Faculty Bibliography

L-selectin, a lectin-like receptor on all leukocyte classes, functions in adhesive and signaling roles in the recruitment of myeloid cells from the blood to sites of inflammation. Here, we consider L-selectin as a determinant of neurological recovery in a murine model of spinal cord injury (SCI). Spinal cord-injured, L-selectin knock-out (KO) mice (male) showed improved long-term recovery with greater white matter sparing relative to wild-type (WT) mice and reduced oxidative stress in the injured cord at 72 h post-SCI. There was a partial and transient reduction in accumulation of neutrophils in the injured spinal cords of KOs at 24 h post-injury. To complement these findings with KO mice, we sought a pharmacologic means for lowering L-selectin levels. We found that diclofenac, a nonsteroidal anti-inflammatory drug (NSAID), induced the shedding of L-selectin from the cell surface of myeloid subsets, specifically neutrophils and non-classical monocytes, in the blood and the injured spinal cord. Diclofenac administration to injured WT mice enhanced neurological recovery to a level comparable to that of KOs but did not improve recovery in KOs. While diclofenac treatment had no effect on myeloid cell accumulation, there was a reduction in oxidative stress at 72 h post-SCI. These findings implicate L-selectin in secondary pathogenesis beyond a role in leukocyte recruitment and raise the possibility of repurposing diclofenac for the treatment of SCI.

Learning Objective #1: Recognize the incidence of posterior circulation stroke after cardiac catheterization Learning Objective #2: Recognize how cognitive biases affect clinical decision making CASE: A 57 year old man with hypertension, type 2 diabetes, depression, coronary artery disease s/p PCI and 4-vessel CABG presented with nausea, vomiting, and syncope. He was found to be in complete heart block and underwent emergent pacemaker placement and cardiac catheterization with stent placement to the left circumflex artery. After catheterization, patient reported lightheadedness and cloudiness when walking. He was transferred to the medicine service with sign-out to follow up with physical therapy given "deconditioning" after his acute illness. PT sessions were limited by his hesitancy to walk beyond a few steps. Four days after downgrade, patient reported left sided visual changes. Physical exam was notable for left homon-ymous hemianopia without somatosensory deficits. A non-contrast head CT revealed a new acute to sub-acute right posterior cerebral artery infarction. He was determined to have had an embolic ischemic stroke secondary to cardiac catheterization. His lightheadedness and cloudiness were believed to be secondary to hemianopia. He was medically managed and discharged to SAR. IMPACT: This case involves a common post-catheterization complication as an unusual presentation described as lightheadedness and cloudiness. We attributed the symptoms to overall deconditioning secondary to diagnostic momentum. Furthermore, visual fields were not accurately assessed in this post-procedure patient. Our personal practice now includes exam maneuvers to evaluate posterior circulation on patients post-cardiac catheterization given the high incidence of these strokes in cardiac patients. DISCUSSION: Post-cardiac catheterization strokes are common, with most occurring within 24 hours of the procedure. Of these, approximately 25% involve the posterior circulation often leading to visual field deficits without gross somatosensory deficits. As a result, neurological deficits may often go unnoticed if visual fields are not accurately assessed. Furthermore, patients may not realize a true visual field deficit as they can compensate with neck rotation; initial descriptors may be vague such as lightheadedness or cloudiness. Our case was further complicated by cognitive biases that influenced our decision making; namely, the case was framed as overall deconditioning. As a result, we anchored to a single diagnosis and did not consider neurological deficit as an explanation for our patient's symptoms. We encourage all medical professionals to be cognizant of variability in presentation of visual field deficits and also be keen to their own cognitive biases

Neurotrophins play critical roles in the survival, maintenance and death of neurons. In particular, proneurotrophins have been shown to mediate cell death following brain injury induced by status epilepticus (SE) in rats. Previous studies have shown that pilocarpine-induced seizures lead to increased levels of proNGF, which binds to the p75NTR-sortilin receptor complex to elicit apoptosis. A screen to identify compounds that block proNGF binding and uptake into cells expressing p75 and sortilin identified lithium citrate as a potential inhibitor of proNGF and p75NTR-mediated cell death. In this study, we demonstrate that low, submicromolar doses of lithium citrate effectively inhibited proNGF-induced cell death in cultured neurons and protected hippocampal neurons following pilocarpine-induced SE in vivo. We analyzed specific mechanisms by which lithium citrate afforded neuroprotection and determined that lithium citrate prevented the association and internalization of the p75NTR-sortilin receptor complex. Our results demonstrate a novel mechanism by which low-dose treatments of lithium citrate are effective in attenuating p75NTR-mediated cell death in vitro and in vivo.

Background: Conflicting data exists on the relationship between outpatient visits and emergency department (ED) visit and admission rates. While some have shown outpatient access prevents ED visits and admissions, others show that factors such as continuity are more important. A mental health diagnosis is consistently cited as a factor associated with increased inpatient utilization. There is little published data about resident-run outpatient clinics and their outcomes, including how these ambulatory contacts affect ED visit and admission rates. Methods: The medical record was used to collect data for all patients seen at least once in the primary care resident clinic at a large, public New York City hospital over the course of 1 academic year. We counted the number of outpatient visits per patient, regardless of type, including both primary care visits and clinic visits for all medical and surgical subspecialties. We controlled for the level of health of each patient using locally developed scores. Our primary outcomes were total number of ED visits and total number of inpatient admissions; secondary outcomes were inpatient length of stay (LOS) and admissions for ambulatory care sensitive conditions (ACSC). We conducted bivariate analyses, using T-Tests and ANOVA, and multivariate analysis, using ordinary least of squares regression, to determine whether increased contact with outpatient clinics was associated with ED visit and admission rates. A separate analysis was conducted for patients with a mental health diagnosis. Results: Our sample consisted of 2,988 patients, seen at least once in the resident-run primary care clinic, averaging 7 outpatient visits across all sub-specialties. There were 2,544 ED visits (1317 unique patients), 571 inpatient admissions (368 unique patients), and 126 ACSC admissions (97 unique patients). Patients who were hospitalized averaged 2 admissions; average LOS was 9.5 days. Multivariate analysis, controlling for sociodemographic and health factors, found more ambulatory care visits were associated with more ED visits and more inpatient admissions (p < 0.01). There was no statistically significant association between ambulatory care visits and LOS or ACSC admissions. A mental health diagnosis was associated with increased ambulatory care visits, and increased ED visits and inpatient admissions, and a 4 day longer LOS. Conclusions: Among patients seen in the resident internal medicine clinic, we were surprised to find that more outpatient visits were positively associated with more ED visits and admissions when controlling for all sociodemographic factors and health status. Our study adds to the body of literature, as there has been little previously published about resident clinic outcomes. Further studies are needed on how to improve these resident run clinics in order to help prevent ED visits and admission. Our study also showed that a mental health diagnosis was positively associated with ambulatory care visits, consistent with the previous literature