Outcomes of Chronically Anticoagulated Patients Undergoing Split-Thickness Skin Grafting for Diabetic Foot Ulcers.

OBJECTIVE: Split-thickness skin grafting (STSG) is commonly used for wound closure in diabetic foot ulcers (DFUs). In many cases, patients with diabetes present on long-term anticoagulation therapy. The complications associated with anticoagulants can be discouraging to surgeons considering STSG. The goal of this study was to evaluate STSG outcomes in the setting of chronic anticoagulation across a large, multicenter database. METHODS: The authors queried the TriNetX Network, which provides access to electronic medical records for more than 75 million patients, to search for patients with a history of DFUs treated with STSG. They divided those found into two groups: long-term anticoagulant use prior to grafting and no long-term anticoagulant use. After matching, the researchers evaluated outcomes following STSG after 1 month and 5 years. RESULTS: The authors identified 722 patients on chronic anticoagulation with DFUs who were treated with STSG; 446 of these patients were matched to 446 patients with no prior anticoagulation. One month following STSG, the anticoagulated group showed no significant increase in death, graft failure, or regrafting. At 5 years, there was no significant increase in mortality, graft failure, regrafting, or lower extremity amputation rates. CONCLUSIONS: Chronic anticoagulation therapy does not lead to increased short- or long-term postoperative complications such as graft failure, regrafting, or increased amputation rates following STSG for wound closure. Negative outcomes following STSG for DFUs in chronically anticoagulated individuals are minimal, and grafting should be performed without hesitation.

Glove and instrument changing to prevent bacterial contamination in infected wound debridement and closure procedures: A prospective observational study.

Many surgeons use a single table of instruments for both excisional debridement and coverage/closure of infected wounds. This study investigates the effectiveness of a two-table set-up of sterile instruments, in addition to glove exchange, to reduce instrument cross-contamination during these procedures. This is a prospective, single-site, institutional review board-approved observational study of surgical debridements of infected wounds over a 17-month period. Two separate sterile surgical tables were used for each case: Table A for initial wound debridement (debridement set-up) and Table B for wound coverage/closure (clean set-up). Swabs of each table and its respective instruments were taken after debridement but prior to coverage/closure. The primary outcome of interest was bacterial growth at 48 hours. There were 72 surgical cases included in this study. Culture results of Table A demonstrated bacterial growth in 23 of 72 (32%) cases at 48 hours compared with 5of 72 (7%) from Table B (P = .001). These data suggest that there is significant bacterial contamination of surgical instruments used for debridement of infected wounds. Use of a two-table set-up reduced instrument cross-contamination by 78%, suggesting avoidable re-contamination of the wound.

Plantar Foot Ulcer Recurrence in Neuropathic Patients Undergoing Percutaneous Tendo-Achilles Lengthening.

Equinus contracture carries 3- and 4-fold associations with diabetes and plantar foot ulceration, respectively. Percutaneous tendo-Achilles lengthening is a useful method to alleviate peak plantar pressure resulting from equinus. We aimed to evaluate the effectiveness of percutaneous tendo-Achilles lengthening and estimate the relative longevity of the approach in reducing ulcer recurrence. The medical records of patients with equinus contracture who underwent percutaneous tendo-Achilles lengthening from 2010 to 2017 were reviewed. Included patients presented with plantar ulcers and a gastroc-soleus equinus of any angle <10° of ankle dorsiflexion with the affected knee extended and flexed. Patients who received concomitant tendon lengthening procedures (including anterior tibial tendon or flexor digitorum longus) were excluded. Outcome measures included time to wound healing, time to ulcer recurrence, and development of transfer lesion. Ninety-one patients underwent percutaneous tendo-Achilles lengthening with subsequent pedal ulceration without concomitant procedures. A total of 69 (75.8%) patients had a plantar forefoot ulcer, 7 (7.7%) had midfoot ulcers, 5 (5.5%) had hindfoot ulcers, and 3 (3.3%) had ulcers in multiple locations. Seven patients received prophylactic tendo-Achilles lengthening. At a mean follow-up of 31.6 months (±26), 66 (78.6%) wounds healed at a median 12.9 weeks. A total of 29 patients (43.9%) experienced ulcer recurrence at a mean of 12 months. Twelve patients (13%) experienced a transfer lesion at a mean of 16.6 months. Tendo-Achilles lengthening can be an effective adjunctive approach to achieve wound healing and reduce long-term ulcer recurrence in patients with equinus contracture and neuropathic plantar foot ulcers. A relengthening procedure may be needed within approximately 12 months from index surgery.

Long Term Outcomes of Split-Thickness Skin Grafting to the Plantar Foot.

The most common consequence of neuropathy is a diabetic foot ulcer, which usually occurs on the plantar surface of the foot. Split-thickness skin grafting (STSG) has been shown in numerous studies to be an effective treatment for rapid coverage of diabetic ulcers. The purpose of this study is to retrospectively examine the outcomes of STSG to the plantar foot and determine the durability of this treatment compared to non-plantar surface STSG. This is a retrospective, single-center, institutional review board approved, case-control study of all patients who received STSG to their lower extremity for chronic ulcers from November 2013 to February 2017. Patients with ulcers on the plantar surface were considered cases, and non-plantar surface ulcers were considered controls. There were 182 patients who received STSG to the lower extremity, 52 to the plantar surface foot and 130 to non-plantar surface locations. Healing at 30 days was not significantly different between plantar and nonplantar ulcers (19% versus 28%, p = .199) but did become significant at 60, 90, and 365 days (21% versus 45%, p = .003; 33% versus 49%, p = .043; 38% versus 64%, p = .002, respectively). However, time to full healing was not significantly different between plantar and nonplantar groups (18.2 ± 19.5 versus 17.4 ± 21.6 weeks, mean ± standard deviation, p = .84). Recurrence was low for both groups (17% versus 10%, respectively), and there was no significant difference between groups (p = .17). Patients with plantar surface ulcers can achieve a durable coverage/closure of their wounds with STSG. When combined with appropriate patient selection and postoperative offloading, acceptable recurrence rates can be achieved.

Quantitative Results of Perfusion Utilising Hyperspectral Imaging on Non-diabetics and Diabetics: A Pilot Study.

There is a paucity of quantitative measures of microvascular perfusion values in the skin. Newly developed, handheld hyperspectral imaging devices identify unique spectral fingerprints of oxygenated and deoxygenated haemoglobin in the superficial microvasculature. Establishing value ranges for healthy patients without vascular complications will subsequently help standardise assessments for perfusion defects. In particular, diabetics who are prone to vascular calcifications and lower extremity wounds may benefit. A total of 73 subjects were enrolled in the study and split in two cohorts: 36 'non-diabetic' non-vascularly compromised patients and 37 'diabetic' patients with a formal diagnosis of diabetes but without history of pedal ulceration. Values of oxygenated haemoglobin (HT-Oxy) and deoxygenated haemoglobin (HT-DeOxy) from both devices are analysed.

Use of hyperbaric oxygen therapy for tissue ischemia after breast reconstruction.

INTRODUCTION: Mastectomy skin flap necrosis represents a significant complication of breast reconstructive procedures and is reported to occur in 30%-52% of patients undergoing breast reconstruction. Early identification of ischemia and early initiation of hyperbaric oxygen (HBO2) therapy can mitigate the effects of ischemia and rescue otherwise non-viable breast flap tissue. METHODS: We retrospectively examined the outcomes of HBO2 therapy in eight breasts with compromised mastectomy skin flaps between September 2015 and January 2017. Indocyanine green angiography (ICGA) was used to assess perfusion intraoperatively and post-HBO2 administration. RESULTS: Seven patients were referred for HBO2 within 24 hours of mastectomy. One patient failed to improve despite starting hyperbaric treatment within 24 hours. All other patients manifested successful healing of their mastectomy skin flaps with acceptable cosmesis after 10 HBO2 treatments. The mean relative perfusion of the at-risk area was 13.8% (±3.7%) pre-HBO2 and 101.6% (±37.3%) post-HBO2. The average area at-risk pre-HBO2 was 17.1 cm2 and reduced to zero post-HBO2. Relative perfusion values after HBO2 were found to be 6.8 (±3.4) times greater than those measured prior to HBO2. CONCLUSIONS: A short course of HBO2 may be sufficient to successfully rescue at risk post-mastectomy breast flaps. ICGA is a useful adjunct for evaluating post-mastectomy breast flap perfusion before and after HBO2 therapy.

Peripheral Vascular Disease Diagnostic Related Outcomes in Diabetic Charcot Reconstruction.

Postreconstructive outcomes were compared in diabetic patients with Charcot neuroarthropathy (CN) who had peripheral arterial disease (PAD) diagnosed with angiography versus patients who were diagnosed clinically. A retrospective review was performed of patients with diabetic CN requiring reconstruction secondary to ulceration and/or acute infection. Of the 284 patients in the CN osseous reconstruction cohort, after accounting for exclusion criteria, 59 (20.8%) patients with PAD were included in the analyses. Forty (67.8%) of these 59 patients were diagnosed with PAD clinically and 19 (32.2%) were diagnosed with the use of angiography. Bivariate analysis was used to compare outcomes between those diagnosed with PAD via angiography versus those diagnosed clinically for the following postreconstruction outcomes: wound healing, delayed healing, surgical site infection, pin tract infection, osteomyelitis, dehiscence, transfer ulcer, new site of Charcot collapse, contralateral Charcot event, nonunion, major lower extremity amputation, and return to ambulation. Bivariate analysis found return to ambulation postreconstruction (p = .0054) to be the only statistically significant factor. There was a trend toward significance for major lower extremity amputation, with higher rates of amputation in the clinically diagnosed PAD arm. Return to ambulation indicates improved functional outcomes. The main goal of limb salvage should be focused on improving the patient's functional performance. With significantly faster rates of return to ambulation and a trend toward decreased rates of major amputation, angiography was found to be a better assessor of PAD than clinical evaluations.

Noninvasive Vascular Assessment of Lower Extremity Wounds in Diabetics: Are We Able to Predict Perfusion Deficits?

Vascular assessment of the lower extremity is a critical step in any patient presenting with lower extremity chronic wounds to predict the likelihood of healing and risk of amputation. This concept is vital in patients with diabetes due to their complex vascular anatomy and disease distribution. Three arteries supply the six angiosomes of the lower extremity (i.e., three-dimensional blocks of tissue fed by a "source" artery in the foot and ankle). In diabetic patients, assessment of adequate blood flow to the lower extremities is complicated by the presence of arterial calcification, associated neuropathy, and inflammation. This review focuses on noninvasive vascular assessment methods to better understand perfusion and direct therapy to improve diabetic wound healing. Clinical examination of pulses and Ankle Brachial Index (ABI) can be supplemented by handheld Doppler assessment of direction of blood flow and pulse volume recordings to understand the site and extent of peripheral arterial disease. Duplex ultrasound has been used, but is operator dependent. CT angiogram has limitations in the presence of calcifications and renal insufficiency, prevalent in the diabetic population. Novel modalities, like hyperspectral imaging, ICG fluorescence angiography, and nuclear imaging are being studied for their potential to overcome some of these challenges, but the data is limited. At present, these newer modalities are not widely available, but once validated by robust data, they may supplant older, less reliable techniques and improve our ability to predict wound healing. This will help reduce healthcare costs and improve outcomes as wound care specialists will be able to more accurately direct patients to the best treatment plan to preserve mobility and reduce mortality.

Chronic Nicotine Exposure Attenuates Methamphetamine-Induced Dopaminergic Deficits.

Repeated methamphetamine (METH) administrations cause persistent dopaminergic deficits resembling aspects of Parkinson's disease. Many METH abusers smoke cigarettes and thus self-administer nicotine; yet few studies have investigated the effects of nicotine on METH-induced dopaminergic deficits. This interaction is of interest because preclinical studies demonstrate that nicotine can be neuroprotective, perhaps owing to effects involving α4ß2 and α6ß2 nicotinic acetylcholine receptors (nAChRs). This study revealed that oral nicotine exposure beginning in adolescence [postnatal day (PND) 40] through adulthood [PND 96] attenuated METH-induced striatal dopaminergic deficits when METH was administered at PND 89. This protection did not appear to be due to nicotine-induced alterations in METH pharmacokinetics. Short-term (i.e., 21-day) high-dose nicotine exposure also protected when administered from PND 40 to PND 61 (with METH at PND 54), but this protective effect did not persist. Short-term (i.e., 21-day) high-dose nicotine exposure did not protect when administered postadolescence (i.e., beginning at PND 61, with METH at PND 75). However, protection was engendered if the duration of nicotine exposure was extended to 39 days (with METH at PND 93). Autoradiographic analysis revealed that nicotine increased striatal α4ß2 expression, as assessed using [(125)I]epibatidine. Both METH and nicotine decreased striatal α6ß2 expression, as assessed using [(125)I]α-conotoxin MII. These findings indicate that nicotine protects against METH-induced striatal dopaminergic deficits, perhaps by affecting α4ß2 and/or α6ß2 expression, and that both age of onset and duration of nicotine exposure affect this protection.

Risk factors for opioid use disorder after severe burns in adults.

INTRODUCTION: Risk factors for opioid dependence amongst burn patients have not been well-explored compared to other surgical fields. METHODS: The TrinetX database was queried for patients diagnosed with opioid use disorder (OUD) after thermal or chemical burn. Propensity score matching was performed. Opioid and non-opioid analgesia use, ICU care, surgery, and comparative risks among common opiates were examined using descriptive and univariate regression models, including odds ratios. Subgroup analysis evaluated the impact of multimodal analgesia. RESULTS: Odds of receiving IV opioids for acute analgesia (p = <0.0001, OR = 1.80, CI = 1.45-2.25), undergoing surgery (p = <0.0001, OR = 1.58, CI = 1.26-1.98), and ICU care (p = <0.0001, OR = 3.60, CI = 2.00-3.83) after burn injury were higher in patients who developed OUD. Patients receiving multimodal therapy within 24 hours of admission had lower odds of developing OUD (OR = 0.74, CI = 2.76-4.68, p = 0.0001) and chronic pain (OR = 0.89, CI = 0.78-1.00, p = 0.05) regardless of TBSA. CONCLUSION: Patients who developed opioid use disorder following burn injury had higher odds of receiving opioid exclusive pain management, more frequent surgery, ICU care.

The Burn Wound.

Skin serves as a protective barrier against infection, prevents excessive fluid and electrolyte losses, performs crucial thermoregulation, and provides tactile feedback of surroundings. The skin also plays an essential role in human perception of body image, personal appearance, and self-confidence. With these many diverse functions, understanding normal anatomic composition of skin is pivotal to evaluating the extent of its disruption from burn injury. This article discusses the pathophysiology, initial evaluation, subsequent progression, and healing of burn wounds. By delineating the various microcellular and macrocellular alterations of burn injury, this review also augments providers' capacity to deliver patient-centered, evidence-based burn care.

Opioid use disorder in adult burn patients: Implications for future mental health, behavioral and substance use patterns.

BACKGROUND: Burn patients continue to have a high opioid requirement, despite current national trends to decrease opioid prescribing. While effective, long-term opioid use results in opioid dependence and possibly other mental health comorbidities. This retrospective cohort study seeks to evaluate implications of diagnosed opioid use disorder in the development of subsequent psychiatric, behavioral and substance abuse patterns. METHODS: The TriNetX database was queried for patients 18 years and older with a diagnosis of thermal or chemical burn who developed opioid use disorder after their burn injury. Two matched cohorts were studied, opioid use disorder versus non-opioid use disorder, to evaluate risk of developing subsequent mental health and behavioral conditions, use of psychiatric health services, and future substance abuse. RESULTS: A total of 2020 patients were identified in each cohort, matched for demographics, external trauma, and burn size. Patients in the opioid use disorder group had a significantly higher incidence of mental health diagnoses (79.7 % versus 57.7 %, OR 1.973, CI 1.741-2.236, p < 0.0001), including major depressive disorder, generalized anxiety disorder, and post-traumatic stress disorder. This group was also more likely to utilize psychiatric services (16.0 % versus 10.3 %, OR 1.926, CI 1.595-2.326, p < 0.0001) and psychotherapy (12.6 % versus 7.2 %, OR 2.046, CI 1.650-2.536, p<0.0001). Furthermore, the opioid use disorder group had higher rates of polysubstance abuse (29.9 % versus 12.3 %, OR 3.048, CI 2.588-3.589, p<0.0001), suicidal / homicidal ideations (8.2 % versus 3.2 %, OR 3.057, CI 2.274-4.109, p<0.0001), and suicide attempts (2.0 % versus 0.7 %, OR 2.971, CI 1.611-5.478, p = 0.003). CONCLUSIONS: Burn patients who develop opioid use disorder have significantly higher rates of future psychiatric diagnoses, behavioral disturbances, and polysubstance abuse. A multidisciplinary team approach, including early involvement of pain and mental health services, could potentially reduce the development of opioid use disorder and its consequences.

The impact of COVID-19 on clinical outcomes of burn patients.

Background: Multiple studies have shown the SARS-CoV-2 virus (COVID-19) to be associated with deleterious outcomes in a wide range of patients. The impact of COVID-19 has not been well investigated among burned patients. We suspect that patients will have worsened respiratory and thrombotic complications, ultimately leading to increased mortality. The objective of this study is to determine the impact a concurrent infection of COVID-19 has on clinical outcomes after a burn injury. Methods: This is a retrospective, propensity matched, cohort study. We examined a de-identified database of electronic medical records of over 75 million patients across 75 health care associations in the United States for patients treated for thermal burns from 1 January 2020, to 31 July 2021, and those who also were diagnosed with COVID-19 infection within one day before or after injury based on International Classification of Disease, tenth revision (ICD-10) codes. Study participants included adults who were treated for a burn injury during the study period. Results: We included 736 patients with burn injury and concomitant COVID-19 infection matched to 736 patients with burn injury and no concurrent COVID-19 infection (total 1472 patients, mean age 36.3 ± 24.3). We found no significant increase in mortality observed for patients with concurrent COVID-19 (OR 1.203, 95% CI 0.517-2.803; p = 0.6675). We did observe significant increase in infections (OR 3.537, 95% CI 2.798-4.471; p = 0.0001), thrombotic complications (OR 2.342, 95% CI 1.351-4.058; p = 0.0018), as was the incidence of hypertrophic scarring (OR 3.368, 95% CI 2.326-4.877; p = 0.0001). Conclusions: We observed that concurrent COVID-19 infection was associated with an increase in infections, thrombosis and hypertrophic scarring but no increase in mortality in our cohort of burn patients.

Implications of COVID-19 Infection on Arteriovenous Fistula Thrombosis.

Objective: This study aims to identify and analyze implications of COVID-19 positivity on AVF occlusion, subsequent treatment patterns, and ESRD patient outcomes. Our aim is to provide a quantitative context for vascular access surgeons in order to optimize surgical decision making and minimize patient morbidity. Methods: The de-identified national TriNetX database was queried to extracted all adult patients who had a known AVF between January 1, 2020 and December 31, 2021. From this cohort individuals who also were diagnosed with COVID-19 prior to creation of their AVF were identified. Cohorts were propensity score matched according to age at AVF surgery, gender, ethnicity, diabetes mellitus, nicotine dependence, tobacco use, use of anticoagulant medications, and use of platelet aggregation inhibitors, hypertensive diseases, hyperlipidemia, and prothrombotic states. Results: After propensity score matching there were 5170 patients; 2585 patients in each group. The total patient population had 3023 (58.5%) males and 2147 (41.5%) females. The overall rate of thrombosis of AV fistulas was 300 (11.6%) in the cohort with COVID-19 and 256 (9.9%) in the control group (OR 1.199, CI 1.005-1.43, P =.0453). Open revisions of AVF with thrombectomy were significantly higher in the COVID-19 cohort compared to the non-COVID-19 group (1.5% vs .5% P = .0002, OR 3.199, CI 1.668-6.136). Regarding the time from AVF creation to intervention, the median days for open thrombectomy in COVID-19 patients was 72 vs 105 days in controls. For endovascular thrombectomy, the median was 175 vs 168 days for the COVID-19 and control cohorts respectively. Conclusion: As for this study, there were significant differences in rates of thrombosis and open revisions of recent created AVF, however endovascular interventions remained remarkably low. As noted in this study, the persistent prothrombotic state of patients with a history of COVID-19 may persist beyond the acute infectious period of the disease.

The Role of Skin Substitutes in Acute Burn and Reconstructive Burn Surgery: An Updated Comprehensive Review.

Burns disrupt the protective skin barrier with consequent loss of cutaneous temperature regulation, infection prevention, evaporative losses, and other vital functions. Chronically, burns lead to scarring, contractures, pain, and impaired psychosocial well-being. Several skin substitutes are available and replace the skin and partially restore functional outcomes and improve cosmesis. We performed a literature review to update readers on biologic and synthetic skin substitutes to date applied in acute and reconstructive burn surgery. Improvement has been rapid in the development of skin substitutes in the last decade; however, no available skin substitute fulfills criteria as a perfect replacement for damaged skin.

Neither Antiplatelet nor Anticoagulant Therapy Increases Graft Failure after Split-thickness Skin Grafting.

Split-thickness skin grafts (STSG) are an effective modality for lower extremity wound coverage. Many patients in the highly comorbid chronic wound population present with cardiovascular disease requiring chronic antiplatelet or anticoagulant therapy, theoretically increasing risk for bleeding complications, donor site morbidity, and poor graft take. Some surgeons advocate temporary cessation of antithrombotic therapy, which may increase cardiovascular risk. The objective of this study was to examine the effects of anticoagulation use on STSG outcomes. Methods: All patients receiving STSGs for lower extremity wounds from 2014 to 2016 at a single institution were retrospectively reviewed. Successful grafts were defined as greater than 99.5% wound coverage. Patients were divided into two groups: anticoagulation/antiplatelet or no anticoagulation/antiplatelet. Continuous variables were described by means and SDs and analyzed using student's t-test. Categorical variables were described by frequencies and percentages and analyzed using Chi-square or Fisher exact tests as appropriate. Results: In total, 231 wounds were identified among 189 patients; 124 patients were receiving at least one antiplatelet/anticoagulant at time of grafting. Three hematomas were reported during 30 days of follow-up; there was no significant difference between groups (P > 0.05). Anticoagulation/antiplatelet therapy in the perioperative period had no significant impact on STSG take and overall healing. Conclusions: The findings from this study demonstrate that administration of anticoagulant/antiplatelet agents in the perioperative period does not increase the risk of skin graft failure. Based on these findings, STSG can be performed without cessation of anticoagulation or antiplatelet therapy.

Surgical Management of Lower Extremity Wounds in the Solid Organ Transplant Patient Population: Surgeon Beware.

Objective: To evaluate our institutional outcomes of surgical management of lower extremity (LE) wounds in the solid organ transplant recipient population. Approach: An 8-year retrospective review was conducted for all solid organ transplantation (SOT) recipients with LE wounds necessitating surgical management at our tertiary limb salvage center. Outcomes of interest included wound healing, surgical treatment, progression to amputation, and amputation level. Factors contributing to amputation progression were analyzed. The article adheres to the Strengthening the Reporting of Observational Studies in Epidemiology statement. Results: Sixty-four SOT recipients underwent surgical management for their LE wounds between 2010 and 2018. Median number of surgeries per patient was 5 (interquartile range = 2-8); 47 of 64 patients (73.4%) underwent amputation, and 17 of 64 patients (26.6%) underwent nonamputation surgical management. In the amputation group, the majority of primary amputations were minor (42/47, 89.4%); 24 of 42 (57.1%) patients progressed to a higher amputation level, 16 of 42 (38.1%) healed after their index procedure, and 2 of 42 (4.8%) were lost to follow-up (LTFU) after their primary minor amputation. Five of 47 (10.6%) patients undergoing amputations required primary below-knee amputations. In the nonamputation group, 15 of 17 (88.2%) healed, 1 of 17 (5.9%) expired, and 1 of 17 (5.9%) was LTFU. Innovation: To identify the outcomes of patients undergoing surgical management for LE wounds after SOT and elucidate clinical factors that impact the rate of limb salvage. Conclusions: This is the first comprehensive analysis of LE wounds in the transplant population. Our analysis indicates high rates of failed minor amputation, and frequent progression to major amputation in SOT patients. Preexisting comorbidities and immunosuppressive regimens complicate limb salvage; therefore, further research is warranted to optimize surgical LE wound management in this population.

Methamphetamine treatment during development attenuates the dopaminergic deficits caused by subsequent high-dose methamphetamine administration.

Administration of high doses of methamphetamine (METH) causes persistent dopaminergic deficits in both nonhuman preclinical models and METH-dependent persons. Noteworthy, adolescent [i.e., postnatal day (PND) 40] rats are less susceptible to this damage than young adult (PND90) rats. In addition, biweekly treatment with METH, beginning at PND40 and continuing throughout development, prevents the persistent dopaminergic deficits caused by a "challenge" high-dose METH regimen when administered at PND90. Mechanisms underlying this "resistance" were thus investigated. Results revealed that biweekly METH treatment throughout development attenuated both the acute and persistent deficits in VMAT2 function, as well as the acute hyperthermia, caused by a challenge METH treatment. Pharmacokinetic alterations did not appear to contribute to the protection afforded by the biweekly treatment. Maintenance of METH-induced hyperthermia abolished the protection against both the acute and persistent VMAT2-associated deficits suggesting that alterations in thermoregulation were caused by exposure of rats to METH during development. These findings suggest METH during development prevents METH-induced hyperthermia and the consequent METH-related neurotoxicity.

Utility of Porcine-Derived Xenograft as an Adjunct to Split-Thickness Skin Grafting in Lower-Extremity Wounds.

OBJECTIVE: Porcine-derived xenograft biological dressings (PXBDs) are occasionally used to prepare chronic wound beds for definitive closure before split-thickness skin grafts (STSGs). We sought to determine whether PXBD influences rate of STSG take in lower-extremity wounds. METHODS: Lower-extremity wounds treated with STSGs were retrospectively reviewed. Patients were included in one of two groups: wound bed preparation with PXBD before STSG or no preparation. Patients were excluded if they received wound bed preparation via another method. Patient demographics, comorbidities, wound history, wound bed preparation, and 30- and 60-day outcomes were collected. RESULTS: There was no difference in healing outcomes between the PXBD (n = 27) and no preparation (n = 39) groups. At 30- and 60-day follow-up, percentage of STSG take was not significantly different between groups (77.9% versus 79.0%, P30 = .818; 82.2% versus 80.9%, P60 = .422). Mean wound sizes at these follow-up periods were not different (4.4 cm2 versus 5.1 cm2, P30 = .902; 1.2 cm2 versus 1.1 cm2, P60 = .689). The PXBD group had a higher mean ± SD hemoglobin A1c level (8.3 ± 3.5 versus 6.9 ± 1.6; P = .074) and age (64.9 ± 12.8 years versus 56.3 ± 11.9 years; P = .007) versus the no preparation group. CONCLUSIONS: Application of PXBDs for wound bed preparation had no effect on wound healing compared with no wound bed preparation. The two groups varied only by mean age and hemoglobin A1c level. The PXBD may be beneficial, but these results call for randomized controlled trials to determine the true impact of PXBDs on wound healing. In addition, PXBDs may have utility outside of clinically oriented outcomes, and future work should address patient-reported outcomes and pain scores with this adjunct.

Day-of-Free Tissue Transfer Qualitative Cultures Do Not Predict Limb Salvage Outcomes.

BACKGROUND: Successful free tissue transfer is critical for lower extremity salvage in the chronic wound population. The rates of lower extremity free tissue transfer success lag behind those for other anatomical sites. The aim of this study was to evaluate whether positive qualitative day-of-free tissue transfer cultures or pathogen virulence negatively impacts short- and long-term outcomes of lower extremity free tissue transfer. METHODS: Between April of 2011 and January of 2018, 105 lower extremity free tissue transfer procedures were performed. Growth level and speciation were identified from qualitative cultures taken during free tissue transfer. The relationship between demographics, comorbidities, culture data, postoperative infection, free tissue transfer survival, and long-term limb salvage was examined using logistic regression. RESULTS: The median Charlson Comorbidity Index was 3. Intraoperative free tissue transfer cultures were positive in 39.1 percent. Flap survival was 93.3 percent. Postoperative infection developed in 12.4 percent. The limb salvage rate was 81.0 percent. Positive culture was not significant for flap survival, postoperative infection, or amputation. Cultures positive for Enterococcus species had a significant relationship with flap success (OR, 0.08; p = 0.01) and amputation (OR, 7.32; p = 0.04). Insufficient antimicrobial coverage had a significant relationship with postoperative infection (OR, 6.56; p = 0.01) despite the lack of pathogen concordance. On multivariate analysis, postoperative infection (OR, 12.85; p < 0.01) and Charlson Comorbidity Index were predictive of eventual amputation (OR, 1.44; p = 0.01). CONCLUSIONS: Positive day-of-free tissue transfer cultures, regardless of pathogen, had limited predictive value for short- and long-term outcomes of free tissue transfer in the authors' cohort. These findings call for a broader multicenter prospective analysis and consideration of health care-associated infections and their impact on limb salvage outcomes. CLINICAL QUESTION/LEVEL OF EVIDENCE: Risk, III.