Peptide-based capture-and-release purification of extracellular vesicles and statistical algorithm enabled quality assessment.

Circulating extracellular vesicles (EVs) have gained significant attention for discovering tumor biomarkers. However, isolating EVs with well-defined homogeneous populations from complex biological samples is challenging. Different isolation methods have been found to derive different EV populations carrying different molecular contents, which confounds current investigations and hinders subsequent clinical translation. Therefore, standardizing and building a rigorous assessment of isolated EV quality associated with downstream molecular analysis is essential. To address this need, we introduce a statistical algorithm (ExoQuality Index, EQI) by integrating multiple EV characterizations (size, particle concentration, zeta potential, total protein, and RNA), enabling direct EV quality assessment and comparisons between different isolation methods. We also introduced a novel capture-release isolation approach using a pH-responsive peptide conjugated with NanoPom magnetic beads (ExCy) for simple, fast, and homogeneous EV isolation from various biological fluids. Bioinformatic analysis of next-generation sequencing (NGS) data of EV total RNAs from pancreatic cancer patient plasma samples using our novel EV isolation approach and quality index strategy illuminates how this approach improves the identification of tumor associated molecular markers. Results showed higher human mRNA coverage compared to existing isolation approaches in terms of both pancreatic cancer pathways and EV cellular component pathways using gProfiler pathway analysis. This study provides a valuable resource for researchers, establishing a workflow to prepare and analyze EV samples carefully and contributing to the advancement of reliable and rigorous EV quality assessment and clinical translation.

Impact of Biopsy Attempts, Race, and Access on Time to Initiation of Treatment for Pancreatic Cancer.

BACKGROUND: Biopsy of suspected pancreatic cancer (PDAC) in surgical candidates is informative however not always necessary. Biopsies impact treatment options as histological diagnosis are presently required for neo-adjuvant therapy, but not surgical resection. We explored the impact of pursuing tissue diagnosis by endoscopic ultrasound (EUS) biopsy on time to treatment in patients with resectable and borderline resectable PDAC. METHODS: A retrospective review of surgical patients with ultimately proven PDAC was performed (2011-2021). Milestone dates (cancer suspected, biopsy(ies), surgical or neo-adjuvant treatment) were collected. Mann-Whitney-Wilcoxon tests, Pearson's chi-squared tests, Fisher's exact tests, linear regressions, and Cox proportional hazard models were used for data analysis. RESULTS: Among 131 resectable and 58 borderline resectable patients, the borderline resectable group underwent more biopsies (1.2 vs 0.7, p < 0.0001), were more likely to undergo biopsy at tertiary care centers (67.2% vs 30.5%, p < 0.0001), and trended toward longer time to treatment (49 vs 44 days, p = 0.070). Significant increases in days to treatment were seen in patients with Black race (29 days, p = 0.0002) and Medicare insurance (22 days, p = 0.038) and no biopsies at a tertiary care center (10 days, p = 0.039). After adjusting for covariates, additional biopsies significantly delayed treatment (1 biopsy: 21 days, p = 0.0001; 2 biopsies: 44 days, p < 0.0001; 3 biopsies: 68 days, p < 0.0001). CONCLUSIONS: EUS biopsy significantly impacts time between suspicion and treatment of PDAC. This may be exacerbated by clinical practices increasingly favoring neo-adjuvant therapy that necessitates biopsy-proven disease. Time to treatment may also be impacted by access to tertiary centers and racial disparities.

It's more than just cancer biology: Health disparities in patients with pancreatic neuroendocrine tumors.

BACKGROUND AND OBJECTIVES: Pancreatic neuroendocrine tumors (PNETs) represent a rare form of pancreatic cancer. Racial/ethnic disparities have been documented in pancreatic ductal adenocarcinoma, but health disparities have not been well described in patients with PNETs. METHODS: A retrospective review of patients with PNETs in the National Cancer Database was performed for 2004-2014. Approximately 16 605 patients with PNETs and available vital status were identified. Survival was compared by race/ethnicity and socioeconomic status using Kaplan-Meier methods and Cox regression. RESULTS: There were no significant differences in survival between Non-Hispanic, White; Hispanic, White; or Non-Hispanic, Black patients on univariate analysis. Kaplan-Meier analysis showed that patients from communities with lower median household income and education level had worse survival (p < 0.001). Patients age less than 65 without insurance, similarly, had worse survival (p < 0.001). Multivariable modeling found no association between race/ethnicity and risk of mortality (p = 0.37). Lower median household income and lower education level were associated with increased mortality (p < 0.001). CONCLUSIONS: Unlike most other malignancies, race/ethnicity is not associated with survival differences in patients with PNETs. Patients with lower socioeconomic status had worse survival. The presence of identifiable health disparities in patients with PNETs represents a target for intervention and opportunity to improve survival in patients with this malignancy.

The use of a functional test battery as a non-invasive method of fatigue assessment.

To assess whether a battery of performance markers, both individually and as group, would be sensitive to fatigue, a within group random cross-over design compared multiple variables during seated control and fatigue (repeated sprint cycling) conditions. Thirty-two physically active participants completed a neuromuscular fatigue questionnaire, Stroop task, postural sway, squat jump, countermovement jump, isometric mid-thigh pull and 10 s maximal sprint cycle (Sprintmax) before and after each condition (15 min, 1 h, 24 h and 48 h). In comparison to control, larger neuromuscular fatigue questionnaire total score decrements were observed 15 min (5.20 ± 4.6), 1 h (3.33 ± 3.9) and 24 h (1.83 ± 4.8) after cycling. Similarly, the fatigue condition elicited greater declines than control at 15 min and 1 h post in countermovement jump height (1.67 ± 1.90 cm and 1.04 ± 2.10 cm), flight time-contraction time ratio (0.03 ± 0.06 and 0.05 ± 0.11), and velocity (0.06 ± 0.07 m∙s-1 and 0.04 ± 0.08 m∙s-1). After fatigue, decrements were observed up to 48 h for average Sprintmax cadence (4-6 RPM), up to 24 h in peak Sprintmax cadence (2-5 RPM) and up to 1 h in average and peak Sprintmax power (45 ± 60 W and 58 ± 71 W). Modelling variables in a stepwise regression demonstrated that CMJ height explained 53.2% and 51.7% of 24 h and 48 h Sprintmax average power output. Based upon these data, the fatigue induced by repeated sprint cycling coincided with changes in the perception of fatigue and markers of performance during countermovement and squat jumps. Furthermore, multiple regression modelling revealed that a single variable (countermovement jump height) explained average power output.

PROspective Evaluation of Chronic Pancreatitis for EpidEmiologic and Translational StuDies: Rationale and Study Design for PROCEED From the Consortium for the Study of Chronic Pancreatitis, Diabetes, and Pancreatic Cancer.

Prospective Evaluation of Chronic Pancreatitis for Epidemiologic and Translational Studies (PROCEED) is the first prospective, observational cohort study of chronic pancreatitis (CP) in the United States. The primary goals of PROCEED are to define disease progression, test the predictive capability of candidate biomarkers, and develop a platform to conduct translational and mechanistic studies in CP. Using objective and consensus-driven criteria, PROCEED will enroll adults at different stages of CP-controls, suspected CP, and definite CP. In addition to collecting detailed information using structured case report forms and protocol-mandated evaluations at baseline and during follow-up, PROCEED will establish a linked biorepository of blood, urine, saliva, stool, pancreatic fluid, and pancreatic tissue. Enrollment for PROCEED began in June 2017. As of July 1, 2018, nine clinical centers of the Consortium for the Study of Chronic Pancreatitis, Diabetes, and Pancreatic Cancer are enrolling, and 350 subjects have completed baseline evaluation. In conclusion, PROCEED will provide the most accurate and reliable estimates to date on progression of CP. The established cohort and biorepository will facilitate numerous analyses, leading to new strategies for diagnosis, methods to monitor disease progression, and treatment of CP.

Analysis of the Cost Effectiveness of Laparoscopic Pancreatoduodenectomy.

OBJECTIVE: We sought to determine if laparoscopic pancreatoduodenectomy (LPD) is a cost-effective alternative to open pancreatoduodenectomy (OPD). METHODS: Hospital cost data, discharge disposition, readmission rates, and readmission costs from periampullary cancer patient cohorts of LPD and OPD were compared. The surgical cohorts over a 40-month period were clinically similar, consisting of 52 and 50 patients in the LPD and OPD groups, respectively. RESULTS: The total operating room costs were higher in the LPD group as compared to the OPD group (median US$12,290 vs US$11,299; P = 0.05) due to increased costs for laparoscopic equipment and regional nerve blocks (P ≤ 0.0001). Although hospital length of stay was shorter in the LPD group (median 7 vs 8 days; P = 0.025), the average hospital cost was not significantly decreased compared to the OPD group (median $28,496 vs $28,623). Surgery-related readmission rates and associated costs did not differ between groups. Compared to OPD patients, significantly more LPD patients were discharged directly home rather than to other healthcare facilities (88% vs 72%; P = 0.047). CONCLUSION: For the index hospitalization, the cost of LPD is equivalent to OPD. Total episode-of-care costs may favor LPD via reduced post-hospital needs for skilled nursing and rehabilitation.

Cost Effectiveness of a Novel Attempt to Reduce Readmission after Ileostomy Creation.

BACKGROUND AND OBJECTIVES: Dehydration is a common complication after ileostomy creation and is the most frequent reason for postoperative readmission to the hospital. We sought to determine the clinical and economic impact of an outpatient intervention to decrease readmissions for dehydration after ileostomy creation. METHODS: All new ileostomates from 09/2011 through 10/2012 at the University of Florida were enrolled to receive an ileostomy education and management protocol and a daily telephone call for 3 weeks after discharge. Counseling and medication adjustments were provided, with a satisfaction survey at the end. Outcomes of these patients were compared to those in a historical control cohort. A cost analysis was conducted to calculate the savings to the hospital. RESULTS: Thirty-eight patients were enrolled. All patients required telephone counseling, and the mean satisfaction score rating was 4.69, on a scale of 1 to 5. The readmission rate for dehydration within 30 days of discharge decreased significantly from 65% before intervention to 16% (5/32 patients) after intervention (P = .002). The length of readmission hospital stay decreased from a mean of 4.2 days before the introduction of the intervention to 3 days after. Cost analysis revealed that the actual total hospital cost of dehydration-specific readmission decreased from $88,858 to $25,037, a saving of $63,821. CONCLUSION: A standardized ileostomy pathway with comprehensive patient education and outpatient telephone follow-up is cost effective, has a positive influence on patient satisfaction, and reduces dehydration-related readmission rates.

The impact of interhospital transfers on surgical quality metrics for academic medical centers.

The emergence of pay-for-performance systems pose a risk to an academic medical center's (AMC) mission to provide care for interhospital surgical transfer patients. This study examines quality metrics and resource consumption for a sample of these patients from the University Health System Consortium (UHC) and our Department of Surgery (DOS). Standard benchmarks, including mortality rate, length of stay (LOS), and cost, were used to evaluate the impact of interhospital surgical transfers versus direct admission (DA) patients from January 2010 to December 2012. For 1,423,893 patients, the case mix index for transfer patients was 38 per cent (UHC) and 21 per cent (DOS) greater than DA patients. Mortality rates were 5.70 per cent (UHC) and 6.93 per cent (DOS) in transferred patients compared with 1.79 per cent (UHC) and 2.93 per cent (DOS) for DA patients. Mean LOS for DA patients was 4 days shorter. Mean total costs for transferred patients were greater $13,613 (UHC) and $13,356 (DOS). Transfer patients have poorer outcomes and consume more resources than DA patients. Early recognition and transfer of complex surgical patients may improve patient rescue and decrease resource consumption. Surgeons at AMCs and in the community should develop collaborative programs that permit collective assessment and decision-making for complicated surgical patients.

Esophageal perforation management using a multidisciplinary minimally invasive treatment algorithm.

BACKGROUND: The surgical management of esophageal perforation (EP) often results in mortality and significant morbidity. Recent less invasive approaches to EP management include endoscopic luminal stenting and minimally invasive surgical therapies. We wished to establish therapeutic efficacy of minimally invasive therapies in a consecutive series of patients. STUDY DESIGN: An IRB-approved retrospective review of all acute EPs between 2007 and 2013 at a single institution was performed. Patient demographic, clinical outcomes data, and hospital charges were collected. RESULTS: We reviewed 76 consecutive patients with acute EP presenting to our tertiary care center. Median age was 64 ± 16 years (range 25 to 87 years), with 50 men and 26 women. Ninety percent of EPs were in the distal esophagus, with 67% of iatrogenic perforations occurring within 4 cm of the gastroesophageal junction. All patients were treated within 24 hours of initial presentation with a removable covered esophageal stent. Leak occlusion was confirmed within 48 hours of esophageal stent placement in 68 patients. Median lengths of ICU and hospital stay were 3 and 10 days, respectively (range 1 to 86 days). One-third of the patients were noted to have prolonged intubation (>7 days) and pneumonia that required a tracheostomy. One in-hospital (1.3%) mortality occurred within 30 days. Median total hospital charges for EP were $85,945. CONCLUSIONS: Endoscopically placed removable esophageal stents with minimally invasive repair of the perforation and feeding access is an effective treatment method for patients with EP. This multidisciplinary method enabled us to care for severely ill patients while minimizing morbidity and mortality and avoiding open esophageal surgery.

Faculty clinical quality goals drive improvement in University HealthSystem Consortium outcome measures.

Mortality, length of stay (LOS), patient safety indicators (PSIs), and hospital-acquired conditions (HACs) are routinely reported by the University HealthSystem Consortium (UHC) to measure quality at academic health centers. We hypothesized that a clinical quality measurable goal assigned to individual faculty members would decrease UHC measures of mortality, LOS, PSIs, and HACs. For academic year (AY) 2010-2011, faculty members received a clinical quality goal related to mortality, LOS, PSIs, and HACs. The quality metric constituted 25 per cent of each faculty member's annual evaluation clinical score, which is tied to compensation. The outcomes were compared before and after goal assignment. Outcome data on 6212 patients from AY 2009-2010 were compared with 6094 patients from AY 2010-2011. The mortality index (0.89 vs 0.93; P = 0.73) was not markedly different. However, the LOS index decreased from 1.01 to 0.97 (P = 0.011), and department-wide PSIs decreased significantly from 285 to 162 (P = 0.011). Likewise, HACs decreased from 54 to 18 (P = 0.0013). Seven (17.9%) of 39 faculty had quality grades that were average or below. Quality goals assigned to individual faculty members are associated with decreased average LOS index, PSIs, and HACs. Focused, relevant quality assignments that are tied to compensation improve patient safety and outcomes.

Outcomes of operative management of appendicitis.

BACKGROUND: There has not been an appraisal of outcomes of appendectomy for more than 10 years. More reliable diagnostic techniques and minimally invasive surgery are now in widespread use, yet the impact of these advances remains unknown. METHODS: A retrospective review was performed of 453 patients who underwent appendectomy for appendicitis at a single hospital from 2004 to 2009. Patient demographics, operative characteristics, procedure cost, and pathologic diagnoses were analyzed. RESULTS: The overall rate of complicated appendicitis was 13%, with a negative appendectomy rate of 4.9%. The average age was significantly greater for patients with complicated versus uncomplicated appendicitis (47 vs. 33 years, respectively; p<0.001), and by logistic regression, age (as a continuous variable) was a significant factor for complicated appendicitis (p<0.001). The hospital length of stay was 2.3 times longer for patients with complicated appendicitis (4.4 vs. 1.9 days; p<0.001), and the average cost was 86% higher ($14,125 vs. $7,595; p<0.001), the difference in cost being attributable mostly to pharmacy and nursing costs. CONCLUSIONS: Advances in diagnostic and surgical technique may be altering traditionally accepted rates of complicated appendicitis and negative appendectomy. For the first time, age is shown to be related to the rate of complicated appendicitis as a continuous variable rather than simply an extreme. Patients with complicated appendicitis still stay in the hospital longer, and there is a large cost difference as a result.

Delayed operating room availability significantly impacts the total hospital costs of an urgent surgical procedure.

BACKGROUND: Financial pressures drive efforts to optimize hospital resource use, but inefficiencies occur in systems as volume nears total capacity. We examined how operating room use impacts efficiency and costs of treating an urgent surgical condition. METHODS: A retrospective review of patients who underwent appendectomy for appendicitis at a single hospital from 2004 to 2009 was performed. Patient demographics, operative characteristics, pathologic diagnoses, hospital time intervals, and costs were analyzed. Gap time (time from case booking to surgery start) was used to measure operating room availability. RESULTS: In all, 453 patients met inclusion criteria. Longer gap times were associated with increased hospital-based costs. A gap time of greater than 2 h was associated with 39% higher costs to the hospital, which could not be accounted for by any single cost center. The patients in the 2 groups had similar medical and surgical complexity, as well as similar clinical outcomes and hospital duration of stay. Gap times were greatest during peak elective operating room activity (7 am to 11 pm); however, the total hospital costs were not related to the time of day of the case. CONCLUSION: A short delay in operating room availability for urgent cases is associated with significantly increased total hospital costs. Our data suggest this finding is attributable to inefficient care when the operating room volume nears total capacity.

Short- and long-term costs of laparoscopic colectomy are significantly less than open colectomy.

BACKGROUND: The financial impact of laparoscopic colectomy remains poorly defined. We report the short-term costs of laparoscopic colectomy (LC) as compared with open colectomy (OC) in a high-volume tertiary care hospital, and are the first to incorporate the costs of late, colectomy-related complications in an analysis of long-term costs. METHODS: A retrospective analysis of patients undergoing elective laparoscopic (n = 76) or open (n = 162) colon resection between January 2004 and December 2006 was performed. Primary endpoints were total hospital cost of the index admission and total hospital cost for any subsequent admission for treatment of a colectomy-related complication. RESULTS: Two-hundred thirty-eight patients met inclusion criteria. Mean total hospital cost was significantly greater for patients undergoing OC (US $17,686 per patient versus US $14,518, P = 0.0003). Mean total operative costs were equivalent (US $7,451 OC versus US $7,794 LC, P = 0.274). Average length of stay was shorter for LC (5.2 versus 6.9 days, P < 0.0001). Late complication rates were 5.6% (OC) and 2.6% (LC). Integrating the cost of late complications further increased the disparity between the total cost of OC (US $18,296 per patient, 3.4% increase) as compared with LC (US $14,789, 1.9% increase). CONCLUSION: We demonstrate both short- and long-term financial benefits of LC in a high-volume tertiary care hospital.

Transition from open access to quota based fishery management regimes in Alaska increased the safety of operations.

During the past 12 years fishery managers responsible for federal fisheries off Alaska have developed and implemented three new fishery management limited access/quota share programs in place of traditional open access management. The three limited access programs are unique but each provides for the allocation of quota shares to individual participants in the halibut and sablefish longline fishery, in the Bering Sea pollock trawl fishery and in the Bering Sea king and Tanner crab fishery, respectively. New management programs are briefly described and contrasted with traditional management. For each of the three fisheries, management changes over time have generated substantial changes in fishing fleets, their operations, crew employment, economics and safety records. Under quota share management, fleet consolidations have occurred, particularly in the more over capitalized fisheries. The intense speed and inflexible timing associated with open access fisheries have greatly lessened as have the risk taking and incentives to maximize fishing power. Active vessel economic viability has strengthened due to a combination of increased efficiency, higher product yields, reduced costs, greater crew stability and safer operations.