PURPOSE: The aim of this study was to explore a difference in medication use (defined by medication selection and medication self-discontinuation) between patients with limited and adequate health literacy. This study also investigated whether the association between medication use and clinical remission of CD was different across the health literacy spectrum. METHODS: A cross-sectional study was conducted by analyzing an existing dataset from the IBD Health Literacy study in the Department of Gastroenterology at Boston Medical Center (BMC). Among 61 patients who were enrolled, 26 had limited health literacy and 35 had adequate health literacy. Medication use was defined by medication selection and medication self-discontinuation. Medication selection was further defined as whether patients with monotherapy were on one of the following medications including 5-ASAs, immunomodulators (including thiopurines and methotrexate), biologics and prednisone; medication self-discontinuation was further defined as whether patients had ever discontinued medications (including thiopurines and biologics) without physician recommendation. Harvey Bradshaw Index score was the assessment of clinical remission of CD. Newest Vital Sign scores were applied to assess health literacy. RESULTS: The odds ratios for patients who were on 5-ASAs and immune modulators (including thiopurines and methotrexate) monotherapy at the time of visit to have limited health literacy, compared to patients who were on monotherapy of biologic agent, were 3.75 (95%CI (0.46-38.26), p = 0.22) and 1.25 (95%CI (0.13-9.67), p = 0.83), respectively. The odds ratio for those whoever self-discontinued any medications to have limited health literacy versus those who did not was 1.62 (95%CI (0.42-6.24), p = 0.48). The odds ratio for patients whoever self-discontinued any medications to be in clinical remission against those who did not was 0.46 (95%CI (0.1-1.85), p = 0.27). The odds ratio for associations between medication self-discontinuation and clinical remission were 0.6 (95%CI (0.06-4.58), p = 0.63) in patients with limited health literacy and 0.5 (95%CI (0.06-4.62), p = 0.51) in patients with adequate health literacy. CONCLUSION: There were no differences of medication use between limited and adequate health literacy. The association between medication self-discontinuation and clinical remission of CD was indifferent across the health literacy levels. The results of this study provides a foundation for future studies on health literacy associated differences in CD populations and helps promote the effectiveness of treatment for CD by arousing more attention to different health literacy populations.

Lenalidomide is an FDA approved immunomodulatory drug (IMID) that is highly efficacious in myelodysplastic syndrome with del(5q), multiple myeloma, as well as other B cell malignancies.1 Furthermore, lenalidomide promotes a multitude of physiological effects, which include increased IL-2 cytokine production, inhibition of TNF alpha by monocytes and teratogenicity.3 The molecular mechanism of action responsible for these pleiotropic effects has eluded researchers for nearly 50 years.5 Recently, we identified lenalidomide to bind to and activate CRBN E3 ligase to specifically ubiquitinate two lymphoid transcription factors named IKZF1 (Ikaros) and IKZF3 (Aiolos), resulting in their proteasomal degradation. Targeted depletion of IKZF1 and IKZF3 inhibits growth of myeloma cells and IL-2 release in T cells, explaining two properties of the drug.8 Another identified lenalidomide regulated substrate of CRBN is casein kinase 1α (CSNK1A1), potentially connecting lenalidomide's activity in MDS with del(5q).8 While lenalidomide promotes these effects in human cells, the drug does not show activity in murine cells.7 Using this distinction as a vehicle to study the lenalidomide-CRBN interaction, we tested human-mouse chimera CRBN proteins in order to characterize the region of CRBN that is critical for lenalidomide activity. We were able to identify a group of non-conserved amino acids on CRBN necessary for lenalidomide activity. A single amino acid substitution is responsible for the different effects observed in humans and mice. Our findings will not only allow for the use of murine models in the study of lenalidomide and its analogs, but also help provide further insight into the drug's molecular mechanism.

BACKGROUND: Spondyloarthritis (SpA) is associated with increased risk of myocardial infarction (MI); the risk may be due to the underlying inflammatory disease, or also due to medications that increase MI risk, such as certain non-steroidal anti-inflammatory drugs (NSAIDs). OBJECTIVES: 1. To describe the risk of myocardial infarction (MI) among patients with spondyloarthritis who are prescribed NSAIDs 2. To compare the pattern of MI risk with specific NSAID use among spondyloarthritis patients with the pattern of risk among patients with osteoarthritis (OA) METHODS: Nested case-control studies were performed using 1994–2015 data from The Health Improvement Network (THIN). Underlying cohorts included adult patients with incident SpA or OA had >1 NSAID prescriptions and no history of MI. In each cohort, we matched cases of incident MI to four controls without MI. NSAID use was categorized as: (A) current (prescription end date 0–180 days prior to index date), (B) recent (181–365 days), or (C) remote (>365 days). We performed conditional logistic regression to compare the odds of current or recent NSAID use relative to remote use of any NSAID, considering diclofenac and naproxen specifically. RESULTS: Within the SpA cohort of 8140 and the OA cohort of 244,399, there were 115 and 6287 MI cases, respectively. After adjustment, among SpA subjects, current diclofenac use was associated with an OR of 3.05 (95% CI 1.48–6.29; Table 2) for MI. Naproxen use was not associated with any increase (adjusted OR 1.25, 95% CI 0.56–2.78). A ratio of ORs for SpA/diclofenac relative to OA/diclofenac was 2.35 (1.10–4.90). / 2019-06-12T00:00:00Z

BACKGROUND: Cutaneous scarring is a reparative response to wounding in an attempt to restore homeostasis. Pathologic scars include hypertrophic and keloidal scars. No defined dermal scar fibroblast phenotype has been described. This study examines for such a phenotype, looking at expression patterns and spatial relationships of CD90, CD34 and smooth muscle actin (SMA) expressing fibroblasts in cutaneous scars. Additionally, this work investigates for evidence of scar fibroblast transition from the background CD34+ stromal cell network. It also delineates a timeline for the appearance/disappearance of this phenotype in physiologic scarring. Finally, it assesses the relative contributions of CD90+ and SMA+ fibroblasts to scar collagenization. METHODS: 117 scars were classified as reparative (n=47), hypertrophic (n= 40) or keloidal (n=30). Where possible, scar age was calculated. Immunohistochemistry with CD90, CD34 and SMA was performed on all scars. Double-staining immunohistochemistry for CD90/CD34 was applied to all scars assessing for the presence of dual CD90+/CD34+ transitioning cells. Double-color immunofluorescence was also performed to further identify transition. A subset of scars was double stained with CD90/SMA to evaluate spatial relationships. Additional scars were double-stained with CD90/procollagen-1 or SMA/procollagen-1 to assess for active collagen synthesis. Expression was graded as diffuse, focal/rare (i.e. minority) and negative. RESULTS: A CD90diffuse/CD34negative/minority pattern was the most commonly observed phenotype among all scars. SMA expression was variable. Transitioning CD90+/CD34+ fibroblasts were observed in 90.6% of scars. In reparative scars, a CD90diffuse/CD34negative/minority phenotype was time-limited, developing within 48 hours and reverting to a CD34diffuse state at 160-180 days. Many pathologic scars exhibited prolonged CD90diffuse expression. Both CD90+ fibroblasts and myofibroblasts express procollagen-1. CD90+ fibroblasts contributed more cells to scar mass than myofibroblasts. When spatial relationships were examined, myofibroblasts exclusively localized to CD90+ areas and exhibited CD90 double-positivity. CD90 expression was not limited to SMA+ zones. CONCLUSIONS: Scar fibroblasts predominantly exhibit a CD90diffuse/CD34negative/minority phenotype. These CD90+ fibroblasts likely transition from the background CD34+ network. This phenotype is reversible in reparative scars, but is prolonged in some pathologic scars. Both CD90+ fibroblasts and myofibroblasts collagenize scars. The co-localization of myofibroblasts to CD90-rich areas and CD90 dual-positivity may suggest a common origin. / 2018-07-31T00:00:00Z

To date, the blood oxygenated-level dependent (BOLD) functional magnetic resonance imaging (fMRI) technique has enabled an objective and deeper understanding of pain processing mechanisms embedded within the human central nervous system (CNS). In order to further comprehend the benefits and limitations of BOLD fMRI in the context of pain as well as the corresponding subjective pain ratings, we evaluated the univariate response, test-retest reliability and confidence intervals (CIs) at the 95% level of both data types collected during evoked stimulation of 40°C (non-noxious), 44°C (mildly noxious) and a subject-specific temperature eliciting a 7/10 pain rating. The test-retest reliability between two scanning sessions was determined by calculating group-level interclass correlation coefficients and at the single-subject level. Across the three stimuli, we initially observed a graded response of increasing magnitude for both visual analogue scale (VAS) pain ratings and fMRI data. Test-retest reliability was observed to be highest for VAS pain ratings obtained during the 7/10 pain stimulation (intraclass correlation coefficient (ICC) = 0.938), while ICC values of pain fMRI data for a distribution of CNS structures ranged from 0.5 to 0.859 (p < 0.05). Importantly, the upper and lower CI bounds reported herein could be utilized in subsequent trials involving healthy volunteers to hypothesize the magnitude of effect required to overcome inherent variability of either VAS pain ratings or BOLD responses evoked during innocuous or noxious thermal stimulation.

Numerous analyses have explored the role of statins in reducing stroke incidence, reducing cerebral ischemia in hypercholesterolemic patients, and preventing ischemic stroke. This paper aims to assess the effect of statins in lowering the risk of stroke and preventing cerebral ischemia in patients with hypercholesterolemia. To achieve this objective, the literature was reviewed, randomized control tests were analyzed, and a systematic review was performed. The risk of developing cerebral ischemia was found to be reduced in hypercholesterolemic patients and patients with a history of cerebrovascular disease. However, it is unknown whether this reduction in incidence is a result of the drug, which reduces low-density lipoprotein levels in the blood, or to statins’ pleotropic effects on the vascular endothelium. Since their discovery, statins have proven to be beneficial in controlling cholesterol blood levels. Moreover, statins have been shown to have pleotropic effects after a certain period of use, one of which is lowering ischemic stroke incidence in hypercholesterolemic patients. Most recently, statins have been found to lower systolic blood pressure. It is not yet clear whether it has a significant effect on mortality or whether or not it is linked to statins.

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