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1.
Orthop J Sports Med ; 10(11): 23259671221132555, 2022 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-36425010

RESUMEN

Background: Different surgical techniques have been described for the treatment of knee dislocation (KD). Nonoperative approaches are frequently combined with surgical reconstruction using auto- or allograft. Purpose: To evaluate the midterm results of primary surgical repair and suture augmentation to treat KD. Study Design: Case series; Level of evidence, 4. Methods: A total of 22 patients (5 women, 17 men; mean age, 45 ± 15 years) with KD were evaluated at a mean of 49 ± 16 months after surgical treatment that included primary repair and suture augmentation. Magnetic resonance imaging, stress radiographs, and outcome scores were obtained at the follow-up. Clinical examination including hop tests and force measurements for flexion and extension was performed. Results: The mean difference in pre- to postinjury Tegner scores was -2 ± 1. The outcome scores showed mean values of 84 ± 15 (Lysholm), 73 ± 15 (International Knee Documentation Committee) and 65 ± 25 (Anterior Cruciate Ligament-Return to Sport after Injury scale). Compared with the uninjured knee, the range of motion of the injured knee was reduced by 21° ± 12°. Twelve patients felt fit enough to perform hop tests and showed a mean deficit of 7% ± 17%° compared with the uninjured leg. The mean force deficit was 19% ± 18% for extension and 8% ± 16% for flexion. Stress radiographs revealed an 11 ± 7-mm higher anteroposterior translation on the injured side. Four patients had secondary ligament reconstructions due to persistent instability and 7 underwent arthroscopic arthrolysis due to stiffness. A significant increase of osteoarthritis was found for the medial, lateral, and patellofemoral compartments (P = .007, .004, and .006, respectively). Conclusion: Primary repair and suture augmentation of KD led to satisfactory clinical midterm results despite persistent radiological instability and a significant increase in osteoarthritis. This technique allows the return to activities of daily living without subjective instability in most nonathletic patients. Secondary ligament reconstructions should be performed if relevant instability persists to decrease the risk of secondary meniscal and cartilage damage.

2.
Front Immunol ; 12: 701626, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34140958

RESUMEN

High-fat diets (HFD) are linked to obesity and associated comorbidities and induce pathogenic T helper (Th) 17 cells while decreasing regulatory T cells (Treg). This pro-inflammatory environment also aggravates immunopathology in experimental autoimmune encephalomyelitis (EAE) as a prototype model of T cell mediated autoimmunity. The strong association of HFD to obesity as well as the increasing risk of autoimmunity in the Western world stresses the importance to identify compounds that counteract this metabolically induced pro-inflammatory state in humans. One prominent candidate is the short-chain fatty acid propionate (PA) that was recently identified as potent therapy in the autoimmune disease multiple sclerosis by enhancing Treg cell frequencies and functionality. Mice were fed a HFD rich lauric acid (LA) and treated either with water or PA during MOG35-55-EAE. We analyzed Treg and Th17 cell frequencies in different tissues, antigen-specific cell proliferation and cytokine secretion, investigated Treg cell functionality by suppression assays and IL-10 signaling blockade and employed Western blotting to investigate the involvement of p38-MAPK signaling. Finally, we performed an explorative study in obese and non-obese MS patients, investigating fecal PA concentrations as well as peripheral Th17 and Treg frequencies before and after 90 days of daily PA intake. As compared to controls, mice on a HFD displayed a more severe course of EAE with enhanced demyelination and immune cell infiltration in the spinal cord. PA treatment prevented this disease enhancing effect of HFD by inhibiting Th17 mediated inflammatory processes in the gut and the spleen. Blocking experiments and signaling studies revealed p38-MAPK and IL-10 signaling as important targets linking the beneficial effects of PA treatment and reduced inflammation due to enhanced Treg frequency and functionality. An explorative study in a small group of MS patients revealed reduced PA concentrations in fecal samples of obese MS patients compared to the non-obese group, coinciding with increased Th17 but decreased Treg cells in obese patients. Importantly, PA intake could restore the Treg-Th17 homeostasis. Our data thus identify Th17 responses as an important target for the beneficial effects of PA in HFD and obesity in addition to the recently identified potential of PA as a Treg inducing therapy in T cell mediated autoimmunity.


Asunto(s)
Autoinmunidad/efectos de los fármacos , Dieta Alta en Grasa/efectos adversos , Propionatos/farmacología , Células Th17/efectos de los fármacos , Animales , Proliferación Celular/efectos de los fármacos , Citocinas/metabolismo , Encefalomielitis Autoinmune Experimental/tratamiento farmacológico , Encefalomielitis Autoinmune Experimental/metabolismo , Femenino , Humanos , Inflamación/tratamiento farmacológico , Inflamación/metabolismo , Masculino , Ratones , Ratones Endogámicos C57BL , Esclerosis Múltiple/tratamiento farmacológico , Esclerosis Múltiple/metabolismo , Transducción de Señal/efectos de los fármacos , Médula Espinal/efectos de los fármacos , Médula Espinal/metabolismo , Bazo/efectos de los fármacos , Bazo/metabolismo , Linfocitos T Reguladores/efectos de los fármacos , Linfocitos T Reguladores/metabolismo , Células Th17/metabolismo
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