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BACKGROUND: Prior literature has demonstrated that ipsilateral hindfoot arthrodesis may increase the risk for reoperation after total ankle arthroplasty (TAA) and that simultaneous hindfoot arthrodesis with TAA could result in short-term clinical and radiologic improvements. The purpose of this study is to compare the reoperation rates after TAA with prior hindfoot arthrodesis vs simultaneous arthrodesis and TAA. METHODS: Patients who underwent primary TAA were identified in the PearlDiver database. Patients were sorted into 2 study cohorts: hindfoot arthrodesis prior to TAA and simultaneous arthrodesis and TAA. Propensity matched control cohorts were identified for each study group. Multivariate analysis was conducted to account for any confounding variables and covariates when identifying differences in complications between cohorts. RESULTS: 297 patients underwent TAA with prior hindfoot arthrodesis and 174 underwent TAA and hindfoot arthrodesis concurrently. The incidence of reoperation (13.8% vs 5.2%, P < .001) and infection (12.6% vs 5.9%, P = .011) for the simultaneous cohort was higher when compared to the matched control cohort. In contrast, there was no statistically significant difference when comparing the prior arthrodesis cohort to the matched control cohort in reoperation rates (5.1% vs 4.7%, P = .787) or infection rates (4.4% vs 4.8%, P = .734). Those undergoing simultaneous procedures had increased incidences of reoperation, wound complications, infection, and emergency department visits (P < .0167) when compared to the TAA with prior arthrodesis cohort. CONCLUSION: Patients undergoing TAA and hindfoot arthrodesis concurrently were found to have higher rates of reoperation and infection when compared to the matched control cohort . In contrast, there was no difference in these rates in patients undergoing TAA with prior hindfoot arthrodesis compared with their matched control cohort. Patients undergoing simultaneous procedures had increased rates of reoperations, wound complications, infection, and emergency department visits compared to the TAA with prior arthrodesis cohort.
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Artrodesis , Artroplastia de Reemplazo de Tobillo , Reoperación , Artrodesis/métodos , Reoperación/estadística & datos numéricos , Humanos , Artroplastia de Reemplazo de Tobillo/efectos adversos , Persona de Mediana Edad , Masculino , Femenino , Anciano , Estudios Retrospectivos , Complicaciones Posoperatorias/epidemiología , Factores de TiempoRESUMEN
BACKGROUND: First metatarsophalangeal (MTP) arthrodesis is a common surgical procedure for addressing hallux MTP pathology. In the setting of revision procedures with significant bone loss, porous titanium wedges may provide an alternative to structural bone autograft or allograft. OBJECTIVE: The purpose of this study is to report the clinical and radiographic outcomes achieved in first MTP interposition arthrodesis using porous titanium wedges. METHODS: A retrospective analysis of 9 patients with a mean age 65.4 years (45-82 years) who underwent first MTP interposition arthrodesis with the use of porous titanium wedges from February 2014 to September 2017 was performed. Outcomes were assessed using both plain-film radiographs and computed tomography (CT) scans, as well as patient-reported outcome measures, including Foot and Ankle Ability Measure (FAAM) (Sports and Activities of Daily Living), pain Visual Analogue Scale (VAS), and 36-Item Short Form Survey (SF-36). Average follow-up time was 34.2 months (14-72 months). RESULTS: At final follow-up, the average FAAM score was 91.1 ± 14.7 (75.1 ± 5.3 FAAM Activities of Daily Living; 17.9 ± 9.9 FAAM Sports). Average pain VAS score was 1.9 ± 1.7. Postoperative computed tomography (CT) imaging was obtained for 5 patients, all of which demonstrated good bony apposition or osseous integration of the wedge. Four patients underwent subsequent surgical procedures, including 3 isolated dorsal fixation revisions, and 1 complete MTP arthrodesis revision. CONCLUSION: To our knowledge, this study represents the first reported clinical and radiographic outcomes in patients undergoing first MTP interposition arthrodesis with use of porous titanium wedges. While we found this technique to be a viable alternative to bone grafting for this difficult problem, further research should focus on comparative data with other commonly performed operative techniques. LEVEL OF EVIDENCE: Level IV: Case series.
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BACKGROUND: The objective of this study was to evaluate return to activity following flatfoot reconstruction with lateral column lengthening (LCL) by assessing functional postoperative data and identifying patient characteristics associated with poor function following surgery. METHODS: Consecutive patients that underwent operative flatfoot correction including LCL and other necessary procedures from 2014 to 2019 by 3 fellowship trained foot and ankle orthopedic surgeons were retrospectively administered Foot and Ankle Ability Measure (FAAM) Activities of Daily Living (ADL) and FAAM Sports questionnaires with no preoperative scoring available. Patient demographic factors, comorbidities, and radiographic features were evaluated as predictors of outcome scores to simulate return to activity. Statistical analysis, including student's t-tests and analysis of variance, was performed. RESULTS: A total of 54 patients were included. A body mass index (BMI) of 30 kg/m2 or greater was associated with a lower ADL score (P = .002) and Sports score (P = .002). Preoperative hindfoot valgus of 9° or higher was associated with higher ADL scores (P = .040). Neither age nor any flatfoot radiographic parameters yielded significant differences in functional scores. CONCLUSION: This study demonstrated relatively high average FAAM scores in both the ADL and the sports subscales, consistent with previous studies. This study also identified lower BMI and greater preoperative hindfoot valgus as potential predictors of improved functional outcome following reconstruction. LEVEL OF EVIDENCE: Level III: Retrospective case control.
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BACKGROUND: Revision or conversion to arthrodesis following metatarsophalangeal (MTP) joint arthroplasty are salvage procedures to manage complications of MTP joint arthroplasty. The purpose of this study is to use a national administrative database to characterize nationwide trends of patients undergoing hallux MTP arthrodesis vs arthroplasty for hallux rigidus. Additionally, the authors sought to evaluate demographic trends and evaluate influence of patient-related risk factors in those undergoing MTP arthroplasty revision to arthrodesis. METHODS: Patients who underwent MTP arthroplasty for diagnosis of hallux rigidus from 2010 to 2019 were identified in the Mariner subset of the PearlDiver database. Patients were included if they had undergone MTP arthroplasty for the diagnosis of hallux rigidus. Notably, the database lacks resolution about critical features of the arthroplasty design and materials. The revision cohort encompassed patients who underwent subsequent ipsilateral MTP arthrodesis or arthroplasty within 2 years of index arthroplasty procedure. Demographic characteristics and medical comorbidities were examined as potential patient-related risk factors for arthroplasty revision or revision to fusion. Univariate analyses were performed to analyze differences in patient demographics, comorbidities, and risk factors. A multivariate regression analysis was subsequently conducted to control for confounding variables. RESULTS: 2750 patients underwent primary MTP arthroplasty for diagnosis of hallux rigidus. Of these, 44 (1.6%) underwent revision arthroplasty and 188 patients (6.8%) were revised to arthrodesis within the first 2 years after the index procedure. Multivariate regression analysis indicates that obesity (odds ratio [OR] 1.48, 95% CI 1.05-2.09), depression (OR 1.59, 95% CI 1.15-2.20), and steroid use (OR 2.94, 95% CI 1.30-6.65) were associated with a statistically significant increase in revision to arthrodesis from primary arthroplasty. CONCLUSION: Revision arthrodesis following primary MTP arthroplasty for hallux rigidus within 2 years was found to be a relatively common occurrence in this national insurance database study. Risk factors for revision arthroplasty to arthrodesis within 2 years of primary arthroplasty include obesity, depression, and steroid use. LEVEL OF EVIDENCE: Level III, case-control study.
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Hallux Rigidus , Articulación Metatarsofalángica , Artrodesis/métodos , Artroplastia/métodos , Estudios de Casos y Controles , Hallux Rigidus/cirugía , Humanos , Articulación Metatarsofalángica/cirugía , Obesidad , Factores de Riesgo , Esteroides , Resultado del TratamientoRESUMEN
In the setting of an opioid epidemic, this study aims to provide evidence on opioid use trends, risk factors for prolonged use, and complications from perioperative opioid consumption in hallux valgus surgery. A national database was queried for patients who underwent hallux valgus correction. Regression analysis identified: (1) risk factors for prolonged postoperative narcotic use; and (2) association between preoperative/prolonged postoperative narcotic use and postoperative complications. A linear regression analysis was used to determine trends. About 20,749 patients were included, of which 3464 patients were prescribed narcotics preoperatively and 4339 were identified as prolonged postoperative narcotic prescription users. Preoperative prescriptions were identified as risk factors for prolonged use. Perioperative narcotic use was observed to be a risk factor for poor outcomes. About 21% of patients were identified as prolonged postoperative narcotic prescription users. Patients undergoing hallux valgus corrective surgery should be counseled regarding their increased risk of complications when using narcotics.
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BACKGROUND: Hepatitis C is associated with increased adverse events following surgery. The goals of this study were therefore to evaluate postoperative outcomes in patients with hepatitis C following ankle arthrodesis. MATERIALS AND METHODS: A review of Medicare patients was performed to identify patients who underwent ankle arthrodesis. Patients were then divided into those with a preoperative history of hepatitis C and those who did not and were matched using propensity scores. Outcomes of interest were analyzed using multivariate logistic regression. RESULTS: A diagnosis of hepatitis C was associated with a significantly increased risk of myocardial infarction, emergency department visits, and readmission within 90 days following surgery. In addition, hepatitis C is associated with an increased length of stay, cost of hospitalization, and total hospital charge. CONCLUSIONS: A diagnosis of hepatitis C was associated with a significant increase in hospital resource utilization during the initial inpatient stay and the immediate post-discharge period.Level of Evidence: III.
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Obese patients undergoing orthopedic procedure have been reported to have higher rates of postoperative complications, but the published associations have numerous confounders. This study aims to evaluate the independent effect of obesity on postoperative complications and hospital utilization following ankle arthrodesis. A database review of a Medicare database was performed on patients less than 85 years old who underwent ankle arthrodesis between 2005 and 2014. Patient cohorts were defined using International Classification of Diseases-9 coding for body mass index (BMI)-obese (30-40 kg/m2), and morbidly obese (>40 kg/m2). Normal BMI patients were defined as those without the respect codes for obesity (30-40 kg/m2), morbidly obese (>40 kg/m2), or underweight (<19 kg/m2). All groups were propensity score matched by demographics and comorbidities. Outcomes of interest included 90-day major and minor medical complications, and hospital burden. Morbid obesity was associated with an increased risk of acute kidney injury (4.4% vs 2.4%, OR 1.94, 95% CI 1.37-2.74, p < .001), urinary tract infection (5.2% vs 3.2%, OR 1.66, 95% CI 1.21-2.25, p = .001), readmission (13.6% vs 10.8%, OR 1.33, 95% CI 1.10-1.61, p = .003), and overall minor complications (16.0% vs 11.8%, OR 1.44, 95% CI 1.19-1.74, p < .001) compared to normal BMI patients, and an increased risk for acute kidney injury (4.4% vs 1.9%, OR 2.25, 95% CI 1.32-3.97, p = .003) compared to obese patients. Obesity was not associated with increased medical complications (p > .05). While morbid obesity was associated with an increase in the postoperative complications, obesity was not associated with any increase in postoperative complications following ankle arthrodesis.
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Obesidad Mórbida , Anciano , Anciano de 80 o más Años , Tobillo , Artrodesis/efectos adversos , Índice de Masa Corporal , Humanos , Medicare , Complicaciones Posoperatorias/epidemiología , Complicaciones Posoperatorias/etiología , Puntaje de Propensión , Estudios Retrospectivos , Resultado del Tratamiento , Estados Unidos/epidemiologíaRESUMEN
PURPOSE: The purpose of this study was to investigate the effect of the length of the dorsal locking plate on the failure rate of first MTP joint arthrodesis for severe hallux valgus deformities. METHODS: A retrospective review was conducted for all patients who underwent first MTP joint arthrodesis using solely a specific locked plating system (Depuy-Synthes, Raynham, MA) for severe hallux valgus deformities between January 2014 to June 2017. Patients were divided into subgroups according to the length of the plate and the failure rate was investigated. Furthermore, radiographic parameters including intermetatarsal angle (IMA) and hallux valgus angle (HVA) were evaluated in weightbearing AP foot radiographs. RESULTS: A total of 25 patients were included in this study. There were 16 (64%) patients in the medium-sized plate cohort and 9 (36%) patients in the small-sized plate cohort. We found a significant difference in the failure rate between the two groups; only 1 (6.25%) failure case occurred in the medium-sized plate cohort while 4 (44.44%) failure cases occurred in the small-sized plate cohort (P = .040, Odds ratio (OR) = 12.000, 95% Confidence Interval (CI) = 1.074, 134.110). The mean postoperative IMA and HVA were significantly improved in both cohorts. However, significant differences were found between the two cohorts in final follow-up IMA and HVA (P = .002 and P < .001, respectively). CONCLUSIONS: For severe hallux valgus deformities, the use of longer plates to gain additional purchase in the diaphyseal bone may help mitigate the increased stresses placed on the fixation constructs for first MTP joint arthrodesis and decrease failure rate. LEVEL OF EVIDENCE: Level III, case control study.
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Hallux Valgus , Hallux , Articulación Metatarsofalángica , Artrodesis , Estudios de Casos y Controles , Hallux Valgus/diagnóstico por imagen , Hallux Valgus/cirugía , Humanos , Articulación Metatarsofalángica/diagnóstico por imagen , Articulación Metatarsofalángica/cirugía , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
Common peroneal nerve dysfunction after a multiligament knee injury can be devastating. In patients with persistent foot drop, posterior tibial tendon transfer to the dorsum of the foot is a reliable and safe procedure to restore dorsiflexion. These authors favor passing the posterior tibial tendon through the interosseous membrane and docking it into the lateral/middle cuneiforms. A Strayer procedure or tendo-Achilles lengthening must be performed in patients unable to achieve at least 10° of passive dorsiflexion. Despite the operative limb having 30% to 40% of ankle dorsiflexion strength of the uninjured limb, short- and long-term functional outcomes are excellent.
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Traumatismos de la Rodilla/cirugía , Traumatismos de los Nervios Periféricos/cirugía , Nervio Peroneo/lesiones , Transferencia Tendinosa/métodos , Humanos , Traumatismos de la Rodilla/diagnóstico , Traumatismos de los Nervios Periféricos/diagnóstico , Nervio Peroneo/cirugía , Resultado del TratamientoRESUMEN
BACKGROUND: Midfoot joint impairment is likely following lateral ankle sprain (LAS) that may benefit from mobilization. OBJECTIVE: To investigate the effects of midfoot joint mobilizations and a one-week home exercise program (HEP) compared to a sham intervention and HEP on pain, patient-reported outcomes (PROs), ankle-foot joint mobility, and neuromotor function in young adults with recent LAS. METHODS: All participants were instructed in a stretching, strengthening, and balance HEP and were randomized a priori to receive midfoot joint mobilizations (forefoot supination, cuboid glide and plantar 1st tarsometatarsal) or a sham laying-of-hands. Changes in pain, physical, psychological, and functional PROs, foot morphology, joint mobility, pain-to-palpation, neuromotor function, and dynamic balance were assessed pre-to-post treatment and one-week following. Participants crossed-over following a one-week washout to receive the alternate treatment and were assessed pre-to-post treatment and one-week following. ANOVAs, t-tests, proportions, and 95% confidence intervals (CI) were calculated to assess changes in outcomes. Cohen's d and 95% CI compared treatment effects at each time-point. RESULTS: Midfoot joint mobilization had greater effects (p < .05) in reducing pain 1-week post (d = 0.8), and increasing Single Assessment Numeric Evaluation (immediate: d = 0.6) and Global Rating of Change (immediate: d = 0.6) compared to a sham treatment and HEP. CONCLUSION: Midfoot joint mobilizations and HEP yielded greater pain reduction and perceived improvement compared to sham and is recommended in a comprehensive rehabilitation program following LAS.
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Traumatismos del Tobillo/rehabilitación , Ejercicios de Estiramiento Muscular , Esguinces y Distensiones/rehabilitación , Adolescente , Adulto , Traumatismos del Tobillo/fisiopatología , Estudios Cruzados , Femenino , Humanos , Masculino , Dimensión del Dolor , Medición de Resultados Informados por el Paciente , Recuperación de la Función , Esguinces y Distensiones/fisiopatologíaRESUMEN
Chronic ankle instability is associated with intra-articular and extra-articular ankle pathologies, including osteochondral lesions of the talus. Patients with these lesions are at risk for treatment failure for their ankle instability. Identifying these patients is important and helps to guide operative versus nonoperative treatment. There is no literature examining which patient characteristics may be used to predict concomitant osteochondral lesions of the talus. A retrospective chart review was performed on patients (N = 192) who underwent a primary Broström-Gould lateral ankle ligament reconstruction for chronic ankle instability from 2010 to 2014. Preoperative findings, magnetic resonance imaging, and operative procedures were documented. Patients with and without a lesion were divided into 2 cohorts. Fifty-three (27.6%) patients had 1 lesion identified on preoperative magnetic resonance imaging. Forty (69.0%) of these lesions were medial, 18 (31.0%) were lateral, and 5 patients had both. Female sex was a negative predictor of a concomitant lesion (p = .013). Patients were less likely to have concomitant peroneal tendinopathy (30.2% vs 48.9%; p = .019) in the presence of a lesion. However, sports participation was a positive predictor of a concomitant lesion (p = .001). The remainder of the variables (age, body mass index, smoking, trauma, duration, contralateral instability, global laxity) did not show a significant difference. In patients who underwent lateral ankle ligament reconstruction, females were less likely to have a lesion than males. Patients with peroneal tendinopathy were less likely to have a lesion compared with patients without. Additionally, athletic participation was a positive predictor of a concomitant lesion.
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Articulación del Tobillo , Enfermedades de los Cartílagos/diagnóstico , Enfermedades de los Cartílagos/cirugía , Inestabilidad de la Articulación/cirugía , Ligamentos Laterales del Tobillo/cirugía , Astrágalo , Adulto , Enfermedades de los Cartílagos/etiología , Femenino , Humanos , Inestabilidad de la Articulación/diagnóstico por imagen , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
PURPOSE: To investigate the clinical measures of foot posture and morphology, multisegmented joint motion and play, strength, and dynamic balance in recreationally active young adults with and without a history of a lateral ankle sprain (LAS), copers, and chronic ankle instability (CAI). METHODS: Eighty recreationally active individuals (healthy: n = 22, coper: n = 21, LAS: n = 17, CAI: n = 20) were included. Foot posture index (FPI), morphologic measures, joint motion (weight-bearing dorsiflexion (WBDF), rearfoot dorsiflexion, plantar flexion, inversion, eversion; forefoot inversion, eversion; hallux flexion, extension), joint play (proximal and distal tibiofibular; talocrural and subtalar, forefoot; 1st tarsometatarsal and metatarsophalangeal), strength (dorsiflexion, plantar flexion, inversion, eversion, hallux flexion, lesser toe flexion), and Star Excursion Balance Test (SEBT) (anterior, posteromedial, posterolateral) were assessed. RESULTS: There were no group differences in FPI or morphological measures. LAS and CAI groups had decreased ankle dorsiflexion (p = 0.001) and greater frontal plane motion (p < 0.001), first MT plantar flexion, and sagittal excursion (p < 0.001); increased talocrural glide (p = 0.02) and internal rotation (p < 0.001) and decreased forefoot inversion joint play (p < 0.001); and decreased strength in all measures (p < 0.001) except dorsiflexion compared to healthy controls. The LAS group also demonstrated decreased distal tibiofibular (p = 0.04) and forefoot general laxity (p = 0.05) and SEBT performance (anterior: p = 0.02; posteromedial: p < 0.001; posterolateral: p < 0.001). CONCLUSION: Individuals with LAS or CAI have increased pain, impaired physiologic and accessory joint motion, ligamentous tenderness, and strength in the foot and ankle. Clinicians should assess the multiple segments of the ankle-foot complex when caring for individuals with an LAS or CAI. LEVEL OF EVIDENCE: II.
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Traumatismos del Tobillo/fisiopatología , Tobillo/fisiopatología , Pie/fisiopatología , Inestabilidad de la Articulación/fisiopatología , Esguinces y Distensiones/fisiopatología , Adolescente , Adulto , Estudios de Casos y Controles , Enfermedad Crónica , Femenino , Pie/anatomía & histología , Humanos , Masculino , Persona de Mediana Edad , Fuerza Muscular/fisiología , Equilibrio Postural/fisiología , Rango del Movimiento Articular/fisiología , Rotación , Soporte de Peso/fisiología , Adulto JovenRESUMEN
BACKGROUND: Hallux valgus and lesser toe deformities are common foot disorders with substantial functional consequences. While the exact etiologies are multi-factorial, it is unknown if certain endocrine abnormalities, such as thyroid dysfunction, may be associated with these pathologies. The current study sought to investigate the prevalence of thyroid disease in patients with hallux valgus or lesser toe deformities. METHODS: Every new patient who presented to our institution's foot and ankle clinic during a three-month time period was given a survey to determine the presence of a known thyroid disorder. The diagnosis for each visit was then recorded. Additionally, a national, publicly available database was queried for patients diagnosed with thyroid disease and concomitant hallux valgus or specific forefoot pathology. Odds ratios for the presence of thyroid dysfunction were then calculated for each patient group. RESULTS: Three-hundred and fifty initial visit patient surveys were collected, and 74 (21.1%) patients had a known diagnosis of thyroid disease. The most common diagnoses were primary hypothyroidism (n = 61, 17.4%), secondary hypothyroidism (n = 6, 1.7%), thyroiditis (n = 4, 1.1%), and hyperthyroidism (n = 3, 0.9%). Thyroid disease was present in 16 of 26 patients (61.5%) with a diagnosis of hallux valgus (OR 7.3, CI[3.16-16.99], p < 0.0001). Lesser toe deformities, including hammertoes, mallet toes, bunionettes and crossover toes, were also significantly associated with thyroid disease (OR 5.45, CI[1.83-16.26], p < 0.002). The national database revealed 905,924 patients with a diagnosis of a specific forefoot deformity, and 321,656 of these patients (35.5%) had a concomitant diagnosis of a thyroid condition (OR 2.11, CI[2.10-2.12], p < 0.0001). CONCLUSIONS: The current study suggests a significant association between forefoot pathology and thyroid dysfunction, especially hallux valgus and lesser toe deformities. Increased understanding of these correlations may offer an important opportunity in population health management, both in diagnosis and treatment. While further studies with long-term outcomes are necessary, the early diagnosis of thyroid disease may provide an opportunity to predict and potentially alter the course of forefoot pathology.
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Deformidades del Pie/complicaciones , Enfermedades de la Tiroides/epidemiología , Adulto , Anciano , Femenino , Deformidades del Pie/diagnóstico , Humanos , Incidencia , Masculino , Persona de Mediana Edad , Prevalencia , Enfermedades de la Tiroides/complicaciones , Enfermedades de la Tiroides/etiología , Estados Unidos/epidemiologíaRESUMEN
BACKGROUND: Individuals with lateral ankle sprain and chronic ankle instability have impaired postural control and altered motor strategies during walking. However, little is known regarding foot mechanics during gait. The purpose of this study was to compare three-dimensional multisegmented ankle-foot kinematics during stance phase following gait-initiation in acute lateral ankle sprain (Ankle-sprain), chronic ankle instability (Chronic-instability), Coper, and Control groups. METHODS: 80 recreationally-active individuals (Control: nâ¯=â¯22, Coper: nâ¯=â¯21, Ankle-sprain: nâ¯=â¯17, Chronic-instability: nâ¯=â¯20) participated. Three-dimensional kinematics of the hallux, medial forefoot, lateral forefoot, medial midfoot, lateral midfoot, and rearfoot on shank were collected during the stance phase following gait initiation using an electromagnetic motion capture system. The average joint excursions of 10 steps were normalized to 101 points and analyzed using Statistical Parametric Mapping ANOVA and post hoc t-tests comparing Coper, Ankle-sprain, or Chronic-instability versus Control groups. Secondary analysis was performed comparing Chronic-instability versus Coper groups. FINDINGS: The Ankle-sprain group had up to 4.1° more rearfoot inversion during midstance (mean difference: 3.1°) from 42 to 49% of stance phase compared to healthy controls. The Chronic-instability group had up to 5.3° more rearfoot inversion (mean difference: 3.6°) from 34% to 91% of stance phase compared to controls. There were no further statistical differences found between Chronic-instability and Copers, other planes, or segments of the ankle-foot complex. INTERPRETATION: Ankle-sprain and Chronic-instability groups demonstrated more rearfoot inversion compared to controls with no differences in midfoot or forefoot mechanics. Clinicians and researchers should include interventions that control inversion and increase eversion following lateral ankle sprain.
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Traumatismos del Tobillo/fisiopatología , Articulación del Tobillo/fisiopatología , Marcha , Inestabilidad de la Articulación/fisiopatología , Adolescente , Adulto , Tobillo/fisiopatología , Fenómenos Biomecánicos , Estudios Transversales , Femenino , Pie , Humanos , Imagenología Tridimensional , Masculino , Equilibrio Postural , Caminata , Adulto JovenRESUMEN
Streptococcus equi subsp. zooepidemicus (SEZ) is a zoonotic pathogen capable of causing meningitis in humans. The mechanisms that enable pathogens to traverse the blood-brain barrier (BBB) are incompletely understood. Here, we investigated the role of a newly identified Fic domain-containing protein, BifA, in SEZ virulence. BifA was required for SEZ to cross the BBB and to cause meningitis in mice. BifA also enhanced SEZ translocation across human Brain Microvascular Endothelial Cell (hBMEC) monolayers. Purified BifA or its Fic domain-containing C-terminus alone were able to enter into hBMECs, leading to disruption of monolayer barrier integrity. A SILAC-based proteomic screen revealed that BifA binds moesin. BifA's Fic domain was required for its binding to this regulator of host cell cytoskeletal processes. BifA treatment of hBMECs led to moesin phosphorylation and downstream RhoA activation. Inhibition of moesin activation or moesin depletion in hBMEC monolayers abrogated BifA-mediated increases in barrier permeability and SEZ's capacity to translocate across monolayers. Thus, BifA activation of moesin appears to constitute a key mechanism by which SEZ disrupts endothelial monolayer integrity to penetrate the BBB.