Metepec, Mexico

Dextran 40 Plus Ringer's Lactate Vs. Ringer's Lactate Alone for Fluid Resuscitation in Acute Pancreatitis

Detailed Description Acute pancreatitis (AP) is a common gastrointestinal disorder requiring hospitalization, with an incidence of approximately 40 cases per 100,000 individuals. The severity of AP ranges from mild to severe, with 15-20% of cases progressing to severe acute pancreatitis (SAP), which is characterized by organ failure and local complications. The mortality rate for severe acute pancreatitis remains high, reaching 20-30%, highlighting the critical need for early and adequate fluid resuscitation in emergency settings. Despite universal recommendations for early-volume resuscitation, there is no clear consensus regarding the optimal fluid type, infusion rate, total volume, or monitoring strategy. Fluid resuscitation's primary objective is to prevent or minimize systemic inflammatory response syndrome (SIRS), which significantly contributes to AP progression. This randomized controlled trial (RCT) will compare the effectiveness of a colloid-crystalloid combination (Dextran 40 in sodium chloride [NaCl] 0.9 grams per liter [g/L] solution and Ringer's lactate solution in a 1:3 ratio) versus Ringer's lactate solution alone in preventing disease progression and reducing complications in patients with mild or moderate AP. Study Design This randomized clinical trial (RCT) will be conducted at Satu Mare County Emergency Hospital and enroll approximately 100 patients diagnosed with mild or moderate AP. Fluid Administration Rate: 1,5 mL/kg/h, based on patient hemodynamic status. - Data Collection and Assessment - Clinical and Demographic Data: - Age, sex. - Lifestyle factors (alcohol consumption, smoking). - Symptom onset time and severity classification (based on the Revised Atlanta -Classification, 2012). =Diagnostic Criteria (Requires ≥2 of 3): - Acute upper abdominal pain. - Serum amylase/lipase levels ≥3 times the upper standard limit (ULN). - Imaging findings (CT, ultrasound, or MRI) consistent with AP. Organ Failure Assessment: -Modified Marshall Scoring System (2012). Severity Scoring: - Modified Glasgow Score. - Acute Physiology and Chronic Health Evaluation II (APACHE II). - Bedside Index for Severity in Acute Pancreatitis (BISAP). - CT Severity Index. Laboratory Biomarkers & Monitoring Blood samples will be collected at admission and every 24 hours to assess: - Pancreatic Enzymes: Amylase, lipase. - Inflammatory Markers & Organ Function Parameters: - C-reactive protein (CRP). - Erythrocyte sedimentation rate (ESR). - Hematocrit. - Urea, creatinine. - Systemic inflammatory response syndrome (SIRS) markers. - Fibrinogen, ferritin. - Procalcitonin at enrollment and 72 hours. Additional Monitoring: An ultrasound will measure the Inferior vena cava (IVC) diameter and collapsibility index to estimate central venous pressure (CVP) and hemodynamic status. Urine output every 24 hours (target ≥0.5 mL/kg/h as an adequate resuscitation marker). Primary and Secondary Outcome Measures Primary Outcomes: Reduction in C-reactive protein (CRP) and SIRS Secondary Outcomes: - Reduced duration of hospitalization and lower ICU admission rates. - Reduction of erythrocyte sedimentation rate (ESR) and other inflammatory markers. - Complication rates (e.g., pancreatic necrosis, organ failure). - Hospitalization costs. - In-hospital mortality and follow-up mortality at 3 months. Follow-up and Study Endpoints Patients will be monitored throughout hospitalization and followed up at 12 weeks post-discharge. Expected Impact This study aims to identify the optimal fluid resuscitation strategy for mild and moderate AP. If the colloid-crystalloid combination proves superior, it could lead to changes in clinical guidelines for AP management, potentially reducing organ failure, ICU admissions, and mortality rates.

Bowel Sound in Predicting the Severity of Acute Pancreatitis: Protocol of a Prospective, Multi-center Study

Pancreatitis - Microbiome As Predictor of Severity II

Despite intensive research, early prediction of the course of acute pancreatitis (AP) is still not satisfactorily possible. Results of a European multicenter study showed that the intestinal microbiome is superior to established scores as a marker of severity in patients with AP. Hereby, a classifier was established using 16 differentially abundant rectal species and systemic inflammatory response syndrome (SIRS) and achieved an AUROC of 85%. Surprisingly, all species in the severe AP group were members of taxonomic families known for their short-chain fatty acid (SFCA) production. This observation contrasts with translational pancreatitis studies in mice. Based on these publications, a clinical trial is currently being initiated to treat severe AP with SCFA (NCT06147635). However, previous well-designed RCT that analyzed the effects of probiotics in predicted severe AP resulted in a worse outcome for patients in the probiotic arm. Consequently, national and international guidelines recommend against the usage of probiotics in AP. Collectively, more research is needed to further elucidate the role of the oro-intestinal microbiota in the development of severe AP. To validate the results of previously mentioned multicenter study and to profoundly analyze the role of microbial metabolites and the fungeome, patients with AP will be prospectively recruited. 1. Buccal and rectal swabs, stool and plasma will be obtained to analyze the orointestinal microbiome and microbial derived metabolites. 2. Centers from different continents with different ethical background and dietary habits will enroll patients to gain a more generalizable microbial profile. 3. Microbial shifts were observed between severe AP (RAC 3) and mild/ moderate severe (RAC 1+2). 4. It is expected that the microbial compositions change during the inflammatory process upon early phase of pancreatitis. To minimize this microbial alternating effect a short time frame from hospital admission to recruitment (48h) is set.

Study's Care of Acute Pancreatitis at Saint-Etienne University Hospital.

A Trial on the Recurrence Free Survival Rate of Type I AIP With High-risk of Recurrence

Autoimmune pancreatitis (AIP) is an autoimmune disease with low incidence rate and involving the pancreas. It can be divided into type I AIP and type II AIP. In China, type I AIP is predominant, accompanied by elevated IgG4 levels, diffuse or segmental pancreatic enlargement, and irregular narrowing of the pancreatic duct. Glucocorticoids (GC) have a significant therapeutic effect. Even though a consensus has been reached on the effective initial GC treatment dose, type I AIP is prone to recurrence after GC induction and maintenance therapy. Currently, there is no consensus on how to reduce the disease recurrence rate in high-risk type I AIP patients. The International Pancreatic Society has released an international consensus on AIP, indicating that the risk factors for AIP recurrence are still unclear. The following are possible signs of recurrence: IgG4>4 times the upper limit of normal value before treatment; The serum IgG4 level remained high after GC treatment; Pancreatic diffuse enlargement; IgG4-SC with proximal bile duct involvement; Involvement of extrapancreatic organs.Multiple studies have shown that immunosuppressants (IM) combined with GC can effectively reduce the disease recurrence rate in IgG4 RD patients, including azathioprine, mycophenolate mofetil (MMF), etc. Among them, the incidence of adverse reactions in MMF is relatively low. As a special type of IgG4-RD, there is currently no prospective study evaluating the efficacy and safety of GC combined with MMF treatment in high-risk recurrent type I AIP patients. The smooth implementation of this project can provide new treatment ideas and evidence-based medicine for reducing the recurrence rate of high-risk type I AIP.Main research objective: To evaluate the impact of corticosteroid monotherapy and corticosteroid combined with MMF maintenance therapy on disease remission rate in high-risk type I AIP patients with recurrence within 3 years Secondary research objective: (I) To evaluate the impact on endocrine function; (II) Evaluate the impact on external secretion function; (III) Evaluate the impact on the incidence of malignant tumors; (IV) Adverse reactions; (V) Treatment costs

Diabetes RElated to Acute Pancreatitis and Its Mechanisms: Metabolic Outcomes Using Novel CGM Metrics

The primary objective of the DREAM-ON study is to determine if continuous glucose monitoring (CGM) metrics can predict the incidence of prediabetes mellitus (PDM) and diabetes mellitus (DM) after an episode of acute pancreatitis (AP). Secondary objectives of the DREAM-ON study include determining if CGM metrics predict the need for insulin therapy in participants who develop diabetes mellitus after AP, and if CGM metrics correlate with measures of insulin secretion and insulin resistance. The specific aims of the DREAM-ON study are as follows: Aim 1: To test whether standard CGM metrics predict incident DM. The investigators will perform blinded CGM in DREAM-ON participants at their scheduled visits at months 3, 12, 24 and subsequent annual visits. The investigators will test whether standard CGM metrics (mean glucose, time in tight range 70-140, time in range 70-180, time above 180 mg/dL, time above 250 mg/dL and glucose CV) predict incident DM determined by fasting plasma glucose (FPG), HbA1c, oral glucose tolerance testing (OGTT) and clinical report. Aim 2: To test whether CGM metrics predict need for insulin therapy in patients who develop DM after AP. From blinded CGM, we will test whether standard CGM metrics (mean glucose, time in tight range 70-140, time in range 70-180, time above 180 mg/dL, time above 250 mg/dL and glucose CV) as well as other indices of glucose variability, including mean amplitude of glycemic excursions (MAGE), predict need for long-term insulin therapy. Aim 3: To determine whether CGM metrics correlate with measures of insulin secretion and insulin resistance. The investigators will test whether standard and advanced CGM metrics correlate with measures of insulin secretion and insulin resistance derived from the OGTT, the mixed meal tolerance test (MMT) and the frequently sampled intravenous glucose tolerance test (FSIGTT). The investigators also will test whether these metrics can be used as a surrogate to predict diabetes subtype (i.e., insulin deficient vs. insulin resistant).

Evaluation of Intravenous Fluid Therapy Within Dallas Acute Pancreatitis Protocol

In the last 20 years, the incidence of AP and rate of hospitalization have steadily increased. Approximately, two-thirds of AP patients will have a mild and self-limiting course of the disease, leaving the remaining one-third experiencing moderately severe to severe disease that is associated with worse outcomes. Overall, the estimated mortality of pancreatitis is 1% however, mortality can be as high as 30% to 40% among patients with AP and organ failure or pancreatic necrosis. Despite numerous randomized clinical trials, there is no medication shown to be successful at treating AP. AP is associated with fluid deficit secondary to low intake and vomiting. Early intravenous fluid (IVF) resuscitation has been long-established as the initial cornerstone treatment to prevent hypovolemia and subsequent organ failure within the first 48 to 72 hours. The rationale for such intervention is to provide adequate intravascular volume support to counteract fluid shift into the third space. However, available evidence for an effective fluid regimen is lacking with regard to the type of fluid, the optimal rate of administration, and how to assess appropriate goals/targets for adequate resuscitation. Furthermore, the literature has presented conflicting results on whether aggressive versus goal-directed fluid resuscitation will lead to a reduction in mortality and improve outcomes. Although early supportive care with IVF therapy is recommended by the major guidelines, there are potential, serious complications associated with aggressive resuscitation, including volume overload, respiratory failures, intra-abdominal compartments.

Comparative Clinical Study to Evaluate the Possible Efficacy and Safety of Oral N-Acetyl Cysteine Versus Rectal Diclofenac in the Prevention of Post Endoscopic Retrograde Cholangiopancreatography Pancreatitis

Endoscopic retrograde cholangiopancreatography (ERCP) , a key tool that is used in diagnosis and treatment of pancreato-biliary diseases. Post-ERCP pancreatitis (PEP) is the most common and serious complication that can occur following this procedure and can lead to significant morbidity and mortality. A variety of patient-related and procedure-related factors have been associated with higher rates of PEP. Two definitions were used for diagnosis of PEP. In both definitions, PEP is diagnosed if two of the three criteria are found in the patient .The consensus criteria that was developed by Cotton and Colleagues in 1991 defined PEP as the presence of a new pancreatic-type abdominal pain associated with at least a threefold elevation in pancreatic enzyme concentration occurring 24 hours following the ERCP procedure, with the necessity for a new or extended hospitalization for at least two nights. Severity of pancreatitis is defined based on the number of hospitalized days following ERCP as mild (< 4 days), moderate (4 to 10 days), or severe (>10 days). The revised Atlanta Classification in 2012 lists abdominal pain consistent with acute pancreatitis, amylase or lipase elevation to more than 3 times the upper limit of normal, and abdominal imaging that reveals pancreatic inflammation. Several potential triggers can contribute to PEP. Mechanical trauma caused by ERCP instrumentation can harm the papilla and pancreatic duct, affecting pancreatic drainage. Thermal injury can occur during biliary or pancreatic sphincterotomy electrosurgical current. Chemical damage can occur when contrast medium is introduced into the pancreatic duct. Hydrostatic damage can occur when injecting contrast media into the pancreatic duct or infusing fluids such as water or saline solution during sphincter manometry. Regardless of the cause, the initial injury sets in motion a chain of events that include premature activation of proteolytic enzymes, autodigestion of pancreatic tissue, and impaired secretion from acinar cells. These events result in pancreatitis clinical symptoms, which have an influence both locally and systemically. Most PEP prevention techniques try to disrupt one or more steps in this cascade. While the precise mechanism of PEP remains unknown, it is most likely induced by a proinflammatory cascade initiated by pancreatic acinar cell damage, which results in systemic cytokine release. Cytokines play a major role in the pathogenesis of acute pancreatitis as part of the underlying systemic inflammatory response, tissue damage, and organ dysfunction. Tumor necrosis factor alpha (TNF-α) is a pro-inflammatory cytokine that promotes the inflammatory response, whereas Interleukin-10 (IL-10) is an immunosuppressive cytokine that inhibits inflammation. These markers can be used in measurement of the degree of systemic inflammation as predictors of the development of PEP. Phospholipase A2 is essential in this signaling cascade. Diclofenac is a nonsteroidal anti-inflammatory drug (NSAID) that effectively inhibits phospholipase A2 activity. According to this notion, anti-inflammatory drugs such as diclofenac can stop or attenuate the first cascade that leads to clinical PEP. Previous meta-analyses have suggested that NSAIDs are effective in preventing PEP. The European Society of Gastrointestinal Endoscopy guidelines recommend routine rectal administration of 100 mg of diclofenac or indomethacin immediately before ERCP procedure in all patients without contraindications to NSAIDs administration. Rectal administration route of diclofenac is the most effective in the prevention of PEP. Rectal diclofenac is a cheap, widely available agent with easy administration method and favorable side effect profile. Oxidative stress and active oxygen species can activate inflammatory cascade and immune responses. N-acetyl cysteine (NAC), an antioxidant drug with anti-inflammatory properties can inhibit oxidative stress as well as inflammatory intermediates, suggesting that it could aid in the prevention of PEP. Despite the failure of intravenous N-acetyl cysteine studies, 2013 pilot research revealed that oral NAC may be useful in reducing PEP. This would be due to the different pharmacokinetics of NAC followed in different studies. In a multicenter global randomized controlled trial investigation, It is reported that oral NAC is more effective than indomethacin in the prevention of PEP. Although both oral NAC and rectal diclofenac are widely used pharmacological agents, till now no study has evaluated their comparative safety and efficacy in preventing PEP. Hence this study is planned to evaluate and compare their efficacy and safety in preventing PEP.

Short-term Intravenous Fluids for Prevention of Post-ERCP Pancreatitis

Early Pancreatic Stent Placement for Preventing PEP

Patients with challenging biliary access using pancreatic guidewire-assisted method will be enrolled in the study. Recruitment will take place among individuals referred to the four participating centers for therapeutic biliary procedures. After obtaining signed consent forms, participants who meet all the inclusion criteria and have no exclusion criteria will be randomly grouped (with a 1:1 ratio) into EPSP and LPSP