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The latest information about the 2019 Novel Coronavirus, including vaccine clinics for children ages 6 months and older.

La información más reciente sobre el nuevo Coronavirus de 2019, incluidas las clínicas de vacunación para niños de 6 meses en adelante.


Paige Fox, MD, PhD

  • Paige McCarthy Fox


Plastic & Reconstructive Surgery

Work and Education

Professional Education

Virginia Commonwealth University, Richmond, VA, 12/28/2007


Stanford University Dept of Plastic Surgery, Palo Alto, CA, 6/30/2014


Mayo Clinic Upper Extremity Reconstructive Surgery Fellowship, Rochester, MN, 7/31/2015

Board Certifications

Surgery of the Hand, American Board of Plastic Surgery

Conditions Treated

Brachial Plexus Injury

All Publications

Capacity Assessment Tool to Promote Capacity Building in Global Orthopaedic Surgical Outreach. The Journal of bone and joint surgery. American volume Shapiro, L. M., Welch, J., Leversedge, C., Katarincic, J. A., Leversedge, F. J., Dyer, G. S., Kozin, S. H., Fox, P. M., McCullough, M., Agins, B., Kamal, R. N. 2023


A growing number of nongovernmental organizations from high-income countries aim to provide surgical outreach for patients in low- and middle-income countries in a manner that builds capacity. There remains, however, a paucity of measurable steps to benchmark and evaluate capacity-building efforts. Based on a framework for capacity building, the present study aimed to develop a Capacity Assessment Tool for orthopaedic surgery (CAT-os) that could be utilized to evaluate and promote capacity building.To develop the CAT-os tool, we utilized methodological triangulation-an approach that incorporates multiple different types of data. We utilized (1) the results of a systematic review of capacity-building best practices in surgical outreach, (2) the HEALTHQUAL National Organizational Assessment Tool, and (3) 20 semistructured interviews to develop a draft of the CAT-os. We subsequently iteratively used a modified nominal group technique with a consortium of 8 globally experienced surgeons to build consensus, which was followed by validation through member-checking.The CAT-os was developed and validated as a formal instrument with actionable steps in each of 7 domains of capacity building. Each domain includes items that are scaled for scoring. For example, in the domain of partnership, items range from no formalized plans for sustainable, bidirectional relationships (no capacity) to local surgeons and other health-care workers independently participating in annual meetings of surgical professional societies and independently creating partnership with third party organizations (optimal capacity).The CAT-os details steps to assess capacity of a local facility, guide capacity-improvement efforts during surgical outreach, and measure the impact of capacity-building efforts. Capacity building is a frequently cited and commendable approach to surgical outreach, and this tool provides objective measurement to aid in improving the capacity in low and middle-income countries through surgical outreach.

View details for DOI 10.2106/JBJS.23.00020

View details for PubMedID 37319177

Tenolysis and Salvage Procedures. Hand clinics Cholok, D., Burgess, J., Fox, P. M., Chang, J. 2023; 39 (2): 203-214


Complications in flexor tendon repair are common and include tendon rupture, adhesion formation, and joint contracture. Risk factors include preexisting conditions, gross contamination, concurrent fracture, early unplanned loading of the repaired tendon, premature cessation of splinting, and aggressive early active range of motion protocols with insufficient repair strength. Rupture of a repaired tendon should be followed by early operative exploration, debridement, and revision with a four-core strand suture and nonbraided epitendinous suture. Wide-awake flexor tenolysis should be considered when adhesion formation results in the plateaued range of motion, and passive motion exceeds active motion. Two-staged reconstruction is recommended when injury results in excessive scaring, joint contracture, or an incompetent pulley apparatus.

View details for DOI 10.1016/j.hcl.2022.08.021

View details for PubMedID 37080652

Scoping Review of Hydrogel Therapies in the Treatment of Diabetic Chronic Wounds. Plastic and reconstructive surgery. Global open Sharma, A. D., Jarman, E. H., Fox, P. M. 2023; 11 (5): e4984


Chronic diabetic wounds are a significant issue that can be treated with topical hydrogel therapies. The aim of this study was to review the different compositions of hydrogel that have been developed and analyze their clinical relevance in the treatment of chronic diabetic wounds.Methods: We conducted a scoping review in which twelve articles were selected for review after applying relevant inclusion and exclusion criteria using a two-reviewer strategy. Data extracted from these studies was used to answer the following research question: What is the composition of hydrogels used to treat chronic diabetic wounds and how effective are they?Results: We analyzed five randomized controlled trials, two retrospective studies, three reviews, and two case reports. Hydrogel compositions discussed included mesenchymal stem cell sheets, carbomer, collagen, and alginate hydrogels, as well as hydrogels embedded with platelet-derived growth factor. Synthetic hydrogels, largely composed of carbomers, were found to have high levels of evidence supporting their wound healing properties, though few articles described their routine use in a clinical setting. Collagen hydrogels dominate the present-day hydrogel market in the clinical treatment of chronic diabetic wounds. The augmentation of hydrogels with therapeutic biomaterials is a new field of hydrogel research, with studies demonstrating promising early in vitro and in vivo animal studies demonstrating promising early results for in vitro and in vivo animal investigations.Conclusions: Current research supports hydrogels as a promising topical therapy in the treatment of chronic diabetic wounds. Augmenting Food & Drug Administration-approved hydrogels with therapeutic substances remains an interesting early area of investigation.

View details for DOI 10.1097/GOX.0000000000004984

View details for PubMedID 37250833

The Impact of Virtual Reality on the Patients and Providers Experience in Wide-Awake, Local-Only Hand Surgery. Journal of hand surgery global online McCullough, M., Osborne, T. F., Rawlins, C., Reitz, R. J., Fox, P. M., Curtin, C. 2023; 5 (3): 290-293


Virtual reality (VR) is an emerging technology with the potential to enhance patient care by reducing pain and anxiety for a variety of medical procedures. The aim of this study was to evaluate an immersive VR program as a nonpharmacologic intervention to reduce anxiety and increase satisfaction in patients undergoing wide-awake, local-only hand surgery. The secondary aim was to assess providers' experience with the program.An implementation evaluation was employed to assess the experience of 22 patients who used VR during outpatient, wide-awake hand surgery at a veterans affairs hospital. We assessed the patients' anxiety scores and vital signs before and after the procedure as well as postprocedural satisfaction measures. The providers' experience was also assessed.Patients who used VR exhibited lower anxiety scores after the procedure compared with what they exhibited before the procedure and had high satisfaction levels with their VR experience. Surgeons who used the system reported that VR improved their ability to teach learners and better focus on the procedure.Virtual reality, as a nonpharmacologic intervention, reduced anxiety and contributed to the patients' perioperative satisfaction with wide-awake, local-only hand surgery. As a secondary finding, VR positively impacted the providers' experience by increasing their ability to concentrate on tasks during the surgery.Virtual reality represents a novel technology that can reduce anxiety and contribute to a positive experience for both patients and providers during wide-awake, local-only hand procedures.

View details for DOI 10.1016/j.jhsg.2023.01.014

View details for PubMedID 37323984

View details for PubMedCentralID PMC10264860

Management of Brachial Plexus Birth Palsies: The Stanford Experience SEMINARS IN PLASTIC SURGERY Park, E., Fox, P. M., Curtin, C., Hentz, V. R. 2023
Is Hand Surgery in the Procedure Room Setting Associated with Increased Surgical Site Infection? A Cohort Study of 2,717 Patients in the Veterans Affairs Population. The Journal of hand surgery Zhuang, T., Fox, P., Curtin, C., Shah, K. N. 2023


Procedure rooms (PRs) are increasingly used for hand surgeries, but few studies have directly compared surgical site infection (SSI) rates between the PR and operating room. We tested the hypothesis that procedure setting is not associated with an increased SSI incidence in the VA population.We identified carpal tunnel, trigger finger, and first dorsal compartment releases performed at our VA institution from 1999 to 2021 of which 717 were performed in the main operating room and 2,000 were performed in the PR. The incidence of SSI, defined as signs of wound infection within 60 days of the index procedure, which was treated with oral antibiotics, intravenous antibiotics, and/or operating room irrigation and debridement, was compared. We constructed a multivariable logistic regression analysis to assess the association between procedure setting and SSI incidence, adjusting for age, sex, procedure type, and comorbidities.Surgical site infection incidence was 55/2,000 (2.8%) in the PR cohort and 20/717 (2.8%) in the operating room cohort. In the PR cohort, five (0.3%) cases required hospitalization for intravenous antibiotics of which two (0.1%) cases required operating room irrigation and debridement. In the operating room cohort, two (0.3%) cases required hospitalization for intravenous antibiotics of which one (0.1%) case required operating room irrigation and debridement. All other SSIs were treated with oral antibiotics alone. The procedure setting was not independently associated with SSI (adjusted odds ratio, 0.84 [95% confidence interval, 0.49, 1.48]). The only risk factor for SSI was trigger finger release (odds ratio, 2.13 [95% confidence interval, 1.32, 3.48] compared with carpal tunnel release), which was independent of setting.Minor hand surgeries can be performed safely in the PR without an increased rate of SSI.Prognostic II.

View details for DOI 10.1016/j.jhsa.2023.03.001

View details for PubMedID 36973100

Impact of Adding Carpal Tunnel Release or Trigger Finger Release to Carpometacarpal Arthroplasty on Postoperative Complications". Plastic and reconstructive surgery Trinh, P., Luan, A., Tawfik, V. L., Sheckter, C., Rochlin, D., Fox, P., Curtin, C. 2023


BACKGROUND: This study assessed whether adding trigger finger or carpal tunnel release at the time of thumb carpometacarpal (CMC) arthroplasty would increase postoperative opioid use, readmissions, complications, and development of CRPS.METHODS: Using the IBM MarketScan Research Databases from 2012 to 2016, we identified a two groups of CMC arthroplasty patients. The "CMC only" group only had a CMC arthroplasty on the day of operation. The "multiple procedures" group had a CMC arthroplasty and concurrent carpal tunnel and / or trigger finger release. Between the two groups, we compared persistent opioid use, 30-day readmissions, 30-day complications, and diagnosis of complex regional pain syndrome (CRPS).RESULTS: The CMC only group consisted of 18,010 patients. The multiple procedures group consisted of 4,064 patients. These patients received a CMC arthroplasty and a carpal tunnel release (74%), a trigger finger release (20%), or both (6%). CMC only patients had lower rates of persistent opioid use compared to patients who underwent multiple procedures (16% vs 18%). Readmission rates were also lower for CMC only patients (3% vs 4%). CMC only patients had decreased odds of persistent opioid use (OR=0.85; 95% CI, 0.75-0.97, p=0.013) and readmissions (OR=0.80; 95% CI, 0.67-0.96, p=0.016). The most common reason for readmission was pain (16%).CONCLUSIONS: Adding another procedure to a CMC arthroplasty slightly increases the odds of adverse outcomes such as persistent opioid use and readmission. Patients and providers should weigh the efficiency of doing these procedures concurrently against the risk of performing multiple procedures at once.CLINICAL QUESTION / LEVEL OF EVIDENCE: Risk, II.

View details for DOI 10.1097/PRS.0000000000010144

View details for PubMedID 36728633

Assessment of a Synergistic Effect of Platelet-Rich Plasma and Stem Cell-Seeded Hydrogel for Healing of Rat Chronic Rotator Cuff Injuries. Cell transplantation Oda, H., Kaizawa, Y., Franklin, A., Sanchez Rangel, U., Storaci, H., Min, J. G., Wang, Z., Abrams, G. D., Chang, J., Fox, P. M. 2023; 32: 9636897231190174


Outcomes after repair of chronic rotator cuff injuries remain suboptimal. Type-1 collagen-rich tendon hydrogel was previously reported to improve healing in a rat chronic rotator cuff injury model. Stem cell seeding of the tendon hydrogel improved bone quality in the same model. This study aimed to examine whether there was a synergistic and dose-dependent effect of platelet-rich plasma (PRP) on tendon-bone interface healing by combining PRP with stem cell-seeded tendon hydrogel. Human cadaveric tendons were processed into a hydrogel. PRP was prepared at two different platelet concentrations: an initial concentration (initial PRP group) and a higher concentration (concentrated PRP group). Tendon hydrogel was mixed with adipose-derived stem cells and one of the platelet concentrations. Methylcellulose, as opposed to saline, was used as a negative control due to comparable viscosity. The supraspinatus tendon was detached bilaterally in 33 Sprague-Dawley rats (66 shoulders). Eight weeks later, each detached tendon was repaired, and a hydrogel mixture or control was injected at the repair site. Eight weeks after repair, shoulder samples were harvested and assigned for biomechanical testing (n = 42 shoulders) or a combination of bone morphological and histological assessment (n = 24 shoulders). Biomechanical testing showed significantly higher failure load and stiffness in the concentrated PRP group than in control. Yield load in the initial and concentrated PRP groups were significantly higher than that in the control. There were no statistically significant differences between the initial and concentrated PRP groups. The addition of the highly concentrated PRP to stem cells-seeded tendon hydrogel improved healing biomechanically after chronic rotator cuff injury in rats compared to control. However, synergistic and dose-dependent effects were not seen.

View details for DOI 10.1177/09636897231190174

View details for PubMedID 37592455

The Environmental Impact of Orthopaedic Surgery. The Journal of bone and joint surgery. American volume Saleh, J. R., Mitchell, A., Kha, S. T., Outterson, R., Choi, A., Allen, L., Chang, T., Ladd, A. L., Goodman, S. B., Fox, P., Chou, L. 2022


: There are a growing number of opportunities within the field of orthopaedic surgery to address climate change and investigate ways to promote sustainability.: Orthopaedic surgeons can take a proactive role in addressing climate change and its impacts within the areas of operating-room waste, carbon emissions from transportation and implant manufacturing, anesthetic gases, and water usage.: Future studies are needed to further these initiatives on quantifying and decreasing environmental impact and furthering sustainable use of our resources.

View details for DOI 10.2106/JBJS.22.00548

View details for PubMedID 36574633

Thinking Outside the Operating Room: Guidance on Designing a Safe and Effective Minor Procedure Room. The Journal of hand surgery Silverstein, M., Fox, P. M., Curtin, C. 2022


The minor procedure room (MPR) offers numerous advantages over the traditional operating room for performing many common hand surgeries. MPRs require less space, are subject to more practical architectural design standards, and facilitate more judicious use of disposable materials and unnecessary instruments than common hand surgeries. MPRs reduce costs to the system and patient at every step of the surgical workflow and improve efficiency by removing preoperative and postoperative monitoring requirements. Hand surgeons sometimes face resistance when attempting surgery in MPRs, often because of confusion about their design characteristics and capabilities. This article aims to clarify many of the major requirements for establishing an MPR and provide a guide to hand surgeons for performing safe, efficient surgery outside the operating room.

View details for DOI 10.1016/j.jhsa.2022.10.005

View details for PubMedID 36351850

Biomechanical, Histologic, and Micro-Computed Tomography Characterization of Partial-Width Full-Thickness Supraspinatus Tendon Injury in Rats. The Journal of hand surgery Oda, H., Kaizawa, Y., Franklin, A., Rangel, U. S., Min, J. G., Akerman, J., Storaci, H., Wang, Z., Abrams, G. D., Chang, J., Fox, P. M. 2022


PURPOSE: Partial rotator cuff tears can cause shoulder pain and dysfunction and are more common than complete tears. However, few studies examine partial injuries in small animals and, therefore a robust, clinically relevant model may be lacking. This study aimed to fully characterize the established rat model of partial rotator cuff injury over time and determine if it models human partial rotator cuff tears.METHODS: We created a full-thickness, partial-width injury at the supraspinatus tendon-bone interface bilaterally in 31 Sprague-Dawley rats. Rats were euthanized immediately, and at 2-, 3-, 4-, and 8-weeks after surgery. Fourteen intact shoulders were used as controls. Samples were assessed biomechanically, histologically, and morphologically.RESULTS: Biomechanically, load to failure in controls and 8 weeks after injury was significantly greater than immediately and 3 weeks after injury. Load to failure at 8 weeks was comparable to control. However, the locations of failure were different between intact shoulders and partially injured samples. Bone mineral density at 8 weeks was significantly greater than that at 2 and 3 weeks. Although no animals demonstrated propagation to complete tear and the injury site remodeled histologically, the appearance at 8 weeks was not identical to that in the controls.CONCLUSIONS: The biomechanical properties and bone quality decreased after the injury and was restored gradually over time with full restoration by 8 weeks after injury. However, the findings were not equivalent to the intact shoulder. This study demonstrated the limitations of the current model in its application to long-term outcome studies, and the need for better models that can be used to assess chronic partial rotator cuff injuries.CLINICAL RELEVANCE: There is no small animal model that mimics human chronic partial rotator cuff tears, which limits our ability to improve care for this common condition.

View details for DOI 10.1016/j.jhsa.2022.08.027

View details for PubMedID 36280554

A Framework and Blueprint for Building Capacity in Global Orthopaedic Surgical Outreach. The Journal of bone and joint surgery. American volume Shapiro, L. M., Welch, J. M., Chatterjee, M., Katarincic, J. A., Leversedge, F. J., Dyer, G. S., Fufa, D. T., Kozin, S. H., Chung, K. C., Fox, P. M., Chang, J., Kamal, R. N. 2022


BACKGROUND: Nongovernmental organizations (NGOs) from high-income countries provide surgical outreach for patients in low and middle-income countries (LMICs); however, these efforts lack a coordinated measurement of their ability to build capacity. While the World Health Organization and others recommend outreach trips that aim to build the capacity of the local health-care system, no guidance exists on how to accomplish this. The objective of this paper is to establish a framework and a blueprint to guide the operations of NGOs that provide outreach to build orthopaedic surgical capacity in LMICs.METHODS: We conducted a qualitative analysis of semistructured interviews with 16 orthopaedic surgeons and administrators located in 7 countries (6 LMICs) on the necessary domains for capacity-building; the analysis was guided by a literature review of capacity-building frameworks. We subsequently conducted a modified nominal group technique with a consortium of 10 U.S.-based surgeons with expertise in global surgical outreach, which was member-checked with 8 new stakeholders from 4 LMICs.RESULTS: A framework with 7 domains for capacity-building in global surgical outreach was identified. The domains included professional development, finance, partnerships, governance, community impact, culture, and coordination. These domains were tiered in a hierarchical system to stratify the level of capacity for each domain. A blueprint was developed to guide the operations of an organization seeking to build capacity.CONCLUSIONS: The developed framework identified 7 domains to address when building capacity during global orthopaedic surgical outreach. The framework and its tiered system can be used to assess capacity and guide capacity-building efforts in LMICs. The developed blueprint can inform the operations of NGOs toward activities that focus on building capacity in order to ensure a measured and sustained impact.

View details for DOI 10.2106/JBJS.22.00353

View details for PubMedID 35984012

Wellness: Building a Meaningful and Effective Program PLASTIC AND RECONSTRUCTIVE SURGERY Chavez, J. F., Fox, P. M. 2022; 150 (2): 494E
The Development and Validation of Data Elements and Process Steps for an Electronic Health Record for Hand Surgery Outreach Trips JOURNAL OF HAND AND MICROSURGERY Shapiro, L. M., Chang, J., Fox, P. M., Kozin, S., Chung, K. C., Dyer, G. M., Fufa, D., Leversedge, F., Katarincic, J., Kamal, R. 2022
The environmental impact of surgery: A systematic review. Surgery Shoham, M. A., Baker, N. M., Peterson, M. E., Fox, P. 2022


BACKGROUND: Climate change is a significant public health threat. Health care comprises 10% of greenhouse gas emissions in the United States, where surgery is especially resource intensive. We did a systematic review to assess and summarize the published evidence of the environmental impact of surgery.METHODS: We searched Medline, Embase, Web of Science, and GreenFILE databases for publications that report any environmental impact measure by all surgical subspecialties, including anesthesia. Inclusion criteria were published in English, original research, and passed peer review. Because data were heterogeneous and the aim was broad, we conducted a qualitative summary of data. Where possible, we compare impact measures.RESULTS: In the study, 167 articles were identified by our search strategy and reviewed, of which 55 studies met criteria. Eight were about anesthesia, 27 about operating room waste, and 6 were life cycle assessments. Other topics include carbon footprint and greenhouse gas emissions. Nine papers fell into 2 or more categories. Overall, the operating room is a significant source of emissions and waste. Using anesthetic gases with low global warming potential reduces operating room emissions without compromising patient safety. Operating room waste is often disposed of improperly, often due to convenience or knowledge gaps. There are environmental benefits to replacing disposable materials with reusable equivalents, and to proper recycling. Surgeons can help implement these changes at their institution.CONCLUSION: Although there is a clear need to lower the carbon footprint of surgery, the quality of research with which to inform protocol changes is deficient overall. Our attempt to quantify surgery's carbon footprint yielded heterogeneous data and few standardized, actionable recommendations. However, this data serves as a starting point for important future initiatives to decrease the environmental impact of surgery.

View details for DOI 10.1016/j.surg.2022.04.010

View details for PubMedID 35788282

Wellness: Building a Meaningful and Effective Program. Plastic and reconstructive surgery Chavez, J. E., Fox, P. M. 2022

View details for DOI 10.1097/PRS.0000000000009281

View details for PubMedID 35724411

Partial Tendon Injury at the Tendon-to-Bone Enthesis Activates Skeletal Stem Cells. Stem cells translational medicine Titan, A. L., Davitt, M., Foster, D., Salhotra, A., Menon, S., Chen, K., Fahy, E., Lopez, M., Jones, R. E., Baiu, I., Burcham, A., Januszyk, M., Gurtner, G., Fox, P., Chan, C., Quarto, N., Longaker, M. 2022


The tendon enthesis plays a critical role in facilitating movement and reducing stress within joints. Partial enthesis injuries heal in a mechanically inferior manner and never achieve healthy tissue function. The cells responsible for tendon-to-bone healing remain incompletely characterized and their origin is unknown. Here, we evaluated the putative role of mouse skeletal stem cells (mSSCs) in the enthesis after partial-injury. We found that mSSCs were present at elevated levels within the enthesis following injury and that these cells downregulated TGF signaling pathway elements at both the RNA and protein levels. Exogenous application of TGF post-injury led to a reduced mSSC response and impaired healing, whereas treatment with a TGF inhibitor (SB43154) resulted in a more robust mSSC response. Collectively, these data suggest that mSSCs may augment tendon-to-bone healing by dampening the effects of TGF signaling within the mSSC niche.

View details for DOI 10.1093/stcltm/szac027

View details for PubMedID 35640155

Use of Tendon Allograft for Recurrent Extensor Carpi Ulnaris Instability in Ehlers-Danlos Syndrome: A Case Report. Journal of wrist surgery Christie, B. M., Fox, P. M. 2022; 11 (1): 81-83


Background Subluxation of the extensor carpi ulnaris (ECU) tendon can be a challenging problem to the surgeon, with no options described for failure following autologous reconstruction. It is our intention to provide guidance on technique by describing our experience in a 20-year-old male with Ehlers-Danlos syndrome. Case Description The patient presented with pain and snapping of the ECU tendon, and failed both immobilization and ECU reconstruction with autologous extensor retinaculum. A gracilis tendon allograft was used to reconstruct the ECU sheath, in addition to ulnar groove deepening. At 1-year follow-up, the patient had no pain and the ECU was stable without recurrent subluxation. Literature Review To the authors' knowledge, the use of tendon allograft for stabilization of recurrent ECU subluxation following surgical repair or reconstruction has not been previously described in the medical literature. Clinical Relevance Utilization of tendon allograft is a viable technique to stabilize the ECU tendon while minimizing the risk in relying on compromised autologous tissue. This report represents the first account of successful reconstruction following failed autologous reconstruction.

View details for DOI 10.1055/s-0041-1729760

View details for PubMedID 35127269

View details for PubMedCentralID PMC8807098

Predicting Academic Performance during Plastic Surgery Residency: Can Step 2 Scores Reliably Replace Step 1? Journal of surgical education Sergesketter, A. R., Shammas, R. L., Langdell, H. C., Geng, Y., Eberlin, K. R., Fox, P., Ko, J. H., Lifchez, S. D., Momoh, A. O., Nguyen, V., Tenenbaum, M., Thanik, V., Phillips, B. T. 1800


OBJECTIVE: Step 1 will transition to a pass/fail system in 2022. This study aimed to characterize the effects of this change on integrated plastic surgery program directors' selection criteria and assess whether Step 2 Clinical Knowledge (CK) can replace Step 1 as an application selection metric.DESIGN: Online survey that was administered to a collaborative group of ten plastic surgery program directors collecting USMLE Step 1, Step 2 CK, In-Service, and written board scores for 3 years of graduated integrated residents.SETTING: Ten academic integrated plastic surgery programs.PARTICIPANTS: Data from 80 graduated integrated plastic surgery residents.RESULTS: Across 80 included integrated residents, mean (SD) Step 1 score was 247 (13), Step 2 CK was 249 (13), PGY1-6 In-Service percentiles varied from 45 to 53 percentile, and written board pass rate was 98.3%. Both Step 1 and Step 2 CK correlated highly with In-Service percentiles (both p < 0.001), with Step 2 CK scores correlating similarly with In-Service performance compared to Step 1 (rho 0.359 vs. 0.355, respectively). Across applicant characteristics, program directors reported the highest relative increase in Step 2 CK importance after Step 1 transitions to pass/fail.CONCLUSIONS: Step 2 CK correlates similarly with plastic surgery In-Service performance compared to Step 1. While Step scores do not necessarily correlate with residency performance, Step 2 CK may also be used as an application screening metric for programs seeking objective data to differentiate plastic surgery applicants.

View details for DOI 10.1016/j.jsurg.2021.11.015

View details for PubMedID 34952820

The Environmental Impact of Surgery Shoham, M., Baker, N., Peterson, M., Fox, P. ELSEVIER SCIENCE INC. 2021: S133
Use of Hand Therapy After Distal Radius Fracture: A National Perspective. The Journal of hand surgery Trinh, P., Rochlin, D., Sheckter, C., Moore, W., Fox, P., Curtin, C. 2021


PURPOSE: To assess whether certain distal radius fracture (DRF) patients, such as opioid users or complex regional pain syndrome (CRPS) patients, receive more hand therapy.METHODS: Using the IBM MarketScan Research Databases from January 1, 2012, to December 31, 2016, we identified a cohort of DRF patients and created 4 subgroups of interest: frequent follow-up patients, persistent opioid users, prior opioid users, and patients with CRPS. We measured rates and demographic characteristics associated with therapy use in our populations of interest.RESULTS: In this cohort of 87,313 patients, 21% received hand therapy after primary DRF treatment. Patients with CRPS had a higher rate of therapy than non-CRPS patients (44% vs 21%, respectively). Frequent follow-up patients used more therapy than those with less follow-up (30% vs 17%, respectively). Persistent opioid users demonstrated slightly increased therapy use compared to the remaining population (25% vs 22%, respectively). Prior opioid users underwent less therapy than patients without prior opioid use (19% vs 22%, respectively). Female sex, residing in the Northeast, being on a preferred provider organization plan, and having more intense surgical treatments were associated with increased therapy use.CONCLUSIONS: This study showed variations in therapy use after DRF in subpopulations of interest. Patients with CRPS, persistent opioid use, and frequent follow-ups had higher rates of therapy. Patients with prior opioid use had lower rates of therapy.CLINICAL RELEVANCE: Therapy is more common in patients with DRF with CRPS, persistent opioid use, or more follow-up visits.

View details for DOI 10.1016/j.jhsa.2021.08.018

View details for PubMedID 34666936

Post-surgical wireless monitoring of arterial health progression. iScience Ruth, S. R., Kim, M., Oda, H., Wang, Z., Khan, Y., Chang, J., Fox, P. M., Bao, Z. 2021; 24 (9): 103079


Early detection of limb ischemia, strokes, and heart attacks may be enabled via long-term monitoring of arterial health. Early stenosis, decreased blood flow, and clots are common after surgical vascular bypass or plaque removal from a diseased vessel and can lead to the above diseases. Continuous arterial monitoring for the early diagnosis of such complications is possible by implanting a sensor during surgery that is wirelessly monitored by patients after surgery. Here, we report the design of a wireless capacitive sensor wrapped around the artery during surgery for continuous post-operative monitoring of arterial health. The sensor responds to diverse artery sizes and extents of occlusion invitro to at least 20cm upstream and downstream of the sensor. It demonstrated strong capability to monitor progression of arterial occlusion in human cadaver and small animal models. This technology is promising for wireless monitoring of arterial health for pre-symptomatic disease detection and prevention.

View details for DOI 10.1016/j.isci.2021.103079

View details for PubMedID 34568798

Short Message Service-Based Collection of Patient-Reported Outcome Measures on Hand Surgery Global Outreach Trips: A Pilot Feasibility Study. The Journal of hand surgery Shapiro, L. M., Dinh, M. P., Tran, L., Fox, P. M., Richard, M. J., Kamal, R. N. 2021


PURPOSE: As the burden of surgical care and the associated outreach trips to low- and middle-income countries increases, it is important to collect postoperative data to assess and improve the quality, safety, and efficacy of the care provided. In this pilot study, we aimed to evaluate the feasibility of short message service (SMS)-based mobile phone follow up to obtain patient-reported outcome measures after hand surgery during a surgical outreach trip to Vietnam.METHODS: Patients undergoing surgery during a week-long outreach trip to Hospital 175 in Ho Chi Minh City, Vietnam, who owned a mobile phone, were included in this study. Eight eligible patients elected to participate and were sent an SMS-based, Health Insurance Portability and Accountability Act-compliant text message with a link to a contextualized shortened Disabilities of the Arm, Shoulder and Hand questionnaire at 1 day, 1 week, 2 weeks, 4 weeks, and 12 weeks after the surgery. The patient characteristics and instrument completion rates were reported.RESULTS: The 8 patients had a mean age of 45.4 years and lived at a mean distance of 72.7 km from the hospital. Seven (87.5%), 7 (87.5%), 8 (100%), 6 (75%), and 8 (100%) patients completed the follow-up questionnaires at 1 day, 1 week, 2 weeks, 4 weeks, and 12 weeks after the surgery, respectively.CONCLUSIONS: This pilot study demonstrates that the collection of patient-reported outcome measures after hand surgery outreach trips to low- and middle-income countries via SMS-based messaging is feasible for up to 12 weeks after the surgery.CLINICAL RELEVANCE: Short message service-based messaging can be used to obtain postoperative outcome measures for up to 12 weeks after surgical outreach trips to low- and middle-income countries. This technology can be scaled and contextualized based on location to ensure that patient care during outreach trips is safe and effective.

View details for DOI 10.1016/j.jhsa.2021.05.001

View details for PubMedID 34148790

Optimizing Treatment of Hand Infections: Is MRSA Coverage Always Necessary? Plastic and reconstructive surgery. Global open Oliver, J. D., Pridgen, B. C., desJardins-Park, H. E., Curtin, C., Fox, P. M. 2021; 9 (6): e3619


Multiple publications have highlighted the prevalence of methicillin resistant Staphylococcus aureus (MRSA) as a cause of hand infections. We hypothesized that these publications have shifted the empiric treatment of hand infections. The aim of this study was to identify the current standard of care, the most common causative bacteria, and factors leading to extended length of stay for hand infection patients at a suburban hospital to improve treatment and establish an optimized care protocol.Methods: Retrospective cohort analysis was conducted to identify all patients admitted for hand infections over an 8-year period. A comprehensive chart review of each patient's hospital course was completed.Results: A total of 70 patients were included. Maximum white blood cell count 12 was associated with a significantly longer hospital length of stay (9.1 days versus 5.4 days) compared to WBC values < 12 (P < 0.05). Also, 11 out of 23 (47.8%) underwent two or more incision and drainages (I&D's), compared with patients with maximum WBC < 12. Vancomycin use as an empiric antibiotic was widespread (68 patients, 97.1%), despite only 14 (20%) having MRSA positive cultures. Univariate analysis identified a significant increased likelihood for increased length of stay (P < 0.05) and rise in creatinine (P < 0.05) in patients with an initial vancomycin trough level > 20.Conclusions: This analysis of hand infection treatment in a suburban hospital demonstrates the incidence of MRSA hand infections may not be universally high across institutions. Each hospital should review its own data to optimize hand infection treatment and its associated costs.

View details for DOI 10.1097/GOX.0000000000003619

View details for PubMedID 34150420

Life Happens, Even to Surgical Trainees. JAMA surgery George, E. L., Fox, P., Hawn, M. T. 2021

View details for DOI 10.1001/jamasurg.2021.1811

View details for PubMedID 34009251

Use of Tendon Allograft for Recurrent Extensor Carpi Ulnaris Instability in Ehlers-Danlos Syndrome: A Case Report JOURNAL OF WRIST SURGERY Christie, B. M., Fox, P. M. 2021
Autologous Fat Grafting in Hand Surgery. The Journal of hand surgery Deptula, P., Fox, P. 2021


Autologous fat grafting is commonly used in plastic and reconstructive surgery, but its indications are less well known in the hand surgery literature. Autologous fat grafting is frequently used for its anti-inflammatory, proangiogenic, and regenerative properties, which can be useful in treating the hand and upper extremity. We present a summary of the current literature on autologous fat grafting in the hand and upper extremity and discuss the applications, outcomes, techniques, safety, and level of evidence.

View details for DOI 10.1016/j.jhsa.2021.02.015

View details for PubMedID 33858716

Barriers and Facilitators of Outcome Collection During Hand Surgery Outreach: A Quality Improvement Study. Hand (New York, N.Y.) Shapiro, L. M., Dinh, M. P., Fox, P. M., Richard, M. J., Eppler, S. L., Kamal, R. N. 2021: 15589447211003183


BACKGROUND: Surgical outreach trips to low- and middle-income countries have been increasing. Outcome collection on these trips, however, has been inconsistent and often incomplete. We conducted a qualitative study of surgeons, administrators, and patients to identify the barriers and facilitators to outcome collection on hand surgery outreach trips to Hospital 175 in Ho Chi Minh City, Vietnam.METHODS: A purposive sample of surgeons, administrators, and patients from Hospital 175 were interviewed about their beliefs regarding outcome collection. We used a semi-structured interview guide based on the Theoretical Domains Framework to systematically explore barriers and facilitators. Interviews were recorded, transcribed, and analyzed using content analysis. Beliefs underlying similar responses were identified and aggregated to describe barriers and facilitators of outcome measurement.RESULTS: Twelve surgeons and administrative staff (3 visiting and 9 local) and 5 patients were interviewed before saturation was achieved. All stakeholders believed outcome collection on hand surgery outreach trips is important. Barriers identified were primarily related to environmental context and resources (eg, cost of returning) and memory, attention, and decision process (eg, difficulty in remembering patient follow-up intervals). The most commonly identified barriers address the distance patients live from the hospital/clinic, the resources required for them to return, and the lack of an organized system to assist in follow-up.CONCLUSIONS: Multiple barriers to outcome collection exist at Hospital 175 in Vietnam. Understanding these barriers informs context-specific implementation approaches to collect outcomes on hand surgery outreach trips, which may improve the safety and quality of care provided.

View details for DOI 10.1177/15589447211003183

View details for PubMedID 33789491

Proceed with Caution: Mouse Deep Digit Flexor Tendon Injury Model. Plastic and reconstructive surgery. Global open Titan, A. L., Fahy, E. n., Chen, K. n., Foster, D. S., Bennett-Kennett, R. n., Dauskardt, R. H., Gurtner, G. C., Chang, J. n., Fox, P. M., Longaker, M. T. 2021; 9 (1): e3359


The purpose of this study was to determine the feasibility of using mouse models for translational study of flexor tendon repair and reconstruction.Quantitative data detailing the gross anatomy, biomechanical characteristics, and microscopic structure of the deep digit flexor tendon (DDF) of the mouse hindpaw were obtained. Histological characterization of the DDF and the anatomy of the digit in the mouse hindpaw are detailed. Biomechanical testing determined the load-to-failure, stress, elastic modulus, and the site of tendon failure.In gross anatomy, the origins and insertions of the mouse deep digit flexor tendon are similar to those of the human digit, surrounded by a synovial sheath that is only 1- to 2-cells thick. A neurovascular network runs on each side of the digit outside the synovial sheath, but does not clearly penetrate it. The thickness of the DDF is 0.14 0.03mm and the width is 0.3 0.03mm. The thickness of the DDF is less than that of 9-0 nylon needle. The mean failure force of the deep flexor tendon was 2.79 0.53N.The gross anatomy of the mouse hindpaw digit is similar to that of the human digit except for key differences seen in the synovial sheath and vascular supply. The dimensions of the mouse DDF make it challenging to create a clinically translatable repair model using currently available surgical techniques. Despite the similarities between the human and mouse anatomy, and the powerful basic science tools available in murine models, mice are an unreliable model for assessing flexor tendon injury and repair.

View details for DOI 10.1097/GOX.0000000000003359

View details for PubMedID 33552814

View details for PubMedCentralID PMC7859083

Are All Posts Created Equal? A Review of Academic Plastic Surgery Residency Programs' Social Media Engagement Statistics. Plastic and reconstructive surgery Irwin, T. J., Ortiz, R., Leto Barone, A. A., Veeravagu, L., Sherif, R. D., Lifchez, S. D., Fox, P. M., Momoh, A. O., Liao, E. C., Eberlin, K. R. 2021

View details for DOI 10.1097/PRS.0000000000008379

View details for PubMedID 34495905

Characteristics of Patients With Complex Limb Pain Evaluated Through an Interdisciplinary Approach Utilizing Magnetic Resonance Neurography Frontiers in Pain Research Johnson, E. M., Yoon, D., Biswal, S., Curtin, C., Fox, P., Wilson, T. J., Carroll, I., Lutz, A., Tawfik, V. 2021
Hand Surgery Transfers to Level 1 Center: Variables Affecting Transfer Method and Diagnostic Accuracy. Plastic and reconstructive surgery. Global open Putnam, J., Pedreira, R., Fox, P. 2020; 8 (12): e3279


We hypothesize that some costly patient transfers to a level 1 trauma center for hand specialist management may be unnecessary. This analysis evaluates transfer cost effectiveness and whether time of consult, transfer distance, diagnosis at time of transfer, and provider level influence diagnostic accuracy and transport method.Methods: Two hundred and sixty-five patients transferred to a suburban level 1 trauma center for hand surgeon evaluation between 2014 and 2019 were evaluated for patient and injury characteristics, time of consult, transfer distance, provider level, transport method, treatment cost, and diagnostic accuracy.Results: The average patient age was 36.2 years, and 80.3% were men. 21% of transfers had inaccurate pre-transfer diagnoses, and certain pre-transfer diagnoses correlated with an increased likelihood of inaccuracy, including flexor tenosynovitis and vascular injury. Patients with a language barrier had a greater likelihood of being transferred with an inaccurate diagnosis (P < 0.05). Compared with ground transport, air ambulance was associated with a higher cost of treatment ($225,679 versus $133,887, P < 0.00001). Of all transfers, 14 (5%) were discharged from the emergency department (ED) without a procedure, 9 (3%) were admitted for observation, 73 (27%) had an ED procedure before discharge, and 166 (62%) received operative management.Conclusions: Over 30% of transfers to a level 1 trauma center likely could have been managed at the transferring facility at a decreased cost. Certain diagnoses are associated with increased risk for diagnostic error and unnecessarily urgent transport. Providers can use this information to consider transfer patterns and to educate transferring providers.

View details for DOI 10.1097/GOX.0000000000003279

View details for PubMedID 33425593

Separating Fact From Fiction: A Nationwide Longitudinal Examination of Complex Regional Pain Syndrome Following Treatment of Dupuytren Contracture. Hand (New York, N.Y.) Rochlin, D. H., Sheckter, C. C., Satteson, E. S., Swan, C. C., Fox, P. M., Curtin, C. 2020: 1558944720963915


BACKGROUND: One of the most feared complications following treatment of Dupuytren contracture is complex regional pain syndrome (CRPS). This study aims to provide a national perspective on the incidence of CRPS following treatment of Dupuytren contracture and identify patient factors to target for risk reduction.METHODS: Using the Truven MarketScan databases from 2007 to 2016, individuals aged 18 years who developed CRPS within 1 year of treatment of Dupuytren contracture were identified using the International Classification of Disease diagnosis code for CRPS. Predictor variables included: age, sex, employment status, region, type of procedure, and concurrent carpal tunnel surgery. Multivariable logistic regression was used to analyze outcomes.RESULTS: In all, 48327 patients received treatment for Dupuytren contracture, including collagenase injection (13.6%); percutaneous palmar fasciotomy (10.3%); open palmar fasciotomy (3.9%); palmar fasciectomy with 0 (10.8%), 1 (29.2%), or multiple (19.6%) digit releases; or a combination of these procedures (12.8%). One hundred forty-five patients (0.31%) were diagnosed with CRPS at a mean of 3.4 months (standard deviation, 2.3) following treatment. Significant predictors of CRPS included female sex (odds ratio [OR], 2.02; P < .001), Southern region (OR, 1.80; P = .022), long-term disability status (OR, 4.73; P = .035), palmar fasciectomy with release of 1 (OR, 5.91; P = .003) or >1 digit (OR, 13.32; P < .001), or multiple concurrent procedures for Dupuytren contracture (OR, 8.23; P = .001).CONCLUSIONS: Based on national commercial claims data, there is a lower incidence of CRPS following treatment of Dupuytren contracture than previously reported. Risk factors identified should help with preoperative counseling and assist clinicians in targeting risk reduction measures.

View details for DOI 10.1177/1558944720963915

View details for PubMedID 33081519

Analysis of Cell-seeded, Collagen-rich Hydrogel for Wound Healing Sotelo Leon, D., Williams, T., Wang, Z., Leyden, J., Franklin, A., Kaizawa, Y., Chang, J., Fox, P. M. LIPPINCOTT WILLIAMS & WILKINS. 2020: e3049


Our laboratory has previously developed a novel collagen-rich hydrogel (cHG), which significantly increases the speed of wound healing in diabetic rats.In this study, we examine the in vitro survival and migration of fibroblasts, endothelial cells, and adipose-derived stem cells in a novel cHG. Furthermore, we test the ability of adipose-derived stem cell-seeded cHG to support cell survival and accelerate healing in vivo.In vitro, cell survival within the cHG was retained for 25 days. We were unable to detect cellular migration into, out of, or through cHG. In the in vivo model, bioluminescence of stem cells seeded within the cHG in diabetic rat wounds was detected until day 10. Rate of wound closure was higher for cHG plus adipose-derived stem cells versus control from day 2 until day 16 and significant on days 6, 8, and 12 (P < 0.05). This significant difference was also observed on day 16 by histology (P 0.05).We conclude that cHG is a good candidate for delivering adipose-derived stem cells, endothelial cells, and fibroblasts to wounds. Future studies will determine whether the delivery of combinations of different cell lines in cHG further enhances wound healing.

View details for DOI 10.1097/GOX.0000000000003049

View details for Web of Science ID 000572118600049

View details for PubMedID 32983797

View details for PubMedCentralID PMC7489666

Topical Antibiotic Elution in a Collagen-Rich Hydrogel is Successful for Inhibiting Bacterial Growth and Biofilm Formation in Vitro. Antimicrobial agents and chemotherapy Min, J. G., Sanchez Rangel, U. J., Franklin, A., Oda, H., Wang, Z., Chang, J., Fox, P. M. 2020


BACKGROUND: Chronic wounds are a prominent concern, accounting for $25 billion of healthcare costs annually. Biofilms have been implicated in delayed wound closure, but treatment options continue to be limited and susceptible to developing antibiotic resistance. A novel collagen-rich hydrogel derived from human extracellular matrix presents an avenue for treating chronic wounds by providing appropriate extracellular proteins for healing and promoting neovascularization. Using the hydrogel as a delivery system for localized secretion of therapeutic dosage of antibiotics presents an attractive means of maximizing delivery while minimizing systemic side-effects. We hypothesize that the hydrogel can provide controlled elution of antibiotics leading to inhibition of bacterial growth and disruption of biofilm formation.METHOD: The rate of antibiotic elution from the collagen-rich hydrogel and the efficacy of biofilm disruption was assessed with Pseudomonas aeruginosa Bacterial growth inhibition, biofilm disruption, and mammalian cell cytotoxicity were quantified using in vitro models.RESULTS: The antibiotic-loaded hydrogel showed sustained release of antibiotics for up to 24 hours at therapeutic levels. The treatment inhibited bacterial growth and disrupted biofilm formation at multiple time points. The hydrogel was capable of accommodating various classes of antibiotics and did not result in cytotoxicity in mammalian fibroblasts or adipose stem cellsConclusion: An antibiotic-loaded collagen-rich hydrogel is capable of controlled antibiotic release effective for bacteria cell death without native cell death. A human-derived hydrogel that is capable of eluting therapeutic levels of antibiotic is an exciting prospect in the field of chronic wound healing.

View details for DOI 10.1128/AAC.00136-20

View details for PubMedID 32690648

Measuring and Improving the Quality of Care During Global Outreach Trips: A Primer for Safe and Sustainable Surgery. The Journal of hand surgery Shapiro, L. M., Global-Quest Investigators, Shapiro, L. M., Chang, J., Fox, P. M., Kozin, S. H., Chung, K. C., Dyer, G. S., Fufa, D. T., Leversedge, F. J., Katarincic, J. A., Kamal, R. N. 2020


Trauma is the leading cause of mortality in patients aged 5 years and older. Globally, trauma kills more people than malaria, tuberculosis, and HIV/AIDs combined. As the number of surgical outreach trips to low- and middle-income countries and resources provided for such trips increase, hand surgeons are uniquely positioned to address this global burden. However, the delivery of surgical care alone is insufficient without effectively evaluating the quality of care delivered. It is critical that the care provided on outreach trips improves patient and population health, does not harm patients, and develops the local health care ecosystem. An estimated 8 million lives could be saved annually in low- and middle-income countries with higher-quality health systems. Currently, data collection systems for evaluating quality during outreach trips are lacking. Insight into current methods of quality assessment and improvement in both developing and developed countries can help inform future efforts to implement innovative data collection systems. Thoughtful and sustainable collaboration with host sites in low- and middle-income countries can ensure that care delivery is culturally competent and improves population health.

View details for DOI 10.1016/j.jhsa.2020.04.027

View details for PubMedID 32680787

Homing of Adipose-Derived Stem Cells to a Tendon-Derived Hydrogel: A Potential Mechanism for Improved Tendon-Bone Interface and Tendon Healing. The Journal of hand surgery Franklin, A., Gi Min, J., Oda, H., Kaizawa, Y., Leyden, J., Wang, Z., Chang, J., Fox, P. M. 2020


PURPOSE: Tendons are difficult to heal owing to their hypocellularity and hypovascularity. Our laboratory has developed a tendon-derived hydrogel (tHG) that significantly improves tendon healing in an animal model. We hypothesized that a potential mechanism for improved healing with tHG is through the attraction of systemic stem cells.METHODS: Homing of systemic adipose-derived stem cells (ADSCs) to tendon injuries was assessed with acute and chronic injury models. Injury sites were treated with saline or tHG, and animals given a tail vein injection (TVI) of labeled ADSCs 1 week after treatment. One week following TVI, rats were harvested for histology. To further evaluate a potential difference in homing to tHG, a subcutaneous injection (SQI) model was used. Rats were treated with an SQI of saline, silicone, ADSCs in media, tHG, tHG+ fibroblasts (FBs), or tHG+ ADSCs on day 0. One week after SQI, rats underwent TVI with labeled ADSCs. Samples were harvested 2 or 3 weeks after SQI for analysis. Flow cytometry confirmed homing in the SQI model.RESULTS: Systemically delivered ADSCs homed to both acute tendon and chronic tendon-bone interface (TBI) injury sites. Despite their presence at the injury site, there was no difference in the number of macrophages, amount of cell proliferation, or angiogenesis 1 week after stem cell delivery.In an SQI model, ADSCs homed to tHG. There was no difference in the number of ADSCs homing to tHG alone versus tHG+ ADSCs. However, there was an increase in the number of living cells, general immune cells, and T-cells present at tHG+ ADSC versus tHG alone.CONCLUSIONS: The ADSCs home to tendon injury sites and tHG. We believe the attraction of additional systemic ADSCs is one mechanism for improved tendon and TBI healing with tHG.CLINICAL RELEVANCE: Treatment of tendon and TBI injuries with tHG can augment healing via homing of systemic stem cells.

View details for DOI 10.1016/j.jhsa.2020.05.003

View details for PubMedID 32605739

Neonatal Compartment Syndrome and Compound Presentation at Birth. Journal of hand surgery global online Shen, A. H., Tevlin, R., Kwan, M. D., Ho, O. H., Fox, P. M. 2020; 2 (3): 166-170


Neonatal compartment syndrome is a rare condition. Early diagnosis and timely surgical intervention are paramount to optimize outcome. Time to fasciotomy is the most important prognostic factor. The purposes of this study were to describe a case presentation of neonatal compartment syndrome associated with a compound birth presentation and to perform a literature review. In this case, the neonate's fingers were noted to be present on maternal cervical examination 24 hours before delivery. The patient then was noted to have a sentinel skin lesion. A diagnosis of neonatal compartment syndrome was suspected, and she underwent urgent fasciotomy. Literature review identified a total of 60 patients from 26 studies. Most patients were managed operatively. All patients presented with a sentinel skin lesion, emphasizing the importance of this clinical sign in diagnosis. Manometry is not routinely performed and no standards are available for acceptable pressure gradients.

View details for DOI 10.1016/j.jhsg.2020.04.001

View details for PubMedID 35415493

View details for PubMedCentralID PMC8991503

A Human-Derived, Collagen-Rich Hydrogel Augments Wound Healing in a Diabetic Animal Model. Annals of plastic surgery Williams, T. n., Sotelo Leon, D. n., Kaizawa, Y. n., Wang, Z. n., Leyden, J. n., Chang, J. n., Fox, P. M. 2020


Application of collagen products to wounds has been shown to improve wound healing. Using a collagen-based hydrogel (cHG) capable of cellular support previously developed by our laboratory, we hypothesize that our hydrogel will increase the speed of wound healing by providing a 3-dimensional framework for cellular support, increasing angiogenesis and cell-proliferation at the wound bed.Two, 10-mm excisional wounds were created over the dorsum of 12 male, genetically modified Zucker diabetic rats. Wounds were splinted open to limit healing by wound contracture. One wound was treated with an occlusive dressing (OD), whereas the adjacent wound was treated with an OD plus cHG. Occlusive dressings were changed every other day. Hydrogel was applied on day 2 and every 4 days after until complete wound closure. Rate of wound closure was monitored with digital photography every other day. Wounds were harvested at days 10 and 16 for histological and immunohistochemical analysis.Wound closure was significantly faster in cHG-treated wounds compared with OD-treated wounds. By day 10, cHG-treated wounds achieved 63% wound closure, compared with 55% wound closure in OD-treated wounds (P < 0.05). By day 16, cHG-treated wounds achieved 84% wound closure, compared with 68% wound closure in OD-treated wounds (P < 0.05).Histologically, wound depth was not different between the cHG and OD groups on days 10 and 16. However, wound length was significantly less in the cHG group compared with the OD group (P < 0.05) consistent with digital photographic analysis. Immunohistochemical analysis for RECA-1 demonstrated that blood vessel density in the wound bed was 2.3 times higher in the cHG group compared with the OD group (P = 0.01) on day 16. Cell proliferation was 3.8 times higher in the cHG group versus the OD group (P < 0.05) on day 10.Collagen-based hydrogel-treated wounds demonstrated significantly improved healing compared with control. The thermoresponsive feature of collagen hydrogel and its structural stability at body temperature demonstrate promising clinical potential as a vehicle for the delivery of therapeutic cells to the wound bed.

View details for DOI 10.1097/SAP.0000000000002380

View details for PubMedID 32349080

Quality Measures to Deliver Safe, High-Quality Care on Hand Surgery Outreach Trips to Low and Middle-Income Countries. The Journal of bone and joint surgery. American volume Shapiro, L. M. 2020; Publish Ahead of Print


The burden of hand surgery in low and middle-income countries (LMICs) is immense and growing. Although outreach trips to LMICs have been increasing, there has remained a gap regarding assessment of quality of care on outreach trips. We developed quality measures to assess hand surgery outreach trips to LMICs.We followed the recommendations set forth by the World Health Organization for practice guideline development. We used the results of a systematic review to inform the development of quality measures. Eight hand and upper-extremity surgeons with extensive global outreach experience (mean surgical outreach experience of >15 years, completed >3,000 surgeries in 24 countries) completed a modified RAND/UCLA (University of California Los Angeles) Delphi process to evaluate the importance, the feasibility, the usability, and the scientific acceptability of 83 measures. Validity was defined according to established methods.A tiering system that was based on the resources available at an outreach site (essential, intermediate, and advanced) was developed to classify the application of the measures since care delivery in LMICs often is constrained by local resources. Twenty-two (27%) of 83 measures were validated. All 22 (100%) were classified as essential (e.g., availability of interpretation services for the visiting team); no measures that were classified as intermediate or advanced were validated.Field-testing and implementation of quality measures served to identify the safety and the quality of hand surgical care that was provided on outreach trips to LMICs and inform improvement efforts. Tiers of care can be applied to quality measures to incorporate resource and capacity limitations when assessing their performance.Ensuring safety and high-quality care on hand surgical outreach trips to LMICs is foundational to all participating organizations and physicians. Valid quality measures can be implemented by organizations undertaking outreach trips to LMICs.

View details for DOI 10.2106/JBJS.19.01506

View details for PubMedID 33337798

Prevalence of Ganglion Cyst Formation After Wrist Arthroscopy: A Retrospective Longitudinal Analysis of 2420 Patients. Hand (New York, N.Y.) Rochlin, D. H., Perrault, D. n., Sheckter, C. C., Fox, P. n., Yao, J. n. 2020: 1558944720939203


Dorsal wrist ganglion cysts arise from the leakage of synovial fluid through tears in the scapholunate ligament and/or dorsal wrist capsule. An analogous disruption of the dorsal capsule is created with routine portal placement during wrist arthroscopy. We hypothesized that wrist arthroscopy would predispose to wrist ganglions.Using the Truven MarketScan Outpatient Services Database from 2015 to 2016, patients who underwent wrist arthroscopy and developed an ipsilateral wrist ganglion were identified. Exclusion criteria included ganglion diagnosis preceding arthroscopy and bilateral pathology. Postoperative ganglion diagnosis was modeled with logistic regression. Predictor variables included age, gender, comorbidities, and arthroscopic procedure.In all, 2420 patients underwent wrist arthroscopy. Thirty (1.24%) were diagnosed with an ipsilateral wrist ganglion at a mean time of 4.0 months (standard deviation: 2.4, range: 0.2-9.0). Significant predictors of ganglion diagnosis included female gender (odds ratio [OR]: 4.0, P < .01) and triangular fibrocartilage complex and/or joint debridement (OR: 0.13, P < .01). By comparison, among all 24,718,751 outpatients who had not undergone wrist arthroscopy, 39,832 patients had a diagnosis of a wrist ganglion cyst (0.16%).Wrist arthroscopy is associated with a postoperative rate of ganglion cyst formation that is nearly 8 times the rate in the general population. Additional studies are needed to investigate techniques that minimize the risk of this complication.

View details for DOI 10.1177/1558944720939203

View details for PubMedID 32935572

Patient Willingness to Pay for Faster Return to Work or Smaller Incisions. Hand (New York, N.Y.) Alokozai, A., Lindsay, S. E., Eppler, S. L., Fox, P. M., Ladd, A. L., Kamal, R. N. 2019: 1558944719890039


Background: Value-based health care models such as bundled payments and accountable care organizations can penalize health systems and physicians for excess costs leading to low-value care. Health systems can minimize these extra costs by constraining diagnostic (eg, magnetic resonance imaging utilization) or treatment options with debatable necessity in the setting of clinical equipoise. Instead of restricting more expensive treatments, it is plausible that health systems could instead recoup the extra costs of these treatments by charging patients supplementary out-of-pocket charges (cost sharing). The primary aim of this exploratory study was to assess hand surgery patient willingness to pay supplementary out-of-pocket charges for a procedure that theoretically leads to an earlier return to work or smaller incisions when there are 2 procedures that lead to similar results (clinical equipoise). Methods: A total of 122 patients completed a questionnaire that included demographic information, a financial distress assessment, a series of scenarios asking patients the degree to which they are willing to pay extra for the procedure choice, as well as their perspective of how much insurers should be responsible for these additional costs. Results: Patients were willing to pay out-of-pocket to some degree for a procedure that leads to earlier return to work and smaller incision size when compared with a similar alternative procedure, but noted that insurers should bear a greater burden of costs. Approximately 10% of patients were willing to pay maximum amounts ($2500+) for earlier return to work (3, 7, and 14 days earlier) and smaller incision sizes of any length. Conclusions: Some patients may be willing to pay out-of-pocket and cost share for procedures that lead to earlier return to work and smaller incisions in the setting of clinical equipoise. As such, when developing and implementing alternative payment models, health systems could potentially offer services with debatable necessity in the setting of equipoise for a supplementary out-of-pocket charge.

View details for DOI 10.1177/1558944719890039

View details for PubMedID 31791156

A Novel Technology for Free Flap Monitoring: Pilot Study of a Wireless, Biodegradable Sensor. Journal of reconstructive microsurgery Oda, H., Beker, L., Kaizawa, Y., Franklin, A., Min, J. G., Leyden, J., Wang, Z., Chang, J., Bao, Z., Fox, P. M. 2019


BACKGROUND: Accurate monitoring of free flap perfusion after complex reconstruction is critical for early recognition of flap compromise. Surgeons use a variety of subjective and objective measures to evaluate flap perfusion postoperatively. However, these measures have some limitations. We have developed a wireless, biodegradable, and flexible sensor that can be applied to real-time postoperative free flap monitoring. Here we assess the biocompatibility and function of our novel sensor.METHODS: Seven Sprague-Dawley (SD) rats were used for biocompatibility studies. The sensor was implanted around the femoral artery near the inguinal ligament on one leg (implant side) and sham surgery was performed on the contralateral leg (control side). At 6 and 12 weeks, samples were harvested to assess the inflammation within and around the implant and artery. Two animals were used to assess sensor function. Sensor function was evaluated at implantation and 7 days after the implantation. Signal changes after venous occlusion were also assessed in an epigastric artery island flap model.RESULTS: In biocompatibility studies, the diameter of the arterial lumen and intima thickness in the implant group were not significantly different than the control group at the 12-week time point. The number of CD-68 positive cells that infiltrated into the soft tissue, surrounding the femoral artery, was also not significantly different between groups at the 12-week time point. For sensor function, accurate signaling could be recorded at implantation and 7 days later. A change in arterial signal was noted immediately after venous occlusion in a flap model.CONCLUSION: The novel wireless, biodegradable sensor presented here is biocompatible and capable of detecting arterial blood flow and venous occlusion with high sensitivity. This promising new technology could combat the complications of wired sensors, while improving the survival rate of flaps with vessel compromise due to its responsive nature.

View details for DOI 10.1055/s-0039-1700539

View details for PubMedID 31675757

Electromyographic Analysis of Grip ORTHOPEDICS Fox, P. M., Oliver, J. D., Viet Nguyen, Hentz, V. R., Curtin, C. M. 2019; 42 (6): E555E558


This prospective cohort study used video electromyography synchronized analysis to determine the dynamic use of extrinsic and intrinsic finger flexion during grasp. Light fist formation primarily involved the flexor digitorum profundus with either the flexor digitorum superficialis or intrinsics. In contrast, both the flexor digitorum superficialis and intrinsics were recruited in all tight fist video electromyography. However, the sequence of recruitment differed between patients in tight fist formation. Injured patients demonstrated a unique pattern of recruitment based on injury. The authors conclude that the flexor digitorum profundus is the workhorse in composite fist formation but the roles of the flexor digitorum superficialis and the intrinsic muscles are less consistent across patients. [Orthopedics. 2019; 42(6):e555-e558.].

View details for DOI 10.3928/01477447-20190812-06

View details for Web of Science ID 000498511000012

View details for PubMedID 31408520

Human TendoneDerived Collagen Hydrogel Significantly Improves Biomechanical Properties of the Tendon-Bone Interface in a Chronic Rotator Cuff Injury Model JOURNAL OF HAND SURGERY-AMERICAN VOLUME Kaizawa, Y., Leyden, J., Behn, A. W., Tulu, U., Franklin, A., Wang, Z., Abrams, G., Chang, J., Fox, P. M. 2019; 44 (10)
Augmentation of chronic rotator cuff healing using adipose-derived stem cell-seeded human tendon-derived hydrogel JOURNAL OF ORTHOPAEDIC RESEARCH Kaizawa, Y., Franklin, A., Leyden, J., Behn, A. W., Tulu, U. S., Leon, D., Wang, Z., Abrams, G. D., Chang, J., Fox, P. M. 2019; 37 (4): 87786

View details for DOI 10.1002/jor.24250

View details for Web of Science ID 000467082100008

Quality of Randomized Controlled Trials for Surgical Treatment of Carpal Tunnel Syndrome: A Systematic Review. Plastic and reconstructive surgery Long, C., Azad, A. D., desJardins-Park, H. E., Fox, P. M. 2019; 143 (3): 79199


BACKGROUND: Randomized controlled trials are considered the gold standard in evidence-based medicine. The authors conducted a systematic review to evaluate the quantity, quality, and trends of randomized controlled trials that assess surgical treatment of carpal tunnel syndrome.METHODS: The authors identified randomized controlled trials comparing two or more surgical interventions for carpal tunnel syndrome in PubMed, Cochrane, Scopus, Google Scholar, and Two independent reviewers evaluated articles for inclusion, extracted data, and assessed randomized controlled trial quality using the Jadad score.RESULTS: Of 2253 identified studies, 58 met full inclusion criteria. They were published between 1985 and 2015, with a significant increase over time (p = 0.003). They were most frequently published in Journal of Hand Surgery (European Volume) [n = 15 (25.9 percent)]. Most randomized controlled trials were single-center studies [n = 54 (93.1 percent)] conducted in the United Kingdom [n = 13 (22.4 percent)] or the United States [n = 10 (17.2 percent)], with a mean study size of 80.1 55.5 patients. Funding source was unknown in 62.1 percent (n = 36). Three-quarters [n = 44 (75.9 percent)] of randomized controlled trials did not define the primary outcome measure(s). Less than 30 percent (n = 17) of randomized controlled trials conducted a power analysis. Only four studies with patients reported lost to follow-up provided an explanation for each patient. Six randomized controlled trials (10.3 percent) conducted intention-to-treat analysis. The mean Jadad score was 2.14 1.26, with no significant improvement over time (p = 0.245).CONCLUSIONS: Despite the significant increase in the number of randomized controlled trials published studying surgical treatment of carpal tunnel syndrome over time, a mean Jadad score of 2.14 with no change over time indicates a need for improvement in quality. Proper study design is key to avoiding introduction of bias and ensuring the validity of conclusions drawn.

View details for PubMedID 30822284

Quality of Randomized Controlled Trials for Surgical Treatment of Carpal Tunnel Syndrome: A Systematic Review PLASTIC AND RECONSTRUCTIVE SURGERY Long, C., Azad, A. D., desJardins-Park, H. E., Fox, P. M. 2019; 143 (3): 791-799
Biodegradable and flexible arterial-pulse sensor for the wireless monitoring of blood flow. Nature biomedical engineering Boutry, C. M., Beker, L., Kaizawa, Y., Vassos, C., Tran, H., Hinckley, A. C., Pfattner, R., Niu, S., Li, J., Claverie, J., Wang, Z., Chang, J., Fox, P. M., Bao, Z. 2019; 3 (1): 47-57


The ability to monitor blood flow is critical to patient recovery and patient outcomes after complex reconstructive surgeries. Clinically available wired implantable monitoring technology requires careful fixation for accurate detection and needs to be removed after use. Here, we report the design of a pressure sensor, made entirely of biodegradable materials and based on fringe-field capacitor technology, for measuring arterial blood flow in both contact and non-contact modes. The sensor is operated wirelessly through inductive coupling, has minimal hysteresis, fast response times, excellent cycling stability, is highly robust, allows for easy mounting and eliminates the need for removal, thus reducing the risk of vessel trauma. We demonstrate the operation of the sensor with a custom-made artificial artery model and in vivo in rats. This technology may be advantageous in real-time post-operative monitoring of blood flow after reconstructive surgery.

View details for DOI 10.1038/s41551-018-0336-5

View details for PubMedID 30932072

Patient Preferences for Shared Decision Making: Not All Decisions Should Be Shared. The Journal of the American Academy of Orthopaedic Surgeons E Lindsay, S. n., Alokozai, A. n., Eppler, S. L., Fox, P. n., Curtin, C. n., Gardner, M. n., Avedian, R. n., Palanca, A. n., Abrams, G. D., Cheng, I. n., Kamal, R. N. 2019


To assess bounds of shared decision making in orthopaedic surgery, we conducted an exploratory study to examine the extent to which patients want to be involved in decision making in the management of a musculoskeletal condition.One hundred fifteen patients at an orthopaedic surgery clinic were asked to rate preferred level of involvement in 25 common theoretical clinical decisions (passive [0], semipassive [1 to 4], equally shared involvement between patient and surgeon [5], semiactive [6 to 9], active [10]).Patients preferred semipassive roles in 92% of decisions assessed. Patients wanted to be most involved in scheduling surgical treatments (4.75 2.65) and least involved in determining incision sizes (1.13 1.98). No difference exists in desired decision-making responsibility between patients who had undergone orthopaedic surgery previously and those who had not. Younger and educated patients preferred more decision-making responsibility. Those with Medicare desired more passive roles.Despite the importance of shared decision making on delivering patient-centered care, our results suggest that patients do not prefer to share all decisions.

View details for DOI 10.5435/JAAOS-D-19-00146

View details for PubMedID 31567900

Biodegradable and flexible arterial-pulse sensor for the wireless monitoring of blood flow NATURE BIOMEDICAL ENGINEERING Boutry, C. M., Beker, L., Kaizawa, Y., Vassos, C., Tran, H., Hinckley, A. C., Pfattner, R., Niu, S., Li, J., Claverie, J., Wang, Z., Chang, J., Fox, P. M., Bao, Z. 2019; 3 (1): 4757
Quality of surgical randomized controlled trials in hand surgery: a systematic review JOURNAL OF HAND SURGERY-EUROPEAN VOLUME Long, C., desJardins-Park, H. E., Popat, R., Fox, P. M. 2018; 43 (8): 801-807
Quality of surgical randomized controlled trials in hand surgery: a systematic review. The Journal of hand surgery, European volume Long, C., desJardins-Park, H. E., Popat, R., Fox, P. M. 2018: 1753193418780184


We assessed the quantity, quality and trends of randomized controlled trials comparing hand surgical interventions. Study characteristics were collected for 125 randomized controlled trials comparing hand surgical interventions. The Jadad scale (0-5), which assesses methodological quality of trials, was calculated. Logistic regressions were conducted to determine associations with the Jadad score. The studies were published between 1981 and 2015, with an increase over time, most often in Journal of Hand Surgery (European). Mean study size was 68 patients. Mean Jadad score was 2.1, without improvement over time. Thirty percent conducted a power analysis and 8% an intention-to-treat analysis. Studies conducted in the United Kingdom and with smaller sample sizes, power analysis and intention-to-treat analysis were associated with a higher Jadad score. The quantity of trials has increased over time while methodological quality has remained low, indicating a need to improve quality of trials in hand surgery literature.

View details for PubMedID 29896997

Treating the Proximal Interphalangeal Joint in Swan Neck and Boutonniere Deformities. Hand clinics Fox, P. M., Chang, J. n. 2018; 34 (2): 16776


Swan neck and boutonniere deformities of the proximal interphalangeal (PIP) joint are challenging to treat. In a swan neck deformity, the PIP joint is hyperextended with flexion at the distal interphalangeal (DIP) joint. In a boutonniere deformity, there is flexion the PIP joint with hyperextension of the DIP joint. When the deformities are flexible, treatment begins with splinting. However, when the deformity is fixed, serial casting or surgery is often necessary to restore joint motion before surgical correction. Many surgical techniques have been described to treat both conditions. Unfortunately, incomplete correction and deformity recurrence are common.

View details for PubMedID 29625636

Molecular Biology of Flexor Tendon Healing in Relation to Reduction of Tendon Adhesions. The Journal of hand surgery Legrand, A., Kaufman, Y., Long, C., Fox, P. M. 2017


Tendon injuries are encountered after major and minor hand trauma. Despite meticulous repair technique, adhesion formation can occur, limiting recovery. Although a great deal of progress has been made toward understanding the mechanism of tendon healing and adhesions, clinically applicable solutions to prevent adhesions remain elusive. The goal of this paper is to review the most recent literature relating to the tendon healing and adhesion prevention.

View details for DOI 10.1016/j.jhsa.2017.06.013

View details for PubMedID 28709791

Intratendinous Injection of Hydrogel for Reseeding Decellularized Human Flexor Tendons. Plastic and reconstructive surgery Long, C., Galvez, M. G., Legrand, A., Joubert, L., Wang, Z., Chattopadhyay, A., Chang, J., Fox, P. M. 2017; 139 (6): 1305e-1314e


Decellularized cadaveric tendons are a potential source for reconstruction. Reseeding to enhance healing is ideal; however, cells placed on the tendon surface result in inadequate delivery. The authors used an injection technique to evaluate intratendinous cell delivery.Decellularized tendons were reseeded with adipose-derived stem cells in culture, and injected with fetal bovine serum or hydrogel. PKH26-stained cells in cross-section were quantified. To evaluate cell viability, the authors delivered luciferase-labeled cells and performed bioluminescent imaging. To evaluate synthetic ability, the authors performed immunohistochemistry of procollagen. Adipose-derived stem cells' ability to attract tenocytes was assessed using transwell inserts. Cell-to-cell interaction was assessed by co-culturing, measuring proliferation and collagen production, and quantifying synergy. Finally, tensile strength was tested.Both fetal bovine serum (p < 0.001) and hydrogel (p < 0.001) injection led to more cells inside the tendon compared with culturing. Hydrogel injection initially demonstrated greater bioluminescence than culturing (p < 0.005) and fetal bovine serum injection (p < 0.05). Injection groups demonstrated intratendinous procollagen staining correlating with the cells' location. Co-culture led to greater tenocyte migration (p < 0.05). Interaction index of proliferation and collagen production assays were greater than 1 for all co-culture ratios, demonstrating synergistic proliferation and collagen production compared with controls (p < 0.05). There were no differences in tensile strength.Hydrogel injection demonstrated the greatest intratendinous seeding efficiency and consistency, without compromising tensile strength. Intratendinous cells demonstrated synthetic capabilities and can potentially attract tenocytes inside the tendon, where synergy would promote intrinsic tendon healing.Therapeutic, V.

View details for DOI 10.1097/PRS.0000000000003359

View details for PubMedID 28538572

De Novo Upper Extremity Lymphedema After Elective Hand Surgery in Breast Cancer Survivors. Annals of plastic surgery Baltzer, H. L., Harvey, J., Fox, P. M., Moran, S. L. 2017


The safety of elective hand surgery in breast cancer (BC) survivors is controversial because of concerns of developing upper extremity lymphedema. This study aimed to evaluate the risk of developing lymphedema after elective hand surgery among patients that underwent ipsilateral axillary lymph node dissection (ALND), sentinel lymph node biopsy (SLNB), and/or radiation therapy (RT).A retrospective cohort of BC patients treated with ALND, SLNB, and/or RT was identified (1997-2012). Patients with subsequent ipsilateral elective hand surgery were included if greater than 1 year of follow-up and no preexisting lymphedema. The primary outcome was lymphedema after hand surgery. Comparisons between patients with and without lymphedema were made to identify potential lymphedema risk factors. Dichotomous and continuous variables were compared with Fisher exact and Student t tests, respectively.The analysis included 103 patients, of which 4 (3.8%) had documented lymphedema after hand surgery. Lymphedema developed early and was self-limited. Lymphedema was not related to age and type of hand surgery. Tourniquet time was longer in the nonlymphedema group. The lymphedema group all received adjuvant chemotherapy and RT with either ALND or SLNB. Patients with lymphedema had a shorter interval between hand surgery and completion of BC surgery (2.1 vs 6.2 years) and RT (2.0 vs 3.3 years).Lymphedema is uncommon after elective hand surgery among survivors and was not associated with tourniquet use. The combination of adjuvant therapies and axillary procedures and a short temporal relationship of these to hand surgery may increase lymphedema risk.

View details for DOI 10.1097/SAP.0000000000000986

View details for PubMedID 28187025

Tendon Tissue Engineering: Mechanism and Effects of Human Tenocyte Coculture With Adipose-Derived Stem Cells. The Journal of hand surgery Long, C. n., Wang, Z. n., Legrand, A. n., Chattopadhyay, A. n., Chang, J. n., Fox, P. M. 2017


Adipose-derived stem cells (ASCs) are a potential candidate for cell-based therapy targeting tendon injury; however, their therapeutic benefit relies on their ability to interact with native tenocytes. This study examines the mechanism and effects of coculturing human tenocytes and ASCs.Tenocytes (T) were directly cocultured with either ASCs (A) or fibroblasts (F) (negative control) in the following ratios: 50% T/50% A or F; 25% T/75% A or F; and 75% T/25% A or F. Cells were indirectly cocultured using a transwell insert that allowed for exchange of soluble factors only. Proliferation and collagen I production were measured and compared with monoculture controls. Synergy was quantified using the interaction index (II), which normalizes measured values by the expected values assuming no interaction (no synergy when II= 1). The ability of ASCs to elicit tenocyte migration was examined invitro using a transwell migration assay and exvivo using decellularized human flexor tendon explants.Compared with monoculture controls, II of proliferation was greater than 1 for all tenocyte and ASC direct coculture ratios, but not for tenocyte and fibroblast direct coculture ratios or for tenocyte and ASC indirect coculture. The ASCs elicited greater tenocyte migration invitro and exvivo. The II of collagen I production was greater than 1 for direct coculture groups with 25% T/75% A and 75% T/25% A.Direct coculture of ASCs and tenocytes demonstrated synergistic proliferation and collagen I production, and ASCs elicited tenocyte migration invitro and exvivo. These interactions play a key role in tendon healing and were absent when ASCs were replaced with fibroblasts, supporting the use of ASCs for cell-based therapy targeting tendon injuries.When ASCs are delivered for cell-based therapy, they directly interact with native tenocytes to increase cell proliferation, collagen I production, and tenocyte migration, which may enhance tendon healing.

View details for PubMedID 28888566

A sensor measuring deformation and pressure, entirely biodegradable, for orthopedic applications Boutry, C. M., Schroeder, B. C., Bao, Z., Legrand, A., Fox, P., IEEE IEEE. 2016: 144-147
Access to surgical upper extremity care for people with tetraplegia: an international perspective SPINAL CORD Fox, P. M., Suarez, P., Hentz, V. R., Curtin, C. M. 2015; 53 (4): 302-305


Survey.To determine whether upper extremity reconstruction in patients with tetraplegia is underutilized internationally and, if so, what are the barriers to care.International-attendees of a meeting in Paris, France.One hundred and seventy attendees at the Tetrahand meeting in Paris in 2010 were sent a 13-question survey to determine the access and utilization of upper limb reconstruction in tetraplegic patients in their practice.Respondents ranged the globe including North America, South America, Europe, Asia and Australia. Fifty-nine percent of respondents had been practicing for more than 10 years. Sixty-four percent of respondents felt that at least 25% of people with tetraplegia would be candidates for surgery. Yet the majority of respondents found that <15% of potential patients underwent upper extremity reconstruction. Throughout the world direct patient referral was the main avenue of surgeons meeting patients with peer networking a distant second. Designated as the top three barriers to this care were lack of knowledge of surgical options by patients, lack of desire for surgery and poor referral patterns to appropriate upper extremity surgeons.The results of this survey, of a worldwide audience, indicate that many of the same barriers to care exist regardless of the patient's address. This was a preliminary opinion survey and thus the results are subjective. However, these results provide a roadmap to improving access to care by improving patient education and interdisciplinary physician communication.

View details for DOI 10.1038/sc.2015.3

View details for Web of Science ID 000352725500008

View details for PubMedID 25687516

Grafting the alar rim: application as anatomical graft. Plastic and reconstructive surgery Gruber, R. P., Fox, P., Peled, A., Belek, K. A. 2014; 134 (6): 880e-7e


Alar rim contour and alar rim grafts have become essential components of rhinoplasty. Ideally, grafts of the nose should be anatomical in shape. So doing might make grafts of the alar rim more robust. The authors considered doing that by applying the graft as a continuous extension of the lateral crus.Twelve patients (two men and 10 women) constituted the study group (seven primary and five secondary cases). Of those, there were five concave rims, two concave rims with rim retraction, two boxy tips, and three cephalically oriented lateral crura. Surgical technique included the following: (1) an open approach was used; (2) a marginal incision that ignored the caudal margin of the lateral crus (the incision went straight posteriorly to a point 5 to 6 mm from the rim margin) was used; (3) a triangular graft was made to cover the exposed vestibular skin; (4) it was secured end to end to the caudal border of the lateral crus; and (5) the poster end was allowed to sit in a small subcutaneous pocket.Follow-up was 11 to 19 months. All 12 patients exhibited good rims as judged by a blinded panel. Rim retraction was not fully corrected in one patient, but no further treatment was required. One patient did require a secondary small rim graft for residual rim concavity.The concept of grafting the alar rim is strongly supported by the authors' results. The modifications the authors applied by designing the graft to be anatomical in shape has been a technical help.

View details for DOI 10.1097/PRS.0000000000000764

View details for PubMedID 25415110

Management of Frontal Sinus Fractures: Treatment Modality Changes at a Level I Trauma Center JOURNAL OF CRANIOFACIAL SURGERY Fox, P. M., Garza, R., Dusch, M., Hwang, P. H., Girod, S. 2014; 25 (6): 2038-2042


The optimal management of frontal sinus fractures remains controversial, and previously accepted indications for surgical intervention are being challenged. The goals of this study were to determine how frontal sinus fracture management has changed at a single institution across multiple disciplines and to evaluate the long-term outcomes of operative and nonoperative treatment modalities.Patients treated for a frontal sinus fracture at Stanford Hospital and Clinics between June 1998 and June 2009 were included in the study. Inpatient records, clinic notes, operative reports, and radiographic studies were reviewed. The patients were invited for a follow-up clinic visit, physical examination, and focused sinus computed tomography. For a period of 11 years, 124 patients were treated for a frontal sinus fracture by physicians from 3 surgical subspecialties: otolaryngology, plastic surgery, and neurosurgery. A low short-term complication rate was observed (5.6%), and there was a trend toward nonsurgical management within the study population. Ten patients returned for a long-term follow-up. Of these, the 2 patients who underwent cranialization experienced as many or more long-term complications compared with the patients treated by other modalities. These complications included abnormal frontal bone contour with bony discontinuity and altered sensation in the distribution of the trigeminal nerve.The demonstrated trend toward nonsurgical management of frontal sinus fractures seems to be safe. In the limited group of patients who returned for follow-up, more long-term complications were observed in the patients who underwent cranialization. However, a larger long-term follow-up cohort will be necessary to elucidate the relationship between treatment modality and long-term outcomes and complications.

View details for DOI 10.1097/SCS.0000000000001105

View details for Web of Science ID 000345012000054

Management of frontal sinus fractures: treatment modality changes at a level I trauma center. journal of craniofacial surgery Fox, P. M., Garza, R., Dusch, M., Hwang, P. H., Girod, S. 2014; 25 (6): 2038-2042


The optimal management of frontal sinus fractures remains controversial, and previously accepted indications for surgical intervention are being challenged. The goals of this study were to determine how frontal sinus fracture management has changed at a single institution across multiple disciplines and to evaluate the long-term outcomes of operative and nonoperative treatment modalities.Patients treated for a frontal sinus fracture at Stanford Hospital and Clinics between June 1998 and June 2009 were included in the study. Inpatient records, clinic notes, operative reports, and radiographic studies were reviewed. The patients were invited for a follow-up clinic visit, physical examination, and focused sinus computed tomography. For a period of 11 years, 124 patients were treated for a frontal sinus fracture by physicians from 3 surgical subspecialties: otolaryngology, plastic surgery, and neurosurgery. A low short-term complication rate was observed (5.6%), and there was a trend toward nonsurgical management within the study population. Ten patients returned for a long-term follow-up. Of these, the 2 patients who underwent cranialization experienced as many or more long-term complications compared with the patients treated by other modalities. These complications included abnormal frontal bone contour with bony discontinuity and altered sensation in the distribution of the trigeminal nerve.The demonstrated trend toward nonsurgical management of frontal sinus fractures seems to be safe. In the limited group of patients who returned for follow-up, more long-term complications were observed in the patients who underwent cranialization. However, a larger long-term follow-up cohort will be necessary to elucidate the relationship between treatment modality and long-term outcomes and complications.

View details for DOI 10.1097/SCS.0000000000001105

View details for PubMedID 25377963

Fascia-only anterolateral thigh flap for extremity reconstruction. Annals of plastic surgery Fox, P., Endress, R., Sen, S., Chang, J. 2014; 72: S9-S13


The ability to use the anterolateral thigh (ALT) flap as a vascularized fascial flap, without skin or muscle, was first documented by Koshima et al in 1989. The authors mention the possibility of using the fascia alone for dural reconstruction. Despite its description more than 20 years ago, little literature exists on the application of the ALT flap as a vascularized fascial flap. In our experience, the ALT flap can be used as a fascia-only flap for thin, pliable coverage in extremity reconstruction.After approval from the institutional review board, the medical records and photographs of patients who had undergone fascia-only ALT free flaps for extremity reconstruction were reviewed. Photographic images of patients were then matched to patients who had undergone either a muscle-only or a fasciocutaneous free flap reconstruction of an extremity. Photographs of the final reconstruction were then given to medical and nonmedical personnel for analysis, focusing on aesthetics including color and contour.Review of cases performed over a 2-year period demonstrated similar ease of harvest for fascia-only ALT flaps compared to standard fasciocutaneous ALT flaps. Fascia-only flaps were used for thin, pliable coverage in the upper and lower extremities. There was no need for secondary procedures for debulking or aesthetic flap revision. In contrast to muscle flaps, which require muscle atrophy over time to achieve their final appearance, there was a similar flap contour from approximately 1 month postoperatively throughout the duration of follow-up. When a large flap is required, the fascia-only ALT has the advantage of a single-line donor-site scar. Photograph comparison to muscle flaps with skin grafts and fasciocutaneous flaps demonstrated improved color, contour, and overall aesthetic appearance of the fascia-only ALT over muscle and fasciocutaneous flaps.The fascia-only ALT flap provides reliable, thin, and pliable coverage with improved contour and color over muscle and fasciocutaneous flaps. The fascia-only ALT is another excellent option for reconstructive surgery of the extremities.

View details for DOI 10.1097/SAP.0000000000000146

View details for PubMedID 24691305

Decellularized human tendon-bone grafts for composite flexor tendon reconstruction: a cadaveric model of initial mechanical properties. The Journal of hand surgery Fox, P. M., Farnebo, S., Lindsey, D., Chang, J., Schmitt, T., Chang, J. 2013; 38 (12): 2323-8


After complex hand trauma, restoration of tendon strength is challenging. Tendon insertion tears typically heal as fibrous scars after surgical reconstruction and create a weak point at the tendon-bone interface. In addition, major tendon loss may overwhelm the amount of available autograft for reconstruction. An off-the-shelf product may help address these challenges. We hypothesized that decellularized human flexor digitorum profundus and distal phalanx tendon-bone composite grafts were a feasible option for flexor tendon reconstruction after complex hand trauma. By replacing the entire injured composite segment, the need for tendon repair within the tendon sheath, reconstruction of the tendon-bone interface, and use of limited autograft could be eliminated.Paired human cadaver forearms were dissected to obtain the flexor digitorum profundus tendon with an attached block of distal phalanx. Tendon-bone grafts were pair-matched and divided into 2 groups: decellularized grafts (n = 12) and untreated (control) grafts (n = 11). Grafts in the decellularized group were subjected to physiochemical decellularization. Pair-matched tendon-bone grafts (decellularized and untreated) were placed back into the flexor tendon sheath and secured distally using a tie-over button and proximally by weaving the graft into the flexor digitorum superficialis tendon in the distal forearm. The ultimate load, location of failure, and excursion were determined.Decellularized tendon-bone composite grafts demonstrated no significant difference in ultimate failure load or stiffness compared with untreated grafts. Both groups eventually failed in varied locations along the repair. The most common site of failure in both groups was the tie-over button. The decellularized group failed at the tendon-bone insertion in 3 specimens (25%) compared with none in the untreated group. Both groups demonstrated an average tendon excursion of approximately 82 mm before failure.Decellularization of human flexor tendon-distal phalanx tendon-bone constructs did not compromise initial strength despite chemical and mechanical decellularization in a cadaveric model. At the time of repair, decellularized flexor tendon-bone grafts can exceed the strength and excursion needed for hand therapy immediately after reconstruction.These tendon-bone grafts may become an option for complex hand reconstruction at or near tendon-bone insertions and throughout the tendon sheath. Further work is required to assess the role of reseeding in an in vivo model.

View details for DOI 10.1016/j.jhsa.2013.08.092

View details for PubMedID 24055133

Human flexor tendon tissue engineering: in vivo effects of stem cell reseeding. Plastic and reconstructive surgery Schmitt, T., Fox, P. M., Woon, C. Y., Farnebo, S. J., Bronstein, J. A., Behn, A., Pham, H., Chang, J. 2013; 132 (4): 567e-76e


Tissue-engineered human flexor tendons may be an option to aid in reconstruction of complex upper extremity injuries with significant tendon loss. The authors hypothesize that human adipose-derived stem cells remain viable following reseeding on human tendon scaffolds in vivo and aid in graft integration.Decellularized human flexor tendons harvested from fresh-frozen cadavers and reseeded with green fluorescent protein-labeled pooled human adipose-derived stem cells were examined with bioluminescent imaging and immunohistochemistry. Reseeded repaired tendons were compared biomechanically with unseeded controls following implantation in athymic rats at 2 and 4 weeks. The ratio of collagen I to collagen III at the repair site was examined using Sirius red staining. To confirm cell migration, reseeded and unseeded tendons were placed either in contact or with a 1-mm gap for 12 days. Green fluorescent protein signal was then detected.Following reseeding, viable cells were visualized at 12 days in vitro and 4 weeks in vivo. Biomechanical testing revealed no significant difference in ultimate load to failure and 2-mm gap force. Histologic evaluation showed host cell invasion and proliferation of the repair sites. No increase in collagen III was noted in reseeded constructs. Cell migration was confirmed from reseeded constructs to unseeded tendon scaffolds with tendon contact.Human adipose-derived stem cells reseeded onto decellularized allograft scaffolds are viable over 4 weeks in vivo. The movement of host cells into the scaffold and movement of adipose-derived stem cells along and into the scaffold suggests biointegration of the allograft.

View details for DOI 10.1097/PRS.0b013e3182a033cf

View details for PubMedID 24076704

Management of the hand in systemic sclerosis. journal of hand surgery Fox, P., Chung, L., Chang, J. 2013; 38 (5): 1012-1016

View details for DOI 10.1016/j.jhsa.2013.02.012

View details for PubMedID 23561724

White light spectroscopy for free flap monitoring MICROSURGERY Fox, P. M., Zeidler, K., Carey, J., Lee, G. K. 2013; 33 (3): 198-202


White light spectroscopy non-invasively measures hemoglobin saturation at the capillary level rendering an end-organ measurement of perfusion. We hypothesized this technology could be used after microvascular surgery to allow for early detection of ischemia and thrombosis. The Spectros T-Stat monitoring device, which utilizes white light spectroscopy, was compared with traditional flap monitoring techniques including pencil Doppler and clinical exam. Data were prospectively collected and analyzed. Results from 31 flaps revealed a normal capillary hemoglobin saturation of 40-75% with increase in saturation during the early postoperative period. One flap required return to the operating room 12 hours after microvascular anastomosis. The T-stat system recorded an acute decrease in saturation from ~50% to less than 30% 50 min prior to identification by clinical exam. Prompt treatment resulted in flap salvage. The Spectros T-Stat monitor may be a useful adjunct for free flap monitoring providing continuous, accurate perfusion assessment postoperatively.

View details for DOI 10.1002/micr.22069

View details for Web of Science ID 000316335400005

View details for PubMedID 23280724

Computed tomography angiography in microsurgery: indications, clinical utility, and pitfalls. Eplasty Lee, G. K., Fox, P. M., Riboh, J., Hsu, C., Saber, S., Rubin, G. D., Chang, J. 2013; 13


Computed tomographic angiography (CTA) can be used to obtain 3-dimensional vascular images and soft-tissue definition. The goal of this study was to evaluate the reliability, usefulness, and pitfalls of CTA in preoperative planning of microvascular reconstructive surgery.A retrospective review of patients who obtained preoperative CTA in preparation for planned microvascular reconstruction was performed over a 5-year period (2001-2005). The influence of CTA on the original operative plan was assessed for each patient, and CTA results were correlated to the operative findings.Computed tomographic angiography was performed on 94 patients in preparation for microvascular reconstruction. In 48 patients (51%), vascular abnormalities were noted on CTA. Intraoperative findings correlated with CTA results in 97% of cases. In 42 patients (45%), abnormal CTA findings influenced the original operative plan, such as the choice of vessels, side of harvest, or nature of the reconstruction (local flap instead of free tissue transfer). Technical difficulties in performing CTA were encountered in 5 patients (5%) in whom interference from external fixation devices was the main cause.This large study of CTA obtained for preoperative planning of reconstructive microsurgery at both donor and recipient sites study demonstrates that CTA is safe and highly accurate. Computed tomographic angiography can alter the surgeon's reconstructive plan when abnormalities are noted preoperatively and consequently improve results by decreasing vascular complication rates. The use of CTA should be considered for cases of microsurgical reconstruction where the vascular anatomy may be questionable.

View details for PubMedID 24023972

Tissue expander with acellular dermal matrix for breast reconstruction infected by an unusual pathogen: Candida parapsilosis JOURNAL OF PLASTIC RECONSTRUCTIVE AND AESTHETIC SURGERY Fox, P. M., Lee, G. K. 2012; 65 (10): E286-E289


Infections occur in approximately 2-5% percent of women undergoing breast reconstruction by tissue expansion depending on patient characteristics and timing of reconstruction. Bacteria, specifically Staphylococci, are the most common pathogens. Treatment varies depending on the surgeon and the aggressiveness of the infection. We report a case of unilateral tissue expander infection with Candida parapsilosis in an otherwise healthy female undergoing immediate tissue expander placement after bilateral nipple-sparing mastectomies. The patient was treated with a one-stage irrigation, debridement, and tissue expander exchange as well as a 21-day course of oral antifungal therapy. Her infection resolved and she was able to complete her implant-based reconstruction. C. parapsilosis is usually responsible for infections in critically ill patients found in association with central lines, peritoneal dialysis catheters and prosthetic heart valves. The affinity of C. parapsilosis for foreign material makes it a causative agent worth considering in difficult to treat tissue expander infections.

View details for DOI 10.1016/j.bjps.2012.04.049

View details for Web of Science ID 000308995700003

View details for PubMedID 22633394

Supercharged Free Fibula for Complex Ankle Arthrodesis A Case Report ANNALS OF PLASTIC SURGERY Fox, P. M., Chou, L., Lee, G. K. 2012; 68 (4): 342-345


We report the successful use of a supercharged free fibula for tibial reconstruction and ankle arthrodesis. A 28-year-old woman underwent resection of a giant cell tumor of the distal tibia and reconstruction using a methyl methacrylate cement spacer 12 years prior. The spacer eroded into her ankle joint causing significant pain with ambulation. Therefore, she required ankle arthrodesis but lacked distal tibia bone stock. The ipsilateral fibula was harvested for reconstruction and transferred on its distal blood supply into the bony tibial defect. The proximal blood supply of the fibula flap was then anastomosed to the posterior tibial vessels to supercharge the blood supply. An Ilizarov was placed for external fixation. The combination of a supercharged free fibula and stable external fixation for tibial reconstruction led to timely bony union and ambulation, as well as avoiding the potential complications that can occur with other reconstructive options.

View details for DOI 10.1097/SAP.0b013e31824189d0

View details for PubMedID 22421475

Spontaneous deletion of the methicillin resistance determinant, mecA, partially compensates for the fitness cost associated with high-level vancomycin resistance in Staphylococcus aureus ANTIMICROBIAL AGENTS AND CHEMOTHERAPY Noto, M. J., Fox, P. M., Archer, G. L. 2008; 52 (4): 1221-1229


Treatment of infections caused by Staphylococcus aureus is often confounded by the bacterium's ability to develop resistance to chemotherapeutic agents. Methicillin-resistant S. aureus (MRSA) arises through the acquisition of staphylococcal chromosomal cassette mec (SCCmec), a genomic island containing the methicillin resistance determinant, mecA. In contrast, resistance to vancomycin can result from exposure to the drug, a mechanism that is not dependent upon a gene acquisition event. Here we describe three MRSA strains that became resistant to vancomycin during passage in the presence of increasing concentrations of the drug. In each case two derivative strains were isolated, one that had lost mecA and one that retained mecA during passage. Strain 5836VR lost mecA by the site-specific chromosomal excision of SCCmec, while the other two strains (strains 3130VR and VP32) deleted portions of their SCCmec elements in a manner that appeared to involve IS431. Conversion to vancomycin resistance caused a decrease in the growth rate that was partially compensated for by the deletion of mecA. In mixed-culture competition experiments, vancomycin-resistant strains that lacked mecA readily outcompeted their mecA-containing counterparts, suggesting that the loss of mecA during conversion to vancomycin resistance was advantageous to the organism.

View details for DOI 10.1128/AAC.01164-07

View details for Web of Science ID 000254881900003

View details for PubMedID 18212094

View details for PubMedCentralID PMC2292509

Lack of relationship between purine biosynthesis and vancomycin resistance in Staphylococcus aureus: a cautionary tale for microarray interpretation ANTIMICROBIAL AGENTS AND CHEMOTHERAPY Fox, P. M., Climo, M. W., Archer, G. L. 2007; 51 (4): 1274-1280


Previous microarray data (E. Mongodin, J. Finan, M. W. Climo, A. Rosato, S. Gill, and G. L. Archer, J. Bacteriol. 185:4638-4643, 2003) noted an association in two vancomycin-intermediate Staphylococcus aureus (VISA) strains between high-level, passage-induced vancomycin resistance, a marked increase in the transcription of purine biosynthetic genes, and mutation of the putative purine regulator purR. Initial studies to report on the possible association between vancomycin resistance and alterations in purine metabolism in one of these strains (VP-32) confirmed, by Western analysis, an increase in the translation of PurH and PurM, two purine pathway enzymes. In addition, PurR was identified, by knockout and complementation in a vancomycin-susceptible strain, as a repressor of the purine biosynthetic operon in S. aureus, and the PurR missense mutation was shown to inactivate the repressor. However, despite the apparent relationship between increased purine biosynthesis and increased vancomycin resistance in VP-32, neither the addition of exogenous purines to a defined growth medium nor the truncation or inactivation of purR improved the growth of vancomycin-susceptible S. aureus in the presence of vancomycin. Furthermore, the passage of additional vancomycin-susceptible and VISA strains to high-level vancomycin resistance occurred without changes in cellular purine metabolism or mutation of purR despite the development of thickened cell walls in passaged strains. Thus, we could confirm neither a role for altered purine metabolism in the development of vancomycin resistance nor its requirement for the maintenance of a thickened cell wall. The failure of biochemical and physiological studies to support the association between transcription and phenotype initially found in careful microarray studies emphasizes the importance of follow-up investigations to confirm microarray observations.

View details for DOI 10.1128/AAC.01060-06

View details for Web of Science ID 000245416500022

View details for PubMedID 17242154

View details for PubMedCentralID PMC1855472

Vancomycin-intermediate Staphylococcus aureus strains have impaired acetate catabolism: Implications for polysaccharide intercellular adhesin synthesis and autolysis ANTIMICROBIAL AGENTS AND CHEMOTHERAPY Nelson, J. L., Rice, K. C., Slater, S. R., Fox, P. M., Archer, G. L., Bayles, K. W., Fey, P. D., Kreiswirth, B. N., Somerville, G. A. 2007; 51 (2): 616-622


The most common mechanism by which Staphylococcus aureus gains resistance to vancomycin is by adapting its physiology and metabolism to permit growth in the presence of vancomycin. Several studies have examined the adaptive changes occurring during the transition to vancomycin-intermediate resistance, leading to a model of vancomycin resistance in which decreased cell wall turnover and autolysis result in increased cell wall thickness and resistance to vancomycin. In the present study, we identified metabolic changes common to vancomycin-intermediate S. aureus (VISA) strains by assessing the metabolic and growth characteristics of two VISA strains (vancomycin MICs of 8 microg/ml) and two isogenic derivative strains with vancomycin MICs of 32 microg/ml. Interestingly, we observed the parental strains had impaired catabolism of nonpreferred carbon sources (i.e., acetate), and this impairment became more pronounced as vancomycin resistance increased. To determine if acetate catabolism impairment is common to VISA strains, we assessed the ability of VISA and vancomycin-sensitive S. aureus (VSSA) clinical isolates to catabolize acetate. As expected, a significantly greater percentage of VISA strains (71%) had impaired acetate catabolism relative to VSSA (8%). This is an important observation because staphylococcal acetate catabolism is implicated in growth yield and antibiotic tolerance and in regulating cell death and polysaccharide intercellular adhesin synthesis.

View details for DOI 10.1128/AAC.01057-06

View details for Web of Science ID 000243900600030

View details for PubMedID 17130298

View details for PubMedCentralID PMC1797750

Successful therapy of experimental endocarditis caused by vancomycin-resistant Staphylococcus aureus with a combination of vancomycin and beta-lactam antibiotics ANTIMICROBIAL AGENTS AND CHEMOTHERAPY Fox, P. M., Lampert, R. J., Stumpf, K. S., Archer, G. L., Climo, M. W. 2006; 50 (9): 2951-2956


VRS1 is the first isolated strain of vancomycin-resistant Staphylococcus aureus (VRSA) found to carry the vanA gene complex previously described in Enterococcus. Under vancomycin pressure, VRS1 makes aberrant cell walls consisting of stem tetrapeptide and depsipeptide that lack the terminal D-Ala-D-Ala residues targeted by vancomycin. Previous data have suggested that this aberrant cell wall is not cross-linked by PBP2a, the enzyme responsible for cell wall transpeptidation in the presence of beta-lactam antibiotics. We examined the efficacy of treating VRS1 with a combination of vancomycin and beta-lactam antibiotics in vitro and in vivo. We found that the MIC of oxacillin for VRS1 decreased from >256 microg/ml to <1 microg/ml in the presence of vancomycin. Using the rabbit model of endocarditis, we treated VRS1-infected rabbits with nafcillin alone, vancomycin alone, or a combination of nafcillin and vancomycin. Treatment with nafcillin in combination with vancomycin cleared bloodstream infections within 24 h and sterilized 12/13 spleens (92%), as well as 8/13 kidneys (62%), following 3 days of treatment. Mean aortic valve vegetation counts were reduced 3.48 log(10) CFU/g with the combination therapy (compared to untreated controls) and were significantly lower than with either vancomycin or nafcillin given alone. VRS1 was extremely virulent in this model, as no untreated rabbits survived the 3-day trial. Treatment of clinical infections due to VRSA with the combination of vancomycin and beta-lactams may be an option, based on these results.

View details for DOI 10.1128/AAC.00232-06

View details for Web of Science ID 000240297000008

View details for PubMedID 16940087

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The up-regulation of ferritin expression using a small-molecule ligand to the native mRNA PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA Tibodeau, J. D., Fox, P. M., Ropp, P. A., Theil, E. C., Thorp, H. H. 2006; 103 (2): 253-257


The binding of small molecules to distinctive three-dimensional structures in mRNA provides a new dimension in RNA control, previously limited to the targeting of secondary structures with antisense and RNA interference; such targeting can modulate mRNA function and rates of protein biosynthesis. Small molecules that selectively bind the iron-responsive element (IRE), a specific three-dimensional structure in the noncoding region of the ferritin mRNA model that is recognized by the iron-regulatory protein repressor, were identified by using chemical footprinting. The assay used involved an oxoruthenium(IV) complex that oxidizes guanine bases in RNA sequences. Small molecules that blocked oxidation of guanines in the internal loop region were expected to selectively increase the rate of ferritin synthesis, because the internal loop region of the ferritin IRE is distinctive from those of other IREs. The natural product yohimbine was found (based on gel mobility shifts) to block cleavage of the internal loop RNA site by >50% and seemed to inhibit protein binding. In the presence of yohimbine, the rate of biosynthesis of ferritin in a cell-free expression system (rabbit reticulocyte lysate) increased by 40%. Assignment of the IRE-yohimbine interaction as the origin of this effect was supported by a similar increase in synthesis of luciferase protein in a chimera of the IRE and luciferase gene. The identification of a small, drug-like molecule that recognizes a naturally occurring three-dimensional mRNA structure and regulates protein biosynthesis rates raises the possibility that small molecules can regulate protein biosynthesis by selectively binding to mRNA.

View details for DOI 10.1073/pnas.0509744102

View details for Web of Science ID 000234624100002

View details for PubMedID 16381820

View details for PubMedCentralID PMC1326178