ABSTRACT
2018 Winners at the Maryland Chapter, ACP Mulholland Mohler Residents Meeting
KEYWORDS:
1st Place Oral Research Winner Mulholland Mohler Residents Meeting – Maryland Chapter 2018 – Dr. Rachit Vakil, Johns Hopkins/Broadway – The Association of Baseline ST. Point Elevations and Mortality: Results from MESA and ARIC
Drs. Rachit M. Vakil, David Tian, Yiyi Zhang, Eliseo Guallar, Elsayed Z. Soliman, Susan R. Heckbert, Gordon Tomaselli, Wendy Post, David A. Bluemke, Leonard Ilkhanoff, Joao Lima, Moyses Szklo, Saman Nazarian
Purpose: Prior studies suggest that ST elevation at the J-point is associated with elevated risk of death. We sought to examine the prevalence and prognostic importance of elevation at various ST points in a large multi-ethnic population.
Methods: After confirming data harmonization, we combined ECG, demographics, and mortality data for 19,578 participants from the Atherosclerosis Risk in Communities Study and the Multi-ethnic Study of Atherosclerosis population-based cohorts. The average age at baseline was 56.1 ± 8.1 years and 56.2% of the participants were female. Participants were stratified by the presence of ≥ 1 mm inferior (0.5%), lateral (27.8%), inferior or lateral (29.3%), and inferior and lateral (0.2%) ST elevation (at the J-point, mid-point, 60ms after the J-point, and end-point). We utilized models adjusted for age, gender, ethnicity, source cohort, BMI, education, heart rate, hypertension, left ventricular hypertrophy, smoking status, diabetes, LDL, HDL, and aspirin and/or statin therapy.
Results: Inferior ST elevation at any ST point was associated with increased mortality (HR 1.94, 95%CI 1.32 – 2.84). In contrast, lateral elevation at any ST point was associated with decreased mortality (HR 0.88, 95%CI 0.81 – 0.95). ST-end elevation was more common and drove the association of lateral elevation with decreased mortality. The magnitude of association between inferior ST elevation and increased mortality was strongest when occurred at the mid-ST or J-points. Although the prevalence of elevation varied among subgroups, no additive or multiplicative interactions were noted with gender or ethnicity.
Conclusions: We found that asymptomatic inferior lead ST elevation is uncommon and is associated with elevated risk of mortality regardless of ethnicity. In contrast, asymptomatic lateral ST elevation at the ST-end point is common and is associated with lower risk of mortality.
1st Place Oral Clinical Vignette Mulholland Mohler Residents Meeting – Maryland Chapter 2018 – Dr. Shayam Kolangara – Sinai Hospital – A case of Strongyloides Stercoralis Superinfection Treated with Veterinary Ivermectin Preparation
Drs. Shyam Kolangara, James Ladd, Jeremy Gradon
Introduction: Strongyloides stercoralis is a parasitic infection endemic to tropical countries, usually affecting the immigrant population in the USA. The cycle of autoinfection permits its presence for decades in an immunocompetent host with only minor symptoms. However, when the host becomes immunocompromised, such as in the event of a severe illness, a disseminated disease or hyperinfection syndrome can develop that often proves to be fatal.
Case presentation: A 77-year-old man from Trinidad and Tobago presented with nausea, vomiting, poor appetite, abdominal pain and altered mental status. He also noted coffee ground emesis and melena. On examination, he was cachectic with marked epigastric tenderness and decreased bowel sounds. Patient’s mental status deteriorated upon admission and he soon became unresponsive and hypotensive, which prompted a transfer to the intensive care unit for intubation, mechanical ventilation and vasopressor support. An esophagogastroduodenoscopy was done and biopsy revealed the presence of strongyloides stercoralis. Albendazole and oral ivermectin were initiated through a nasogastric tube, but given the intestinal ileus, absorption was questionable. Therefore, measures were taken to obtain a veterinary subcutaneous ivermectin formulation and a request was submitted to the Food and Drug Administration (FDA) for compassionate use. Following the FDA approval, oral preparation was discontinued, and the subcutaneous formulation was administered along with oral albendazole. A lumbar puncture was unrevealing, but the patient was given empiric meropenem for suspected concurrent gram-negative meningitis. Since the patient remained intubated for 21 days, a tracheostomy and percutaneous gastrostomy tube placement were performed. He was eventually weaned from ventilator and vasopressor support, and was subsequently transferred to the acute care floor.
Discussion: Critically ill patients infected with strongyloides stercoralis can develop hyperinfection syndrome, which is dangerous and challenging to treat, especially if concomitant intestinal malabsorption is present. Since parenteral ivermectin is not approved in humans, an unorthodox approach may be needed with the use of a veterinary formulation of subcutaneous ivermectin, which will require FDA approval. Thus, when dealing with a patient population at risk for strongyloides infection, it is prudent to have different formulations of antiparasitic agents readily available and seek early FDA approval for the use of veterinary preparations.
1st Place Poster Research Winner Mulholland Mohler Residents Meeting – Maryland Chapter 2018 – Dr. Amir Ansari, Medstar Health Internal Medicine, Baltimore, MD – Blockade of Sonic Hedgehog Signalling Pathway; A Novel Preventive Approach for Esophageal Adenocarcinoma
Drs. Amir Ansari, Tomoharu Miyashita, Guy P. Marti, Ken-ichi Mukaisho, Elizabeth Montgomery, Michelle Rudek-Renaut PharmD, Christine Chung, Ronan Joseph Kelly, John W. Harmon, FACS, Johns Hopkins University School of Medicine, Baltimore MD
Background: Up-regulated progenitor cell proliferation induced by abnormal activation of the Sonic Hedgehog (SHH) signalling pathway contributes to carcinogenesis in the esophagus and SHH is considered a leading candidate as a molecular mediator of Barrett’s Esophagus. Inhibitors of the SHH cascade, such as the antifungal itraconazole, could potentially play a useful role in preventing this devastating disease.
Methods: A surgical model of Barrett’s metaplasia and Esophageal cancer was utilized to investigate the potential of Itraconazole, a SHH inhibitor, to prevent adenocarcinoma in laboratory rats. The jejunum was anastomosed to the Esophagus using a previously published, reflux model. A pharmacokinetic experiment showed that 200 mg/kg of Itraconazole intraperitoneally weekly, produced a mean esophageal tissue concentration of 0.7uM. Weekly intraperitoneal injections of saline (control group) or Itraconazole were performed starting at 24 weeks subsequent to surgery when Barrett’s metaplasia first appears. Esophageal tissues were harvested 40 weeks after the surgery. H&E stained sections were evaluated according to the presence or absence of adenocarcinoma.
Results: Barrett’s metaplasia was present in almost all the rats: Control Saline 29/31 (93%), versus Itraconazole 22/24 (91%). The incidence of adenocarcinoma was lower in the Itraconazole group: Control Saline 10/31 (32%) versus Itraconazole 2/24 (8%). P-value < 0.05.
Conclusion: The weekly dosage of 200 mg/kg Itraconazole was selected as it produced tissue levels that were in the effective range at a dosage that could be tolerated in humans. Rats in the Itraconazole treatment group displayed significantly fewer adenocarcinomas than did the control group rats receiving saline. Itraconazole, a known Hedgehog pathway inhibitor, deserves consideration as an agent to impede the progression of Barrett’s metaplasia to oesophageal adenocarcinoma.
1st Place Clinical Vignette – Mulholland Mohler Residents Meeting- Maryland Chapter 2018 – Dr. Puneet Ghotra, Medstar Health Internal Medicine, Baltimore, MD – Trimethroprim-Sulfamethoxazole-induced Hypoglycaemia in a Non-diabetic Patient with AIDS & Normal Renal Function
Drs. Puneet Ghotra, Nargiz Muganlinskaya; MedStar Health Internal Medicine, Baltimore, MD
Trimethoprim-sulfamethoxazole (TMP-SMX)-induced hypoglycaemia has been reported with concomitant use of sulfonylureas or meglitinides in diabetic patients and in patients with renal insufficiency, albeit rarely. Chemical similarities between sulfamethoxazole and sulfonylureas may cause cross-reactivity resulting in a sulfonylurea-like effect associated with TMP-SMX.
A 62-year-old female with AIDS (CD4 40) not on HAART and hepatitis C presented with diarrhoea for 2 months and was also found to be in acute hypoxemic respiratory distress. Physical examination was unremarkable other than HIV-associated wasting syndrome. Based on laboratory findings and radiographic data, TMP-SMX prednisone were started due to a high suspicion for severe Pneumocystis jirovecii pneumonia (PCP). PCP was confirmed by bronchoalveolar lavage. Stool testing confirmed cryptosporidiosis. Diarrhoea was managed supportively and did not persist beyond day 2 of hospitalization. On day 4 of hospitalization, she developed hypoglycaemia with blood glucose in the 40s. A supplemental dextrose infusion, multiple dextrose ampules, carbohydrate-rich food, and glucagon were ineffective. TMP-SMX was discontinued and replaced by clindamycin and primaquine for treatment of PCP. Normoglycaemia was achieved and maintained without supplemental dextrose 24 h following the last administered dose of TMP-SMX. Cortisol level was normal and C-peptide level was elevated at 7.78 ng/mL, suggesting that the hypoglycaemia was due to increased endogenous insulin secretion.
Case reports of hypoglycaemia following TMP-SMX administration in non-diabetic patients or those without renal insufficiency are extremely rare. Our patient was not diabetic and had normal renal function but was significantly malnourished and glycogen-deficient in the setting of AIDS. Stimulants of insulin secretion in such patients can have catastrophic consequences. In addition to diabetic patients on sulfonylureas or meglitinides or patients with renal impairment, patients with malnutrition alone should be monitored closely for hypoglycaemia.
1st Place Chief Resident Clinical Vignette Award – Mulholland Mohler Residents Meeting – Maryland Chapter 2018 – Dr. Rajarajeshwari Ramachandran – Adult Xanthogranulomatous Disease – An Exceedingly Rare Case with Ocular and Systemic Involvement
Drs. Rajarajeshwari Ramachandran, Katherine Duncan
Introduction: Adult orbital xanthogranulomatous disease is a heterogeneous group of rare idiopathic inflammatory disorders characterized by localized or systemic proliferation of histiocytes.
Case report: A 71-year-old man with coronary artery disease, diabetes insipidus and hypothyroidism, presented with progressively worsening bilateral painless visual loss for 6 months. ROS – positive for unintentional weight loss of 20 pounds over 4 months and night sweats. Physical exam: Visual acuity – no light perception in the left eye and hand movement perception in the right eye. Both pupils – minimally reactive to light. Intraocular pressure – normal bilaterally. Abnormal limitation of horizontal and vertical movements of both eyes. Fundus exam – both optic discs showed elevation. Investigative studies: MRI orbits – mild bilateral proptosis, contrast enhancing bilateral intra-orbital masses filling the intra-conal fat and encasing the optic nerves. CT chest/abdomen/pelvis – multiple enlarged mediastinal nodes, bilateral moderate pleural effusions, soft tissue density surrounding the aortic arch, mesenteric vessels, adrenal glands, abdominal aorta, inferior vena cava, both kidneys and paraspinal tissues with sclerosis of T6 vertebral body and multiple posterior ribs. PET scan – hypermetabolic bilateral intra-conal masses, mediastinal adenopathy and sclerotic osseous T6 lesion with mildly increased FDG activity within the poorly defined mesenteric mass and bilateral perirenal space. Clinical course: He was started on intravenous steroids and underwent biopsy of the left orbital mass, which demonstrated CD68+ histiocytes with fibrosis. His overall clinical picture was consistent with a subtype of adult xanthogranulomatous disease called Erdheim–Chester disease. His vision gradually improved and was 20/60 in the right eye and able to count fingers in the left eye at the time of discharge. He was discharged home on oral steroid and close outpatient oncology and ophthalmology follow up for further management.
Discussion: Erdheim–Chester disease is a rare form of adult xanthogranulomatous disease with very heterogeneous manifestations. Skeletal involvement is present in up to 96% of the patients and more than 50% of patients have at least 1 extra-skeletal manifestation, such as exophthalmos, xanthelasma, interstitial lung disease, retroperitoneal fibrosis, renal failure, diabetes insipidus, central nervous system, or cardiovascular involvement. Histological examination is required for definitive diagnosis.
Baltimore Chapter, Society of Critical Care Award – Mulholland Mohler Residents Meeting – Maryland Chapter 2018 – Dr. Brittany Duchene/Dr. David Blackwood, Medstar Harbor Hospital – The Effects of Verbal CAM-ICU reporting in Academic Rounds on ICU Patient Mortality and Length of Stay
Drs. Brittany Duchene, David Blackwood, M. Brown, K. Brownell, F.Gregoire, M. Gosnell
Purpose: Delirium has been established as an independent risk factor for prolonged hospital length of stay (LOS) and is a significant contributor to increased morbidity and mortality in the hospitalized patient. Nursing documentation of CAM-ICU (confusion assessment method-intensive care unit), a validated tool for assessing delirium, is standard of care. This study aims to elucidate the effects on hospital mortality and LOS when the CAM-ICU is verbally reported during academic physician ICU rounds.
Methods: This is a single centre retrospective observational study of 279 adult ICU patients, who were admitted for at least 12 h, over a 1-year period (July 2016–July 2017). The CAM-ICU statuses of 144 patients were verbally reported during academic ICU rounds (reporting group) and 135 patients did not have their CAM-ICU status verbally reported (non-reporting group). The hospital mortality and LOS between these groups were analyzed using binary logistical regression, Student’s t-test and Chi-squared test as appropriate.
Results: Correcting for age, gender, APACHE II score, and admission diagnosis, the hospital mortality rate of the CAM-ICU reporting group was 7% lower than those in the non-reporting group (32.6% vs 25.7%, p = 0.040; OR = 1.92). LOS was not statistically different between groups, however, the reporting group had a mean LOS 0.8 days less than in the non-reporting group (6.13 days vs 5.27 days, p = 0.595). Post-hoc analyses revealed decreased hospital mortality in those admitted for neurological causes in the reporting group (61.5% vs 38.5%, p = 0.036). When analyzing subgroups of APACHE II scores, those admitted with an APACHE score between 11–20 had significantly lower hospital mortality in the reporting group (40.7% vs 23.5%, p = 0.038). Finally, subgroup analysis of LOS found that the reporting group had significantly lower hospital mortality if their LOS was between 6 and 10 days (73.4% vs 28.6%, p = 0.007).
Discussion: Verbal reporting of CAM-ICU status during academic rounds decreases all-cause hospital mortality and may lead to decreased hospital LOS. Delirium is complex and there may be specific subgroups of patients who will benefit the most from verbal reporting of their CAM-ICU status.
Conclusion: Verbal CAM-ICU reporting is a cost-effective and non-invasive intervention that has potentially considerable benefits for ICU patients and the healthcare system as a whole.