Early Stage Of Severe Acute Pancreatitis Research Articles

Early Predictors of Infected Pancreatic Necrosis in Severe Acute Pancreatitis: Implications of Neutrophil to Lymphocyte Ratio, Blood Procalcitonin Concentration, and Modified CT Severity Index

Background: Infected pancreatic necrosis (IPN) accounts for 30% mortality in severe acute pancreatitis (SAP). Early prediction of IPN occurrence is critical for prophylactic measures to be taken. This study aimed to evaluate the predicting value for IPN of combined markers at early stages of SAP. Methods: The clinical records of 324 SAP patients admitted within 48 h after disease onset were retrospectively analyzed. As potential predictors, the neutrophil to lymphocyte ratio (NLR), blood procalcitonin (PCT) concentration on the 1st, 4th, and 7th day post admission, as well as modified computerized tomography severity index (MCTSI) on the 5–7th day post admission, were extracted. Correlations between these features with IPN were analyzed using logistic regression, and predictive values were estimated using the receiver operating characteristic curve analyses. Results: NLR, PCT, body mass index, and MCTSI were significantly higher in the IPN group (p < 0.001) compared to the control, among which NLR, PCT, and MCTSI were identified as independent predictors for IPN in logistic regression model. Combination of these parameters yielded significant predicting values with an area under curve of 0.92, sensitivity of 97.2%, and specificity of 77.2% in receiver operating characteristic curve analysis. Conclusion: Combination of NLR, PCT, MCTSI might facilitate the prediction of IPN occurrence in SAP patients.

Association between albumin or prealbumin levels at different stages and prognosis in severe acute pancreatitis: a 5-year retrospective study

Severe acute pancreatitis (SAP) is a common abdominal disorder contributing to high mortality and open laparotomy rates. The role of exogenous infused albumin in fluid resuscitation or continuous therapy has always been an unanswered question. In early stage after onset, SAP patients with higher serum albumin or prealbumin show a better prognosis. In this study, we tried to disclose the linkage between albumin/prealbumin and SAP prognosis and establish a new goal-directed therapy involving albumin and prealbumin. Pearson’s chi-squared test and the Mann–Whitney U test were used to compare the descriptive data between surviving and non-surviving patients. Three days, 4–7 days, 8–14 days and 15–28 days after SAP onset were defined as stages 1–4. The average concentrations of albumin and prealbumin were calculated, and receiver operating characteristic (ROC) curves were drawn to screen out the best cutoff values associated with poor prognostic outcomes, including laparotomy and failure to survive. Kaplan–Meier survival curves and log-rank tests were used to validate the effect of the cut-off values. A total of 199 admitted patients were enrolled in this study. According to the analysis of the ROC curve, the serum albumin value should be raised to 35, 37, 40 and 42 g/L in the 1–4 stage after onset. Serum prealbumin values should be raised to 108, 180, and 181 g/L in stages 2–4 after onset. The validity of the above data was confirmed by Kaplan–Meier survival curves. Serum albumin and prealbumin levels in the early stage of SAP are significantly relevant to prognosis. Albumin should be infused from the fluid resuscitation stage to continuous therapy in order to reach the targets mentioned above. The increase in prealbumin depends on the early initiation of enteral nutrition and this also helps to ameliorate the prognosis.

“PERFUSION CT IN PREDICTING THE DEVELOPMENT OF PANCREATIC NECROSIS IN EARLY STAGE OF SEVERE ACUTE PANCREATITIS”

PURPOSE: To evaluate the role of perfusion CT (PCT) scan in predicting the development of pancreatic necrosis (PN) in early stage of severe acute pancreatitis (SAP). MATERIALS AND METHODS: A total of 20 adult patients with a clinical diagnosis of SAP presenting within 72 hours of onset of symptoms with a positive SIRS criteria were included in the study. All the patients underwent PCT on a 128 slice MDCT scannerusing 40 ml of non-ionic iodinated contrast followed by post processing using vendor provided CT perfusion software whereby perfusion parameters were calculated. Perfusion defect (PD) was dened as pancreatic BF and/or BV qualitatively less than hepatic BF and/or BV respectively on the color coded maps. A follow up CECT abdomen was done after 2 weeks as a 'gold standard' to assess whether PN developed in the corresponding region of PD. RESULTS: 8 out of 20 patients developed perfusion defect (PD) on the PCT, of which 6 patients developed PN on the follow up scan. Patients who did not show any PD on the PCT (12 out of 20) did not develop necrosis on the follow up CECT. The sensitivity, specicity, PPV, NPV and accuracy of PCT in predicting necrosis was 100%, 85.71%, 75%, 100% and 90% respectively. The cut off values of pancreatic BF and BV in predicting the development of PN were 34.87 ml/100ml/min and 11.70ml/100ml respectively based on the ROC curve. CONCLUSION: PCT is a useful technique that can predict development of PN in the early stage of SAP so that early aggressive management can be initiated.

Luzhou-Feier powder reduces inflammatory response and improves intestinal immune barrier in rats with severe acute pancreatitis.

As we know, nutritional support plays a key role in the treatment of severe acute pancreatitis (SAP). Since total parenteral nutrition (TPN) was discovered, the mortality of SAP had been greatly reduced. But researchers recently demonstrated that the prognosis of SAP could be improved by early enteral nutrition (EEN), which has been a priority for nutritional support in patients with SAP. However, implementation of total enteral nutrition is often challenging in the early stage of SAP. If the enteral nutrition is overused, the burden on the gastrointestinal tract will be aggravated. Under such circumstances, the combination of enteral and parenteral nutrition for nutritional support of SAP patients would be a better choice. Therefore, in this study, we compared the efficacy of two enteral nutrition agents: traditional nutritional supplement named Luzhou-Feier powder (LZ-FP) and enteral nutritional suspension (TPF) combined with parenteral nutrition to total parenteral nutrition (TPN) in the treatment of SAP rats. Our analysis revealed that the combination of enteral nutrition and parenteral nutrition was more effective than TPN in SAP. And LZ-FP met the requirements for enteral nutrition of SAP supporting its clinical application in SAP. PRACTICAL APPLICATIONS: Luzhou-Feier powder (LZ-FP) is a traditional Chinese nutritional supplement that was originally developed as a nutritional supplement for infants and is currently used for nutritional support in patients with chronic and consumptive diseases. Our research investigated the effect and its possible mechanisms of LZ-FP as early trophic enteral nutrition in SAP rats and compared it with TPF and TPN which have been used clinically. We found that LZ-FP helped to reduce inflammatory response and improve the intestinal immune barrier of SAP. The curative effect of LZ-FP was comparable to that of TPF. And this effect may be achieved by inducing the secretion of gut hormones. Our research indicates that LZ-FP should be considered as an enteral nutrition preparation for SAP.

Cardiac indicator CK-MB might be a predictive marker for severity and organ failure development of acute pancreatitis.

BackgroundThe prediction of severe acute pancreatitis (SAP) is the key to providing timely and targeted intensive care for acute pancreatitis (AP). The heart is one of multiple organs involved in the early stage of SAP, but the predictive ability of cardiac dysfunction for SAP remains elusive. We sought to determine if the serum levels of three cardiac indicators (CI) including N-terminal pro-brain natriuretic peptide (NT-proBNP), cardiac troponin I (cTNI), and creatine kinase myocardial band (CK-MB) at admission could predict the occurrence of SAP and the development of related organ failure (OF).MethodsA retrospective, single-center cohort study was conducted on the files of patients presenting to the emergency intensive care unit and medical ward of a regional hospital in Shanghai. Patients diagnosed as having AP and who met the 2012 Atlanta guideline were admitted within 48 hours after disease onset.ResultsOf the 670 AP patients screened, 238 were enrolled into the study and divided into mild acute pancreatitis (MAP) (n=59), moderate severe acute pancreatitis (MSAP) (n=123), and SAP (n=56) groups. No significant difference was found in baseline age, gender, duration from disease onset to admission, comorbidity, or substance abuse. As the levels of three CIs were significantly higher in the SAP group than in the MAP and MSAP groups, the enrolled patients were regrouped into non-SAP and SAP groups for predictive evaluation. Multivariate analysis and nomogram modelling showed that CK-MB, but not cTNI or NT-proBNP predicted the occurrence of SAP [area under curve (AUC) =0.805, confidence interval (CI): 0.794–0.905]. Specifically, 89 patients with OF (Modified Marshall score ≥2) upon admission were selected and CK-MB was shown to predict (AUC =0.805, CI: 0.794–0.905) persistent OF (n=48, duration of OF >48 hours) compared to transient organ failure (TOF) (n=41, duration of OF <48 hours).ConclusionsCIs including NT-proBNP, cTNI, and CK-MB were elevated in the early stage of AP. CK-MB might be used as an efficient predictive biomarker for SAP occurrence and OF development at admission.

Adoption of Computerized Tomography Quantitative Imaging Data in the Evaluation of Severe Acute Pancreatitis by Pleural Effusion

In order to study the pleural effusion (PE) in Severe acute pancreatitis (SAP) in patients with the clinical value of diagnosis, in this study, 78 patients with SAP who were included in Shandong Jinan Municipal Hospital of Traditional Chinese Medicine from January 31, 2017 to December 30, 2019 were selected as the experimental group (EG) and 78 patients with mild acute pancreatitis (MAP) as the control group (CG). The PE was diagnosed by computerized tomography (CT) imaging technology, and the patients with PE in the two groups were divided into small group, medium group and large group according to the volume of PE. The concurrent symptoms of SAP were recorded, and the relation between the occurrence of PE and the complications of SAP was analyzed by a multivariate Logistic regression model (LRM). It was concluded that the concurrent rate of PE in the EG was greatly higher than that in the CG, and the number of cases in the medium and multiple groups was also greatly higher than that in the CG (P &lt; 0.05). There were statistically significant differences (SSD) in acute renal failure, hypovolemic shock and pancreatic pseudocyst in the PE small amount group, medium amount group and large amount group (P &lt; 0.05). The complications of SAP in patients with acute renal failure, hypovolemic shock and pancreatic pseudocyst were positively correlated with age and PE (P &lt; 0.05), which showed that CT could present the PE more directly, which was beneficial to the diagnosis of SAP. In addition, the increased amount of PE indicated the aggravation of SAP and the occurrence of concurrent symptoms, which is helpful for early assessment of patients’ condition and prediction of poor prognosis as an independent indicator to evaluate the early stage of SAP.

Role of gut microbiota on intestinal barrier function in acute pancreatitis.

Acute pancreatitis (AP) is a common gastrointestinal disorder. Approximately 15%-20% of patients develop severe AP. Systemic inflammatory response syndrome and multiple organ dysfunction syndrome may be caused by the massive release of inflammatory cytokines in the early stage of severe AP, followed by intestinal dysfunction and pancreatic necrosis in the later stage. A study showed that 59% of AP patients had associated intestinal barrier injury, with increased intestinal mucosal permeability, leading to intestinal bacterial translocation, pancreatic tissue necrosis and infection, and the occurrence of multiple organ dysfunction syndrome. However, the real effect of the gut microbiota and its metabolites on intestinal barrier function in AP remains unclear. This review summarizes the alterations in the intestinal flora and its metabolites during AP development and progression to unveil the mechanism of gut failure in AP.

Fluid resuscitation via the rectum ameliorates hemodynamic disorders through adjusting aquaporin expression in an experimental severe acute pancreatitis model

Acute pancreatitis is an acute abdominal disease, with 10-20% of the cases deteriorating rapidly, accompanied by persistent organ failure and further development into severe acute pancreatitis (SAP). The aim of the present study was to investigate the mechanism of fluid resuscitation via the rectum in the early stages of SAP and the role of aquaporins (AQPs). An SAP model was constructed by injection of 5% sterile sodium taurocholate into the biliopancreatic duct of Sprague Dawley rats, and the mean arterial pressure (MAP) was continuously monitored via femoral artery catheterization. At 30 min after the construction of the SAP model, the rats in the fluid resuscitation groups were resuscitated with normal saline at a rate of 4 ml/kg/h through the venous or the rectal route. The AQP and Na+-K+-ATPase levels, and the correlation of the MAP and colon AQPs at the early stages of SAP were analyzed. The results demonstrated that the mRNA level of AQP-3 and AQP-4 in the distal colon decreased significantly in the group subjected to fluid resuscitation via the rectum, while no significant differences were identified in the Na+-K+-ATPase levels of the colon in that group. Furthermore, a negative correlation was identified between the expression of AQPs and the MAP (P<0.01). Thus, fluid resuscitation via the rectum appears to ameliorate hemodynamic disorders through adjusting the expression of AQP-3 and AQP-4 in the distal colon in an experimental SAP model.

Portosplenomesenteric vein thrombosis in patients with early-stage severe acute pancreatitis.

AIMTo investigate the incidence and risk factors of portosplenomesenteric vein thrombosis (PSMVT) in the early stage of severe acute pancreatitis (SAP).METHODSPatients with SAP in a tertiary care setting from January 2014 to December 2016 were retrospectively reviewed. All contrast-enhanced computed tomography (CT) studies were reassessed and reviewed. Clinical outcome measures were compared between SAP patients with and without PSMVT in the early stage of the disease. Univariate and multivariate logistic regression analyses were sequentially performed to assess potential risk factors for the development of PSMVT in SAP patients. A receiver operating characteristic (ROC) curve was generated for the qualifying independent risk factors.RESULTSTwenty-five of the one hundred and forty (17.86%) SAP patients developed PSMVT 6.19 ± 2.43 d after acute pancreatitis (AP) onset. PSMVT was confirmed by contrast-enhanced CT. Multivariate stepwise logistic regression analyses showed that Balthazar’s CT severity index (CTSI) scores [odds ratio (OR): 2.742; 95% confidence interval (CI): 1.664-4.519; P = 0.000], hypoalbuminemia (serum albumin level < 25 g/L) (OR: 32.573; 95%CI: 2.711-391.353; P = 0.006) and gastrointestinal wall thickening (OR: 4.367, 95%CI: 1.218-15.658; P = 0.024) were independent risk factors for PSMVT developed in patients with SAP. The area under the ROC curve for Balthazar’s CTSI scores was 0.777 (P = 0.000), the sensitivity was 52%, and the specificity was 93% at a cut-off value of 5.5.CONCLUSIONHigh Balthazar’s CTSI scores, hypoalbuminemia and gastrointestinal wall thickening are independent risk factors for PSMVT developed in the early stage of SAP.

Effects of inhibiting peritoneal macrophage caspase recruitment domain-containing protein 9 on inflammatory reaction of severe acute pancreatitis in rats

Objective To investigate the effects of caspase recruitment domain-containing protein 9 (CARD9) expression in peritoneal macrophages on severe acute pancreatitis (SAP) in rats and its mechanism. Methods A total of 60 male Sprague Dawley rats were divided into control group (n=6), SAP group (n=18), small interfering RNA (siRNA) control group (n=18) and siRNA CARD9 group (n=18). SAP rat models were established. At three, six and twelve hours after the models were established, ascites was collected, peritoneum was lavaged and peritoneal macrophages were isolated and cultured. The expressions of CARD9, nuclear factor-kappaB (NF-κB), p38 mitogen-activated protein kinase (p38MAPK) at mRNA level in peritoneal macrophages was measured by real-time polymerase chain reaction (RT-PCR). The levels of tumor necrosis factor-α (TNF-α), interleukin (IL)-1β and IL-6 in peripheral blood were detected by enzyme-linked immunosorbent assay (ELISA). LSD or Tamhane′s T2 methods were performed for statistical analysis. Results At three, six and twelve hours after the models were established, CARD9 mRNA levels of peritoneal macrophages in SAP group were 1.63±0.05, 1.68±0.24 and 2.61±0.02, respectively, which were all higher than that of control group (1.01±0.23), and the differences were statistically significant (t=25.97, 6.86 and 131.59; all P<0.05); the levels of CARD9 mRNA of siRNA CARD9 group were 1.45±0.02, 1.24±0.03 and 1.63±0.03, respectively, which were lower than that of SAP group at the same time points, and the differences were statistically significant (t=-7.81, -4.46 and -62.13; all P<0.05). At three, six and twelve hours after the models were established, the mRNA levels of NF-κB and p38MAPK of peritoneal macrophages of rats in SAP group were 1.51±0.08, 1.81±0.10, 2.30±0.05 and 1.37±0.13, 1.69±0.18, 2.42±0.23, respectively, which were higher than those of control group (1.00±0.01, 1.03±0.08), and the differences were statistically significant (tNF-κB=15.10, 19.95 and 60.36; tp38MAPK=5.37, 8.34 and 14.11; all P<0.05); the levels of NF-κB mRNA in siRNA CARD9 group were 1.38±0.05, 1.57±0.06 and 1.76±0.09, respectively, which were lower than that of SAP group at the same time points, and the differences were statistically significant (t=-3.32, -5.07 and -12.70; all P<0.05). At six and twelve hours after the models were established, the p38MAPK mRNA levels of siRNA CARD9 group were 1.50±0.10 and 2.00±0.09, respectively, which were lower than that of SAP group, and the differences were statistically significantly (t=-2.30 and -4.17, both P<0.05). At three, six and twelve hours after the models were established, the levels of TNF-α, IL-1β and IL-6 in peripheral blood of SAP group were (53.49±21.64) pg/mL, (108.62±22.76) pg/mL and (139.00±15.35) pg/mL; (43.86±18.30) pg/mL, (87.51±17.10) pg/mL and (117.27±14.57) pg/mL; (78.38±32.70) pg/mL, (156.39±30.56) pg/mL and (209.56±26.09) pg/mL, respectively, which were higher than those of control group ((2.79±1.17), (7.13±4.52), (12.73±8.08) pg/mL), and the differences were statistically significant (tTNF-α=5.73, 11.37 and 21.69; tIL-1β=4.77, 11.13 and 17.68; tIL-6=4.77, 11.32 and 17.68; all P<0.05). At six and twelve hours after the models were established, the levels of TNF-α, IL-1β and IL-6 of siRNA CARD9 group were (75.73±16.93) pg/mL, (108.23±14.02) pg/mL; (63.05±11.98) pg/mL, (91.56±14.28) pg/mL and (112.67±21.40) pg/mL, (163.62±25.51) pg/mL, respectively, which were lower than those of SAP group, and the differences were statistically significant (tTNF-α=-2.84, -3.63; tIL-1β=-2.88, -3.09; tIL-6=-2.88, -3.09; all P<0.05). Conclusions There are CARD9-related NF-κB and p38MAPK pathways in peritoneal macrophages of SAP rats. Intervention of the expression of CARD9 in peritoneal macrophages, especially at early stage of SAP may relieve the inflammation reaction and pancreatic injury, which may provide a new method for SAP treatment. Key words: Macrophages, abdominal cavity; NF-kappaB; p38 mitogen-activated protein kinases; RNA, small interfering; Rats; Pancreatitis, severe acute; Caspase recruitment domain-containing protein 9

Adenovirus-mediated artificial miRNA targetting fibrinogen-like protein 2 attenuates the severity of acute pancreatitis in mice.

Severe acute pancreatitis (SAP) remains to be challenging for its unpredictable inflammatory progression from acute pancreatitis to SAP. Apoptosis is an important pathology of SAP. Fibrinogen-like protein 2 (FGL2) has been reported to be involved in apoptosis. The present study aimed to explore the therapeutic effect of an adenovirus-mediated artificial miRNA targetting FGL2 (Ad-FGL2-miRNA) in taurocholate-induced murine pancreatitis models. Sodium taurocholate was retrogradely injected into the biliopancreatic ducts of the C57/BL mice to induce SAP. FGL2 expression was measured with reverse transcription-PCR, Western blotting, and immunohistochemical staining. ELISA was used to detect the activity of amylase and the concentrations of tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β). In addition, the mRNA levels of TNF-α and IL-1β were also detected. Finally, apoptosis was assessed by terminal deoxynucleotidyl transferase mediated dUTP-biotin nick-end labeling (TUNEL) method and Western blotting. Ad-FGL2-miRNA significantly suppressed FGL2 expression and alleviated pancreatic injury. Also, Ad-FGL2-miRNA markedly inhibited a post-SAP increase in the activation of TNF-α and IL-1β. Finally, pretreatment with Ad-FGL2-miRNA ameliorated apoptosis at the early stage of SAP by modulating cleaved caspase-3 and therefore played a protective role. These results indicated that FGL2 might be a promising target for attenuating the severity of SAP and adenovirus-mediated artificial miRNAs targetting FGL2 represented a potential therapeutic approach for the treatment of SAP.

582: THE IMPACT OF INTRACRANIAL PRESSURE MONITOR USE ON OUTCOMES IN CHILDREN WITH HEPATIC ENCEPHALOPATHY

582: THE IMPACT OF INTRACRANIAL PRESSURE MONITOR USE ON OUTCOMES IN CHILDREN WITH HEPATIC ENCEPHALOPATHY

Early prediction of intestinal mucosal barrier function impairment by elevated serum procalcitonin in rats with severe acute pancreatitis.

The aim of this study was to evaluate serum procalcitonin (PCT) levels as a prognostic indicator of intestinal barrier function impairment in rats with severe acute pancreatitis (SAP). Thirty-six male Sprague Dawley rats were randomly grouped into SAP group (injected sodium taurocholate via biliopancreatic duct), Gln group (gavaged with glutamine after modeling), and control group. Blood, pancreatic, and terminal ileum tissues were obtained from the rats after 6hof modeling. Serum amylase (Amy) levels were determined using an automatic biochemical detector, while endotoxin (ET), diamine oxidase (DAO), and PCT levels were measured by ELISA test. The pathology of pancreatic and small intestine tissues were observed. PCT protein expression in intestinal tissues were detected by immunohistochemistry and western blot. Pancreatic and intestinal injuries in Gln group were significantly lower than SAP group. Serum amylase, DAO, and PCT levels in SAP and Gln groups differed greatly and were significantly higher than control group. Immuno-histochemistry and western blot results showed that PCT protein expression levels in small intestine tissues of SAP group were higher than Gln group and control group. Serum PCT levels had a significant correlation with serum endotoxin, DAO levels and intestinal mucosal injury scores. PCT expression in serum and intestinal tissues in SAP rats increased significantly in the early stages of SAP, and was closely related to the onset and degree of intestinal barrier function impairment. Thus, our results showed that measuring serum PCT can be used to predict intestinal mucosal barrier function impairment in SAP rats.

Ultrastructural changes in the pulmonary mechanical barriers in a rat model of severe acute pancreatitis-associated acute lung injury

ABSTRACTThis study examined the ultrastructural changes in the pulmonary mechanical barriers in a rat model of severe acute pancreatitis (SAP)-associated acute lung injury (ALI). Animals were randomized into the SAP group (n = 60) and the control group (n = 60). SAP was induced by retrograde injection of 5% taurocholic acid into the biliopancreatic duct. The morphological abnormalities assessed by histology and the lung wet/dry weight ratio and the ultrastructural abnormalities assessed by transmission electron microscope and scanning electron microscope examinations plus lanthanum nitrate tracing were compared between the two groups at 6, 12, and 24 h post-SAP induction (n = 10/group/time point). The SAP group had significantly greater extravascular effusion than the control group at each time point as assessed by the lung wet/dry weight ratio (p < .001). The severity of the tissue damage increased in the lung and pancreas over time in the SAP group (all p < .001). In the SAP group, ultrastructural damages to the endothelial, epithelial, and pleural barriers were apparent and the damages to the endothelial barrier were detected earlier than the other two barriers, suggesting its fundamental role in preventing the further development of SAP-associated ALI. Moreover, the ultrastructural abnormalities were detected earlier than symptoms and morphological changes. The ultrastructural damages in the endothelial, epithelial, and pleural barriers occurred in the early stage of SAP. The endothelial barrier is likely to be the first line to prevent the further development in this rat model of SAP-associated ALI.

Beneficial effects of fluid resuscitation via the rectum on hemodynamic disorders and multiple organ injuries in an experimental severe acute pancreatitis model.

Exaggerated hydration is harmful for patients with severe acute pancreatitis (SAP), and it can increase mortality rate. In this study, we investigated the role of fluid resuscitation via the rectum (FRVR) on the hemodynamic state and compared FRVR with intravenous fluid resuscitation (IVFR) on resuscitation effect and organ function in an early stage of SAP. We studied whether FRVR corrects hemodynamic disorders at an early stage of SAP in Spraque-Dawley (SD) rats and whether it mitigates organ dysfunction and whether FRVR is superior to IVFR. In both IVFR and FRVR groups, we observed a rebound in the mean arterial pressure (MAP) after 5 h and 6 h of administration (p < 0.05), respectively. MAP of the FRVR group reached the same level as the SHAM group at the end of the treatment, with hematocrit declining compared with the non-fluid resuscitation (NFR) group (p < 0.05). A concomitant increase in abdominal ascites and the lung wet/dry ratio by IVFR was depressed in the FRVR group (p < 0.05). Liver function was ameliorated in both fluid resuscitation groups (p < 0.05), consistent with histopathological improvement. TNF-α in serum and MPO in the lungs and jejunum of the FRVR group were lower than the IVFR group (p < 0.05). Pancreas histopathological injuries were ameliorated by both IVFR and FRVR (p < 0.05). Our findings suggested FRVR is a potential supplementary method for fluid management in an early stage of SAP and FRVR should be studied further.

The imbalance between matrix metalloproteinase 9 and tissue inhibitor of metalloproteinase 1 in acute pancreatitis.

The balanced activity of matrix metalloproteinases and their tissue inhibitors is an important, albeit still not completely understood, determinant of extracellular matrix homeostasis, a factor involved in the pathogenesis of acute pancreatitis (AP). The aim of this study was to compare serum concentrations of matrix metalloproteinase 9 (MMP-9) and its tissue inhibitor (TIMP-1) in patients with AP of various severity and to investigate their relationship with prognostic indicators of AP severity, e.g., polymorphonuclear leukocyte elastase (PMN-E). The study included 37 patients with mild (n = 18) or severe AP (n = 19) and 15 healthy controls. Serum concentrations of MMP-9 and TIMP-1 were determined on admission (day 1) and on days 2, 3, 5 and 10. Throughout the study period, the serum MMP-9 concentration in patients with severe AP was significantly higher than those in individuals with mild AP and in healthy controls. In turn, the serum MMP-9 concentrations in persons with mild AP did not differ significantly from those of the controls. The serum TIMP-1 concentrations in both groups were significantly higher than in the controls. Beginning from the 2(nd) day of hospital stay, the serum TIMP-1 concentration in patients with severe AP was significantly higher than in individuals with mild AP. There were significant correlations between: MMP-9 and PMN-E, TIMP-1 and PMN-E, and MMP-9 and TIMP-1. A disturbed balance between MMP-9 and TIMP-1 observed during the early stages of severe AP suggests that endogenous TIMP-1 is unable to prevent excessive activation and release of MMP-9. MMP-9 may represent a new marker of AP severity.

Perirenal space blocking restores gastrointestinal function in patients with severe acute pancreatitis

To investigate effects of perirenal space blocking (PSB) on gastrointestinal function in patients with severe acute pancreatitis (SAP). Forty patients with SAP were randomly allocated to receive PSB or no PSB (NPSB). All the SAP patients received specialized medical therapy (SMT). Patients in the PSB group received PSB + SMT when hospitalized and after diagnosis, whereas patients in the NPSB group only received SMT. A modified gastrointestinal failure (GIF) scoring system was used to assess the gastrointestinal function in SAP patients after admission. Pain severity (visual analog scale, 0 to 100) was monitored every 24 h for 72 h. Modified GIF score decreased in both groups during the 10-d study period. The median score decrease was initially significantly greater in the PSB group than in the NPSB group after PSB was performed. During the 72-h study period, pain intensity decreased in both groups. The median pain decrease was significantly greater in the PSB group than in the NPSB group at single time points. Patients in the PSB group had significantly lower incidences of hospital mortality, multiple organ dysfunction syndrome, systemic inflammatory response syndrome, and pancreatic infection, and stayed in the intensive care unit for a shorter duration. However, no difference in terms of operation incidence was found between the two groups. PSB could ameliorate gastrointestinal dysfunction or failure during the early stage of SAP. Moreover, PSB administration could improve prognosis and decrease the mortality of SAP patients.

Effects of early enteral nutrition on immune function of severe acute pancreatitis patients

To investigate the effects of early enteral nutrition (EEN) on the immune function and clinical outcome of patients with severe acute pancreatitis (SAP). Patients were randomly allocated to receive EEN or delayed enteral nutrition (DEN). Enteral nutrition was started within 48 h after admission in EEN group, whereas from the 8(th) day in DEN group. All the immunologic parameters and C-reactive protein (CRP) levels were collected on days 1, 3, 7 and 14 after admission. The clinical outcome variables were also recorded. Sixty SAP patients were enrolled to this study. The CD4+ T-lymphocyte percentage, CD4+/CD8+ ratio, and the CRP levels in EEN group became significantly lower than in DEN group from the 7(th) day after admission. In contrast, the immunoglobulin G (IgG) levels and human leukocyte antigen-DR expression in EEN group became significantly higher than in DEN group from the 7(th) day after admission. No difference of CD8+ T-lymphocyte percentage, IgM and IgA levels was found between the two groups. The incidences of multiple organ dysfunction syndrome, systemic inflammatory response syndrome, and pancreatic infection as well as the duration of intensive care unit stay were significantly lower in EEN group than in DEN group. However, there was no difference of hospital mortality between the two groups. EEN moderates the excessive immune response during the early stage of SAP without leading to subsequent immunosuppression. EEN can improve the clinical outcome, but not decrease the hospital mortality of SAP patients.

The Role of Sphingosine Kinase 1 in Patients With Severe Acute Pancreatitis

To investigate the role of sphingosine kinase 1 (SphK1)/sphingosine 1-phosphate (S1P) signaling in inflammatory response in severe acute pancreatitis (SAP). SAP is an acute inflammatory process of the pancreas, which may lead to systemic inflammatory response syndrome and multiorgan dysfunction syndrome. SphK1 and its product S1P have been implicated in inflammatory response and various immune cell functions. However, the potential role for SphK1/S1P in inflammatory response in SAP is still unclear. Twenty-two patients with SAP were enrolled in this study. SphK1 expression on peripheral neutrophils, monocytes, and lymphocytes was evaluated by flow cytometry. SphK enzymatic activity in neutrophils and lymphocytes was measured using a radiometric assay. The expression of S1P1 and S1P3 mRNA was determined by reverse transcriptase-polymerase chain reaction (RT-PCR). The serum levels of tumor necrosis factor-α (TNF-α), interleukin-1 (IL-1β), and IL-6 were measured by ELISA. The expression of SphK1 and SphK activity were markedly increased in peripheral immune cells in the early stage of SAP and then reduced in the restoration stage in the patients. Moreover, we found that the level of S1P3 mRNA in peripheral neutrophils and lymphocytes of SAP patients was significantly elevated in the early stage as compared with the healthy volunteers, and it reduced in the restoration period. SphK1 expression on human peripheral neutrophils, monocytes, and CD4(+) T lymphocytes were positively correlated with the APACHE (Acute Physiological and Chronic Health Evaluation) II scores in patients with SAP. The levels of serum proinflammatory cytokines including TNF-α, IL-1β, and IL-6 showed similar shifts with intracellular SphK1 expression in SAP patients. The authors identified a link between the SphK1 expression on peripheral immune cells and the severity of SAP. Observations showed a possible immunomodulating role for SphK1/S1P signaling in inflammatory response in SAP, suggesting that regulation of SphK1/S1P pathway may represent novel targets in the treatment of SAP.

Hydroxyethyl Starch Resuscitation Reduces the Risk of Intra-Abdominal Hypertension in Severe Acute Pancreatitis

This study aimed to address whether hydroxyethyl starch (HES) is beneficial for intra-abdominal pressure (IAP) in severe acute pancreatitis (SAP) in early stages. Forty-one patients with SAP were randomized to HES group (n = 20) and the Ringer's lactate (RL) group (n = 21). The groups received 6% HES 130/0.4 for 8 days and RL solution without colloid, respectively. The primary end point was the IAP. The secondary end points were fluid balance, major organ complications, the Acute Physiology and Chronic Heath Evaluation II score, and the serum levels of C-reactive protein, interleukin-6, and interleukin-8. The characteristics of baseline data were similar in the 2 groups. In the HES group, the IAP was significantly lower in 2 to 7 days, and fewer patients received mechanical ventilation (15.0% vs 47.6%). A negative fluid balance was observed earlier in the HES group than in the RL group (2.5 ± 2.2 vs 4.0 ± 2.5 days). Fluid resuscitation with HES in the early stages of SAP can decrease the risk of intra-abdominal hypertension and reduce the use of mechanical ventilation.