RESUMO
We report on 12 consecutive patients with advanced/metastatic Ewing's sarcoma who were treated as a separate cohort of a phase 1 trial of FANG autologous immunotherapy (1 × 10(6)-2.5 × 10(7) cells/intradermal injection each month for minimum 4 months). Safety and clinical response were monitored. Patient immune response to unmodified autologous tumor cells was assessed by gamma interferon-enzyme-linked immunospot (γIFN-ELISPOT) assay using peripheral blood mononuclear cells from baseline (pretreatment) and multiple postvaccination time points. None of the 12 patients (47 vaccinations) developed grade 2/3/4 drug-related toxicity. Median product release granulocyte-macrophage colony-stimulating factor expression was 1,941 pg/10(6) cells, and TGFß1and TGFß2 knockdown were 99 and 100%, respectively. Eight patients were assessed for ELISPOT response to autologous tumor cells at baseline and all (100%) were negative. In contrast, follow-up ELISPOT response at month 1 or month 4 (one patient) after FANG was positive in all eight patients. One patient achieved a partial tumor response (38% tumor reduction, RECIST 1.1). The Kaplan-Meier estimated survival of these 12 patients at 1 year was 75%. In this phase 1 study in patients with Ewing's sarcoma, FANG immunotherapy was well tolerated, elicited a tumor-specific systemic immune response in all patients, and was associated with favorable 1-year survival. Further clinical testing is indicated.
Assuntos
Imunoterapia/métodos , Sarcoma de Ewing/terapia , Adolescente , Adulto , Feminino , Regulação da Expressão Gênica , Fator Estimulador de Colônias de Granulócitos e Macrófagos/genética , Fator Estimulador de Colônias de Granulócitos e Macrófagos/metabolismo , Humanos , Interferon gama/metabolismo , Leucócitos Mononucleares/metabolismo , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica/terapia , Projetos Piloto , Fator de Crescimento Transformador beta1/genética , Fator de Crescimento Transformador beta1/metabolismo , Fator de Crescimento Transformador beta2/genética , Fator de Crescimento Transformador beta2/metabolismo , Resultado do Tratamento , Adulto JovemRESUMO
Background: Patellar instability is frequently encountered in patients with Ehlers-Danlos syndrome (EDS). The clinical outcomes of isolated medial patellofemoral ligament reconstruction (MPFLR) for patellar instability in patients with EDS are unknown. Purpose: To evaluate midterm clinical outcomes of isolated MPFLR for patellar instability in patients with EDS and factors affecting these outcomes. Study Design: Case series; Level of evidence, 4. Methods: In a retrospective study, 31 patients (n = 47 knees) with EDS and patellar instability who underwent isolated MPFLR for recurrent patellar instability between 2008 and 2017 and had a minimum 2-year follow-up were identified. Preoperative radiographic images were measured for anatomic risk factors. Clinical outcomes-including postoperative complications-were evaluated. Factors associated with MPFLR failure were identified. Postoperative patient-reported outcomes (PROs)-including the pediatric version of the International Knee Documentation Committee, the Kujala score, the Hospital for Special Surgery Pediatric Functional Activity Brief Scale, the Banff Patellofemoral Instability Instrument 2.0, and the Knee injury and Osteoarthritis Outcome Score-were collected, and factors affecting PRO scores were analyzed. Results: The mean age of the cohort was 14.9 ± 2 years. At a mean follow-up of 7.2 years, 18 of 47 (38.3%) knees required reoperations, of which 9 of 47 (19.1%) knees required revision stabilization for recurrent patellar instability. Also, 7 of 31 knees (22.6%) with autografts failed compared with 2 of 16 (12.5%) with allografts (P = .69). For autografts, 6 of 17 (35.3%) failures occurred with gracilis, but 0 of 13 (0%) occurred with semitendinosus (P = .02). Compared with patients without failures, patients with failed primary MPFLR were significantly younger (P = .0005) and were able to touch the palm to the floor with their knees extended (P = .03). For radiographic parameters, the patellar height and tilt were significantly higher in the failure group. The postoperative PROs were suboptimal at a mean follow-up of 5.2 years. All but 1 patient were satisfied with the final outcome. Conclusion: At the midterm follow-up, 38.3% of patients with EDS required further surgery after isolated MPFLR for patellar instability; half of these revisions (19.1%) were to address recurrent instability. Recurrent instability after isolated MPFLR was more likely in younger patients and those who could touch the palm to the floor with their knees extended. Postoperative PROs were inferior; nonetheless, patient satisfaction was high.
RESUMO
Introduction. Acute compartment syndrome (ACS) occurs secondary to increasing pressure within a fascial compartment that exceeds perfusion pressure. This can be caused by spontaneous hematomas, which can be secondary to prolonged anticoagulation therapy. Eliquis® has not been associated with ACS of the thigh in any of the currently published literature. Identifying ACS early is important because it can reduce the risk of permanent structural damage, limb amputations, and mortality rates. Case Report. A 43-year-old male with past medical history of unprovoked Deep Vein Thrombosis (DVT) eight months prior to presentation on Eliquis® presented to the emergency department for significant right thigh pain after riding a roller coaster. There was increased tone/firmness of the anterior compartment and tenderness on palpation of the proximal two-thirds of the anterior thigh. Imaging, clinical findings, and Stryker needle measurements confirmed ACS secondary to hematoma, which required fasciotomy and evacuation of the hematoma. The patient was temporarily switched to aspirin for DVT prophylaxis postoperatively to prevent new hematoma formation. Six weeks later, the patient arrived at the ED with a DVT that was treated with Eliquis®. Eight months later, the same patient presented with acute right thigh pain that started while lying in bed. A diagnosis of recurrent ACS in the right anterior thigh was made, requiring a fasciotomy. Surgery was successful without any complications. Discussion. Eliquis® is associated with an increased risk of hematoma formation, which can lead to ACS. This is a rare adverse effect that providers should be aware of because it requires early management to prevent ACS-associated complications. This is significant because no currently published literature has identified an association of Eliquis® with ACS in the thigh. In cases of atraumatic ACS, we were unable to find any protocols advocating for or against the use of DVT prophylaxis postfasciotomy in the literature.