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BACKGROUND: With the cost of health care rising, the potential to avoid costs from an unplanned return to the emergency department (ED) or urgent care center (UC) after elective outpatient rotator cuff repair (RCR) has been discussed but not extensively assessed. METHODS: Outpatient RCR procedures were queried in a closed health care system, and all unplanned ED and UC visits within 7 days of procedures were collected and compared with other typical outpatient orthopedic procedures (knee arthroscopy, carpal tunnel release, and anterior cruciate ligament reconstruction). Avoidable diagnoses (ADs) for the unplanned visits were defined in advance as visits for (1) constipation, (2) nausea or vomiting, (3) pain, and (4) urinary retention. Final tallies of all visits versus visits with ADs were compared. RESULTS: From June 2015 to May 2016, 1306 outpatient RCRs were performed (729 male and 577 female patients; average age, 60 years). Of the patients, 90 returned for ED or UC visits (6.9%), with 34 for ADs (2.6%). Pain was the most common AD. However, when RCR was compared with other case types, ED or UC visits for urinary retention were significantly more common (P = .007), whereas there was no significant difference with the other ADs. The 1306 RCRs led to a greater proportion of ED or UC visits than the combined 5825 other cases studied (P < .001). DISCUSSION AND CONCLUSIONS: Unplanned ED visits within 7 days of outpatient RCR are measurable and in many cases, such as ED or UC visits for pain, are avoidable. Visits for urinary retention are seen more commonly after RCR. Outpatient RCR led to more unplanned ED and UC visits than other common outpatient orthopedic surgical procedures.
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Atención Ambulatoria/estadística & datos numéricos , Procedimientos Quirúrgicos Ambulatorios/efectos adversos , Artroscopía/efectos adversos , Servicio de Urgencia en Hospital/estadística & datos numéricos , Complicaciones Posoperatorias/etiología , Lesiones del Manguito de los Rotadores/cirugía , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Reconstrucción del Ligamento Cruzado Anterior/efectos adversos , Síndrome del Túnel Carpiano/cirugía , Niño , Preescolar , Estreñimiento/etiología , Costos y Análisis de Costo , Femenino , Humanos , Lactante , Recién Nacido , Articulación de la Rodilla/cirugía , Masculino , Persona de Mediana Edad , Náusea/etiología , Dolor Postoperatorio/etiología , Retención Urinaria/etiología , Vómitos/etiología , Adulto JovenRESUMEN
Historically, since the metabolism of administered peptide/protein drugs ("biotherapeutics") has been expected to undergo predictable pathways similar to endogenous proteins, comprehensive biotherapeutic metabolism studies have not been widely reported in the literature. However, since biotherapeutics have rapidly evolved into an impressive array of eclectic modalities, there has been a shift toward understanding the impact of metabolism on biotherapeutic development. For biotherapeutics containing non-native chemical linkers and other moieties besides natural amino acids, metabolism studies are critical as these moieties may impart undesired toxicology. For biotherapeutics that are composed solely of natural amino acids, where end-stage peptide and amino acid catabolites do not generally pose toxicity concerns, the understanding of biotherapeutic biotransformation, defined as in vivo modifications such as peripherally generated intermediate circulating catabolites prior to end-stage degradation or elimination, may impact in vivo stability and potency/clearance. As of yet, there are no harmonized methodologies for understanding biotherapeutic biotransformation and its impact on drug development, nor is there clear guidance from regulatory agencies on how and when these studies should be conducted. This review provides an update on biotherapeutic biotransformation studies and an overview of lessons learned, tools that have been developed, and suggestions of approaches to address issues. Biotherapeutic biotransformation studies, especially for certain modalities, should be implemented at an early stage of development to 1) understand the impact on potency/clearance, 2) select the most stable candidates or direct protein re-engineering efforts, and 3) select the best bioanalytical technique(s) for proper drug quantification and subsequent pharmacokinetic profiling and exposure/response assessment.
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Productos Biológicos/farmacocinética , Proteínas/farmacocinética , Animales , Productos Biológicos/uso terapéutico , Biotransformación , Humanos , Proteínas/uso terapéuticoRESUMEN
OBJECTIVE: Superior capsule reconstruction (SCR) is a treatment option for irreparable massive rotator cuff tears (MRCT). The purpose of this study is to describe a classification system for graft integrity and tear location. METHODS: Patients who underwent SCR at a single institution were included. Pre-operative age, gender, prior surgery, Hamada grade, and Goutallier stage were recorded. An MRI was performed postoperatively to assess graft integrity and tear location. RESULTS: 53 patients met inclusion criteria. Mean age was 60.1 ± 7.9 years. A post-operative MRI was performed in 42 (80%) patients at a mean of 14 ± 7 months (range, 6-40 months). MRIs demonstrated an intact graft in 16 (38%) shoulders. Of the 26 graft tears, 14 (54%) were from the glenoid, 5 (19%) mid-substance, 6 (23%) from the tuberosity, and 1 (3.8%) had complete graft absence. CONCLUSION: Graft tears are common following SCR. We describe four different graft tear locations and submit a classification system that can be used in future studies to better compare outcomes based on graft integrity and tear location. Clinical correlation with graft integrity and graft tear location needs to be further investigated.
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Lesiones del Manguito de los Rotadores , Articulación del Hombro , Anciano , Artroscopía , Humanos , Persona de Mediana Edad , Rango del Movimiento Articular , Lesiones del Manguito de los Rotadores/cirugía , Articulación del Hombro/cirugía , Resultado del TratamientoRESUMEN
Osteochondritis dissecans (OCD) of the capitellum is an uncommon disorder seen primarily in the adolescent overhead athlete. Unlike Panner disease, a self-limiting condition of the immature capitellum, OCD is multifactorial and likely results from microtrauma in the setting of cartilage mismatch and vascular susceptibility. The natural history of OCD is poorly understood, and degenerative joint disease may develop over time. Multiple modalities aid in diagnosis, including radiography, MRI, and magnetic resonance arthrography. Lesion size, location, and grade determine management, which should attempt to address subchondral bone loss and articular cartilage damage. Early, stable lesions are managed with rest. Surgery should be considered for unstable lesions. Most investigators advocate arthroscopic débridement with marrow stimulation. Fragment fixation and bone grafting also have provided good short-term results, but concerns persist regarding the healing potential of advanced lesions. Osteochondral autograft transplantation appears to be promising and should be reserved for larger, higher grade lesions. Clinical outcomes and return to sport are variable. Longer-term follow-up studies are necessary to fully assess surgical management, and patients must be counseled appropriately.
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Articulación del Codo/cirugía , Procedimientos Ortopédicos/métodos , Osteocondritis Disecante/cirugía , Trasplante Óseo , Articulación del Codo/diagnóstico por imagen , Humanos , Imagen por Resonancia Magnética , Osteocondritis Disecante/diagnóstico por imagen , Radiografía , Trasplante Autólogo , UltrasonografíaRESUMEN
To what extent are research results influenced by subjective decisions that scientists make as they design studies? Fifteen research teams independently designed studies to answer five original research questions related to moral judgments, negotiations, and implicit cognition. Participants from 2 separate large samples (total N > 15,000) were then randomly assigned to complete 1 version of each study. Effect sizes varied dramatically across different sets of materials designed to test the same hypothesis: Materials from different teams rendered statistically significant effects in opposite directions for 4 of 5 hypotheses, with the narrowest range in estimates being d = -0.37 to + 0.26. Meta-analysis and a Bayesian perspective on the results revealed overall support for 2 hypotheses and a lack of support for 3 hypotheses. Overall, practically none of the variability in effect sizes was attributable to the skill of the research team in designing materials, whereas considerable variability was attributable to the hypothesis being tested. In a forecasting survey, predictions of other scientists were significantly correlated with study results, both across and within hypotheses. Crowdsourced testing of research hypotheses helps reveal the true consistency of empirical support for a scientific claim. (PsycInfo Database Record (c) 2020 APA, all rights reserved).
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Colaboración de las Masas , Psicología/métodos , Proyectos de Investigación , Adulto , Humanos , Distribución AleatoriaRESUMEN
Platelet-rich plasma is defined as autologous blood with a concentration of platelets above baseline values. Platelet-rich plasma has been used in maxillofacial and plastic surgery since the 1990s; its use in sports medicine is growing given its potential to enhance muscle and tendon healing. In vitro studies suggest that growth factors released by platelets recruit reparative cells and may augment soft-tissue repair. Although minimal clinical evidence is currently available, the use of platelet-rich plasma has increased, given its safety as well as the availability of new devices for outpatient preparation and delivery. Its use in surgery to augment rotator cuff and Achilles tendon repair has also been reported. As the marketing of platelet-rich plasma increases, orthopaedic surgeons must be informed regarding the available preparation devices and their differences. Many controlled clinical trials are under way, but clinical use should be approached cautiously until high-level clinical evidence supporting platelet-rich plasma efficacy is available.
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Sistema Musculoesquelético/lesiones , Plasma Rico en Plaquetas , Cicatrización de Heridas , Tendón Calcáneo/lesiones , Tendón Calcáneo/cirugía , Ligamento Cruzado Anterior/cirugía , Lesiones del Ligamento Cruzado Anterior , Humanos , Ortopedia/tendencias , Manguito de los Rotadores/cirugía , Lesiones del Manguito de los Rotadores , Medicina Deportiva/tendencias , Traumatismos de los Tendones/cirugía , Codo de Tenista/terapia , Terapias en Investigación , Cicatrización de Heridas/fisiologíaRESUMEN
A potential risk factor for immunogenicity of a biotherapeutic is the low levels of host cell protein (HCP) impurities that remain in the product following the purification process. During process development, significant attention has been devoted to removing HCPs due to their potential safety risk. Samples from different purification steps of several monoclonal antibodies (mAbs) purified by one type of platform were evaluated for their residual Chinese Hamster Ovary (CHO) cell-derived HCP content. HCPs in both in-process (high levels of HCP) and highly purified (low levels of HCP) samples were identified and quantitated by proteomic analysis via mass spectrometry. The responses to HCPs were evaluated in an in vitro assay using PBMC from a population of healthy and disease state individuals. Results indicated that samples with up to 4000 ppm HCP content (levels 200 times greater than the drug substance) did not pose a higher immunogenicity risk than highly purified mAb samples. As an orthogonal method to predict immunogenicity risk, in silico algorithms that probe amino acid sequence for foreign epitope content were used to evaluate over 20 common HCPs (identified in the different mAb samples). Only a few HCPs were identified as high risk by the algorithms; however, the in vitro assay results indicated that the concentration of these HCPs from in-process biotherapeutic mAb samples was not sufficient to stimulate an immune response. This suggests that high levels of HCP in mAb biotherapeutics purified by this type of platform do not increase the potential risk of immunogenicity of these molecules. Insights from these studies can be applied to HCP control and risk assessment strategies.
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Anticuerpos/inmunología , Productos Biológicos/inmunología , Contaminación de Medicamentos , Proteínas/inmunología , Algoritmos , Animales , Células CHO , Proliferación Celular , Cricetinae , Cricetulus , Citocinas/metabolismo , Cinética , Espectrometría de Masas , Monocitos/metabolismoRESUMEN
Protein A chromatography is commonly used as the initial step for purifying monoclonal antibody biotherapeutics expressed in mammalian tissue culture cells. The purpose of this step, as well as later chromatography steps, is, in part, to remove host cell proteins (HCPs) and other related impurities. Understanding the retention mechanism for the subset of HCPs retained during this step is of great interest to monoclonal antibody (mAb) process developers because it allows formation of a guided HCP clearance strategy. However, only limited information is available about the specific HCPs that co-purify with mAbs at this step. In this study, a comprehensive comparison of HCP subpopulations that associated with 15 different mAbs during protein A chromatography was conducted by a 2D-LC-HDMS(E) approach. We found that a majority of CHO HCPs binding to and eluting with the mAbs were common among the mAbs studied, with only a small percentage (â¼10% on average) of a mAb's total HCP content in the protein A (PrA) eluate specific for a particular antibody. The abundance of these HCPs in cell culture fluids and their ability to interact with mAbs were the two main factors determining their prevalence in protein A eluates. Potential binding segments for HCPs to associate with mAbs were also studied through their co-purification with individual Fc and (Fab')2 antibody fragments. © 2016 American Institute of Chemical Engineers Biotechnol. Prog., 32:708-717, 2016.
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Anticuerpos Monoclonales/química , Anticuerpos Monoclonales/aislamiento & purificación , Proteína Estafilocócica A/química , Animales , Células CHO , Células Cultivadas , Cromatografía Liquida , Cricetulus , Espectrometría de MasasRESUMEN
Stable isotope tagging methods provide a useful means of determining the relative expression level of individual proteins between samples in a mass spectrometer with high precision (coefficients of variation less than 10%). Because two or more samples tagged with different numbers of stable isotopes can be mixed before any processing steps, sample-to-sample recovery differences are eliminated. Mass spectrometry also allows post-translational modifications, splice variations and mutations (often unnoticed in immunoassays) to be detected and identified, increasing the clinical relevance of the assay and avoiding the issues of non-specific binding and cross-reactivity observed in immunoassays. Several stable isotope tagging methods are available for use in proteomics research. We discuss the advantages and disadvantages of each technique with respect to biomarker discovery, target validation, efficacy and toxicology screening and clinical diagnostic applications.
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Marcaje Isotópico/métodos , Proteómica/métodos , Espectrometría de Masas/métodosRESUMEN
BACKGROUND: Criteria for return to unrestricted activity after anterior cruciate ligament (ACL) reconstruction varies, with some using time after surgery as the sole criterion-most often at 6 months. Patients may have residual neuromuscular deficits, which may increase the risk of ACL injury. A single-leg squat test (SLST) can dynamically assess for many of these deficits prior to return to unrestricted activity. HYPOTHESIS: A significant number of patients will continue to exhibit neuromuscular deficits with SLST at 6 months after ACL reconstruction. STUDY DESIGN: Cross-sectional study; Level of evidence, 3. METHODS: Patients using a standardized accelerated rehabilitation protocol at their 6-month follow-up after primary ACL reconstruction were enrolled. Evaluation included bilateral SLST, single-leg hop distance, hip abduction strength, and the subjective International Knee Documentation Committee (IKDC) score. RESULTS: Thirty-three patients were enrolled. Poor performance of the operative leg SLST was found in 15 of 33 patients (45%). Of those 15 patients, 7 (45%) had concomitant poor performance of the nonoperative leg compared with 2 of 18 patients (11%) in those who demonstrated good performance in the operative leg. The poor performers were significantly older (33.6 years) than the good performers (24.2 years) (P = .007). Those with poor performance demonstrated decreased hip abduction strength (17.6 kg operative leg vs 20.5 kg nonoperative leg) (P = .024), decreased single-leg hop distance (83.3 cm operative leg vs 112.3 cm nonoperative leg) (P = .036), and lower IKDC scores (67.9 vs 82.3) (P = .001). CONCLUSION: Nearly half of patients demonstrated persistent neuromuscular deficits on SLST at 6 months, which is when many patients return to unrestricted activity. Those with poor performance were of a significantly older age, decreased hip abduction strength, decreased single-leg hop distance, and lower IKDC subjective scores. CLINICAL RELEVANCE: The SLST can be used to identify neuromuscular risk factors for ACL rupture. Many patients at 6 months have persistent neuromuscular deficits on SLST. Caution should be used when using time alone to determine when patients can return to unrestricted activity.
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RATIONALE AND OBJECTIVES: Coronary artery calcium (CAC) scoring is an excellent imaging tool for subclinical atherosclerosis detection and risk stratification. We hypothesize that although CAC has been underreported in the past on computed tomography (CT) scans of the abdomen, specialized resident educational intervention can improve on this underreporting. MATERIALS AND METHODS: Beginning July 2009, a dedicated radiology resident cardiac imaging rotation and curriculum was initiated. A retrospective review of the first 500 abdominal CT reports from January 2009, 2011, and 2013 was performed including studies originally interpreted by a resident and primary attending physician interpretations. Each scan was reevaluated for presence or absence of CAC and coronary artery disease (CAD) by a cardiovascular CT expert reader. These data were then correlated to determine if the presence of CAC had been properly reported initially. The results of the three time periods were compared to assess for improved rates of CAC and CAD reporting after initiation of a resident cardiac imaging curriculum. RESULTS: Statistically significant improvements in the reporting of CAC and CAD on CT scans of the abdomen occurred after the initiation of formal resident cardiac imaging training which included two rotations (4 weeks each) of dedicated cardiac CT and cardiac magnetic resonance imaging interpretation during the resident's second, third, or fourth radiology training years. The improvement was persistent and increased over time, improving from 1% to 72% after 2 years and to 90% after 4 years. CONCLUSIONS: This single-center retrospective analysis shows association between implementation of formal cardiac imaging training into radiology resident education and improved CAC detection and CAD reporting on abdominal CT scans.
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Enfermedad de la Arteria Coronaria/diagnóstico por imagen , Internado y Residencia , Mejoramiento de la Calidad , Radiografía Abdominal , Tomografía Computarizada por Rayos X , Calcificación Vascular/diagnóstico por imagen , Anciano , Anciano de 80 o más Años , Vasos Coronarios/diagnóstico por imagen , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios RetrospectivosRESUMEN
Mass spectrometry has proved to be an important tool for protein biomarker discovery, identification and characterization. However, global proteomic profiling strategies often fail to identify known low-abundance biomarkers as a result of the limited dynamic range of mass spectrometry (two to three orders of magnitude) compared with the large dynamic range of protein concentrations in biologic fluids (11 to 12 orders of magnitude for serum). In addition, the number of peptides generated in such methods vastly overwhelms the resolution capacity of mass spectrometers, requiring extensive sample clean-up (e.g., affinity tag, retentate chromatography and/or high-performance liquid chromatography) before mass spectrometry analysis. Baiting and affinity pre-enrichment strategies, which overcome the dynamic range and sample complexity issues of global proteomic strategies, are very difficult to couple to mass spectrometry. This is due to the fact that it is nearly impossible to sort target peptides from those of the bait since there will be many cases of isobaric peptides. IDBEST (Target Discovery, Inc.) is a new tagging strategy that enables such pre-enrichment of specific proteins or protein classes as the resulting tagged peptides are distinguishable from those of the bait by a mass defect shift of approximately 0.1 atomic mass units. The special characteristics of these tags allow: resolution of tagged peptides from untagged peptides through incorporation of a mass defect element; high-precision quantitation of up- and downregulation by using stable isotope versions of the same tag; and potential analysis of protein isoforms through more complete peptide coverage from the proteins of interest.
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Biomarcadores/análisis , Proteínas/análisis , Cromatografía/métodos , Cromatografía Líquida de Alta Presión/métodos , Humanos , Marcaje Isotópico/métodos , Espectrometría de Masas/métodos , Biblioteca de Péptidos , Reproducibilidad de los Resultados , Sensibilidad y EspecificidadRESUMEN
We present a new class of "mass defect" tags with utility in biomolecular mass spectrometry. These tags, incorporating element(s) with atomic numbers between 17 (Cl) and 77 (Ir), have a substantially different nuclear binding energy (mass defect) from the elements common to biomolecules. This mass defect yields a readily resolvable mass difference between tagged and untagged species in high-resolution mass spectrometers. We present the use of a subset of these tags in a new protein sequencing application. This sequencing technique has advantages over existing mass spectral protein identification methodologies: intact proteins are quickly sequenced and unambiguously identified using only an inexpensive, robust mass spectrometer. We discuss the potential broader utility of these tags for the sequencing of other biomolecules, differential display applications and combinatorial methods.
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Espectrometría de Masas/métodos , Proteínas/análisis , Análisis de Secuencia de Proteína/métodos , Animales , Mioglobina/análisis , Unión Proteica , Proteínas/metabolismoRESUMEN
Platelet rich plasma (PRP), an autologous sample of blood with a platelet concentration above baseline values, is hypothesized to augment soft tissue healing. Its use in sports medicine has risen dramatically, with common applications including the treatment of refractory tendinopathy and augmenting tendon repair. Many commercial preparation systems are available, but the optimal preparation remains unknown. Increasing numbers of clinical studies evaluating PRP have been reported and have provided both positive and negative evidence for its effectiveness. Well-designed, controlled studies are still lacking, but PRP may have a benefit for patients with tendinopathy that is refractory to other non-surgical treatments. Its use in tendon repair is currently not supported. Randomized, controlled studies with documentation of platelet, white blood cell, and growth factor concentration in the PRP preparation are necessary for future comparative research. Use of PRP should be approached judiciously until further evidence is available.
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Transfusión de Sangre Autóloga , Procedimientos Ortopédicos , Transfusión de Plaquetas , Plasma Rico en Plaquetas , Tendinopatía/terapia , Tendones/cirugía , Animales , Humanos , Tendinopatía/sangre , Tendinopatía/diagnóstico , Tendinopatía/fisiopatología , Tendinopatía/cirugía , Tendones/metabolismo , Tendones/fisiopatología , Resultado del Tratamiento , Cicatrización de HeridasRESUMEN
UNLABELLED: The outcomes of ACL reconstructions in terms of patient satisfaction and function are well known. Most orthopaedic surgeons feel that Medicare and other payors do not reimburse enough for this surgery. The purpose of this study is to determine how much patients are willing to pay for this surgery and compare it to reimbursement rates. METHODS: We constructed a survey which described the function and limitations of an ACL deficient knee and the expected function of that knee after an ACL reconstruction. We then asked the volunteers how much they would be willing to pay for an ACL reconstruction if it were their knee. We also gathered data on the yearly earnings and Tegner activity level of the volunteers. In all, 143 volunteers completed the survey. We computed correlation coefficients between willingness to pay and both yearly earnings and Tegner activity level. RESULTS: The average amount that the volunteers were willing to pay for an ACL reconstruction was $4,867.00. There was no correlation between yearly earnings and willingness to pay. The correlation coefficient was 0.34. There was a weak correlation between Tegner activity level and willingness to pay. This correlation coefficient was 0.81. The Medicare allowable rate for ACL reconstruction (CPT 29888) in the geographic area of the study was $1,132.00. CONCLUSION: The data demonstrates that patients are willing to pay much more than traditional payors for ACL reconstruction. These payors undervalue the benefit of this surgery to the patient. There is increasing pressure on orthopaedic surgeons to not participate in insurance plans that reimburse poorly. This places an increasing financial burden on the patient. This study suggests that patients may be willing to pay more for their surgery than their insurance plan and accept more of this burden.
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Reconstrucción del Ligamento Cruzado Anterior/economía , Costos de la Atención en Salud , Gastos en Salud , Conocimientos, Actitudes y Práctica en Salud , Reembolso de Seguro de Salud/economía , Articulación de la Rodilla/cirugía , Adolescente , Adulto , Anciano , Fenómenos Biomecánicos , Femenino , Encuestas de Atención de la Salud , Humanos , Articulación de la Rodilla/fisiopatología , Masculino , Medicare/economía , Persona de Mediana Edad , Recuperación de la Función , Características de la Residencia , Salarios y Beneficios/economía , Encuestas y Cuestionarios , Resultado del Tratamiento , Estados Unidos , Adulto JovenRESUMEN
Femoral tunnel intersection in combined anterior cruciate ligament and posterolateral corner reconstruction has been reported to be high. The purpose of this study was to examine the risk of intersection between an anatomic femoral anterior cruciate ligament tunnel created with a retrograde reaming device and femoral lateral collateral ligament reconstruction tunnels of varying trajectory in a synthetic femur model.
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Reconstrucción del Ligamento Cruzado Anterior/efectos adversos , Reconstrucción del Ligamento Cruzado Anterior/métodos , Ligamento Cruzado Anterior/cirugía , Traumatismos de la Rodilla/etiología , Traumatismos de la Rodilla/prevención & control , Osteotomía/efectos adversos , Osteotomía/métodos , Ligamento Cruzado Anterior/diagnóstico por imagen , Terapia Combinada , Humanos , Traumatismos de la Rodilla/diagnóstico por imagen , Radiografía , Resultado del TratamientoRESUMEN
No established guidelines currently exist to assist orthopedic surgeons in determining when a patient may safely control a motor vehicle after undergoing simple right knee arthroscopy. Despite this lack of concrete evidence, premature postoperative driving could expose orthopedic surgeons to legal liability and, more importantly, patients to danger and further injury. Through questionnaires directed at physicians, patients, and insurance companies, the authors attempted to identify common postoperative management trends among orthopedic surgeons in an effort to better identify patterns that could help direct practice for the optimized treatment of patients after right knee arthroscopy.Although 29.7% of physicians always incorporated postoperative driving instructions during routine preoperative consultation, 57% of physicians brought up these conversations half of the time or less. In addition, when the preoperative discussions were conducted, approximately 23.6% of physicians never initiated the conversation. The majority of physicians recommended driving after narcotics were discontinued (70%), when the patient felt they could subjectively control their vehicle (57.1%), and when postoperative symptoms would allow safe driving (38.8%); these achievements were most commonly reached at 1 week postoperatively. After simple right knee arthroscopy, the common consensus indicates that patients may safely return to driving 1 week postoperatively when they are narcotic-free and feel safe to control their vehicle.
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Artroscopía/estadística & datos numéricos , Conducción de Automóvil/estadística & datos numéricos , Articulación de la Rodilla/cirugía , Educación del Paciente como Asunto/estadística & datos numéricos , Seguridad del Paciente , Médicos/estadística & datos numéricos , Pautas de la Práctica en Medicina/estadística & datos numéricos , Humanos , Encuestas y Cuestionarios , Estados Unidos/epidemiologíaRESUMEN
BACKGROUND: There has been an increasing number of arthroscopic surgeries performed in general orthopedic surgery practice, as well as a rapid evolution of arthroscopic techniques. The objective of this investigation was to assess the adequacy of arthroscopic training in U.S. orthopedic residency programs from a resident and program director perspective. MATERIALS AND METHODS: The study was performed with a mail-in survey to orthopaedic surgery residents and program directors. Out of 151 programs contacted, we received responses from 24 program directors (15.9%) and 272 residents (11.1% of 2447 possible residents in years 2 through 5 in 2006). Program demographics and resident and program director assessments of arthroscopic surgical training was obtained from the questionnaire. Assessment of open surgical techniques was used as a control. The responses from fifth-year residents (83 of a possible 612 in 2006 (13.6%)) and program directors were used for detailed analysis. RESULTS: Only 32% (27/83) of fifth-year residents felt there was adequate time dedicated to arthroscopic training, compared to 66% (16/24) of program directors (p < 0.01). Thirty-four percent (28/83) of fifth-year residents felt as prepared in arthroscopy as open techniques, in contrast to 58% (14/24) of program directors, who felt fifth-year residents were appropriately prepared in arthroscopic techniques (p = 0.03). The amount of surgery that residents are allowed to perform correlated significantly (p < 0.01) with confidence levels. CONCLUSIONS: Fifth-year residents who were surveyed felt less prepared in arthroscopic training, compared to open surgical procedures. Program directors surveyed over estimated confidence levels in fifth-year residents performing arthroscopic procedures. To ensure that graduating residents are appropriately prepared for the current demands of a clinical setting, it may be necessary to reexamine residency requirements to ensure adequate practice in developing arthroscopic surgical skills.
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Artroscopía , Educación de Postgrado en Medicina , Internado y Residencia , Procedimientos Ortopédicos/educación , Personal Administrativo , Competencia Clínica , Curriculum , Educación de Postgrado en Medicina/organización & administración , Humanos , Desarrollo de Programa , Evaluación de Programas y Proyectos de Salud , Autoevaluación (Psicología) , Encuestas y Cuestionarios , Estados UnidosRESUMEN
The knowledge of in vivo biotransformation (e.g., proteolysis) of protein therapeutic candidates reveals structural liabilities that impact stability. This information aids the development and confirmation of ligand-binding assays with the required specificity for bioactive moieties (including intact molecule and metabolites) for appropriate PK profiling. Furthermore, the information can be used for re-engineering of constructs to remove in vivo liabilities in order to design the most stable candidates. We have developed a strategic approach of ligand-binding mass spectrometry (LBMS) to study biotransformation of fusion proteins of peptides fused to human Fc ("peptibodies") using anti-human Fc immunoaffinity capture followed by tiered mass spectrometric interrogation. LBMS offers the combined power of selectivity of ligand capture with the specificity and detailed molecular-level information of mass spectrometry. In this paper, we demonstrate the preclinical application of LBMS to three peptibodies, AMG531 (romiplostim), AMG195(linear), and AMG195(loop), that target the thrombopoietin receptor. The data show that ligand capture offers excellent sample cleanup and concentration of intact peptibodies and metabolites for subsequent query by matrix-assisted laser desorption ionization time-of-flight mass spectrometry for identification of in vivo proteolytic points. Additional higher-resolution analysis by nanoscale liquid chromatography interfaced with electrospray ionization mass spectrometry is required for identification of heterogeneous metabolites. Five proteolytic points are accurately identified for AMG531 and two for AMG195(linear), while AMG195(loop) is the most stable construct in rats. We recommend the use of LBMS to assess biotransformation and in vivo stability during early preclinical phase development for all novel fusion proteins.
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Inmunoensayo/métodos , Péptidos/química , Receptores de Trombopoyetina/química , Espectrometría de Masa por Láser de Matriz Asistida de Ionización Desorción/métodos , Secuencia de Aminoácidos , Animales , Biotransformación , Ligandos , Datos de Secuencia Molecular , Ratas , Ratas Sprague-Dawley , Receptores Fc/sangre , Proteínas Recombinantes de Fusión/sangre , Proteínas Recombinantes de Fusión/farmacocinética , Trombopoyetina/sangre , Trombopoyetina/farmacocinéticaRESUMEN
Graft fixation in anterior cruciate ligament (ACL) reconstruction is commonly performed with bioabsorbable devices. This article presents a case of a broken bioabsorbable tibial interference screw (Gentle Threads; Biomet, Warsaw, Indiana) that presented as an intra-articular loose body 4 months after ACL reconstruction with posterior tibialis tendon allograft. A 19-year-old man presented with symptoms of pain and catching for 1 week but reported no history of trauma. The broken screw tip was identified on magnetic resonance imaging examination, and the remaining screw appeared to be overinserted into the tibia. During arthroscopic removal, a 10-mm screw tip was found in the lateral gutter. The ACL graft was found to be well fixed, but small areas of chondral damage were found in the patellofemoral and medial compartment. The patient's symptoms resolved postoperatively. To our knowledge, this is the earliest report of a broken bioabsorbable interference screw and only the second report of subsequent chondral injury due to intra-articular migration. Although rare, late breakage and intra-articular migration of bioabsorbable interference screws should be considered during the postoperative evaluation of any patient with pain or mechanical symptoms, regardless of trauma. This case also supports the importance of both measurement of tibial tunnel length and inspection of the intercondylar notch following interference screw insertion. Orthopedic surgeons performing ACL reconstruction must be aware of this possible complication and its potential for devastating chondral injury.