RESUMO
Arthritis of the patellofemoral compartment affects up to 24% of women and 11% of men over the age of 55 years who have symptomatic osteoarthritis of the knee. Patellofemoral cartilage lesions have been associated with several different geometric measures of patellar alignment, including the tibial tubercle-trochlear groove (TTTG) distance, trochlear sulcus angle, trochlear depth, and patellar height. Recently, there has been interest in the sagittal TTTG distance, which measures the position of the tibial tubercle with respect to the trochlear groove. This measurement is now being used in patients presenting with patellofemoral pain and/or cartilage pathology and may help guide surgical decision making as we gain more data on how changing the tibial tubercle alignment relative to the patellofemoral joint can improve outcomes. For now, there are not enough data to support isolated anteriorization tibial tubercle osteotomy in patients with patellofemoral chondral wear based on the sagittal TTTG distance. However, as we better understand geometric measures as risk factors for patellofemoral arthritis, realignment at a young age might be recommended as a preventative measure against end-stage osteoarthritis.
Assuntos
Instabilidade Articular , Osteoartrite , Articulação Patelofemoral , Masculino , Humanos , Feminino , Pessoa de Meia-Idade , Articulação do Joelho/cirurgia , Articulação do Joelho/patologia , Tíbia/cirurgia , Tíbia/patologia , Articulação Patelofemoral/cirurgia , Patela/cirurgia , Patela/patologia , Osteoartrite/patologia , Instabilidade Articular/cirurgiaRESUMO
PURPOSE: The purpose of this descriptive study was to define patterns of ossification and fusion of growth centers around the pediatric and adolescent glenoid as a function of age using 3-dimensional, frequency-selective, fat-suppressed spoiled gradient recalled echo magnetic resonance (MR) imaging sequences, with a particular focus on the anterior glenoid rim because of its clinical relevance as a potential confounder of glenohumeral instability. METHODS: Picture Archiving and Communication System records at an urban academic tertiary care orthopaedic facility from October 2005 to December 2018 were queried for shoulder MRI in patients aged 9 to 17 years. Patients were excluded if they had any diagnoses that could alter glenoid development. All images were independently evaluated by a musculoskeletal fellowship-trained radiologist. Secondary ossification centers were characterized as cartilage anlage, ossified, or fused at 3 anatomic sites: the anterior glenoid rim, coracoid, and superior glenoid rim. RESULTS: A total of 250 MR examinations (143 males, 107 females) were assessed in this study. The glenoid develops in a predictably sequential manner with ossification at the anterior glenoid rim lagging behind the coracoid and superior glenoid rim. The earliest age of anterior glenoid rim ossification was 11 years for both males (range 11-17) and females (range 11-12). Anterior glenoid rim ossification peaked at age 16 among males (34.8%, 8/23) and age 11 among females (27.3%, 3/11). CONCLUSIONS: Glenoid ossification and fusion progress in a predictable and chronological manner. This pattern should be used as a guideline when interpreting pediatric shoulder MRI examinations. In particular, an anterior glenoid ossification center should not be confused with an anterior glenoid injury (e.g., Bankart lesion), particularly in males 11 to 17 years old and females 11 to 12 years old. LEVEL OF EVIDENCE: IV (case series).
Assuntos
Imageamento por Ressonância Magnética , Osteogênese/fisiologia , Articulação do Ombro/diagnóstico por imagem , Adolescente , Lesões de Bankart/diagnóstico , Cartilagem Articular/diagnóstico por imagem , Criança , Diagnóstico Diferencial , Feminino , Humanos , Imageamento Tridimensional , Masculino , Articulação do Ombro/fisiologiaRESUMO
BACKGROUND: The cost-effectiveness of bariatric surgery to achieve weight loss prior to total hip arthroplasty (THA), and decrease the complications and costs associated with THA in the morbidly obese, is unknown. This study evaluated the cost-effectiveness of bariatric surgery prior to THA for morbidly obese patients with end-stage hip osteoarthritis (OA). METHODS: A state-transition Markov model was constructed to compare the cost-utility of 2 treatment protocols for patients with morbid obesity and end-stage hip OA: (1) immediate THA and (2) bariatric surgery 2 years prior to THA (combined protocol). The analysis was performed from both a payer and a societal perspective using direct and indirect costs over a 40-year time horizon. Utilities, associated costs, and probabilities for health state transitions were derived from the literature. One-way, 2-way and probabilistic sensitivity analyses were performed to validate the robustness of the base case results, using the standard willingness-to-pay threshold of $100,000/quality-adjusted life years. RESULTS: From the societal perspective, the combined protocol was more effective (13.16 vs 12.26) with less cost ($91,717 vs $92,684) and thus was the dominant strategy over immediate THA. These results were stable across broad ranges for independent model variables. Monte Carlo simulation with 100,000 samples demonstrated that bariatric surgery prior to THA was the preferred cost-effective strategy over 95% of the time from both a societal and payer perspective. CONCLUSION: In the morbidly obese patient with end-stage hip OA, bariatric surgery prior to THA is a cost-effective strategy for improving quality of life and decreasing societal and payer costs. LEVEL OF EVIDENCE: II.
Assuntos
Artroplastia de Quadril , Cirurgia Bariátrica , Obesidade Mórbida , Análise Custo-Benefício , Humanos , Cadeias de Markov , Obesidade Mórbida/complicações , Obesidade Mórbida/cirurgia , Qualidade de Vida , Anos de Vida Ajustados por Qualidade de VidaRESUMO
BACKGROUND: The optimal retreatment strategy for chronic hepatitis C virus (HCV) patients who fail directly-acting antiviral agent (DAA)-based treatment is unknown. In this study, we assessed the efficacy and safety of ledipasvir (LDV) and sofosbuvir (SOF) for 12 weeks in HCV genotype-1 (GT-1) patients who failed LDV/SOF-containing therapy. METHODS: In this single-center, open-label, phase 2a trial, 34 participants with HCV (GT-1) and early-stage liver fibrosis who previously failed 4-6 weeks of LDV/SOF with GS-9669 and/or GS-9451 received LDV/SOF for 12 weeks. The primary endpoint was HCV viral load below the lower limit of quantification 12 weeks after completion of therapy (sustained virological response [SVR]12). Deep sequencing of the NS3, NS5A, and NS5B regions were performed at baseline, at initial relapse, prior to retreatment, and at second relapse with Illumina next-generation sequencing technology. RESULTS: Thirty-two of 34 enrolled participants completed therapy. Two patients withdrew after day 0. Participants were predominantly male and black, with median baseline HCV viral load of 1.3 × 10(6) IU/mL and Metavir fibrosis stage 1 and genotype-1a. Median time from relapse to retreatment was 22 weeks. Prior to retreatment, 29 patients (85%) had NS5A-resistant variants. The SVR12 rate was 91% (31/34; intention to treat, ITT) after retreatment. One patient relapsed. CONCLUSIONS: In patients who previously failed short-course combination DAA therapy, we demonstrate a high SVR rate in response to 12 weeks of LDV/SOF, even for patients with NS5A resistance-associated variants. CLINICAL TRIALS REGISTRATION: NCT01805882.
Assuntos
Antivirais/administração & dosagem , Benzimidazóis/administração & dosagem , Fluorenos/administração & dosagem , Hepatite C Crônica/tratamento farmacológico , Sofosbuvir/administração & dosagem , Adulto , Idoso , Antivirais/efeitos adversos , Benzimidazóis/efeitos adversos , Feminino , Fluorenos/efeitos adversos , Genótipo , Hepacivirus/classificação , Hepacivirus/genética , Hepacivirus/isolamento & purificação , Hepatite C Crônica/virologia , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Masculino , Pessoa de Meia-Idade , Retratamento/efeitos adversos , Análise de Sequência de DNA , Sofosbuvir/efeitos adversos , Resultado do Tratamento , Carga Viral , Proteínas não Estruturais Virais/genéticaRESUMO
BACKGROUND: Treatment of genotype 1 hepatitis C virus (HCV) infection with combination directly acting antivirals (DAA) for 8-24 weeks is associated with high rates of sustained virologic response (SVR). We previously demonstrated that adding a third DAA to ledipasvir and sofosbuvir (LDV/SOF) can result in high SVR rates in patients without cirrhosis. In this study, we investigated whether a similar regimen would yield equivalent rates of cure in patients with advanced liver fibrosis. METHODS: Fifty patients were enrolled at the Clinical Research Center of the National Institutes of Health and associated healthcare centers. Enrollment and follow-up data from April 2014 to June 2015 are reported here. Eligible participants were aged ≥18 years, had chronic HCV genotype 1 infection (serum HCV RNA ≥2000 IU/mL), and stage 3-4 liver fibrosis. HCV RNA was measured using a reverse-transcription polymerase chain reaction assay. RESULTS: Of patients treated with LDV, SOF, and the NS3/4A protease inhibitor GS-9451 for 6 weeks, 76% (38 of 50; 95% confidence interval, 60%-85%) had SVR achieved 12 weeks after the end of treatment. There was no statistically significant difference in treatment efficacy between treatment-naive patients (72%, 18 of 25) and those with treatment experience (80%; 20 of 25) (P = .51). Overall, 11 patients (22%) experienced virologic relapse, and 1 (2%) was lost to follow-up at 4 weeks after treatment. No serious adverse events, discontinuations, or deaths were associated with this regimen. CONCLUSIONS: Adding a third DAA to LDV/SOF may result in a moderate SVR rate, lower than that observed in patients without cirrhosis. Significant liver fibrosis remains an impediment to achieving SVR with short-duration DAA therapy. CHINESE CLINICAL TRIALS REGISTRATION: CT01805882.
Assuntos
Antivirais/uso terapêutico , Hepatite C Crônica/tratamento farmacológico , Hepatite C Crônica/patologia , Cirrose Hepática/patologia , Quinolinas/administração & dosagem , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Benzimidazóis/administração & dosagem , Estudos de Coortes , Quimioterapia Combinada/métodos , Feminino , Fluorenos/administração & dosagem , Genótipo , Hepacivirus/classificação , Hepacivirus/genética , Hepacivirus/isolamento & purificação , Hepatite C Crônica/complicações , Hepatite C Crônica/virologia , Humanos , Masculino , Pessoa de Meia-Idade , Sofosbuvir/administração & dosagem , Resultado do Tratamento , Adulto JovemRESUMO
BACKGROUND: Direct-acting antiviral drugs have a high cure rate and favourable tolerability for patients with hepatitis C virus (HCV). Shorter courses could improve affordability and adherence. Sofosbuvir and ledipasvir with ribavirin have high efficacy when taken for 8 weeks but not for 6 weeks. We assessed whether the addition of a third direct-acting antiviral drug to sofosbuvir and ledipasvir would allow a shorter treatment duration. METHODS: In this single-centre, open-label, phase 2A trial, we sequentially enrolled treatment-naive patients with HCV genotype 1 infection into three treatment groups: 12 weeks of sofosbuvir and ledipasvir; 6 weeks of sofosbuvir, ledipasvir, and GS-9669; or 6 weeks of sofosbuvir, ledipasvir, and GS-9451. Patients and investigators were not masked to treatment assignment. The primary endpoint was the propotion of patients with sustained viral response at 12 weeks after treatment completion (SVR12), assessed by serum HCV RNA concentrations lower than 43 IU/mL (the lower limit of quantification). We did an intention-to-treat analysis for the primary endpoint and adverse events. This study is registered with ClinicalTrials.gov, number NCT01805882. FINDINGS: Between Jan 11, 2013, and Dec 17, 2013, we enrolled 60 patients, and sequentially assigned them into three groups of 20. We noted an SVR12 in all 20 patients (100%, 95% CI 83-100) allocated to sofosbuvir and ledipasvir for 12 weeks; in 19 (95%, 75-100) of the 20 patients allocated to sofosbuvir, ledipasvir, and GS-9669 for 6 weeks (one patient relapsed 2 weeks after completion of treatment); and in 19 (95%, 75-100%) of the 20 patients allocated to sofosbuvir, ledipasvir, and GS-9451 for 6 weeks (one patient was lost to follow-up after reaching sustained viral response at 4 weeks). Most adverse events were mild and no patients discontinued treatment. Two serious adverse events occurred (pain after a post-treatment liver biopsy and vertigo), both unrelated to study drugs. INTERPRETATION: In this small proof-of-concept study, two different three-drug regimens that were given for 6 weeks resulted in high cure rates for HCV infection with excellent tolerability. Addition of a third potent direct-acting antiviral drug can reduce the duration of treatment required to achieve sustained viral response in patients with chronic HCV genotype 1 infection without cirrhosis. FUNDING: National Institute of Allergy and Infectious Diseases (NIAID), National Cancer Institute and Clinical Center Intramural Program, German Research Foundation, National Institutes of Health, Gilead Sciences.
Assuntos
Antivirais/uso terapêutico , Benzimidazóis/uso terapêutico , Fluorenos/uso terapêutico , Furanos/uso terapêutico , Hepatite C Crônica/tratamento farmacológico , Quinolinas/uso terapêutico , RNA Viral/sangue , Ribavirina/uso terapêutico , Tiofenos/uso terapêutico , Uridina Monofosfato/análogos & derivados , Idoso , Estudos de Coortes , Quimioterapia Combinada/métodos , Feminino , Hepacivirus/genética , Humanos , Análise de Intenção de Tratamento , Masculino , Pessoa de Meia-Idade , Sofosbuvir , Resultado do Tratamento , Uridina Monofosfato/uso terapêutico , Carga ViralRESUMO
BACKGROUND: Treatment of chronic hepatitis C virus (HCV) infection with direct-acting antivirals (DAAs) for 6 weeks achieves sustained virologic response (SVR) rates of 95% in some patients. If effective, shorter therapeutic courses could improve adherence and treatment costs. OBJECTIVE: To determine factors predictive of SVR to 4 weeks of DAA treatment in patients with stage F0 to F2 liver fibrosis. DESIGN: Open-label, nonrandomized, phase 2a trial. (Clinical Trials.gov: NCT01805882). SETTING: Single-center. PATIENTS: 50 treatment-naive and predominantly African American patients with HCV genotype 1 infection and early-stage liver fibrosis were sequentially enrolled into 2 treatment groups. INTERVENTION: 25 participants received a 3-drug regimen consisting of ledipasvir and sofosbuvir plus GS-9451 for 4 weeks, and 25 received a 4-drug regimen consisting of ledipasvir, sofosbuvir, GS-9451, and GS-9669 for 4 weeks. MEASUREMENTS: The primary efficacy end point was SVR12 (HCV RNA level below the lower limit of quantification at posttreatment week 12). RESULTS: Forty percent (10 of 25) (95% CI, 21% to 61%) of patients in the 3-drug group and 20% (5 of 25) (CI, 7% to 41%) of those in the 4-drug group achieved SVR12. Exploratory analysis suggested that lower baseline HCV viral load, younger age, and HCV genotype 1b were associated with SVR12. Ten patients had baseline HCV variants conferring greater than 20-fold resistance in vitro to at least 1 study DAA; all had viral relapse. Forty-eight percent (12 of 25) of patients receiving the 3-drug regimen and 72% (18 of 25) of those receiving the 4-drug regimen had adverse events, most of which were mild. One participant was lost to follow-up. LIMITATION: Nonrandomized study design and small sample of patients with early-stage fibrosis. CONCLUSION: Combination DAA therapy with 3 or 4 drugs for 4 weeks was well-tolerated but resulted in limited cure rates. PRIMARY FUNDING SOURCE: National Institute of Allergy and Infectious Diseases, National Cancer Institute, and Clinical Center Intramural Program; supported in part by a cooperative research and development agreement between the National Institutes of Health and Gilead Sciences.
Assuntos
Antivirais/uso terapêutico , Hepatite C Crônica/tratamento farmacológico , Antivirais/efeitos adversos , Benzimidazóis/efeitos adversos , Benzimidazóis/uso terapêutico , Farmacorresistência Viral/genética , Quimioterapia Combinada , Feminino , Fluorenos/efeitos adversos , Fluorenos/uso terapêutico , Furanos/efeitos adversos , Furanos/uso terapêutico , Genótipo , Hepatite C/genética , Hepatite C Crônica/virologia , Humanos , Masculino , Pessoa de Meia-Idade , Quinolinas/efeitos adversos , Quinolinas/uso terapêutico , RNA Viral/sangue , Sofosbuvir/efeitos adversos , Sofosbuvir/uso terapêutico , Tiofenos/efeitos adversos , Tiofenos/uso terapêutico , Resultado do Tratamento , Carga ViralRESUMO
BACKGROUND: Hepatitis C virus (HCV) RNA loads serve as predictors of treatment response during interferon-based therapy. We evaluated the predictive ability of HCV RNA levels at end of treatment (EOT) for sustained virologic response (SVR12) during interferon-sparing direct-acting antiviral therapies. METHODS: HCV genotype 1-infected, treatment-naive patients were treated with sofosbuvir and ribavirin for 24 weeks (n = 55), sofosbuvir and ledipasvir for 12 weeks (n = 20), sofosbuvir, ledipasvir, and GS-9669 for 6 weeks (n = 20), or sofosbuvir, ledipasvir, and GS-9451 for 6 weeks (n = 19). Measurements of HCV RNA were performed using the Roche COBAS TaqMan HCV test and the Abbott RealTime HCV assay. Positive predictive value (PPV) and negative predictive value (NPV) of HCV RNA less than the lower limit of quantification (Assuntos
Antivirais/uso terapêutico
, Monitoramento de Medicamentos/métodos
, Hepacivirus/efeitos dos fármacos
, Hepatite C/tratamento farmacológico
, Carga Viral/efeitos dos fármacos
, Adulto
, Idoso
, Antivirais/farmacologia
, Feminino
, Hepatite C/epidemiologia
, Hepatite C/virologia
, Humanos
, Masculino
, Pessoa de Meia-Idade
, Valor Preditivo dos Testes
, RNA Viral/sangue
RESUMO
Hepatitis C (HCV) treatment for patients coinfected with human immunodeficiency virus (HIV) and HCV is associated with modest rates of sustained virologic response (SVR) and an increased rate of relapse when compared to HCV monoinfected patients. As patients who attain SVR and patients who relapse are clinically indistinguishable during treatment, where both groups have fully suppressed HCV viral load, it has not been possible to identify in advance those who will relapse. Biomarkers that may distinguish patients with differential treatment response may be clinically useful and provide insight into mechanisms of relapse. In this retrospective study, serum and PBMCs were obtained from 41 HIV/HCV co-infected patients and 17 healthy volunteers. Changes in antibody titers to various regions of the HCV proteome during treatment for HCV were determined using a novel luciferase immunoprecipitation assay. Changes in B-cell subtypes in patients with differential treatment response as well as healthy volunteers were compared. This study demonstrates that elevated anti-HCV core antibody titers persisted during HCV treatment in patients who relapsed when compared to those who attained SVR. Furthermore, characterization of B cells in patients who relapsed demonstrated an abnormal B-cell phenotype distribution characterized by elevated frequencies of exhausted B cells among relapsers at baseline, which persisted despite suppression of HCV viremia at 24 weeks, along with increased frequencies of plasmablasts. These data suggest that anti-HCV specific B cells may be responding to ongoing subclinical HCV replication in patients who will relapse.
Assuntos
Linfócitos B/imunologia , Biomarcadores/análise , Infecções por HIV/complicações , Anticorpos Anti-Hepatite C/sangue , Hepatite C/imunologia , Proteínas do Core Viral/imunologia , Adulto , Feminino , Hepatite C/diagnóstico , Humanos , Imunoprecipitação , Masculino , Pessoa de Meia-Idade , Prognóstico , Recidiva , Estudos RetrospectivosRESUMO
IMPORTANCE: There is an unmet need for interferon- and ribavirin-free treatment for chronic hepatitis C virus (HCV) infection in patients co-infected with human immunodeficiency virus (HIV). OBJECTIVE: To evaluate the rates of sustained virologic response (SVR) and adverse events in previously untreated patients with HCV genotype 1 and HIV co-infection following a 12-week treatment of the fixed-dose combination of ledipasvir and sofosbuvir. DESIGN, SETTING, AND PARTICIPANTS: Open-label, single-center, phase 2b pilot study of previously untreated, noncirrhotic patients with HCV genotype 1 and HIV co-infection conducted at the Clinical Research Center of the National Institutes of Health, Bethesda, Maryland, from June 2013 to September 2014. Patients included those receiving antiretroviral therapy with HIV RNA values of 50 copies/mL or fewer and a CD4 T-lymphocyte count of 100 cells/mL or greater or patients with untreated HIV infection with a CD4 T-lymphocyte count of 500 cells/mL or greater. Serial measurements of safety parameters, virologic and host immune correlates, and adherence were performed. INTERVENTIONS: Fifty patients with HCV genotype 1 never before treated for HCV were prescribed a fixed-dose combination of ledipasvir (90 mg) and sofosbuvir (400 mg) once daily for 12 weeks. MAIN OUTCOMES AND MEASURES: The primary study outcome was the proportion of patients with sustained viral response (plasma HCV RNA level <12 IU/mL) 12 weeks after end of treatment. RESULTS: Forty-nine of 50 participants (98% [95% CI, 89% to 100%]) achieved SVR 12 weeks after end of treatment, whereas 1 patient experienced relapse at week 4 following treatment. In the patient with relapse, deep sequencing revealed a resistance associated mutation in the NS5A region conferring resistance to NS5A inhibitors, such as ledipasvir. The most common adverse events were nasal congestion (16% of patients) and myalgia (14%). There were no discontinuations or serious adverse events attributable to study drug. CONCLUSIONS AND RELEVANCE: In this open-label, uncontrolled, pilot study enrolling patients co-infected with HCV genotype 1 and HIV, administration of an oral combination of ledipasvir and sofosbuvir for 12 weeks was associated with high rates of SVR after treatment completion. Larger studies that also include patients with cirrhosis and lower CD4 T-cell counts are required to understand if the results of this study generalize to all patients co-infected with HCV and HIV. TRIAL REGISTRATION: clinicaltrials.gov Identifier:NCT01878799.
Assuntos
Antivirais/uso terapêutico , Benzimidazóis/uso terapêutico , Fluorenos/uso terapêutico , Infecções por HIV/tratamento farmacológico , Hepacivirus/genética , Hepatite C Crônica/tratamento farmacológico , Uridina Monofosfato/análogos & derivados , Administração Oral , Adulto , Benzimidazóis/efeitos adversos , Coinfecção , Quimioterapia Combinada , Feminino , Fluorenos/efeitos adversos , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Mialgia/induzido quimicamente , RNA Viral , Sofosbuvir , Resultado do Tratamento , Uridina Monofosfato/efeitos adversos , Uridina Monofosfato/uso terapêutico , Carga ViralRESUMO
PURPOSE: To highlight important diagnostic and treatment considerations in patients who present with bifocal patellar tendon avulsion fractures from the tibial tubercle and inferior patellar pole. METHODS: Radiographic presentation, surgical technique, and complications of 5 children who sustained bifocal patellar tendon avulsion fractures with ≥6 months postoperative follow-up were retrospectively reviewed. Hospital for Special Surgery (HSS) Brief Functional Activity Scale (HSS Pedi-FABS), Patient-Reported Outcomes Measurement Information System (PROMIS) pain interference, PROMIS mobility, and Pediatric International Knee Documentation Committee Scale (Pedi-IKDC) were assessed at most recent follow-up. RESULTS: Five children (4 boys, 1 girl) presented with bifocal patellar tendon avulsion fractures with a median follow-up of 12.8 months (range 7.7 to 26.4). In 1 case, advanced imaging was not pursued, and the bifocal nature of injury was subsequently discovered intraoperatively. In all other cases, magnetic resonance imaging (MRI) correctly characterized the bifocal injuries and revealed the full extent of fractures and soft tissue injury. Surgical management involved suture anchor repair with heavy nonabsorbable sutures. Postoperative functional and patient-reported outcomes were within the range of population healthy/normative values (for those that were available for comparison, e.g., Pedi-IKDC), and clinically relevant improvement was noted when comparing preoperative and postoperative patient-reported outcome measures of both pain and mobility. CONCLUSIONS: Advanced imaging (e.g., MRI) is required to understand the full extent of injury and should be obtained in the setting of traumatic patella alta to evaluate for the presence of a bifocal lesion and plan surgical intervention accordingly. These patients demonstrate satisfactory functional and patient-reported outcomes after operative repair. LEVEL OF EVIDENCE: IV, therapeutic case series.
RESUMO
PURPOSE: To establish normative values for articular cartilage thickness in pediatric and adolescent knees using magnetic resonance imaging (MRI) and investigate for any associations with age and skeletal maturity. METHODS: MRI scans were analyzed in patients 7 to 18 years old without osteochondral lesions, chondral wear/pathology, intra-articular fractures, or history of knee surgery. Measurements of articular cartilage thickness at the patella (medial facet, lateral facet, median ridge), femur (medial condyle, lateral condyle, lateral trochlea), and tibia (medial plateau, lateral plateau) were made on axial, coronal, and sagittal MRI. Descriptive statistics were used to calculate mean cartilage thickness by age and sex. Analysis of variance with repeated measures, analysis of covariance, independent samples t test, and linear regression were performed to determine differences in mean cartilage thickness by anatomic location, sex, physeal status, and age, respectively. RESULTS: A total of 240 knee MRI scans were included. Articular cartilage was thickest at the patella and did not vary with age or skeletal maturity. On the femur, articular cartilage was thickest at the lateral trochlea with mean cartilage thickness of 4.4 ± 1.4 mm in male patients and 3.6 ± 1.3 mm in female patients (P < .001). Patients with open distal femoral physes had significantly thicker cartilage at the medial femoral condyle, lateral femoral condyle, and lateral trochlea compared to patients with closing/closed physes (P < .001). Linear regression analysis revealed a significant inverse association between cartilage thickness at the femur and age. CONCLUSIONS: In pediatric and adolescent knees, articular cartilage is thickest at the patella, where it does not strongly correlate with age. In contrast, there is a strong inverse association between increasing age and articular cartilage thickness of the distal femoral condyles. CLINICAL RELEVANCE: The longitudinal reference data presented in this study can aid in pre-operative interpretation of knee cartilage under pathologic conditions in pediatric and adolescent patients.
RESUMO
Patellofemoral instability is a common problem affecting children and adolescents, with recurrent instability often requiring surgical intervention. Medial patellofemoral ligament (MPFL) reconstruction has become a mainstay for the treatment of patellofemoral instability because of the biomechanical importance of the MPFL against lateral dislocation as well as the high frequency of MPFL injury following traumatic patellar dislocation. The concern in managing skeletally immature patients is the potential for injury to the distal femoral physis. Here, we highlight 2 techniques for MPFL reconstruction. The first technique utilizes a hamstring autograft. The steps include: Step 1: Harvest the semitendinosus graft from a 2-cm posteromedial incision with use of an open tendon harvester proximally and a closed tendon harvester distally. Step 2: Prepare the graft for double-bundle reconstruction, allowing for approximately 50 to 60 mm for the reconstructed MPFL and 15 to 20 mm for graft placement within the patella and femoral sockets. Step 3: Use a guidewire and reamer to create 2 patellar sockets approximately 15 mm long each. Step 4: Use a guidewire under fluoroscopy to position and create a femoral socket distal to the distal femoral physis approximately 15 mm long. Step 5: Fix the graft on the femur with use of a tenodesis screw, pass the graft through the soft-tissue space between the fascia and synovium to the superior half of the patella, then dock the free ends of the graft onto the 2 patellar sockets with "PEEK (polyetheretherketone) SwiveLocks (Arthrex)" while the knee is in 30° of flexion. We also review a second technique of docking the hamstring graft onto the adductor tubercle and suturing it proximally to the deep distal medial aspect of the quadriceps tendon. Although only a limited number of studies have reported the outcomes of MPFL reconstruction in skeletally immature patients, such studies have demonstrated a high return to preoperative level of sports activity and a reduced prevalence of recurrent patellar instability.
RESUMO
BACKGROUND: Osgood-Schlatter disease (OSD) is a traction apophysitis of the tibial tubercle caused by repetitive strain and chronic avulsion from the patellar tendon. No widely accepted anatomic risk factors have been associated with OSD. PURPOSE: To determine if OSD is associated with increased posterior tibial slope (PTS). STUDY DESIGN: Cross-sectional study; Level of evidence, 3. METHODS: Forty knees with OSD and 32 control knees examined by the senior author between 2008 and 2019 were included. Patients 10 to 15 years of age with a clinical diagnosis of OSD and available lateral radiograph and magnetic resonance imaging (MRI) were eligible. Age- and sex-matched patients with a history of knee pain but no evidence of OSD on clinical examination and without significant pathology on lateral radiograph and MRI were included in the control group. PTS was defined as the angle between a reference line perpendicular to the proximal anatomic axis and a line drawn tangent to the uppermost anterior and posterior edges of the medial tibial plateau. Measurements were carried out in duplicate on true lateral radiographs by 2 blinded investigators. Interrater reliability of PTS measurements was evaluated using intraclass correlation coefficient (ICC). The independent samples t test was used to compare PTS between the OSD and control knees. RESULTS: The mean age was 12.6 ± 1.6 years and 51% (37/72) of the knees were from male youth. There were no differences in age, sex, and laterality of knees between the OSD and control groups. The mean PTS was significantly higher in the OSD group (12.23°± 3.58°) compared with the control group (8.82°± 2.76°; P < .001). The ICC was 0.931 (95% CI, 0.890-0.957), indicating almost perfect interrater reliability. CONCLUSION: This study identifies an association between OSD and increased PTS. The clinical implications of this finding have not yet been elucidated. It may be speculated that in patients with OSD, stress from the extensor mechanism through the patellar tendon loads the anterior portion of the tibia disproportionately to the posterior segment, thereby resulting in asymmetric growth and an increased PTS.
Assuntos
Articulação do Joelho/patologia , Osteocondrose/fisiopatologia , Tíbia/patologia , Adolescente , Criança , Estudos Transversais , Feminino , Humanos , Imageamento por Ressonância Magnética , Masculino , Dor/etiologia , Ligamento Patelar , Radiografia , Reprodutibilidade dos TestesRESUMO
Patellofemoral instability is a common orthopedic condition in children and adolescents, with recurrent instability often requiring surgical intervention. Age, bilateral instability, and various anatomic features such as trochlear dysplasia, patella alta, increased tibial tubercle to trochlear groove distance, and patellar tilt have all been described as risk factors for recurrent patellar instability. Medial patellofemoral ligament reconstruction has become the mainstay of treatment for addressing recurrent patellar instability in skeletally immature patients. For some patients, additional interventions such as distal realignment and guided growth procedures may be required to address anatomic pathology. This article discusses various risk factors associated with patellofemoral instability, reconstruction techniques, and a case example.
Assuntos
Instabilidade Articular/cirurgia , Ligamentos Articulares/cirurgia , Luxação Patelar/cirurgia , Adolescente , Criança , Feminino , Humanos , Patela , Articulação Patelofemoral/cirurgia , Procedimentos de Cirurgia Plástica , RecidivaRESUMO
Chronic hepatitis C virus (HCV) infection is associated with lower serum concentration of low-density lipoprotein (LDL-C), the primary cholesterol metabolite targeted pharmaceutically to modulate cardiovascular risk. Chronic infection with human immunodeficiency virus (HIV) and treatment with antiretrovirals (ARVs) are associated with dyslipidemia and increased risk of cardiovascular disease. In subjects coinfected with HIV and HCV, lipid abnormalities associated with either infection alone are often attenuated. Treatment of chronic HCV infection in HIV/HCV-coinfected subjects is now possible with interferon (IFN)-free regimens composed of directly acting antivirals (DAAs). We previously observed a marked increase in serum LDL-C in HCV-monoinfected subjects treated with sofosbuvir and ribavirin (SOF/RBV) that correlated with viral decline in serum, suggesting a direct influence of HCV clearance on serum cholesterol. In the present study, we assessed longitudinal changes in cholesterol in HIV/HCV-coinfected subjects during treatment of HCV genotype-1 (GT1) infection with combination DAA therapy. We report a rapid increase in LDL-C and LDL particle size by week 2 of treatment that was sustained during and after treatment in HIV/HCV-coinfected subjects. No change in serum LDL-C was observed at day 3 of treatment, in spite of a marked reduction in serum HCV viral load, suggesting LDL-C increases do not directly reflect HCV clearance as measured in peripheral blood. After effective DAA therapy for HCV, an increase in LDL should be anticipated in HIV/HCV-coinfected subjects.
Assuntos
Antivirais/uso terapêutico , LDL-Colesterol/sangue , Coinfecção/tratamento farmacológico , Dislipidemias/induzido quimicamente , Infecções por HIV/tratamento farmacológico , HIV-1/efeitos dos fármacos , Hepacivirus/efeitos dos fármacos , Hepatite C Crônica/tratamento farmacológico , Antivirais/efeitos adversos , Benzimidazóis/efeitos adversos , Benzimidazóis/uso terapêutico , Doenças Cardiovasculares , Coinfecção/virologia , Quimioterapia Combinada , Dislipidemias/sangue , Feminino , Fluorenos/efeitos adversos , Fluorenos/uso terapêutico , Furanos/efeitos adversos , Furanos/uso terapêutico , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Quinolinas/efeitos adversos , Quinolinas/uso terapêutico , Ribavirina/efeitos adversos , Ribavirina/uso terapêutico , Sofosbuvir/efeitos adversos , Sofosbuvir/uso terapêutico , Tiofenos/efeitos adversos , Tiofenos/uso terapêutico , Uridina Monofosfato/efeitos adversos , Uridina Monofosfato/análogos & derivados , Uridina Monofosfato/uso terapêuticoRESUMO
BACKGROUND: As treatment for chronic hepatitis C (HCV) virus has evolved to all-oral, interferon-free directly acting antiviral (DAA) therapy, the impact of these improvements on patient adherence has not been described. METHODS: Medication adherence was measured in 60 HCV, genotype-1, treatment-naïve participants enrolled in a phase 2a clinical trial at the National Institutes of Health and community clinics. Participants received either ledipasvir/sofosbuvir (LDV/SOF) (90 mg/400 mg) (one pill) daily for 12 weeks, LDV/SOF + GS-9451 (80 mg/day) (two pills) daily for 6 weeks, or LDV/SOF + GS-9669 (500 mg twice daily; three pills, two in the morning, one in the evening) for 6 weeks. Adherence was measured using medication event monitoring system (MEMS) caps, pill counts and patient report. RESULTS: Overall adherence to DAAs was high. Adherence declined over the course of the 12-week treatment (p = 0.04). While controlled psychiatric disease or symptoms of depression did not influence adherence, recent drug use was a risk factor for non-adherence to 12-week (p = 0.01), but not 6-week regimens. Adherence as measured by MEMS was lower than by patient report. CONCLUSIONS: Adherence to short courses of DAA therapy with 1-3 pills a day was excellent in an urban population with multiple risk factors for non-adherence.
Assuntos
Antivirais/administração & dosagem , Hepatite C Crônica/tratamento farmacológico , Adesão à Medicação , Administração Oral , Esquema de Medicação , Quimioterapia Combinada , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Resultado do Tratamento , População UrbanaRESUMO
BACKGROUND: Worldwide, although predominantly in low-income countries in the Middle East and Africa, up to 13% of hepatitis C virus (HCV) infections are caused by HCV genotype 4. For patients with HCV genotype 1, the combination of ledipasvir and sofosbuvir has been shown to cure high proportions of patients with excellent tolerability, but this regimen has not been assessed for the treatment of HCV genotype 4. We assessed the efficacy, safety, and tolerability of 12 weeks of combination therapy with ledipasvir and sofosbuvir for patients with chronic HCV genotype 4 infections. METHODS: In this single-centre, open-label cohort, phase 2a trial, patients with HCV genotype 4 who were treatment naive or interferon treatment experienced (HIV-negative) were sequentially enrolled at the Clinical Center of the National Institutes of Health, Bethesda, MD, USA. We gave patients 12 weeks of ledipasvir (90 mg) and sofosbuvir (400 mg) as a single combination tablet once per day. The primary efficacy endpoint was sustained viral response at 12 weeks (SVR12), as measured by the proportion of patients with HCV RNA concentrations less than the lower limit of quantification (COBAS TaqMan HCV test, version 1.0, 43 IU/mL). The primary safety endpoint was the frequency and severity of adverse events. We did our analyses on an intention-to-treat basis. This study is registered with ClinicalTrials.gov, number NCT01805882. FINDINGS: Between Sept 16, 2013, and Nov 2, 2014, we recruited 21 patients. 20 (95%) of 21 patients completed 12 weeks of treatment and achieved SVR12 (95% CI 76-100), including seven patients with cirrhosis. One patient was non-adherent to study drugs and withdrew from the study, but was included in the intention-to-treat analysis. No patients discontinued treatment because of adverse events and no grade 3 or 4 adverse events occurred that were related to study medications. The most common adverse events were diarrhoea (two patients), fatigue (three patients), nausea (two patients), and upper respiratory infections (two patients). INTERPRETATION: Ledipasvir and sofosbuvir treatment for 12 weeks was well tolerated by patients with HCV genotype 4 and resulted in 100% SVR for all patients who received all 12 weeks of study drugs, irrespective of previous treatment status and underlying liver fibrosis. This is the first report of a single-pill, all-oral, interferon-free, ribavirin-free treatment for patients with HCV genotype 4. FUNDING: NIAID, National Cancer Institute and Clinical Center Intramural Program. The study was also supported in part by a Cooperative Research and Development Agreement between NIH and Gilead Sciences.
Assuntos
Benzimidazóis/uso terapêutico , DNA Viral/sangue , Fluorenos/uso terapêutico , Hepacivirus/genética , Hepatite C Crônica/tratamento farmacológico , Sofosbuvir/uso terapêutico , Idoso , Benzimidazóis/efeitos adversos , Combinação de Medicamentos , Feminino , Fluorenos/efeitos adversos , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Sofosbuvir/efeitos adversos , Carga ViralRESUMO
Chronic alcohol abuse is a major risk factor for hepatocellular carcinoma (HCC), the third leading cause of cancer deaths worldwide. Alcohol can also function synergistically with other risk factors to cause HCC. Hence, alcohol consumption is a major factor affecting hepatic carcinogenesis in millions and the cause of a substantial public health burden. Chronic alcohol consumption interferes with several host anti-tumor mechanisms, thereby facilitating hepatocyte proliferation and tumorigenesis. This review summarizes the major mechanisms of alcohol-induced HCC. These include pathways of ethanol metabolism, alcohol-induced oxidative stress and hypomethylation of DNA, and interplay of alcohol with iron elevation, retinoid metabolism, the immune system, inflammatory pathways, and neoangiogenesis. The relevance of each pathway in affecting HCC transformation is a topic of intense investigation. Ongoing research will enhance our insight into the alcohol-induced occurrence of HCC and offer hope in developing better therapeutics.