Pancreatic Infection Research Articles

Challenging antibiotic stewardship: antibiotic use in the management of acute pancreatitis without waiting for a CT scan or CRP marker

Madam, Acute pancreatitis is an acute inflammation of the pancreas presenting as severe abdominal pain and elevated pancreatic enzymes. The global burden of Acute pancreatitis has increased by 3.07% per year, for the last 56 years.1 Gallstones, chronic alcohol, and hypertriglyceridemia are the main risk factors involved in the pathogenesis of Acute pancreatitis worldwide.2 However, in Pakistan gall stones impacting the common bile duct and hypertriglyceridemia are the main culprits. There has been an extensive debate regarding the use of prophylactic antibiotics and the outcome of acute pancreatitis. The cumulative evidence suggests that the prompt use of antibiotics, before obtaining serum markers, is not associated with a significant decrease in secondary pancreatic infection.3 Multiple studies have shown that the use of antibiotics, deviating from the recent guidelines, boosts antibiotic resistance and the risk of invasive fungal infections. A 2020 study conducted by Soulountsi has also rendered this practice unjustified.4 In studies supporting the use of prophylactic antibiotics in improving outcomes, the quality of evidence is low suggesting that the approach should be more tailored to individual patient conditions while adhering to the guidelines. Despite the sterile nature of the early stages of acute pancreatitis, some clinicians continue to opt for prophylactic use, however, it is strictly against the international consensus. Unfortunately, in Pakistan, there is a common practice of using antibiotics in acute pancreatitis within 72hrs, without waiting for the CT scan results and inflammatory markers screening. Antimicrobial resistance is an anticipated outcome of such practice. The prevalence of antimicrobial resistance to commonly prescribed antibiotics is already very high.5 Not weighing the risk-benefit ratio will not only contribute to increasing resistance but also predispose to avoidable and potentially fatal fungal infections. The appropriate approach to management of Acute pancreatitis should be based on a thorough knowledge of recent guidelines, carrying out proper investigations, and making an individualized plan for the patient based on clinical findings. This will not only minimize the burden of complications but also provide more room for improvements in the management of acute pancreatitis.

Atlantic salmon type I interferon genes revisited

Type I interferons (IFN–I) play a pivotal role in vertebrate innate immunity against viruses. This study is an analysis of IFN-I genes in an updated version of the Atlantic salmon genome published in 2021 (version Ssal_v3.1), revealing 47 IFN-I genes in the Atlantic salmon genome. The GH1 locus of chromosome (Chr) 3 harbors 9 IFNa genes, 5 IFNb genes, 6 IFNc genes, 11 IFNe genes and 1 IFNf gene. The GH2 locus on Chr6 contains 1 IFNa gene, 12 IFNc genes and 1 IFNf gene while Chr19 carries a single IFNd gene. Intraperitoneal injection of Atlantic salmon presmolts with poly I:C, a mimic of virus double-stranded RNA, significantly up-regulated IFNc genes from both Chr3 and Chr6 in heart, with lower expression in head kidney. IFNe expression increased in the heart, but not in the head kidney while IFNf was strongly up-regulated in both tissues. Antiviral activity of selected IFNs was assessed by transfection of salmon cells with IFN-expressing plasmids followed by infectious pancreatic necrosis virus infection, and by injection of fish with IFN-plasmids followed by measuring expression of the antiviral Mx1 gene. The results demonstrated that IFNc from both Chr3 and Chr6 provided full protection of cells against virus infection, whereas IFNe and IFNf showed lesser protection. IFNc from Chr3 and Chr6 along with IFNe and IFNf, up-regulated the Mx1 gene in the muscle, while only the IFNcs caused induction of Mx1 in liver. Overall, this study reveals that Atlantic salmon possesses an even more potent innate immune defense against viruses than previously understood.

An early warning model for sepsis complicated with acute respiratory distress syndrome based on synthetic minority oversampling technique algorithm

To explore the independent risk factors of acute respiratory distress syndrome (ARDS) in patients with sepsis, establish an early warning model, and verify the predictive value of the model based on synthetic minority oversampling technique (SMOTE) algorithm. A retrospective case-control study was conducted. 566 patients with sepsis who were admitted to Jinan People's Hospital from October 2016 to October 2022 were enrolled. General information, underlying diseases, infection sites, initial cause, severity scores, blood and arterial blood gas analysis indicators at admission, treatment measures, complications, and prognosis indicators of patients were collected. The patients were grouped according to whether ARDS occurred during hospitalization, and the clinical data between the two groups were observed and compared. Univariate and binary multivariate Logistic regression analysis were used to select the independent risk factors of ARDS during hospitalization in septic patients, and regression equation was established to construct the early warning model. Simultaneously, the dataset was improved using the SMOTE algorithm to build an enhanced warning model. Receiver operator characteristic curve (ROC curve) was drawn to validate the prediction efficiency of the model. 566 patients with sepsis were included in the final analysis, of which 163 developed ARDS during hospitalization and 403 did not. Univariate analysis showed that there were statistically significant differences in age, body mass index (BMI), malignant tumor, blood transfusion history, pancreas and peripancreatic infection, gastrointestinal tract infection, pulmonary infection as the initial etiology, acute physiology and chronic health evaluation II (APACHE II) score, sequential organ failure assessment (SOFA) score, albumin (Alb), blood urea nitrogen (BUN), mechanical ventilation therapy, septic shock and length of intensive care unit (ICU) stay between the two groups. Binary multivariate Logistic regression analysis showed that age [odds ratio (OR) = 3.449, 95% confidence interval (95%CI) was 2.197-5.414, P = 0.000], pulmonary infection as the initial etiology (OR = 2.309, 95%CI was 1.427-3.737, P = 0.001), pancreas and peripancreatic infection (OR = 1.937, 95%CI was 1.236-3.035, P = 0.004), septic shock (OR = 3.381, 95%CI was 1.890-6.047, P = 0.000), SOFA score (OR = 9.311, 95%CI was 5.831-14.867, P = 0.000) were independent influencing factors of ARDS during hospitalization in septic patients. An early warning model was established based on the above risk factors: P1 = -4.558+1.238×age+0.837×pulmonary infection as the initial etiology+0.661×pancreas and peripancreatic infection+1.218×septic shock+2.231×SOFA score. ROC curve analysis showed that the area under the ROC curve (AUC) of the model for ARDS during hospitalization in septic patients was 0.882 (95%CI was 0.851-0.914) with sensitivity of 79.8% and specificity of 83.4%. The dataset was improved based on the SMOTE algorithm, and the early warning model was rebuilt: P2 = -3.279+1.288×age+0.763×pulmonary infection as the initial etiology+0.635×pancreas and peripancreatic infection+1.068×septic shock+2.201×SOFA score. ROC curve analysis showed that the AUC of the model for ARDS during hospitalization in septic patients was 0.890 (95%CI was 0.867-0.913) with sensitivity of 85.3% and specificity of 79.1%. This result further confirmed that the early warning model constructed by the independent risk factors mentioned above had high predictive performance. Risk factors for the occurrence of ARDS during hospitalization in patients with sepsis include age, pulmonary infection as the initial etiology, pancreatic and peripancreatic infection, septic shock, and SOFA score. Clinically, the probability of ARDS in patients with sepsis can be assessed based on the warning model established using these risk factors, allowing for early intervention and improvement of prognosis.

Metagenomic next-generation sequencing, instead of procalcitonin, could guide antibiotic usage in patients with febrile acute necrotizing pancreatitis: a multicenter, prospective cohort study.

The effectiveness of procalcitonin-based algorithms in guiding antibiotic usage for febrile acute necrotizing pancreatitis (ANP) remains controversial. Metagenomic next-generation sequencing (mNGS) has been applied to diagnose infectious diseases. The authors aimed to evaluate the effectiveness of blood mNGS in guiding antibiotic stewardship for febrile ANP. The prospective multicenter clinical trial was conducted at seven hospitals in China. Blood samples were collected during fever (T ≥38.5°C) from ANP patients. The effectiveness of blood mNGS, procalcitonin, and blood culture in diagnosing pancreatic infection was evaluated and compared. Additionally, the real-world utilization of antibiotics and the potential mNGS-guided antimicrobial strategy in febrile ANP were also analyzed. From May 2023 to October 2023, a total of 78 patients with febrile ANP were enrolled and 30 patients (38.5%) were confirmed infected pancreatic necrosis (IPN). Compared with procalcitonin and blood culture, mNGS showed a significantly higher sensitivity rate (86.7% vs. 56.7% vs. 26.7%, P <0.001). Moreover, mNGS outperformed procalcitonin (89.5 vs. 61.4%, P <0.01) and blood culture (89.5 vs. 69.0%, P <0.01) in terms of negative predictive value. Blood mNGS exhibited the highest accuracy (85.7%) in diagnosing IPN and sterile pancreatic necrosis, significantly superior to both procalcitonin (65.7%) and blood culture (61.4%). In the multivariate analysis, positive blood mNGS (OR=60.2, P <0.001) and lower fibrinogen level (OR=2.0, P <0.05) were identified as independent predictors associated with IPN, whereas procalcitonin was not associated with IPN, but with increased mortality (Odds ratio=11.7, P =0.006). Overall, the rate of correct use of antibiotics in the cohort was only 18.6% (13/70) and would be improved to 81.4% (57/70) if adjusted according to the mNGS results. Blood mNGS represents important progress in the early diagnosis of IPN, with particular importance in guiding antibiotic usage for patients with febrile ANP.

A prospective study on assessment of risk factors, clinical characteristics and outcomes of acute pancreatitis in a tertiary care center

This prospective study at RVS Hospital Chittoor targets acute pancreatitis, a severe pancreatic condition with significant health risks. Its goal is to improve patient care by analyzing risk factors, clinical features, and outcomes. Adult patients with acute pancreatitis will participate, providing comprehensive demographic, clinical, and lab data. The research will focus on key risk factors like alcohol use, gallstones, and prior pancreatitis episodes. Clinical aspects, including pain severity, systemic symptoms, and complications, will be documented, utilizing CT scans and MRI for accurate diagnosis and classification. The primary aims are identifying acute pancreatitis risk factors, understanding patient presentations, and monitoring complications during hospitalization. Secondary goals include evaluating the impact of risk factors on disease severity and mortality and exploring connections between specific risks and major complications like pancreatic necrosis and infections. This study is crucial for advancing understanding of acute pancreatitis, guiding healthcare professionals in early diagnosis, risk stratification, and effective management, ultimately enhancing patient outcomes in this complex medical issue.

Radical surgery for highly advanced gastric cancer with direct invasion to transverse colon, splenic serosa, and pancreas inducing pancreatic duct infection: A case report

Background: According to the GLOBOCAN 2020 results, gastric cancer is the fifth most commonly diagnosed cancer, and fourth most common cause of cancer death worldwide. An estimated 6-27% of patients with gastric cancer show invasion of the adjacent organs at diagnosis. In a previous study, curative resection was shown to significantly improve the prognosis of patients without peritoneal or liver metastases. Herein, we present a case of gastric cancer with invasion of the adjacent organs in a patient who underwent curative surgery. Case presentation: An 80-year-old woman presented with body weight loss and slight fever. Upper gastrointestinal endoscopy revealed Borrmann type 3 gastric cancer extending from the gastric fundus to the corpus. Contrast-enhanced computed tomography (eCT) revealed extensive invasion of the gastric cancer into the transverse colon and pancreas. The eCT also revealed gas in the pancreatic duct, indicating that the gastric lumen was connected to the pancreatic duct because of the tumor. We performed en-bloc tumor resection via total gastrectomy with D2 lymph node dissection, distal pancreatectomy, and partial colectomy. The patient was postoperatively diagnosed with T4b (SI: pancreatic, transverse colon, and splenic serosa), N0 Stage IIIA gastric cancer. The histological type was poorly differentiated adenocarcinoma. Adjuvant chemotherapy was initiated two months after surgery, but was continued for only two months because of severe adverse events. Two years after surgery, the patient remains well. Conclusion: Advanced gastric cancer with extensive invasion of the adjacent organs but no distant metastasis can be treated with en-bloc tumor resection.

Guiding post-pancreaticoduodenectomy interventions for pancreatic cancer patients utilizing decision tree models.

Pancreatic ductal adenocarcinoma (PDAC) is frequently diagnosed in advanced stages, necessitating pancreaticoduodenectomy (PD) as a primary therapeutic approach. However, PD surgery can engender intricate complications. Thus, understanding the factors influencing postoperative complications documented in electronic medical records and their impact on survival rates is crucial for improving overall patient outcomes. A total of 749 patients were divided into two groups: 598 (79.84%) chose the RPD (Robotic pancreaticoduodenectomy) procedure and 151 (20.16%) chose the LPD (Laparoscopic pancreaticoduodenectomy) procedure. We used correlation analysis, survival analysis, and decision tree models to find the similarities and differences about postoperative complications and prognostic survival. Pancreatic cancer, known for its aggressiveness, often requires pancreaticoduodenectomy as an effective treatment. In predictive models, both BMI and surgery duration weigh heavily. Lower BMI correlates with longer survival, while patients with heart disease and diabetes have lower survival rates. Complications like delayed gastric emptying, pancreatic fistula, and infection are closely linked post-surgery, prompting conjectures about their causal mechanisms. Interestingly, we found no significant correlation between nasogastric tube removal timing and delayed gastric emptying, suggesting its prompt removal post-decompression. This study aimed to explore predictive factors for postoperative complications and survival in PD patients. Effective predictive models enable early identification of high-risk individuals, allowing timely interventions. Higher BMI, heart disease, or diabetes significantly reduce survival rates in pancreatic cancer patients post-PD. Additionally, there's no significant correlation between DGE incidence and postoperative extubation time, necessitating further investigation into its interaction with pancreatic fistula and infection.

Exploring the gut microbiota's crucial role in acute pancreatitis and the novel therapeutic potential of derived extracellular vesicles.

During acute pancreatitis, intestinal permeability increases due to intestinal motility dysfunction, microcirculatory disorders, and ischemia-reperfusion injury, and disturbances in the intestinal flora make bacterial translocation easier, which consequently leads to local or systemic complications such as pancreatic and peripancreatic necrotic infections, acute lung injury, systemic inflammatory response syndrome, and multiple organ dysfunction syndrome. Therefore, adjusting intestinal ecosystem balance may be a promising approach to control local and systemic complications of acute pancreatitis. In this paper, we reviewed the causes and manifestations of intestinal flora disorders during acute pancreatitis and their complications, focused on the reduction of acute pancreatitis and its complications by adjusting the intestinal microbial balance, and innovatively proposed the treatment of acute pancreatitis and its complications by gut microbiota-derived extracellular vesicles.

Bone Marrow Mesenchymal Stem Cells Alleviate Acute Severe Pancreatitis and Promote Lung Repair via Inhibiting NLRP3 Inflammasome in Rat.

Acute severe pancreatitis (SAP) is a severe acute abdominal disease, which can lead to pancreatic infection and necrosis as well as distant organ damage. Bone marrow mesenchymal stem cells (BMSCs) can exert anti-inflammatory effect on SAP, while NLRP3 inflammasomes play an important role in the inflammatory response. This study aimed to investigate whether BMSCs exert anti-inflammatory effect on SAP by inhibiting NLRP3 inflammasome. The rat SAP model was established. Serum amylase, lipase and inflammatory factor levels were measured by ELISA, and the level of tissue injury was assessed by HE staining. The expression of NLRP3 inflammasome was detected by PCR, Western Blot and immunohistochemistry. ML385 was used to block Nrf2 pathway, aiming to investigate whether Nrf2 pathway was involved in the therapeutic effect of BMSCs on SAP by regulating NLRP3 inflammasome expression. In SAP rats, NLRP3 inflammasome was activated, which became more evident over time. After transplantation of BMSCs, the NLRP3 inflammasome expression decreased at both mRNA and protein levels, the serum levels of amylase, lipase and inflammatory factors decreased, and the pathological scores of the pancreas and lung were both improved. After blocking the Nrf2 pathway, the NLRP3 inflammasome expression increased in the injured pancreas and lung, and the inflammation deteriorated, which inhibited the therapeutic effects of BMSCs on SAP. The therapeutic effect of BMSC on SAP is at least partially ascribed to the inhibition of NLRP3 inflammasome, and Nrf2 pathway mediates the therapeutic effect of BMSC on SAP by inhibiting NLRP3 inflammasome.

Pancreatic necrosis infection as a determinant of multiple organ failure and mortality in patients with acute pancreatitis using a step-up approach and the concept of enhanced recovery after surgery

Pancreatic necrosis infection as a determinant of multiple organ failure and mortality in patients with acute pancreatitis using a step-up approach and the concept of enhanced recovery after surgery

The Effect of Prophylactic Carbapenem Use on Outcomes in Acute Pancreatitis: A Systematic Review and Meta-Analysis.

This study aimed to determine the effect of prophylactic use of carbapenems for acute pancreatitis on clinical outcomes. It was conducted according to the preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines by using the keywords "Pancrea * AND carbapenem OR imipenem OR ertapenem OR meropenem OR doripenem." Primer outcomes were mortality, surgical intervention, and pancreatic and non-pancreatic infection. Subgroup analyses were also performed to reduce the risk of bias. Ten studies with 4038 patients were included in the meta-analyses. While eight of ten were randomized controlled trials, two were observational studies. The prophylactic use of carbapenems had no statistically significant effect on mortality (OR=0.82, 95% CI=0.65-1.04, I²=0%) and surgical intervention. (OR=0.81, 95% CI=0.57-1.17, I²=0%). However, the real impact of prophylaxis on reducing the incidence of mortality and surgical intervention was uncertain due to the insufficient sample size. The prophylactic use of carbapenems was significantly associated with a lower risk of peripancreatic (OR=0.37, 95% CI=0.25-0.55, I²=61%) and non-pancreatic infection risk (OR=0.60, 95% CI=0.46-0.78, I²=65%). The definitions of infection in the articles were not clear, and the diagnostic approach to infection was based on subjective criteria. In addition, there was inadequate collateral damage and safety assessments. In high-quality studies with a low risk of bias, prophylactic carbapenems had no effect on peripancreatic infection (RR=1.54, 95% CI=0.65-3.47, I²=0%) and non-pancreatic infection (RR=0.72, 95% CI=0.48-1.07, I²=0%). Although there is a reduction in the infection risk, routine carbapenem use in acute pancreatitis cases should not be recommended based on current evidence. Cooperation with Infectious Disease specialists and developing diagnostic algorithms are required instead of routine prophylaxis to prevent infection, especially non-pancreatic infection.

Epidemiology and risk factors for mortality in critically ill patients with pancreatic infection

BackgroundThe AbSeS-classification defines specific phenotypes of patients with intra-abdominal infection based on the (1) setting of infection onset (community-acquired, early onset, or late-onset hospital-acquired), (2) presence or absence of either localized or diffuse peritonitis, and (3) severity of disease expression (infection, sepsis, or septic shock). This classification system demonstrated reliable risk stratification in intensive care unit (ICU) patients with intra-abdominal infection. This study aimed to describe the epidemiology of ICU patients with pancreatic infection and assess the relationship between the components of the AbSeS-classification and mortality. MethodsThis was a secondary analysis of an international observational study (“AbSeS”) investigating ICU patients with intra-abdominal infection. Only patients with pancreatic infection were included in this analysis (n=165). Mortality was defined as ICU mortality within 28 days of observation for patients discharged earlier from the ICU. Relationships with mortality were assessed using logistic regression analysis and reported as odds ratio (OR) and 95% confidence interval (CI). ResultsThe overall mortality was 35.2% (n=58). The independent risk factors for mortality included older age (OR=1.03, 95% CI: 1.0 to 1.1 P=0.023), localized peritonitis (OR=4.4, 95% CI: 1.4 to 13.9 P=0.011), and persistent signs of inflammation at day 7 (OR=9.5, 95% CI: 3.8 to 23.9, P<0.001) or after the implementation of additional source control interventions within the first week (OR=4.0, 95% CI: 1.3 to 12.2, P=0.013). Gram-negative bacteria were most frequently isolated (n=58, 49.2%) without clinically relevant differences in microbial etiology between survivors and non-survivors. ConclusionsIn pancreatic infection, a challenging source/damage control and ongoing pancreatic inflammation appear to be the strongest contributors to an unfavorable short-term outcome. In this limited series, essentials of the AbSeS-classification, such as the setting of infection onset, diffuse peritonitis, and severity of disease expression, were not associated with an increased mortality risk.ClinicalTrials.gov number: NCT03270345

Clinical characteristics and outcomes of pancreatic fungal infection in patients with necrotizing pancreatitis.

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.

Identification and characterization of pancreatic infections in severe and critical acute pancreatitis patients using 16S rRNA gene next generation sequencing.

This study aimed to identify the bacterial composition in the pancreatic fluid of severe and critical acute pancreatitis (SAP and CAP) patients. A total of 78 pancreatic fluid samples were collected from 56 SAP and CAP patients and analyze using aerobic culture and 16S rRNA gene next-generation sequencing. The clinical data of the patients were obtained from the electronic medical records. 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. 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.

Implementation of ERAS in pancreaticoduodenectomy in an Australian tertiary centre

Background/objectivesRecent studies have demonstrated that enhanced recovery after surgery (ERAS) protocols in pancreaticoduodenectomy (PD) may decrease morbidity and length of stay. This study aimed to critically assess the implementation of ERAS in patients who have undergone a PD in a tertiary centre. MethodsA retrospective cohort study of all patients who underwent a PD prior to ERAS, compared to following implementation were assessed. Outcome measures of length of stay, morbidity, mortality and readmission rates between the two groups were evaluated. Results169 patients were included in the study (pre-ERAS, n = 29; stage 1, n = 14; stage 2, n = 53, stage 3, n = 73) with mean age of 64 ± 11.3 years. ERAS significantly increased the proportion of patients reaching the target length of stay of nine days (P = 0.017). It did not significantly impact overall mortality, morbidity, radiological intervention, reoperation or readmission (P > 0.05). ERAS did not have a significant impact on development of pancreatic fistula, ileus, infection or haemorrhage (P > 0.05). ERAS did significantly reduce rates of delayed gastric emptying (DGE) from 82.8% pre-ERAS to 49.0% in the stage 2 of implementation phase (P < 0.001). ConclusionsThe early implementation of the ERAS programme was safe although some obstacles were encountered. ERAS was beneficial in increasing the proportion of patients reaching the target length of stay without increasing readmission, reoperation, or morbidity. Our findings support the continued development of ERAS in PD in order to standardise care and improve patient recovery.

A modified Ranson score to predict disease severity, organ failure, pancreatic necrosis, and pancreatic infection in patients with acute pancreatitis.

Although there are several scoring systems currently used to predict the severity of acute pancreatitis, each of them has limitations. Determine the accuracy of a modified Ranson score in predicting disease severity and prognosis in patients with acute pancreatitis (AP). AP patients admitted or transferred to our institution were allocated to a modeling group (n = 304) or a validation group (n = 192). A modified Ranson score was determined by excluding the fluid sequestration parameter and including the modified computed tomography severity index (CTSI). The diagnostic performance of the modified Ranson score was compared with the Ranson score, modified CTSI, and bedside index of severity in acute pancreatitis (BISAP) score in predicting disease severity, organ failure, pancreatic necrosis and pancreatic infection. The modified Ranson score had significantly better accuracy that the Ranson score in predicting all four outcome measures in the modeling group and in the validation group (all p < 0.05). For the modeling group the modified Ranson score had the best accuracy for predicting disease severity and organ failure, and second-best accuracy for predicting pancreatic necrosis and pancreatic infection. For the verification group, it had the best accuracy for predicting organ failure, second-best accuracy for predicting disease severity and pancreatic necrosis, and third-best accuracy for predicting pancreatic infection. The modified Ranson score provided better accuracy than the Ranson score in predicting disease severity, organ failure, pancreatic necrosis and pancreatic infection. Relative to the other scoring systems, the modified Ranson system was superior in predicting organ failure.

Clinical characteristics and risk factors for tigecycline-induced pancreatitis in a tertiary hospital: a retrospective study.

To analyze the clinical characteristics and risk factors for tigecycline-induced pancreatitis (TIP) and evaluate the safety and efficiency of tigecycline use in non-TIP. A retrospective case-control study was conducted on adult and juvenile patients administered tigecycline for >3 days. The adults were classified as TIP, non-TIP (pancreatitis with other causes), and non-pancreatitis. Univariate analyses were performed to compare TIP and non-pancreatitis, and multivariate analysis was used to identify risk factors for TIP. The clinical characteristics of TIP and the safety and efficiency of tigecycline use in non-TIP were evaluated. A total of 3910 patients (3823 adults and 87 juveniles) were enrolled. The adult patients comprised 21 TIP, 82 non-TIP, and 3720 non-pancreatitis. The TIP prevalences were 0.56% in adults and 1.15% in juveniles. The mean time from tigecycline use to symptom onset was 7.2 days, and all cases were mild pancreatitis. The mean time from tigecycline withdrawal to symptom relief was 3.6 days. The multivariate analysis identified comorbid renal insufficiency as an independent risk factor for TIP (odds ratio = 3.032). Among the 82 non-TIP patients, 81.7% had severe pancreatitis and 47.6% had necrotizing pancreatitis. The modified computed tomography severity score after tigecycline use was similar to that before tigecycline use, but the pancreatic enzymes and infection indices were significantly decreased. The prevalence of TIP was low. Comorbid renal insufficiency was as an independent risk factor for TIP. Tigecycline is safe and efficient for treatment of pancreatitis, especially necrotizing pancreatitis, with intra-abdominal infection.

Identification of Plant Peptides as Novel Inhibitors of Orthohepevirus A (HEV) Capsid Protein by Virtual Screening.

Hepatitis E virus (HEV) is the notable causative agent of acute and chronic hepatic, renal, pancreatic, neurological, and hematopoietic blood cell infections with high risk in immunocompromised patients. Hepatic failure is mostly documented among adults, pregnant women, and patients with preexisting liver disease. HEV is a positive sense RNA virus of 7.2 kb genome size with typically three open reading frames (ORFs) which play essential roles in viral replication, genome assembly, and transcription. The mutational substitution in the viral RNA genome makes more it difficult to understand the actual relationship in the host-virus association. ORFs of HEV encode different structural and non-structural proteins and one of them is the capsid protein which is coded by ORF2. The capsid protein mediates the encapsulation of the viral genome as well as being involved in virion assembly. In the current study, the ligand-based docking approach was employed to inhibit the active amino acids of the viral capsid protein. Depending upon S-score, ADMET profiling, and drug scanning, the top ten tetrapeptides were selected as potential drug candidates with no toxicity counter to HEV receptor protein. The S-score or docking score is a mathematical function which predicts the binding affinities of docked complexes. The binding affinity of the predicted drug-target complexes helps in the selectivity of the desired compound as a potential drug. The best two selected peptides (i.e., TDGH with S-score of -8.5 and EGDE with S-score of -8.0) interacted with the active site amino acids of the capsid protein (i.e., Arg399, Gln420, and Asp444). The molecular dynamics simulations of RMSD trajectories of TDGH-capsid protein and EDGE-capsid protein have revealed that both docked complexes were structurally stable. The study revealed that these tetrapeptides would serve as strong potential inhibitors and a starting point for the development of new drug molecules against the HEV capsid protein. In future, in vivo studies are needed to explore selected peptides as potential drug candidates.

Pancreatic Necrosis Infection as a Determinant of Multiple Organ Failure and Mortality in Acute Pancreatitis.

Several recommendations and data on the treatment of acute necrotizing pancreatitis (ANP) are conflicting and different surgical approaches continue to exist. We conducted a study on 148 patients with ANP, who were divided into two groups: the main group (n = 95) when the tactics of the step-up approach were applied with the principles of the concept of Enhanced Recovery After Surgery (ERAS) in order to determine this approach on effectiveness in reducing complications and 30-day mortality (2017-2022); the comparison group (n = 53) when the same tactic of the treatment was used without ERAS principles (2015-2016). Treatment time for the main group in the intensive care unit was minimized (p ≤ 0.004); it has been shown to reduce the frequency of complications in these patients (p < 0.001) requiring conservative or surgical treatment without general anaesthesia (Clavien-Dindo I-IIIa); no statistically significant differences were observed for the total incidence of Clavien-Dindo IIIb-IVb complications (p > 0.05); the median duration of treatment for patients in the primary group was 23 days, and in the reference group-34 days (p ≤ 0.003). Pancreatic infections have been observed in 92 (62.2%) patients and gram-negative bacteria predominated in the overall pathogen structure with 222 (70.7%) strains. The only evidence of multiple organ failure before (AUC = 0.814) and after surgery (AUC = 0.931) was found to be predictive of mortality. Antibiotic sensitivity of all isolated bacteria better understood local epidemiology and identified the most effective antibiotics when treating patients.

Efficacy and safety of early enteral and intravenous fluid resuscitation in severe acute pancreatitis: a systematic review and meta-analysis.

To compare the efficacy and safety of enteral fluid resuscitation (via nasointestinal tube or colorectal tube) and intravenous fluid resuscitation (via intravenous route) in the early treatment of severe acute pancreatitis. In this study, 8 electronic databases (PubMed, Web of Science, Embase, Cochrane Library, Scopus, China HowNet database, Wanfang database, and VIP database) were searched to collect clinical studies from inception to June 12, 2022. After the quality evaluation and data extraction of the included studies, the RevMan 5.3 software was used for analysis. A total of seven studies including 580 patients were studied in this meta-analysis, in which 291 cases were treated with enteral fluid resuscitation and 289 cases were treated with intravenous fluid resuscitation. Compared with the intravenous route group, the enteral route resuscitation group reduced the incidence of new organ failure (OR = 0.23, 95% CI: 0.12-0.43, P < 0.00001), the incidence of persistent organ failure (OR = 0.38, 95% CI: 0.22-0.64, P = 0.0003), the incidence of mechanical ventilation (OR = 0.15, 95% CI: 0.03-0.69, P = 0.01), the incidence of ICU care (OR = 0.49, 95% CI: 0.27-0.88, P = 0.02), and the incidence of pancreatic infection (OR = 0.38, 95% CI: 0.17-0.83, P = 0.02). There were no statistically significant differences in mortality (OR = 0.77, 95% CI: 0.35-1.66, P = 0.50), surgical intervention rate (OR = 0.47, 95% CI: 0.19-1.18, P = 0.11), and incidence of localized ascites (OR = 0.65, 95% CI: 0.25-1.73, P = 0.39). Early enteral fluid resuscitation is safe and effective for in severe pancreatitis. But this conclusion needs to be verified by more additional multi-centre randomized controlled trials with large samples.