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Severe asthma is a syndromic label assigned to patients based on clinical parameters, yet there are diverse underlying molecular endotypes in severe asthma pathobiology. Immunophenotyping of asthma biospecimens commonly includes a mixture of granulocytes and lymphocytes. Recently, a subset of severe asthma patients was defined as non-type 2 with neutrophil-enriched inflammation associated with increased Th17 CD4+ T cells and IL-17 levels. Here, we used an allergen-driven mouse model of increased IL-17 and mixed granulocyte lung inflammation to determine the impact of upstream regulation by an Anticalin protein that specifically binds IL-23. Airway administration of the IL-23 binding Anticalin protein (AcIL-23) decreased lung neutrophils, eosinophils, macrophages, and lymphocytes, IL-17+ CD4 T cells, mucous cell metaplasia and methacholine-induced airway hyperresponsiveness. Selective targeting of IL-23 with a monoclonal antibody (IL-23p19) (αIL-23) also decreased macrophages, IL-17+ CD4 T cells and airway hyperresponsiveness. In contrast, a monoclonal antibody against IL-17A (αIL-17A) had no significant effect on airway hyperresponsiveness, but did decrease lung neutrophils, macrophages, and IL-17+ CD4 T cells. Targeting the IL-23 pathway did not significantly change IL-5+ or IL-13+ CD4 T cells. Together, these data indicate that airway AcIL-23 mirrored the activity of systemic anti-IL-23 antibody to decrease airway hyperresponsiveness in addition to mixed granulocytic inflammation, and that these protective actions were broader than blocking only IL-17A or IL-5, which selectively decreased airway neutrophils and eosinophils, respectively.
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Specialized proresolving mediators (SPMs) promote local macrophage efferocytosis but excess leukocytes early in inflammation require additional leukocyte clearance mechanism for resolution. Here, neutrophil clearance mechanisms from localized acute inflammation were investigated in mouse dorsal air pouches. 15-HEPE (15-hydroxy-5Z,8Z,11Z,13E,17Z-eicosapentaenoic acid) levels were increased in the exudates. Activated human neutrophils converted 15-HEPE to lipoxin A5 (5S,6R,15S-trihydroxy-7E,9E,11Z,13E,17Z-eicosapentaenoic acid), 15-epi-lipoxin A5 (5S,6R,15R-trihydroxy-7E,9E,11Z,13E,17Z-eicosapentaenoic acid), and resolvin E4 (RvE4; 5S,15S-dihydroxy-6E,8Z,11Z,13E,17Z-eicosapentaenoic acid). Exogenous 15-epi-lipoxin A5, 15-epi-lipoxin A4 and a structural lipoxin mimetic significantly decreased exudate neutrophils and increased local tissue macrophage efferocytosis, with comparison to naproxen. 15-epi-lipoxin A5 also cleared exudate neutrophils faster than the apparent local capacity for stimulated macrophage efferocytosis, so the fate of exudate neutrophils was tracked with CD45.1 variant neutrophils. 15-epi-lipoxin A5 augmented the exit of adoptively transferred neutrophils from the pouch exudate to the spleen, and significantly increased splenic SIRPa+ and MARCO+ macrophage efferocytosis. Together, these findings demonstrate new systemic resolution mechanisms for 15-epi-lipoxin A5 and RvE4 in localized tissue inflammation, which distally engage the spleen to activate macrophage efferocytosis for the clearance of tissue exudate neutrophils.
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Lipoxinas , Macrófagos , Neutrófilos , Baço , Animais , Neutrófilos/metabolismo , Neutrófilos/efeitos dos fármacos , Macrófagos/metabolismo , Camundongos , Humanos , Lipoxinas/metabolismo , Lipoxinas/farmacologia , Baço/metabolismo , Baço/citologia , Ácido Eicosapentaenoico/análogos & derivados , Ácido Eicosapentaenoico/farmacologia , Ácido Eicosapentaenoico/metabolismo , Camundongos Endogâmicos C57BL , Fagocitose , Masculino , Inflamação/metabolismo , Ácidos HeptanoicosRESUMO
Purpose: To report the clinical outcomes and reoperation rates of arthroscopic and endoscopic iliopsoas release at short-term follow-up after ipsilateral total hip arthroplasty (THA) at 2 separate medical institutions and to evaluate whether demographic and radiographic parameters are associated with postoperative patient-reported outcomes (PROs). Methods: Patients with iliopsoas tendinitis in the setting of prior THA who underwent arthroscopic iliopsoas fractional lengthening from 1988 to 2023 at 2 academic institutions were reviewed. Patients were included if they had 12 months of follow-up and underwent evaluation of preoperative anterior acetabular component overhang, surgery satisfaction, postoperative subjective hip flexion strength and anterior groin pain improvement, modified Harris Hip Score, Single Assessment Numeric Evaluation score, Tegner activity scale score, visual analog scale (VAS) score, and revision hip arthroplasty. Results: Sixty hips in 58 patients (19 male and 39 female patients) were followed up for a mean of 39.3 months (range, 12.0-105.9 months) postoperatively. Of the patients, 77% reported feeling "much better" or "slightly better," 75% reported improved anterior groin pain, and 60% reported improved subjective hip flexion strength. The surgery satisfaction rating was 7.2 ± 3.3 (scale of 0 to 10). The mean postoperative modified Harris Hip Score, VAS score for pain at rest, VAS score for pain with use, and Single Assessment Numeric Evaluation score were 73.9 ± 19.4, 1.3 ± 2.4, 3.8 ± 2.9, and 71.9 ± 21.9, respectively. Preoperative anterior acetabular component overhang was 3.3 ± 6.5 mm and did not significantly correlate with postoperative PROs (P ≥ .45). The Tegner score improved from 2.5 ± 1.7 preoperatively to 2.9 ± 1.4 postoperatively (P = .0253). Three patients underwent revision arthroplasty at a mean of 25.3 months (range, 11.6-40.4 months) postoperatively, with an acetabular component revision rate of 3.3%. Conclusions: Satisfactory outcomes and low revision arthroplasty rates were observed in patients undergoing arthroscopic iliopsoas lengthening after THA. There was no statistically significant relation between anterior acetabular component overhang and final PROs. Level of Evidence: Level IV, therapeutic case series.
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Combined ACL/MCL injuries are relatively common and multiple factors are involved in surgical decision-making, particularly when it comes to the MCL. Historically, most surgeons treated the MCL conservatively, and performed staged MCL reconstruction after MCL reconstruction only if there was persistent medial instability. This was followed by a non-operative approach for the MCL (when reconstructing the ACL) unless there was evidence of extreme (Grade III or > 1 cm) valgus instability, valgus malalignment, or mid-substance or tibial sided injury, avulsion, or Stener lesion. However, the most recent research demonstrates that combined ACL/MCL injuries present a higher risk of ACL reconstruction failure and subsequent revision compared to ACL injuries alone. With growing biomechanical and clinical evidence, more surgeons are repairing or reconstructing the MCL in these combined injuries. Although there is no clear consensus, we recommend surgeons consider surgically treating the MCL to avoid not only excessive force on the ACL graft but also persistent valgus laxity, which can lead to ACL failure. For distal MCL avulsions, repairs have shown excellent midterm outcomes, especially if the tissue quality is pristine. If the tissue quality is not repairable, then we would advocate for repairing whatever tissue is repairable and augmenting with an MCL reconstruction. For mid substance MCL injuries, if surgical intervention is required, we advocate for MCL reconstruction. For proximal tears, the same criteria used for distal tears apply with management based on tissue quality and joint stability after repair. The ACL is a secondary stabilizer to valgus loads, and MCL deficiency results in tremendous strain on ACL graft reconstructions. If the MCL is even mildly incompetent, we strongly advocate for treating the MCL surgically in this setting.
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Mucus plugs occlude airways to obstruct airflow in asthma. Studies in patients and in mouse models show that mucus plugs occur in the context of type 2 inflammation, and studies in human airway epithelial cells (HAECs) show that IL-13-activated cells generate pathologic mucus independently of immune cells. To determine how HAECs autonomously generate pathologic mucus, we used a magnetic microwire rheometer to characterize the viscoelastic properties of mucus secreted under varying conditions. We found that normal HAEC mucus exhibited viscoelastic liquid behavior and that mucus secreted by IL-13-activated HAECs exhibited solid-like behavior caused by mucin cross-linking. In addition, IL-13-activated HAECs shows increased peroxidase activity in apical secretions, and an overlaid thiolated polymer (thiomer) solution shows an increase in solid behavior that was prevented by peroxidase inhibition. Furthermore, gene expression for thyroid peroxidase (TPO), but not lactoperoxidase (LPO), was increased in IL-13-activated HAECs and both TPO and LPO catalyze the formation of oxidant acids that cross-link thiomer solutions. Finally, gene expression for TPO in airway epithelial brushings was increased in patients with asthma with high airway mucus plug scores. Together, our results show that IL-13-activated HAECs autonomously generated pathologic mucus via peroxidase-mediated cross-linking of mucin polymers.
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Células Epiteliais , Interleucina-13 , Muco , Humanos , Interleucina-13/metabolismo , Interleucina-13/farmacologia , Células Epiteliais/metabolismo , Muco/metabolismo , Mucinas/metabolismo , Asma/metabolismo , Asma/patologia , Mucosa Respiratória/metabolismo , Mucosa Respiratória/patologia , Lactoperoxidase/metabolismo , GéisRESUMO
By incompletely understood mechanisms, type 2 (T2) inflammation present in the airways of severe asthmatics drives the formation of pathologic mucus which leads to airway mucus plugging. Here we investigate the molecular role and clinical significance of intelectin-1 (ITLN-1) in the development of pathologic airway mucus in asthma. Through analyses of human airway epithelial cells we find that ITLN1 gene expression is highly induced by interleukin-13 (IL-13) in a subset of metaplastic MUC5AC+ mucus secretory cells, and that ITLN-1 protein is a secreted component of IL-13-induced mucus. Additionally, we find ITLN-1 protein binds the C-terminus of the MUC5AC mucin and that its deletion in airway epithelial cells partially reverses IL-13-induced mucostasis. Through analysis of nasal airway epithelial brushings, we find that ITLN1 is highly expressed in T2-high asthmatics, when compared to T2-low children. Furthermore, we demonstrate that both ITLN-1 gene expression and protein levels are significantly reduced by a common genetic variant that is associated with protection from the formation of mucus plugs in T2-high asthma. This work identifies an important biomarker and targetable pathways for the treatment of mucus obstruction in asthma.
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Asma , Proteínas Ligadas por GPI , Interleucina-13 , Lectinas , Mucina-5AC , Muco , Criança , Humanos , Asma/genética , Asma/metabolismo , Citocinas , Células Epiteliais/metabolismo , Proteínas Ligadas por GPI/genética , Proteínas Ligadas por GPI/metabolismo , Interleucina-13/genética , Interleucina-13/metabolismo , Lectinas/genética , Lectinas/metabolismo , Mucina-5AC/genética , Mucina-5AC/metabolismo , Muco/metabolismo , Mucosa Nasal/metabolismo , Polimorfismo Genético , Mucosa Respiratória/metabolismoRESUMO
Background: Patients with isolated anterior cruciate ligament (ACL) reconstruction have demonstrated an increased risk of ACL graft failure and lower patient-reported outcome (PRO) scores when increased posterior tibial slope (PTS) is present. However, there is a paucity of literature evaluating the effect of PTS on outcomes after combined bicruciate multiligamentous knee reconstruction. Purpose: To determine whether differences exist for graft failure rates or PRO scores based on PTS after combined bicruciate multiligamentous knee reconstruction. Study Design: Cohort study; Level of evidence, 3. Methods: All patients who underwent combined ACL and posterior cruciate ligament (PCL) reconstruction between 2000 and 2020 at our institution were identified. Exclusion criteria were age <18 years, knee dislocation grade 5 injuries, concomitant osteotomy procedures, and <2 years of clinical follow-up. Demographic and outcomes data were collected from our prospectively gathered multiligamentous knee injury database. Lysholm and International Knee Documentation Committee (IKDC) scores were analyzed in relation to PTS. Outcomes were compared for patients with a PTS above and below the mean for the total cohort, PTS >12° versus <12°, positive versus negative Lachman test at follow-up, and positive versus negative posterior drawer test at follow-up. Results: A total of 98 knees in 98 patients were included in the study, with a mean clinical follow-up of 5.1 years (median, 4.6 years; range, 2-16 years). The mean PTS was 8.7° (range, 0.4°-16.9°). Linear regression analysis showed no significant correlation between PTS and IKDC or Lysholm scores. Patients with a PTS above the mean of 8.7° trended toward lower IKDC (P = .08) and Lysholm (P = .06) scores. Four patients experienced ACL graft failure and 5 patients experienced PCL graft failure. There were no differences in graft failure rates or PRO scores for patients with a PTS >12°. Patients with a positive Lachman test trended toward higher PTS (9.6° vs 8.5°, P = .15). Conclusion: In this series of bicruciate multiligamentous knee reconstructions at midterm follow-up, no differences in graft failures, complications, reoperations, revisions, or PRO scores based on PTS were identified. Patients with a positive Lachman test were found to have a slightly higher PTS, although this did not reach statistical significance.
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Secreted deoxyribonucleases (DNases), such as DNase-I and DNase-IL3, degrade extracellular DNA, and endogenous DNases have roles in resolving airway inflammation and guarding against autoimmune responses to nucleotides. Subsets of patients with asthma have high airway DNA levels, but information about DNase activity in health and in asthma is lacking. To characterize DNase activity in health and in asthma, we developed a novel kinetic assay using a Taqman probe sequence that is quickly cleaved by DNase-I to produce a large product signal. We used this kinetic assay to measure DNase activity in sputum from participants in the Severe Asthma Research Program (SARP)-3 (n = 439) and from healthy controls (n = 89). We found that DNase activity was lower than normal in asthma [78.7 relative fluorescence units (RFU)/min vs. 120.4 RFU/min, P < 0.0001]. Compared to patients with asthma with sputum DNase activity in the upper tertile activity levels, those in the lower tertile of sputum DNase activity were characterized clinically by more severe disease and pathologically by airway eosinophilia and airway mucus plugging. Carbamylation of DNase-I, a post-translational modification that can be mediated by eosinophil peroxidase, inactivated DNase-I. In summary, a Taqman probe-based DNase activity assay uncovers low DNase activity in the asthma airway that is associated with more severe disease and airway mucus plugging and may be caused, at least in part, by eosinophil-mediated carbamylation.NEW & NOTEWORTHY We developed a new DNase assay and used it to show that DNase activity is impaired in asthma airways.
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Asma , Desoxirribonuclease I , Escarro , Humanos , Asma/metabolismo , Asma/enzimologia , Feminino , Masculino , Escarro/metabolismo , Escarro/enzimologia , Adulto , Pessoa de Meia-Idade , Desoxirribonuclease I/metabolismo , Desoxirribonucleases/metabolismoRESUMO
BACKGROUND: The relative utility of eosinophil peroxidase (EPX) and blood and sputum eosinophil counts as disease biomarkers in asthma is uncertain. OBJECTIVE: We sought to determine the utility of EPX as a biomarker of systemic and airway eosinophilic inflammation in asthma. METHODS: EPX protein was measured by immunoassay in serum and sputum in 110 healthy controls to establish a normal reference range and in repeated samples of serum and sputum collected during 3 years of observation in 480 participants in the Severe Asthma Research Program 3. RESULTS: Over 3 years, EPX levels in patients with asthma were higher than normal in 27% to 31% of serum samples and 36% to 53% of sputum samples. Eosinophils and EPX correlated better in blood than in sputum (rs values of 0.74 and 0.43, respectively), and high sputum EPX levels occurred in 27% of participants with blood eosinophil counts less than 150 cells/µL and 42% of participants with blood eosinophil counts between 150 and 299 cells/µL. Patients with persistently high sputum EPX values for 3 years were characterized by severe airflow obstruction, frequent exacerbations, and high mucus plug scores. In 59 patients with asthma who started mepolizumab during observation, serum EPX levels normalized in 96% but sputum EPX normalized in only 49%. Lung function remained abnormal even when sputum EPX normalized. CONCLUSIONS: Serum EPX is a valid protein biomarker of systemic eosinophilic inflammation in asthma, and sputum EPX levels are a more sensitive biomarker of airway eosinophilic inflammation than sputum eosinophil counts. Eosinophil measures in blood frequently miss airway eosinophilic inflammation, and mepolizumab frequently fails to normalize airway eosinophilic inflammation even though it invariably normalizes systemic eosinophilic inflammation.
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Capsular management in hip arthroscopy has recently become a popular topic in the literature. Various approaches have been developed around the critical balance between safe and satisfactory exposure while maintaining hip joint stability and the restoration of capsular integrity at the conclusion of the case. Advocates for capsular closure recognize the role of the capsule in providing hip joint stability and aim to reestablish normal hip biomechanics through capsule preservation. Several recent studies have also shown capsular management strategies to influence both clinical outcomes and risk of revision surgery. We present an effective method for capsular management in hip arthroscopy that consistently allows excellent exposure and working space while allowing for facile, anatomic closure.
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Vitamin D possesses immunomodulatory functions and vitamin D deficiency has been associated with the rise in chronic inflammatory diseases, including asthma (Litonjua and Weiss, 2007). Vitamin D supplementation studies do not provide insight into the molecular genetic mechanisms of vitamin D-mediated immunoregulation. Here, we provide evidence for vitamin D regulation of two human chromosomal loci, Chr17q12-21.1 and Chr17q21.2, reliably associated with autoimmune and chronic inflammatory diseases. We demonstrate increased vitamin D receptor (Vdr) expression in mouse lung CD4+ Th2 cells, differential expression of Chr17q12-21.1 and Chr17q21.2 genes in Th2 cells based on vitamin D status and identify the IL-2/Stat5 pathway as a target of vitamin D signaling. Vitamin D deficiency caused severe lung inflammation after allergen challenge in mice that was prevented by long-term prenatal vitamin D supplementation. Mechanistically, vitamin D induced the expression of the Ikzf3-encoded protein Aiolos to suppress IL-2 signaling and ameliorate cytokine production in Th2 cells. These translational findings demonstrate mechanisms for the immune protective effect of vitamin D in allergic lung inflammation with a strong molecular genetic link to the regulation of both Chr17q12-21.1 and Chr17q21.2 genes and suggest further functional studies and interventional strategies for long-term prevention of asthma and other autoimmune disorders.
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Asma , Pneumonia , Deficiência de Vitamina D , Camundongos , Animais , Humanos , Vitamina D/farmacologia , Interleucina-2 , Inflamação , Células Th2 , Deficiência de Vitamina D/metabolismo , VitaminasRESUMO
Although isolated posterior cruciate ligament (PCL) injuries often can be treated successfully without surgical intervention, in the setting of persistent instability or multiligamentous knee injury, PCL reconstruction is indicated. PCL reconstructions often have resulted in persistent postoperative laxity. Recent research suggests there may be a role for suture tape-augmented grafts, which have demonstrated decreased clinical and radiographic laxity as well as improved rates of return to previous level of activity, as compared with PCL reconstruction alone. Several biomechanical studies also have supported the use of suture tape augmentation in PCL reconstruction, and the use of suture tape augmentation or internal bracing and ligament surgery is gaining widespread popularity. These ultrahigh molecular weight polyethylene/polyester suture tapes have been shown to be safe and effective. We may be at the point at which the evidence supports the use of suture tape augmentation of PCL reconstruction.
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Reconstrução do Ligamento Cruzado Posterior , Ligamento Cruzado Posterior , Humanos , Ligamento Cruzado Posterior/cirurgia , Ligamento Cruzado Posterior/lesões , Instabilidade Articular/cirurgia , Suturas , Traumatismos do Joelho/cirurgia , Técnicas de Sutura , Fita CirúrgicaRESUMO
RATIONALE: Respiratory virus-induced inflammation is the leading cause of asthma exacerbation, frequently accompanied by induction of interferon-stimulated genes (ISGs). How asthma-susceptibility genes modulate cellular response upon viral infection by fine-tuning ISG induction and subsequent airway inflammation in genetically susceptible asthma patients remains largely unknown. OBJECTIVES: To decipher the functions of gasdermin B (encoded by GSDMB) in respiratory virus-induced lung inflammation. METHODS: In two independent cohorts, we analysed expression correlation between GSDMB and ISG s. In human bronchial epithelial cell line or primary bronchial epithelial cells, we generated GSDMB-overexpressing and GSDMB-deficient cells. A series of quantitative PCR, ELISA and co-immunoprecipitation assays were performed to determine the function and mechanism of GSDMB for ISG induction. We also generated a novel transgenic mouse line with inducible expression of human unique GSDMB gene in airway epithelial cells and infected the mice with respiratory syncytial virus to determine the role of GSDMB in respiratory syncytial virus-induced lung inflammation in vivo. RESULTS: GSDMB is one of the most significant asthma-susceptibility genes at 17q21 and acts as a novel RNA sensor, promoting mitochondrial antiviral-signalling protein (MAVS)-TANK binding kinase 1 (TBK1) signalling and subsequent inflammation. In airway epithelium, GSDMB is induced by respiratory viral infections. Expression of GSDMB and ISGs significantly correlated in respiratory epithelium from two independent asthma cohorts. Notably, inducible expression of human GSDMB in mouse airway epithelium led to enhanced ISGs induction and increased airway inflammation with mucus hypersecretion upon respiratory syncytial virus infection. CONCLUSIONS: GSDMB promotes ISGs expression and airway inflammation upon respiratory virus infection, thereby conferring asthma risk in risk allele carriers.
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Proteínas Adaptadoras de Transdução de Sinal , Asma , Gasderminas , Proteínas Serina-Treonina Quinases , Transdução de Sinais , Animais , Humanos , Asma/metabolismo , Asma/genética , Camundongos , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Proteínas Adaptadoras de Transdução de Sinal/genética , Proteínas Serina-Treonina Quinases/metabolismo , Proteínas Serina-Treonina Quinases/genética , Camundongos Transgênicos , Proteínas de Neoplasias/genética , Proteínas de Neoplasias/metabolismo , Predisposição Genética para Doença , Infecções por Vírus Respiratório Sincicial/metabolismo , Infecções por Vírus Respiratório Sincicial/genética , Células Epiteliais/metabolismo , Linhagem Celular , Brônquios/metabolismo , Brônquios/patologia , Pneumonia/metabolismo , Pneumonia/genética , Pneumonia/virologia , Feminino , Pulmão/metabolismo , Pulmão/patologiaRESUMO
The rise of online platforms like YouTube for health information has prompted scrutiny over the quality of medical/surgical-related video content. Recent research on YouTube videos regarding anterior cruciate ligament reconstruction (ACLR) with quadriceps tendon autograft shows low educational quality and reliability using established assessment tools. Physicians primarily published content, with longer videos, and physician-generated videos, generally correlating with higher quality. However, YouTube's inadequacy as a reliable source for ACLR information underscores the need for alternative educational resources. Orthopaedic health care professionals must play a pivotal role in guiding patients toward credible sources and take aim at improving online content quality. Understanding patient preferences for online resources is essential for enhancing patient education, the patient-provider relationship, and decision-making in orthopaedic care.
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Reconstrução do Ligamento Cruzado Anterior , Mídias Sociais , Gravação em Vídeo , Humanos , Educação de Pacientes como Assunto , Revisão por ParesRESUMO
Background: Increased posterior tibial slope (PTS) leads to a relative anterior translation of the tibia on the femur. This is thought to decrease the stress on posterior cruciate ligament (PCL) reconstruction (PCLR) grafts. Purpose/Hypothesis: The purpose of this study was to analyze the effect of PTS on knee laxity, graft failure, and patient-reported outcome (PRO) scores after PCLR without concomitant anterior cruciate ligament reconstruction (ACLR). It was hypothesized that patients with higher PTS would have less knee laxity, fewer graft failures, and better PROs compared with patients with lower PTS. Study Design: Case-control study; Level of evidence, 3. Methods: All patients who underwent PCLR between 2001 and 2020 at a single institution were identified. Patients were excluded if they underwent concomitant or prior ACLR or proximal tibial osteotomy, were younger than 18 years, had <2 years of in-person clinical follow-up, and did not have documented PRO scores (Lysholm score and International Knee Documentation Committee [IKDC] score). Data were collected retrospectively from a prospectively gathered database. PTS measurements were recorded from perioperative lateral knee radiographs. A linear regression model was created to analyze PTS in relation to PRO scores. Patients with a grade 1 (1-5 mm) or higher posterior drawer were compared with those who had a negative posterior drawer. Results: A total of 37 knees met inclusion criterion; the mean age was 30.7 years at the time of surgery. The mean clinical follow-up was 5.8 years. No significant correlation was found between either the Lysholm score or the IKDC score and the PTS. Twelve knees (32.4%) had a positive posterior drawer at final follow-up. The mean PTS in knees with a positive posterior drawer was 6.2°, whereas that for knees with a negative posterior drawer was 8.3° (P = .08). No significant differences in PRO scores were identified for knees with versus knees without a positive posterior drawer. No documented graft failures or revisions were found. Conclusion: No significant differences were found in PROs or graft failure rates based on PTS at a mean of 5.8 years after PCLR. Increased tibial slope trended toward being protective against a positive posterior drawer, although this did not reach statistical significance.
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BACKGROUND: Hip arthroscopy is rapidly advancing, with positive published outcomes at short- and midterm follow-up; however, available long-term data remain limited. PURPOSE: To evaluate outcomes of primary hip arthroscopy at a minimum 10-year follow-up at 2 academic centers by describing patient-reported outcomes and determining reoperation and total hip arthroplasty (THA) rates. STUDY DESIGN: Case series; Level of evidence, 4. METHODS: Patients with primary hip arthroscopy performed between January 1988 and April 2013 at 2 academic centers were evaluated for postoperative patient-reported outcomes-including the visual analog scale, Tegner Activity Scale score, Hip Outcome Score Activities of Daily Living and Sport Specific subscales, modified Harris Hip Score, Nonarthritic Hip Score, 12-item International Hip Outcome Tool, surgery satisfaction, and reoperations. RESULTS: A total of 294 patients undergoing primary hip arthroscopy (age, 40 ± 14 years; 66% women; body mass index, 27 ± 6) were followed for 12 ± 3 years (range, 10-24 years) postoperatively. Labral debridement and repair were performed in 41% and 59% of patients, respectively. Of all patients who underwent interportal capsulotomy, 2% were extended to a T-capsulotomy, and 11% underwent capsular repair. At final follow-up, patients reported a mean visual analog scale at rest of 2 ± 2 and with use of 3 ± 3, a 12-item International Hip Outcome Tool of 68 ± 27, a Nonarthritic Hip Score of 81 ± 18, a modified Harris Hip Score of 79 ± 17, and a Hip Outcome Score Activities of Daily Living of 82 ± 19 and Sport Specific subscale of 74 ± 25. The mean surgical satisfaction was 8.4 ± 2.4 on a 10-point scale, with 10 representing the highest level of satisfaction. In total, 96 hips (33%) underwent reoperation-including 65 hips (22%) converting to THA. THA risk factors included older age, higher body mass index, lower lateral center-edge angle, larger alpha angle, higher preoperative Tönnis grade, as well as labral debridement and capsular nonrepair (P≤ .039). Patients undergoing combined labral and capsular repair demonstrated a THA conversion rate of 3% compared with 31% for patients undergoing combined labral debridement and capsular nonrepair (P = .006). Labral repair trended toward increased 10-year THA-free survival (84% vs 77%; P = .085), while capsular repair demonstrated significantly increased 10-year THA-free survival (97% vs 79%; P = .033). CONCLUSION: At a minimum 10-year follow-up, patients undergoing primary hip arthroscopy demonstrated high satisfaction and acceptable outcome scores. In total, 33% of patients underwent reoperation-including 22% who underwent THA. Conversion to THA was associated with patient factors including older age, higher Tönnis grade, and potentially modifiable surgical factors such as labral debridement and capsular nonrepair.
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Impacto Femoroacetabular , Satisfação do Paciente , Humanos , Feminino , Adulto , Pessoa de Meia-Idade , Masculino , Resultado do Tratamento , Seguimentos , Artroscopia/efeitos adversos , Atividades Cotidianas , Articulação do Quadril/cirurgia , Medidas de Resultados Relatados pelo Paciente , Impacto Femoroacetabular/cirurgia , Impacto Femoroacetabular/etiologia , Estudos RetrospectivosRESUMO
BACKGROUND: Osteochondral allograft transplantation (OCAT) is an accepted knee joint-preserving treatment strategy for focal osteochondral lesions that is often conducted in combination with meniscal allograft transplantation (MAT). Despite its frequent and simultaneous utilization, there remains a lack in the literature reporting on outcomes and failure rates after concomitant procedures. PURPOSE: To determine (1) the midterm clinical success rate after OCAT+MAT in comparison with a matched-pair cohort undergoing isolated OCAT, (2) whether patient-specific and procedural variables influence the risk of failure, and (3) patient-reported outcome measures over time. STUDY DESIGN: Cohort study; Level of evidence, 3. METHODS: A single-center matched-pair cohort study was conducted investigating outcomes in patients who underwent OCAT of the medial or lateral femoral condyle with and without MAT between 2004 and 2020. Patients were matched 1:1 by age (±5 years), sex (male or female), body mass index (±5), and grouped Kellgren and Lawrence grade (grades 0-1 or 2-4). The minimum follow-up time was 2 years. Radiographic variables (International Cartilage Regeneration & Joint Preservation Society [ICRS] grade and Kellgren and Lawrence grade) were assessed preoperatively and at follow-up. Subjective patient-reported outcome measures (Lysholm score, Knee injury and Osteoarthritis Outcome Score [KOOS] including subscores, International Knee Documentation Committee [IKDC] score, and visual analog scale score) were collected preoperatively and at follow-up. Clinical failure was defined as revision surgery for graft failure or conversion to total knee arthroplasty. Patient-reported, clinical, and radiographic outcomes were compared between groups. RESULTS: In total, 66 patients (33 treated with isolated OCAT, 33 treated with OCAT+MAT; 57.6% male) with a mean age of 26.3 years (range, 18-62 years) were followed for a mean of 5.6 years (minimum, 2 years; range, 24-218 months). The 2 cohorts showed no difference in Kellgren and Lawrence grade postoperatively (P = .59). There was a significantly higher ICRS grade detected at follow-up in the OCAT+MAT group (2.81 ± 1.10) compared with the OCAT group (2.04 ± 0.96) (P < .05). There were no statistically significant differences between the groups regarding reoperation rate (OCAT: n = 6; OCAT+MAT: n = 13; P = .116), time to reoperation (OCAT: 46.67 ± 47.27 months vs OCAT+MAT: 28.08 ± 30.16 months; P = .061), and failure rate (OCAT: n = 4 [12.1%] vs OCAT+MAT: n = 5 [15.2%]; P = .66). In the OCAT+MAT group, an increase of tibial slope by 1° conferred a 1.65-fold increase in the hazard for failure over decreased slope (hazard ratio, 1.65; 95% CI, 1.10-2.50; P < .05). The overall survival rate was 86% at a mean follow-up of 5.6 years. Patient-reported outcome scores were significantly improved at the final follow-up compared with preoperative status. No significant differences were seen between groups with respect to subjective IKDC, Lysholm, Tegner, and KOOS results, except for the KOOS Symptoms subscale score, which was significantly higher in the OCAT+MAT group than in the OCAT group (mean difference, 14.6; P < .05) and did exceed the minimal clinically important difference threshold of 10.7. CONCLUSION: Midterm results after isolated OCAT and OCAT+MAT show high rates of healing and sustainable subjective improvement of knee function and quality of life. However, it should be noted that the difference in reoperation rate and time to reoperation between the groups is arguably clinically important and that lack of statistical significance may be because of low power. These results imply that isolated OCAT is an efficient joint-preserving treatment that can be combined with MAT in well-selected patients with meniscal insufficiency without negative influence on global clinical outcomes.
Assuntos
Meniscos Tibiais , Qualidade de Vida , Humanos , Masculino , Feminino , Adulto , Estudos de Coortes , Seguimentos , Meniscos Tibiais/transplante , Análise por Pareamento , Articulação do Joelho/cirurgia , Reoperação , AloenxertosRESUMO
The medial collateral ligament serves as the primary stabilizer to valgus stress on the medial side of the knee and is the most commonly injured ligament in the knee. Medial collateral ligament reconstruction can provide improved stability and clinical outcomes for patients. Advancements in techniques, including the use of an adjustable-length-loop suspensory fixation device through a longitudinal incision, have been introduced in recent years. The purpose of this Technical Note and video is to provide a minimally invasive method for medial collateral ligament reconstruction with adjustable-loop femoral fixation and posteromedial corner plication.
RESUMO
Although patellar tendon grafts are most commonly used for anterior cruciate ligament reconstruction in the United States, hamstring autograft is most commonly used worldwide. Hamstring advantages include easy, quick harvest; low morbidity; ease of rehabilitation (compared with patellar tendon grafts); and relatively less pain. Historically, both the semitendinosus (ST) and gracilis are harvested, but by doubling, tripling, or quadrupling the ST to achieve an 8-mm graft, the gracilis can be spared, resulting in less knee flexion weakness. However, recent research has shown no clinically important difference between ST and ST-gracilis patient outcomes.
Assuntos
Reconstrução do Ligamento Cruzado Anterior , Músculo Grácil , Tendões dos Músculos Isquiotibiais , Humanos , Reconstrução do Ligamento Cruzado Anterior/métodos , Tendões dos Músculos Isquiotibiais/transplante , Músculo Grácil/transplante , Lesões do Ligamento Cruzado Anterior/cirurgia , Coleta de Tecidos e Órgãos/métodos , Resultado do Tratamento , Ligamento Cruzado Anterior/cirurgiaRESUMO
INTRODUCTION: Previous bronchoalveolar lavage fluid (BALF) proteomic analysis has evaluated limited numbers of subjects for only a few proteins of interest, which may differ between asthma and normal controls. Our objective was to examine a more comprehensive inflammatory biomarker panel in quantitative proteomic analysis for a large asthma cohort to identify molecular phenotypes distinguishing severe from nonsevere asthma. METHODS: Bronchoalveolar lavage fluid from 48 severe and 77 nonsevere adult asthma subjects were assessed for 75 inflammatory proteins, normalized to BALF total protein concentration. Validation of BALF differences was sought through equivalent protein analysis of autologous sputum. Subjects' data, stratified by asthma severity, were analysed by standard statistical tests, principal component analysis and 5 machine learning algorithms. RESULTS: The severe group had lower lung function and greater health care utilization. Significantly increased BALF proteins for severe asthma compared to nonsevere asthma were fibroblast growth factor 2 (FGF2), TGFα, IL1Ra, IL2, IL4, CCL8, CCL13 and CXCL7 and significantly decreased were platelet-derived growth factor a-a dimer (PDGFaa), vascular endothelial growth factor (VEGF), interleukin 5 (IL5), CCL17, CCL22, CXCL9 and CXCL10. Four protein differences were replicated in sputum. FGF2, PDGFaa and CXCL7 were independently identified by 5 machine learning algorithms as the most important variables for discriminating severe and nonsevere asthma. Increased and decreased proteins identified for the severe cluster showed significant protein-protein interactions for chemokine and cytokine signalling, growth factor activity, and eosinophil and neutrophil chemotaxis differing between subjects with severe and nonsevere asthma. CONCLUSION: These inflammatory protein results confirm altered airway remodelling and cytokine/chemokine activity recruiting leukocytes into the airways of severe compared to nonsevere asthma as important processes even in stable status.