Pre-operative anemia and peri-operative transfusion are associated with poor oncologic outcomes in cancers of the esophagus: potential impact of patient blood management on cancer outcomes.

BACKGROUND: Both Red Blood Cell (RBC) transfusion and anemia are thought to negatively impact cancer survival. These effects have been reported with mixed findings in cancer of the esophagus. The potential impact of the application of restrictive transfusion strategies on this patient population has not been defined. MATERIALS AND METHODS: We conducted a retrospective study of esophagectomies and studied cases based on whether they were anemic or were transfused peri-operatively. Clinical characteristics and known clinicopathologic prognosticators were compared between these groups. Survival was compared by Cox proportional hazard modeling. Post-operative transfusions were assessed for compliance with restrictive transfusion thresholds. RESULTS: Three-hundred ninety-nine esophagectomy cases were reviewed and after exclusions 348 cases were analyzed. The median length of follow-up was 33 months (range 1-152 months). Sixty-four percent of patients were anemic pre-operatively and 22% were transfused. Transfusion and anemia were closely related to each other. Microcytic anemia was uncommon but was evaluated and treated in only 50% of cases. Most anemic patients had normocytic RBC parameters. Transfusion but not anemia was associated with a protracted/prolonged post-operative stay. Transfusion and anemia were both associated with reduced survival however only anemia was associated with decreased survival in multi-variable modeling. Sixty-eight percent of patients were transfused post-operatively and 11% were compliant with the restrictive threshold of 7 g/dL. CONCLUSIONS: Pre-operative anemia and transfusion are closely associated, however only anemia was found to compromise survival in our esophageal cancer cohort, supporting the need for more aggressive evaluation and treatment of anemia. Adherence to restrictive transfusion guidelines offers an opportunity to reduce transfusion rates which may also improve short-term outcomes.

Aortic arch replacement and autologous pericardial tracheal patch for an aorto-tracheal fistula.

Aorto-tracheal fistulas are rare and highly lethal, with few reports of successful surgical intervention. We present a 48-year-old man with an aorto-tracheal fistula induced by radiation therapy for tracheal squamous cell carcinoma. He presented with hemoptysis and chest pain and workup revealed the aorta-tracheal fistula between the posterior aortic arch and anterior distal trachea. He was emergently taken to surgery. To our knowledge, this is the first report of an aorto-tracheal fistula successfully treated with a transverse aortic arch replacement and complex tracheal repair using autologous pericardium with an omental buttress.

Accuracy of a drilling with a custom 3D printed guide or free-hand technique in canine experimental sacroiliac luxations.

OBJECTIVE: To improve the accuracy of drilling during the repair of sacroiliac luxations (SILs) with a 3D-printed patient-specific drill guide (3D-GDT) compared to free-hand drilling technique (FHDT). STUDY DESIGN: Blinded, randomized, prospective ex vivo study. SAMPLE POPULATION: Sixteen canine cadavers (20-25 kg). METHODS: Dorsal, bilateral SILs were created. Pelvic CT was performed pre- and post-drilling. The FHDT was drilled followed by 3D-GDT. CT and 3D measurements of craniocaudal and dorsoventral angles were compared between FHDT and 3D-GDT, as well as deviations of entry and exit points relative to optimal trajectory. RESULTS: Mean craniocaudal and dorsoventral angles for both CT- and 3D-measured 3D-GDT (CT 4.2 ± 3.9° and 3.9 ± 3.2°, respectively; 3D 5.1 ± 5.1° and 2.8 ± 2.3°, respectively p = .0006) were lower compared to FHDT (CT 11.8 ± 4.0°, p < .0001 and 8.9 ± 6.1°, p = .01; 3D 12.4 ± 5.9°, p = .0006 and 5.3 ± 5.24°, p = .05). Entry dorsoventral and end craniocaudal, dorsoventral, and 3D linear deviations were reduced with 3D-GDT. Sacral corridor disruption was present in 20% (3/15) for FHDT compared with 0% for 3D-GDT. CT and 3D analyses were in strong agreement (r = 0.77). CONCLUSION: Deviations of drill trajectories were minimized relative to optimal trajectories with 3D-GDT compared to FHDT in the dorsoventral and craniocaudal planes. CLINICAL SIGNIFICANCE: The use of 3D-GDT improves accuracy of sacral drilling compared with FHDT in canine cadavers. These results justify further evaluation in a clinical, prospective study.

Extracorporeal Cardiopulmonary Resuscitation: A Narrative Review and Establishment of a Sustainable Program.

The rates of survival with functional recovery for out of hospital cardiac arrest remain unacceptably low. Extracorporeal cardiopulmonary resuscitation (ECPR) quickly resolves the low-flow state of conventional cardiopulmonary resuscitation (CCPR) providing valuable perfusion to end organs. Observational studies have shown an association with the use of ECPR and improved survivability. Two recent randomized controlled studies have demonstrated improved survival with functional neurologic recovery when compared to CCPR. Substantial resources and coordination amongst different specialties and departments are crucial for the successful implementation of ECPR. Standardized protocols, simulation based training, and constant communication are invaluable to the sustainability of a program. Currently there is no standardized protocol for the post-cannulation management of these ECPR patients and, ideally, upcoming studies should aim to evaluate these protocols.

Polysubstance use among frequent marijuana users: an examination of John Henryism Active Coping, psychiatric symptoms, and family social support among African American incarcerated men.

Incarcerated African American men who use marijuana are vulnerable to polysubstance use, which is associated with greater risk for negative health and psychosocial outcomes than marijuana use alone. It is imperative to understand risk and protective factors for polysubstance use among this vulnerable population to inform the development of culturally tailored substance use interventions. The current study examined the association between John Henryism Active Coping (JHAC), family social support, psychiatric symptoms, and polysubstance use among African American incarcerated men who frequently use marijuana. Results indicated that higher John Henryism Active Coping (JHAC) is associated with decreased likelihood of engaging in polysubstance use, while psychiatric symptoms are associated with increased likelihood of polysubstance use. Incorporating elements of JHAC into concurrent mental health and substance use treatment may reduce risk for overdose and reincarceration among African American incarcerated men upon release into the community.

Helpful sternal wound vacuum-assisted closure techniques in two open chest situations: Central extracorporeal membrane oxygenation and sternal infection.

BACKGROUND: Dressing open sternal wounds after cardiac surgery can be challenging. In cases where extracorporeal membrane oxygenation (ECMO) is required, the sternum is left open with cannulae traversing the wound, making it difficult to create a water-tight seal and maintain sterility. Patients with a deep sternal infection may also be left with an open sternum between the time of debridement and reconstruction; in such cases, stabilizing the dressing in an ambulatory patient can pose a challenge. METHODS: Two cases are reviewed, each highlighting the solutions to the problems mentioned above. RESULTS: In case 1, a patient with an open sternum and central ECMO, we describe construction of a dressing that achieves air seal and blood seal, and helps maintain the cannulae in a safe, stable position. In case 2, an ambulatory patient, we describe a modification of a recently published "Two Bridge Technique" that provides a stable dressing in three dimensions. CONCLUSION: Performance of specific techniques and attention to detail in complex situations can make a big difference in open sternum patients treated with temporary, vacuum-assisted dressings. Achieving vacuum and fluid seal is important for sterility, integrity of adjacent skin, and caregiver safety.

Perineal evisceration secondary to a bite injury in a dog with an untreated perineal hernia.

Emergency surgery was performed on a 6-year-old castrated male springer spaniel dog with evisceration of most of the small intestinal tract through the perineal region, secondary to a dog attack. This is the first report describing successful treatment of perineal evisceration secondary to dog attack at an untreated perineal hernia, employing abdominal and perineal approaches.

Éviscération périnéale secondaire à une blessure de morsure chez un chien ayant une hernie périnéale non traitée. Une chirurgie d'urgence a été réalisée chez un chien épagneul Springer mâle stérilisé âgé de 6 ans présentant l'éviscération de la majeure partie du tractus du petit intestin dans la région périnéale secondaire à une attaque par un chien. Il s'agit du premier rapport décrivant le traitement réussi d'une éviscération périnéale secondaire à une attaque de chien sur une hernie périnéale non traitée à l'aide des approches abdominale et périnéale.(Traduit par Isabelle Vallières).

A study of the norcaradiene-cycloheptatriene equilibrium in a series of azulenones by NMR spectroscopy; the impact of substitution on the position of equilibrium.

A systematic investigation of the influence of substitution at positions C-2 and C-3 on the azulenone skeleton, based on NMR characterisation, is discussed with particular focus on the impact of the steric and electronic characteristics of substituents on the position of the norcaradiene-cycloheptatriene (NCD-CHT) equilibrium. Variable temperature (VT) NMR studies, undertaken to enable the resolution of signals for the equilibrating valence tautomers revealed, in addition, interesting shifts in the equilibrium.

Lung Transplantation from hepatitis C+ donor lungs: Reassuring midterm outcomes.

BACKGROUND: The development of modern antiviral therapy for hepatitis C virus (HCV) has allowed for the transplantation of HCV nucleic acid amplification testing-positive (NAT+) donor lungs with acceptable short-term outcomes. We sought to evaluate trends and midterm outcomes of lung transplant recipients of HCV NAT+ donor allografts. METHODS: All adults undergoing isolated lung transplantation in the United Network for Organ Sharing database from January 2016 to December 2022 were included in the study. Lung transplant recipients were stratified based on donor HCV status (HCV NAT+ vs NAT-). Propensity score matching was used to adjust for differences between groups. Several outcomes, including acute rejection by 1 year, early (30-day and in-hospital) mortality, and both 1- and 3-year survival, were compared between matched groups. RESULTS: A total of 16,725 patients underwent lung transplantation during the study period, with 489 (3%) receiving HCV NAT+ donor lungs. Regions 1 (18%) and 6/8 (both 0%) had the highest and lowest proportions, respectively, of HCV NAT+ donor transplants. Utilization of HCV NAT+ donors increased throughout the study period from 2 (0.1%) in 2016 to a peak of 117 (5%) in 2019. Donors who were HCV NAT+ were younger (34 vs 36 years, p < 0.001), more often female (44% vs 39%, p < 0.01), and more commonly died due to drug intoxication (56% vs 15%, p < 0.001). Recipients of HCV NAT+ donor lungs were similar in age (62 vs 62 years, p = 0.69) and female gender (43% vs 39%, p = 0.15) but had lower lung allocation scores (38 vs 41, p < 0.001) compared to others. Rates of acute rejection (13% vs 17%, p = 0.09), early mortality (30-day: 2% vs 1%, p = 0.59, in-hospital: 3% vs 4%, p = 0.38), as well as 1-year (90% vs 92%, p = 0.29) and 3-year survival (69% vs 75%, p = 0.13) were not significantly different between matched groups. CONCLUSIONS: Lung transplant recipients of HCV NAT+ donor allografts experience similar rates of acute rejection, early mortality, and 3-year survival compared to all other lung recipients. Increased use of HCV NAT+ donor allografts may help to expand the donor pool and alleviate donor shortages.

Microwave dielectric properties of normal, fibroelastotic, and malignant human lung tissue.

Technological development of microwave treatment and detection techniques for lung cancer requires accurate and comprehensive knowledge of the microwave dielectric properties of human lung tissue. We characterize the dielectric properties of room temperature human lung tissue from 0.5 to 10 GHz for three lung tissue groups: normal, fibroelastotic, and malignant. We fit a two-pole Debye model to the measured frequency-dependent complex permittivity and calculate the median Debye parameters for the three groups. We find that malignant lung tissue is approximately 10% higher in relative permittivity and conductivity compared to normal lung tissue; this trend matches previously reported normal versus malignant data for other biological tissues. There is little contrast between benign lung tissue with fibroelastosis and malignant lung tissue. We extrapolate our data from room temperature to 37 °C using a temperature-dependence model for animal lung tissue and use the Maxwell-Garnett dielectric mixing model to predict the dielectric properties of inflation-dynamic human lung tissue; both approximations correspond with previously reported dielectric data of bovine and porcine lung tissue.

Operationalizing ambiguity in sustainability science: embracing the elephant in the room.

Ambiguity is often recognized as an intrinsic aspect of addressing complex sustainability challenges. Nevertheless, in the practice of transdisciplinary sustainability research, ambiguity is often an 'elephant in the room' to be either side-stepped or reduced rather than explicitly mobilized in pursuit of solutions. These responses threaten the salience and legitimacy of sustainability science by masking the pluralism of real-world sustainability challenges and how research renders certain frames visible and invisible. Critical systems thinking (CST) emerged from the efforts of operational researchers to address theoretical and practical aspects of ambiguity. By adapting key concepts, frameworks, and lessons from CST literature and case studies, this paper aims to establish (1) an expansive conceptualization of ambiguity and (2) recommendations for operationalizing ambiguity as a valuable means of addressing sustainability challenges. We conceptualize ambiguity as an emergent feature of the simultaneous and interacting boundary processes associated with being, knowing, and intervening in complex systems, and propose Reflexive Boundary Critique (RBC) as a novel framework to help navigate these boundary processes. Our characterization of ambiguity acknowledges the boundary of a researcher's subjective orientation and its influence on how ambiguity is exposed and mediated in research (being), characterizes knowledge as produced through the process of making boundary judgments, generating a partial, contextual, and provisional frame (knowing), and situates a researcher as part of the complexity they seek to understand, rendering any boundary process as a form of intervention that reinforces or marginalizes certain frames and, in turn, influences action (intervening). Our recommendations for sustainability scientists to operationalize ambiguity include (1) nurturing the reflexive capacities of transdisciplinary researchers to navigate persistent ambiguity (e.g., using our proposed framework of RBC), and (2) grappling with the potential for and consequences of theoretical incommensurability and discordant pluralism. Our findings can help sustainability scientists give shape to and embrace ambiguity as a fundamental part of rigorous sustainability science.

Use of a colorimeter is a viable method to measure melanin and erythema content in the context of laser beam attenuation by use of a class IV laser in different tissues in dogs.

OBJECTIVE: Patient factors may alter laser photon attenuation, but these factors have not been adequately evaluated in live dogs. Our objective was to evaluate class IV laser beam attenuation (LBA) by canine tissues using a colorimeter to evaluate melanin and erythema indices. We hypothesized that greater melanin and erythema indices and unclipped hair would increase LBA, and these properties would vary among tissues. ANIMALS: 20 client-owned dogs. PROCEDURES: Between October 1 and December 1, 2017, colorimeter measurements and LBA in various tissues before and after clipping overlying hair were evaluated. Data were analyzed using generalized linear mixed models. Statistical significance was set at P < .05. RESULTS: LBA was greater in unclipped (98.6 ± 0.4%) than clipped hair (94.6 ± 0.4%). The least LBA occurred in the pinna (93%) while the greatest occurred in the caudal vertebra (100%) and caudal semitendinosis muscles (100%). Each mm of tissue thickness resulted in LBA of 11.6%. Each unit increase in melanin index resulted in a 3.3% increase in LBA. There was no association of LBA with erythema index. CLINICAL RELEVANCE: To our knowledge, this is the first study that evaluated LBA by different tissues in live dogs using a colorimeter to evaluate melanin and erythema indices. We recommend clipping hair prior to photobiomodulation to decrease laser beam attenuation and using increased laser doses in thicker tissues and dogs with high melanin content. The colorimeter may be helpful in customizing patient treatment dosimetry. Future studies are necessary to determine therapeutic laser doses for adequate photobiomodulation effects.

Medically Smart, Fiscally Illiterate: Lack of Financial Education Leads to Poor Retirement Savings Strategies in Surgical Trainees.

INTRODUCTION: Resident physicians are uniquely at high financial risk given their long training programs, lack of financial education, and documented poor financial literacy. Budgeting for retirement savings is an important metric for financial literacy. METHODS: Semi-structured interviews were conducted with residents from two distinct surgery programs to assess their current financial status and their knowledge of and attitudes toward retirement savings strategies. Qualitative analysis was performed and the themes identified were examined in the context of previously reported quantitative survey data. RESULTS: As previously reported, 105 residents at Site 1 completed a comprehensive financial survey 56% of respondents reported having no retirement savings. On additional analysis, only 26% residents surveyed reported optimal savings habits defined as contributing $5000/year to a retirement account starting their first year of training. 23 residents from both sites and representing all post-graduate-year (PGY) levels then participated in the focused, semi-structured interviews. Site 2 residents were less likely to be female (P = .02) and carried a significantly larger debt burden (p < .01) but were otherwise comparable to residents from Site 1. On qualitative analysis three consistent themes emerged: (1) Resident understanding of strategies for retirement savings is poor; (2) Lack of knowledge is the primary barrier; (3) Surgical residents desire financial education. CONCLUSIONS: Surgery residents have a large debt burden, minimal retirement savings and an overall lack of understanding of savings strategies. Well-designed, early, and accessible educational interventions may improve the "financial vital signs" of surgical trainees and establish habits for long-term financial success.

A combined, supraclavicular, infraclavicular, transaxillary, and posterior subscapular approaches for en bloc resection of giant myxofibrosarcoma.

Background: Myxofibrosarcoma (MFS) is a rare and locally infiltrative tumor that commonly occurs in extremities in older adults; however, truncal and head and neck cases have been reported. They are characterized by multinodular growth, incomplete fibrous septa, and myxoid stroma. Surgical resection is the mainstay of treatment. Case Description: The authors report a case of a combined, supraclavicular, infraclavicular, transaxillary, and posterior subscapular approaches for resection of giant MFS. Conclusion: The anatomical complexity and rarity of tumors involving the brachial plexus impose many challenges onto surgeons performing surgical resections. Treatment choices and surgical outcomes rely heavily on meticulous multidisciplinary planning, anatomical knowledge, careful dissection, and extent of resection. This case is unique in utilizing four different approaches to the brachial plexus to resect one tumor.

Body mass Index does not impact long-term survival of patients with idiopathic pulmonary fibrosis undergoing lung transplantation.

Objective: We investigated the impact of body mass index (BMI) on post-operative outcomes and survival of patients with interstitial pulmonary fibrosis (IPF) undergoing lung transplantation. Methods: We retrospectively reviewed 222 patients with IPF that underwent lung transplant (LT) at our institution from 2005 to 2019. Recipients were divided in 4 groups: group-1 consisted of underweight patients (BMI ≤18.5 kg/m2), group-2 of normal weight patients (BMI 18.5-25 kg/m2), group-3 of over-weight patients (BMI 25-29.9 kg/m2) and group-4 of obese patients (BMI ≥30 kg/m2). Results: Group-1 consisted of 13 (6%) patients, group-2 of 67 (30%) patients, group-3 of 79 (36%) patients, group-4 consisted of 63 (28%) patients. Median BMI for group-1 was 17 [interquartile range (IQR): 17, 18], for group-2 was 23 (22, 24), for group-3 was 29 (28, 29.5) and group-4 was 32 (31, 33). Patients in group-1 were significantly younger (p < 0.01). Single LT comprised the majority of operation type in group-2 to group-4 and it was significantly higher than group 1 (p < 0.01). Median follow-up time was 39 months (13-76). A total of 79 (35.5%) patients died by the end of study. Overall, five deaths occurred in group-1, 17 in group-2, 33 in group-3, and 24 in group-4. Kaplan-Meier analysis showed that mortality was not statistically significant between the groups (p = 0.24). Cox-regression analysis was used to assess other possible risk factors that could influence the effect of BMI on mortality, including transplant type (single, double), lung allocation score, and age, diabetes and creatinine levels at surgery. None of these factors were shown to affect patient mortality (p > 0.05). Overall reasons for death included graft failure (24%), infection (23%), respiratory failure (14%), and malignancy (13%). Conclusions: Body mass index does not impact long-term survival of patients with IPF undergoing lung transplantation.

Consequences of anastomotic leaks after minimally invasive esophagectomy: A single-center experience.

Background: Anastomotic leak (AL) after minimally invasive esophagectomy (MIE) is a well-described source of morbidity for patients undergoing surgical treatment of esophageal neoplasm. With improved early recognition and endoscopic management techniques, the long-term impact remains unclear. Methods: A retrospective review was conducted of patients who underwent MIE for esophageal neoplasm between January 2015 and June 2021 at a single institution. Cohorts were stratified by development of AL and subsequent management. Baseline demographics, perioperative data, and post-operative outcomes were examined. Results: During this period, 172 MIEs were performed, with 35 of 172 (20.3%) complicated by an AL. Perioperative factors independently associated with AL were post-operative blood transfusion (leak rate 52.9% versus 16.8%; p = 0.0017), incompleteness of anastomotic rings (75.0% vs 19.1%; p = 0.027), and receiving neoadjuvant therapy (18.5% vs 30.8%; p < 0.0001). Inferior short-term outcomes associated with AL included number of esophageal dilations in the first post-operative year (1.40 vs 0.46, p = 0.0397), discharge disposition to a location other than home (22.9% vs 8.8%, p = 0.012), length of hospital stay (17.7 days vs 9.6 days; p = 0.002), and time until jejunostomy tube removal (134 days vs 79 days; p = 0.0023). There was no significant difference in overall survival between patients with or without an AL at 1 year (79% vs 83%) or 5 years (50% vs 47%) (overall log rank p = 0.758). Conclusions: In this large single-center series of MIEs, AL was associated with inferior short-term outcomes including hospital length of stay, discharge disposition other than to home, and need for additional endoscopic procedures, without an accompanying impact on 1-year or 5-year survival. Key message: In this large, single-center series of minimally invasive esophagectomies, anastomotic leak was associated with worse short-term outcomes including hospital length of stay, discharge disposition other than to home, and need for additional endoscopic procedures, but was not associated with worse long-term survival. The significant association between neoadjuvant therapy and decreased leak rates is difficult to interpret, given the potential for confounding factors, thus careful attention to modifiable pre- and peri-operative patient factors associated with anastomotic leak is warranted.

One hundred cases of primary spontaneous pneumomediastinum: leukocytosis is common, pleural effusions and age over 40 are rare.

Background: Primary spontaneous pneumomediastinum (PSPM) is a benign condition, but it can be difficult to discriminate from Boerhaave syndrome. The diagnostic difficulty is attributable to a shared constellation of history, signs, and symptoms combined with a poor understanding of the basic vital signs, labs, and diagnostic findings characterizing PSPM. These challenges likely contribute to high resource utilization for diagnosis and management of a benign process. Methods: Patients aged 18 years or older with PSPM were identified from our radiology department's database. A retrospective chart review was performed. Results: Exactly 100 patients with PSPM were identified between March 2001 and November 2019. Demographics and histories correlated well with prior studies: mean age (25 years); male predominance (70%); association with cough (34%), asthma (27%), retching or emesis (24%), tobacco abuse (11%), and physical activity (11%); acute chest pain (75%), and dyspnea (57%) as the first and second most frequent symptoms and subcutaneous emphysema (33%) as the most common sign. We provide the first robust data on presenting vital signs and laboratory values of PSPM, showing that tachycardia (31%) and leukocytosis (30%) were common. No pleural effusion was found in the 66 patients who underwent computed tomography (CT) of the chest. We provide the first data on inter-hospital transfer rates (27%). 79% of transfers were due to concern for esophageal perforation. Most patients were admitted (57%), with an average length of stay (LOS) of 2.3 days, and 25% received antibiotics. Conclusions: PSPM patients frequently present in their twenties with chest pain, subcutaneous emphysema, tachycardia, and leukocytosis. Approximately 25% have a history of retching or emesis and it is this population that must be discriminated from those with Boerhaave syndrome. An esophagram is rarely indicated and observation alone is appropriate in patients under age 40 with a known precipitating event or risk factors for PSPM (e.g., asthma, smoking) if they have no history of retching or emesis. Fever, pleural effusion, and age over 40 are rare in PSPM and should raise concern for esophageal perforation in a patient with a history of retching, emesis, or both.

Successful Lung Transplantation for Severe Post-COVID-19 Pulmonary Fibrosis.

Lung transplantation has been well described for patients with coronavirus disease 2019 (COVID-19) in the acute setting, but less so for the resulting pulmonary sequelae. This report describes a case of lung transplantation for post-COVID-19 pulmonary fibrosis. A 52-year-old woman contracted COVID-19 in July 2020 and mounted a partial recovery, but she went on to have declining function over the ensuing 3 months, with development of fibrocystic lung changes. She underwent bilateral lung transplantation and recovered rapidly, was discharged home on postoperative day 14, and has done well in follow-up. This case report demonstrates that lung transplantation is an acceptable therapy for post-COVID-19 pulmonary fibrosis.

Long-term safety and efficacy of gene-corrected autologous keratinocyte grafts for recessive dystrophic epidermolysis bullosa.

BACKGROUND: Recessive dystrophic epidermolysis bullosa (RDEB) is a rare, devastating blistering genodermatosis caused by mutations in the COL7A1 gene, which encodes for type VII collagen and is necessary for dermal-epidermal adhesion and integrity. Disease manifestations include severe and debilitating wounds, aggressive squamous cell carcinomas, and premature death; however, there are currently no approved therapies. This Phase 1/2a, open-label study evaluated the long-term efficacy and safety of gene-corrected autologous keratinocyte grafts (EB-101) for chronic RDEB wounds. METHODS: Autologous keratinocytes were harvested from participants with severe RDEB, transduced with a retrovirus containing the full-length COL7A1 gene, and grown into 5 × 7 cm (35 cm2) sheets. Gene-corrected keratinocyte sheets were then transplanted onto chronic RDEB wounds present for ≥ 12 weeks. RESULTS: Seven adult participants with severe RDEB were grafted with six sheets each (42 total sheets) onto wounds and followed for a mean of 5.9 years (range 4-8 years). Long-term improvements in wound healing and symptoms were observed. At year five, 70% (21/30) of treated sites demonstrated ≥ 50% wound healing compared to baseline by investigator global assessment. No sites with ≥ 50% wound healing were painful or pruritic, compared to 67% (6/9) of sites with < 50% wound healing (p < 0.001) at year five. Grafts were well-tolerated throughout long-term follow-up. No serious adverse events related to treatment were reported over a mean of 5.9 years of follow-up. No persistent systemic autoimmunity against type VII collagen or replication-competent retrovirus infections were identified, and no participants developed squamous cell carcinomas related to treatment during long-term follow-up. CONCLUSIONS: Treatment with EB-101 appears safe and efficacious, and produces long-term improvements in wound healing, pain, and itch for RDEB patients. Results from the Phase 3 randomized controlled trial are forthcoming. TRIAL REGISTRATION: ClinicalTrials.gov, NCT01263379. Registered December 15, 2010. https://clinicaltrials.gov/ct2/show/NCT01263379.