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1.
Artigo em Inglês | MEDLINE | ID: mdl-38729387

RESUMO

BACKGROUND & AIMS: Large language models including Chat Generative Pretrained Transformers version 4 (ChatGPT4) improve access to artificial intelligence, but their impact on the clinical practice of gastroenterology is undefined. This study compared the accuracy, concordance, and reliability of ChatGPT4 colonoscopy recommendations for colorectal cancer rescreening and surveillance with contemporary guidelines and real-world gastroenterology practice. METHODS: History of present illness, colonoscopy data, and pathology reports from patients undergoing procedures at 2 large academic centers were entered into ChatGPT4 and it was queried for the next recommended colonoscopy follow-up interval. Using the McNemar test and inter-rater reliability, we compared the recommendations made by ChatGPT4 with the actual surveillance interval provided in the endoscopist's procedure report (gastroenterology practice) and the appropriate US Multisociety Task Force (USMSTF) guidance. The latter was generated for each case by an expert panel using the clinical information and guideline documents as reference. RESULTS: Text input of de-identified data into ChatGPT4 from 505 consecutive patients undergoing colonoscopy between January 1 and April 30, 2023, elicited a successful follow-up recommendation in 99.2% of the queries. ChatGPT4 recommendations were in closer agreement with the USMSTF Panel (85.7%) than gastroenterology practice recommendations with the USMSTF Panel (75.4%) (P < .001). Of the 14.3% discordant recommendations between ChatGPT4 and the USMSTF Panel, recommendations were for later screening in 26 (5.1%) and for earlier screening in 44 (8.7%) cases. The inter-rater reliability was good for ChatGPT4 vs USMSTF Panel (Fleiss κ, 0.786; 95% CI, 0.734-0.838; P < .001). CONCLUSIONS: Initial real-world results suggest that ChatGPT4 can define routine colonoscopy screening intervals accurately based on verbatim input of clinical data. Large language models have potential for clinical applications, but further training is needed for broad use.

2.
Am J Gastroenterol ; 119(7): 1383-1391, 2024 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-38235741

RESUMO

INTRODUCTION: Adenoma per colonoscopy (APC) has recently been proposed as a quality measure for colonoscopy. We evaluated the impact of a novel artificial intelligence (AI) system, compared with standard high-definition colonoscopy, for APC measurement. METHODS: This was a US-based, multicenter, prospective randomized trial examining a novel AI detection system (EW10-EC02) that enables a real-time colorectal polyp detection enabled with the colonoscope (CAD-EYE). Eligible average-risk subjects (45 years or older) undergoing screening or surveillance colonoscopy were randomized to undergo either CAD-EYE-assisted colonoscopy (CAC) or conventional colonoscopy (CC). Modified intention-to-treat analysis was performed for all patients who completed colonoscopy with the primary outcome of APC. Secondary outcomes included positive predictive value (total number of adenomas divided by total polyps removed) and adenoma detection rate. RESULTS: In modified intention-to-treat analysis, of 1,031 subjects (age: 59.1 ± 9.8 years; 49.9% male), 510 underwent CAC vs 523 underwent CC with no significant differences in age, gender, ethnicity, or colonoscopy indication between the 2 groups. CAC led to a significantly higher APC compared with CC: 0.99 ± 1.6 vs 0.85 ± 1.5, P = 0.02, incidence rate ratio 1.17 (1.03-1.33, P = 0.02) with no significant difference in the withdrawal time: 11.28 ± 4.59 minutes vs 10.8 ± 4.81 minutes; P = 0.11 between the 2 groups. Difference in positive predictive value of a polyp being an adenoma among CAC and CC was less than 10% threshold established: 48.6% vs 54%, 95% CI -9.56% to -1.48%. There were no significant differences in adenoma detection rate (46.9% vs 42.8%), advanced adenoma (6.5% vs 6.3%), sessile serrated lesion detection rate (12.9% vs 10.1%), and polyp detection rate (63.9% vs 59.3%) between the 2 groups. There was a higher polyp per colonoscopy with CAC compared with CC: 1.68 ± 2.1 vs 1.33 ± 1.8 (incidence rate ratio 1.27; 1.15-1.4; P < 0.01). DISCUSSION: Use of a novel AI detection system showed to a significantly higher number of adenomas per colonoscopy compared with conventional high-definition colonoscopy without any increase in colonoscopy withdrawal time, thus supporting the use of AI-assisted colonoscopy to improve colonoscopy quality ( ClinicalTrials.gov NCT04979962).


Assuntos
Adenoma , Inteligência Artificial , Pólipos do Colo , Colonoscopia , Neoplasias Colorretais , Detecção Precoce de Câncer , Humanos , Colonoscopia/métodos , Masculino , Pessoa de Meia-Idade , Feminino , Adenoma/diagnóstico , Adenoma/diagnóstico por imagem , Estudos Prospectivos , Pólipos do Colo/diagnóstico , Pólipos do Colo/diagnóstico por imagem , Pólipos do Colo/patologia , Detecção Precoce de Câncer/métodos , Idoso , Neoplasias Colorretais/diagnóstico , Estados Unidos , Valor Preditivo dos Testes , Análise de Intenção de Tratamento
3.
Endoscopy ; 2024 Jul 19.
Artigo em Inglês | MEDLINE | ID: mdl-39029912

RESUMO

BACKGROUND: The role of endoscopic mucosal resection (EMR) for laterally spreading lesions (LSLs) in inflammatory bowel disease (IBD) remains controversial despite its effectiveness in the general population. We aim to characterize outcomes of EMR for IBD-associated LSLs compared to controls without IBD. METHODS: We performed a retrospective observational cohort study of patients with IBD who underwent EMR and endoscopic follow-up for LSLs, compared to a control group without IBD. The primary outcome was histologic recurrence; secondary outcomes included en bloc resection and adverse events. Factors associated with recurrence were identified using multivariate mixed effects logistic regression. RESULTS: A total of 210 pre-malignant lesions in 155 patients were included. By histology, 91% were adenoma/low-grade dysplasia or sessile serrated lesions. Average lesion size was 22.9 mm (SD 11.3 mm) in the IBD group, and 21.5 mm (SD 12.4 mm) in the control group. Recurrence occurred in 30.4% of IBD-associated lesions (7/23) compared to 20.9% of controls (39/187; OR=2.51, CI .59-10.71). En bloc resection was less common in the IBD group (2/23, 8.7%, 95% CI 1.1-28.0) versus controls (106/187, 57.9%, 95% CI 50.4-65.2). After adjusting for lesion size and histology, recurrence appeared more common in patients with IBD compared to controls (OR=3.08, 95% CI 1.04-9.13). CONCLUSIONS: Recurrence of LSLs after EMR appears more frequent in patients with IBD. Given the added complexity, EMR in patients with IBD should be performed in expert centers with close endoscopic surveillance.

4.
J Clin Gastroenterol ; 58(5): 487-493, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-37339277

RESUMO

GOALS: This study aims to investigate associated mortality with inpatient endoscopic retrograde cholangiopancreatography (ERCP) with and without resistant infections. The co-primary objective compares frequencies of inpatient ERCP with resistant infections to overall hospitalizations with resistant infections. BACKGROUND: The risks of inpatient antibiotic-resistant organisms are known, but the associated mortality for inpatient ERCP is unknown. We aim to use a national database of hospitalizations and procedures to understand trends and mortality for patients with antibiotic-resistant infections during inpatient ERCP. STUDY: The largest publicly available all-payer inpatient database in the United States (National Inpatient Sample) was used to identify hospitalizations associated with ERCPs and antibiotic-resistant infections for MRSA, VRE, ESBL, and MDRO. National estimates were generated, frequencies were compared across years, and multivariate regression for mortality was performed. RESULTS: From 2017 to 2020, national weighted estimates of 835,540 inpatient ERCPs were generated, and 11,440 ERCPs had coincident resistant infections. Overall resistant infection, MRSA, VRE, and MDRO identified at the same hospitalization of inpatient ERCPs were associated with higher mortality (OR CI(95%): Overall: 2.2(1.77-2.88), MRSA: 1.90 (1.34-2.69), VRE: 3.53 (2.16-5.76), and MDRO: 2.52 (1.39-4.55)). While overall hospitalizations with resistant infections have been decreasing annually, there has been a yearly increase in admissions requiring ERCPs with simultaneous resistant infections ( P =0.001-0.013), as well as infections with VRE, ESBL, and MDRO ( P =0.001-0.016). Required Research Practices for Studies Using the NIS scoring was 0, or the most optimal. CONCLUSIONS: Inpatient ERCPs have increasing coincident resistant infections and are associated with higher mortality. These rising infections during ERCP highlight the importance of endoscopy suite protocols and endoscopic infection control devices.


Assuntos
Colangiopancreatografia Retrógrada Endoscópica , Pacientes Internados , Humanos , Estados Unidos/epidemiologia , Colangiopancreatografia Retrógrada Endoscópica/efeitos adversos , Estudos Transversais , Antibacterianos/uso terapêutico , Estudos de Coortes , Estudos Retrospectivos
5.
Gastrointest Endosc ; 2023 Dec 11.
Artigo em Inglês | MEDLINE | ID: mdl-38092125

RESUMO

BACKGROUND AND AIMS: Endoscopic mucosal resection (EMR) with use of electrocautery (conventional EMR) has historically been used to remove large duodenal adenomas, however, use of electrocautery can predispose to adverse events including delayed bleeding and perforation. Cold snare EMR (cs-EMR) has been shown to be safe and effective for removal of colon polyps, but data regarding its use in the duodenum is limited. The aim of this study is to evaluate the efficacy and safety of cs-EMR for nonampullary duodenal adenomas ≥1 cm. METHODS: This was a multicenter retrospective study of patients with nonampullary duodenal adenomas ≥1 cm who underwent cs-EMR between October 2014 and May 2023. Patients who received any form of thermal therapy were excluded. Primary outcomes were technical success and rate of recurrent adenoma. Secondary outcomes were adverse events and predictors of recurrence. RESULTS: A total of 125 patients underwent resection of 127 nonampullary duodenal adenomas with cs-EMR. Follow up data was available in 89 cases (70.1%). The recurrent adenoma rate was 31.5% (n=28). Adverse events occurred in 3.9% (n=5) with four cases of immediate bleeding (3.1%) and one case of delayed bleeding (0.8%). There were no cases of perforation. The presence of high-grade dysplasia was found to be an independent predictor of recurrence (OR: 10.9 [95% CI: 1.1-102.1], p=0.036). CONCLUSION: This retrospective multicenter study demonstrates that cs-EMR for nonampullary duodenal adenomas is safe and technically feasible with an acceptable recurrence rate. Future prospective studies are needed to directly compare outcomes of cs-EMR with conventional and underwater EMR.

6.
Surg Endosc ; 37(11): 8166-8177, 2023 11.
Artigo em Inglês | MEDLINE | ID: mdl-37730854

RESUMO

BACKGROUND: Obesity is a major threat to public health and traditional bariatric surgery continues to have low utilization. Endoscopic treatments for obesity have emerged that offer less risk, but questions remain regarding efficacy, durability, and safety. We compared the efficacy of endoscopic bariatric procedures as compared to other existing treatments. METHODS: A literature search of Embase, Cochrane Central, and Pubmed was conducted from January 1, 2014 to December 7, 2021, including endoscopic bariatric therapies that were FDA or CE approved at the time of search to non-endoscopic treatments. Thirty-seven studies involving 15,639 patients were included. Primary outcomes included % total body weight loss (%TBWL), % excess body weight loss (%EBWL), and adverse events. Secondary outcomes included quality of life data and differences in hemoglobin A1C levels. Strength of clinical trial and observational data were graded according to the Cochrane methods. RESULTS: Intragastric balloons achieved greater %TBWL with a range of 7.6-14.1% compared to 3.3-6.7% with lifestyle modification at 6 months, and 7.5-14.0% compared to 3.1-7.9%, respectively, at 12 months. When endoscopic sleeve gastroplasty (ESG) was compared to laparoscopic sleeve gastrectomy (LSG), ESG had less %TBWL at 4.7-14.4% compared to 18.8-26.5% after LSG at 6 months, and 4.5-18.6% as compared to 28.4-29.3%, respectively, at 12 months. For the AspireAssist, there was greater %TBWL with aspiration therapy compared to lifestyle modification at 12 months, 12.1-18.3% TBWL versus 3.5-5.9% TBWL, respectively. All endoscopic interventions had higher adverse events rates compared to lifestyle modification. CONCLUSION: This review is the first to evaluate various endoscopic bariatric therapies using only RCTs and observational studies for evaluation of weight loss compared with conservative management, lifestyle modification, and bariatric surgery. Endoscopic therapies result in greater weight loss compared to lifestyle modification, but not as much as bariatric surgery. Endoscopic therapies may be beneficial as an alternative to bariatric surgery.


Assuntos
Gastroplastia , Obesidade Mórbida , Humanos , Qualidade de Vida , Resultado do Tratamento , Obesidade/cirurgia , Obesidade/etiologia , Endoscopia/métodos , Gastroplastia/métodos , Redução de Peso , Obesidade Mórbida/cirurgia
8.
Clin Gastroenterol Hepatol ; 17(3): 469-476, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-29857147

RESUMO

BACKGROUND & AIMS: Colorectal cancer is common yet largely preventable. The fecal immunochemical test (FIT) is a highly recommended screening method, but patients with positive results must receive a follow-up colonoscopy to determine if they have precancerous or cancerous lesions. We characterized colonoscopic follow-up evaluations and reasons for lack of follow-up in a Veterans Affairs (VA) cohort. METHODS: We conducted a retrospective cross-sectional analysis of patients 50 to 75 years old with a positive FIT result from January 1, 2014, through May 31, 2016, in a network of 12 VAs sites in southern California. We determined the proportion of patients who received a follow-up colonoscopy, median time to colonoscopy, and colonoscopy findings. For patients who did not undergo colonoscopy, we determined the documented reason for lack of colonoscopy and factors associated with declining the colonoscopy examination. RESULTS: Of the 10,635 FITs performed, 916 (8.6%) produced positive results; 569 of these (62.1%) were followed by colonoscopy. The median time to colonoscopy after a positive FIT result was 83 days (interquartile range, 54-145 d), which did not vary between veterans who received a colonoscopy at a VA facility (81 d; interquartile range, 52-143 d) vs a non-VA site (87 d; interquartile range, 60-154 d) (P = .2). For the 347 veterans (37.9%) who did not undergo follow-up colonoscopy, the reasons were patient-related (49.3%), provider-related (16.4%), system-related (12.1%), or multifactorial (22.2%). Overall, patient decline of colonoscopy (35.2%) was the most common reason. CONCLUSIONS: In a cohort of veterans with positive results from FITs during CRC screening, reasons for lack of follow-up colonoscopy varied and included patient, provider, and system factors. These findings can be used to reduce barriers to follow-up colonoscopy and to address system-level challenges in scheduling and attrition for colonoscopy.


Assuntos
Colonoscopia/estatística & dados numéricos , Neoplasias Colorretais/diagnóstico , Detecção Precoce de Câncer/estatística & dados numéricos , Utilização de Instalações e Serviços/estatística & dados numéricos , Idoso , California , Estudos Transversais , Testes Diagnósticos de Rotina/métodos , Fezes/química , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Veteranos
9.
J Clin Gastroenterol ; 53(2): 142-146, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-29912761

RESUMO

BACKGROUND: Nonalcoholic steatohepatitis (NASH) is a common cause of liver disease which can progress to cirrhosis and hepatocellular carcinoma (HCC). American Association for the Study of Liver Diseases (AASLD) guidelines recommend abdominal ultrasound, with or without serum alpha-fetoprotein, every 6 months for HCC surveillance in cirrhotic patients. GOALS: Describe HCC surveillance rates in NASH cirrhosis compared with hepatitis C (HCV) cirrhosis and the impact of surveillance on tumor size, treatment, and mortality. STUDY: Adults with NASH and HCV cirrhosis diagnosed with HCC from 2009 to 2016 were retrospectively evaluated. Patients were categorized into 3 mutually exclusive disease screening groups based on abdominal imaging with or without serum alpha-fetoprotein testing before HCC diagnosis. RESULTS: In total, 99 patients with NASH cirrhosis and 162 patients with HCV cirrhosis were evaluated. In total, 51.5% of NASH cirrhosis patients and 25.9% of HCV cirrhosis patients had no screening before HCC diagnosis. Patients with HCV cirrhosis were significantly more likely to undergo surveillance compared with patients with NASH cirrhosis (P=0.002). NASH cirrhosis patients who underwent complete screening had smaller tumors compared with those with incomplete screening and no screening (P=0.006). There were no differences in number of tumors at diagnosis or mortality between screening groups in patients with NASH cirrhosis (P=0.281 and 0.468, respectively). CONCLUSIONS: There is suboptimal HCC surveillance in NASH and HCV cirrhotic patients, with a greater proportion of patients with NASH cirrhosis not undergoing surveillance. Patients with NASH cirrhosis who had complete surveillance had smaller tumors at diagnosis, but there were no differences in treatment outcomes or mortality.


Assuntos
Carcinoma Hepatocelular/diagnóstico , Neoplasias Hepáticas/diagnóstico , Programas de Rastreamento/estatística & dados numéricos , Hepatopatia Gordurosa não Alcoólica/complicações , Idoso , Carcinoma Hepatocelular/etiologia , Carcinoma Hepatocelular/patologia , Detecção Precoce de Câncer/estatística & dados numéricos , Feminino , Hepatite C/complicações , Humanos , Cirrose Hepática/complicações , Neoplasias Hepáticas/etiologia , Neoplasias Hepáticas/patologia , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , alfa-Fetoproteínas/análise
10.
J Clin Gastroenterol ; 53(4): 309-313, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-29912756

RESUMO

BACKGROUND: Hepatocellular carcinoma (HCC) accounts for 90% of primary hepatic malignancies. With the exception of chronic hepatitis B (CHB), other etiologies of chronic liver disease require progression to cirrhosis before HCC development. Case reports have described HCC in noncirrhotic patients with hepatitis C (HCV) and nonalcoholic fatty liver disease. GOAL: The aim of this study was to determine the prevalence of patients without cirrhosis and CHB who developed HCC among a large cohort of HCC patients and to identify independent variables that are associated with no cirrhosis among patients with HCC. STUDY: From 2005 to 2015, hepatobiliary cancer patients seen in our liver cancer and liver transplant clinics were evaluated. Patients were included if above18 years old and had histologically confirmed HCC from liver biopsy, resection specimen, or explanted livers. Patients with CHB, non-HCC tumors, or missing paired tumor and nontumor liver histology were excluded. Demographic information, pertinent laboratory values, and comorbid conditions were recorded. Potential predictors were evaluated using both backward stepwise logistic regression model and classification tree model. RESULTS: Of the 1927 patients screened, 545 HCC patients (411 transplanted, 43 resected, 74 transarterial chemoembolization/radiofrequency ablation, 17 untreated) included, 29 (5.3%) patients had no cirrhosis histologically. Eleven patients had HCV, 3 had alcoholic liver disease, 3 had nonalcoholic fatty liver, and 12 had cryptogenic liver disease. Logistic regression models show that patients with hyperlipidemia and elevated serum alanine aminotransferase are more likely to develop HCC without cirrhosis (odds ratio, 1.73 and 0.40; P<0.05). CONCLUSIONS: This large cohort, histology-confirmed case-controlled study shows that patients with nonalcoholic fatty liver disease and hyperlipidemia with elevated serum alanine aminotransferase (most likely nonalcoholic steatohepatitis) are significantly associated with the development of HCC in the absence of cirrhosis.


Assuntos
Carcinoma Hepatocelular/epidemiologia , Hiperlipidemias/epidemiologia , Neoplasias Hepáticas/epidemiologia , Hepatopatia Gordurosa não Alcoólica/epidemiologia , Idoso , Alanina Transaminase/sangue , Carcinoma Hepatocelular/etiologia , Estudos de Casos e Controles , Estudos de Coortes , Progressão da Doença , Feminino , Humanos , Hiperlipidemias/complicações , Cirrose Hepática/epidemiologia , Neoplasias Hepáticas/etiologia , Masculino , Pessoa de Meia-Idade , Hepatopatia Gordurosa não Alcoólica/complicações , Fatores de Risco
11.
Curr Gastroenterol Rep ; 20(7): 32, 2018 Jun 09.
Artigo em Inglês | MEDLINE | ID: mdl-29886564

RESUMO

PURPOSE OF REVIEW: The goal of this review is to critically analyze the current literature regarding the management of incidental pancreatic cysts. Given their increased rates of detection due to the frequent use of cross-sectional imaging, correctly identifying the subset of high risk lesions that are appropriate for surgical resection is critical. However, the existing consensus and societal guidelines discussed in this review lack high quality data to create evidence-based recommendations, making achieving this important aim challenging. RECENT FINDINGS: Several recent studies have focused on the natural history of pancreatic cysts and defining the role of endoscopic ultrasound, which remains unclear. EUS-guided diagnostic tools include molecular analysis of obtained fluid; EUS-guided FNA, FNB, and intracystic forceps biopsy of the cyst wall; and confocal endomicroscopy. While their precise role in diagnosing pancreatic cystic neoplasms remains to be defined, they represent promising innovations that may play a future role in cyst assessment and management. Large, long-term, prospective studies of incidentally identified pancreatic cysts are essential to fully understand their natural history and potential for neoplastic progression. Given the absence of such data at present, an individualized patient approach is recommended.


Assuntos
Cisto Pancreático/terapia , Humanos , Achados Incidentais
14.
Exp Lung Res ; 42(1): 24-36, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-26789411

RESUMO

PURPOSE: Recent studies have employed animal models to investigate links between rhinovirus infection and allergic airways disease, however, most do not involve early life infection, and none consider the effects of sex on responses. MATERIALS AND METHODS: Here, we infected male and female mice with human rhinovirus 1B (or control) on day 7 of life. Mice were then subjected to 7 weeks of exposure to house-dust-mite prior to assessment of bronchoalveolar inflammation, serum antibodies, lung function, and responsiveness to methacholine. RESULTS: There were significant differences in responses between males and females in most outcomes. In males, chronic house-dust-mite exposure increased bronchoalveolar inflammation, house-dust-mite specific IgG1 and responsiveness of the lung parenchyma, however, there was no additional impact of rhinovirus infection. Conversely, in females, there were additive and synergistic effects of rhinovirus infection and house-dust-mite exposure on neutrophilia, airway resistance, and responsiveness of the lung parenchyma. CONCLUSIONS: We conclude that early life rhinovirus infection influences the development of house-dust-mite induced lung disease in female, but not male mice.


Assuntos
Pneumopatias/imunologia , Pneumopatias/virologia , Pyroglyphidae/imunologia , Rhinovirus/imunologia , Animais , Líquido da Lavagem Broncoalveolar/imunologia , Líquido da Lavagem Broncoalveolar/virologia , Feminino , Hipersensibilidade/imunologia , Hipersensibilidade/virologia , Imunoglobulina G/imunologia , Inflamação/imunologia , Inflamação/virologia , Pulmão/imunologia , Pulmão/virologia , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Infecções por Picornaviridae/imunologia , Infecções por Picornaviridae/virologia
16.
J Hepatol ; 60(5): 1002-9, 2014 May.
Artigo em Inglês | MEDLINE | ID: mdl-24365171

RESUMO

BACKGROUND & AIMS: Fibroblast Growth Factors (FGFs) promote the proliferation and survival of hepatic progenitor cells (HPCs) via AKT-dependent ß-catenin activation. Moreover, the emergence of hepatocytes expressing the HPC marker A6 during 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC)-induced liver injury is mediated partly by FGF and ß-catenin signaling. Herein, we investigate the role of FGF signaling and AKT-mediated ß-catenin activation in acute DDC liver injury. METHODS: Transgenic mice were fed DDC chow for 14days concurrent with either Fgf10 over-expression or inhibition of FGF signaling via expression of soluble dominant-negative FGF Receptor (R)-2IIIb. RESULTS: After 14days of DDC treatment, there was an increase in periportal cells expressing FGFR1, FGFR2, and AKT-activated phospho-Serine 552 (pSer552) ß-Catenin in association with up-regulation of genes encoding the FGFR2IIIb ligands, Fgf7, Fgf10, and Fgf22. In response to Fgf10 over-expression, there was an increase in the number of pSer552-ß-Catenin((positive)+ive) periportal cells as well as cells co-positive for A6 and hepatocyte marker, Hepatocyte Nuclear Factor-4α (HNF4α). A similar expansion of A6(+ive) cells was observed after Fgf10 over-expression with regular chow and after partial hepatectomy during ethanol toxicity. Inhibition of FGF signaling increased the periportal A6(+ive)HNF4α(+ive) cell population while reducing centrolobular A6(+ive) HNF4α(+ive) cells. AKT inhibition with Wortmannin attenuated FGF10-mediated A6(+ive)HNF4α(+ive) cell expansion. In vitro analyses using FGF10 treated HepG2 cells demonstrated AKT-mediated ß-Catenin activation but not enhanced cell migration. CONCLUSIONS: During acute DDC treatment, FGF signaling promotes the expansion of A6-expressing liver cells partly via AKT-dependent activation of ß-Catenin expansion of A6(+ive) periportal cells and possibly by reprogramming of centrolobular hepatocytes.


Assuntos
Fatores de Crescimento de Fibroblastos/metabolismo , Hepatócitos/citologia , Hepatócitos/metabolismo , Proteínas dos Microfilamentos/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , beta Catenina/metabolismo , Animais , Biomarcadores/metabolismo , Proliferação de Células , Doença Hepática Induzida por Substâncias e Drogas/genética , Doença Hepática Induzida por Substâncias e Drogas/metabolismo , Doença Hepática Induzida por Substâncias e Drogas/patologia , Fator 10 de Crescimento de Fibroblastos/genética , Fator 10 de Crescimento de Fibroblastos/metabolismo , Fatores de Crescimento de Fibroblastos/genética , Células Hep G2 , Fator 4 Nuclear de Hepatócito/genética , Fator 4 Nuclear de Hepatócito/metabolismo , Hepatócitos/efeitos dos fármacos , Humanos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Inibidores de Fosfoinositídeo-3 Quinase , Proteínas Tirosina Quinases/metabolismo , Piridinas/toxicidade , Receptores de Fatores de Crescimento de Fibroblastos/genética , Receptores de Fatores de Crescimento de Fibroblastos/metabolismo , Transdução de Sinais/efeitos dos fármacos , Células-Tronco/citologia , Células-Tronco/metabolismo , Regulação para Cima/efeitos dos fármacos
18.
Inhal Toxicol ; 26(7): 409-18, 2014 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-24862975

RESUMO

CONTEXT: Mice are commonly used in studies investigating the effects of diesel exhaust exposure on respiratory health. A plethora of studies in this field has resulted in a range of exposure protocols, from inhalation of diesel exhaust, to the administration (via various routes) of diesel exhaust particles in solution. OBJECTIVE: In this study, we compared the physiological consequences of short-term exposure to diesel exhaust via inhalation to those due to exposure to the same diesel exhaust particles suspended in solution and delivered intranasally. MATERIALS AND METHODS: Adult BALB/c mice were exposed to diesel exhaust via inhalation for 2 hours per day for 8 days. A representative, simultaneous sample of particles was collected and a second group of mice then exposed to them suspended in saline. A low and a high-dose were studied, with these matched based on respiratory parameters. Six and twenty-four hours after the last exposure we measured bronchoalveolar inflammation, lung volume, lung function and the amount of elemental carbon in alveolar macrophages. RESULTS: Exposure via either route elicited pulmonary inflammation and changes in lung function. We identified significant differences in response between the two routes of exposure, with mice exposed via inhalation generally displaying more realistic dose-response relationships. Mice exposed via intranasal instillation responded more variably, with little influence of dose. CONCLUSIONS: Our results suggest that selection of the route of exposure is of critical importance in studies such as this. Further, inhalation exposure, while more methodologically difficult, resulted in responses more akin to those seen in humans.


Assuntos
Poluentes Atmosféricos/toxicidade , Exposição por Inalação/efeitos adversos , Pulmão/efeitos dos fármacos , Macrófagos Alveolares/efeitos dos fármacos , Pneumonia/induzido quimicamente , Mucosa Respiratória/efeitos dos fármacos , Emissões de Veículos/toxicidade , Administração Intranasal , Animais , Câmaras de Exposição Atmosférica , Líquido da Lavagem Broncoalveolar/química , Líquido da Lavagem Broncoalveolar/imunologia , Relação Dose-Resposta a Droga , Feminino , Humanos , Instilação de Medicamentos , Pulmão/imunologia , Pulmão/fisiopatologia , Macrófagos Alveolares/química , Macrófagos Alveolares/imunologia , Camundongos Endogâmicos BALB C , Material Particulado/administração & dosagem , Material Particulado/química , Material Particulado/toxicidade , Pneumonia/imunologia , Pneumonia/fisiopatologia , Reprodutibilidade dos Testes , Testes de Função Respiratória , Mucosa Respiratória/imunologia , Mucosa Respiratória/fisiopatologia , Testes de Toxicidade Subaguda
19.
Case Rep Psychiatry ; 2024: 5184741, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38482162

RESUMO

Catatonia is a neuropsychiatric syndrome typically marked by disturbances in motor activity, speech, and behavior. It has historically been associated with psychiatric illness, but acute medical illness, neurocognitive disorders, and neurodevelopmental disorders can cause catatonia as well. Catatonia is likely underrecognized and underdiagnosed in the general medical hospital, despite high risks of morbidity and mortality and the availability of rapidly effective treatment. Here, we present a case of catatonia secondary to traumatic brain injury that responded to lorazepam after a delayed diagnosis. A young male patient who was incarcerated and assaulted was sent to the emergency department multiple times for unresponsive and unpredictable behavior, including not agreeing to be released home. After being admitted with the diagnosis of postconcussive syndrome, he was ultimately diagnosed with catatonia, and intravenous lorazepam resulted in a return to his baseline mental status. We discuss factors that led to the delay in diagnosis, including lack of training in recognition of catatonia, suspicion of feigned symptoms for secondary gain, and the implication of stigma in an African American young male arrested for a drug-related crime.

20.
VideoGIE ; 8(3): 130-133, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-36935803

RESUMO

Video 1Over-the-scope clip to the rescue: solution for duodenal perforation from migrated biliary stent.

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