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Background Methods Results Conclusion Infected pancreatic necrosis (IPN) is a major determinant of mortality in acute pancreatitis (AP). Non‐invasive diagnosis of IPN could guide the intervention in AP. We aimed to investigate the role of non‐invasive methods like diffusion weighted magnetic resonance imaging (DW‐MRI) and clinico‐laboratory parameters as predictors of IPN.Prospective evaluation for predictors of IPN by diffusion restriction (DR) on DW‐MRI and clinico‐laboratory parameters was performed.Out of 39 patients included, 31 were analysed after exclusion. Twenty‐six (83.8%) patients had moderately severe AP, and the rest had severe disease. They were categorized into Group A: patients with documented infection after intervention (n = 17) and Group B: successfully managed without intervention or negative culture after intervention (n = 14). On univariate analysis, Group A had significantly more incidence of fever (P = 0.020), persistent unwellness (P = 0.003), elevated neutrophil count (P = 0.007), lymphocyte count (P = 0.007), neutrophil lymphocyte ratio (NLR) (P = 0.028), DR on DW‐MRI (P = 0.001) and low apparent diffusion coefficient (ADC) (P = 0.086). Multivariate analysis revealed DR on DW‐MRI (P = 0.004) and NLR (P = 0.035) as significant predictors of IPN, among other factors. The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of DW‐MRI were 94.1%, 78.6%, 91.66%, and 84.21%, respectively. The area under curve of NLR on the ROC plot was 0.85 and the best cutoff was >3.5, with sensitivity, specificity, PPV, and NPV of 70.6%, 78.6%, 80%, and 68.7% respectively.DW‐MRI and NLR are promising non‐invasive tools for accurate prediction of IPN and hence can guide the need for intervention in acute pancreatitis. [ABSTRACT FROM AUTHOR]

Zhiyang Wu,1,* Wenjun Lu,2,* Xin Zhang,1 Qiaoying Xia,2 Han Zuo,2 Xi Guo,1 Yu Liu,1 Fan Zhang,3 Xin Zhang,4 Luyao Zhang2 1Department of Critical Care Medicine, Qilu Hospital (Qingdao), Cheeloo College of Medicine, Shandong University, Qingdao, Shandong, People’s Republic of China; 2Department of Pathology and Pathophysiology, School of Medicine, Nanjing University of Chinese Medicine, Nanjing, Jiangsu, People’s Republic of China; 3Department of Critical Care Medicine, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Qingdao, Shandong, People’s Republic of China; 4Department of General Surgery, Qilu Hospital (Qingdao), Cheeloo College of Medicine, Shandong University, Qingdao, Shandong, People’s Republic of China*These authors contributed equally to this workCorrespondence: Luyao Zhang, Department of Pathology and Pathophysiology, School of Medicine, Nanjing University of Chinese Medicine, Nanjing, Jiangsu, People’s Republic of China, Email zhangluyao@njucm.edu.cn Xin Zhang, Department of General Surgery, Qilu Hospital (Qingdao), Cheeloo College of Medicine, Shandong University, Qingdao, Shandong, People’s Republic of China, Email 514557061@qq.comPurpose: Protectin D1 (PD1), a biologically active molecule derived from docosahexaenoic acid (DHA), plays a major role in the body’s endogenous lipid-mediated inflammatory response. The study aims to explore the relationship between PD1, inflammatory response and the severity of acute pancreatitis (AP).Patients and Methods: Sixty consecutive AP patients within 72h of disease onset were enrolled as the study group, a further thirty healthy people were enrolled as the control group. General demographics collected at the time of enrollment. Serum PD1, Citrullinated Histone 3 (CitH3), myeloperoxidase-Deoxyribonucleic acid (MPO-DNA), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) level were measured in AP patients on enrollment day 0, day 1, day 3 and day 7. Meanwhile, the Acute Physiology and Chronic Health evaluation II (APACHE II) scores, Sequential Organ Failure Assessment (SOFA) scores were also evaluated on day 0, day 1, day 3 and day 7.Results: AP was severe in 29 patients (48.3%), moderately severe acute pancreatitis (MSAP) was found in 9 patients (15%), and mild acute pancreatitis (MAP) was found in 22 patients (36.7%). The level of PD1, CitH3 and MPO-DNA were statistically significantly higher in AP patients than in the healthy population. Serum PD1, CitH3 and MPO-DNA concentration increased with AP severity. In AP patients, PD1 has a strong linear association with TNF-α, CitH3 and MPO-DNA. The AUC for SAP predicted by PD1 was 0.938. The calculated cut-off point for prognosis SAP is 7.94 pg/mL. The AUC for infected pancreatic necrosis (IPN) predicted by PD1 was 0.836 and the cut-off point was 8.65 pg/mL. The AUC for organ failure (OF) predicted by PD1 was 0.719 and the cut-off point was 7.94 pg/mL.Conclusion: PD1 is associated with both the presence of AP and the severity of pancreatitis.Keywords: PD1, acute pancreatitis, CitH3, MPO-DNA, infected pancreatic necrosis, organ failure

Rui Bai,1,2 Yuhang Sui,1,2 Tianqi Lu,1,2 Hua Chen,1,2 Gang Wang,1,2 Rui Kong,1,2 Hongtao Tan,1,2 Yongwei Wang,1,2 Guanqun Li,1,2 Bei Sun1,2 1Department of Pancreatic and Biliary Surgery, The First Affiliated Hospital of Harbin Medical University, Harbin, 150001, People’s Republic of China; 2Key Laboratory of Hepatosplenic Surgery, Ministry of Education, The First Affiliated Hospital of Harbin Medical University, Harbin, 150001, People’s Republic of ChinaCorrespondence: Guanqun Li; Bei Sun, Department of Pancreatic and Biliary Surgery, The First Affiliated Hospital of Harbin Medical University, No. 23 Youzheng Street, Nangang District, Harbin, 150001, People’s Republic of China, Email liguanqun@hrbmu.edu.cn; sunbei70@hrbmu.edu.cnPurpose: The effects of the step-jump approach on the survival and prognosis of infected pancreatic necrosis (IPN) patients have not yet been determined.Patients and Methods: Between November 2018 and June 2023, 188 patients were included in this study. There were 144 patients in the step-up group (the SU group) and 44 in the step-jump group (the SJ group). In the SU group, patients successfully treated with percutaneous catheter drainage (PCD) alone were classified into the SU-1 group (n=101), while those requiring additional surgery after PCD were categorized into the SU-2 group (n=43). In the SJ group, patients who underwent minimally invasive necrosectomy (MIN) without PCD were assigned to the SJ-1 group (n=34), whereas those who initially underwent PCD followed by immediate open surgery were placed in the SJ-2 group (n=10). Propensity score matching (PSM) was used to mitigate bias.Results: After PSM, a total of 34 pairs were successfully matched. A comparison of the SU group with the SJ-1 group (upfront MIN without PCD) revealed similar mortality rates (P=0.239); however, the incidences of multiple drug-resistant organisms (MDROs) (P=0.029) and surgical complications (P< 0.001) were significantly lower in the SJ-1 group. After comparing the SU-2 and SJ-2 groups (patients who underwent direct open necrosectomy without MIN after PCD failure), the incidences of surgical complications and MDRO in the SJ-2 group were significantly lower (P< 0.05).Conclusion: Compared with the step-up approach, the step-jump approach is safer and more effective and can significantly reduce the incidence of MDRO and surgical complications.Keywords: infected pancreatic necrosis, step-up approach, step-jump approach, propensity score match

Background: While selective use of antibiotics for infected pancreatic necrosis (IPN) in acute pancreatitis (AP) is recommended, studies indicate a high rate of inadequate treatment. Methods: A search of PubMed, Scopus, and Cochrane databases was conducted, focusing on primary research and meta-analyses. Data were categorized based on core concepts, and a narrative synthesis was performed. Results: The search identified a total of 1016 publications. After evaluating 203 full texts and additional sources from the grey literature, 80 studies were included in the review. The answers obtained were: (1) Preventive treatment does not decrease the incidence of IPN or mortality. Given the risks of bacterial resistance and fungal infections, antibiotics should be reserved for highly suspected or confirmed IPN; (2) The diagnosis of IPN does not always require microbiological samples, as clinical suspicion or computed tomography signs can suffice. Early diagnosis and treatment may be improved by using biomarkers such as procalcitonin and novel microbiological methods; (3) When indicated, early initiation of antibiotics is a key determinant in reducing mortality associated with IPN; (4) Antibiotics with good penetration into pancreatic tissue covering Gram-negative and Gram-positive bacteria should be used. Routine antifungal therapy is not recommended; (5) The step-up approach, including antibiotics, is the standard for IPN management; (6) Antibiotic duration should be kept to a minimum and should be based on the quality of source control and patient condition. Conclusions: Early antibiotic therapy is essential for the treatment of IPN, but prophylactic antibiotics are not recommended in AP. High-quality randomized controlled trials are required to better understand the role of antibiotics and antifungals in AP management. [ABSTRACT FROM AUTHOR]

Objectives: As a serious complication of moderately severe acute pancreatitis (MSAP) and severe acute pancreatitis (SAP), infected pancreatic necrosis (IPN) can lead to a prolonged course of interventional therapy. Most predictive models designed to identify such patients are complex or lack validation. The aim of this study was to develop a predictive model for the early detection of IPN in MSAP and SAP. Methods: A total of 594 patients with MSAP or SAP were included in the study. To reduce dimensionality, least absolute shrinkage and selection operator regression analysis was used to screen potential predictive variables, a nomogram was then constructed using logistic regression analysis. The receiver operating characteristic (ROC) curve, calibration curve, and decision curve analysis (DCA) were used to evaluate the discrimination, accuracy, and clinical efficacy of the model. External data were also obtained to further validate the constructed model. Results: There were 476, 118, and 82 patients in the training, internal validation, and external validation cohorts, respectively. Platelet count, hematocrit, albumin/globulin, severity of acute pancreatitis, and modified computed tomography severity index score were independent factors for predicting IPN in MSAP and SAP. The area under the ROC curves were 0.923, 0.940, and 0.817, respectively, in the three groups. There was a good consistency between the actual probabilities and the predicted probabilities. DCA revealed excellent clinical utility. Conclusion: The constructed nomogram is a simple and feasible model that has good clinical predictive value and efficacy in clinical decision‐making for IPN in MSAP and SAP. [ABSTRACT FROM AUTHOR]

BackgroundSurgical pancreatic necrosectomy (SPN) is an option for the management of infected pancreatic necrosis. The literature indicates that an escalating, combined endoscopic, interventional radiology and minimally invasive surgery "step-up" approach, such as video-assisted retroperitoneal debridement, may reduce the number of required SPNs and ICU complications, such as multiple organ failure. We hypothesized that complications for surgically treated severe necrotizing pancreatitis patients decreased during the period of adoption of the "step-up" approach.MethodsThe American college of surgeons national surgery quality improvement program database (ACS-NSQIP) was used to find SPN cases from 2007 to 2019 in ACS-NSQIP submitting hospitals. Mortality and Clavien-Dindo class 4 (CD4) ICU complications were collected. Predictors of outcomes were identified by univariate and multivariate analyses.ResultsThere were 2457 SPN cases. SPN cases decreased from 0.09% in 2007 to 0.01% in 2019 of NSQIP operative cases (p

Abstract Objective Infectious pancreatic necrosis (IPN) is a serious complication of acute pancreatitis, and early recognition and timely intervention are the keys to improving clinical outcomes. The purpose of this study was to investigate the predictive capacity of the neutrophil CD64 index (nCD64 index) on IPN in patients with acute pancreatitis Methods This study comprises two independent cohorts: the training cohort consisted of 202 patients from Hunan Provincial People's Hospital, and the validation cohort consisted of 100 patients from Changsha Central Hospital. Peripheral blood samples were collected on the day of admission and on the 3rd, 5th, 7th, and 10th days of hospitalization, and the nCD64 index was detected by flow cytometry. Additionally, relevant clinical characteristics and laboratory biomarkers were collected and analyzed. Results We observed that nCD64 index on admission was significantly higher in the IPN group than Non-IPN group (p

Background: Infected pancreatic necrosis (IPN) is a severe complication of acute pancreatitis, with mortality rates ranging from 15 to 35%. However, limited studies exist to predict the survival of IPN patients and nomogram has never been built. This study aimed to identify predictors of mortality, estimate conditional survival (CS), and develop a CS nomogram and logistic regression nomogram for real-time prediction of survival in IPN patients. Methods: A prospective cohort study was performed in 335 IPN patients consecutively enrolled at a large Chinese tertiary hospital from January 2011 to December 2022. The random survival forest method was first employed to identify the most significant predictors and capture clinically relevant nonlinear threshold effects. Instantaneous death risk and CS was first utilized to reveal the dynamic changes in the survival of IPN patients. A Cox model-based nomogram incorporating CS and a logistic regression-based nomogram were first developed and internally validated with a bootstrap method. Results: The random survival forest model identified seven foremost predictors of mortality, including the number of organ failures, duration of organ failure, age, time from onset to first intervention, hemorrhage, bloodstream infection, and severity classification. Duration of organ failure and time from onset to first intervention showed distinct thresholds and nonlinear relationships with mortality. Instantaneous death risk reduced progressively within the first 30 days, and CS analysis indicated gradual improvement in real-time survival since diagnosis, with 90-day survival rates gradually increasing from 0.778 to 0.838, 0.881, 0.974, and 0.992 after surviving 15, 30, 45, 60, and 75 days, respectively. After further variables selection using step regression, five predictors (age, number of organ failures, hemorrhage, time from onset to first intervention, and bloodstream infection) were utilized to construct both the CS nomogram and logistic regression nomogram, both of which demonstrated excellent performance with 1000 bootstrap. Conclusion: Number of organ failures, duration of organ failure, age, time from onset to first intervention, hemorrhage, bloodstream infection, and severity classification were the most crucial predictors of mortality of IPN patients. The CS nomogram and logistic regression nomogram constructed by these predictors could help clinicians to predict real-time survival and optimize clinical decisions. [ABSTRACT FROM AUTHOR]

Hypertriglyceridemia is a common cause of acute pancreatitis. Pregnant women are at risk of developing hypertriglyceridemia-induced acute pancreatitis (HTG-AP); however, whether pregnancy increases the risk of infected pancreatic necrosis (IPN) is unknown. We aimed to assess the association between pregnancy and IPN. This 10-year retrospective cohort study was conducted at Jinling Hospital. Adult female patients of childbearing age with HTG-AP between January 2013 and September 2022 were screened. Logistic regression analyses were performed to assess the risk factors for IPN. Patients admitted within 7 days were assigned to the training and validation sets to develop a dynamic nomogram for IPN prediction. 489 patients were included, and 144 developed IPN. Logistic regression analyses revealed pregnancy (OR: 2.578 95% CI: 1.474–4.510) as an independent risk factor for IPN. Gestation weeks, ARDS, albumin level, and serum creatinine level were selected as the predictors of the dynamic nomogram for IPN prediction, with good discrimination in the training set (AUC 0.867 95% CI: 0.794–0.940) and validation set (AUC 0.957 95% CI: 0.885–1.000). Pregnancy increases the risk of IPN in adult patients of childbearing age with HTG-AP, and the dynamic nomogram may help risk stratification for IPN. [ABSTRACT FROM AUTHOR]

Background: While selective use of antibiotics for infected pancreatic necrosis (IPN) in acute pancreatitis (AP) is recommended, studies indicate a high rate of inadequate treatment. Methods: A search of PubMed, Scopus, and Cochrane databases was conducted, focusing on primary research and meta-analyses. Data were categorized based on core concepts, and a narrative synthesis was performed. Results: The search identified a total of 1016 publications. After evaluating 203 full texts and additional sources from the grey literature, 80 studies were included in the review. The answers obtained were: (1) Preventive treatment does not decrease the incidence of IPN or mortality. Given the risks of bacterial resistance and fungal infections, antibiotics should be reserved for highly suspected or confirmed IPN; (2) The diagnosis of IPN does not always require microbiological samples, as clinical suspicion or computed tomography signs can suffice. Early diagnosis and treatment may be improved by using biomarkers such as procalcitonin and novel microbiological methods; (3) When indicated, early initiation of antibiotics is a key determinant in reducing mortality associated with IPN; (4) Antibiotics with good penetration into pancreatic tissue covering Gram-negative and Gram-positive bacteria should be used. Routine antifungal therapy is not recommended; (5) The step-up approach, including antibiotics, is the standard for IPN management; (6) Antibiotic duration should be kept to a minimum and should be based on the quality of source control and patient condition. Conclusions: Early antibiotic therapy is essential for the treatment of IPN, but prophylactic antibiotics are not recommended in AP. High-quality randomized controlled trials are required to better understand the role of antibiotics and antifungals in AP management.

Background: The conventional open necrosectomy was associated with high mortality and morbidities like secondary organ failure, incisional hernia, enterocutaneous fistula, and external pancreatic fistula. In acute pancreatitis, collections are primarily confined to the retroperitoneal space. Hence, the retroperitoneal approach can be used to drain the collection and necrotic material. It benefits smaller incisions and better outcomes in terms of morbidity and mortality than the conventional open necrosectomy. This study primarily aims to describe the effects of minimal incision retroperitoneal necrosectomy versus conventional open necrosectomy for treating INP. Moreover, it provides evidence supporting the efficacy and safety of this method. Methods: A single-center retrospective study of the prospectively maintained database from April 2008 to December 2021. Results: A total of 122 patients were included in the study. Seventy-eight patients had an open necrosectomy, 30 had a MIRN, and 14 had a VARD procedure. These three groups were comparable in demographic variables. Preoperative variables like APACHE II at presentation, Modified CTSI, percentage of necrosis, multi-organ failure, time to surgery, and need for preoperative ICU stay were comparable among the three groups. Postoperative mortality was low in the MIRN group{open 35.8 % vs. MIRN 20.5 % vs. VARD 35.7 %, p = 0.066}. The postoperative stay was also significantly low in the MIRN and VARD group {open 23.62 ± 16.61 vs. MIRN 11.77 ± 7.73, VARD 8.86 ± 2.98, p = 0.00}. No significant difference in re-intervention rate, postoperative bleeding, and enterocutaneous fistula. Conclusion: MIRN is a simple and easy-to-adapt procedure for infected pancreatic necrosis in the appropriately selected patient group.

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. [ABSTRACT FROM AUTHOR]

Pancreatic fluid collections (PFC) are debris or fluid of the pancreas that needs to be drained out. This may result from surgery or necrotizing pancreatitis. This meta-analysis compared the outcomes of PFC through endoscopic and percutaneous interventions. A medical database was searched up to June 2022, comparing the outcomes of endoscopic drainage (ED) and percutaneous drainage (PD) for the PFC. Eligible studies reporting clinical and technical success and adverse events were selected. Seventeen studies with 1170 patients were included for meta-analysis, of which 543 patients underwent ED and 627 underwent PD. The odd ratio (OR) of technical success was 0.81 (95% confidence interval (CI) 0.31, 2.1) and clinical success was in the favor of the ED group at OR 2.23 (95% CI 1.45, 3.41). Adverse events OR 0.62 (95% CI 0.27, 1.39) and stent migration OR 0.61 (95% CI 0.10, 3.88) were the same in both groups, but hospital stay pooled mean difference of 15.02 days (95% CI 9.86, 20.18), mortality OR 0.24 (95% CI 0.09, 0.67), and re-interventions OR 0.25 (95% CI 0.16, 0.40) favored ED. ED is safe and efficient for PFC with higher clinical success, lower mortality rate, hospital stay, and re-interventions compared with PD. [ABSTRACT FROM AUTHOR]

Objective To analyze the efficacy and safety of ultrasound endoscopic treatment of infected pancreatic necrosis (IPN). Methods The technical success rate, clinical success rate, complication rate, unplanned re-endoscopic operation rate and recurrence rate of 36 patients with IPN treated by endoscopy-guided puncture and drainage in this unit from November 2018 to November 2021, and how to reduce the postoperative complication rate was discussed. One patient was lost to follow-up, and the patient did not return to the hospital for further treatment or follow-up after discharge. Results The technical success rate of 36 patients with IPN treated by endoscopic stent drainage was 100. 0% (36/36). One case failed in treatment, and finally got better after percutaneous drainage. The clinical success rate was 97. 1% (34/35), the operation rate of unplanned reoperation was 25. 7% (9/35), and the recurrence rate was 5. 7% (2/35). Postoperative infection occurred in 9 patients, and incomplete intestinal obstruction occurred in one patient. The incidence of complications was 27. 8% (10/36), and there were no postoperative bleeding, perforation and death. Conclusion Ultrasound endoscopy-guided stent drainage is a safe and effective endoscopic treatment for IPN, which is worth further popularization and application. [ABSTRACT FROM AUTHOR]

AbstractBackground/Aims Pancreatic fluid collections (PFC) are debris or fluid of the pancreas that needs to be drained out. This may result from surgery or necrotizing pancreatitis. This meta-analysis compared the outcomes of PFC through endoscopic and percutaneous interventions.Methods A medical database was searched up to June 2022, comparing the outcomes of endoscopic drainage (ED) and percutaneous drainage (PD) for the PFC. Eligible studies reporting clinical and technical success and adverse events were selected.Results Seventeen studies with 1170 patients were included for meta-analysis, of which 543 patients underwent ED and 627 underwent PD. The odd ratio (OR) of technical success was 0.81 (95% confidence interval (CI) 0.31, 2.1) and clinical success was in the favor of the ED group at OR 2.23 (95% CI 1.45, 3.41). Adverse events OR 0.62 (95% CI 0.27, 1.39) and stent migration OR 0.61 (95% CI 0.10, 3.88) were the same in both groups, but hospital stay pooled mean difference of 15.02 days (95% CI 9.86, 20.18), mortality OR 0.24 (95% CI 0.09, 0.67), and re-interventions OR 0.25 (95% CI 0.16, 0.40) favored ED.Conclusions ED is safe and efficient for PFC with higher clinical success, lower mortality rate, hospital stay, and re-interventions compared with PD.

Infected pancreatic necrosis (IPN) is a major cause of mortality in acute pancreatitis (AP). Currently, no specific strategies are available to predict the development of IPN. Earlier we reported that persistent down-regulation of HLA-DR increases risk of developing IPN. Altered kynurenine pathway (KP) metabolites showed poor prognosis in sepsis. Here we evaluated the role of HLA-DR and KP in IPN. Patients with ANP and healthy controls were enrolled. Demographic and clinical parameters were recorded. Circulating interleukin (IL)-8, 6, 1β, 10, Tumor necrosis factor-α were quantified using flowcytometry. Plasma procalcitonin, endotoxin, and KP (tryptophan, kynurenine) concentrations were estimated using ELISA. qRT-PCR was conducted to evaluate mRNA expression of HLA-DR, IL-10, Toll like receptor-4 (TLR-4), and kynurenine-3-monooxygenase (KMO) genes on peripheral blood mononuclear cells. Plasma metabolites were quantified using gas chromatography mass spectrometry (GC-MS/MS). Standard statistical methods were used to compare study groups. Metaboanalyst was used to analyse/visualize the metabolomics data. We recruited 56 patients in Cohort-1 (IPN:26,Non-IPN:30), 78 in Cohort-2 (IPN:57,Non-IPN:21), 26 healthy controls. Increased cytokines, endotoxin, and procalcitonin were observed in patients with IPN compared to Non-IPN. HLA-DR and KMO gene expressions were significantly down-regulated in IPN groups, showed positive correlation with one another but negatively correlated with IL-6 and endotoxin concentrations. Increased IDO and decreased plasma tryptophan were observed in IPN patients. Metabolome analysis showed significant reduction in several essential amino acids including tryptophan in IPN patients. Tryptophan, at a concentration of 9 mg/ml showed an AUC of 91.9 (95%CI 86.5–97.4) in discriminating IPN. HLA-DR downregulation and KP alteration are related to IPN. The KP metabolite plasma tryptophan can act as a potential biomarker for IPN. [ABSTRACT FROM AUTHOR]

Pancreatic fungal infection (PFI) in patients with necrotizing pancreatitis can lead to significant morbidity and mortality. The incidence of PFI has increased during the past decade. Our study aimed to provide contemporary observations on the clinical characteristics and outcomes of PFI in comparison to pancreatic bacterial infection and necrotizing pancreatitis without infection. We conducted a retrospective study of patients with necrotizing pancreatitis (acute necrotic collection or walled-off necrosis), who underwent pancreatic intervention (necrosectomy and/or drainage) and had tissue/fluid culture between 2005 and 2021. We excluded patients with pancreatic procedures prior to hospitalization. Multivariable logistic and Cox regression models were fitted for in-hospital and 1-year survival outcomes. A total of 225 patients with necrotizing pancreatitis were included. Pancreatic fluid and/or tissue was obtained from endoscopic necrosectomy and/or drainage (76.0%), CT-guided percutaneous aspiration (20.9%), or surgical necrosectomy (3.1%). Nearly half of the patients had PFI with or without concomitant bacterial infection (48.0%), while the remaining patients had either bacterial infection alone (31.1%) or no infection (20.9%). In multivariable analysis to assess the risk of PFI or bacterial infection alone, only previous pancreatitis was associated with an increased odds of PFI vs. no infection (OR 4.07, 95% CI 1.13-14.69, p  = .032). Multivariable regression analyses revealed no significant differences in in-hospital outcomes or one-year survival between the 3 groups. Pancreatic fungal infection occurred in nearly half of necrotizing pancreatitis. Contrary to many of the previous reports, there was no significant difference in important clinical outcomes between the PFI group and each of the other two groups. [ABSTRACT FROM AUTHOR]

Abstract Background Surgical pancreatic necrosectomy (SPN) is an option for the management of infected pancreatic necrosis. The literature indicates that an escalating, combined endoscopic, interventional radiology and minimally invasive surgery “step-up” approach, such as video-assisted retroperitoneal debridement, may reduce the number of required SPNs and ICU complications, such as multiple organ failure. We hypothesized that complications for surgically treated severe necrotizing pancreatitis patients decreased during the period of adoption of the “step-up” approach. Methods The American college of surgeons national surgery quality improvement program database (ACS-NSQIP) was used to find SPN cases from 2007 to 2019 in ACS-NSQIP submitting hospitals. Mortality and Clavien-Dindo class 4 (CD4) ICU complications were collected. Predictors of outcomes were identified by univariate and multivariate analyses. Results There were 2457 SPN cases. SPN cases decreased from 0.09% in 2007 to 0.01% in 2019 of NSQIP operative cases (p

Jiongdi Lu,1,2 Yixuan Ding,1,2 Yuanxu Qu,1,2 Wentong Mei,1,2 Yulin Guo,1,2 Zhen Fang,1,2 Chang Qu,1,2 Chongchong Gao,1,2 Feng Cao,1,2,&ast; Fei Li,1,2,&ast; Yulu Feng3 1Clinical Center of Acute Pancreatitis, Capital Medical University, Beijing, People’s Republic of China; 2Department of General Surgery, Xuanwu Hospital, Capital Medical University, Beijing, People’s Republic of China; 3Department of Pediatric, Chui Yang Liu Hospital Affiliated Tsinghua University, Beijing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Fei Li; Feng Cao, Clinical Center of Acute Pancreatitis, Capital Medical University, Department of General Surgery, Department of Surgery, Xuanwu Hospital, Capital Medical University, No. 45, Changchun Street, Xicheng District, Beijing, 100053, People’s Republic of China, Tel +86-10-83198731, Fax +86-10-83198868, Email feili36@ccmu.edu.cn; f.cao@xwhosp.orgObjective: The incidence of acute pancreatitis (AP) is increasing. Twenty percent of AP patients with developing necrotizing pancreatitis (NP), while ~40– 70% of NP patients develop potentially fatal infectious complications. When patients are suspected or confirmed infected pancreatic necrosis (IPN), antibiotics should be administered timeously to control the infection, but long-term use of antibiotics can lead to multidrug-resistant bacteria (MDRB) infection and eventually to increased mortality. Our study aimed to determine the incidence of MDRB infection and evaluate the risk factors for MDRB infection in IPN patients.Methods: Clinical data of IPN patients admitted to the general surgery department of Xuanwu Hospital of Capital Medical University between January 1, 2014, and December 31, 2021, were retrospectively analyzed.Results: IPN patients (n = 267) were assigned to MDRB infection (n = 124) and non-MDRB infection (n = 143) groups. On admission, patients in the MDRB group had a higher modified computer tomography severity index (CTSI) score (P < 0.05), pancreatic necrosis degree, and PCT level (P < 0.05) than those in the non-MDRB group, and the prognosis of patients in MDRB group was poor. The most common gram-negative bacteria were Acinetobacter baumannii (n = 117), the most common gram-positive bacteria were Enterococcus faecium (n = 98), and the most common fungal infection was Candida albicans (n = 47). Multivariable analysis showed that complications of EPI (OR: 4.116, 95% CI: 1.381– 12.271, P = 0.011), procalcitonin (PCT) level at admission (OR: 2.728, 95% CI: 1.502– 4.954, P = 0.001), and degree of pancreatic necrosis (OR: 2.741, 95% CI: 1.109– 6.775, P = 0.029) were independent risk factors for MDRB infection in IPN patients.Conclusion: We identified common infectious strains and risk factors for MDRB infection in IPN patients.Keywords: infected pancreatic necrosis, extra-pancreatic infection, multidrug-resistant bacteria, risk factor analysis

Objectives: This study aimed to identify the bacterial composition in the pancreatic fluid of severe and critical acute pancreatitis (SAP and CAP) patients. Methods: A total of 78 pancreatic fluid samples were collected from 56 SAP and CAP patients and analyze using aerobic culture and 16S rRNA gene nextgeneration sequencing. The clinical data of the patients were obtained from the electronic medical records. Results: Among the total 78 samples, 16S rRNA gene NGS identified a total of 660 bacterial taxa, belonging to 216 species in 123 genera. The dominant aerobic bacteria included Klebsiella pneumoniae, Acinetobacter baumannii, and Enterococcus faecium, while the dominant anaerobic bacteria included Bacteroides, Dialister invisus, and Olsenella uli. As compared to aerobic culturing, 95.96% (95/99) of the aerobic cultured bacteria were detected using the 16S rRNA gene NGS. Conclusion: The pancreatic infections in SAP and CAP patients might originate not only from the gut but also from the oral cavity and airways as well as related environments. Dynamic analysis of bacterial profile and abundance showed that some bacteria with low abundance might become the main pathogenic bacteria. There were no significant differences in the bacterial diversity between SAP and CAP. [ABSTRACT FROM AUTHOR]

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The identification of high-risk patients in the early stages of infected pancreatic necrosis (IPN) is critical, because it could help the clinicians to adopt more effective management strategies. We conducted a post hoc analysis of the MANCTRA-1 international study to assess the association between clinical risk factors and mortality among adult patients with IPN. Univariable and multivariable logistic regression models were used to identify prognostic factors of mortality. We identified 247 consecutive patients with IPN hospitalised between January 2019 and December 2020. History of uncontrolled arterial hypertension (p = 0.032; 95% CI 1.135–15.882; aOR 4.245), qSOFA (p = 0.005; 95% CI 1.359–5.879; aOR 2.828), renal failure (p = 0.022; 95% CI 1.138–5.442; aOR 2.489), and haemodynamic failure (p = 0.018; 95% CI 1.184–5.978; aOR 2.661), were identified as independent predictors of mortality in IPN patients. Cholangitis (p = 0.003; 95% CI 1.598–9.930; aOR 3.983), abdominal compartment syndrome (p = 0.032; 95% CI 1.090–6.967; aOR 2.735), and gastrointestinal/intra-abdominal bleeding (p = 0.009; 95% CI 1.286–5.712; aOR 2.710) were independently associated with the risk of mortality. Upfront open surgical necrosectomy was strongly associated with the risk of mortality (p < 0.001; 95% CI 1.912–7.442; aOR 3.772), whereas endoscopic drainage of pancreatic necrosis (p = 0.018; 95% CI 0.138–0.834; aOR 0.339) and enteral nutrition (p = 0.003; 95% CI 0.143–0.716; aOR 0.320) were found as protective factors. Organ failure, acute cholangitis, and upfront open surgical necrosectomy were the most significant predictors of mortality. Our study confirmed that, even in a subgroup of particularly ill patients such as those with IPN, upfront open surgery should be avoided as much as possible. Study protocol registered in ClinicalTrials.Gov (I.D. Number NCT04747990). [ABSTRACT FROM AUTHOR]

Introduction: Infected pancreatic necrosis (IPN) is a severe complication of acute necrotizing pancreatitis with increasing morbidity. Escherichia coli is the most frequently cultured microorganism in IPN. However, the implications of Escherichia coli infection on the outcomes of patients with IPN remain unclear. Therefore, this study aimed to evaluate the clinical impacts of Escherichia coli infection on IPN. Methods: A prospective database with consecutive patients with IPN between January 2010 and April 2022 at a tertiary hospital was post-hoc analyzed. The clinical and microbiological characteristics, surgical management, and follow-up data of patients with and without Escherichia coli infection were compared. Results: A total of 294 IPN patients were enrolled in this cohort. Compared with non-Escherichia coli infection cases (n=80, 27.2%), patients with Escherichia coli infection (n=214, 72.8%) were characterized by more frequent polymicrobial infections (77.5% vs. 65.0%, P=0.04) but a lower occurrence of severe acute pancreatitis (SAP) (42.5% vs. 61.7%, P=0.003). In addition, significantly lower mortality (12.5% vs. 30.4%, p=0.002), fewer step-up surgical interventions (73.8% vs. 85.1%, P=0.025), and a lower rate of multiple organ failure (MOF) (25.0% vs. 40.2%, P=0.016) were also observed in patients with Escherichia coli infection. Multivariate analysis of mortality predictors indicated that MOF (odds ratio [OR], 6.197; 95% confidence interval [CI], 2.373-16.187; P<0.001) and hemorrhage (OR, 3.485; 95% CI, 1.623-7.487; P=0.001) were independent predictors associated with higher mortality in patients with IPN. Escherichia coli infection was significantly associated with a lower mortality (OR, 0.302; 95% CI, 0.121-0.751; P= 0.01). Conclusion: Escherichia coli infection indicates a favorable prognosis in patients with IPN, although the mechanism needs further investigation. [ABSTRACT FROM AUTHOR]

Abstract Background Currently, the minimally invasive “Step-up” surgical strategy is still the main treatment for infected pancreatic necrosis (IPN). However, indiscriminate implementation of the “Step-up” strategy can lead to increased numbers of operations and prolonged hospital stay. The “Step-up” approach is not appropriate for some patients due to unavailabilty of a safe puncture path. Therefore, we developed the “One-step” surgical approach to treat IPN, which is safety. However, there is still a lack of comparison of the short and long-term efficacy between the “One-step” and “Step-up” approach. Consequently, we are conducting this clinical trial to provide a reference for IPN treatment. Methods This is an ongoing, single-center, randomized controlled trial of patients with IPN. The total sample size required for the trial (May 2021–December 2023) is approximately 128 patients. Patients will be randomly assigned to either an experimental group (One-step) or a control group (Step-up) at a ratio of 1:1 using the block randomization method. We used the case report forms and electronic data capture systems to obtain demographic information, preoperative laboratory examination, auxiliary examination results, surgery data, postoperative recovery outcomes, and follow-up outcomes. The patients will be followed up for 2 years after surgery. The primary endpoint is a composite endpoint, consisting of mortality and severe complications. The secondary endpoints include the incidence of organ dysfunction, the number of surgical procedures, mortality (the incidence of death in hospital and deaths within 30 days of discharge), hospital stay, intensive care unit stay, hospitalization costs, perioperative inflammatory marker changes, and short-and long-term complications. Discussion Compared with the “Step-up,” the “One-step” minimally invasive surgery can significantly reduce the number of operations, reduce the length of hospital stay and hospitalization costs without increasing the incidence of composite endpoint events, and has better short- and long-term efficacy and safety. Additionally, there was no statistically significant difference in perioperative complications and mortality between “Step-up” and “One-step”. This study will assist with the formulation of an effective and scientific “One-step” minimally invasive treatment strategy for IPN, and an understanding of this technique will facilitate clinical decision-making for IPN. Trial Registration ChiCTR2100044348. Trial status: Ongoing.

Yingying Sun,1 Jie Jin,2 Aying Zhu,1 Hong Hu,1 Yingying Lu,1 Yue Zeng,1 Dadao Jing1 1Department of Gastroenterology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 201600, People’s Republic of China; 2Department of Geriatrics, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200080, People’s Republic of ChinaCorrespondence: Dadao JingDepartment of Gastroenterology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, NO. 650 Xinsongjiang Road, Shanghai, 201600, People’s Republic of China, Tel +86-13816958050, Email dadaojing@126.comBackground: In recent years, the cure rate of acute pancreatitis (AP) has increased gradually, but the morbidity of recurrent acute pancreatitis (RAP) has not decreased. Patients with RAP have a poor quality of life and are more likely to develop into chronic pancreatitis. To investigate the risk factors of RAP after first pancreatitis attack is very necessary.Methods: Patients with first episode AP admitted to Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine from January 2018 to May 2021 were included in this retrospective study, and follow-up was 3– 45 months after discharge. The patients information were collected from medical records including laboratory tests and auxiliary inspection of their hospitalization. Univariate and multivariate Cox regression analysis were used to explore the risk factors of RAP. Cumulative risk of RAP was plotted using Kaplan–Meier curves.Results: A total of 592 patients were enrolled in the study and 81 (13.7%) of the patients developed RAP. Among those RAP patients, the majority (67.9%) were men, with a median age of 43 years. The most common etiology of RAP was hypertriglyceridemia (38.3%). Multivariate Cox analysis showed that smoking history (p < 0.001), infected pancreatic necrosis occurred during first admission (p = 0.005), and high low-density lipoprotein cholesterol (LDLc) level (p < 0.001) were significant independent risk factors for RAP. Patients with the above independent risk factors had increased 3-year cumulative risk of recurrence (32.2%, 45.5%, 28.9%, respectively).Conclusion: Smoking history, infected pancreatic necrosis, and high LDLc level were the most decisive risk factors for RAP. Attention should be paid to the patients with the above factors.Keywords: first episode pancreatitis, recurrent acute pancreatitis, risk factors, low-density lipoprotein cholesterol, infected pancreatic necrosis

Background and Objectives: Acute pancreatitis (AP) is defined as an acute inflammatory disorder of the pancreas and is a common gastrointestinal disease. Since currently used indicators lack specifics and cannot accurately reflect the phase of disease, better diagnostic approaches need to be explored. Fibrinogen-like protein 1 (FGL-1) is a reactant in acute inflammatory diseases and is increased in the plasma of AP patients. In the current study, we aim to investigate the clinical benefits of FGL-1 in predicting the severity of AP and infected pancreatic necrosis (IPN), which can improve the diagnostic efficiency of AP. Materials and Methods: In this study, 63 patients diagnosed with AP from December 2018 to September 2019 were enrolled. Regarding the severity of AP, patients were separated into severe acute pancreatitis (SAP, n = 12) and No-SAP groups (n = 51). On the basis of infective conditions, patients were divided into IPN (n = 9) and No-IPN (n = 54) groups. The demographic data (sex and age) and blood parameters (WBC, HCT, glucose, calcium, FIB, APTT, PCT, CRP, and FGL-1) were retrospectively analyzed. Results: The plasma FGL-1 levels were increased in both SAP (p < 0.01) and IPN (p < 0.05) subgroups compared to the healthy control group. Multivariate analysis showed that elevated plasma FGL-1 (p < 0.01) and PCT levels (p < 0.05) within 72 h after the onset of AP were positively correlated with the severity of AP, while increased plasma FGL-1 (p < 0.01) and CRP (p < 0.05) levels were positively correlated with the occurrence of IPN. The combination of FGL-1 and PCT showed superiority to both individual markers in SAP prediction. However, the combination of FGL-1 and CRP showed no diagnostic advantage over CRP in IPN prediction. Conclusions: Plasma FGL-1 within 72 h after the onset could be used for the stratification of AP and its infectious complications. The combination of PCT and FGL-1 presents an enormous advantage for the early identification of SAP. [ABSTRACT FROM AUTHOR]

Introduction: Multiple drug-resistant Gram-negative bacterial (MDR-GNB) bacteraemia poses a serious threat to patients in hospital. Infected pancreatic necrosis (IPN) patients are a vulnerable population to infectious complications during hospitalization. This study aims to evaluate the impact of MDR Gramnegative bacteraemia on IPN patients. Methods: A case–control study was performed with data collected from 1 January 2016 to 1 July 2022 in a Chinese tertiary teaching hospital. Clinical data of the IPN patients with MDR-GNB bacteraemia were analyzed and compared to those of a matched control group without MDR-GNB bacteraemia (case– control ratio of 1:2). Comparisons were performed between with/without MDR-GNB bacteraemia and different severities of acute pancreatitis (AP). Independent predictors of overall mortality were identified via univariate and multivariate binary logistic regression analyses. Results: MDR-GNB bacteraemia was related to a higher mortality rate (62.5% vs. 8.3%, p < 0.001). Severe AP combined with MDR-GNB bacteraemia further increased mortality up to 81.3% (p = 0.025). MDR-GNB bacteraemia (odds ratio (OR) = 8.976, 95% confidence interval (CI) = 1.805 –44.620, p = 0.007) and severe AP (OR = 9.414, 95% CI = 1.742 –50.873, p = 0.009) were independent predictors of overall mortality. MDR- Klebsiella pneumoniae was the most common causative pathogen. Conclusion: A higher mortality rate in IPN patients was related to MDR-GNB bacteraemia and further increased in severe AP patients combined with MDRGNB bacteraemia. [ABSTRACT FROM AUTHOR]

Introduction: This study aimed to identify whether interleukin-6 (IL-6) is better than C-reactive protein (CRP) for the prediction of severe acute pancreatitis (SAP), infected pancreatic necrosis (IPN), and mortality. Methods: Sixty-seven patients with acute pancreatitis (AP) who were hospitalized within 48 h of onset and received serum CRP and IL-6 tests from September 2018 to September 2019 were included. Spearman's correlation was performed to assess their associations with severity. The areas under the curve (AUCs) for the prediction of SAP, organ failure, pancreatic necrosis, IPN, and mortality were estimated using receiver operating characteristic curves. Result: Serum CRP and IL-6 levels were significantly positively correlated with the severity of AP (p < 0.05). The AUC for the prediction of SAP based on the CRP level was 0.78 (95% CI, 0.66-0.89) and that based on the IL-6 level was 0.69 (95% CI, 0.56-0.82). For the prediction of organ failure and pancreatic necrosis, CRP was more accurate than IL-6 (AUC 0.80 vs. 0.72 and 0.75 vs. 0.68, respectively). However, CRP was less accurate than IL-6 for predicting mortality and IPN (AUC 0.70 vs. 0.75 and 0.65 vs. 0.81, respectively). Systemic inflammatory response syndrome plus CRP was more accurate than systemic inflammatory response syndrome plus IL-6 (AUC 0.79 vs. 0.72) for the prediction of SAP. Conclusions: IL-6 was more accurate than CRP for predicting mortality and IPN in patients with AP. [ABSTRACT FROM AUTHOR]

Emphysematous pancreatitis (EP) is a subtype of infected pancreatic necrosis (IPN) characterized by presence of gas in (peri)pancreatic necrosis. However, the impacts of EP on outcomes of IPN are still controversial. A prospective database of consecutive patients with IPN in a tertiary hospital was post-hoc analyzed. Patients were assigned to EP and non-EP groups to perform a comprehensive comparison. A total of 178 patients with IPN were enrolled and the overall mortality was 30.9%. EP accounted for 20.8% (n = 37) of cases and was significantly associated with higher incidences of Escherichia coli (45.9 versus 18.4%, P = 0.001) and Klebsiella pneumoniae (56.8 versus 33.3%, P = 0.009) infection. There was scarcely any disparity in clinical characteristics and outcomes between IPN patients with and without EP. However, patients with early-onset EP defined as air bubble signs occurring within 2 weeks from disease onset were significantly older and have higher prevalence of history of diabetes, and they were also associated with significantly higher mortality (57.1 versus 8.7%, P = 0.015) compared with late-onset patients. The clinical outcomes of EP might be like those of non-emphysematous infection. However, when EP occurs within 2 weeks from disease onset, it is highly lethal. [ABSTRACT FROM AUTHOR]

Metagenomic next-generation sequencing (mNGS) is increasingly used for the clinical diagnosis of infectious diseases, but there is a paucity of data regarding the application of mNGS in the early diagnosis of infected pancreatic necrosis (IPN). To investigate the clinical application value of mNGS in the pathogenic diagnosis of IPN. Forty-two patients with suspected IPN were prospectively and consecutively enrolled from August 2019 to August 2021. Blood samples were collected for mNGS and microbial culture simultaneously during fever (T ≥ 38.5 °C). For patients who had indications of surgical interventions, peri-pancreatic specimens were collected for mNGS and microbial culture simultaneously during the first surgical intervention to confirm IPN. The clinical performance of mNGS and microbial culture were compared. A total of 21 patients (50.0%) were confirmed to have IPN during hospitalization. The sensitivity of blood mNGS was significantly higher than blood culture (95.2% vs. 23.8%, P < 0.001) in diagnosing IPN. The negative predictive value of blood mNGS was 90.0%. The turnaround time of mNGS was significantly shorter than that of microbial culture [(37.70 ± 1.44) vs. (115.23 ± 8.79) h, P < 0.01] and the average costs of mNGS accounted for 1.7% of the average total cost of hospitalization. The survival analysis demonstrates that the positive blood mNGS result was not associated with increased mortality (P = 0.119). With more valuable diagnostic performance and shorter turnaround time, clinical mNGS represents a potential step forward in the early diagnosis of IPN. Established knowledge: · Determining the microbiological profile in the early stage of infected pancreatic necrosis is difficult. · Metagenomic next-generation sequencing is a useful tool in diagnosing infectious diseases. · There is a paucity of data regarding the application of Metagenomic next-generation sequencing in suspected IPN. New findings: · Compared with blood culture, metagenomic next-generation sequencing had better diagnostic performance. · With high negative predictive value, metagenomic next-generation sequencing can avoid antibiotic overuse. · Metagenomic next-generation sequencing represents a potential step forward in the early diagnosis of IPN. [ABSTRACT FROM AUTHOR]

Introduction: Acute pancreatitis (AP) is a prevalent emergency. The clinical spectrum of the condition is varied, ranging from a mild to a malignant course with higher mortality rates. Infection of pancreatic/peri necrosis, extrapancreatic infections, and organ failure are significant complications in AP. In the recent era, microbiological composition has shifted more towards multi-drug-resistant organisms due to irrational antibiotic use., Objective: This study aims to understand the natural history of patients with suspected infected pancreatic necrosis (IPN), the prevalence of multi-drug-resistant organisms (MDROs), and their antibiotic susceptibility patterns., Methods: This prospective, observational study was performed on 130 cases of acute necrotizing pancreatitis (ANP) with suspected IPN that were evaluated during their period of admission in the department of gastroenterology, emergency medicine, or surgery ward of the Postgraduate Institute of Medical Education and Research, Chandigarh, India, a tertiary hospital. The details of outcomes were recorded. The organisms in cases with IPN and antibiotic resistance patterns of various organisms were studied., Results: The most prevalent site of necrosis was combined pancreatic and peripancreatic tissues in 111 (85.4%) patients. The computed tomography severity index (CTSI) had a mean of 8.72±1.43. Of all participants, 36 (27.7%) patients had <30% necrosis, 47 (36.2%) had 30%-50% necrosis, and 47 (36.2%) had >50% necrosis. Overall, 80 (61.5%) patients had organ failure, with acute lung injury (ALI) being the most common. Rates of complications were markedly greater in cases with higher pancreatic necrosis and with infected necrosis (p<0.05). The most common organism isolated from necrotic tissue was Escherichia coli ( E. coli ) in 17 (32.07%) cases, followed by Acinetobacter baumannii ( A. baumannii ) in 12 (22.64%) cases. The most common extrapancreatic infection site was respiratory tract infections. Pseudomonas aeruginosa ( P. aeruginosa ) and A. baumannii revealed maximum resistance to most of the drugs.  Conclusion: Infected pancreatic necrosis is linked to high rates of morbidity and mortality. Our study suggests that irrational usage of antibiotics increases the incidence of combined infection, especially with higher rates of multi-drug-resistant infections., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. Institutional Ethics Committee, Postgraduate Institute of Medical Education and Research issued approval (NK/6218/MD/725). Animal subjects: All authors have confirmed that this study did not involve animal subjects or tissue. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Loganathan et al.)

Jiangtao Yin,1,2,&ast; Wenjian Mao,1,&ast; Xiaojia Xiao,3 Xianqiang Yu,4 Baiqiang Li,5 Faxi Chen,5 Jiajia Lin,5 Jing Zhou,1 Jing Zhou,4 Zhihui Tong,5 Lu Ke,5 Weiqin Li1,5 1Department of Critical Care Medicine, Jinling Hospital, Nanjing Medical University, Nanjing, People’s Republic of China; 2Department of Intensive Care Unit, Affiliated Hospital of Jiangsu University, Zhenjiang, People’s Republic of China; 3Department of Critical Care Medicine, Jinling Hospital of Southern Medical University, Nanjing, People’s Republic of China; 4Southeast University School of Medicine, Nanjing, People’s Republic of China; 5Department of Critical Care Medicine, Jinling Hospital, Nanjing University, Nanjing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Lu Ke; Weiqin LiDepartment of Critical Care Medicine, Jinling Hospital, Medical School of Nanjing University, 305 East Zhongshan Road, Nanjing, 225001, People’s Republic of ChinaEmail ctgkelu@nju.edu.cn; njzy_pancrea@163.comObjective: Immunosuppression is common in patients with infected pancreatic necrosis (IPN) and associated with morbidity and mortality. This study aimed to investigate the impact of immune status on mortality and readmission after hospital discharge in patients with IPN-related sepsis.Methods: In this prospective observational study, eligible adult patients with IPN-related sepsis requiring ICU admission were included. Monocytic human leukocyte antigen DR (mHLA-DR), expression of regulatory T cells (Treg), and neutrophil CD88 (nCD88) were measured on the diagnosis of sepsis, ICU discharge, hospital discharge, and 15, 30, 60 days after hospital discharge. Logistic regression model was used to assess potential risk factors for readmission 60-days within the index discharge.Results: A total of 53 patients were included, 13 died during hospitalization and one withdrew the consent soon after discharge. Among the survivors, a tendency of immune recovery was observed during the consecutive follow-ups, evidenced by the increased expression of mHLA-DR. Sixteen patients (41.03%) were readmitted within 60 days after the index discharge. In the multivariable regression model, APACHE II score when sepsis was diagnosed > 9 and mHLA-DR at discharged < 14,591 AB/C were found to be independent risk factors affecting readmission.Conclusion: Immunosuppression is common in patients with IPN-related sepsis and can persist until two months after discharge. The compromised mHLA-DR level at discharge was associated with readmission within two months after discharge.Keywords: infected pancreatic necrosis, sepsis, immunosuppression, monocyte HLA-DR, readmissions

IntroductionMultiple drug-resistant Gram-negative bacterial (MDR-GNB) bacteraemia poses a serious threat to patients in hospital. Infected pancreatic necrosis (IPN) patients are a vulnerable population to infectious complications during hospitalization. This study aims to evaluate the impact of MDR Gram-negative bacteraemia on IPN patients.MethodsA case–control study was performed with data collected from 1 January 2016 to 1 July 2022 in a Chinese tertiary teaching hospital. Clinical data of the IPN patients with MDR-GNB bacteraemia were analyzed and compared to those of a matched control group without MDR-GNB bacteraemia (case–control ratio of 1:2). Comparisons were performed between with/without MDR-GNB bacteraemia and different severities of acute pancreatitis (AP). Independent predictors of overall mortality were identified via univariate and multivariate binary logistic regression analyses.ResultsMDR-GNB bacteraemia was related to a higher mortality rate (62.5% vs. 8.3%, p < 0.001). Severe AP combined with MDR-GNB bacteraemia further increased mortality up to 81.3% (p = 0.025). MDR-GNB bacteraemia (odds ratio (OR) = 8.976, 95% confidence interval (CI) = 1.805 –44.620, p = 0.007) and severe AP (OR = 9.414, 95% CI = 1.742 –50.873, p = 0.009) were independent predictors of overall mortality. MDR- Klebsiella pneumoniae was the most common causative pathogen.ConclusionA higher mortality rate in IPN patients was related to MDR-GNB bacteraemia and further increased in severe AP patients combined with MDR-GNB bacteraemia.

BACKGROUND: The surgical step-up approach often requires multiple debridements and might not be suitable for infected pancreatic necrosis (IPN) patients with various abscesses or no safe route for percutaneous catheter drainage (PCD). This case-control study aimed to investigate the safety and effectiveness of one-step laparoscopic pancreatic necrosectomy (LPN) in treating IPN. METHODS: This case-control study included IPN patients undergoing one-step LPN or surgical step-up in our center from January 2015 to December 2020. The short-term and long-term complications after surgery, length of hospital stay, and postoperative ICU stays in both groups were analyzed. Univariate and multivariate logistic regression analyses were performed to explore the risk factors of major complications or death. RESULTS: A total of 53 IPN patients underwent one-step LPN and 37 IPN patients underwent surgical step-up approach in this study. There was no significant difference in the incidence of death, major complications, new-onset diabetes, or new-onset pancreatic exocrine insufficiency between the two groups. However, the length of hospital stay in the one-step LPN group was significantly shorter than that in the surgical step-up group. Univariate regression analysis showed that the surgical approach (one-step/step-up) was not the risk factor for major complications or death. Multivariate logistic regression analysis indicated that computed tomography (CT) severity index, American Society of Anesthesiologists (ASA) class IV, and white blood cell (WBC) were the significant risk factors for major complications or death. CONCLUSION: One-step LPN is as safe and effective as the surgical step-up approach for treating IPN patients, and reduces total hospital stay. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

AimTo explore the indications for early intervention in patients with acute necrotizing pancreatitis (ANP) and evaluate the effect of early intervention on the prognosis of ANP patients.MethodsThe clinical data of patients with ANP who underwent general surgery at Xuanwu Hospital of Capital Medical University from January 1, 2014, to December 31, 2020, were collected retrospectively. The patients were followed-up every 6 months after discharge, and the last follow-up date was June 30, 2021.ResultsA total of 98 patients with ANP were included in the study. They were divided into an early group (n= 43) and a delayed group (n = 55) according to the first percutaneous drainage (PCD) intervention time (≤ 4 weeks or > 4 weeks). Body temperature, inflammatory factor levels, and the number of patients with persistent organ failure (POF) were higher in the early group than in the delayed group. After the minimally invasive intervention, the body temperature and inflammatory factors of the two groups decreased significantly, most patients with POF improved, and the number of patients with reversal of POF in the early group was higher than that in the delayed group. Although the patients in the early group required more surgical intervention than those in the delayed group, there was no significant difference in mortality, incidence of postoperative complications, total length of hospital stay, or operation cost between the two groups. During long-term follow-up, there was no significant difference in the incidence of short-term and long-term complications and overall survival between the two groups.ConclusionsCompared to patients in the delayed group, early intervention did not affect the prognosis of patients with ANP. It may be more suitable for patients with ANP with deterioration [such as POF or infected pancreatic necrosis (IPN)].

Background: Currently, the minimally invasive "Step-up" surgical strategy is still the main treatment for infected pancreatic necrosis (IPN). However, indiscriminate implementation of the "Step-up" strategy can lead to increased numbers of operations and prolonged hospital stay. The "Step-up" approach is not appropriate for some patients due to unavailabilty of a safe puncture path. Therefore, we developed the "One-step" surgical approach to treat IPN, which is safety. However, there is still a lack of comparison of the short and long-term efficacy between the "One-step" and "Step-up" approach. Consequently, we are conducting this clinical trial to provide a reference for IPN treatment.Methods: This is an ongoing, single-center, randomized controlled trial of patients with IPN. The total sample size required for the trial (May 2021-December 2023) is approximately 128 patients. Patients will be randomly assigned to either an experimental group (One-step) or a control group (Step-up) at a ratio of 1:1 using the block randomization method. We used the case report forms and electronic data capture systems to obtain demographic information, preoperative laboratory examination, auxiliary examination results, surgery data, postoperative recovery outcomes, and follow-up outcomes. The patients will be followed up for 2 years after surgery. The primary endpoint is a composite endpoint, consisting of mortality and severe complications. The secondary endpoints include the incidence of organ dysfunction, the number of surgical procedures, mortality (the incidence of death in hospital and deaths within 30 days of discharge), hospital stay, intensive care unit stay, hospitalization costs, perioperative inflammatory marker changes, and short-and long-term complications.Discussion: Compared with the "Step-up," the "One-step" minimally invasive surgery can significantly reduce the number of operations, reduce the length of hospital stay and hospitalization costs without increasing the incidence of composite endpoint events, and has better short- and long-term efficacy and safety. Additionally, there was no statistically significant difference in perioperative complications and mortality between "Step-up" and "One-step". This study will assist with the formulation of an effective and scientific "One-step" minimally invasive treatment strategy for IPN, and an understanding of this technique will facilitate clinical decision-making for IPN. Trial Registration ChiCTR2100044348. Trial status: Ongoing. [ABSTRACT FROM AUTHOR]

Mortality in infected pancreatic necrosis (IPN) is dynamic over the course of the disease, with type and timing of interventions as well as persistent organ failure being key determinants. The timing of infection onset and how it pertains to mortality is not well defined. To determine the association between mortality and the development of early IPN. International multicenter retrospective cohort study of patients with IPN, confirmed by a positive microbial culture from (peri) pancreatic collections. The association between timing of infection onset, timing of interventions and mortality were assessed using Cox regression analyses. A total of 743 patients from 19 centers across 3 continents with culture-confirmed IPN from 2000 to 2016 were evaluated, mortality rate was 20.9% (155/734). Early infection was associated with a higher mortality, when early infection occurred within the first 4 weeks from presentation with acute pancreatitis. After adjusting for comorbidity, advanced age, organ failure, enteral nutrition and parenteral nutrition, early infection (≤4 weeks) and early open surgery (≤4 weeks) were associated with increased mortality [HR: 2.45 (95% CI: 1.63–3.67), p < 0.001 and HR: 4.88 (95% CI: 1.70–13.98), p = 0.003, respectively]. There was no association between late open surgery, early or late minimally invasive surgery, early or late percutaneous drainage with mortality (p > 0.05). Early infection was associated with increased mortality, independent of interventions. Early surgery remains a strong predictor of excess mortality. [ABSTRACT FROM AUTHOR]

Abstract Background Acute pancreatitis is a common inflammatory pancreatic disorder, often caused by gallstone disease and frequently requiring hospitalization. In 80% of cases, a rapid and favourable outcome is described, while a necrosis of pancreatic parenchyma or extra-pancreatic tissues is reported in 10–20% of patients. The onset of pancreatic necrosis determines a significant increase of early organ failure rate and death that has higher incidence if infection of pancreatic necrosis (IPN) or extra-pancreatic collections occur. IPN always requires an invasive intervention, and, in the last decade, the advent of minimally invasive techniques has gradually replaced the employment of the open traditional approach. We report a series of three severe cases of IPN managed with primary open necrosectomy (ON) and a systematic review of the literature, in order to understand if emergency surgery still has a role in the current clinical practice. Methods From January 2010 to January 2020, 3 cases of IPN were treated in our Academic Department of General and Emergency Surgery. We performed a PubMed MEDLINE search on the ON of IPN, selecting 20 from 654 articles for review. Results The 3 cases were male patients with a mean age of 61.3 years. All patients referred to our service complaining an evolving severe clinical condition evocating a sepsis due to IPN. CT scan was the main diagnostic tool. Patients were initially conservatively managed. In consideration of clinical worsening conditions, and at the failure of conservative and minimal invasive treatment, they were, finally, managed with emergency ON. Patients reported no complications nor procedure-related sequelae in the follow-up period. Conclusion The ON is confirmed to be the last resort, useful in selected severe cases, with a defined timing and in case of proven non-feasibility and no advantage of other minimally invasive approaches.

Abstract Background To evaluate an innovative open necrosectomy strategy with continuous positive drainage and prophylactic diverting loop ileostomy for the management of late infected pancreatic necrosis (LIPN). Methods Consecutive patients were divided into open necrosectomy (ON) group (n = 23), open necrosectomy with colonic segment resection (ON+CSR) group (n = 8) and open necrosectomy with prophylactic diverting loop ileostomy (ON+PDLI) group (n = 11). Continuous positive drainage (CPD) via double-lumen irrigation–suction tube (DLIST) was performed in ON+PDLI group. The primary endpoints were duration of organ failure after surgery, postoperative complication, the rate of re-surgery and mortality. The secondary endpoints were duration of hospitalization, cost, time interval between open surgery and total enteral nutrition (TEN). Results The recovery time of organ function in ON+PDLI group was shorter than that in other two groups. Colonic complications occurred in 13 patients (56.5%) in the ON group and 3 patients (27.3%) in the ON+PDLI group (p = 0.11). The length of stay in the ON+PDLI group was shorter than the ON group (p = 0.001). The hospitalization cost in the ON+PDLI group was less than the ON group (p = 0.0052). Conclusion ON+PDLI can avoid the intestinal dysfunction, re-ileostomy, the resection of innocent colon and reduce the intraoperative trauma. Despite being of colonic complications before or during operation, CPD + PDLI may show superior effectiveness, safety, and convenience in LIPN.

Abstract Background Recent guidelines advise against prophylactic antibiotics in patients with necrotizing pancreatitis, advocating instead a step-up drainage and necrosectomy strategy with antibiotics as dictated by microbiological findings. However, prompt antibiotic therapy is recommended in patients with sepsis or septic shock, a possible presentation of infected pancreatic necrosis (IPN). Consequently, in many critically ill patients with IPN, pancreatic samples are collected only after broad-spectrum antibiotic therapy initiation. Whether this prior antibiotic exposure alters the microbiological findings is unknown. The main objective was to determine whether prior antibiotic exposure sterilized the samples collected during procedures for suspected IPN in patients admitted to the intensive care unit (ICU) for acute pancreatitis with suspected IPN. We retrospectively studied 56 consecutive ICU patients admitted with suspected IPN. We collected details on the microbiological samples and antimicrobials used. A definite diagnosis of IPN was given when bacteria were identified in pancreatic samples. Results In all, 137 pancreatic samples were collected, including 91 (66.4%) after antibiotic therapy initiation. IPN was confirmed in 48 (86%) patients. The proportion of positive samples was 74 (81.3%) in antibiotic-exposed patients and 32/46 (69.5%) in unexposed patients (p = 0.58). Of the 74 positive samples from exposed patients, 62 (84%) had organisms susceptible to the antibiotics used. One-third of samples contained more than one organism. Among patients with IPN, 37.5% had positive blood cultures. Multidrug- or extensively drug-resistant bacteria were identified at some point in half the patients. Enterobacter cloacae complex was more frequent in the exposed group (p = 0.02), as were Gram-negative anaerobic bacteria (p = 0.03). Conclusion Antibiotic exposure before sampling did not seem to affect culture positivity of pancreatic samples to confirm IPN, but may affect microbiological findings. Our results suggest that, in patients with sepsis and suspected IPN, antibiotics should be started immediately and pancreatic samples obtained as soon as possible thereafter. In other situations, antibiotics can be withheld until the microbiological results of pancreatic samples are available, to ensure accurate targeting of the spectrum to bacterial susceptibility patterns. ClinicalTrials.gov number NCT03253861

Abstract Background Multiple organ failure and early surgery are associated with high morbimortality after open necrosectomy. Data are mostly derived from historical cohorts with early necrosectomy bereft of step-up treatment algorithm implementation. Thus, mostly circumstantial evidence suggests a better clinical course following mini-invasive surgical and endoscopic necrosectomy. We studied the results of open necrosectomy in a contemporary cohort of patients with complicated pancreatic necrosis treated at a tertiary center. Methods A retrospective cohort study from a university teaching hospital. Results of 109 consecutive patients treated with open necrosectomy during a 12-year period are reported. Results The overall 90-day mortality rate was 22.9%. The 90-day mortality rate was 10.6% if necrosectomy could be delayed until 4 weeks from symptom onset and the necrosis had become walled off on preoperative imaging. The risk factors for 90-day mortality were age over 60 years (OR 19.4), pre-existing co-morbidities (OR 16.9), necrosectomy within 4 weeks (OR 6.5), multiple organ failure (OR 12.2), white blood cell count over 23 × 109 (OR 21.4), and deterioration or prolonged organ failure as an indication for necrosectomy (OR 10.4). None or one of these risk factors was present in 52 patients (47.7% of all patients), and these patients had no mortality. Conclusion Late open necrosectomy for walled-off necrosis has a low mortality risk. Open necrosectomy can be done without mortality in the absence of multiple risk factors for surgery.

In order to make correct diagnosis of acute pancreatitis (AP) and prevention of complications, especially infected pancreatic necrosis (IPN), there were made a wide range of examinations of people with abdominal pain and appropriate anamnesis. Clinical, laboratory and instrumental examination methods were carried out in dynamics during the first 5-7 days of illness. Attention was paid to some laboratory methods (levels of procalcitonin (PCT), amylase, diastasis, ALT, AST) due to results of correlation analysis in our previous researches.

Background. In recent years, the problem of pancreatic necrosis in urgent surgery has been at the forefront. Infected pancreatic necrosis (IPN) occurs in 38–69 % of patients with severe acute pancreatitis, mortality in this pathology reaches 8–49 %. The aim of the work – to increase the efficiency of treatment of patients with infected pancreatic necrosis and acute destructive pancreatitis by using an original drainage device. Materials and methods. The analysis of the results of treatment of 102 patients with IPN, who underwent different types of operations, depending on the prevalence of the process, was carried out. Women were 29 (28.4 %), men – 73 (71.6 %), aged from 27 to 74 years. We used traditional methods of patient examination. Two groups were formed. The 1st group (main) consisted of 43 (42.1 %) patients, in whom the traditional complex of therapeutic and diagnostic measures was used in combination with the developed “drainage device”. 59 (57.9 %) patients of the 2nd group (control) underwent standard medical and diagnostic practice. Results. A total of 102 patients underwent 186 operations: 96 - minimally invasive and 90 – by the traditional “open” method. The number of postoperative complications in the 1st group of patients was 8 (7.8 %), in the 2nd group – 18 (17.6 %) with a mortality rate of 5 (11.6 %) and 16 (27.1 %), respectively. The most common cause of death was sepsis with multiple organ failure. Conclusions. It is necessary to combine minimally invasive and “open” operations for infected pancreatic necrosis against the background of complex therapy. In 23.4 % of patients, minimally invasive technologies are the final method of treatment. The use of the developed “drainage device” leads to a significant reduction in complications and mortality.

Aims: We investigated whether faecal microbiota transplantation (FMT) decreases intra-abdominal pressure (IAP) and improves gastrointestinal (GI) dysfunction and infectious complications in acute pancreatitis (AP).Methods: In this first randomised, single-blind, parallel-group, controlled study, we recruited and enrolled consecutive patients with AP complicated with GI dysfunction. Eligible participants were randomly assigned to receive faecal transplant (n = 30) or normal saline (n = 30) via a nasoduodenal tube once and then again 2 days later. The primary endpoint was the rate of IAP decline; secondary endpoints were GI function, infectious complications, organ failure, hospital stay and mortality. Analyses were based on intention to treat.Results: We enrolled 60 participants and randomly assigned them to the FMT (n = 30) or control (n = 30) group. Baseline characteristics and disease severity were similar for both groups. IAP decreased significantly 1 week after intervention in both groups, with no difference in the IAP decline rate between FMT and Control group [0.1 (−0.6, 0.5) vs. 0.2 (−0.2, 0.6); P = 0.27]. Normal gastrointestinal failure (GIF) scores were achieved in 12 (40%) patients in the FMT group and 14 (47%) in the control group, with no significant difference (P = 0.60). However, D-lactate was significantly elevated in the FMT group compared to the control group, as calculated by the rate of decline [−0.3 (−3.7, 0.8) vs. 0.4 (−1.1, 0.9); P = 0.01]. Infectious complications occurred in 15 (50%) and 16 (53.33%) patients in the FMT and control groups, respectively (P = 0.80). However, interleukin-6 (IL-6) was significantly elevated in the FMT group compared to the control group, as calculated by the rate of decline [0.4 (−3.6, 0.9) vs. 0.8 (−1.7, 1.0); P = 0.03]. One participant experienced transient nausea immediately after FMT, but no serious adverse events were attributed to FMT.Conclusion: FMT had no obvious effect on IAP and infectious complications in AP patients, though GI barrier indictors might be adversely affected. Further multi-centre studies are needed to confirm our findings. The study was registered at https://clinicaltrials.gov (NCT02318134).