Allergen-Encapsulating Nanoparticles Reprogram Pathogenic Allergen-Specific Th2 Cells to Suppress Food Allergy.

Food allergy is a prevalent, potentially deadly disease caused by inadvertent sensitization to benign food antigens. Pathogenic Th2 cells are a major driver for disease, and allergen-specific immunotherapies (AIT) aim to increase the allergen threshold required to elicit severe allergic symptoms. However, the majority of AIT approaches require lengthy treatments and convey transient disease suppression, likely due to insufficient targeting of pathogenic Th2 responses. Here, the ability of allergen-encapsulating nanoparticles to directly suppress pathogenic Th2 responses and reactivity is investigated in a mouse model of food allergy. NPs associate with pro-tolerogenic antigen presenting cells, provoking accumulation of antigen-specific, functionally suppressive regulatory T cells in the small intestine lamina propria. Two intravenous doses of allergen encapsulated in poly(lactide-co-glycolide) nanoparticles (NPs) significantly reduces oral food challenge (OFC)-induced anaphylaxis. Importantly, NP treatment alters the fates of pathogenic allergen-specific Th2 cells, reprogramming these cells toward CD25+FoxP3+ regulatory and CD73+FR4+ anergic phenotypes. NP-mediated reductions in the frequency of effector cells in the gut and mast cell degranulation following OFC are also demonstrated. These studies reveal mechanisms by which an allergen-encapsulating NP therapy and, more broadly, allergen-specific immunotherapies, can rapidly attenuate allergic responses by targeting pathogenic Th2 cells.

Biodegradable nanoparticles targeting circulating immune cells reduce central and peripheral sensitization to alleviate neuropathic pain following spinal cord injury.

ABSTRACT: Neuropathic pain is a critical source of comorbidity following spinal cord injury (SCI) that can be exacerbated by immune-mediated pathologies in the central and peripheral nervous systems. In this article, we investigate whether drug-free, biodegradable, poly(lactide- co -glycolide) (PLG) nanoparticle treatment mitigates the development of post-SCI neuropathic pain in female mice. Our results show that acute treatment with PLG nanoparticles following thoracic SCI significantly reduces tactile and cold hypersensitivity scores in a durable fashion. Nanoparticles primarily reduce peripheral immune-mediated mechanisms of neuropathic pain, including neuropathic pain-associated gene transcript frequency, transient receptor potential ankyrin 1 nociceptor expression, and MCP-1 (CCL2) chemokine production in the subacute period after injury. Altered central neuropathic pain mechanisms during this period are limited to reduced innate immune cell cytokine expression. However, in the chronic phase of SCI, nanoparticle treatment induces changes in both central and peripheral neuropathic pain signaling, driving reductions in cytokine production and other immune-relevant markers. This research suggests that drug-free PLG nanoparticles reprogram peripheral proalgesic pathways subacutely after SCI to reduce neuropathic pain outcomes and improve chronic central pain signaling.

The necessity of healthcare supply chain resilience for crisis preparedness.

Prior to and during the COVID-19 pandemic, Canadian provincial health systems and governments did not sufficiently consider healthcare supply chain in their crisis preparedness plans, leading to an exposed and vulnerable healthcare system. There have been many opportunities to learn from past Canadian and global crises, which have emphasized the importance of healthcare supply chain resilience in providing essential care to patients; however, considerations of healthcare supply chain resilience remain a significant gap in preparedness planning. Illustrated through the Canadian response to COVID-19 pandemic, this article will explore how healthcare supply chain resilience should be a necessary consideration in any crisis preparedness plans. Further, without this consideration of healthcare supply chain resilience, it is the person (the patient and healthcare worker), and especially vulnerable populations, that are most put at risk in the event of a future crisis.

Building-Block Size Mediates Microporous Annealed Particle Hydrogel Tube Microenvironment Following Spinal Cord Injury.

Spinal cord injury (SCI) is a life-altering event, which often results in loss of sensory and motor function below the level of trauma. Biomaterial therapies have been widely investigated in SCI to promote directional regeneration but are often limited by their pre-constructed size and shape. Herein, the design parameters of microporous annealed particles (MAPs) are investigated with tubular geometries that conform to the injury and direct axons across the defect to support functional recovery. MAP tubes prepared from 20-, 40-, and 60-micron polyethylene glycol (PEG) beads are generated and implanted in a T9-10 murine hemisection model of SCI. Tubes attenuate glial and fibrotic scarring, increase innate immune cell density, and reduce inflammatory phenotypes in a bead size-dependent manner. Tubes composed of 60-micron beads increase the cell density of the chronic macrophage response, while neutrophil infiltration and phenotypes do not deviate from those seen in controls. At 8 weeks postinjury, implantation of tubes composed of 60-micron beads results in enhanced locomotor function, robust axonal ingrowth, and remyelination through both lumens and the inter-tube space. Collectively, these studies demonstrate the importance of bead size in MAP construction and highlight PEG tubes as a biomaterial therapy to promote regeneration and functional recovery in SCI.

Body composition measured by multi-frequency bioelectrical impedance following creatine supplementation.

BACKGROUND: Acute fluid ingestion increases estimated body fat percentage (BF%) measurements by single frequency (SF-BIA) and multi-frequency bioelectrical impedance (MF-BIA). It is unknown if MF-BIA accurately measures total BF% and total body water (TBW) after creatine supplementation, which causes fluid retention, and resultant increases in fat-free mass and TBW. The purpose of this study was to analyze the effect of creatine supplementation on body composition and TBW measured through a popular MF-BIA device (InBody 770). METHODS: Thirteen male and 14 female subjects (18-22 years) completed one week of creatine monohydrate (0.3 g/kg body weight) or maltodextrin. Pre- and post-supplementation body composition measurements included dual-energy X-ray absorptiometry (DEXA), SF-BIA measured by an Omron HBF-306C device, and MF-BIA measured by an InBody 770 device to measure BF%, fat free mass (FFM), and fat mass (FM). Additionally, intracellular water (ICW), extracellular water (ECW), and TBW were estimated by MF- BIA. RESULTS: FFM increased more in the creatine group than the placebo group measured by all body composition modes (1.2 kg, 1.9 kg, and 1.1 kg increase for SF-BIA, MF-BIA, and DEXA respectively, P<0.05). Creatine supplementation resulted in a 2% increase (P<0.05) in TBW measured by MF-BIA (40.4±9.5 to 41.2±9.6 kg). CONCLUSIONS: One week of creatine supplementation increased TBW as detected by the InBody 770 device. Changes in body composition that occurred due to the increase in TBW were detected as an increase in FFM measured by SF-BIA, MF-BIA, and DEXA.

The effect of acute hydration on body composition assessed by multi-frequency and single-frequency bioelectrical impedance.

BACKGROUND: Multi-frequency bioelectrical impedance (MF-BIA) provides an estimate of total body water. However, it is unknown if MF-BIA detects body water increases due to acute hydration, thus affecting the validity of MF-BIA body composition measurements. The purpose of this study was to compare the effects of pre-testing fluid ingestion on body composition estimation using single-frequency bioelectrical impedance (SF-BIA) and MF-BIA. METHODS: Thirty-nine subjects (20 male, 19 female) were tested for body composition using DXA, SF-BIA and MF-BIA before and after consumption of 2 L of water. RESULTS: Hydration significantly increased fat percentage in men and women for MF-BIA (+2.1±0.7% for men, +2.6±0.7% for women) and SF-BIA (+1.3±0.7% for men, +2.1±0.9% for women). Additionally, hydration significantly increased fat-free mass (FFM) for DXA (+1.4±0.8 kg for men, +1.7±0.4 kg for women) and SF-BIA (+0.5±0.6 kg) in men. Hydration significantly increased fat mass (FM) for all modes (DXA +0.3±0.3 kg, MF-BIA +2.0±0.7 kg, SF-BIA +1.3±0.6 kg) in males, and only for MF-BIA (+2.2±0.3 kg) and SF-BIA (+1.7±0.5 kg) in females. Increases in FM were highest for MF-BIA for both males and females. Total body water was unchanged in males and significantly decreased with acute hydration in females. CONCLUSIONS: MF-BIA improperly categorizes increased mass due to acute hydration as fat mass, resulting in an increase in measured body fat percentage. These findings confirm the need to standardize hydration status for body composition measurements using MF-BIA.

Caffeine Enhances 10-km Cycling Performance in Habitual Users Only When Preceded by Caffeine Abstinence.

PURPOSE: The primary objective was to assess the performance benefits of caffeine (CAF) supplementation in habitual users. Importantly, this investigation was designed to account for the potential confounding effects of CAF withdrawal (CAFW), which are inherent and common in previous work. METHODS: Ten CAF-consuming (394 [146] mg·d-1) recreational cyclists (age 39.1 [14.9] y; maximum oxygen consumption 54.2 [6.2] mL·kg-1·min-1) completed four 10-km time trials (TTs) on a cycle ergometer. On each trial day, 8 hours before reporting to the laboratory, subjects consumed 1.5 mg·kg-1 CAF to prevent withdrawal (no withdrawal [N]) or a placebo (PLA; withdrawal [W]). Then, 1 hour prior to exercise, they received either 6 mg·kg-1 CAF or PLA. These protocols were repeated 4 times, employing all combinations of N/W and CAF/PLA. RESULTS: CAFW did not impair TT power output (PLAW vs PLAN P = .13). However, preexercise CAF only improved TT performance when compared to PLA in the W condition (CAFN vs PLAW P = .008, CAFW vs PLAW P = .04), not when W was mitigated (PLAN vs CAFN P = .33). CONCLUSIONS: These data indicate that preexercise CAF only improves recreational cycling performance when compared to bouts preceded by CAF abstinence, suggesting that habitual users may not benefit from 6 mg·kg-1 of CAF and that previous work may have overstated the value of CAF supplementation for habitual users. Future work should examine higher doses of CAF for habitual users.

The impact of COVID-19 on pulmonary function and airway reactivity after recovery in college-aged adults.

The purpose of this study was to determine (1) whether pulmonary function is reduced, and airway reactivity is increased after recovery from COVID-19 in individuals who did not have severe illness, and (2) whether physical activity levels had any impact on pulmonary function or airway reactivity. An exploratory aim of the study was also to assess whether number of symptoms was associated with pulmonary function outcomes. The maximal flow volume loop was used to measure pulmonary function in individuals who had previously tested positive for COVID-19 (COV; n = 20, 23.0 ± 5.4 years) and those who had not (CON; n = 20, 23.7 ± 5.5 years) before and after a hypertonic saline challenge (HSC) designed to increase airway reactivity. Self-reported symptoms and physical activity levels (MET (min/week)) were collected to examine their correlation with pulmonary outcomes. There were no significant differences in any pulmonary function outcomes between the COV and CON groups before or after the HSC. There were also no associations between physical activity and pulmonary function outcomes. However, among participants who reported greater than four symptoms, there was a larger decline in forced expiratory volume in 1 s divided by forced vital capacity following HSC (p = 0.035). Pulmonary function and airway reactivity are not impacted after recovery from COVID-19 in young individuals; however, it appears that the number of symptoms reported may be associated with increased airway reactivity even after recovery in young adults who were not hospitalized with the virus.

Plain Language Summary of Publication of the safety and efficacy of ARRY-371797 in people with dilated cardiomyopathy and a faulty LMNA gene.

WHAT IS THIS PLAIN LANGUAGE SUMMARY ABOUT?: This plain language summary describes the results of a study looking at the effects of a medicine called ARRY-371797 (also known as PF-07265803) in people with dilated cardiomyopathy (DCM for short) caused by a faulty LMNA gene. This condition is called LMNA-related DCM. DCM happens when the heart becomes bigger and weaker than normal, impacting functional capacity and leading to symptoms of heart failure. This means the heart is not able to pump blood around the body as easily, and people are unable to do as much in their daily lives (like getting dressed and going shopping). People may inherit a faulty LMNA gene from one of their parents, or a faulty LMNA gene may develop when mistakes happen during cell growth and replication. ARRY-371797 targets a specific mechanism in the body that can lead to heart problems in people with a faulty LMNA gene. As ARRY-371797 is not currently approved for use outside of clinical trials, it doesn't currently have an easily recognizable trade name. WHAT WERE THE RESULTS?: 12 American people (average age 50 years) with LMNA-related DCM took part in the study and received 400 mg or 100 mg of ARRY-371797 twice daily for 48 weeks. People knew which dose of ARRY-371797 they were taking. People were checked after 4, 12, 24, 36 and 48 weeks of taking ARRY-371797 to see how far they could walk in the 6-minute walk test (6MWT for short). The level of NT-proBNP in their blood was also measured. NT-proBNP is a biomarker used to measure the severity of heart failure. A biomarker is something found in the body that can be measured to indicate the extent of a disease. -After taking ARRY-371797 for 12 weeks, people were able to walk further in the 6MWT and had lower levels of NT-proBNP in their blood. This suggests improvement in functional capacity (exercise tolerance) and heart function. Researchers also asked people about their quality of life using the Kansas City Cardiomyopathy Questionnaire (KCCQ for short), and looked for any side effects. -Researchers saw some improvement in KCCQ scores. -Researchers saw no major side effects that they considered to be related to ARRY-371797 treatment. A side effect is something that people feel was caused by a medicine or treatment. Overall, this study showed that people with LMNA-related DCM who took ARRY-371797 had improved functional capacity (exercise tolerance), improved heart function, and improved quality of life. Phase 2 study (NCT02057341) Phase 2 long-term extension study (NCT02351856) Phase 3 REALM-DCM study (NCT03439514).

Efficacy and Safety of ARRY-371797 in LMNA-Related Dilated Cardiomyopathy: A Phase 2 Study.

BACKGROUND: Lamin A/C gene (LMNA)-related dilated cardiomyopathy is a serious and life-threatening condition with a high unmet medical need. This phase 2 study assessed the effects of the oral selective p38 mitogen-activated protein kinase inhibitor ARRY-371797 on functional capacity and cardiac function in patients with LMNA-related dilated cardiomyopathy. METHODS: Patients with LMNA-related dilated cardiomyopathy in New York Heart Association class II-IIIA, on background heart failure treatment, received ARRY-371797 100 or 400 mg twice daily for 48 weeks. The primary end point was change from baseline in the 6-minute walk test distance at 12 weeks. Secondary end points included changes over time in 6-minute walk test distance, NT-proBNP (N-terminal pro-B-type natriuretic peptide) concentration, left ventricular ejection fraction, and quality-of-life scores on the Kansas City Cardiomyopathy Questionnaire. Data from the 2 dose groups were combined. RESULTS: Twelve patients were enrolled; median (minimum, maximum) 6-minute walk test distance at baseline was 314 (246, 412) m. At week 12, the mean (80% CI) increase from baseline in 6-minute walk test distance was 69 (39, 100) m (median, 47 m). Median NT-proBNP concentration declined from 1409 pg/mL at baseline to 848 pg/mL at week 12. Mean left ventricular ejection fraction was stable at week 12. There was a trend toward improvement in Kansas City Cardiomyopathy Questionnaire Overall and Clinical Summary scores at week 12. No clinically significant drug-related safety concerns were identified. CONCLUSIONS: ARRY-371797 was well tolerated and resulted in potential increases in functional capacity and lower concentrations of cardiac biomarker NT-proBNP in patients with LMNA-related dilated cardiomyopathy. REGISTRATION: URL: https://clinicaltrials.gov; Unique identifier: NCT02057341.

The influence of the CYP1A2-163 C>A polymorphism on the hemostatic response to exercise following caffeine supplementation.

BACKGROUND: Prior work from our group suggests that caffeine increases thrombotic potential after acute exercise. The aim of this study was to determine if hemostatic responses to exercise affected by caffeine are influenced by the CYP1A2-163 C>A polymorphism. METHODS: Forty-two healthy men performed two trials in which a graded maximal exercise test was completed one hour after consuming either 6 mg/kg of caffeine or placebo. Subjects were categorized as possessing the C allele (N.=21) or being homozygous for the A allele (N.=21). RESULTS: Factor VIII increased more (265%) during exercise in the caffeinated condition than the placebo condition (178%) (P<0.05). Tissue plasminogen activator (tPA) activity also increased more following caffeine as compared to placebo (increase of 8.70±4.32 IU/mL vs. 6.77±3.79 IU/mL respectively, P<0.05). There was no treatment × genotype or treatment × time × genotype interactions. CONCLUSIONS: Although caffeine increases factor VIII and tPA responses to maximal exercise, these changes are not influenced by the CYP1A2-163 C>A polymorphism.

Dietary nitrate supplementation enhances heavy load carriage performance in military cadets.

PURPOSE: To determine the effects of dietary nitrate (NO3-) supplementation on physiological responses, cognitive function, and performance during heavy load carriage in military cadets. METHODS: Ten healthy males (81.0 ± 6.5 kg; 180.0 ± 4.5 cm; 56.2 ± 3.7 ml·kg·min-1 VO2max) consumed 140 mL·d-1 of beetroot juice (BRJ; 12.8 mmol NO3-) or placebo (PL) for six d preceding an exercise trial, which consisted of 45 min of load carriage (55% body mass) at 4.83 km·h-1 and 1.5% grade, followed by a 1.6-km time-trial (TT) at 4% grade. Gas exchange, heart rate, and perceptual responses were assessed during constant-load exercise and the TT. Cognitive function was assessed immediately prior to, during, and post-exercise via the psychomotor vigilance test (PVT). RESULTS: Post-TT HR (188 ± 7.1 vs. 185 ± 7.4; d = 0.40; p = 0.03), mean tidal volume (2.15 ± 0.27 vs. 2.04 ± 0.23; p = 0.02; d = 0.47), and performance (770.9 ± 78.2 s vs. 809.8 ± 61.4 s; p = 0.03; d = 0.63) were increased during the TT with BRJ versus PL. There were no effects of BRJ on constant-load gas exchange or perceptual responses, and cognitive function was unchanged at all time points. CONCLUSION: BRJ supplementation improves heavy load carriage performance in military cadets possibly as a result of attenuated respiratory muscle fatigue, rather than enhanced exercise economy.

The Emerging Features of Healthcare Supply Chain Resilience: Learning from a Pandemic.

The COVID-19 pandemic exposed significant fragilities in the configuration of global healthcare supply chains. This was felt acutely by citizens, patients and healthcare workers across Canada. As demand for critical medical products surged in Canada, and globally, provincial healthcare supply chain teams worked to rapidly stabilize their supply chains. These efforts indicate the emerging features of healthcare supply chain resilience. Results suggest that there are five emerging features: (1) redundancy of supply inventory; (2) diversification of suppliers across geographies; (3) maturity of digital infrastructure to create transparency; (4) proactivity; and (5) equity of distribution to protect the lives of all.

Masked Delivery of Allergen in Nanoparticles Safely Attenuates Anaphylactic Response in Murine Models of Peanut Allergy.

Food allergy is a growing health concern worldwide. Current allergen-specific immunotherapy (AIT) approaches require frequent dosing over extended periods of time and may induce anaphylaxis due to allergen-effector cell interactions. A critical need remains to develop novel approaches that refine AIT for the treatment of food allergies. Previous studies show that poly(lactide-co-glycolide) (PLG) nanoscale particles (NP) effectively suppress Th1- and Th17-driven immune pathologies. However, their ability to suppress the distinct Th2-polarized immune responses driving food allergy are unknown. Herein, we describe the safety and efficacy of NPs containing encapsulated peanut allergen in desensitizing murine models of peanut allergy. Peanut extract encapsulation allowed for the safe intravenous delivery of allergen relative to non-encapsulated approaches. Application of 2-3 doses, without the need for dose escalation, was sufficient to achieve prophylactic and therapeutic efficacy, which correlated with suppression of Th2-mediated disease and reduced mast cell degranulation. Efficacy was associated with strong reductions in a broad panel of Th1, Th2, and Th17 cytokines. These results demonstrate the ability of PLG NPs to suppress allergen-specific immune responses to induce a more tolerogenic phenotype, conferring protection from intragastric allergen challenge. These promising studies represent a step forward in the development of improved immunotherapies for food allergy.

Mechanistic contributions of Kupffer cells and liver sinusoidal endothelial cells in nanoparticle-induced antigen-specific immune tolerance.

The intravenous delivery of disease-relevant antigens (Ag) by polymeric nanoparticles (NP-Ags) has demonstrated Ag-specific immune tolerance in autoimmune and allergic disorders as well as allogeneic transplant rejection. NP-Ags are observed to distribute to the spleen, which has an established role in the induction of immune tolerance. However, studies have shown that the spleen is dispensable for NP-Ag-induced tolerance, suggesting significant contributions from other immunological sites. Here, we investigated the tolerogenic contributions of Kupffer cells (KCs) and liver sinusoidal endothelial cells (LSECs) to NP-Ag-induced tolerance in a mouse model of multiple sclerosis, experimental autoimmune encephalomyelitis (EAE). Intravenously delivered Ag-conjugated poly(lactide-co-glycolide) NPs (PLG-Ag) distributed largely to the liver, where they associated with both KCs and LSECs. This distribution was accompanied by CD4 T cell accumulation, clonal deletion, and PD-L1 expression by KCs and LSECs. Ex vivo co-cultures of PLG-Ag-treated KCs or LSECs with Ag-specific CD4 T cells resulted in PGE2 and IL-10 or PGE2 secretion, respectively. KC depletion and adoptive transfer experiments demonstrated that KCs were sufficient, but not necessary, to mediate PLG-Ag-induced tolerance in EAE. The durability of PLG-Ag-induced tolerance in the absence of KCs may be attributed to the distribution of PLG-Ags to LSECs, which demonstrated similar levels of PD-L1, PGE2, and T cell stimulatory ability. Collectively, these studies provide mechanistic support for the role of liver KCs and LSECs in Ag-specific tolerance for a biomaterial platform that is currently being evaluated in clinical trials.

Supply chain capacity to respond to COVID-19 in Newfoundland and Labrador: An integrated leadership strategy.

This provincial case study, one of seven conducted as part of a national research program on healthcare supply chain management during COVID-19, focuses on Newfoundland and Labrador (NL). Faced with the destabilization of its traditional supply chain, NL leveraged an existing centralized healthcare supply chain structure to organize its supply chain response to the pandemic. To overcome product shortages, health leaders collaborated with their local business community and industries to source and procure personal protective equipment and create domestic manufacturing capacity for critical supplies. The healthcare supply chain response in NL demonstrates the value of a highly integrated and centralized healthcare supply chain management strategy. It also makes clear the value of a diversified healthcare supply chain, one which draws on local manufacturing capacity to create a domestic source of critical supplies and overcome shortages from global suppliers.

Supply chain integration as a strategy to strengthen pandemic responsiveness in Nova Scotia.

This provincial case study, one of seven conducted as part of a national research program on healthcare supply chain management during COVID-19, focuses on Nova Scotia. During the first wave of the pandemic, Nova Scotia faced the massive destabilization of its traditional supply channels and had to grapple with role clarity and communication in its emergency response structure. Nova Scotia was able to centralize its pandemic sourcing, procurement, and management efforts to its provincial health authority. Healthcare supply chain teams were able to rapidly modify their sourcing and procurement processes in order to compensate for the destabilization of their standard supply channels and assume responsibility for the province-wide management and distribution of pandemic supplies. The Nova Scotia case findings make clear both the value of a centralized and dedicated healthcare supply chain response-that integrates all provincial care delivery organizations-and the diversification of the healthcare supply chain.

Physiological differences in cardiovascular hemodynamics across treadmill and cycle exercise as assessed through impedance cardiography.

Impedance cardiography (IC) is a non-invasive method for assessing cardiovascular hemodynamics, and has been utilised during exercise, exclusively on a cycle ergometer. Mode-specific differences in cardiovascular hemodynamics during exercise have previously been identified, but the ability of IC to identify these differences has not been explored. Therefore, we examined the repeatability of cardiovascular hemodynamics within and between exercise modes on the treadmill (TM) and cycle (CY) ergometer. Twenty-one men (age = 21.4 ± 0.5 yr) performed four maximal exercise, two TM and two CY. Within each test, two, five-minute stages were completed corresponding to moderate and vigorous exercise intensities, respectively. Oxygen consumption (VO2) was measured continuously during each test. Hemodynamic measures were obtained via IC, and included cardiac output (CO), heart rate (HR), stroke volume (SV), end diastolic volume (EDV), ejection fraction (EF), and systemic vascular resistance (SVR). Repeated measures ANOVA revealed that within TM exercise, there was a main effect for trial with HR only. There were no main effects for trial within CY exercise. Across exercise modes, there were significant main effects for mode with HR, EDV, and SVR. CY exercise resulted in a higher HR, lower SV and EDV, consistent with previous findings, utilising more criterion and invasive methods. Results suggest that hemodynamics, as assessed by IC, are repeatable within TM and CY exercise. In addition, it appears as though IC is capable of detecting mode-specific differences in hemodynamics, suggesting IC to be a useful assessment tool during exercise.

Standardization of EUS imaging and reporting in high-risk individuals of pancreatic adenocarcinoma: consensus statement of the Pancreatic Cancer Early Detection Consortium.

BACKGROUND AND AIMS: Pancreatic ductal adenocarcinoma is an aggressive disease most often diagnosed after local progression or metastatic dissemination, precluding resection and resulting in a high mortality rate. For individuals with elevated personal risk of the development of pancreatic cancer, EUS is a frequently used advanced imaging and diagnostic modality. However, variability in the expertise and definition of EUS findings exists among gastroenterologists, as well as a lack of standardized reporting of relevant findings at the time of examination. Adoption of standardized EUS reporting, using a universally accepted and agreed on terminology, is needed. METHODS: A consensus statement designed to create a standardized reporting template was authored by a multidisciplinary group of experts in pancreatic diseases that includes gastroenterologists, radiologists, surgeons, oncologists, and geneticists. This statement was developed using a modified Delphi process as part of the Pancreatic Cancer Early Detection Consortium, and >75% agreement was required to reach consensus. RESULTS: We identified reporting elements and present standardized reporting templates for EUS indications, procedural data, EUS image capture, and descriptors of findings, tissue sampling, and postprocedural assessment of adequacy. CONCLUSIONS: Adoption of this standardized EUS reporting template should improve consistency in clinical decision-making for individuals with elevated risk of pancreatic cancer by providing complete and accurate reporting of pancreatic abnormalities. Standardization will also help to facilitate research and clinical trial design by using clearly defined and consistent imaging descriptions, thus allowing for comparison of results across different centers.