Fabrication and characterization of apremilast-loaded zinc oxide-mesoporous silica nanoparticles for psoriasis treatment.

Aim: The study was aimed to formulate and evaluate apremilast-loaded zinc oxide-mesoporous silica nanoparticles for treatment of psoriasis. Materials & methods: Mesoporous silica nanoparticles were prepared by using sol-gel method and evaluated for particle size, in vitro drug release, in vitro cytotoxicity study and in vivo pharmacodynamic study. Results: The synthesized mesoporous silica nanoparticles showed particle size of 319.9 ± 3.9 nm, with 24 ± 0.217% of loading capacity. In vitro cytotoxicity study on A-431 cell line showed increased anti-psoriatic activity of apremilast-loaded zinc oxide-mesoporous silica nanoparticles. In vivo pharmacodynamic study and histological studies showed improved efficacy of drug in imiquimod-induced psoriasis mice model. Conclusion: The apremilast-loaded zinc oxide-mesoporous silica nanoparticles showed improved therapeutic efficacy, suggesting that they are promising approach for topical treatment of psoriasis.

[Box: see text].

Exosomes in diagnostic and therapeutic applications of ovarian cancer.

Ovarian cancer accounts for more deaths than any other female reproductive tract cancer. The major reasons for the high mortality rates include delayed diagnoses and drug resistance. Hence, improved diagnostic and therapeutic options for ovarian cancer are a pressing need. Extracellular vesicles (EVs), that include exosomes provide hope in both diagnostic and therapeutic aspects. They are natural lipid nanovesicles secreted by all cell types and carry molecules that reflect the status of the parent cell. This facilitates their potential use as biomarkers for an early diagnosis. Additionally, EVs can be loaded with exogenous cargo, and have features such as high stability and favorable pharmacokinetic properties. This makes them ideal for tumor-targeted delivery of biological moieties. The International Society of Extracellular Vesicles (ISEV) based on the Minimal Information for Studies on Extracellular Vesicles (MISEV) recommends the usage of the term "small extracellular vesicles (sEVs)" that includes exosomes for particles that are 30-200 nm in size. However, majority of the studies reported in the literature and relevant to this review have used the term "exosomes". Therefore, this review will use the term "exosomes" interchangeably with sEVs for consistency with the literature and avoid confusion to the readers. This review, initially summarizes the different isolation and detection techniques developed to study ovarian cancer-derived exosomes and the potential use of these exosomes as biomarkers for the early diagnosis of this devastating disease. It addresses the role of exosome contents in the pathogenesis of ovarian cancer, discusses strategies to limit exosome-mediated ovarian cancer progression, and provides options to use exosomes for tumor-targeted therapy in ovarian cancer. Finally, it states future research directions and recommends essential research needed to successfully transition exosomes from the laboratory to the gynecologic-oncology clinic.

Tumor-targeted exosomes for delivery of anticancer drugs.

Exosomes are small phospholipid bilayer vesicles that are naturally produced by all living cells, both prokaryotes and eukaryotes. The exosomes due to their unique size, reduced immunogenicity, and their ability to mimic synthetic liposomes in carrying various anticancer drugs have been tested as drug delivery vehicles for cancer treatment. An added advantage of developing exosomes as a drug carrier is the ease of manipulating their intraluminal content and their surface modification to achieve tumor-targeted drug delivery. In the past ten-years, there has been an exponential increase in the number of exosome-related studies in cancer. Preclinical studies demonstrate exosomes-mediated delivery of chemotherapeutics, biologicals and natural products produce potent anticancer activity both, in vitro and in vivo. In contrast, the number of exosome-based clinical trials are few due to challenges in the manufacturing and scalability related to large-scale production of exosomes and their storage and stability. Herein, we discuss recent advances in exosome-based drug delivery for cancer treatment in preclinical and clinical studies and conclude with challenges to be overcome for translating a larger number of exosome-based therapies into the clinic.

Case Report: Idiopathic Subcutaneous Thrombotic Vasculopathy.

Lower extremity ulcers have significant morbidity, with treatment determined by the underlying disorder. Reported is a 32-year-old female presenting with small skin nodules and bruises across her legs 4 weeks following her second COVID vaccination. These lesions progressed into large, necrotic ulcers over several months. Initial work-up showed widespread pannicular thrombotic vasculopathy with ischemic skin necrosis. The tissue was negative for calcification on Von Kossa histochemistry, and a working diagnosis of subcutaneous thrombotic vasculopathy was suggested. The ulcers progressed despite treatments with corticosteroids, therapeutic anticoagulation, intravenous immunoglobulin, plasmapheresis, sodium thiosulfate, wound care, and repeat debridement. Later debridement specimens demonstrated rare vascular and pannicular calcifications. This finding supports the hypothesis that subcutaneous thrombotic vasculopathy is a precursor to calciphylaxis, the patient's current working diagnosis. However, based on the patient's entire clinical picture, a definitive diagnosis has yet to be found. This report highlights the challenges of working with rare diseases and the importance of multidisciplinary cooperation.

Evaluation of Liposomal Bupivacaine at Split-Thickness Skin Graft Donor Sites Through a Randomized, Controlled Trial.

Split-thickness skin grafts (STSG) are commonly required in reconstructive surgery but may cause significant pain. The goal of this investigator-initiated trial is to evaluate the effect of liposomal bupivacaine on donor site pain and opioid consumption. A parallel, randomized, controlled trial of adult acute burn patients with <20% TBSA burns was conducted to evaluate the efficacy of liposomal bupivacaine at STSG donor sites. The control group received standard subcutaneous infiltration of dilute lidocaine solution at the STSG donor site, and the experimental group received dilute liposomal bupivacaine infiltration in a similar fashion. Donor site pain scores and opioid consumption in morphine equivalents (MEE) were evaluated. A total of 25 patients were enrolled in each group. There were no statistical differences in demographic variables, and TBSA was 4.0% in both groups (P = .94). There were no statistical differences in pain scores at any time point postoperatively (mean control range 3.1/10-4.9/10, experimental range 3.3/10-4.3/10, P = .12-.96). There were no statistical differences in opioid consumption at 24, 48, or 72 h postoperatively between the groups (mean control MEE range 49.3-71.1, experimental MEE range 63.6-75.8, P = .34-.85). The average length of stay was 7.7 days in both groups (P = .88). No adverse events occurred in either group. There is no statistical benefit to the use of liposomal bupivacaine for infiltration at STSG donor sites compared to standard of care with respect to pain control, opioid use, or length of stay when evaluated in a randomized, controlled fashion.

Giant Congenital Blue Nevus Presenting as Cutis Verticis Gyrata: A Case Report and Review of the Literature.

OBJECTIVES: Cerebriform intradermal nevus and giant congenital blue nevi are rarely reported melanocytic nevi with clinical and histopathologic similarities. Both are known to produce cutis verticis gyrata. We report a significantly large occipital scalp congenital blue nevus with secondary cutis verticis gyrata. The aim of this report is to increase clinical awareness of this entity, highlight histopathologic and mutational features of cerebriform intradermal nevi and giant congenital blue nevi, and stress the importance of clinicopathologic correlation for diagnosis. METHODS: Case report and review of the literature. RESULTS: A 20-year-old Asian male presented with a long-standing, large (20 cm × 30 cm), exophytic tumor at the occipital scalp and posterior neck. The skin overlying the lesion was arranged in thick folds resembling the surface of the brain, devoid of hair follicles, and discolored by salt-and-pepper pattern hyperpigmentation. After correlating the clinical and histopathologic findings, we diagnosed giant congenital blue nevus with secondary cutis verticis gyrata. Staged surgical excision was performed with subsequent treatment for hypertrophic scarring and occipital alopecia. CONCLUSIONS: Cerebriform intradermal nevus and giant congenital blue nevus have overlapping histologic and clinical features. Head and neck surgeons should be aware that nomenclature of these tumors is subjective and often imprecise. Diagnosis requires correlation of clinical findings, patient history, and histopathology. Surgical excision is advised due to rare malignant transformation potential.

Design and characterization of dual responsive mesoporous silica nanoparticles for breast cancer targeted therapy.

The main reason for limited efficacy of anticancer drug is the poor accretion of administered amount of drug within the tumor. Here, chitosan folate capped dual responsive mesoporous silica nanoparticles (MSNs) which can actively target cancer cells, and provide burst release of loaded anticancer drug within tumor cells and ultimately leading to improved therapeutic efficacy were synthesized. MSNs were synthesized using most economic silica source, sodium silicate. Doxorubicin (DOX) was loaded within the pores of MSNs and these drug loaded MSNs were first reacted with cystamine dihydrochloride followed by capping with chitosan-folate conjugate (CH-FA) to produce dual (redox and pH) responsive nanoparticles with the ability to actively target breast cancer cells. A triggered release of DOX from MSNs under acidic redox (pH 5.5, 10 mM GSH) environment was confirmed by in vitro release studies. The formulation exhibited 2.14 and 1.65 folds higher cytotoxicity than free drug against MCF-7 and MDA-MB-231 cells. DOX-MSN-SS-CH-FA showed superior tumor suppressing activity as compared to DOX-MSN or DOX alone in the treatment of Ehrlich Ascites Carcinoma (EAC) induced breast cancer with significantly reduced hematological and organ specific toxicities associated with DOX treatment.

Sedation and Analgesia for Adult Outpatient Burn Dressing Change: A Survey of American Burn Association Centers.

The management of pain and sedation during burn dressing change is challenging. Previous reviews and studies have identified wide variability in such practices in hospitalized burn patients. This survey-based study aimed to determine the most commonly utilized sedation and analgesia practices in adult burn patients treated in the outpatient setting. The goal was to identify opportunities for improvement and to assist burn centers in optimizing sedation procedures. A 23-question survey was sent to members of the American Burn Association. Nonpharmacological interventions including music, television, games, and virtual reality were used by 68% of survey respondents. Eighty-one percent reported premedicating with oral opioids, 32% with intravenous opioids, and 45% with anxiolytics. Fifty-nine percentage of respondents indicated that the initial medication regimen for outpatient dressing changes consisted of the patient's existing oral pain medications. Forty-three percent indicated that there were no additional options if this regimen provided inadequate analgesia. Fifty-six percentage of respondents felt that pain during dressing change was adequately controlled 75% to 100% of the time, and 32% felt it was adequately controlled 50% to 75% of the time. Nitrous oxide was used by 8%. Anesthesia providers and an acute pain service are available in a minority of cases (13.7% and 28%, respectively) and are rarely consulted. Procedural burn pain remains significantly undertreated in the outpatient setting and the approach to treatment is variable among burn centers in the United States. Such variation likely represents an opportunity for identifying and implementing optimal practices and developing guidelines for burn pain management in the outpatient setting.

Inhalation Injury Does Not Influence the Amount of Blood Transfused to Major Burn Patients: A Secondary Analysis from the Transfusion Requirement in Burn Care Evaluation Study.

Patients with major burn injuries typically require numerous blood transfusions. It is not known if an inhalation injury (INHI) directly influences the need for blood transfusion. The purpose of this study was to determine whether INHI increases the amount of blood transfused to major burn patients. A secondary analysis from the Transfusion Requirement in Burn Care Evaluation (TRIBE) study was conducted. Patients with INHI were compared with patients without INHI. The number of red blood cell (RBC) transfusions per day (RBC per day) between INHI and No INHI was analyzed with a multivariable regression. Patients with INHI (n = 78) had significantly larger burns (P = .0004), larger full-thickness burns (P = .0007), greater admission APACHE score (P < .0001), higher admission multiple organ dysfunction scores (P < .0001), and were transfused more RBC per day (P = .009) than No INHI patients (n = 267). In the multivariable regression analysis, RBC per day was significantly associated with the %TBSA burn (P < .0001), age of the patient (P = .004), the need for more than 1 day of mechanical ventilation (P < .0001), the occurrence of at least one blood stream infection (BSI; P = .044), and being assigned to the liberal transfusion arm of TRIBE (P < .001) but not the presence of INHI (P = .056). The null hypothesis that INHI exerts no influence on the amount of blood transfused could not be rejected. Larger burn size, advanced patient age, mechanical ventilation, and BSIs are important determinants of the blood transfusion rate in major burn patients.

Effects of Intraoperative Dexamethasone Administration in Adult Diabetic Burn Patients.

The steroid dexamethasone is used intraoperatively to prevent postoperative nausea. Studies of intraoperative steroid use in diabetic patients have shown conflicting effects on blood glucose and complications, and their use has not yet been studied in the burn population. A review of adult diabetic acute burn patients undergoing surgery at a verified burn center from 2012 to 2017 was conducted. Statistical analysis compared those who did and did not receive an intraoperative steroid. A total of 74 patients who underwent 121 operations were identified; steroid was administered in 14.0% of cases. There were no statistically significant differences in preoperative glucose, insulin requirements, TBSA, or hemoglobin A1C. Postoperatively, the steroid group had a 16.7 mg/dl (SD = 11.1) increase in blood glucose (P = .042) and 53.5 unit/24 hour (SD = 28.4) increase in insulin requirement (P = .019), compared with no change in controls. The complication rate in the steroid group was 52.9% compared with 20.1% in controls (P = .003); partial graft loss was the most common complication. Diabetic burn patients who receive intraoperative steroid have increased postoperative blood glucose levels, insulin requirements, and complication rates compared with patients who do not receive steroids. Discussion is warranted to avoid intraoperative steroid in this population.

The Prevalence of Psychiatric Disorders Among Elective Plastic Surgery Patients.

Purpose: Psychiatric disorder is one of the predictors of poor outcome in cosmetic plastic surgery patients. A US study in 1960 showed that 72.4% of 98 cosmetic plastic surgery patients had a psychiatric disorder. In our study, we predict that the prevalence of psychiatric disorders will be statistically significant among patients seeking elective plastic surgery in comparison with the general US population. Methods: We conducted a retrospective review study of 1000 adult patients seeking elective plastic surgery at The University of Kansas Medical Center Plastic Surgery Department from 2011 to 2016. Results: From 1000 patients seeking elective plastic surgery procedure, 441 (44.1%) patients have or had a history of psychiatric disorder. Most common psychiatric disorders were major depressive disorder (n = 223; 50.6%) and generalized anxiety disorder (n = 145; 32.9%). Conclusion: Our study indicates that psychiatric disorders are prevalent in patients seeking elective plastic surgery at our institution. Anxiety and depression were the most common diagnoses, and this is possibly due to these being the most common psychiatric disorders in the US population. Results highlight the importance of provider vigilance for psychiatric patients seeking elective plastic surgery.

Sedation and Analgesia During Pediatric Burn Dressing Change: A Survey of American Burn Association Centers.

Sedation practices for pediatric burn patients during dressing changes vary between institutions and providers. To better understand the current trends in pediatric sedation practice, a survey was conducted among the members of the American Burn Association (ABA). Questions asked about nonoperating room sedation and analgesia practices for burn patients (ages 0-17) having dressing changes in the intensive care unit, inpatient unit, and outpatient clinics. ABA members providing sedation for pediatric patients undergoing burn dressing changes are diverse. Physician respondents included surgeons, critical care intensivists, and anesthesiologists. Others included physician assistants, nurse anesthetists, nurse practitioners, and sedation credentialed nurses. Opioids for pain control were prescribed by 100% of respondents, but use of adjuvant nonopioid analgesics was utilized <50% of the time. Benzodiazepines and ketamine were prescribed more than twice as often as other sedatives. Many noted that up to 50% of children did not have adequately controlled anxiety and pain with initial sedation plans, and escalation of care was needed to complete dressing changes. Self-reported adverse events were infrequent. In outpatient settings, benzodiazepines, ketamine, oral opioids, and topical lidocaine were used frequently, as were nonpharmacologic methods of distraction and comfort. Sedation in pediatric burn patients is challenging. Responses highlighted areas for improvement regarding pain control during dressing changes and increasing use of multimodal analgesia. Commonly used medications including opioids, benzodiazepine, and ketamine are well established in the treatment of burn patients, as are nonpharmacologic methods. A collaborative effort among institutions is needed to formulate practice guidelines for sedation during burn dressing changes.

Restrictive Transfusion Strategy Is More Effective in Massive Burns: Results of the TRIBE Multicenter Prospective Randomized Trial.

OBJECTIVES: Studies suggest that a restrictive transfusion strategy is safe in burns, yet the efficacy of a restrictive transfusion policy in massive burn injury is uncertain. Our objective: compare outcomes between massive burn (≥60% total body surface area (TBSA) burn) and major (20-59% TBSA) burn using a restrictive or a liberal blood transfusion strategy. METHODS: Patients with burns ≥20% were block randomized by age and TBSA to a restrictive (transfuse hemoglobin <7 g/dL) or liberal (transfuse hemoglobin <10 g/dL) strategy throughout hospitalization. Data collected included demographics, infections, transfusions, and outcomes. RESULTS: Three hundred and forty-five patients received 7,054 units blood, 2,886 in massive and 4,168 in restrictive. Patients were similar in age, TBSA, and inhalation injury. The restrictive group received less blood (45.57 ± 47.63 vs. 77.16 ± 55.0, p < 0.03 massive; 11.0 ± 16.70 vs. 16.78 ± 17.39, p < 0.001) major). In massive burn, the restrictive group had fewer ventilator days (p < 0.05). Median ICU days and LOS were lower in the restrictive group; wound healing, mortality, and infection did not differ. No significant outcome differences occurred in the major (20-59%) group (p > 0.05). CONCLUSIONS: A restrictive transfusion strategy may be beneficial in massive burns in reducing ventilator days, ICU days and blood utilization, but does not decrease infection, mortality, hospital LOS or wound healing.

Parameters for Ordering Blood Cultures in Major Burn Injury Patients: Improving Clinical Assessment.

Hypermetabolic and catabolic states in large TBSA burns lead to higher basal body temperature and tachycardia. These metabolic changes complicate the diagnosis of bacteremia and sepsis. Current indications for obtaining blood cultures (BCs) in this population are poorly described and nonstandardized. Fever, leukocytosis, and lactic acidosis are common during sepsis. This study aims to identify limits of these parameters with the highest rates of bacteremia. A retrospective review was performed for burn patients with > 20% TBSA between January 2009 and June 2011. BCs were collected with corresponding body temperature, white blood cell (WBC) count, and serum lactate levels. Positive culture rates were analyzed with univariate and multivariate analysis. Seventy-one patients met inclusion criteria and 360 BCs were included in data analysis. Cultures taken with temperature > 38.9°C were significantly more positive (P = .01) than temperatures between 38 and 38.9°C. There were significantly more positive cultures when the WBC count was < 4.5 compared with those ≥ 4.5 × 103/µl (P = .04). Lactate was an independent predictor of bacteremia (OR, 1.81; 95% CI, 1.21-12.71). Cultures were significantly more positive when the lactate level was ≥ 2.5 compared with < 2.5 mg/dL (P = .02). A temperature ≥ 38.5°C and a lactate ≥ 2.5 mg/dL corresponded to a 28.6% positive culture rate compared with 4.8% for all other scenarios (P = .001). This study demonstrates that body temperature > 38.9°C, WBC < 4.5 × 103/µl, and serum lactate ≥ 2.5 mg/dL have the highest rate for positive BCs in severe burn patients. A combination of leukopenia and pyrexia as well as lactic acidosis and pyrexia represent even higher specificity for positive BC in these patients.

Transfusion Requirement in Burn Care Evaluation (TRIBE): A Multicenter Randomized Prospective Trial of Blood Transfusion in Major Burn Injury.

OBJECTIVE: Our objective was to compare outcomes of a restrictive to a liberal red cell transfusion strategy in 20% or more total body surface area (TBSA) burn patients. We hypothesized that the restrictive group would have less blood stream infection (BSI), organ dysfunction, and mortality. BACKGROUND: Patients with major burns have major (>1 blood volume) transfusion requirements. Studies suggest that a restrictive blood transfusion strategy is equivalent to a liberal strategy. However, major burn injury is precluded from these studies. The optimal transfusion strategy in major burn injury is thus needed but remains unknown. METHODS: This prospective randomized multicenter trial block randomized patients to a restrictive (hemoglobin 7-8 g/dL) or liberal (hemoglobin 10-11 g/dL) transfusion strategy throughout hospitalization. Data collected included demographics, infections, transfusions, and outcomes. RESULTS: Eighteen burn centers enrolled 345 patients with 20% or more TBSA burn similar in age, TBSA burn, and inhalation injury. A total of 7054 units blood were transfused. The restrictive group received fewer blood transfusions: mean 20.3 ±â€Š32.7 units, median = 8 (interquartile range: 3, 24) versus mean 31.8 ±â€Š44.3 units, median = 16 (interquartile range: 7, 40) in the liberal group (P < 0.0001, Wilcoxon rank sum). BSI incidence, organ dysfunction, ventilator days, and time to wound healing (P > 0.05) were similar. In addition, there was no 30-day mortality difference: 9.5% restrictive versus 8.5% liberal (P = 0.892, χ test). CONCLUSIONS: A restrictive transfusion strategy halved blood product utilization. Although the restrictive strategy did not decrease BSI, mortality, or organ dysfunction in major burn injury, these outcomes were no worse than the liberal strategy (Clinicaltrials.gov identifier NCT01079247).

Sedation and Analgesia for Dressing Change: A Survey of American Burn Association Burn Centers.

Pain and sedation management for patients undergoing burn dressing change can be challenging. Variations appear to exist in the selection of medications before and during burn dressing change. To determine if institutional variations exist in pain and sedation management for burn dressing change, an online survey was sent to ABA Burn Center nurses and physicians. Three hundred seventy-eight anonymous responses were received from nurses (72%), nurse practitioners (10%), and physicians (18%). Burn centers had adult (22%), pediatric (12%), or pediatric and adult (66%) patients. Eighty percentage of centers had >200 patients/year. Sixty-eight percentage always used a premedication. Oxycodone and morphine or fentanyl was the most frequently used per oral (PO) and intravenous (IV) opioid premedication, respectively. The most common IV premedication anxiolytic were benzodiazepines. Sixty-eight percentage always used a long-acting opioid. Anesthetic regimen was decided case-by-case (47%) or specific protocol (24%). Protocol was followed always (18%) or mostly (55%). Patients' procedural pain could be better controlled 20% of the time. Pain regimen was altered most of the time (25%). Providers differed rarely (39%) and sometimes (44%) regarding preferred regimen. Ketamine was the most common deep sedative. A dedicated anesthesiologist was rarely (33%) consulted, determined case-by-case (33%) or prior failure/excess pain (19%). Acute pain service was never (51%) or rarely (35%) consulted. Pain and sedation management for burn dressing change is difficult and variations in approach exist among burn centers. Such management needs individualized care. Providers must be responsive to pain alterations. Consultation with anesthesia providers may be needed in specific cases. Further studies need to be completed to demonstrate the most effective means of controlling burn pain and evaluating patient outcomes.

Potential mechanisms underlying ectodermal differentiation of Wharton's jelly mesenchymal stem cells.

Wharton's jelly mesenchymal stem cells (WJMSCs) are being increasingly recognized for their ectodermal differentiation potential. Previously, we demonstrated that when WJMSC were seeded onto an acellular matrix material derived from Wharton's jelly and cultured in osteogenic induction media, generated CK19 positive cells and hair-like structures indicative of ectodermal differentiation of WJMSCs. In this manuscript, we examine the underlying mechanism behind this observation using a variety of microscopy and molecular biology techniques such as western blotting and qPCR. We demonstrate that these hair-like structures are associated with live cells that are positive for epithelial and mesenchymal markers such as cytokeratin-19 and α-smooth muscle actin, respectively. We also show that up-regulation of ß-catenin and noggin, along with the expression of TGF-ß and SMAD and inhibition of BMP4 could be the mechanism behind this ectodermal differentiation and hair-like structure formation.

The rapidly increasing trend of cannabis use in burn injury.

The use of cannabis is currently increasing according to U.S. Department of Health and Human Services (HHS). Surprisingly, cannabis use among burn patients is poorly reported in literature. In this study, rates of cannabis use in burn patients are compared with general population. Data from the National Burn Repository (NBR) were used to investigate incidence, demographics, and outcomes in relation to use of cannabis as evidenced by urine drug screen (UDS). Thousands of patients from the NBR from 2002 to 2011 were included in this retrospective study. Inclusion criteria were patients older than 12 years of age who received a drug screen. Data points analyzed were patients' age, sex, UDS status, mechanism of burn injury, total body surface area, length of stay, ICU days, and insurance characteristics. Incidence of cannabis use in burn patients from the NBR was compared against national general population rates (gathered by Health and Human Services) using chi-square tests. Additionally, the burn patient population was analyzed using bivariate analysis and t-tests to find differences in the characteristics of these patients as well as differences in outcomes. Seventeen thousand eighty out of over 112,000 patients from NBR had information available for UDS. The incidence of cannabis use is increasing among the general population, but the rate is increasing more quickly among patients in the burn patient population (P = .0022). In 2002, 6.0% of patients in burn units had cannabis+ UDS, which was comparable with national incidence of 6.2%. By 2011, 27.0% of burn patients tested cannabis+ while national incidence of cannabis use was 7.0%. Patients who test cannabis+ are generally men (80.1%, P < .0001) and are younger on average (35 years old vs 42, P < .0001). The most common mechanisms of injury among patients who test cannabis+ or cannabis- are similar. Flame injury makes up >60% of injuries, followed by scalds that are >15%. In comparing cannabis+/- patients, cannabis+ patients are more likely to be uninsured (25.2% vs 17.26%, P < .0001). Finally, patients who test cannabis+ have larger burns (TBSA% of 12.94 vs 10.98, P < .0001), have a longer length of stay (13.31 days vs 12.6, P = .16), spend more days in the ICU (7.84 vs 6.39, P = .0006), and have more operations (2.78 vs 2.05, P < .0001). The rate patients testing positive for cannabis in burn units is growing quickly. These patients are younger and are less likely to be insured. These patients also have larger burns, spend more time in ICUs, and have a greater number of operations. The increasing use of cannabis, as expected from legalization of cannabis in multiple states, among burn patient population may lead to increased burden on already tenuous health care resources.

Necrotizing metachronous facial ulcerations after "stem cell face lift".

INTRODUCTION: A 63-year-old woman underwent face and neck lift with autologous fat transfer-called by her physician a "stem cell face lift." METHODS: Fatty aspirate from her abdominal wall was enriched by hyaluronic acid, triiodothyronine, thyroxine, insulin, dimethylaminoethanol, estriol, dexamethasone, indomethacin, and fibroblast growth factor before injection into the face. RESULTS: At approximately 4-weeks postoperative, the patient developed facial swellings, erythema, necrotizing ulcers, and an orocutaneous fistula. New lesions continued occurring up to 16 weeks after surgery. After multiple surgical debridements and an oral course of rifampin, a decisive reduction in inflammation and healing was observed. Differential diagnosis included (1) mistaken transfer of allogeneic fat (ruled out), (2) toxic impurities in transferred material, (3) microbial contaminant(s) from multiple use liposuction cannula or tissue markers, and (4) endogenous anaerobic orofacial infection (history of previous radiation for tonsillar cancer and dental implants). CONCLUSIONS: The most probable etiology was mycobacterial infection. This is based on a single colony of mycobacterium isolated, histologic finding revealing granulomatous inflammation, and the favorable response to rifampin. The patient underwent subsequent autologous fat transfers, which successfully reduced some disfigurement and scarring.