Faculty Bibliography

Learning Objective #1: Recognize that PTLD as part of the differential when post transplant individuals present with unexplained pain, fever, or organ dysfunction. Learning Objective #2: Burkitt Lymphoma subtype as well as CNS involvement represent more aggressive manifestations of PTLD and should be managed more aggressively. CASE: 72 year-old man with end stage renal disease secondary to diabetic nephropathy status post living donor renal transplant on tacro-limus presents with headache, diplopia, and blurry vision found to have CNIII palsy on neurologic examination. Facial CT and Gadolinium enhanced Brain MRI showed complete bilateral maxillary sinus opacification and leptomeningeal enhancement. He was started on broad spectrum antibiotics, but given continuous headache and concern for meningitis a lumbar puncture was performed. CSF studies showed atypical lymphocytes of predominantly monoclonal B cells. CSF FISH showed rearrangement of c-myc oncogene negative for rearrangement of bcl6 or bcl2. Serum LDH was elevated and peripheral EBV PCR was positive. Bone marrow biopsy was negative for malignancy. Further CT imaging revealed thickening of the small bowel and mesenteric lymph-adenopathy. Patient was started on dexamethasone, intrathecal metho-trexate, and R-Hyper CVAD with interval regression of abdominal LAD, mass, improvement in ptosis, and decrease in LDH. IMPACT: The case represents an uncommon manifestation of an rare variant of disease that should warrant a different approach to diagnosis and treatment. DISCUSSION: PTLD is a well recognized, heterogenous group of disorders. The mechanism of PTLD involves EBV-induced B cell proliferation and antigen mediated T cell activation which upregulate pro-growth factors such as c-Myc. The result of which ranges from early mononucleosis-like illness, polyclonal lymphoid infiltrates, to lymphomas. Therapy involves immune reconstitution, local surgical excision, corticosteroids, antiviral agents, radiation and chemotherapy. Burkitt Lymphoma (BL) is a distinct form of PTLD. BL is an aggressive, mature B cell lymphoma composed of a monomorphic population of lymphoid cells with high mitotic and proliferation rates. Monoclonality is shown as isolated c-myc rearrangement as opposed to rear-rangements in c-myc, bcl6, and bcl2 seen in diffuse large B cell lymphoma, the most common form of PTLD. BL represents a distinct monomorphic PTLD and should be managed more aggressively with lymphoma specific chemotherapy rather than simply decreasing immunosuppression. CNS involvement of PTLD is rare, reportedly in 7-15% of all PTLD, when present is predictive of inferior survival. Compared to non-PCNS PTLD, primary CNS PTLD has a higher incidence of monomorphic EBV related disease, and late involvement with poor survival. Prior kidney transplant were also more frequent in primary CNS PTLD compared to other forms of PTLD. As a parallel, in systemic non hodgkins lymphoma, renal localization is also associated with high rates of CNS involvement

BACKGROUND:Despite decreasing rates of HIV among many populations, HIV-related health disparities among gay, bisexual and other men who have sex with men persist, with disproportional percentages of new HIV diagnoses among racial and ethnic minority men. Despite increasing awareness of HIV pre-exposure prophylaxis (PrEP), PrEP use remains low. In addition to exploring individual-level factors for this slow uptake, structural drivers of PrEP use must also be identified in order to maximize the effectiveness of biomedical HIV prevention strategies. METHOD/METHODS:Using cross-sectional data from an ongoing cohort study of young sexual minority men (N=492), we examine the extent to which structural-level barriers, including access to health care, medication logistics, counseling support, and stigma are related to PrEP use. RESULTS:While almost all participants indicated awareness of PrEP, only 14% had ever used PrEP. PrEP use was associated with lower concerns about health care access, particularly paying for PrEP. Those with greater concerns talking with their provider about their sexual behaviors were less likely to use PrEP. CONCLUSION/CONCLUSIONS:Paying for PrEP and talking to one's provider about sexual behaviors are concerns for young sexual minority men. In particular, stigma from healthcare providers poses a significant barrier to PrEP use in this population. Providers need not only to increase their own awareness of and advocacy for PrEP as an effective risk-management strategy for HIV prevention, but also must work to create open and non-judgmental spaces in which patients can discuss sexual behaviors without the fear of stigma.

Background/UNASSIGNED:A growing body of research continues to elucidate health inequities experienced by transgender individuals and further underscores the need for medical providers to be appropriately trained to deliver care to this population. Medical education in transgender health can empower physicians to identify and change the systemic barriers to care that cause transgender health inequities as well as improve knowledge about transgender-specific care. Methods/UNASSIGNED:We conducted structured searches of five databases to identify literature related to medical education and transgender health. Of the 1272 papers reviewed, 119 papers were deemed relevant to predefined criteria, medical education, and transgender health topics. Citation tracking was conducted on the 119 papers using Scopus to identify an additional 12 relevant citations (a total of 131 papers). Searches were completed on October 15, 2017 and updated on December 11, 2017. Results/UNASSIGNED:Transgender health has yet to gain widespread curricular exposure, but efforts toward incorporating transgender health into both undergraduate and graduate medical educations are nascent. There is no consensus on the exact educational interventions that should be used to address transgender health. Barriers to increased transgender health exposure include limited curricular time, lack of topic-specific competency among faculty, and underwhelming institutional support. All published interventions proved effective in improving attitudes, knowledge, and/or skills necessary to achieve clinical competency with transgender patients. Conclusion/UNASSIGNED:Transgender populations experience health inequities in part due to the exclusion of transgender-specific health needs from medical school and residency curricula. Currently, transgender medical education is largely composed of one-time attitude and awareness-based interventions that show significant short-term improvements but suffer methodologically. Consensus in the existing literature supports educational efforts to shift toward pedagogical interventions that are longitudinally integrated and clinical skills based, and we include a series of recommendations to affirm and guide such an undertaking.

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:Through diet and exercise interventions, community centers offer an opportunity to address health-related issues for some of the oldest, most vulnerable members of our society. OBJECTIVES/OBJECTIVE:The purpose of this investigation is to draw upon nationwide data to better characterize the population served by the congregate meals program and to gather more detailed information on a local level to identify opportunities for service enhancement to improve the health and well-being of older adults. DESIGN/METHODS:We examined community center data from two sources: 2015 National Survey of Older Americans Act and surveys from two New York City community centers. To assess nationwide service delivery, we analyzed participant demographics, functional status defined by activities of daily living, and perceptions of services received. MEASUREMENTS/METHODS:Participants from the two New York City community centers completed a four-day food record. Functional measures included the short physical performance battery, self-reported physical function, grip strength, and the Montreal Cognitive Assessment. RESULTS:Nationwide (n=901), most participants rated the meal quality as good to excellent (91.7%), and would recommend the congregate meals program to a friend (96.0%). Local level data (n=22) were collected for an in-depth understanding of diet, physical activity patterns, body weight, and objective functional status measures. Diets of this small, local convenience sample were higher in fat, cholesterol, and sodium, and lower in calcium, magnesium, and fiber than recommended by current United States Dietary Guidelines. Average time engaged in moderate physical activity was 254 minutes per week (SD=227), exceeding the recommended 150 minutes per week, but just 41% (n=9) and 50% (n=11) of participants engaged in strength or balance exercises, respectively. CONCLUSION/CONCLUSIONS:Research is warranted to test whether improvements in the nutritional quality of food served and access/supports for engaging in strength training within community centers could help older adults achieve diet and physical activity recommendations.