Implementation of Direct-to-Patient Mobile Teledermatology in VA.

BACKGROUND: Innovative technology can enhance patient access to healthcare but must be successfully implemented to be effective. OBJECTIVE: We evaluated Department of Veterans Affairs' (VA's) implementation of My VA Images, a direct-to-patient asynchronous teledermatology mobile application enabling established dermatology patients to receive follow-up care remotely instead of in-person. DESIGN /PARTICIPANTS/APPROACH: Following pilot testing at 3 facilities, the app was introduced to 28 facilities (4 groups of 7) every 3 months using a stepped-wedge cluster-randomized design. Using the Organizational Theory of Implementation Effectiveness, we examined the app's implementation using qualitative and quantitative data consisting of encounter data from VA's corporate data warehouse; app usage from VA's Mobile Health database; bi-monthly reports from facility representatives; phone interviews with clinicians; and documented communications between the operational partner and facility staff. KEY RESULTS: Implementation policies and practices included VA's vision to expand home telehealth and marketing/communication strategies. The COVID-19 pandemic dominated the implementation climate by stressing staffing, introducing competing demands, and influencing stakeholder attitudes to the app, including its fit to their values. These factors were associated with mixed implementation effectiveness, defined as high quality consistent use. Nineteen of 31 exposed facilities prepared to use the app; 10 facilities used it for actual patient care, 7 as originally intended. Residents, nurse practitioners, and physician assistants were more likely than attendings to use the app. Facilities exposed to the app pre-pandemic were more likely to use and sustain the new process. CONCLUSIONS: Considerable heterogeneity existed in implementing mobile teledermatology, despite VA's common mission, integrated healthcare system, and stakeholders' broad interest. Identifying opportunities to target favorable facilities and user groups (such as teaching facilities and physician extenders, respectively) while addressing internal implementation barriers including incomplete integration with the electronic health record as well as inadequate staffing may help optimize the initial impact of direct-to-patient telehealth. The COVID pandemic was a notable extrinsic barrier. CLINICAL TRIALS REGISTRATION: NCT03241589.

Review of Teledermatology: Lessons Learned from the COVID-19 Pandemic.

Utilization of telemedicine for dermatology has greatly expanded since the start of the COVID-19 pandemic, with over 500 new teledermatology studies published since 2020. An updated review on teledermatology is necessary to incorporate new findings and perspectives, and educate dermatologists on effective utilization. We discuss teledermatology in terms of diagnostic accuracy and clinical outcomes, patient and physician satisfaction, considerations for special patient populations, published practice guidelines, cost effectiveness and efficiency, as well as administrative regulations and policies. Our findings emphasize the need for dermatologist education, prioritization of reliable reimbursement systems, and technological innovations to support the continued development of teledermatology in the post-pandemic era.

Using the RE-AIM framework to assess national teledermatology expansion.

Background: Teledermatology has been utilized in the United States Department of Veterans Affairs (VA) for decades but continues to have incomplete penetration. VA has funded an initiative to enhance access to dermatology services since 2017 to support asynchronous teledermatology for Veterans living in rural areas. As part of an ongoing evaluation of this program, we assessed the teledermatology activity between the fiscal years 2020 and 2022. We focused on the second cohort of the initiative, comprising six VA facilities and their 54 referral clinics. Methods: We studied teledermatology programs at cohort facilities using the reach, effectiveness, adoption, implementation, and maintenance framework. We used a mixed-methods design including annual online reports completed by participating facilities and VA administrative data. When possible, we compared the data from the 3 years of teledermatology funding with the baseline year prior to the start of funding. Findings: Reach: Compared with the baseline year, there was a 100% increase in encounters and a 62% increase in patients seen at the funded facilities. Over 500 clinicians and support staff members were trained. Effectiveness: In FY 2022, primary or specialty care clinics affiliated with the funded facilities had more dermatology programs than primary or specialty care clinics across the VA (83% vs. 71% of sites). Adoption: By the end of the funding period, teledermatology constituted 16% of dermatology encounters at the funded facilities compared with 12% nationally. This reflected an increase from 9.2% at the funded facilities and 10.3% nationally prior to the funding period. Implementation: The continued funding for staff and equipment facilitated the expansion to rural areas. Maintenance: By the end of the funding period, all facilities indicated that they had fully implemented their program for patients of targeted primary care providers. The Program Sustainability Index scores generally increased during the funding period. Conclusions: Targeted funding to support asynchronous teledermatology implementation for rural Veterans increased its reach, adoption, and implementation, ultimately improving access. Providing program guidance with staffing and training resources can increase the impact of these programs. Ongoing efforts to maintain and increase communication between primary care and dermatology will be needed to sustain success.

Vitamin D receptor cross-talk with p63 signaling promotes epidermal cell fate.

The vitamin D receptor with its ligand 1,25 dihydroxy vitamin D3 (1,25D3) regulates epidermal stem cell fate, such that VDR removal from Krt14 expressing keratinocytes delays re-epithelialization of epidermis after wound injury in mice. In this study we deleted Vdr from Lrig1 expressing stem cells in the isthmus of the hair follicle then used lineage tracing to evaluate the impact on re-epithelialization following injury. We showed that Vdr deletion from these cells prevents their migration to and regeneration of the interfollicular epidermis without impairing their ability to repopulate the sebaceous gland. To pursue the molecular basis for these effects of VDR, we performed genome wide transcriptional analysis of keratinocytes from Vdr cKO and control littermate mice. Ingenuity Pathway analysis (IPA) pointed us to the TP53 family including p63 as a partner with VDR, a transcriptional factor that is essential for proliferation and differentiation of epidermal keratinocytes. Epigenetic studies on epidermal keratinocytes derived from interfollicular epidermis showed that VDR is colocalized with p63 within the specific regulatory region of MED1 containing super-enhancers of epidermal fate driven transcription factor genes such as Fos and Jun. Gene ontology analysis further implicated that Vdr and p63 associated genomic regions regulate genes involving stem cell fate and epidermal differentiation. To demonstrate the functional interaction between VDR and p63, we evaluated the response to 1,25(OH)2D3 of keratinocytes lacking p63 and noted a reduction in epidermal cell fate determining transcription factors such as Fos, Jun. We conclude that VDR is required for the epidermal stem cell fate orientation towards interfollicular epidermis. We propose that this role of VDR involves cross-talk with the epidermal master regulator p63 through super-enhancer mediated epigenetic dynamics.

Regulation of XPC Binding Dynamics and Global Nucleotide Excision Repair by p63 and Vitamin D Receptor.

p63 and the vitamin D receptor (VDR) play important roles in epidermal development and differentiation, but their roles and relationship in the response to ultraviolet (UV) radiation are less clear. Using TERT-immortalized human keratinocytes expressing shRNA targeting p63 in concert with exogenously applied siRNA targeting VDR, we assessed p63 and VDR's separate and combined effect on nucleotide excision repair (NER) of UV-induced 6-4 photoproducts (6-4PP). Knockdown of p63 reduced VDR and XPC expression relative to nontargeting controls, while knockdown of VDR had no effect on p63 and XPC protein expression, though alone it modestly reduced XPC mRNA. Upon UV irradiation through filters with 3 µm pores to create spatially discrete spots of DNA damage, keratinocytes depleted of p63 or VDR exhibited slower removal of 6-4PP than control cells over the first 30 min. Costaining of control cells with antibodies to XPC revealed that XPC accumulated at DNA damage foci, peaking within 15 min and gradually fading over 90 min as NER proceeded. In either p63- or VDR-depleted keratinocytes, XPC overaccumulated at spots of DNA damage so that 50% more XPC was retained at 15 min and 100% more XPC was retained at 30 min than in control cells, suggesting dissociation of XPC after binding was also delayed. Concurrent knockdown of VDR and p63 resulted in similar impairment of 6-4PP repair and XPC overaccumulation but even slower release of XPC from DNA damage sites such that 200% more XPC was retained relative to controls at 30 min post-UV. These results suggest that VDR accounts for some of p63's effects in delaying 6-4PP repair associated with overaccumulation and slower dissociation of XPC, though p63's regulation of basal XPC expression appears to be VDR-independent. The results are consistent with a model where XPC dissociation is an important step during NER and that failure to do so may inhibit subsequent repair steps. This work further links two important regulators of epidermal growth and differentiation to the DNA repair response to UV.

The New England Neurosurgical Society: growth and evolution over 70 years.

The New England Neurosurgical Society (NENS) was founded in 1951 under the leadership of its first President (Dr. William Beecher Scoville) and Secretary-Treasurer (Dr. Henry Thomas Ballantine). The purpose of creating the NENS was to unite local neurosurgeons in the New England area; it was one of the first regional neurosurgical societies in America. Although regional neurosurgical societies are important supplements to national organizations, they have often been overshadowed in the available literature. Now in its 70th year, the NENS continues to serve as a platform to represent the needs of New England neurosurgeons, foster connections and networks with colleagues, and provide research and educational opportunities for trainees. Additionally, regional societies enable discussion of issues uniquely relevant to the region, improve referral patterns, and allow for easier attendance with geographic proximity. In this paper, the authors describe the history of the NENS and provide a roadmap for its future. The first section portrays the founders who led the first meetings and establishment of the NENS. The second section describes the early years of the NENS and profiles key leaders. The third section discusses subsequent neurosurgeons who steered the NENS and partnerships with other societies. In the fourth section, the modern era of the NENS and its current activities are highlighted.

Organizational Readiness for Patient-Facing Mobile Teledermatology to Care for Established Veteran Patients in the United States.

Purpose: To improve patient access to skin care, the Department of Veterans Affairs (VA) developed a patient-facing asynchronous mobile teledermatology application (app), which allows patients to follow up remotely with dermatologists. To understand how the app would be received in VA, we examined Organizational Readiness for Change (ORC), an important prelude to effective implementation, which includes the shared resolve and collective ability of organizational members to implement a change. Methods: We used a mixed-methods multiple case study approach to assess ORC at three VA facilities. Data derived from a site process call, surveys, and semistructured telephone interviews of VA staff, field notes, and administrative data. Results: Participants at all three facilities supported the intervention and recognized the value of using the app to increase patients' access to dermatologists, but expressed concerns largely related to disruption of the pre-existing clinical workflow. Participants at the facility most actively using the app had the highest overall ORC score and reported the most facilitators. Facility leadership support when guided by a clinical champion minimized barriers by recognizing the complexities of health care provision at specialty clinics. Discussion: While provider buy-in remained a barrier, leadership, guided by the clinical champion, played a critical role instituting implementation strategies. The strong association between the ORC survey score and the presence of facilitators and barriers suggests that the ORC survey may be a rapid, convenient, and effective tool for health care systems to identify favorable sites for wider implementation of mobile telehealth care. Clinical Trials Identifier: NCT03241589.

Time and Distance Cost of Longer Acting Anti-VEGF Therapies for Macular Degeneration: Contributions to Drug Cost Comparisons.

Purpose: To evaluate the holistic cost of longer acting anti-VEGF therapy for macular degeneration when considering the associated costs of travel to the retina clinic. Design: Theoretical evaluation of cost using publicly available pricing data and reimbursements at the Veterans Affairs (VA) Medical Center. Patients and Methods: Setting: VA Medical Center. Study population: Patients with age related macular degeneration. Main outcome measures: Three-year cost of therapy when considering medication as well as travel costs and time spent in transit. Results: Based on cost data derived purely from wholesale acquisition cost and projected injection frequency over the first three years of treatment, faricimab is less expensive than ranibizumab and aflibercept by $37,709 and $6359, respectively. Aflibercept is less expensive ranibizumab by $31,350 over the first 3 years of treatment. When considering even small distances traveled by patients, these cost differences grow, amplified at even larger distances: at 25 miles, ranibizumab becomes $38,814 and $32,133 more expensive than faricimab and aflibercept, respectively. Aflibercept becomes $6681 more expensive than faricimab. At 100 miles, ranibizumab becomes $41,502 and $34,038 more expensive than faricimab and aflibercept, respectively. Aflibercept becomes $7464 more expensive than faricimab. Conclusion: Longer acting anti-VEGF therapies may differ not only in their wholesale acquisition cost, but also in the frequency of per label injections and associated clinic visits. Taking into account distance and time cost of travel may contribute to a more holistic view of cost differences among these therapies.

Limited impact of teledermoscopy on referrals to face-to-face dermatology.

BACKGROUND: Teledermoscopy improves teledermatology clinical outcomes, but the practical impact of this and other teleconsultation variables on patient management are unclear. We assessed the impact of these variables, including dermoscopy, on face-to-face (F2F) referrals to optimize effort by imagers and dermatologists. METHODS: Using retrospective chart review, we retrieved demographic, consultation, and outcome variables from 377 interfacility teleconsultations sent to San Francisco Veterans Affairs Health Care System (SFVAHCS) between September 2018 to March 2019 from another VA facility and its satellite clinics. Data were analyzed using descriptive statistics and logistic regression models. RESULTS: Of 377 consults, 20 were excluded due to patient F2F self-referral without teledermatologist recommendation. Analysis of consults showed that age, clinical image, and problem number but not dermoscopy were associated with F2F referral. Analysis of problems contained in consults showed that lesion location and diagnostic category were also associated with F2F referral. Skin cancer history and problems on the head/neck were independently associated with skin growths in multivariate regression. CONCLUSIONS: Teledermoscopy was associated with variables related to neoplasms but did not affect F2F referral rates. Rather than utilize teledermoscopy for all cases, our data suggests that referring sites prioritize teledermoscopy for consultations with variables associated with a likelihood of malignancy.

The Utilization and Impact of Live Interactive and Store-and-Forward Teledermatology in a Veterans Affairs Medical Center During the COVID-19 Pandemic.

Introduction: Teledermatology has emerged as a promising method of continuing dermatologic care during the coronavirus 2019 (COVID-19) pandemic, including in the Department of Veterans Affairs (VA). Analysis of the utilization and impact of teledermatology within the San Francisco Veterans Affairs Health Care System (SFVAHCS) may elucidate the ways that teledermatology programs can continue to be optimized. Methods: We conducted a retrospective analysis of live interactive encounters, Veterans Affairs Video Connect (VVC), store-and-forward telehealth (SFT), and face-to-face (FTF) consultations, performed within the SFVAHCS from March 2020 to December 2020. To assess utilization, we analyzed numbers of encounters throughout 2020. To assess impact, we analyzed primary diagnoses for each encounter and rates of recommendations for medications and lesion biopsies. Additionally, we assessed diagnostic accuracy associated with each teledermatology type by measuring concordance between teledermatologists' clinical diagnoses and histopathological diagnoses. Results: Two thousand two hundred fifty FTF, 347 VVC, and 470 SFT encounters were conducted from March to December 2020. More female patients utilized VVC, and patients who utilized VVC were younger than SFT and FTF users (p < 0.01). SFT was utilized more by patients from rural areas (p < 0.01). Diagnoses addressed were significantly different between VVC and SFT. A majority of VVC encounters involved referrals for inflammatory conditions; primary diagnoses associated with SFT consultations were most frequently neoplasms. Comparison of VVC and SFT outcomes showed that more VVC visits resulted in a medication recommendation, while more SFT consultations resulted in a biopsy recommendation. Conclusions: Teledermatology contributed to meeting patient needs throughout 2020 and created an impact on clinical management. Patient characteristics, diagnoses, and type of impact associated with encounters varied between SFT and VVC. This analysis provides insight into teledermatology utilization within the VA system and can contribute to efforts to improve the quality of teledermatology care for veterans.

The Effect of Telehealth Services on Provider Productivity.

BACKGROUND: Telehealth services historically have played a small role in the provision of health care in the United States. However during the coronavirus disease 2019 (COVID-19) pandemic, public and private insurers rapidly expanded access to telehealth in order to reduce exposure and avoid transmission. It is unknown whether telehealth will become a more regular substitute for in-person care beyond the pandemic. OBJECTIVE: Our objective was to provide evidence on the value of telehealth by comparing the productivity of physicians and other specialized clinicians who provide telehealth with the productivity of those who do not. RESEARCH DESIGN: We conducted a retrospective data analysis of 17,705 unique providers in the areas of internal medicine, cardiology, dermatology, psychiatry, psychology, and optometry practicing in the US veterans affairs health care system during the period 2015 to 2018. For each year, we measured individual providers productivity by the total number of relative value units (RVUs) per full-time equivalent (FTE). We estimated the impact of providing telehealth on RVUs/FTE using fixed effects regression models estimated on a panel dataset of 58,873 provider-year observations and controlling for provider and patient characteristics. RESULTS: Overall provider productivity increased in veterans affairs over the period, particularly in cardiology and dermatology. Providers of telehealth had above average productivity by 124 RVUs/FTE, or ∼4% of average total provider productivity. For the highest quartile of telehealth providers, average productivity was 188 RVUs/FTE higher than productivity of other providers. CONCLUSION: Strategies that encourage long-term integration of telehealth into provider practices may contribute to overall health care value.

Implementation of Mobile Teledermatology: Challenges and Opportunities.

Background: While teledermatology is well-established in the Department of Veterans Affairs (VA), its implementation is far from complete. To facilitate consultative teledermatology and extend its reach, VA introduced a mobile teledermatology application (app) at three VA sites. Methods: We evaluated the initial implementation process using a mixed-methods, multiple case study approach to assess organizational readiness for change (ORC), which included examining facilitators, barriers, and contextual factors that affected implementation. We conducted: (1) group interviews and bimonthly reports to understand site processes; (2) semistructured interviews and surveys of individual participants representing a range of implementation roles; and (3) a review of internal organizational documents. We identified themes from interviews using an iterative process, and computed an ORC score based on surveys. Results: Forty-three individuals participated in the study. Qualitative data from all sites, corroborated by survey data available from one site, revealed a high readiness for change with an ORC score of 4.2, where 5 = maximal readiness for change. Facilitators included support from leadership and clinical champions, active telehealth programs, and an understanding and appreciation of the program and the resources needed. At all sites, however, technical issues negatively affected adoption; these included a suboptimal information technology infrastructure, which led to the inoperability of the app at two sites, and technical inefficiencies related to users' unfamiliarity with new devices and inconsistent internet access. Conclusions: Although a strong commitment to change and a confidence to effect change existed, these alone were insufficient to surmount barriers to implementation effectiveness. Clinical Trials Registration: NCT03241589.

Vitamin D Receptor Promotes Global Nucleotide Excision Repair by Facilitating XPC Dissociation from Damaged DNA.

Vitamin D receptor (VDR) is important for normal DNA repair, although the mechanism by which it acts is unclear. After focal UV irradiation to create subnuclear spots of DNA damage, epidermal keratinocytes from VDR-null mice as well as human epidermal keratinocytes depleted of VDR with small interfering RNA removed pyrimidine-pyrimidone (6-4) photoproducts more slowly than control cells. Costaining with antibodies to XPC, the DNA damage recognition sensor that initiates nucleotide excision repair, showed that XPC rapidly accumulated at spots of damage and gradually faded in control human keratinocytes. In VDR-depleted keratinocytes, XPC associated with DNA damage with comparable efficiency; however, XPC's dissociation dynamics were altered so that significantly more XPC was bound and retained over time than in control cells. The XPF endonuclease, which acts subsequently in nucleotide excision repair, bound and dissociated with comparable kinetics in control and VDR-depleted cells, but the extent of binding was reduced in the latter. These results as well as kinetic modeling of the data suggest that VDR's importance in the repair of UV-induced DNA damage is mediated in part by its ability to facilitate the dissociation of XPC from damaged DNA for the normal recruitment and assembly of other repair proteins to proceed.

Implementing Teledermatology for Rural Veterans: An Evaluation Using the RE-AIM Framework.

Introduction: Few systematic evaluations of implementing teledermatology programs in large health care systems exist. We conducted a longitudinal evaluation of a U.S. Department of Veterans Affairs (VA) initiative to expand asynchronous consultative teledermatology services for rural veterans. Methods: The reach, effectiveness, adoption, implementation, and maintenance framework guided the evaluation, which included analysis of quantitative VA administrative data as well as an online survey completed by participating facilities. The first 2 years of the program were compared with the year before the start of funding. Results: Sixteen hub facilities expanded teledermatology's reach over the 2-year period, increasing the number of referral spoke sites, unique patients served, and teledermatology encounters. Effectiveness was reflected as teledermatology constituted an increasing fraction of dermatology activity and served more remotely located patients. Adoption through defined stages of implementation progressed as facilities engaged in a variety of strategies to enhance teledermatology implementation, and facilitators and barriers were identified. Program maintenance was assessed by Program Sustainability Index scores, which reflected the importance of executive support, and ongoing concerns about staffing and longitudinal funding. Discussion: Enabling hubs to create solutions that best fit their needs and culture likely increased reach and effectiveness. Important facilitators included organizational leadership and encouraging communication between stakeholders before and during the intervention. Conclusions: A systematic analysis of teledermatology implementation to serve rural sites in VA documented a high degree of implementation and sustainability as well as areas for improvement.

VA Telederm study: protocol for a stepped-wedge cluster randomised trial to compare access to care for a mobile app versus a workstation-based store-and-forward teledermatology process.

INTRODUCTION: Teledermatology has emerged as an important strategy to enhance access to high-quality skin care. VA Telederm is a provider-facing, web-based mobile app designed to integrate into the existing teledermatology workflow in the US Veterans Health Administration (VHA). In this study, we will conduct a systematic evaluation of VA Telederm on access outcomes in VHA facilities using a pragmatic trial guided by clinical and operational leaders. METHODS AND ANALYSIS: The study is a prospective, stepped-wedge cluster randomised trial with cross-sectional exposure and outcome measurement via retrospective database analysis of administrative records. Each cluster is a VHA facility deemed eligible for the trial. We assign the intervention using a cluster-level balanced randomisation scheme based on facility size, baseline teledermatology uptake and geographic location. The trial will test whether patients receiving dermatological care at participating facilities will have better access compared with patients receiving care through the current standard process. The primary outcomes proxy for patient-level access to dermatology services, including (1) consult completion time for teledermatology consults; (2) appointment completion time for new dermatology consults; and (3) travel distance for dermatology services. As secondary outcomes, we will assess facility-level adoption outcomes, that is, the number of dermatology encounters and the proportion of teledermatology consults out of all dermatology encounters. To account for secular trends in outcomes and for correlation across individuals within clusters, we will assess the impact of the intervention using generalised linear mixed regression models. DISCUSSION: Streamlining the current practice for store-and-forward teledermatology in the VHA can improve access to expert dermatological care for US veterans. The lessons learnt in this trial could validate the use of mobile technology for consultative store-and-forward dermatology in a large healthcare organisation. The results may also be of interest to other medical specialties assessing the merits of implementing mobile telehealth. PROTOCOL VERSION: Version 3; 7 November 2018. TRIAL REGISTRATION NUMBER: NCT03241589; Pre-results.

Teledermatology in the United States: An Update in a Dynamic Era.

BACKGROUND: Teledermatology is rapidly advancing in the United States. The last comprehensive survey of U.S. teledermatology programs was conducted in 2011. INTRODUCTION: This article provides an update regarding the state of teledermatology programs in the United States. MATERIALS AND METHODS: Active programs were identified and surveyed from November 2014 to January 2017. Findings regarding practice settings, consult volumes, payment methods, and delivery modalities were compared to those from the 2011 survey. Findings from the Veterans Affairs (VA) were reported as an aggregate. RESULTS: There were 40 active nongovernmental programs, amounting to a 48% increase and 30% discontinuation rate over five years. Academia remained the most common practice setting (50%). Median annual consultation volume was comparable with 263 consultations, but maximum annual consultation volume increased (range: 20-20,000). The most frequent payment method was self-pay (53%). Store-and-forward continued to be the most common delivery modality. In Fiscal Year 2016, the VA System consisted of 62 consultation sites and performed a total of 101,507 consultations. DISCUSSION: The limitations of this study were that consult volume and payment methods were not available from all programs. CONCLUSION: U.S. teledermatology programs have increased in number and annual consultation volume. Academia is the most prevalent practice setting, and self-pay is the dominant accepted payment method. Innovative platforms and the provision of direct-to-patient care are changing the practice of teledermatology.

A Heparin Binding Motif Rich in Arginine and Lysine is the Functional Domain of YKL-40.

The heparin-binding glycoprotein YKL-40 (CHI3L1) is intimately associated with microvascularization in multiple human diseases including cancer and inflammation. However, the heparin-binding domain(s) pertinent to the angiogenic activity have yet been identified. YKL-40 harbors a consensus heparin-binding motif that consists of positively charged arginine (R) and lysine (K) (RRDK; residues 144-147); but they don't bind to heparin. Intriguingly, we identified a separate KR-rich domain (residues 334-345) that does display strong heparin binding affinity. A short synthetic peptide spanning this KR-rich domain successfully competed with YKL-40 and blocked its ability to bind heparin. Three individual point mutations, where alanine (A) substituted for K or R (K337A, K342A, R344A), led to remarkable decreases in heparin-binding ability and angiogenic activity. In addition, a neutralizing anti-YKL-40 antibody that targets these residues and prevents heparin binding impeded angiogenesis in vitro. MDA-MB-231 breast cancer cells engineered to express ectopic K337A, K342A or R344A mutants displayed reduced tumor development and compromised tumor vessel formation in mice relative to control cells expressing wild-type YKL-40. These data reveal that the KR-rich heparin-binding motif is the functional heparin-binding domain of YKL-40. Our findings shed light on novel molecular mechanisms underlying endothelial cell angiogenesis promoted by YKL-40 in a variety of diseases.

The ROI-C zero-profile anchored spacer for anterior cervical discectomy and fusion: biomechanical profile and clinical outcomes.

INTRODUCTION: Anterior cervical discectomy and fusion (ACDF) has been the gold standard for treating cervical degenerative disc disease (cDDD). The use of anterior plates in ACDF poses an increased risk of complications such as screw or plate dislodgement, soft tissue injury, esophagus perforation, and dysphagia. The ROI-C™ implant system consists of a zero-profile interbody fusion cage with self-locking plates designed for stand-alone fusion without external plates or screws. OBJECTIVE: The purpose of this report is to describe the ROI-C™ implant system with VerteBRIDGE™ anchor plates, including indications for use, surgical technique, preclinical testing, and clinical study results. The objectives of the clinical study were to assess fusion status, incidence of dysphagia and other device-related complications, and patient reported outcomes. METHODS: This was a retrospective, multicenter cohort study of 110 patients who underwent ACDF with ROI-C at seven study centers. Patient charts and radiographs were reviewed for any complications or device malfunction. The final follow-up was conducted prospectively and included collection of neck disability index, and visual analog scale (VAS) neck and arm pain scores. RESULTS: The mean operation time was 73 minutes, and mean blood loss was 25 mL (range 0-75 mL). Mean follow-up was 20.7 months (range 9.5-42.2). Dysphagia was reported in two patients (1.8%), and 99.1% of patients achieved fusion. One patient had radiographically confirmed pseudarthrosis at 12 months that was asymptomatic and did not require surgery. One patient had subsequent surgery owing to adjacent level degeneration. The mean neck disability index, VAS neck pain, and VAS right and left arm pain scores at final follow-up were 19, 26.5, 12.5, and 15.3, respectively. CONCLUSION: The ROI-C interbody cage with VerteBRIDGE anchor plates achieved a high rate of fusion, with a low incidence of dysphagia. These patients had similar or better outcomes compared to ACDF with anterior plating reported in peer-reviewed literature.

Practice Guidelines for Teledermatology.

Previous American Telemedicine Association (ATA) Teledermatology Practice Guidelines were issued in 2007. This updated version reflects new knowledge in the field, new technologies, and the need to incorporate teledermatology practice in a variety of settings, including hospitals, urgent care centers, Federally Qualified Health Centers, school-based clinics, public health facilities, and patient homes.

Deficient Nucleotide Excision Repair in Squamous Cell Carcinoma Cells.

Squamous cell carcinomas (SCCs) are associated with ultraviolet radiation and multiple genetic changes, but the mechanisms leading to genetic instability are unclear. SCC cell lines were compared to normal keratinocytes for sensitivity to ultraviolet radiation, DNA repair kinetics and DNA repair protein expression. Relative to normal keratinocytes, four SCC cell lines were all variably sensitive to ultraviolet radiation and, except for the SCC25 cell line, were deficient in global repair of cyclobutane pyrimidine dimers, although not 6-4 photoproducts. Impaired DNA repair of cyclobutane pyrimidine dimers was associated with reduced mRNA expression from XPC but not DDB2 genes which each encode key DNA damage recognition proteins. However, levels of XPC or DDB2 proteins or both were variably reduced in repair-deficient SCC cell lines. p53 levels did not correlate with DNA repair activity or with XPC and DDB2 levels, but p63 levels were deficient in cell lines with reduced global repair. Repair-proficient SCC25 cells depleted of p63 lost XPC expression, early global DNA repair activity and UV resistance. These results demonstrate that some SCC cell lines are deficient in global nucleotide excision repair and support a role for p63 as a regulator of nucleotide excision repair in SCCs.