treatment of polyarticular gout-induced delirium can lead to rapid improvement in mental status.
Research Winner
Comparative Genome Sequencing of an Isogenic Pair of Clinical MRSA Isolates Obtained during and after Daptomycin Treatment Failure
By Brett Gourley, M.D., Susan Boyle-Vavra, M.D., Marcus Jones, M.D., Mike Holmes, M.D., Rebecca Ruf, M.D., and Aaron DeVries, M.D., University of Minnesota
Staphylococcus aureus is a pathogen that causes a variety of human syndromes including skin and soft-tissue infections, endocarditis, osteomyelitis, and septic shock. The increasing prevalence of methicillin-resistant S. aureus (MRSA) infection in both community and health care settings has made beta-lactam antibiotics unreliable for empiric therapy of S. aureus infection. Moreover, the emergence of MRSA isolates with resistance to the glycopeptide vancomycin (Van) suggests that this agent may also become unreliable for treating MRSA infection.
Daptomycin (Dap) is a bactericidal lipopeptide antimicrobial that is effective against a broad spectrum of gram-positive bacteria including MRSA and vancomycin-resistant S. aureus. It was approved in 2003 by the U.S. Food and Drug Administration for treatment of complicated skin and soft-tissue structure infection, and in 2006 for bloodstream infection and right-sided endocarditis. However, failed treatment of S. aureus infection concomitant with the development of resistance to Dap has increased. Complicating matters is the fact that development of Van-intermediate resistance resulting from therapy with Van can sometimes lead to Dap cross-resistance. Conversely, stepwise incubation in increasing concentrations of Dap can increase the MICs of both Dap and Van.
Since Dap is often used as an alternative therapy for MRSA infection following treatment failure with Van, a better understanding of the mechanism of cross-resistance between Dap and Van is needed. Several recent studies have provided insight into the basis for development of Dap resistance in S. aureus. By performing comparative genomic sequencing, Friedman et al. identified polymorphisms in four genes (mprF, yycG, rpoB, and rpoC) associated with the development of Dap resistance following stepwise in vitro incubation of a Dap-susceptible MRSA isolate in Dap. Polymorphisms in mprF and yycG were subsequently found in clinical isolates by performing targeted DNA sequence comparisons of these genes between isogenic Dap-S and Dap-R clinical isolate pairs obtained pre- and post-Dap therapy. However, a genomewide sequence comparison has not been performed to date between a clinical Dap-R isolate and an isogenic Dap-S isolate.
We documented clinical Dap treatment failure in a patient with persistent MRSA bacteremia. Dap was administered after failure of initial therapy with Van and piperacillin/tazobactam. A pair of Dap-S/Dap-R isogenic MRSA isolates obtained before and after initiation of Dap therapy provided us with the opportunity to explore the mechanism of Dap resistance by performing a genomewide comparative analysis. To this end, we applied pyrosequencing technology to determine and compare the genome sequences of the two isolates. This allowed us to identify polymorphisms associated with Dap resistance obtained in vivo in association with Dap treatment failure.
Quality Improvement Winner
Improving Utilization of Palliative Care in End-Stage Heart Failure
By Andrew Olson, M.D., Sandra Schultz, M.D., Hamza Khalid, M.D., Yoel Korenfeld-Kaplan, M.D., James McCabe, M.D., Simon Lick, M.D., Malinda Jorgensen, M.D., and Paula Skarda, M.D., University of Minnesota
Heart failure is a leading cause of hospitalization and mortality in the United States. The progression of heart failure is characterized by a relapsing and remitting course that occurs over months to years. Unlike with other diseases that lead to death, it is difficult to provide an accurate prognosis for patients with heart failure. Thus, referrals to and utilization of palliative care are low among patients with end-stage heart failure.
Methods: We performed a literature review to identify risk factors for death within six months of admission for heart failure and examined these risk factors in 257 consecutive patients admitted to Regions Hospital in St. Paul from January 2009 to January 2010 using the heart failure order set. We analyzed this cohort of patients to determine which factors could be used to predict death within six months of admission for heart failure and which of these patients were referred to palliative care. We then used this information to create additional interventions to increase palliative care referrals for patients with severe heart failure.
Results: Our literature review identified four risk factors for death from heart failure within six months of hospital admission: decreased sodium level, decreased systolic blood pressure (SBP), increased blood urea nitrogen, and presence of peripheral arterial disease. Overall, 257 consecutive patients admitted with the heart failure order set between January 2009 and January 2010 were included in the analysis; 22% of these patients died within six months. Sixteen percent of patients were referred to palliative care. Those who were referred to palliative care were statistically more likely to be older (79 years versus 68 years, p< 0.05), have SBP lower than 120 mmHg (38% versus 23%, p<0.05), have two or more of the risk factors identified in the literature review (40% versus 12%, p<0.05), and have NYHA Class IV heart failure (40% versus 20%, p<0.05). Patients referred to palliative care were more likely to die within six months (40% versus 18%, p<0.05).
The four criteria identified, in conjunction with accurate classification according to the NYHA classification system, are useful in determining which patients with heart failure are appropriate candidates for referral to palliative care. Using these data, we modified the heart failure order set to include information for providers about risk factors for death within six months from heart failure and created a decision-support tool for providers to better identify which patients with heart failure are likely to benefit from palliative care. The order set encourages consideration of palliative care referrals for patients meeting the risk factors for death from heart failure within six months. A similar analysis will be conducted to determine whether the provider education and decision-support tool are helpful for increasing the number of appropriate palliative care referrals in hospitalized patients with heart failure.
Medical Student Winner
An Uncommon Cause of Chronic Diarrhea and Peptic Ulcer Disease
By Daniel C. Chan, Douglas A. Simonetto, Daniel K. Rogstad, Josephine F. Haung, Michael D. Leise, and Stephen C. Hauser, Mayo Medical School
Case: A 60-year-old male presents with a five-year history of progressively worsening daily, watery diarrhea. One year ago, the patient began vomiting daily and experienced progressive weight loss. During the past month, he experienced four episodes of intractable, voluminous diarrhea with ascending muscle cramps, upper extremity paresthesias, and near-syncope. Each of these episodes required hospitalization with electrolyte replenishment.
The patient’s medical history was significant for gastroesophageal reflux. Beginning four years ago, he was treated with 40 mg esomeprazole daily. His family history was unremarkable, and he denied significant tobacco or alcohol use. Before the patient was transferred to our center, he underwent laboratory testing and an EGD exam. His labs were remarkable for magnesium (0.0 mg/dL) and potassium (2.9 mmol/L). His VIP was normal at 44 pg/mL, albumin normal at 4.2 g/dL, and gastrin elevated at 663 pg/mL (normal < 100). The EGD revealed hypertrophic gastric folds of the body and antrum and a duodenal ulcer. Biopsies showed nonspecific hypertrophic hyperplastic gastropathy of the stomach with negative immunohistochemical staining for H. pylori and normal duodenum.
After arrival at our institution, the physical exam revealed a gentleman in mild distress with normal vital signs and an otherwise normal physical exam. The differential included screening for Menetrier disease, gastrinoma, lymphoma, and infiltrative diseases. A repeat EGD with EUS revealed a large quantity of gastric fluid, multiple duodenal ulcers extending well beyond the bulb, and a peri-pancreatic lymph node suspicious for an islet cell tumor. A triphase CT scan of the abdomen demonstrated a 7 mm hypervascular nodule in the medial wall of the descending duodenum, confirmed with an Indium In-111 pentetreotide study (OctreoScan). There was no evidence of hepatic metastasis on EUS, CT, or OctreoScan.
The patient subsequently underwent duodenotomy. A firm, mobile nodule on the medial wall of the duodenum was identified and excised. Pathology determined it was a 0.9 X 0.8 X 0.5 cm well-differentiated neuroendocrine neoplasm. The patient had no postoperative complications and reports complete resolution of his symptoms.
Discussion: This case highlights the classic features of a gastrinoma (Zollinger-Ellison syndrome) including pyrosis, dyspepsia, and large volume watery diarrhea accompanied by endoscopic findings of multiple duodenal ulcers. Sporadic gastrinomas have an incidence of only 0.1 to 0.2 per 100,000 persons. Gastrinomas consist of neuroendocrine cells that autonomously secrete gastrin, a peptide that normally stimulates acid secretion from parietal cells. Most gastrinomas originate in the duodenum and are less common in the pancreas. Gastrin has a trophic effect on the stomach resulting in hypertrophic gastropathy. Because of acid hypersecretion, multiple ulcers may be found and located as far distally as the jejunum. Treatment consists of high-dose proton pump inhibitor therapy and surgical resection. Prognosis is good for gastrinomas without liver metastasis, with patient survival being greater than 80% at 15 years as compared with only 30% at 10 years for those with liver metastasis. Sporadic gastrinoma is an uncommon cause of chronic diarrhea and peptic ulcer disease. MM