RESUMO
BACKGROUND: A subset of women with breast implants have reported a myriad of nonspecific systemic symptoms collectively termed systemic symptoms associated with breast implants (SSBI). SSBI symptoms are similar to manifestations associated with autoimmune and connective tissue disorders Breast tissue is rich in adipose cells, comprised of lipids. Insertion of an implant creates an oxidative environment leading to lipid oxidation. Oxylipins can influence immune responses and inflammatory processes. OBJECTIVES: This study explores the abundance of a spectrum of oxylipins in the peri-prosthetic tissue surrounding the breast implant. Since oxylipins are immunogenic, we sought to determine if they are associated with the SSBI subjects. We have also attempted to determine if the common manifestations exhibited by such subjects have any association with oxylipin abundance. METHODS: The study included 120 subjects divided in three cohorts. Forty-six subjects with breast implants exhibiting manifestation associated with SSBI, 29 in control cohort I subjects with breast implants not exhibiting manifestation associated with SSBI (non-SSBI) and 45 in control cohort II subjects without implants (normal tissue) were analyzed. Lipid extraction and oxylipin quantification was performed using LCMS. LC-MS/MS targeted analysis from the breast adipose tissue was performed. RESULTS: Of the fifteen oxylipins analyzed, four exhibited increased abundance in the SSBI cohort compared to the non-SSBI and normal cohorts. CONCLUSIONS: The study documents the association of the oxylipins with each manifestation reported by the subject. This study provides an objective assessment on the subjective questionnaire highlighting which symptoms could be more relevant than the others.
RESUMO
OBJECTIVE: This work addressing complexities in wound infection, seeks to test the reliance of bacterial pathogen Pseudomonas aeruginosa (PA) on host skin lipids to form biofilm with pathological consequences. BACKGROUND: PA biofilm causes wound chronicity. Both CDC as well as NIH recognizes biofilm infection as a threat leading to wound chronicity. Chronic wounds on lower extremities often lead to surgical limb amputation. METHODS: An established preclinical porcine chronic wound biofilm model, infected with PA or Pseudomonas aeruginosa ceramidase mutant (PA ∆Cer ), was used. RESULTS: We observed that bacteria drew resource from host lipids to induce PA ceramidase expression by three orders of magnitude. PA utilized product of host ceramide catabolism to augment transcription of PA ceramidase. Biofilm formation was more robust in PA compared to PA ∆Cer . Downstream products of such metabolism such as sphingosine and sphingosine-1-phosphate were both directly implicated in the induction of ceramidase and inhibition of peroxisome proliferator-activated receptor (PPAR)δ, respectively. PA biofilm, in a ceram-idastin-sensitive manner, also silenced PPARδ via induction of miR-106b. Low PPARδ limited ABCA12 expression resulting in disruption of skin lipid homeostasis. Barrier function of the wound-site was thus compromised. CONCLUSIONS: This work demonstrates that microbial pathogens must co-opt host skin lipids to unleash biofilm pathogenicity. Anti-biofilm strategies must not necessarily always target the microbe and targeting host lipids at risk of infection could be productive. This work may be viewed as a first step, laying fundamental mechanistic groundwork, toward a paradigm change in biofilm management.
Assuntos
PPAR delta , Pseudomonas aeruginosa , Animais , Ceramidases , Extremidade Inferior , SuínosRESUMO
More than 1300 women with breast implants have developed an anaplastic large cell lymphoma (ALCL) in fluid (seroma) around their implant. More often, seromas are due to benign causes, for example, capsule contracture, leakage, or trauma. Our report in American Journal of Hematology identified several cytokines (IL-9, IL-10, IL-13) as significantly elevated only in seromas due to ALCL. We further showed that the most robust biomarker, IL-10, could be detected by a lateral flow assay (similar to COVID detection) within minutes allowing physicians to quickly plan management, eliminate or reduce costly testing and patient time away from family. Early detection of ALCL in seromas before infiltration may avoid need for cytotoxic or immunotherapy and is possibly life-saving.
Assuntos
Implantes de Mama , Neoplasias da Mama , COVID-19 , Linfoma Anaplásico de Células Grandes , Feminino , Humanos , Linfoma Anaplásico de Células Grandes/diagnóstico , Linfoma Anaplásico de Células Grandes/etiologia , Linfoma Anaplásico de Células Grandes/patologia , Implantes de Mama/efeitos adversos , Interleucina-10 , Seroma/diagnóstico , Seroma/etiologia , Seroma/patologia , Citocinas , COVID-19/complicações , Neoplasias da Mama/diagnóstico , Neoplasias da Mama/complicações , Teste para COVID-19RESUMO
BACKGROUND: Deep inferior epigastric artery perforator (DIEP) flap is a common method of breast reconstruction. Enhanced recovery after surgery (ERAS) postoperative protocols have been used to optimize patient outcomes and facilitate shorter hospital stays. The effect of patient expectations on length of stay (LOS) after DIEP has not been evaluated. The purpose of this study was to investigate whether patient expectations affect LOS. METHODS: A retrospective chart review was performed for patients undergoing DIEP flaps for breast reconstruction from 2017 to 2020. All patients were managed with the same ERAS protocol. Patients were divided in Group I (early expectations) and Group II (standard expectations). Group I patients had expectations set for discharge postoperative day (POD) 2 for unilateral DIEP and POD 3 for bilateral DIEP. Group II patients were given expectations for POD 3 to 4 for unilateral DIEP and POD 4 to 5 for bilateral. The primary outcome variable was LOS. RESULTS: The study included 215 DIEP flaps (45 unilateral and 85 bilateral). The average age was 49.8 years old, and the average body mass index (BMI) was 31.4. Group I (early expectations) included 56 patients (24 unilateral DIEPs, 32 bilateral). Group II (standard expectations) had 74 patients (21 unilateral, 53 bilateral). LOS for unilateral DIEP was 2.9 days for Group I compared with 3.7 days for Group II (p = 0.004). Group I bilateral DIEP patients had LOS of 3.5 days compared with 3.9 days for Group II (p = 0.02). Immediate timing of DIEP (Group I 42.9 vs. Group II 52.7%) and BMI (Group I 32.1 vs. Group II 30.8) were similar (p = 0.25). CONCLUSION: Our study found significantly shorter hospital stay after DIEP flap for patients who expected an earlier discharge date despite similar patient characteristics and uniform ERAS protocol. Patient expectations should be considered during patient counseling and as a confounding variable when analyzing ERAS protocols.
Assuntos
Mamoplastia , Retalho Perfurante , Artérias Epigástricas/cirurgia , Humanos , Tempo de Internação , Pessoa de Meia-Idade , Motivação , Alta do Paciente , Complicações Pós-Operatórias , Estudos RetrospectivosRESUMO
OBJECTIVE: The objective of this work was to causatively link biofilm properties of bacterial infection to specific pathogenic mechanisms in wound healing. BACKGROUND: Staphylococcus aureus is one of the four most prevalent bacterial species identified in chronic wounds. Causatively linking wound pathology to biofilm properties of bacterial infection is challenging. Thus, isogenic mutant stains of S. aureus with varying degree of biofilm formation ability was studied in an established preclinical porcine model of wound biofilm infection. METHODS: Isogenic mutant strains of S. aureus with varying degree (ΔrexBâ>âUSA300â>âΔsarA) of biofilm-forming ability were used to infect full-thickness porcine cutaneous wounds. RESULTS: Compared with that of ΔsarA infection, wound biofilm burden was significantly higher in response to ΔrexB or USA300 infection. Biofilm infection caused degradation of cutaneous collagen, specifically collagen 1 (Col1), with ΔrexB being most pathogenic in that regard. Biofilm infection of the wound repressed wound-edge miR-143 causing upregulation of its downstream target gene matrix metalloproteinase-2. Pathogenic rise of collagenolytic matrix metalloproteinase-2 in biofilm-infected wound-edge tissue sharply decreased collagen 1/collagen 3 ratio compromising the biomechanical properties of the repaired skin. Tensile strength of the biofilm infected skin was compromised supporting the notion that healed wounds with a history of biofilm infection are likely to recur. CONCLUSION: This study provides maiden evidence that chronic S. aureus biofilm infection in wounds results in impaired granulation tissue collagen leading to compromised wound tissue biomechanics. Clinically, such compromise in tissue repair is likely to increase wound recidivism.
Assuntos
Biofilmes , Colágeno/metabolismo , Tecido de Granulação/metabolismo , Staphylococcus aureus/isolamento & purificação , Cicatrização/fisiologia , Infecção dos Ferimentos/microbiologia , Animais , Células Cultivadas , Modelos Animais de Doenças , Ensaio de Imunoadsorção Enzimática , Tecido de Granulação/patologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Infecções Estafilocócicas/microbiologia , Suínos , Infecção dos Ferimentos/diagnósticoRESUMO
Milk fat globule epidermal growth factor-factor 8 (MFG-E8) is a peripheral glycoprotein that acts as a bridging molecule between the macrophage and apoptotic cells, thus executing a pivotal role in the scavenging of apoptotic cells from affected tissue. We have previously reported that apoptotic cell clearance activity or efferocytosis is compromised in diabetic wound macrophages. In this work, we test the hypothesis that MFG-E8 helps resolve inflammation, supports angiogenesis, and accelerates wound closure. MFG-E8(-/-) mice displayed impaired efferocytosis associated with exaggerated inflammatory response, poor angiogenesis, and wound closure. Wound macrophage-derived MFG-E8 was recognized as a critical driver of wound angiogenesis. Transplantation of MFG-E8(-/-) bone marrow to MFG-E8(+/+) mice resulted in impaired wound closure and compromised wound vascularization. In contrast, MFG-E8(-/-) mice that received wild-type bone marrow showed improved wound closure and improved wound vascularization. Hyperglycemia and exposure to advanced glycated end products inactivated MFG-E8, recognizing a key mechanism that complicates diabetic wound healing. Diabetic db/db mice suffered from impaired efferocytosis accompanied with persistent inflammation and slow wound closure. Topical recombinant MFG-E8 induced resolution of wound inflammation, improvements in angiogenesis, and acceleration of closure, upholding the potential of MFG-E8-directed therapeutics in diabetic wound care.
Assuntos
Antígenos de Superfície/imunologia , Antígenos de Superfície/metabolismo , Diabetes Mellitus/fisiopatologia , Inflamação/tratamento farmacológico , Proteínas do Leite/imunologia , Proteínas do Leite/metabolismo , Cicatrização , Proteínas Angiogênicas/imunologia , Proteínas Angiogênicas/isolamento & purificação , Proteínas Angiogênicas/metabolismo , Animais , Antígenos de Superfície/genética , Antígenos de Superfície/farmacologia , Apoptose , Diabetes Mellitus/imunologia , Humanos , Macrófagos/imunologia , Camundongos , Camundongos Endogâmicos C57BL , Proteínas do Leite/genética , Proteínas do Leite/farmacologia , FagocitoseRESUMO
Hyperglycemia (HG) induces genome-wide cytosine demethylation. Our previous work recognized miR-200b as a critical angiomiR, which must be transiently downregulated to initiate wound angiogenesis. Under HG, miR-200b downregulation is not responsive to injury. Here, we demonstrate that HG may drive vasculopathy by epigenetic modification of a miR promoter. In human microvascular endothelial cells (HMECs), HG also lowered DNA methyltransferases (DNMT-1 and DNMT-3A) and compromised endothelial function as manifested by diminished endothelial nitric oxide (eNOS), lowered LDL uptake, impaired Matrigel tube formation, lower NO production, and compromised VE-cadherin expression. Bisulfite-sequencing documented HG-induced miR-200b promoter hypomethylation in HMECs and diabetic wound-site endothelial cells. In HMECs, HG compromised endothelial function. Methyl donor S-adenosyl-L-methionine (SAM) corrected miR-200b promoter hypomethylaton and rescued endothelial function. In vivo, wound-site administration of SAM to diabetic mice improved wound perfusion by limiting the pathogenic rise of miR-200b. Quantitative stable isotope labeling by amino acids in cell culture (SILAC) proteomics and ingenuity pathway analysis identified HG-induced proteins and principal clusters in HMECs sensitive to the genetic inhibition of miR-200b. This work presents the first evidence of the miR-200b promoter methylation as a critical determinant of diabetic wound angiogenesis.
Assuntos
Angiopatias Diabéticas/genética , Epigênese Genética , MicroRNAs/genética , Animais , Linhagem Celular , Metilação de DNA , DNA Metiltransferase 3A , Diabetes Mellitus Experimental , Angiopatias Diabéticas/metabolismo , Angiopatias Diabéticas/patologia , Modelos Animais de Doenças , Células Endoteliais/metabolismo , Epigênese Genética/efeitos dos fármacos , Regulação da Expressão Gênica/efeitos dos fármacos , Humanos , Hiperglicemia/genética , Camundongos , Camundongos Transgênicos , Neovascularização Patológica/genética , Neovascularização Patológica/metabolismo , Regiões Promotoras Genéticas , Selenometionina/análogos & derivados , Selenometionina/farmacologiaRESUMO
Heterogeneity and high versatility are the characteristic features of the cells of monocyte-macrophage lineage. The mononuclear phagocyte system, derived from the bone marrow progenitor cells, is primarily composed of monocytes, macrophages, and dendritic cells. In regenerative tissues, a central role of monocyte-derived macrophages and paracrine factors secreted by these cells is indisputable. Macrophages are highly plastic cells. On the basis of environmental cues and molecular mediators, these cells differentiate to proinflammatory type I macrophage (M1) or anti-inflammatory or proreparative type II macrophage (M2) phenotypes and transdifferentiate into other cell types. Given a central role in tissue repair and regeneration, the review focuses on the heterogeneity of monocytes and macrophages with current known mechanisms of differentiation and plasticity, including microenvironmental cues and molecular mediators, such as noncoding RNAs.
Assuntos
Diferenciação Celular/fisiologia , Plasticidade Celular/fisiologia , Macrófagos/metabolismo , Monócitos/metabolismo , Regeneração/fisiologia , Cicatrização/fisiologia , Animais , HumanosRESUMO
MicroRNAs (miR) are emerging as biomarkers and potential therapeutic targets in tumor management. Endothelial cell tumors are the most common soft tissue tumors in infants, yet little is known about the significance of miR in regulating their growth. A validated mouse endothelial cell (EOMA) tumor model was used to demonstrate that post-transcriptional gene silencing of dicer, the enzyme that converts pre-miR to mature miR, can prevent tumor formation in vivo. Tumors were formed in eight of eight mice injected with EOMA cells transfected with control shRNA but formed in only four of ten mice injected with EOMA cells transfected with dicer shRNA. Tumors that formed in the dicer shRNA group were significantly smaller than tumors in the control group. This response to dicer knockdown was mediated by up-regulated miR 21a-3p activity targeting the nox-4 3'-UTR. EOMA cells were transfected with miR 21a-3p mimic and luciferase reporter plasmids containing either intact nox-4 3'-UTR or with mutation of the proposed 3'-UTR miR21a-3p binding sites. Mean luciferase activity was decreased by 85% in the intact compared with the site mutated vectors (p < 0.01). Attenuated Nox-4 activity resulted in decreased cellular hydrogen peroxide production and decreased production of oxidant-inducible monocyte chemoattractant protein-1, which we have previously shown to be critically required for endothelial cell tumor formation. These findings provide the first evidence establishing the significance of dicer and microRNA in promoting endothelial cell tumor growth in vivo.
Assuntos
Células Endoteliais/patologia , Técnicas de Silenciamento de Genes , Hemangioendotelioma/patologia , MicroRNAs/genética , NADPH Oxidases/genética , Ribonuclease III/deficiência , Ribonuclease III/genética , Animais , Proliferação de Células , Hemangioendotelioma/genética , Humanos , Camundongos , NADPH Oxidase 4RESUMO
In chronic wounds, biofilm infects host tissue for extended periods of time. This work establishes the first chronic preclinical model of wound biofilm infection aimed at addressing the long-term host response. Although biofilm-infected wounds did not show marked differences in wound closure, the repaired skin demonstrated compromised barrier function. This observation is clinically significant, because it leads to the notion that even if a biofilm infected wound is closed, as observed visually, it may be complicated by the presence of failed skin, which is likely to be infected and/or further complicated postclosure. Study of the underlying mechanisms recognized for the first time biofilm-inducible miR-146a and miR-106b in the host skin wound-edge tissue. These miRs silenced ZO-1 and ZO-2 to compromise tight junction function, resulting in leaky skin as measured by transepidermal water loss (TEWL). Intervention strategies aimed at inhibiting biofilm-inducible miRNAs may be productive in restoring the barrier function of host skin.
Assuntos
Acinetobacter baumannii/fisiologia , Biofilmes , Permeabilidade da Membrana Celular/fisiologia , Epiderme/fisiopatologia , Pseudomonas aeruginosa/fisiologia , Cicatrização/fisiologia , Animais , Desbridamento , Técnicas In Vitro , Masculino , Camundongos , Camundongos Endogâmicos C57BL , MicroRNAs/metabolismo , Modelos Animais , Pele/metabolismo , Suínos , Proteína da Zônula de Oclusão-1/metabolismo , Proteína da Zônula de Oclusão-2/metabolismoRESUMO
Breast cancer-related lymphedema results in chronic upper limb swelling with subcutaneous deposition of fluid and fibroadipose tissue. Morbidity includes psychosocial distress, infection, and difficulty using the extremity. Operative management includes excisional procedures such as suction-assisted lipectomy to reduce abnormal subcutaneous fibroadipose tissue to improve limb volume. Patients who have had postmastectomy breast reconstruction often benefit from fat grafting. This report introduces the concept of fat grafting the breast using the lymphedematous arm as a donor site. This technique improves the volume of the limb by removing the excess subcutaneous adipose, and at the same time reconstructs the breast without adding a donor site not related to the breast cancer-related lymphedema.
RESUMO
Lymphedema is chronic limb swelling resulting from lymphatic dysfunction. There is no cure for the disease. Clinically, a preventive surgical approach called immediate lymphatic reconstruction (ILR) has gained traction. Experimental gene-based therapeutic approaches (e.g., using viral vectors) have had limited translational applicability. Tissue nanotransfection (TNT) technology uses a direct, transcutaneous nonviral vector, gene delivery using a chip with nanochannel poration in response to a rapid (<100 ms) focused electric field. The purpose of this study was to experimentally prevent lymphedema using focal delivery of a specific gene Prox1 (a master regulator of lymphangiogenesis). TNT was applied to the previously optimized lymphedematous mice tail (day 0) directly at the surgical site with genetic cargo loaded into the TNT reservoir: group I (sham) was given pCMV6 (expression vector backbone alone) and group II was treated with pCMV6-Prox1. Group II mice had decreased tail volume (47.8%) compared to sham and greater lymphatic clearance on lymphangiography. Immunohistochemistry showed greater lymphatic vessel density and RNA sequencing exhibited reduced inflammatory markers in group II compared to group I. Prox1 prophylactically delivered using TNT to the surgical site on the day of injury decreased the manifestations of lymphedema in the murine tail model compared to control.
RESUMO
Infection after implant-based breast reconstruction remains challenging, with infection rates up to 24%. Best clinical practice indicates prophylactic oral antibiotics are ineffective at preventing infection. Absorbable antibiotic beads have been routinely used in other surgical subspecialties such as orthopedic and vascular procedures for continuous local antibiotic delivery to the surgical site when implants are placed. Biodegradable calcium sulfate antibiotic beads have been shown to normalize incidence of infection when used prophylactically for a high-risk prepectoral patient population. The purpose of this study is to evaluate the effect of prophylactic biodegradable antibiotic beads when used non-selectively for all prepectoral immediate tissue expander (TE) reconstruction. Patients who underwent mastectomy and immediate prepectoral TE reconstruction on the same day between 2018 and 2024 were reviewed. Patients were divided into two groups: those who received antibiotic beads (Group 1) and those who did not (Group 2). Absorbable calcium-sulfate beads were reconstituted with 1 g vancomycin and 240 mg gentamicin. There were 33 patients (63 TEs) in Group 1 and 330 patients (545 TEs) in Group 2. TE loss was present in 1.5% (1/65 TEs) Group 1 compared to 9.4% (51/545 TEs) in Group 2 (p = 0.032). The mean follow-up time was 178 days (range 93-266 days). Prophylactic biodegradable antibiotic beads used during immediate tissue expander reconstruction decreased implant loss rate. There was one occurrence of SSI in the antibiotic bead group. Antibiotic beads may potentially decrease complications in immediate TE reconstruction when used non-selectively for all patients.
Assuntos
Implantes Absorvíveis , Antibacterianos , Antibioticoprofilaxia , Gentamicinas , Humanos , Feminino , Pessoa de Meia-Idade , Antibacterianos/administração & dosagem , Antibioticoprofilaxia/métodos , Gentamicinas/administração & dosagem , Estudos Retrospectivos , Implantes de Mama/efeitos adversos , Mastectomia , Sulfato de Cálcio/administração & dosagem , Implante Mamário/métodos , Implante Mamário/efeitos adversos , Vancomicina/administração & dosagem , Adulto , Neoplasias da Mama/cirurgia , Infecção da Ferida Cirúrgica/prevenção & controle , Dispositivos para Expansão de Tecidos , Expansão de Tecido/métodos , Expansão de Tecido/instrumentação , Infecções Relacionadas à Prótese/prevenção & controle , Infecções Relacionadas à Prótese/etiologia , Mamoplastia/métodosRESUMO
Background: Lymphedema is chronic limb swelling resulting from lymphatic dysfunction. It affects an estimated five million Americans. There is no cure for this disease. Assessing lymphatic growth is essential in developing novel therapeutics. Intravital microscopy (IVM) is a powerful imaging tool for investigating various biological processes in live animals. Tissue nanotransfection technology (TNT) facilitates a direct, transcutaneous nonviral vector gene delivery using a chip with nanochannel poration in a rapid (<100 ms) focused electric field. TNT was used in this study to deliver the genetic cargo in the murine tail lymphedema to assess the lymphangiogenesis. The purpose of this study is to experimentally evaluate the applicability of IVM to visualize and quantify lymphatics in the live mice model. Methods and Results: The murine tail model of lymphedema was utilized. TNT was applied to the murine tail (day 0) directly at the surgical site with genetic cargo loaded into the TNT reservoir: TNTpCMV6 group receives pCMV6 (expression vector backbone alone) (n = 6); TNTProx1 group receives pCMV6-Prox1 (n = 6). Lymphatic vessels (fluorescein isothiocyanate [FITC]-dextran stained) and lymphatic branch points (indicating lymphangiogenesis) were analyzed with the confocal/multiphoton microscope. The experimental group TNTProx1 exhibited reduced postsurgical tail lymphedema and increased lymphatic distribution compared to TNTpCMV6 group. More lymphatic branching points (>3-fold) were observed at the TNT site in TNTProx1 group. Conclusions: This study demonstrates a novel, powerful imaging tool for investigating lymphatic vessels in live murine tail model of lymphedema. IVM can be utilized for functional assessment of lymphatics and visualization of lymphangiogenesis following gene-based therapy.
Assuntos
Modelos Animais de Doenças , Microscopia Intravital , Linfangiogênese , Vasos Linfáticos , Linfedema , Cauda , Animais , Linfedema/patologia , Linfedema/diagnóstico por imagem , Linfedema/metabolismo , Linfedema/genética , Camundongos , Microscopia Intravital/métodos , Vasos Linfáticos/diagnóstico por imagem , Vasos Linfáticos/patologia , Vasos Linfáticos/metabolismo , Feminino , Técnicas de Transferência de GenesRESUMO
Scope and Significance: Pressure ulcers are very difficult to treat and pose an economic burden, just below cancer and cardiovascular illness, at 4.82 billion U.S. dollars. It is important to understand the pathophysiology of the condition, risk stratification, and ways of preventing it. Prevention forms the most important aspect of their management. The authors systematically evaluated the existing risk prediction scales and explored the evidence from literature regarding the role of additional factors including body mass index, obesity, subcutaneous tissue thickness, and skin integrity in pressure ulcers. With this review it is hoped that the future management of pressure ulcers will concentrate on the preventable and alterable factors in its pathophysiology. Translational Relevance: The review focuses on how adipose tissue thickness can predict the occurrence of pressure ulcer. If adequately proved that a definite thickness of peripheral adipose tissue is efficient in prevention of pressure ulcers, then methods of maintaining the thickness of this tissue will be the next effective strategy in the management of this chronic issue. Clinical Relevance: The review addresses the management of pressure ulcers to wound care providers and emphasize on confounding parameters of obesity, subcutaneous tissue thickness, and skin integrity during the treatment regimen of pressure ulcers. Objectives: The main objective of this review is to draw a consensus concerning the role of adipose tissue in pressure ulcers, based on the published research. A review of the various preexisting predictive scales for pressure ulcers is a secondary objective to highlight the shortcomings in ulcer management. This review finally aims in the future at paving a way to refine our prognosticating scales for pressure sores based on these results. Accurate preventative injury risk scales are needed so that preventative resources can be directed to the patients for whom they are the most appropriate.
Assuntos
Úlcera por Pressão , Humanos , Úlcera por Pressão/terapia , Obesidade/complicações , Tecido AdiposoRESUMO
Infections are problematic in postmastectomy implant-based reconstruction with infection rates as high as 30%. Strategies to reduce the risk of infection have demonstrated various efficacies. A prolonged course of systemic, oral antibiotics has not shown evidence-based benefit. Although absorbable antibiotic beads have been described for orthopedic procedures and pressure wounds, their use has not been well studied during breast reconstruction, particularly for prepectoral implant placement. The purpose of this study was to evaluate the selective use of prophylactic absorbable calcium sulfate antibiotic beads during high-risk implant-based, prepectoral breast reconstruction after mastectomy. Patients who underwent implant-based, prepectoral breast reconstruction between 2019 and 2022 were reviewed. Groups were divided into those who received antibiotic beads and those who did not. Outcome variables included postoperative infection at 90 days. A total of 148 patients (256 implants) were included: 15 patients (31 implants) who received biodegradable antibiotic beads and 133 patients (225 implants) in the control group. Patients who received antibiotic beads were more likely to have a history of infection (66.7%) compared with the control group (0%) (P < 0.01). Surgical site infection occurred in 3.2% of implants in the antibiotic bead group compared with 7.6%, but this did not reach statistical significance. The incidence of infection in high-risk patients who have absorbable antibiotic beads placed during the time of reconstruction seems to be normalized to the control group in this pilot study. We present a novel use of prophylactic absorbable antibiotic beads in prepectoral breast implant reconstruction.
RESUMO
The α-tocotrienol (TCT) form of natural vitamin E is more potent than the better known α-tocopherol against stroke. Angiographic studies of canine stroke have revealed beneficial cerebrovascular effects of TCT. This work seeks to understand the molecular basis of such effect. In mice, TCT supplementation improved perfusion at the stroke-affected site by inducing miR-1224. miRNA profiling of a laser-capture-microdissected stroke-affected brain site identified miR-1224 as the only vascular miR induced. Lentiviral knockdown of miR-1224 significantly blunted the otherwise beneficial effects of TCT on stroke outcomes. Studies on primary brain microvascular endothelial cells revealed direct angiogenic properties of miR-1224. In mice not treated with TCT, advance stereotaxic delivery of an miR-1224 mimic to the stroke site markedly improved stroke outcomes. Mechanistic studies identified Serpine1 as a target of miR-1224. Downregulation of Serpine1 augmented the angiogenic response of the miR-1224 mimic in the brain endothelial cells. The inhibition of Serpine1, by dietary TCT and pharmacologically, increased cerebrovascular blood flow at the stroke-affected site and protected against stroke. This work assigns Serpine1, otherwise known to be of critical significance in stroke, a cerebrovascular function that worsens stroke outcomes. miR-1224-dependent inhibition of Serpine1 can be achieved by dietary TCT as well as by the small-molecule inhibitor TM5441.
RESUMO
Fetal skin achieves scarless wound repair. Dermal fibroblasts play a central role in extracellular matrix deposition and scarring outcomes. Both fetal and gingival wound repair share minimal scarring outcomes. We tested the hypothesis that compared to adult skin fibroblasts, human fetal skin fibroblast diversity is unique and partly overlaps with gingival skin fibroblasts. Human fetal skin (FS, n = 3), gingiva (HGG, n = 13), and mature skin (MS, n = 13) were compared at single-cell resolution. Dermal fibroblasts, the most abundant cluster, were examined to establish a connectome with other skin cells. Annexin1-FPR1 signaling pathway was dominant in both FS as well as HGG fibroblasts and related myeloid cells while scanty in MS fibroblasts. Myeloid-specific FPR1-ORF delivered in murine wound edge using tissue nanotransfection (TNT) technology significantly enhanced the quality of healing. Pseudotime analyses identified the co-existence of an HGG fibroblast subset with FPR1high myeloid cells of fetal origin indicating common underlying biological processes.
RESUMO
INTRODUCTION: Breast Implant-Associated Anaplastic Large Cell Lymphoma (BIA-ALCL) commonly presents as a peri-implant effusion (seroma). CD30 (TNFRSF8) is a consistent marker of tumor cells but also can be expressed by activated lymphocytes in benign seromas. Diagnosis of BIA-ALCL currently includes cytology and detection of CD30 by immunohistochemistry or flow cytometry, but these studies require specialized equipment and pathologists' interpretation. We hypothesized that a CD30 lateral flow assay (LFA) could provide a less costly rapid test for soluble CD30 that eventually could be used by non-specialized personnel for point-of-care diagnosis of BIA-ALCL. METHODS: We performed LFA for CD30 and enzyme-linked immunosorbent assay (ELISA) for 15 patients with pathologically confirmed BIA-ALCL and 10 patients with benign seromas. To determine the dynamic range of CD30 detection by LFA, we added recombinant CD30 protein to universal buffer at seven different concentrations ranging from 125 pg/mL to 10,000 pg/mL. We then performed LFA for CD30 on cryopreserved seromas of 10 patients with pathologically confirmed BIA-ALCL and 10 patients with benign seromas. RESULTS: Recombinant CD30 protein added to universal buffer produced a distinct test line at concentrations higher than 1000 pg/mL and faint test lines at 250-500 pg/mL. LFA produced a positive test line for all BIA-ALCL seromas undiluted and for 8 of 10 malignant seromas at 1:10 dilution, whereas 3 of 10 benign seromas were positive undiluted but all were negative at 1:10 dilution. Undiluted CD30 LFA had a sensitivity of 100.00%, specificity of 70.00%, positive predictive value of 76.92%, and negative predictive value of 100.00% for BIA-ALCL. When specimens were diluted 1:10, sensitivity was reduced to 80.00% but specificity and positive predictive values increased to 100.00%, while negative predictive value was reduced to 88.33%. When measured by ELISA, CD30 was below 1200 pg/mL in each of six benign seromas, whereas seven BIA-ALCL seromas contained CD30 levels > 2300 pg/mL, in all but one case calculated from dilutions of 1:10 or 1:50. CONCLUSIONS: BIA-ALCL seromas can be distinguished from benign seromas by CD30 ELISA and LFA, but LFA requires less time (<20 min) and can be performed without special equipment by non-specialized personnel, suggesting future point-of-care testing for BIA-ALCL may be feasible.
RESUMO
This study investigates a mechanistic link of bacterial biofilm-mediated host-pathogen interaction leading to immunological complications associated with breast implant illness (BII). Over 10 million women worldwide have breast implants. In recent years, women have described a constellation of immunological symptoms believed to be related to their breast implants. We report that periprosthetic breast tissue of participants with symptoms associated with BII had increased abundance of biofilm and biofilm-derived oxylipin 10-HOME compared with participants with implants who are without symptoms (non-BII) and participants without implants. S. epidermidis biofilm was observed to be higher in the BII group compared with the non-BII group and the normal tissue group. Oxylipin 10-HOME was found to be immunogenically capable of polarizing naive CD4+ T cells with a resulting Th1 subtype in vitro and in vivo. Consistently, an abundance of CD4+Th1 subtype was observed in the periprosthetic breast tissue and blood of people in the BII group. Mice injected with 10-HOME also had increased Th1 subtype in their blood, akin to patients with BII, and demonstrated fatigue-like symptoms. The identification of an oxylipin-mediated mechanism of immune activation induced by local bacterial biofilm provides insight into the possible pathogenesis of the implant-associated immune symptoms of BII.