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1.
Ann Surg ; 279(4): 555-560, 2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-37830271

RESUMO

OBJECTIVE: To evaluate severe complications and mortality over years of independent practice among general surgeons. BACKGROUND: Despite concerns that newly graduated general surgeons may be unprepared for independent practice, it is unclear whether patient outcomes differ between early and later career surgeons. METHODS: We used Medicare claims for patients discharged between July 1, 2007 and December 31, 2019 to evaluate 30-day severe complications and mortality for 26 operations defined as core procedures by the American Board of Surgery. Generalized additive mixed models were used to assess the association between surgeon years in practice and 30-day outcomes while adjusting for differences in patient, hospital, and surgeon characteristics. RESULTS: The cohort included 1,329,358 operations performed by 14,399 surgeons. In generalized mixed models, the relative risk (RR) of mortality was higher among surgeons in their first year of practice compared with surgeons in their 15th year of practice [5.5% (95% CI: 4.1%-7.3%) vs 4.7% (95% CI: 3.5%-6.3%), RR: 1.17 (95% CI: 1.11-1.22)]. Similarly, the RR of severe complications was higher among surgeons in their first year of practice compared with surgeons in their 15th year of practice [7.5% (95% CI: 6.6%-8.5%) versus 6.9% (95% CI: 6.1%-7.9%), RR: 1.08 (95% CI: 1.03-1.14)]. When stratified by individual operation, 21 operations had a significantly higher RR of mortality and all 26 operations had a significantly higher RR of severe complications in the first compared with the 15th year of practice. CONCLUSIONS: Among general surgeons performing common operations, rates of mortality and severe complications were higher among newly graduated surgeons compared with later career surgeons.


Assuntos
Medicare , Cirurgiões , Humanos , Estados Unidos/epidemiologia , Idoso , Hospitais , Mortalidade Hospitalar , Competência Clínica , Complicações Pós-Operatórias/epidemiologia , Estudos Retrospectivos
2.
Immunity ; 42(3): 457-70, 2015 Mar 17.
Artigo em Inglês | MEDLINE | ID: mdl-25769609

RESUMO

Little is known about the role of negative regulators in controlling natural killer (NK) cell development and effector functions. Foxo1 is a multifunctional transcription factor of the forkhead family. Using a mouse model of conditional deletion in NK cells, we found that Foxo1 negatively controlled NK cell differentiation and function. Immature NK cells expressed abundant Foxo1 and little Tbx21 relative to mature NK cells, but these two transcription factors reversed their expression as NK cells proceeded through development. Foxo1 promoted NK cell homing to lymph nodes by upregulating CD62L expression and inhibited late-stage maturation and effector functions by repressing Tbx21 expression. Loss of Foxo1 rescued the defect in late-stage NK cell maturation in heterozygous Tbx21(+/-) mice. Collectively, our data reveal a regulatory pathway by which the negative regulator Foxo1 and the positive regulator Tbx21 play opposing roles in controlling NK cell development and effector functions.


Assuntos
Fatores de Transcrição Forkhead/imunologia , Regulação Neoplásica da Expressão Gênica , Células Matadoras Naturais/imunologia , Neoplasias Pulmonares/genética , Melanoma Experimental/genética , Neoplasias Cutâneas/genética , Proteínas com Domínio T/imunologia , Animais , Diferenciação Celular , Proteína Forkhead Box O1 , Fatores de Transcrição Forkhead/genética , Heterozigoto , Células Matadoras Naturais/patologia , Selectina L/genética , Selectina L/imunologia , Pulmão/imunologia , Pulmão/patologia , Neoplasias Pulmonares/imunologia , Neoplasias Pulmonares/secundário , Linfonodos/imunologia , Linfonodos/patologia , Depleção Linfocítica , Melanoma Experimental/imunologia , Melanoma Experimental/patologia , Camundongos , Camundongos Knockout , Transplante de Neoplasias , Transdução de Sinais , Neoplasias Cutâneas/imunologia , Neoplasias Cutâneas/secundário , Proteínas com Domínio T/genética
3.
J Vasc Surg ; 78(3): 806-814.e2, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37164236

RESUMO

OBJECTIVE: As medical education systems increasingly move toward competency-based training, it is important to understand the tools available to assess competency and how these tools are utilized. The Society for Improving Medical Professional Learning (SIMPL) offers a smart phone-based assessment system that supports workplace-based assessment of residents' and fellows' operative autonomy, performance, and case complexity. The purpose of this study was to characterize implementation of the SIMPL app within vascular surgery integrated residency (0+5) and fellowship (5+2) training programs. METHODS: SIMPL operative ratings recorded between 2018 and 2022 were collected from all participating vascular surgery training institutions (n = 9 institutions with 5+2 and 0+5 programs; n = 4 institutions with 5+2 program only). The characteristics of programs, trainees, faculty, and SIMPL operative assessments were evaluated using descriptive statistics. RESULTS: Operative assessments were completed for 2457 cases by 85 attendings and 86 trainees, totaling 4615 unique operative assessment ratings. Attendings included dictated feedback in 52% of assessments. Senior-level residents received more assessments than junior-level residents (postgraduate year [PGY]1-3, n = 439; PGY4-5, n = 551). Performance ratings demonstrated increases from junior to senior trainees for both resident and fellow cohorts with "performance-ready" or "exceptional performance" ratings increasing by nearly two-fold for PGY1 to PGY5 residents (28.1% vs 40.6%), and from first- to second-year fellows (PGY6, 46.7%; PGY7, 60.3%). Similar gains in autonomy were demonstrated as trainees progressed through training. Senior residents were more frequently granted autonomy with "supervision only" than junior residents (PGY1, 8.7%; PGY5, 21.6%). "Supervision only" autonomy ratings were granted to 21.8% of graduating fellows. Assessment data included a greater proportion of complex cases for senior compared with junior fellows (PGY6, 20.9% vs PGY7, 26.5%). Program Directors felt that faculty and trainee buy-in were the main barriers to implementation of the SIMPL assessment app. CONCLUSIONS: This is the first description of the SIMPL app as an operative assessment tool within vascular surgery that has been successfully implemented in both residency and fellowship programs. The assessment data demonstrates expected progressive gains in trainees' autonomy and performance, as well as increasing case complexity, across PGY years. Given the selection of SIMPL as the assessment platform for required American Board of Surgery and Vascular Surgery Board Entrustable Professional Activities assessments, understanding facilitators and barriers to implementation of workplace-based assessments using this app is imperative, particularly as we move toward competency-based medical education.


Assuntos
Cirurgia Geral , Internato e Residência , Humanos , Bolsas de Estudo , Educação de Pós-Graduação em Medicina , Competência Clínica , Procedimentos Cirúrgicos Vasculares , Local de Trabalho , Cirurgia Geral/educação
4.
Ann Surg ; 275(3): 617-620, 2022 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-32511125

RESUMO

OBJECTIVE: To describe the quality of operative performance feedback using evaluation tools commonly used by general surgery residency training programs. SUMMARY OF BACKGROUND DATA: The majority of surgical training programs administer an evaluation through which faculty members may rate and comment on trainee operative performance at the end of the rotation (EOR). Many programs have also implemented the system for improving and measuring procedural learning (SIMPL), a workplace-based assessment tool with which faculty can rate and comment on a trainee's operative performance immediately after a case. It is unknown how the quality of narrative operative performance feedback delivered with these tools compares. METHODS: The authors collected EOR evaluations and SIMPL narrative comments on trainees' operative performance from 3 university-based surgery training programs during the 2016-2017 academic year. Two surgeon raters categorized comments relating to operative skills as being specific or general and as encouraging and/or corrective. Comments were then classified as effective, mediocre, ineffective, or irrelevant. The frequencies with which comments were rated as effective were compared using Chi-square analysis. RESULTS: The authors analyzed a total of 600 comments. 10.7% of EOR and 58.3% of SIMPL operative performance evaluation comments were deemed effective (P < 0.0001). CONCLUSIONS: Evaluators give significantly higher quality operative performance feedback when using workplace-based assessment tools rather than EOR evaluations.


Assuntos
Competência Clínica , Feedback Formativo , Cirurgia Geral/educação , Internato e Residência , Procedimentos Cirúrgicos Operatórios/educação , Procedimentos Cirúrgicos Operatórios/normas , Humanos , Estudos Retrospectivos
5.
Ann Surg ; 276(6): e1095-e1100, 2022 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-34132692

RESUMO

OBJECTIVE: To examine the alignment between graduating surgical trainee operative performance and a prior survey of surgical program director expectations. BACKGROUND: Surgical trainee operative training is expected to prepare residents to independently perform clinically important surgical procedures. METHODS: We conducted a cross-sectional observational study of US general surgery residents' rated operative performance for Core general surgery procedures. Residents' expected performance on those procedures at the time of graduation was compared to the current list of Core general surgery procedures ranked by their importance for clinical practice, as assessed via a previous national survey of general surgery program directors. We also examined the frequency of individual procedures logged by residents over the course of their training. RESULTS: Operative performance ratings for 29,885 procedures performed by 1861 surgical residents in 54 general surgery programs were analyzed. For each Core general surgery procedure, adjusted mean probability of a graduating resident being deemed practice-ready ranged from 0.59 to 0.99 (mean 0.90, standard deviation 0.08). There was weak correlation between the readiness of trainees to independently perform a procedure at the time of graduation and that procedure's historical importance to clinical practice ( p = 0.22, 95% confidence interval 0.01-0.41, P = 0.06). Residents also continue to have limited opportunities to learn many procedures that are important for clinical practice. CONCLUSION: The operative performance of graduating general surgery residents may not be well aligned with surgical program director expectations.


Assuntos
Cirurgia Geral , Internato e Residência , Humanos , Competência Clínica , Estudos Transversais , Motivação , Inquéritos e Questionários , Cirurgia Geral/educação , Educação de Pós-Graduação em Medicina
6.
Bioorg Med Chem ; 74: 117034, 2022 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-36272185

RESUMO

The three complement pathways comprising the early phase of the complement system (the classical, lectin, and alternative pathways) act together with the innate and adaptive immune systems to protect against foreign entities and maintain tissue homeostasis. While these systems are normally under tight regulatory control, several diseases have been reported to correlate with uncontrolled activation and amplification of the alternative pathway, including paroxysmal nocturnal hemoglobinuria, atypical hemolytic uremic syndrome, C3 glomerulopathy, and age-related macular degeneration. Complement FactorD (CFD), a serine protease, is the rate-limiting enzyme for the activity of alternative pathway. CFD activates the alternative pathway by cleaving Complement Factor B complexed to C3b (C3bB) to generate alternative pathway C3 convertase (C3bBb). In our search for novel CFD inhibitors with therapeutic potential, we employed a hot-spot analysis of an ensemble of apo and holo CFD structures. This analysis identified potential pharmacophore features that aided in the design of a series of compounds based on an l-proline core. While these compounds inhibited CFD in an esterolytic assay (for example, a proline-based compound, IC50 = 161 nM), the pharmacokinetic (PK) properties were poor. A strategy of scaffold hopping via ring opening led to a novel series of acyclic compounds, with subsequent structure-based ligand design and lead optimization producing several novel CFD inhibitors. One of these inhibitors, 1-(2-((2-(3-chloro-2-fluorobenzylamino)-2-oxoethyl)(cyclopropyl)amino)-2-oxoethyl)-5-(3-methyl-3-(1-methylpiperidin-4-yl)ureido)-1H-indazole-3-carboxamide, showed good potency with IC50s of 37 nM in the esterolytic assay and 30 nM in a hemolytic assay and PK assessments following oral administration to rats revealed a Cmax of 113 ng/mL and an AUC0-24h of 257 hr.ng/mL.


Assuntos
Fator D do Complemento , Serina Endopeptidases , Ratos , Animais , Fator D do Complemento/metabolismo , Hemólise , Ligantes
7.
Bioorg Med Chem ; 73: 117035, 2022 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-36208543

RESUMO

Hereditary angioedema (HAE) is a rare and potentially life-threatening disease that affects an estimated 1 in 50,000 individuals worldwide. Berotralstat (BCX7353) is the only small molecule approved by the US Food and Drug Administration (FDA) for the prophylactic treatment of HAE attacks in patients 12 years and older. During the discovery of BCX7353, we also identified a novel series of small molecules containing a quaternary carbon as potent and orally bioavailable Plasma Kallikrein (PKal) inhibitors. Lead compound was identified as a potent inhibitor following a detailed lead optimization process that balanced the lipophilic efficiency (LipE) and pharmacokinetic (PK) profile.


Assuntos
Angioedemas Hereditários , Calicreína Plasmática , Angioedemas Hereditários/tratamento farmacológico , Angioedemas Hereditários/prevenção & controle , Antivirais/uso terapêutico , Carbono , Humanos , Estados Unidos
8.
Ann Surg ; 274(2): 220-226, 2021 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-33351453

RESUMO

OBJECTIVE: To determine if initial American Board of Surgery certification in general surgery is associated with better risk-adjusted patient outcomes for Medicare patients undergoing partial colectomy by an early career surgeon. BACKGROUND: Board certification is a voluntary commitment to professionalism, continued learning, and delivery of high-quality patient care. Not all surgeons are certified, and some have questioned the value of certification due to limited evidence that board-certified surgeons have better patient outcomes. In response, we examined the outcomes of certified versus noncertified early career general surgeons. METHODS: We identified Medicare patients who underwent a partial colectomy between 2008 and 2016 and were operated on by a non-subspecialty trained surgeon within their first 5 years of practice. Surgeon certification status was determined using the American Board of Surgery data. Generalized linear mixed models were used to control for patient-, procedure-, and hospital-level effects. Primary outcomes were the occurrence of severe complications and occurrence of death within 30 days. RESULTS: We identified 69,325 patients who underwent a partial colectomy by an early career general surgeon. The adjusted rate of severe complications after partial colectomy by certified (n = 4239) versus noncertified (n = 191) early-career general surgeons was 9.1% versus 10.7% (odds ratio 0.83, P = 0.03). Adjusted mortality rate for certified versus noncertified early-career general surgeons was 4.9% versus 6.1% (odds ratio 0.79, P = 0.01). CONCLUSION: Patients undergoing partial colectomy by an early career general surgeon have decreased odds of severe complications and death when their surgeon is board certified.


Assuntos
Certificação , Competência Clínica/normas , Colectomia/normas , Cirurgia Geral/normas , Avaliação de Processos e Resultados em Cuidados de Saúde , Cirurgiões/normas , Idoso , Colectomia/mortalidade , Feminino , Humanos , Masculino , Medicare , Complicações Pós-Operatórias/epidemiologia , Conselhos de Especialidade Profissional , Estados Unidos/epidemiologia
9.
Br J Haematol ; 189(1): 72-83, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-31960419

RESUMO

Lymphoma-associated haemophagocytic lymphohistiocytosis (L-HLH) is characterized by excessively activated macrophages and cytotoxic T lymphocytes, but few reliable markers for activated macrophages are available clinically. This study, designed to discover novel biomarkers for the diagnosis of lymphoma patients with L-HLH, was initiated between 2016 and 2018. Fifty-seven adult lymphoma patients were enrolled - 39 without HLH and 18 with HLH. The differential serum protein expression profile was first screened between lymphoma patients with and without L-HLH by a quantitative mass spectrometric approach. Soluble V-set and immunoglobulin domain-containing 4 (sVSIG4), specifically expressed by macrophages, was significantly upregulated in the L-HLH group. Subsequently, sVSIG4 concentration was confirmed by enzyme-linked immunosorbent assay to be significantly increased in lymphoma patients with L-HLH. When it was exploited for the diagnosis of lymphoma patients with L-HLH, the area under a receiver operating characteristic curve was 0·98 with an optimal cut-off point of 2195 pg/ml and the corresponding sensitivity and specificity were 94·44% and 94·87% respectively. In addition, the one-year overall survival was significantly worse in patients with a sVSIG4 concentration above 2195 pg/ml compared with those below 2195 pg/ml (5·3% vs. 72·2%, P < 0·0001). sVSIG4 may be a surrogate marker of activated macrophages for the diagnosis of lymphoma patients with L-HLH.


Assuntos
Biomarcadores Tumorais/sangue , Linfo-Histiocitose Hemofagocítica , Linfoma , Proteínas de Neoplasias/sangue , Receptores de Complemento/sangue , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Seguimentos , Humanos , Linfo-Histiocitose Hemofagocítica/sangue , Linfo-Histiocitose Hemofagocítica/diagnóstico , Linfo-Histiocitose Hemofagocítica/etiologia , Linfoma/sangue , Linfoma/complicações , Linfoma/diagnóstico , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos
10.
Nature ; 508(7496): 402-5, 2014 Apr 17.
Artigo em Inglês | MEDLINE | ID: mdl-24590073

RESUMO

Filoviruses are emerging pathogens and causative agents of viral haemorrhagic fever. Case fatality rates of filovirus disease outbreaks are among the highest reported for any human pathogen, exceeding 90% (ref. 1). Licensed therapeutic or vaccine products are not available to treat filovirus diseases. Candidate therapeutics previously shown to be efficacious in non-human primate disease models are based on virus-specific designs and have limited broad-spectrum antiviral potential. Here we show that BCX4430, a novel synthetic adenosine analogue, inhibits infection of distinct filoviruses in human cells. Biochemical, reporter-based and primer-extension assays indicate that BCX4430 inhibits viral RNA polymerase function, acting as a non-obligate RNA chain terminator. Post-exposure intramuscular administration of BCX4430 protects against Ebola virus and Marburg virus disease in rodent models. Most importantly, BCX4430 completely protects cynomolgus macaques from Marburg virus infection when administered as late as 48 hours after infection. In addition, BCX4430 exhibits broad-spectrum antiviral activity against numerous viruses, including bunyaviruses, arenaviruses, paramyxoviruses, coronaviruses and flaviviruses. This is the first report, to our knowledge, of non-human primate protection from filovirus disease by a synthetic drug-like small molecule. We provide additional pharmacological characterizations supporting the potential development of BCX4430 as a countermeasure against human filovirus diseases and other viral diseases representing major public health threats.


Assuntos
Adenosina/análogos & derivados , Antivirais/farmacologia , Infecções por Filoviridae/prevenção & controle , Infecções por Filoviridae/virologia , Filoviridae/efeitos dos fármacos , Nucleosídeos de Purina/farmacologia , Adenina/análogos & derivados , Administração Oral , Animais , Antivirais/administração & dosagem , Antivirais/química , Antivirais/farmacocinética , RNA Polimerases Dirigidas por DNA/antagonistas & inibidores , RNA Polimerases Dirigidas por DNA/metabolismo , Modelos Animais de Doenças , Ebolavirus/efeitos dos fármacos , Filoviridae/enzimologia , Doença pelo Vírus Ebola/prevenção & controle , Doença pelo Vírus Ebola/virologia , Humanos , Injeções Intramusculares , Macaca fascicularis/virologia , Doença do Vírus de Marburg/prevenção & controle , Doença do Vírus de Marburg/virologia , Marburgvirus/efeitos dos fármacos , Nucleosídeos de Purina/administração & dosagem , Nucleosídeos de Purina/química , Nucleosídeos de Purina/farmacocinética , Pirrolidinas , RNA/biossíntese , Fatores de Tempo
12.
HPB (Oxford) ; 20(12): 1181-1188, 2018 12.
Artigo em Inglês | MEDLINE | ID: mdl-30005992

RESUMO

BACKGROUND: The Risk Analysis Index (RAI) for frailty is a rapid survey for comorbidities and performance status, which predicts mortality after general surgery. We aimed to validate the RAI in predicting outcomes after hepatopancreatobiliary surgery. METHODS: Associations of RAI, determined in 162 patients prior to undergoing hepatopancreatobiliary surgery, with prospectively collected 30-day post-operative outcomes were analyzed with multivariate logistic and linear regression. RESULTS: Patients (age 62 ± 14, 51% female) had a median RAI of 7, range 0-25. With every unit increase in RAI, length of stay increased by 5% (95% CI: 2-7%), odds of ICU admission increased by 10% (0-20%), ICU length of stay increased by 21% (9-34%), and odds of discharge to a nursing facility increased by 8% (0-17%) (all P < 0.05). Particularly in patients who suffered a first post-operative complication, RAI was associated with additional complications (1.6 unit increase in Comprehensive Complication Index per unit increase in RAI, P = 0.002). In a direct comparison in a subset of 74 patients, RAI and the ACS-NSQIP Risk Calculator performed comparably in predicting outcomes. CONCLUSION: While RAI and ACS-NSQIP Risk Calculator comparatively predicted short-term outcomes after HPB surgery, RAI has been specifically designed to identify frail patients who can potentially benefit from preoperative prehabilitation interventions.


Assuntos
Técnicas de Apoio para a Decisão , Procedimentos Cirúrgicos do Sistema Digestório/efeitos adversos , Fragilidade/diagnóstico , Complicações Pós-Operatórias/etiologia , Idoso , Procedimentos Cirúrgicos do Sistema Biliar/efeitos adversos , Tomada de Decisão Clínica , Feminino , Idoso Fragilizado , Fragilidade/complicações , Hepatectomia/efeitos adversos , Humanos , Masculino , Pessoa de Meia-Idade , Pancreatectomia/efeitos adversos , Pancreaticoduodenectomia/efeitos adversos , Valor Preditivo dos Testes , Estudos Prospectivos , Medição de Risco , Fatores de Risco , Fatores de Tempo , Resultado do Tratamento
13.
Infect Immun ; 85(6)2017 06.
Artigo em Inglês | MEDLINE | ID: mdl-28348052

RESUMO

In addition to their chemical antimicrobial nature, bile acids are thought to have other functions in the homeostatic control of gastrointestinal immunity. However, those functions have remained largely undefined. In this work, we used ileal explants and mouse models of bile acid administration to investigate the role of bile acids in the regulation of the intestinal antimicrobial response. Mice fed on a diet supplemented with 0.1% chenodeoxycholic acid (CDCA) showed an upregulated expression of Paneth cell α-defensins as well as an increased synthesis of the type-C lectins Reg3b and Reg3g by the ileal epithelium. CDCA acted on several epithelial cell types, by a mechanism independent from farnesoid X receptor (FXR) and not involving STAT3 or ß-catenin activation. CDCA feeding did not change the relative abundance of major commensal bacterial groups of the ileum, as shown by 16S analyses. However, administration of CDCA increased the expression of ileal Muc2 and induced a change in the composition of the mucosal immune cell repertoire, decreasing the proportion of Ly6G+ and CD68+ cells, while increasing the relative amount of IgGκ+ B cells. Oral administration of CDCA to mice attenuated infections with the bile-resistant pathogens Salmonella enterica serovar Typhimurium and Citrobacter rodentium, promoting lower systemic colonization and faster bacteria clearance, respectively. Our results demonstrate that bile acid signaling in the ileum triggers an antimicrobial program that can be potentially used as a therapeutic option against intestinal bacterial infections.


Assuntos
Ácido Quenodesoxicólico/administração & dosagem , Infecções por Enterobacteriaceae/imunologia , Íleo/microbiologia , Imunidade nas Mucosas , Infecções por Salmonella/imunologia , alfa-Defensinas/imunologia , Animais , Carga Bacteriana , Citrobacter rodentium/efeitos dos fármacos , Íleo/imunologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Celulas de Paneth/imunologia , Celulas de Paneth/microbiologia , Salmonella typhimurium/efeitos dos fármacos
14.
Biol Blood Marrow Transplant ; 22(1): 71-9, 2016 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-26256940

RESUMO

Statins possess potent immunomodulatory effects that may play a role in preventing acute graft-versus-host disease (aGVHD) after allogeneic hematopoietic cell transplantation (allo-HCT). We performed a phase II study of atorvastatin for aGVHD prophylaxis when given to allo-HCT recipients and their HLA-matched sibling donors. Atorvastatin (40 mg/day) was administered to sibling donors, beginning 14 days before the anticipated start of stem cell collection. Allo-HCT recipients (n = 40) received atorvastatin (40 mg/day) in addition to standard aGVHD prophylaxis. The primary endpoint was cumulative incidence of grades II to IV aGVHD at day 100. Atorvastatin was well tolerated, with no attributable grades III to IV toxicities in donors or their recipients. Day 100 and 180 cumulative incidences of grades II to IV aGVHD were 30% (95% confidence interval [CI], 17% to 45%) and 40% (95% CI, 25% to 55%), respectively. One-year cumulative incidence of chronic GVHD was 43% (95% CI, 32% to 69%). One-year nonrelapse mortality and relapse incidences were 5.5% (95% CI, .9% to 16.5%) and 38% (95% CI, 18% to 47%), respectively. One-year progression-free and overall survival rates were 54% (95% CI, 38% to 71%) and 82% (95% CI, 69% to 94%). One-year GVHD-free, relapse-free survival was 27% (95% CI, 16% to 47%). These results did not differ from our historical control subjects (n = 96). Although safe and tolerable, the addition of atorvastatin did not appear to provide any benefit to standard GVHD prophylaxis alone.


Assuntos
Atorvastatina/administração & dosagem , Doença Enxerto-Hospedeiro/mortalidade , Doença Enxerto-Hospedeiro/prevenção & controle , Transplante de Células-Tronco Hematopoéticas , Teste de Histocompatibilidade , Doadores de Tecidos , Doença Aguda , Adulto , Idoso , Aloenxertos , Intervalo Livre de Doença , Feminino , Doença Enxerto-Hospedeiro/etiologia , Humanos , Masculino , Pessoa de Meia-Idade , Taxa de Sobrevida
15.
Hepatogastroenterology ; 62(140): 790-3, 2015 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-26902002

RESUMO

BACKGROUND/AIMS: Intraoperative blood loss is an independent predictor of recurrence and survival after resection of hepatocellular carcinoma (HCC). The aim of this study was to identify the risk factors associated with intraoperative major blood loss in patients undergoing liver resection for HCC. METHODOLOGY: Clinicopathologic data and perioperative outcomes of 386 patients who underwent liver resection for HCC were retrospectively reviewed. The patients were divided into high (> 1,000 mL) and low (51,000 mL) blood loss groups according to the intraoperative blood loss. Intraoperative blood loss,more than 1,000 mL was defined as major blood loss. The risk factors associated with intraoperative major blood loss were analyzed by univariate and multivariate analyses. RESULTS: Vascular invasion, major hepatectomy and prolonged operation time were risk factors associated with intraoperative major blood loss during resection of HCC on multivariate analysis. Moreover, HCC patients with intraoperative major blood loss had prolonged hospital stay, higher incidence of postoperative complication and mortality compared with patients' with blood loss 1,000 mL. CONCLUSIONS: Vascular invasion, major hepatectomy and prolonged operation time are independent predictors of intraoperative major blood loss during resection of HCC.


Assuntos
Perda Sanguínea Cirúrgica/estatística & dados numéricos , Carcinoma Hepatocelular/cirurgia , Hepatectomia , Neoplasias Hepáticas/cirurgia , Adulto , Idoso , Idoso de 80 Anos ou mais , Fosfatase Alcalina/sangue , Aspartato Aminotransferases/sangue , Transfusão de Sangue , Carcinoma Hepatocelular/sangue , Carcinoma Hepatocelular/patologia , Estudos de Coortes , Feminino , Hemorragia/epidemiologia , Hemorragia/terapia , Artéria Hepática/patologia , Veias Hepáticas/patologia , Humanos , Complicações Intraoperatórias/epidemiologia , Complicações Intraoperatórias/terapia , Tempo de Internação , Neoplasias Hepáticas/sangue , Neoplasias Hepáticas/patologia , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Invasividade Neoplásica , Duração da Cirurgia , Estudos Retrospectivos , Fatores de Risco , Carga Tumoral
16.
Nano Lett ; 14(5): 2628-35, 2014 May 14.
Artigo em Inglês | MEDLINE | ID: mdl-24707978

RESUMO

Lithium- and manganese-rich (LMR) layered-structure materials are very promising cathodes for high energy density lithium-ion batteries. However, their voltage fading mechanism and its relationships with fundamental structural changes are far from being well understood. Here we report for the first time the mitigation of voltage and energy fade of LMR cathodes by improving the atomic level spatial uniformity of the chemical species. The results reveal that LMR cathodes (Li[Li0.2Ni0.2M0.6]O2) prepared by coprecipitation and sol-gel methods, which are dominated by a LiMO2 type R3̅m structure, show significant nonuniform Ni distribution at particle surfaces. In contrast, the LMR cathode prepared by a hydrothermal assisted method is dominated by a Li2MO3 type C2/m structure with minimal Ni-rich surfaces. The samples with uniform atomic level spatial distribution demonstrate much better capacity retention and much smaller voltage fade as compared to those with significant nonuniform Ni distribution. The fundamental findings on the direct correlation between the atomic level spatial distribution of the chemical species and the functional stability of the materials may also guide the design of other energy storage materials with enhanced stabilities.

17.
Nano Lett ; 14(12): 6889-96, 2014 Dec 10.
Artigo em Inglês | MEDLINE | ID: mdl-25419865

RESUMO

Suppressing lithium (Li) dendrite growth is one of the most critical challenges for the development of Li metal batteries. Here, we report for the first time the growth of dendrite-free lithium films with a self-aligned and highly compacted nanorod structure when the film was deposited in the electrolyte consisting of 1.0 M LiPF6 in propylene carbonate with 0.05 M CsPF6 as an additive. Evolution of both the surface and the cross-sectional morphologies of the Li films during repeated Li deposition/stripping processes were systematically investigated. It is found that the formation of the compact Li nanorod structure is preceded by a solid electrolyte interphase (SEI) layer formed on the surface of the substrate. Electrochemical analysis indicates that an initial reduction process occurred at ∼ 2.05 V vs Li/Li(+) before Li deposition is responsible for the formation of the initial SEI, while the X-ray photoelectron spectroscopy indicates that the presence of CsPF6 additive can largely enhance the formation of LiF in this initial SEI. Hence, the smooth Li deposition in Cs(+)-containing electrolyte is the result of a synergistic effect of Cs(+) additive and preformed SEI layer. A fundamental understanding on the composition, internal structure, and evolution of Li metal films may lead to new approaches to stabilize the long-term cycling stability of Li metal and other metal anodes for energy storage applications.


Assuntos
Eletrodos , Lítio/química , Nanopartículas Metálicas/química , Nanopartículas Metálicas/ultraestrutura , Nanotubos/química , Nanotubos/ultraestrutura , Cristalização/métodos , Galvanoplastia/métodos , Teste de Materiais , Propriedades de Superfície
18.
Mol Cell Biochem ; 393(1-2): 283-91, 2014 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-24792036

RESUMO

Glioma-associated oncogene homolog-1 (Gli-1) is considered a marker of Hedgehog pathway activation and is associated with the progression of several cancers. We have previously reported that Gli-1 was correlated with invasion and metastasis in hepatocellular carcinoma (HCC). However, the exact roles and mechanisms of Gli-1 in HCC invasion are unclear. In this study, we found that small interfering RNA mediated down-regulation of Gli-1 expression significantly suppressed adhesion, motility, migration, and invasion of both SMMC-7721 and SK-Hep1 cells. Furthermore, down-regulation of Gli-1 significantly reduced expressions and activities of both matrix metalloproteinase (MMP)-2 and MMP-9. In addition, we found that down-regulation of Gli-1 resulted in up-regulation of E-cadherin and concomitant down-regulation of Snail and Vimentin, consistent with inhibition of epithelial-mesenchymal transition (EMT). Taken together, our results suggest that down-regulation of Gli-1 suppresses HCC cell migration and invasion likely through inhibiting expressions and activations of MMP-2, 9 and blocking EMT.


Assuntos
Carcinoma Hepatocelular/genética , Movimento Celular/genética , Neoplasias Hepáticas/genética , Fatores de Transcrição/genética , Carcinoma Hepatocelular/patologia , Linhagem Celular Tumoral , Transição Epitelial-Mesenquimal/genética , Regulação Neoplásica da Expressão Gênica , Humanos , Neoplasias Hepáticas/patologia , Metaloproteinase 2 da Matriz/biossíntese , Metaloproteinase 9 da Matriz/biossíntese , Invasividade Neoplásica/genética , RNA Interferente Pequeno , Transdução de Sinais/genética , Fatores de Transcrição/antagonistas & inibidores , Proteína GLI1 em Dedos de Zinco
19.
Microsc Microanal ; 20(2): 484-92, 2014 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-24755142

RESUMO

The recent development of in-situ liquid stages for (scanning) transmission electron microscopes now makes it possible for us to study the details of electrochemical processes under operando conditions. As electrochemical processes are complex, care must be taken to calibrate the system before any in-situ/operando observations. In addition, as the electron beam can cause effects that look similar to electrochemical processes at the electrolyte/electrode interface, an understanding of the role of the electron beam in modifying the operando observations must also be understood. In this paper we describe the design, assembly, and operation of an in-situ electrochemical cell, paying particular attention to the method for controlling and quantifying the experimental parameters. The use of this system is then demonstrated for the lithiation/delithiation of silicon nanowires.

20.
Nano Lett ; 13(8): 3909-14, 2013 Aug 14.
Artigo em Inglês | MEDLINE | ID: mdl-23879207

RESUMO

Sodium ion (Na(+)) batteries have attracted increased attention for energy storage due to the natural abundance of sodium, but their development is hindered by poor intercalation property of Na(+) in electrodes. This paper reports a detailed study of high capacity, high rate sodium ion energy storage in functionalized high-surface-area nanocellular carbon foams (NCCF). The energy storage mechanism is surface-driven reactions between Na(+) and oxygen-containing functional groups on the surface of NCCF. The surface reaction, rather than a Na(+) bulk intercalation reaction, leads to high rate performance and cycling stability due to the enhanced reaction kinetics and the absence of electrode structure change. The NCCF makes more surface area and surface functional groups available for the Na(+) reaction. It delivers 152 mAh/g capacity at the rate of 0.1 A/g and a capacity retention of 90% for over 1600 cycles.

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