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1.
Surg Endosc ; 36(9): 6696-6704, 2022 09.
Artigo em Inglês | MEDLINE | ID: mdl-34981223

RESUMO

BACKGROUND: Laparoscopic cholecystectomies continue to pose trouble for surgeons in the face of severe inflammation. In the advent of inability to perform an adequate dissection, a "bailout cholecystectomy" is advocated. Conversion to open or subtotal cholecystectomy is among the standard bailout procedures in such instances. METHODS: We performed a retrospective single institution review from January 2016 to August 2019. All patients who underwent a cholecystectomy were included, while those with a concurrent operation, malignancy, planned as an open cholecystectomy, or performed by a low volume surgeon were excluded. Patient characteristics, operative reports, and outcomes were collected, as were surgeon characteristics such as years of experience, case volume, and bailout rate. Univariable and multivariable analysis were performed. RESULTS: 2458 (92.6%) underwent laparoscopic total cholecystectomy (LTC) and 196 (7.4%) underwent a bailout cholecystectomy (BOC). BOC patients tended to be older (p < 0.001), male (p < 0.001), have a longer duration of symptoms (p < 0.001), and higher ASA class (p < 0.001). They also had more signs of biliary inflammation, as evidenced by increased leukocytosis (p < 0.001), tachycardia (p < 0.001), bilirubinemia (p = 0.003), common bile duct dilation (p < 0.001), and gallbladder wall thickening (p < 0.001). The BOC cohort also had increased rates of complications, including bile leak (16%, p < 0.001), retained stone (5.1%, p = 0.005), operative time (114 min vs 79 min, p < 0.001), and secondary interventions (22.7%, p < 0.001). Male gender (aOR = 2.8, p < 0.001), preoperative diagnosis of acute cholecystitis (aOR = 2.2, p = 0.032), right upper quadrant tenderness (aOR = 3.0, p = 0.008), Asian race (aOR = 2.7, p = 0.014), and intraoperative adhesions (aOR = 13.0, p < 0.001) were found to carry independent risk for BOC. Surgeon bailout rate ≥ 7% was also found to be an independent risk factor for conversion to BOC. CONCLUSIONS: Male gender, signs of biliary inflammation (tachycardia, leukocytosis, dilated CBD, and diagnosis of acute cholecystitis), as well as surgeon bailout rate of 7% were independent risk factors for BOC.


Assuntos
Colecistectomia Laparoscópica , Colecistite Aguda , Cirurgiões , Colecistectomia/métodos , Colecistectomia Laparoscópica/efeitos adversos , Colecistectomia Laparoscópica/métodos , Colecistite Aguda/etiologia , Colecistite Aguda/cirurgia , Humanos , Inflamação/etiologia , Leucocitose/etiologia , Leucocitose/cirurgia , Masculino , Estudos Retrospectivos
2.
JCI Insight ; 5(20)2020 10 15.
Artigo em Inglês | MEDLINE | ID: mdl-32910808

RESUMO

Focal adhesion kinase (FAK) is an important mediator of extracellular matrix-integrin mechano-signal transduction that regulates cell motility, survival, and proliferation. As such, FAK is being investigated as a potential therapeutic target for malignant and fibrotic diseases, and numerous clinical trials of FAK inhibitors are underway. The function of FAK in nonmalignant, nonmotile epithelial cells is not well understood. We previously showed that hepatocytes demonstrated activated FAK near stiff collagen tracts in fibrotic livers. In this study, we examined the role of liver epithelial FAK by inducing fibrotic liver disease in mice with liver epithelial FAK deficiency. We found that mice that lacked FAK in liver epithelial cells developed more severe liver injury and worse fibrosis as compared with controls. Increased fibrosis in liver epithelial FAK-deficient mice was linked to the activation of several profibrotic pathways, including the hedgehog/smoothened pathway. FAK-deficient hepatocytes produced increased Indian hedgehog in a manner dependent on matrix stiffness. Furthermore, expression of the hedgehog receptor, smoothened, was increased in macrophages and biliary cells of hepatocyte-specific FAK-deficient fibrotic livers. These results indicate that liver epithelial FAK has important regulatory roles in the response to liver injury and progression of fibrosis.


Assuntos
Células Epiteliais/metabolismo , Quinase 1 de Adesão Focal/genética , Cirrose Hepática/genética , Receptor Smoothened/genética , Animais , Movimento Celular/genética , Proliferação de Células/genética , Células Epiteliais/patologia , Matriz Extracelular/genética , Matriz Extracelular/metabolismo , Proteínas Hedgehog/genética , Hepatócitos/metabolismo , Hepatócitos/patologia , Humanos , Fígado/lesões , Fígado/patologia , Cirrose Hepática/metabolismo , Cirrose Hepática/patologia , Camundongos , Camundongos Knockout , Transdução de Sinais/genética
3.
Am J Physiol Regul Integr Comp Physiol ; 308(6): R480-8, 2015 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-25568077

RESUMO

Healthy immune function depends on precise regulation of lymphocyte activation. During the National Aeronautics and Space Administration (NASA) Apollo and Shuttle eras, multiple spaceflight studies showed depressed lymphocyte activity under microgravity (µg) conditions. Scientists on the ground use two models of simulated µg (sµg): 1) the rotating wall vessel (RWV) and 2) the random positioning machine (RPM), to study the effects of altered gravity on cell function before advancing research to the true µg when spaceflight opportunities become available on the International Space Station (ISS). The objective of this study is to compare the effects of true µg and sµg on the expression of key early T-cell activation genes in mouse splenocytes from spaceflight and ground animals. For the first time, we compared all three conditions of microgravity spaceflight, RPM, and RWV during immune gene activation of Il2, Il2rα, Ifnγ, and Tagap; moreover, we confirm two new early T-cell activation genes, Iigp1 and Slamf1. Gene expression for all samples was analyzed using quantitative real-time PCR (qRT-PCR). Our results demonstrate significantly increased gene expression in activated ground samples with suppression of mouse immune function in spaceflight, RPM, and RWV samples. These findings indicate that sµg models provide an excellent test bed for scientists to develop baseline studies and augment true µg in spaceflight experiments. Ultimately, sµg and spaceflight studies in lymphocytes may provide insight into novel regulatory pathways, benefiting both future astronauts and those here on earth suffering from immune disorders.


Assuntos
Tolerância Imunológica/genética , Ativação Linfocitária/genética , Voo Espacial , Baço/imunologia , Linfócitos T/imunologia , Simulação de Ausência de Peso , Animais , Técnicas de Cultura de Células , Células Cultivadas , Regulação para Baixo , Feminino , Proteínas Ativadoras de GTPase/genética , Proteínas Ativadoras de GTPase/metabolismo , Interferon gama/genética , Interferon gama/metabolismo , Interleucina-2/genética , Interleucina-2/metabolismo , Subunidade alfa de Receptor de Interleucina-2/genética , Subunidade alfa de Receptor de Interleucina-2/metabolismo , Camundongos Endogâmicos C57BL , RNA Mensageiro/metabolismo , Reação em Cadeia da Polimerase em Tempo Real , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Baço/citologia , Baço/metabolismo , Linfócitos T/metabolismo
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