Mesenchymal Stem Cells Inhibits the Shh/GLi (Sonic Hedgehog/GLi) Axis and Promotes Repair of Tissue Injury in Severe Acute Pancreatitis

Mesenchymal stem cells (MSCs) are indicated to severe pancreatitis (SAP), whilst level of Shh/GLi axis varies in severe acute pancreatitis (SAP). However, little is known the interaction between MSCs and Shh in SAP. In this study, we established animal model of SAP in 10 rats and transplanted MSCs into 10 rats, with another 10 sham-operated rats as control group. The pathological changes of rat pancreatic tissue were observed. ELISA was conducted to determine the MPO level of pancreatic inflammation, and Western blot to detect the expression level of Shh, Gli1 and Gli2 in tissues. Administration of MSCs remarkably alleviated the pancreatic tissue necrosis and inflammation and decreased blood loss in SAP rats. Up-regulated expression of Shh, Gli1 and Gli2 was observed in SAP tissues when compared to tissues in control group, but their expressions declined in the presence of MSCs, and 24 hour later returned to normal levels. Collectively, MSCs regulates the balance of Shh/GLi axis by decreasing Shh and Gli1, thereby attenuating progression and symptoms of SAP.

A Severe Acute Pancreatitis Mouse Model Transited from Mild Symptoms Induced by a “Two-Hit” Strategy with L-Arginine

To develop a severe acute pancreatitis (SAP) model transited from mild symptoms, we investigated a “two-hit” strategy with L-arginine in mice. The mice were intraperitoneally injected with ice-cold L-arginine (4 g/kg) twice at an interval of 1 h on the first day and subjected to the repeated operation 72 h afterwards. The results showed the “two-hit” strategy resulted in the destructive damage and extensive necrosis of acinar cells in the pancreas compared with the “one-hit” model. Meanwhile, excessive levels of pro-inflammatory mediators, namely IL-6 and TNF-α, were released in the serum. Remarkably, additional deleterious effects on multiple organs were observed, including high intestinal permeability, kidney injury, and severe acute lung injury. Therefore, we confirmed that the SAP animal model triggered by a “two-hit” strategy with L-arginine was successfully established, providing a solid foundation for a deeper understanding of SAP initiation and therapy research to prevent worsening of the disease.

Assessment of Prophylactic Carbapenem Antibiotics Administration for Severe Acute Pancreatitis: An Updated Systematic Review and Meta-Analysis

<b><i>Background:</i></b> The effectiveness of prophylactic antibiotics in severe acute pancreatitis (SAP) remains a debatable issue. This meta-analysis aimed to determine the efficacy of prophylactic carbapenem antibiotics in SAP. <b><i>Methods:</i></b> This meta-analysis of prophylactic carbapenem antibiotics for SAP was conducted in PubMed, EMBASE, Web of Science, MEDLINE, and Cochrane Library up to February 2021. The related bibliographies were manually searched. The primary outcomes involved infected pancreatic or peripancreatic necrosis, mortality, complications, infections, and organ failure. <b><i>Results:</i></b> Seven articles comprised 5 randomized controlled trials and 2 retrospective observational studies, including 3,864 SAP participants. Prophylactic carbapenem antibiotics in SAP were associated with a statistically significant reduction in the incidence of infections (odds ratio [OR]: 0.27; <i>p</i> = 0.03) and complications (OR: 0.48; <i>p</i> = 0.009). Nevertheless, no statistically significant difference was demonstrated in the incidence of infected pancreatic or peripancreatic necrosis (OR: 0.74; <i>p</i> = 0.24), mortality (OR: 0.69; <i>p</i> = 0.17), extrapancreatic infection (OR: 0.64, <i>p</i> = 0.54), pulmonary infection (OR: 1.23; <i>p</i> = 0.69), blood infection (OR: 0.60; <i>p</i> = 0.35), urinary tract infection (OR: 0.97; <i>p</i> = 0.97), pancreatic pseudocyst (OR: 0.59; <i>p</i> = 0.28), fluid collection (OR: 0.91; <i>p</i> = 0.76), organ failure (OR: 0.63; <i>p</i> = 0.19), acute respiratory distress syndrome (OR: 0.80; <i>p</i> = 0.61), surgical intervention (OR: 0.97; <i>p</i> = 0.93), dialysis (OR: 2.34; <i>p</i> = 0.57), use of respirator or ventilator (OR: 1.90; <i>p</i> = 0.40), intensive care unit treatment (OR: 2.97; <i>p</i> = 0.18), and additional antibiotics (OR: 0.59; <i>p</i> = 0.28) between the experimental and control groups. <b><i>Conclusions:</i></b> It is not recommended to administer routine prophylactic carbapenem antibiotics in SAP.

Efficacy of Nasogastric and Nasojejunal Enteral Feeding in the Early Phase of Acute Pacreatitis

Enteral nutrition in the early phase of predicted severe acute pancreatitis can be administered via a nasogastric or nasojejunal tube. Finding the most effective method in terms of daily balance, the volume of feeding and residual gastric volume in the early period of moderate and severe acute pancreatitis is a current challenge.The aim of the study was to estimate the efficacy of nasogastric and nasojejunal early enteral feeding duringthe early phase of predicted severe acute pancreatitis.Material and methods. The study was prospective, single-center, and randomized. The data were collected from November 2012 to October 2018. The study included 64 ICU patients in the early period of acute pancreatitis exhibiting predictors of severity. During randomization, the patients were assigned to either nasogastric (group 1) or nasojejunal (group 2) feeding for the next four days. The volume of enteral feeding on Day 1 was 250 ml/day, and on each successive day it was increased by 250 ml/day. During group allocation, the disease severity and the way of nutrient administration were taken into account. Daily balance was calculated using the difference between enterally administered and residual gastric volume. Statistical analysis was performed using SPSS v.23 software package. The null hypothesis was rejected at P0.05.Results. The volume of enteral nutrition administered over 4 days did not differ between the study groups. Patients with severe acute pancreatitis had significantly better nutrient absorption over 4 days when the postpyloric route was used (1.63±0.98 l/d) vs the nasogastric one (0.55±0.29 l/d) (P=0.001). In moderate pancreatitis, the enteral nutrition absorption over 4 days did not differ (P=0.107) between the groups with nasogastric (2.06±0.87 l/day) and nasojejunal (2.6±0.45 l/day) feeding.Conclusion. Nasojejunal route is the preferred way to start enteral feeding in patients with severe acute pancreatitis. In moderate acute pancreatitis, feeding can be initiated via the gastric route and only in case of intolerance it should be switched to the nasojejunal one.

Acute Pancreatitis Coincided with Multiple Arteriolar Aneurysms in a Patient with Polyarteritis Nodosa

A 78-year-old man presented to our hospital with a history of 10kg weight loss within 6 months previously, and general fatigue and fever for 2 and 1 months, respectively. On hospitalization, the patient was diagnosed with polyarteritis nodosa after multiple microaneurysms were observed in the liver, kidney, pancreas, and mesenteries. He achieved remission with the administration of 1,000mg methylprednisolone for 3 days, followed by prednisolone (55mg/day). Steroids were successfully tapered with no re-elevation in inflammation. Two months after the administration of steroids, the patient complained of acute abdominal pain, and developed severe acute pancreatitis. During treatment for pancreatitis, the patient died due to septic shock and disseminated intravascular coagulation. An autopsy revealed necrotizing vasculitis in the intrapancreatic arteries and ischemia of the downstream arterioles resulting in acute pancreatitis.

Features of treatment of severe acute pancreatitis in obese patients

The purpose of the work is to improve the results of treatment of severe acute pancreatitis in obese patients and to develop an algorithm for comprehensive treatment. Materials and methods. Patients with severe acute pancreatitis and obesity (mean BMI 37.48 ± 2.19 kg/m2) were randomized into two groups. In the experimental group (n = 18; step-up approach),early resuscitation with Ringer's lactate solution and ulinastatin in the first 5 days of the disease was used. Unilastatin was administered at a dose of 200,000IU by 1-hourintra­venous infusion TID for 5 days. The first stage of surgery was a drainage under ultrasound control, the second stage (if necessary) was laparos­copic retroperitoneal necrectomy (video-assisted­retroperitoneal debri­de­ment — VARD). Open surgery was performed in case of development of abdominal compartment syndrome. In the control group (n = 18; standard approach), resuscita­tion was performed with 0.9 % sodium chlo­ride solution without ulinastatin. The first stage of surgery was draina­ge under ultrasound control, the second stage was traditional median laparotomy with laparostomy. Results. The use of resuscitation with Ringer’s lactate solution in combination with ulinastatin for 5 days contributed to a decrease of procalcitoninlevels by 1.8 times (2.89 ± 0.88 compared with 1.8 ± 0.23 ng/mg; p = 0.001; α = 0.05). The level of CRP during the period of ulinastatin decreased by 41.68 mg/l (267.28 ± 114.11 compared with 225.6 ± 84.9 mg/l; p = 0.01; α = 0.05). There was a statistically significant difference in procalcitonin levels between groups on the 10th day (1.83 compared with 3.32 ng/mg; p = 0.001; α = 0.05), on the 15th day (1.15 compared with 1 .83 ng/mg; p = 0.001; α = 0.05) and on the 45th day (0.35 compared with 0.55 ng/mg; p = 0.001; α = 0.05). These results confirm the effect of the proposed method of treatment by reducing the risk of infection. Conclusions. The effectiveness of the proposed treatment algorithm is evidenced by a statistically significant difference in the level of CRP between groups on the 10th day (p = 0.035; α = 0.05). The use of VARD in the experimental group as a second stage of surgery is a less traumatic but effective method (p = 0.001; α = 0.05), which reduces the total number of complications (χ² = 4.012; p = 0.046). Evaluation of data «before—after» revealed the effectiveness of treatment by step-up approach (χ² = 5.4; p = 0.021).