Faculty Bibliography

Immunomodulators and biologic agents are effective in treating inflammatory bowel diseases (IBDs), and recent evidence supports their introduction earlier in the disease course. An important concern to both patients and physicians considering immunosuppression (IS) for the treatment of IBD is the potential associated cancer risk. Several important clinical questions deserve attention with respect to IBD therapy and cancer. First, does medical therapy for IBD predispose to developing cancer? Second, in an IBD patient with a history of cancer, does IBD therapy impact cancer recurrence? Third, once cancer develops in an IBD patient, is the cancer outcome different? Finally, in an IBD patient with current cancer, does the cancer therapy affect IBD outcomes? In a recent multicentric study, patients were identified based on a diagnosis of IBD and cancer with subsequent exposure to anti-tumor necrosis factor α (anti-TNFα arm), thiopurines or methotrexate (antimetabolite arm) or without subsequent IS exposure (control arm). Two hundred and fifty-five patients met the inclusion criteria. Prior cancers included 121 solid, 62 gastrointestinal, 55 dermatologic and 17 hematologic malignancies. During the follow-up period, 75 (29.4%) patients developed incident cancer: 36 (14.1%) a new cancer, 33 (12.9%) a recurrent cancer and 6 (2.4%) a new and recurrent cancer. Incident cancer rate per 100 person-years for patients exposed to anti-TNFα, anti-metabolites and controls was 2.6 with 795 person-years of follow-up, 14.8 with 122 person-years of follow-up and 8.52 with 422 person-years of follow-up, respectively. In this series of IBD patients with a history of cancer, exposure to IS following a cancer diagnosis was not associated with an increased risk of incident cancer compared to patients who did not receive these agents. Prospective data are needed to confirm these findings.

Despite known benefits, only 19-28% of HIV-infected Americans are virologically suppressed (defined as ≤200 copies/mL). Engagement in HIV care represents a continuum from patients unaware they are infected to virological suppression. The electronic medical record of all newly diagnosed HIV-infected MSM seen at Fenway Health between 2000 and 2010 were reviewed. Patients were "engaged" if they had one negative HIV test and/or one physical exam within 24 months prior to their HIV diagnosis (n=291). All others were considered "new" (n=463). MSM engaged in care prior to HIV diagnosis were more often identified in acute retroviral syndrome or on routine screening, more rapidly linked to care, and less often diagnosed with a concomitant STI than those who were not engaged in care. Nearly 19% of all patients were diagnosed with AIDS the same time they were diagnosed with HIV. Blacks and those with higher CD4 counts at diagnosis were less likely to be virologically suppressed at 1 year. Between 2000 and 2010, patients retained in care were more likely to initiate ART and be virologically suppressed within 1 year independent of initial HIV viral load and CD4 count. Engagement in care prior to seroconversion influences important HIV outcomes. Programs that care for at risk populations should institute routine opt-out HIV testing and test-and-treat programs to optimize HIV care and prevention.

BACKGROUND & AIMS/OBJECTIVE:Little is known about the effects of cancer therapy for extraintestinal malignancy in patients with inflammatory bowel diseases (IBDs). METHODS:We analyzed data from the Massachusetts General Hospital and the Brigham and Women's Hospital on 84 patients diagnosed with Crohn's disease, ulcerative colitis, or indeterminate colitis found to have a solid malignant extraintestinal neoplasm between January 15, 1993, and December 15, 2011. We investigated the incidence of remission with cancer treatment (cytotoxic chemotherapy, hormone therapy, or both) among patients with active IBD (n = 15) and time to disease activation after cancer treatment of those with inactive disease (n = 69). Cox proportional hazards models and survival curves were constructed to identify independent predictors of these outcomes. RESULTS:Among patients with active IBD at cancer diagnosis, 66.7% (n = 10/15) achieved remission during cancer treatment; the median duration of remission was 27 months. Ninety percent of these patients had received cytotoxic chemotherapy. For patients with IBD in remission at cancer diagnosis, 17.4% (n = 12/69) developed active IBD; the type of treatment was the strongest predictor of IBD reactivation. The risk of IBD reactivation was greatest among patients who received a combination of cytotoxic chemotherapy and adjuvant hormone therapy (hazard ratio, 12.25; 95% confidence interval, 1.51-99.06) or only hormone therapy (hazard ratio, 11.56; 95% confidence interval, 1.39-96.43). Ninety percent of patients who received cytotoxic chemotherapy remained in remission at 5 years compared with 64% of those who received only hormone therapy or the combination of cytotoxic chemotherapy and adjuvant hormone therapy (log rank, P = .02). CONCLUSIONS:IBD is more likely to remit among patients who receive cytotoxic chemotherapy for solid malignancies than those who receive only hormone therapy or the combination of cytotoxic chemotherapy and adjuvant hormone therapy. Among patients with inactive IBD at the time of cancer diagnosis, hormonal therapy, alone or in combination with cytotoxic chemotherapy, increases the risk of IBD reactivation.

BACKGROUND:Clinical and functional imaging evidence suggests that cerebellar dysfunction occurs in essential tremor (ET). In recent postmortem studies, we documented increased numbers of torpedoes (Purkinje cell axonal swellings) in ET patients without Lewy bodies. Purkinje cell loss, however, has never been rigorously assessed. OBJECTIVE:To quantitatively assess the number of Purkinje cells in brains of ET patients and similarly aged controls. METHODS:Postmortem cerebellar tissue was available in 14 ET cases (6 with Lewy bodies and 8 without Lewy bodies) and 11 controls. Calbindin immunohistochemistry was performed on paraffin sections of the cerebellum. Images were digitally recorded and blinded measurements of the number of Purkinje cells per millimeter of cell layer (linear density) were made. RESULTS:Purkinje cell linear density was inversely correlated with age (r= - 0.53, P= .006) and number of torpedoes (r= - 0.42, P= .04). Purkinje cell linear density differed by diagnosis (mean [SD], controls, 3.46 [1.27] cells/mm; ET cases with Lewy bodies, 3.33 [1.06] cells/mm; and ET cases without Lewy bodies, 2.14 [0.82] cells/mm; P= .04), with the most significant difference between ET cases without Lewy bodies and controls, where the reduction was 38.2% (P= .04). In an adjusted linear regression analysis that compared ET cases without Lewy bodies with controls, decreased linear density (outcome variable) was associated with ET (beta= .56, P= .03). CONCLUSIONS:We demonstrated a reduction in Purkinje cell number in the brains of patients with ET who do not have Lewy bodies. These data further support the view that the cerebellum is anatomically, as well as functionally, abnormal in these ET cases.