RESUMO
Bisphosphonates are a class of drugs which have shown good efficacy in the treatment of post-menopausal osteoporosis, as well as a good safety profile. However, side-effects such as risk for atypical femoral fractures (AFF) have appeared, leading to a decline in use of the drugs by many patients who would benefit from the treatment. While patient characteristics have contributed to improved understanding of risk factors, the mechanisms involved that explain AFF risk have not appeared. Recently, the possibility that the mechanism(s) involved drug-induced modification of cells of the nutrient canals of the femur and subsequent compromise in the bone matrix has been published. The present Hypothesis article builds on the concept presented earlier and expands into biomechanical considerations. An analogy of the mechanisms involved to a real-life scenario is also presented. While this analogy has limitations, consideration of the biomechanical implications of progressive alterations to defects presented by compromised nutrient canal-bone matrix also presents potential relationships with AFF risk.
Assuntos
Fraturas do Fêmur , Osteoporose , Humanos , Difosfonatos/efeitos adversos , Osteoporose/induzido quimicamente , Osteoporose/tratamento farmacológico , Ósteon , Fraturas do Fêmur/induzido quimicamente , Fraturas do Fêmur/tratamento farmacológico , Fatores de RiscoRESUMO
BACKGROUND: Recent studies suggested that genetic variants associated with monogenic bone disorders were involved in the pathogenesis of atypical femoral fractures (AFF). Here, we aim to identify rare genetic variants by whole exome sequencing in genes involved in monogenic rare skeletal diseases in 12 women with AFF and 4 controls without any fracture. RESULTS: Out of 33 genetic variants identified in women with AFF, eleven (33.3%) were found in genes belonging to the Wnt pathway (LRP5, LRP6, DAAM2, WNT1, and WNT3A). One of them was rated as pathogenic (p.Pro582His in DAAM2), while all others were rated as variants of uncertain significance according to ClinVar and ACMG criteria. CONCLUSIONS: Osteoporosis, rare bone diseases, and AFFs may share the same genes, thus making it even more difficult to identify unique risk factors.
Assuntos
Sequenciamento do Exoma , Fraturas do Fêmur , Proteína-5 Relacionada a Receptor de Lipoproteína de Baixa Densidade , Proteína-6 Relacionada a Receptor de Lipoproteína de Baixa Densidade , Humanos , Feminino , Fraturas do Fêmur/genética , Fraturas do Fêmur/patologia , Proteína-5 Relacionada a Receptor de Lipoproteína de Baixa Densidade/genética , Proteína-6 Relacionada a Receptor de Lipoproteína de Baixa Densidade/genética , Pessoa de Meia-Idade , Idoso , Predisposição Genética para Doença , Proteína Wnt1/genética , Proteína Wnt3A/genética , Via de Sinalização Wnt/genética , Osteoporose/genética , Osteoporose/patologia , Doenças Ósseas/genética , Estudos de Casos e ControlesRESUMO
Osteoporosis (OP) is a bone disease which affects a number of post-menopausal females and puts many at risk for fractures. A large number of patients are taking bisphosphonates (BPs) to treat their OP and a rare complication is the development of atypical femoral fractures (AFF). No real explanations for the mechanisms underlying the basis for development of where AFF develop while on BPs has emerged. The present hypothesis will discuss the possibility that part of the risk for an AFF is a secondary effect of BPs on a subset of vascular cells in a genetically at-risk population, leading to localized deregulation of the endothelial cell (EC)-bone cell-matrix units in nutrient channels/canals of the femur and increased risk for AFF. This concept of targeting ECs is consistent with location of AFF in the femur, the bilateral risk for occurrence of AFF, and the requirement for long term exposure to the drugs.
Assuntos
Fraturas do Fêmur , Osteoporose , Feminino , Humanos , Difosfonatos/efeitos adversos , Fraturas do Fêmur/induzido quimicamente , Fraturas do Fêmur/complicações , Fraturas do Fêmur/epidemiologia , Osteoporose/tratamento farmacológico , Osteoporose/induzido quimicamente , Osteoporose/complicações , Fatores de RiscoRESUMO
Autophagy may play an important role in the occurrence and development of glucocorticoid-induced osteonecrosis of the femoral head (GC-ONFH). Lithium is a classical autophagy regulator, and lithium can also activate osteogenic pathways, making it a highly promising therapeutic agent for GC-ONFH. We aimed to evaluate the potential therapeutic effect of lithium on GC-ONFH. For in vitro experiments, primary osteoblasts of rats were used for investigating the underlying mechanism of lithium's protective effect on GC-induced autophagy levels and osteogenic activity dysfunction. For in vivo experiments, a rat model of GC-ONFH was used for evaluating the therapeutic effect of oral lithium on GC-ONFH and underlying mechanism. Findings demonstrated that GC over-activated the autophagy of osteoblasts and reduced their osteogenic activity. Lithium reduced the over-activated autophagy of GC-treated osteoblasts through PI3K/AKT/mTOR signalling pathway and increased their osteogenic activity. Oral lithium reduced the osteonecrosis rates in a rat model of GC-ONFH, and restrained the increased expression of autophagy related proteins in bone tissues through PI3K/AKT/mTOR signalling pathway. In conclusion, lithium can restrain over-activated autophagy by activating PI3K/AKT/mTOR signalling pathway and up-regulate the expression of genes for bone formation both in GC induced osteoblasts and in a rat model of GC-ONFH. Lithium may be a promising therapeutic agent for GC-ONFH. However, the role of autophagy in the pathogenesis of GC-ONFH remains controversial. Studies are still needed to further explore the role of autophagy in the pathogenesis of GC-ONFH, and the efficacy of lithium in the treatment of GC-ONFH and its underlying mechanisms.
Assuntos
Autofagia , Necrose da Cabeça do Fêmur , Glucocorticoides , Lítio , Osteoblastos , Transdução de Sinais , Serina-Treonina Quinases TOR , Animais , Autofagia/efeitos dos fármacos , Glucocorticoides/farmacologia , Glucocorticoides/efeitos adversos , Ratos , Necrose da Cabeça do Fêmur/induzido quimicamente , Necrose da Cabeça do Fêmur/patologia , Necrose da Cabeça do Fêmur/tratamento farmacológico , Necrose da Cabeça do Fêmur/metabolismo , Serina-Treonina Quinases TOR/metabolismo , Transdução de Sinais/efeitos dos fármacos , Lítio/farmacologia , Osteoblastos/efeitos dos fármacos , Osteoblastos/metabolismo , Masculino , Osteogênese/efeitos dos fármacos , Ratos Sprague-Dawley , Proteínas Proto-Oncogênicas c-akt/metabolismo , Modelos Animais de Doenças , Fosfatidilinositol 3-Quinases/metabolismo , Cabeça do Fêmur/patologia , Cabeça do Fêmur/efeitos dos fármacos , Cabeça do Fêmur/metabolismo , Osteonecrose/induzido quimicamente , Osteonecrose/patologia , Osteonecrose/tratamento farmacológico , Osteonecrose/metabolismo , Osteonecrose/prevenção & controleRESUMO
Glucocorticoids induced osteonecrosis of the femoral head (GIONFH) is a devastating orthopedic disease. Previous studies suggested that connexin43 is involved in the process of osteogenesis and angiogenesis. However, the role of Cx43 potentiates in the osteogenesis and angiogenesis of bone marrow-derived stromal stem cells (BMSCs) in GIONFH is still not investigated. In this study, BMSCs were isolated and transfected with green fluorescent protein or the fusion gene encoding GFP and Cx43. The osteogenic differentiation of BMSCs were detected after transfected with Cx43. In addition, the migration abilities and angiogenesis of human umbilical vein endothelial cells (HUVECs) were been detected after induced by transfected BMSCs supernatants in vitro. Finally, we established GC-ONFH rat model, then, a certain amount of transfected or controlled BMSCs were injected into the tibia of the rats. Immunohistological staining and micro-CT scanning results showed that the transplanted experiment group had significantly promoted more bone regeneration and vessel volume when compared with the effects of the negative or control groups. This study demonstrated for the first time that the Cx43 overexpression in BMSCs could promote bone regeneration as seen in the osteogenesis and angiogenesis process, suggesting that Cx43 may serve as a therapeutic gene target for GIONFH treatment.
Assuntos
Necrose da Cabeça do Fêmur , Glucocorticoides , Ratos , Humanos , Animais , Glucocorticoides/efeitos adversos , Glucocorticoides/metabolismo , Osteogênese , Conexina 43/metabolismo , Cabeça do Fêmur/metabolismo , Cabeça do Fêmur/patologia , Necrose da Cabeça do Fêmur/induzido quimicamente , Necrose da Cabeça do Fêmur/patologia , Necrose da Cabeça do Fêmur/terapia , Ratos Sprague-Dawley , Regeneração Óssea , Diferenciação Celular , Células Endoteliais da Veia Umbilical Humana/metabolismo , Células Endoteliais da Veia Umbilical Humana/patologiaRESUMO
With the prevalence of coronavirus disease 2019, the administration of glucocorticoids (GCs) has become more widespread. Treatment with high-dose GCs leads to a variety of problems, of which steroid-induced osteonecrosis of the femoral head (SONFH) is the most concerning. Since hypoxia-inducible factor 1α (HIF-1α) is a key factor in cartilage development and homeostasis, it may play an important role in the development of SONFH. In this study, SONFH models were established using methylprednisolone (MPS) in mouse and its proliferating chondrocytes to investigate the role of HIF-1α in cartilage differentiation, extracellular matrix (ECM) homeostasis, apoptosis and glycolysis in SONFH mice. The results showed that MPS successfully induced SONFH in vivo and vitro, and MPS-treated cartilage and chondrocytes demonstrated disturbed ECM homeostasis, significantly increased chondrocyte apoptosis rate and glycolysis level. However, compared with normal mice, not only the expression of genes related to collagens and glycolysis, but also chondrocyte apoptosis did not demonstrate significant differences in mice co-treated with MPS and HIF-1α inhibitor. And the effects observed in HIF-1α activator-treated chondrocytes were similar to those induced by MPS. And HIF-1α degraded collagens in cartilage by upregulating its downstream target genes matrix metalloproteinases. The results of activator/inhibitor of endoplasmic reticulum stress (ERS) pathway revealed that the high apoptosis rate induced by MPS was related to the ERS pathway, which was also affected by HIF-1α. Furthermore, HIF-1α affected glucose metabolism in cartilage by increasing the expression of glycolysis-related genes. In conclusion, HIF-1α plays a vital role in the pathogenesis of SONFH by regulating ECM homeostasis, chondrocyte apoptosis, and glycolysis.
Assuntos
Apoptose , Cartilagem , Condrócitos , Glucocorticoides , Glicólise , Homeostase , Subunidade alfa do Fator 1 Induzível por Hipóxia , Metilprednisolona , Animais , Masculino , Camundongos , Apoptose/efeitos dos fármacos , Cartilagem/metabolismo , Cartilagem/patologia , Cartilagem/efeitos dos fármacos , Condrócitos/metabolismo , Condrócitos/efeitos dos fármacos , Condrócitos/patologia , Modelos Animais de Doenças , Matriz Extracelular/metabolismo , Cabeça do Fêmur/patologia , Cabeça do Fêmur/metabolismo , Necrose da Cabeça do Fêmur/induzido quimicamente , Necrose da Cabeça do Fêmur/patologia , Necrose da Cabeça do Fêmur/metabolismo , Necrose da Cabeça do Fêmur/genética , Glucocorticoides/efeitos adversos , Glucocorticoides/farmacologia , Glicólise/efeitos dos fármacos , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Subunidade alfa do Fator 1 Induzível por Hipóxia/genética , Metilprednisolona/efeitos adversos , Metilprednisolona/farmacologia , Camundongos Endogâmicos C57BLRESUMO
Copy-number variations (CNVs) are a common cause of congenital limb malformations and are interpreted primarily on the basis of their effect on gene dosage. However, recent studies show that CNVs also influence the 3D genome chromatin organization. The functional interpretation of whether a phenotype is the result of gene dosage or a regulatory position effect remains challenging. Here, we report on two unrelated families with individuals affected by bilateral hypoplasia of the femoral bones, both harboring de novo duplications on chromosome 10q24.32. The â¼0.5 Mb duplications include FGF8, a key regulator of limb development and several limb enhancer elements. To functionally characterize these variants, we analyzed the local chromatin architecture in the affected individuals' cells and re-engineered the duplications in mice by using CRISPR-Cas9 genome editing. We found that the duplications were associated with ectopic chromatin contacts and increased FGF8 expression. Transgenic mice carrying the heterozygous tandem duplication including Fgf8 exhibited proximal shortening of the limbs, resembling the human phenotype. To evaluate whether the phenotype was a result of gene dosage, we generated another transgenic mice line, carrying the duplication on one allele and a concurrent Fgf8 deletion on the other allele, as a control. Surprisingly, the same malformations were observed. Capture Hi-C experiments revealed ectopic interaction with the duplicated region and Fgf8, indicating a position effect. In summary, we show that duplications at the FGF8 locus are associated with femoral hypoplasia and that the phenotype is most likely the result of position effects altering FGF8 expression rather than gene dosage effects.
Assuntos
Duplicação Cromossômica , Cromossomos Humanos Par 10/química , Variações do Número de Cópias de DNA , Fator 8 de Crescimento de Fibroblasto/genética , Deformidades Congênitas das Extremidades Inferiores/genética , Adolescente , Alelos , Animais , Sistemas CRISPR-Cas , Pré-Escolar , Cromatina/química , Cromatina/metabolismo , Cromossomos Humanos Par 10/metabolismo , Elementos Facilitadores Genéticos , Família , Feminino , Fêmur/anormalidades , Fêmur/diagnóstico por imagem , Fêmur/metabolismo , Fator 8 de Crescimento de Fibroblasto/metabolismo , Edição de Genes , Heterozigoto , Humanos , Lactente , Deformidades Congênitas das Extremidades Inferiores/diagnóstico por imagem , Deformidades Congênitas das Extremidades Inferiores/metabolismo , Deformidades Congênitas das Extremidades Inferiores/patologia , Masculino , Camundongos , Camundongos Transgênicos , Linhagem , FenótipoRESUMO
BACKGROUND: Osteoclast hyperactivation due to the pathological overproduction of reactive oxygen species (ROS) stimulated by glucocorticoids (GCs) is one of the key drivers behind glucocorticoid-induced osteonecrosis of the femoral head (GIONFH). The insulin degrading enzyme (IDE), a conserved Zn2+ metallo-endopeptidase, facilitates the DNA binding of glucocorticoid receptor and plays a substantial role in steroid hormone-related signaling pathways. However, the potential role of IDE in the pathogenesis of GIONFH is yet undefined. METHODS: In this study, we employed network pharmacology and bioinformatics analysis to explore the impact of IDE inhibition on GIONFH with 6bK as an inhibitory agent. Further evidence was collected through in vitro osteoclastogenesis experiments and in vivo evaluations involving methylprednisolone (MPS)-induced GIONFH mouse model. RESULTS: Enrichment analysis indicated a potential role of 6bK in redox regulation amid GIONFH development. In vitro findings revealed that 6bK could attenuate GCs-stimulated overactivation of osteoclast differentiation by interfering with the transcription and expression of key osteoclastic genes (Traf6, Nfatc1, and Ctsk). The use of an H2DCFDA probe and subsequent WB assays introduced the inhibitory effects of 6bK on osteoclastogenesis, linked with the activation of the nuclear factor erythroid-derived 2-like 2 (Nrf2)-mediated antioxidant system. Furthermore, Micro-CT scans validated that 6bK could alleviate GIONFH in MPS-induced mouse models. CONCLUSIONS: Our findings suggest that 6bK suppresses osteoclast hyperactivity in GCs-rich environment. This is achieved by reducing the accumulation of intracellular ROS via promoting the Nrf2-mediated antioxidant system, thus implying that IDE could be a promising therapeutic target for GIONFH.
Assuntos
Modelos Animais de Doenças , Necrose da Cabeça do Fêmur , Glucocorticoides , Fator 2 Relacionado a NF-E2 , Osteoclastos , Animais , Fator 2 Relacionado a NF-E2/metabolismo , Camundongos , Osteoclastos/metabolismo , Osteoclastos/efeitos dos fármacos , Necrose da Cabeça do Fêmur/metabolismo , Necrose da Cabeça do Fêmur/induzido quimicamente , Necrose da Cabeça do Fêmur/etiologia , Necrose da Cabeça do Fêmur/patologia , Antioxidantes/metabolismo , Antioxidantes/farmacologia , Espécies Reativas de Oxigênio/metabolismo , Masculino , Osteogênese/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos , Osteonecrose/metabolismo , Osteonecrose/induzido quimicamenteRESUMO
Steroid (glucocorticoid)-induced necrosis of the femoral head (SONFH) represents a prevalent, progressive, and challenging bone and joint disease characterized by diminished osteogenesis and angiogenesis. Omaveloxolone (OMA), a semi-synthetic oleanocarpane triterpenoid with antioxidant, anti-inflammatory, and osteogenic properties, emerges as a potential therapeutic agent for SONFH. This study investigates the therapeutic impact of OMA on SONFH and elucidates its underlying mechanism. The in vitro environment of SONFH cells was simulated by inducing human bone marrow mesenchymal stem cells (hBMSCs) and human umbilical vein endothelial cells (HUVECs) using dexamethasone (DEX).Various assays, including CCK-8, alizarin red staining, Western blot, qPCR, immunofluorescence, flow cytometry, and TUNNEL, were employed to assess cell viability, STING/NF-κB signaling pathway-related proteins, hBMSCs osteogenesis, HUVECs migration, angiogenesis, and apoptosis. The results demonstrate that OMA promotes DEX-induced osteogenesis, HUVECs migration, angiogenesis, and anti-apoptosis in hBMSCs by inhibiting the STING/NF-κB signaling pathway. This experimental evidence underscores the potential of OMA in regulating DEX-induced osteogenesis, HUVECs migration, angiogenesis, and anti-apoptosis in hBMSCs through the STING/NF-κB pathway, thereby offering a promising avenue for improving the progression of SONFH.
Assuntos
Necrose da Cabeça do Fêmur , Glucocorticoides , Neovascularização Fisiológica , Osteogênese , Humanos , Angiogênese , Apoptose/efeitos dos fármacos , Movimento Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Células Cultivadas , Dexametasona/farmacologia , Cabeça do Fêmur/patologia , Cabeça do Fêmur/efeitos dos fármacos , Cabeça do Fêmur/irrigação sanguínea , Cabeça do Fêmur/metabolismo , Necrose da Cabeça do Fêmur/induzido quimicamente , Necrose da Cabeça do Fêmur/patologia , Necrose da Cabeça do Fêmur/tratamento farmacológico , Necrose da Cabeça do Fêmur/metabolismo , Glucocorticoides/farmacologia , Células Endoteliais da Veia Umbilical Humana/efeitos dos fármacos , Células-Tronco Mesenquimais/efeitos dos fármacos , Células-Tronco Mesenquimais/metabolismo , Células-Tronco Mesenquimais/citologia , Neovascularização Fisiológica/efeitos dos fármacos , NF-kappa B/metabolismo , Osteogênese/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos , Triterpenos/farmacologiaRESUMO
With the substantial increase in the overuse of glucocorticoids (GCs) in clinical medicine, the prevalence of glucocorticoid-induced osteonecrosis of the femoral head (GC-ONFH) continues to rise in recent years. However, the optimal treatment for GC-ONFH remains elusive. Rotating magnetic field (RMF), considered as a non-invasive, safe and effective approach, has been proved to have multiple beneficial biological effects including improving bone diseases. To verify the effects of RMF on GC-ONFH, a lipopolysaccharide (LPS) and methylprednisolone (MPS)-induced invivo rat model, and an MPS-induced invitro cell model have been employed. The results demonstrate that RMF alleviated bone mineral loss and femoral head collapse in GC-ONFH rats. Meanwhile, RMF reduced serum lipid levels, attenuated cystic lesions, raised the expression of anti-apoptotic proteins and osteoprotegerin (OPG), while suppressed the expression of pro-apoptotic proteins and nuclear factor receptor activator-κB (RANK) in GC-ONFH rats. Besides, RMF also facilitated the generation of ALP, attenuated apoptosis and inhibits the expression of pro-apoptotic proteins, facilitated the expression of OPG, and inhibited the expression of RANK in MPS-stimulated MC3T3-E1 cells. Thus, this study indicates that RMF can improve GC-ONFH in rat and cell models, suggesting that RMF have the potential in the treatment of clinical GC-ONFH.
Assuntos
Diferenciação Celular , Necrose da Cabeça do Fêmur , Glucocorticoides , Osteoblastos , Ratos Sprague-Dawley , Animais , Osteoblastos/metabolismo , Osteoblastos/efeitos dos fármacos , Necrose da Cabeça do Fêmur/induzido quimicamente , Necrose da Cabeça do Fêmur/patologia , Necrose da Cabeça do Fêmur/metabolismo , Necrose da Cabeça do Fêmur/terapia , Ratos , Diferenciação Celular/efeitos dos fármacos , Masculino , Campos Magnéticos , Magnetoterapia/métodos , Cabeça do Fêmur/patologia , Cabeça do Fêmur/metabolismo , Modelos Animais de Doenças , Rotação , CamundongosRESUMO
Acute thrombosis and its complications are leading global causes of disability and death. Existing thrombolytic drugs, such as alteplase and urokinase (UK), carry a significant bleeding risk during clinical treatments. Thus, the development of a novel thrombolysis strategy is of utmost urgency. Based on the previous work, the hollow structure of microcapsules (MC) is fabricated. Subsequently, armor-piercing MC, known as Fucoidan/S-Nitrosoglutathione/Melanin@MC (FGM@MC) is obtained, using a layer-by-layer (LBL) self-assembly method. Utilizing near-infrared (NIR) light as a trigger, the FGM@MC demonstrated photothermal thrombolysis at the site of thrombus due to its stable and outstanding photothermal properties. Simultaneously, photothermal stimulation leads to the release of a significant amount of nitric oxide from the FGM@MC, resulting in cavitation effects for mechanical thrombolysis. In vivo experiments confirmed the stable release of nitric oxide under NIR light irradiation. Treatment of femoral vein thrombosis in rats revealed that the thrombolytic effectiveness of FGM@MC+NIR (53.71%) is comparable to that of UK (59.70%). Notably, FGM@MC does not interfere with the coagulation function of rats and exhibits a favorable safety profile. In conclusion, this study demonstrates that the drug-free armor-piercing microcapsule has significant potential in the treatment of thrombosis, offering a safe and effective alternative to traditional thrombolytic therapies.
RESUMO
OBJECTIVES: Patients with antiphospholipid syndrome (APS) carry a substantial burden of cardiovascular disease and subclinical atherosclerosis. We aimed to assess a 7-year follow-up atherosclerotic plaque progression in APS patients vs diabetes mellitus (DM) and healthy controls (HC). METHODS: Eighty-six patients with thrombotic APS, 86 with DM and 86 HC (all age- and sex-matched) who underwent a baseline ultrasound of carotid and femoral arteries were invited for a 7-year follow-up ultrasonography examination. We compared atherosclerosis progression among the three groups and examined determinants of plaque progression in APS patients. RESULTS: Sixty-four APS patients (75% females, 43.8% with primary APS), 58 patients with DM and 66 HC were included in the 7-year ultrasound re-evaluation. New plaque was detected in 51.6%, 36.2% and 25.8% of APS, DM and HC subjects, respectively. After adjusting for traditional cardiovascular risk factors (CVRFs) and baseline plaque presence, APS patients showed a 3-fold (OR = 3.07, p= 0.007) higher risk for atherosclerosis progression vs HC and 2-fold (OR = 2.25, p= 0.047) higher risk than DM patients. In multivariate analysis in the APS group, plaque progression was independently associated with systemic lupus erythematosus (SLE) co-existence (OR = 7.78, p= 0.005) and number of CVRFs (OR = 3.02, p= 0.002), after adjusting for disease-related parameters and CVRF-related medications. Sustained low-density lipoprotein target attainment reduced plaque progression risk (OR = 0.34, p= 0.021). CONCLUSION: Half of APS patients develop new atherosclerotic plaques over a 7-year follow-up, having a three-times higher risk vs HC. Concomitant SLE and number of traditional CVRFs are associated with plaque progression, supporting the need for thorough CVRF assessment and control.
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INTRODUCTION: Transvenous lead extractions (TLEs) for cardiac implantable electronic device complications often encounter difficulties with strong adhesions to the myocardium or vessels. In this report, we introduce a novel "Four-Stage Rocket" technique for effective TLE in cases where conventional methods fail. METHODS AND RESULTS: Two challenging cases where conventional TLE methods failed were treated using a combination of four devices: Needle's Eye Snare, Agilis NxT Steerable Introducer, GlideLight Laser sheath, and GORE® DrySeal Flex Introducer sheath, employed via the inferior vena cava. The "Four-Stage Rocket" technique successfully detached firmly adhered leads near the tricuspid valve annulus, where the traditional superior vena cava approach was inadequate. CONCLUSION: The "Four-Stage Rocket" technique offers a potential alternative in complex TLE cases, aligning the laser direction with the adhesion detachment and reducing the tissue damage risk.
Assuntos
Desfibriladores Implantáveis , Remoção de Dispositivo , Veia Femoral , Lasers , Marca-Passo Artificial , Humanos , Remoção de Dispositivo/instrumentação , Remoção de Dispositivo/métodos , Masculino , Idoso , Resultado do Tratamento , Feminino , Pessoa de Meia-Idade , Cateterismo Periférico/instrumentaçãoRESUMO
Femoroacetabular impingement (FAI), characterized by a pathological contact between the proximal femur and acetabulum, is a common precursor of hip osteoarthritis. Cam morphology is a bony prominence that causes FAI and frequently forms on the anterosuperior femoral head-neck junction. Despite anatomical consensus regarding the femoral head-neck junction as a boundary area covered by the articular cartilage and joint capsule, it remains unclear whether the joint capsule is continuous with the anterosuperior articular cartilage. For the anatomical consideration of cam morphology formation, this study aimed to investigate the histological characteristics of the capsular attachment on the anterosuperior femoral head-neck junction, particularly focusing on the presence or absence of continuity of the joint capsule to the articular cartilage. A total of 21 anterosuperior regions (seven hips each for the 12:00, 1:30, and 3:00 positions) from seven hips (three males and four females; mean age at death, 68.7 years) were histologically analyzed in this study for quantitative evaluation of the capsular thickness using histological sections stained with Masson's trichrome, as well as qualitative evaluation of the capsular attachment. The present study showed that the joint capsule, which folded proximally to the femoral head-neck junction from the recess, exhibited a blend of the fibrous and synovial regions. Notably, it not only continued with the superficial layer of the articular cartilage, but also attached to the articular cartilage via the fibrocartilage. This continuous region was relatively fibrous with dense connective tissue running in the longitudinal direction. The capsular thickness at the recess point (mean, 1.7 ± 0.9 mm) and those at the distal end of the articular cartilage (0.35 ± 0.16 mm) were significantly greater than the control value for the most superficial layer thickness of the articular cartilage (0.019 ± 0.003 mm) (Dunnett's T3, both p-value <0.001). Based on the fibrous continuity between the joint capsule and articular cartilage and its thickness, this study suggests the anatomical possibility that some mechanical stress can be transmitted from the joint capsule to the articular cartilage at the frequent sites of cam morphology.
Assuntos
Impacto Femoroacetabular , Cabeça do Fêmur , Colo do Fêmur , Cápsula Articular , Humanos , Masculino , Feminino , Impacto Femoroacetabular/patologia , Cabeça do Fêmur/patologia , Cápsula Articular/patologia , Idoso , Colo do Fêmur/patologia , Pessoa de Meia-Idade , Cartilagem Articular/patologia , Articulação do Quadril/patologiaRESUMO
OBJECTIVE: Common femoral endarterectomy (CFE) comprises the current standard-of-care for symptomatic common femoral artery occlusive disease. Although it provides effective inflow revascularization via a single incision, it remains an invasive procedure in an often-frail patient population. The purpose of this retrospective clinical study was to assess the morbidity and mortality of CFE in a contemporary cohort. METHODS: Consecutive CFEs performed at a large, urban hospital were reviewed. Six-month mortality, local complications (hematoma, lymphatic leak, pseudoaneurysm, wound infection, and/or dehiscence), and systemic complications were analyzed using univariate and multivariate analyses. RESULTS: A total of 129 isolated CFEs were performed over 7 years for claudication (36%), rest pain (16%), tissue loss (29%), or acute on chronic limb ischemia (21%). Mean age was 75 ± 9 years, and 68% of patients were male. Comorbidities were prevalent, including coronary artery disease (54%), diabetes (41%), chronic pulmonary disease (25%), and congestive heart failure (22%). The majority of CFEs were performed under general anesthesia (98%) with patch angioplasty using bovine pericardium (73% vs 27% Dacron). Twenty-two patients (17%) sustained local complications following the procedure; their occurrence was significantly associated with obesity (P = .002) but no technical or operative factors. Nineteen patients (15%) sustained serious systemic complications; their occurrence was significantly associated with chronic limb-threatening ischemia (P < .001), and a high American Society of Anesthesiologists (ASA) class (P = .002). By 6 months, 17 patients (13%) had died. Being on dialysis, presenting with chronic limb-threatening ischemia, and being in a high ASA class at the time of operation were all associated with 6-month mortality; a high ASA class at the time of operation was independently predictive of mortality (odds ratio, 3.08; 95% confidence interval, 1.03-9.24; P = .044). CONCLUSIONS: Although commonly performed, CFE is not a benign vascular procedure. Disease presentation, anesthetic risk, and expected longevity play an important role in clinical outcomes. Evolving endovascular approaches to the common femoral artery could serve to reduce morbidity and mortality in the future.
Assuntos
Endarterectomia , Artéria Femoral , Humanos , Masculino , Feminino , Endarterectomia/efeitos adversos , Endarterectomia/mortalidade , Idoso , Estudos Retrospectivos , Artéria Femoral/cirurgia , Fatores de Risco , Idoso de 80 Anos ou mais , Resultado do Tratamento , Fatores de Tempo , Comorbidade , Complicações Pós-Operatórias/mortalidade , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/epidemiologia , Claudicação Intermitente/cirurgia , Claudicação Intermitente/mortalidade , Medição de Risco , Doença Arterial Periférica/cirurgia , Doença Arterial Periférica/mortalidade , Isquemia/mortalidade , Isquemia/cirurgia , Hospitais Urbanos/estatística & dados numéricos , Arteriopatias Oclusivas/cirurgia , Arteriopatias Oclusivas/mortalidade , Pessoa de Meia-IdadeRESUMO
OBJECTIVE: Superficial femoral artery (SFA) stenting is a common treatment for peripheral artery disease. It is effective in the short term; however, in-stent restenosis (ISR) limits long-term success. Surveillance with duplex ultrasound (DUS) can identify patients who develop ISR leading to early reintervention, but data to support this practice is sparce. The purpose of this study was to evaluate whether surveillance and subsequent reintervention improves outcomes in patients with SFA stents. METHODS: A single-center, retrospective study was performed with patients undergoing SFA stenting between 2005 and 2020 who had a follow-up with DUS. Five groups were identified based on the presence of ISR on DUS (ISR vs no ISR [NISR]), recurrence of symptoms (symptomatic [SX] vs asymptomatic [ASX]), and if any reintervention was performed (reintervention [R] vs no reintervention [NR]): (1) ISR+SX+R; (2) ISR+SX+NR; (3) ISR+ASX+R; (4) ISR+ASX+NR; and (5) NISR+NR. The primary endpoint was amputation-free survival, and the secondary endpoint was patency. Predictors of mortality and surveillance were identified by multivariable logistic regressions and Cox multivariate regression models. Survival curves were presented as Kaplan-Meier plots using log-rank test for subgroup comparison. RESULTS: Two hundred fifty-seven patients were included in the analysis. The indication for intervention was claudication in 28% and chronic limb-threatening ischemia in 72%. A total of 161 patients (63%) underwent reintervention for ISR. Of patients who had restenosis on DUS, those who were symptomatic and did not undergo reintervention (ISR+SX+NR) did the worst, with 50% amputation rate. In contrast, those who were asymptomatic but did undergo reintervention (ISR+ASX+R) had the lowest amputation rate of 13%. Active smoking was a predictor of both loss of patency and amputation (1.72; 95% confidence interval [CI], 1.00-2.98; P = .050; 3.55; 95% CI, 1.53-8.25; P = .003). Post procedure dual antiplatelet therapy had a positive association with limb salvage (hazard ratio [HR], 0.23; 95% CI, 0.09-0.58; P = .001), whereas diabetes (HR, 2.61; 95% CI, 1.21-6.01; P = .019), stent occlusion (HR, 17.0; 95% CI, 5.93-63.1; P < .001), and chronic limb-threatening ischemia presentations (HR, 4.31; 95% CI, 1.86-11.7; P=.002) were negatively associated with limb salvage. CONCLUSIONS: Routine surveillance DUS and subsequent reintervention on ISR after SFA stenting is associated with improved patency and amputation-free survival. Surveillance DUS should be routine for patients after stenting, with reintervention strongly considered if ISR is identified for both symptomatic and asymptomatic.
Assuntos
Artéria Femoral , Doença Arterial Periférica , Humanos , Artéria Femoral/diagnóstico por imagem , Artéria Femoral/cirurgia , Isquemia Crônica Crítica de Membro , Estudos Retrospectivos , Resultado do Tratamento , Fatores de Risco , Grau de Desobstrução Vascular , Stents , Doença Arterial Periférica/diagnóstico por imagem , Doença Arterial Periférica/terapia , Constrição PatológicaRESUMO
OBJECTIVE: The aim of this study was to report the results of a prospective, single-arm, registry-based study assessing the safety and performance of a paclitaxel drug-coated balloon (DCB) for the treatment of superficial femoral artery (SFA) or popliteal artery in-stent restenosis (ISR) in a United States population. METHODS: We conducted a prospective, non-randomized, multi-center, single-arm, post-market registry of the IN.PACT Admiral DCB for the treatment of ISR lesions in the SFA or popliteal artery at 43 sites within the Society for Vascular Surgery (SVS) Vascular Quality Initiative (VQI) Registry from December 2016 to January 2020. Clinical outcomes were assessed at 12, 24, and 36 months. The primary endpoint was target lesion revascularization at 12 months. Secondary endpoints included technical success, target vessel revascularization, major limb amputation, and all-cause mortality. Results are presented as survival probabilities based on Kaplan-Meier survival estimates. RESULTS: Patients (N = 300) were 58% male, with a mean age of 68 ± 10 years. Diabetes was present in 56%, 80% presented with claudication, and 20% with rest pain. Lesions included ISR of the SFA in 68%, SFA-popliteal in 26%, and popliteal arteries in 7%. The mean lesion length was 17.8 ± 11.8 cm. Lesions were categorized as occlusions in 43% (mean occluded length, 16 ± 10 cm). TASC type was A (17%), B (29%), C (38%), and D (15%). Technical success was 99%. Re-stenting was performed in 5% and thrombolysis in 0.6% of patients. Kaplan-Meier estimates for freedom from target lesion revascularization were 90%, 72%, and 62% at 12, 24, and 36 months. Freedom from target vessel revascularization was 88%, 68%, and 59% and freedom from major target limb amputation was 99.6%, 98.9%, and 98.9%, respectively, at 12, 24, and 36 months. Survival was 95%, 89%, and 85% at 12, 24, and 36 months. CONCLUSIONS: This post-market registry-based study shows promising results in treating femoral-popliteal ISR with paclitaxel DCB in comparison to the results of plain balloon angioplasty reported in the literature. These results demonstrate the ability of the SVS VQI to conduct post-market evaluation of peripheral devices in partnership with industry and federal regulators.
Assuntos
Angioplastia com Balão , Reestenose Coronária , Doença Arterial Periférica , Humanos , Masculino , Pessoa de Meia-Idade , Idoso , Feminino , Artéria Femoral/diagnóstico por imagem , Artéria Poplítea/diagnóstico por imagem , Paclitaxel/efeitos adversos , Estudos Prospectivos , Doença Arterial Periférica/diagnóstico por imagem , Doença Arterial Periférica/terapia , Salvamento de Membro , Fatores de Tempo , Constrição Patológica , Sistema de Registros , Materiais Revestidos Biocompatíveis , Resultado do TratamentoRESUMO
OBJECTIVE: Adverse iliofemoral anatomy may preclude complex endovascular aortic aneurysm repair (EVAR). In our practice, staged iliofemoral endoconduits (ECs) are planned prior to complex EVAR to improve vascular access and decrease operative time while allowing the stented vessel to heal. This study describes the long-term results of iliofemoral ECs prior to complex EVAR. METHODS: Between 2012 and 2023, 59 patients (44% male; median age, 75 ± 6 years) underwent ECs before complex EVAR using self-expanding covered stents (Viabahn). For common femoral artery (CFA) disease, ECs were delivered percutaneously from contralateral femoral access and extended into the CFA to preserve the future access site for stent graft delivery. Internal iliac artery patency was maintained when feasible. During complex EVAR, the EC extended into the CFA was directly accessed and sequentially dilated until it could accommodate the endograft. Technical success was defined as successful access, closure, and delivery of the endograft during complex EVAR. Endpoints were vascular injury or EC disruption, secondary interventions, and EC patency. RESULTS: Unilateral EC was performed in 45 patients (76%). ECs were extended into the CFA in 21 patients (35%). Median diameters of the native common iliac, external iliac, and CFA were 7 mm (interquartile range [IQR], 6-8 mm), 6 mm (IQR, 5-7 mm), and 6 mm (IQR, 6-7 mm), respectively. Internal iliac artery was inadvertently excluded in 10 patients (17%). Six patients (10%) had an intraoperative vascular injury during the EC procedure, and six patients (10%) had EC disruption during complex EVAR, including five EC collapses requiring re-stenting and one EC fracture requiring open cut-down and reconstruction with patch angioplasty. In 23 patients (39%), 22 Fr OD devices were used; 20 Fr were used in 22 patients (37%), and 18 Fr in 14 patients (24%). Technical success for accessing EC was 89%. There was no difference in major adverse events at 30 days between the iliac ECs and iliofemoral ECs. Primary patency by Kaplan-Meier estimates at 1, 3, and 5 years were 97.5%, 89%, and 82%, respectively. There was no difference in primary patency between iliac and iliofemoral ECs. Six secondary interventions (10%) were required. The mean follow-up was 34 ± 27 months; no limb loss or amputations occurred during the follow-up. CONCLUSIONS: ECs improve vascular access, and their use prior to complex EVAR is associated with low rates of vascular injury, high technical success, and optimal long-term patency. Complex EVAR procedures can be performed percutaneously by accessing the EC directly under ultrasound guidance and using sequential dilation to avoid EC disruption.
Assuntos
Implante de Prótese Vascular , Prótese Vascular , Procedimentos Endovasculares , Artéria Femoral , Artéria Ilíaca , Stents , Grau de Desobstrução Vascular , Humanos , Masculino , Idoso , Feminino , Procedimentos Endovasculares/instrumentação , Procedimentos Endovasculares/efeitos adversos , Resultado do Tratamento , Fatores de Tempo , Implante de Prótese Vascular/instrumentação , Implante de Prótese Vascular/efeitos adversos , Idoso de 80 Anos ou mais , Artéria Femoral/cirurgia , Artéria Femoral/fisiopatologia , Artéria Femoral/diagnóstico por imagem , Estudos Retrospectivos , Artéria Ilíaca/cirurgia , Artéria Ilíaca/fisiopatologia , Artéria Ilíaca/diagnóstico por imagem , Desenho de Prótese , Aneurisma da Aorta Abdominal/cirurgia , Aneurisma da Aorta Abdominal/diagnóstico por imagem , Aneurisma da Aorta Abdominal/fisiopatologia , Fatores de Risco , Complicações Pós-Operatórias/etiologiaRESUMO
OBJECTIVE: Vascular access is difficult in patients without suitable arm veins and prior graft infections. The use of femoral vein translocation (FVT) to the upper extremity or contralateral lower extremity for hemodialysis access may be associated with low infection rates and high patency rates. FVT is used for patients without central venous occlusion who have failed prior access either owing to graft infection or repetitive graft thrombosis. The largest case series consists of 30 cases. The objective of this study is to determine the infection incidence, primary patency, primary-assisted patency, and secondary patency rates among FVTs. METHODS: A retrospective chart review was performed on all patients who underwent FVT by a single vascular practice over a 10-year period (2013-2023). Study variables included length to last follow-up (months), prior access, prior graft infection, comorbid conditions, primary patency, primary-assisted patency, secondary patency, postoperative steal syndrome, postoperative graft infection, postoperative harvest site complication, and postoperative lower extremity compartment syndrome. RESULTS: A total of 131 FVTs were performed from 2013 to 2023; 126 patients (47% male, 53% female; 76% Black, 24% White) with a mean age of 52 ± 14 years and a mean body mass index of 29 ± 8 had at least 1 month of follow-up and were included for analysis. The median follow-up was 46 months (interqurtile range, 19-72 months). The mean number of prior permanent accesses was 2.5 ± 1.4. Forty-eight percent of patients had prior graft infections. The primary, primary-assisted, and secondary patency rates were 66%, 93%, and 98%, respectively, at 6 months; 43%, 85%, and 96% at 12 months; 25%, 70%, and 92% at 24 months; 16%, 61%, and 88% at 36 months; and 14%, 56%, and 82% at 48 months. Postoperative steal syndrome and postoperative access infection requiring excision was observed 16% and 5% of patients, respectively. Harvest site complications requiring an additional procedure occurred in 19% of cases. Three patients developed lower extremity compartment syndrome postoperatively, requiring fasciotomy. Six patients developed chronic lower extremity edema after femoral vein harvest. The mean procedure time and hospital length of stay were 197 ± 40 minutes and 3.5 ± 2.8 days, respectively. CONCLUSIONS: FVT is associated with low infection rates and high long-term patency rates. Significant postoperative complications include steal syndrome and harvest site complications. FVT remains a viable option for patients who have failed prior access owing to graft infection or repetitive graft thrombosis.
RESUMO
OBJECTIVE: Occlusive disease of the common femoral artery can generate profound lower extremity ischemia as the normal collateral pathways from the profunda to the superficial femoral artery cannot adequately develop. In patients with lifestyle-limiting claudication, isolated common femoral endarterectomy (CFE) is highly effective. Because CFE does not provide direct, in-line flow to the plantar arch, it has been felt to provide inadequate revascularization to patients with chronic limb-threatening ischemia (CLTI). The purpose of this retrospective clinical study was to report and assess the natural history of selected patients with CLTI treated with isolated CFE (without concomitant infrainguinal revascularization). METHODS: Consecutive CFEs performed in a large, urban hospital for CLTI between 2014 and 2021 were reviewed. Patient characteristics, limb, and anatomical stages using the Wound, Ischemia, foot Infection (WIfI) and Global Limb Anatomic Staging System were tabulated. Limb-specific and survival-related end points were analyzed. RESULTS: Fifty-eight patients presenting with CLTI underwent isolated CFE (mean age, 74 ± 10 years; 62% male, 90% current or prior smoker). Comorbidities included diabetes (52%), coronary artery disease (55%), congestive heart failure (22%), and end-stage renal failure on hemodialysis (5%). Patients presented with either rest pain (36%) or tissue loss (64%); the latter group exhibited advanced limb threat (68% in WIfI stage 3 or 4). The majority of patients had associated severe infrainguinal disease (50% Global Limb Anatomic Staging Systems 3). After a median follow-up of 17 months (range, 10-29 months), vascular reintervention was required in 7 patients (12%). One patient (2%) required major limb amputation after presentation in WIfI stage 4 (W3I3fI0). Indeed, WIfI stage 4 was a significant univariate predictor of the need for subsequent infrainguinal bypass (P = .034). CONCLUSIONS: Isolated CFE as primary therapy in highly selected patients with CLTI was safe and effective. Index limb stage is predictive of the need for associated infrainguinal revascularization in this complex population.