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J Immunother ; 44(5): 185-192, 2021 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-33935273


Despite its increased application in pancreatic ductal adenocarcinoma (PDAC), complete response to neoadjuvant therapy (NAT) is rare. Given the critical role of host immunity in regulating cancer, we sought to correlate baseline inflammatory profiles to significant response to NAT. PDAC patients receiving NAT were classified as responders (R) or nonresponders (NR) by carbohydrate antigen 19-9 response, pathologic tumor size, and lymph node status in the resected specimen. Baseline (treatment-naive) plasma was analyzed to determine levels of 27 inflammatory mediators. Logistic regression was used to correlate individual mediators with response. Network analysis and Pearson correlation maps were derived to determine baseline inflammatory mediator profiles. Forty patients (20R and 20NR) met study criteria. The R showed significantly higher overall survival (59.4 vs. 21.25 mo, P=0.002) and disease-free survival (50.97 vs. 10.60 mo, P=0.005), compared with NR. soluble interleukin-2 receptor alpha was a significant predictor of no response to NAT (P=0.045). Analysis of inflammatory profiles using the Pearson heat map analysis followed by network analysis depicted increased inflammatory network complexity in NR compared with R (1.69 vs. 1), signifying a more robust baseline inflammatory status of NR. A panel of inflammatory mediators identified by logistic regression and Fischer score analysis was used to create a potential decision tree to predict NAT response. We demonstrate that baseline inflammatory profiles are associated with response to NAT in PDAC, and that an upregulated inflammatory status is associated with a poor response to NAT. Further analysis into the role of inflammatory mediators as predictors of chemotherapy response is warranted.

PLoS One ; 16(2): e0246669, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33556123


BACKGROUND: Processes for transferring patients to higher acuity facilities lack a standardized approach to prognostication, increasing the risk for low value care that imposes significant burdens on patients and their families with unclear benefits. We sought to develop a rapid and feasible tool for predicting mortality using variables readily available at the time of hospital transfer. METHODS AND FINDINGS: All work was carried out at a single, large, multi-hospital integrated healthcare system. We used a retrospective cohort for model development consisting of patients aged 18 years or older transferred into the healthcare system from another hospital, hospice, skilled nursing or other healthcare facility with an admission priority of direct emergency admit. The cohort was randomly divided into training and test sets to develop first a 54-variable, and then a 14-variable gradient boosting model to predict the primary outcome of all cause in-hospital mortality. Secondary outcomes included 30-day and 90-day mortality and transition to comfort measures only or hospice care. For model validation, we used a prospective cohort consisting of all patients transferred to a single, tertiary care hospital from one of the 3 referring hospitals, excluding patients transferred for myocardial infarction or maternal labor and delivery. Prospective validation was performed by using a web-based tool to calculate the risk of mortality at the time of transfer. Observed outcomes were compared to predicted outcomes to assess model performance. The development cohort included 20,985 patients with 1,937 (9.2%) in-hospital mortalities, 2,884 (13.7%) 30-day mortalities, and 3,899 (18.6%) 90-day mortalities. The 14-variable gradient boosting model effectively predicted in-hospital, 30-day and 90-day mortality (c = 0.903 [95% CI:0.891-0.916]), c = 0.877 [95% CI:0.864-0.890]), and c = 0.869 [95% CI:0.857-0.881], respectively). The tool was proven feasible and valid for bedside implementation in a prospective cohort of 679 sequentially transferred patients for whom the bedside nurse calculated a SafeNET score at the time of transfer, taking only 4-5 minutes per patient with discrimination consistent with the development sample for in-hospital, 30-day and 90-day mortality (c = 0.836 [95%CI: 0.751-0.921], 0.815 [95% CI: 0.730-0.900], and 0.794 [95% CI: 0.725-0.864], respectively). CONCLUSIONS: The SafeNET algorithm is feasible and valid for real-time, bedside mortality risk prediction at the time of hospital transfer. Work is ongoing to build pathways triggered by this score that direct needed resources to the patients at greatest risk of poor outcomes.

Mortalidade Hospitalar , Transferência de Pacientes/métodos , Medição de Risco/métodos , Idoso , Idoso de 80 Anos ou mais , Estudos de Coortes , Serviço Hospitalar de Emergência , Feminino , Previsões/métodos , Hospitalização , Hospitais , Humanos , Masculino , Pessoa de Meia-Idade , Modelos Estatísticos , Transferência de Pacientes/estatística & dados numéricos , Estudos Retrospectivos
Ann Surg Oncol ; 28(7): 3779-3788, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-33231769


BACKGROUND: Neoadjuvant therapy is increasingly used for patients with pancreatic ductal adenocarcinoma (PDAC). It is unknown whether neoadjuvant chemoradiotherapy is more effective than chemotherapy (NCRT vs. NAC). We aim to compare pathological and survival outcomes of NCRT and NAC in patients with PDAC. PATIENTS AND METHODS: Single-center analysis of PDAC patients treated with NCRT or NAC followed by resection between December 2008 and December 2018 was performed. Average treatment effect (ATE) was estimated after case-control matching using Mahalanobis distance nearest-neighbor matching. Inverse probability weighted estimates (IPWE)-based ATE was estimated for disease-free survival (DFS) and overall survival (OS). RESULTS: Among the 418 patients (mean age 66.8 years, 51% female) included in the study, 327 received NAC and 91 received NCRT. NCRT patients had higher rates of locally advanced disease, number of neoadjuvant chemotherapy cycles, more chemotherapy regimen crossover (gemcitabine and 5-FU based), and were more likely to undergo open surgical procedures and/or vascular resection (all p < 0.05). After matched analysis, NCRT was associated with a significant reduction in lymph node positive disease [ATE = (-)0.24, p = 0.007] and lymphovascular invasion [ATE = (-)0.20, p = 0.02]. While NCRT was associated with significantly improved DFS by 9.5 months (p = 0.006), it did not affect OS by IPWE-based ATE after adjusting for adjuvant therapy (ATE = 5.5 months; p = 0.32). CONCLUSION: Compared with NAC alone, NCRT is associated with improved pathologic surrogates and disease-free survival, but not overall survival in patients with PDAC.

Terapia Neoadjuvante , Neoplasias Pancreáticas , Idoso , Quimiorradioterapia , Intervalo Livre de Doença , Feminino , Humanos , Masculino , Estadiamento de Neoplasias , Neoplasias Pancreáticas/terapia , Estudos Retrospectivos
J Vasc Surg ; 72(4): 1427-1435.e1, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32972588


OBJECTIVE: This study aimed to develop risk predictive models of 30-day mortality, morbidity, and major adverse limb events (MALE) after bypass surgery for aortoiliac occlusive disease (AIOD) and to compare their performances with a 5-Factor Frailty Index. METHODS: The American College of Surgeons National Surgical Quality Improvement Program 2012-2017 Procedure Targeted Aortoiliac (Open) Participant Use Data Files were queried to identify all patients who had elective bypass for AIOD: femorofemoral bypass, aortofemoral bypass, and axillofemoral bypass (AXB). Outcomes assessed included mortality, major morbidity, and MALE within 30 days postoperatively. Major morbidity was defined as pneumonia, unplanned intubation, ventilator support for >48 hours, progressive or acute renal failure, cerebrovascular accident, cardiac arrest, or myocardial infarction. Demographics, comorbidities, procedure type, and laboratory values were considered for inclusion in the risk predictive models. Logistic regression models for mortality, major morbidity and MALE were developed. The discriminative ability of these models (C-indices) were compared with that of the 5-Factor Modified Frailty Index (mFI-5): a general frailty tool determined from diabetes, functional status, history of chronic obstructive pulmonary disease, history of congestive heart failure, and hypertension. Calculators were derived using the most significant variables for each of the three risk predictive models. RESULTS: A total of 2612 cases (mean age 65.0, 60% male) were identified, of which 1149 (44.0%) were femorofemoral bypass, 1138 (43.6%) were aortofemoral bypass, and 325 (12.4%) were axillofemoral bypass. Overall, the rates of mortality, major morbidity, and MALE were 2.0%, 8.5%, and 4.9%, respectively. Twenty preoperative risk factors were considered for incorporation in the risk tools. Apart from procedure type, age was the most statistically significant predictor of both mortality and morbidity. Preoperative anemia and critical limb ischemia were the most significant predictors of MALE. All three constructed models demonstrated significantly better discriminative ability (P < .001) on the outcomes of interest as compared with the mFI-5. CONCLUSIONS: Our models outperformed the mFI-5 in predicting 30-day mortality, major morbidity, and adverse limb events in patients with AIOD undergoing elective bypass surgery. Calculators were created using the most statistically significant variables to help calculate individual patient's postoperative risks and allow for better informed consent and risk-adjusted comparison of provider outcomes.

Procedimentos Cirúrgicos Eletivos/efeitos adversos , Fragilidade/diagnóstico , Doença Arterial Periférica/cirurgia , Complicações Pós-Operatórias/epidemiologia , Procedimentos Cirúrgicos Vasculares/efeitos adversos , Idoso , Idoso de 80 Anos ou mais , Aorta/patologia , Aorta/cirurgia , Artéria Axilar/cirurgia , Procedimentos Cirúrgicos Eletivos/métodos , Feminino , Artéria Femoral/cirurgia , Fragilidade/complicações , Mortalidade Hospitalar , Humanos , Artéria Ilíaca/patologia , Extremidade Inferior/irrigação sanguínea , Masculino , Pessoa de Meia-Idade , Doença Arterial Periférica/etiologia , Doença Arterial Periférica/mortalidade , Complicações Pós-Operatórias/etiologia , Prognóstico , Estudos Retrospectivos , Medição de Risco/métodos , Fatores de Risco , Resultado do Tratamento , Procedimentos Cirúrgicos Vasculares/métodos
JAMA Surg ; 155(7): 607-615, 2020 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-32432666


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.

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
J Am Geriatr Soc ; 68(8): 1818-1824, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32310317


BACKGROUND: Frailty is a marker of dependency, disability, hospitalization, and mortality in community-dwelling older adults. However, existing tools for measuring frailty are too cumbersome for rapid point-of-care assessment. The Risk Analysis Index (RAI) of frailty is validated in surgical populations, but its performance outside surgical populations is unknown. OBJECTIVE: Validate the RAI in ambulatory patients. DESIGN, SETTING, AND PARTICIPANTS: Observational cohort study of outpatient surgical clinics within the University of Pittsburgh Medical Center Healthcare System between July 1, 2016, and December 31, 2016. Frailty was assessed using the RAI. Current Procedural Terminology codes following RAI assessment identified patients with and without minor office-based procedures (eg, joint injection, laryngoscopy). MAIN OUTCOMES AND MEASURES: All-cause 1-year mortality, assessed by stratified Cox proportional hazard models. RESULTS: Of 28,059 patients, 13,861 were matched to a minor, office-based procedure and 14,198 did not undergo any procedure. The mean (SD) age was 56.7 (17.2) years; women constituted 15,797 (56.3%) of the cohort. Median time (interquartile range 25th-75th percentile) to measure RAI was 30 (22-47) seconds. Mortality among the frail was two to five times that of patients with normal RAI scores. For example, the hazard ratio for frail ambulatory patients without a minor procedure was 3.69 (95% confidence interval [CI] = 2.51-5.41), corresponding to 30-, 180-, and 365-day mortality rates of 2.9%, 11.2%, and 17.4%, respectively, compared to 0.3%, 2.3%, and 4.0% among patients with normal RAI scores. Discrimination of mortality (overall, and censored at 30, 180, and 365 days) was excellent, ranging from c = 0.838 (95% CI = 0.773-0.902) for 30-day mortality after minor procedures to c = 0.909 (95% CI = 0.855-0.964) without a procedure. CONCLUSION: RAI is a valid, easily administered tool for point-of-care frailty assessment in ambulatory populations that may help clinicians and patients make better informed decisions about care choices-especially among patients considered high risk with a potentially limited life span. J Am Geriatr Soc 68:1818-1824, 2020.

Fragilidade/diagnóstico , Fragilidade/mortalidade , Indicadores Básicos de Saúde , Pacientes Ambulatoriais/estatística & dados numéricos , Medição de Risco/normas , Idoso , Idoso de 80 Anos ou mais , Assistência Ambulatorial/estatística & dados numéricos , Feminino , Idoso Fragilizado/estatística & dados numéricos , Avaliação Geriátrica/métodos , Humanos , Vida Independente/estatística & dados numéricos , Masculino , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Reprodutibilidade dos Testes , Medição de Risco/métodos