Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 29
Filtrar
1.
Blood Adv ; 4(5): 880-884, 2020 03 10.
Artigo em Inglês | MEDLINE | ID: mdl-32130406

RESUMO

Despite achieving a hematologic complete response after treatment, many patients with AL amyloidosis do not attain recovery of organ function and/or experience hematologic relapse. A persistent plasma cell clone producing amyloidogenic light chains at levels below the detection threshold of traditional serologic methods is hypothesized to impede organ response in some patients. Assessment of minimal residual disease (MRD) may therefore have clinical importance as a more stringent treatment response tool for patients in a hematologic complete response. We used 2-tube, 10-color combination multiparametric flow cytometry to assess for MRD at a minimum sensitivity of 1 in 105 nucleated cells. Of 65 patients in hematologic complete response, 36 (55%) were found to have a residual clonal plasma cell population in the bone marrow. Comparing the MRD-negative and MRD-positive groups, renal response was observed in 88% vs 64% (P = .06), cardiac response in 75% vs 59% (P = .45), and any organ response in 90% vs 75% (P = .20) of patients. Depth of organ response as measured by the percent decrease in 24-hour proteinuria and brain natriuretic peptide was 96% vs 91% (P = .16) and 55% vs 46% (P = .66), respectively. These data suggest a possible correlation between MRD negativity and higher probability of organ response after treatment in AL amyloidosis. Future prospective studies with a larger cohort are needed to determine the clinical relevance of these improvements. This trial was registered at www.clinicaltrials.gov as #NCT00898235.


Assuntos
Amiloidose de Cadeia Leve de Imunoglobulina , Citometria de Fluxo , Humanos , Amiloidose de Cadeia Leve de Imunoglobulina/diagnóstico , Amiloidose de Cadeia Leve de Imunoglobulina/tratamento farmacológico , Recidiva Local de Neoplasia , Neoplasia Residual , Estudos Prospectivos
2.
Clin Anat ; 33(4): 516-521, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-31066935

RESUMO

The splenic surface can be anatomically divided into the visceral surface connected to major blood vessels and the diaphragmatic surface attached to the diaphragm. This study aimed to investigate differences in future treatment and outcomes according to the anatomical location of splenic injuries following abdominal trauma. Patients who were treated at a single trauma center between January 2011 and April 2018 were included. The presence of lacerations or hematoma on the visceral surface was evaluated via computed tomography. Differences in the location of splenic surgery between a group that underwent surgical or radiologic intervention and a group that received conservative care only were analyzed. Of 355 patients with splenic injury analyzed, the total mortality rate was 15.2%. A total of 167 patients underwent surgery and angiographic embolization, and 168 received conservative care only. Splenic injuries involved the visceral surface in 127 and 105 patients in the respective groups. Significant differences in the incidence of splenic injuries involving the visceral surface were found between the two groups in the univariate and logistic regression analyses. The likelihood of needing surgery and treatments such as embolization was higher for cases of splenic injury involving the visceral surface than for splenic injuries that did not involve the visceral surface. Through additional research, it may become possible to analyze the location of a splenic injury to determine an effective and safe method of treatment and accurately predict a prognosis. Clin. Anat. 33:516-521, 2020. © 2019 Wiley Periodicals, Inc.


Assuntos
Traumatismos Abdominais/cirurgia , Baço/lesões , Baço/cirurgia , Traumatismos Abdominais/diagnóstico por imagem , Adolescente , Adulto , Tomada de Decisões , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Baço/diagnóstico por imagem , Tomografia Computadorizada por Raios X , Adulto Jovem
3.
Am J Surg Pathol ; 41(6): 795-800, 2017 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-28248818

RESUMO

We report 2 cases of Kaposi sarcoma-associated herpesvirus (KSHV)-and Epstein-Barr Virus (EBV) associated germinotropic lymphoproliferative disorder. Both cases arose in patients from regions endemic for KSHV, Cape Verde, and the Democratic Republic of the Congo, presenting as localized lymphadenopathy. The affected lymph nodes showed colonization of the follicles by clusters of large atypical plasmablasts, but also showed regressive changes with vascular proliferation and interfollicular plasmacytosis, both reminiscent of human herpesvirus 8 (HHV-8) positive multicentric Castleman disease. The atypical plasmablasts showed dual positivity for HHV-8 and EBV, being positive for LANA and viral interleukin 6, as well as Epstein-Barr virus-encoded small RNA by in situ hybridization. They showed a latency I phenotype, being negative for LMP1, EBNA2, and BZLF-1. The plasmablasts were negative for immunoglobulin light chains, and in 1 case with successful DNA amplification had a polyclonal immunoglobulin rearrangement pattern. Germinotropic lymphoproliferative disorder is a rare disorder, with only 6 cases reported in the literature. We demonstrate for the first time the expression of HHV-8 viral interleukin 6 and provide evidence for latency I phenotype for EBV. In addition, 1 case progressed to an EBV-positive diffuse large B-cell lymphoma, but interestingly was negative for KSHV/HHV-8, likely indicative of tumor derived from an independent clone.


Assuntos
Infecções por Vírus Epstein-Barr/complicações , Herpesvirus Humano 8/isolamento & purificação , Transtornos Linfoproliferativos/virologia , Idoso de 80 Anos ou mais , Biomarcadores/metabolismo , Infecções por Vírus Epstein-Barr/diagnóstico , Infecções por Vírus Epstein-Barr/metabolismo , Feminino , Infecções por Herpesviridae/complicações , Infecções por Herpesviridae/diagnóstico , Infecções por Herpesviridae/metabolismo , Humanos , Transtornos Linfoproliferativos/diagnóstico , Transtornos Linfoproliferativos/metabolismo , Masculino , Pessoa de Meia-Idade
4.
Protoplasma ; 254(3): 1163-1173, 2017 May.
Artigo em Inglês | MEDLINE | ID: mdl-27943021

RESUMO

Tubulin is the target for very widely used anti-tumor drugs, including Vinca alkaloids, taxanes, and epothilones, which are an important component of chemotherapy in breast cancer and other malignancies. Paclitaxel and other tubulin-targeting drugs bind to the ß subunit of tubulin, which is a heterodimer of α and ß subunits. ß-Tubulin exists in the form of multiple isotypes, which are differentially expressed in normal and neoplastic cells and differ in their ability to bind to drugs. Among them, the ßIII isotype is overexpressed in many aggressive and metastatic cancers and may serve as a prognostic marker in certain types of cancer. The underpinning mechanisms accounting for the overexpression of this isotype in cancer cells are unclear. To better understand the role of ß-tubulin isotypes in cancer, we analyzed over 1000 clones from 90 breast cancer patients, sequencing their ß-tubulin isotypes, in search of novel mutations. We have elucidated two putative emerging molecular subgroups of invasive breast cancer, each of which involve mutations in the ßI-, ßIIA-, or ßIVB isotypes of tubulin that increase their structural, and possibly functional, resemblance to the ßIII isotype. A unifying feature of the first of the two subgroups is the mutation of the highly reactive C239 residue of ßI- or ßIVB-tubulin to L239, R239, Y239, or P239, culminating in probable conversion of these isotypes from ROS-sensitive to ROS-resistant species. In the second subgroup, ßI, ßIIA, and ßIVB have up to seven mutations to the corresponding residues in ßIII-tubulin. Given that ßIII-tubulin has emerged as a pro-survival factor, overexpression of this isotype may confer survival advantages to certain cancer cell types. In this mini-review, we bring attention to a novel mechanism by which cancer cells may undergo adaptive mutational changes involving alternate ß-tubulin isotypes to make them acquire some of the pro-survival properties of ßIII-tubulin. These "hybrid" tubulins, combining the sequences and/or properties of two wild-type tubulins (ßIII and either ßI, ßIIA, or ßIVB), are novel isotypes expressed solely in cancer cells and may contribute to the molecular understanding and stratification of invasive breast cancer and provide novel molecular targets for rational drug development.


Assuntos
Neoplasias da Mama/genética , Microtúbulos/metabolismo , Isoformas de Proteínas/metabolismo , Tubulina (Proteína)/genética , Sequência de Aminoácidos , Animais , Antineoplásicos , Sequência de Bases , Neoplasias da Mama/tratamento farmacológico , Linhagem Celular Tumoral , Galinhas , Resistencia a Medicamentos Antineoplásicos/genética , Feminino , Humanos , Camundongos , Paclitaxel/farmacologia , Ligação Proteica/efeitos dos fármacos , Isoformas de Proteínas/genética , Salmão , Análise de Sequência de DNA/veterinária , Homologia de Sequência de Aminoácidos , Tubulina (Proteína)/metabolismo , Xenopus laevis
5.
Invest New Drugs ; 34(1): 129-37, 2016 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-26686345

RESUMO

The subunit protein of microtubules is tubulin, which has been the target for some of the most successful and widely used anti-tumor drugs. Most of the drugs that target tubulin bind to the ß subunit. There are many isotypes of ß-tubulin and their distributions differ among different tissues. The ßIII isotype is over-expressed in many tumors, particularly those that are aggressive, metastatic, and drug resistant. We have previously reported the design and synthesis of a series of compounds to fit the colchicine site on ßIII but not on the other isotypes. In the current study, we tested the toxicity and the anti-tumor activity of one of these compounds, CH-35, on the human breast tumor MDA-MB-231 over-expressing ßIII in a xenogeneic mouse model. We found that CH-35 was as toxic as Taxol® in vivo. Although the ßIII-over-expressing cells developed into very fast-growing tumors, CH-35 was more effective against this tumor than was Taxol. Our results suggest that CH-35 is a promising candidate for future drug development.


Assuntos
Antineoplásicos/farmacologia , Neoplasias da Mama/tratamento farmacológico , Colchicina/análogos & derivados , Tubulina (Proteína)/genética , Animais , Antineoplásicos/toxicidade , Neoplasias da Mama/genética , Neoplasias da Mama/patologia , Linhagem Celular Tumoral , Colchicina/química , Colchicina/farmacologia , Colchicina/toxicidade , Feminino , Humanos , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Paclitaxel/farmacologia , Paclitaxel/toxicidade , Testes de Toxicidade
6.
Allergy Rhinol (Providence) ; 6(2): 133-7, 2015 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-26302736

RESUMO

INTRODUCTION: Epithelial myoepithelial carcinoma (EMC) of the nasal cavity is a rare tumor, and here we describe the first case of EMC of the nasal cavity presenting with epiphora. A case presentation and review of the literature is provided. METHODS: A case report is described of a 63-year-old man who presented with unilateral epiphora and was found via a thorough history and physical examination to have a nasal tumor. The physical examination consisted of an ocular examination, including probing and irrigation, and a detailed nasal examination (anterior rhinoscopy, nasal endoscopy). The nasal examination was prompted by the patient's report of concurrent nasal symptoms during history taking. Immunohistochemistry subsequently identified the nasal tumor as EMC. A literature search was performed to gain insights into similar malignancies of the nasal cavity. RESULTS: Eight cases of EMC of the nasal cavity were identified in the literature, none of the patients presented with epiphora. The case presented here resulted in resolution of the patient's symptoms and no evidence of disease after surgical excision. CONCLUSION: Epithelial myoepithelial is a rare salivary gland malignancy that can arise in the nasal cavity. Unilateral epiphora with concurrent nasal symptoms should prompt nasal cavity examination for the possibility of an obstructive tumor.

8.
J Trauma Acute Care Surg ; 76(1): 191-5, 2014 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-24368378

RESUMO

BACKGROUND: As we enter the brave new world of the Patient Protection and Affordable Care Act of 2010, it is imperative that trauma centers provide not only excellent but also cost-effective trauma care. To that end, we sought to determine those factors that contribute significantly to barrier days (BDs), when a patient is medically cleared for discharge but unable to leave the hospital. We hypothesized that there would be significant demographic and payor factors associated with BDs. METHODS: All trauma admissions to a Level II trauma center discharged alive from 2010 to 2012 were queried from the trauma registry. BDs were identified and recorded at daily sign-out. Patients with a hospital length of stay of 24 hours or less or transferred to another hospital were excluded. Univariate logistic regression was used to analyze which factors were significant (p ≤ 0.05) for BDs. Significant variables were then included in a multivariate logistic regression model. RESULTS: A total of 3,056 patients were included in the study, 105 (3.44%) of whom had at least one BD. Multivariate analysis revealed that patients awaiting nursing home placement and rehabilitation placement were at 6.39 and 2.79 times higher odds of having significant barriers to discharge, respectively, compared with patients who were discharged home. The multivariate model also showed that Medicaid coverage, one or more comorbidities, Injury Severity Score of 9 or greater, and one or more ventilation days had a significant correlation with the incidence of BDs. CONCLUSION: This study suggests that discharge destination is a significant factor associated with BDs. Understanding what type of patient is prone to develop barriers to discharge will allow case managers and social workers to intervene with discharge planning early in that patient's hospital course to secure placement and possibly reduce health care costs and improve functional outcome. LEVEL OF EVIDENCE: Prognostic/epidemiologic study, level III.


Assuntos
Alta do Paciente/estatística & dados numéricos , Centros de Traumatologia/estatística & dados numéricos , Idoso , Feminino , Humanos , Escala de Gravidade do Ferimento , Masculino , Medicaid/estatística & dados numéricos , Medicare/estatística & dados numéricos , Pessoa de Meia-Idade , Casas de Saúde , Alta do Paciente/normas , Sistema de Registros/estatística & dados numéricos , Centros de Reabilitação , Respiração Artificial/estatística & dados numéricos , Fatores de Tempo , Centros de Traumatologia/normas , Estados Unidos
9.
Int J Gynecol Pathol ; 32(3): 283-92, 2013 May.
Artigo em Inglês | MEDLINE | ID: mdl-23518912

RESUMO

Squamous differentiation (SD) and morular metaplasia (MM) are frequently present in uterine endometrioid adenocarcinoma (EAC) and can mimic areas of solid tumor. We used immunohistochemical stains to further characterize these lesions, and to determine which markers would help to distinguish these metaplasias from areas of solid growth in EAC. The pathology database was searched for diagnoses of EAC from 1997 to 2007, the hematoxylin and eosin-stained slides were reviewed, and 143 cases with SD, MM, or both (SD+MM) were identified. A panel of immunohistochemical stains was performed. In particular, we were interested in PAX2 and PAX8, recently studied markers of Müllerian tissue as potential markers for differentiation of metaplasias and tumor. In addition, estrogen receptor and progesterone receptor, and Her-2/neu, were examined to determine whether there was a differential expression between the metaplasias and solid tumor that may be diagnostically useful. In addition, to further characterize MM and SD, bcl-2 as a marker of cell regulation and inhibition of apoptosis, p16 as a surrogate marker for human papillomavirus, and p63 as a marker of mature SD were studied. Adjacent normal endometrium (NEM), when present, and 20 EAC cases (FIGO Grades 1-3) without SD or MM served as controls. PAX2 was positive in NEM (58/61, 95%) and was lost in SD (15/136, 11%), MM (1/25, 4%), and EAC (57/163, 35%), whereas PAX8 was positive in all NEM (61/61, 100%) and in the majority of SD (125/136, 92%), MM (19/25, 73%), and EAC (162/163, 99%). The estrogen receptor and the progesterone receptor were expressed by the majority of EAC (148/163, 91% and 144/163, 88%, respectively), whereas both were markedly diminished in SD (56/136, 41% and 58/136, 43%) and MM (4/25, 16% and 2/25, 8%). Approximately half of the MM was positive for bcl-2 (12/25, 48%), making it an unreliable marker. Her-2/neu was negative in all cases (0%). p16 was patchy in SD (111/136, 82%), MM (22/25, 88%), and EAC (154/163, 94%), whereas p63 was predominantly positive only in SD (96/136, 71%). Estrogen receptor and progesterone receptor, PAX2, and PAX8 were helpful in differentiating MM from SD, EAC, or NEM (P<0.05). In addition, p63 distinguished between SD and MM, supporting the theory that morules do not show characteristic mature SD.


Assuntos
Carcinoma Endometrioide/patologia , Diferenciação Celular , Neoplasias Ovarianas/patologia , Biomarcadores Tumorais/análise , Carcinoma Endometrioide/metabolismo , Feminino , Humanos , Imuno-Histoquímica , Metaplasia/metabolismo , Metaplasia/patologia , Neoplasias Ovarianas/metabolismo
10.
Hum Pathol ; 44(7): 1328-40, 2013 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-23363648

RESUMO

Follicular lymphoma (FL) in situ (FLIS) was first described and proposed as a distinct entity associated with an indolent clinical course in 2002. To gain further insight into the biology of this enigmatic lymphoproliferation, we analyzed morphologic, phenotypic, cytogenetic and molecular features of tissue specimens manifesting a pattern of follicular colonization by Bcl-2(bright+)CD10(+) B-cells and associated lymphomas from 13 adults and evaluated their clinical outcomes. We observed this immunoarchitectural pattern in lymph nodes (n = 8), at extranodal sites (n = 4), or at both locations (n = 1) at diagnosis. All except 3 cases showed concomitant bright CD10 expression. Six (46%) patients had synchronous and 2 (15%) developed metachronous B-cell lymphomas, with 5 representing high-grade lymphomas. The Bcl-2(bright+)CD10(+) B-cells colonizing reactive follicles and synchronous lymphomas were clonally related in 4/5 (80%) cases analyzed and 5/6 (83%) displayed BCL2 translocations. Two cases exhibited complex karyotypes in both components; a genetic "triple hit" was detected in one instance and 2 copies of t(14,18) were observed in a lymph node biopsy lacking evidence of lymphoma from an individual with stage 4 disease, suspected on imaging, who subsequently displayed a mantle zone/perifollicular infiltrate of Bcl-2(bright+)CD10(+) B-cells in the adenoids. Our findings suggest that bright Bcl-2, and often bright CD10 expression, by B-cells colonizing reactive follicles might represent a phenomenon related to follicular homing of lymphoma, rather than being an attribute of preneoplastic FL precursors. Furthermore, due to the relatively high frequency of overt lymphomas observed, complete staging workup is recommended for patients exhibiting a Bcl-2(bright+)CD10(+) B-cell follicular colonization pattern on biopsy.


Assuntos
Linfócitos B/patologia , Linfonodos/patologia , Linfoma de Células B/patologia , Linfoma Folicular/patologia , Neprilisina/metabolismo , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Adulto , Idoso , Bandeamento Cromossômico , Feminino , Rearranjo Gênico , Humanos , Cadeias Pesadas de Imunoglobulinas/genética , Hibridização in Situ Fluorescente , Linfoma de Células B/genética , Linfoma de Células B/imunologia , Linfoma Folicular/genética , Linfoma Folicular/imunologia , Masculino , Pessoa de Meia-Idade , Neoplasias Primárias Múltiplas , Estudos Retrospectivos
11.
J Cell Biochem ; 114(8): 1760-71, 2013 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-23444145

RESUMO

Bone morphogenetic proteins (BMPs) promote osteoblast differentiation and bone formation in vitro and in vivo. BMPs canonically signal through Smad transcription factors, but BMPs may activate signaling pathways traditionally stimulated by growth factor tyrosine kinase receptors. Of these, the mTOR pathway has received considerable attention because BMPs activate P70S6K, a downstream effector of mTOR, suggesting that BMP-induced osteogenesis is mediated by mTOR activation. However, contradictory effects of the mTOR inhibitor rapamycin (RAPA) on bone formation have been reported. Since bone formation is thought to be inversely related to lipid accumulation and mTOR is also important for lipid synthesis, we postulated that BMP-7 may stimulate lipogenic enzyme expression in a RAPA-sensitive mechanism. To test this hypothesis, we determined the effects of RAPA on BMP-7-stimulated expression of osteogenic and lipogenic markers in cultured fetal rat calvarial cells. Our study showed that BMP-7 promoted the expression of osteogenic and lipogenic markers. The effect of BMP-7 on osteogenic markers was greater in magnitude than on lipogenic markers and was temporally more sustained. RAPA inhibited basal and BMP-7-stimulated osteogenic and lipogenic marker expression and bone nodule mineralization. The acetyl CoA carboxylase inhibitor TOFA stimulated the expression of osteoblast differentiation markers, whereas palmitate suppressed their expression. We speculate that the BMP-7-stimulated adipogenesis is part of the normal anabolic response to BMPs, but that inappropriate activation of the lipid biosynthetic pathway by mTOR could have deleterious effects on bone formation and could explain paradoxical effects of RAPA to promote bone formation.


Assuntos
Antibacterianos/farmacologia , Antígenos de Diferenciação/biossíntese , Proteína Morfogenética Óssea 7/biossíntese , Regulação da Expressão Gênica/efeitos dos fármacos , Lipídeos/biossíntese , Osteogênese/efeitos dos fármacos , Sirolimo/farmacologia , Crânio/metabolismo , Animais , Calcificação Fisiológica/efeitos dos fármacos , Células Cultivadas , Ratos , Crânio/citologia , Serina-Treonina Quinases TOR/antagonistas & inibidores , Serina-Treonina Quinases TOR/metabolismo
12.
Hematol Oncol ; 31(1): 49-53, 2013 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-22618860

RESUMO

Post-transplant lymphoproliferative disorders of T-cell origin are quite uncommon, and the vast majority represent neoplasms of mature, post-thymic T- or natural killer cells. Here, we report a rare case of T-cell acute lymphoblastic leukaemia (T-ALL), which occurred in an 18-year-old man who had undergone three liver transplants, initially for biliary atresia and subsequently for graft failure due to chronic rejection. He had received immunosuppression with cyclosporine and tacrolimus, as well as short-term treatment with OKT3. The T-ALL occurred 16 years after the first liver transplant. This case highlights the challenge for classifying rare neoplasms occurring in recipients of solid organ transplants that are currently not recognized to lie within the spectrum of post-transplant lymphoproliferative disorders. Given the long interval between the liver transplants and the development of T-ALL, a coincidental occurrence of the leukaemia cannot be ruled out. However, the potential roles of immunosuppressive therapy and other co-morbid conditions of the individual as possible risk factors for the pathogenesis of T-ALL are discussed.


Assuntos
Transplante de Fígado , Complicações Pós-Operatórias/etiologia , Leucemia-Linfoma Linfoblástico de Células T Precursoras/etiologia , Adolescente , Atresia Biliar/cirurgia , Causalidade , Células Clonais/patologia , Comorbidade , Ciclosporina/efeitos adversos , Ciclosporina/uso terapêutico , Diagnóstico Diferencial , Suscetibilidade a Doenças , Rearranjo Gênico da Cadeia beta dos Receptores de Antígenos dos Linfócitos T , Rejeição de Enxerto/tratamento farmacológico , Rejeição de Enxerto/cirurgia , Humanos , Hospedeiro Imunocomprometido , Imunossupressores/efeitos adversos , Imunossupressores/uso terapêutico , Leucemia Induzida por Radiação/diagnóstico , Transtornos Linfoproliferativos/diagnóstico , Masculino , Muromonab-CD3/efeitos adversos , Muromonab-CD3/uso terapêutico , Leucemia-Linfoma Linfoblástico de Células T Precursoras/genética , Leucemia-Linfoma Linfoblástico de Células T Precursoras/imunologia , Radiografia/efeitos adversos , Indução de Remissão , Reoperação , Tacrolimo/efeitos adversos , Tacrolimo/uso terapêutico , Fatores de Tempo
13.
J Trauma Acute Care Surg ; 73(2): 326-31; discussion 331, 2012 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-22846935

RESUMO

BACKGROUND: The Trauma and Injury Severity Score (TRISS) has been the approach to trauma outcome prediction during the past 20 years and has been adopted by many commercial registries. Unfortunately, its survival predictions are based upon coefficients that were derived from a data set collected in the 1980s and updated only once using a data set collected in the early 1990s. We hypothesized that the improvements in trauma care during the past 20 years would lead to improved survival in a large database, thus making the TRISS biased. METHODS: The TRISSs from the Pennsylvania statewide trauma registry (Collector, Digital Innovations) for the years 1990 to 2010. Observed-to-expected mortality ratios for each year of the study were calculated by taking the ratio of actual deaths (observed deaths, O) to the summation of the probability of mortality predicted by the TRISS taken over all patients (expected deaths, E). For reference, O/E ratio should approach 1 if the TRISS is well calibrated (i.e., has predictive accuracy). RESULTS: There were 408,489 patients with complete data sufficient to calculate the TRISSs. There was a significant trend toward improved outcome (i.e., decreasing O/E ratio; nonparametric test of trend, p < 0.001) over time in both the total population and the blunt trauma subpopulation. In the penetrating trauma population, there was a trend toward improved outcome (decreasing O/E ratio), but it did not quite reach significance (nonparametric test of trend p = 0.073). CONCLUSION: There is a steady trend toward improved O/E survival in the Pennsylvania database with each passing year, suggesting that the TRISS is drifting out of calibration. It is likely that improvements in care account for these changes. For the TRISS to remain an accurate outcome prediction model, new coefficients would need to be calculated periodically to keep up with trends in trauma care. This requirement for occasional updating is likely to be a requirement of any trauma prediction model, but because many other deficiencies in the TRISS have been reported, we think that rather than updating the TRISS, it would be more productive to replace the TRISS with a modern statistical model.


Assuntos
Bases de Dados Factuais , Mortalidade Hospitalar/tendências , Escala de Gravidade do Ferimento , Índices de Gravidade do Trauma , Ferimentos e Lesões/mortalidade , Adolescente , Adulto , Distribuição por Idade , Idoso , Idoso de 80 Anos ou mais , Causas de Morte , Criança , Pré-Escolar , Intervalos de Confiança , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Modelos Estatísticos , Razão de Chances , Pennsylvania , Controle de Qualidade , Estudos Retrospectivos , Sensibilidade e Especificidade , Distribuição por Sexo , Análise de Sobrevida , Centros de Traumatologia , Resultado do Tratamento , Ferimentos e Lesões/diagnóstico , Ferimentos e Lesões/terapia , Adulto Jovem
14.
Am J Surg ; 202(4): 382-6, 2011 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-21816386

RESUMO

BACKGROUND: The aim of this study was to determine if prolonged immobility and tissue injury from a prehospital entrapment would place patients at higher risk for in-hospital venous thromboembolism (VTE) complications. It was hypothesized that entrapment would increase in-hospital VTE. METHODS: All consecutive trauma admissions over a 10-year period were retrospectively reviewed. Patients were divided into those who were entrapped according to defined prehospital criteria for entrapment and those who were not entrapped. The complications of deep vein thrombosis and pulmonary embolism were noted. RESULTS: There were 15,159 patients admitted between 1999 and 2008. Of these, 1,176 met the criteria for prehospital entrapment. Those patients who met the criteria for entrapment had a significant risk for developing both deep vein thrombosis (P < .001, χ(2) test) and pulmonary embolism (P = .005, Fisher's exact test). Multiple logistic regression analysis revealed entrapment to be a significant contributing risk factor to the development of VTE (odds ratio, 1.54; P = .04). CONCLUSIONS: Patients with prehospital entrapment are at higher risk for VTE. These results mandate aggressive VTE prophylaxis in patients with histories of prehospital entrapment.


Assuntos
Imobilização/efeitos adversos , Embolia Pulmonar/epidemiologia , Tromboembolia Venosa/epidemiologia , Ferimentos e Lesões/complicações , Adulto , Idoso , Humanos , Modelos Logísticos , Pessoa de Meia-Idade , Embolia Pulmonar/etiologia , Sistema de Registros , Estudos Retrospectivos , Tromboembolia Venosa/etiologia
15.
AJR Am J Roentgenol ; 195(2): W105-17, 2010 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-20651169

RESUMO

OBJECTIVE: We will illustrate the imaging features of gastrointestinal and nongastrointestinal mucosa-associated lymphoid tissue (MALT) lymphoma and their correlation with histopathologic findings. The radiologic features to distinguish gastrointestinal MALT lymphoma from other types of lymphomas will also be described. CONCLUSION: Differences in clinical behavior and management make it exceedingly important to differentiate MALT lymphoma from other types of lymphomas. Radiologic and histopathologic findings need to be taken into account before making a diagnosis and treatment plan.


Assuntos
Diagnóstico por Imagem/métodos , Linfoma de Zona Marginal Tipo Células B/diagnóstico , Humanos
17.
Breast Cancer Res ; 11(2): R18, 2009.
Artigo em Inglês | MEDLINE | ID: mdl-19320967

RESUMO

INTRODUCTION: We investigated clinical and pathologic features of breast cancers (BC) in an unselected series of patients diagnosed in a tertiary care hospital serving a diverse population. We focused on triple-negative (Tneg) tumours (oestrogen receptor (ER), progesterone receptor (PR) and HER2 negative), which are associated with poor prognosis. METHODS: We identified female patients with invasive BC diagnosed between 1998 and 2006, with data available on tumor grade, stage, ER, PR and HER2 status, and patient age, body mass index (BMI) and self-identified racial/ethnic group. We determined associations between patient and tumour characteristics using contingency tables and multivariate logistic regression. RESULTS: 415 cases were identified. Patients were racially and ethnically diverse (born in 44 countries, 36% white, 43% black, 10% Hispanic and 11% other). 47% were obese (BMI > 30 kg/m2). 72% of tumours were ER+ and/or PR+, 20% were Tneg and 13% were HER2+. The odds of having a Tneg tumour were 3-fold higher (95% CI 1.6, 5.5; p = 0.0001) in black compared with white women. Tneg tumours were equally common in black women diagnosed before and after age 50 (31% vs 29%; p = NS), and who were obese and non-obese (29% vs 31%; p = NS). Considering all patients, as BMI increased, the proportion of Tneg tumours decreased (p = 0.08). CONCLUSIONS: Black women of diverse background have 3-fold more Tneg tumours than non-black women, regardless of age and BMI. Other factors must determine tumour subtype. The higher prevalence of Tneg tumours in black women in all age and weight categories likely contributes to black women's unfavorable breast cancer prognosis.


Assuntos
Negro ou Afro-Americano/estatística & dados numéricos , Neoplasias da Mama/etnologia , Neoplasias da Mama/patologia , Receptor ErbB-2/metabolismo , Receptores de Estrogênio/metabolismo , Receptores de Progesterona/metabolismo , Fatores Etários , Índice de Massa Corporal , Neoplasias da Mama/metabolismo , Etnicidade , Feminino , Hispânico ou Latino/estatística & dados numéricos , Humanos , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Prognóstico , População Branca/estatística & dados numéricos
18.
Growth Factors ; 27(2): 121-31, 2009 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-19180354

RESUMO

Bone remodeling is a process consisting of bone formation and resorption. The present study compared the relative osteoclastic and osteoblastic potency of bone morphogenetic proteins (BMP)-2, -4, -5, -6, and -7 in primary murine bone marrow cultures. All five BMPs stimulated, to varying degree, formation of tartrate-resistant acid phosphatase (TRAP)-positive multinucleated cells in a time- and protein concentration-dependent manner. The TRAP staining intensity correlated positively with the number of nuclei per TRAP-positive cell and the mRNA levels of colony-stimulating factor (CSF-1), receptor activator of nuclear factor kappaB ligand (RANKL), TRAP, and cathepsin K. Under osteogenic conditions, all five BMPs stimulated AP activity and mineralized bone nodule formation in a protein concentration-dependent manner in the same primary murine bone marrow cell culture system. These findings should be useful in designing treatment strategies for bone regeneration.


Assuntos
Células da Medula Óssea/efeitos dos fármacos , Proteínas Morfogenéticas Ósseas/farmacologia , Remodelação Óssea/efeitos dos fármacos , Fosfatase Ácida/genética , Fosfatase Ácida/metabolismo , Animais , Células da Medula Óssea/citologia , Células da Medula Óssea/metabolismo , Regeneração Óssea/efeitos dos fármacos , Regeneração Óssea/genética , Regeneração Óssea/fisiologia , Remodelação Óssea/genética , Remodelação Óssea/fisiologia , Reabsorção Óssea/induzido quimicamente , Reabsorção Óssea/genética , Reabsorção Óssea/metabolismo , Reabsorção Óssea/patologia , Catepsina K , Catepsinas/genética , Contagem de Células , Diferenciação Celular/efeitos dos fármacos , Células Cultivadas , Expressão Gênica/efeitos dos fármacos , Isoenzimas/genética , Isoenzimas/metabolismo , Fator Estimulador de Colônias de Macrófagos/genética , Osteoblastos/citologia , Osteoblastos/efeitos dos fármacos , Osteoblastos/metabolismo , Osteoclastos/citologia , Osteoclastos/efeitos dos fármacos , Osteoclastos/metabolismo , Ligante RANK/genética , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Ratos , Proteínas Recombinantes/farmacologia , Fosfatase Ácida Resistente a Tartarato
19.
Am J Dermatopathol ; 31(1): 88-93, 2009 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-19155734

RESUMO

We report an unusual case of a lymph node interdigitating dendritic cell sarcoma (IDCS), metastatic to skin, in a 73-year-old patient. The patient initially presented as having a primary skin tumor with lymph node metastasis. The metastatic IDCS was initially read as an atypical fibroxanthoma. However, the morphology seen on the lymph node excision, paired with immunohistochemistry and electron microscopy studies, was diagnostic for an IDCS. Additional immunohistochemistry was performed on the shave biopsy, confirming that the skin tumor was a metastasis. IDCS is a rare tumor that belongs to the histiocytic and dendritic cell group of tumors. Diagnosing this entity is difficult without the aid of ancillary testing such as immunohistochemistry and electron microscopy. In the workup of a spindle cell neoplasm, IDCS should be included in the differential diagnosis.


Assuntos
Sarcoma de Células Dendríticas Interdigitantes/patologia , Linfonodos/patologia , Neoplasias Cutâneas/secundário , Idoso , Sarcoma de Células Dendríticas Interdigitantes/complicações , Sarcoma de Células Dendríticas Interdigitantes/metabolismo , Diagnóstico Diferencial , Histiocitoma Fibroso Benigno/patologia , Humanos , Hiperlipidemias/complicações , Hipertensão/complicações , Imuno-Histoquímica , Linfonodos/metabolismo , Segunda Neoplasia Primária/patologia , Neoplasias Cutâneas/complicações , Neoplasias Cutâneas/metabolismo
20.
Curr Opin Crit Care ; 12(4): 346-50, 2006 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-16810046

RESUMO

PURPOSE OF REVIEW: This article summarizes the current state of damage-control laparotomy as practiced in trauma surgery. Since the first description of deliberately abbreviated laparotomy 20 years ago, damage-control laparotomy has been widely applied. The purpose of this review is to discuss current concepts in damage-control laparotomy in trauma and general surgery patients. RECENT FINDINGS: The immediate, essential goals of control of surgical bleeding and containment of gastrointestinal soilage are achieved at a truncated laparotomy. Ongoing resuscitation of the injured patient with severe physiologic derangements is continued in the intensive care unit. Only when the lethal triad of hypothermia, metabolic acidosis, and coagulopathy is corrected does the patient subsequently undergo definitive surgery. Recent studies have better defined the subset of patients that benefit from such an approach. SUMMARY: Application of abbreviated laparotomy has been widely applied in the trauma population. Breaking the pathophysiologic cycle of hypothermia, coagulopathy, and acidosis with this approach has improved survivorship in this critically injured group of patients. The extension of the abbreviated laparotomy concept has also been described in the general surgery population, and raises the possibility of extending this concept to broader surgical fields.


Assuntos
Laparotomia/métodos , Ferimentos e Lesões/cirurgia , Acidose/etiologia , Acidose/prevenção & controle , Transtornos da Coagulação Sanguínea/etiologia , Transtornos da Coagulação Sanguínea/prevenção & controle , Humanos , Hipotermia/etiologia , Hipotermia/prevenção & controle , Ferimentos e Lesões/complicações
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA