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1.
J Surg Oncol ; 2024 Jul 17.
Artigo em Inglês | MEDLINE | ID: mdl-39016067

RESUMO

BACKGROUND & OBJECTIVES: Screening for pancreatic cancer is recommended for individuals with a strong family history, certain genetic syndromes, or a neoplastic cyst of the pancreas. However, limited data supports a survival benefit attributable to screening these higher-risk individuals. METHODS: All patients enrolled in screening at a High-Risk Pancreatic Cancer Clinic (HRC) from July 2013 to June 2020 were identified from a prospectively maintained institutional database and compared to patients evaluated at a Surgical Oncology Clinic (SOC) at the same institution during the same period. Clinical outcomes of patients selected for surgical resection, particularly clinicopathologic stage and overall survival, were compared. RESULTS: Among 826 HRC patients followed for a median (IQR) of 2.3 (0.8-4.2) years, 128 were selected for surgical resection and compared to 402 SOC patients selected for resection. Overall survival was significantly longer among HRC patients (median survival: not reached vs. 2.6 years, p < 0.001). Among 31 HRC and 217 SOC patients with a diagnosis of pancreatic ductal adenocarcinoma (PDAC), the majority of HRC patients were diagnosed with stage 0 disease (carcinoma in situ), while the majority of SOC patients were diagnosed with stage II disease (p < 0.001). Overall survival after resection of invasive PDAC was also significantly longer among HRC patients compared to SOC patients (median survival 5.5 vs. 1.6 years, p = 0.002). CONCLUSION: Patients at increased risk for PDAC and followed with guideline-based screening exhibited downstaging of disease and improved survival from PDAC in comparison to patients who were not screened.

2.
Ann Intern Med ; 177(7): 911-918, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38768450

RESUMO

BACKGROUND: Real-time prediction of histologic features of small colorectal polyps may prevent resection and/or pathologic evaluation and therefore decrease colonoscopy costs. Previous studies showed that computer-aided diagnosis (CADx) was highly accurate, though it did not outperform expert endoscopists. OBJECTIVE: To assess the diagnostic performance of histologic predictions by general endoscopists before and after assistance from CADx in a real-life setting. DESIGN: Prospective, multicenter, single-group study. (ClinicalTrials.gov: NCT04437615). SETTING: 6 centers across the United States. PARTICIPANTS: 1252 consecutive patients undergoing colonoscopy and 49 general endoscopists with variable experience in real-time prediction of polyp histologic features. INTERVENTION: Real-time use of CADx during routine colonoscopy. MEASUREMENTS: The primary end points were the sensitivity and specificity of CADx-unassisted and CADx-assisted histologic predictions for adenomas measuring 5 mm or less. For clinical purposes, additional estimates according to location and confidence level were provided. RESULTS: The CADx device made a diagnosis for 2695 polyps measuring 5 mm or less (96%) in 1252 patients. There was no difference in sensitivity between the unassisted and assisted groups (90.7% vs. 90.8%; P = 0.52). Specificity was higher in the CADx-assisted group (59.5% vs. 64.7%; P < 0.001). Among all 2695 polyps measuring 5 mm or less, 88.2% and 86.1% (P < 0.001) in the CADx-assisted and unassisted groups, respectively, could be resected and discarded without pathologic evaluation. Among 743 rectosigmoid polyps measuring 5 mm or less, 49.5% and 47.9% (P < 0.001) in the CADx-assisted and unassisted groups, respectively, could be left in situ without resection. LIMITATION: Decision making based on CADx might differ outside a clinical trial. CONCLUSION: CADx assistance did not result in increased sensitivity of optical diagnosis. Despite a slight increase, the specificity of CADx-assisted diagnosis remained suboptimal. PRIMARY FUNDING SOURCE: Olympus America Corporation served as the clinical study sponsor.


Assuntos
Inteligência Artificial , Pólipos do Colo , Colonoscopia , Diagnóstico por Computador , Sensibilidade e Especificidade , Humanos , Pólipos do Colo/patologia , Estudos Prospectivos , Feminino , Masculino , Pessoa de Meia-Idade , Idoso , Adenoma/patologia , Adenoma/diagnóstico , Neoplasias Colorretais/patologia , Competência Clínica , Adulto
3.
Surg Open Sci ; 13: 35-40, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-37151961

RESUMO

Background: Americas Hepato-Pancreato-Biliary Association (AHPBA) established the Hepato-Pancreato-Biliary (HPB) ultrasound (US) and Advanced Technology Post-Graduate Course in 2012 in response to a perceived gap in training and practice. Methods: The HPB US and Advanced Technology Post-Graduate Course consists of both didactic and hands-on skills sessions. The didactic sessions are divided into foundational, organ-focused, and application content. Hands-on sessions are constructed to immediately practice skills in the simulation setting which were taught during the didactic sessions. Course participant demographic data (practice location and practice type) and participant evaluations were reported. Results: Since the first course in 2012, 298 participants have taken the post-graduate course. Most participants reported the content quality, delivery effectiveness, and practice relevance to be either excellent or above average (93.6 %, 91.1 %, 93.6 %, respectively). Participants' motivations to take the course included to enhance skills, knowledge, to incorporate US into practice, or to obtain formal training or qualification/certification, or to teach. Conclusion: The HPB US and Advanced Technology Post-Graduate Course has filled a gap in HPB US training for practicing HPB surgeons. The annual course has been well-received by participants (Kirkpatrick Level 1 Program Evaluation) and will continue to fill the gap in training in operative US for the HPB surgeon. Key message: Americas Hepato-Pancreato-Biliary Association established the HPB Ultrasound and Advanced Technology Post-Graduate Course in 2012. The Course has been well-received by participants and will continue to address a gap in surgical HPB training.

4.
Surg Open Sci ; 10: 182-207, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-36324368

RESUMO

Background: Ultrasound is an essential tool for the hepatobiliary and pancreatic surgeon. Methods: This review focuses on transabdominal, open intraoperative, and laparoscopic ultrasonography of the liver, biliary tract, and pancreas. The goal is to obtain optimal ultrasound images through an understanding of the equipment setup, transducer (probe) selection, terminology, and general scanning principles. Outlined is a structured, standardized approach necessary to obtain complete information when doing intraoperative ultrasound. When done by the surgeon, the goal of the examination typically is to answer a question or questions through a focused rather than a comprehensive diagnostic examination. Finally, presented are the details of techniques specific to scanning each of the major organs. Results: A structured, standardized ultrasound scanning approach provides for optimal image acquisition. It allows one to develop standardized views of common structures resulting in "pattern recognition," making learning and interpreting images easier. A standardized approach ensures a complete ultrasound examination, and it minimizes the chance of missed findings. Summary: The general principles for transabdominal, open intraoperative, and laparoscopic ultrasonography scanning are similar. One can gather considerable information using these modalities during a clinical examination, procedure, or operation. For success, it is critical to develop a standardized approach to scanning and use it every time. This facilitates familiarity when viewing images, making it easier for the novice to learn and gain experience. Using a systematic approach ensures that the experienced ultrasonographer obtains all the essential information needed at the time of surgery.

5.
Ann Surg ; 276(6): e698-e705, 2022 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-33156066

RESUMO

OBJECTIVE: Our objective was to examine the associations between early discharge and readmission after major abdominal operations. BACKGROUND: Advances in patient care resulted in earlier patient discharge after complex abdominal operations. Whether early discharge is associated with patient readmissions remains controversial. METHODS: Patients who had colorectal, liver, and pancreas operations abstracted in 2011-2017 American College of Surgeons National Surgical Quality Improvement Program Participant Use Data Files were included. Patient readmission was stratified by 6 operative groups. Patients who were discharged before median discharge date within each operative group were categorized as an early discharge. Analyses tested associations between early discharge and likelihood of 30-day postoperative unplanned readmission. RESULTS: A total of 364,609 patients with major abdominal operations were included. Individual patient groups and corresponding median day of discharge were: laparoscopic colectomy (n = 152,575; median = 4), open colectomy (n =137,462; median = 7), laparoscopic proctectomy (n = 12,238; median = 5), open proctectomy (n = 24,925; median = 6), major hepatectomy (n = 9,805; median = 6), pancreatoduodenectomy (n = 27,604; median = 8). Early discharge was not associated with an increase in proportion of readmissions in any operative group. Early discharge was associated with a decrease in average proportion of patient readmissions compared to patients discharged on median date in each of the operative groups: laparoscopic colectomy 6% versus 8%, open colectomy 11% versus 14%, laparoscopic proctectomy 13% versus 16%, open proctectomy 13% vs 17%, major hepatectomy 8% versus 12%, pancreatoduodenectomy 16% versus 20% (all P ≤ 0.02). Serious morbidity composite was significantly lower in patients who were discharged early than those who were not in each operative group (all P < 0.001). CONCLUSIONS: Early discharge in selected patients after major abdominal operations is associated with lower, and not higher, rate of 30-day unplanned readmission.


Assuntos
Readmissão do Paciente , Protectomia , Humanos , Alta do Paciente , Fatores de Risco , Colectomia/efeitos adversos , Complicações Pós-Operatórias/epidemiologia , Estudos Retrospectivos
6.
Infect Immun ; 90(1): e0051621, 2022 01 25.
Artigo em Inglês | MEDLINE | ID: mdl-34662214

RESUMO

Salmonella invades and disrupts gut epithelium integrity, creating an infection-generated electric field that can drive directional migration of macrophages, a process called galvanotaxis. Phagocytosis of bacteria reverses the direction of macrophage galvanotaxis, implicating a bioelectrical mechanism to initiate life-threatening disseminations. The force that drives direction reversal of macrophage galvanotaxis is not understood. One hypothesis is that Salmonella can alter the electrical properties of the macrophages by modifying host cell surface glycan composition, which is supported by the fact that cleavage of surface-exposed sialic acids with a bacterial neuraminidase severely impairs macrophage galvanotaxis, as well as phagocytosis. Here, we utilize N-glycan profiling by nanoLC-chip QTOF mass cytometry to characterize the bacterial neuraminidase-associated compositional shift of the macrophage glycocalyx, which revealed a decrease in sialylated and an increase in fucosylated and high mannose structures. The Salmonella nanH gene, encoding a putative neuraminidase, is required for invasion and internalization in a human colonic epithelial cell infection model. To determine whether NanH is required for the Salmonella infection-dependent direction reversal, we constructed and characterized a nanH deletion mutant and found that NanH is partially required for Salmonella infection in primary murine macrophages. However, compared to wild type Salmonella, infection with the nanH mutant only marginally reduced the cathode-oriented macrophage galvonotaxis, without canceling direction reversal. Together, these findings strongly suggest that while neuraminidase-mediated N-glycan modification impaired both macrophage phagocytosis and galvanotaxis, yet to be defined mechanisms other than NanH may play a more important role in bioelectrical control of macrophage trafficking, which potentially triggers dissemination.


Assuntos
Quimiotaxia de Leucócito/imunologia , Macrófagos/imunologia , Macrófagos/metabolismo , Neuraminidase/metabolismo , Infecções por Salmonella/imunologia , Infecções por Salmonella/metabolismo , Salmonella/fisiologia , Animais , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo , Feminino , Interações Hospedeiro-Patógeno/imunologia , Masculino , Camundongos , Modelos Biológicos , Mutação , Fagocitose/imunologia , Polissacarídeos/metabolismo , Infecções por Salmonella/microbiologia , Ácidos Siálicos/metabolismo , Virulência
8.
Immunity ; 53(4): 733-744.e8, 2020 10 13.
Artigo em Inglês | MEDLINE | ID: mdl-32946741

RESUMO

Discovering potent human monoclonal antibodies (mAbs) targeting the Plasmodium falciparum circumsporozoite protein (PfCSP) on sporozoites (SPZ) and elucidating their mechanisms of neutralization will facilitate translation for passive prophylaxis and aid next-generation vaccine development. Here, we isolated a neutralizing human mAb, L9 that preferentially bound NVDP minor repeats of PfCSP with high affinity while cross-reacting with NANP major repeats. L9 was more potent than six published neutralizing human PfCSP mAbs at mediating protection against mosquito bite challenge in mice. Isothermal titration calorimetry and multiphoton microscopy showed that L9 and the other most protective mAbs bound PfCSP with two binding events and mediated protection by killing SPZ in the liver and by preventing their egress from sinusoids and traversal of hepatocytes. This study defines the subdominant PfCSP minor repeats as neutralizing epitopes, identifies an in vitro biophysical correlate of SPZ neutralization, and demonstrates that the liver is an important site for antibodies to prevent malaria.


Assuntos
Anticorpos Monoclonais/imunologia , Anticorpos Neutralizantes/imunologia , Anticorpos Antiprotozoários/imunologia , Antimaláricos/imunologia , Plasmodium falciparum/imunologia , Proteínas de Protozoários/imunologia , Esporozoítos/imunologia , Adolescente , Adulto , Animais , Linhagem Celular , Linhagem Celular Tumoral , Epitopos/imunologia , Feminino , Células HEK293 , Hepatócitos/imunologia , Hepatócitos/parasitologia , Humanos , Fígado/imunologia , Fígado/parasitologia , Malária/imunologia , Malária/parasitologia , Vacinas Antimaláricas/imunologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Pessoa de Meia-Idade , Adulto Jovem
9.
Am J Surg ; 220(3): 682-686, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-31983407

RESUMO

BACKGROUND: Independent associations between chronic liver disease, MELD, and postoperative outcomes among patients selected for liver resection have not been completely established. We hypothesized independent associations between MELD, cirrhosis, and postoperative mortality. METHODS: Patient-level data from the targeted hepatectomy module and ACS NSQIP PUF during 2014-2015 were merged. Multivariable regression models with interaction effect between MELD and liver texture (normal, congested/fatty, cirrhotic) tested the independent effects of covariates on mortality and morbidity. RESULTS: 3,530 patients were included, of whom 668 patients (19%) had cirrhosis. ACS NSQIP defined mortality (3.9%vs1.1%) and morbidity (23.5%vs15.8%) were higher in patients with cirrhosis (both p < 0.001). In multivariable models, cirrhosis (OR = 2.24; 95%CI:1.16-4.34, p = 0.016) and MELD (OR = 1.10; 95%CI:1.03-1.18, p = 0.007) were independently associated with mortality. MELD (OR = 1.04; 95%CI:1.002-1.08, p = 0.038) was associated with postoperative morbidity. CONCLUSIONS: Higher MELD and presence of cirrhosis have an independent negative effect on mortality after liver resection. MELD could be used to estimate postoperative risk in patients with and without cirrhosis.


Assuntos
Hepatectomia , Cirrose Hepática/complicações , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Idoso , Estudos de Coortes , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Morbidade , Seleção de Pacientes , Complicações Pós-Operatórias/mortalidade , Estudos Retrospectivos , Medição de Risco , Índice de Gravidade de Doença
11.
Am Surg ; 85(2): 150-155, 2019 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-30819290

RESUMO

Optimal treatment for small hepatocellular carcinoma (HCC) ≤ 3 cm remains controversial. Ablation and chemoembolization are considered for nonoperative candidates. This study compares survival among patients with solitary HCC ≤ 3 cm treated with radiofrequency ablation (RFA) and transarterial chemoembolization (TACE). Patients diagnosed with HCC ≤ 3 cm between 2005 and 2014 were included. Kaplan-Meier survival functions with log-rank tests were used to estimate recurrence-free survival and overall survival (OS) survival. Among 161 patients with solitary HCC ≤ 3 cm, 145 patients with mean age of 65.2 years (±9.2) and 95 per cent prevalence of cirrhosis had operative treatment or TACE, and/or RFA. From this cohort, 27 (19%) patients had TACE, 27 (19%) patients had RFA, and 15 (10%) patients had TACE/RFA. The patients treated with definitive TACE, RFA, or TACE/RFA had a similar 1-year recurrence-free survival (23% vs 27% vs 36%, respectively, P = 0.445) and similar 5-year OS (21% vs 24% vs 33%, respectively, P = 0.287). Thirty-five (24%) patients were bridged to transplantation with TACE and/or RFA. The 5-year OS was significantly improved in patients bridged to transplantation (P < 0.001). Survival does not differ between patients with solitary HCC ≤ 3 cm treated with TACE or RFA. Patients who were bridged to transplantation had significantly greater OS compared with patients who were not transplanted.


Assuntos
Carcinoma Hepatocelular/patologia , Carcinoma Hepatocelular/terapia , Quimioembolização Terapêutica , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/terapia , Ablação por Radiofrequência , Idoso , Carcinoma Hepatocelular/mortalidade , Intervalo Livre de Doença , Feminino , Humanos , Estimativa de Kaplan-Meier , Neoplasias Hepáticas/mortalidade , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Taxa de Sobrevida , Resultado do Tratamento
12.
J Surg Res ; 231: 304-308, 2018 11.
Artigo em Inglês | MEDLINE | ID: mdl-30278945

RESUMO

BACKGROUND: Safety of pancreaticoduodenectomy has improved significantly in the past 3 decades. Current inpatient and 30-d mortality rates are low. However, incidence and causes of 90-d and 1-y mortality are poorly defined and largely unexplored. METHODS: All patients who had pancreaticoduodenectomy between 2007 and 2016 were included in this single institution, retrospective cohort study. Distributions of pancreaticoduodenectomy-specific morbidity and cause-specific mortality were compared between early (within 90 d) and late (91-365 d) postoperative recovery periods. RESULTS: A total of 551 pancreaticoduodenectomies were performed during the study period. Of these, 6 (1.1%), 20 (3.6%), and 91 (16.5%) patients died within 30, 90, and 365 d after pancreaticoduodenectomy, respectively. Causes of early and late mortality varied significantly (all P ≤ 0.032). The most common cause of death within 90 d was due to multisystem organ failure from sepsis or aspiration in 9 (45%) patients, followed by post-pancreatectomy hemorrhage in 5 (25%) patients, and cardiopulmonary arrest from myocardial infarction or pulmonary embolus in 3 (15%) patients. In contrast, recurrent cancer was the most common cause of death in 46 (65%) patients during the late postoperative period between 91 and 365 d. Mortality from failure to thrive and debility was similar between early and late postoperative periods (15% versus 19.7%, P = 0.76). CONCLUSIONS: Most quality improvement initiatives in patients selected for pancreaticoduodenectomy have focused on reduction of technical complications and improvement of early postoperative mortality. Further reduction in postoperative mortality after pancreaticoduodenectomy can be achieved by improving patient selection, mitigating postoperative malnutrition, and optimizing preoperative cancer staging and management strategies.


Assuntos
Causas de Morte , Pancreaticoduodenectomia/mortalidade , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Avaliação de Resultados em Cuidados de Saúde , Pancreaticoduodenectomia/métodos , Seleção de Pacientes , Assistência Perioperatória/métodos , Estudos Retrospectivos , Fatores de Risco , Adulto Jovem
13.
Endosc Ultrasound ; 7(1): 29-33, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29451166

RESUMO

BACKGROUND AND OBJECTIVES: DNA molecular analysis has been suggested as a tool to evaluate pancreatic cysts. This study assesses whether the addition of DNA molecular analysis alters clinical management. METHODS: This is a retrospective review of 46 consecutive patients who underwent EUS-FNA of pancreatic cysts with DNA molecular analysis at two major academic institutions. Cases were presented to two pancreaticobiliary surgeons first without and then with DNA molecular analysis data. The primary outcome was the frequency with which clinical management was altered with the addition of DNA molecular analysis. RESULTS: Forty-six patients with a mean age of 62.0 (±13.4) years and mean cyst size of 3.2 (±2.3) cm were included in the study. Cyst carcinoembryonic antigen (CEA) was available in 30 patients and ranged from 0.4 to 15,927 ng/mL. DNA molecular analysis was described as benign in 23 (50%), statistically indolent in 13 (28%), statistically higher risk in 9 (20%), and indeterminate in 1 (2%). Surgeon #1 changed the management in 13/46 cases (28%) and surgeon #2 changed the management in 12/46 cases (26%) with the addition of DNA molecular analysis. When organized by CEA concentration, those with an intermediate CEA (45-800 ng/mL) or without a CEA concentration had a management changed more frequently (40%) compared to all others (P < 0.05). CONCLUSIONS: The addition of DNA molecular analysis alters the clinical management of pancreatic cystic lesions most often when CEA levels are intermediate (45-800 ng/mL) or when no CEA concentration is available. Use of DNA molecular analysis can be considered in this cohort. Further study of molecular markers in pancreatic cystic lesions is recommended.

14.
J Gastrointest Surg ; 22(4): 661-667, 2018 04.
Artigo em Inglês | MEDLINE | ID: mdl-29247421

RESUMO

BACKGROUND: Despite technical advances, bile leak remains a significant complication after hepatectomy. The current study uses a targeted multi-institutional dataset to characterize perioperative factors that are associated with bile leakage after hepatectomy to better understand the impact of bile leak on morbidity and mortality. METHODS: Adult patients in the 2014-2015 ACS NSQIP targeted hepatectomy dataset were linked to the ACS NSQIP PUF dataset. Bivariable and multivariable regression analyses were used to assess the associations between clinical factors and post-hepatectomy bile leak. RESULTS: Of 6859 patients, 530 (7.7%) had a postoperative bile leak. Proportion of bile leaks was significantly greater in patients after major compared to minor hepatectomy (12.6 vs. 5.1%, p < 0.001). The proportion of patients with bile leak was significantly greater in patients after major hepatectomy who had concomitant enterohepatic reconstruction (31.8 vs. 10.1%, p < 0.001). Postoperative mortality was significantly greater in patients with bile leaks (6.0 vs. 1.7%, p < 0.001). After adjusting for significant covariates, bile leak was independently associated with increased risk of postoperative morbidity (OR = 4.55; 95% CI 3.72-5.56; p < 0.001). After adjusting for significant effects of postoperative complications, liver failure, and reoperation (all p<0.001), bile leak was not independently associated with increased risk of postoperative mortality (p = 0.262). CONCLUSION: Major hepatectomy and enterohepatic biliary reconstruction are associated with significantly greater rates of bile leak after liver resection. Bile leak is independently associated with significant postoperative morbidity. Mitigation of bile leak is critical in reducing morbidity and mortality after liver resection.


Assuntos
Fístula Anastomótica/etiologia , Fístula Anastomótica/mortalidade , Hepatectomia/efeitos adversos , Hepatectomia/mortalidade , Idoso , Bile , Feminino , Hepatectomia/métodos , Humanos , Masculino , Pessoa de Meia-Idade , Procedimentos de Cirurgia Plástica/estatística & dados numéricos , Fatores de Risco , Estados Unidos/epidemiologia
16.
Am J Surg ; 214(2): 347-357, 2017 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-28325588

RESUMO

BACKGROUND: Pain secondary to chronic pancreatitis is a difficult clinical problem to manage. Many patients are treated medically or undergo endoscopic therapy and surgical intervention is often reserved for those who have failed to gain adequate pain relief from a more conservative approach. RESULTS: There have been a number of advances in the operative management of chronic pancreatitis over the last few decades and current therapies include drainage procedures (pancreaticojejunostomy, etc.), resection (pancreticoduodenectomy, etc.) and combined drainage/resection procedures (Frey procedure, etc.). Additionally, many centers currently perform total pancreatectomy with islet autotransplantation, in addition to minimally invasive options that are intended to tailor therapy to individual patients. DISCUSSION: Operative management of chronic pancreatitis often improves quality of life, and is associated with low rates of morbidity and mortality. The decision as to which procedure is optimal for each patient should be based on a combination of pathologic changes, prior interventions, and individual surgeon and center experience.


Assuntos
Pancreatectomia , Pancreatite Crônica/cirurgia , Árvores de Decisões , Drenagem , Humanos , Dor/etiologia , Dor/cirurgia , Manejo da Dor/métodos , Pancreatite Crônica/complicações , Pancreatite Crônica/diagnóstico
17.
Sci Rep ; 7: 44636, 2017 03 16.
Artigo em Inglês | MEDLINE | ID: mdl-28300162

RESUMO

Functional and molecular cell-to-cell variability is pivotal at the cellular, tissue and whole-organism levels. Yet, the ultimate goal of directly correlating the function of the individual cell with its biomolecular profile remains elusive. We present a platform for integrated analysis of functional and transcriptional phenotypes in the same single cells. We investigated changes in the cellular respiration and gene expression diversity resulting from adaptation to repeated episodes of acute hypoxia in a premalignant progression model. We find differential, progression stage-specific alterations in phenotypic heterogeneity and identify cells with aberrant phenotypes. To our knowledge, this study is the first demonstration of an integrated approach to elucidate how heterogeneity at the transcriptional level manifests in the physiologic profile of individual cells in the context of disease progression.


Assuntos
Análise de Célula Única/métodos , Respiração Celular/genética , Perfilação da Expressão Gênica , Regulação da Expressão Gênica , Humanos , Anotação de Sequência Molecular , Consumo de Oxigênio , Fenótipo , Análise de Componente Principal
18.
J Surg Res ; 206(1): 106-112, 2016 11.
Artigo em Inglês | MEDLINE | ID: mdl-27916348

RESUMO

BACKGROUND: Previous studies have indicated that blood transfusion is associated with increased risk of worse outcomes among patients selected for hepatectomy. However, the independent effect of transfusion has not been confirmed. We hypothesize that blood transfusion is an independent factor that affects outcomes in patients undergoing hepatectomy. MATERIALS AND METHODS: Patients at tertiary care center who underwent hepatectomy between 2006 and 2013 were identified and linked with the American College of Surgeons National Surgical Quality Improvement Program PUF data set. Multivariable logistic regression analysis was used to estimate the effect of blood transfusion on 30-d mortality and morbidity, adjusted for differences in extent of resection and estimated probabilities of morbidity and mortality. RESULTS: Among 522 patients in the study, 48 (9.2%) patients required perioperative blood transfusion within 72 h of resection, and 172 (33%) underwent major hepatectomy. Indications for hepatectomy included metastatic neoplasm (n = 229, 44%), primary hepatic neoplasm (n = 108, 21%), primary extra-hepatic biliary neoplasm (n = 23, 4%), and nonmalignant indications (n = 162, 31%). Eighty-eight (17%) patients had a postoperative morbidity. Blood transfusion was significantly associated with postoperative morbidity (odds ratio [OR] = 4.18, 95% CI = 2.18-8.02, P = 0.0001) and mortality (OR = 14.5, 95% CI = 3.08-67.8, P = 001), after adjustment for the concurrent effect of National Surgical Quality Improvement Program estimated probability of morbidity (OR = 1.15, 95% CI = 0.11-12.2, P = 0.042). The extent of resection was not significantly associated with morbidity (OR = 1.30, 95% CI, 0.74-2.28, P = 0.366) or mortality (OR = 1.14, 95% CI = 0.24-5.50, P = 0.870). CONCLUSIONS: Blood transfusion is a highly statistically significant independent predictor of morbidity and mortality after hepatectomy. Judicious use of perioperative transfusion is indicated in patients with benign and malignant indications for liver resection.


Assuntos
Hepatectomia/mortalidade , Assistência Perioperatória/efeitos adversos , Complicações Pós-Operatórias/etiologia , Reação Transfusional , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Bases de Dados Factuais , Feminino , Seguimentos , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/epidemiologia , Estudos Retrospectivos , Fatores de Risco , Adulto Jovem
19.
Org Biomol Chem ; 14(35): 8289-300, 2016 Sep 21.
Artigo em Inglês | MEDLINE | ID: mdl-27529405

RESUMO

The photochemical release of chemical reagents and bioactive molecules provides a useful tool for spatio-temporal control of biological processes. However, achieving this goal requires the development of highly efficient one- and two-photon sensitive photo-cleavable protecting groups. Thiol-containing compounds play critical roles in biological systems and bioengineering applications. While potentially useful for sulfhydryl protection, the 6-bromo-7-hydroxy coumarin-4-ylmethyl (Bhc) group can undergo an undesired photoisomerization reaction upon irradiation that limits its uncaging efficiency. To address this issue, here we describe the development of 6-bromo-7-hydroxy-3-methylcoumarin-4-ylmethyl (mBhc) as an improved group for thiol-protection. One- and two-photon photolysis reactions demonstrate that a peptide containing a mBhc-caged thiol undergoes clean and efficient photo-cleavage upon irradiation without detectable photoisomer production. To test its utility for biological studies, a K-Ras-derived peptide containing an mBhc-protected thiol was prepared by solid phase peptide synthesis using Fmoc-Cys(mBhc)-OH for the introduction of the caged thiol. Irradiation of that peptide using either UV or near IR light in presence of protein farnesyltransferase (PFTase), resulted in generation of the free peptide which was then recognized by the enzyme and became farnesylated. To show the utility of this caging group in biomaterial applications, we covalently modified hydrogels with mBhc-protected cysteamine. Using multi-photon confocal microscopy, highly defined volumes of free thiols were generated inside the hydrogels and visualized via reaction with a sulfhydryl-reactive fluorophore. The simple synthesis of mBhc and its efficient removal by one- and two-photon processes make it an attractive protecting group for thiol caging in a variety of applications.

20.
J Gastrointest Surg ; 20(9): 1554-64, 2016 09.
Artigo em Inglês | MEDLINE | ID: mdl-27364726

RESUMO

BACKGROUND: Morbidity after gastrectomy remains high. The potentially modifiable risk factors have not been well described. This study considers a series of potentially modifiable patient-specific and perioperative characteristics that could be considered to reduce morbidity and mortality after gastrectomy. METHODS: This retrospective cohort study includes adults in the ACS NSQIP PUF dataset who underwent gastrectomy between 2011 and 2013. Sequential multivariable models were used to estimate effects of clinical covariates on study outcomes including morbidity, mortality, readmission, and reoperation. RESULTS: Three thousand six hundred and seventy-eight patients underwent gastrectomy. A majority of patients had distal gastrectomy (N = 2,799, 76.1 %) and had resection for malignancy (N = 2,316, 63.0 %). Seven hundred and ninety-eight patients (21.7 %) experienced a major complication. Reoperation was required in 290 patients (7.9 %). Thirty-day mortality was 5.2 %. Age (OR = 1.01, 95 % CI = 1.01-1.02, p = 0.001), preoperative malnutrition (OR = 1.65, 95 % CI = 1.35-2.02, p < 0.001), total gastrectomy (OR = 1.63, 95 % CI = 1.31-2.03, p < 0.001), benign indication for resection (OR = 1.60, 95 % CI = 1.29-1.97, p < 0.001), blood transfusion (OR = 2.57, 95 % CI = 2.10-3.13, p < 0.001), and intraoperative placement of a feeding tubes (OR = 1.28, 95 % CI = 1.00-1.62, p = 0.047) were independently associated with increased risk of morbidity. Association between tobacco use and morbidity was statistically marginal (OR = 1.23, 95 % CI = 0.99-1.53, p = 0.064). All-cause postoperative morbidity had significant associations with reoperation, readmission, and mortality (all p < 0.001). CONCLUSIONS: Mitigation of perioperative risk factors including smoking and malnutrition as well as identified operative considerations may improve outcomes after gastrectomy. Postoperative morbidity has the strongest association with other measures of poor outcome: reoperation, readmission, and mortality.


Assuntos
Gastrectomia/efeitos adversos , Gastrectomia/mortalidade , Desnutrição/complicações , Complicações Pós-Operatórias/etiologia , Fumar/efeitos adversos , Fatores Etários , Idoso , Feminino , Gastrectomia/métodos , Humanos , Intubação Gastrointestinal/efeitos adversos , Masculino , Pessoa de Meia-Idade , Readmissão do Paciente/estatística & dados numéricos , Reoperação/estatística & dados numéricos , Estudos Retrospectivos , Fatores de Risco , Reação Transfusional
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