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1.
Nucleic Acids Res ; 52(12): 7225-7244, 2024 Jul 08.
Artigo em Inglês | MEDLINE | ID: mdl-38709899

RESUMO

Emerging evidence indicates that arginine methylation promotes the stability of arginine-glycine-rich (RGG) motif-containing RNA-binding proteins (RBPs) and regulates gene expression. Here, we report that post-translational modification of FXR1 enhances the binding with mRNAs and is involved in cancer cell growth and proliferation. Independent point mutations in arginine residues of FXR1's nuclear export signal (R386 and R388) and RGG (R453, R455 and R459) domains prevent it from binding to RNAs that form G-quadruplex (G4) RNA structures. Disruption of G4-RNA structures by lithium chloride failed to bind with FXR1, indicating its preference for G4-RNA structure containing mRNAs. Furthermore, loss-of-function of PRMT5 inhibited FXR1 methylation both in vivo and in vitro, affecting FXR1 protein stability, inhibiting RNA-binding activity and cancer cell growth and proliferation. Finally, the enhanced crosslinking and immunoprecipitation (eCLIP) analyses reveal that FXR1 binds with the G4-enriched mRNA targets such as AHNAK, MAP1B, AHNAK2, HUWE1, DYNC1H1 and UBR4 and controls its mRNA expression in cancer cells. Our findings suggest that PRMT5-mediated FXR1 methylation is required for RNA/G4-RNA binding, which promotes gene expression in cancer cells. Thus, FXR1's structural characteristics and affinity for RNAs preferentially G4 regions provide new insights into the molecular mechanism of FXR1 in oral cancer cells.


Assuntos
Arginina , Proliferação de Células , Proteína-Arginina N-Metiltransferases , Proteínas de Ligação a RNA , Humanos , Proteína-Arginina N-Metiltransferases/metabolismo , Proteína-Arginina N-Metiltransferases/genética , Proteínas de Ligação a RNA/metabolismo , Proteínas de Ligação a RNA/genética , Arginina/metabolismo , Arginina/genética , Metilação , RNA Mensageiro/metabolismo , RNA Mensageiro/genética , Linhagem Celular Tumoral , Ligação Proteica , Quadruplex G , Regulação Neoplásica da Expressão Gênica , Proteínas Repressoras/metabolismo , Proteínas Repressoras/genética , Proteínas Repressoras/química , Processamento de Proteína Pós-Traducional , Neoplasias/genética , Neoplasias/metabolismo , Células HEK293 , Estabilidade Proteica
2.
J Arthroplasty ; 39(3): 831-838, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-37633509

RESUMO

BACKGROUND: The neutrophil-to-lymphocyte ratio (NLR) has shown promising results as a diagnostic tool for periprosthetic joint infection (PJI) after total joint arthroplasty. We conducted a systematic review and meta-analysis to determine the utility of NLR in the diagnosis of PJI. METHODS: We searched PubMed, Scopus, and Web of Science from inception up to 2022 and evaluated the quality of the included literature. RESULTS: Based on the 12 eligible studies, NLR levels were significantly higher in patients who had PJI compared to those who had aseptic loosening (standard mean difference (SMD) = 1.05, 95% Confidence Interval (CI) = 0.71 to 1.40, P < .001). In the subgroup analysis according to type of PJI, NLR levels were significantly higher in patients who had either acute (SMD = 1.04, 95% CI = 0.05 to 2.03, P < .001) or chronic PJI (SMD = 1.08, 95% CI = 0.55 to 1.61, P < .001), compared to those who had aseptic loosening. According to type of arthroplasty, NLR levels were significantly higher in patients who had either total knee arthroplasty (SMD = 1.81, 95% CI = 1.48 to 2.13, P < .001) or total hip arthroplasty (SMD = 1.76, 95% CI = 1.54 to 1.98, P < .001) compared to aseptic loosening. The pooled sensitivity of the 12 studies was 0.73 (95% CI, 0.65 to 0.79), and the pooled specificity was 0.75 (95% CI, 0.71 to 0.78). The pooled positive likelihood ratio, negative likelihood ratio, and diagnostic odds ratio of NLR were 2.94 (95% CI = 2.44 to 3.54), 0.35 (95% CI = 0.27 to 0.46), and 8.26 (95% CI = 5.42 to 12.58), respectively. CONCLUSION: In summary, this meta-analysis indicates that NLR is a reliable marker in the diagnosis of PJI.


Assuntos
Artrite Infecciosa , Artroplastia de Quadril , Artroplastia do Joelho , Infecções Relacionadas à Prótese , Humanos , Infecções Relacionadas à Prótese/diagnóstico , Neutrófilos , Artroplastia do Joelho/efeitos adversos , Artroplastia de Quadril/efeitos adversos , Artrite Infecciosa/diagnóstico , Biomarcadores/análise , Sensibilidade e Especificidade
3.
Surg Technol Int ; 36: 304-308, 2020 May 28.
Artigo em Inglês | MEDLINE | ID: mdl-31821525

RESUMO

INTRODUCTION: The tibial tubercle-trochlear groove (TT-TG) distance is commonly used to evaluate and guide treatment for patellar instability. There is limited data available regarding TT-TG variability based on patient demographics and anthropometric factors. MATERIALS AND METHODS: TT-TG was measured on magnetic resonance imaging (MRI) for 384 consecutive adult patients. Demographic information for the corresponding was then gathered from the medical record and analyzed. Demographic variables analyzed included age, sex, race, height, weight, and body mass index (BMI). RESULTS: Mean TT-TG among the 384 patients was 12.68mm (standard deviation [SD]: 4.13mm, 95% confidence interval [CI] 12.26-13.10mm, range, 3.2-27.0mm), and there was a significant correlation with height (p=0.009), weight (p=0.017), and race (p<0.001). However, there was no significant correlation seen with sex (p=0.854), BMI (p=0.253), or age (p=0.096). Height and African American race were identified as independent predictors of increased TT-TG (p=0.007 and p<0.001, respectively); and females were found to have an increased TT-TG relative to height (p=0.015). CONCLUSION: Tibial tubercle-trochlear groove distance was significantly correlated with race and height in the 384 patients examined. These findings may help explain clinical differences in these patients and help establish "norms" for patients of various ethnic and anthropometric variability.


Assuntos
Articulação Patelofemoral , Demografia , Feminino , Humanos , Instabilidade Articular , Articulação do Joelho , Imageamento por Ressonância Magnética , Tíbia
4.
J Biol Chem ; 292(15): 6039-6046, 2017 04 14.
Artigo em Inglês | MEDLINE | ID: mdl-28193840

RESUMO

Piwi-interacting RNAs (piRNAs) are 26-30-nucleotide germ line-specific small non-coding RNAs that have evolutionarily conserved function in mobile genetic element (transposons) silencing and maintenance of genome integrity. Drosophila Hsp70/90-organizing protein homolog (Hop), a co-chaperone, interacts with piRNA-binding protein Piwi and mediates silencing of phenotypic variations. However, it is not known whether Hop has a direct role in piRNA biogenesis and transposon silencing. Here, we show that knockdown of Hop in the germ line nurse cells (GLKD) of Drosophila ovaries leads to activation of transposons. Hop GLKD females can lay eggs at the same rate as wild-type counterparts, but the eggs do not hatch into larvae. Hop GLKD leads to the accumulation of γ-H2Av foci in the germ line, indicating increased DNA damage in the ovary. We also show that Hop GLKD-induced transposon up-regulation is due to inefficient piRNA biogenesis. Based on these results, we conclude that Hop is a critical component of the piRNA pathway and that it maintains genome integrity by silencing transposons.


Assuntos
Proteínas Argonautas/metabolismo , Elementos de DNA Transponíveis , Proteínas de Drosophila/metabolismo , Inativação Gênica , Células Germinativas/metabolismo , Janus Quinases/metabolismo , Ovário/metabolismo , RNA Interferente Pequeno/biossíntese , Fatores de Transcrição/metabolismo , Animais , Animais Geneticamente Modificados/genética , Animais Geneticamente Modificados/metabolismo , Proteínas Argonautas/genética , Dano ao DNA , Proteínas de Drosophila/genética , Drosophila melanogaster , Feminino , Instabilidade Genômica , Células Germinativas/citologia , Janus Quinases/genética , RNA Interferente Pequeno/genética , Fatores de Transcrição/genética
5.
Ann Vasc Surg ; 29(2): 363.e9-363.e11, 2015 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-25452084

RESUMO

We report a case of cryptococcal aortitis in a 59-year-old man presenting as a symptomatic suprarenal abdominal aortic aneurysm (AAA). The patient underwent repair of his aneurysm using a rifampin-soaked graft with omental wrapping. Intraoperative Gram stains showed yeast organisms, the cultures eventually grew Cryptococcus neoformans with results available 43 days postoperatively. He was started on antifungal therapy intraoperatively and will be on lifelong antifungal treatment. Our case is the first report of cryptoccocal aortitis presenting as a symptomatic AAA; the diagnosis of a true mycotic aneurysm was made intraoperatively.


Assuntos
Aneurisma Infectado/diagnóstico , Aneurisma da Aorta Abdominal/diagnóstico , Aortite/diagnóstico , Criptococose/diagnóstico , Aneurisma Infectado/terapia , Aneurisma da Aorta Abdominal/terapia , Aortite/terapia , Criptococose/terapia , Diagnóstico Diferencial , Humanos , Masculino , Pessoa de Meia-Idade
6.
J Arthroplasty ; 30(5): 758-61, 2015 May.
Artigo em Inglês | MEDLINE | ID: mdl-25583683

RESUMO

Increasing numbers of total joint arthroplasty (TJA) patients have a history, or an active diagnosis, of cancer. We aimed to evaluate the risk of early postoperative complications in these patients. In our series, a history of malignancy was associated with an elevated risk of ischemic cardiac events and postoperative deep vein thrombosis (DVT), while active malignancy was associated with increased respiratory and renal complications, hematoma/seroma formation and early postoperative mortality. Both groups presented increased rates of overall in-hospital complications. Patients with bone metastasis to the hip demonstrated increased DVT and 90-day mortality rates. Cancer patients have increased morbidity and mortality after TJA and should undergo comprehensive medical optimization and adapted thromboprophylaxis.


Assuntos
Artroplastia de Substituição/efeitos adversos , Artropatias/complicações , Neoplasias/complicações , Complicações Pós-Operatórias/etiologia , Trombose Venosa/etiologia , Idoso , Artroplastia de Quadril/efeitos adversos , Artroplastia do Joelho/efeitos adversos , Índice de Massa Corporal , Feminino , Hospitalização , Humanos , Artropatias/cirurgia , Masculino , Pessoa de Meia-Idade , Morbidade , Estudos Retrospectivos , Resultado do Tratamento
7.
Clin Orthop Relat Res ; 472(5): 1489-95, 2014 May.
Artigo em Inglês | MEDLINE | ID: mdl-24615425

RESUMO

BACKGROUND: Elevated temperatures after total joint arthroplasty (TJA) are common and can be a source of anxiety both for the patient and the surgical team. Although such fevers rarely are caused by acute infection, many patients are subjected to extensive testing for elevated body temperature after surgery. We recently implemented a multimodal pain management regimen for TJA, which includes acetaminophen, pregabalin, and celecoxib or toradol, and because some of these medications have antipyrexic properties, it was speculated that this protocol might influence the frequency of postoperative pyrexia. QUESTIONS/PURPOSES: The purpose of this study was to determine whether patients treated under this protocol were less likely to exhibit postoperative fever after primary TJA, compared with a historical control group, and whether they were less likely to receive postoperative testing as part of a fever workup. METHODS: We compared 1484 primary TJAs in which pain was controlled primarily with opioid-based relief from July 2004 to December 2006 with 2417 procedures from July 2009 to December 2011 during which time multimodal agents were used. The same three surgeons were responsible for care in both of these cohorts. Oral temperature readings in the first 5 postoperative days (POD) were drawn from a review of medical records, which also were evaluated for fever workup tests, including urinalysis, urine culture, chest radiograph, and blood culture. Fever was defined by the presence of a temperature measurement over 38.5 °C. Patients having preoperative fever or postoperative fever starting later than POD 5 were excluded. Before surgery, there were no differences between the groups' temperature measurements. RESULTS: Fewer patients developed fever in the multimodal analgesia group than in the control group (5% versus 25%, p < 0.001). Furthermore, fewer patients underwent workup for fever in the multimodal analgesia cohort (1.8% of patients undergoing 155 individual tests) compared with the control cohort (9.8% of patients undergoing 247 individual tests; p < 0.001). CONCLUSIONS: In addition to fewer adverse effects and better pain control, the multimodal analgesia protocol has the hidden benefit of dampening the temperature response to the surgical insult of TJA. The decreased rate of postoperative fever avoids unnecessary anxiety for the patient and the treating team and reduces healthcare resource use occasioned by working up postoperative fever. LEVEL OF EVIDENCE: Level III, therapeutic study. See Guidelines for Authors for a complete description of levels of evidence.


Assuntos
Analgésicos/uso terapêutico , Antipiréticos/uso terapêutico , Artroplastia de Substituição/efeitos adversos , Febre/prevenção & controle , Manejo da Dor/métodos , Dor Pós-Operatória/prevenção & controle , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Regulação da Temperatura Corporal/efeitos dos fármacos , Quimioterapia Combinada , Feminino , Febre/diagnóstico , Febre/etiologia , Febre/fisiopatologia , Humanos , Masculino , Pessoa de Meia-Idade , Dor Pós-Operatória/diagnóstico , Dor Pós-Operatória/etiologia , Estudos Retrospectivos , Fatores de Tempo , Resultado do Tratamento , Adulto Jovem
8.
J Arthroplasty ; 29(3): 501-3, 2014 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-24051240

RESUMO

Tranexamic acid (TA) has been reported to reduce blood loss after total joint arthroplasty; however, the literature is sparse in evaluating its efficacy in simultaneous bilateral total knee arthroplasty (TKA). In this retrospective study of consecutive patients, TA use in bilateral TKA was associated with a significant reduction in perioperative serum hemoglobin drop, as well as allogeneic blood transfusion needs from 50% to 11% of patients. No autologous blood donation or drains were used. There were no venous thromboembolic events reported. Implementation of a systematic intravenous TA protocol in simultaneous bilateral TKA appears highly effective in reducing transfusion requirements, potentially reducing healthcare resource utilization as well as the morbidity and complications associated with allogeneic blood transfusions.


Assuntos
Antifibrinolíticos/administração & dosagem , Artroplastia do Joelho/efeitos adversos , Perda Sanguínea Cirúrgica/prevenção & controle , Hemorragia Pós-Operatória/prevenção & controle , Ácido Tranexâmico/administração & dosagem , Administração Intravenosa , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Hemorragia Pós-Operatória/etiologia , Estudos Retrospectivos , Resultado do Tratamento
9.
J Arthroplasty ; 29(6): 1098-100, 2014 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-24405622

RESUMO

An effort to prevent PJI has led to the development of antimicrobial dressings that support wound healing. We sought to determine whether Aquacel Surgical dressing independently reduces the rate of acute PJI following TJA. A single institution retrospective chart review of 903 consecutive cases who received the Aquacel Surgical dressing and 875 consecutive cases who received standard gauze dressing was conducted to determine the incidence of acute PJI (within 3 months). The incidence of acute PJI is 0.44% in the Aquacel dressing group compared to 1.7% in the standard gauze dressing group (P = 0.005). Multivariate analysis revealed that use of Aquacel dressing was an independent risk factor for reduction of PJI (odds ratio of 0.165, 95% confidence interval: 0.051-0.533). Aquacel Surgical dressing significantly reduces the incidence of acute PJI.


Assuntos
Anti-Infecciosos/administração & dosagem , Artroplastia de Substituição/efeitos adversos , Bandagens , Carboximetilcelulose Sódica/administração & dosagem , Infecções Relacionadas à Prótese/prevenção & controle , Artroplastia de Substituição/métodos , Estudos de Casos e Controles , Humanos , Infecções Relacionadas à Prótese/etiologia , Estudos Retrospectivos , Cicatrização
10.
J Arthroplasty ; 29(6): 1110-3, 2014 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-24530206

RESUMO

Clostridium difficile is an antibiotic-associated gastrointestinal infection that has detrimental consequences. We sought to determine the incidence of C. difficile in TJA patients with postoperative diarrhea, to determine risk factors for C. difficile infection, and to establish the incidence of C. difficile-related complications. Our institutional protocol includes screening for C. difficile in all patients with diarrhea after TJA. We identified 121 such patients over four years with twenty-eight (23%) testing positive for C. difficile. Revision arthroplasty and prolonged postoperative antibiotic use were risk factors for C. difficile infection. With our protocol of screening and immediate treatment of C. difficile positive patients, we found no C. difficile-associated complications.


Assuntos
Artroplastia de Quadril/efeitos adversos , Artroplastia do Joelho/efeitos adversos , Clostridioides difficile , Diarreia/etiologia , Enterocolite Pseudomembranosa/etiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Enterocolite Pseudomembranosa/microbiologia , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Risco
13.
J Exp Orthop ; 11(3): e12088, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38974053

RESUMO

Purpose: This paper investigates the biomechanical benefits of using hybrid constructs that combine cannulated screws with tension band wiring (TBW) cerclage compared to cannulated screws with anterior Variable Angle locking neutralisation plates (VA LNP). These enhancements can bear heavier loads and maintain the repaired patella's integrity, in contrast to traditional methods. Method: Eighteen fresh-frozen human cadaver patellae were carefully fractured transversely at their midpoints using a saw. They were then divided into two groups of nine for subsequent utilisation. Fixation methods included Cannulated Screw Fixation added with either TBW or VA LNP Fixation Technique. Cyclic loading simulations (500 cycles) were conducted to mimic knee motion, tracking fracture displacement with Optotrak. After that, the constructs were secured over a servo-hydraulic testing machine to determine the load-to-failure on axial mode. Results: The average fracture displacement for the anterior neutralisation plate group was 0.09 ± 0.12 mm, compared to 0.77 ± 0.54 mm for the tension band wiring with cannulated screw group after 500 cyclic loading. This result is statistically significant (p = 0.004). The anterior neutralisation plate group exhibited a mean load-to-failure of 1359 ± 21.53 N, whereas the tension band wiring group showed 780.1 ± 22.62 N, resulting in a significant difference between the groups (p = 0.007). Conclusion: This research highlights the superior biomechanical advantage of VA LNP over TBW for treating simple transverse patella fractures with two cannulated screws. It also highlights how the TBW is still a valuable option considering the load-to-failure limit. Level of Evidence: Not Applicable.

14.
Obes Sci Pract ; 10(1): e727, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38187124

RESUMO

Objective: Bariatric procedures have become safer in recent years, warranting new data on long-term costs. This study examined the impact of bariatric procedures on a person's long-term healthcare costs up to 10 years and if it differed by socio-economic status (SES). Methods: This retrospective observational study compared the downstream health care cost of patients with obesity who had undergone bariatric surgery (BS) between 2009 and 2018 to a 1:1 matched group of members with obesity but no surgery. Results: 167,764 individuals from administrative claims data with an obesity diagnosis were included; 83,882 in the BS group and 83,882 in the non-surgical group. In follow-up years 2-10, the BS group was associated with lower total medical healthcare cost compared to the non-surgical group (cost ratios ranged 0.85-0.93, p values < 0.05). When stratifying the BS group by SES quartiles, there were no significant cost differences by SES (cost ratios ranged from 0.96 to 1.05, most p values > 0.05). Conclusions: BS was associated with lower long-term follow-up medical cost and cost savings appeared similar among the SES quartiles in the BS group. The study results may help policy makers and employers in designing benefits and extending coverage for bariatric surgical procedures.

15.
J Orthop Surg Res ; 19(1): 77, 2024 Jan 18.
Artigo em Inglês | MEDLINE | ID: mdl-38233950

RESUMO

Transverse patella fractures, accounting for approximately 1% of Orthopedic injuries, pose intricate challenges due to their vital role in knee mechanics. This study aimed to compare the biomechanical performance of a construct, integrating cannulated screws and an anterior locking neutralization plate, with the conventional tension band wiring technique for treating these fractures. Experimental testing and Finite Element Analysis were employed to evaluate the constructs and gain profound insights into their mechanical behavior. Sixteen cadaveric knees were prepared, and transverse patella fractures were induced at the midpoints using a saw. The plate construct and tension band wire fixation were randomly assigned to the specimens. A cyclic test evaluated the implants' durability and stability, simulating knee movement during extension and flexion. Tensile testing assessed the implants' maximum failure force after cyclic testing, while Finite Element Analysis provided detailed insights into stress distribution and deformation patterns. Statistical analysis was exclusively performed for the experimental data. Results showed the plate enhanced stability with significantly lower deformation (0.09 ± 0.12 mm) compared to wire fixation (0.77 ± 0.54 mm) after 500 cycles (p = 0.004). In tensile testing, the construct also demonstrated higher failure resistance (1359 ± 21.53 N) than wire fixation (780.1 ± 22.62N) (p = 0.007). Finite Element Analysis highlighted distinct stress patterns, validating the construct's superiority. This research presents a promising treatment approach for transverse patella fractures with potential clinical impact and future research prospects. This study presents a promising advancement in addressing the intricate challenges of transverse patella fractures, with implications for refining clinical practice. The construct's improved stability and resistance to failure offer potential benefits in postoperative management and patient outcomes.


Assuntos
Fraturas Ósseas , Traumatismos do Joelho , Fratura da Patela , Humanos , Análise de Elementos Finitos , Cadáver , Fraturas Ósseas/diagnóstico por imagem , Fraturas Ósseas/cirurgia , Fixação Interna de Fraturas/métodos , Parafusos Ósseos , Fios Ortopédicos , Patela/cirurgia , Patela/lesões , Fenômenos Biomecânicos
16.
Front Surg ; 11: 1331902, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38645507

RESUMO

Introduction: The varus and valgus knee deformities result from imbalance in tension between medial and lateral soft tissue compartments. These conditions need to be addressed during total knee arthroplasty (TKA). However, there is no consensus on optimal soft-tissue release techniques for correcting varus and valgus deformities during TKA. We assessed the efficacy of a novel grid-based pie-crusting technique on soft-tissue release. Methods: Cadaver knees were dissected, leaving only the femur and tibia connected by an isolated MCL or the femur and fibula connected by an isolated LCL. Bone cuts were made as performed during primary TKA. Mechanical testing was performed using an MTS machine. A 3D-printed 12-hole grid was placed directly over the MCL and LCL. Using an 18-gauge needle, horizontal in-out perforations were made 3 mm apart. Deformation and stiffness of the ligaments were collected after every 2 perforations. Means were calculated, and regression analyses were performed. Results: A total of 7 MCL and 6 LCL knees were included in our analysis. The mean medial femorotibial (MFT) space increased from 6.018 ± 1.4 mm-7.078 ± 1.414 mm (R2 = 0.937) following 12 perforations. The mean MCL stiffness decreased from 32.15 N/mm-26.57 N/mm (R2 = 0.965). For the LCL group, the mean gap between the femur and fibula increased from 4.287 mm-4.550 mm following 8 perforations. The mean LCL stiffness decreased from 29.955 N/mm-25.851 N/mm. LCL stiffness displayed a strong inverse relationship with the number of holes performed (R2 = 0.988). Discussion: Our results suggest that using this novel grid for pie-crusting of the MCL and LCL allows for gradual lengthening of the ligaments without sacrificing their structural integrity. Our proposed technique may serve as a valuable piece in the soft-tissue release toolkit for orthopaedic surgeons performing TKA in varus and valgus deformed knees.

17.
Cell Mol Immunol ; 21(1): 33-46, 2024 01.
Artigo em Inglês | MEDLINE | ID: mdl-38105293

RESUMO

A novel rheumatoid arthritis (RA) synovial fluid protein, Syntenin-1, and its receptor, Syndecan-1 (SDC-1), are colocalized on RA synovial tissue endothelial cells and fibroblast-like synoviocytes (FLS). Syntenin-1 exacerbates the inflammatory landscape of endothelial cells and RA FLS by upregulating transcription of IRF1/5/7/9, IL-1ß, IL-6, and CCL2 through SDC-1 ligation and HIF1α, or mTOR activation. Mechanistically, Syntenin-1 orchestrates RA FLS and endothelial cell invasion via SDC-1 and/or mTOR signaling. In Syntenin-1 reprogrammed endothelial cells, the dynamic expression of metabolic intermediates coincides with escalated glycolysis along with unchanged oxidative factors, AMPK, PGC-1α, citrate, and inactive oxidative phosphorylation. Conversely, RA FLS rewired by Syntenin-1 displayed a modest glycolytic-ATP accompanied by a robust mitochondrial-ATP capacity. The enriched mitochondrial-ATP detected in Syntenin-1 reprogrammed RA FLS was coupled with mitochondrial fusion and fission recapitulated by escalated Mitofusin-2 and DRP1 expression. We found that VEGFR1/2 and Notch1 networks are responsible for the crosstalk between Syntenin-1 rewired endothelial cells and RA FLS, which are also represented in RA explants. Similar to RA explants, morphological and transcriptome studies authenticated the importance of VEGFR1/2, Notch1, RAPTOR, and HIF1α pathways in Syntenin-1 arthritic mice and their obstruction in SDC-1 deficient animals. Consistently, dysregulation of SDC-1, mTOR, and HIF1α negated Syntenin-1 inflammatory phenotype in RA explants, while inhibition of HIF1α impaired synovial angiogenic imprint amplified by Syntenin-1. In conclusion, since the current therapies are ineffective on Syntenin-1 and SDC-1 expression in RA synovial tissue and blood, targeting this pathway and its interconnected metabolic intermediates may provide a novel therapeutic strategy.


Assuntos
Artrite Reumatoide , Sinoviócitos , Animais , Camundongos , Trifosfato de Adenosina/farmacologia , Angiogênese , Artrite Reumatoide/metabolismo , Células Cultivadas , Células Endoteliais/metabolismo , Fibroblastos/metabolismo , Inflamação/metabolismo , Reprogramação Metabólica , Membrana Sinovial , Sinoviócitos/metabolismo , Sinteninas/genética , Sinteninas/metabolismo , Serina-Treonina Quinases TOR/metabolismo
18.
J Vasc Surg ; 58(5): 1276-82, 2013 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-23830311

RESUMO

BACKGROUND: The most definitive outcome data on lower extremity amputation (LEA) comes from the Veterans Administration (VA) system. Because of the unique nature of VA patients (more chronic disease, greater functional disability, and lower socioeconomic status), it is not clear these results can be generalized to the private sector. This study was undertaken to determine the short-term outcome of LEA in private sector patients and to define predictors of operative mortality. METHODS: After Institutional Review Board approval and under the National Surgical Quality Improvement Program public use agreement, a data set of LEA based on Current Procedural Terminology coding was assembled for the years 2005 to 2008. Patient demographics, comorbidities, and laboratory values were compiled and linked to operative mortality. Dichotomous variables were analyzed using χ(2) test with odds ratios (ORs) and continuous variables with Student t-test. Predictive modeling was done using stepwise logistic regression. Data were analyzed in SPSS. RESULTS: A total of 6839 patients underwent 4001 amputations below-knee (BK) and 2838 above-knee (AK) with a 9.1% operative mortality (6.5% BK, 12.7% AK; P < .001). Age >60 years (OR, 2.4; 95% confidence interval [CI], 1.9-2.9), white race (OR, 1.2; 95% CI, 1.0-1.4), and American Society of Anesthesiologists classification (II, 2.3% vs IV, 13.8%) were significant predictors of mortality. Preoperative functional status (20% for totally dependent vs 4.3% for independent), renal failure (OR, 2.3; 95% CI, 1.7-3.2), and congestive heart failure (OR, 2.6; 95% CI, 2.1-3.3) also predicted death. Postoperative complications associated with mortality included pneumonia (OR, 5.4; 95% CI, 4.1-7.0), ventilator dependence (OR, 5.1; 95% CI, 3.8-6.8), and need for transfusion (OR, 3.7; 95% CI, 2.0-6.7). Hispanic and African-American race (OR, 0.6; 95% CI, 0.4-0.9 and OR, 0.8; 95% CI, 0.7-1), history of peripheral arterial disease (OR, 0.6; 95% CI, 0.5-0.8), and smoking (OR, 0.5; 95% CI, 0.4-0.7) were protective (all ORs had P values < .001). CONCLUSIONS: The mortality of LEA in private sector patients remains high, with risk factors similar to those identified in previous studies of VA patients. These results should serve as a benchmark for future attempts to improve the outcome of LEA and serve to improve patient and family counseling.


Assuntos
Amputação Cirúrgica/mortalidade , Extremidade Inferior/irrigação sanguínea , Extremidade Inferior/cirurgia , Melhoria de Qualidade , Idoso , Amputação Cirúrgica/efeitos adversos , Benchmarking , Distribuição de Qui-Quadrado , Feminino , Mortalidade Hospitalar , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Razão de Chances , Setor Privado , Medição de Risco , Fatores de Risco , Fatores de Tempo , Resultado do Tratamento , Estados Unidos/epidemiologia
19.
Ann Vasc Surg ; 27(7): 904-8, 2013 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-23711971

RESUMO

BACKGROUND: Frailty has been established as an important predictor of health-care outcomes. We hypothesized that the use of a modified frailty index would be a predictor of mortality and adverse occurrences in vascular surgery patients. METHODS: Under the data use agreement of the American College of Surgeons, and with institutional review board (IRB) approval, the National Surgical Quality Improvement Program (NSQIP) Participant Utilization File was accessed for the years 2005-2008 for inpatient vascular surgery patients. Using the Canadian Study of Health and Aging Frailty Index (FI), 11 variables were matched to the NSQIP database. An increase in FI implies increased frailty. The outcomes assessed were mortality, wound infection, and any occurrence. We then compared the effect of FI, age, functional status, relative value units (RVU), American Society of Anesthesiology (ASA) score, and wound status on mortality. Statistical analysis was done using chi-square analysis and stepwise logistic regression. RESULTS: A total of 67,308 patients were identified in the database, 3913 wound occurrences, 6691 infections, 12,847 occurrences of all kinds, and 2800 deaths. As the FI increased, postoperative wound infection, all occurrences, and mortality increased (P < 0.001). Stepwise logistic regression using the FI with the NSQIP variables of age, work RVU, ASA class, wound classification, emergency status, and functional status showed FI to have the highest odds ratio (OR) for mortality (OR = 2.058, P < 0.001). CONCLUSIONS: A simplified FI can be obtained by easily identifiable patient characteristics, allowing for accurate prediction of postoperative morbidity and mortality in the vascular surgery population.


Assuntos
Técnicas de Apoio para a Decisão , Idoso Fragilizado , Indicadores Básicos de Saúde , Complicações Pós-Operatórias/mortalidade , Procedimentos Cirúrgicos Vasculares/efeitos adversos , Procedimentos Cirúrgicos Vasculares/mortalidade , Atividades Cotidianas , Fatores Etários , Idoso , Distribuição de Qui-Quadrado , Feminino , Nível de Saúde , Humanos , Modelos Logísticos , Masculino , Análise Multivariada , Razão de Chances , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Infecção da Ferida Cirúrgica/etiologia , Infecção da Ferida Cirúrgica/mortalidade , Resultado do Tratamento
20.
Cureus ; 15(3): e35856, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-37033582

RESUMO

Work hour restrictions imposed on orthopedic surgery residents since the early 2000s have reduced educational opportunities at the workplace and encouraged alternative strategies for teaching outside the clinical setting. Preoperative templating is essential for safe and effective total hip arthroplasty (THA) and is accurate in predicting final implants. We sought to determine the effectiveness of a video tool for teaching orthopedic residents basic THA templating skills. We developed a video-based teaching tool with instructions on proper THA templating techniques. Ten cases were selected for testing, after excluding patients with severe hip deformities and poor-quality radiographs and only retaining those with concordance between templating by the senior authors and implanted components. The study subjects included three postgraduate year 1 (PGY-1), three PGY-2, and three PGY-5 residents, and three adult reconstruction fellows (PGY-6). Templating skills were assessed before and after watching the instructional video. The evaluation included the size and positioning of femoral and acetabular components, as well as the restoration of leg length. Each templating session was repeated twice. Variance was measured to evaluate consistency in measurements. A linear mixed model and F-test were used for statistical analyses. The number of years in training significantly affected performance prior to exposure to the instructional video. Post-exposure, there was a significant improvement in the accuracy of sizing and positioning of acetabular and femoral components for PGY-1, PGY-2, and PGY-5 residents. The results achieved were comparable to PGY-6 examiners, who did not gain substantial performance benefits from the instructional video. Limb length restoration was less affected by experience or exposure to the video. Component positioning and sizing, as well as leg length discrepancy (LLD), showed a significant decrease in variance after the intervention in all study groups. Video learning is reliable in teaching invaluable skills to orthopedic surgery residents without encroaching on work hours. We conceived a concise video to train orthopedic residents to perform THA templating with proper technique and demonstrated its efficiency and reproducibility.

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