IMPACT: The Journal of the Center for Interdisciplinary Teaching and Learning. Volume 8, Issue 1, Winter 2019

IMPACT: The Journal of the Center for Interdisciplinary Teaching & Learning is a peer-reviewed, biannual online journal that publishes scholarly and creative non-fiction essays about the theory, practice and assessment of interdisciplinary education. Impact is produced by the Center for Interdisciplinary Teaching & Learning at the College of General Studies, Boston University (www.bu.edu/cgs/citl).In this issue of Impact you will find a humanities scholar deeply engaged with the arcing out of a new territory: the interdisciplinary study of the Grateful Dead. Impact’s own Christopher Coffman’s review essay should be required reading for scholars of popular music, performance studies and history. His review also serves as an important reference for those who aspire to teach a course on the Grateful Dead, as well as for those who wish to write review essays. In this issue we also hear from those who are engaged in teaching people who are incarcerated. Importantly, Stephanie Cage’s essay looks to incarcerated people themselves to find out what they think about prison education. Peter Wakefield encourages us to see The Great Gatsby anew, in particular in the context of American racism and White supremacy. Wakefield’s essay is important too because it had its genesis in Writing, the State, and the Rise of Neo-Nationalism: Historical Contexts and Contemporary Concerns, a conference sponsored by the Center for Interdisciplinary Teaching & Learning

The effect of matrix metalloproteinase 2 and matrix metalloproteinase 2/9 deletion in experimental post-thrombotic vein wall remodeling

BackgroundVein wall fibrotic injury following deep venous thrombosis (VT) is associated with elevated matrix metalloproteinases (MMPs). Whether and by what mechanism MMP2 contributes to vein wall remodeling after VT is unknown.MethodsStasis VT was produced by ligation of the inferior vena cava and tissue was harvested at 2, 8, and 21 days in MMP2 -/- and genetic wild type (WT) mice. Tissue analysis by immunohistochemistry, enzyme-linked immunosorbent assay, real-time polymerase chain reaction, and zymography was performed.ResultsThrombus resolution was less at 8 days in MMP2 -/- compared with WT, evidenced by a 51% increase in VT size (P < .01), and threefold fewer von Willebrand's factor positive channels (P < .05). In MMP2 -/- mice, the main phenotypic fibrotic differences occurred at 8 days post-VT, with significantly less vein wall collagen content (P = .013), fourfold lower procollagen III gene expression (P < .01), but no difference in procollagen I compared with WT. Decreased inflammation in MMP2 -/- vein walls was suggested by ∼ threefold reduced TNFα and IL-1β at 2 days and 8 days post-VT (P < .05). A fourfold increase in vein wall monocytes (P = .03) with threefold decreased apoptosis (P < .05), but no difference in cellular proliferation at 8 days was found in MMP2 -/- compared with WT. As increased compensatory MMP9 activity was observed in the MMP2 -/-mice, MMP2/9 double null mice had thrombus induced with VT harvest at 8 days. Consistently, twofold larger VT, a threefold decrease in vein wall collagen, and a threefold increase in monocytes were found (all P < .05). Similar findings were observed in MMP9 -/- mice administered an exogenous MMP2 inhibitor.ConclusionsIn stasis VT, deletion of MMP2 was associated with less midterm vein wall fibrosis and inflammation, despite an increase in monocytes. Consideration that VT resolution was impaired with MMP2 (and MMP2/9) deletion suggests direct inhibition will likely also require anticoagulant therapy.Clinical RelevancePost-thrombotic syndrome has no direct therapies and causes significant morbidity. Anticoagulation limits thrombosis but does not clinically impact directly the vein wall response to injury as well as has bleeding risks. In this experimental study, we show that matrix metalloproteinase 2 genetic deletion lessens fibrotic injury and inflammation at the midterm timepoint, yet is also important for thrombus resolution. Future therapies that positively impact vein wall remodeling will need to account for how the thrombus responds as well

Decreased venous thrombosis with an oral inhibitor of P selectin

BackgroundP-selectin inhibition with protein therapeutics such as antibodies or soluble ligands given intravenously can decrease thrombosis in a mouse ligation model of venous thrombosis. In this study, we hypothesized that oral inhibition of P selectin with a novel oral nonprotein inhibitor (PSI-697) would decrease thrombosis and circulating microparticle populations. This study evaluated the effects on thrombosis and circulating microparticle populations in this murine venous thrombosis model.MethodsMice underwent inferior vena cava ligation to induce thrombosis. Mice with high circulating level of P selectin, Delta Cytoplasmic Tail (^CT), mice gene-deleted for both E- and P-selectin knockout (EPKO), and wild-type C57BL/6 mice (WT) were studied without and with administration of PSI-697 in food (100 mg/kg daily) from 2 days before thrombosis until the end of the study. Animals were killed 2 and 6 days later. Evaluations included thrombus weight (TW), vein wall morphometrics, microparticle quantification by using fluorescence-activated cell sorter analysis, and vein wall enzyme-linked immunosorbent assays for interleukin (IL)-10, P selectin, and monocyte chemotactic protein 1.ResultsPSI-697 significantly decreased TW in WT and ^CT mice, with a treated vs nontreated TW of 132 ± 24 vs 228 ± 29 × 10−4 g (P = .014) and 166 ± 19 vs 281 ± 16 × 10−4 g (P = .001), respectively. At day 6, the effect was significant only in the ^CT group (P < .05). Drug therapy at day 2 significantly increased vein wall monocytes in WT mice and increased monocytes and total inflammatory cells in ^CT animals. A significant decrease in neutrophils and total inflammatory cells was seen in EPKO mice at day 2 with therapy. Therapy significantly increased platelet-derived microparticles and total microparticles in ^CT mice on day 2. Changes in treated WT and treated EPKO animals were not significant compared with respective vehicle treatments at day 2. On day 6, therapy significantly decreased total microparticles in EPKO animals. Vein wall expression of IL-10 increased in all groups with therapy at day 2 (n = 18) and was significantly increased in WT (2687.5 ± 903 pg/mL vs 636 ± 108 pg/mL total protein; P = .038) and ^CT (2078 ± 295 pg/mL vs 432 ± 62 pg/mL total protein; P = .001) mice. Therapy significantly decreased vein wall P selectin, monocyte chemotactic protein 1, and IL-10 levels at day 6.ConclusionsPSI-697 decreased thrombosis. P-selectin inhibition allowed vein wall inflammatory cell extravasation in this model of complete ligation. Circulating microparticles (platelet-derived microparticles and total microparticles) increased with P-selectin inhibition, possibly because of decreased consumption into the thrombus. In summary, the oral administration of an inhibitor to P selectin provides significant TW reduction.Clinical RelevanceDeep venous thrombosis is a significant national health problem in the general population. The average annual incidence of deep venous thrombosis is approximately 250,000 cases per year. The selectin family of adhesion molecules is thought to be largely responsible for the initial attachment and rolling of leukocytes on stimulated vascular endothelium. Recent studies have explored the possible therapeutic implications of P-selectin inhibition to modulate venous thrombosis. For example, prophylactic dosing of a recombinant P-selectin ligand decreases venous thrombosis in a dose-dependent fashion in both feline and nonhuman primate animal models. Additionally, treatment of 2-day iliac thrombi with a recombinant protein, P-selectin inhibitor, significantly improves vein reopening in nonhuman primates. It is interesting to note that P-selectin inhibition decreases thrombosis without adverse anticoagulation. On the basis of the results from these previous studies, the use of P-selectin antagonism is a logical therapeutic approach to treat venous thrombosis. All inhibitors developed to date are either proteins or small molecules with low oral bioavailability that require intravenous or subcutaneous injection. This study evaluates, for the first time, a novel orally bioavailable inhibitor of P-selectin (PSI-697)

Severe Chronic Venous Insufficiency: Magnitude of the Problem and Consequences

The aim of this study was to characterize patients requiring hospitalization for severe chronic venous insufficiency (CVI) at the local and national levels and to analyze factors related to primary amputation. An administrative database (Nationwide Inpatient Sample, 1988-2000) and a single institution (1992-2000) were reviewed using the International Classification of Diseases, 9th ed., Clinical Modification , codes for CVI, excluding phlegmasia and concomitant peripheral vascular occlusive disease codes. Demographics, clinical course, and outcomes were assessed. Descriptive, univariate, and multivariate statistical analyses were used; p < 0.05 was considered significant. Nationally, CVI occurred with a mean incidence of 92/100,000 admissions, of which 55% were women, having a mean age of 65 years and a median length of stay of 7 days. Mean hospital charges were $13,900 and did not change significantly over time. Acute deep vein thrombosis affected 1.3%, amputation was performed in 1.2%, and in-hospital mortality was 1.6% The local cohort included 67 patients with a mean age of 51 years; a majority were men (60%), and 85% were C6 (of Clinical-Etiologic-Anatomic-Pathophysiology [CEAP]). Patients averaged 23 clinic visits and a median of one hospitalization for CVI care over a 44-month follow-up. Twelve patients (18%) underwent a CVI-related amputation (one transmetatarsal amputation, nine below-knee amputations, and two above-knee amputations). They had fourfold more CVI-related hospitalizations, greater preoperative chronic narcotic use than nonamputee patients (85% vs. 58%), but less ongoing wound care needs (25% vs. 89%) (all p values < 0.05). However, no significant difference in long-term mortality, number of clinic visits, duration of symptoms, antibiotic courses, or prior venous-related surgeries was found. In those with amputation, ambulatory status was maintained in 75% at 15-month follow-up. The physiological and economic costs of severe CVI are significant and have not decreased over more than a decade. Amputation for CVI-related nonhealing wounds has a reasonable outcome. Future therapy must focus on prevention of CVI sequelae.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/41369/1/10016_2005_Article_5425.pd

The care of patients with varicose veins and associated chronic venous diseases: Clinical practice guidelines of the Society for Vascular Surgery and the American Venous Forum

The Society for Vascular Surgery (SVS) and the American Venous Forum (AVF) have developed clinical practice guidelines for the care of patients with varicose veins of the lower limbs and pelvis. The document also includes recommendations on the management of superficial and perforating vein incompetence in patients with associated, more advanced chronic venous diseases (CVDs), including edema, skin changes, or venous ulcers. Recommendations of the Venous Guideline Committee are based on the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) system as strong (GRADE 1) if the benefits clearly outweigh the risks, burden, and costs. The suggestions are weak (GRADE 2) if the benefits are closely balanced with risks and burden. The level of available evidence to support the evaluation or treatment can be of high (A), medium (B), or low or very low (C) quality. The key recommendations of these guidelines are: We recommend that in patients with varicose veins or more severe CVD, a complete history and detailed physical examination are complemented by duplex ultrasound scanning of the deep and superficial veins (GRADE 1A). We recommend that the CEAP classification is used for patients with CVD (GRADE 1A) and that the revised Venous Clinical Severity Score is used to assess treatment outcome (GRADE 1B). We suggest compression therapy for patients with symptomatic varicose veins (GRADE 2C) but recommend against compression therapy as the primary treatment if the patient is a candidate for saphenous vein ablation (GRADE 1B). We recommend compression therapy as the primary treatment to aid healing of venous ulceration (GRADE 1B). To decrease the recurrence of venous ulcers, we recommend ablation of the incompetent superficial veins in addition to compression therapy (GRADE 1A). For treatment of the incompetent great saphenous vein (GSV), we recommend endovenous thermal ablation (radiofrequency or laser) rather than high ligation and inversion stripping of the saphenous vein to the level of the knee (GRADE 1B). We recommend phlebectomy or sclerotherapy to treat varicose tributaries (GRADE 1B) and suggest foam sclerotherapy as an option for the treatment of the incompetent saphenous vein (GRADE 2C). We recommend against selective treatment of perforating vein incompetence in patients with simple varicose veins (CEAP class C2; GRADE 1B), but we suggest treatment of pathologic perforating veins (outward flow duration ≥500 ms, vein diameter ≥3.5 mm) located underneath healed or active ulcers (CEAP class C5-C6; GRADE 2B). We suggest treatment of pelvic congestion syndrome and pelvic varices with coil embolization, plugs, or transcatheter sclerotherapy, used alone or together (GRADE 2B)

Current state of musculoskeletal ultrasound training and implementation in Europe: results of a survey of experts and scientific societies

Objective. To document the current state of musculoskeletal US (MSUS) training and extent of implementation among rheumatologists in the member countries of EULAR. Methods. An English-language questionnaire, divided into five sections (demographics, clinical use of MSUS, overall MSUS training for rheumatologists, MSUS education in the rheumatology training curriculum and education in MSUS offered by the national rheumatology society) was sent by e-mail to three different groups: (i) all national rheumatology societies of EULAR; (ii) all national societies of the European Federation of Societies for Ultrasound in Medicine and Biology; and (iii) 19 senior rheumatologists involved in MSUS training from 14 European countries. Results. Thirty-one (70.5%) out of 44 countries responded to the questionnaire (59.1% of national rheumatology societies, 34.5% of the national US societies and 100% of expert ultrasonographers). Rheumatology was listed among medical specialities that mainly perform MSUS in 20 (64.5%) countries; however, in most [19 (63.3%)] countries <10% of rheumatologists routinely perform MSUS in clinical practice. Training varies widely from country to country, with low rates of competency assessment. MSUS education is part of the rheumatology training curriculum in over half the surveyed countries, being compulsory in 7 (22.6%) countries and optional in 11 (35.5%). Conclusions. This study confirms the high uptake of MSUS across Europe. The reported variation in training and practice between countries suggests a need for standardization in areas including training guideline

Self-directed learning of basic musculoskeletal ultrasound among rheumatologists in the United States

Objective Because musculoskeletal ultrasound (MSUS) is highly user dependent, we aimed to establish whether non-mentored learning of MSUS is sufficient to achieve the same level of diagnostic accuracy and scanning reliability as has been achieved by rheumatologists recognized as international experts in MSUS. Methods A group of 8 rheumatologists with more experience in MSUS and 8 rheumatologists with less experience in MSUS participated in an MSUS exercise to assess patients with musculoskeletal abnormalities commonly seen in a rheumatology practice. Patients' established diagnoses were obtained from chart review (gout, osteoarthritis, rotator cuff syndrome, rheumatoid arthritis, and seronegative arthritis). Two examining groups were formed, each composed of 4 less experienced and 4 more experienced examiners. Each group scanned 1 predefined body region (hand, wrist, elbow, shoulder, knee, or ankle) in each of 8 patients, blinded to medical history and physical examination. Structural abnormalities were noted with dichotomous answers, and an open-ended answer was used for the final diagnosis. Results Less experienced and more experienced examiners achieved the same diagnostic accuracy (US-established diagnosis versus chart review diagnosis). The interrater reliability for tissue pathology was slightly higher for more experienced versus less experienced examiners (Κ = 0.43 versus Κ = 0.34; P = 0.001). Conclusion Non-mentored training in MSUS can lead to the achievement of diagnostic accuracy in MSUS comparable to that achieved by highly experienced international experts. Reliability may increase slightly with additional experience. Further study is needed to determine the minimal training requirement to achieve proficiency in MSUS.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/65036/1/20063_ftp.pd

Practice of ultrasound-guided arthrocentesis and joint injection, including training and implementation, in Europe: results of a survey of experts and scientific societies

Objectives. To document the practice and training opportunities of US-guided arthrocentesis and joint injection (UGAJ) among rheumatologists in the member countries of the European League Against Rheumatism (EULAR). Methods. An English-language questionnaire, containing questions on demographics, clinical and practical aspects of UGAJ, training options in UGAJ for rheumatologists, UGAJ education in the rheumatology training curriculum and other structured education programmes in UGAJ was sent to three different groups: (i) all national rheumatology societies of EULAR; (ii) all national societies of the European Federation of Societies for Ultrasound in Medicine and Biology (EFSUMB); and (iii) 22 senior rheumatologists involved in EULAR musculoskeletal US training from 14 European countries, who were also asked to circulate the questionnaire among relevant colleagues. Results. Thirty-three (75%) of 44 countries responded to the questionnaire (61.3% of national rheumatology societies, 25% of the national US societies and 100% of expert ultrasonographers). In the majority of countries (85%) 80%) rate of rheumatologists performing conventional joint injection in most of the surveyed countries. The reported variations in practice and the lack of available structured training programmes for trainees in most countries indicates the need for standardization in areas including training guideline