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Aim To evaluate the surgical seminars given for medical students at Auckland University and factors affecting them, so as to define areas for improvement. Methods A confidential questionnaire was completed by fourth-year medical students for each surgical seminar they attended during an academic year. The seminars were repeated four times during the year. The questionnaire consisted of five statements relating to whether the seminar was stimulating, problem- oriented, patient-centred, evidence-based and interactive. The students rated each statement on a 7-point scale. Results 556 questionnaires evaluating 28 clinical teachers were collected. A generalized linear model showed that the clinical teachers (F=4·16, P = 0·0001), the attachment (F=4·39, P=0·005) and the interaction between the seniority and institute (F=6·38, P=0·019) had a significant effect on the rating of the seminars. University consultants and hospital registrars had the highest overall least-squares mean, followed by hospital consultants, while university lecturers had the lowest overall least-squares mean (5·56, 5·4, 5·18, and 4·36, respectively). Ratings for problem-oriented approach improved over the studied period, while ratings of evidence-based and patient-centred approaches remained lower. University consultants and hospital registrars had the best patient-centred approach compared with hospital consultants and university lecturers (least-squares means 5·52, 5·4, 5·01, 4·18, respectively). Hospital registrars showed the best interactive ability ratings (least-squares mean 5·51) while university lecturers had the least stimulating seminars (least-squares mean 4·46). Conclusions Surgical seminars which were introduced to cover surgical topics had acceptable ratings in each of the teaching domains, although there is a need for improvement in the patient-centred and evidence-based approaches. [ABSTRACT FROM AUTHOR]

Pulsed-field ablation (PFA) is an emerging ablative technology that has been used successfully to eliminate cardiac arrhythmias. As a nonthermal technique, it has significant benefits over traditional radiofrequency ablation with improved target tissue specificity and reduced risk of adverse events during cardiac applications. We investigated whether PFA is safe for use in the stomach and whether it could modulate gastric slow waves. Female weaner pigs were fasted overnight before anesthesia was induced using tiletamine hydrochloride (50 mg·mL -1 ) and zolazepam hydrochloride (50 mg·mL -1 ) and maintained with propofol (Diprivan 2%, 0.2-0.4 mg·kg -1 ·min -1 ). Pulsed-field ablation was performed on their gastric serosa in vivo. Adjacent point lesions ( n = 2-4) were used to create a linear injury using bipolar pulsed-field ablation consisting of 40 pulses (10 Hz frequency, 0.1 ms pulse width, 1,000 V amplitude). High-resolution electrical mapping defined baseline and postablation gastric slow-wave patterns. A validated five-point scale was used to evaluate tissue damage in hematoxylin and eosin-stained images. Results indicated that PFA successfully induced complete conduction blocks in all cases, with lesions through the entire thickness of the gastric muscle layers. Consistent postablation slow-wave patterns emerged immediately following ablation and persisted over the study period. Pulsed-field ablation induces rapid conduction blocks as a tool to modulate slow-wave patterns, indicating it may be suitable as an alternative to radiofrequency ablation. NEW & NOTEWORTHY Results show that pulsed-field ablation can serve as a gastric slow-wave intervention by preventing slow-wave propagation across the lesion site. Stable conduction blocks were established immediately following energy delivery, faster than previous examples of radiofrequency gastric ablation. Pulsed-field ablation may be an alternative for gastric slow-wave intervention, and further functional and posthealing studies are now warranted.

Background: The incidence of hypertriglyceridemia-associated acute pancreatitis (HTG-AP) is increasing globally and more so in China. The characteristics of liver-mediated metabolites and related key enzymes are rarely reported in HTG-AP. Chaiqin chengqi decoction (CQCQD) has been shown to protect against AP including HTG-AP in both patients and rodent models, but the underlying mechanisms in HTG-AP remain unexplored., Purpose: To assess the characteristics of liver-mediated metabolism and the therapeutic mechanisms of CQCQD in HTG-AP., Methods: Male human apolipoprotein C3 transgenic (hApoC3-Tg; leading to HTG) mice or wild-type littermates received 7 intraperitoneal injections of cerulein (100 μg/kg) to establish HTG-AP and CER-AP, respectively. In HTG-AP, some mice received CQCQD (5.5 g/kg) gavage at 1, 5 or 9 h after disease induction. AP severity and related liver injury were determined by serological and histological parameters; and underlying mechanisms were identified by lipidomics and molecular biology. Molecular docking was used to identify key interactions between CQCQD compounds and metabolic enzymes, and subsequently validated in vitro in hepatocytes., Results: HTG-AP was associated with increased disease severity indices including augmented liver injury compared to CER-AP. CQCQD treatment reduced severity and liver injury of HTG-AP. Glycerophospholipid (GPL) metabolism was the most disturbed pathway in HTG-AP in comparison to HTG alone. In HTG-AP, the mRNA level of GPL enzymes involved in phosphocholine (PC) and phosphatidylethanolamine (PE) synthesis (Pcyt1a, Pcyt2, Pemt, and Lpcat) were markedly upregulated in the liver. Of the GPL metabolites, lysophosphatidylethanolamine LPE(16:0) in serum of HTG-AP was significantly elevated and positively correlated with the pancreas histopathology score (r = 0.65). In vitro, supernatant from Pcyt2-overexpressing hepatocytes co-incubated with LPE(16:0) or phospholipase A2 (a PC- and PE-hydrolyzing enzyme) alone induced pancreatic acinar cell death. CQCQD treatment downregulated PCYT1a and PCYT2 enzyme levels in the liver. Hesperidin and narirutin were identified top two CQCQD compounds with highest affinity docking to PCYT1a and PCYT2. Both hesperidin and narirutin reduced the level of some GPL metabolites in hepatocytes., Conclusion: Liver-mediated GPL metabolism is excessively activated in HTG-AP with serum LPE(16:0) level correlating with disease severity. CQCQD reduces HTG-AP severity partially via modulating key enzymes in GPL metabolism pathway., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier GmbH. All rights reserved.)

Consumption of a diet rich in saturated fat increases lipid absorption from the intestine, assembly into chylomicrons, and delivery to metabolic tissues via the lymphatic and circulatory systems. Accumulation of ceramide lipids, composed of sphingosine and a fatty acid, in metabolic tissues contributes to the pathogenesis of cardiovascular diseases, type 2 diabetes mellitus and cancer. Using a mesenteric lymph duct cannulated rat model, we showed that ceramides are generated by the intestine and assembled into chylomicrons, which are transported via the mesenteric lymphatic system. A lipidomic screen of intestinal-derived chylomicrons identified a diverse range of fatty acid, sphingolipid, and glycerolipid species that have not been previously detected in chylomicrons, including the metabolically deleterious C 16:0 ceramide that increased in response to high-fat feeding in rats and human high-lipid meal replacement enteral feeding. In conclusion, high-fat feeding increases the export of intestinal-derived C 16:0 ceramide in chylomicrons, identifying a potentially unknown mechanism through which ceramides are transported systemically to contribute to metabolic dysfunction.

Historically, the intestinal lymphatics were considered passive conduits for fluids, immune cells, dietary lipids, lipid soluble vitamins and lipophilic drugs. Studies of intestinal lymphatic drug delivery in the late 20 th century focussed primarily on the drug physicochemical properties, especially high lipophilicity, that resulted in intestinal lymphatic transport. More recent discoveries have changed our traditional view by demonstrating that the lymphatics are active, plastic and tissue-specific players in a range of biological and pathological processes, including within the intestine. These findings have, in turn, inspired exploration of lymph-specific therapies for a range of diseases, as well as the development of more sophisticated strategies to actively deliver drugs or vaccines to the intestinal lymph, including a range of nanotechnologies, lipid prodrugs and lipid-conjugated materials that 'hitchhike' on lymphatic transport pathways. With the increasing development of novel biological therapeutics there has been interest in whether these novel therapeutics are absorbed and transported through intestinal lymph after oral administration. Here we review the current state of understanding of the anatomy and physiology of the gastrointestinal lymphatic system in health and disease, with a focus on aspects relevant to drug delivery. We summarise the current state-of-the-art approaches to deliver drugs and quantify their uptake into the intestinal lymphatic system. Finally, and excitingly, we discuss recent examples of significant pharmacokinetic and therapeutic benefits achieved via intestinal lymphatic drug delivery. We also propose approaches to advance the development and clinical application of intestinal lymphatic delivery strategies into the future. Significance Statement This comprehensive review details understanding of the anatomy and physiology of the intestinal lymphatic system in health and disease, with a focus on aspects relevant to drug delivery. It highlights current state-of-the-art approaches to deliver drugs to the intestinal lymphatics and the shift toward the use of these strategies to achieve pharmacokinetic and therapeutic benefits for patients., (Copyright © 2024 American Society for Pharmacology and Experimental Therapeutics.)

Dabigatran etexilate (DABE) is a lipophilic double alkyl ester prodrug of dabigatran (DAB) which is a serine protease inhibitor used clinically as an anticoagulant. Recently, translocation of serine protease enzymes, including trypsin, from the gut into the mesenteric lymph and then blood has been associated with organ failure in acute and critical illnesses (ACIs). Delivery of DABE into mesenteric lymph may thus be an effective strategy to prevent organ failure in ACIs. Most drugs access the mesenteric lymph in low quantities following oral administration, as they are rapidly transported away from the intestine via the blood. Here, we examine the potential to deliver DABE into the mesenteric lymph by promoting association with lymph lipid transport pathways via co-administration with a lipid-based formulation (LBF). A series of self-emulsifying LBFs were designed and tested in vitro for their potential to form stable DABE loaded emulsions and keep DABE solubilised and stable over time in simulated gastrointestinal conditions. The LBFs were found to form fine emulsions with a droplet size of 214 ± 30 nm and DABE was stable in the formulation. The stability of DABE in vitro in simulated intestinal conditions, plasma and lymph samples was also evaluated to ensure stability in collected samples and to evaluate whether the prodrug is likely to release active DAB. Ultimately, a highly uniform and stable self-emulsifying Type III A LBF of DABE was chosen for progression into in vivo studies in male Sprague Dawley rats to confirm the lymphatic uptake and plasma pharmacokinetics. Both in vitro and in vivo in plasma and lymph, DABE was rapidly converted to an intermediate and DAB. The main species present in vivo in both plasma and lymph was DAB and mass transport of DABE and DAB in lymph was minimal (∼0.5 % of dose). Importantly, the concentration of DABE in lymph was substantially (20-176 fold) higher than in plasma, supporting that if the prodrug were stable and did not convert to DAB in the intestine, it would be lymphatically transported. Future studies will therefore focus on optimizing the design of the prodrug and formulation to improve stability during absorption and further promote lymphatic uptake., Competing Interests: Declaration of competing interest N.L. Trevaskis is an Editorial Board Member for Journal of Pharmaceutical Sciences and was not involved in the editorial review or the decision to publish this article. The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: N.L. Trevaskis, C.J.H. Porter, S. Han are inventors of a lymph-directing glyceride prodrug technology that has been patented and licensed to PureTech Health, Boston. The current work is not related to the glyceride prodrug technology. It evaluates and describe lymphatic uptake of a lipophilic ester prodrug of different molecular structure., (Copyright © 2024 American Pharmacists Association. Published by Elsevier Inc. All rights reserved.)

Acute pancreatitis (AP) is an acute inflammatory disorder that is common, costly, and is increasing in incidence worldwide with over 300,000 hospitalizations occurring yearly in the United States alone. As its course and outcomes vary widely, a critical knowledge gap in the field has been a lack of accurate prognostic tools to forecast AP patients' outcomes. Despite several published studies in the last three decades, the predictive performance of published prognostic models has been found to be suboptimal. Recently, non-regression machine learning models (ML) have garnered intense interest in medicine for their potential for better predictive performance. Each year, an increasing number of AP models are being published. However, their methodologic quality relating to transparent reporting and risk of bias in study design has never been systematically appraised. Therefore, through collaboration between a group of clinicians and data scientists with appropriate content expertise, we will perform a systematic review of papers published between January 2021 and December 2023 containing artificial intelligence prognostic models in AP. To systematically assess these studies, the authors will leverage the CHARMS checklist, PROBAST tool for risk of bias assessment, and the most current version of the TRIPOD-AI. (Research Registry ( http://www.reviewregistry1727 .)., (© 2024. The Author(s).)

Postoperative pancreatic fistula (POPF) is a frequent complication after pancreatectomy, leading to increased morbidity and mortality. Optimizing prediction models for POPF has emerged as a critical focus in surgical research. Although over sixty models following pancreaticoduodenectomy, predominantly reliant on a variety of clinical, surgical, and radiological parameters, have been documented, their predictive accuracy remains suboptimal in external validation and across diverse populations. As models after distal pancreatectomy continue to be progressively reported, their external validation is eagerly anticipated. Conversely, POPF prediction after central pancreatectomy is in its nascent stage, warranting urgent need for further development and validation. The potential of machine learning and big data analytics offers promising prospects for enhancing the accuracy of prediction models by incorporating an extensive array of variables and optimizing algorithm performance. Moreover, there is potential for the development of personalized prediction models based on patient- or pancreas-specific factors and postoperative serum or drain fluid biomarkers to improve accuracy in identifying individuals at risk of POPF. In the future, prospective multicenter studies and the integration of novel imaging technologies, such as artificial intelligence-based radiomics, may further refine predictive models. Addressing these issues is anticipated to revolutionize risk stratification, clinical decision-making, and postoperative management in patients undergoing pancreatectomy., Competing Interests: Conflict-of-interest statement: We declare no conflicts of interest., (©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.)

Objectives: In patients with acute pancreatitis (AP), minimally invasive treatment and the step-up approach have been widely used to deal with infected pancreatic necrosis (IPN) in the last decade. It is unclear whether IPN has become a less important determinant of mortality relative to organ failure (OF). We aimed to statistically aggregate recent evidence from published studies to determine the relative importance of IPN and OF as determinants of mortality in patients with AP (PROSPERO: CRD42020176989)., Methods: Relevant studies were sourced from MEDLINE and EMBASE databases. Relative risk (RR) or weighted mean difference (WMD) was analyzed as outcomes. A two-sided P value of less than 0.05 was regarded as statistical significance., Results: Forty-three studies comprising 11 601 patients with AP were included. The mortality was 28% for OF patients and 24% for those with IPN. Patients with OF without IPN had a significantly higher risk of mortality compared to those with IPN but without OF (RR 3.72, P < 0.0001). However, patients with both OF and IPN faced the highest risk of mortality. Additionally, IPN increased length of stay in hospital for OF patients (WMD 28.75, P = 0.032)., Conclusion: Though IPN remains a significant concern, which leads to increased morbidity and longer hospital stay, it is a less critical mortality determinant compared to OF in AP., (© 2023 Chinese Medical Association Shanghai Branch, Chinese Society of Gastroenterology, Renji Hospital Affiliated to Shanghai Jiaotong University School of Medicine and John Wiley & Sons Australia, Ltd.)

Background: The incidence of clinically relevant postoperative pancreatic fistula (CR-POPF) after central pancreatectomy (CP) is high, yet an effective predictive method is currently lacking. This study aimed to predict CR-POPF after CP by utilizing existing fistula risk scores (FRSs) for pancreaticoduodenectomy (PD) and distal pancreatectomy (DP)., Methods: A retrospective analysis was conducted on patients undergoing CP at our institution between January 2010 and July 2022. The primary outcome was CR-POPF (grade B/C) according to the 2016 International Study Group of Pancreatic Surgery definition. To establish predictive models for CR-POPF after CP, we combined the FRSs for PD and DP using a calculation formula that considers the probability of the union of two events. As a result, we obtained twelve central FRS (C-FRS) models. The performance of each C-FRS was assessed using the area under the curves (AUC) and calibration plots., Results: A total of 115 patients undergoing CP were included. Among them, 38 (33%) were male, with a median age of 53 years. CR-POPF occurred in 35 (30.4%) patients, specifically 33 (28.7%) with grade B and 2 (1.7%) with grade C. Multivariate analysis showed that body mass index (BMI) [odds ratio (OR) 1.260, 95% confidence interval (CI) 1.039-1.528, P = 0.019), pancreatic thickness at the cephalic transection site (OR 1.228, 95% CI 1.074-1.405, P = 0.003), cephalic main pancreatic duct (MPD) size (OR 41.872, 95%CI 7.614-230.265, P < 0.001), and distal MPD size (OR 0.142, 95% CI 0.036-0.561, P = 0.005) were independent predictive factors for CR-POPF. Discrimination was generally acceptable for all C-FRS models, with an AUC ranging from 0.748 (DISPAIR-a-FRS: 95% CI, 0.659-0.824) to 0.847 (Intraop-D-a-FRS: 95% CI, 0.768-0.907). The models were calibrated with adequate Brier scores ranging from 0.157 to 0.183. The performance in all subgroups was similar as that of the entire cohort. Three preoperative risk groups (low, intermediate, and high) were identified based on the clinical applicability of the Preop-D-Roberts-FRS, with corresponding incidences of CR-POPF as 0% (0/24), 30% (21/70), and 66.7% (14/21), respectively., Conclusion: The derived C-FRS models show potential for accurately predicting the development of CR-POPF after CP. However, further validation studies are required to determine the most effective model. In the meantime, the Preop-D-Roberts-FRS is recommended for clinical practice due to its ease of use and preoperative predictability., Competing Interests: Declaration of competing interest We declared no conflict of interest., (Copyright © 2023 IAP and EPC. Published by Elsevier B.V. All rights reserved.)

Background/aims: Early and accurate identification of patients with acute pancreatitis (AP) at high risk of persistent acute respiratory failure (PARF) is crucial. We sought to determine the accuracy of simplified Lung Injury Prediction Score (sLIPS) and simplified Early Acute Lung Injury (sEALI) for predicting PARF in ward AP patients., Methods: Consecutive AP patients in a training cohort from West China Hospital of Sichuan University (n = 912) and a validation cohort from The First Affiliated Hospital of Nanchang University (n = 1033) were analyzed. PARF was defined as oxygen in arterial blood/fraction of inspired oxygen < 300 mmHg that lasts for > 48 h. The sLIPS was composed by shock (predisposing condition), alcohol abuse, obesity, high respiratory rate, low oxygen saturation, high oxygen requirement, hypoalbuminemia, and acidosis (risk modifiers). The sEALI was calculated from oxygen 2 to 6 L/min, oxygen > 6 L/min, and high respiratory rate. Both indices were calculated on admission., Results: PARF developed in 16% (145/912) and 22% (228/1033) (22%) of the training and validation cohorts, respectively. In these patients, sLIPS and sEALI were significantly increased. sLIPS ≥ 2 predicted PARF in the training (AUROC 0.87, 95% CI 0.84-0.89) and validation (AUROC 0.81, 95% CI 0.78-0.83) cohorts. sLIPS was significantly more accurate than sEALI and current clinical scoring systems in both cohorts (all P < 0.05)., Conclusions: Using routinely available clinical data, the sLIPS can accurately predict PARF in ward AP patients and outperforms the sEALI and current existing clinical scoring systems., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Following significant advances in lymphatic biology, the important role of kidney lymphatics in kidney function and dysfunction is now being more fully appreciated. Kidney lymphatics begin in the cortex as blind-ended lymphatic capillaries and then coalesce into larger lymphatics that follow the main blood vessels out through the kidney hilum. Their function in draining interstitial fluid, macromolecules, and cells underpins their important role in kidney fluid and immune homeostasis. This article provides a comprehensive overview of recent and more established research findings on kidney lymphatics and the implications of these findings for kidney function and disease. The use of lymphatic molecular markers has greatly expanded our knowledge of the development, anatomy, and pathophysiology of kidney lymphatics. Significant recent discoveries include the diverse embryological source of kidney lymphatics, the hybrid nature of the ascending vasa recta, and the effects of lymphangiogenesis on kidney diseases such as acute kidney injury and renal fibrosis. On the basis of these recent advances, there is now an opportunity to link information from across multiple research disciplines to drive a new era of lymphatic-targeted therapies for kidney disease. © 2023 American Physiological Society. Compr Physiol 13:4945-4984, 2023., (Copyright © 2023 American Physiological Society. All rights reserved.)

Importance: The incidence of hypertriglyceridemia-associated acute pancreatitis (HTG-AP) is increasing. Plasmapheresis is theoretically effective in removing triglyceride from plasma, but whether it confers clinical benefits is unclear., Objective: To assess the association between plasmapheresis and the incidence and duration of organ failure among patients with HTG-AP., Design, Setting, and Participants: This is an a priori analysis of data from a multicenter, prospective cohort study with patients enrolled from 28 sites across China. Patients with HTG-AP were admitted within 72 hours from the disease onset. The first patient was enrolled on November 7th, 2020, and the last on November 30th, 2021. The follow-up of the 300th patient was completed on January 30th, 2022. Data were analyzed from April to May 2022., Exposures: Receiving plasmapheresis. The choice of triglyceride-lowering therapies was at the discretion of the treating physicians., Main Outcomes and Measures: The primary outcome was organ failure-free days to 14 days of enrollment. Secondary outcomes included other measures for organ failure, intensive care unit (ICU) admission, duration of ICU and hospital stays, incidence of infected pancreatic necrosis, and 60-day mortality. Propensity score matching (PSM) and inverse probability of treatment weighting (IPTW) analyses were used to control potential confounders., Results: Overall, 267 patients with HTG-AP were enrolled (185 [69.3%] were male; median [IQR] age, 37 [31-43] years), among whom 211 underwent conventional medical treatment and 56 underwent plasmapheresis. PSM created 47 pairs of patients with balanced baseline characteristics. In the matched cohort, no difference was detected concerning organ failure-free days between patients undergoing plasmapheresis or not (median [IQR], 12.0 [8.0-14.0] vs 13.0 [8.0-14.0]; P = .94). Moreover, more patients in the plasmapheresis group required ICU admission (44 [93.6%] vs 24 [51.1%]; P < .001). The IPTW results conformed to the results from the PSM analysis., Conclusions and Relevance: In this large multicenter cohort study of patients with HTG-AP, plasmapheresis was commonly used to lower plasma triglyceride. However, after adjusting for confounders, plasmapheresis was not associated with the incidence and duration of organ failure, but with increased ICU requirements.

Background: Acute Mesenteric Ischaemic (AMI) is a rare condition with significant morbidity and mortality. Many causes of AMI exist, which usually begin with mucosal injury. Onset is insiduous and there is frequent diagnostic delay. Current treatments can only control established injury and prevent propagation, hence new interventions are needed. The prevention and treatment of AMI by intraluminal delivery of oxygen has yet to be investigated in the clinical setting. This article aims to systemically review experimental studies investigating this novel therapy., Methods: Following the PRISMA guidelines, searches of PubMed and Ovid MEDLINE databases were performed up to June 2022. Two independent investigators extracted the data., Results: There were 20 experimental studies, 16 of which used an occlusive ischaemia reperfusion model. Six different formulations were used to deliver intraluminal oxygen, with perflurocarbon being the most common. Studies consistently showed local and systemic benefits. Intraluminal oxygen therapy improved histological severity of mucosal injury in all studies when oxygen was delivered during the ischaemia phase, but could cause harm if given during the reperfusion phase. Improvement was also demonstrated in endpoints assessing intestinal function, biomarkers of intestinal damage, measures of systemic physiological derangement and mortality., Conclusion: Intraluminal oxygenation appears to be an effective treatment for AMI. There remain significant questions regarding optimal timing and delivery formulation before clinical translation of this treatment strategy., (© 2022 The Authors. ANZ Journal of Surgery published by John Wiley & Sons Australia, Ltd on behalf of Royal Australasian College of Surgeons.)

Background: Acute on chronic pancreatitis (ACP) is a relatively common condition, but there are significant gaps in our knowledge on the definition, incidence, diagnosis, treatment and prognosis., Methods: A systematic review that followed PICO (Population; Intervention; Comparator; Outcome) recommendation for quantitative questions and PICo (Population, Phenomenon of Interest, Context) for qualitative research was done to answer 10 of the most relevant questions about ACP. Quality of evidence was judged by the GRADE criteria (Grades of Recommendation, Assessment, Development and Evaluation). The manuscript was sent for review to 12 international experts from various disciplines and continents using a Delphi process., Results: The quality of evidence, for most statements, was low to very low, which means that the recommendations in general are only conditional. Despite that, it was possible to reach strong levels of agreement by the expert panel for all 10 questions. A new consensus definition of ACP was reached. Although common, the real incidence of ACP is not known, with alcohol as a major risk factor. Although pain dominates, other non-specific symptoms and signs can be present. Serum levels of pancreatic enzymes may be less than 3 times the upper limit of normal and cross-sectional imaging is considered more accurate for the diagnosis in many cases. It appears that it is less severe and with a lower mortality risk than acute pancreatitis., Conclusions: Although the evidence base is poor, this position statement provides a foundation from which to advance management of ACP., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

Pancreatic ductal adenocarcinoma remains a highly debilitating condition with no effective disease-modifying interventions. In our search for natural products with promising anticancer activity, we identified the aminolipopeptide trichoderin A as a potential candidate. While it was initially isolated as an antitubercular peptide, we provide evidence that it is also selectively toxic against BxPC-3 and PANC-1 human pancreatic ductal adenocarcinoma cells cultured under glucose deprivation. This has critical implications for the pancreatic ductal adenocarcinoma, which is characterized by nutrient deprivation due to its hypovascularized network. We have also successfully simplified the trichoderin A peptide backbone, allowing greater accessibility to the peptide for further biological testing. In addition, we also conducted a preliminary investigation into the role of peptide lipidation at the N -terminus. This showed that analogues with longer fatty acyl chains exhibited superior cytotoxicity than those with shorter acyl chains. Further structural optimization of trichoderin A is anticipated to improve its biological activity, whilst ongoing mechanistic studies to elucidate its intracellular mechanism of action are conducted in parallel.

Background: Measuring intra-abdominal pressure (IAP) is important for management of patients with severe acute pancreatitis (SAP). Intra-bladder pressure (IBP) is an indirect index that reflects IAP, but measuring techniques vary. We sought to optimise IBP measuring techniques in predicted SAP patients., Methods: Predicted SAP patients consecutively admitted between June 2018 and January 2020 were scrutinised. Eligible patients had their IBP monitored for the first 72 h at 6-h intervals, and were then sequentially allocated into three research scenarios: (1) in the supine position along with head of bed elevation(HoBE)of 0, 15 and 30° at various points including the iliac crest the midaxillary line, pubic symphysis, and right atrium level, instilled with 25 mL normal saline (NS) at room temperature (RT); (2) NS instillation volume from 0, 10, 25, 40-50 mL at the iliac crest with HoBE15 at RT; and (3) NS instillation (25 mL) at either RT or 37 °C with HoBE15., Results: The dynamic IBP values measured at the pubic symphysis and iliac crest were fairly similar between HoBE0 and HoBE15 (all P > 0.05), but greatly increased at HoBE30 (all P < 0.01). IBP was significantly increased with escalating instillation volumes of NS (all P < 0.01 versus 0 mL NS), while there was no significant difference between 25 mL and 10 mL (P = 0.055). IBP was similar between NS at RT and under 37 °C (P = 0.643)., Conclusion: In predicted SAP patients, measuring IBP at the iliac crest with HoBE15 after instilling 10 mL of NS seems to be appropriate for monitoring IAP., Competing Interests: Declaration of competing interest These authors declare that there is no conflict of interests regarding the publication of this paper., (Copyright © 2022 The Authors. Published by Elsevier B.V. All rights reserved.)

Gastrointestinal dysfunction/failure (GDF) is a common cause of concern in critically ill patients. Although the gut plays an important role in the genesis of organ failure, its exclusion from organ severity scoring systems has made it challenging for intensivists to score it sufficiently at the bedside. We aimed to survey intensive care specialists about their perceptions, attitudes, and approaches towards the assessment of the gut in Australia and New Zealand intensive care units (ICUs). An electronic (online) questionnaire was used to survey intensive care specialists from the Australia and New Zealand Intensive Care Society (ANZICS). The survey comprised 10 questions focused on four key areas: (i) the extent of the problem with GDF in ICUs, (ii) the use and reliability of the current gut scoring tools, (iii) personal approaches and practices associated with GDF assessment, and (4) potential value of a novel GDF scoring system and its incorporation into an organ severity score. Our results showed that GDF was a significant concern amongst ICUs in Australia and New Zealand intensivists (84%; 66/79), with a small number of participants (14%; 3/79) using a gut scoring tool in their ICUs. Despite this, we have no established objective scoring tool for its assessment. The survey highlighted the need for developing a novel scoring tool to assess the gut was considered important amongst majority of the intensivists (92%; 72/78), which would prove useful in clinical practice and potentially lead to incorporation into an organ severity score in the future., (Copyright © 2021 Australian College of Critical Care Nurses Ltd. Published by Elsevier Ltd. All rights reserved.)

Background: The goals and approaches to fluid therapy vary through different stages of resuscitation. This pilot study was designed to test the safety and feasibility of a fluid therapy protocol for the second or optimisation stage of resuscitation in patients with predicted severe acute pancreatitis (SAP)., Methods: Spontaneously breathing patients with predicted SAP were admitted after initial resuscitation and studied over a 24-h period in a tertiary hospital ward. Objective clinical assessment (OCA; heart rate, mean arterial pressure, urine output, and haematocrit) was done at 0, 4, 8, 12, 18-20, and 24 h. All patients had mini-fluid challenge (MFC; 250 ml intravenous normal saline within 10 min) at 0 h and repeated at 4 and 8 h if OCA score ≥2. Patients who were fluid responsive (>10% change in stroke volume after MFC) received 5-10 ml/kg/h, otherwise 1-3 ml/kg/h until the next time point. Passive leg raising test (PLRT) was done at each time point and compared with OCA for assessing volume status and predicting fluid responsiveness., Results: This fluid therapy protocol based on OCA, MFC, and PLRT and designed for the second stage of resuscitation was safe and feasible in spontaneously breathing predicted SAP patients. The PLRT was superior to OCA (at 0 and 8 h) for predicting fluid responsiveness and guiding fluid therapy., Conclusions: This pilot study found that a protocol for intravenous fluid therapy specifically for the second stage of resuscitation in patients with predicted SAP was safe, feasible, and warrants further investigation., (Copyright © 2022 The Authors. Published by Elsevier B.V. All rights reserved.)

The cisterna chyli is a lymphatic structure found at the caudal end of the thoracic duct that receives lymph draining from the abdominal and pelvic viscera and lower limbs. In addition to being an important landmark in retroperitoneal surgery, it is the key gateway for interventional radiology procedures targeting the thoracic duct. A detailed understanding of its anatomy is required to facilitate more accurate intervention, but an exhaustive summary is lacking. A systematic review was conducted, and 49 published human studies met the inclusion criteria. Studies included both healthy volunteers and patients and were not restricted by language or date. The detectability of the cisterna chyli is highly variable, ranging from 1.7 to 98%, depending on the study method and criteria used. Its anatomy is variable in terms of location (vertebral level of T10 to L3), size (ranging 2-32 mm in maximum diameter and 13-80 mm in maximum length), morphology, and tributaries. The size of the cisterna chyli increases in some disease states, though its utility as a marker of disease is uncertain. The anatomy of the cisterna chyli is highly variable, and it appears to increase in size in some disease states. The lack of well-defined criteria for the structure and the wide variation in reported detection rates prevent accurate estimation of its natural prevalence in humans.

Background: Early prediction of persistent organ failure (POF) is important for triage and timely treatment of patients with acute pancreatitis (AP)., Methods: All AP patients were consecutively admitted within 48 h of symptom onset. A nomogram was developed to predict POF on admission using data from a retrospective training cohort, validated by two prospective cohorts. The clinical utility of the nomogram was defined by concordance index (C-index), decision curve analysis (DCA), and clinical impact curve (CIC), while the performance by post-test probability., Results: There were 816, 398, and 880 patients in the training, internal and external validation cohorts, respectively. Six independent predictors determined by logistic regression analysis were age, respiratory rate, albumin, lactate dehydrogenase, oxygen support, and pleural effusion and were included in the nomogram (web-based calculator: https://shina.shinyapps.io/DynNomapp/). This nomogram had reasonable predictive ability (C-indexes 0.88/0.91/0.81 for each cohort) and promising clinical utility (DCA and CIC). The nomogram had a positive likelihood ratio and post-test probability of developing POF in the training, internal and external validation cohorts of 4.26/31.7%, 7.89/39.1%, and 2.75/41%, respectively, superior or equal to other prognostic scores., Conclusions: This nomogram can predict POF of AP patients and should be considered for clinical practice and trial allocation., (Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: To determine the impact of glucose levels at admission and during first week (early phase) on clinical outcomes in patients with acute pancreatitis (AP) and to investigate the relationship between stress hyperglycaemia (SHG) and hypertriglyceridaemia (HTG)., Methods: Two independent and prospective databases were retrospectively analysed (n = 1792). Patients admitted with pain of less than 48 hours and confirmed AP were included. SHG was defined as admission blood glucose ≥ 10.00 mmol/L (non-diabetic) or ≥ 16.67 mmol/L (diabetic). Blood glucose records for the first week were inspected to determine whether SHG lasted ≥ 48 hours (persistent) or < 48 hours (transient). Clinical outcomes were compared between designated patient groups using multivariate and trend analyses. The correlation between SHG and HTG (serum triglyceride ≥ 5.65 mmol/L) was also analysed., Results: On admission, SHG was present in 27.8% (499/1792) patients; during the first 48 hours of admission, transient and persistent SHG was found in 31% (556/1792) and 8.0% (144/1792) patients, respectively. Admission SHG was associated with higher incidence of persistent organ failure, acute necrotic collection, major infection, and mortality as well as prolonged length of hospital stay (all P < 0.05). Duration of SHG was also associated with worsened clinical outcomes (all P < 0.05). In HTG-AP patients, more severe clinical outcomes were observed in those who concomitantly had SHG ( P  < 0.05)., Conclusions: Admission and persistent SHG during the first week of admission worsens clinical outcomes of AP patients. These effects are more pronounced when admission HTG co-existed., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Yang, Shi, Yao, He, Zhu, Li, Li, Li, Liu, Deng, Jin, Liu, Lu, Windsor, Sutton, Zhu, Xia and Huang.)

Objective: Conventionally, in vivo mesenteric lymphatic contractile function is measured using a high magnification transmission microscope (field of view 0.3-1.5 mm), which precludes visualization of extended lengths of vessels embedded in mesenteric fat. Existing software is not optimized for imaging at a low magnification using a contrast agent. We aimed to develop a simple and clinically transferable method for in situ visualization, image analysis, and quantitative assessment of mesenteric lymphatic contractile function over an extended area., Methods: Subserosal injection of various blue dyes was taken up by mesenteric lymphatics and visualized under a stereomicroscope (25×), allowing for video recording of 1.4 × 1.1 cm of intact mesentery. A new R package ("vmeasur") that combines multiple high-performance image analyses into a single workflow was developed. The edges of each vessel were determined by applying an automated threshold to each frame (with real-time manual verification). The vessel width at every point in each frame was plotted to provide contractile parameters over time and along the lymphatic vessel length., Results: Contractile parameters and their differences along the length of the vessel were accurately calculated in a rodent model. In a human mesenteric lymphatic, the algorithm was also able to measure changes in diameter over length., Conclusion: This software offers a low cost, rapid, and accessible method to measure lymphatic contractile function over a wide area, showing differences in contractility along the length of a vessel. Because the presence of mesenteric fat has less of an impact on imaging, due to the use of an exogenous contrast agent, there is potential for clinical application., (© 2022 The Authors. Microcirculation published by John Wiley & Sons Ltd.)

Objectives: Splanchnic venous thrombosis (SpVT) is a complication of acute pancreatitis (AP). There is scarce literature on the prevalence and treatment of SpVT in AP. The aim of this international survey was to document current approaches to the management of SpVT in patients with AP., Methods: An online survey was designed by a group of international experts in the management of AP. Twenty-eight questions covered the level of experience of the respondents, disease demographics, and management of SpVT., Results: There were 224 respondents from 25 countries. Most respondents (92.4%, n = 207) were from tertiary hospitals and predominantly consultants (attendings, 86.6%, n = 194). More than half of the respondents (57.2%, n = 106) "routinely" prescribed prophylactic anticoagulation for AP. Less than half of the respondents (44.3%, n = 82) "routinely" prescribed therapeutic anticoagulation for SpVT. A clinical trial was considered justified by most respondents (85.4%, n = 157) and 73.2% (n = 134) would be willing to enroll their patients., Conclusions: The approach to anticoagulation in the treatment of patients with SpVT complicating AP was highly variable. Respondents indicate that a position of equipoise exists to justify randomized evaluation., Competing Interests: The authors declare no conflict of interest., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Chronic nausea and vomiting syndromes (NVSs) are prevalent and debilitating disorders. Putative mechanisms include gastric neuromuscular disease and dysregulation of brain-gut interaction, but clinical tests for objectively defining gastric motor function are lacking. A medical device enabling noninvasive body surface gastric mapping (BSGM) was developed and applied to evaluate NVS pathophysiology. BSGM was performed in 43 patients with NVS and 43 matched controls using Gastric Alimetry (Alimetry), a conformable high-resolution array (8 × 8 electrodes; 20-mm interelectrode spacing), wearable reader, and validated symptom-logging app. Continuous measurement encompassed a fasting baseline (30 minutes), 482-kilocalorie meal, and 4-hour postprandial recording, followed by spectral and spatial biomarker analyses. Meal responses were impaired in NVS, with reduced amplitudes compared to controls (median, 23.3 microvolts versus 38.0 microvolts, P < 0.001), impaired fed-fasting power ratios (1.1 versus 1.6, P = 0.02), and disorganized slow waves (spatial frequency stability, 13.6 versus 49.5; P < 0.001). Two distinct NVS subgroups were evident with indistinguishable symptoms (all P > 0.05). Most patients (62%) had normal BSGM studies with increased psychological comorbidities (43.5% versus 7.7%; P = 0.03) and anxiety scores (median, 16.5 versus 13.0; P = 0.035). A smaller subgroup (31%) had markedly abnormal BSGM, with biomarkers correlating with symptoms (nausea, pain, excessive fullness, early satiety, and bloating; all r > 0.35, P < 0.05). Patients with NVS share overlapping symptoms but comprise distinct underlying phenotypes as revealed by a BSGM device. These phenotypes correlate with symptoms, which should inform clinical management and therapeutic trial design.

The lymphatic system and the cardiovascular (CV) system work together to maintain body fluid homeostasis. Despite that, the lymphatic system has been relatively neglected as a potential drug target and a source of adverse effects from CV drugs. Like the heart, the lymphatic vessels undergo phasic contractions to promote lymph flow against a pressure gradient. Dysfunction or failure of the lymphatic pump results in fluid imbalance and tissue oedema. While this can be due to drug effects, it is also a feature of breast cancer-associated lymphoedema, chronic venous insufficiency, congestive heart failure, and acute systemic inflammation. There are currently no specific drug treatments for lymphatic pump dysfunction in clinical use despite the wealth of data from pre-clinical studies. The aim of this study was to identify (i) drugs with direct effects on lymphatic tonic and phasic contractions with potential for clinical application, and (ii) drugs in current clinical use that have a positive or negative side effect on lymphatic function. We comprehensively reviewed all studies that tested the direct effect of a drug on the contractile function of lymphatic vessels. Of the 208 drugs identified from 193 studies, about a quarter had only stimulatory effects on lymphatic tone, contraction frequency, and/or contraction amplitude. Of Food and Drug Administration-approved drugs, there were 14 that increased lymphatic phasic contractile function. The most frequently used class of drugs with inhibitory effects on lymphatic pump function were the calcium channels blockers. This review highlights the opportunity for specific drug treatments of lymphatic dysfunction in various disease states and for avoiding adverse drug effects on lymphatic contractile function., Competing Interests: Conflict of interest: N.T. is an inventor of a lymph-directing glyceride prodrug technology, which enhances delivery of drugs to intestinal lymph. This technology has been patented and licensed via a commercial agreement with PureTech Health, Boston. PureTech Health has subsequently entered into a collaboration agreement with Boehringer Ingelheim to explore the technology in immune modulation. N.T. receives payments and royalties from PureTech Health as part of the agreement., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2021. For permissions, please email: journals.permissions@oup.com.)

Abstract: Recurrent acute pancreatitis and chronic pancreatitis represent high morbidity diseases, which are frequently associated with chronic abdominal pain, pancreatic insufficiencies, and reduced quality of life. Currently, there are no therapies to reverse or delay disease progression, and clinical trials are needed to investigate potential interventions that would address this important gap. This conference report provides details regarding information shared during a National Institute of Diabetes and Digestive and Kidney Diseases-sponsored workshop on Clinical Trials in Pancreatitis that sought to clearly delineate the current gaps and opportunities related to the design and conduct of patient-focused trials in recurrent acute pancreatitis and chronic pancreatitis. Key stakeholders including representatives from patient advocacy organizations, physician investigators (including clinical trialists), the US Food and Drug Administration, and the National Institutes of Health convened to discuss challenges and opportunities with particular emphasis on lessons learned from trials in participants with other painful conditions, as well as the value of incorporating the patient perspective throughout all stages of trials., Competing Interests: The following authors disclose potential conflicts of interest: P.A.H. (honoraria for consulting from Kangen Pharmaceuticals and Sagent Pharmaceuticals paid to his institution; honorarium for advisory board from Horizon Therapeutics USA, Inc, paid to his institution); G.A.C. (honoraria for consulting from Olympus Corporation of the Americas); I.G. (honoraria from Adynxx, Biogen, Eupraxia, Novaremed and GW Research); R.H.D. (past 5 years, research grants and contracts from the US Food and Drug Administration and the US National Institutes of Health and compensation forf serving on advisory boards or consulting on clinical trial methods from Abide, Acadia, Adynxx, Analgesic Solutions, Aptinyx, Aquinox, Asahi Kasei, Astellas, Beckley, Biogen, Biohaven, Biosplice, Boston Scientific, Braeburn, Cardialen, Celgene, Centrexion, Chiesi, Chromocell, Clexio, Collegium, Concert, Confo, Decibel, Editas, Eli Lilly, Endo, Ethismos (equity), Eupraxia, Exicure, Glenmark, Gloriana, Grace, Hope, Lotus, Mainstay, Merck, Mind Medicine (also equity), Neumentum, Neurana, NeuroBo, Novaremed, Novartis, OCT, OliPass, Pfizer, Q-State, Reckitt Benckiser, Regenacy (also equity), Sangamo, Sanifit, Scilex, Semnur, SIMR Biotech, Sinfonia, SK Biopharmaceuticals, Sollis, SPRIM, Teva, Theranexus, Toray, Vertex, Vizuri, and WCG); C.E.F. (research funding from Abbvie, consulting fees from Nestlé, and board member for National Pancreas Foundation); J.A.R. (consulting for Pediatrics Steering Committee, Pacira Pharmaceuticals); and D.C.W. (cofounder and chief scientific offer of Ariel Precision Medicine, consultant to Nestlé, Regeneron, and Ariel Precision Medicine). The rest of the authors declare no conflict of interest., (Copyright © 2022 “Written work prepared by employees of the Federal Government as part of their official duties is, under the U.S. Copyright Act, a “work of the United States Government” for which copyright protection under Title 17 of the United States Code is not available. As such, copyright does not extend to the contributions of employees of the Federal Government.”.)

The lymphatic system continues to gain importance in a range of conditions, and therefore, imaging of lymphatic vessels is becoming more widespread for research, diagnosis, and treatment. Fluorescent lymphatic imaging offers advantages over other methods in that it is affordable, has higher resolution, and does not require radiation exposure. However, because the lymphatic system is a one-way drainage system, the successful delivery of fluorescent tracers to lymphatic vessels represents a unique challenge. Each fluorescent tracer used for lymphatic imaging has distinct characteristics, including size, shape, charge, weight, conjugates, excitation/emission wavelength, stability, and quantum yield. These characteristics in combination with the properties of the target tissue affect the uptake of the dye into lymphatic vessels and the fluorescence quality. Here, we review the characteristics of visible wavelength and near-infrared fluorescent tracers used for in vivo lymphatic imaging and describe the various techniques used to specifically target them to lymphatic vessels for high-quality lymphatic imaging in both clinical and pre-clinical applications. We also discuss potential areas of future research to improve the lymphatic fluorescent tracer design., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The handling editor SH declared a past co-authorship with authors JH, AP, JW., (Copyright © 2022 Russell, Velivolu, Maldonado Zimbrón, Hong, Kavianinia, Hickey, Windsor and Phillips.)

Background: Pancreatic cancer remains a highly fatal disease with a 5-year overall survival of less than 10%. In seeking to improve clinical outcomes, there is ongoing debate about the weight that should be given to patient volume in centralization models. The aim of this systematic review is to examine the relationship between patient volume and clinical outcome after pancreatic resection for cancer in the contemporary literature., Methods: The Google Scholar, PubMed, and Cochrane Library databases were systematically searched from February 2015 until June 2021 for articles reporting patient volume and outcomes after pancreatic cancer resection., Results: There were 46 eligible studies over a 6-year period comprising 526,344 patients. The median defined annual patient volume thresholds varied: low-volume 0 (range 0-9), medium-volume 9 (range 3-29), high-volume 19 (range 9-97), and very-high-volume 28 (range 17-60) patients. The latter 2 were associated with a significantly lower 30-day mortality (P < .001), 90-day mortality (P < .001), overall postoperative morbidity (P = .005), failure to rescue rate (P = .006), and R0 resection rate (P = .008) compared with very-low/low-volume hospitals. Centralization was associated with lower 30-day mortality in 3 out of 5 studies, while postoperative morbidity was similar in 4 out of 4 studies. Median survival was longer in patients traveling greater distance for pancreatic resection in 2 out of 3 studies. Median and 5-year survival did not differ between urban and rural settings., Conclusion: The contemporary literature confirms a strong relationship between patient volume and clinical outcome for pancreatic cancer resection despite expected bias toward more complex surgery in high-volume centers. These outcomes include lower mortality, morbidity, failure-to-rescue, and positive resection margin rates., (Copyright © 2021. Published by Elsevier Inc.)

Background: Abdominal pain is the most distressing symptom of chronic pancreatitis (CP), and current treatments show limited benefit. Pain phenotypes may be more useful than diagnostic categories when planning treatments, and the presence or absence of constant pain in CP may be a useful prognostic indicator., Aims: This cross-sectional study examined dimensions of pain in CP, compared pain in CP with chronic primary pain (CPP), and assessed whether constant pain in CP is associated with poorer outcomes., Methods: Patients with CP (N = 91) and CPP (N = 127) completed the Comprehensive Pancreatitis Assessment Tool. Differences in clinical characteristics and pain dimensions were assessed between a) CP and CPP and b) CP patients with constant versus intermittent pain. Latent class regression analysis was performed (N = 192) to group participants based on pain dimensions and clinical characteristics., Results: Compared to CPP, CP patients had higher quality of life (p < 0.001), lower pain severity (p < 0.001), and were more likely to use strong opioids (p < 0.001). Within CP, constant pain was associated with a stronger response to pain triggers (p < 0.05), greater pain spread (p < 0.01), greater pain severity, more features of central sensitization, greater pain catastrophising, and lower quality of life compared to intermittent pain (all p values ≤ 0.001). Latent class regression analysis identified three groups, that mapped onto the following patient groups 1) combined CPP and CP-constant, 2) majority CPP, and 3) majority CP-intermittent., Conclusions: Within CP, constant pain may represent a pain phenotype that corresponds with poorer outcomes. CP patients with constant pain show similarities to some patients with CPP, potentially indicating shared mechanisms., (Copyright © 2022 IAP and EPC. Published by Elsevier B.V. All rights reserved.)

Background: While the management of infected pancreatic necrosis (IPN) has evolved in the last two decades with the adoption of minimally invasive interventions (drainage ± debridement), it is unknown whether the principle of delaying intervention inherited from the open surgery era still applies. The aim of the current study was to investigate the impact of the timing of minimally invasive intervention on the outcomes of patients with IPN requiring intervention., Methods: PubMed, Embase, MEDLINE and Web of Science databases were searched for appropriate studies. The primary outcome of interest was hospital mortality, the secondary outcomes were the incidence of complications during the hospitalization, including new-onset organ failure, gastrointestinal fistula or perforation, bleeding and length of hospital or intensive care unit (ICU) stay., Results: Seven clinical studies were included with a total of 742 patients with IPN requiring intervention, of whom 321 received early intervention and 421 delayed intervention. Results from the meta-analysis showed that early minimally invasive intervention did not increase hospital mortality (odds ratio 1.65, 95% confidence interval 0.97-2.81; p = 0.06) but was associated with a remarkably prolonged hospital stay and an increased incidence of gastrointestinal fistula or perforation when compared with delayed intervention., Conclusions: Although no firm conclusion can be drawn because of the quality of available studies, it does appear that timing of intervention is a risk factor for adverse outcomes and ought to be investigated more rigorously in prospective studies., (© 2022. Japanese Society of Gastroenterology.)

Background: Gut-lymph in animal models of acute disease is altered by intestinal ischemia and contributes to the development of systemic inflammation and organ dysfunction. Investigating gut-lymph in humans is hampered difficulty in accessing the thoracic duct (TD) for lymph sampling. The aims of this study were to develop and pilot a technique of intraoperative TD cannulation with delayed embolization to serially measure TD lymph pressure, flow, and composition (including markers of intestinal injury) during the early postoperative period and in response to enteral feeding and vasopressor treatment. Methods: A Seldinger technique was used for percutaneous TD cannulation during an Ivor Lewis esophagogastrectomy. Lymph flow rate and pressure were measured. TD lymph and plasma were sampled at 12 hourly intervals for up to 120 hours after surgery and before TD embolization. Biochemistry, lipids, cytokines, and markers of intestinal injury were measured before and after enteral feeding commenced at 36 hours. Results: Intraoperative TD cannulation was technically feasible in three of four patients. Delayed TD embolization was only successful in one of three patients, with two patients requiring a re-thoracotomy to treat chylothorax. Profound changes in TD composition, but not flow rate, occurred over time and in response to enteral feeding and vasopressors. TD lymph compared with plasma had significantly higher lipase (1.4-17 × ), interleukin-6 (8-108 × ), tumor necrosis factor-α (2.7-17 × ), d-lactate (0.3-23 × ), endotoxin (0.1-41 × ), and intestinal fatty acid binding protein (1.1-853 × ). Conclusions: Although TD cannulation and lymph sampling were successful, TD embolization failed in two of three patients. The composition of sampled TD lymph changed dramatically in response to enteral feeding, indicating intestinal ischemia that could be exacerbated by nonselective vasopressors. The higher concentration of proinflammatory cytokines and gut injury markers in TD lymph, compared with plasma, lends support to the gut-lymph concept.

The thoracic duct (TD) drains most of the body's lymph back to the venous system via its lymphovenous junction (LVJ), playing a pivotal role in fluid homeostasis, fat absorption and the systemic immune response. The respiratory cycle is thought to assist with lymph flow, but the precise mechanism underpinning terminal TD lymph flow into the central veins is not well understood. The aim of this study was to use ultrasonography (US) to explore the relationship between terminal TD lymph flow, the respiratory cycle, and gravity. The left supraclavicular fossa was scanned in healthy non-fasted volunteers using high-resolution (13-5 MHz) US to identify the terminal TD and the presence of a lymphovenous valve (LVV). The TD's internal diameter was measured in relation to respiration (inspiration vs. expiration) and body positioning (supine vs. Trendelenburg). The terminal TD was visualized in 20/33 (61%) healthy volunteers. An LVV was visualized in only 4/20 (20%) cases. The mean terminal TD diameter in the supine position was 1.7 mm (range 0.8-3.1 mm); this increased in full inspiration (mean 1.8 mm, range 0.9-3.2 mm, p < 0.05), and in the Trendelenburg position (mean 1.8 mm, range 1.2-3.1 mm, p < 0.05). The smallest mean terminal TD diameter occurred in full expiration (1.6 mm, range 0.7-3.1 mm, p < 0.05). Respiration and gravity impact the terminal TD diameter. Due to the challenges of visualizing the TD and LVJ, other techniques such as dynamic magnetic resonance imaging will be required to fully understand the factors governing TD lymph flow., (© 2021 American Association of Clinical Anatomists.)

Background/aims: Stress hyperglycemia is common in critical illness but it has not been clearly studied in patients with acute pancreatitis (AP). This study aimed to investigate the specific blood glucose (BG) level that defines stress hyperglycemia and to determine the impact of stress hyperglycemia on clinical outcomes in AP patients., Methods: AP patients admitted ≤ 48 h after abdominal pain onset were retrospectively analyzed. Patients were stratified by pre-existing diabetes and stress hyperglycemia was defined using stratified BG levels for non-diabetes and diabetes with clinical outcomes compared., Results: There were 967 non-diabetic and 114 diabetic (10.5%) patients met the inclusion criteria and the clinical outcomes between these two groups were not significantly different. In non-diabetes, the cut-off BG level of ≥ 180 mg/dl was selected to define stress hyperglycemia with an 8.8-fold higher odds ratio for persistent organ failure (POF) (95% CI 5.4-14.3; P < 0.001). For diabetes, ≥ 300 mg/dl was selected with a 7.5-fold higher odds ratio for POF (95% CI 1.7-34.3; P = 0.009). In multivariable logistic regression, stress hyperglycemia was independently associated with POF, acute necrotic collection, major infection and mortality. The combination of BG and systemic inflammatory response syndrome (SIRS) score in predicting POF was better than SIRS or Glasgow score alone., Conclusions: This study identifies a cut-off BG level of ≥ 180 mg/dl and ≥ 300 mg/dl was optimal to define stress hyperglycemia for non-diabetic and diabetic AP patients, respectively. There was a significant relationship between stress hyperglycemia and adverse clinical outcomes., (© 2021. The Author(s).)

Background: The consequences of even mild inadvertent perioperative hypothermia (IPH) are significant. There is a perception laparoscopic abdominal surgery is less prone to cause hypothermia than open surgery. However, during laparoscopic surgery, the peritoneal cavity is insufflated with carbon dioxide, which has a greater evaporative capacity than ambient air. This study compared the intra-operative temperature profile of patients undergoing open and laparoscopic colorectal surgery to define the incidence and severity of hypothermia., Methods: All adult patients undergoing colorectal surgery between May 2005 and August 2013 were identified from an electronic database. Cases were categorized into laparoscopic and open cases. Hypothermic episodes were defined as a temperature less than 36°C lasting for more than two consecutive minutes. The incidence of hypothermic episodes, the total time under 36°C and the area under the curve (degree-minutes) were calculated., Results: A total of 1547 cases were analysed. The overall incidence of hypothermia was 67.0%. The incidence of cases with a hypothermic episode was greater in the laparoscopic group compared to the open group (71.23% versus 63.16%; chi-squared P-value 0.001). However, when other factors were considered, there was no significant difference in the relative risk of a hypothermic episode between types of surgery. There were significant differences in the severity of hypothermia., Conclusion: Despite current measures to reduce the incidence, IPH remains a significant problem in colorectal surgery irrespective of the surgical approach. Further research is required to better characterize techniques that can reduce its incidence., (© 2022 Royal Australasian College of Surgeons.)

Introduction: The prevalence of increased pancreatic enzymes (elevated serum amylase and/or lipase) and its relationship to clinical outcomes in patients with coronavirus disease 2019 (COVID-19) infection is not known., Methods: A systematic review and meta-analysis of relevant studies reporting prevalence and impact of increased pancreatic enzymes (defined as an elevation in amylase and/or lipase levels above the upper limit of normal [ULN] value) in COVID-19 was undertaken., Results: A total of 36,496 patients from 21 studies were included for this meta-analysis. The overall prevalence and mortality for increased pancreatic enzymes (>ULN) in COVID-19 were 25.4% (95% CI, 15.8%-36.2%) and 34.6% (95% CI, 25.5%-44.4%), respectively. The overall prevalence and mortality for increased pancreatic enzymes (>3 × ULN) were 6.1% (95% CI, 3.6%-9.2%) and 39.2% (95% CI, 18.7%-61.6%), respectively. Patients with increased pancreatic enzymes, including elevated serum lipase or amylase of either type, had worse clinical outcomes, including need for ICU admission, mechanical ventilation and mortality., Discussion: Increased pancreatic enzymes is frequent and may exacerbate the consequences of COVID-19 infection., Competing Interests: Declaration of competing interest We declare no conflicts of interest., (Copyright © 2022 IAP and EPC. Published by Elsevier B.V. All rights reserved.)

Background: Current approaches to predicting intervention needs and mortality have reached 65-85% accuracy, which falls below clinical decision-making requirements in patients with acute pancreatitis (AP). We aimed to accurately predict therapeutic intervention needs and mortality on admission, in AP patients, using machine learning (ML)., Methods: Data were obtained from three databases of patients admitted with AP: one retrospective (Chengdu) and two prospective (Liverpool and Chengdu) databases. Intervention and mortality differences, as well as potential predictors, were investigated. Univariate analysis was conducted, followed by a random forest ML algorithm used in multivariate analysis, to identify predictors. The ML performance matrix was applied to evaluate the model's performance., Results: Three datasets of 2846 patients included 25 potential clinical predictors in the univariate analysis. The top ten identified predictors were obtained by ML models, for predicting interventions and mortality, from the training dataset. The prediction of interventions includes death in non-intervention patients, validated with high accuracy (96%/98%), the area under the receiver-operating-characteristic curve (0.90/0.98), and positive likelihood ratios (22.3/69.8), respectively. The post-test probabilities in the test set were 55.4% and 71.6%, respectively, which were considerably superior to existing prognostic scores. The ML model, for predicting mortality in intervention patients, performed better or equally with prognostic scores., Conclusions: ML, using admission clinical predictors, can accurately predict therapeutic interventions and mortality in patients with AP.

Background: The optimal analgesic strategy for patients with acute pancreatitis (AP) remains unknown., Objective: The present systematic review and meta-analysis aims to compare the efficacy of different analgesic modalities trialled in AP., Methods: A systematic search of PubMed, MEDLINE, EMBASE, CENTRAL, SCOPUS and Web of Science conducted up until June 2021, identified all randomised control trials (RCTs) comparing analgesic modalities in AP. A pooled analysis was undertaken of the improvement in pain scores as reported on visual analogue scale (VAS) on day 0, day 1 and day 2., Results: Twelve RCTs were identified including 542 patients. Seven trial drugs were compared: opiates, non-steroidal anti-inflammatories (NSAIDs), metamizole, local anaesthetic, epidural, paracetamol, and placebo. Across all modalities, the pooled VAS scores showed global improvement from baseline to day 2. Epidural analgesia appears to provide the greatest improvement in VAS within the first 24 h but is equivalent to opiates by 48 h. Within 24 h, NSAIDs offered similar pain-relief to opiates, while placebo also showed equivalence to other modalities but then plateaued. Local anaesthetics demonstrated least overall efficacy. VAS scores for opiate and non-opiate analgesics were comparable at baseline and day 1. The identified RCTs demonstrated significant statistical and methodological heterogeneity in pain-relief reporting., Conclusions: There is remarkable paucity of level 1 evidence to guide pain management in AP with small datasets per study. Epidural administration appears effective within the first 24 h of AP although infrequently used and featured in only a single RCT. NSAIDs are an effective opiate sparing alternative during the first 24 h., (© 2021. The Author(s) under exclusive licence to Société Internationale de Chirurgie.)

Background & Aims: Pain is the foremost complication to chronic pancreatitis (CP), but no validated questionnaires for assessment exist. The COMPAT questionnaire includes all relevant pain dimensions in CP, but a short form is needed to make it usable in clinical practice., Methods: The full COMPAT questionnaire was completed by 91 patients and systematically reduced to 6 questions. Pain severity and analgesic use were merged, leaving 5 pain dimensions. The pain dimension ratings were normalized to a 0-100 scale, and the weighted total score was calculated, where 3 dimensions were weighted double. Reliability of the short form was tested in a test-retest study in 76 patients, and concurrent validity tested against the Brief Pain Inventory and Izbicki pain questionnaire. Convergent validity was verified using confirmatory factor analysis, and criterion validity tested against quality-of-life and hospitalization rates., Results: The COMPAT-SF questionnaire consisted of the following pain dimensions: a) pain severity, b) pain pattern, c) factors provoking pain, d) widespread pain, and e) a qualitative pain-describing dimension. Quality of life correlated with the total score and all pain dimensions (P <.05). The total score, pain severity, pain pattern, and factors provoking pain were correlated with hospitalization rates (P <.05). The total score correlated with the Izbicki and Brief Pain Inventory scores (P <.0001). The reliability of the questionnaire in patients in a stable phase was good with an interclass correlation coefficient of 0.89., Conclusion: The COMPAT-SF questionnaire includes the most relevant aspects of pain in CP and is a feasible, reliable, and valid pain assessment instrument recommended to be used in future trials., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Objectives: Chronic pancreatitis (CP) is a fibroinflammatory disease complicated by episodes of acute inflammation (acute on chronic pancreatitis (ACP)). This entity is common, variably defined and can reflect different pathological mechanisms that requires different interventions. The aim of this study is to conduct a systematic review of how ACP is described, defined and diagnosed in the literature., Methods: A systematic search was conducted from January 1993 to June 2020. All articles that used a term to describe ACP in adults were reviewed and definitions and diagnostic criteria were sought., Results: After reviewing 2271 abstracts, 848 articles included a term to describe ACP. The most common descriptions were 'acute on/in CP' (374), 'acute exacerbation of CP' (345) and 'flare(-up) of CP' (43). Among the 848 articles, 14 included a pragmatic definition of ACP, and only 2 papers stated diagnostic criteria. These covered both acute inflammation and acute exacerbation of chronic abdominal pain., Conclusion: There is no universally accepted term, definition or diagnostic criteria for ACP. A consensus definition is needed to improve quality and comparability of future articles as well as clinical management.