2017 American College of Rheumatology/American Association of Hip and Knee Surgeons Guideline for the Perioperative Management of Antirheumatic Medication in Patients With Rheumatic Diseases Undergoing Elective Total Hip or Total Knee Arthroplasty

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/137753/1/acr23274.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/137753/2/acr23274_am.pd

2017 American College of Rheumatology/American Association of Hip and Knee Surgeons Guideline for the Perioperative Management of Antirheumatic Medication in Patients With Rheumatic Diseases Undergoing Elective Total Hip or Total Knee Arthroplasty

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/137769/1/art40149.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/137769/2/art40149_am.pd

VAMP7 modulates ciliary biogenesis in kidney cells

Epithelial cells elaborate specialized domains that have distinct protein and lipid compositions, including the apical and basolateral surfaces and primary cilia. Maintaining the identity of these domains is required for proper cell function, and requires the efficient and selective SNARE-mediated fusion of vesicles containing newly synthesized and recycling proteins with the proper target membrane. Multiple pathways exist to deliver newly synthesized proteins to the apical surface of kidney cells, and the post-Golgi SNAREs, or VAMPs, involved in these distinct pathways have not been identified. VAMP7 has been implicated in apical protein delivery in other cell types, and we hypothesized that this SNARE would have differential effects on the trafficking of apical proteins known to take distinct routes to the apical surface in kidney cells. VAMP7 expressed in polarized Madin Darby canine kidney cells colocalized primarily with LAMP2-positive compartments, and siRNA-mediated knockdown modulated lysosome size, consistent with the known function of VAMP7 in lysosomal delivery. Surprisingly, VAMP7 knockdown had no effect on apical delivery of numerous cargoes tested, but did decrease the length and frequency of primary cilia. Additionally, VAMP7 knockdown disrupted cystogenesis in cells grown in a three-dimensional basement membrane matrix. The effects of VAMP7 depletion on ciliogenesis and cystogenesis are not directly linked to the disruption of lysosomal function, as cilia lengths and cyst morphology were unaffected in an MDCK lysosomal storage disorder model. Together, our data suggest that VAMP7 plays an essential role in ciliogenesis and lumen formation. To our knowledge, this is the first study implicating an R-SNARE in ciliogenesis and cystogenesis. © 2014 Szalinski et al

Absence of TGFBR2 mutations in patients with spontaneous spinal CSF leaks and intracranial hypotension.

A heritable connective-tissue-disorder often is suspected in patients with spontaneous spinal CSF leaks and intracranial hypotension, but the nature of the disorder remains unknown in most patients. The aim of this study was to assess the gene encoding TGF-beta receptor-2 (TGFBR2) as a candidate gene for spinal CSF leaks. We searched the TGFBR2 gene for mutations in eight patients with spontaneous spinal CSF leaks who also had other features associated with TGFBR2 mutations, i.e., skeletal features of Marfan syndrome, arterial tortuosity, and(or) thoracic aortic aneurysm. The mean age of these 7 women and 1 man was 38 years (range 14-60 years). We detected no TGFBR2 mutations and conclude that TGFBR2 mutations are not a major factor in spontaneous spinal CSF leaks

Painting a portrait: Analysis of national health survey data for cancer genetic counseling.

BACKGROUND: Despite a growing body of literature describing the geographic and sociodemographic distribution of cancer genetic testing, work focused on these domains in cancer genetic counseling is limited. Research describing the epidemiology of cancer genetic counseling has mainly focused on isolated populations, a single gender (women) and a single condition (hereditary breast and ovarian cancer). Study findings to date are contradictory, making it unclear what, if any, disparities in receipt of cancer genetic counseling exist. METHODS: Utilizing the 2015 National Health Interview Survey (NHIS)-a cross-sectional, in person interview survey collecting self-reported health data for the US population-geographic and sociodemographic factors were compared between those receiving genetic counseling and the national sample. Bivariate analysis and subsequent multivariable logistic regression were performed with stratification by cancer status (affected/unaffected). Reason for (eg, doctor recommended) and focus of (eg, breast/ovarian) genetic counseling were also assessed. To generate nationally representative estimates, all analyses were adjusted for survey weights. RESULTS: An estimated 4.8 million individuals in the United States had cancer genetic counseling. On bivariate analysis, there were significant differences in proportions undergoing genetic counseling by sex, race/ethnicity, insurance, citizenship, education, age, and cancer status (P \u3c 0.01). After adjustment, however, only female sex (Odds Ratio [OR]: 1.78 [95% CI: 1.18-2.67]) remained a significant predictor of genetic counseling among the affected. Among the unaffected, female sex (OR: 1.70 [1.30-2.21]), non-Hispanic black race (OR: 1.44 [1.02-2.05], reference: non-Hispanic white), graduate education (OR: 1.76 [1.03-2.98], reference: less than high school), and age (OR: 1.06 [1.01-1.11]) predicted higher rates of genetic counseling. An estimated 2.1 million individuals have undergone genetic counseling focused on breast/ovarian cancer, 1.3 million on colorectal cancer, and 1.4 million on other cancers. Of those receiving genetic counseling focused on breast/ovarian cancer, 3% were male and 97% female (breast cancer alone-4% male, 96% female); for colorectal cancer, 49% male and 51% female, and for other cancers, 60% male and 40% female. The majority of individuals receiving genetic counseling reported they did so because their doctor recommended it (66%), with smaller proportions describing self (12%), family (10%), or media (5%) influences as the primary reason. CONCLUSION: This is the first study to depict the sociodemographic and geographic distribution of cancer genetic counseling at the national level. Despite perceived disparities in access, cancer genetic counseling in the United States appears to be accessed by individuals of diverse racial/ethnic backgrounds, with various insurance coverage and educational levels, and across a broad range of ages and geographic regions. The only sociodemographic factor that independently predicted receipt of genetic counseling across both the affected and unaffected population was sex. With physician recommendation as the predominant driver for counseling, targeting physician education, and awareness is crucial to utilization

Table1_Participation in genetic screening: testing different outreach methods across a diverse hospital system based patient population.docx

Introduction: Genomics has the potential to transform medicine by identifying genetic risk factors that predispose people to certain illnesses. Use of genetic screening is rapidly expanding and shifting towards screening all patients regardless of known risk factors, but research is limited on the success of broad population-level outreach for genetic testing and the effectiveness of different outreach methods across diverse populations. In this study, we tested the effectiveness of Digital Only (emailing and texting) and Brochure Plus Digital (mailed brochure, emailing, and texting) outreach to encourage a diverse patient population to participate in a large hospital system’s whole genome sequencing program.Methods: Disproportionate stratified sampling was used to create a study population more demographically diverse than the eligible population and response rates were analyzed overall and by demographics to understand the effectiveness of different outreach strategies.Results: 7.5% of all eligible patients enrolled in the program. While approximately 70% of patients invited to complete genetic testing identified in their EHR as being Hispanic, Black or African America, Asian, or another non-White race, these patients generally enrolled at lower rates than the overall population. Other underrepresented groups had higher enrollment rates including people with Medicaid coverage (8.7%) and those residing in rural areas (10.6%). We found no significant difference in enrollment rates between our Digital-Only and our Brochure Plus Digital outreach approaches in the overall population, but enrollment rates were significantly higher for Asian patients and patients who resided in rural areas in the Brochure Plus Digital group. Across both outreach approaches, links provided in emails were most commonly used for enrollment.Discussion: Our study reveals expected enrollment rates for proactive outreach by a hospital system for genetic testing in a diverse population. As more hospital systems are adopting population-scale genetic testing, these findings can inform future outreach efforts to recruit patients for genetic testing including those patients traditionally underrepresented in genomics.</p

Novel LMNA Mutations in Patients With Emery-Dreifuss Muscular Dystrophy and Functional Characterization of Four LMNA Mutations

International audienceMutations in <i>LMNA</i> cause a variety of diseases affecting striated muscle including autosomal-Emery-Dreifuss muscular dystrophy (EDMD), <i>LMNA</i>-associated congenital muscular dystrophy (L-CMD) and limb-girdle muscular dystrophy type 1B (LGMD1B). Here, we describe novel and recurrent <i>LMNA</i> mutations identified in 50 patients from the USA and Canada, which is the first report of the distribution of <i>LMNA</i> mutations from a large cohort outside Europe. This augments the number of <i>LMNA</i> mutations known to cause EDMD by 16.5%, equating to an increase of 5.9% in the total known <i>LMNA</i> mutations. Eight patients presented with p.R249W/Q or p.E358K mutations and an early onset EDMD phenotype: two mutations recently associated with L-CMD. Importantly, 15 mutations are novel and include eight missense mutations (p.R189P, p.F206L, p.S268P, p.S295P, p.E361K, p.G449D, p.L454P and p.W467R), three splice site mutations (c.IVS4+1G>A, c.IVS6-2A>G, c.IVS8+1G>A), one duplication/in frame insertion (p.R190dup), one deletion (p.Q355del) and two silent mutations (p.R119R and p.K270K). Analysis of 4 of our lamin A mutations showed that some caused nuclear deformations and lamin B re-distribution in a mutation specific manner. Together, this study significantly augments the number of EDMD patients on the database and describes 15 novel mutations that underlie EDMD, which will contribute to establishing genotype-phenotype correlations