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ABSTRACT: The purpose of this study is to estimate the incidence of fixation-related complications following ultrasound-activated biodegradable osteosynthesis (UBO) in the treatment of craniosynostosis. The authors searched MEDLINE, PubMed, Embase, Google Scholar, and Cochrane Library from January 2005 to January 2020 for clinical studies reporting the use of UBO for fixation in the treatment of craniosynostosis. The primary outcome was the incidence of fixation-related complications, including unstable fixation; swelling, plate visibility, or palpability; infection; inflammation, sinus formation, and discharge; implant exposure; reoperation or implant removal. The pooled incidence rates were estimated using random-effects models. Of 155 studies identified, 10 were included, representing 371 patients. Forty-six (12.4%) patients presented fixation-related complications. The incidence rates of swelling/visibility/palpability, infection, and reoperation/implant removal were pooled based on the available data. The pooled incidence rate of chronic swelling/visibility/palpability was 0.21 (95% confidence interval [CI], 0.05-0.43). Sensitivity analysis by omitting the outlier study demonstrates that the incidence of swelling/visibility/palpability was 0.07 (95% CI, 0.04-0.11). The pooled incidence rate of infection and reoperation/implant removal was 0.07 (95% CI, 0.01-0.16) and 0.04 (95% CI, 0.01-0.09), respectively. Results show that although UBO can provide stable fixation, chronic swelling/visibility/palpability, infection, and reoperation for removal are not uncommon. Based on the literature, the authors recommend judicious use of UBO in patients with large frontorbital advancement and in the area of the coronal suture or other sites with thin overlying skin/subcutaneous tissue. The high possibility of chronic swelling/palpability/visibility during degradation, needs to be discussed preoperatively.
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Craniossinostoses , Implantes Dentários , Implantes Absorvíveis , Placas Ósseas , Craniossinostoses/diagnóstico por imagem , Craniossinostoses/cirurgia , Fixação Interna de Fraturas , Humanos , Resultado do TratamentoRESUMO
PURPOSE: Although osteoporosis is associated with increased risks of complications of fracture fixation in the orthopedic literature, the association between local bone quality (LBQ) and complications of facial fracture fixation is unknown. The authors aim to identify that if decreased LBQ is an independent risk factor for complications following facial fracture fixation? METHODS: The authors conducted a prospective cohort study on patients over age of 50 years who underwent open reduction and rigid internal fixation for facial fractures. The primary predictor was LBQ (low or normal), decided by a combination of 3 panoramic indices. Other predictors included age, gender, body mass index (BMI), comorbidities, trauma-related characteristics, etc. The outcome variable was the presence of hardware-related, fracture-healing, wound, or neurosensory complications during 2-year follow-up. Univariate and multivariate regressions were performed to identify any significant association between predictor and outcome variables. RESULTS: The sample was composed of 69 patients (27 females) with an average age of 58.6â±â8.6 years and BMI of 25â±â3.8. Low-LBQ patients were significantly older, more females, had lower BMI, mainly injured from falls, had more complications compared to their normal-LBQ counterparts. However, multivariable logistic regressions demonstrated that only age (adjusted OR: 1.12, Pâ=â0.031, 95% CI: 1.01, 1.23) and diabetes (adjusted OR: 12.63, Pâ=â0.029, 95% CI: 1.3, 122.53) were significantly associated with overall complications after confounding adjustment. CONCLUSIONS: The results of the present study indicate that reduced LBQ is not an independent risk factor for complications following facial fracture fixation. The increased risk of complications in low-LBQ patients is more likely to be attributed to other age-related comorbidities such as diabetes. Therefore, the authors recommend detailed workup and good control of comorbidities in elderly trauma patient.
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Fixação Interna de Fraturas , Fixação de Fratura , Idoso , Ossos Faciais , Feminino , Fixação Interna de Fraturas/efeitos adversos , Humanos , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Estudos Prospectivos , Estudos Retrospectivos , Fatores de Risco , Resultado do TratamentoRESUMO
ABSTRACT: This meta-analysis aimed to provide an up-to-date comparison of donor site morbidity (DSM) between patients who underwent head and neck reconstruction with Anterolateral thigh (ALT) and radial forearm free (RFF) flaps. We searched the PubMed, Web of Science, EMBASE, and Cochrane Library databases to identify studies that compared DSM between ALT and RFF patients. Study quality was assessed using the Newcastle-Ottawa Scale. The pooled odds ratio (OR) of each DSM between ALT and RFF patients was estimated using a random- or fixed-effect model depending on the degree of interstudy heterogeneity. Sensitivity and subgroup analyses were performed if substantial heterogeneity was detected. Eighteen cohort studies with 1,018 patients (535 ALT and 483 RFF patients) were included. Compared with RFF, ALT were associated with lower risks of wound dehiscence (ORâ=â0.2, 95%CI: 0.10-0.42, Pâ<â0.01), strength impairment (ORâ=â0.18, 95%CI: 0.07-0.47, Pâ<â0.01), and movement impairment (ORâ=â0.19, 95%CI:0.07-0.49, Pâ<â0.01). A subgroup analysis showed that ALT were associated with a lower risk of donor site numbness among patients undergoing tongue reconstruction (ORâ=â0.05, 95%CI: 0.01-0.25, Pâ<â0.01), but not among all patients undergoing head and neck reconstruction. The pooled ORs of other DSMs demonstrated no significant difference between ALT and RFF patients. ALT are superior to RFF for head and neck reconstruction in terms of donor site wound dehiscence, strength impairment, movement impairment, and for tongue reconstruction specifically in terms of donor site numbness. No significant differences in the incidence of donor site hematoma/seroma, infection, or dissatisfaction with donor site appearance were identified between ALT and RFF patients.
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Retalhos de Tecido Biológico , Procedimentos de Cirurgia Plástica , Antebraço/cirurgia , Humanos , Morbidade , Estudos Retrospectivos , Coxa da Perna/cirurgiaRESUMO
BACKGROUND: Facial thread-lifting (FTL) has gained more popularity, but the incidences of complications following FTL remain controversial. We aimed to perform a meta-analysis and systematic review to estimate the incidences of complications and to compare the short- and long-term satisfaction rates following FTL. METHODS: We searched PubMed, Web of Science, Embase and Cochrane library for eligible studies. The primary outcome was the incidences of complications following FTL. The secondary outcome was the satisfaction rate immediately and 6-month after FTL. The pooled incidences of complications and 95% confidence intervals were estimated using random-effects models. RESULTS: A total of 26 studies were included in this meta-analysis. Swelling was the most commonly reported complication with a pooled incidence of 35%, followed by skin dimpling (10%), paresthesia (6%), thread visibility/palpability (4%), infection (2%), and thread extrusion (2%). Absorbable threads were associated with a significantly lower risk of paresthesia (3.1% vs. 11.7%) and thread extrusion (1.6% vs. 7.6%) than non-absorbable threads. Patients older than 50 years had a significantly higher risk of dimpling (16% vs. 5.6%) and infection (5.9% vs. 0.7%) than their younger counterparts. In addition, the pooled long-term satisfaction rate was significantly decreased compared to it immediately after FTL (88% vs. 98%). CONCLUSION: Non-absorbable threads and older age of patients are associated with higher risks of complications. Therefore, we recommend a judicious use of non-absorbable threads and FLT in older patients. Furthermore, it should be discussed with patients preoperatively that the rejuvenation effect of FTL may not maintain in the long-term. LEVEL OF EVIDENCE III: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .
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Remoção , Rejuvenescimento , Idoso , Face , Humanos , Incidência , Resultado do TratamentoRESUMO
PURPOSE: We sought to compare cricothyroid membrane puncture-guided tracheostomy (CMPGT) with surgical cricothyroidotomy (SC) and percutaneous tracheostomy with Griggs' guidewire dilating forceps (GWDF) for establishing an emergency airway in a porcine model. We hypothesized that CMPGT would be associated with a shorter time to ventilation and more rapid restoration of oxygenation. MATERIALS AND METHODS: We implemented a small pilot animal study. Eighteen miniature pigs were randomly assigned to undergo CMPGT, SC, or GWDF. The predictor variable was the technique used. The primary outcome variable was time to ventilation. Other outcome variables were efficiency of oxygenation restoration, procedure duration, and procedure-related complications. The data were assessed using 1-way analysis of variance and Bonferroni correction. The oxygen saturation (SpO2) changes over time were graphed using a time-series line plot. Statistical significance was set at P < .05. RESULTS: Airways were successfully established in all 18 pigs. SC (68 ± 4 seconds) showed the shortest procedure duration compared with GWDF (95 ± 3 seconds) and CMPGT (96 ± 4 seconds); however, the time to ventilation using CMPGT (21 ± 2 seconds) was significantly shorter than that with SC (68 ± 4 seconds) and GWDF (95 ± 3 seconds) (P < .01). Spo2 in each group increased postoperatively, reaching 95% at 120 seconds, 131 seconds, and 144 seconds in the CMPGT, SC, and GWDF groups, respectively. The slope of the ascending phase of the Spo2 curve was 0.38 for CMPGT, 0.42 for SC, and 0.53 for GWDF (P < .05). Two pigs in each group had minor intraoperative bleeding, and 1 pig in the SC group had moderate bleeding. CONCLUSIONS: The results of this animal study suggest that CMPGT is a time-efficient and safe technique for emergency airway access that allows for a more rapid return of ventilation and obviates conversion to definitive tracheostomy. Further cadaveric study is ongoing.
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Cartilagem Cricoide , Cartilagem Tireóidea , Traqueostomia , Animais , Cartilagem Cricoide/cirurgia , Modelos Animais de Doenças , Complicações Pós-Operatórias , Punções , Distribuição Aleatória , Suínos , Porco Miniatura , Cartilagem Tireóidea/cirurgia , Traqueostomia/métodosRESUMO
BACKGROUND: The success of an autologous fat graft depends in part on its total stromal vascular fraction (SVF) and adipose-derived stem cells (ASCs). However, variations in the yields of ASCs and SVF cells as a result of different harvesting techniques and donor sites are poorly understood. OBJECTIVE: To investigate the effects of adipose tissue harvesting technique and donor site on the yield of ASCs and SVF cells. METHODS: Subcutaneous fat tissues from the abdomen, flank, or axilla were harvested from patients of various ages by mechanical liposuction, direct surgical excision, or Coleman's technique with or without centrifugation. Cells were isolated and then analyzed with flow cytometry to determine the yields of total SVF cells and ASCs (CD11b-, CD45-, CD34+, CD90+, D7-FIB+). Differences in ASC and total SVF yields were assessed with one-way analysis of variance. Differentiation experiments were performed to confirm the multilineage potential of cultured SVF cells. RESULTS: Compared with Coleman's technique without centrifugation, direct excision yielded significantly more ASCs (P < .001) and total SVF cells (P = .007); liposuction yielded significantly fewer ASCs (P < .001) and total SVF cells (P < .05); and Coleman's technique with centrifugation yielded significantly more total SVF cells (P < .005), but not ASCs. The total number of SVF cells in fat harvested from the abdomen was significantly larger than the number in fat harvested from the flank or axilla (P < .05). Cultured SVF cells differentiated to adipocytes, osteocytes, and chondrocytes. CONCLUSIONS: Adipose tissue harvested from the abdomen through direct excision or Coleman's technique with centrifugation was found to yield the most SVF cells and ASCs.
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Células-Tronco/citologia , Gordura Subcutânea/citologia , Coleta de Tecidos e Órgãos/métodos , Adipócitos/citologia , Adulto , Diferenciação Celular/fisiologia , Células Cultivadas , Condrócitos/citologia , Feminino , Citometria de Fluxo , Humanos , Lipectomia/métodos , Pessoa de Meia-Idade , Osteócitos/citologiaRESUMO
There are multiple methods to prepare lipoaspirate for autologous fat transfer; however, graft retention remains unpredictable. The purpose of this study was to compare the cellular and protein composition of adipose grafts and the stromal vascular fraction (SVF) resulting from three common techniques to prepare adipose grafts. Adipose grafts were harvested from healthy donors and processed via three techniques: centrifugation (C), a single-filter (SF) device, and a double-filtration (DF) system. Part of each graft was analyzed or further processed to isolate the SVF. Cell viability, surface markers, cytokine, and growth factors were compared between the graft and SVF as well as adipose-derived stem cells (ASCs). Overall, we found variations across the three processing techniques and among the graft components (ASCs, SVF, and fat). Cell viability within the grafts was similar (94.6%, 92.3%, and 93.6%; P = 0.93). The trend was a greater percentage of ASCs from SF versus DF or centrifugation (6.95%, 4.63%, and 1.93%, respectively, P = 0.06). Adipogenic markers (adiponectin and leptin) were similar among all three grafts (P = 0.45). Markers of tissue remodeling were greatest in the SVF compared with fat and ASCs, regardless of processing technique. There was higher relative expression of MMP-9 (2×), Extracellular matrix metalloproteinase inducer (EMMPRIN) (2.5×), endoglin (5×), and IL-8 (1.5×) in the SVF (P < 0.005). Our study identified differences in cytokine expression in adipose grafts and the SVF, particularly in cytokines important in inflammation and wound healing. These secretomes may impact graft retention and fat necrosis and have the potential implications in cell-assisted lipotransfer. There were no significant differences between the final products of any of the processing techniques.
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Antibody-drug conjugates (ADCs) are a new type of targeting antibodies that conjugate with highly toxic anticancer drugs via chemical linkers to exert high specificity and efficient killing of tumor cells, thereby attracting considerable attention in precise oncology therapy. Cetuximab (Cet) is a typical antibody that offers the benefits of good targeting and safety for individuals with advanced and inoperable cutaneous squamous cell carcinoma (cSCC); however, its anti-tumor activity is limited to a single use. Cisplatin (CisPt) shows good curative effects; however, its adverse effects and non-tumor-targeting ability are major drawbacks. In this study, we designed and developed a new ADC based on a new cytotoxic platinum (IV) prodrug (C8Pt(IV)) and Cet. The so-called antibody-platinum (IV) prodrugs conjugates, named Cet-C8Pt(IV), showed excellent tumor targeting in cSCC. Specifically, it accurately delivered C8Pt(IV) into tumor cells to exert the combined anti-tumor effect of Cet and CisPt. Herein, metabolomic analysis showed that Cet-C8Pt(IV) promoted cellular apoptosis and increased DNA damage in cSCC cells by affecting the vitamin B6 metabolic pathway in tumor cells, thereby further enhancing the tumor-killing ability and providing a new strategy for clinical cancer treatment using antibody-platinum (IV) prodrugs conjugates.
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Background: Tracheal reconstruction presents a challenge because of the difficulty in maintaining the rigidity of the trachea to ensure an open lumen and in achieving an intact luminal lining that secretes mucus to protect against infection. Methods: On the basis of the finding that tracheal cartilage has immune privilege, researchers recently started subjecting tracheal allografts to "partial decellularization" (in which only the epithelium and its antigenicity are removed), rather than complete decellularization, to maintain the tracheal cartilage as an ideal scaffold for tracheal tissue engineering and reconstruction. In the present study, we combined a bioengineering approach and a cryopreservation technique to fabricate a neo-trachea using pre-epithelialized cryopreserved tracheal allograft (ReCTA). Results: Our findings in rat heterotopic and orthotopic implantation models confirmed that tracheal cartilage has sufficient mechanical properties to bear neck movement and compression; indicated that pre-epithelialization with respiratory epithelial cells can prevent fibrosis obliteration and maintain lumen/airway patency; and showed that a pedicled adipose tissue flap can be easily integrated with a tracheal construct to achieve neovascularization. Conclusion: ReCTA can be pre-epithelialized and pre-vascularized using a 2-stage bioengineering approach and thus provides a promising strategy for tracheal tissue engineering.
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Muscle flaps must have a strong vascular network to support a large tissue volume and ensure successful engraftment. We developed porcine stomach musculofascial flap matrix (PDSF) comprising extracellular matrix (ECM) and intact vasculature. PDSF had a dominant vascular pedicle, microcirculatory vessels, a nerve network, well-retained 3-dimensional (3D) nanofibrous ECM structures, and no allo- or xenoantigenicity. In-depth proteomic analysis demonstrated that PDSF was composed of core matrisome proteins (e.g., collagens, glycoproteins, proteoglycans, and ECM regulators) that, as shown by Gene Ontology term enrichment analysis, are functionally related to musculofascial biological processes. Moreover, PDSF-human adipose-derived stem cell (hASC) synergy not only induced monocytes towards IL-10-producing M2 macrophage polarization through the enhancement of hASCs' paracrine effect but also promoted the proliferation and interconnection of both human skeletal muscle myoblasts (HSMMs) and human umbilical vein endothelial cells (HUVECs) in static triculture conditions. Furthermore, PDSF was successfully prevascularized through a dynamic perfusion coculture of hASCs and HUVECs, which integrated with PDSF and induced the maturation of vascular networks in vitro. In a xenotransplantation model, PDSF demonstrated myoconductive and immunomodulatory properties associated with the predominance of M2 macrophages and regulatory T cells. In a volumetric muscle loss (VML) model, prevascularized PDSF augmented neovascularization and constructive remodeling, which was characterized by the predominant infiltration of M2 macrophages and significant musculofascial tissue formation. These results indicate that hASCs' integration with PDSF enhances the cells' dual function in immunomodulation and angiogenesis. Owing in part to this PDSF-hASC synergy, our platform shows promise for vascularized muscle flap engineering for VML reconstruction.
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The cyclic guanosine monophosphate-adenosine monophosphate synthase (cGAS)/stimulator of interferon genes (STING) signalling pathway has been a promising target for anticancer immunity, but rationally activating and enhancing this pathway in tumour cells is critical. Herein, a glutathione sensitive ZnFe2O4-based nanosystem is developed to programmatically initiate and enhance the STING signalling pathway in tumour cells. The prepared ZnFe2O4 nanoparticles were coated with cancer cell membrane (CCM), which enabled the nanosystem target tumour cells. In tumour cells, ZnFe2O4 nanoparticles could be disintegrated by responding to high level glutathione, and the released Fe3+ generated reactive oxygen species to induce the DNA leakage into the cytoplasm to stimulate cGAS. Then Zn2+ promoted cGAS-DNA phase separation to intensify the cGAS enzymatic activity. In addition, the low dose encapsulation of paclitaxel (PTX) acting as an antimitotic agent (ZnFe2O4-PTX@CCM) ensured the sustained activation of cGAS/STING pathway. The in vitro and in vivo results confirmed that ZnFe2O4-PTX@CCM elevated the cGAS/STING activity, promoted dendritic cell maturation, increased cytotoxic T lymphocyte and natural killer cells infiltration, eventually inhibiting the tumour progress and postoperative recurrence. This study provided feasible references on constructing STING activation nanosystem for tumour immunotherapy.
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Purpose: Fatty acid metabolism (FAM) affects the immune phenotype in a metabolically dynamic tumor microenvironment (TME), but the use of FAM-related genes (FAMGs) to predict the prognosis and immunotherapy response of cutaneous melanoma (CM) patients has not been investigated. In this study, we aimed to construct FAM molecular subtypes and identify key prognostic biomarkers in CM. Methods: We used a CM dataset in The Cancer Genome Atlas (TCGA) to construct FAM molecular subtypes. We performed Kaplan-Meier (K-M) analysis, gene set enrichment analysis (GSEA), and TME analysis to assess differences in the prognosis and immune phenotype between subtypes. We used weighted gene co-expression network analysis (WGCNA) to identify key biomarkers that regulate tumor metabolism and immunity between the subtypes. We compared overall survival (OS), progression-free survival (PFS), and disease-specific survival (DSS) between CM patients with high or low biomarker expression. We applied univariable and multivariable Cox analyses to verify the independent prognostic value of the FAM biomarkers. We used GSEA and TME analysis to investigate the immune-related regulation mechanism of the FAM subtype biomarker. We evaluated the immune checkpoint inhibition (ICI) response and chemotherapy sensitivity between CM patients with high or low biomarker expression. We performed real-time fluorescent quantitative PCR (qRT-PCR) and semi-quantitative analysis of the immunohistochemical (IHC) data from the Human Protein Atlas to evaluate the mRNA and protein expression levels of the FAM biomarkers in CM. Results: We identified 2 FAM molecular subtypes (cluster 1 and cluster 2). K-M analysis showed that cluster 2 had better OS and PFS than cluster 1 did. GSEA showed that, compared with cluster 1, cluster 2 had significantly upregulated immune response pathways. The TME analysis indicated that immune cell subpopulations and immune functions were highly enriched in cluster 2 as compared with cluster 1. WGCNA identified 6 hub genes (ACSL5, ALOX5AP, CD1D, CD74, IL4I1, and TBXAS1) as FAM biomarkers. CM patients with high expression levels of the six biomarkers had better OS, PFS, and DSS than those with low expression levels of the biomarkers. The Cox regression analyses verified that the 6 FAM biomarkers can be independent prognostic factors for CM patients. The single-gene GSEA showed that the high expression levels of the 6 genes were mainly enriched in T-cell antigen presentation, the PD-1 signaling pathway, and tumor escape. The TME analysis confirmed that the FAM subtype biomarkers were not only related to immune infiltration but also highly correlated with immune checkpoints such as PD-1, PD-L1, and CTLA-4. TIDE scores confirmed that patients with high expression levels of the 6 biomarkers had worse immunotherapy responses. The 6 genes conveyed significant sensitivity to some chemotherapy drugs. qRT-PCR and IHC analyses verified the expression levels of the 6 biomarkers in CM cells. Conclusion: Our FAM subtypes verify that different FAM reprogramming affects the function and phenotype of infiltrating immune cells in the CM TME. The FAM molecular subtype biomarkers can be independent predictors of prognosis and immunotherapy response in CM patients.
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Melanoma , Neoplasias Cutâneas , Humanos , Melanoma/genética , Neoplasias Cutâneas/genética , Receptor de Morte Celular Programada 1 , Biomarcadores , Ácidos Graxos , Microambiente Tumoral/genética , L-Aminoácido Oxidase , Melanoma Maligno CutâneoRESUMO
Purpose: Ferroptosis-related lncRNAs are promising biomarkers for predicting the prognosis of many cancers. However, a ferroptosis-related signature to predict the prognosis of cutaneous melanoma (CM) has not been identified. The purpose of this study was to construct a ferroptosis-related lncRNA signature to predict prognosis and immunotherapy efficacy in CM. Methods: Ferroptosis-related differentially expressed genes (FDEGs) and lncRNAs (FDELs) were identified using TCGA, GTEx, and FerrDb datasets. We performed Cox and LASSO regressions to identify key FDELs, and constructed a risk score to stratify patients into high- and low-risk groups. The lncRNA signature was evaluated using the areas under the receiver operating characteristic curves (AUCs) and Kaplan-Meier analyses in the training, testing, and entire cohorts. Multivariate Cox regression analyses including the lncRNA signature and common clinicopathological characteristics were performed to identify independent predictors of overall survival (OS). A nomogram was developed for clinical use. We performed gene set enrichment analyses (GSEA) to identify significantly enriched pathways. Differences in the tumor microenvironment (TME) between the 2 groups were assessed using 7 algorithms. To predict the efficacy of immune checkpoint inhibitors (ICI), we analyzed the association between PD1 and CTLA4 expression and the risk score. Finally, differences in Tumor Mutational Burden (TMB) and molecular drugs Sensitivity between the 2 groups were performed. Results: We identified 5 lncRNAs (AATBC, AC145423.2, LINC01871, AC125807.2, and AC245041.1) to construct the risk score. The AUC of the lncRNA signature was 0.743 in the training cohort and was validated in the testing and entire cohorts. Kaplan-Meier analyses revealed that the high-risk group had poorer prognosis. Multivariate Cox regression showed that the lncRNA signature was an independent predictor of OS with higher accuracy than traditional clinicopathological features. The 1-, 3-, and 5-year survival probabilities for CM patients were 92.7%, 57.2%, and 40.2% with an AUC of 0.804, indicating a good accuracy and reliability of the nomogram. GSEA showed that the high-risk group had lower ferroptosis and immune response. TME analyses confirmed that the high-risk group had lower immune cell infiltration (e.g., CD8+ T cells, CD4+ memory-activated T cells, and M1 macrophages) and lower immune functions (e.g., immune checkpoint activation). Low-risk patients whose disease expressed PD1 or CTLA4 were likely to respond better to ICIs. The analysis demonstrated that the TMB had significantly difference between low- and high- risk groups. Chemotherapy drugs, such as sorafenib, Imatinib, ABT.888 (Veliparib), Docetaxel, and Paclitaxel showed Significant differences in the estimated IC50 between the two risk groups. Conclusion: Our novel ferroptosis-related lncRNA signature was able to accurately predict the prognosis and ICI outcomes of CM patients. These ferroptosis-related lncRNAs might be potential biomarkers and therapeutic targets for CM.
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Purpose: The purpose of this study was to construct a gene signature comprising genes related to both inflammation and pyroptosis (GRIPs) to predict the prognosis of patients with cutaneous melanoma patients and the efficacy of immunotherapy, chemotherapy, and targeted therapy in these patients. Methods: Gene expression profiles were collected from The Cancer Genome Atlas. Weighted gene co-expression network analysis was performed to identify GRIPs. Univariable Cox regression and Lasso regression further selected key prognostic genes. Multivariable Cox regression was used to construct a risk score, which stratified patients into high- and low-risk groups. Areas under the ROC curves (AUCs) were calculated, and Kaplan-Meier analyses were performed for the two groups, following validation in an external cohort from Gene Expression Omnibus (GEO). A nomogram including the GRIP signature and clinicopathological characteristics was developed for clinical use. Gene set enrichment analysis illustrated differentially enriched pathways. Differences in the tumor microenvironment (TME) between the two groups were assessed. The efficacies of immune checkpoint inhibitors (ICIs), chemotherapeutic agents, and targeted agents were predicted for both groups. Immunohistochemical analyses of the GRIPs between the normal and CM tissues were performed using the Human Protein Atlas data. The qRT-PCR experiments validated the expression of genes in CM cell lines, Hacat, and PIG1 cell lines. Results: A total of 185 GRIPs were identified. A novel gene signature comprising eight GRIPs (TLR1, CCL8, EMP3, IFNGR2, CCL25, IL15, RTP4, and NLRP6) was constructed. The signature had AUCs of 0.714 and 0.659 for predicting 3-year overall survival (OS) in the TCGA entire and GEO validation cohorts, respectively. Kaplan-Meier analyses revealed that the high-risk group had a poorer prognosis. Multivariable Cox regression showed that the GRIP signature was an independent predictor of OS with higher accuracy than traditional clinicopathological features. The nomogram showed good accuracy and reliability in predicting 3-year OS (AUC = 0.810). GSEA and TME analyses showed that the high-risk group had lower levels of pyroptosis, inflammation, and immune response, such as lower levels of CD8+ T-cell infiltration, CD4+ memory-activated T-cell infiltration, and ICI. In addition, low-risk patients whose disease expressed PD-1 or CTLA-4 were likely to respond better to ICIs, and several chemotherapeutic and targeted agents. Immunohistochemical analysis confirmed the distinct expression of five out of the eight GRIPs between normal and CM tissues. Conclusion: Our novel 8-GRIP signature can accurately predict the prognosis of patients with CM and the efficacies of multiple anticancer therapies. These GRIPs might be potential prognostic biomarkers and therapeutic targets for CM.
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The authors describe their experience with the use of the distally based dorsal pedal neurocutaneous flap for distal foot coverage. Ten patients underwent reconstruction with 13 flaps between 2004 and 2008. One patient suffered from a traffic accident and 9 from electrical injury. All of the soft tissue defects resulted in metatarsophalangeal joint and phalanx bone exposure. The size of the flaps ranged from 6 × 2 cm to 11 × 6 cm. The flaps were elevated based on intermediate or medial dorsal pedal nerves. Nine flaps were harvested in first stage to repair the distal foot. Among them, 3 showed partial necrosis in the distal region because of venous insufficiency. Four flaps underwent a surgical delay procedure in the first stage and were then transferred to reconstruct phalanx wounds in the second stage, surviving completely. All patients were satisfied with their reconstruction and donor site contour. The distally based dorsal pedal neurocutaneous flap can be used to repair the distal foot soft tissue defects, providing sufficient skin territory and excellent aesthetic and functional recovery. Surgical delay effectively enhances the distally based dorsal pedal neurocutaneous flap survival, particularly for the large size flaps.
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Traumatismos do Pé/cirurgia , Antepé Humano/cirurgia , Procedimentos de Cirurgia Plástica/métodos , Lesões dos Tecidos Moles/cirurgia , Retalhos Cirúrgicos/irrigação sanguínea , Humanos , Masculino , Pessoa de Meia-Idade , Transplante de Pele , Resultado do Tratamento , CicatrizaçãoRESUMO
Gradual distraction with an external fixator is a widely used treatment for severe postburn ankle contracture (SPAC). However, application of external fixators is complex, and conventional two-dimensional (2D) imaging-based surgical planning is not particularly helpful due to a lack of spatial geometry. The purpose of this study was to evaluate the surgical planning process for this procedure with patient-specific three-dimension-printed models (3DPMs). In this study, patients coming from two centers were divided into two cohorts (3DPM group vs. control group) depending on whether a 3DPM was used for preoperative surgical planning. Operation duration, improvement in metatarsal-tibial angle (MTA), range of motion (ROM), the American Orthopedic Foot and Ankle Society (AOFAS) scores, complications, and patient-reported satisfaction were compared between two groups. The 3DPM group had significantly shorter operation duration than the control group ((2.0±0.3) h vs. (3.2±0.3) h, P<0.01). MTA, ROM, and AOFAS scores between the two groups showed no significant differences pre-operation, after the removal of the external fixator, or at follow-up. Plantigrade feet were achieved and gait was substantially improved in all patients at the final follow-up. Pin-tract infections occurred in two patients (one in each group) during distraction and were treated with wound care and oral antibiotics. Patients in the 3DPM group reported higher satisfaction than those in the control group, owing to better patient-surgeon communication. Surgical planning using patient-specific 3DPMs significantly reduced operation duration and increased patient satisfaction, while providing similar improvements in ankle movement and function compared to traditional surgical planning for the correction of SPAC with external fixators.
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Articulação do Tornozelo/cirurgia , Queimaduras/complicações , Contratura/cirurgia , Fixadores Externos , Impressão Tridimensional , Adolescente , Adulto , Articulação do Tornozelo/fisiopatologia , Criança , Pré-Escolar , Contratura/fisiopatologia , Fixadores Externos/efeitos adversos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Satisfação do Paciente , Amplitude de Movimento Articular , Estudos Retrospectivos , Adulto JovemRESUMO
The anterolateral thigh (ALT) flap has gained popularity, yet the donor site remains problematic. With increased knowledge of the vascular anatomy, we anticipated that we would be able to contour the ALT adipofascial flap when reconstructing facial deformities and micromastia without sacrificing skin at the donor site. A total of 24 cases of hemifacial atrophy and 1 case of micromastia underwent anterolateral thigh adipofascial flap transplantation with vascular anastomosis. All surgical reconstructions resulted in satisfactory results with minimal donor-site morbidity. The anterolateral thigh adipofascial perforator flap is an ideal choice for autologous tissue reconstruction with primary defatting.
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Face/cirurgia , Mamoplastia/métodos , Procedimentos de Cirurgia Plástica/métodos , Retalhos Cirúrgicos/irrigação sanguínea , Coxa da Perna/cirurgia , Tecido Adiposo/transplante , Adolescente , Adulto , Estudos de Coortes , Estética , Face/anormalidades , Hemiatrofia Facial/cirurgia , Fáscia/transplante , Feminino , Rejeição de Enxerto , Sobrevivência de Enxerto , Humanos , Masculino , Estudos Retrospectivos , Medição de Risco , Cicatrização/fisiologia , Adulto JovemRESUMO
The purpose of this article is to describe the author's experience using the anterolateral thigh (ALT) flap for the reconstruction of a variety of soft tissue defects. The flap utility and donor site morbidity were evaluated in 126 cases from March 1985 to August 2007. The ALT flaps were harvested as either free fasciocutaneous, free adipofascial, fasciocutaneous island, or reversed fasciocutaneous island flaps to repair facial, neck, breast, trunk, and extremity defects. In 40 cases (32%), the skin vessels were found to be septocutaneous perforators, and in 86 cases (68%), they were found as musculocutaneous perforators. Of the 126 flaps, 121 survived completely, providing a success rate of 96.0%. There were four cases undergoing multidetector-row computed tomographic angiography (CTA) for preoperative perforator mapping, and all perforators were confirmed intraoperatively. In conclusion, the ALT flap is a versatile and reliable flap that could well be a priority option for soft tissue reconstruction. CTA can provide more valuable and accurate anatomic information about the pedicle and perforators, making it safer and faster to harvest a targeted ALT perforator flap with less donor site morbidity.
Assuntos
Procedimentos de Cirurgia Plástica/métodos , Lesões dos Tecidos Moles/cirurgia , Retalhos Cirúrgicos/irrigação sanguínea , Adolescente , Adulto , Idoso , Angiografia , Criança , Pré-Escolar , Feminino , Sobrevivência de Enxerto , Humanos , Masculino , Pessoa de Meia-Idade , Coxa da Perna , Tomografia Computadorizada por Raios XRESUMO
BACKGROUND: Secondary lymphedema is a common condition that affects patients with malignant tumors. Conservative treatments fail to provide lasting relief because they do not address the underlying pathological accumulation of excessive fat. Our aim is to clarify the molecular mechanisms of abnormal adipogenic differentiation in lymphedema adipose tissue. METHODS: We compared the proliferation and adipogenesis potential of adipose-derived mesenchymal stem cells (ASCs) from the lymphedema adipose tissue from liposuction specimens of 10 patients with extremity lymphedema with that of ASCs from adipose tissue from the normal upper abdomen of the same patients. Transcriptome analysis were performed to identify the differences between the two kinds of ASCs. Cyclin-dependent kinase 1 (CDK1) inhibitors were used to treat the abnormal ASCs in lymphedema adipose tissue. RESULTS: Our results demonstrate that significant functional and transcriptomic differences exist between the two kinds of ASCs. Up-regulated genes were mainly involved in cell proliferation and division while down-regulated genes were mainly associated with immune responses and inflammatory as well as osteogenic and myogenic differentiation. Furthermore, we find that the excessive proliferation and adipogenesis of ASCs from lymphedema adipose tissue returned to the normal phenotype by CDK1 inhibitors. ASCs from lymphedema adipose tissues have higher immunosuppressive effect and the cytokines related to immunosuppressive was significantly up-regulated. CONCLUSIONS: In conclusion, lymphedema-associated ASCs had more rapid proliferation and a higher adipogenic differentiation capacity. CDK1 may be a key driver of proliferation and adipogenic differentiation in these cells, which might expound the accumulation of adipose tissue extensively observed in secondary lymphedema. ASCs from lymphedema adipose tissues showed immunomodulation dysfunction and immunomodulation may play an important role in the pathogenesis of lymphedema.
RESUMO
Preoperative radiation is associated with an increased risk of wound complications. However, the influences of radiation on musculofascial wound healing remains unclear. The purpose of the study was to investigate the short-term effects of preoperative local radiation on the musculofascial healing of laparotomy incisions in a rat model. Eighteen Fischer 344 rats received radiation doses of 0, 10, or 20 Gy to the abdominal wall and underwent laparotomy 4 weeks later. Two weeks after laparotomy, samples of irradiated muscle were harvested for mechanical tests, histological (Hematoxylin & Eosin, and Masson's Trichrome) and immunohistochemical analyses using KI67, CD31, TGF-ß, and MYOD1 antibodies. The elastic modulus (EM), maximum strain (MS), and ultimate tensile strength (UTS) in the 20-Gy group were significantly weaker than those in the 0-Gy group. The EM and UTS in the 20-Gy group were significantly lower than those in the 10-Gy group. The UTS and MS in the 10-Gy group were significantly lower than those in the 0-Gy group. The mean number of inflammatory cells per mm2 in the 20-Gy group was significantly larger than those in the 10- and 0-Gy groups. The mean numbers of CD31-, KI67-, and MYOD1-positive cells, the optical density of TGF-ß, and the microvessel density in the 20-Gy group were significantly smaller than those in the 10- and 0-Gy groups. These results indicated that radiation delays musculofascial healing and decreases mechanical strength of the laparotomy incision by creating a chronic inflammatory environment, inhibiting cell proliferation, angiogenesis, granulation maturation, collagen deposition, and muscular regeneration in a dose-dependent manner. The impaired biomechanical, histological and molecular properties may be associated with the higher risk of wound complications in patients who undergo radiotherapy prior to laparotomy.