Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 121
Filtrar
1.
HPB (Oxford) ; 2019 Nov 12.
Artigo em Inglês | MEDLINE | ID: mdl-31732463

RESUMO

BACKGROUND: Whether the risk of venous thromboembolism (VTE) may be reduced by preoperative administration of prophylactic heparin is unknown. We hypothesized that timing of heparin administration does not significantly alter the incidence of VTE in pancreatic surgery. METHODS: An analysis was conducted using data from Massachusetts General Hospital's National Surgical Quality Improvement Program from 2012 to 2017. All patients admitted for elective pancreatic resection were included. The primary outcome was development of VTE. Multivariable regression was performed, adjusting for patient demographics and various clinical factors. RESULTS: In total, 1448 patients were analyzed, of whom 1062 received preoperative heparin (73.3%). Overall, 36 (2.5%) patients developed VTE. On unadjusted analysis, there was no statistically significant difference between patients who received preoperative heparin compared with those who did not (2.6% vs. 1.3%, respectively; p = 0.079). On adjusted analysis, there was an association with increased VTE rates among patients who received preoperative heparin (OR 2.93, 95% CI 1.10-7.81; p = 0.031). CONCLUSION: There was an association between preoperative heparin administration and increased incidence of VTE on adjusted analysis, possibly reflecting appropriate surgical judgment in patient selection for prophylaxis. These data question the inclusion of preoperative VTE pharmacologic prophylaxis as a reliable quality indicator.

3.
Am J Surg ; 218(1): 230, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31202435
5.
J Am Coll Surg ; 228(4): 708-714, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30677526
7.
Surgery ; 164(4): 665-672, 2018 10.
Artigo em Inglês | MEDLINE | ID: mdl-30077391

RESUMO

BACKGROUND: Severe injury can lead to immune dysfunction and predispose patients to infection and death. Micro-RNAs regulate gene expression and may act as biomarkers for susceptibility to infection. The aim of this study was to examine the temporal and differential expression of previously identified dysregulated micro-RNAs in patients with severe injury. METHODS: Fourteen severely injured patients requiring transfusion were enrolled prospectively in this study approved by our institutional review board. Inclusion criteria consisted of adult patients deemed clinically to be in hemorrhagic shock necessitating transfusion in the acute phase of their injury care. Peripheral blood samples were obtained after admission to the surgical intensive care unit and again at 6, 12, 24, and 48 hours after admission. The samples obtained at arrival to the intensive care unit and 24 and 48 hours later were analyzed in this data set. Fourteen healthy volunteers served as controls. The 10 dysregulated micro-RNAs identified in a prior study at the 12-hour time point and important genes in innate immunity were measured using quantitative reverse transcription-polymerase chain reaction. RESULTS: The participants were 21-77 years old (median, 42), 78% were male, and their Injury Severity Score ranged from 11 to 43 (median, 27); 11 had blunt and 3 had penetrating injuries. Three were intubated and 5 had received blood products before arrival at the hospital. Base deficit on hospital admission was 3-20 (median, 9). All patients required blood transfusion secondary to blood loss sustained during injury. Eleven of the 14 patients went directly to the operating room from the emergency department for control of the source of hemorrhage. Survival to discharge was 93%. Seven patients developed infection. Compared with healthy controls, miR-106a was downregulated at all time points compared with controls (P < .05). miR-618 was upregulated in initial blood draws (P < .05) and at 24 and 48 hours (P < .06). Tumor necrosis factor α and human leukocyte antigen-DR (HLA-DR) were downregulated, and interleukin-10 and PD-L1 were upregulated (P < .05). In patients who developed infection, miR-106a levels appeared more downregulated than those who did not develop infection. CONCLUSION: miR-106a was downregulated in trauma patients after major injury for up to 48 hours after intensive care unit admission. Tumor necrosis factor α and interleukin-10 are targeted by miR-106a, which are regulators of the immune response. Manipulation of micro-RNA expression may be a therapeutic target for immune dysfunction.


Assuntos
MicroRNAs/sangue , Choque Hemorrágico/sangue , Choque Hemorrágico/etiologia , Ferimentos não Penetrantes/sangue , Ferimentos Penetrantes/sangue , Adulto , Idoso , Transfusão de Sangue , Estudos de Casos e Controles , Feminino , Humanos , Escala de Gravidade do Ferimento , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Choque Hemorrágico/terapia , Fatores de Tempo , Ferimentos não Penetrantes/complicações , Ferimentos não Penetrantes/terapia , Ferimentos Penetrantes/complicações , Ferimentos Penetrantes/terapia , Adulto Jovem
8.
J Am Coll Surg ; 226(4): 498-504, 2018 04.
Artigo em Inglês | MEDLINE | ID: mdl-29449123

RESUMO

BACKGROUND: In January 2014, Kentucky expanded Medicaid coverage to include all individuals and families with incomes up to 33% above the federal poverty line. This study evaluated the early impact of Medicaid expansion on some aspects of the quality of breast cancer care in Kentucky. STUDY DESIGN: The Kentucky Cancer Registry was queried for all women aged 20 to 64 years diagnosed with breast cancer between 2011 and 2016. Demographic, tumor, and treatment characteristics were assessed for each year during this interval. To evaluate the association between Medicaid expansion and these parameters, these variables, along with quality metrics deriving from said variables, were compared for the years 2011 to 2013 (pre) and the years 2014 to 2016 (post). RESULTS: Of 13,625 women with breast cancer, 11,915 (59.5%) were diagnosed and treated from 2011 to 2013, and 8,127 (40.5%) were diagnosed and treated from 2014 to 2016. After Medicaid expansion, fewer patients were uninsured (3.7% post vs 1.0% pre) and more were covered by Medicaid (15.9% post vs 10.9% pre) (p < 0.001). There was increased diagnosis of early stage (I and II) breast cancer (p = 0.002) and an increasing proportion of women undergoing breast-conservation therapy (p < 0.001). Time from diagnosis to operation increased (p < 0.001), time from operation to chemotherapy remained unchanged (p = 0.26) and time from operation to radiation decreased (p < 0.001). CONCLUSIONS: The expansion of Kentucky Medicaid in 2014 has been associated with earlier diagnosis and somewhat improved quality of breast cancer care, despite a stable disease incidence. Additional improvements in treatment expediency will require improvements in patient outreach and healthcare infrastructure.


Assuntos
Neoplasias da Mama/terapia , Cobertura do Seguro , Seguro Saúde , Medicaid , Qualidade da Assistência à Saúde , Adulto , Idoso , Neoplasias da Mama/patologia , Feminino , Humanos , Kentucky , Pessoa de Meia-Idade , Estudos Retrospectivos , Estados Unidos , Adulto Jovem
10.
Am J Surg ; 216(2): 189-193, 2018 08.
Artigo em Inglês | MEDLINE | ID: mdl-28666579

RESUMO

BACKGROUND: There are an increasing number of women in surgery. Previously, many questions focused upon their ability to complete surgical training and contribute fully to the surgical workforce. More meaningful information lies in identifying the long-term follow-up of where, and in what specialty, women residents eventually practice. METHODS: All residents entering general surgery training at the University of Louisville between 1996 and 2009 were studied. Comparison between men and women was performed for program completion, length of residency training, and eventual specialty practice. RESULTS: One hundred and eight residents entered general surgery residency. Twenty-three (21%) did not complete training. There was no difference in attrition rates between men or women (22% vs. 19%, p = 0.77). Women completing residency were just as likely to practice general surgery (either private or academic practice) as their male counterparts (67% vs. 67% p = 0.96). CONCLUSIONS: Women are a valuable resource in surgery and are able to complete a vigorous residency. Long-term follow-up is crucial and permits us to evaluate this important group of trainees practicing surgery today.


Assuntos
Escolha da Profissão , Educação Médica/tendências , Cirurgia Geral/educação , Internato e Residência/tendências , Médicas , Feminino , Seguimentos , Humanos , Masculino , Estudos Retrospectivos
11.
Immunobiology ; 223(4-5): 365-373, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29126656

RESUMO

This study focuses on impaired monocyte function, which occurs in some patients after trauma, major elective surgery, or sepsis. This monocyte impairment increases the risk of secondary infection and death. We aimed to determine the influence IκK-16 had on monocytes using an ex-vivo model of human monocyte impairment. We included the effects of the well-studied comparators interferon-gamma (IFN-γ) and granulocyte-macrophage colony-stimulating factor (GM-CSF) on impaired monocytes. Primary human monocytes were stimulated with 10ng/mL of lipopolysaccharide (LPS) for 16h and then challenged with 100ng/mL LPS to assess the monocyte inflammatory response. Treatment regimens, consisting of either IκK-16, IFN-γ, or GM-CSF, were administered to impaired monocytes near the time of initial LPS stimulation. Stimulation with 10ng/mL LPS initially promoted a pro-inflammatory response but subsequently impaired production of both tumor necrosis factor-α (TNF-α) and interleukin-10 (IL-10) and decreased HLA-DR expression. IκK-16 treatment attenuated TNF-α production and programmed death-ligand 1 (PD-L1) expression and increased IL-10 and CD14 expression. IFN-γ treatment increased TNF-α production as well as PD-L1 and HLA-DR expression. In conclusion, limiting early inflammation with IκK-16 suppresses TNF-α production and PD-L1 expression but enhances IL-10 production and preserves CD14 expression for potential future exposure to infective stimuli.


Assuntos
Transtornos Traumáticos Cumulativos/imunologia , Cirurgia Geral , Quinase I-kappa B/antagonistas & inibidores , Inflamação/imunologia , Monócitos/imunologia , Piperidinas/farmacologia , Complicações Pós-Operatórias/imunologia , Inibidores de Proteínas Quinases/farmacologia , Pirrolidinas/farmacologia , Sepse/imunologia , Adulto , Células Cultivadas , Procedimentos Cirúrgicos Eletivos , Feminino , Humanos , Separação Imunomagnética , Receptores de Lipopolissacarídeos/metabolismo , Lipopolissacarídeos/imunologia , Masculino , Adulto Jovem
12.
J Surg Res ; 217: 3-5, 2017 09.
Artigo em Inglês | MEDLINE | ID: mdl-28918961

RESUMO

This reflection retraces the evolution of early followers and leaders. Social change and early contributions set the stage for the current Association for Academic Surgery. Perhaps the most important contribution was Dr. George Zuidema's theme of inclusiveness. AAS was a decade ahead of its time in that regard.


Assuntos
Cirurgia Geral/organização & administração , Sociedades Médicas/história , História do Século XX
13.
PLoS One ; 12(9): e0183987, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28910312

RESUMO

Excessive inflammatory responses in the surgical patient may result in cellular hypo-responsiveness, which is associated with an increased risk of secondary infection and death. microRNAs (miRNAs), such as miR-155, are powerful regulators of inflammatory signalling pathways including nuclear factor κB (NFκB). Our objective was to determine the effect of IκK-16, a selective blocker of inhibitor of kappa-B kinase (IκK), on miRNA expression and the monocyte inflammatory response. In a model of endotoxin tolerance using primary human monocytes, impaired monocytes had decreased p65 expression with suppressed TNF-α and IL-10 production (P < 0.05). miR-155 and miR-138 levels were significantly upregulated at 17 h in the impaired monocyte (P < 0.05). Notably, IκK-16 decreased miR-155 expression with a corresponding dose-dependent decrease in TNF-α and IL-10 production (P < 0.05), and impaired monocyte function was associated with increased miR-155 and miR-138 expression. In the context of IκK-16 inhibition, miR-155 mimics increased TNF-α production, while miR-155 antagomirs decreased both TNF-α and IL-10 production. These data demonstrate that IκK-16 treatment attenuates the monocyte inflammatory response, which may occur through a miR-155-mediated mechanism, and that IκK-16 is a promising approach to limit the magnitude of an excessive innate inflammatory response to LPS.


Assuntos
Regulação da Expressão Gênica/efeitos dos fármacos , MicroRNAs/biossíntese , Monócitos/metabolismo , Inibidores de Proteínas Quinases/farmacologia , Feminino , Humanos , Inflamação/induzido quimicamente , Inflamação/tratamento farmacológico , Inflamação/metabolismo , Inflamação/patologia , Interleucina-10/biossíntese , Lipopolissacarídeos/toxicidade , Masculino , Monócitos/patologia , Fator de Necrose Tumoral alfa/biossíntese
14.
PLoS One ; 12(4): e0174899, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28380006

RESUMO

We have reported a new phenomenon in acute wound healing following the use of intracellular ATP delivery-extremely rapid tissue regeneration, which starts less than 24 h after surgery, and is accompanied by massive macrophage trafficking, in situ proliferation, and direct collagen production. This unusual process bypasses the formation of the traditional provisional extracellular matrix and significantly shortens the wound healing process. Although macrophages/monocytes are known to play a critical role in the initiation and progression of wound healing, their in situ proliferation and direct collagen production in wound healing have never been reported previously. We have explored these two very specific pathways during wound healing, while excluding confounding factors in the in vivo environment by analyzing wound samples and performing in vitro studies. The use of immunohistochemical studies enabled the detection of in situ macrophage proliferation in ATP-vesicle treated wounds. Primary human macrophages and Raw 264.7 cells were used for an in vitro study involving treatment with ATP vesicles, free Mg-ATP alone, lipid vesicles alone, Regranex, or culture medium. Collagen type 1α 1, MCP-1, IL-6, and IL-10 levels were determined by ELISA of the culture supernatant. The intracellular collagen type 1α1 localization was determined with immunocytochemistry. ATP-vesicle treated wounds showed high immunoreactivity towards BrdU and PCNA antigens, indicating in situ proliferation. Most of the cultured macrophages treated with ATP-vesicles maintained their classic phenotype and expressed high levels of collagen type 1α1 for a longer duration than was observed with cells treated with Regranex. These studies provide the first clear evidence of in situ macrophage proliferation and direct collagen production during wound healing. These findings provide part of the explanation for the extremely rapid tissue regeneration, and this treatment may hold promise for acute and chronic wound care.


Assuntos
Trifosfato de Adenosina/uso terapêutico , Cicatrização/efeitos dos fármacos , Trifosfato de Adenosina/administração & dosagem , Animais , Quimiocina CCL2/metabolismo , Colágeno Tipo I/metabolismo , Humanos , Interleucina-10/metabolismo , Interleucina-6/metabolismo , Lipossomos , Macrófagos/efeitos dos fármacos , Macrófagos/fisiologia , Camundongos , Células RAW 264.7/efeitos dos fármacos , Células RAW 264.7/fisiologia , Fatores de Tempo
15.
Surg Infect (Larchmt) ; 17(5): 563-9, 2016 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-27309382

RESUMO

BACKGROUND: Patients who survive the early phases of major sepsis and trauma can have greater susceptibility to nosocomial infection later. One cause may be impaired monocyte function, which can leave the patient at risk of overwhelming sepsis and multi-organ dysfunction. Efforts to target this immune defect have been fraught with challenges, with many questions unanswered. We summarized the past and current and likely future therapeutic approaches to augmentation of monocyte function in the surgical patient. METHODS: A literature search was conducted using PubMed to determine the evidence to date for immunoadjuvant therapy specifically for monocyte impairment. The search terms were "monocyte," "immunoparalysis," "tolerance," and "deactivation" cross-referenced with "trauma," "major surgery," and "sepsis." We supplemented our search with "interferon-γ," "granulocyte colony-stimulating factor" (G-CSF), and "granulocyte-macrophage colony-stimulating factor" (GM-CSF), known agents used for this purpose. We limited our findings to clinical trials in human beings. Relevant currently registered trials relating to impaired monocyte function also were included. RESULTS: Interferon-γ appears to be the most commonly studied therapeutic agent to augment monocyte function, followed in decreasing order by GM-CSF and G-CSF. Studies were heterogeneous, generally under-powered, and enrolled few target patients with documented monocyte impairment. Finally, current studies are focusing on personalized therapy in order to treat those with monocyte impairment, with attention to programmed cell death protein 1 (PD-1) and programmed cell death ligand (PD-L1) as both markers and therapeutic targets. CONCLUSION: Early studies have been promising in identifying patients who are likely to benefit from monocyte augmentation; i.e., those with low HLA-DR or ex-vivo tumor necrosis factor (TNF)-α production. The surgeon remains incompletely equipped to enhance monocyte function consistently and specifically in order to reduce the mortality rate. Although there is little evidence to support the routine use of any of these immunotherapies, the issues of patient selection, timing of administration, and treatment duration have hampered any true answers to this important clinical problem. The challenge remains in identifying the right patients, at the right time, to receive the right therapy.


Assuntos
Monócitos , Procedimentos Cirúrgicos Operatórios , Adjuvantes Imunológicos , Fator Estimulador de Colônias de Granulócitos/imunologia , Fator Estimulador de Colônias de Granulócitos/farmacologia , Humanos , Interferon gama/imunologia , Interferon gama/farmacologia , Monócitos/efeitos dos fármacos , Monócitos/imunologia , Monócitos/fisiologia , Sepse/imunologia
16.
Surg Infect (Larchmt) ; 17(3): 303-12, 2016 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-26958709

RESUMO

BACKGROUND: Trauma, major elective surgery, and overt sepsis can lead to a cascade of immunological change. A subset of these patients will have a degree of immune suppression that leads to hyporesponsive innate defenses, increasing the risk of infective co-morbidity and death. This article is an overview of monocyte impairment in the high-risk surgical patient. Specifically, our primary focus is on observations made pertaining to monocyte function and pathophysiological mechanisms underpinning this impairment. Clinical factors influencing monocyte function are also discussed. METHODS: A Pubmed search was conducted to review aspects of monocyte impairment in the surgical patient. Search terms included "monocyte impairment," "immunoparalysis," and "endotoxin tolerance" cross-referenced against terms including "trauma," "major surgery," and "sepsis." RESULTS: Findings revealed a broad variety of monocyte defects reported in surgical patients. They ranged from altered cytokine responses, particularly ex vivo TNF-α production, to impaired antigen presentation such as depressed HLA-DR expression. The latter is the most commonly described marker of secondary infection and death. Studies of underlying mechanisms have commonly utilized a model of endotoxin tolerance with in vitro monocytes, revealing a complex array of dysregulated pathways. For our purposes, endotoxin tolerance and monocyte impairment are sufficiently similar entities to permit further study as a single subject. In the high risk patient, microRNAs (also referred to as miRNA or miR) are emerging as potential biomarkers that may modify such pathways. Creation of a reliable impaired human monocyte model could be important to all such considerations. CONCLUSION: Impairment of monocyte function continues to be predictive of nosocomial infection, multi-organ failure, and death in some surgical patients. However, the optimal marker that could identify a patient as high risk early enough, and whether it might guide potential therapy, still is yet to be proven.


Assuntos
Monócitos/imunologia , Monócitos/fisiologia , Complicações Pós-Operatórias/imunologia , Infecção Hospitalar/diagnóstico , Infecção Hospitalar/etiologia , Infecção Hospitalar/imunologia , Infecção Hospitalar/mortalidade , Humanos , Insuficiência de Múltiplos Órgãos/diagnóstico , Insuficiência de Múltiplos Órgãos/etiologia , Insuficiência de Múltiplos Órgãos/imunologia , Insuficiência de Múltiplos Órgãos/mortalidade , Complicações Pós-Operatórias/diagnóstico , Complicações Pós-Operatórias/mortalidade , Prognóstico , Medição de Risco , Infecção da Ferida Cirúrgica/diagnóstico , Infecção da Ferida Cirúrgica/imunologia , Infecção da Ferida Cirúrgica/mortalidade
17.
Ann Surg ; 263(3): 601-7, 2016 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-25719808

RESUMO

OBJECTIVE: To investigate whether warming to normal body temperature or to febrile range temperature (39°C) is able to reverse the detrimental effects of hypothermia. BACKGROUND: Unintentional intraoperative hypothermia is a well-described risk factor for surgical site infections but also sepsis. We have previously shown that hypothermia prolongs the proinflammatory response whereas normothermia and especially febrile range temperature enhance the anti-inflammatory response. METHODS: Primary human monocytes were isolated from healthy volunteers. After stimulation with LPS (Lipopolysaccharide), the monocytes were exposed to 32°C for 3  hours or 6  hours and then warmed at either 37°C or 39°C for the remaining 33  hours or 36  hours, respectively. Tumor necrosis factor α, interleukin 10, and the expression of miR-155 and miR-101 were assessed at 24  hours and 36  hours. RESULTS: Warming to 37°C does not normalize monocyte cytokine secretion within 36  hours, whereas warming to 39°C partially reverses the effects of hypothermia on monocyte function. Both miR-155 and miR-101 were suppressed after the warming episode. However, 39°C had a stronger suppressive effect than 37°C. The duration of hypothermia and the warming temperature seem to be critical for a full reversibility of the effects of hypothermia. CONCLUSION: Warming to normal body temperature (37°C) does not restore normal monocyte function in vitro. These data suggest that hypothermic patients should be warmed to febrile range temperatures. Furthermore, febrile range temperatures should be investigated as a means to modulate the inflammatory response in patients with systemic infections.


Assuntos
Citocinas/metabolismo , Hipotermia/metabolismo , Hipotermia/terapia , Monócitos/metabolismo , Reaquecimento/métodos , Biomarcadores/metabolismo , Ensaio de Imunoadsorção Enzimática , Imunofluorescência , Humanos , Interleucina-10/metabolismo , Interleucina-12/metabolismo , Interleucina-6/metabolismo , MicroRNAs/metabolismo , Fator de Necrose Tumoral alfa/metabolismo
18.
Surgery ; 158(3): 646-54, 2015 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-26054320

RESUMO

INTRODUCTION: Hypothermia is a well-known risk factor for postoperative complications because it prolongs the monocyte inflammatory response. The purpose of this study was to investigate whether temperature-activated ion channels (transient receptor protein channels [TRP] A1 and V1) mediate the effects of temperature on monocytes. METHODS: Primary human monocytes were isolated and stimulated with lipopolysaccharide at 32°C or 39°C. RNA was isolated for analysis of microRNA (miR)-155 expression, and cytokines in the supernatant were measured with an enzyme-linked immunosorbent assay. Specific inhibitors of TRPA1 (HC- 030031) and a specific activator of TRPV1 (capsaicin) were used to block or activate TRPA1 and TRPV1, respectively. Statistical analysis was performed using the Wilcoxon signed-rank test. RESULTS: TRPM8 mRNA was not expressed in primary human monocytes, whereas TRPA1 and TRPV1 were expressed. TRPV1 mRNA expression was suppressed at 32°C but not at 39°C. TRPA1 was induced strongly at 32°C and 39°C. Immunofluorescence microscopy confirmed that monocytes express TRPA1 and TRPV1 on their cell surface. Interleukin-10 secretion was increased by blocking TRPA1 (77.8 ± 3 2.8 pg/mL) and activating TRPA1 (79.4 ± 16.1 pg/mL) after 24 hours at 32°C (control 37.4 ± 17.1 pg/mL, P < .05). At 36 hours, tumor necrosis factor secretion was decreased after TRPA1 blockade (2,321 ± 439 pg/mL) and TRPV1 activation (2,137 ± 411 pg/mL) compared with control (2,567 ± 495 pg/mL, P < .05). Furthermore, miR-155 expression also was suppressed at 24 hours by TRPA1 blockade and TRPV1 activation (both P < .05). Silencing of TRPA1 normalized monocyte IL-10 secretion at 32°C. CONCLUSION: These results demonstrate that hypothermia mediates its effects on monocytes through TRPA1. Blockade of TRPA1 or activation of TRPV1 may be used to modify the effects of hypothermia on the monocyte inflammatory response.


Assuntos
Canais de Cálcio/metabolismo , Temperatura Baixa/efeitos adversos , Hipotermia/imunologia , Monócitos/metabolismo , Proteínas do Tecido Nervoso/metabolismo , Canais de Cátion TRPV/metabolismo , Canais de Receptores Transientes de Potencial/metabolismo , Biomarcadores/metabolismo , Western Blotting , Células Cultivadas , Citocinas/metabolismo , Ensaio de Imunoadsorção Enzimática , Humanos , Hipotermia/metabolismo , Microscopia de Fluorescência , Proteínas do Tecido Nervoso/antagonistas & inibidores , Canal de Cátion TRPA1 , Canais de Cátion TRPV/antagonistas & inibidores , Canais de Receptores Transientes de Potencial/antagonistas & inibidores
19.
FASEB J ; 28(12): 5322-36, 2014 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-25231976

RESUMO

Therapeutic hypothermia is commonly used to improve neurological outcomes in patients after cardiac arrest. However, therapeutic hypothermia increases sepsis risk and unintentional hypothermia in surgical patients increases infectious complications. Nonetheless, the molecular mechanisms by which hypothermia dysregulates innate immunity are incompletely understood. We found that exposure of human monocytes to cold (32°C) potentiated LPS-induced production of TNF and IL-6, while blunting IL-10 production. This dysregulation was associated with increased expression of microRNA-155 (miR-155), which potentiates Toll-like receptor (TLR) signaling by negatively regulating Ship1 and Socs1. Indeed, Ship1 and Socs1 were suppressed at 32°C and miR-155 antagomirs increased Ship1 and Socs1 and reversed the alterations in cytokine production in cold-exposed monocytes. In contrast, miR-155 mimics phenocopied the effects of cold exposure, reducing Ship1 and Socs1 and altering TNF and IL-10 production. In a murine model of LPS-induced peritonitis, cold exposure potentiated hypothermia and decreased survival (10 vs. 50%; P < 0.05), effects that were associated with increased miR-155, suppression of Ship1 and Socs1, and alterations in TNF and IL-10. Importantly, miR-155-deficiency reduced hypothermia and improved survival (78 vs. 32%, P < 0.05), which was associated with increased Ship1, Socs1, and IL-10. These results establish a causal role of miR-155 in the dysregulation of the inflammatory response to hypothermia.


Assuntos
Hipotermia/complicações , Inflamação/fisiopatologia , Interleucina-10/antagonistas & inibidores , MicroRNAs/fisiologia , Animais , Células Cultivadas , Citocinas/biossíntese , Humanos , Inflamação/etiologia , Interleucina-10/biossíntese , Camundongos , Monócitos/metabolismo , Transdução de Sinais , Receptores Toll-Like/metabolismo
20.
Am J Surg ; 208(5): 835-840, 2014 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-25113797

RESUMO

BACKGROUND: We present a comprehensive systematic review of the effect of Surgical Care Improvement Project (SCIP) measures on surgical site infections (SSIs) as related to SCIP compliance. DATA SOURCES: A systematic review of the peer-reviewed literature was performed on PubMed, Medline, and Cochrane database group using their own search engines. Keywords used were Surgical Care Improvement Project (SCIP), adherence, compliance, surgical site infection (SSI), infection bundle, antibiotics, perioperative antibiotics, and combinations thereof. Furthermore, reference lists of selected articles were cross-searched for additional literature. Papers published from January 1, 1998 to January 1, 2014 were included. RESULTS: A comprehensive analysis of these data demonstrated an 18% decrease in the odds of developing SSI and a cumulative 4% decrease in SSI. The largest increases in compliance for individual SCIP measures were reported between 2004 and 2006. However, compliance with multiple measures simultaneously had the sharpest increase between 2006 and 2009 without a definitive asymptote ascertained from the current data. CONCLUSIONS: These results represent some positive progress toward the SCIP task force's 2006 goal of a 25% decrease in SSI by 2010. Suggestions for improved future papers in this area were also added.


Assuntos
Fidelidade a Diretrizes/estatística & dados numéricos , Assistência Perioperatória/normas , Melhoria de Qualidade/estatística & dados numéricos , Infecção da Ferida Cirúrgica/prevenção & controle , Humanos , Assistência Perioperatória/métodos , Guias de Prática Clínica como Assunto , Avaliação de Programas e Projetos de Saúde , Estados Unidos
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA