Post-doc, Massachusetts General Hospital
We leverage population genetics to find risk factors and pathophysiological mechanism of stroke
Stroke, also called brain attack, occurs when blood flow to the brain is disrupted. Disruption in blood flow is caused when either a blood clot blocks one of the vital blood vessels in the brain (ischemic stroke), or when a blood vessel in the brain bursts, spilling blood into surrounding tissues (hemorrhagic stroke). We analyze all of our patients data to answer the following questions: Why are some of us more likely to suffer a stroke than others? Why, if we suffer a stroke, do some of us recover more fully than others? Why, after we suffer an initial stroke, are some of us at higher risk of a recurrent stroke than others? The answers to these questions hold vital clues to finding effective ways to prevent stroke and to finding the new treatments our patients so desperately need. We use genetics to answer these questions. We examine genetic information from tens of thousands of patients with and without stroke and seek to identify those genetic variants that alter human biology in such a way that risk of disease is increased, or recovery enhanced. As we discover these variants, we and our collaborators then determine the precise mechanisms through which they alter human biology. Opening a window onto the mysteries of human biology is the key to developing novel effective treatments.
Abstract: The frequency of Listeria monocytogenes (Lm) infection of the central nervous system is increasing. We report a patient recently treated with chemotherapeutic drugs for pulmonary adenocarcinoma who suddenly developed hemiparesis, was initially diagnosed with stroke, and was then found to be affected by Lm rhombencephalitis accompanied by a brain abscess. Lm meningoencephalitis mimicking ischemic stroke is rare but must be considered, especially in specific patients.
Pub.: 26 Jun '14, Pinned: 30 Jun '17
Abstract: Lymphopenia is increasingly recognized as a consequence of acute illness and may predispose to infections. We investigated whether admission lymphopenia (AL) is associated with increased risk of infectious complications and poor outcome in patients with spontaneous intracerebral hemorrhage (ICH).We retrospectively analyzed a prospectively collected cohort of ICH patients ascertained between 1994 and 2015. We identified subjects with lymphocyte count obtained within 24 h from onset, and AL was defined as lymphocyte count <1000/μL. Infectious complications were assessed through retrospective chart review. Association between AL, infections, and mortality was investigated using multivariable logistic regression.Of the 2014 patients meeting inclusion criteria, 548 (27.2%) had AL and 605 (30.0%) developed an infectious complication. Case-fatality at 90 days was 36.9%. Patients with AL had larger hematoma volumes, higher frequency of intraventricular hemorrhage, and lower Glasgow Coma Scale score on presentation (all p < 0.001). AL was independently associated with increased risk of pneumonia [odds ratio (OR) 1.97, 95% confidence interval (CI) 1.50-2.58, p < 0.001] and multiple infections (OR 1.84, 95% CI 1.24-2.71, p = 0.003). AL was also an independent predictor of 90-day mortality (OR 1.55, 95% CI 1.18-2.04, p = 0.002) after adjusting for confounders.AL is common in ICH patients and independently associated with increased risk of infectious complications and poor outcome. Further studies will be needed to determine whether prophylactic antibiotics in ICH patients with AL can improve outcome.
Pub.: 23 Dec '16, Pinned: 30 Jun '17
Abstract: Low levels of serum albumin may increase the risk of infections and mortality in critically ill patients. We tested the hypothesis that admission hypoalbuminemia predicted infectious complications and poor outcome in subjects with acute intracerebral hemorrhage (ICH). We analyzed a single center cohort of ICH patients collected between 1994 and 2015. Pneumonia, urinary tract infection and sepsis were retrospectively identified, according to validated criteria. Serum albumin was measured on admission and hypoalbuminemia was defined as total albumin ≤3.5 g/dL. The association between albumin levels, infections, and mortality at 90 days was tested with multivariable logistic regression analyses. A total of 2010 patients were included (median age 74 years, 54.5% males) of whom 444 (22.1%) had hypoalbuminemia on admission and 763 (38%) died within 90 days. The frequency of pneumonia, urinary tract infection, and sepsis was 19.9, 15.1, and 2.7%, respectively. Hypoalbuminemic patients had lower admission Glasgow coma scale, higher frequency of intraventricular hemorrhage and were more likely to have a history of chronic kidney or liver disease. After adjustment for potential confounders, hypoalbuminemia was an independent predictor of pneumonia [odds ratio (OR) 1.76, 95% confidence interval (CI) 1.34-2.33, p < 0.001] and sepsis (OR 2.29, 95% CI 1.22-4.30, p = 0.010). Low levels of albumin were also independently associated with higher mortality at 90 days (OR 1.78, 95% CI 1.30-2.44, p < 0.001). In conclusion, early hypoalbuminemia is common and predicts poor outcome in ICH patients. Increased susceptibility to pneumonia and sepsis may be the pathophysiological mechanism underlying this association.
Pub.: 12 Mar '17, Pinned: 30 Jun '17
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