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Aim: The goal of this study was to compare success rates of a regenerative limb salvage approach (rLS) using dehydrated human chorion amnion membrane (dHACM) to traditional flap-based limb salvage (fLS). Materials & methods: This prospective RTC enrolled patients presenting with complex extremity wounds over a 3-year period. Primary outcomes included success of primary reconstruction, persistence of exposed structures, time to definitive closure, and time to weight bearing. Results: Patients meeting inclusion criteria were randomized to fLS (n = 14) or rLS (n = 25). The primary reconstructive method was successful for 85.7% of fLS subjects and 80% of rLS subjects (p = 1.00). Conclusion: This trial provides strong evidence that rLS is an effective option in the setting of complex extremity wounds, with success rates comparable to traditional flaps. Clinical Trial Registration: NCT03521258 (ClinicalTrials.gov) Chronic and traumatic wounds may result in loss of limb without appropriate medical treatment. Traditionally large wounds with exposed bone or other important structures require surgery to transfer healthy soft tissue (a tissue flap) from one area of the body to the defect created by the wound. Our study seeks to demonstrate an approach to similar wounds using a biologic dressing to avoid extensive surgery. We demonstrate that this biologic dressing made from human membranes has a similar success rate to flap surgery for achieving wound healing. Comparison of flap-based reconstruction to regenerative limb salvage yields similar success rates for complex extremity wounds. [ABSTRACT FROM AUTHOR]

Background and Aims: Minimally adherent silver dressings (SILVER MASD) are antimicrobial, nonirritating, provide a moist wound healing environment, and low cost. The purpose of this pilot, single‐center, non‐blinded randomized controlled trial was to quantify the outcomes of acute surgical wounds treated with MASD versus standard of care (SoC) dressings. Methods: Thirty‐two patients with acute wounds were randomized 1:1 to be treated with MASD once weekly or SoC following surgical excision of skin and/or subcutaneous tissue between September 13, 2016 and November 28, 2017. The outcome variables included clinical infection, time to wound closure, and pain scores at dressing changes. Two independent, one‐sided sample t‐tests were performed to assess statistical significance. Results: There was no difference in wound healing between SILVER MASD and SoC. Dressing changes were less painful for wounds managed with MASD silver dressings. Conclusions: The results of this study suggest that MASD are not less effective in wound healing compared to SoC while also providing the benefit of decreased pain at dressing changes. Therefore, minimally adherent silver dressings can and should be considered a viable option in the management of acute surgical wounds. [ABSTRACT FROM AUTHOR]

COVID‐19 morbidity and mortality are driven by poor immune regulation. Narrowband ultraviolet B (NB‐UVB) phototherapy is standard of care in a number of immune‐dysregulated diseases. To assess the efficacy of NB‐UVB phototherapy for improving COVID‐19 outcomes in high‐risk, hospitalized, we developed the Adaptive Photo‐Protection Trial. This is a multi‐center, prospective, double‐blinded, randomized, placebo‐controlled trial. The pilot phase results are reported here. Consecutive patients admitted with a positive COVID‐19 PCR were screened for eligibility. Enrolled subjects were computer randomized 1:1 to NB‐UVB or placebo phototherapy. Subjects were treated daily with escalating doses on 27% of their body surface area for up to 8 consecutive days. Primary outcomes were safety and efficacy, defined as persistent or painful erythema and 28‐day mortality. Comparisons were made via non‐parametric exact tests. Patients in treatment (n = 15) and placebo (n = 15) arms had similar demographics. No adverse events occurred. Twenty eight‐day mortality was 13.3% in treatment vs. 33.3% in placebo arms (p = 0.39). NB‐UVB phototherapy in hospitalized COVID‐19 patients was safe. Decreased mortality was observed in treated patients but this was statistically non‐significant. Given its low‐cost, scalability, and adjunctive nature, NB‐UVB has the potential to improve COVID‐19 outcomes. Continuation of this trial is warranted. [ABSTRACT FROM AUTHOR]

Obesity rates are climbing, representing a confounding and contributing factor to many disease states, including cancer. With respect to breast cancer, obesity plays a prominent role in the etiology of this disease, with certain subtypes such as triple-negative breast cancer having a strong correlation between obesity and poor outcomes. Therefore, it is critical to examine the obesity-related alterations to the normal stroma and the tumor microenvironment (TME). Adipocytes and adipose stem cells (ASCs) are major components of breast tissue stroma that have essential functions in both physiological and pathological states, including energy storage and metabolic homeostasis, physical support of breast epithelial cells, and directing inflammatory and wound healing responses through secreted factors. However, these processes can become dysregulated in both metabolic disorders, such as obesity and also in the context of breast cancer. Given the well-established obesity-neoplasia axis, it is critical to understand how interactions between different cell types in the tumor microenvironment, including adipocytes and ASCs, govern carcinogenesis, tumorigenesis, and ultimately metastasis. ASCs and adipocytes have multifactorial roles in cancer progression; however, due to the plastic nature of these cells, they also have a role in regenerative medicine, making them promising tools for tissue engineering. At the physiological level, the interactions between obesity and breast cancer have been examined; here, we will delineate the mechanisms that regulate ASCs and adipocytes in these different contexts through interactions between cancer cells, immune cells, and other cell types present in the tumor microenvironment. We will define the current state of understanding of how adipocytes and ASCs contribute to tumor progression through their role in the tumor microenvironment and how this is altered in the context of obesity. We will also introduce recent developments in utilizing adipocytes and ASCs in novel approaches to breast reconstruction and regenerative medicine. [ABSTRACT FROM AUTHOR]

Pressure ulcers (PUs) affect 2.5 million patients per year. Even after successful reconstruction, 50% of PUs recur. Patients with multiply recurrent PUs eventually consume all locoregional donor sites. This underscores the need for novel, less invasive approaches in PU reconstruction. Here, we report the first successful use of mesenchymal stem cell exosomes in PU reconstruction. The patient presented with a right ischial ulcer that persisted despite 9 months of wound care and appropriate antibiotic therapy. After six subcutaneous ExoFlo exosome injections over 8 weeks, the PU was completely healed. Additional studies of this promising technology should be performed. [ABSTRACT FROM AUTHOR]

Background  Harvest of the radial forearm flap (RFF) for reconstructive surgery is proceeded by the Allen test to assess for adequate contralateral perfusion of the hand, yet the Allen test may fail to detect anatomical variations in the radial artery such as aberrant branching. Therefore, the goal of this study was to systematically review the literature regarding anatomical abnormalities of the radial artery that can affect flap harvest and to perform a meta-analysis to estimate the prevalence of such abnormalities. Methods  A systematic review of the literature was conducted using five online databases to identify all instances of radial artery anatomical variations. Abstracts were reviewed and categorized into either (1) large cohort studies of anatomical variations identified by angiogram or (2) case reports specifically mentioning anomalous or accessory branches of the radial artery. Data from the large cohort studies were included in a random effect meta-analysis to estimate the prevalence of such variations. Results  Eighteen angiogram cohort studies containing a total of 18,115 patients were included in the meta-analysis. Accessory branches were the least common anatomical variant reported, with an estimated average prevalence of 0.5%. Prevalence estimates for more common anatomical variants, including radial artery loops (0.9%), stenosis (1.3%), hypoplasia (1.9%), tortuosity (4.3%), and abnormal origin (5.6%), were also calculated. Thirteen case reports detailing anomalous branches of the radial artery were identified, seven of which involved accessory branches encountered during RFF harvest with no incidence of flap loss. Conclusion  Radial artery accessory branches are exceedingly rare, but the prevalence of other anatomical variations that can affect harvest of the RFF warrants consideration. We recommend surgeons consider comprehensive screening prior to RFF harvest to avoid intraoperative discovery of anatomical variants and suggest a low threshold for repeat perfusion testing intraoperatively if radial artery accessory branches are encountered. [ABSTRACT FROM AUTHOR]

Breast tissue expanders (TEs) with magnetic infusion ports are labeled "MR Unsafe." Therefore, patients with these implants are typically prevented from undergoing magnetic resonance imaging (MRI). We report a patient with a total submuscular breast TE who inadvertently underwent an MRI exam. She subsequently developed expander exposure, requiring explantation and autologous reconstruction. The safety profile of TEs with magnetic ports and the use of MRI in patients with these implants is surprisingly controversial. Therefore, we present our case report, a systematic literature review, and propose procedural guidelines to help ensure the safety of patients with TEs with magnetic ports that need to undergo MRI exams. [ABSTRACT FROM AUTHOR]

Objective: Naringenin, a citrus flavonoid, prevents diet-induced weight gain and improves glucose and lipid metabolism in rodents. There is evidence that naringenin activates brown fat and increases energy expenditure in mice, but little is known about its effects in humans. The goal of this study was to examine the effects of naringenin on energy expenditure in adipose tissue.Methods: Human white adipocyte cultures (hADSC) and abdominal subcutaneous adipose tissue (pWAT) were treated with naringenin for 7 to 14 days. Expression (quantitative real-time polymerase chain reaction, immunoblotting) of candidate genes involved in thermogenesis and glucose metabolism was measured. Oxygen consumption rate was measured in hADSC using a Seahorse flux analyzer.Results: In hADSC, naringenin increased expression of the genes associated with thermogenesis and fat oxidation, including uncoupling protein 1 and adipose triglyceride lipase, and key factors associated with insulin sensitivity, including glucose transporter type 4, adiponectin, and carbohydrate-responsive element-binding protein (P < 0.01). Similar responses were observed in pWAT. Basal, ATP-linked, maximal and reserve oxygen consumption rate increased in the naringenin-treated hADSC (P < 0.01).Conclusions: Naringenin increases energy expenditure in hADSC and stimulates expression of key enzymes involved in thermogenesis and insulin sensitivity in hADSC and pWAT. Naringenin may promote conversion of human white adipose tissue to a brown/beige phenotype. [ABSTRACT FROM AUTHOR]

Background Variations in anterolateral thigh (ALT) arterial anatomy are well documented. Ethnicity is a known risk factor for vascular variation in several organ systems, but its impact on ALT anatomy has not been studied. Anecdotally, we observed frequent ALT arterial variation in African American (AA) patients.We thus hypothesized that AA patients have higher rates of anomalous branching. Materials and Methods A total of 277 computed tomography angiograms (513 lower extremities) captured between May 1, 2013 and May 31, 2015 at a tertiary academic medical center were retrospectively analyzed to determine ALT arterial branching. Patient records were examined to ascertain demographics. Data were analyzed using descriptive statistics and multinomial logistic regression. Results Males comprised 84.5%. Ethnic distribution was 55.2% AA and 36.5% Caucasian. The descending branch of the lateral circumflex femoral artery (dLCFA) originated from non-LCFA arteries (deep femoral, common femoral, or superficial femoral arteries) in 18.9% of Caucasian versus 9.1% of AA (odds ratio [OR]: 2.28; 95% confidence interval [CI]: 1.33-3.93, p < 0.01). An oblique branch was identified in 41.1% of Caucasian versus 51.9% of AA (OR: 1.56; 95% CI: 1.08-2.24, p = 0.02). Ethnicity was the only driving factor of dLCFA and oblique branch of the LCFA (oLCFA) anatomy (Wald chi-square: 14 and 11, p = 0.03 and 0.02, respectively). Conclusions Ethnicity significantly affects ALT arterial anatomy. AA aremore likely to have classical dLCFA branching with a fourth oLCFA branch. A flap with an unrecognized oLCFA-dominant supply places patients at a higher risk for flap failure and loss. We recommend preoperative imaging before undertaking an ALT flap reconstruction. [ABSTRACT FROM AUTHOR]

Fascial healing following acute injury, such as that occurring during surgical procedures, is defined functionally. For example, failure of fascial healing following celiotomy is only identified when incisional hernias are diagnosed. Such hernias incur billions of dollars per year in medical costs. Despite the importance of fascial healing, there is a paucity of data regarding the quality such healing. In clinical settings, the quantification of fascial wound healing is limited to a binary state: either there is no clinically apparent functional deficit and full fascia healing is assumed, or an incisional hernia or other functional failure is visible and the fascia did not heal. There are no clinical methods to isolate and functionally test fascia in patients. Recent studies have revealed unexpected findings regarding the recovery of tensile strength, specific surgical methods that optimize fascial healing, and the potential impact of biological pharmaceuticals in eliminating fascial healing failure. However, much remains unknown about the biology of fascial healing. [ABSTRACT FROM AUTHOR]

Macrodactyly is a rare family of congenital disorders characterized by the diffuse enlargement of 1 or more digits. Multiple tissue types within the affected digits are involved, but skeletal patterning and gross morphological features are preserved. Not all tissues are equally involved and there is marked heterogeneity with respect to clinical phenotype. The molecular mechanisms responsible for these growth disturbances offer unique insight into normal limb growth and development, in general. To date, no genes or loci have been implicated in the development of macrodactyly. In this study, we performed the first transcriptional profiling of macrodactyly tissue. We found that pleiotrophin (PTN) was significantly overexpressed across all our macrodactyly samples. The mitogenic functions of PTN correlate closely with the clinical characteristics of macrodactyly. PTN thus represents a promising target for further investigation into the etiology of overgrowth phenotypes. [ABSTRACT FROM AUTHOR]

The utility of human pluripotent stem cells is dependent on efficient differentiation protocols that convert these cells into relevant adult cell types. Here we report the robust and efficient differentiation of human pluripotent stem cells into white or brown adipocytes. We found that inducible expression of PPARG2 alone or combined with CEBPB and/or PRDM16 in mesenchymal progenitor cells derived from pluripotent stem cells programmed their development towards a white or brown adipocyte cell fate with efficiencies of 85%-90%. These adipocytes retained their identity independent of transgene expression, could be maintained in culture for several weeks, expressed mature markers and had mature functional properties such as lipid catabolism and insulin-responsiveness. When transplanted into mice, the programmed cells gave rise to ectopic fat pads with the morphological and functional characteristics of white or brown adipose tissue. These results indicate that the cells could be used to faithfully model human disease. [ABSTRACT FROM AUTHOR]

Human pluripotent stem cells (hPSC) hold great promise as models for understanding disease and as a source of cells for transplantation therapies. However, the lack of simple, robust and efficient culture methods remains a significant obstacle for realizing the utility of hPSCs. Here we describe a platform for the culture of hPSCs that 1) allows for dissociation and replating of single cells, 2) significantly increases viability and replating efficiency, 3) improves freeze/thaw viability 4) improves cloning efficiency and 5) colony size variation. When combined with standard methodologies for genetic manipulation, we found that the enhanced culture platform allowed for lentiviral transduction rates of up to 95% and electroporation efficiencies of up to 25%, with a significant increase in the total number of antibiotic-selected colonies for screening for homologous recombination. We further demonstrated the utility of the enhanced culture platform by successfully targeting the ISL1 locus. We conclude that many of the difficulties associated with culturing and genetic manipulation of hPSCs can be addressed with optimized culture conditions, and we suggest that the use of the enhanced culture platform could greatly improve the ease of handling and general utility of hPSCs. [ABSTRACT FROM AUTHOR]

Cardiovascular disease (CVD) remains the leading cause of morbidity and mortality in the United States. Recent studies suggest that pericardial adipose tissue (PCAT) secretes inflammatory factors that contribute to the development of CVD. To better characterize the role of PCAT in the pathogenesis of disease, we performed a large-scale unbiased analysis of the transcriptional differences between PCAT and subcutaneous adipose tissue, analysing 53 microarrays across 19 individuals. As it was unknown whether PCAT-secreted factors are produced by adipocytes or cells in the supporting stromal fraction, we also sought to identify differentially expressed genes in isolated pericardial adipocytes vs. isolated subcutaneous adipocytes. Using microarray analysis, we found that: 1) pericardial adipose tissue and isolated pericardial adipocytes both overexpress atherosclerosis-promoting chemokines and 2) pericardial and subcutaneous fat depots, as well as isolated pericardial adipocytes and subcutaneous adipocytes, express specific patterns of homeobox genes. In contrast, a core set of lipid processing genes showed no significant overlap with differentially expressed transcripts. These depot-specific homeobox signatures and transcriptional profiles strongly suggest different functional roles for the pericardial and subcutaneous adipose depots. Further characterization of these inter-depot differences should be a research priority. [ABSTRACT FROM AUTHOR]

Bipolar disorder (BD) is a common neuropsychiatric disorder characterized by chronic recurrent episodes of depression and mania. Despite evidence for high heritability of BD, little is known about its underlying pathophysiology. To develop new tools for investigating the molecular and cellular basis of BD we applied a family-based paradigm to derive and characterize a set of 12 induced pluripotent stem cell (iPSC) lines from a quartet consisting of two BD-affected brothers and their two unaffected parents. Initially, no significant phenotypic differences were observed between iPSCs derived from the different family members. However, upon directed neural differentiation we observed that CXCR4 (CXC chemokine receptor-4) expressing central nervous system (CNS) neural progenitor cells (NPCs) from both BD patients compared to their unaffected parents exhibited multiple phenotypic differences at the level of neurogenesis and expression of genes critical for neuroplasticity, including WNT pathway components and ion channel subunits. Treatment of the CXCR4+ NPCs with a pharmacological inhibitor of glycogen synthase kinase 3 (GSK3), a known regulator of WNT signaling, was found to rescue a progenitor proliferation deficit in the BD-patient NPCs. Taken together, these studies provide new cellular tools for dissecting the pathophysiology of BD and evidence for dysregulation of key pathways involved in neurodevelopment and neuroplasticity. Future generation of additional iPSCs following a family-based paradigm for modeling complex neuropsychiatric disorders in conjunction with in-depth phenotyping holds promise for providing insights into the pathophysiological substrates of BD and is likely to inform the development of targeted therapeutics for its treatment and ideally prevention.

William Darrach popularized subperiosteal resection of the distal ulna for distal radioulnar joint dysfunction, a procedure also known as the Darrach procedure. He was also a major contributor to academic surgery and medical education, publishing at least 70 articles, most on the treatment of fractures. He was influential in organized medicine and served as Dean of the Columbia College of Physicians and Surgeons, Governor and Regent of the American College of Surgeons, President of the American Surgical Association, and President of the Association of the American Medical Colleges. His contributions to education, hand surgery, and fracture treatment methodology make him an important figure in medicine. [Copyright &y& Elsevier]

The article focuses on a case study of a young man suffering from primary erythromelalgia who experienced remission of pain and symptoms through epidural infusion of ropivacaine, with the relief persisting for two years. Topics include the rarity of erythromelalgia cases in the United States, the genetic and secondary causes of the disease, and the challenges in pain control and treatment methods, including self-cooling practices that can lead to severe complications.

Currently there are no standard of care treatment strategies for IH prevention (IHP). Dehydrated human amnion-chorion (dHACM) is a healing adjunct that elutes growth factors including several that have reduced IH in animal models. We therefore performed a double-blinded, prospective randomized controlled trial (RCT) to test the hypothesis that dHACM significantly reduces IH formation in a well-studied animal model of acute IH. Forty 16-week-old male Sprague-Dawley rats were randomized to one of four groups: No Treatment vs. dHACM Sheet (Group A), and Saline vs. dHACM Injection (Group B). Each animal underwent a 5-cm midline laparotomy which was incompletely closed with 5-0 plain gut sutures; this was performed by a surgeon blinded to treatment group (first blind). After 28 days, the primary endpoints of IH formation and hernia size were determined by study staff blinded to treatment (second blind). Secondary endpoints included healed fascia tensile strength as determined by tensiometry, systemic and local inflammatory markers as measured by ELISA, and fascial scar collagen I/III ratios per Western blotting. In Group A, No Treatment developed IH at 87.5% vs. 62.5% for Sheet (P = 0.28). Hernias that formed in the Sheet group were significantly smaller (P = 0.036). In Group B, Injection and Saline yielded identical IH rates of 77.8%. Molecular characterization of fascial scar demonstrated non-inferior tensile strength, collagen I/III ratios, and inflammatory markers in dHACM-treated animals. dHACM sheets significantly reduced the size of IH following laparotomy when compared to no treatment. [ABSTRACT FROM AUTHOR]

Introduction: Incisional hernias (IH) are iatrogenically created in 400 000 new patients annually. Without repair, IH-associated complications can result in major illness and death. The health disparities literature suggests that under-represented patients present more frequently with surgical emergencies. The health disparities associated with IH remain relatively unstudied.Methods: Inpatient admission data were obtained from the Healthcare Cost and Utilization Project National Inpatient Sample for 2012-2014. Patients with IH International Classification of Diseases ninth revision were included. Analyses were completed using survey specific procedures (SAS v.9.4). Type of admission within groups was compared via Rao-Scott chi-square tests. The probability of an elective admission was modeled via SurveyLogistic Procedure.Results: Of 39 296 cases, 38.5% IH admissions were urgent or emergent (nonelective). The proportion of nonelective admission was statistically higher (P < .0001) in patients >65 (40.9%) and females (40.3%). Among insurance types, self-paying patients had the highest proportion of nonelective admissions (64.3%). Racial disparities remained significant after adjusting for age, sex, and insurance. Compared with white patients, the odds of an admission being nonelective were significantly higher for black (odds ratio [OR] [95% CI]: 1.65 [1.53-1.77]], Hispanic (OR [95% CI]: 1.39 [1.28-1.51]), and other (OR [95% CI]: 1.2 [1.06-1.37]) patients.Discussion: These data show that multiple at-risk patient populations are significantly more likely to require urgent admission for IH-related complications. These include older, female, non-white, and uninsured patients. Systematic efforts to ameliorate these disparities should be developed. [ABSTRACT FROM AUTHOR]