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OBJECTIVES: To analyze our patient's complication profile and rate after removal of hardware (ROH) surgery, and survey our patients to ask their overall status and improvement in symptomatology post-operatively. DESIGN: Retrospective chart review and survey. SETTING: Academic, tertiary referral center. PATIENTS/PARTICIPANTS: 173 patients with 314 pieces of hardware. Seventy-six patients (43.9%) responded to our survey. INTERVENTION: ROH surgery. MAIN OUTCOME MEASUREMENTS: Patient demographics and complications were recorded. All patients were sent a brief 3-question survey which asked: (1) Why did you get your hardware removed? (2) How did your overall status change after ROH? (3) How did the ROH affect your stiffness, pain, swelling, and mobility? RESULTS: There were 10 complications (5.5%): 5 infections, 2 with unresolved pain, 1 hematoma, 1 chronic regional pain syndrome exacerbation, and 1 recurrent deformity. All infections were treated with oral antibiotics and improved. All other complications resolved with treatment except for the patient who developed recurrent deformity. Patients underwent ROH surgery because their doctor suggested it (76.3%) and to improve mobility (39.5%). 86.9% reported their overall status improved after ROH. They improved regarding stiffness (73.7%), pain (73.6%), swelling (61.8%), and mobility (76.3%). Similar results were seen among different implants removed. CONCLUSIONS: The majority of patients who underwent percutaneous ROH were satisfied. They reported improvement in stiffness, pain, swelling and mobility (greatest improvement). The complication rate was low (5.5%). ROH can be a meaningful operation to patients allowing them to improve their quality of life with a low complication rate. LEVEL OF EVIDENCE: Level IV.
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This paper presents results from the integration of a compact quantum magnetometer system and an agile underwater glider for magnetic survey. A highly maneuverable underwater glider, ROUGHIE, was customized to carry an increased payload and reduce the vehicle's magnetic signature. A sensor suite composed of a vector and scalar magnetometer was mounted in an external boom at the rear of the vehicle. The combined system was deployed in a constrained pool environment to detect seeded magnetic targets and create a magnetic map of the test area. Presented is a systematic magnetic disturbance reduction process, test procedure for anomaly mapping, and results from constrained operation featuring underwater motion capture system for ground truth localization. Validation in the noisy and constrained pool environment creates a trajectory towards affordable littoral magnetic anomaly mapping infrastructure. Such a marine sensor technology will be capable of extended operation in challenging areas while providing high-resolution, timely magnetic data to operators for automated detection and classification of marine objects.
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Gi/o-coupled G protein-coupled receptors can inhibit neurotransmitter release at synapses via multiple mechanisms. In addition to Gßγ-mediated modulation of voltage-gated calcium channels (VGCC), inhibition can also be mediated through the direct interaction of Gßγ subunits with the soluble N-ethylmaleimide attachment protein receptor (SNARE) complex of the vesicle fusion apparatus. Binding studies with soluble SNARE complexes have shown that Gßγ binds to both ternary SNARE complexes, t-SNARE heterodimers, and monomeric SNAREs, competing with synaptotagmin 1(syt1) for binding sites on t-SNARE. However, in secretory cells, Gßγ, SNAREs, and synaptotagmin interact in the lipid environment of a vesicle at the plasma membrane. To approximate this environment, we show that fluorescently labeled Gßγ interacts specifically with lipid-embedded t-SNAREs consisting of full-length syntaxin 1 and SNAP-25B at the membrane, as measured by fluorescence polarization. Fluorescently labeled syt1 undergoes competition with Gßγ for SNARE-binding sites in lipid environments. Mutant Gßγ subunits that were previously shown to be more efficacious at inhibiting Ca2+-triggered exocytotic release than wild-type Gßγ were also shown to bind SNAREs at a higher affinity than wild type in a lipid environment. These mutant Gßγ subunits were unable to inhibit VGCC currents. Specific peptides corresponding to regions on Gß and Gγ shown to be important for the interaction disrupt the interaction in a concentration-dependent manner. In in vitro fusion assays using full-length t- and v-SNAREs embedded in liposomes, Gßγ inhibited Ca2+/synaptotagmin-dependent fusion. Together, these studies demonstrate the importance of these regions for the Gßγ-SNARE interaction and show that the target of Gßγ, downstream of VGCC, is the membrane-embedded SNARE complex.
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Subunidades beta de la Proteína de Unión al GTP/metabolismo , Subunidades gamma de la Proteína de Unión al GTP/metabolismo , Membrana Dobles de Lípidos , Modelos Moleculares , Proteína 25 Asociada a Sinaptosomas/metabolismo , Sinaptotagmina I/metabolismo , Sintaxina 1/metabolismo , Animales , Unión Competitiva , Señalización del Calcio , Bovinos , Línea Celular , Subunidades beta de la Proteína de Unión al GTP/química , Subunidades beta de la Proteína de Unión al GTP/genética , Subunidades gamma de la Proteína de Unión al GTP/química , Subunidades gamma de la Proteína de Unión al GTP/genética , Humanos , Liposomas , Fusión de Membrana , Mutación , Proteínas del Tejido Nervioso/química , Proteínas del Tejido Nervioso/metabolismo , Fragmentos de Péptidos/química , Fragmentos de Péptidos/genética , Fragmentos de Péptidos/metabolismo , Conformación Proteica , Dominios y Motivos de Interacción de Proteínas , Multimerización de Proteína , Ratas , Proteínas Recombinantes de Fusión/química , Proteínas Recombinantes de Fusión/metabolismo , Proteínas Recombinantes/química , Proteínas Recombinantes/metabolismo , Proteína 25 Asociada a Sinaptosomas/química , Sinaptotagmina I/química , Sinaptotagmina I/genética , Sintaxina 1/químicaRESUMEN
The optimal treatment approach to patients with coronary artery disease (CAD), including those with type 2 diabetes mellitus (T2DM), has been extensively evaluated. Several trials of stable ischemic heart disease including patients with T2DM have demonstrated that medical management is comparable to revascularization in terms of mortality and rates of major adverse cardiovascular events (MACE). There has been a growing appreciation for optimal medical therapy's (OMT) role in improving clinical outcomes. It is vital to target T2DM patients to prevent or delay MACE events through advanced OMT, ultimately delaying if not avoiding the need for revascularization. There has been significant evolution in the development of pharmacologic management of T2DM patients. Sodium-glucose co-transporter-2 (SGLT2) inhibitors are a new pharmacologic therapy with tremendous potential to alter clinical practice and influence practice guidelines. SGLT2-inhibitors have great potential in reducing MACE in patients with T2DM and CAD. Empagliflozin should be considered as a part of OMT among these patients. If results similar to the EMPA-REG OUTCOMES trial are replicated in other trials, the use of these pharmacologic agents as a part of OMT may narrow the gap between revascularization and OMT alone in patients with T2DM and multi-vessel disease. Future studies on the role of SLGT-2 inhibitors with regard to heart failure outcomes are needed to elucidate the mechanisms and clinical effects in this vulnerable population.
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Enfermedades Cardiovasculares/prevención & control , Sistema Cardiovascular/efectos de los fármacos , Enfermedad de la Arteria Coronaria/tratamiento farmacológico , Inhibidores del Cotransportador de Sodio-Glucosa 2 , Animales , Diabetes Mellitus Tipo 2 , HumanosRESUMEN
Hibernating myocardium is an adaptive response to repetitive myocardial ischemia that is clinically common, but the mechanism of adaptation is poorly understood. Here we compared the proteomes of hibernating versus normal myocardium in a porcine model with 24 biological replicates. Using the ion-current-based proteomic strategy optimized in this study to expand upon previous proteomic work, we identified differentially expressed proteins in new molecular pathways of cardiovascular interest. The methodological strategy includes efficient extraction with detergent cocktail; precipitation/digestion procedure with high, quantitative peptide recovery; reproducible nano-LC/MS analysis on a long, heated column packed with small particles; and quantification based on ion-current peak areas. Under the optimized conditions, high efficiency and reproducibility were achieved for each step, which enabled a reliable comparison of 24 the myocardial samples. To achieve confident discovery of differentially regulated proteins in hibernating myocardium, we used highly stringent criteria to define "quantifiable proteins". These included the filtering criteria of low peptide FDR and S/N > 10 for peptide ion currents, and each protein was quantified independently from ≥2 distinct peptides. For a broad methodological validation, the quantitative results were compared with a parallel, well-validated 2D-DIGE analysis of the same model. Excellent agreement between the two orthogonal methods was observed (R = 0.74), and the ion-current-based method quantified almost one order of magnitude more proteins. In hibernating myocardium, 225 significantly altered proteins were discovered with a low false-discovery rate (â¼3%). These proteins are involved in biological processes including metabolism, apoptosis, stress response, contraction, cytoskeleton, transcription, and translation. This provides compelling evidence that hibernating myocardium adapts to chronic ischemia. The major metabolic mechanisms include a down-regulation of mitochondrial respiration and an increase in glycolysis. Meanwhile, cardioprotective and cytoskeletal proteins are increased, while cardiomyocyte contractile proteins are reduced. These intrinsic adaptations to regional ischemia maintain long-term cardiomyocyte viability at the expense of contractile function.
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Modelos Animales , Miocardio/metabolismo , Proteoma/metabolismo , Proteómica/métodos , Adaptación Fisiológica/fisiología , Animales , Cromatografía Liquida , Humanos , Espectrometría de Masas , Isquemia Miocárdica/metabolismo , Isquemia Miocárdica/fisiopatología , Reproducibilidad de los Resultados , Porcinos , Electroforesis Bidimensional Diferencial en GelRESUMEN
VIDEO AVAILABLE AT: https://ota.org/education/ota-online-resources/video-library-procedures-techniques/anterior-iliac-crest-bone-0.
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Acetábulo , Trasplante Óseo , Ilion , Humanos , Ilion/trasplante , Ilion/cirugía , Trasplante Óseo/métodos , Acetábulo/cirugía , Recolección de Tejidos y Órganos/métodosRESUMEN
OBJECTIVES: To report a case series of extra-articular osteotomies for the management of intra-articular tibial plateau malunions and to assess the ability to correct deformity and improve knee range of motion (ROM). METHODS: . DESIGN: Retrospective case series. SETTING: Academic, tertiary, referral center. PATIENT SELECTION CRITERIA: Adult patients with tibial plateau fracture malunion treated with extra-articular osteotomy of the femur and/or tibia between 2014 and 2023. OUTCOME MEASURES AND COMPARISON: Mechanical axis deviation (MAD), medial proximal tibia angle (MPTA), lateral distal femoral angle (LDFA), and posterior proximal tibia angle (PPTA) correction; knee ROM; and time to weight bearing. RESULTS: There were 7 patients included, 6 (85.7%) were female and 1 (14.3%) were male. The median age was 43.5 years (IQR 38.5-51, range 32-62). Four (57.1%) patients were treated with a high tibial osteotomy (HTO), and 3 (42.9%) patients were treated with an HTO and distal femoral osteotomy. One patient had concomitant supramalleolar osteotomy with HTO to address distal tibia procurvatum and valgus. Four were treated with hexapod frames, and 3 were treated with plates and screws. Median follow-up was 22.5 months (IQR 10.5-107 months, range 7-148 months). Surgical intervention corrected median radiographic measures of valgus malalignment preoperatively relative to postoperative values. This included MAD (42.5 mm-0 mm), valgus angle (12.5 degrees-1.5 degrees), MPTA (95 degrees-88.0°), and LDFA (86.0°-87.3 degrees). Surgical intervention increased maximal knee range of motion preoperatively to postoperatively. Median time to full weight bearing was 81.5 days (IQR 46-57 days, range 41-184 days). Two patients were converted to total knee arthroplasty after 5 and 10 years following HTO with hexapod frame. CONCLUSIONS: Extra-articular osteotomy is an effective treatment for addressing intra-articular malunion after tibia plateau fractures. It is effective in correcting the MAD, valgus deformity, MPTA, LDFA, PPTA, and improving knee ROM (measured through knee extension and flexion). LEVEL OF EVIDENCE: Therapeutic Level IV. See Instructions for Authors for a complete description of levels of evidence.
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Fracturas Mal Unidas , Osteotomía , Rango del Movimiento Articular , Fracturas de la Tibia , Humanos , Osteotomía/métodos , Masculino , Femenino , Fracturas de la Tibia/cirugía , Fracturas de la Tibia/diagnóstico por imagen , Persona de Mediana Edad , Adulto , Estudios Retrospectivos , Fracturas Mal Unidas/cirugía , Fracturas Mal Unidas/diagnóstico por imagen , Resultado del Tratamiento , Fracturas Intraarticulares/cirugía , Fracturas Intraarticulares/diagnóstico por imagen , Fijación Interna de Fracturas/métodos , Tibia/cirugía , Tibia/diagnóstico por imagenRESUMEN
The reversibility of viable dysfunctional myocardium after revascularization is variable and the reasons for this are unknown. Using 2D-DIGE, we tested the hypothesis that this could reflect the extent of molecular remodeling of myocardial tissue in the absence of infarction. Swine with a progressive left anterior descending (LAD) stenosis were studied 2 months (n = 18) or 3 months (n = 22) post-instrumentation. Coronary flow reserve (vasodilated/rest) was severely reduced at 2 months (LAD 2.6 ± 0.4 versus 5.1 ± 0.4 in normal, p < 0.05) and became critically impaired after 3 months (LAD 1.1 ± 0.2, p < 0.05 vs. 2 months). Despite progression in stenosis severity, reductions in wall thickening at 2 months (LAD 37 ± 4% vs. remote 86 ± 9%, p < 0.05) were unchanged at 3 months (LAD 32 ± 3%, p = ns). Contractile dysfunction was primarily related to reductions (LAD/normal) in contractile proteins which were not affected by stenosis severity (e.g., troponin T, 2 months 0.82 ± 0.03 vs. 0.74 ± 0.03 at 3 months, p-ns). In contrast, mitochondrial function and proteins were normal at 2 months but declined with progression to a critical stenosis (state 3 respiration at 3 months 145 ± 13 vs. 216 ± 5 ng-atoms O2 mg(-1) min(-1) at 2 months, p < 0.05). In a similar fashion, increases in stress (e.g., αB-crystalline 2.13 ± 0.2 vs. 1.17 ± 0.13 at 2 months, p < 0.05) and cytoskeletal proteins (e.g., desmin 1.63 ± 0.12 vs. 1.24 ± 0.10 at 2 months, p < 0.05) only developed with more advanced remodeling from a critical stenosis. We conclude that similar degrees of chronic contractile dysfunction can have diverse intrinsic molecular adaptations to ischemia. This spectrum of adaptations may underlie variability in the time course and extent of reversibility in viable chronically dysfunctional myocardium after revascularization.
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Estenosis Coronaria/fisiopatología , Corazón/fisiopatología , Mitocondrias Cardíacas/fisiología , Contracción Miocárdica/fisiología , Animales , Vasos Coronarios/fisiopatología , Modelos Animales de Enfermedad , Progresión de la Enfermedad , Flujo Sanguíneo Regional/fisiología , Índice de Severidad de la Enfermedad , PorcinosRESUMEN
INTRODUCTION: Bone defects may be managed with bone transport or acute shortening and lengthening using circular external fixation devices. We performed a multicenter retrospective cohort study to compare the outcomes between the Ilizarov frames and hexapod frames for the management of bone defects. METHODS: Patients treated for bone defects using either Ilizarov or hexapod frames were included for analysis in two specialist institutions. Primary outcomes were time to consolidation, bone healing index (BHI), and external fixator index (EFI). Radiographic parameters included the medial proximal tibial angle, lateral distal tibial angle, posterior proximal tibial angle, and anterior distal tibial angle. RESULTS: There were 137 hexapods and 90 Ilizarov frames in total. The mean time to follow-up was 3.7 years in the hexapod group and 4.0 years in the Ilizarov group. Hexapods had a significantly lower time to consolidation (253 days versus 449 days) (P < 0.0001) and BHI (59.1 days/cm versus 87.5 days/cm) (P < 0.0001). Hexapods had a significantly better EFI (72.3 days/cm versus 96.1 days/cm) (P = 0.0009). CONCLUSION: Hexapods may confer a significant advantage over Ilizarov frames in the management of bone defects. Time to consolidation, radiographic parameters, BHI, and EFI are all superior in hexapods.
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Alargamiento Óseo , Técnica de Ilizarov , Humanos , Estudios Retrospectivos , Tibia/diagnóstico por imagen , Tibia/cirugía , Fijadores ExternosRESUMEN
An elevated brain natriuretic peptide (BNP) level has been shown to be associated with mortality and cardiac events in cardiac surgery, but its utility in the prediction of morbidity and mortality in hip fracture surgery is unknown. The primary aim of this study was to determine if there is a difference in BNP level at the time of injury between patients who do and do not develop complications after hip fracture surgery. The secondary aim was to determine if there is a predictive relationship between complications associated with the initial BNP level and mortality. Methods: A retrospective chart review of 455 hip fractures in patients ≥60 years old that were operatively treated between February 2014 and July 2018 was performed. Patients were included if they had a BNP level within 48 hours after injury (BNPi). Specific perioperative (≤7 days), 30-day, 1-year, and 2-year postoperative complications were recorded. Wilcoxon rank-sum tests were used to determine if higher BNPi values were associated with greater morbidity. The complications associated with higher BNPi values were further analyzed to assess if they were predictive of mortality, using univariate and multivariable analyses. Results: Higher BNPi was significantly associated with greater morbidity at all postoperative time points and with higher mortality at 1 and 2 years postoperatively. Furthermore, several complications including cardiac failure or exacerbation and altered mental status were associated with mortality at all time points in univariate analysis and at many time points in multivariable analysis. Conclusions: Patients with higher BNPi levels were more likely to develop complications up to 1 year postoperatively, and several of these complications were associated with increased mortality. Future studies to determine if delaying surgery until BNP levels are normalized or lowered may help guide management, and may be useful in determining the need for further medical optimization. Future studies aimed at defining a threshold BNP value at the time of injury may also help in better managing patients preoperatively. Level of Evidence: Prognostic Level III. See Instructions for Authors for a complete description of levels of evidence.
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Background: Osseointegration (OI) limb has been performed for over 30 years and is an example of an advance in technology and surgical technique which has led to improvements in patient mobility and quality of life. An increasing number of patients seek information about osseointegration. The aim of this study was to categorise the most frequently asked questions by patients using the Google search engine and the most frequently accessed websites with the highest return on answers. The secondary aims of this study were to assess the quality of the information provided on those websites and to stratify, by category, which websites provide the best quality information. Materials and methods: Ten permutations and conjugations of the word 'osseointegration' were entered into Google. The first fifty 'People also ask' and associated websites by Google's machine learning and natural language processing engine were collected for each search term. The Rothwell classification system of questions by topic (Fact, Value, Policy) and websites by category was used (Commercial, Academic, Medical Practice, Single Surgeon Personal, Government, Social Media). Website quality was assessed using the Journal of the American Medical Association (JAMA) benchmark criteria (Likert-style rating 0-4). Pearson's Chi-squared and Student's t-tests were performed for statistical analysis as appropriate (significance, p < 0.05). Results: The 10 search terms generated 454 questions and referenced 408 websites. Of the 454 questions generated, the most common question categories were fact (70.8%), value (19.2%), and policy (10%). The most common website type was social media (37.4%). The most common question types were technical details (30.4%), specific activity (20.6%), and cost (14.1%). Only 1.6% of questions related to risks and complications. Generally, website quality was poor with 64.1% having a JAMA score of 0 or 1. Websites that were categorised as 'Government' had the highest overall JAMA scores: 71.4% had a score of 4. Conclusion: Based on Google search engine's results, the most commonly asked questions about osteointegration related to technical details, specific activities and cost; only 1.6% related to risks and complications. Interestingly, social media websites represented the highest volume of search result referrals. Overall, the quality of websites was poor with the most factual information coming from governmental websites. How to cite this article: Murphy EP, Sheridan GA, Page BJ, et al. Modern Internet Search Analytics and Osseointegration: What Are Patients Asking and Reading Online? Strategies Trauma Limb Reconstr 2023;18(3):163-168.
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OBJECTIVES: To assess the effects of Krackow suture technique on the vascularity of the patellar tendon. METHODS: Six fresh-frozen matched pair cadaveric knee specimens were used. The superficial femoral arteries were cannulated in all knees. The experimental knee underwent an anterior approach, patellar tendon transection from the inferior pole of the patella, 4-strand Krackow stitch placement, patellar tendon repair via 3-bone tunnels, and standard skin closure. The control knee underwent the identical procedure without Krackow stitching. All specimens then underwent precontrast and postcontrast enhanced quantitative magnetic resonance imaging assessment (with gadolinium-based contrast agent). Region of interest analysis was performed to assess for variation in signal enhancement between the experimental and control limbs in various patellar tendon regions and subregions. Latex infusion and anatomical dissection were performed to further evaluate vessel integrity and assess extrinsic vascularity. RESULTS: Quantitative magnetic resonance imaging analysis demonstrated no statistically significant difference in overall arterial contributions. A small but nonsignificant decrease of 7.5% (SD ± 7.1%) in arterial contributions to the entire tendon was observed. Small nonstatistically significant regional decreases throughout the tendon were also detected. In the regional analysis, the largest to smallest decreases in arterial contributions after suture placement were found in the inferomedial, superolateral, lateral, and inferior tendon subregions. In the anatomical dissection, nutrient branches were seen dorsally and posteroinferiorly. CONCLUSION: The vascularity of the patellar tendon was not significantly affected by Krackow suture placement. Analysis demonstrated small and not statistically significant decreases in arterial contributions, suggesting this technique does not significantly compromise arterial perfusion.
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Ligamento Rotuliano , Humanos , Ligamento Rotuliano/diagnóstico por imagen , Ligamento Rotuliano/cirugía , Tendones , Imagen por Resonancia Magnética , Rótula/cirugía , Técnicas de SuturaRESUMEN
OBJECTIVES: To determine whether there is an association between surgical approach and dislocation risk in patients with cognitive impairment compared with those without cognitive impairment treated with hemiarthroplasty for femoral neck fracture. DESIGN: Retrospective study. SETTING: Large, multicenter health system. PATIENTS/PARTICIPANTS: One thousand four hundred eighty-one patients who underwent hemiarthroplasty for femoral neck fractures. 828 hips met inclusion criteria, 290 (35.0%) were cognitively impaired, and 538 (65.0%) were cognitively intact. INTERVENTION: Hemiarthroplasty. MAIN OUTCOME MEASURE: Prosthetic hip dislocation. RESULTS: The overall dislocation rate was 2.1% (17 of 828), 3.4% (10 of 290) in the cognitively impaired group, and 1.3% (7 of 538) in the cognitively intact group with a median time to dislocation of 20.5 days (range 2-326 days), 24.5 days (range 3-326 days), and 19.0 days (range 2-36 days), respectively. In the entire cohort, there were no dislocations (0 of 58) with the direct anterior approach (DA); 1.1% (6 of 553) and 5.1% (11 of 217) dislocated with the modified Hardinge (MH) and posterior approaches (PA), respectively. In the cognitively impaired group, there were no dislocations with the DA (0 of 19); 1.5% (3 of 202) and 10.1% (7 of 69) dislocated with the MH and PA, respectively. In the cognitively intact group, there were no dislocations (0 of 39) with the DA; 0.85% (3 of 351) and 2.7% (4 of 148) dislocated with the MH and PA, respectively. There were statistically significant associations between surgical approach and dislocation in the entire cohort and the cognitively impaired group when comparing the MH and PA groups. This was not observed in the cognitively intact group. Patients who dislocated had 3.2 times (95% CI 1.2, 8.7) ( P = 0.0226) the hazard of death compared with patients who did not dislocate. Dislocation effectively increased the risk of death by 221% (HR 3.2 95% CI 1.2, 8.7) ( P = 0.0226). CONCLUSIONS: In this patient population, the PA has a higher dislocation rate than other approaches and has an especially high rate of dislocation when the patients were cognitively impaired. The authors of this study suggest careful consideration of surgical approach when treating these injuries. LEVEL OF EVIDENCE: Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.
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Artroplastia de Reemplazo de Cadera , Disfunción Cognitiva , Fracturas del Cuello Femoral , Hemiartroplastia , Luxación de la Cadera , Luxaciones Articulares , Humanos , Anciano , Estudios Retrospectivos , Hemiartroplastia/efectos adversos , Fracturas del Cuello Femoral/cirugía , Luxaciones Articulares/cirugía , Luxación de la Cadera/epidemiología , Luxación de la Cadera/cirugía , Luxación de la Cadera/etiología , Artroplastia de Reemplazo de Cadera/efectos adversos , Disfunción Cognitiva/epidemiología , Disfunción Cognitiva/etiología , Disfunción Cognitiva/cirugíaRESUMEN
The plasma proteome holds enormous clinical potential, yet an in-depth analysis of the plasma proteome remains a daunting challenge due to its high complexity and the extremely wide dynamic range in protein concentrations. Furthermore, existing antibody-based approaches for depleting high-abundance proteins are not adaptable to the analysis of the animal plasma proteome, which is often essential for experimental pathology/pharmacology. Here we describe a highly comprehensive method for the investigation of the animal plasma proteome which employs an optimized combinatorial peptide ligand library (CPLL) treatment to reduce the protein concentration dynamic range and a dual-enzyme, dual-activation strategy to achieve high proteomic coverage. The CPLL treatment enriched the lower abundance proteins by >100-fold when the samples were loaded in moderately denaturing conditions with multiple loading-washing cycles. The native and the CPLL-treated plasma were digested in parallel by two enzymes (trypsin and GluC) carrying orthogonal specificities. By performing this differential proteolysis, the proteome coverage is improved where peptides produced by only one enzyme are poorly detectable. Digests were fractionated with high-resolution strong cation exchange chromatography and then resolved on a long, heated nano liquid chromatography column. MS analysis was performed on a linear triple quadrupole/orbitrap with two complementary activation methods (collisionally induced dissociation (CID) and electron transfer dissociation). We applied this optimized strategy to investigate the plasma proteome from swine, a prominent animal model for cardiovascular diseases (CVDs). This large-scale analysis results in identification of a total of 3421 unique proteins, spanning a concentration range of 9-10 orders of magnitude. The proteins were identified under a set of commonly accepted criteria, including a precursor mass error of <15 ppm, Xcorr cutoffs, and ≥2 unique peptides at a peptide probability of ≥95% and a protein probability of ≥99%, and the peptide false-positive rate of the data set was 1.8% as estimated by searching the reversed database. CPLL treatment resulted in 55% more identified proteins over those from native plasma; moreover, compared with using only trypsin and CID, the dual-enzyme/activation approach enabled the identification of 2.6-fold more proteins and substantially higher sequence coverage for most individual proteins. Further analysis revealed 657 proteins as significantly associated with CVDs (p < 0.05), which constitute five CVD-related pathways. This study represents the first in-depth investigation of a nonhuman plasma proteome, and the strategy developed here is adaptable to the comprehensive analysis of other highly complex proteomes.
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Cromatografía Líquida de Alta Presión/métodos , Espectrometría de Masas/métodos , Proteoma/análisis , Animales , Proteínas Sanguíneas/análisis , Enfermedades Cardiovasculares/metabolismo , Transporte de Electrón , Electroforesis en Gel Bidimensional/métodos , Ligandos , Nanotecnología , Biblioteca de Péptidos , Serina Endopeptidasas/metabolismo , Porcinos , Tripsina/metabolismoRESUMEN
One of the main limiting factors in deployment of marine robots is the issue of energy sustainability. This is particularly challenging for traditional propeller-driven autonomous underwater vehicles which operate using energy intensive thrusters. One emerging technology to enable persistent performance is the use of autonomous recharging and retasking through underwater docking stations. This paper presents an integrated navigational algorithm to facilitate reliable underwater docking of autonomous underwater vehicles. Specifically, the algorithm dynamically re-plans Dubins paths to create an efficient trajectory from the current vehicle position through approach into terminal homing. The path is followed using integral line of sight control until handoff to the terminal homing method. A light tracking algorithm drives the vehicle from the handoff location into the dock. In experimental testing using an Oceanserver Iver3 and Bluefin SandShark, the approach phase reached the target handoff within 2 m in 48 of 48 tests. The terminal homing phase was capable of handling up to 5 m offsets with approximately 70% accuracy (12 of 17 tests). In the event of failed docking, a Dubins path is generated to efficiently drive the vehicle to re-attempt docking. The vehicle should be able to successfully dock in the majority of foreseeable scenarios when re-attempts are considered. This method, when combined with recent work on docking station design, intelligent cooperative path planning, underwater communication, and underwater power transfer, will enable true persistent undersea operation in the extremely dynamic ocean environment.
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BACKGROUND: Immune checkpoint inhibitors (ICI) have emerged as a front-line therapy for a variety of solid tumors. With the widespread use of these agents, immune-associated toxicities are increasingly being recognized, including fatal myocarditis. There are limited data on the outcomes and prognostic utility of biomarkers associated with ICI-associated myocarditis. Our objective was to examine the associations between clinical biomarkers of cardiomyocyte damage and mortality in patients with cancer treated with ICIs. METHODS: We retrospectively studied 23 patients who developed symptomatic and asymptomatic troponin elevations while receiving ICI therapy at a National Cancer Institute-designated comprehensive cancer center. We obtained serial ECGs, troponin I, and creatine kinase-MD (CK-MB), in addition to other conventional clinical biomarkers, and compared covariates between survivors and non-survivors. RESULTS: Among patients with myocarditis, higher troponin I (p=0.037) and CK-MB (p=0.034) levels on presentation correlated with progression to severe myocarditis. Higher troponin I (p=0.016), CK (p=0.013), and CK-MB (p=0.034) levels were associated with increased mortality, while the presence of advanced atrioventricular block on presentation (p=0.088) trended toward increased mortality. Weekly troponin monitoring lead to earlier hospitalization for potential myocarditis (p=0.022) and was associated with decreased time to steroid initiation (p=0.053) and improved outcomes. CONCLUSIONS: Routine troponin surveillance may be helpful in predicting mortality in ICI-treated patients with cancer in the early phase of ICI therapy initiation. Early detection of troponin elevation is associated with earlier intervention and improved outcomes in ICI-associated myocarditis. The recommended assessment and diagnostic studies guiding treatment decisions are presented.
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Inhibidores de Puntos de Control Inmunológico/efectos adversos , Miocarditis/inducido químicamente , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios RetrospectivosRESUMEN
Patients with type 2 diabetes mellitus (T2DM) are at increased risk for cardiovascular clinical events, adverse nonfatal outcomes, and death. There has been considerable improvement in the medical management of patients with T2DM in an attempt to alter the metabolic cascade that is triggered by insulin resistance. Recent trials have demonstrated that medical management of patients with diabetes mellitus and stable coronary artery disease (CAD) is equivalent to revascularization in terms of morality benefit and rates of major adverse cardiovascular events, particularly in patients who do not have extensive CAD. Nonetheless, in those diabetic patients with additional high-risk features including left main disease, reduced left ventricular ejection fraction (LVEF), severe ischemia, or acute coronary syndrome, revascularization remains the best treatment option. Although the evidence still supports coronary artery bypass grafting (CABG) as the standard of care for revascularization of diabetic patients with multivessel CAD and/or reduced LVEF, percutaneous coronary intervention (PCI) with drug-eluting stents (DES) has resulted in at least partial closure of the gap in benefit between surgery and catheter-based intervention. Ongoing trials of diabetic patients with CAD randomized to PCI or CABG will help further elucidate the role of PCI with DES as a potential revascularization option for this patient population.
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Enfermedad de la Arteria Coronaria/complicaciones , Enfermedad de la Arteria Coronaria/terapia , Diabetes Mellitus Tipo 2/complicaciones , Diabetes Mellitus Tipo 2/terapia , Revascularización Miocárdica/métodos , Angioplastia Coronaria con Balón , Puente de Arteria Coronaria , HumanosRESUMEN
Hibernating myocardium is accompanied by a downregulation in energy utilization that prevents the immediate development of ischemia during stress at the expense of an attenuated level of regional contractile function. We used a discovery based proteomic approach to identify novel regional molecular adaptations responsible for this phenomenon in subendocardial samples from swine instrumented with a chronic LAD stenosis. After 3 months (n=8), hibernating myocardium was present as reflected by reduced resting LAD flow (0.75+/-0.14 versus 1.19+/-0.14 mL x min(-1) x g(-1) in remote) and wall thickening (1.93+/-0.46 mm versus 5.46+/-0.41 mm in remote, P<0.05). Regionally altered proteins were quantified with 2D Differential-in-Gel Electrophoresis (2D-DIGE) using normal myocardium as a reference with identification of candidates using MALDI-TOF mass spectrometry. Hibernating myocardium developed a significant downregulation of many mitochondrial proteins and an upregulation of stress proteins. Of particular note, the major entry points to oxidative metabolism (eg, pyruvate dehydrogenase complex and Acyl-CoA dehydrogenase) and enzymes involved in electron transport (eg, complexes I, III, and V) were reduced (P<0.05). Multiple subunits within an enzyme complex frequently showed a concordant downregulation in abundance leading to an amplification of their cumulative effects on activity (eg, "total" LAD PDC activity was 21.9+/-3.1 versus 42.8+/-1.9 mU, P<0.05). After 5-months (n=10), changes in mitochondrial and stress proteins persisted whereas cytoskeletal proteins (eg, desmin and vimentin) normalized. These data indicate that the proteomic phenotype of hibernating myocardium is dynamic and has similarities to global changes in energy substrate metabolism and function in the advanced failing heart. These proteomic changes may limit oxidative injury and apoptosis and impact functional recovery after revascularization.
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Metabolismo Energético/genética , Regulación de la Expresión Génica/fisiología , Aturdimiento Miocárdico/genética , Proteínas/análisis , Proteómica/métodos , Estrés Fisiológico/genética , Adaptación Fisiológica/genética , Animales , Enfermedad Crónica , Modelos Animales de Enfermedad , Regulación hacia Abajo , Enzimas , Regulación Enzimológica de la Expresión Génica , Proteínas Mitocondriales , Proteínas/genética , Porcinos , Regulación hacia ArribaRESUMEN
Distal humerus fractures in elderly patients are challenging due to poor bone quality and may threaten the independence of elderly patients due to loss of functional range of motion. Total elbow arthroplasty has gained popularity in the treatment of these injuries. This video demonstrates total elbow arthroplasty in an elderly patient with a comminuted distal humerus fracture.
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Artroplastia de Reemplazo de Codo , Articulación del Codo , Fracturas Conminutas , Fracturas del Húmero , Anciano , Codo , Articulación del Codo/diagnóstico por imagen , Articulación del Codo/cirugía , Fijación Interna de Fracturas , Fracturas Conminutas/diagnóstico por imagen , Fracturas Conminutas/cirugía , Humanos , Fracturas del Húmero/diagnóstico por imagen , Fracturas del Húmero/cirugía , Húmero , Rango del Movimiento Articular , Resultado del TratamientoRESUMEN
OBJECTIVE: To document angles, from 2 difference starting points, or danger zones that should be avoided to minimize risk of injury or irritation to the saphenous neurovascular bundle (SNVB) during suture button (SB) fixation for distal tibiofibular syndesmosis injuries. DESIGN: Retrospective imaging study. SETTING: Academic Level 1 trauma center. PATIENTS: Forty-eight randomly selected patients with healthy ankles and computed tomography scans for nonankle diagnoses. MAIN OUTCOME MEASURES: Computed tomography scans and 3D reconstructed images were used to define the angle between the SNVB and 2 different fibular starting points, using the direct lateral (DL) and the posterolateral (PL) starting points. Descriptive analyses were performed to identify angles that should be avoided during suture button fixation. Distances from the SNVB using preset angles of 0, 10, 20, and 30 degrees were analyzed. In addition, the width of the SNVB, the midsubstance angle of the SNVB, and the distance from the 30-degree point to the tibialis anterior were recorded. RESULTS: The mean angle between the SNVB and the standard DL starting point was 13.7 ± 5.0 degrees (P < 0.05), whereas the mean angle using the alternate PL starting point was 17.2 ± 5.3 degrees (P < 0.05). The SNVB width was 5.2 mm [range, 2.6-9.1 mm] (P < 0.05). The distances from the SNVB were greatest for the DL 30-degree group and the PL 0-degree group. CONCLUSIONS: The results document angles that should be avoided when using suture button fixation for syndesmosis injuries. Device characteristics and surgery-related variables may require intraoperative modifications, and knowledge of this anatomical relationship may reduce SNVB injury during those situations. Considering our results, we recommend that surgeons place suture buttons from the DL starting point with a 30-degree trajectory to avoid injuries to the SNVB.