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.

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.

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.

Growth differentiation factor 15 is an early predictor for persistent organ failure and mortality in acute pancreatitis.

OBJECTIVES: Early prediction of persistent organ failure (POF) is crucial for patients with acute pancreatitis (AP). Growth differentiation factor 15 (GDF15), also known as macrophage inhibitory cytokine 1 (MIC-1), is associated with inflammatory responses. We investigated changes in plasma GDF15 and assessed its predictive value in AP. METHODS: The study included 290 consecutive patients with AP admitted within 36 h after symptoms onset. Clinical data obtained during hospitalization were collected. Plasma GDF15 levels were determined using enzyme-linked immunosorbent assays. The predictive value of GDF15 for POF was analyzed. RESULTS: There were 105 mild, 111 moderately severe, and 74 severe AP patients. Plasma GDF15 peak level were measured on admission, and significantly declined on the 3rd and 7th day. Admission GDF15 predicted POF and mortality with areas under the curve (AUC) of 0.847 (95% confidence interval [CI] 0.798-0.895) and 0.934 (95% CI 0.887-0.980), respectively. Admission GDF15, Bedside Index of Severity in Acute Pancreatitis, and hematocrit were independent factors for POF by univariate and multivariate logistic regression, and the nomogram built on these variables showed good performance (optimism-corrected c-statistic = 0.921). The combined predictive model increased the POF accuracy with an AUC 0.925 (95% CI 0.894-0.956), a net reclassification improvement of 0.3024 (95% CI: 0.1482-0.4565, P < 0.001), and an integrated discrimination index of 0.11 (95% CI 0.0497-0.1703; P < 0.001). CONCLUSIONS: Plasma GDF15 measured within 48 h of symptom onset could help predict POF and mortality in AP patients.

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.

Predicting persistent organ failure on admission in patients with acute pancreatitis: development and validation of a mobile nomogram.

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.

Acid suppression therapy, gastrointestinal bleeding and infection in acute pancreatitis - An international cohort study.

BACKGROUND: Acid suppressing drugs (ASD) are generally used in acute pancreatitis (AP); however, large cohorts are not available to understand their efficiency and safety. Therefore, our aims were to evaluate the association between the administration of ASDs, the outcome of AP, the frequency of gastrointestinal (GI) bleeding and GI infection in patients with AP. METHODS: We initiated an international survey and performed retrospective data analysis on AP patients hospitalized between January 2013 and December 2018. RESULTS: Data of 17,422 adult patients with AP were collected from 59 centers of 23 countries. We found that 23.3% of patients received ASDs before and 86.6% during the course of AP. ASDs were prescribed to 57.6% of patients at discharge. ASD administration was associated with more severe AP and higher mortality. GI bleeding was reported in 4.7% of patients, and it was associated with pancreatitis severity, mortality and ASD therapy. Stool culture test was performed in 6.3% of the patients with 28.4% positive results. Clostridium difficile was the cause of GI infection in 60.5% of cases. Among the patients with GI infections, 28.9% received ASDs, whereas 24.1% were without any acid suppression treatment. GI infection was associated with more severe pancreatitis and higher mortality. CONCLUSIONS: Although ASD therapy is widely used, it is unlikely to have beneficial effects either on the outcome of AP or on the prevention of GI bleeding during AP. Therefore, ASD therapy should be substantially decreased in the therapeutic management of AP.

Early Rapid Fluid Therapy Is Associated with Increased Rate of Noninvasive Positive-Pressure Ventilation in Hemoconcentrated Patients with Severe Acute Pancreatitis.

BACKGROUND/AIMS: Hematocrit is a widely used biomarker to guide early fluid therapy for patients with acute pancreatitis (AP), but there is controversy over whether early rapid fluid therapy (ERFT) should be used in hemoconcentrated patients. This study investigated the association of hematocrit and ERFT with clinical outcomes of patients with AP. METHODS: Data from prospectively maintained AP database and retrospectively collected fluid management details were stratified according to actual severity defined by revised Atlanta classification. Hemoconcentration and "early" were defined as hematocrit > 44% and the first 6 h of general ward admission, respectively, and "rapid" fluid rate was defined as ≥ 3 ml/kg/h. Patients were allocated into 4 groups for comparisons: group A, hematocrit ≤ 44% and fluid rate < 3 ml/kg/h; group B, hematocrit ≤ 44% and fluid rate ≥ 3 ml/kg/h; group C, hematocrit > 44% and fluid rate < 3 ml/kg/h; and group D, hematocrit > 44% and fluid rate ≥ 3 ml/kg/h. Primary outcome was rate of noninvasive positive-pressure ventilation (NPPV). RESULTS: A total of 912 consecutive AP patients were analyzed. ERFT has no impact on clinical outcomes of hemoconcentrated, non-severe or all non-hemoconcentrated AP patients. In hemoconcentrated patients with severe AP (SAP), ERFT was accompanied with increased risk of NPPV (odds ratio 5.96, 95% CI 1.57-22.6). Multivariate regression analyses confirmed ERFT and hemoconcentration were significantly and independently associated with persistent organ failure and mortality in patients with SAP. CONCLUSIONS: ERFT is associated with increased rate of NPPV in hemoconcentrated patients with SAP.

Exocrine Pancreatic Insufficiency Following Acute Pancreatitis: Systematic Review and Meta-Analysis.

BACKGROUND/OBJECTIVES: The epidemiology of exocrine pancreatic insufficiency (EPI) after acute pancreatitis (AP) is uncertain. We sought to determine the prevalence, progression, etiology and pancreatic enzyme replacement therapy (PERT) requirements for EPI during follow-up of AP by systematic review and meta-analysis. METHODS: Scopus, Medline and Embase were searched for prospective observational studies or randomized clinical trials (RCTs) of PERT reporting EPI during the first admission (between the start of oral refeeding and before discharge) or follow-up (≥ 1 month of discharge) for AP in adults. EPI was diagnosed by direct and/or indirect laboratory exocrine pancreatic function tests. RESULTS: Quantitative data were analyzed from 370 patients studied during admission (10 studies) and 1795 patients during follow-up (39 studies). The pooled prevalence of EPI during admission was 62% (95% confidence interval: 39-82%), decreasing significantly during follow-up to 35% (27-43%; risk difference: - 0.34, - 0.53 to - 0.14). There was a two-fold increase in the prevalence of EPI with severe compared with mild AP, and it was higher in patients with pancreatic necrosis and those with an alcohol etiology. The prevalence decreased during recovery, but persisted in a third of patients. There was no statistically significant difference between EPI and new-onset pre-diabetes/diabetes (risk difference: 0.8, 0.7-1.1, P = 0.33) in studies reporting both. Sensitivity analysis showed fecal elastase-1 assay detected significantly fewer patients with EPI than other tests. CONCLUSIONS: The prevalence of EPI during admission and follow-up is substantial in patients with a first attack of AP. Unanswered questions remain about the way this is managed, and further RCTs are indicated.

Hypertriglyceridaemia-associated acute pancreatitis: diagnosis and impact on severity.

BACKGROUND: The level of hypertriglyceridaemia (HTG) at which the risk of acute pancreatitis (AP) increases and the impact of HTG on AP attributable to other aetiologies remains unclear. METHODS: We compared clinical outcomes of patients admitted within 48 h of the onset of abdominal pain from a first episode of AP and admission serum triglyceride levels of either <5.65 mmol/l (<500 mg/dl) or ≥5.65 to <11.3 mmol/l (moderate HTG) or ≥11.3 mmol/l (≥1000 mg/dl, severe HTG). RESULTS: Among a cohort of 1,233 patients with AP there were significant progressive increases in all major deleterious clinical outcomes including mortality (all Ptrend < 0.05) that were directly dependent on admission triglyceride levels. Outcomes were improved by earlier presentation (<24 h compared to 24-48 h from abdominal pain onset). Patients with severe HTG and a concomitant aetiology (n = 68) had significantly more persistent organ failure, pancreatic necrosis and longer hospital stays (P < 0.05) than those with severe HTG alone (n = 206). CONCLUSIONS: There appears to be an association between HTG grade and the severity of AP. Severe HTG significantly increased the severity of AP, over AP attributable to other aetiologies. Moderate as well as severe HTG can be used as a criterion for the diagnosis of HTG-associated AP.

Response and outcome from fluid resuscitation in acute pancreatitis: a prospective cohort study.

BACKGROUND: Intravenous (IV) fluid resuscitation remains the cornerstone for early management of acute pancreatitis (AP), but many questions remain unanswered, including how to determine whether patients will benefit from additional fluids. The aim was to investigate the utility of serum biomarkers of responsiveness IV fluid resuscitation in patients with AP and systemic inflammatory response syndrome (SIRS). METHODS: Eligible adult patients had abdominal pain for <36 h and ≥2 SIRS criteria. Mean arterial pressure (>65 mmHg) and urine output (>0.5 ml/kg/h) were used to assess responsiveness at 2 and 6-8 h after initiation of IV fluids. Comparison was made between responsive and refractory patients at time points for fluid volume, biomarkers and outcomes. RESULTS: At 2 h 19 patients responded to fluids (Group 1) while 4 were refractory (Group 2); at 6-8 h 14 responded (Group 3) and 9 were refractory (Group 4). No demographic differences between patient groups, but Group 4 had worse prognostic features than Group 3. Refractory patients received significantly more fluid (Group 4 mean 7082 ml vs. Group 3 5022 mL, P < 0.001) in first 24 h and had worse outcome. No significant differences in biomarkers between the groups. CONCLUSIONS: The serum biomarkers did not discriminate between fluid responsive and refractory patients. Refractory patients at 6-8 h had more severe disease on admission, did not benefit from additional fluids and had a worse outcome. New approaches to guide fluid resuscitation in patients with AP are required.

Continuous regional arterial infusion for the treatment of severe acute pancreatitis: a meta-analysis.

BACKGROUND: Continuous regional arterial infusion (CRAI) is a drug delivery system, which dramatically increases the drug concentration in the pancreas. Previous clinical and basic studies have demonstrated the possible therapeutic efficacy of CRAI for severe acute pancreatitis (SAP). This meta-analysis of all published randomized controlled trials (RCTs) was conducted to assess the efficacy and safety of CRAI for the treatment of SAP. DATA SOURCES: Up to August 10, 2014, RCTs comparing CRAI with intravenous infusion for SAP in PubMed, Embase, EBSCO, MEDLINE, Science Citation Index Expanded, Cochrane Library, China Academic Journals Full-Text Database, Chinese Biomedical Literature Database, and Chinese Scientific Journals Database were selected by two independent reviewers. The relative risk (RR) and their 95% confidence intervals (CI) for duration of elevated serum amylase and urine amylase, duration of abdominal pain, infection rate, incidence of complication, overall mortality, curative rate, hospital stay and details of subgroup analysis were extracted. Meta-analyses were made using the software Review Manager (RevMan version 5.10). RESULTS: Six RCTs with 390 patients meeting the inclusion criteria were included in the final analysis. Compared with intravenous infusion route, CRAI significantly shortened the duration of elevated urine amylase (MD=-2.40, 95% CI=-3.20, -1.60; P<0.00001) and the duration of abdominal pain (MD=-1.46, 95% CI=-1.94, -0.98; P<0.00001), decreased the incidence of complication (RR=0.35, 95% CI=0.15, 0.81; P=0.01) and overall mortality (RR=0.25, 95% CI=0.08, 0.78; P=0.02), shortened the duration of hospital stay (MD=-10.36, 95% CI=-17.05, -3.68; P=0.002), and increased the curative rate (RR=1.66, 95% CI=1.13, 2.46; P=0.01). No mortality and catheter-related infections due to CRAI administration was reported in these studies. Subgroup analysis showed that the combination of drug administration via CRAI did not significantly improve the outcomes. CONCLUSION: CRAI is effective for the treatment of SAP, and the combination of drug administration via CRAI did not have a significant effect on the improvement of the outcomes.

Chaiqinchengqi decoction regulates necrosis-apoptosis via regulating the release of mitochondrial cytochrome c and caspase-3 in rats with acute necrotizing pancreatitis.

OBJECTIVE: To explore the effect and the mechanism of Chaiqinchengqi decoction (CQCQD) on the apoptosis-necrosis switch of pancreatic acinar cells in acute necrotizing pancreatitis (ANP) in rats. METHODS: Sixty Sprague-Dawley rats were randomized into the control group, the ANP group and the CQCQD group. The acute pancreatitis (AP) model was induced by intraperitoneal injections of 4 g/kg 8% L-Arginine (PH 7.0) twice with a 1 h interval. Rats in the CQCQD group were intragastrically administered CQCQD (20 mL/kg every 2 h, 3 times, then 20 mL/kg every 6 h, 3 times). Rats were killed at the 6 and 24 h after the induction of AP. The pancreatic tissues were collected for pathology and to isolate pancreatic acinar cells and mitochondria. RESULTS: CQCQD significantly ameliorated the severity of ANP by reducing the pancreatic histopathology score, indicated by lactate dehydrogenase levels at the 6 and 24 h. The CQCQD group promoted the apoptosis of pancreatic acinar cells by raising the apoptosis index compared with the ANP group and the control group. Mitochondrial cytochrome c at the 6 and 24 h in the ANP group were lower than that in the control group or the CQCQD group (0.67 +/- 0.13 vs 1.54 +/- 0.03 vs 0.81 +/- 0.09; 0.71 +/- 0.08 vs 1.55 +/- 0.09 vs 0.89 +/- 0.16, P < 0.01). The cytochrome c levels in the cytoplasm at the 6 and 2 h in the CQCQD group were higher than in the control group (1.36 +/- 0.15 vs 0.67 +/- 0.04, 1.46 +/- 0.08 vs 0.59 +/- 0.09, P < 0.01), or the ANP group (0.96 +/- 0.13, P > 0.05; 0.97 +/- 0.09, P < 0.05). CQCQD increased caspase-3 activity over the ANP group at the 6 h. CONCLUSION: CQCQD can induce apoptosis and relieve the necrosis of pancreatic acinar cells via promoting the release of mitochondrial cytochrome c and increasing pancreatic caspase-3 activity in ANP rats.

Invariant feature based label correction for DNN when Learning with Noisy Labels.

Learning with Noisy Labels (LNL) methods have been widely studied in recent years, which aims to improve the performance of Deep Neural Networks (DNNs) when the training dataset contains incorrectly annotated labels. Popular existing LNL methods rely on semantic features extracted by the DNN to detect and mitigate label noise. However, these extracted features are often spurious and contain unstable correlations with the label across different environments (domains), which can occasionally lead to incorrect prediction and compromise the efficacy of LNL methods. To mitigate this insufficiency, we propose Invariant Feature based Label Correction (IFLC), which reduces spurious features and accurately utilizes the learned invariant features that contain stable correlation to correct label noise. To the best of our knowledge, this is the first attempt to mitigate the issue of spurious features for LNL methods. IFLC consists of two critical processes: The Label Disturbing (LD) process and the Representation Decorrelation (RD) process. The LD process aims to encourage DNN to attain stable performance across different environments, thus reducing the captured spurious features. The RD process strengthens independence between each dimension of the representation vector, thus enabling accurate utilization of the learned invariant features for label correction. We then utilize robust linear regression for the feature representation to conduct label correction. We evaluated the effectiveness of our proposed method and compared it with state-of-the-art (sota) LNL methods on four benchmark datasets, CIFAR-10, CIFAR-100, Animal-10N, and Clothing1M. The experimental results show that our proposed method achieved comparable or even better performance than the existing sota methods. The source codes are available at https://github.com/yangbo1973/IFLC.

[Hot issues on the treatment of severe acute pancreatitis by Integrated Traditional Chinese and Western Medicine].

Severe acute pancreatitis (SAP) is recognized as critical refractory disease. The case fatality rate of SAP is as high as 36%-50%. Although significant progress has been achieved on the treatment of severe acute pancreatitis (SAP) by Integrated Traditional Chinese Medicine (TCM) and Western Medicine (WM), there still exist some difficulties hindering the further improvement of therapeutic efficacy. The hot issues includes: unconfirmative curative effects and diverse treatment principles, complicated predictive scoring systems and inaccurate markers for the severity stratification, unproved new therapeutic tools and controversial methods waiting more high qualified evidence, unclarified mechanism of Integrated TCM and WM. In order to overcome the difficulties, we aim to launch the clinical pathway of Integrated TCM and WM, to strengthen the unity of multidisciplinary cooperation. We also need to keep the efforts on screening the markers for early evaluation and prediction of disease severity, improving the diagnosis and treatment, exploring the mechanism of Traditional Chinese Medicine in treating SAP with more high quality basic and clinical research. Based on these efforts, we could provide better treatments and prognosis for SAP patients.

A predictive model for residual lesions after LEEP surgery in CIN III patients.

Background and aims: The residual lesions after Loop Electrosurgical Excision Procedure (LEEP) contributes to poor prognosis in patients with Cervical Intraepithelial Neoplasia Grade 3 (CIN3). The aim of this study is to establish an effective clinical predictive model for residual lesions in CIN3 patients after LEEP. Methods: A retrospective analysis was performed on 436 CIN3 patients who underwent total hysterectomy within 3 months after LEEP. Based on the post-hysterectomy pathologic, the patients were divided into the no residual group and residual group. Clinical parameters were compared between the two groups, and univariate and multivariate logistic regression analyses were conducted to identify independent risk factors for residual lesions in CIN3 patients after LEEP. Using R software, a nomogram model was established and its effectiveness was evaluated using calibration plots. Results: There were 178 cases in the residual group and 258 cases in the no residual group. The two groups had no significant difference in general characteristics (p > 0.05). It was found that Post-LEEP follow-up HPV, Post-LEEP follow-up TCT, and the Gland involvement were independent risk factors for residual lesions in CIN3 patients after LEEP (all p < 0.05). The consistency index (C-index) of the nomogram model for predicting residual lesions was 0.975 (0.962-0.988). Conclusion: The Post-LEEP follow-up HPV, Post-LEEP follow-up TCT, and Gland involvement are independent risk factors related to residual tissue after LEEP surgery in CIN3 patients. The constructed nomogram can effectively predict the presence of residual tissue after LEEP surgery in CIN3 patients and has good practical value.

Deep Learning Models for Severity Prediction of Acute Pancreatitis in the Early Phase From Abdominal Nonenhanced Computed Tomography Images.

OBJECTIVES: To develop and validate deep learning (DL) models for predicting the severity of acute pancreatitis (AP) by using abdominal nonenhanced computed tomography (CT) images. METHODS: The study included 978 AP patients admitted within 72 hours after onset and performed abdominal CT on admission. The image DL model was built by the convolutional neural networks. The combined model was developed by integrating CT images and clinical markers. The performance of the models was evaluated by using the area under the receiver operating characteristic curve. RESULTS: The clinical, Image DL, and the combined DL models were developed in 783 AP patients and validated in 195 AP patients. The combined models possessed the predictive accuracy of 90.0%, 32.4%, and 74.2% for mild, moderately severe, and severe AP. The combined DL model outperformed clinical and image DL models with 0.820 (95% confidence interval, 0.759-0.871), the sensitivity of 84.76% and the specificity of 66.67% for predicting mild AP and the area under the receiver operating characteristic curve of 0.920 (95% confidence interval, 0.873-0.954), the sensitivity of 90.32%, and the specificity of 82.93% for predicting severe AP. CONCLUSIONS: The DL technology allows nonenhanced CT images as a novel tool for predicting the severity of AP.

What should be measured and reported in clinical trials for the treatment of patients with acute pancreatitis? A study protocol for establishing a core outcome set.

INTRODUCTION: Acute pancreatitis (AP) is characterised by inflammation of the exocrine pancreas, which potentially leads to local complications and organ failure resulting in significant morbidity and mortality. A long-term follow-up by an experienced team is needed. Currently, a variety of outcome measures are used in clinical trials for patients with AP. However, due to heterogeneous and selective outcome reporting across trials of interventions, it is hard to combine or compare the trial results compromising systematic evaluations of effectiveness and safety. A core outcome set is demanded to standardise reporting for the management of AP in clinical trials, so as to conduct systematic reviews and to improve the quality of the existing evidence base on the management of AP. We designed a study to establish a core outcome set (COS) on what indicators should be measured and reported in clinical trials of patients with AP (COS-AP). METHODS AND ANALYSIS: This study protocol outlines the following five phases: Phase I will be a systematic review of randomised control trials and semistructured interviews with patients to initially establish a preliminary list of potential outcomes. Phase II will be the recruitment of key stakeholders' groups comprising experts in pancreatic disease, clinical researchers, methodologists, journal editors and patients. Phase III will be two rounds of the Delphi surveys with key stakeholder groups. Phase IV will be a consensus on the outcomes that should be included in a final COS-AP. Phase V will be dissemination of COS-AP. ETHICS AND DISSEMINATION: Ethical approval for this study was obtained from the Biomedical Research Ethics Committee (BREC) of West China Hospital of Sichuan University (2020 No.691). The findings will be disseminated in peer-reviewed journals and meetings. TRIAL REGISTRATION: This study was registered with Core Outcome Measures in Effectiveness Trials (COMET) database as study 2573.

Extracellular histones cause intestinal epithelium injury and disrupt its barrier function in vitro and in vivo.

Extracellular histones are cytotoxic to various cells and have been extensively proven a vital mediator of multiple organ injuries. However, the effect of extracellular histones on the intestine remains largely unknown. This study aimed to clarify the effect of extracellular histones on the intestine. IEC-6, a cell line of rat small intestinal epithelial crypt, and C57BL/6 or ICR mice were treated with histones. The IEC-6 cells treated with histones from 20 µg/mL to 200 µg/mL for 0-24 h displayed a decline of cell viability and an increase of cell death in a concentration- and time-dependent manner. Moreover, histones (100 µg/mL) induced IEC-6 apoptosis through activating caspase 3 and necroptosis through up-regulation of receptor-interacting serine/threonine protein kinase 1 and 3 (RIPK1 and RIPK3), phosphorylated mixed-lineage kinase domain-like protein (p-MLKL) along with the decrease of caspase-8. Histones treatment disturbed zonular occludens 1 (ZO-1) expression and increased permeability of IEC-6 cell monolayer. In vivo, histones 50 mg/kg injection caused mice intestinal edema, loss apex of villus, epithelial lifting down the sides of the villi, and increased neutrophil infiltration. Elevation of serum intestinal fatty acid binding protein (I-FABP), d-lactate, or Diamine oxidase (DAO) and loss of tight junction protein, ZO-1, at 3 h and 6 h after histones injection strongly indicated severe intestinal epithelium injury, which led to increased permeability of the intestine. In conclusion, extracellular histones cause intestinal epithelial damage via direct cytotoxicity. Consequently, intestinal epithelial tight junction and barrier integrity are disrupted, which may play pivotal roles in diverse diseases.