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1.
Cell ; 159(5): 1126-1139, 2014 Nov 20.
Artigo em Inglês | MEDLINE | ID: mdl-25416950

RESUMO

The MYC oncoproteins are thought to stimulate tumor cell growth and proliferation through amplification of gene transcription, a mechanism that has thwarted most efforts to inhibit MYC function as potential cancer therapy. Using a covalent inhibitor of cyclin-dependent kinase 7 (CDK7) to disrupt the transcription of amplified MYCN in neuroblastoma cells, we demonstrate downregulation of the oncoprotein with consequent massive suppression of MYCN-driven global transcriptional amplification. This response translated to significant tumor regression in a mouse model of high-risk neuroblastoma, without the introduction of systemic toxicity. The striking treatment selectivity of MYCN-overexpressing cells correlated with preferential downregulation of super-enhancer-associated genes, including MYCN and other known oncogenic drivers in neuroblastoma. These results indicate that CDK7 inhibition, by selectively targeting the mechanisms that promote global transcriptional amplification in tumor cells, may be useful therapy for cancers that are driven by MYC family oncoproteins.


Assuntos
Quinases Ciclina-Dependentes/antagonistas & inibidores , Modelos Animais de Doenças , Neuroblastoma/tratamento farmacológico , Proteínas Nucleares/metabolismo , Proteínas Oncogênicas/metabolismo , Fenilenodiaminas/uso terapêutico , Inibidores de Proteínas Quinases/farmacologia , Pirimidinas/uso terapêutico , Animais , Ciclo Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Quinases Ciclina-Dependentes/metabolismo , Humanos , Proteína Proto-Oncogênica N-Myc , Transcrição Gênica/efeitos dos fármacos , Quinase Ativadora de Quinase Dependente de Ciclina
2.
Eur Spine J ; 33(6): 2190-2197, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38630247

RESUMO

PURPOSE: To determine the impact of poor mental health on patient-reported and surgical outcomes after microdiscectomy. METHODS: Patients ≥ 18 years who underwent a single-level lumbar microdiscectomy from 2014 to 2021 at a single academic institution were retrospectively identified. Patient-reported outcomes (PROMs) were collected at preoperative, three-month, and one-year postoperative time points. PROMs included the Oswestry Disability Index (ODI), Visual Analog Scale Back and Leg (VAS Back and VAS Leg, respectively), and the mental and physical component of the short form-12 survey (MCS and PCS). The minimum clinically important differences (MCID) were employed to compare scores for each PROM. Patients were categorized as having worse mental health or better mental health based on a MCS threshold of 50. RESULTS: Of 210 patients identified, 128 (61%) patients had a preoperative MCS score ≤ 50. There was no difference in 90-day surgical readmissions or spine reoperations within one year. At 3- and 12-month time points, both groups demonstrated improvements in all PROMs (p < 0.05). At three months postoperatively, patients with worse mental health had significantly lower PCS (42.1 vs. 46.4, p = 0.004) and higher ODI (20.5 vs. 13.3, p = 0.006) scores. Lower mental health scores were associated with lower 12-month PCS scores (43.3 vs. 48.8, p < 0.001), but greater improvements in 12-month ODI (- 28.36 vs. - 18.55, p = 0.040). CONCLUSION: While worse preoperative mental health was associated with lower baseline and postoperative PROMs, patients in both groups experienced similar improvements in PROMs. Rates of surgical readmissions and reoperations were similar among patients with varying preoperative mental health status.


Assuntos
Discotomia , Medidas de Resultados Relatados pelo Paciente , Humanos , Discotomia/métodos , Masculino , Feminino , Pessoa de Meia-Idade , Adulto , Estudos Retrospectivos , Resultado do Tratamento , Vértebras Lombares/cirurgia , Idoso , Saúde Mental
3.
Skeletal Radiol ; 2023 Sep 25.
Artigo em Inglês | MEDLINE | ID: mdl-37749413

RESUMO

A 76-year-old male diagnosed with sarcoidosis presented with atraumatic left anterior knee pain. Initial imaging of the left lower extremity revealed an eccentrically-based lytic lesion in the mid-distal femur with cortical erosion and an additional lytic lesion in the proximal tibia. Magnetic resonance imaging (MRI) demonstrated an aggressive lesion in the proximal tibia with surrounding marrow edema, cortical breach, and erosion into the distal patellar tendon. Given concern for metastatic bone lesions, a18-fluorodeoxyglucose positron emission tomography/computed tomography scan (FDG PET/CT) was performed which demonstrated concordant hypermetabolic lytic lesions at the left mid-distal femur and the left proximal tibia, as well as hypermetabolic diffuse lymphadenopathy. The patient was presumed to have metastatic lung cancer based on the presence of lung nodules. Due to concern for impending pathologic fracture, the patient underwent open biopsy with a plan for prophylactic fixation of both lesions. Intra-operatively, however, both lesions were found to contain pus, from which cultures ultimately grew Cryptococcus neoformans. This is a case of disseminated skeletal cryptococcosis masquerading as metastatic cancer in a patient without classic risk factors for disseminated cryptococcosis (defined as extrapulmonary evidence of infection). Classically, disseminated cryptococcosis is thought to occur in severely immunocompromised patients, such as those with human immunodeficiency virus (HIV) or organ transplant recipients. This case highlights the need to maintain a high index of suspicion in patients with underlying immunocompromising conditions, including less common conditions such as sarcoid, who present with bony lesions. This case report then discusses the diagnostic evaluation and treatment of disseminated skeletal cryptococcosis.

4.
J Hand Surg Am ; 2023 May 03.
Artigo em Inglês | MEDLINE | ID: mdl-37140516

RESUMO

PURPOSE: Trigger finger release (TFR) is one of the most commonly performed hand surgeries; nevertheless, the time until patients subjectively feel recovered has not been well documented. The limited literature on patient perceptions of recovery after any type of surgery has described that patients and surgeons may have differing views on the time until full recovery. Our primary study question was to determine how long it takes for patients to subjectively feel fully recovered after TFR. METHODS: In this prospective study, patients who underwent isolated TFR completed questionnaires before surgery and at multiple time points following surgery until they reported full recovery. Patients completed visual analog scale (VAS) pain scores and QuickDASH (Disabilities of the Arm, Shoulder, and Hand) and were asked if they felt fully recovered at 4 weeks, 6 weeks, and 3, 6, 9, and 12 months. RESULTS: The average time to self-reported full recovery was 6.2 months (SD 2.6), and the median time to self-reported full recovery was 6 months (IQR 4 months). At 12 months, four out of 50 patients (8%) did not feel fully recovered. QuickDASH and VAS pain scores improved significantly from preoperative assessment to final follow-up. All patients reported improvement in both VAS pain scores and QuickDASH scores greater than the minimal clinically important difference between 6 weeks and 3 months after surgery. Higher preoperative VAS and QuickDASH scores were associated with failure to fully recover by 12 months after surgery. CONCLUSIONS: The length of time after surgery until patients felt fully recovered after isolated TFR is longer than the senior authors' expectations. This suggests that patients and surgeons may consider distinctly different parameters when discussing recovery. Surgeons should be aware of this discrepancy when discussing recovery after surgery. TYPE OF STUDY/LEVEL OF EVIDENCE: Prognostic II.

5.
J Shoulder Elbow Surg ; 32(11): 2286-2295, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37263478

RESUMO

BACKGROUND: Multiple techniques have been described to treat humeral diaphyseal bone tumors requiring curettage or excision. Recent studies have suggested that carbon fiber-reinforced polyetheretherketone (CFR-PEEK) intramedullary nails (IMNs) may be preferable to titanium IMNs for patients with musculoskeletal tumors due to CFR-PEEK's high tensile strength, radiolucency, a modulus of elasticity closer to native bone, and improved postoperative surveillance/radiation dosing. In this study, we describe the rate of fixation failure for both CFR-PEEK and titanium humeral IMNs when used for humeral diaphyseal bone tumors requiring curettage or excision. METHODS: This was a single-institution retrospective cohort study including 81 patients (27 CFR-PEEK and 54 titanium) treated for a humeral diaphyseal bone tumor using an IMN ± methylmethacrylate between January 2017 and December 2022. Primary outcome was revision surgery due to soft tissue complications, nonunions, structural complications such as periprosthetic fracture or IMN breakage, periprosthetic infection, tumor progression, and implant failure due to rejection or fatigue. RESULTS: No failures were observed in either patients treated with titanium nails or patients treated with CFR-PEEK not requiring curettage. Fixation failure due to implant failure was observed in 2 cases-at 214 days and 469 days after surgery-where CFR-PEEK IMN was used for stabilization after a wide segmental resection for oncologic control with a cement spacer reconstruction. In both cases, the resection was larger than 6 cm, the remaining distal humerus was less than 5 cm, and failures occurred at the interface of the residual bone and spacer. Both patients were revised using a titanium distal posterolateral humeral plate fixed with screws and cables without any subsequent complications. One additional CFR-PEEK IMN required revision surgery after 744 days due to progression of the tumor and subsequent nonunion. One revision surgery was observed after 63 days for the titanium IMN because of nonunion and tumor progression. CONCLUSIONS: Humeral diaphyseal bone tumors requiring large segmental resection with small residual bone and a large cement spacer may fail via tension due to bending forces at the distal portion. In this clinical scenario, the use of larger-diameter CFR-PEEK IMNs may be indicated when available. In the interim, use of intercalary allografts instead of cement spacers, additional fixation with a titanium plate distally, or the use of a titanium nail when using a cement spacer may be considered.


Assuntos
Neoplasias Ósseas , Fixação Intramedular de Fraturas , Fraturas do Úmero , Humanos , Fibra de Carbono , Titânio , Fixação Intramedular de Fraturas/métodos , Estudos Retrospectivos , Resultado do Tratamento , Polietilenoglicóis/química , Cetonas/química , Neoplasias Ósseas/cirurgia , Úmero/cirurgia , Placas Ósseas , Carbono , Fraturas do Úmero/cirurgia
6.
Eur Spine J ; 30(8): 2102-2108, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34241698

RESUMO

PURPOSE: Remote patient monitoring (RPM) has revolutionized the landscape of healthcare. From humble beginnings rooted in landline home telephone calls to present-day devices with near instantaneous wireless connectivity, the evolution of technology has ushered in an era of digital medicine and remote care. Presently, a vast array of healthcare data points can be automatically generated, analyzed, and forwarded to providers to supplement clinical decision-making. While RPM originated and was popularized within medicine, its role in orthopedics, and particularly within spine surgery, is evolving. We sought to provide an overview of RPM within orthopedics, with specific attention on spine care, analyzing its origins, present-day form, and prospects. METHODS: We reviewed the literature to date as it pertains to RPM within healthcare at large, orthopedics, and spine care. RESULTS: We detail the development and clinical use of wearable technology and smart implants, examining the underlying technology and evaluating the spectrum of their present-day and potential applications. CONCLUSIONS: Technological advancements are not only reshaping the paradigm of musculoskeletal care but are also redefining the physician-patient relationship as well as reimagining traditional perspectives on healthcare data collection and privacy.


Assuntos
Telemedicina , Atenção à Saúde , Humanos , Monitorização Fisiológica
7.
Clin Orthop Relat Res ; 479(9): 1970-1979, 2021 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-33930000

RESUMO

BACKGROUND: Risk adjustment has implications across orthopaedics, including informing clinical care, improving payment models, and enabling observational orthopaedic research. Although comorbidity indices (such as the American Society of Anesthesiologists [ASA] classification, Charlson comorbidity index [CCI], and Elixhauser comorbidity index [ECI]) have been examined extensively in the immediate perioperative period, there is a dearth of data on their three-way comparative effectiveness and long-term performance. Moreover, the discriminative ability of the CCI and ECI after orthopaedic surgery has not been validated in the ICD-10 era, despite new diagnosis codes from which they are calculated. QUESTION/PURPOSE: Which comorbidity index (ASA, CCI, or ECI) is associated with the greatest accuracy on receiver operating curve (ROC) analysis with respect to the endpoint of death at 90 days and 1 year after hip fracture surgery in the ICD-10 era? METHODS: A retrospective study was conducted on all patients undergoing surgical fixation of primary hip fractures at two Level I trauma centers and three community hospitals from October 2016 to May 2019. This time frame allowed for a 1-year baseline period of ICD-10 data to assess comorbidities and at least a 1-year follow-up period to assess mortality. Initially 1516 patients were identified using Common Procedural Terminology and ICD codes, of whom 4% (60 of 1516) were excluded after manual review; namely, those with pathologic fractures (n = 38), periprosthetic fractures (n = 12), and age younger than 18 years (n = 10). Of the patients who were studied, 69% (998 of 1456) were women and the mean ± SD age was 77 ± 14 years; 45% (656 of 1456) were treated with intramedullary nails, 32% (464 of 1456) underwent hemiarthroplasties, 10% (149 of 1456) underwent THAs, 7% (104 of 1456) underwent percutaneous fixations, and 6% (83 of 1456) were treated with plates and screws. The mean ± SD ASA score was 2.8 ± 0.6, CCI was 3.1 ± 3.2, and ECI was 5.2 ± 3.5. Hip fracture fixation was chosen as the operation of interest given the high incidence of this injury, the well-documented effects of comorbidities on complications, and the critical importance of risk stratification and perioperative medical management for these patients. Demographics, comorbidities, surgical details, as well as 90-day and 1-year mortality were collected. Logistic regressions with ROC curves were used to determine the accuracy and comparative effectiveness of the three measures. The 90-day mortality rate was 7.4%, and the 1-year mortality rate was 15.0%. RESULTS: The accuracy (area under the curve [AUC]) for 1-year mortality was 0.685 (95% CI 0.656 to 0.714) for the ASA, 0.755 (95% CI 0.722 to 0.788) for the ECI, and 0.769 (95% CI 0.739 to 0.800) for the CCI. The CCI and ECI were more accurate than ASA (p < 0.001 for both), while the CCI and ECI did not differ (p = 0.30). The ECI (AUC 0.756 [95% CI 0.712 to 0.800]) was more accurate for 90-day mortality than the ASA (AUC 0.703 [95% CI 0.663 to 0.744]; p = 0.04), while CCI (AUC 0.742 [95% CI 0.698 to 0.785]) with ASA (p = 0.17) and CCI with ECI (p = 0.46) did not differ at 90 days. CONCLUSION: Performance measures and research results may vary depending on what comorbidity index is used. We found that the CCI and ECI were more accurate than the ASA score for 1-year mortality after hip fracture surgery. Moreover, these data validate that the CCI and ECI can perform reliably in the ICD-10 era. If other studies from additional practice settings confirm these findings, as would be expected because of the objective nature of these indices, the CCI or ECI may be a useful preoperative measure for surgeons to assess 1-year mortality for hip fracture patients and should likely be used for institutional orthopaedic research involving outcomes 90 days and beyond. LEVEL OF EVIDENCE: Level III, diagnostic study.


Assuntos
Artroplastia de Quadril/métodos , Fixação de Fratura/métodos , Hemiartroplastia/métodos , Fraturas do Quadril/mortalidade , Fraturas do Quadril/cirurgia , Medição de Risco/métodos , Idoso , Idoso de 80 Anos ou mais , Comorbidade , Feminino , Humanos , Classificação Internacional de Doenças , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos
8.
J Arthroplasty ; 36(3): 1101-1108, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33160807

RESUMO

BACKGROUND: Prosthetic joint infection (PJI) is a morbid complication following total joint arthroplasty (TJA). PJI diagnosis and treatment has changed over time, and patient co-management with a high-volume musculoskeletal infectious disease (MSK ID) specialist has been implemented at our institution in the last decade. METHODS: We retrospectively evaluated all consecutive TJA patients treated for PJI between 1995 and 2018 by a single high-volume revision TJA surgeon. Microbial identities, antibiotic resistance, prior PJI, and MSK ID consultation were investigated. RESULTS: In total, 261 PJI patients (median age 66 years, interquartile range 57-75) were treated. One-year and 5-year reinfection rates were 15.8% (95% confidence interval [CI] 11.6-20.7) and 22.1% (95% CI 17.0-27.7), respectively. Microbial identities and antibiotic resistances did not change significantly over time. Despite seeing more prior PJI patients (53.3% vs 37.6%, P = .012), MSK ID-managed patients had similar infection rates as non-MSK ID-managed patients (hazard ratio [HR] 1.02, 95% CI 0.6-1.75, P = .93). Prior PJI was associated with higher reinfection risk (HR 2.39, 95% CI 1.39-4.12, P = .002) overall and in patients without MSK ID consultation, specifically (HR 2.78, 95% CI 1.37-5.65, P = .005). This risk was somewhat lower and did not reach significance in prior PJI patients with MSK ID consultation (HR 1.97, 95% CI 0.87-4.48, P = .106). CONCLUSION: We noted minimal differences in microbial/antibiotic resistances for PJI over 20 years in a single institution, suggesting current standards of PJI treatment remain encouragingly valid in most cases. MSK ID involvement was not associated with lower reinfection risk overall; however, in patients with prior PJI, the risk of reinfection appeared to be somewhat lower with MSK ID involvement. LEVEL OF EVIDENCE: Level IV-Case Series.


Assuntos
Artrite Infecciosa , Artroplastia de Quadril , Infecções Relacionadas à Prótese , Cirurgiões , Idoso , Artroplastia de Quadril/efeitos adversos , Humanos , Infecções Relacionadas à Prótese/epidemiologia , Infecções Relacionadas à Prótese/etiologia , Infecções Relacionadas à Prótese/cirurgia , Reoperação , Estudos Retrospectivos , Fatores de Risco
9.
J Arthroplasty ; 35(11): 3261-3268, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-32709562

RESUMO

BACKGROUND: Knee arthrodesis (KA) and above-knee amputation (AKA) have been used for salvage of failed total knee arthroplasty (TKA) after periprosthetic joint infection (PJI). However, few studies have assessed the outcomes of KA after TKA PJI, as it remains an uncommon procedure. We investigated rates of AKA, control of infection, and ambulatory status after KA for TKA PJI treatment. METHODS: This was a retrospective and single-surgeon series of 51 failed TKAs due to PJI treated with two-stage KA between 2000 and 2016 with a minimum of 2-year follow-up. Patient demographics, comorbidities, surgical history, radiographic data, and outcomes of KA treatment were recorded. RESULTS: Infection was successfully controlled in 48 of 51 patients (94.1%); of these, 24 knees (50.0%) required no reoperation subsequent to the index KA, whereas the remaining 24 (50.0%) patients required a median of 1 additional operation. Nonunion, malunion, or delayed union was noted in 10 patients (19.6%). Of the 48 patients who were successfully treated with KA, 41 patients (85.4%) remained ambulatory after KA and 9 of these patients (18.8%) did not require assistive devices. Three of 51 patients (5.9%) progressed to AKA after KA. CONCLUSION: Patients undergoing KA for TKA PJI had high rates of infection control and preservation of ambulatory status, with low rates of progression to AKA in our study. LEVEL OF EVIDENCE: Level IV-case series.


Assuntos
Artroplastia do Joelho , Prótese do Joelho , Infecções Relacionadas à Prótese , Artrodese , Artroplastia do Joelho/efeitos adversos , Humanos , Prótese do Joelho/efeitos adversos , Infecções Relacionadas à Prótese/epidemiologia , Infecções Relacionadas à Prótese/cirurgia , Reoperação , Estudos Retrospectivos
10.
J Surg Oncol ; 120(6): 994-1007, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31407350

RESUMO

BACKGROUND AND OBJECTIVES: Large scale data on the treatment of pathologic proximal femur fractures (PPFFs) are lacking. The purpose of this study was to evaluate trends in patient demographics, complication rates, and relative utilization rates of various techniques associated with PPFFs. METHODS: The American College of Surgeons-National Surgical Quality Improvement Program (NSQIP) database was queried for PPFFs from 2009 to 2017. Patient demographics, 30-day complications, and utilization rates were recorded. Trends in these variables were determined over the study period. RESULTS: Most patient demographics did not change during the study period. There were no trends toward decreasing rates of major complications (P = .82), reoperations (P = .65), non-home discharges (P = .17), readmissions (P = .07), or deaths (P = .75); transfusion rates significantly decreased (P < .001). Rates of hemiarthroplasty decreased (P = .03) and rates of intramedullary nailing increased (P = .001). DISCUSSION: Despite advances in cancer therapeutics, the average PPFF patient has not significantly changed over the past decade. Similarly, most short-term outcomes after PPFF surgery have not improved, demonstrating a need for improved perioperative protocols. Finally, rates of IMN fixation are increasing while rates of HA are falling at NSQIP hospitals. Given that orthopedic oncologists favor endoprosthetic reconstruction in most cases, there may be a need for increased communication between orthopedic oncologists and other members of the orthopedic community treating PPFFs.


Assuntos
Fraturas do Fêmur/cirurgia , Fêmur/cirurgia , Ortopedia/tendências , Complicações Pós-Operatórias , Idoso , Feminino , Fraturas do Fêmur/epidemiologia , Fraturas do Fêmur/patologia , Fêmur/patologia , Seguimentos , Humanos , Masculino , Prognóstico , Estudos Prospectivos , Estudos Retrospectivos , Estados Unidos/epidemiologia
11.
J Shoulder Elbow Surg ; 28(1): 71-76, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30243904

RESUMO

BACKGROUND: Aneurysmal bone cyst (ABC) is a benign but locally aggressive bone tumor occurring most commonly in the first 2 decades of life. The clavicle is a rare location for tumors, and ABCs of the clavicle have been sparsely described in the literature. We present the largest known series of ABCs of the clavicle to describe this rare condition. METHODS: Patients were identified retrospectively from an orthopedic oncology database to obtain demographic, diagnostic, and treatment information. A literature search was performed to identify all English language reports of ABC of the clavicle. RESULTS: We identified 13 patients with ABC of the clavicle, 77% of which were in the acromial end. Most patients (77%) presented with pain or swelling or both. The initial treatment in 11 patients was by curettage, with or without allograft bone packing, and 1 underwent resection/reconstruction of the lateral clavicle. Seven patients (58%) had 1 or more recurrences at an average of 6 months, for which 2 were treated with partial resection of the clavicle. CONCLUSIONS: ABC of the clavicle is a rare condition that we found to occur most frequently in the acromial end of the bone. Most patients were initially treated with curettage and showed a higher rate of recurrence than in other locations. The unique anatomy of the clavicle makes resection a feasible and very functional option, especially if the coracoclavicular ligaments can be preserved. However, the potential resulting deformity may cause patients to opt for a less aggressive and, consequently, less effective treatment method.


Assuntos
Cistos Ósseos Aneurismáticos/cirurgia , Clavícula , Acrômio , Adolescente , Adulto , Transplante Ósseo , Criança , Curetagem , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Resultado do Tratamento , Adulto Jovem
12.
J Arthroplasty ; 34(11): 2698-2703, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31279601

RESUMO

BACKGROUND: As oncology patients have increasing life expectancies, total hip arthroplasty (THA) may become an important treatment option for pathologic proximal femur fractures (PPFFs). Although THA and hemiarthroplasty (HA) have been compared for native hip fracture treatment, no data on short-term morbidity and mortality are available in the pathologic setting. The purpose of this study is to compare short-term morbidity and mortality of HA vs THA for PPFFs. METHODS: The National Surgical Quality Improvement Program database was queried from 2007 to 2017 for patients with PPFFs treated with HA or THA. Propensity-adjusted logistic regressions were implemented to compare 30-day morbidity and mortality between procedures. Backwards stepwise regression was then used to determine independent predictors of treatment with HA compared to THA. RESULTS: In adjusted analysis, THA was associated with longer operative times (120.3 ± 5.6 vs 98.7 ± 4.9 minutes, P < .001); however, there were no differences between THA and HA with regard to 30-day rates of major complications (P = .3), minor complications (P = .77), reoperations (P = .99), readmissions (P = .35), or deaths (P = .63). Older age (P < .001), dependent functional status (P = .02), and the presence of disseminated cancer (P = .049) were predictive of undergoing HA compared to THA. CONCLUSION: As patients with metastatic cancer continue to live longer with their disease, the durability of surgical reconstruction to treat PPFFs is becoming increasingly important. This study demonstrated no significant differences in 30-day complications between PPFF patients treated with THA or HA after controlling for underlying confounders. These results suggest that THA can be utilized to treat certain patients with PPFFs, and future work is warranted to examine long-term functional outcomes.


Assuntos
Artroplastia de Quadril/mortalidade , Fraturas do Colo Femoral/cirurgia , Fraturas Espontâneas/cirurgia , Hemiartroplastia/mortalidade , Complicações Pós-Operatórias/epidemiologia , Idoso , Idoso de 80 Anos ou mais , Artroplastia de Quadril/efeitos adversos , Bases de Dados Factuais , Feminino , Fraturas Espontâneas/etiologia , Hemiartroplastia/efeitos adversos , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/etiologia , Melhoria de Qualidade , Reoperação , Estudos Retrospectivos , Estados Unidos/epidemiologia
13.
Alzheimer Dis Assoc Disord ; 28(4): 326-32, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-24614266

RESUMO

OBJECTIVE: The aim of this study was to determine whether bilingualism is associated with dementia in cross-sectional or prospective analyses of older adults. METHODS: In 1991, 1616 community-living older adults were assessed and were followed 5 years later. Measures included age, sex, education, subjective memory loss (SML), and the modified Mini-mental State Examination (3MS). Dementia was determined by clinical examination in those who scored below the cut point on the 3MS. Language status was categorized based upon self-report into 3 groups: English as a first language (monolingual English, bilingual English) and English as a Second Language (ESL). RESULTS: The ESL category had lower education, lower 3MS scores, more SML, and were more likely to be diagnosed with cognitive impairment, no dementia at both time 1 and time 2 compared with those speaking English as a first language. There was no association between being bilingual (ESL and bilingual English vs. monolingual) and having dementia at time 1 in bivariate or multivariate analyses. In those who were cognitively intact at time 1, there was no association between being bilingual and having dementia at time 2 in bivariate or multivariate analyses. CONCLUSIONS: We did not find any association between speaking >1 language and dementia.


Assuntos
Demência/epidemiologia , Multilinguismo , Idoso , Idoso de 80 Anos ou mais , Canadá , Estudos Transversais , Emigrantes e Imigrantes , Feminino , Humanos , Masculino , Estudos Prospectivos
14.
Spine (Phila Pa 1976) ; 49(1): 46-57, 2024 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-37732462

RESUMO

STUDY DESIGN: A literature review. OBJECTIVE: The aim of this review is to provide an overview of benign and malignant primary spine tumors and a balanced analysis of the benefits and limitations of (and alternatives to) surgical treatment with en bloc resection. SUMMARY OF BACKGROUND DATA: Primary spine tumors are rare but have the potential to cause severe morbidity, either from the disease itself or as a result of treatment. The prognosis, goals, and treatment options vary significantly with the specific disease entity. Appropriate initial management is critical; inappropriate surgery before definitive treatment can lead to recurrence and may render the patient incurable, as salvage options are often inferior. METHODS: We performed a comprehensive search of the PubMed database for articles relevant to primary spine neoplasms and en bloc spine surgery. Institutional review board approval was not needed. RESULTS: Although Enneking-appropriate en bloc surgery can be highly morbid, it often provides the greatest chance for local control and/or patient survival. However, there is growing data to support modern radiotherapy as a feasible and less morbid approach to certain primary neoplasms that historically were considered radioresistant. CONCLUSIONS: Choosing the optimal approach to primary spine tumors is complex. A comprehensive and up-to-date assessment of the evidence is required to guide patient care and to balance the often-competing goals of prolonging life and preserving quality of life.


Assuntos
Qualidade de Vida , Neoplasias da Coluna Vertebral , Humanos , Resultado do Tratamento , Coluna Vertebral/cirurgia , Prognóstico , Recidiva Local de Neoplasia/cirurgia
15.
J Bone Joint Surg Am ; 106(13): 1205-1211, 2024 Jul 03.
Artigo em Inglês | MEDLINE | ID: mdl-38728434

RESUMO

BACKGROUND: While sustainable long-term function has been established for biological reconstruction with distraction osteogenesis (DO) following osseous resections, there is a paucity of published data informing surgeons and patients on important milestones in the reconstructive process. The objectives of this study were to determine when to expect complete bone healing and full weight-bearing as well as to quantify the influence of chemotherapy on the osseous regeneration process. METHODS: Prospectively, pathological and clinical data were collected for 30 consecutive patients who underwent primary or secondary DO-based reconstruction following osseous resection from 2018 to 2021. Serial radiographs indicated the times to cortex formation and full union. An unpaired t test was used to compare the time required for full bone remodeling of segments transported with and without concurrent chemotherapy. RESULTS: The average resection length was 13.6 cm (range, 4 to 22 cm). Patients underwent an average of 6.1 procedures (range, 1 to 14 procedures). Half (50%) of all procedures were planned, while half were unplanned procedures. All patients achieved full, independent weight-bearing at a median of 12 months (interquartile range [IQR], 9 to 16 months). For the 34 segments transported concurrently with chemotherapy, the mean bone healing index (BHI) was 2.3 ± 0.7, and the mean BHI was 1.2 ± 0.4 for the 25 segments without chemotherapy at any point during their transport (p < 0.0001). CONCLUSIONS: All 30 patients achieved full bone healing and independent weight-bearing at a median of 1 year postoperatively and continued to show functional improvement afterward. Surgeons and patients can expect bone healing to be nearly twice as fast for segments transported after completion of systemic chemotherapy compared with segments transported concurrently with adjuvant chemotherapy. LEVEL OF EVIDENCE: Therapeutic Level II . See Instructions for Authors for a complete description of levels of evidence.


Assuntos
Neoplasias Ósseas , Osteogênese por Distração , Humanos , Osteogênese por Distração/métodos , Masculino , Feminino , Neoplasias Ósseas/cirurgia , Adulto , Estudos Prospectivos , Pessoa de Meia-Idade , Adolescente , Adulto Jovem , Osteossarcoma/cirurgia , Resultado do Tratamento , Criança , Procedimentos de Cirurgia Plástica/métodos , Suporte de Carga/fisiologia , Regeneração Óssea/efeitos dos fármacos , Idoso
16.
Clin Spine Surg ; 37(7): 305-309, 2024 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-38366348

RESUMO

STUDY DESIGN: A retrospective case series study. OBJECTIVE: To analyze the epidemiology of diagnoses of back and neck strains and sprains among Major League (MLB) and Minor League (MiLB) Baseball players. BACKGROUND: Baseball players perform unique sets of repetitive movements that may predispose to neck and back strains and sprains. Data are lacking concerning the epidemiology of these diagnoses in this population. MATERIALS AND METHODS: De-identified data on neck/back strains and sprains were collected from all MLB and MiLB teams from 2011 to 2016 using the MLB-commissioned Health and Injury Tracking System database. Diagnosis rates of conditions related to cervical, thoracic, and lumbar musculature and their impact on days missed due to injury, player participation, and season or career-ending status were assessed. Injury rates were reported as injuries per 1000 athlete exposures (AEs). RESULTS: There were 3447 cases of neck/back strains and sprains in professional baseball players from 2011 to 2016. Seven hundred twenty-one of these occurred in MLB versus 2726 in MiLB. Of injuries 136 were season-ending (26 in MLB, 110 in MiLB); 22 were career-ending (2 in MLB, 20 in MiLB). The total days missed were 39,118 (8838 from MLB and 30,280 from MiLB). Excluding season or career-ending injuries, the mean days missed were 11.8 (12.7 and 11.6 in MLB and MiLB, respectively). The median days missed were 4 (3 and 5 in MLB and MiLB, respectively). Combining MLB and MiLB, the pitcher injury rate was 1.893 per 1000 AEs versus 0.743 per 1000 Aes for other position players ( P < 0.0001). CONCLUSION: There was a high incidence of neck/back strains and sprains in MLB and MiLB players, with nearly 40,000 aggregate days missed in our 6-year study period. The median days missed were lower than the mean days missed, indicating rightward outliers. Pitchers had over double the rates of injuries compared with other position players. LEVEL OF EVIDENCE: Level III.


Assuntos
Beisebol , Entorses e Distensões , Humanos , Beisebol/lesões , Entorses e Distensões/epidemiologia , Masculino , Lesões do Pescoço/epidemiologia , Lesões nas Costas/epidemiologia , Traumatismos em Atletas/epidemiologia , Estudos Retrospectivos , Atletas , Adulto , Efeitos Psicossociais da Doença
17.
Spine J ; 24(9): 1759-1772, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-38704096

RESUMO

BACKGROUND CONTEXT: The opioid epidemic is a public health crisis affecting spine care and pain management. Medical marijuana is a potential nonopioid analgesic yet to be studied in the surgical setting since its effects on bone healing are not fully understood. Studies have demonstrated analgesic and potentially osteoinductive properties of cannabinoids with endocannabinoid receptor expression in bone tissue. PURPOSE: We hypothesize that tetrahydrocannabinol (THC) and cannabidiol (CBD) will not decrease bone healing in spinal fusion. STUDY DESIGN: Seventy-eight adult Sprague-Dawley rats were used for this study. Utilizing allogenic bone grafts (6 donor rats), posterolateral inter-transverse lumbar fusion at the L4-L5 level was performed. The animals were equally divided into four treatment groups, each receiving 0.1 ml intraperitoneal injections weekly as follows: placebo (saline), 5 mg/kg THC, 5 mg/kg CBD, and a combination of 5 mg/kg THC and 5mg/kg CBD (Combo). METHODS: Callus tissue was harvested 2- and 8-weeks postsurgery for qPCR assessment to quantify changes in the expression of osteogenic genes. Manual palpation was done to assess the strength of the L4-L5 arthrodesis on all rats. µCT image-based callus analysis and histology were performed. One-way ANOVA followed by post hoc comparisons was performed. RESULTS: µCT demonstrated no significant differences. Treatment groups had slightly increased bone volume and density compared to control. qPCR at 2 weeks indicated downregulated RANKL/OPG ratios skewing towards osteogenesis in the CBD group, with the THC and CBD+THC groups demonstrating a downward trend (p>.05). ALPL, BMP4, and SOST were significantly higher in the CBD group, with CTNNB1 and RUNX2 also showing an upregulating trend. The CBD group showed elevation in Col1A1 and MMP13. Data at eight weeks showed ALPL, RUNX2, BMP4, and SOST were downregulated for all treatment groups. In the CBD+THC group, RANK, RANKL, and OPG were downregulated. OPG downregulation reached significance for the THC and CBD+THC group compared to saline. Interestingly, the RANKL/OPG ratio showed upregulation in the CBD and CBD+THC groups. RANKL showed upregulation in the CBD group. At 2 and 8 weeks, the CBD treatment group showed superior histological progression, increasing between time points. CONCLUSION: This study demonstrates that CBD and THC have no adverse effect on bone healing and the rate of spinal fusion in rats. Osteogenic factors were upregulated in the CBD-treated groups at 2 weeks, which indicates a potential for bone regeneration. In this group, compared to control, the RANKL/OPG ratio at the early healing phase demonstrates the inhibition of osteoclast differentiation, enhancing bone formation. Interestingly, it shows promoted osteoclast differentiation at the later healing phase, enhancing bone remodeling. This aligns with the physiological expectation of a lower ratio in the early phases and a higher ratio in the later remodeling phases. CLINICAL SIGNIFICANCE: CBD and THC showed no inhibitory effects on bone healing in a spinal fusion model. Moreover, histologic and gene expression analysis demonstrated that CBD may, in fact, enhance bone healing. Further research is needed to confirm the safe usage of THC and CBD in the postoperative setting following spinal fusions.


Assuntos
Dronabinol , Vértebras Lombares , Ratos Sprague-Dawley , Fusão Vertebral , Animais , Ratos , Vértebras Lombares/efeitos dos fármacos , Vértebras Lombares/cirurgia , Fusão Vertebral/métodos , Dronabinol/farmacologia , Dronabinol/administração & dosagem , Canabidiol/farmacologia , Canabidiol/administração & dosagem , Canabinoides/farmacologia , Masculino , Transplante Ósseo/métodos
18.
N Am Spine Soc J ; 19: 100336, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-39040946

RESUMO

Background: The North American Spine Society (NASS) assembled the first ever comprehensive naming system for describing lumbar disc disease, including lumbar disc herniation. The objectives of this study were (1) to determine which NASS descriptors are most predictive of independent patient-reported outcomes after microdiscectomy and (2) to identify the inter-rater reliability of each NASS descriptor. Methods: Adult patients (≥18 years) who underwent a lumbar microdiscectomy from 2014-2021 were retrospectively identified. Patient-reported outcome measures (PROMs) were collected at preoperative, 3-month, and 1-year postoperative time points. Lumbar disc herniations were evaluated and classified on preoperative MRI using the NASS lumbar disc nomenclature specific to disc herniation. Results: About 213 microdiscectomy patients were included in the final analysis. Herniation descriptors exhibiting the greatest reliability included sequestration status (κ=0.83), axial disc herniation area (κ=0.83), and laterality (κ=0.83). The descriptor with the lowest inter-rater reliability was direction of migration (κ=0.53). At 3 months, a sequestered herniation was associated with lower odds of achieving the minimal clinically important difference (MCID) for ODI (p=.004) and MCS (p=.032). At 12 months, a similar trend was observed for Oswestry Disability Index (ODI) MCID achievement (p=.001). At 3 months, a herniation with larger axial area was a predictor of MCID achievement in ODI (p=.004) and the mental component summary (MCS) (p=.009). Neither association persisted at 12 months; however, larger axial disc herniation area was able to predict MCID achievement in the Visual Analogue Scale (VAS) leg (p=.031) at 12 months. Conclusions: The utility of the NASS nomenclature system in predicting postoperative outcomes after microdiscectomy has yet to be studied. We showed that sequestration status and disc area are both reliable and able to predict the odds of achieving MCID in certain clinical outcomes at 3 months and 12 months after surgery. Hence, preoperative imaging analysis of lumbar disc herniations may be useful in accurately setting patient expectations.

19.
J Am Acad Orthop Surg ; 32(3): e134-e145, 2024 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-37824083

RESUMO

BACKGROUND: Intramedullary nail fixation is commonly used for prophylactic stabilization of impending and fixation of complete pathological fractures of the long bones. However, metallic artifacts complicate imaging evaluation for bone healing or tumor progression and postoperative radiation planning. Carbon-fiber implants have gained popularity as an alternative, given their radiolucency and superior axial bending. This study evaluates incidences of mechanical and nonmechanical complications. METHODS: Adult patients (age 18 years and older) treated with carbon-fiber nails for impending/complete pathological long bone fractures secondary to metastases from 2013 to 2020 were analyzed for incidences and risk factors of mechanical and nonmechanical complications. Mechanical complications included aseptic screw loosening and structural failures of host bone and carbon-fiber implants. Deep infection and tumor progression were considered nonmechanical. Other complications/adverse events were also reported. RESULTS: A total of 239 patients were included; 47% were male, and 53% were female, with a median age of 68 (IQR, 59 to 75) years. Most common secondary metastases were related to breast cancer (19%), lung cancer (19%), multiple myeloma (18%), and sarcoma (13%). In total, 17 of 30 patients with metastatic sarcoma received palliative intramedullary nail fixation for impending/complete pathological fractures, and 13 of 30 received prophylactic nail stabilization of bone radiated preoperatively to manage juxta-osseous soft-tissue sarcomas, where partial resection of the periosteum or bone was necessary for negative margin resection. 33 (14%) patients had complications. Mechanical failures included 4 (1.7%) structural host bone failures, 7 (2.9%) implant structural failures, and 1 (0.4%) aseptic loosening of distal locking screws. Nonmechanical failures included 8 (3.3%) peri-implant infections and 15 (6.3%) tumor progressions with implant contamination. The 90-day and 1-year mortalities were 28% (61/239) and 53% (53/102), respectively. The literature reported comparable failure and mortality rates with conventional titanium treatment. CONCLUSIONS: Carbon-fiber implants might be an alternative for treating impending and sustained pathological fractures secondary to metastatic bone disease. The seemingly comparable complication profile warrants further cohort studies comparing carbon-fiber and titanium nail complications.


Assuntos
Fixação Intramedular de Fraturas , Fraturas Espontâneas , Sarcoma , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Pinos Ortopédicos , Fibra de Carbono , Fixação Intramedular de Fraturas/métodos , Fraturas Espontâneas/etiologia , Titânio , Resultado do Tratamento
20.
J Neurosci ; 32(23): 7806-18, 2012 Jun 06.
Artigo em Inglês | MEDLINE | ID: mdl-22674257

RESUMO

Malignant gliomas, including glioblastoma multiforme, constitute the most common and aggressive primary brain tumors in adults. The transcription factor signal transducer and activator of transcription 3 (STAT3) plays an essential role in glioblastoma pathogenesis downstream of the major oncogenic protein epidermal growth factor receptor variant III (EGFRvIII). However, the critical gene targets of STAT3 that mediate EGFRvIII-induced glial transformation have remained unknown. Here, we identify inducible nitric oxide synthase (iNOS) as a novel target gene of STAT3 in EGFRvIII-expressing mouse astrocytes. Endogenous STAT3 occupies the endogenous iNOS promoter and stimulates iNOS transcription in EGFRvIII-expressing astrocytes. STAT3 does not appear to control iNOS transcription in astrocytes deficient in the major glioblastoma tumor suppressor protein phosphatase and tensin homolog (PTEN), suggesting that STAT3 regulates iNOS transcription specifically in EGFRvIII-expressing astrocytes. Importantly, inhibition of iNOS by distinct approaches, including knockdown by RNA interference, reduces cell population growth and invasiveness of EGFRvIII-expressing astrocytes. In addition, upon iNOS knockdown or administration of a small-molecule inhibitor of iNOS, EGFRvIII-expressing astrocytes form smaller tumors in vivo. These findings suggest that inhibition of iNOS may have potential therapeutic value for EGFRvIII-activated brain tumors.


Assuntos
Proliferação de Células , Transformação Celular Neoplásica/patologia , Receptores ErbB/fisiologia , Neuroglia/fisiologia , Óxido Nítrico Sintase Tipo II/antagonistas & inibidores , Óxido Nítrico Sintase Tipo II/fisiologia , Fator de Transcrição STAT3/fisiologia , Transdução de Sinais/fisiologia , Animais , Animais Geneticamente Modificados , Astrócitos/efeitos dos fármacos , Astrócitos/fisiologia , Sítios de Ligação , Transformação Celular Neoplásica/efeitos dos fármacos , Células Cultivadas , Imunoprecipitação da Cromatina , Inibidores Enzimáticos/farmacologia , Glioblastoma/genética , Glioblastoma/patologia , Imuno-Histoquímica , Lentivirus/genética , Camundongos , Óxido Nítrico Sintase Tipo II/genética , PTEN Fosfo-Hidrolase/genética , PTEN Fosfo-Hidrolase/fisiologia , Plasmídeos/genética , Reação em Cadeia da Polimerase , Interferência de RNA , Transdução de Sinais/efeitos dos fármacos , Transcrição Gênica
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