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1.
PLoS One ; 18(12): e0290659, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38127930

RESUMO

A liquid-based perinatal life support system (PLS) for extremely premature infants (born before 28 week of gestational age) envisions a connection between the infant's native umbilical cord and an artificial placenta system through cannulation. This system mimics a natural mothers' womb to achieve better organ maturations. The objective of this study is to gain insight into the clinical focus points of umbilical cord cannulation and how cannulation should be addressed in extremely premature infants during the transfer from the uterus to an in-utero simulating liquid-based PLS system. We performed an explorative qualitative study. Twelve medical specialists with knowledge of vessel cannulation participated. We collected data through twelve interviews and two focus group discussions. Data were analyzed using inductive content and constant comparison analysis via open and axial coding. Results were derived on the following topics: (1) cannulation technique, (2) cannula fixation, (3) local and systemic anticoagulation, and (4) vasospasm. A side-entry technique is preferred as this may decrease wall damage, stabilizes the vessel better and ensures continuous blood flow. Sutures, especially via an automatic microsurgery instrument, are favored above glue, stents, or balloons as these may be firmer and faster. Medication possibilities for both vasospasm and anticoagulation should function locally since there were uncertainties regarding the systemic effects. According to the findings of this research, the needed umbilical cord cannulation method should include minimal wall damage, improved vascular stability, blood flow maintenance, a strong fixation connection, and local anticoagulation effect.


Assuntos
Lactente Extremamente Prematuro , Sistemas de Manutenção da Vida , Recém-Nascido , Gravidez , Lactente , Feminino , Humanos , Cordão Umbilical , Cateterismo , Útero , Anticoagulantes
2.
Clin Transl Gastroenterol ; 13(3): e00468, 2022 02 14.
Artigo em Inglês | MEDLINE | ID: mdl-35166713

RESUMO

INTRODUCTION: The IMMray PanCan-d test combines an 8-plex biomarker signature with CA19-9 in a proprietary algorithm to detect pancreatic ductal adenocarcinoma (PDAC) in serum samples. This study aimed to validate the clinical performance of the IMMray PanCan-d test and to better understand test performance in Lewis-null (le/le) individuals who cannot express CA19-9. METHODS: Serum samples from 586 individuals were analyzed with the IMMray PanCan-d biomarker signature and CA19-9 assay, including 167 PDAC samples, 203 individuals at high risk of familial/hereditary PDAC, and 216 healthy controls. Samples were collected at 11 sites in the United States and Europe. The study was performed by Immunovia, Inc (Marlborough, MA), and sample identity was blinded throughout the study. Test results were automatically generated using validated custom software with a locked algorithm and predefined decision value cutoffs for sample classification. RESULTS: The IMMray PanCan-d test distinguished PDAC stages I and II (n = 56) vs high-risk individuals with 98% specificity and 85% sensitivity and distinguished PDAC stages I-IV vs high-risk individuals with 98% specificity and 87% sensitivity. We identified samples with a CA19-9 value of 2.5 U/mL or less as probable Lewis-null (le/le) individuals. Excluding these 55 samples from the analysis increased the IMMray PanCan-d test sensitivity to 92% for PDAC stages I-IV (n = 157) vs controls (n = 379) while maintaining specificity at 99%; test sensitivity for PDAC stages I and II increased from 85% to 89%. DISCUSSION: These results demonstrate the IMMray PanCan-d blood test can detect PDAC with high specificity (99%) and sensitivity (92%).


Assuntos
Adenocarcinoma , Carcinoma Ductal Pancreático , Neoplasias Pancreáticas , Adenocarcinoma/diagnóstico , Biomarcadores Tumorais , Antígeno CA-19-9 , Carcinoma Ductal Pancreático/diagnóstico , Carcinoma Ductal Pancreático/genética , Humanos , Neoplasias Pancreáticas/patologia
3.
Sci Rep ; 12(1): 1186, 2022 01 24.
Artigo em Inglês | MEDLINE | ID: mdl-35075163

RESUMO

Cancer biomarker discovery is critically dependent on the integrity of biofluid and tissue samples acquired from study participants. Multi-omic profiling of candidate protein, lipid, and metabolite biomarkers is confounded by timing and fasting status of sample collection, participant demographics and treatment exposures of the study population. Contamination by hemoglobin, whether caused by hemolysis during sample preparation or underlying red cell fragility, contributes 0-10 g/L of extraneous protein to plasma, serum, and Buffy coat samples and may interfere with biomarker detection and validation. We analyzed 617 plasma, 701 serum, and 657 buffy coat samples from a 7-year longitudinal multi-omic biomarker discovery program evaluating 400+ participants with or at risk for pancreatic cancer, known as Project Survival. Hemolysis was undetectable in 93.1% of plasma and 95.0% of serum samples, whereas only 37.1% of buffy coat samples were free of contamination by hemoglobin. Regression analysis of multi-omic data demonstrated a statistically significant correlation between hemoglobin concentration and the resulting pattern of analyte detection and concentration. Although hemolysis had the greatest impact on identification and quantitation of the proteome, distinct differentials in metabolomics and lipidomics were also observed and correlated with severity. We conclude that quality control is vital to accurate detection of informative molecular differentials using OMIC technologies and that caution must be exercised to minimize the impact of hemolysis as a factor driving false discovery in large cancer biomarker studies.


Assuntos
Biomarcadores/sangue , Hemólise , Lipidômica/normas , Neoplasias Pancreáticas/sangue , Pancreatite/sangue , Proteômica/normas , Estudos de Casos e Controles , Feminino , Humanos , Masculino , Espectrometria de Massas , Medicina de Precisão
4.
Surg Endosc ; 36(1): 621-630, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-33543349

RESUMO

INTRODUCTION: Treatment of pancreaticobiliary pathology following Roux-en-Y gastric bypass (RYGB) poses significant technical challenges. Laparoscopic-assisted endoscopic retrograde cholangiopancreatography (LA-ERCP) can overcome those anatomical hurdles, allowing access to the papilla. Our aims were to analyze our 12-year institutional outcomes and determine the learning curve for LA-ERCP. METHODS: A retrospective review of cases between 2007 and 2019 at a high-volume pancreatobiliary unit was performed. Logistic regression was used to identify predictors of specific outcomes. To identify the learning curve, CUSUM analyses and innovative methods for standardizing the surgeon's timelines were performed. RESULTS: 131 patients underwent LA-ERCP (median age 60, 81% females) by 17 surgeons and 10 gastroenterologists. Cannulation of the papilla was achieved in all cases. Indications were choledocholithiasis (78%), Sphincter of Oddi dysfunction/Papillary stenosis (18%), management of bile leak (2%) and stenting/biopsy of malignant strictures (2%). Median total, surgical and ERCP times were 180, 128 and 48 min, respectively, and 47% underwent concomitant cholecystectomy. Surgical site infection developed in 9.2% and post-ERCP pancreatitis in 3.8%. Logistic regression revealed multiple abdominal operations and magnitude of BMI decrease (between RYGB and LA-ERCP) to be predictive of conversion to open approach. CUSUM analysis of operative time demonstrated a learning curve at case 27 for the surgical team and case 9 for the gastroenterology team. On binary cut analysis, 3-5 cases per surgeon were needed to optimize operative metrics. CONCLUSION: LA-ERCP is associated with high success rates and low adverse events. We identify outcome benchmarks and a learning curve for new adopters of this increasingly performed procedure.


Assuntos
Coledocolitíase , Derivação Gástrica , Laparoscopia , Colangiopancreatografia Retrógrada Endoscópica/métodos , Coledocolitíase/cirurgia , Feminino , Derivação Gástrica/efeitos adversos , Derivação Gástrica/métodos , Humanos , Laparoscopia/métodos , Curva de Aprendizado , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos
6.
Ann Transl Med ; 9(18): 1408, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34733960

RESUMO

BACKGROUND: This study compares standard of care (SOC) open and robotic D2-gastrectomy for locally advanced gastric cancer (LAGC) in the Western context of low disease prevalence, reduced surgical volume, and neoadjuvant chemotherapy (NAC). We hypothesized that robotic gastrectomy (RG) after NAC reduces treatment burden for LAGC across multiple outcome domains vs. SOC. METHODS: Single institution, interrupted time series comparing SOC (2008-2013) for LAGC (T2-4Nany/TanyN+) vs. NAC + RG (2013-2018). Treatment burden was a composite metric of narcotic consumption, oncologic efficacy, cumulative morbidity, and 90-day resource utilization. Predictors were evaluated via multivariate modeling. Learning curve analysis was done using CUSUM. RESULTS: After exclusions, 87 subjects with equivalent baseline characteristics, aside from male sex, were treated via SOC (n=55) or NAC + RG (n=32). All four domains of treatment burden were significantly reduced in the NAC + RG cohort compared to SOC (P=0.003). The odds ratio for excess treatment burden in the NAC/RG was 0.23 (95% CI: 0.07-0.72, P=0.0117) vs. SOC upon multivariable modeling, whereas the extent of resection (total/subtotal), tumor size, T-stage, sex, and early learning curve had no effect. Differences in treatment burden persisted in subgroup analysis for NAC (n=51). CONCLUSIONS: NAC + RG was associated with decreased treatment burden relative to SOC for LAGC. Frequencies of unfavorable hospitalization, adverse oncological outcomes, major morbidity, and narcotic consumption all decreased in this interrupted time series.

7.
Surg Oncol Clin N Am ; 30(4): 747-758, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34511194

RESUMO

There is increasing interest in the role of minimally invasive surgery (MIS) for pancreatectomy. Prospective data indicate significant advantages for MIS when performed for left-sided pancreatic pathologies and may be deemed as the standard of care. However, there is reluctance in implementing this technique to pancreaticoduodenectomy because of the complexity of the operation and the mixed results from randomized trials. A detailed description of the technical aspects of robotic pancreaticoduodenectomy and distal pancreatectomy is presented in this article in addition to a summary of the most important prospective and cohort studies. We also provide insights into patient selection and the learning curve of MIS surgery for pancreatectomy.


Assuntos
Laparoscopia , Neoplasias Pancreáticas , Procedimentos Cirúrgicos Robóticos , Humanos , Procedimentos Cirúrgicos Minimamente Invasivos , Pancreatectomia , Neoplasias Pancreáticas/cirurgia , Pancreaticoduodenectomia , Estudos Prospectivos
8.
HPB (Oxford) ; 23(12): 1849-1855, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34059420

RESUMO

BACKGROUND: Minimally invasive distal pancreatectomy is the accepted standard of care. The robotic distal (RDP) learning curve is 20-40 surgeries with operating time (ORT) as the most significant factor. This study evaluates how formal mentorship and a robotic skills curriculum impact the learning curve for subsequent generation surgeons. METHODS: Consecutive RDP from 2008 to 2017 were evaluated. First Generation was two surgeons who started program without training or mentorship. Second Generation was the two surgeons who joined the program with mentorship. Third Generation was fellows who benefited from both formal training and mentorship. Multivariable models (MVA) were performed for ORT, clinically relevant pancreatic fistula (CR-POPF), and major complications (Clavien≥3). RESULTS: A total of 296 RDP were performed of which 187 did not include other procedures: First Generation (n = 71), Second Generation (n = 50), and Third Generation (n = 66). ORT decreased by generation (p < 0.001) without any differences in CR-POPF or Clavien≥3. On MVA, earlier generation (p = 0.019), pre-operative albumin (p = 0.001) and pancreatic adenocarcinoma (p = 0.019) were predictive of ORT. Increased BMI (p = 0.049) and neoadjuvant therapy (p = 0.046) were predictive of CR-POPF. Fellow participation at the console increased over time. CONCLUSION: Formal mentorship and a skills curriculum decreased the learning curve and complications were largely dependent on patient factors.


Assuntos
Adenocarcinoma , Neoplasias Pancreáticas , Procedimentos Cirúrgicos Robóticos , Currículo , Humanos , Curva de Aprendizado , Mentores , Pancreatectomia/efeitos adversos , Neoplasias Pancreáticas/cirurgia , Complicações Pós-Operatórias , Estudos Retrospectivos , Procedimentos Cirúrgicos Robóticos/efeitos adversos
9.
Sci Rep ; 11(1): 5749, 2021 03 11.
Artigo em Inglês | MEDLINE | ID: mdl-33707480

RESUMO

Reactive oxygen species (ROS) are implicated in triggering cell signalling events and pathways to promote and maintain tumorigenicity. Chemotherapy and radiation can induce ROS to elicit cell death allows for targeting ROS pathways for effective anti-cancer therapeutics. Coenzyme Q10 is a critical cofactor in the electron transport chain with complex biological functions that extend beyond mitochondrial respiration. This study demonstrates that delivery of oxidized Coenzyme Q10 (ubidecarenone) to increase mitochondrial Q-pool is associated with an increase in ROS generation, effectuating anti-cancer effects in a pancreatic cancer model. Consequent activation of cell death was observed in vitro in pancreatic cancer cells, and both human patient-derived organoids and tumour xenografts. The study is a first to demonstrate the effectiveness of oxidized ubidecarenone in targeting mitochondrial function resulting in an anti-cancer effect. Furthermore, these findings support the clinical development of proprietary formulation, BPM31510, for treatment of cancers with high ROS burden with potential sensitivity to ubidecarenone.


Assuntos
Apoptose , Mitocôndrias/metabolismo , Neoplasias Pancreáticas/patologia , Espécies Reativas de Oxigênio/metabolismo , Ubiquinona/análogos & derivados , Animais , Linhagem Celular Tumoral , Proliferação de Células , Respiração Celular , Sobrevivência Celular , Complexo II de Transporte de Elétrons/metabolismo , Glicerol-3-Fosfato Desidrogenase (NAD+) , Humanos , Potencial da Membrana Mitocondrial , Camundongos Nus , Organoides/patologia , Estresse Oxidativo , Consumo de Oxigênio , Neoplasias Pancreáticas/metabolismo , Especificidade por Substrato , Ubiquinona/metabolismo
10.
Ann Surg ; 274(1): e18-e27, 2021 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-30946088

RESUMO

OBJECTIVE: To train practicing surgeons in robot-assisted distal pancreatectomy (RADP) and assess the impact on 5 domains of healthcare quality. BACKGROUND: RADP may reduce the treatment burden compared with open distal pancreatectomy (ODP), but studies on institutional training and implementation programs are scarce. METHODS: A retrospective, single-center, cohort study evaluating surgical performance during a procedure-specific training program for RADP (January 2006 to September 2017). Baseline and unadjusted outcomes were compared "before training" (ODP only; June 2012). Exclusion criteria were neoadjuvant therapy, vascular- and unrelated organ resection. Run charts evaluated index length of stay (LOS) and 90-day comprehensive complication index. Cumulative sum charts of operating time (OT) assessed institutional learning. Adjusted outcomes after RADP versus ODP were compared using a secondary propensity-score-matched (1:1) analysis to determine clinical efficacy. RESULTS: After screening, 237 patients were included in the before-training (133 ODP) and after-training (24 ODP, 80 RADP) groups. After initiation of training, mean perioperative blood loss decreased (-255 mL, P<0.001), OT increased (+65 min, P < 0.001), and median LOS decreased (-1 day, P < 0.001). All other outcomes remained similar (P>0.05). Over time, there were nonrandom (P < 0.05) downward shifts in LOS, while comprehensive complication index was unaffected. We observed 3 learning curve phases in OT: accumulation (<31 cases), optimization (case 31-65), and a steady-state (>65 cases). Propensity-score-matching confirmed reductions in index and 90-day LOS and blood loss with similar morbidity between RADP and ODP. CONCLUSION: Supervised procedure-specific training enabled successful implementation of RADP by practicing surgeons with immediate improvements in length of stay, without adverse effects on safety.


Assuntos
Educação Médica Continuada/métodos , Pancreatectomia/educação , Pancreatectomia/métodos , Procedimentos Cirúrgicos Robóticos/educação , Adulto , Idoso , Perda Sanguínea Cirúrgica , Feminino , Seguimentos , Humanos , Curva de Aprendizado , Tempo de Internação/estatística & dados numéricos , Masculino , Massachusetts , Pessoa de Meia-Idade , Duração da Cirurgia , Avaliação de Resultados em Cuidados de Saúde , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/prevenção & controle , Pontuação de Propensão , Estudos Retrospectivos
11.
Ann Surg ; 274(6): e966-e973, 2021 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-31756173

RESUMO

OBJECTIVE: To quantify the nationwide impact of minimally invasive distal pancreatectomy (MIDP) on major morbidity as compared with open distal pancreatectomy (ODP). BACKGROUND: A recent randomized controlled trial (RCT) demonstrated significant reduction in time to functional recovery after MIDP compared with ODP, but was not powered to assess potential risk reductions in major morbidity. METHODS: International cohort study using the American College of Surgeons' National Quality Improvement Program (ACS-NSQIP) (88 centers; 2014-2016) to evaluate the association between surgical approach (MIDP vs ODP) and 30-day composite major morbidity (CMM; death or severe complications) with external model validation using Dutch Pancreatic Cancer Group data (17 centers; 2005-2016). Multivariable logistic regression assessed the impact of nationwide MIDP rates between 0% and 100% on postoperative CMM at conversion rates between 0% and 25%, using estimated marginal effects. A sensitivity analysis tested the impact at various scenarios and patient populations. RESULTS: Of 2921 ACS-NSQIP patients, 1562 (53%) underwent MIDP with 18% conversion, and 1359 (47%) underwent ODP. MIDP was independently associated with reduced CMM [odds ratio (OR) 0.50, 95% confidence interval (CI) 0.42-0.60, P < 0.001], confirmed by external model validation (n = 637, P < 0.003). The association between rising MIDP implementation rates and falling postoperative morbidity was linear between 0% (all ODP) and 100% (all MIDP). The absolute risk reduction for CMM was 11% (95% CI 7.3%-15%) at observed conversion rates and improved to 14% (95% CI 11%-18%) as conversion approached 0%. Similar effects were seen across subgroups. CONCLUSION: This international study predicted a nationwide 11% risk reduction for CMM after MIDP versus ODP, which is likely to improve as conversion rates decrease. These findings confirm secondary outcomes of the recent LEOPARD RCT.


Assuntos
Procedimentos Cirúrgicos Minimamente Invasivos , Pancreatectomia/métodos , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Morbidade , Melhoria de Qualidade , Recuperação de Função Fisiológica , Fatores de Tempo
12.
Ann Surg ; 273(5): 966-972, 2021 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-31851003

RESUMO

OBJECTIVES: This study aims to present the outcomes of our decade-long experience of robotic pancreatoduodenectomy and provide insights into successful program implementation. BACKGROUND: Despite significant improvement in mortality over the past 30 years, morbidity following open pancreatoduodenectomy remains high. We implemented a minimally invasive pancreatic surgery program based on the robotic platform as one potential method of improving outcomes for this operation. METHODS: A retrospective review of a prospectively maintained institutional database was performed to identify patients who underwent robotic pancreatoduodenectomy (RPD) between 2008 and 2017 at the University of Pittsburgh. RESULTS: In total, 500 consecutive RPDs were included. Operative time, conversion to open, blood loss, and clinically relevant postoperative pancreatic fistula improved early in the experience and have remained low despite increasing complexity of case selection as reflected by increasing number of patients with pancreatic cancer, vascular resections, and higher Charlson Comorbidity scores (all P<0.05). Operating room time plateaued after 240 cases at a median time of 391 minutes (interquartile rang 340-477). Major complications (Clavien >2) occurred in less than 24%, clinically relevant postoperative pancreatic fistula in 7.8%, 30- and 90-day mortality were 1.4% and 3.1% respectively, and median length of stay was 8 days. Outcomes were not impacted by integration of trainees or expansion of selection criteria. CONCLUSIONS: Structured implementation of robotic pancreatoduodenectomy can be associated with excellent outcomes. In the largest series of RPD, we establish benchmarks for the surgical community to consider when adopting this approach.


Assuntos
Neoplasias Pancreáticas/cirurgia , Pancreaticoduodenectomia/estatística & dados numéricos , Procedimentos Cirúrgicos Robóticos/estatística & dados numéricos , Idoso , Feminino , Seguimentos , Humanos , Masculino , Estudos Retrospectivos , Resultado do Tratamento
13.
J Nutr Health Aging ; 24(6): 591-597, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32510111

RESUMO

OBJECTIVES: Interventions to increase fruit and vegetable intake among community-dwelling older people have shown mixed effects. We investigated whether an intervention based on an initial multidimensional health risk assessment and subsequent physician-lead nutrition counselling has favourable effects on dietary intake among community-dwelling older people. DESIGN: Randomised controlled trial comparing the intervention versus usual care. SETTING AND PARTICIPANTS: Non-disabled persons aged 65 years or older at an ambulatory geriatric clinic in Bucharest, Romania, allocated to intervention (n=100) and control (n=100) groups. INTERVENTION: Participants received a computer-generated health profile report based on answers to a health risk assessment questionnaire, followed by monthly individual counselling sessions with a geriatrician on topics related to health promotion and disease prevention, with a special focus on adequate fruit and vegetable consumption. MEASUREMENTS: Fruit and vegetable intake at baseline and at 6-month follow-up. RESULTS: At baseline, fruit and vegetable intake was below the recommended five portions per day in most study participants (85% in the intervention group, and 86% among controls, respectively). At six months, intake increased in the intervention group from a median of 3.8 to 4.6 portions per day, and decreased in the control group due to a seasonal effect from a median of 3.8 to 3.1 portions per day. At six months, fruit and vegetable consumption was significantly higher among persons in the intervention group as compared to controls (median difference 1.4 portions per day, 95% confidence interval 1.1-1.7, p<0.001). CONCLUSION: Personalised food-based dietary guidance, delivered as part of multidimensional preventive health counselling during geriatric clinic visits, results in relevant improvement of fruit and vegetable intake in community-dwelling older adults.


Assuntos
Aconselhamento/métodos , Frutas/química , Medição de Risco/métodos , Verduras/química , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino
14.
Nat Commun ; 11(1): 3071, 2020 06 17.
Artigo em Inglês | MEDLINE | ID: mdl-32555162

RESUMO

Unlimited access to calorie-dense, palatable food is a hallmark of Western societies and substantially contributes to the worldwide rise of metabolic disorders. In addition to promoting overconsumption, palatable diets dampen daily intake patterns, further augmenting metabolic disruption. We developed a paradigm to reveal differential timing in the regulation of food intake behavior in mice. While homeostatic intake peaks in the active phase, conditioned place preference and choice experiments show an increased sensitivity to overeating on palatable food during the rest phase. This hedonic appetite rhythm is driven by endogenous circadian clocks in dopaminergic neurons of the ventral tegmental area (VTA). Mice with disrupted clock function in the VTA lose their hedonic overconsumption rhythms without affecting homeostatic intake. These findings assign a functional role of VTA clocks in modulating palatable feeding behaviors and identify a potential therapeutic route to counteract hyperphagy in an obesogenic environment.


Assuntos
Ritmo Circadiano , Neurônios Dopaminérgicos/fisiologia , Comportamento Alimentar , Área Tegmentar Ventral/fisiologia , Animais , Apetite , Comportamento Animal , Comportamento de Escolha , Homeostase , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Obesidade/metabolismo , Oscilometria
15.
Metabolites ; 10(6)2020 May 29.
Artigo em Inglês | MEDLINE | ID: mdl-32485899

RESUMO

Widespread application of omic technologies is evolving our understanding of population health and holds promise in providing precise guidance for selection of therapeutic interventions based on patient biology. The opportunity to use hundreds of analytes for diagnostic assessment of human health compared to the current use of 10-20 analytes will provide greater accuracy in deconstructing the complexity of human biology in disease states. Conventional biochemical measurements like cholesterol, creatinine, and urea nitrogen are currently used to assess health status; however, metabolomics captures a comprehensive set of analytes characterizing the human phenotype and its complex metabolic processes in real-time. Unlike conventional clinical analytes, metabolomic profiles are dramatically influenced by demographic and environmental factors that affect the range of normal values and increase the risk of false biomarker discovery. This review addresses the challenges and opportunities created by the evolving field of clinical metabolomics and highlights features of study design and bioinformatics necessary to maximize the utility of metabolomics data across demographic groups.

16.
JAMA Surg ; 155(7): 607-615, 2020 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-32432666

RESUMO

Importance: Learning curves are unavoidable for practicing surgeons when adopting new technologies. However, patient outcomes are worse in the early stages of a learning curve vs after mastery. Therefore, it is critical to find a way to decrease these learning curves without compromising patient safety. Objective: To evaluate the association of mentorship and a formal proficiency-based skills curriculum with the learning curves of 3 generations of surgeons and to determine the association with increased patient safety. Design, Setting, and Participants: All consecutive robotic pancreaticoduodenectomies (RPDs) performed at the University of Pittsburgh Medical Center between 2008 and 2017 were included in this study. Surgeons were split into generations based on their access to mentorship and a proficiency-based skills curriculum. The generations are (1) no mentorship or curriculum, (2) mentorship but no curriculum, and (3) mentorship and curriculum. Univariable and multivariable analyses were used to create risk-adjusted learning curves by surgical generation and to analyze factors associated with operating room time, complications, and fellows completing the full resection. The participants include surgical oncology attending surgeons and fellows who participated in an RPD at University of Pittsburgh Medical Center between 2008 and 2017. Main Outcomes and Measures: The primary outcome was operating room time (ORT). Secondary outcomes were postoperative pancreatic fistula and Clavien-Dindo classification higher than grade 2. Results: We identified 514 RPDs completed between 2008 and 2017, of which 258 (50.2%) were completed by first-generation surgeons, 151 (29.3%) were completed by the second generation, and 82 (15.9%) were completed by the third generation. There was no statistically significant difference between groups with respect to age (66.3-67.3 years; P = .52) or female sex (n = 34 [41.5%] vs n = 121 [46.9%]; P = .60). There was a significant decrease in ORT (P < .001), from 450.8 minutes for the first-generation surgeons to 348.6 minutes for the third generation. Additionally, across generations, Clavien-Dindo classification higher than grade 2 (n = 74 [28.7%] vs n = 30 [9.9%] vs n = 12 [14.6%]; P = .01), conversion rates (n = 18 [7.0%] vs n = 7 [4.6%] vs n = 0; P = .006), and estimated blood loss (426 mL vs 288.6 mL vs 254.7 mL; P < .001) decreased significantly with subsequent generations. There were no significant differences in postoperative pancreatic fistula. Conclusions and Relevance: In this study, ORT, conversion rates, and estimated blood loss decreased across generations without a concomitant rise in adverse patient outcomes. These findings suggest that a proficiency-based curriculum coupled with mentorship allows for the safe introduction of less experienced surgeons to RPD without compromising patient safety.


Assuntos
Competência Clínica , Curva de Aprendizado , Mentores , Pancreaticoduodenectomia/educação , Pancreaticoduodenectomia/métodos , Procedimentos Cirúrgicos Robóticos/educação , Idoso , Currículo , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fístula Pancreática/epidemiologia , Segurança do Paciente , Complicações Pós-Operatórias/epidemiologia , Estudos Retrospectivos
17.
HPB (Oxford) ; 22(4): 563-569, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-31537457

RESUMO

BACKGROUND: Standard of care guidelines endorse self-expanding metal stents (SEMS) rather than open surgical biliary bypass (OSBB) for biliary palliation in the setting of unresectable pancreatic ductal adenocarcinoma (PDAC). This study used competing risk analysis to compare short- and long-term morbidity and overall survival among patients undergoing SEMS or OSBB after unresectable or metastatic disease is identified at the time of exploration. METHODS: Single institution retrospective cohort study (n = 127) evaluating outcomes after OSBB and SEMS for biliary palliation in patients found to have unresectable PDAC at exploration. Short-term, long-term, and lifetime risk of biliary occlusion and survival were compared after adjustment for stage and comprehensive complication index (CCI). RESULTS: Baseline demographics and tumor characteristics were equivalent between cohorts. Short-term complications were more frequent after OSBB, whereas late complications were greater after SEMS. The cumulative incidence of recurrent biliary obstruction was greater after SEMS, but lifetime complication burden and median survival were equivalent. CONCLUSION: OSBB was associated with longer hospital stays and more short-term complications, and SEMS was associated with a higher risk of recurrent biliary obstruction among surgical patients with unresectable PDAC. Patient preference should be defined pre-operatively in the case the unresectable disease is encountered during attempted resection.


Assuntos
Adenocarcinoma/patologia , Colestase/cirurgia , Cuidados Paliativos , Neoplasias Pancreáticas/patologia , Complicações Pós-Operatórias/epidemiologia , Stents Metálicos Autoexpansíveis , Adenocarcinoma/mortalidade , Adenocarcinoma/cirurgia , Idoso , Colestase/etiologia , Colestase/mortalidade , Feminino , Humanos , Tempo de Internação , Masculino , Pessoa de Meia-Idade , Neoplasias Pancreáticas/mortalidade , Neoplasias Pancreáticas/cirurgia , Estudos Retrospectivos , Taxa de Sobrevida , Resultado do Tratamento
18.
Pancreatology ; 19(7): 979-984, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31522961

RESUMO

BACKGROUND/OBJECTIVES: To determine the prevalence of incidental pulmonary embolism (PE) detected during initial staging CT among patients with newly diagnosed pancreatic ductal adenocarcinoma (PDAC) and assess their association with underlying tumor burden. MATERIALS AND METHODS: This retrospective cohort study evaluated staging chest CT scans (2013-2017) to identify PE among patients with treatment naïve, biopsy-proven PDAC. Data included age, sex, T stage, AJCC stage, presence/absence of metastases and their location at diagnosis. The association of PE with tumor (T1-T4) and AJCC stage were assessed using Pearson Chi-square and Fischer's exact test. A threshold p-value of <0.05 indicated statistical significance. RESULTS: A total of 174 patients (90 female, mean age, 68 years; range: 34-93) were identified, of which 10 patients harbored incidental PE (prevalence, 5.7%). In the PE group, two patients presented with distant metastasis (liver, 20%), while eight patients had T4 tumors (80%). No statistical association was detected between PE and age, sex, and the presence/absence or location of distant metastasis (p = 0.065, p = 0.59, p = 0.687 and p = 0.933, respectively). Patients with T4 tumors and higher AJCC stages (stage III/IV) were significantly more likely to present with PE than those with lower T stage (p = 0.045) and AJCC stage (stage I/II; p = 0.017). CONCLUSION: The prevalence of incidental PE among PDAC patients undergoing initial CT staging is 5.7%. Patients with T4 and AJCC stages III/IV are at higher risk of PE. Caution should be exercised during radiographic interpretation of initial staging chest CTs, as incidental PE may be lurking and require treatment.


Assuntos
Carcinoma Ductal Pancreático/complicações , Carcinoma Ductal Pancreático/patologia , Embolia/diagnóstico , Embolia/patologia , Neoplasias Pancreáticas/complicações , Neoplasias Pancreáticas/patologia , Idoso , Idoso de 80 Anos ou mais , Carcinoma Ductal Pancreático/terapia , Estudos de Coortes , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias Pancreáticas/terapia , Estudos Retrospectivos
19.
BJS Open ; 3(3): 252-259, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-31183440

RESUMO

Background: Adverse events in the operating theatre related to non-technical skills and teamwork are still an issue. The influence of minimally invasive techniques on team performance and subsequent impact on patient safety remains unclear. The aim of this review was to assess the methodology used to objectify and rate team performance in minimally invasive abdominal surgery. Methods: A systematic literature search was conducted according to the PRISMA guidelines. Studies on assessment of surgical team performance or non-technical skills of the surgical team in the setting of minimally invasive abdominal surgery were included. Study aim, methodology, results and conclusion were extracted for qualitative synthesis. Results: Sixteen studies involving 677 surgical procedures were included. All studies consisted of observational case series that used heterogeneous methodologies to assess team performance and were of low methodological quality. The most commonly used team performance objectification tools were 'construct'- and 'incident'-based tools. Evidence of validity for the assessed outcome was spread widely across objectification tools, ranging from low to high. Diverse and poorly defined outcomes were reported. Conclusion: Team demands for minimally invasive approaches to abdominal procedures remain unclear. The current literature consists of studies with heterogeneous methodology and poorly defined outcomes.


Assuntos
Abdome/cirurgia , Competência Clínica/estatística & dados numéricos , Procedimentos Cirúrgicos Minimamente Invasivos/métodos , Medicina Baseada em Evidências/métodos , Humanos , Procedimentos Cirúrgicos Minimamente Invasivos/estatística & dados numéricos , Estudos Observacionais como Assunto , Avaliação de Resultados em Cuidados de Saúde , Segurança do Paciente , Pesquisa Qualitativa
20.
HPB (Oxford) ; 21(11): 1585-1591, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31076257

RESUMO

BACKGROUND: Enucleation of low-grade pancreatic tumors achieves oncological outcomes equivalent to resection but conserves parenchyma. Given strict selection criteria, we hypothesized that minimally-invasive (MI) enucleation is associated with decreased composite major morbidity (CMM) compared to open. METHODS: Pancreas-targeted ACS NSQIP (2014 -2016) was queried for enucleation (CPT code: 48120) and analyzed by intended surgical approach regardless of conversion. The primary outcome was CMM, a validated 30-day composite metric of adverse events. RESULTS: Enucleation was performed using an open (n = 71; 62.3%) or MI (n = 43; 37.7%) approach with 7 conversions (16.2%). Both cohorts had interchangeable baseline characteristics. No selection factors governing MI were identified. MI-enucleation reduced median length of stay (4 vs. 5 days; p = 0.003), whereas rates of CMM after open (24; 34%) and MIenucleation (12; 28%) were equivalent (p = 0.541). Multivariable analysis demonstrated an association between CMM and prolonged operative time (OR 2.7, 95% CI 1.14 -6.74), female sex (OR 0.38, 95% CI 0.16 -0.94), and ASA score <3 (OR 0.39, 95% CI 0.16 -0.96) but not surgical approach. CONCLUSION: MI-enucleation was not associated with reduced 30-day CMM compared to open, whereas prolonged operating time and unmodifiable patient factors were correlated with adverse outcomes.


Assuntos
Pancreatectomia/métodos , Neoplasias Pancreáticas/cirurgia , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Procedimentos Cirúrgicos Minimamente Invasivos , Gradação de Tumores , Neoplasias Pancreáticas/patologia , Estudos Retrospectivos
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