BACKGROUND Post-endoscopic retrograde cholangiopancreatography pancreatitis(PEP)is a prevalent and potentially serious complication in patients undergoing endoscopic retrograde cholangiopancreatography.AIM To comprehe...BACKGROUND Post-endoscopic retrograde cholangiopancreatography pancreatitis(PEP)is a prevalent and potentially serious complication in patients undergoing endoscopic retrograde cholangiopancreatography.AIM To comprehensively assess the efficacy of indomethacin therapy in reducing PEP risk.METHODS We searched PubMed,EMBASE,Scopus,and Cochrane Library databases to identify randomized controlled trials(RCTs)that compared rectal indomethacin with a control group to prevent PEP.Duplicates were removed,and studies were included based on the established inclusion criteria.We used the Cochrane Collaboration’s tool to assess the risk of bias in the RCTs.A random-effects model was applied to produce pooled risk ratios(RRs)with 95%confidence intervals(CIs).RESULTS We included a total of 30 RCTs involving 16977 patients.Compared to the control group,rectal indomethacin showed comparable rates of overall PEP(PEP;RR=0.85,95%CI:0.69-1.04,I2=79%)with no statistically significant difference of RR in mild(RR=0.92,95%CI:0.74-1.14),moderate(RR=0.78,95%CI:0.59-1.02),or severe PEP(RR=1.12,95%CI:0.75-1.67).There was also no difference in cases of adverse events(RR=0.97,95%CI:0.69-1.35),abdominal pain(RR=1.14,95%CI:0.80-1.62),bleeding(RR=1.07,95%CI:0.70-1.63),or mortality(RR=0.86,95%CI:0.56-1.33)between the two groups.Subgroup analyses were also performed.CONCLUSION Rectal indomethacin appears to be safe and may offer benefit in selected high-risk patients,though findings should be interpreted with caution due to high heterogeneity.展开更多
Acute pancreatitis(AP)is sudden inflammation of the pancreas,which can lead to multiple organ dysfunction in severe cases.Hypertriglyceridemia(HTG)is the third most common cause.In recent years,HTG-induced AP(HTG-AP)h...Acute pancreatitis(AP)is sudden inflammation of the pancreas,which can lead to multiple organ dysfunction in severe cases.Hypertriglyceridemia(HTG)is the third most common cause.In recent years,HTG-induced AP(HTG-AP)has garnered increasing attention.Compared to AP caused by other causes,HTG-AP often has a more subtle onset but is more likely to progress to a severe,critical illness that poses a serious threat to a patient’s life and health.Research suggests a potential connection between the gut microbiota and AP,which could be mediated by bacterial metabolites,immune cells,and inflammatory factors.This is supported by observations of microbial imbalance and higher intestinal permeability in patients with AP.In addition,studies have shown that HTG-induced changes in gut microbiota can worsen AP by negatively impacting the host metabolism,immune response,and function of the intestinal barrier.In this review,we summarize recent clinical and animal studies on the role and mechanism of gut microbiota in the severity of AP aggravated by HTG.The application prospects of the newly proposed microbial-host-isozyme concept are summarized,focusing on its potential for the precision diagnosis and treatment of HTG-AP through gut microbiota regulation.展开更多
Pancreatitis is a prevalent inflammatory disorder of the pan-creas that poses a substantial global health burden.It is broadly categorized into acute pancreatitis(AP),chronic pancreatitis(CP),and other less common typ...Pancreatitis is a prevalent inflammatory disorder of the pan-creas that poses a substantial global health burden.It is broadly categorized into acute pancreatitis(AP),chronic pancreatitis(CP),and other less common types.The annual incidence of AP ranges from 13 to 49 cases per 100000 individuals[1].AP is character-ized by an abrupt onset and rapid disease progression.Approxi-mately 20%of patients develop moderate to severe AP,which are associated with a high risk of organ failure and mortality due to local and systemic complications[1].The global incidence of CP is approximately 10 cases per 100000 individuals annually.展开更多
BACKGROUND Celiac disease(CD)is an autoimmune disorder associated with an increased risk of pancreatitis,yet large-scale studies examining long-term risk and specific etiologies in CD patients are scarce.AIM To assess...BACKGROUND Celiac disease(CD)is an autoimmune disorder associated with an increased risk of pancreatitis,yet large-scale studies examining long-term risk and specific etiologies in CD patients are scarce.AIM To assess the long-term risk of pancreatitis in CD patients.METHODS We conducted a population-based cohort study with consecutive patients diagnosed with CD using the TriNeTx research network.Each patient was matched to a patient in the control group using a 1:1 propensity score matching to minimize confounding effects.The primary outcomes were the incidence of acute pancreatitis and chronic pancreatitis,and the secondary outcome was to assess the etiologies of pancreatitis.The incidence was estimated using a Cox proportional hazards model with a hazard ratio(HR)and 95%confidence interval(CI).RESULTS A total of 160228 patients were identified to have CD,and the remaining 250725 individuals without CD were considered as controls.At 7-year follow-up,CD patients exhibited a significantly higher risk of acute pancreatitis(HR=2.05;95%CI:1.93-2.17)and chronic pancreatitis(HR=1.42;95%CI:1.31-1.54)compared to controls.Elevated risks for alcohol-induced(HR=1.35),biliary(HR=1.37),and idiopathic pancreatitis(HR=1.49)were also observed.Findings remained robust across all follow-up intervals and sensitivity analyses.CONCLUSION Patients with CD have a substantially increased long-term risk of acute and chronic pancreatitis,including alcoholrelated,biliary,and idiopathic subtypes.These findings support the routine surveillance of pancreatitis in CD management and highlight the need for further research into disease-specific risk factors and mitigation approaches.展开更多
Acute pancreatitis(AP)is a prevalent gastrointestinal disease necessitating hospitalization globally,with an annual incidence ranging from 13 to 45 per 100,000 individuals[1]and a mortality rate of 5%-10%.[2]While mos...Acute pancreatitis(AP)is a prevalent gastrointestinal disease necessitating hospitalization globally,with an annual incidence ranging from 13 to 45 per 100,000 individuals[1]and a mortality rate of 5%-10%.[2]While most cases follow a self-limiting course,approximately 20%-30%of cases progress to severe acute pancreatitis(SAP),characterized by pancreatic necrosis and multiorgan failure,with the mortality rate increasing to 36%-50%.展开更多
BACKGROUND Painless acute pancreatitis(PAP)is a slowly progressive disease that involves inflammation,scarring,and thickening of pancreatic cells,which can happen due to either alcohol,idiopathic,or genetic.Clinicians...BACKGROUND Painless acute pancreatitis(PAP)is a slowly progressive disease that involves inflammation,scarring,and thickening of pancreatic cells,which can happen due to either alcohol,idiopathic,or genetic.Clinicians usually miss PAP due to lack of pain and additional symptoms of hypotension and fever can lead to an infectious work-up instead.In this case report,we discuss the importance of the rapid discovery of this condition to prevent devastating complications like diabetes,necrotizing pancreatitis,or even death.CASE SUMMARY A 47-years old male with past medical history of hypotension and alcohol abuse presented for loss of consciousness.Patient was found with pinpoint pupils,hypoglycemia,and hypotensive.He received Narcan,dextrose,and IV fluids and became responsive.In the emergency department,the patient was hypotensive and the physical exam was only significant for diaphoresis.Patient denied abdominal or radiating pain.Labs significant for elevated lipase,metabolic acidosis,and hyponatremia with imaging positive for AP without chronic inflammation.Based on imaging,lipase and absence of pain,PAP was diagnosed.Patient had multiple episodes of hypoglycemia and remained hypotensive requiring pressor support and intubation.After intubation,he had pulseless electrical activity cardiac arrest.Return of spontaneous circulation achieved but the patient had worsening acidosis,acute kidney injury,liver injury,and bandemia.Empiric antibiotics started,dexamethasone,and maxed on five pressors and transferred to the medical intensive care unit for management of severe AP(SAP).CONCLUSION This case report featured PAP without chronic inflammation which is an even rarer disease than PAP which progressed to SAP.展开更多
We read the article by Karim MM et al discusses the presentation of primary hyperparathyroidism as recurrent acute pancreatitis,a rare clinical condition in pediatric patients presenting to the emergency department.As...We read the article by Karim MM et al discusses the presentation of primary hyperparathyroidism as recurrent acute pancreatitis,a rare clinical condition in pediatric patients presenting to the emergency department.As emergency medicine clinicians,we frequently encounter diverse and complex cases,and such rare conditions pose significant challenges in the diagnostic process.This article will discuss the management and diagnostic approach of such cases encountered in the emergency department.展开更多
Hereditary Pancreatitis(HP)has emerged as a significant cause of acute,acute recurrent and chronic pancreatitis in the pediatric population.Given that it presents similarly to other causes of pancreatitis,a positive f...Hereditary Pancreatitis(HP)has emerged as a significant cause of acute,acute recurrent and chronic pancreatitis in the pediatric population.Given that it presents similarly to other causes of pancreatitis,a positive family history and/or isolation of a gene mutation are vital in its designation.Inheritance patterns remain complex,but mutations involving the PRSS1,SPINK1,CFTR and CTRC genes are commonly implicated.Since being first described in 1952,dozens of genetic alterations that modify the action of pancreatic enzymes have been identified.Among children,these variants have been isolated in more than 50%of patients with chronic pancreatitis.Recent research has noted that such mutations in PRSS1,SPINK1 and CFTR genes are also associated with a faster progression from acute pancreatitis to chronic pancreatitis.Patients with HP are at increased risk of developing diabetes mellitus,exocrine pancreatic insufficiency,and pancreatic adenocarcinoma.Management follows a multi-disciplinary approach with avoidance of triggers,surveillance of associated conditions,treatment of pancreatic insufficiency and use of endoscopic and surgical interventions for complications.With significant sequela,morbidity and a progressive nature,a thorough understanding of the etiology,pathophysiologic mechanisms,diagnostic evaluation,current management strategies and future research considerations for this evolving disease entity in pediatrics is warranted.展开更多
Acute pancreatitis(AP)remains a clinical challenge due to its heterogeneous presentation and potential for rapid progression to severe disease.In their editorial,Wang et al highlight phospholipase D2(PLD2)as a novel c...Acute pancreatitis(AP)remains a clinical challenge due to its heterogeneous presentation and potential for rapid progression to severe disease.In their editorial,Wang et al highlight phospholipase D2(PLD2)as a novel candidate biomarker,proposing its involvement in key inflammatory pathways and its inverse correlation with disease severity.While this represents a promising improvement in precision diagnostics,significant gaps remain that require further investigation.Specifically,the functional role of PLD2 in the molecular cascade of AP is not yet fully understood.Questions still remain,such as:Is the observed downregulation of PLD2 a causal factor or an epiphenomenon?Does PLD2 modulation offer a tangible therapeutic benefit beyond a mere correlation?These questions highlight the necessity of mechanistic in vivo studies to validate the role and therapeutic potential of PLD2.Furthermore,interindividual variability in inflammatory responses raises concerns regarding PLD2’s predictive consistency across genetically diverse populations.The temporal dynamics of PLD2 expression in AP also remain unclear;establishing whether its variations precede clinical deterioration is essential for its use in early risk stratification,integrating multiomics research(proteomics,metabolomics,transcriptomics,and lipidomics),which can clarify the biological interactions and regulatory pathways of PLD2 under complex mechanisms.Likewise,well-designed,multicenter,prospective studies will be essential in determining its true clinical value.The research by Wang et al initiates an intriguing direction in the quest for AP biomarkers,but further research is required before PLD2 can be established as a clinically applicable tool.Additional efforts are required to close this gap and define whether its role transcends a mere association in order for it to become a therapeutic target.展开更多
In this article,we have commented on the article by Augustin et al.The authors presented a systematic review of the diagnosis,treatment,and outcomes of primary hyperparathyroidism-induced acute pancreatitis in pregnan...In this article,we have commented on the article by Augustin et al.The authors presented a systematic review of the diagnosis,treatment,and outcomes of primary hyperparathyroidism-induced acute pancreatitis in pregnant women.Since acute pancreatitis during pregnancy could cause maternal as well as fetal adverse outcomes,understanding this pathology is essential.Although there are various etiologies of acute pancreatitis during pregnancy,primary hyperparathyroidism is one of the causes that complicate hypercalcemia.Along with conventional treatment for acute pancreatitis,parathyroidectomy can effectively normalize calcium levels and improve acute pancreatitis.Augustin et al have provided vital information that can enable physicians to understand and treat hyperparathyroidism-induced acute pancreatitis in pregnant women,which could contribute to better maternal and fetal outcomes.In addition,since primary hyperparathyroidism is associated with multiple endocrine neoplasia,further consideration regarding screening for multiple endocrine neoplasia might lead to better prognoses.展开更多
BACKGROUND Early risk stratification in severe acute pancreatitis(SAP)remains challenging with traditional scoring systems overlooking etiological heterogeneity,particularly in hypertriglyceridemic acute pancreatitis(...BACKGROUND Early risk stratification in severe acute pancreatitis(SAP)remains challenging with traditional scoring systems overlooking etiological heterogeneity,particularly in hypertriglyceridemic acute pancreatitis(HTG-AP).AIM To develop and evaluate a machine learning(ML)model combining intraabdominal pressure(IAP)and procalcitonin(PCT)for SAP prognosis and evaluate its clinical impact across different etiologies.METHODS We retrospectively analyzed 245 patients with pancreatitis(98 patients with SAP).An ML model using 24-h peak IAP and PCT levels was used to predict 28-day mortality.Propensity score matching was used to compare IAP-PCT-guided management with conventional management.RESULTS The ML-IAP-PCT model outperformed the Acute Physiology and Chronic Health Evaluation II score(area under the curve:0.853 vs 0.801,P=0.044)and Bedside Index of Severity in Acute Pancreatitis score.IAP-PCT-guided management was associated with lower mortality(15.8%vs 25.0%,P=0.043)and multiple organ dysfunction syndrome(48.7%vs 61.8%,P=0.027)rates.Patients with HTG-AP showed the greatest benefit(multiple organ dysfunction syndrome:39.3%vs 60.7%,P=0.018).CONCLUSION ML-optimized IAP-PCT monitoring provides superior prognostic accuracy and guides management associated with improved outcomes,especially in patients with HTG-AP.Prospective validation is needed to establish causality for this etiology-stratified approach.展开更多
BACKGROUND Sodium-glucose cotransporter-2(SGLT-2)inhibitors improve cardiovascular and renal outcomes in diabetes but may induce euglycemic diabetic ketoacidosis(euDKA)via insulin-independent mechanisms.Post-pancreati...BACKGROUND Sodium-glucose cotransporter-2(SGLT-2)inhibitors improve cardiovascular and renal outcomes in diabetes but may induce euglycemic diabetic ketoacidosis(euDKA)via insulin-independent mechanisms.Post-pancreatitis diabetes mellitus(PPDM)patients with impairedβ-cell function face undefined risks with these agents.CASE SUMMARY A 29-year-old man with PPDM developed euDKA 1 week after initiating etogliflozin(5 mg/day).On admission,laboratory tests revealed blood ketones>4.5 mmol/L,pH 7.1,and glucose 10.78 mmol/L.Discontinuation of SGLT-2 inhibitor,insulin pump therapy(basal 12 U/day,premeal bolus 4 U),aggressive hydration(6000 mL first 2 days),and nutritional support normalized ketosis and acidosis within 24 hours.CONCLUSION Caution is warranted with SGLT-2 inhibitors in PPDM.Insulin therapy is preferred to prevent euDKA.展开更多
BACKGROUND The objective of the current study was to elucidate the clinical mechanism through which phospholipase D2(PLD2)exerted a regulatory effect on neutrophil migra-tion,thereby alleviating the progression of acu...BACKGROUND The objective of the current study was to elucidate the clinical mechanism through which phospholipase D2(PLD2)exerted a regulatory effect on neutrophil migra-tion,thereby alleviating the progression of acute pancreatitis.AIM To elucidate the clinical mechanism through which PLD2 exerted a regulatory effect on neutrophil migration,thereby alleviating the progression of acute pan-creatitis.METHODS The study involved 90 patients diagnosed with acute pancreatitis,admitted to our hospital between March 2020 and November 2022.A retrospective analysis was conducted,categorizing patients based on Ranson score severity into mild(n=25),moderate(n=30),and severe(n=35)groups.Relevant data was collected for each group.Western blot analysis assessed PLD2 protein expression in patient serum.Real-time reverse transcription polymerase chain reaction was used to evaluate the mRNA expression of chemokine receptors associated with neutrophil migration.Serum levels of inflammatory factors in patients were detected using enzyme-linked immunosorbent assay.Transwell migration tests were conducted to compare migration of neutrophils across groups and analyze the influence of PLD2 on neutrophil migration.RESULTS Overall data analysis did not find significant differences between patient groups(P>0.05).The expression of PLD2 protein in the severe group was lower than that in the moderate and mild groups(P<0.05).The expression level of PLD2 in the moderate group was also lower than that in the mild group(P<0.05).The severity of acute pancreatitis is negatively correlated with PLD2 expression(r=-0.75,P=0.002).The mRNA levels of C-X-C chemokine receptor type 1,C-X-C chemokine receptor type 2,C-C chemokine receptor type 2,and C-C chemokine receptor type 5 in the severe group are significantly higher than those in the moderate and mild groups(P<0.05),and the expression levels in the moderate group are also higher than those in the mild group(P<0.05).The levels of C-reactive protein,tumor necrosis factor-α,interleukin-1β,and interleukin-6 in the severe group were higher than those in the moderate and mild groups(P<0.05),and the levels in the moderate group were also higher than those in the mild group(P<0.05).The number of migrating neutrophils in the severe group was higher than that in the moderate and mild groups(P<0.05),and the moderate group was also higher than the mild group(P<0.05).In addition,the number of migrating neutrophils in the mild group combined with PLD2 inhibitor was higher than that in the mild group(P<0.05),and the number of migrating neutrophils in the moderate group combined with PLD2 inhibitor was higher than that in the moderate group(P<0.05).The number of migrating neutrophils in the severe group+PLD2 inhibitor group was significantly higher than that in the severe group(P<0.05),indicating that PLD2 inhibitors significantly stimulated neutrophil migration.CONCLUSION PLD2 exerted a crucial regulatory role in the pathological progression of acute pancreatitis.Its protein expression varied among patients based on the severity of the disease,and a negative correlation existed between PLD2 expression and disease severity.Additionally,PLD2 appeared to impede acute pancreatitis progression by limiting neutrophil migration.展开更多
Whether acute recurrent pancreatitis is a chronic disease is still debated and a consensus is not still reached as demonstrated by differences in the classification of acute recurrent pancreatitis. There is major evid...Whether acute recurrent pancreatitis is a chronic disease is still debated and a consensus is not still reached as demonstrated by differences in the classification of acute recurrent pancreatitis. There is major evidence for considering alcoholic pancreatitis as a chronic disease ab initio while chronic pancreatitis lesions detectable in biliary acute recurrent pancreatitis (ARP) seem a casual association. Cystic fibrosis transmembrane con-ductance regulator (CFTR) gene mutation, hereditary and obstructive pancreatitis seem an acute disease that progress to chronic pancreatitis, likely as a consequence of the activation and proliferation of pancreatic stellate cells that produce and activate collagen and therefore fibrosis. From the diagnostic point of view, in patients with acute recurrent pancreatitis Endoscopic ultrasound (EUS) seems the more reliable technique for an accurate evaluation and follow-up of some ductal and parenchymal abnormalities suspected for early chronic pancreatitis.展开更多
The close proximity of the endoscopic ultrasound probe to the pancreas results in superior spatial resolution compared to CT scan and MRI. In addition, endoscopic ultrasound (EUS) is a minimally invasive procedure tha...The close proximity of the endoscopic ultrasound probe to the pancreas results in superior spatial resolution compared to CT scan and MRI. In addition, endoscopic ultrasound (EUS) is a minimally invasive procedure that does not share the relatively high complication rate of ERCP. Due to these advantages, EUS has evolved into an important technique to assess pancreatobiliary disease. This review will discuss the role of EUS in patients with pancreatitis. The indications can be divided into acute pancreatitis and chronic pancreatitis. In acute pancreatitis, EUS is used to determine the etiology; in suspected chronic pancreatitis it is helpful to establish the diagnosis. Lastly, this review will discuss biliary pancreatitis with suspicion for persistent choledocholithiasis.展开更多
The mechanism of cell damage during acute pancreatitis (AP) has not been fully elucidated, and there is still a lack of specific or effective treatments. Increasing evidence has implicated mitochondrial dysfunction as...The mechanism of cell damage during acute pancreatitis (AP) has not been fully elucidated, and there is still a lack of specific or effective treatments. Increasing evidence has implicated mitochondrial dysfunction as a key event in the pathophysiology of AP. Mitochondrial dysfunction is closely related to calcium (Ca^(2+)) overload, intracellular adenosine triphosphate depletion, mitochondrial permeability transition pore openings, loss of mitochondrial membrane potential, mitophagy damage and inflammatory responses. Mitochondrial dysfunction is an early triggering event in the initiation and development of AP,and this organelle damage may precede the release of inflammatory cytokines, intracellular trypsin activation and vacuole formation of pancreatic acinar cells. This review provides further insight into the role of mitochondria in both physiological and pathophysiological aspects of AP, aiming to improve our understanding of the underlying mechanism which may lead to the development of therapeutic and preventive strategies for AP.展开更多
BACKGROUND Acute pancreatitis(AP)is a severe condition,and abdominal effusion is a significant predictor of its severity and prognosis.However,the relationship between ascites characteristics and AP outcomes remains u...BACKGROUND Acute pancreatitis(AP)is a severe condition,and abdominal effusion is a significant predictor of its severity and prognosis.However,the relationship between ascites characteristics and AP outcomes remains undefined.AIM To assess the correlation between ascites characteristics and clinical prognosis in AP patients by comparing color depth and turbidity of early ascites.METHODS This study included 667 AP patients with ascites,categorized by color and turbidity into yellow clear(n=54),yellow turbid(n=293),red brown(n=320).The trendχ2 test was employed to analyze the incidence of organ failure(OF),infected pancreatic necrosis(IPN),and mortality across groups.Receiver operating charac teristic(ROC)curves were used to evaluate the predictive value of ascites cell count,amylase,protein,and lactate dehydrogenase(LDH)for abdominal compartment syndrome(ACS)and intra-abdominal hemorrhage.RESULTS AP patients with ascites exhibited higher scores of scoring systems(such as Bedside index for severity in AP,Acute Physiology and Chronic Health Examination II,etc.)and increased complications and mortality rates(all P<0.05)compared to those without ascites.A linear association was observed between ascites color depth and turbidity and the incidence of OF,pancreatic necrosis,IPN,and mortality(P<0.05).LDH in ascites demonstrated high accuracy in predicting ACS and intra-abdominal hemorrhage,with areas under the ROC curve of 0.77 and 0.79,respectively.CONCLUSION Early in AP,ascites correlates with OF,IPN,and mortality,showing linear associations with color depth and turbidity.Ascitic LDH reliably predicts ACS and intra-abdominal hemorrhage in AP patients.展开更多
Infected necrotizing pancreatitis(INP)remains a life-threatening complication of acute pancreatitis.Despite advancements such as endoscopic ultrasound(EUS)-guided drainage,lumen-apposing metal stents,and protocolized ...Infected necrotizing pancreatitis(INP)remains a life-threatening complication of acute pancreatitis.Despite advancements such as endoscopic ultrasound(EUS)-guided drainage,lumen-apposing metal stents,and protocolized step-up strate-gies,the clinical practice remains heterogeneous,with variability in endoscopic strategies,procedural timing,device selection,and adjunctive techniques contri-buting to inconsistent outcomes.This review synthesizes current evidence to contribute to a structured framework integrating multidisciplinary team decision-making,advanced imaging(three-dimensional reconstruction,contrast-enhanced computed tomography/magnetic resonance imaging),EUS assessment,and biomarker-driven risk stratification(C-reactive protein,procalcitonin)to optimize patient selection,intervention timing,and complication management.Key stan-dardization components include endoscopic assessment and procedural strate-gies,optimal timing of intervention,personalized approaches for complex pan-creatic collections,and techniques to reduce the number of endoscopic debride-ments and mitigate complications.This work aims to enhance clinical outcomes,minimize practice heterogeneity,and establish a foundation for future research and guideline development in endoscopic management of INP.展开更多
Acute pancreatitis(AP)is a common but potentially devastating disease characterized at onset patho-physiologically by premature activation of digestive enzymes within the pancreas.Despite an abundance of preclinical r...Acute pancreatitis(AP)is a common but potentially devastating disease characterized at onset patho-physiologically by premature activation of digestive enzymes within the pancreas.Despite an abundance of preclinical research and,until recently,a series of disappointing clinical trials,no specific disease mod-ifying pharmacological treatment has yet been approved for this condition.Recent novel approaches to understanding the molecular pathogenesis of AP provide us with renewed optimism for translational drug discovery.Although digestive enzyme activation is the hallmark of AP,a critical mechanism that initiates AP is intracellular calcium(Ca2+)overload in pancreatic parenchymal cells,which triggers mitochondrial dysfunction,endoplasmic reticulum(ER)stress,and impairs autophagic flux.These processes are piv-otal to the disease and present a range of drug targets,associated with the inflammatory responses that drive local and systemic inflammation in AP.Progress in translation has now been made,targeting the ORAI channel with the inhibitor zegocractin(Auxora)to reduce pancreatic injury and inflammatory re-sponses in human AP.Herein we evaluated potential drug targets for the early treatment of AP,focused on intra-acinar mechanisms of injury central to the onset and severity of AP.Our analysis highlights the opportunities and progress in translating these molecular insights into clinical therapies.展开更多
Background:Previous studies have highlighted the frequent occurrence of sarcopenia in patients with pancreatic diseases,including chronic pancreatitis.We aimed to clarify the prevalence of skeletal muscle(SM)loss and ...Background:Previous studies have highlighted the frequent occurrence of sarcopenia in patients with pancreatic diseases,including chronic pancreatitis.We aimed to clarify the prevalence of skeletal muscle(SM)loss and sarcopenia,and their associations with clinical characteristics,bone mineral density,and pancreatic imaging findings in patients with autoimmune pancreatitis(AIP).Methods:This study included 114 patients with AIP treated at Tohoku University Hospital.The SM index was assessed using a bioelectrical impedance analysis device,grip strength was measured using a hand dynamometer,and bone mineral density was evaluated using dual-energy X-ray absorptiometry.Univari-ate and multivariate logistic regression analyses were used to analyze factors associated with SM loss and sarcopenia.Results:Among 114 patients,57(50.0%)had SM loss,31(27.2%)had reduced grip strength,and 27(23.7%)had both.Patients with SM loss were older and had a lower body mass index,weaker grip strength,higher Controlling Nutritional Status scores,and lower serum lipase and albumin levels compared to those without SM loss.Computed tomography scans revealed a higher prevalence of pancreatic parenchy-mal atrophy in patients with SM loss.Similar differences were observed between patients with sarcopenia and those without.Osteopathy was observed in 35.6%of patients with SM loss and 38.1%of those with sarcopenia,whereas only 4.1%of patients without SM loss had osteopathy.Low BMI(<21.0 kg/m^(2))was also found to be an independent risk factor for SM loss in multivariate analysis.Age>72 years,low BMI(<20.0 kg/m^(2)),and low serum lipase levels(<13 U/L)were independent risk factors for sarcopenia in multivariate analysis.Conclusions:SM loss and sarcopenia are prevalent in patients with AIP and are associated with aging,poor nutritional status,low serum lipase levels,and pancreatic parenchymal atrophy.In addition to the high risk of osteopathy,careful attention should be paid to maintain muscle health in AIP patients.展开更多
文摘BACKGROUND Post-endoscopic retrograde cholangiopancreatography pancreatitis(PEP)is a prevalent and potentially serious complication in patients undergoing endoscopic retrograde cholangiopancreatography.AIM To comprehensively assess the efficacy of indomethacin therapy in reducing PEP risk.METHODS We searched PubMed,EMBASE,Scopus,and Cochrane Library databases to identify randomized controlled trials(RCTs)that compared rectal indomethacin with a control group to prevent PEP.Duplicates were removed,and studies were included based on the established inclusion criteria.We used the Cochrane Collaboration’s tool to assess the risk of bias in the RCTs.A random-effects model was applied to produce pooled risk ratios(RRs)with 95%confidence intervals(CIs).RESULTS We included a total of 30 RCTs involving 16977 patients.Compared to the control group,rectal indomethacin showed comparable rates of overall PEP(PEP;RR=0.85,95%CI:0.69-1.04,I2=79%)with no statistically significant difference of RR in mild(RR=0.92,95%CI:0.74-1.14),moderate(RR=0.78,95%CI:0.59-1.02),or severe PEP(RR=1.12,95%CI:0.75-1.67).There was also no difference in cases of adverse events(RR=0.97,95%CI:0.69-1.35),abdominal pain(RR=1.14,95%CI:0.80-1.62),bleeding(RR=1.07,95%CI:0.70-1.63),or mortality(RR=0.86,95%CI:0.56-1.33)between the two groups.Subgroup analyses were also performed.CONCLUSION Rectal indomethacin appears to be safe and may offer benefit in selected high-risk patients,though findings should be interpreted with caution due to high heterogeneity.
基金Supported by the Innovation Foundation for Doctor Dissertation of Northwestern Polytechnical University,No.CX2023021.
文摘Acute pancreatitis(AP)is sudden inflammation of the pancreas,which can lead to multiple organ dysfunction in severe cases.Hypertriglyceridemia(HTG)is the third most common cause.In recent years,HTG-induced AP(HTG-AP)has garnered increasing attention.Compared to AP caused by other causes,HTG-AP often has a more subtle onset but is more likely to progress to a severe,critical illness that poses a serious threat to a patient’s life and health.Research suggests a potential connection between the gut microbiota and AP,which could be mediated by bacterial metabolites,immune cells,and inflammatory factors.This is supported by observations of microbial imbalance and higher intestinal permeability in patients with AP.In addition,studies have shown that HTG-induced changes in gut microbiota can worsen AP by negatively impacting the host metabolism,immune response,and function of the intestinal barrier.In this review,we summarize recent clinical and animal studies on the role and mechanism of gut microbiota in the severity of AP aggravated by HTG.The application prospects of the newly proposed microbial-host-isozyme concept are summarized,focusing on its potential for the precision diagnosis and treatment of HTG-AP through gut microbiota regulation.
文摘Pancreatitis is a prevalent inflammatory disorder of the pan-creas that poses a substantial global health burden.It is broadly categorized into acute pancreatitis(AP),chronic pancreatitis(CP),and other less common types.The annual incidence of AP ranges from 13 to 49 cases per 100000 individuals[1].AP is character-ized by an abrupt onset and rapid disease progression.Approxi-mately 20%of patients develop moderate to severe AP,which are associated with a high risk of organ failure and mortality due to local and systemic complications[1].The global incidence of CP is approximately 10 cases per 100000 individuals annually.
文摘BACKGROUND Celiac disease(CD)is an autoimmune disorder associated with an increased risk of pancreatitis,yet large-scale studies examining long-term risk and specific etiologies in CD patients are scarce.AIM To assess the long-term risk of pancreatitis in CD patients.METHODS We conducted a population-based cohort study with consecutive patients diagnosed with CD using the TriNeTx research network.Each patient was matched to a patient in the control group using a 1:1 propensity score matching to minimize confounding effects.The primary outcomes were the incidence of acute pancreatitis and chronic pancreatitis,and the secondary outcome was to assess the etiologies of pancreatitis.The incidence was estimated using a Cox proportional hazards model with a hazard ratio(HR)and 95%confidence interval(CI).RESULTS A total of 160228 patients were identified to have CD,and the remaining 250725 individuals without CD were considered as controls.At 7-year follow-up,CD patients exhibited a significantly higher risk of acute pancreatitis(HR=2.05;95%CI:1.93-2.17)and chronic pancreatitis(HR=1.42;95%CI:1.31-1.54)compared to controls.Elevated risks for alcohol-induced(HR=1.35),biliary(HR=1.37),and idiopathic pancreatitis(HR=1.49)were also observed.Findings remained robust across all follow-up intervals and sensitivity analyses.CONCLUSION Patients with CD have a substantially increased long-term risk of acute and chronic pancreatitis,including alcoholrelated,biliary,and idiopathic subtypes.These findings support the routine surveillance of pancreatitis in CD management and highlight the need for further research into disease-specific risk factors and mitigation approaches.
基金supported by National Natural Science Foundation of China(81272737).
文摘Acute pancreatitis(AP)is a prevalent gastrointestinal disease necessitating hospitalization globally,with an annual incidence ranging from 13 to 45 per 100,000 individuals[1]and a mortality rate of 5%-10%.[2]While most cases follow a self-limiting course,approximately 20%-30%of cases progress to severe acute pancreatitis(SAP),characterized by pancreatic necrosis and multiorgan failure,with the mortality rate increasing to 36%-50%.
文摘BACKGROUND Painless acute pancreatitis(PAP)is a slowly progressive disease that involves inflammation,scarring,and thickening of pancreatic cells,which can happen due to either alcohol,idiopathic,or genetic.Clinicians usually miss PAP due to lack of pain and additional symptoms of hypotension and fever can lead to an infectious work-up instead.In this case report,we discuss the importance of the rapid discovery of this condition to prevent devastating complications like diabetes,necrotizing pancreatitis,or even death.CASE SUMMARY A 47-years old male with past medical history of hypotension and alcohol abuse presented for loss of consciousness.Patient was found with pinpoint pupils,hypoglycemia,and hypotensive.He received Narcan,dextrose,and IV fluids and became responsive.In the emergency department,the patient was hypotensive and the physical exam was only significant for diaphoresis.Patient denied abdominal or radiating pain.Labs significant for elevated lipase,metabolic acidosis,and hyponatremia with imaging positive for AP without chronic inflammation.Based on imaging,lipase and absence of pain,PAP was diagnosed.Patient had multiple episodes of hypoglycemia and remained hypotensive requiring pressor support and intubation.After intubation,he had pulseless electrical activity cardiac arrest.Return of spontaneous circulation achieved but the patient had worsening acidosis,acute kidney injury,liver injury,and bandemia.Empiric antibiotics started,dexamethasone,and maxed on five pressors and transferred to the medical intensive care unit for management of severe AP(SAP).CONCLUSION This case report featured PAP without chronic inflammation which is an even rarer disease than PAP which progressed to SAP.
文摘We read the article by Karim MM et al discusses the presentation of primary hyperparathyroidism as recurrent acute pancreatitis,a rare clinical condition in pediatric patients presenting to the emergency department.As emergency medicine clinicians,we frequently encounter diverse and complex cases,and such rare conditions pose significant challenges in the diagnostic process.This article will discuss the management and diagnostic approach of such cases encountered in the emergency department.
文摘Hereditary Pancreatitis(HP)has emerged as a significant cause of acute,acute recurrent and chronic pancreatitis in the pediatric population.Given that it presents similarly to other causes of pancreatitis,a positive family history and/or isolation of a gene mutation are vital in its designation.Inheritance patterns remain complex,but mutations involving the PRSS1,SPINK1,CFTR and CTRC genes are commonly implicated.Since being first described in 1952,dozens of genetic alterations that modify the action of pancreatic enzymes have been identified.Among children,these variants have been isolated in more than 50%of patients with chronic pancreatitis.Recent research has noted that such mutations in PRSS1,SPINK1 and CFTR genes are also associated with a faster progression from acute pancreatitis to chronic pancreatitis.Patients with HP are at increased risk of developing diabetes mellitus,exocrine pancreatic insufficiency,and pancreatic adenocarcinoma.Management follows a multi-disciplinary approach with avoidance of triggers,surveillance of associated conditions,treatment of pancreatic insufficiency and use of endoscopic and surgical interventions for complications.With significant sequela,morbidity and a progressive nature,a thorough understanding of the etiology,pathophysiologic mechanisms,diagnostic evaluation,current management strategies and future research considerations for this evolving disease entity in pediatrics is warranted.
基金Supported by Mexican Association of Gastroenterology 2023 for the scholarship warded.
文摘Acute pancreatitis(AP)remains a clinical challenge due to its heterogeneous presentation and potential for rapid progression to severe disease.In their editorial,Wang et al highlight phospholipase D2(PLD2)as a novel candidate biomarker,proposing its involvement in key inflammatory pathways and its inverse correlation with disease severity.While this represents a promising improvement in precision diagnostics,significant gaps remain that require further investigation.Specifically,the functional role of PLD2 in the molecular cascade of AP is not yet fully understood.Questions still remain,such as:Is the observed downregulation of PLD2 a causal factor or an epiphenomenon?Does PLD2 modulation offer a tangible therapeutic benefit beyond a mere correlation?These questions highlight the necessity of mechanistic in vivo studies to validate the role and therapeutic potential of PLD2.Furthermore,interindividual variability in inflammatory responses raises concerns regarding PLD2’s predictive consistency across genetically diverse populations.The temporal dynamics of PLD2 expression in AP also remain unclear;establishing whether its variations precede clinical deterioration is essential for its use in early risk stratification,integrating multiomics research(proteomics,metabolomics,transcriptomics,and lipidomics),which can clarify the biological interactions and regulatory pathways of PLD2 under complex mechanisms.Likewise,well-designed,multicenter,prospective studies will be essential in determining its true clinical value.The research by Wang et al initiates an intriguing direction in the quest for AP biomarkers,but further research is required before PLD2 can be established as a clinically applicable tool.Additional efforts are required to close this gap and define whether its role transcends a mere association in order for it to become a therapeutic target.
文摘In this article,we have commented on the article by Augustin et al.The authors presented a systematic review of the diagnosis,treatment,and outcomes of primary hyperparathyroidism-induced acute pancreatitis in pregnant women.Since acute pancreatitis during pregnancy could cause maternal as well as fetal adverse outcomes,understanding this pathology is essential.Although there are various etiologies of acute pancreatitis during pregnancy,primary hyperparathyroidism is one of the causes that complicate hypercalcemia.Along with conventional treatment for acute pancreatitis,parathyroidectomy can effectively normalize calcium levels and improve acute pancreatitis.Augustin et al have provided vital information that can enable physicians to understand and treat hyperparathyroidism-induced acute pancreatitis in pregnant women,which could contribute to better maternal and fetal outcomes.In addition,since primary hyperparathyroidism is associated with multiple endocrine neoplasia,further consideration regarding screening for multiple endocrine neoplasia might lead to better prognoses.
基金Supported by Huzhou Science and Technology Bureau Public Welfare Applied Research Project-General Medical and Health Program,No.2021GY21.
文摘BACKGROUND Early risk stratification in severe acute pancreatitis(SAP)remains challenging with traditional scoring systems overlooking etiological heterogeneity,particularly in hypertriglyceridemic acute pancreatitis(HTG-AP).AIM To develop and evaluate a machine learning(ML)model combining intraabdominal pressure(IAP)and procalcitonin(PCT)for SAP prognosis and evaluate its clinical impact across different etiologies.METHODS We retrospectively analyzed 245 patients with pancreatitis(98 patients with SAP).An ML model using 24-h peak IAP and PCT levels was used to predict 28-day mortality.Propensity score matching was used to compare IAP-PCT-guided management with conventional management.RESULTS The ML-IAP-PCT model outperformed the Acute Physiology and Chronic Health Evaluation II score(area under the curve:0.853 vs 0.801,P=0.044)and Bedside Index of Severity in Acute Pancreatitis score.IAP-PCT-guided management was associated with lower mortality(15.8%vs 25.0%,P=0.043)and multiple organ dysfunction syndrome(48.7%vs 61.8%,P=0.027)rates.Patients with HTG-AP showed the greatest benefit(multiple organ dysfunction syndrome:39.3%vs 60.7%,P=0.018).CONCLUSION ML-optimized IAP-PCT monitoring provides superior prognostic accuracy and guides management associated with improved outcomes,especially in patients with HTG-AP.Prospective validation is needed to establish causality for this etiology-stratified approach.
文摘BACKGROUND Sodium-glucose cotransporter-2(SGLT-2)inhibitors improve cardiovascular and renal outcomes in diabetes but may induce euglycemic diabetic ketoacidosis(euDKA)via insulin-independent mechanisms.Post-pancreatitis diabetes mellitus(PPDM)patients with impairedβ-cell function face undefined risks with these agents.CASE SUMMARY A 29-year-old man with PPDM developed euDKA 1 week after initiating etogliflozin(5 mg/day).On admission,laboratory tests revealed blood ketones>4.5 mmol/L,pH 7.1,and glucose 10.78 mmol/L.Discontinuation of SGLT-2 inhibitor,insulin pump therapy(basal 12 U/day,premeal bolus 4 U),aggressive hydration(6000 mL first 2 days),and nutritional support normalized ketosis and acidosis within 24 hours.CONCLUSION Caution is warranted with SGLT-2 inhibitors in PPDM.Insulin therapy is preferred to prevent euDKA.
文摘BACKGROUND The objective of the current study was to elucidate the clinical mechanism through which phospholipase D2(PLD2)exerted a regulatory effect on neutrophil migra-tion,thereby alleviating the progression of acute pancreatitis.AIM To elucidate the clinical mechanism through which PLD2 exerted a regulatory effect on neutrophil migration,thereby alleviating the progression of acute pan-creatitis.METHODS The study involved 90 patients diagnosed with acute pancreatitis,admitted to our hospital between March 2020 and November 2022.A retrospective analysis was conducted,categorizing patients based on Ranson score severity into mild(n=25),moderate(n=30),and severe(n=35)groups.Relevant data was collected for each group.Western blot analysis assessed PLD2 protein expression in patient serum.Real-time reverse transcription polymerase chain reaction was used to evaluate the mRNA expression of chemokine receptors associated with neutrophil migration.Serum levels of inflammatory factors in patients were detected using enzyme-linked immunosorbent assay.Transwell migration tests were conducted to compare migration of neutrophils across groups and analyze the influence of PLD2 on neutrophil migration.RESULTS Overall data analysis did not find significant differences between patient groups(P>0.05).The expression of PLD2 protein in the severe group was lower than that in the moderate and mild groups(P<0.05).The expression level of PLD2 in the moderate group was also lower than that in the mild group(P<0.05).The severity of acute pancreatitis is negatively correlated with PLD2 expression(r=-0.75,P=0.002).The mRNA levels of C-X-C chemokine receptor type 1,C-X-C chemokine receptor type 2,C-C chemokine receptor type 2,and C-C chemokine receptor type 5 in the severe group are significantly higher than those in the moderate and mild groups(P<0.05),and the expression levels in the moderate group are also higher than those in the mild group(P<0.05).The levels of C-reactive protein,tumor necrosis factor-α,interleukin-1β,and interleukin-6 in the severe group were higher than those in the moderate and mild groups(P<0.05),and the levels in the moderate group were also higher than those in the mild group(P<0.05).The number of migrating neutrophils in the severe group was higher than that in the moderate and mild groups(P<0.05),and the moderate group was also higher than the mild group(P<0.05).In addition,the number of migrating neutrophils in the mild group combined with PLD2 inhibitor was higher than that in the mild group(P<0.05),and the number of migrating neutrophils in the moderate group combined with PLD2 inhibitor was higher than that in the moderate group(P<0.05).The number of migrating neutrophils in the severe group+PLD2 inhibitor group was significantly higher than that in the severe group(P<0.05),indicating that PLD2 inhibitors significantly stimulated neutrophil migration.CONCLUSION PLD2 exerted a crucial regulatory role in the pathological progression of acute pancreatitis.Its protein expression varied among patients based on the severity of the disease,and a negative correlation existed between PLD2 expression and disease severity.Additionally,PLD2 appeared to impede acute pancreatitis progression by limiting neutrophil migration.
文摘Whether acute recurrent pancreatitis is a chronic disease is still debated and a consensus is not still reached as demonstrated by differences in the classification of acute recurrent pancreatitis. There is major evidence for considering alcoholic pancreatitis as a chronic disease ab initio while chronic pancreatitis lesions detectable in biliary acute recurrent pancreatitis (ARP) seem a casual association. Cystic fibrosis transmembrane con-ductance regulator (CFTR) gene mutation, hereditary and obstructive pancreatitis seem an acute disease that progress to chronic pancreatitis, likely as a consequence of the activation and proliferation of pancreatic stellate cells that produce and activate collagen and therefore fibrosis. From the diagnostic point of view, in patients with acute recurrent pancreatitis Endoscopic ultrasound (EUS) seems the more reliable technique for an accurate evaluation and follow-up of some ductal and parenchymal abnormalities suspected for early chronic pancreatitis.
文摘The close proximity of the endoscopic ultrasound probe to the pancreas results in superior spatial resolution compared to CT scan and MRI. In addition, endoscopic ultrasound (EUS) is a minimally invasive procedure that does not share the relatively high complication rate of ERCP. Due to these advantages, EUS has evolved into an important technique to assess pancreatobiliary disease. This review will discuss the role of EUS in patients with pancreatitis. The indications can be divided into acute pancreatitis and chronic pancreatitis. In acute pancreatitis, EUS is used to determine the etiology; in suspected chronic pancreatitis it is helpful to establish the diagnosis. Lastly, this review will discuss biliary pancreatitis with suspicion for persistent choledocholithiasis.
基金supported by a grant from the Fund of Chengdu Medical College (CYZYB22-03)。
文摘The mechanism of cell damage during acute pancreatitis (AP) has not been fully elucidated, and there is still a lack of specific or effective treatments. Increasing evidence has implicated mitochondrial dysfunction as a key event in the pathophysiology of AP. Mitochondrial dysfunction is closely related to calcium (Ca^(2+)) overload, intracellular adenosine triphosphate depletion, mitochondrial permeability transition pore openings, loss of mitochondrial membrane potential, mitophagy damage and inflammatory responses. Mitochondrial dysfunction is an early triggering event in the initiation and development of AP,and this organelle damage may precede the release of inflammatory cytokines, intracellular trypsin activation and vacuole formation of pancreatic acinar cells. This review provides further insight into the role of mitochondria in both physiological and pathophysiological aspects of AP, aiming to improve our understanding of the underlying mechanism which may lead to the development of therapeutic and preventive strategies for AP.
基金Supported by National Natural Science Foundation of China,No.82360136Jiangxi Clinical Research Center for Gastroenterology,No.20223BCG74011.
文摘BACKGROUND Acute pancreatitis(AP)is a severe condition,and abdominal effusion is a significant predictor of its severity and prognosis.However,the relationship between ascites characteristics and AP outcomes remains undefined.AIM To assess the correlation between ascites characteristics and clinical prognosis in AP patients by comparing color depth and turbidity of early ascites.METHODS This study included 667 AP patients with ascites,categorized by color and turbidity into yellow clear(n=54),yellow turbid(n=293),red brown(n=320).The trendχ2 test was employed to analyze the incidence of organ failure(OF),infected pancreatic necrosis(IPN),and mortality across groups.Receiver operating charac teristic(ROC)curves were used to evaluate the predictive value of ascites cell count,amylase,protein,and lactate dehydrogenase(LDH)for abdominal compartment syndrome(ACS)and intra-abdominal hemorrhage.RESULTS AP patients with ascites exhibited higher scores of scoring systems(such as Bedside index for severity in AP,Acute Physiology and Chronic Health Examination II,etc.)and increased complications and mortality rates(all P<0.05)compared to those without ascites.A linear association was observed between ascites color depth and turbidity and the incidence of OF,pancreatic necrosis,IPN,and mortality(P<0.05).LDH in ascites demonstrated high accuracy in predicting ACS and intra-abdominal hemorrhage,with areas under the ROC curve of 0.77 and 0.79,respectively.CONCLUSION Early in AP,ascites correlates with OF,IPN,and mortality,showing linear associations with color depth and turbidity.Ascitic LDH reliably predicts ACS and intra-abdominal hemorrhage in AP patients.
基金Supported by the Education and Teaching Reform Project of the First Clinical College of Chongqing Medical University,No.CMER202305Natural Science Foundation of Xizang Autonomous Region,No.XZ2024ZR-ZY100(Z)Program for Youth Innovation in Future Medicine,Chongqing Medical University,China,No.W0138.
文摘Infected necrotizing pancreatitis(INP)remains a life-threatening complication of acute pancreatitis.Despite advancements such as endoscopic ultrasound(EUS)-guided drainage,lumen-apposing metal stents,and protocolized step-up strate-gies,the clinical practice remains heterogeneous,with variability in endoscopic strategies,procedural timing,device selection,and adjunctive techniques contri-buting to inconsistent outcomes.This review synthesizes current evidence to contribute to a structured framework integrating multidisciplinary team decision-making,advanced imaging(three-dimensional reconstruction,contrast-enhanced computed tomography/magnetic resonance imaging),EUS assessment,and biomarker-driven risk stratification(C-reactive protein,procalcitonin)to optimize patient selection,intervention timing,and complication management.Key stan-dardization components include endoscopic assessment and procedural strate-gies,optimal timing of intervention,personalized approaches for complex pan-creatic collections,and techniques to reduce the number of endoscopic debride-ments and mitigate complications.This work aims to enhance clinical outcomes,minimize practice heterogeneity,and establish a foundation for future research and guideline development in endoscopic management of INP.
基金supported by grants from the National Nat-ural Science Foundation of China(82122010 and 82070659)the National High Level Hospital Clinical Research Funding(2022-PUMCH-E-003)+1 种基金the CAMS Innovation Fund for Medical Science(2022-I2M-1-004)an NIHR Senior Investigator Award。
文摘Acute pancreatitis(AP)is a common but potentially devastating disease characterized at onset patho-physiologically by premature activation of digestive enzymes within the pancreas.Despite an abundance of preclinical research and,until recently,a series of disappointing clinical trials,no specific disease mod-ifying pharmacological treatment has yet been approved for this condition.Recent novel approaches to understanding the molecular pathogenesis of AP provide us with renewed optimism for translational drug discovery.Although digestive enzyme activation is the hallmark of AP,a critical mechanism that initiates AP is intracellular calcium(Ca2+)overload in pancreatic parenchymal cells,which triggers mitochondrial dysfunction,endoplasmic reticulum(ER)stress,and impairs autophagic flux.These processes are piv-otal to the disease and present a range of drug targets,associated with the inflammatory responses that drive local and systemic inflammation in AP.Progress in translation has now been made,targeting the ORAI channel with the inhibitor zegocractin(Auxora)to reduce pancreatic injury and inflammatory re-sponses in human AP.Herein we evaluated potential drug targets for the early treatment of AP,focused on intra-acinar mechanisms of injury central to the onset and severity of AP.Our analysis highlights the opportunities and progress in translating these molecular insights into clinical therapies.
基金supported in part by the Japan Pancreas Soci-ety and the MHLW Research Program on Rare and Intractable Dis-eases(Grant Number 23FC1015,Principal investigator:Mitsuhiro Kawano).
文摘Background:Previous studies have highlighted the frequent occurrence of sarcopenia in patients with pancreatic diseases,including chronic pancreatitis.We aimed to clarify the prevalence of skeletal muscle(SM)loss and sarcopenia,and their associations with clinical characteristics,bone mineral density,and pancreatic imaging findings in patients with autoimmune pancreatitis(AIP).Methods:This study included 114 patients with AIP treated at Tohoku University Hospital.The SM index was assessed using a bioelectrical impedance analysis device,grip strength was measured using a hand dynamometer,and bone mineral density was evaluated using dual-energy X-ray absorptiometry.Univari-ate and multivariate logistic regression analyses were used to analyze factors associated with SM loss and sarcopenia.Results:Among 114 patients,57(50.0%)had SM loss,31(27.2%)had reduced grip strength,and 27(23.7%)had both.Patients with SM loss were older and had a lower body mass index,weaker grip strength,higher Controlling Nutritional Status scores,and lower serum lipase and albumin levels compared to those without SM loss.Computed tomography scans revealed a higher prevalence of pancreatic parenchy-mal atrophy in patients with SM loss.Similar differences were observed between patients with sarcopenia and those without.Osteopathy was observed in 35.6%of patients with SM loss and 38.1%of those with sarcopenia,whereas only 4.1%of patients without SM loss had osteopathy.Low BMI(<21.0 kg/m^(2))was also found to be an independent risk factor for SM loss in multivariate analysis.Age>72 years,low BMI(<20.0 kg/m^(2)),and low serum lipase levels(<13 U/L)were independent risk factors for sarcopenia in multivariate analysis.Conclusions:SM loss and sarcopenia are prevalent in patients with AIP and are associated with aging,poor nutritional status,low serum lipase levels,and pancreatic parenchymal atrophy.In addition to the high risk of osteopathy,careful attention should be paid to maintain muscle health in AIP patients.
