Multi-omic biomarker panel in pancreatic cyst fluid and serum predicts patients at a high risk of pancreatic cancer development.

Integration of multi-omic data for the purposes of biomarker discovery can provide novel and robust panels across multiple biological compartments. Appropriate analytical methods are key to ensuring accurate and meaningful outputs in the multi-omic setting. Here, we extensively profile the proteome and transcriptome of patient pancreatic cyst fluid (PCF) (n = 32) and serum (n = 68), before integrating matched omic and biofluid data, to identify biomarkers of pancreatic cancer risk.

Obesity, Sarcopenia and Myosteatosis: Impact on Clinical Outcomes in the Operative Management of Crohn's Disease.

Background: Obesity, sarcopenia, and myosteatosis in inflammatory bowel disease may confer negative outcomes, but their prevalence and impact among patients with Crohn's disease (CD) have not been systematically studied. The aim of this study was to assess nutritional status and body composition among patients undergoing resectional surgery for CD and determine impact on operative outcomes.

Methods: Consecutive patients with CD undergoing resection from 2000 to 2018 were studied.

Development of a clinical score to estimate pancreatitis-related hospital admissions in patients with a new diagnosis of chronic pancreatitis: the trinity score.

Background: The clinical course of chronic pancreatitis is unpredictable and there is no globally accepted score to predict the disease course. We developed a clinical score to estimate pancreatitis-related hospitalisation in patients with newly diagnosed chronic pancreatitis.

Methods: We conducted a retrospective cohort study using two clinical chronic pancreatitis databases held in tertiary referral centres in Dublin, Ireland, and in Tarragona, Spain.

Significantly Lower Physical Activity Participation in Individuals with Chronic Pancreatitis Compared to Controls: An Exploratory Study of Objectively Assessed Physical Activity Levels.

Introduction: The beneficial effects of exercise and physical activity (PA) have been demonstrated in many chronic inflammatory diseases. Knowledge on PA levels is unknown in the chronic pancreatitis population, and there are currently no specific PA recommendations for this condition.

Methods: PA was measured objectively over a 7-day period in 17 individuals with chronic pancreatitis using an accelerometer (ActiGraph) and in 15 controls, matched for age, sex, and body mass index.

Surgical and Oncological Outcomes After Preoperative FOLFIRINOX Chemotherapy in Resected Pancreatic Cancer: An International Multicenter Cohort Study.

Background: Preoperative FOLFIRINOX chemotherapy is increasingly administered to patients with borderline resectable (BRPC) and locally advanced pancreatic cancer (LAPC) to improve overall survival (OS). Multicenter studies reporting on the impact from the number of preoperative cycles and the use of adjuvant chemotherapy in relation to outcomes in this setting are lacking. This study aimed to assess the outcome of pancreatectomy after preoperative FOLFIRINOX, including predictors of OS.

Measurement of Body Composition in Pancreatic Cancer: A Systematic Review, Meta-Analysis, and Recommendations for Future Study Design.

Background/objectives: Sarcopenia in pancreatic cancer may increase the risk of chemotherapy-related toxicity and post-operative morbidity. This systematic review and meta-analysis aimed to quantify the prevalence of sarcopenia in early stage pancreatic cancer.

Methods: Relevant studies were identified using Ovid Medline and Elsevier Embase.

Interleukin-15 augments NK cell-mediated ADCC of alemtuzumab in patients with CD52+ T-cell malignancies.

Interleukin-15 (IL-15) monotherapy substantially increases the number and activity of natural killer (NK) cells and CD8+ T cells but has not produced clinical responses. In a xenograft mouse model, IL-15 enhanced the NK cell-mediated antibody-dependent cell cytotoxicity (ADCC) of the anti-CD52 antibody alemtuzumab and led to significantly more durable responses than alemtuzumab alone. To evaluate whether IL-15 potentiates ADCC in humans, we conducted a phase 1 single-center study of recombinant human IL-15 and alemtuzumab in patients with CD52-positive mature T-cell malignances.

Physical activity for chronic pancreatitis: a systematic review.

Background: Chronic pancreatitis (CP) is a progressive inflammatory disorder of the pancreas. Sarcopenia is a degenerative loss of skeletal muscle mass, quality, and strength and is commonly associated with chronic pancreatitis. Regular physical activity and adequate functional fitness have been found to ameliorate the risk and effects of sarcopenia in other chronic diseases.

Near infrared indocyanine green fluorescent cholangiography versus intraoperative cholangiography to improve safety in laparoscopic cholecystectomy for gallstone disease-a systematic review protocol.

Background: Laparoscopic cholecystectomy has become the standard surgical approach in the treatment of cholelithiasis. Diverse surgical techniques and different imaging modalities have been described to evaluate the biliary anatomy and prevent or early detect bile duct injuries. X-ray intraoperative cholangiography (IOC) and near infrared indocyanine green fluorescent cholangiography (NIR-ICG) are safe and feasible techniques to assess biliary anatomy.

Triple combination of BET plus PI3K and NF-κB inhibitors exhibit synergistic activity in adult T-cell leukemia/lymphoma.

Adult T-cell leukemia/lymphoma (ATL) is an aggressive T-cell lymphoproliferative malignancy caused by human T-cell leukemia virus type 1 (HTLV-1). ATL is an orphan disease with no curative drug treatment regimens urgently needing new combination therapy. HTLV-1-infected cells rely on viral proteins, Tax and HBZ (HTLV-1-b-ZIP factor), to activate the transcription of various host genes that are critical for promoting leukemic transformation.

External validation of postoperative pancreatic fistula prediction scores in pancreatoduodenectomy: a systematic review and meta-analysis.

Background: Multiple risk scores claim to predict the probability of postoperative pancreatic fistula (POPF) after pancreatoduodenectomy. It is unclear which scores have undergone external validation and are the most accurate. The aim of this study was to identify risk scores for POPF, and assess the clinical validity of these scores.

Pre-operative radiomics model for prognostication in resectable pancreatic adenocarcinoma with external validation.

Objectives: In resectable pancreatic ductal adenocarcinoma (PDAC), few pre-operative prognostic biomarkers are available. Radiomics has demonstrated potential but lacks external validation. We aimed to develop and externally validate a pre-operative clinical-radiomic prognostic model.

Dietary intake in patients with chronic pancreatitis: A systematic review and meta-analysis.

Background: A progressive reduction in the secretion of pancreatic enzymes in patients with chronic pancreatitis (CP) results in malabsorption and ultimate malnutrition. However, the pathogenesis of malnutrition is multifactorial and other factors such as chronic inflammation, alcohol excess and poor dietary intake all contribute. Patients may restrict their dietary intake due to poor appetite or to avoid gastrointestinal symptoms and abdominal pain.

Short-course IL-15 given as a continuous infusion led to a massive expansion of effective NK cells: implications for combination therapy with antitumor antibodies.

Background: Full application of cytokines as oncoimmunotherapeutics requires identification of optimal regimens. Our initial effort with intravenous bolus recombinant human interleukin-15 (rhIL-15) was limited by postinfusional reactions. Subcutaneous injection and continuous intravenous infusion for 10 days (CIV-10) provided rhIL-15 with less toxicity with CIV-10 giving the best increases in CD8 lymphocytes and natural killer (NK) cells.

Multi-Omic Biomarkers as Potential Tools for the Characterisation of Pancreatic Cystic Lesions and Cancer: Innovative Patient Data Integration.

Pancreatic cancer (PC) is regarded as one of the most lethal malignant diseases in the world, with GLOBOCAN 2020 estimates indicating that PC was responsible for almost half a million deaths worldwide in 2020. Pancreatic cystic lesions (PCLs) are fluid-filled structures found within or on the surface of the pancreas, which can either be pre-malignant or have no malignant potential. While some PCLs are found in symptomatic patients, nowadays many PCLs are found incidentally in patients undergoing cross-sectional imaging for other reasons-so called 'incidentalomas'.

If in Doubt Don't Act Out! Exploring Behaviours in Clinical Decision Making by General Surgeons Towards Surgical Procedures.

Background: Clinical decision-making (CDM) plays an integral role to surgeons work and has ramifications for patient outcomes and experience. The factors influencing a surgeons decision-making and the utility of cognitive decisional short cuts used in CDM known as 'heuristics' remains unknown. The aim of this paper is to explore how general surgeons make decisions in high-stake biliary tract clinical scenarios.

Selective Resection of Type 1 Gastric Neuroendocrine Neoplasms and the Risk of Progression in an Endoscopic Surveillance Programme.

Background: Current guidance for type 1 gastric neuroendocrine neoplasms (gNENs) recommends either resection of all visible lesions or selective resection of gNENs >10 mm. We adopt a selective strategy targeting lesions approaching 10 mm for endoscopic mucosal resection (EMR) and provide surveillance for smaller lesions.

Objectives: This study aimed to describe the incidence of type 1 gNENs requiring endoscopic/surgical resection and the risk of disease progression (both considered significant disease) on endoscopic surveillance.

Enhanced efficacy of JAK1 inhibitor with mTORC1/C2 targeting in smoldering/chronic adult T cell leukemia.

Adult T-cell leukemia (ATL) is an aggressive T-cell lymphoproliferative malignancy of regulatory T lymphocytes (Tregs), caused by human T-cell lymphotropic virus 1 (HTLV-1). Interleukin 2 receptor alpha (IL-2Rα) is expressed in the leukemic cells of smoldering/chronic ATL patients, leading to constitutive activation of the JAK/STAT pathway and spontaneous proliferation. The PI3K/AKT/mTOR pathway also plays a critical role in ATL cell survival and proliferation.

Evaluation of Adjuvant Chemotherapy in Patients With Resected Pancreatic Cancer After Neoadjuvant FOLFIRINOX Treatment.

Importance: The benefit of adjuvant chemotherapy after resection of pancreatic cancer following neoadjuvant combination treatment with folinic acid, fluorouracil, irinotecan, and oxaliplatin (FOLFIRINOX) is unclear.

Objective: To assess the association of adjuvant chemotherapy with overall survival (OS) in patients after pancreatic cancer resection and neoadjuvant FOLFIRINOX treatment.

Design, Setting, And Participants: This international, multicenter, retrospective cohort study was conducted from January 1, 2012, to December 31, 2018.

A high prevalence of genetic polymorphisms in idiopathic and alcohol-associated chronic pancreatitis patients in Ireland.

Background: Individual genetic architecture is considered central to susceptibility and progression of disease in chronic pancreatitis. The study aimed to evaluate the presence of common pancreatic gene mutations in a defined cohort of idiopathic and alcohol-induced chronic pancreatitis patients in Ireland.

Methods: The study comprised patients with idiopathic and alcohol-induced chronic pancreatitis and historic controls.

Delivery of hepato-pancreato-biliary surgery during the COVID-19 pandemic: an European-African Hepato-Pancreato-Biliary Association (E-AHPBA) cross-sectional survey.

Background: The extent of the COVID-19 pandemic and the resulting response has varied globally. The European and African Hepato-Pancreato-Biliary Association (E-AHPBA), the premier representative body for practicing HPB surgeons in Europe and Africa, conducted this survey to assess the impact of COVID-19 on HPB surgery.

Methods: An online survey was disseminated to all E-AHPBA members to assess the effects of the pandemic on unit capacity, management of HPB cancers, use of COVID-19 screening and other aspects of service delivery.

Metabolic dysfunction and diabetes mellitus during long-term follow-up of severe acute pancreatitis: A case-matched study.

Background/objectives: Endocrine insufficiency following severe acute pancreatitis (SAP) leads to diabetes of the exocrine pancreas, (type 3c diabetes mellitus), however it is not known how this metabolic phenotype differs from that of type 2 diabetes, or how the two subtypes can be differentiated. We sought to determine the prevalence of diabetes following SAP, and to analyse the behaviour of glucose and pancreatic hormones across a 2-h oral glucose tolerance test (OGTT).

Methods: Twenty-six patients following SAP (mean (range) duration of first SAP episode to study time of 119.

IL-15 in the Combination Immunotherapy of Cancer.

We completed clinical trials of rhIL-15 by bolus, subcutaneous, and continuous intravenous infusions (CIV). IL-15 administered by CIV at 2 mcg/kg/day yielded a 38-fold increase in 10- day number of circulating NK cells, a 358-fold increase in CD56 NK cells and a 5.8-fold increase in CD8 T cells.

Medicine and heuristics: cognitive biases and medical decision-making.

Introduction: Clinical decision-making is a daily practice conducted by medical practitioners, yet the processes surrounding it are poorly understood. The influence of 'shortcuts' in clinical decision-making, known as heuristics, remains unknown. This paper explores heuristics and the valuable role they play in medical practice, as well as offering potential solutions to minimize the risk of incorrect decision-making.