Facilitating Success of the Early Stage Surgeon Scientist Trainee: Growing the Surgeon Scientist Pipeline.

OBJECTIVE: Surgeon scientists bring to bear highly specialized talent and innovative and impactful solutions for complicated clinical problems. Our objective is to inform and provide framework for early stage surgeon scientist training and support. SUMMARY OF BACKGROUND DATA: Undergraduate, medical student, and residency experiences impact the career trajectory of surgeon scientists. To combat the attrition of the surgeon scientist pipeline, interventions are needed to engage trainees and to increase the likelihood of success of future surgeon scientists. METHODS: A surgery resident writing group at an academic medical center, with guidance from faculty, prepared this guidance document for early stage surgeon scientist trainees with integration of the published literature to provide context. The publicly available National Institutes of Health RePORTER tool was queried to provide data salient to early stage surgeon scientist training. RESULTS: The educational path of surgeons and the potential research career entry points are outlined. Challenges and critical supportive elements needed to inspire and sustain progress along the surgeon scientist training path are detailed. Funding mechanisms available to support formal scientific training of early stage surgeon scientists are identified and obstacles specific to surgical careers are discussed. CONCLUSIONS: This guidance enhances awareness of essential education, communication, infrastructure, resources, and advocacy by surgery leaders and other stakeholders to promote quality research training in residency and to re-invigorate the surgeon scientist pipeline.

The lysosomal trafficking regulator is necessary for normal wound healing.

Non-healing wounds are a major threat to public health throughout the United States. Tissue healing is complex multifactorial process that requires synchronicity of several cell types. Endolysosomal trafficking, which contributes to various cell functions from protein degradation to plasma membrane repair, is an understudied process in the context of wound healing. The lysosomal trafficking regulator protein (LYST) is an essential protein of the endolysosomal system through an indeterminate mechanism. In this study, we examine the impact of impaired LYST function both in vitro with primary LYST mutant fibroblasts as well as in vivo with an excisional wound model. The wound model shows that LYST mutant mice have impaired wound healing in the form of delayed epithelialization and collagen deposition, independent of macrophage infiltration and polarisation. We show that LYST mutation confers a deficit in MCP-1, IGF-1, and IGFBP-2 secretion in beige fibroblasts, which are critical factors in normal wound healing. Identifying the mechanism of LYST function is important for understanding normal wound biology, which may facilitate the development of strategies to address problem wound healing.

Use of antibiotic impregnated resorbable beads reduces pressure ulcer recurrence: A retrospective analysis.

Recurrence of pressure ulcers remains common. We have employed resorbable antibiotic beads as a therapeutic strategy to deliver high local antibiotic concentrations to the debridement site. Our objective was to determine whether the use of resorbable antibiotic- beads would reduce pressure ulcer recurrence. We reviewed all stage IV pressure ulcers treated with excision, partial ostectomy and flap coverage over 16 years. Baseline patient factors (location of ulcer, presence of osteomyelitis, preoperative prealbumin), surgical factors (type of flap, use of antibiotic beads, bone culture results) and postoperative outcomes (ulcer recurrence at 1 year, dehiscence, seroma, cellulitis) were collected. Outcomes of patients who received antibiotic-impregnated beads were compared to those who did not. Eighty-six patients with 120 stage IV pressure ulcers underwent excision and flap coverage. This included 16 ulcers where antibiotic beads were used and 104 where they were not. The overall ulcer recurrence rate at 12 months was 35.8%. The recurrence rate in the group treated with antibiotic beads was significantly lower than the group without beads (12.5% vs. 39.4%, p = 0.03). Overall, complication rates between the two groups were similar (43.8% vs. 51.9%, p = 0.54). No systemic or local toxicity from antibiotic beads occurred. Scanning electron microscopy images of sacral bone from one case showed bacterial biofilm even after debridement. Pressure ulcer recurrence at 1 year after excision and flap coverage decreased significantly with the use of resorbable antibiotic beads.

A National Curriculum of Fundamental Skills for Plastic Surgery Residency: Report of the Inaugural ACAPS Boot Camp.

BACKGROUND: The Inaugural American Council of Academic Plastic Surgeons Plastic Surgery Boot Camp program was developed in response to ongoing changes in graduate medical education. The Boot Camp is a hands-on, practicum-based, 3-day course to introduce core concepts in plastic surgery for new plastic surgery residents (in both integrated and independent tracks). METHODS: The course was held in Pittsburgh in July to August 2015. There were 43 attendees (35 integrated/8 independent) representing 22 residency programs across 15 states. Faculty was composed of 8 local personnel and 5 visiting. Lecture topics and practical sessions covered the full spectrum of plastic surgery. All trainees completed an online survey evaluation both during the course and at 6 months. RESULTS: Participant responses were overwhelmingly positive. A total of 72% of respondents rated the Boot Camp ≥ 8 on a 1 to 10 scale (10 is excellent) for the overall course rating; 79% of respondents agreed or strongly agreed with the statement that the simulation scenarios were realistic; and 75% of participants agreed or strongly agreed with the statement that they found simulation-based training to be a valuable way to teach this material. Respondents reported an increase in comfort and confidence across topics after attending the Boot Camp at both 0- and 6-month time points. Instructors received positive evaluations across all topics. CONCLUSIONS: This successful inaugural course serves as a benchmark for development of a logistical blueprint, business plan, and curriculum for a proposed expansion to regional centers, to potentially encompass all incoming residents in plastic surgery.

The lysosomal trafficking regulator "LYST": an 80-year traffic jam.

Lysosomes and lysosome related organelles (LROs) are dynamic organelles at the intersection of various pathways involved in maintaining cellular hemostasis and regulating cellular functions. Vesicle trafficking of lysosomes and LROs are critical to maintain their functions. The lysosomal trafficking regulator (LYST) is an elusive protein important for the regulation of membrane dynamics and intracellular trafficking of lysosomes and LROs. Mutations to the LYST gene result in Chédiak-Higashi syndrome, an autosomal recessive immunodeficiency characterized by defective granule exocytosis, cytotoxicity, etc. Despite eight decades passing since its initial discovery, a comprehensive understanding of LYST's function in cellular biology remains unresolved. Accumulating evidence suggests that dysregulation of LYST function also manifests in other disease states. Here, we review the available literature to consolidate available scientific endeavors in relation to LYST and discuss its relevance for immunomodulatory therapies, regenerative medicine and cancer applications.

A survey of ex vivo/in vitro transduction efficiency of mammalian primary cells and cell lines with Nine natural adeno-associated virus (AAV1-9) and one engineered adeno-associated virus serotype.

BACKGROUND: The ability to deliver a gene of interest into a specific cell type is an essential aspect of biomedical research. Viruses can be a useful tool for this delivery, particularly in difficult to transfect cell types. Adeno-associated virus (AAV) is a useful gene transfer vector because of its ability to mediate efficient gene transduction in numerous dividing and quiescent cell types, without inducing any known pathogenicity. There are now a number of natural for that designed AAV serotypes that each has a differential ability to infect a variety of cell types. Although transduction studies have been completed, the bulk of the studies have been done in vivo, and there has never been a comprehensive study of transduction ex vivo/in vitro. METHODS: Each cell type was infected with each serotype at a multiplicity of infection of 100,000 viral genomes/cell and transduction was analyzed by flow cytometry + . RESULTS: We found that AAV1 and AAV6 have the greatest ability to transduce a wide range of cell types, however, for particular cell types, there are specific serotypes that provide optimal transduction. CONCLUSIONS: In this work, we describe the transduction efficiency of ten different AAV serotypes in thirty-four different mammalian cell lines and primary cell types. Although these results may not be universal due to numerous factors such as, culture conditions and/ or cell growth rates and cell heterogeneity, these results provide an important and unique resource for investigators who use AAV as an ex vivo gene delivery vector or who work with cells that are difficult to transfect.

Implanted Tissue-Engineered Vascular Graft Cell Isolation with Single-Cell RNA Sequencing Analysis.

The advent of single-cell RNA sequencing (scRNA-Seq) has brought with it the ability to gain greater insights into the cellular composition of tissues and heterogeneity in gene expression within specific cell types. For tissue-engineered blood vessels, this is particularly impactful to better understand how neotissue forms and remodels into tissue resembling a native vessel. A notable challenge, however, is the ability to separate cells from synthetic biomaterials to generate high-quality single-cell suspensions to interrogate the cellular composition of our tissue-engineered vascular grafts (TEVGs) during active remodeling in situ. We present here a simple, commercially available approach to separate cells within our TEVG from the residual scaffold for downstream use in a scRNA-Seq workflow. Utilizing this method, we identified the cell populations comprising explanted TEVGs and compared these with results from immunohistochemical analysis. The process began with explanted TEVGs undergoing traditional mechanical and enzymatic dissociation to separate cells from scaffold and extracellular matrix proteins. Magnetically labeled antibodies targeting murine origin cells were incubated with enzymatic digests of TEVGs containing cells and scaffold debris in suspension allowing for separation by utilizing a magnetic separator column. Single-cell suspensions were processed through 10 × Genomics and data were analyzed utilizing R to generate cell clusters. Expression data provided new insights into a diverse composition of phenotypically unique subclusters within the fibroblast, macrophage, smooth muscle cell, and endothelial cell populations contributing to the early neotissue remodeling stages of TEVGs. These populations were correlated qualitatively and quantitatively with immunohistochemistry highlighting for the first time the potential of scRNA-Seq to provide exquisite detail into the host cellular response to an implanted TEVG. These results additionally demonstrate magnetic cell isolation is an effective method for generating high-quality cell suspensions for scRNA-Seq. While this method was utilized for our group's TEVGs, it has broader applications to other implantable materials that use biodegradable synthetic materials as part of scaffold composition. Impact statement Single-cell RNA sequencing is an evolving technology with the ability to provide detailed information on the cellular composition of remodeling biomaterials in vivo. This present work details an effective approach for separating nondegraded biomaterials from cells for downstream RNA-sequencing analysis. We applied this method to implanted tissue-engineered vascular grafts and for the first time describe the cellular composition of the remodeling graft at a single-cell gene expression level. While this method was effective in our scaffold, it has broad applicability to other implanted biomaterials that necessitate separation of cell from residual scaffold materials for single-cell RNA sequencing.

Reducing Opioid Overprescribing through Procedure-specific Prescribing Guidelines.

Despite advances in opioid-sparing pain management, postdischarge opioid overprescribing in plastic surgery remains an issue. Procedure-specific prescribing protocols have been implemented successfully in other surgical specialties but not broadly in plastic surgery. This study examined the efficacy of procedure-specific prescribing guidelines for reducing postdischarge opioid overprescribing. Methods: A total of 561 plastic surgery patients were evaluated retrospectively after a prescribing guideline, which recommended postdischarge prescription amounts based on the type of operation, was introduced in July 2020. Prescription and postdischarge opioid consumption amounts before (n = 428) and after (n = 133) guideline implementation were compared. Patient satisfaction and prescription frequency of nonopioid analgesia were also compared. Results: The average number of opioid pills per prescription decreased by 25% from 19.3 (27.4 OME) to 15.0 (22.7 OME; P = 0.001) after guideline implementation, with no corresponding decrease in the average number of postdischarge opioid pills consumed [10.6 (15.1 OME) to 8.2 (12.4 OME); P = 0.147]. Neither patient satisfaction with pain management (9.6-9.6; P > 0.99) nor communication (9.6-9.5; P > 0.99) changed. The rate of opioid-only prescription regimens decreased from 17.9% to 7.6% (P = 0.01), and more patients were prescribed at least two nonopioid analgesics (27.5% to 42.9%; P = 0.003). The rate of scheduled acetaminophen prescription, in particular, increased (54.7% to 71.4%; P = 0.002). Conclusions: A procedure-specific prescribing model is a straight-forward intervention to promote safer opioid-prescribing practices in plastic surgery. Its usage in clinical practice may lead to more appropriate opioid prescribing.

A Personalized Opioid Prescription Model for Predicting Postoperative Discharge Opioid Needs.

BACKGROUND: Opioid overprescribing after surgery is common. There is currently no universal predictive tool available to accurately anticipate postdischarge opioid need in a patient-specific manner. This study examined the efficacy of a patient-specific opioid prescribing framework for estimating postdischarge opioid consumption. METHODS: A total of 149 patients were evaluated for a single-center retrospective cohort study of plastic and reconstructive surgery patients. Patients with length of stay of 2 to 8 days and quantifiable inpatient opioid consumption (n = 116) were included. Each patient's daily postoperative inpatient opioid consumption was used to generate a personalized logarithmic regression model to estimate postdischarge opioid need. The validity of the personalized opioid prescription (POP) model was tested through comparison with actual postdischarge opioid consumption reported by patients 4 weeks after surgery. The accuracy of the POP model was compared with two other opioid prescribing models. RESULTS: The POP model had the strongest association (R2 = 0.899; P < 0.0001) between model output and postdischarge opioid consumption when compared to a procedure-based (R2 = 0.226; P = 0.025) or a 24-hour (R2 = 0.152; P = 0.007) model. Accuracy of the POP model was unaffected by age, gender identity, procedure type, or length of stay. Odds of persistent use at 4 weeks increased, with a postdischarge estimated opioid need at a rate of 1.16 per 37.5 oral morphine equivalents (P = 0.010; 95% CI, 1.04 to 1.30). CONCLUSIONS: The POP model accurately estimates postdischarge opioid consumption and risk of developing persistent use in plastic surgery patients. Use of the POP model in clinical practice may lead to more appropriate and personalized opioid prescribing.

A Primer for Success as an Early Career Academic Plastic Surgeon.

The early career academic plastic surgeon strives to be an expert surgeon, an innovative researcher, and an impactful educator. Navigating these challenges is difficult in a healthcare landscape with diminishing public research funding, increasing demand from institutions for clinical productivity, and decreased value of surgical education. To help the junior academic plastic surgeon, this article discusses the fundamental aspects of developing an early academic plastic surgery practice, rooted in clinical care, research, and education. METHODS: Using published literature, expert opinion, and faculty interviews, the authors prepared this primer for education and guidance of plastic surgery residents considering a career in academic plastic surgery and early career academic plastic surgeons. RESULTS: This primer highlights elements important to succeeding as a junior academic plastic surgeon including defining goals and priorities, institutional and financial support, mentorship, education of students and residents, developing a practice niche, promotion and tenure, and social support and burnout. CONCLUSION: The early career academic plastic surgeon can create an environment for academic success with appropriate institutional support, mentorship, personal, and social support, to progress toward promotion while minimizing burnout and professional exhaustion.

Tamoxifen reduces silicone implant capsule formation in a mouse model.

Capsular contracture as a result of the foreign body response (FBR) is a common issue after implant-based breast reconstruction, affecting up to 20% of patients. New evidence suggests that tamoxifen may mitigate the FBR. C57BL/6 female mice were treated with daily tamoxifen or control injections and implanted with bilateral silicone implants in the submammary glandular plane. Implants were removed en bloc after 2 weeks and the implant capsules were evaluated histologically. Tamoxifen treatment decreased capsule thickness, decreased the number of αSMA+ cells (477 ± 156 cells/mm control vs 295 ± 121 cells/mm tamoxifen, p = 0.005 unpaired t test), and decreased CD31+ cells (173.9 ± 96.1 cells/mm2 control vs 106.3 ± 51.8 cells/mm2 tamoxifen, p = 0.043 unpaired t test). There were similar amounts of pro- and anti-inflammatory macrophages (iNOS 336.1 ± 226.3 cells/mm control vs 290.6 ± 104.2 cells/mm tamoxifen, p > 0.999 Mann-Whitney test and CD163 136.6 ± 76.4 cells/mm control vs 94.1 ± 45.9 cells/mm tamoxifen, p = 0.108 unpaired t test). Tamoxifen treatment in the mouse silicone breast implant model decreased capsule formation through modulation of myofibroblasts, neovascularization, and collagen deposition. Tamoxifen may be useful for reducing or preventing capsule formation in clinical breast implantations.

Gene correction by homologous recombination with zinc finger nucleases in primary cells from a mouse model of a generic recessive genetic disease.

Zinc Finger nucleases (ZFNs) have been used to create precise genome modifications at frequencies that might be therapeutically useful in gene therapy. We created a mouse model of a generic recessive genetic disease to establish a preclinical system to develop the use of ZFN-mediated gene correction for gene therapy. We knocked a mutated GFP gene into the ROSA26 locus in murine embryonic stem (ES) cells and used these cells to create a transgenic mouse. We used ZFNs to determine the frequency of gene correction by gene targeting in different primary cells from this model. We achieved targeting frequencies from 0.17 to 6% in different cell types, including primary fibroblasts and astrocytes. We demonstrate that ex vivo gene-corrected fibroblasts can be transplanted back into a mouse where they retained the corrected phenotype. In addition, we achieved targeting frequencies of over 1% in ES cells, and the targeted ES cells retained the ability to differentiate into cell types from all three germline lineages. In summary, potentially therapeutically relevant frequencies of ZFN-mediated gene targeting can be achieved in a variety of primary cells and these cells can then be transplanted back into a recipient.

Opioid Overprescribing and Procedure-Specific Opioid Consumption Patterns for Plastic and Reconstructive Surgery Patients.

BACKGROUND: Opioid prescribing practices contribute to opioid misuse, dependency, and diversion. There are currently no comprehensive and quantitative evidence-based guidelines that give procedure-specific recommendations regarding opioid prescribing in plastic surgery. METHODS: A retrospective review of 479 plastic surgery patients encompassing 23 different plastic surgery procedure categories was performed. Opioid prescribing patterns and patient-reported opioid use at 1 and 3 months postoperatively are reported. RESULTS: Opioid overprescribing was common, averaging an excess of 13 pills per patient across all procedure categories (prescribed versus consumed, 25.4 ± 23.1 versus 12.1 ± 19.7; p = 3.0 × 10-19), with a total excess of 5895 pills (30,967 oral morphine equivalents) for the study's sample. Fifty-two percent of all opioid pills prescribed went unused. Opioid consumption ranged between four and 37 pills across procedure categories. A greater proportion of patients who reported a history of preoperative opioid use were still using opioids at the time of their 1-month and 3-month follow-up appointments (62 percent versus 9 percent at 1 month, and 31 percent versus 1 percent at 3 months). Most patients (83 percent) did not store opioids in a locked location, and 64 percent did not dispose of opioids at 1 month. CONCLUSIONS: Opioids are commonly overprescribed by plastic surgery providers. This study determined procedure-specific opioid consumption patterns, which can help providers reduce opioid waste. In addition, patients do not properly store or dispose of opioids, demonstrating the need for better patient education.

Sex and Tamoxifen confound murine experimental studies in cardiovascular tissue engineering.

Tissue engineered vascular grafts hold promise for the creation of functional blood vessels from biodegradable scaffolds. Because the precise mechanisms regulating this process are still under investigation, inducible genetic mouse models are an important and widely used research tool. However, here we describe the importance of challenging the baseline assumption that tamoxifen is inert when used as a small molecule inducer in the context of cardiovascular tissue engineering. Employing a standard inferior vena cava vascular interposition graft model in C57BL/6 mice, we discovered differences in the immunologic response between control and tamoxifen-treated animals, including occlusion rate, macrophage infiltration and phenotype, the extent of foreign body giant cell development, and collagen deposition. Further, differences were noted between untreated males and females. Our findings demonstrate that the host-response to materials commonly used in cardiovascular tissue engineering is sex-specific and critically impacted by exposure to tamoxifen, necessitating careful model selection and interpretation of results.

Basics and Best Practices of Multimodal Pain Management for the Plastic Surgeon.

Pain management is a central focus for the plastic surgeon's perioperative planning, and it no longer represents a postoperative afterthought. Protocols that rely on opioid-only pain therapy are outdated and discouraged, as they do not achieve optimal pain relief, increase postoperative morbidity, and contribute to the growing opioid epidemic. A multimodal approach to pain management using non-opioid analgesic techniques is an integral component of enhanced recovery after surgery protocols. Careful perioperative planning for optimal pain management must be achieved in multidisciplinary collaboration with the perioperative care team including anesthesiology. This allows pain management interventions to occur at 3 critical opportunities-preoperative, intraoperative, and postoperative settings.

Tissue Engineered Vascular Graft Recipient Interleukin 10 Status Is Critical for Preventing Thrombosis.

Tissue engineered vascular grafts (TEVGs) are a promising technology, but are hindered by occlusion. Seeding with bone-marrow derived mononuclear cells (BM-MNCs) mitigates occlusion, yet the precise mechanism remains unclear. Seeded cells disappear quickly and potentially mediate an anti-inflammatory effect through paracrine signaling. Here, a series of reciprocal genetic TEVG implantations plus recombinant protein treatment is reported to investigate what role interleukin-10, an anti-inflammatory cytokine, plays from both host and seeded cells. TEVGs seeded with BM-MNCs from wild-type and IL-10 KO mice, plus unseeded grafts, are implanted into wild-type and IL-10 KO mice. Wild-type mice with unseeded grafts also receive recombinant IL-10. Serial ultrasound evaluates occlusion and TEVGs are harvested at 14 d for immunohistochemical analysis. TEVGs in IL-10 KO mice have significantly higher occlusion incidence compared to wild-type mice attributed to acute (<3 d) thrombosis. Cell seeding rescues TEVGs in IL-10 KO mice comparable to wild-type patency. IL-10 from the host and seeded cells do not significantly influence graft inflammation and macrophage phenotype, yet IL-10 treatment shows interesting biologic effects including decreasing cell proliferation and increasing M2 macrophage polarization. IL-10 from the host is critical for preventing TEVG thrombosis and seeded BM-MNCs exert a significant anti-thrombotic effect in IL-10 KO mice.

Early natural history of neotissue formation in tissue-engineered vascular grafts in a murine model.

Aim: To characterize early events in neotissue formation during the first 2 weeks after vascular scaffold implantation. Materials & methods: Biodegradable polymeric scaffolds were implanted as abdominal inferior vena cava interposition grafts in wild-type mice. Results: All scaffolds explanted at day 1 contained a platelet-rich mural thrombus. Within the first few days, the majority of cell infiltration appeared to be from myeloid cells at the peritoneal surface with modest infiltration along the lumen. Host reaction to the graft was distinct between the scaffold and mural thrombus; the scaffold stimulated an escalating foreign body reaction, whereas the thrombus was quickly remodeled into collagen-rich neotissue. Conclusion: Mural thrombi remodel into neotissue that persistently occludes the lumen of vascular grafts.

Preoperative Multimodal Analgesia Decreases Postanesthesia Care Unit Narcotic Use and Pain Scores in Outpatient Breast Surgery.

BACKGROUND: The opioid epidemic demands changes in perioperative pain management. Of the 33,000 deaths attributable to opioid overdose in 2015, half received prescription opioids. Multimodal analgesia is a practice-altering evolution that reduces reliance on opioid medications. Ambulatory breast surgery is an ideal opportunity to implement these strategies. METHODS: A retrospective review of 560 patients undergoing outpatient breast procedures was conducted. Patients received (1) no preoperative analgesia (n = 333); (2) intraoperative intravenous acetaminophen (n = 78); (3) preoperative oral acetaminophen and gabapentin (n = 95); or (4) preoperative oral acetaminophen, gabapentin and celecoxib (n = 54). Outcomes included postanesthesia care unit narcotic use, pain scores, postanesthesia care unit length of stay, rescue antiemetic use, and 30-day complications. RESULTS: Both oral multimodal analgesia regimens significantly reduced postanesthesia care unit narcotic use (oral acetaminophen and gabapentin, 14.3 ± 1.7; oral gabapentin, acetaminophen, and celecoxib, 11.9 ± 2.2; versus no drug, 19.2 ± 1.1 mg oral morphine equivalents; p = 0.0006), initial pain scores (oral acetaminophen and gabapentin, 3.9 ± 0.4; oral gabapentin, acetaminophen, and celecoxib, 3.4 ± 0.7; versus no drug, 5.3 ± 0.3 on a 1 to 10 scale, p = 0.0002) and maximum pain scores (oral acetaminophen and gabapentin, 4.3 ± 0.4; oral gabapentin, acetaminophen, and celecoxib, 3.6 ± 0.7; versus no drug, 5.9 ± 0.3 on a 1 to 10 scale; p < 0.0001). Both oral regimens were better than no medications or intravenous acetaminophen alone in multivariate models after controlling for age, body mass index, American Society of Anesthesiologists class, length of surgery, prior narcotic prescription availability, and intraoperative local anesthetic. Postanesthesia care unit length of stay, antiemetic use, and 30-day complications were not different. CONCLUSIONS: Preoperative oral multimodal analgesia reduces narcotic use and pain scores in outpatient breast plastic surgery. These regimens are inexpensive, improve pain control, and contribute to narcotic-sparing clinical practice in the setting of a national opioid epidemic. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, III.

A Formidable Foe Is Sabotaging Your Results: What You Should Know about Biofilms and Wound Healing.

LEARNING OBJECTIVES: After reading this article, the participant should be able to: 1. Describe biofilm pathogenesis as it relates to problem wounds. 2. Understand the preclinical and clinical evidence implicating biofilm in problem wounds. 3. Explain the diagnostic and treatment challenges that biofilms create for problem wounds. 4. Demonstrate a basic understanding of emerging strategies aimed at counteracting these processes. SUMMARY: Biofilm represents a protected mode of growth for bacteria, allowing them to evade standard diagnostic techniques and avoid eradication by standard therapies. Although only recently discovered, biofilm has existed for millennia and complicates nearly every aspect of medicine. Biofilm impacts wound healing by allowing bacteria to evade immune responses, prolonging inflammation and disabling skin barrier function. It is important to understand why problem wounds persist despite state-of-the-art treatment, why they are difficult to accurately diagnose, and why they recur. The aim of this article is to focus on current gaps in knowledge related to problem wounds, specifically, biofilm infection.

Targeted Peripheral Nerve-directed Onabotulinumtoxin A Injection for Effective Long-term Therapy for Migraine Headache.

BACKGROUND: Onabotulinumtoxin A (BOTOX) is an FDA-approved treatment for chronic migraine headaches (MHs) that involves on-label, high-dose administration across 31 anatomic sites. Anatomically specific peripheral nerve trigger sites have been identified that contribute to MH pathogenesis and are amenable to both BOTOX injection and surgical decompression. These sites do not always correlate with the on-label FDA-approved injection pattern, but represent a more targeted approach. The efficacy of peripheral nerve-directed BOTOX injection as an independent long-term therapeutic option has not been investigated. METHODS: The technique for peripheral nerve-directed therapeutic long-term BOTOX injection is described. A retrospective review was subsequently completed for 223 patients with MH. Sixty-six patients elected to proceed with diagnostic BOTOX injections. Of these, 24 continued long-term therapeutic BOTOX injections, whereas 42 matriculated to surgery. Outcomes were tracked. RESULTS: Initial outcomes included significant improvement in migraine headache index (MHI) (53.5 ± 83.0, P < 0.006), headache days/mo (9.2 ± 12.7, P < 0.0009), and migraine severity (2.6 ± 2.5, P < 0.00008) versus baseline. MHI improved from the initiation of diagnostic injections to the establishment of steady-state injections (P < 0.002), and further improved over time (P < 0.05, mean follow-up 615 days) with no desensitization observed. Decompressive surgery resulted in significant improvement in MHI (100.8 ± 109.7, P < 0.0000005), headache days/mo (10.8 ± 12.7, P < 0.000002), migraine severity (3.0 ± 3.8, P < 0.00001), and migraine duration in hours (16.8 ± 21.6, P < 0.0007). MHI improvement with surgery was better than long-term BOTOX injections (P < 0.05). CONCLUSIONS: Though inferior to surgical decompression, preliminary data demonstrate that targeted peripheral nerve-directed BOTOX injection is an effective primary therapy for MH representing a possible alternative to nondirected BOTOX injection with decreased dosage requirements and potentially decreased cost.