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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.
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Pancreatite Necrosante Aguda , Hospitalização , Humanos , Procedimentos Cirúrgicos Minimamente Invasivos , Estudos Prospectivos , Ensaios Clínicos Controlados Aleatórios como Assunto , Resultado do TratamentoRESUMO
Long non-coding RNAs (lncRNAs) play important functional roles in various biological processes. Early databases were utilized to deposit all lncRNA candidates produced by high-throughput experimental and/or computational techniques to facilitate classification, assessment and validation. As more lncRNAs are validated by low-throughput experiments, several databases were established for experimentally validated lncRNAs. However, these databases are small in scale (with a few hundreds of lncRNAs only) and specific in their focuses (plants, diseases or interactions). Thus, it is highly desirable to have a comprehensive dataset for experimentally validated lncRNAs as a central repository for all of their structures, functions and phenotypes. Here, we established EVLncRNAs by curating lncRNAs validated by low-throughput experiments (up to 1 May 2016) and integrating specific databases (lncRNAdb, LncRANDisease, Lnc2Cancer and PLNIncRBase) with additional functional and disease-specific information not covered previously. The current version of EVLncRNAs contains 1543 lncRNAs from 77 species that is 2.9 times larger than the current largest database for experimentally validated lncRNAs. Seventy-four percent lncRNA entries are partially or completely new, comparing to all existing experimentally validated databases. The established database allows users to browse, search and download as well as to submit experimentally validated lncRNAs. The database is available at http://biophy.dzu.edu.cn/EVLncRNAs.
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Bases de Dados de Ácidos Nucleicos , RNA Longo não Codificante/genética , Animais , Doença/genética , Genoma Humano , Humanos , Internet , Análise de Sequência de RNARESUMO
Objective: To clarify the incidence of colonic complications in patients with NP and their impact on prognosis. Methods: The clinical data of NP patients admitted to the Department of General Surgery of Xuanwu Hospital, Capital Medical University from January 2014 to December 2020 were retrospectively analyzed. Patients were grouped according to the presence or absence of colonic complications, and the clinical prognosis of the two groups was analyzed after matching using a 1:1 propensity score, The primary study endpoint was patient mortality during hospitalization. Data are reported as median (range) or percentage of patients (%). Results: A total of 306 patients with NP were included in this study, and the incidence of colonic complications was 12.4%, including 15 cases of colonic obstruction, 17 cases of colonic fistula, and 9 cases of colonic hemorrhage. Before matching, patients in the colonic group had severe admissions and poor clinical outcomes (P<0.05). After matching, the baseline data and clinical characteristics at admission were comparable between the two groups of patients. In terms of clinical outcomes, although the mortality was similar in the two groups (P>0.05), but patients in the colonic group were more likely to have multiorgan failure, length of nutrition support, number of minimally invasive interventions, number of extra-pancreatic infections, length of ICU stay and total length of stay were significantly higher than those of patients in the group without colonic complications (P<0.05). During long-term follow-up, patients in the colonic group were more likely to develop recurrent pancreatitis. Conclusion: About 12.4% of NP patients developed colonic complications, and after PSM it was found that colonic complications only led to a longer hospital stay and an increased number of clinical interventions in NP patients and did not increase the mortality.
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OBJECTIVE: Exosomes have been identified as important carriers of various genetic materials, including microRNAs (miRNAs). Increasing evidence indicates that the course of severe acute pancreatitis (SAP) is associated with miRNAs transported by exosomes. We aimed to identify the signature miRNAs as biomarkers of SAP. METHODS: We obtained exosomes from the SAP patients' blood. After separation, purification, and identification, we performed high-throughput sequencing and screened the differentially expressed(DE) miRNAs in the exosomes. Bioinformatics analysis was performed to identified the target genes of the miRNAs and the pathways enriched based on Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses, and selected the key miRNAs related to SAP. Total RNA was extracted from patient serum exosomes to detect the expression levels of the selected miRNAs in exosomes of three experimental groups (mild -, moderately severe -, and severe AP) and a control group, using Real-time quantitative polymerase chain reaction (RT-qPCR). RESULTS: 272 DE miRNAs were identified between SAP and control group. Using bioinformatics analysis, we determined that the functions of the target genes were enriched in six signaling pathways including focal adhesion. Based on this, seven candidate signature miRNAs were selected: miR-603, miR-548ad-5p, miR-122-5p, miR-4477a, miR-192-5p, miR-215-5p, and miR-583. The RT-qPCR results of the seven miRNAs in the SAP group were consistent with the sequencing results. CONCLUSION: Exosome-derived miR-603, miR-548ad-5p, miR-122-5p, miR-4477a, miR-192-5p, miR-215-5p, miR-583 are positively correlated with SAP, which might provide new insights into the pathogenesis of SAP and serve as the biomarkers of SAP.
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Exossomos , MicroRNAs , Pancreatite , Humanos , Exossomos/genética , Exossomos/metabolismo , MicroRNAs/genética , MicroRNAs/metabolismo , Pancreatite/genética , Doença Aguda , BiomarcadoresRESUMO
Objective: 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.
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Background: Pancreatic cancer is an insidious and heterogeneous malignancy with poor prognosis that is often locally unresectable. Therefore, determining the underlying mechanisms and effective prognostic indicators of pancreatic cancer may help optimize clinical management. This study was conducted to develop a prognostic model for pancreatic cancer based on a competing endogenous RNA (ceRNA) network. Methods: We obtained transcriptomic data and corresponding clinicopathological information of pancreatic cancer samples from The Cancer Genome Atlas (TCGA) database (training set). Based on the ceRNA interaction network, we screened candidate genes to build prediction models. Univariate Cox regression analysis was performed to screen for genes associated with prognosis, and least absolute shrinkage and selection operator (LASSO) regression analysis was conducted to construct a predictive model. A receiver operating characteristic (ROC) curve was drawn, and the C-index was calculated to evaluate the accuracy of the prediction model. Furthermore, we downloaded transcriptomic data and related clinical information of pancreatic cancer samples from the Gene Expression Omnibus database (validation set) to evaluate the robustness of our prediction model. Results: Eight genes (ANLN, FHDC1, LY6D, SMAD6, ACKR4, RAB27B, AUNIP, and GPRIN3) were used to construct the prediction model, which was confirmed as an independent predictor for evaluating the prognosis of patients with pancreatic cancer through univariate and multivariate Cox regression analysis. By plotting the decision curve, we found that the risk score model is an independent predictor has the greatest impact on survival compared to pathological stage and targeted molecular therapy. Conclusions: An eight-gene prediction model was constructed for effectively and independently predicting the prognosis of patients with pancreatic cancer. These eight genes identified show potential as diagnostic and therapeutic targets.
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Aim: To 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. Methods: The 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. Results: A 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. Conclusions: Compared 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)].
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Acute pancreatitis (AP) is a common gastrointestinal disease with a high risk of mortality. Recently, the exosome and its potential regulatory role in the progression of AP has garnered the interest of researchers. However, effective drug interventions and therapeutic targets for AP remain to be established. Treatment approaches for AP have undergone considerable changes in the recent years: there is a greater preference for minimally invasive therapy (as primary treatment), multidisciplinary participation and the step-up approach. We aimed to discuss AP mechanism and the recent advancement in its treatment strategies to manage AP better in clinical practice.
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Acute pancreatitis (AP) is an inflammatory disease that can progress to severe acute pancreatitis (SAP), which increases the risk of death. AP is characterized by inappropriate activation of trypsinogen, infiltration of inflammatory cells, and destruction of secretory cells. Other contributing factors may include calcium (Ca2+) overload, mitochondrial dysfunction, impaired autophagy, and endoplasmic reticulum (ER) stress. In addition, exosomes are also associated with pathophysiological processes of many human diseases and may play a biological role in AP. However, the pathogenic mechanism has not been fully elucidated and needs to be further explored to inform treatment. Recently, the treatment guidelines have changed; minimally invasive therapy is advocated more as the core multidisciplinary participation and "step-up" approach. The surgical procedures have gradually changed from open surgery to minimally invasive surgery that primarily includes percutaneous catheter drainage (PCD), endoscopy, small incision surgery, and video-assisted surgery. The current guidelines for the management of AP have been updated and revised in many aspects. The type of fluid to be used, the timing, volume, and speed of administration for fluid resuscitation has been controversial. In addition, the timing and role of nutritional support and prophylactic antibiotic therapy, as well as the timing of the surgical or endoscopic intervention, and the management of complications still have many uncertainties that could negatively impact the prognosis and patients' quality of life. Consequently, to inform clinicians about optimal treatment, we aimed to review recent advances in the understanding of the pathogenesis of AP and its diagnosis and management.
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BACKGROUND: Although the "Step-up" strategy is the primary surgical treatment for infected pancreatic necrosis, it is not suitable for all such patients. The "One-step" strategy represents a novel treatment, but the safety, efficacy, and long-term follow-up have not yet been compared between these two approaches. AIM: To compare the safety, efficacy, and long-term follow-up of two surgical approaches to provide a reference for infected pancreatic necrosis treatment. METHODS: This was a retrospective analysis of infectious pancreatic necrosis patients who underwent "One-step" or "Step-up" necrosectomy at Xuan Wu Hospital, Capital Medical University, from May 2014 to December 2020. The primary outcome was the composite endpoint of severe complications or death. Patients were followed up every 6 mo after discharge until death or June 30, 2021. Statistical analysis was performed using SPSS 21.0 and GraphPad Prism 8.0, and statistical significance was set at P < 0.05. RESULTS: One-hundred-and-fifty-eight patients were enrolled, of whom 61 patients underwent "One-step" necrosectomy and 97 patients underwent "Step-up" necrosectomy. During the long-term follow-up period, 40 patients in the "One-step" group and 63 patients in the "Step-up" group survived. The time from disease onset to hospital admission (53.69 ± 38.14 vs 32.20 ± 20.75, P < 0.001) and to initial surgical treatment was longer in the "Step-up" than in the "One-step" group (54.38 ± 10.46 vs 76.58 ± 17.03, P < 0.001). Patients who underwent "Step-up" necrosectomy had a longer hospitalization duration (65.41 ± 28.14 vs 52.76 ± 24.71, P = 0.02), and more interventions (4.26 ± 1.71 vs 3.18 ± 1.39, P < 0.001). Postoperative inflammatory indicator levels were significantly lower than preoperative levels in each group. Although the incisional hernia incidence was higher in the "One-step" group, no significant difference was found in the composite outcomes of severe complications or death, new-onset organ failure, postoperative complications, inflammatory indicators, long-term complications, quality of life, and medical costs between the groups (P > 0.05). CONCLUSION: Compared with the "Step-up" approach, the "One-step" approach is a safe and effective treatment method with better long-term quality of life and prognosis. It also provides an alternative surgical treatment strategy for patients with infected pancreatic necrosis.
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BACKGROUND: Severe acute pancreatitis (SAP) is a common critical disease of the digestive system. In addition to the clinical manifestations and biochemical changes of acute pancreatitis, SAP is also accompanied by organ failure lasting more than 48 h. SAP is characterized by focal or extensive pancreatic necrosis, hemorrhage and obvious inflammation around the pancreas. The peripancreatic fat space, fascia, mesentery and adjacent organs are often involved. The common local complications include acute peripancreatic fluid collection, acute necrotic collection, pancreatic pseudocyst, walled off necrosis and infected pancreatic necrosis. After reviewing the literature, we found that in very few cases, SAP patients have complications with anterior abdominal wall abscesses. CASE SUMMARY: We report a 66-year-old Asian male with severe acute pancreatitis who presented with intermittent abdominal pain and an increasing abdominal mass. The abscess spread from the retroperitoneum to the anterior abdominal wall and the right groin. In the described case, drainage tubes were placed in the retroperitoneal and anterior abdominal wall by percutaneous puncture. After a series of symptomatic supportive therapies, the patient was discharged from the hospital with a retroperitoneal drainage tube after the toleration of oral feeding and the improvement of nutritional status. CONCLUSION: We believe that patients with SAP complicated with anterior abdominal abscess can be treated conservatively to avoid unnecessary exploration or operation.
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Comprehensive reviews and large population-based cohort studies have played an important role in the diagnosis and treatment of pancreatitis and its sequelae. The incidence and mortality of pancreatitis have been reduced significantly due to substantial advancements in the pathophysiological mechanisms and clinically effective treatments. The study of extracellular vesicles (EVs) has the potential to identify cell-to-cell communication in diseases such as pancreatitis. Exosomes are a subset of EVs with an average diameter of 50~150 nm. Their diverse and unique constituents include nucleic acids, proteins, and lipids, which can be transferred to trigger phenotypic changes of recipient cells. In recent years, many reports have indicated the role of EVs in pancreatitis, including acute pancreatitis, chronic pancreatitis and autoimmune pancreatitis, suggesting their potential influence on the development and progression of pancreatitis. Plasma exosomes of acute pancreatitis can effectively reach the alveolar cavity and activate alveolar macrophages to cause acute lung injury. Furthermore, upregulated exosomal miRNAs can be used as biomarkers for acute pancreatitis. Here, we summarized the current understanding of EVs in pancreatitis with an emphasis on their biological roles and their potential use as diagnostic biomarkers and therapeutic agents for this disease.
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Vesículas Extracelulares/fisiologia , Pancreatite/etiologia , Animais , Biomarcadores , Humanos , Pancreatite/diagnósticoRESUMO
Plant long noncoding RNAs (lncRNAs) play important functional roles in various biological processes. Most databases deposit all plant lncRNA candidates produced by high-throughput experimental and/or computational techniques. There are several databases for experimentally validated lncRNAs. However, these databases are small in scale (with a few hundreds of lncRNAs only) and specific in their focuses (plants, diseases, or interactions). Thus, we established EVLncRNAs by curating lncRNAs validated by low-throughput experiments (up to May 1, 2016) and integrating specific databases (lncRNAdb, LncRANDisease, Lnc2Cancer, and PLNIncRBase) with additional functional and disease-specific information not covered previously. The current version of EVLncRNAs contains 1543 lncRNAs from 77 species, including 428 plant lncRNAs from 44 plant species. Compared to PLNIncRBase, our dataset does not contain any lncRNAs from microarray and deep sequencing. Moreover, 40% of entries contain new information (interaction and additional information from NCBI and Ensembl). The database allows users to browse, search, and download as well as to submit experimentally validated lncRNAs. The database is available at http://biophy.dzu.edu.cn/EVLncRNAs .