Zhihui Tong

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

AIM To investigate the effects of early enteral nutrition (EEN) on the immune function and clinical outcome of patients with severe acute pancreatitis (SAP). METHODS 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. RESULTS 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. CONCLUSION 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 Effect of Intra-Abdominal Hypertension Incorporating Severe Acute Pancreatitis in a Porcine Model

Introduction Abdominal compartment syndrome (ACS) and intra abdominal hypertension(IAH) are common clinical findings in patients with severe acute pancreatitis(SAP). It is thought that an increased intra abdominal pressure(IAP) is associated with poor prognosis in SAP patients. But the detailed effect of IAH/ACS on different organ system is not clear. The aim of this study was to assess the effect of SAP combined with IAH on hemodynamics, systemic oxygenation, and organ damage in a 12 h lasting porcine model. Measurements and Methods Following baseline registrations, a total of 30 animals were divided into 5 groups (6 animals in each group): SAP+IAP30 group, SAP+IAP20 group, SAP group, IAP30 group(sham-operated but without SAP) and sham-operated group. We used a N2 pneumoperitoneum to induce different levels of IAH and retrograde intra-ductal infusion of sodium taurocholate to induce SAP. The investigation period was 12 h. Hemodynamic parameters (CO, HR, MAP, CVP), urine output, oxygenation parameters(e.g., SvO2, PO2, PaCO2), peak inspiratory pressure, as well as serum parameters (e.g., ALT, amylase, lactate, creatinine) were recorded. Histological examination of liver, intestine, pancreas, and lung was performed. Main Results Cardiac output significantly decreased in the SAP+IAH animals compared with other groups. Furthermore, AST, creatinine, SUN and lactate showed similar increasing tendency paralleled with profoundly decrease in SvO2. The histopathological analyses also revealed higher grade injury of liver, intestine, pancreas and lung in the SAP+IAH groups. However, few differences were found between the two SAP+IAH groups with different levels of IAP. Conclusions Our newly developed porcine SAP+IAH model demonstrated that there were remarkable effects on global hemodynamics, oxygenation and organ function in response to sustained IAH of 12 h combined with SAP. Moreover, our model should be helpful to study the mechanisms of IAH/ACS-induced exacerbation and to optimize the treatment strategies for counteracting the development of organ dysfunction.

Percutaneous catheter drainage for infective pancreatic necrosis: is it always the first choice for all patients?

Objective To learn the clinical outcome of percutaneous catheter drainage (PCD) for patients with infective pancreatic necrosis and the possible influencing factors. Methods A retrospective review of medical records of patients with infective pancreatic necrosis who received PCD as the first choice for treatment in the recent 2 years. The patients were divided into 2 groups: (1) PCD success group and (2) PCD alteration group. Characteristics, complications, and PCD process were compared. Results In this study, 19 of 34 patients were cured by PCD alone (55.9%), whereas open necrosectomy were needed for 15 patients (44.1%). Between these 2 groups, most baseline and clinical characteristics did not show any statistical difference, including the number and size of catheter used and the bacterial culture result. The PCD alteration group had higher mean computed tomographic density (P = 0.012) and larger distribution range of infected pancreatic necrosis (4.53 ± 1.35 vs 5.93 ± 1.62; P = 0.009) than the PCD success group (P < 0.01). The logistic regression analysis revealed the same facts. Conclusion The mean computed tomographic density and distribution range of infective pancreatic necrosis could significantly influence the success rate of PCD; higher values of them indicate less appropriate for PCD; thus, it should be considered seriously before the treatment decision.

Complement Depletion Deteriorates Clinical Outcomes of Severe Abdominal Sepsis: A Conspirator of Infection and Coagulopathy in Crime?

Background The complement depletion commonly occurred during sepsis, but it was often underestimated compared with severe infection or coagulation dysfunction. Objective This study was designed to investigate the alteration of complement system in patients with severe abdominal sepsis and evaluate the role of complement depletion in prognosis of such patients. The relationship between complement depletion and infection or coagulopathy was also explored. Methods Forty-five patients with severe abdominal sepsis were prospectively conducted among individuals referral to SICU. Currently recommended treatments, such as early goal-directed resuscitation, source control and antibiotics therapy, were performed. Acute physiology and chronic health evaluation II (APACHE II) and sepsis related organ failure assessment (SOFA) scores were employed to evaluate severity. Plasma levels of C3, C4, CRP, PCT, D-dimer and other parameters were detected within eight times of observation. The 28-day mortality, length of stay, and postoperative complications were compared between complement depletion and non-complement depletion groups. Results Within the study period, eight (17.8%) patients died, five of them suffering from complement depletion. The overall incidence of complement depletion was 64.4%. At admission, mean complement C3 and C4 levels were 0.70 and 0.13 mg/mL, respectively. Using ROC analysis for mortality prediction, the area under the curve of C3 was 0.926 (95% CI, 0.845–0.998, P<0.001), with optimal cutpoint value of 0.578 mg/mL. Complement C3 depletion was shown to be no correlation to severity scores, however, strongly correlated with elevated D-dimer, PCT concentrations and increased postoperative complications. Conclusions Complement C3 depletion was found to be connected to poor prognosis in severe abdominal sepsis. This depletion seems to be associated with coagulopathy and aggravated infection during sepsis, which should be paid close attention in critical care. Trial Registration ClinicalTrials.gov NCT01568853

The importance of timing of decompression in severe acute pancreatitis combined with abdominal compartment syndrome.

BACKGROUND Surgical decompression is widely considered as an important treatment in patients with severe acute pancreatitis (SAP) and abdominal compartment syndrome (ACS). Until now, the indication and optimal time of decompression remain unknown, and no experimental data exist, although extremely high mortality has been repeatedly reported in these patients. The aim of this study was to evaluate the effects of three different time points for decompression in a 24-hour lasting porcine model. METHODS Following baseline registrations, 32 animals were divided into four groups (8 animals each group) as follows: one SAP-alone group and three SAP + ACS groups, which received decompression at 6, 9, and 12 hours. We used a N2 pneumoperitoneum to increase the intra-abdominal pressure to 25 mm Hg and retrograde intra-ductal infusion of sodium taurocholate to induce SAP. Global hemodynamic profiles, urine output, systemic oxygenation, and serum biochemical parameters of the animals were studied. At the end of the experiment, histologic examination of the intestine and lung was performed. RESULTS The survival time of the 12-hour group was significantly shortened (p = 0.037 vs. 9 hours and p = 0.008 vs. 6 hours). In SAP + ACS animals, decompression at 6 hours restored systemic hemodynamics, oxygen-derived parameters, organ function, and inflammatory intensity to a level comparable with that of the SAP-alone group. In contrast, animals in the 9 hours and 12 hours developed more severe hemodynamic and organ dysfunction. The histopathologic analyses also revealed higher grade injury of the intestine and lung in animals receiving delayed decompression. CONCLUSION Well-timed decompression in a porcine model of SAP incorporating 25-mm Hg intra-abdominal hypertension/ACS was associated with significantly reduced mortality, improved systemic hemodynamics and organ function, as well as alleviated histologic injury and inflammatory intensity. According to our results and previous reports, both too early and too late decompression should be avoided owing to significant morbidity for the former and unfavorable outcomes for the latter.

Codonopsis pilosula polysaccharide attenuates cecal ligation and puncture sepsis via circuiting regulatory T cells in mice.

ABSTRACT Background: Codonopsis pilosula polysaccharide (CPPS) isolated from one of the Chinese herbs is known to have a variety of immunomodulatory activities. However, it is not clear whether CPPS can exert an effect on the immune functions of regulatory T cells (Tregs). This study was carried out to investigate the effect of CPPS on the immune function of peripheral blood Tregs in sepsis induced by cecal ligation and puncture (CLP). Methodology and Principal Findings: BALB/c mice were randomly divided into five groups: sham group, CLP group, CLP with CPPS (40, 100, and 250 mg/kg) treatment group, and they were killed on days 1, 2, 3, and 4 after CLP, respectively, with eight animals at each time point. Magnetic microbeads were used to isolate peripheral blood Tregs and CD4+ T cells. Phenotypes of Tregs, such as Toll-like receptor 4 (TLR4) and Foxp3, were analyzed by flow cytometry, and coculture medium cytokines levels were determined with enzyme-linked immunosorbent assay. The levels of TLR4 and the expression of Foxp3 in the Treg from CLP group were markedly increased in comparison to the sham group. Administration of CPPS could significantly decrease the TLR4 level and inhibited the expression of Foxp3 on Tregs in sepsis mice. At the same time, proliferative activity and expression of interleukin 2 and interleukin 2R&agr; on CD4+ T cells were restored. In contrast, anti-TLR4 antibody could block the effect of CPPS on Treg immune function. Conclusions: Codonopsis pilosula polysaccharide might suppress excessive Tregs, at least in part, via TLR4 signaling on Tregs and trigger a shift of TH2 to TH1 with activation of CD4+ T cells in sepsis induced by CLP.

Hypertriglyceridemia is a risk factor for acute kidney injury in the early phase of acute pancreatitis.

Objective The aim of this study was to investigate the risk factors for acute kidney injury (AKI) in patients with acute pancreatitis (AP). Methods Patients with AP were retrospectively divided into AKI group and non-AKI group. To investigate the risk factors for AKI, logistic regression analysis was performed with demography, etiologies, and comorbidities. Mortalities of patients with different body mass indexes were compared. Results There were 43 patients with AKI and 202 patients without AKI. The risk factor for AKI in AP was hypertriglyceridemia (odds ratio, 2.964; 95% confidence interval, 1.485–5.915; P = 0.007). Forty-two patients developed AKI within the first 48 hours. The mortalities of normal weight, overweight, and obese groups in patients with AKI were 16.7%, 17.4%, and 62.5%, respectively. All the 4 patients who died in the non-AKI group were of normal weight. Conclusions Hypertriglyceridemia is an independent risk factor for AKI in the early phase of AP. Obesity does not increase mortality of patients without AKI. We hypothesize that the role of pancreatic enzymes on triglyceride accumulated in renal may be an explanation for AKI in the early phase of AP.

Risk factors and outcome of splanchnic venous thrombosis in patients with necrotizing acute pancreatitis.

BACKGROUND Splanchnic venous thrombosis (SVT) is considered a rare but important complication in patients with acute pancreatitis (AP) and literatures regarding this topic were sparse. The aim of the present study was to investigate the risk factors of SVT in necrotizing acute pancreatitis (NAP) and assess the prognosis of these patients. METHODS Both univariate and multivariate logistic regression analyses were applied using 15 indices including age, gender, Acute Physiology and Chronic Health Evaluation II scores (APACHE II), CRP (C - reactive protein) levels, etc to explore potential risk factors for the development of SVT in NAP patients. Moreover, clinical outcome measures such as mortality, organ failure and length of hospital and ICU stay were also compared between NAP patients with or without SVT. RESULTS According to the statistical results, only intra-abdominal pressure (IAP) was proved to be an independent risk factor for SVT (OR, 1.283; 95% CI, 1.091-1.509,P=0.003). In addition, Balthazars CT score and occurrence of IPN (infected pancreatic necrosis) also reached statistical significance (P=0.040 and 0.047, respectively), but the 95% confidence interval shown in the multivariate logistic regression suggested that the observed ORs are not significant (1.326;95% CI 0.984-1.787 and 2.61;95 CI 0.972-7.352, respectively), which indicates weaker association between the two parameters and SVT. Regarding the clinical outcomes, patients with SVT showed higher mortality, longer hospital and intensive care unit duration, higher rates of a variety of complications and more utilization of invasive interventions. CONCLUSIONS IAP is an independent risk factor for the development of SVT in patients with NAP, while Balthazars CT score and occurrence of IPN are also associated with SVT, although not as strong as IAP. Moreover, occurrence of SVT relates with extremely poor prognosis in NAP patients, evidenced by increased mortality, morbidity and need for invasive interventions.

Association Between Severity and the Determinant-Based Classification, Atlanta 2012 and Atlanta 1992, in Acute Pancreatitis: A Clinical Retrospective Study

AbstractRecently, the determinant-based classification (DBC) and the Atlanta 2012 have been proposed to provide a basis for study and treatment of acute pancreatitis (AP). The present study aimed to evaluate the association between severity and the DBC, the Atlanta 2012 and the Atlanta 1992, in AP.Patients admitted to our center with AP from January 2007 to July 2013 were reviewed retrospectively. Patients were assigned to severity categories for all the 3 classification systems. The primary outcomes include long-term clinical prognosis (mortality and length-of-hospital stay), major complications (intraabdominal hemorrhage, multiple-organ dysfunction, single organ failure [OF], and sepsis) and clinical interventions (surgical drainage, continuous renal replace therapy [CRRT] lasting time, and mechanical ventilation [MV] lasting time). The classification systems were validated and compared in terms of these abovementioned primary outcomes.A total of 395 patients were enrolled in this retrospective study with an overall 8.86% in-hospital mortality. Intraabdominal hemorrhage was present in 27 (6.84%) of the patients, multiple-organ dysfunction in 73(18.48%), single OF in 67 (16.96%), and sepsis in 73(18.48%). For each classification system, different categories regarding severity were associated with statistically different clinical mortality, major complications, and clinical interventions (P < 0.05). However, the Atlanta 2012 and the DBC performed better than the Atlanta 1992, and they were comparable in predicting mortality (area under curve [AUC] 0.899 and 0.955 vs 0.585, P < 0.05); intraabdominal hemorrhage (AUC 0.930 and 0.961 vs 0.583, P < 0.05), multiple-organ dysfunction (AUC 0.858 and 0.881 vs 0.595, P < 0.05), sepsis (AUC 0.826 and 0.879 vs 0.590, P < 0.05), and surgical drainage (AUC 0.900 and 0.847 vs 0.606, P < 0.05). For continuous variables, the Atlanta 2012 and the DBC were also better than the Atlanta 1992, and they were similar in predicting CRRT lasting time (Somer D 0.379 and 0.360 vs 0.210, P < 0.05) and MV lasting time (Somer D 0.344 and 0.336 vs 0.186, P < 0.05).All the 3 classification systems accurately classify the severity of AP. However, the Atlanta 2012 and the DBC performed better than the Atlanta 1992, and they were comparable in predicting long-term clinical prognosis, major complications, and clinical interventions.

Aspirin Protects against Acinar Cells Necrosis in Severe Acute Pancreatitis in Mice

Aspirin has a clear anti-inflammatory effect and is used as an anti-inflammatory agent for both acute and long-term inflammation. Previous study has indicated that aspirin alleviated acute pancreatitis induced by caerulein in rat. However, the role of aspirin on severe acute pancreatitis (SAP) and the necrosis of pancreatic acinar cell are not yet clear. The aim of this study was to determine the effects of aspirin treatment on a SAP model induced by caerulein combined with Lipopolysaccharide. We found that aspirin reduced serum amylase and lipase levels, decreased the MPO activity, and alleviated the histopathological manifestations of pancreas and pancreatitis-associated lung injury. Proinflammatory cytokines were decreased and the expression of NF-κB p65 in acinar cell nuclei was suppressed after aspirin treatment. Furthermore, aspirin induced the apoptosis of acinar cells by TUNEL assay, and the expression of Bax and caspase 3 was increased and the expression of Bcl-2 was decreased. Intriguingly, the downregulation of critical necrosis associated proteins RIP1, RIP3, and p-MLKL was observed; what is more, we additionally found that aspirin reduced the COX level of pancreatic tissue. In conclusion, our data showed that aspirin could protect pancreatic acinar cell against necrosis and reduce the severity of SAP. Clinically, aspirin may potentially be a therapeutic intervention for SAP.