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1.
Phys Rev Lett ; 132(10): 106502, 2024 Mar 08.
Artículo en Inglés | MEDLINE | ID: mdl-38518342

RESUMEN

Computing thermal transport from first-principles in UO_{2} is complicated due to the challenges associated with Mott physics. Here, we use irreducible derivative approaches to compute the cubic and quartic phonon interactions in UO_{2} from first principles, and we perform enhanced thermal transport computations by evaluating the phonon Green's function via self-consistent diagrammatic perturbation theory. Our predicted phonon lifetimes at T=600 K agree well with our inelastic neutron scattering measurements across the entire Brillouin zone, and our thermal conductivity predictions agree well with previous measurements. Both the changes due to thermal expansion and self-consistent contributions are nontrivial at high temperatures, though the effects tend to cancel, and interband transitions yield a substantial contribution.

2.
Chem Rev ; 122(3): 3711-3762, 2022 Feb 09.
Artículo en Inglés | MEDLINE | ID: mdl-34919381

RESUMEN

To efficiently capture the energy of the nuclear bond, advanced nuclear reactor concepts seek solid fuels that must withstand unprecedented temperature and radiation extremes. In these advanced fuels, thermal energy transport under irradiation is directly related to reactor performance as well as reactor safety. The science of thermal transport in nuclear fuel is a grand challenge as a result of both computational and experimental complexities. Here we provide a comprehensive review of thermal transport research on two actinide oxides: one currently in use in commercial nuclear reactors, uranium dioxide (UO2), and one advanced fuel candidate material, thorium dioxide (ThO2). In both materials, heat is carried by lattice waves or phonons. Crystalline defects caused by fission events effectively scatter phonons and lead to a degradation in fuel performance over time. Bolstered by new computational and experimental tools, researchers are now developing the foundational work necessary to accurately model and ultimately control thermal transport in advanced nuclear fuels. We begin by reviewing research aimed at understanding thermal transport in perfect single crystals. The absence of defects enables studies that focus on the fundamental aspects of phonon transport. Next, we review research that targets defect generation and evolution. Here the focus is on ion irradiation studies used as surrogates for damage caused by fission products. We end this review with a discussion of modeling and experimental efforts directed at predicting and validating mesoscale thermal transport in the presence of irradiation defects. While efforts in these research areas have been robust, challenging work remains in developing holistic tools to capture and predict thermal energy transport across widely varying environmental conditions.

3.
Inorg Chem ; 62(40): 16464-16474, 2023 Oct 09.
Artículo en Inglés | MEDLINE | ID: mdl-37747902

RESUMEN

α-Sb2O4 (cervantite) and ß-Sb2O4 (clinocervantite) are mixed valence compounds with equal proportions of SbIII and SbV as represented in the formula SbIIISbVO4. Their structure and properties can be difficult to calculate owing to the SbIII lone-pair electrons. Here, we present a study of the lattice dynamics and vibrational properties using a combination of inelastic neutron scattering, Mössbauer spectroscopy, nuclear inelastic scattering, and density functional theory (DFT) calculations. DFT calculations that account for lone-pair electrons match the experimental densities of phonon states. Mössbauer spectroscopy reveals the ß phase to be significantly harder than the α phase. Calculations with O vacancies reveal the possibility for nonstoichiometric proportions of SbIII and SbV in both phases. An open question is what drives the stability of the α phase over the ß phase, as the latter shows pronounced kinetic stability and lower symmetry despite being in the high-temperature phase. Since the vibrational entropy difference is small, it is unlikely to stabilize the α phase. Our results suggest that the α phase is more stable only because the material is not fully stoichiometric.

4.
J Phys Chem A ; 124(39): 7869-7880, 2020 Oct 01.
Artículo en Inglés | MEDLINE | ID: mdl-32894948

RESUMEN

α-Sb2O3 (senarmontite), ß-Sb2O3 (valentinite), and α-TeO2 (paratellurite) are compounds with pronounced stereochemically active Sb and Te lone pairs. The vibrational and lattice properties of each have been previously studied but often lead to incomplete or unreliable results due to modes being inactive in infrared or Raman spectroscopy. Here, we present a study of the relationship between bonding and lattice dynamics of these compounds. Mössbauer spectroscopy is used to study the structure of Sb in α-Sb2O3 and ß-Sb2O3, whereas the vibrational modes of Sb and Te for each oxide are investigated using nuclear inelastic scattering, and further information on O vibrational modes is obtained using inelastic neutron scattering. Additionally, vibrational frequencies obtained by density functional theory (DFT) calculations are compared with experimental results in order to assess the validity of the utilized functional. Good agreement was found between DFT-calculated and experimental density of phonon states with a 7% scaling factor. The Sb-O-Sb wagging mode of α-Sb2O3 whose frequency was not clear in most previous studies is experimentally observed for the first time at ∼340 cm-1. Softer lattice vibrational modes occur in orthorhombic ß-Sb2O3 compared to cubic α-Sb2O3, indicating that the antimony bonds are weakened upon transforming from the molecular α phase to the layer-chained ß structure. The resulting vibrational entropy increase of 0.45 ± 0.1 kB/Sb2O3 at 880 K accounts for about half of the α-ß transition entropy. The comparison of experimental and theoretical approaches presented here provides a detailed picture of the lattice dynamics in these oxides beyond the zone center and shows that the accuracy of DFT is sufficient for future calculations of similar material structures.

5.
Nature ; 515(7528): 535-9, 2014 Nov 27.
Artículo en Inglés | MEDLINE | ID: mdl-25383524

RESUMEN

Phase competition underlies many remarkable and technologically important phenomena in transition metal oxides. Vanadium dioxide (VO2) exhibits a first-order metal-insulator transition (MIT) near room temperature, where conductivity is suppressed and the lattice changes from tetragonal to monoclinic on cooling. Ongoing attempts to explain this coupled structural and electronic transition begin with two alternative starting points: a Peierls MIT driven by instabilities in electron-lattice dynamics and a Mott MIT where strong electron-electron correlations drive charge localization. A key missing piece of the VO2 puzzle is the role of lattice vibrations. Moreover, a comprehensive thermodynamic treatment must integrate both entropic and energetic aspects of the transition. Here we report that the entropy driving the MIT in VO2 is dominated by strongly anharmonic phonons rather than electronic contributions, and provide a direct determination of phonon dispersions. Our ab initio calculations identify softer bonding in the tetragonal phase, relative to the monoclinic phase, as the origin of the large vibrational entropy stabilizing the metallic rutile phase. They further reveal how a balance between higher entropy in the metal and orbital-driven lower energy in the insulator fully describes the thermodynamic forces controlling the MIT. Our study illustrates the critical role of anharmonic lattice dynamics in metal oxide phase competition, and provides guidance for the predictive design of new materials.

6.
Surg Technol Int ; 38: 379-386, 2020 05 20.
Artículo en Inglés | MEDLINE | ID: mdl-33352614

RESUMEN

In the quest for increased surgical precision and improved joint kinematics, Computer-Assisted Orthopedic Surgery (CAOS) shows promising results for both total and partial joint replacement. In the knee, computer-assisted joint design can now be applied to the treatment of younger patients suffering pain and restriction of activity due to focal defects in their femoral articular cartilage. By taking MRI scans of the affected knee and digitally segmenting these scans, we can identify and map focal defects in cartilage and bone. Metallic implants matched to the defect can be fabricated, and guide instrumentation to ensure proper implant alignment and depth of recession in the surrounding cartilage can be designed from segmented MRI scans. Beginning in 2012, a series of 682 patient-specific implants were designed based on MRI analysis of femoral cartilage focal defects, and implanted in 612 knees. A Kaplan-Meier analysis found a cumulative survivorship of 96% at 7-year follow-up from the first implantation. Fourteen (2.3%) of these implants required revision due to disease progression, incorrect implant positioning, and inadequate lesion coverage at the time of surgery. These survivorship data compare favorably with all other modes of treatment for femoral focal cartilage lesions and support the use of patient-specific implants designed from segmented MRI scans in these cases.


Asunto(s)
Artroplastia de Reemplazo de Rodilla , Cartílago Articular , Artroplastia de Reemplazo de Rodilla/efectos adversos , Cartílago Articular/cirugía , Fémur/cirugía , Estudios de Seguimiento , Humanos , Articulación de la Rodilla/diagnóstico por imagen , Articulación de la Rodilla/cirugía , Supervivencia , Resultado del Tratamiento
7.
Am J Pathol ; 187(3): 543-552, 2017 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-28068511

RESUMEN

Overdose of acetaminophen (APAP) is the leading cause of acute liver failure (ALF) in the United States. Timely initiation of compensatory liver regeneration after APAP hepatotoxicity is critical for final recovery, but the mechanisms of liver regeneration after APAP-induced ALF have not been extensively explored yet. Previous studies from our laboratory have demonstrated that activation of ß-catenin signaling after APAP overdose is associated with timely liver regeneration. Herein, we investigated the role of glycogen synthase kinase 3 (GSK3) in liver regeneration after APAP hepatotoxicity using a pharmacological inhibition strategy in mice. Treatment with specific GSK3 inhibitor (L803-mts), starting from 4 hours after 600 mg/kg dose of APAP, resulted in early initiation of liver regeneration in a dose-dependent manner, without modifying the peak regenerative response. Acceleration of liver regeneration was not secondary to alteration of APAP-induced hepatotoxicity, which remained unchanged after GSK3 inhibition. Early cell cycle initiation in hepatocytes after GSK3 inhibition was because of rapid induction of cyclin D1 and phosphorylation of retinoblastoma protein. This was associated with increased activation of ß-catenin signaling after GSK3 inhibition. Taken together, our study has revealed a novel role of GSK3 in liver regeneration after APAP overdose and identified GSK3 as a potential therapeutic target to improve liver regeneration after APAP-induced ALF.


Asunto(s)
Acetaminofén/efectos adversos , Enfermedad Hepática Inducida por Sustancias y Drogas/enzimología , Enfermedad Hepática Inducida por Sustancias y Drogas/patología , Glucógeno Sintasa Quinasa 3/antagonistas & inhibidores , Regeneración Hepática , Animales , Proliferación Celular/efectos de los fármacos , Ciclina D1/metabolismo , Sobredosis de Droga/enzimología , Sobredosis de Droga/patología , Glucógeno Sintasa Quinasa 3/metabolismo , Hepatocitos/efectos de los fármacos , Hepatocitos/patología , Regeneración Hepática/efectos de los fármacos , Ratones , Ratones Endogámicos C57BL , Oligopéptidos/farmacología , Antígeno Nuclear de Célula en Proliferación/metabolismo , Inhibidores de Proteínas Quinasas/farmacología , beta Catenina/metabolismo
8.
Surg Technol Int ; 33: 289-293, 2018 Nov 11.
Artículo en Inglés | MEDLINE | ID: mdl-30029291

RESUMEN

Regardless of the surgical approach used, dislocation remains a complication following total hip replacement. In recent years, newer technologies, such as the use of large femoral heads, have reduced the rate of postoperative dislocation. The combination of such technology, together with a soft tissue repair technique, may reduce the dislocation rate even further. A single surgeon performed 513 primary total hip replacements on 505 patients using a posterior approach utilizing a technique designed to spare the capsule. There were 257 males and 248 females. Age ranged from 39 to 92 years. Surgeries were performed from January 2012 to December 2015. Implants used were cementless dual-mobility cups and cementless femoral stems. In all cases, the posterior capsule was incised and retracted, but not excised. Following implant placement, the capsule was repaired using a fiber reinforced suture. The superior border of the capsular incision, just above the piriformis, was sutured to the superior capsule or gluteus minimus muscle. The intent of this repair was to completely incarcerate the femoral head. Patients were followed at two weeks, six weeks, three months, one year, three years, and five years. Follow up was one to five years post-implantation. The dislocation rate was zero. The combination of a large dual-mobility femoral head, combined with a soft tissue repair that spares the deep capsule, has the potential to significantly reduce dislocation rates when using the posterior approach to the hip.


Asunto(s)
Artroplastia de Reemplazo de Cadera , Luxación de la Cadera/prevención & control , Prótesis de Cadera , Tratamientos Conservadores del Órgano , Complicaciones Posoperatorias/prevención & control , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Articulación de la Cadera/cirugía , Humanos , Cápsula Articular/cirugía , Masculino , Persona de Mediana Edad , Diseño de Prótesis , Estudios Retrospectivos
9.
Gene Expr ; 17(4): 313-326, 2017 11 27.
Artículo en Inglés | MEDLINE | ID: mdl-28915934

RESUMEN

Autosomal recessive polycystic kidney disease/congenital hepatic fibrosis (ARPKD/CHF) is a rare but fatal genetic disease characterized by progressive cyst development in the kidneys and liver. Liver cysts arise from aberrantly proliferative cholangiocytes accompanied by pericystic fibrosis and inflammation. Yes-associated protein (YAP), the downstream effector of the Hippo signaling pathway, is implicated in human hepatic malignancies such as hepatocellular carcinoma, cholangiocarcinoma, and hepatoblastoma, but its role in hepatic cystogenesis in ARPKD/CHF is unknown. We studied the role of the YAP in hepatic cyst development using polycystic kidney (PCK) rats, an orthologous model of ARPKD, and in human ARPKD/CHF patients. The liver cyst wall epithelial cells (CWECs) in PCK rats were highly proliferative and exhibited expression of YAP. There was increased expression of YAP target genes, Ccnd1 (cyclin D1) and Ctgf (connective tissue growth factor), in PCK rat livers. Extensive expression of YAP and its target genes was also detected in human ARPKD/CHF liver samples. Finally, pharmacological inhibition of YAP activity with verteporfin and short hairpin (sh) RNA-mediated knockdown of YAP expression in isolated liver CWECs significantly reduced their proliferation. These data indicate that increased YAP activity, possibly through dysregulation of the Hippo signaling pathway, is associated with hepatic cyst growth in ARPKD/CHF.


Asunto(s)
Proteínas Reguladoras de la Apoptosis/genética , Proliferación Celular/genética , Células Epiteliales/metabolismo , Enfermedades Renales Poliquísticas/genética , Animales , Proteínas Reguladoras de la Apoptosis/metabolismo , Células Cultivadas , Factor de Crecimiento del Tejido Conjuntivo/genética , Factor de Crecimiento del Tejido Conjuntivo/metabolismo , Modelos Animales de Enfermedad , Células Epiteliales/patología , Femenino , Expresión Génica , Humanos , Masculino , Ratones Endogámicos C57BL , Ratones Noqueados , Enfermedades Renales Poliquísticas/metabolismo , Enfermedades Renales Poliquísticas/patología , Interferencia de ARN , Ratas Sprague-Dawley , Proteínas Señalizadoras YAP
10.
Clin Orthop Relat Res ; 475(12): 2926-2937, 2017 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-28108823

RESUMEN

BACKGROUND: The Affordable Care Act of 2010 advanced the economic model of bundled payments for total joint arthroplasty (TJA), in which hospitals will be financially responsible for readmissions, typically at 90 days after surgery. However, little is known about the financial burden of readmissions and what patient, clinical, and hospital factors drive readmission costs. QUESTIONS/PURPOSES: (1) What is the incidence, payer mix, and demographics of THA and TKA readmissions in the United States? (2) What patient, clinical, and hospital factors are associated with the cost of 30- and 90-day readmissions after primary THA and TKA? (3) Are there any differences in the economic burden of THA and TKA readmissions between payers? (4) What types of THA and TKA readmissions are most costly to the US hospital system? METHODS: The recently developed Nationwide Readmissions Database from the Healthcare Cost and Utilization Project (2006 hospitals from 21 states) was used to identify 719,394 primary TJAs and 62,493 90-day readmissions in the first 9 months of 2013 based on International Classification of Diseases, 9th Revision, Clinical Modification codes. We classified the reasons for readmissions as either procedure- or medical-related. Cost-to-charge ratios supplied with the Nationwide Readmissions Database were used to compute the individual per-patient cost of 90-day readmissions as a continuous variable in separate general linear models for THA and TKA. Payer, patient, clinical, and hospital factors were treated as covariates. We estimated the national burden of readmissions by payer and by the reason for readmission. RESULTS: The national rates of 30- and 90-day readmissions after THA were 4% (95% confidence interval [CI], 4.2%-4.5%) and 8% (95% CI, 7.5%-8.1%), respectively. The national rates of 30- and 90-day readmissions after primary TKA were 4% (95% CI, 3.8%-4.0%) and 7% (95% CI, 6.8%-7.2%), respectively. The five most important variables responsible for the cost of 90-day THA readmissions (in rank order, based on the Type III F-statistic, p < 0.001) were length of stay (LOS), all patient-refined diagnosis-related group (APR DRG) severity, type of readmission (that is, medical- versus procedure-related), hospital ownership, and age. Likewise, the five most important variables responsible for the cost of 90-day TKA readmissions were LOS, APR DRG severity, gender, hospital procedure volume, and hospital ownership. After adjusting for covariates, mean 90-day readmission costs reimbursed by private insurance were, on average, USD 1324 and USD 1372 greater than Medicare (p < 0.001) for THA and TKA, respectively. In the 90 days after TJA, two-thirds of the total annual readmission costs were covered by Medicare. In 90 days after THA, more readmissions were still associated with procedure-related complications, including infections, dislocations, and periprosthetic fractures, which in aggregate account for 59% (95% CI, 59.1%-59.6%) of the total readmission costs to the US healthcare system. For TKA, 49% of the total readmission cost (95% CI, 48.8%-49.6%) in 90 days for the United States was associated with procedure issues, most notably including infections. CONCLUSIONS: Hospital readmissions up to 90 days after TJA represent a massive economic burden on the US healthcare system. Approximately half of the total annual economic burden for readmissions in the United States is medical and unrelated to the joint replacement procedure and half is related to procedural complications. CLINICAL RELEVANCE: This national study underscores LOS during readmission as a primary cost driver, suggesting that hospitals and doctors further optimize, to the extent possible, the clinical pathways for the hospitalization of readmitted patients. Because patients readmitted as a result of infection, dislocation, and periprosthetic fractures are the most costly types of readmissions, efforts to reduce the LOS for these types of readmissions will have the greatest impact on their economic burden. Additional clinical research is needed to determine the extent to which, if any, the LOS during readmissions can be reduced without sacrificing quality or access of care.


Asunto(s)
Artroplastia de Reemplazo de Cadera/economía , Artroplastia de Reemplazo de Rodilla/economía , Costos de Hospital , Readmisión del Paciente/economía , Evaluación de Procesos, Atención de Salud/economía , Adulto , Anciano , Anciano de 80 o más Años , Artroplastia de Reemplazo de Cadera/efectos adversos , Artroplastia de Reemplazo de Rodilla/efectos adversos , Minería de Datos , Bases de Datos Factuales , Grupos Diagnósticos Relacionados/economía , Femenino , Hospitales de Alto Volumen , Hospitales de Bajo Volumen/economía , Humanos , Tiempo de Internación/economía , Masculino , Medicare/economía , Persona de Mediana Edad , Complicaciones Posoperatorias/economía , Complicaciones Posoperatorias/terapia , Medición de Riesgo , Factores de Riesgo , Factores Sexuales , Factores de Tiempo , Resultado del Tratamiento , Estados Unidos
11.
J Arthroplasty ; 32(11): 3274-3285, 2017 11.
Artículo en Inglés | MEDLINE | ID: mdl-28669571

RESUMEN

BACKGROUND: The purpose of this study was to determine whether the cost of readmissions after primary total hip and knee arthroplasty (THA and TKA) has decreased since the introduction of health care reform legislation and what patient, clinical, and hospital factors drive such costs. METHODS: The 100% Medicare inpatient dataset was used to identify 1,654,602 primary THA and TKA procedures between 2010 and 2014. The per-patient cost of readmissions was evaluated in general linear models in which the year of surgery and patient, clinical, and hospital factors were treated as covariates in separate models for THA and TKA. RESULTS: The year-to-year risk of 90-day readmission was reduced by 2% and 4% (P < .001) for THA and TKA, respectively. By contrast, the cost of readmissions did not change significantly over time. The 5 most important variables associated with the cost of 90-day THA readmissions (in rank order) were the nature of the readmission (ie, due to medical or procedure-related reasons), the length of stay, hospital's teaching status, discharge disposition, and hospital's overall total joint arthroplasty volume. The top 5 factors associated with the cost of 90-day TKA readmissions were (in rank order) the length of stay, hospital's teaching status, discharge disposition, patient's gender, and age. CONCLUSION: Although readmission rates declined slightly, the results of this study do not support the hypothesis that readmission costs have decreased since the introduction of health care reform legislation. Instead, we found that clinical and hospital factors were among the most important cost drivers.


Asunto(s)
Artroplastia de Reemplazo de Cadera/economía , Artroplastia de Reemplazo de Rodilla/economía , Reforma de la Atención de Salud/legislación & jurisprudencia , Readmisión del Paciente/economía , Anciano , Anciano de 80 o más Años , Femenino , Reforma de la Atención de Salud/economía , Hospitales , Humanos , Masculino , Medicare/estadística & datos numéricos , Alta del Paciente , Readmisión del Paciente/estadística & datos numéricos , Estados Unidos
12.
Am J Physiol Gastrointest Liver Physiol ; 311(1): G91-G104, 2016 07 01.
Artículo en Inglés | MEDLINE | ID: mdl-27151938

RESUMEN

Hepatocellular carcinoma (HCC) is the most common hepatic malignancy and the third leading cause of cancer related deaths. Previous studies have implicated bile acids in pathogenesis of HCC, but the mechanisms are not known. We investigated the mechanisms of HCC tumor promotion by bile acids the diethylnitrosamine (DEN)-initiation-cholic acid (CA)-induced tumor promotion protocol in mice. The data show that 0.2% CA treatment resulted in threefold increase in number and size of DEN-induced liver tumors. All tumors observed in DEN-treated mice were well-differentiated HCCs. The HCCs observed in DEN-treated CA-fed mice exhibited extensive CD3-, CD20-, and CD45-positive inflammatory cell aggregates. Microarray-based global gene expression studies combined with Ingenuity Pathway Analysis revealed significant activation of NF-κB and Nanog in the DEN-treated 0.2% CA-fed livers. Further studies showed significantly higher TNF-α and IL-1ß mRNA, a marked increase in total and phosphorylated-p65 and phosphorylated IκBα (degradation form) in livers of DEN-treated 0.2% CA-fed mice. Treatment of primary mouse hepatocytes with various bile acids showed significant induction of stemness genes including Nanog, KLF4, Sox2, and Oct4. Quantification of total and 20 specific bile acids in liver, and serum revealed a tumor-associated bile acid signature. Finally, quantification of total serum bile acids in normal, cirrhotic, and HCC human samples revealed increased bile acids in serum of cirrhotic and HCC patients. Taken together, these data indicate that bile acids are mechanistically involved pathogenesis of HCC and may promote HCC formation via activation of inflammatory signaling.


Asunto(s)
Carcinoma Hepatocelular/inducido químicamente , Transformación Celular Neoplásica/inducido químicamente , Ácido Cólico/toxicidad , Dietilnitrosamina , Mediadores de Inflamación/metabolismo , Neoplasias Hepáticas Experimentales/inducido químicamente , Adulto , Animales , Apoptosis/efectos de los fármacos , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/patología , Proliferación Celular/efectos de los fármacos , Transformación Celular Neoplásica/genética , Transformación Celular Neoplásica/metabolismo , Transformación Celular Neoplásica/patología , Células Cultivadas , Ácido Cólico/sangre , Estrés del Retículo Endoplásmico/efectos de los fármacos , Femenino , Regulación Neoplásica de la Expresión Génica , Hepatocitos/efectos de los fármacos , Hepatocitos/metabolismo , Hepatocitos/patología , Humanos , Factor 4 Similar a Kruppel , Neoplasias Hepáticas Experimentales/genética , Neoplasias Hepáticas Experimentales/metabolismo , Neoplasias Hepáticas Experimentales/patología , Masculino , Ratones Endogámicos C57BL , Persona de Mediana Edad , Proteínas Quinasas Activadas por Mitógenos/metabolismo , FN-kappa B/metabolismo , Células Madre Neoplásicas/efectos de los fármacos , Células Madre Neoplásicas/metabolismo , Células Madre Neoplásicas/patología , Transducción de Señal/efectos de los fármacos , Carga Tumoral/efectos de los fármacos , Adulto Joven
13.
J Arthroplasty ; 31(10): 2099-107, 2016 10.
Artículo en Inglés | MEDLINE | ID: mdl-27133927

RESUMEN

BACKGROUND: The purpose of this study was to analyze the hospital, clinical, and patient factors associated with inpatient readmission after total knee arthroplasty (TKA) in the Medicare population and to understand the primary reasons for readmission. METHODS: The Medicare 100% national hospital claims database was used to identify 952,593 older patients (65+) with a primary TKA in 3848 hospitals between 2010 and 2013. A multilevel logistic regression analysis with a clustered data structure was used to investigate the risk of all-cause 30- and 90-day readmission, incorporating hospital, clinical, and patient factors. RESULTS: At 30 days, readmission ranged from 0% to 22% (median, 4.9%), whereas at 90 days, readmission ranged from 0% to 32% (median, 8.6%). Geographic census region, hospital procedure volume, rural hospital location, and nonprofit ownership were the only significant hospital factors among those we studied. Evaluation of clinical factors showed use of a perioperative transfusion was associated with 13% greater risk; patients discharged to home had 25% lower risk; and surgeon volume and length of stay were also significant. These effect sizes were at least comparable to patient factors, such as age, gender, comorbidities, and socioeconomic status. The top 5 most frequently reported primary reasons for 30- or 90-day readmission in TKA were surgery and medical related: wound infection, deep infection, atrial fibrillation, cellulitis and abscess of leg, or pulmonary embolism. CONCLUSION: The results of this study support further optimization of anti-infection measures, both intraoperative and postoperative, to reduce the broad variation in hospital readmissions.


Asunto(s)
Artroplastia de Reemplazo de Rodilla/estadística & datos numéricos , Readmisión del Paciente/estadística & datos numéricos , Complicaciones Posoperatorias/epidemiología , Anciano , Anciano de 80 o más Años , Artroplastia de Reemplazo de Rodilla/efectos adversos , Transfusión Sanguínea , Bases de Datos Factuales , Femenino , Hospitales , Humanos , Masculino , Medicare , Alta del Paciente , Complicaciones Posoperatorias/etiología , Estudios Retrospectivos , Riesgo , Estados Unidos/epidemiología
14.
J Arthroplasty ; 31(10): 2130-8, 2016 10.
Artículo en Inglés | MEDLINE | ID: mdl-27129760

RESUMEN

BACKGROUND: The purpose of this study was to analyze the hospital, clinical, and patient factors associated with inpatient readmission after total hip arthroplasty (THA) in the Medicare population and to understand the primary reasons for readmission. METHODS: The Medicare 100% national hospital claims database was used to identify 442,333 older patients (65+) with a primary THA in 3730 hospitals between 2010 and 2013. A multilevel logistic regression analysis with a clustered data structure was used to investigate the risk of all-cause 30- and 90-day readmission, incorporating hospital, clinical, and patient factors. RESULTS: At 30 days, 5.8% (median) of the patients were readmitted, whereas at 90 days, 10.5% (median) were readmitted. Geographic census region, hospital procedure volume, and nonprofit ownership were the only significant hospital factors among those we studied. Overall, clinical factors explained more of the variation in readmission rates than general hospital factors. Use of a perioperative transfusion was associated with 14% greater risk, patients discharged to home had 28% lower risk, and surgeon volume and length of stay were also significant risk factors. The top 5 most frequently reported primary reasons for 30-day readmission in THA were procedure related: dislocation (5.9%), deep infection (5.1%), wound infection (4.8%), periprosthetic fracture (4.4%), or hematoma (3.4%). CONCLUSION: These findings support further optimization of the delivery of care-both intraoperative and postoperative-to reduce the broad variation in hospital readmissions.


Asunto(s)
Artroplastia de Reemplazo de Cadera/estadística & datos numéricos , Hospitales/estadística & datos numéricos , Readmisión del Paciente/estadística & datos numéricos , Complicaciones Posoperatorias/epidemiología , Anciano , Anciano de 80 o más Años , Artroplastia de Reemplazo de Cadera/efectos adversos , Transfusión Sanguínea , Bases de Datos Factuales , Femenino , Humanos , Masculino , Medicare , Alta del Paciente , Complicaciones Posoperatorias/etiología , Periodo Posoperatorio , Estudios Retrospectivos , Factores de Riesgo , Estados Unidos/epidemiología
15.
Am J Pathol ; 184(11): 3013-25, 2014 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-25193591

RESUMEN

Acetaminophen (APAP) overdose results in acute liver failure and has limited treatment options. Previous studies show that stimulating liver regeneration is critical for survival after APAP overdose, but the mechanisms remain unclear. In this study, we identified major signaling pathways involved in liver regeneration after APAP-induced acute liver injury using a novel incremental dose model. Liver injury and regeneration were studied in C57BL/6 mice treated with either 300 mg/kg (APAP300) or 600 mg/kg (APAP600) APAP. Mice treated with APAP300 developed extensive liver injury and robust liver regeneration. In contrast, APAP600-treated mice exhibited significant liver injury but substantial inhibition of liver regeneration, resulting in sustained injury and decreased survival. The inhibition of liver regeneration in the APAP600 group was associated with cell cycle arrest and decreased cyclin D1 expression. Several known regenerative pathways, including the IL-6/STAT-3 and epidermal growth factor receptor/c-Met/mitogen-activated protein kinase pathways, were activated, even at APAP600, where regeneration was inhibited. However, canonical Wnt/ß-catenin and NF-κB pathways were activated only in APAP300-treated mice, where liver regeneration was stimulated. Furthermore, overexpression of a stable form of ß-catenin, where serine 45 is mutated to aspartic acid, in mice resulted in improved liver regeneration after APAP overdose. Taken together, our incremental dose model has identified a differential role of several signaling pathways in liver regeneration after APAP overdose and highlighted canonical Wnt signaling as a potential target for regenerative therapies for APAP-induced acute liver failure.


Asunto(s)
Acetaminofén/toxicidad , Enfermedad Hepática Inducida por Sustancias y Drogas/metabolismo , Regeneración Hepática/fisiología , Transducción de Señal/fisiología , Animales , Ciclo Celular/efectos de los fármacos , Ciclo Celular/fisiología , Hígado/efectos de los fármacos , Hígado/metabolismo , Masculino , Ratones , Ratones Endogámicos C57BL , Transducción de Señal/efectos de los fármacos
17.
J Arthroplasty ; 30(7): 1121-6, 2015 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-25765130

RESUMEN

This study evaluated the trends in discharge patterns and the prevalence and cost of post-discharge PT. The 5% Medicare database (1997-2010) was used to identify 50,886 primary THA and 107,675 TKA patients. More than 50% of patients were discharged from hospital to an inpatient facility. There were an increase in discharges to skilled nursing units and a reduced rate to rehabilitation facilities. In contrast to hospital, surgeon reimbursement, and implant costs, the average annual PT cost per patient rose through the study period. Approximately 25% of PT costs were used on less common modalities. PT costs more than $648 million a year. With the increased pressure to control costs for primary TJA, these patterns may change unless PT effectiveness can be demonstrated.


Asunto(s)
Artroplastia de Reemplazo/economía , Artropatías/cirugía , Medicare/economía , Alta del Paciente/economía , Modalidades de Fisioterapia/economía , Anciano , Anciano de 80 o más Años , Estudios de Cohortes , Femenino , Costos de la Atención en Salud , Hospitales , Humanos , Artropatías/economía , Artropatías/rehabilitación , Tiempo de Internación , Masculino , Prevalencia , Estados Unidos
18.
Nucleic Acids Res ; 40(21): 11139-54, 2012 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-22965134

RESUMEN

LacI/GalR transcription regulators have extensive, non-conserved interfaces between their regulatory domains and the 18 amino acids that serve as 'linkers' to their DNA-binding domains. These non-conserved interfaces might contribute to functional differences between paralogs. Previously, two chimeras created by domain recombination displayed novel functional properties. Here, we present a synthetic protein family, which was created by joining the LacI DNA-binding domain/linker to seven additional regulatory domains. Despite 'mismatched' interfaces, chimeras maintained allosteric response to their cognate effectors. Therefore, allostery in many LacI/GalR proteins does not require interfaces with precisely matched interactions. Nevertheless, the chimeric interfaces were not silent to mutagenesis, and preliminary comparisons suggest that the chimeras provide an ideal context for systematically exploring functional contributions of non-conserved positions. DNA looping experiments revealed higher order (dimer-dimer) oligomerization in several chimeras, which might be possible for the natural paralogs. Finally, the biological significance of repression differences was determined by measuring bacterial growth rates on lactose minimal media. Unexpectedly, moderate and strong repressors showed an apparent induction phase, even though inducers were not provided; therefore, an unknown mechanism might contribute to regulation of the lac operon. Nevertheless, altered growth correlated with altered repression, which indicates that observed functional modifications are significant.


Asunto(s)
Proteínas de Escherichia coli/química , Regulación Bacteriana de la Expresión Génica , Represoras Lac/química , Proteínas Represoras/química , Transcripción Genética , Regulación Alostérica , ADN Bacteriano/química , ADN Bacteriano/metabolismo , Escherichia coli/genética , Escherichia coli/crecimiento & desarrollo , Proteínas de Escherichia coli/genética , Proteínas de Escherichia coli/metabolismo , Operón Lac , Represoras Lac/genética , Represoras Lac/metabolismo , Estructura Terciaria de Proteína , Proteínas Recombinantes de Fusión/química , Proteínas Recombinantes de Fusión/metabolismo , Proteínas Represoras/genética , Proteínas Represoras/metabolismo , Regulación hacia Arriba
19.
J Arthroplasty ; 29(7): 1369-72, 2014 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-24674733

RESUMEN

At a minimum follow-up of ten years we compared clinical and radiographic findings and survivorship in a cohort of 412 patients (447 hips) who received alumina on alumina CoC bearings to findings from a cohort of 216 patients (228 hips) with alumina on highly cross-linked polyethylene (HXLPE) bearings. All patients were operated for osteoarthritis. With bearing-related complications as endpoint, analysis showed no significant difference in survivorship between cohorts (99.8% for the CoC vs. 99.4% for HXLPE). In addition, there were no significant differences in clinical and radiographic findings between cohorts. We concluded that alumina on HXLPE bearings are a reasonable lower cost alternative to ceramic on ceramic bearing couples.


Asunto(s)
Óxido de Aluminio , Artroplastia de Reemplazo de Cadera/métodos , Cerámica/química , Osteoartritis/cirugía , Polietileno/química , Adulto , Anciano , Estudios de Cohortes , Femenino , Estudios de Seguimiento , Prótesis de Cadera , Humanos , Masculino , Persona de Mediana Edad , Diseño de Prótesis , Tasa de Supervivencia
20.
J Arthroplasty ; 29(3): 510-5, 2014 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-23972298

RESUMEN

The purpose of the present study is to determine the differences in cost, complications, and mortality between knee arthroplasty (TKA) patients who stay the standard 3-4 nights in a hospital compared to patients who undergo an outpatient procedure, a shortened stay or an extended stay. TKA patients were identified in the Medicare 5% sample (1997-2009) and separated into the following groups: outpatient, 1-2 days, 3-4 days, or 5+ days inpatient. At two years, costs associated with the outpatient and the 1-2 day stay groups were $8527 and $1967 lower than the 3-4 day stay group, respectively. Out to 2 years, the outpatient and 1-2 day stay groups reported less pain and stiffness, respectively, though the 1-2 day group also had a higher risk for revision.


Asunto(s)
Procedimientos Quirúrgicos Ambulatorios/efectos adversos , Artroplastia de Reemplazo de Rodilla/efectos adversos , Anciano , Anciano de 80 o más Años , Procedimientos Quirúrgicos Ambulatorios/economía , Procedimientos Quirúrgicos Ambulatorios/mortalidad , Artroplastia de Reemplazo de Rodilla/economía , Artroplastia de Reemplazo de Rodilla/mortalidad , Costos y Análisis de Costo , Humanos , Tiempo de Internación , Medicare/estadística & datos numéricos , Complicaciones Posoperatorias/epidemiología , Estados Unidos/epidemiología
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