Devastating Effects of Combined DKA and Acute Pancreatitis in Select Patients: Two Cases.

Most cases of acute pancreatitis are routinely managed in the hospital without complications. However, management could become very complicated when patients present with a combination of acute pancreatitis and diabetic ketoacidosis (DKA). In fact, triad of acute pancreatitis, DKA, and hypertriglyceridemia in patients could result into systemic complications which may lead to fatal consequences. We report 2 cases in which patients presented with acute pancreatitis and DKA. Clinical course was complicated for both cases. While one of the patients expired, the other patient could not be extubated. This combination must be avoided at all costs because the clinical outcome for affected patients is difficult to predict.

Incidence and outcomes of pancreatic encephalopathy in patients with acute pancreatitis: a systematic review and meta-analysis.

Pancreatic encephalopathy (PE) is a lethal complication of acute pancreatitis (AP), but its clinical characteristics and prognosis remain obscure. Herein, we performed a systematic review and meta-analysis to evaluate the incidence and outcomes of PE in AP patients. PubMed, EMBASE, and China National Knowledge Infrastructure were searched. Based on the data from cohort studies, the incidence and mortality of PE in AP patients were pooled. Based on the individual data from case reports, logistic regression analyses were performed to identify the risk factors for death in PE patients. Among 6702 papers initially identified, 148 were included. Based on 68 cohort studies, the pooled incidence and mortality of PE in AP patients were 11% and 43%, respectively. The causes of death were clearly reported in 282 patients, of which the most common was multiple organ failure (n = 197). Based on 80 case reports, 114 AP patients with PE were included. The causes of death were clearly reported in 19 patients, of which the most common was multiple organ failure (n = 8). Univariate analyses showed that multiple organ failure (OR = 5.946; p = 0.009) and chronic cholecystitis (OR = 5.400; p = 0.008) were the significant risk factors of death among patients with PE. PE is not a rare complication of AP and indicates poor prognosis. Such a high mortality of PE patients may be attributed to its coexistence of multiple organ failure.

Effects and mechanism of the etanercept on pancreatic encephalopathy.

Pancreatic encephalopathy (PE) is a common fatal complication of acute pancreatitis (AP). Proinflammatory cytokines such as tumor necrosis factor (TNF)­α and interleukin (IL)­6 are generated during AP, and act synergistically to promote PE and multisystem failure. Caerulein­induced AP provides a convenient model to explore the role of proinflammatory cytokines in PE. The aim of the present study was to examine the effect of the TNF­α inhibitor etanercept in PE models and elucidate the regulatory mechanisms. To model PE in vitro, rat hippocampal H19­7/IGF­IR neuronal cells were treated with 10 nmol/ml caerulein alone or in combination with etanercept (1, 10 or 100 µmol/ml). To model PE in vivo, rats were injected with 50 µg/kg caerulein alone or combined with 10 mg/kg etanercept. At 6 h after administration, it was noted that etanercept downregulated expression of TNF­α, IL­1ß and IL­6 by negatively regulating NF­κB (a master regulator of cytokine expression) signaling, and prevented the accumulation of reactive oxygen species. Conversely, etanercept promoted the expression of the neurotrophic and anti­inflammatory hypoxia­inducible factor 1 α (HIF­1α). In rat hippocampus, etanercept also reduced the levels of TNF­α, IL­1ß and IL­6, upregulated HIF­1α expression and inhibited the inflammatory response to reduce edema and neural necrosis. Together, these data suggested that etanercept could attenuate caerulein­induced PE, at least in part via suppression of NF­κB signaling and alleviation of oxidative stress.

Establishment and Evaluation of A Early Prediction Model for Severe Acute Pancreatitis Complicated With Pancreatic Encephalopathy / 胃肠病学

Background: Pancreatic encephalopathy (PE) is one of the severe systemic complications of severe acute pancreatitis (SAP). In recent years, the incidence of PE was on the rise. There are few tools for early prediction of SAP complicated with PE. Aims: To screen the early independent risk factors of PE from clinical testing indices and scoring system of SAP patients, and then construct an early predictive scoring model of PE and used for intervening in advance. Methods: The clinical data of 130 patients with SAP from Jan. 2016 to Sept. 2020 at Shaanxi Hanzhong 3201 Hospital were analyzed retrospectively. Early independent risk factors of PE was screened by univariate analysis and multivariate Logistic regression analysis. The predictive scoring model was constructed by the weighted least square method. Results: Univariate analysis showed that history of alcohol abuse, lactic acid, intra-abdominal pressure (IAP), CT severity index (CTSI), extrapancreatic inflammation on CT (EPIC) and Glasgow coma scale (GCS) score were correlated to PE (P6), and differences in the incidence of PE in SAP patients among the three groups were statistically significant (P<0.05). Conclusions: The predictive scoring model constructed has the value for early prediction and evaluation of SAP complicated with PE, and risk stratification is helpful for taking intervention measures in advance to reduce the incidence of PE.

The neuroprotective effects of 2-APB in rats with experimentally- -induced severe acute pancreatitis.

AIM: The objective of this study was to determine the neuroprotective effects of 2-aminoethyl diphenyl-borinate (2-APB) on the brains of rats with experimentally-induced severe acute pancreatitis. MATERIALS AND METHODS: Thirty Spraque-Dawley male rats with an average weight of 200-250 grams were randomly divided into three groups. Group 1: Sham group, Group 2: Severe acute pancreatitis group, Group 3: Treatment group with severe acute pancreatitis, given 2 mg/kg 2-APB before pancreatitis onset. In Groups 2 and 3, severe acute pancreatitis was induced by intraperitoneal administration of 1.5 g/kg L-arginine with a 1-hour interval. Tumor necrosis factor-α, interleukin 6, pancreatic amylase were all measured. Brain tissue samples were evaluated histopathologically. TUNEL staining method was used to visualize apoptotic cells. RESULTS: In Group 3, it was determined that the density of TUNEL-positive cells in the cerebral cortex has decreased, while the number of Bcl-2-positive cells had increased. In Group 3, it was observed that glial aggregation areas were diminished and histopathological changes were decreased as compared to Group 2. In Group 2, on the other hand, it was observed that in areas with glial cell aggregation, the density of TUNEL-positive glial cells had increased, while Bcl-2-positive cell reaction has been feeble. CONCLUSIONS: It was observed that 2-APB decreases neuronal apoptosis and glial cell aggregation (Tab. 2, Fig. 3, Ref. 21).

Current status of diagnosis and treatment of pancreatic encephalopathy / 临床肝胆病杂志

Pancreatic encephalopathy (PE)is a serious complication of pancreatitis,with difficulties in early diagnosis and poor prognosis. This article introduces the possible pathogenesis of PE involving pancreatin activation,cytokines,infection,water and electrolyte imbalance, and vitamin deficiency,summarizes the clinical manifestations and laboratory features of PE,and points out that the clinical manifestations of PE lack specificity and there are no reliable biochemical indices or diagnostic criteria.This article also elaborates on the diagnosis and treat-ment strategies for PE and points out that the key to PE treatment is active and effective treatment of the primary disease.Most PE patients are improved with the control of pancreatitis.

Correlation study between the expression of dopamine receptor in brain and the pancreatic encephalopa-thy / 实用医学杂志

Objective To investigate the expression of dopamine receptor in brain of rats with pancreatic encephalopathy and provide a theoretical basis to reveal pathogenesis of pancreatic encephalopathy. Methods A rat model of experimental pancreatic encephalopathy was induced by retrograde injection of 5％sodium taurocholate into the pancreatic duct. The pathological changes of pancreas and brain were detected. The water content in brain tissue was determined. The superoxide dismutase activity and malondialdehyde content in brain tissue homogenate were detected by the chemical colorimetry. Levels of TNF-α,IL-1β,tyrosine hydroxylase and dopamine receptor-2 were detected by immunohistochemistry(SP method). Results Cerebral sulcus was shallow,ventricle was small-er and the superficial veins were dilated and congested. The inflammatory cell infiltration and pancreatic acinar cell necrosis in the pancreas and neuron edema ,inflammatory cell infiltration ,microvessel adherent leukocytes in brain were observed by light microscope in model groups at 3,6,12 hours. Compared with the control group. The activities of superoxide dismutase in brain tissue in model groups at 3,6,12 hours were significantly decreased (P < 0.01). The level of malondialdehyde and the water content of brain tissue were significantly increased (P <0.01 ,respectively). Compared with the control group ,levels of brain TNF-α,IL-1β,tyrosine hydroxylase and dopamine receptor-2 in model groups at 3,6,12 hours were significantly increased(P < 0.01,respectively).Conclusions The incidence of pancreatic encephalopathy may be related to the influx of oxygen free radical and inflammatory factors,invading nerve center by blood-brain barrier and inducing the increased production of dopa-mine and the upregulation of dopamine receptor in brain.

Correlation study between the expression of dopamine receptor in brain and the pancreatic encephalopa-thy / 实用医学杂志

Objective To investigate the expression of dopamine receptor in brain of rats with pancreatic encephalopathy and provide a theoretical basis to reveal pathogenesis of pancreatic encephalopathy. Methods A rat model of experimental pancreatic encephalopathy was induced by retrograde injection of 5％sodium taurocholate into the pancreatic duct. The pathological changes of pancreas and brain were detected. The water content in brain tissue was determined. The superoxide dismutase activity and malondialdehyde content in brain tissue homogenate were detected by the chemical colorimetry. Levels of TNF-α,IL-1β,tyrosine hydroxylase and dopamine receptor-2 were detected by immunohistochemistry(SP method). Results Cerebral sulcus was shallow,ventricle was small-er and the superficial veins were dilated and congested. The inflammatory cell infiltration and pancreatic acinar cell necrosis in the pancreas and neuron edema ,inflammatory cell infiltration ,microvessel adherent leukocytes in brain were observed by light microscope in model groups at 3,6,12 hours. Compared with the control group. The activities of superoxide dismutase in brain tissue in model groups at 3,6,12 hours were significantly decreased (P < 0.01). The level of malondialdehyde and the water content of brain tissue were significantly increased (P <0.01 ,respectively). Compared with the control group ,levels of brain TNF-α,IL-1β,tyrosine hydroxylase and dopamine receptor-2 in model groups at 3,6,12 hours were significantly increased(P < 0.01,respectively).Conclusions The incidence of pancreatic encephalopathy may be related to the influx of oxygen free radical and inflammatory factors,invading nerve center by blood-brain barrier and inducing the increased production of dopa-mine and the upregulation of dopamine receptor in brain.

[Pancreatic encephalopathy: about 2 cases and review of the literature]. / Encéphalopathie pancréatique: à propos de deux cas.

Pancreatic encephalopathy (PE) is a rare complication of acute pancreatitis. Our study reports 2 cases of patients with pancreatic encephalopathy, hospitalized and treated in the Intensive Care Unit of the Military Hospital of Instruction Mohammed V, Rabat. Patient age ranged between 43 and 54 years, our 2 cases involved a woman and a man. The pathophysiologic process of EP is still not well understood, many assumptions have been described in the literature; some authors have suggested that lipase and phospholipase A2 are involved in the pathological process of PE. Other factors including infections, fluid and electrolyte disturbances, hypoxemia and perturbations in blood glucose can be triggers. The diagnosis of pancreatic encephalopathy is easy to establish, clinical symptoms usually include confusion, amazement and psychomotor agitation, sometimes associated with neurological damages such as convulsions, headache, transient hemiparesis, dysarthria, difficulties in verbal expression and amnesia. Paraclinical tests, including brain MRI and electroencephalogram allow a definitive diagnosis. Treatment is primarily symptomatic aiming to fight against factors favoring the onset of neurologic signs using resuscitative measures based on severity of the situation. The prognosis depends on the severity of acute pancreatitis and its complications. In our study data are broadly comparable to those currently published by the majority of authors.

Indoleamine 2,3-dioxygenase is upregulated in the brain of rats with acute pancreatitis.

BACKGROUND: Acute pancreatitis (AP) has an effect on both inflammatory/autoimmune processes and psychological states, but the pathophysiological causes of pancreatic encephalopathy in the brain are unclear. We hypothesized that the peripheral immune/inflammatory response during AP can affect indolamine 2,3-dioxygenase (IDO) expression and serotonin content in the brain. METHODS: About 210 male Sprague Dawley rats were randomly divided into five groups: control (0 h) and 6 h, 24 h, 48 h and 72 h experimental groups. Acute pancreatitis was induced by an injection of a sodium taurocholate solution via a cannulated bile-pancreatic duct. We measured the plasma TNF-α and IL-6 levels; serotonin, 5-HIAA and the protein concentration levels of IDO and monoamine oxidase A (MAO-A) were evaluated in the striatum, hippocampus and left prefrontal cortex. RESULTS: The IL-6 and the TNF-α levels increased in the 24 h, 48 h and 72 h groups. The IDO concentrations of both the 72 h group in the hippocampus and 48 h, 72 h groups in the prefrontal cortex increased; in the corpus striatum, the IDO concentrations fluctuated without statistical significance. The MAO-A protein concentration of the 6 h and 24 h groups decreased in the striatum, hippocampus and prefrontal cortex. There were no statistically significant differences found in the serotonin and 5-HIAA concentrations. CONCLUSIONS: During the process of AP, cytokines, such as IL-6 and TNF-α, may play a role in activation of neuronal pathways utilizing the metabolic enzyme IDO, which may play an important role in determining the mental symptomatology accompanying AP.

Analysis of relationship between demyelinating lesions and myelin basic protein in pancreatic encephalopathy / 临床肝胆病杂志

Pancreatic encephalopathy (PE)is one of the severe complications of severe acute pancreatitis (SAP).Early diagnosis mostly depends on the history of disease as well as clinical symptoms and signs.PE progresses rapidly and is often complicated by multiple organ dysfunction,and it may finally develop into multiple organ failure with a high fatality rate if not treated in time.It is currently known that de-myelination is one of the important pathological features of this disease,with fat -soluble demyelination of cerebral gray matter and white matter,as well as inflammatory changes such as hemorrhage and edema.The target antigen of demyelinating lesions,however,is myelin basic protein (MBP).This paper reviews the changes in MBP levels in the demyelinating lesions of the central nervous system among PE pa-tients,with the purpose of providing clues for the early diagnosis and prognostic study of demyelinating lesions in PE.

Research progress in diagnosis and treatment of pancreatic encephalopathy / 临床外科杂志

Pancreatic encephalopathy(PE)is one of the severe complications in acute pancreati-tis,which is characterized by a group of neurological signs and symptoms. Itˊs very difficult to have an early diagnosis,while the morality of PE is very high and the prognosis is very poor. Eliminating causes of pan-creatic encephalopathy,early diagnosis and combined therapy are the keys to achieve good curative effects. This paper reviewed the recent progress in the main mechanisms,clinical manifestations,diagnosis and therapy of PE.

The Diagnostic Effect of Brainstem Evoked Potential for Pancreatic Encephalopathy in Rats with Severe Acute Pancreatitis / 昆明医科大学学报

Objective The aim of this study is to demonstrate the diagnostic effect of brainstem evoked potential for pancreatic encephalopathy in rats with severe acute pancreatitis. Methods Sixty male Sprague-Dawley (SD) rats were randomly divided into two equal groups: a sham-operated (SO) group and a severe acute pancreatitis (SAP) group. Each group was evaluated at 3, 6, and 12 h during the experiment. To detect the brain stem evoked potential change at different time points. The ultrastructure of brain tissue was observed by transmission electron microscope (TEM). The expressions of the apoptosis-related proteins Bcl-2, Bax and caspase-3 were observed using immunohistochemical and Western Blot technique. Results In SAP group, congestion, edema, inflammatory cell infiltration, mitochondrial swelling and cell apoptosis were apparent. Compared with SO group, the brain stem evoked potential in severe acute pancreatitis group was obviously reduced in SAP group. Compared with SAP group, the expressions of Bcl-2 have increased, whereas the expressions of Bax and caspase-3 have decreased in SO group significantly ( <0.05) . Conclusion Brain stem evoked potential is a sensitive method in detection of rat brain damage. The results showed that the consistency and the damage degree of rats may be important clinical diagnostic index of pancreatic encephalopathy.

Central and extrapontine myelinolysis affecting the brain and spinal cord. An unusual presentation of pancreatic encephalopathy.

Pancreatic encephalopathy refers to a gamut of neuropsychiatric symptoms complicating acute pancreatitis. Osmotic myelinolysis is a known complication of pancreatic encephalopathy. We evaluated a 58-year-old woman with pancreatic encephalopathy associated to pontine and extrapontine myelinolysis involving the brain and spinal cord. To our knowledge, this is the first clinic pathological case report of pancreatic encephalopathy involving the spinal cord.

Expression of aquaporins-4 in brain tissue of rats with pancreatic encephalopathy / 中华胰腺病杂志

Objective To study the expression of aquaporins-4 (AQP4) in the brain tissue of rats with pancreatic encephalopathy (PE) induced by phospholipase A2 and to explore the role of aquaporins-4 in PE.Methods Twenty five healthy Wistar rats were randomized into 3 groups:blank group ( n =5),PE group (n =10 ) and control group (n =10 ).The experimental model was established in rats by injecting phospholipase A2 into carotid artery (0.1 ml/100 g body weight).Same amount of normal saline was used in the control group and no treatment was used in the blank group.One day later,the rats were sacrificed,then the measurement of brain tissue wet/dry (W/D) weight ratio was performed,and brain tissue was routinely pathologically examined,immunohistochemistry and Western blotting were performed in each group to detect the expression of aquaporins-4.Results There was no obvious brain tissue pathological change in the control group and blank group.Neurons in the brain tissue of PE rats presented with significant edema and ballooning degeneration,infiltration of inflammatory cells,leukocyte aggregation around the microvessels.The water contents in the brain tissue in the blank group and control group,PE group were (61.44 ±0.36)％,(63.20±0.32)％ and (78.33 ±0.24)％,and it was significantly higher in PE group than that in the control and blank group (P＜0.05).The expressions of aquaporins-4 in the brain tissue were 0.41 ±0.27,0.49 ±0.13,0.98 ±0.21,respectively,and it was significantly increased in PE group than that in the control and blank group (P ＜ 0.05 ).Conclusions Aquaporins-4 may play important roles in the pathogenesis of pancreatic encephalopathy.

Acute Pancreatitis Complicated with Pancreaticencephalopathy:A Report of 23 Cases / 医学研究杂志

Objective To explore the mechanism 、diagnosis of pancreatic encephalopathy(PE);To evaluate the therapy of PE.Methods To analyze the treatment and diagnosis of 23 PE patients.Results 12 PE patients were cured.11patients were dead,the mortality is 47.8%,5patients in operation group died,the mortality is 62.5%.6 patients in non-operation group were dead,the mortality is 40%,among them,5patients died for multiple organ system falure.one died for septic shock.Conclusions PE is relating to serum amylase inflammatory mediators and infection etc.The diagnosis of PE is based on AP and neurological and mental abnormality.The relative auxiliary diagnosis standard is uncertain.the conventional therapy of PE 、the remedy of MOSF and disorder in water and electroltes were basic therapy.the nerve preserving is necessary for PE's therapy.

Protective effects of tumor necrosis factor-α antibody on pancreatic encephalopathy in rats / 中国康复理论与实践

@#ObjectiveTo study the protective effects of tumor necrosis factor-α(TNF-α) antibody on pancreatic encephalopathy in rats. MethodsSixty SD rats were randomly divided into the normal control group, acute necrotizing pancreatitis induction group and TNF-α antibody treated group. Acute hemorrhage necrotizing pancreatitis model in rats were induced by retrograde injection of 5% sodium taurocholate into the pancreatobiliary duct. Serum TNF-α was detected and animals were killed 12 h after drug administration. The changes of brain water contents, leucocyte accumulation and adhesion were measured, and pathological studies of pancreas and brain were performed. ResultsIn group of TNF-α antibody treated, serum TNF-α level decreased, brain water contents and leucocytes accumulation and adhension decreased significantly than that of acute necrotizing pancreatitis induction group (P<0.05). The histopathological change of pancrea was alleviative. ConclusionTNF-α antibody can alleviate the brain damage in acute hemorrhage necrotizing pancreatitis.

Effects of MDA,SOD and TNF-? on The Experimental Models of Pancreatic Encephalopathy / 中国普外基础与临床杂志

Objective To study the effects of malondialdehyde (MDA), superoxide dismutase (SOD) and tumor necrosis factor-? (TNF-?) on brain tissue in rats with pancreatic encephalopathy (PE). MethodsThirty-six Wistar rats were randomly divided into control group (n=6) and PE model group (n=30). In control group, rats were injected with normal saline by internal carotid artery (0.1 ml/100 g) and were killed on the first day after the injection. In PE model group, rats were injected with phospholipases A2 (0.1 ml/100 g, 1 000 U/0.1 ml) by internal carotid artery, to establish animal model of PE in rat and 10 rats were killed on day 1, 3, 7 respectively after the injection. The changes of water content in the brain were measured. Leucocytes aggregation and margination in the microvessels, and the changes of cerebral cells and nerve fibers were observed. The levels of MDA, TNF-? and the activity of SOD were tested in the brain homogenate in rats. ResultsIn PE model group, water contents of brain increased; The phenomena of leucocytes accumulation and margination, cellular edema of neurons and demyelination of nerve fibers became more obvious; The levels of MDA and TNF-? increased significantly than those in the control group, while the activity of SOD reduced (P

Pancreatic encephalopathy during acute pancreatitis (report of 26 cases) / 临床外科杂志

Objective To discuss the causes,agents and treatment of pancreatic encephalopathy in acute pancreatitis.Method We reviewed 26 cases of acute pancreatitis combined with pancreatic encephalopathy within recent 10 years.Results Pancreatic encephalopathy occurred always accompanied with such agents as hyperpyrexia, waterelectrolyte disturbance,hypoxemia, azotemia and bloodsugar disturbance etc.Conclusions The occurrence of the pancreatic encephalopathy is based on the harm that pancreatin does to the brain.The causes of pancreatic encephalopathy vary.To inhibit the releasing of pancreatin is the principle to prevent pancreatic encephalopathy, and to maintain normal physiological function,to control infection and nutritional support are the important links to prevent the pancreatic encephalopathy from happening.

Pancreatic encephalopathy and Wernicke's encephalopathy in association with acute pancreatitis: 10 cases report / 解放军医学杂志

Objective To investigate the clinical characteristics and the treatment of pancreatic encephalopathy (PE) and Wernicke's encephalopathy (WE). Method A retrospective study was conducted on 596 cases of acute pancreatitis. Results There were 93 cases of severe acute pancreatitis (SAP),among them encephalopathy was discovered in 10 patients (1.7%). All 6 patients of PE developed in SAP (6.5%);3 patients died (3% of SAP,50% of PE). Four cases of WE developed in AP (0.7%);2 patients died (0.3% of AP,50% of WE). Two patients of WE were treated with parenteral thiamine (vitamin B_ 1 ),and they survived. Conclusions PE occurred in early stage of SAP or recrudescence,while WE usually occurred in convalescent stage of SAP/AP. Long fasting,repeated vomiting,and total parenteral nutrition (TPN) without VitB_ 1 were main causes of VitB_ 1 deficiency,which might be the main causative factor in WE.