Pulsed-field ablation: An alternative ablative method for gastric electrophysiological intervention.

Pulsed-field ablation (PFA) is an emerging ablative technology that has been used successfully to eliminate cardiac arrhythmias. As a non-thermal technique it has significant benefits over traditional radio-frequency 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%, 0.2­0.4 mg kg­1 min­1). 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, 1000 V amplitude). High-resolution electrical mapping defined baseline and post-ablation 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 post-ablation 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 radio-frequency ablation.

Balanced Solution versus Normal Saline in Predicted Severe Acute Pancreatitis: A Stepped Wedge Cluster Randomized Trial.

OBJECTIVE: To compare the effect of balanced multielectrolyte solutions(BMES) versus normal saline(NS) for intravenous fluid on chloride levels and clinical outcomes.in patients with predicted severe acute pancreatitis (pSAP). SUMMARY BACKGROUND DATA: Isotonic crystalloids are recommended for initial fluid therapy in acute pancreatitis, but whether the use of BMES in preference to NS confers clinical benefits is unknown. METHODS: In this multicenter, stepped-wedge, cluster-randomized trial, we enrolled patients with pSAP (APACHE II score ≥8 and C-reactive protein >150 mg/L) admitted within 72 hours of the advent of symptoms. The study sites were randomly assigned to staggered start dates for one-way crossover from the NS phase (NS for intravenous fluid) to the BMES phase(Sterofudin for intravenous fluid). The primary endpoint was the serum chloride concentration on trial day3. Secondary endpoints included a composite of clinical and laboratory measures. RESULTS: Overall, 259 patients were enrolled from eleven sites to receive NS(n=147) or BMES(n=112). On trial day3, the mean chloride level was significantly lower in patients who received BMES(101.8 mmol/L(SD4.8) versus 105.8 mmol/L(SD5.9), difference -4.3 mmol/L [95%CI -5.6 to -3.0 mmol/L];P<0.001). For secondary endpoints, patients who received BMES had less systemic inflammatory response syndrome(19/112,17.0% versus 43/147,29.3%, P=0.024) and increased organ failure-free days (3.9 d(SD2.7) versus 3.5days(SD2.7), P<0.001) by trial day7. They also spent more time alive and out of ICU(26.4 d(SD5.2) versus 25.0days(SD6.4), P=0.009) and hospital(19.8 d(SD6.1) versus16.3days(SD7.2), P<0.001) by trial day30. CONCLUSIONS: Among patients with pSAP, using BMES in preference to NS resulted in a significantly more physiological serum chloride level, which was associated with multiple clinical benefits(Trial registration number: ChiCTR2100044432).

Luminal Delivery of Pectin-Modified Oxygen Microbubbles Mitigates Rodent Experimental Intestinal Ischemia.

INTRODUCTION: Ischemic gut injury is common in the intensive care unit, impairs gut barrier function, and contributes to multiorgan dysfunction. One novel intervention to mitigate ischemic gut injury is the direct luminal delivery of oxygen microbubbles (OMB). Formulations of OMB can be modified to control the rate of oxygen delivery. This project examined whether luminal delivery of pectin-modified OMB (OMBp5) can reduce ischemic gut injury in a rodent model. METHODS: The OMBp5 formulation was adapted to improve delivery of oxygen along the length of small intestine. Adult Sprague-Dawley rats (n = 24) were randomly allocated to three groups: sham-surgery (SS), intestinal ischemia (II), and intestinal ischemia plus luminal delivery of OMBp5 (II + O). Ischemia-reperfusion injury was induced by superior mesenteric artery occlusion for 45 min followed by reperfusion for 30 min. Outcome data included macroscopic score of mucosal injury, the histological score of gut injury, and plasma biomarkers of intestinal injury. RESULTS: Macroscopic, microscopic data, and intestinal injury biomarker results demonstrated minimal intestinal damage in the SS group and constant damage in the II group. II + O group had a significantly improved macroscopic score throughout the gut mucosa (P = 0.04) than the II. The mean histological score of gut injury for the II + O group was significantly improved on the II group (P ≤ 0.01) in the proximal intestine only, within 30 cm of delivery. No differences were observed in plasma biomarkers of intestinal injury following OMBp5 treatment. CONCLUSIONS: This proof-of-concept study has demonstrated that luminal OMBp5 decreases ischemic injury to the proximal small intestine. There is a need to improve oxygen delivery over the full length of the intestine. These findings support further studies with clinically relevant end points, such as systemic inflammation and vital organ dysfunction.

Protocol for a national, multicentre study of post-endoscopy colorectal and upper gastrointestinal cancers: The POET study.

AIM: The primary aim of the study is to define the post-colonoscopy colorectal cancer (PCCRC) three-year rate and the post-endoscopy upper gastrointestinal cancer (PEUGIC) three-year rate across public hospitals in Aotearoa New Zealand. METHOD: This retrospective cohort study will be conducted via the trainee-led STRATA Collaborative network. All public hospitals in Aotearoa New Zealand will be eligible to participate. Data will be collected on all adult patients who are diagnosed with colorectal adenocarcinoma within 6 to 48 months of a colonoscopy and all adult patients diagnosed with gastroesophageal cancer within 6 to 48 months of an upper gastrointestinal endoscopy. The study period will be from 2010 to 2022. The primary outcome is the PCCRC 3-year rate and the PEUGIC 3-year rate. Secondary aims are to define and characterize survival after PCCRC or PEUGIC, the cause of PCCRC as based on the World Endoscopy Organization System of Analysis definitions, trends over time, and centre level variation. CONCLUSION: This protocol describes the methodology for a nationwide retrospective cohort study on PCCRC and PEUGIC in Aotearoa New Zealand. These data will lay the foundation for future studies and quality improvement initiatives.

Patient-reported use of pancreatic enzyme replacement treatment (PERT) in pancreatic cancer in New Zealand and Australia: a cross-sectional survey study.

PURPOSE: This study investigated pancreatic enzyme replacement therapy (PERT) use in people diagnosed with pancreatic cancer in New Zealand (NZ) and Australia (AU). METHODS: A cross-sectional survey study was conducted using a mixed-media campaign to recruit people with pancreatic cancer and collect information about current PERT use. The questionnaire gathered data on participant demographics, awareness of PERT, prescribing practices and efficacy of enzyme replacement. RESULTS: Over 300 people with pancreatic cancer were recruited, 135 from New Zealand and 199 from Australia. Every region, state and territory was represented except for the West Coast (NZ) and the Northern Territory (AU), the lowest populated areas in both countries. In New Zealand, 60% of participants had heard about PERT, compared to 69.3% in Australia. Dosing regimens were inconsistent in both countries, with 18% and 27% of participants being prescribed PERT considered best practice in New Zealand and Australia, respectively. Before PERT commencement, 70% of participants experienced symptoms of malabsorption, with all symptoms improving after therapy was established. The majority of participants were compliant with their medication. CONCLUSION: PERT use in pancreatic cancer in New Zealand and Australia was highly variable and not compliant with international guidelines in which PERT is recommended as standard therapy. Enzyme replacement is effective for improving the symptoms of malabsorption in patients with pancreatic cancer. Clinician education may be needed to help improve the use of PERT in people with pancreatic cancer.

Predicting pancreatic fistula after central pancreatectomy using current fistula risk scores for pancreaticoduodenectomy and distal pancreatectomy.

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.

Optimising the measurement of intra-bladder pressure in patients with predicted severe acute pancreatitis.

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.

Position statement on the definition, incidence, diagnosis and outcome of acute on chronic pancreatitis.

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.

Predicting Persistent Acute Respiratory Failure in Acute Pancreatitis: The Accuracy of Two Lung Injury Indices.

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.

The safety and efficacy of epidural anaesthesia in acute pancreatitis: a systematic review and meta-analysis.

BACKGROUND: Acute pancreatitis (AP) has variable clinical courses. This systematic review and meta-analysis aimed to determine the safety, efficacy, and impact of epidural anaesthesia (EA) use in AP. METHODS: The PubMed, EMBASE, SCOPUS and Cochrane library databases were systematically searched between 1980 and 2022 using the PRISMA guidelines, to identify observational and comparative studies reporting on EA in AP. The meta-analysis was performed in R Foundation for Statistical Computing using the meta R Package for Meta-Analysis. RESULTS: A total of 9 studies with 2006 patients of which 726 (36%) patients had EA were included. All studies demonstrated high safety and feasibility of EA in AP with no reported major local or neurological complications. One randomised controlled trial demonstrated an improvement in pain severity using a 0-10 visual analogue scale (VAS) at the outset (1.6 in EA vs 3.5 in non-EA, P = 0.02) and on day 10 (0.2 in EA vs 2.33 in non-EA, P = 0.034). There was also improvement in pancreatic perfusion with EA measured with computerised tomography 13 (43%) in EA vs 2 (7%) in non-EA, P = 0.003. The need for ventilatory support and overall mortality was lower in EA patients 40 (19%) vs 285 (24%) P = 0.025 (OR: 0.49, 95% CI: 0.28-0.84) and 16 (7%) vs 214 (20%), P = 0.050 (OR: 0.39, 95% CI: 0.15-1.00), respectively. CONCLUSION: EA is infrequently used for pain management in AP and yet the available evidence suggests that it is safe and effective in reducing pain severity, improving pancreatic perfusion, and decreasing mortality.

A core set of quality performance indicators for HPB procedures: a global consensus for hepatectomy, pancreatectomy, and complex biliary surgery.

BACKGROUND: Surgery for hepatopancreaticobiliary (HPB) conditions is performed worldwide. This investigation aimed to develop a set of globally accepted procedural quality performance indicators (QPI) for HPB surgical procedures. METHODS: A systematic literature review generated a dataset of published QPI for hepatectomy, pancreatectomy, complex biliary surgery and cholecystectomy. Using a modified Delphi process, three rounds were conducted with working groups composed of self-nominating members of the International Hepatopancreaticobiliary Association (IHPBA). The final set of QPI was circulated to the full membership of the IHPBA for review. RESULTS: Seven "core" indicators were agreed for hepatectomy, pancreatectomy, and complex biliary surgery (availability of specific services on site, a specialised surgical team with at least two certified HPB surgeons, a satisfactory institutional case volume, synoptic pathology reporting, undertaking of unplanned reintervention procedures within 90 days, the incidence of post-procedure bile leak and Clavien-Dindo grade ≥III complications and 90-day post-procedural mortality). Three further procedure specific QPI were proposed for pancreatectomy, six for hepatectomy and complex biliary surgery. Nine procedure-specific QPIs were proposed for cholecystectomy. The final set of proposed indicators were reviewed and approved by 102 IHPBA members from 34 countries. CONCLUSIONS: This work presents a core set of internationally agreed QPI for HPB surgery.

Development of the Comprehensive Pain Assessment Tool Short Form for Chronic Pancreatitis: Validity and Reliability Testing.

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.

The cisterna chyli: a systematic review of definition, prevalence, and anatomy.

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.

Vmeasur: A software package for experimental and clinical measurement of mesenteric lymphatic contractile function over an extended vessel length.

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.

Prevalence and prognosis of increased pancreatic enzymes in patients with COVID-19: A systematic review and meta-analysis.

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.

Optimising fluid requirements after initial resuscitation: A pilot study evaluating mini-fluid challenge and passive leg raising test in patients with predicted severe acute pancreatitis.

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.

Prodromal Signs and Symptoms of Chronic Pancreatitis: A Systematic Review.

GOAL: We aimed to extract the percent of signs and symptoms at the time of diagnosis from published studies and to pool these using meta-analytic techniques. BACKGROUND: Delayed or misdiagnosis of chronic pancreatitis may occur because the signs and symptoms are nonspecific and varied. STUDY: We performed a systematic review of studies reporting the signs and symptoms of chronic pancreatitis at diagnosis. The percentage of patients with each sign and symptom was extracted and random-effects meta-analyses used to calculate pooled percentages. RESULTS: In total, 22 observational studies were included. Across 14 studies, 55% of chronic pancreatitis patients were classified as having alcoholic etiology. Abdominal pain was the most common symptom (76%), and weight loss was reported in 22% of patients. Jaundice occurred in 11% of patients and steatorrhoea in 3%. Half of the patients had a history of acute pancreatitis, and 28% had diabetes mellitus at diagnosis. Heterogeneity between the studies was high for all signs and symptoms. CONCLUSIONS: This research has identified some common features of patients with chronic pancreatitis, but the high heterogeneity makes it difficult to draw solid conclusions. Carefully designed studies to examine the signs and symptoms leading up to a diagnosis of chronic pancreatitis, and common combinations, are required. These would enable the development of a tool to aid in the early identification of chronic pancreatitis in the primary care setting, with potential for improved short-term and long-term outcomes for patients.

Confusion with the definition and diagnostic criteria for acute on chronic pancreatitis: review and recommendations.

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.

Stress Hyperglycemia Is Independently Associated with Persistent Organ Failure in Acute Pancreatitis.

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.

Analgesia in the Initial Management of Acute Pancreatitis: A Systematic Review and Meta-Analysis of Randomised Controlled Trials.

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.