Search

BackgroundCamostat inhibits severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in vitro. We studied the safety and efficacy of camostat in ACTIV-2/A5401, a phase 2/3 platform trial of therapeutics for COVID-19 in nonhospitalized adults.MethodsWe conducted a phase 2 study in adults with mild-to-moderate COVID-19 randomized to oral camostat for 7 days or a pooled placebo arm. Primary outcomes were time to improvement in COVID-19 symptoms through day 28, proportion of participants with SARS-CoV-2 RNA below the lower limit of quantification (LLoQ) from nasopharyngeal swabs through day 14, and grade ≥3 treatment-emergent adverse events (TEAEs) through day 28.ResultsOf 216 participants (109 randomized to camostat, 107 to placebo) who initiated study intervention, 45% reported ≤5 days of symptoms at study entry and 26% met the protocol definition of higher risk of progression to severe COVID-19. Median age was 37 years. Median time to symptom improvement was 9 days in both arms (P = .99). There were no significant differences in the proportion of participants with SARS-CoV-2 RNA ConclusionsIn a phase 2 study of nonhospitalized adults with mild-to-moderate COVID-19, oral camostat did not accelerate viral clearance or time to symptom improvement, or reduce hospitalizations or deaths. Clinical Trials Registration. ClinicalTrials.gov identifier: NCT04518410.

AbstractAcute pancreatitis (AP) is a disease characterized by an acute inflammatory phase followed by a convalescent phase. Diabetes mellitus (DM) was historically felt to be a transient phenomenon related to acute inflammation; however, it is increasingly recognized as an important late and chronic complication. There are several challenges that have prevented precisely determining the incidence rate of DM after AP and understanding the underlying mechanisms. The DREAM (Diabetes RElated to Acute Pancreatitis and its Mechanisms) Study is a prospective cohort study designed to address these and other knowledge gaps to provide the evidence needed to screen for, prevent, and treat DM after AP. In the following article, we summarize literature regarding the epidemiology of DM after AP and provide the rationale and an overview of the DREAM study.

BackgroundPancreatic cancer risk is increasing in countries with high consumption of Western dietary patterns and rising obesity rates. We examined the hypothesis that specific dietary patterns reflecting hyperinsulinemia (empirical dietary index for hyperinsulinemia; EDIH), systemic inflammation (empirical dietary inflammatory pattern; EDIP), and postprandial glycemia [glycemic index (GI); glycemic load (GL)] are associated with pancreatic cancer risk, including the potential modifying role of type 2 diabetes (T2D) and body mass index (BMI).MethodsWe calculated dietary scores from baseline (1993-1998) food frequency questionnaires among 129,241 women, 50-79 years-old in the Women's Health Initiative. We used multivariable-adjusted Cox regression to estimate HRs and 95% confidence intervals (95% CI) for pancreatic cancer risk.ResultsDuring a median 19.9 years of follow-up, 850 pancreatic cancer cases were diagnosed. We observed no association between dietary scores and pancreatic cancer risk overall. However, risk was elevated among participants with longstanding T2D (present >3 years before pancreatic cancer diagnosis) for EDIH. For each 1 SD increment in dietary score, the HRs (95% CIs) were: EDIH, 1.33 (1.06-1.66); EDIP, 1.26 (0.98-1.63); GI, 1.26 (0.96-1.67); and GL, 1.23 (0.96-1.57); although interactions were not significant (all P interaction >0.05). Separately, we observed inverse associations between GI [0.86 (0.76-0.96), P interaction = 0.0068] and GL [0.83 (0.73-0.93), P interaction = 0.0075], with pancreatic cancer risk among normal-weight women.ConclusionsWe observed no overall association between the dietary patterns evaluated and pancreatic cancer risk, although women with T2D appeared to have greater cancer risk.ImpactThe elevated risk for hyperinsulinemic diets among women with longstanding T2D and the inverse association among normal-weight women warrant further examination.

ObjectiveThe empirical dietary index for hyperinsulinemia (EDIH) and empirical dietary inflammatory pattern (EDIP) scores assess the insulinemic and inflammatory potentials of habitual dietary patterns, irrespective of the macronutrient content, and are based on plasma insulin response or inflammatory biomarkers, respectively. The glycemic index (GI) and glycemic load (GL) assess postprandial glycemic potential based on dietary carbohydrate content. We tested the hypothesis that dietary patterns promoting hyperinsulinemia, chronic inflammation, or hyperglycemia may influence type 2 diabetes risk.Research design and methodsWe calculated dietary scores from baseline (1993-1998) food frequency questionnaires among 73,495 postmenopausal women in the Women's Health Initiative, followed through March 2019. We used multivariable-adjusted Cox regression to estimate hazard ratios (HRs) and 95% CIs for type 2 diabetes risk. We also estimated multivariable-adjusted absolute risk of type 2 diabetes.ResultsDuring a median 13.3 years of follow-up, 11,009 incident cases of type 2 diabetes were diagnosed. Participants consuming the most hyperinsulinemic or proinflammatory dietary patterns experienced greater risk of type 2 diabetes; HRs (95% CI) comparing highest to lowest dietary index quintiles were EDIH 1.49 (1.32-1.68; P trend < 0.0001) and EDIP 1.45 (1.29-1.63; P trend < 0.0001). The absolute excess incidence for the same comparison was 220 (EDIH) and 271 (EDIP) cases per 100,000 person-years. GI and GL were not associated with type 2 diabetes risk: GI 0.99 (0.88-1.12; P trend = 0.46) and GL 1.01 (0.89-1.16; P trend = 0.30).ConclusionsOur findings in this diverse cohort of postmenopausal women suggest that lowering the insulinemic and inflammatory potentials of the diet may be more effective in preventing type 2 diabetes than focusing on glycemic foods.

IntroductionDiabetes mellitus (DM) is a complication of chronic pancreatitis (CP). Whether pancreatogenic diabetes associated with CP-DM represents a discrete pathophysiologic entity from type 2 DM (T2DM) remains uncertain. Addressing this question is needed for development of specific measures to manage CP-DM. We approached this question from a unique standpoint, hypothesizing that if CP-DM and T2DM are separate disorders, they should be genetically distinct. To test this hypothesis, we sought to determine whether a genetic risk score (GRS) based on validated single nucleotide polymorphisms for T2DM could distinguish between groups with CP-DM and T2DM.MethodsWe used 60 T2DM single nucleotide polymorphisms to construct a weighted GRS in 1,613 subjects from the North American Pancreatitis Study 2 and 2,685 subjects from the Multi-Ethnic Study of Atherosclerosis, all of European origin.ResultsThe mean GRS was identical between 321 subjects with CP-DM and 423 subjects with T2DM (66.53 vs 66.42, P = 0.95), and the GRS of both diabetic groups was significantly higher than that of nondiabetic controls (n = 3,554, P < 0.0001). Exploratory analyses attempting to enrich the CP-DM group for pancreatogenic diabetes, such as eliminating diabetes diagnosed before CP, requiring pancreas-specific comorbidities, or removing those with a family history of diabetes, did not improve the ability of the GRS to distinguish between CP-DM and T2DM.DiscussionRecognizing that we lacked a gold standard to define CP-DM, our study suggests that CP-DM may be a subtype of T2DM, a notion that should be tested in future, large prospective studies.

Desalination brine can negatively impact the marine environment in several ways, although there are ongoing discussions regarding the severity and magnitude of environmental effects. A fascinating strategy to lessen any adverse effects is to undertake resource recovery from the brine, which also has the potential for additional revenue generation. More recently, the increasing demand for secure and less geographically restricted sources of precious or rare earth minerals, integrated with growing awareness of waste management and environmental sustainability, is driving the development of economically viable technologies to recover valuable materials from waste streams. This article provides an overview of different methods and technologies, including reverse osmosis (RO), electrodialysis (ED), and distillation, that can be used to recover precious materials, including Li, Mg, Na, and Rb and valuable blends from various waste sources and thus create a more sustainable and circular economy. The mechanisms are discussed in detail, including electrochemical processes (electrolysis, ED, and capacitive deionization), thermal desalination (multistage flash distillation and membrane distillation), pressure‐driven desalination (RO and nanofiltration), and microbial desalination cells. Challenges associated with recovering precious materials from waste streams, such as fouling, scaling, and environmental impact, along with further research directions and potential applications of desalination technologies, are also addressed. [ABSTRACT FROM AUTHOR]

Submerged flapping hydrofoils have the capability to directly convert wave energy into thrust, offering a sustainable approach to marine propulsion. This research employs computational fluid dynamics (CFD) to analyze the propulsion mechanism of wave-induced flapping hydrofoils. Initially validated through established benchmarks and experimental results with foil in uniform flow, the CFD model was then applied to examine the generation of thrust by flapping hydrofoils in heading regular wave. The study reveals a distinct transition from drag to thrust, characterized by the patterns of vortex flow. For the first time, the influence of pitch stiffness on this propulsion process is extensively explored, identifying optimal wave conditions and pitch stiffness for the application of future eco-friendly marine systems. [ABSTRACT FROM AUTHOR]

High-quality and well-annotated biorepositories are needed to better understand the pathophysiology and biologic mechanisms of chronic pancreatitis (CP) and its consequences. We report a methodology for the development of a robust standard operating procedure (SOP) for a biorepository based on the experience of the clinical centers within the consortium to study Chronic Pancreatitis, Diabetes and Pancreas Cancer Clinical Centers (CPDPC), supported by the National Cancer Institute and the National Institute for Diabetes and Digestive and Kidney Diseases as a unique multidisciplinary model to study CP, diabetes, and pancreatic cancer in both children and adults. Standard operating procedures from the CPDPC centers were evaluated and consolidated. The literature was reviewed for standard biorepository operating procedures that facilitated downstream molecular analysis. The existing literature on biobanking practices was harmonized with the SOPs from the clinical centers to produce a biorepository for pancreatic research. This article reports the methods and basic principles behind the creation of SOPs to develop a biorepository for the CPDPC. These will serve as a guide for investigators developing biorepositories in pancreas research. Rigorous and meticulous adherence to standardized biospecimen collection will facilitate investigations to better understand the pathophysiology and biologic mechanisms of CP, diabetes, and pancreatic cancer.

The National Cancer Institute and the National Institute for Diabetes and Digestive and Kidney Diseases initiated the Consortium for the Study of Chronic Pancreatitis, Diabetes, and Pancreatic Cancer (CPDPC) in 2015 (the CPDPC's origin, structure, governance, and research objectives are described in another article in this journal). One of the key objectives of CPDPC is to assemble a cohort of 10,000 subjects 50 years or older with new-onset diabetes, called the NOD cohort. Using a define, enrich, and find early detection approach, the aims of the NOD study are to (a) estimate the 3-year probability of pancreatic ductal adenocarcinoma (PDAC) in NOD (define), (b) establish a biobank of clinically annotated biospecimens from presymptomatic PDAC and control new-onset type 2 diabetes mellitus subjects, (c) conduct phase 3 validation studies of promising biomarkers for identification of incident PDAC in NOD patients (enrich), and (d) provide a platform for development of a future interventional screening protocol for early detection of PDAC in patients with NOD that incorporates imaging studies and/or clinical algorithms (find). It is expected that 85 to 100 incidences of PDAC will be diagnosed during the study period in this cohort of 10,000 patients.

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.

Pancreatic ductal adenocarcinoma (PDAC) is among the deadliest types of cancer. The worldwide estimates of its incidence and mortality in the general population are eight cases per 100,000 person-years and seven deaths per 100,000 person-years, and they are significantly higher in the United States than in the rest of the world. The incidence of this disease in the United States is more than 50,000 new cases in 2017. Indeed, total deaths due to PDAC are projected to increase dramatically to become the second leading cause of cancer-related deaths before 2030. Considering the failure to date to efficiently treat existing PDAC, increased effort should be undertaken to prevent this disease. A better understanding of the risk factors leading to PDAC development is of utmost importance to identify and formulate preventive strategies. Large epidemiologic and cohort studies have identified risk factors for the development of PDAC, including obesity and type 2 diabetes mellitus. This review highlights the current knowledge of obesity and type 2 diabetes as risk factors for PDAC development and progression, their interplay and underlying mechanisms, and the relation to diet. Research gaps and opportunities to address this deadly disease are also outlined.