D-dimer as a Marker of Severity and Prognosis in Acute Pancreatitis.

Background and Objectives: Acute pancreatitis (AP) scores need a battery of tests that are not helpful at an early stage. Can a single test predict Complicated Acute Pancreatitis (CAP) which includes moderate and severe AP, local complications, and need for intensive care unit (ICU). Methodology: 30 patients of AP. D-dimer, C-reactive protein levels done within 3 days of AP onset. APACHE II, Ranson's score, CT severity index were done. Inhospital disease course for development of organ failure and need for ICU care was followed daily. Results: D-dimer in CAP was 2732 ng/L (MAP 567 ng/L), in abnormal computed tomography (CT) was 1916 ng/L (normal CT 363 ng/L), and in organ failure was 4776 ng/L (776.5 ng/L absent organ failure). D-dimer increases as the severity of organ failure increases (P = 0.04). D-dimer in ICU patients was significantly elevated (P = 0.021). D-dimer correlates with APACHE II score well, with an increase in predictive mortality rate (P = 0.01). On receiver operator characteristics, D-dimer >933.5 ng/L predicts CAP, >827.5 ng/L predicts positive CT findings (local complications), and >1060.5 ng/L predicts the development of organ failure. Conclusion: Coagulopathy and microthrombi play a significant role in early pathogenesis. D-dimer test acts at the level of this core pathogenesis, even before the complications set in. D-dimer within 72 h of AP correlates well with the CT findings after 72 h. This is the first study that correlates D-dimer levels with CT scores, ICU requirement. D-dimer can guide primary care physicians in selecting AP patients for referral to a higher center in a resource-limited setting.

Case of severe alcoholic hepatitis following acute pancreatitis.

This report describes the clinical course of a 41 year-old African woman who presented with an episode of acute alcoholic pancreatitis followed next by severe alcoholic hepatitis (SAH). Initially admitted for pancreatitis, the patient responded promptly to comprehensive treatment with strict abstinence from alcohol. However, remarkable elevations in white blood cell count to 44,000/µL and total bilirubin level to 12.4 mg/dL were observed 5-7 weeks later. Contrast-enhanced computed tomography revealed rapidly progressing hepatosplenomegaly. Histological analysis of a liver biopsy detected ballooned hepatocytes with Mallory-Denk bodies and significant neutrophilic infiltration in the hepatic parenchyma, which confirmed the diagnosis of SAH. The patient's hepatosplenomegaly and overall condition improved with supportive care alone. The reported case reveals the unexpected fact that SAH can develop after alcoholic acute pancreatitis.

A case of acute obstructive suppurative pancreatic ductitis complicated with acute cholangitis diagnosed only after the removal of a pancreatic duct stent.

Acute obstructive suppurative pancreatic ductitis (AOSPD) is a rare complication of chronic pancreatitis that presents with high fever and abdominal pain. A 63-year-old man underwent plastic bile duct stent and plastic pancreatic duct stent (PDS) placement for benign stricture in the intrapancreatic bile and pancreatic ducts associated with chronic pancreatitis; the stents were routinely replaced. Seven months after the last replacement, the patient presented to our hospital with dark urine but without fever or abdominal pain. Subsequent blood tests revealed elevated levels of hepatobiliary enzymes, white blood cells, and C-reactive protein. However, the pancreatic enzyme levels remained unchanged, and abdominal computed tomography showed the absence of inflammation around the pancreas. He was initially diagnosed with acute cholangitis (AC) due to bile duct stent dysfunction and subsequently underwent emergency endoscopic retrograde cholangiopancreatography. As obstruction of the PDS was suspected, both bile duct stent and PDS were replaced. Although the collected bile did not exhibit purulence, a white purulent fluid was released after replacing the PDS. Cultures from the bile and pancreatic exudates revealed the presence of Klebsiella oxytoca. Consequently, the patient was diagnosed with AOSPD and AC. In this patient, endoscopic retrograde cholangiopancreatography was performed after the diagnosis of AC alone; however, relying solely on AC treatment might not have ameliorated the patient's condition. The patient did not complain of any abdominal pain and was diagnosed with AOSPD only after the replacement of his PDS. Our case suggests that AOSPD may be a pitfall in the identification of the source of inflammation in patients with chronic pancreatitis.

Structured alcohol cessation support program versus current practice in acute alcoholic pancreatitis (PANDA): Study protocol for a multicentre cluster randomised controlled trial.

BACKGROUND/OBJECTIVES: The most important risk factor for recurrent pancreatitis after an episode of acute alcoholic pancreatitis is continuation of alcohol use. Current guidelines do not recommend any specific treatment strategy regarding alcohol cessation. The PANDA trial investigates whether implementation of a structured alcohol cessation support program prevents pancreatitis recurrence after a first episode of acute alcoholic pancreatitis. METHODS: PANDA is a nationwide cluster randomised superiority trial. Participating hospitals are randomised for the investigational management, consisting of a structured alcohol cessation support program, or current practice. Patients with a first episode of acute pancreatitis caused by harmful drinking (AUDIT score >7 and < 16 for men and >6 and < 14 for women) will be included. The primary endpoint is recurrence of acute pancreatitis. Secondary endpoints include cessation or reduction of alcohol use, other alcohol-related diseases, mortality, quality of life, quality-adjusted life years (QALYs) and costs. The follow-up period comprises one year after inclusion. DISCUSSION: This is the first multicentre trial with a cluster randomised trial design to investigate whether a structured alcohol cessation support program reduces recurrent acute pancreatitis in patients after a first episode of acute alcoholic pancreatitis, as compared with current practice. TRIAL REGISTRATION: Netherlands Trial Registry (NL8852). Prospectively registered.

Post-healing perceptions and experiences of alcohol withdrawal and life management in men with alcoholic pancreatitis: a qualitative study.

Introduction: The aim of this study was to examine the perceptions and experiences of male patients with alcoholic pancreatitis after healing regarding alcohol withdrawal and life management. Methods: This study used a qualitative descriptive design, and participants were selected by purposive sampling from two tertiary care hospitals in Shandong Province, China. Semi-structured in-depth interviews were conducted with 18 male patients discharged from the gastroenterology department who had recovered from alcoholic pancreatitis. Colaizzi's method was used to analyze the interview data, and the findings were reported using COREQ criteria. Results: By analyzing the interview data, we summarized five themes, (1) the dilemma of sobriety, (2) role change, (3) illness status, (4) family influence, and (5) life management. Conclusion: By profiling the perceptions and experiences of post-healing alcoholic pancreatitis patients' alcohol cessation and life management in men, it helps to grasp the details of alcohol cessation and health direction of patients' home management, which provides more directional guidance to help patients maintain positive and good lifestyle habits and active management awareness, followed by targeted personalized interventions to provide patients with knowledge of disease care and health management.

The Importance of Clinical Reasoning in Pancreatic Insufficiency: A Case Report.

Evidence-based medicine has demonstrated an extensive list of etiologies for exocrine pancreatic insufficiency (EPI). EPI is defined as inadequate pancreatic enzyme efficacy in digestion due to insufficient enzyme production, activation, or early enzyme degradation. Among the etiologies, acute pancreatitis secondary to chronic and excessive consumption of alcohol has been found to be one of the most common causes. In 2022, a 43-year-old male patient with a past medical history of polysubstance abuse, acute on chronic pancreatitis, alcohol dependence, pulmonary embolism, hypertension, hyperlipidemia and diabetes mellitus type 2 presented to the Emergency Department with three days of epigastric abdominal pain, nausea and non-bloody, non-bilious vomiting. Proper imaging confirmed the diagnosis of acute pancreatitis. The key to treatment and surveillance relies on proper identification of risk factors, pertinent imaging for diagnostic evaluation and appropriate treatment with electrolyte repletion. The patient developed persistent electrolyte deficiencies despite appropriate repletion, indicating high suspicion of pancreatic insufficiency. The treatment most importantly relies on a combination of repletion of electrolytes as well as pancreatic enzymes with a clear patient understanding of their chronic condition, the importance of reducing modifiable risk factors and compliance with medical therapy.

Serum Lipase Amylase Ratio as an Indicator to Differentiate Alcoholic From Non-alcoholic Acute Pancreatitis: A Systematic Review and Meta-Analysis.

A lipase/amylase (L/A) ratio of more than three may be a tool for differentiating alcoholic pancreatitis from non-alcoholic pancreatitis. We conducted a systematic literature review to identify published studies. A thorough data search of various databases was conducted using keywords. Study quality was assessed using the Quality Assessment of Diagnostic Accuracy Studies-2 survey. Data were extracted under the following headings: country, sample size, baseline characteristics, specificity, and sensitivity of the L/A ratio. Studies were analyzed using a bivariate random-effects model, and the sensitivity and specificity of the L/A ratio were pooled separately. Summary receiver operating characteristic (SROC) curves were plotted using the hierarchical method. A total of nine studies with 1,825 patients were identified for inclusion. SROC showed estimates of the area under the curve to be 0.75 (confidence interval (CI) = 0.71-0.79). Forest plots for sensitivity and specificity showed pooled estimates of sensitivity to be 74% (95% CI = 62-83%) while that of specificity was 63% (95% CI = 47-77%). The pooled diagnostic odds ratio was estimated to be 5 (95% CI = 3-9), the pooled positive likelihood ratio was estimated at 2.0, and the pooled negative likelihood ratio was estimated to be 0.41. We concluded that an L/A ratio of more than 3 has moderate accuracy for the diagnosis of alcoholic pancreatitis.

Obesity and alcoholic etiology as risk factors for multisystem organ failure in acute pancreatitis: Multinational study.

BACKGROUND: Multisystem organ failure (MSOF) is the most important determinant of mortality in acute pancreatitis (AP). Obesity and alcoholic etiology have been examined as potential risk factors for MSOF, but prior studies have not adequately elucidated their independent effects on the risk of MSOF. OBJECTIVE: We aimed to determine the adjusted effects of body mass index (BMI) and alcoholic etiology on the risk of MSOF in subjects with AP. METHODS: A prospective observational study of 22 centers from 10 countries was conducted. Patients admitted to an APPRENTICE consortium center with AP between August 2015 and January 2018 were enrolled. Multivariable logistic regression was used to estimate the adjusted effects of BMI, etiology, and other relevant covariates on the risk of MSOF. Models were stratified by sex. RESULTS: Among 1544 AP subjects, there was a sex-dependent association between BMI and the risk of MSOF. Increasing BMI was associated with increased odds of MSOF in males (OR 1.10, 95% confidence interval [CI] 1.04-1.15) but not in females (OR 0.98, 95% CI 0.90-1.1). Male subjects with AP, whose BMIs were 30-34 and >35 kg/m2 , had odds ratios of 3.78 (95% CI 1.62-8.83) and 3.44 (95% CI 1.08-9.99), respectively. In females, neither higher grades of obesity nor increasing age increased the risk of MSOF. Alcoholic etiology was independently associated with increased odds of MSOF compared with non-alcohol etiologies (OR 4.17, 95% CI 2.16-8.05). CONCLUSION: Patients with alcoholic etiology and obese men (but not women) are at substantially increased risk of MSOF in AP.

Retroperitoneal Fibrosis: Still a Diagnostic Challenge.

Retroperitoneal fibrosis (RPF) is a rare fibroinflammatory disorder usually involving the abdominal aorta and surrounding structures. It is divided into primary (idiopathic) and secondary RPF. Primary RPF can be immunoglobulin (Ig) G4-related disease or non-IgG4-related disease. Recently, there has been a rise in case reports regarding the topic, but awareness about the disease is still far from ideal. Hence, we present the case of a 49-year-old female who had repeated admissions for chronic abdominal pain attributed to chronic alcoholic pancreatitis. She had a medical history significant for psoriasis and surgical history significant for cholecystectomy. Her computed tomography (CT) scans on each admission for the last year showed some signs of RPF, but it was never considered the primary etiology of her chronic symptoms. We also obtained magnetic resonance imaging (MRI) which did not show any underlying malignancy but showed the progression of her RPF. She was started on a steroid regimen, which significantly improved her symptoms. She was diagnosed with idiopathic RPF due to unclear etiology, although her underlying risk factors, including psoriasis, past surgeries, and pancreatitis-associated inflammation, were considered predisposing factors. Idiopathic RPF accounts for more than two-thirds of total cases of RPF. Patients with autoimmune diseases can overlap with other autoimmune disorders. For non-malignant RPF, medical management with 1mg/kg/day steroids is deemed effective. Still, there is a lack of prospective trials and consensus for guidelines on treating RPF. The follow-up involves laboratory tests, including erythrocyte sedimentation rate, C-reactive protein, and CT or MRI in an outpatient setting to identify treatment response and relapse. There is a need for more streamlined guidelines to diagnose and manage this disease.

Increased Prevalence of Alcohol-Related Gastrointestinal and Liver Diseases During the COVID-19 Pandemic.

BACKGROUND: Higher prevalence of alcohol-related gastrointestinal (GI) and liver diseases (ARGLDs) were anecdotally reported during the COVID-19 pandemic, but little published evidence exists. METHODS: A healthcare system audit of inpatient GI consults was performed during the pandemic's lockdown phase (3/23/2020-5/10/2020, n=558) and reopening phase (6/1/2020-7/19/2020, n=711) with comparison to those timeframes in 2019. RESULTS: Consult volume decreased by 27.7% during the lockdown, but the proportion of ARGLDs increased by 59.6% (p=0.03). This trend continued during reopening, with potentially more severe disease as more patients required endoscopic intervention. Patients with alcoholic hepatitis during reopening were younger compared to the lockdown. CONCLUSIONS: Our study demonstrates increased prevalence and severity of ARGLDs amongst younger individuals during the COVID-19 pandemic. This increase started during the lockdown but worsened despite relaxation of restrictions. Systems to increase screening for and treatment of alcohol use disorder as society recovers from the pandemic remain imperative.

Urolithin A attenuates severity of chronic pancreatitis associated with continued alcohol intake by inhibiting PI3K/AKT/mTOR signaling.

Heavy alcohol consumption is the dominant risk factor for chronic pancreatitis (CP); however, treatment and prevention strategies for alcoholic chronic pancreatitis (ACP) remains limited. The present study demonstrates that ACP induction in C57BL/6 mice causes significant acinar cell injury, pancreatic stellate cell (PSC) activation, exocrine function insufficiency, and an increased fibroinflammatory response when compared with alcohol or CP alone. Although the withdrawal of alcohol during ACP recovery led to reversion of pancreatic damage, continued alcohol consumption with established ACP perpetuated pancreatic injury. In addition, phosphokinase array and Western blot analysis of ACP-induced mice pancreata revealed activation of the phosphatidylinositol 3 kinase (PI3K)/AKT/mammalian target of rapamycin (mTOR) and cyclic AMP response element binding protein (CREB) signaling pathways possibly orchestrating the fibroinflammatory program of ACP pathogenesis. Mice treated with urolithin A (Uro A, a gut-derived microbial metabolite) in the setting of ACP with continued alcohol intake (during the recovery period) showed suppression of AKT and P70S6K activation, and acinar damage was significantly reduced with a parallel reduction in pancreas-infiltrating macrophages and proinflammatory cytokine accumulation. These results collectively provide mechanistic insight into the impact of Uro A on attenuation of ACP severity through suppression of PI3K/AKT/mTOR signaling pathways and can be a useful therapeutic approach in patients with ACP with continuous alcohol intake.NEW & NOTEWORTHY Our novel findings presented here demonstrate the utility of Uro A as an effective therapeutic agent in attenuating alcoholic chronic pancreatitis (ACP) severity with alcohol continuation after established disease, through suppression of the PI3K/AKT/mTOR signaling pathway.

Spontaneous Cystogastrostomy: A Natural Response.

Pancreatic pseudocysts are a common complication of pancreatitis. Conservative management and repeat imaging are appropriate to monitor spontaneous regression. However, in some cases, rupture and haemorrhage of pseudocysts can lead to life-threatening events requiring urgent intervention. We present a male patient in his 30s who was presented to the emergency department with severe pancreatitis in the context of alcohol excess. Past medical history included pancreatitis with a small pseudocyst and splenic vein thrombosis for which he was anticoagulated six weeks previously. Computer tomography of the abdomen and pelvis showed an interval increase in his pseudocyst with haemorrhage secondary to a suspected splenic artery pseudoaneurysm. He was admitted for attempted embolisation and observation. Serial imaging demonstrated progression of the pancreatic pseudocyst and then spontaneous interval decompression via a transgastric fistula, leading to a natural cystogastrostomy confirmed on subsequent endoscopy. We discuss the uncommon sequelae of a complication of pancreatitis, and consider the hypotheses related to this rare occurrence, with suggestions for management and follow-up of these patients.

[The role of polymorphic variants rs11546155 and rs6119534 of the GGT7 gene and risk factors in the development of acute pancreatitis].

Glutathione is an antioxidant with powerful restorative and detoxifying properties, a progressive decrease in its reserves in erythrocytes and pancreas observed in pancreatic necrosis indicates a lack of functioning of the system for maintaining the level of glutathione in cells and the use of its endogenous reserve. The study of the role of glutathione metabolism enzyme genes in the risk of acute pancreatitis in this regard is especially relevant. The aim of the study was to evaluate the joint contribution of the rs11546155 and rs6119534 polymorphic loci of the GGT7 gene and some risk factors to the development of acute pancreatitis (AP). Material and methods. Molecular genetic analysis of DNA samples of 506 unrelated patients with acute pancreatitis and 524 unrelated individuals of Russian nationality without gastrointestinal diseases, isolated by the standard method of phenol-chloroform extraction, was carried out. The average age of patients was 48.9±13.1 years, healthy persons - 47.8±12.1 years. The diagnosis was established using Clinical guidelines developed by the working group of the Russian Society of Surgeons. All patients signed informed consent to participate in the study. Genotyping was performed using iPLEX technology by time-of-flight mass spectrometry. Associations of gene alleles and genotypes with the risk of acute pancreatitis were assessed by the χ2 criterion and the odds ratio with 95% confidence intervals. Statistical analysis was performed using the SNPStats and Statistica 10.0 programs (Stat-Soft, USA). Results. We have identified an association of the C/T (rs6119534) GGT7 genotype with an increased risk of AP, both in men and women. When analyzing the effect of polymorphic loci on the development of the polymorphic locus rs6119534 of the GGT7 C>T gene with an increased risk of developing acute alcoholic (AAlcP) and biliary pancreatitis (ABP), it was found that the C/T rs6119534 genotype of the GGT7 gene was more common both among patients with AAlcP and ABP, and the G/G GGT7 genotype (rs11546155) was found only among ABP patients. An analysis of the combined influence of polymorphic loci and environmental factors showed that the frequency of drinking alcohol more than 2 times a week and eating fat more than 89 grams per day increased the risk AAlcP in carriers of C/T-T/T rs6119534 of the GGT7 gene. As for ABP, non-smoking carriers of the G/A-A/A GGT7 (rs11546155) genotypes had a reduced risk of the disease, while the consumption of fats over 89 g/day and fresh vegetables and fruits below 27 g/day increased the risk in carriers of genotypes C/T-T/T and C/T rs6119534 of the GGT7 gene, respectively. Conclusion. Polymorphic loci rs6119534 and rs11546155 of the GGT7 gene, when exposed to certain risk factors, increase the risk of acute pancreatitis.

Impaired regulation of PMCA activity by defective CFTR expression promotes epithelial cell damage in alcoholic pancreatitis and hepatitis.

Alcoholic pancreatitis and hepatitis are frequent, potentially lethal diseases with limited treatment options. Our previous study reported that the expression of CFTR Cl- channel is impaired by ethanol in pancreatic ductal cells leading to more severe alcohol-induced pancreatitis. In addition to determining epithelial ion secretion, CFTR has multiple interactions with other proteins, which may influence intracellular Ca2+ signaling. Thus, we aimed to investigate the impact of ethanol-mediated CFTR damage on intracellular Ca2+ homeostasis in pancreatic ductal epithelial cells and cholangiocytes. Human and mouse pancreas and liver samples and organoids were used to study ion secretion, intracellular signaling, protein expression and interaction. The effect of PMCA4 inhibition was analyzed in a mouse model of alcohol-induced pancreatitis. The decreased CFTR expression impaired PMCA function and resulted in sustained intracellular Ca2+ elevation in ethanol-treated and mouse and human pancreatic organoids. Liver samples derived from alcoholic hepatitis patients and ethanol-treated mouse liver organoids showed decreased CFTR expression and function, and impaired PMCA4 activity. PMCA4 co-localizes and physically interacts with CFTR on the apical membrane of polarized epithelial cells, where CFTR-dependent calmodulin recruitment determines PMCA4 activity. The sustained intracellular Ca2+ elevation in the absence of CFTR inhibited mitochondrial function and was accompanied with increased apoptosis in pancreatic epithelial cells and PMCA4 inhibition increased the severity of alcohol-induced AP in mice. Our results suggest that improving Ca2+ extrusion in epithelial cells may be a potential novel therapeutic approach to protect the exocrine pancreatic function in alcoholic pancreatitis and prevent the development of cholestasis in alcoholic hepatitis.

Accidental Acetone Ingestion in Liver Transplant Patient With Alcohol Relapse: A Case Report.

Acetone is one of the three main types of ketone bodies that can be found in ketoacidosis, along with acetoacetate, and beta-hydroxybutyrate. Any of these three ketone bodies can be found in the blood after the natural breakdown of fatty acids in diabetes, starvation, or alcoholic ketoacidosis. However, a patient can also develop acetone poisoning from ingestion of common household products such as nail polish removers, paint removers, isopropyl alcohol, or other detergents and cleaners. Ingestion is usually accidental in adults and children and can lead to severe damage to the liver, heart, nervous system, and kidneys. In rare cases, large amounts of ingestion can lead to life-threatening conditions or death. Our case reports a man with a history of alcoholic cirrhosis status post liver transplantation, who unintentionally ingested acetone, mistaking the contents of small bottles for vodka. The patient presented with several syncopal episodes, anion gap metabolic acidosis, transaminitis with hyperbilirubinemia, and pancreatitis.

Changes in alcohol-related hospital visits during COVID-19 in New York City.

BACKGROUND AND AIMS: Increased alcohol consumption has been proposed as a potential consequence of the coronavirus disease 2019 (COVID-19) pandemic. There has been little scrutiny of alcohol use behaviors resulting in hospital visits, which is essential to guide pandemic public policy. We aimed to determine whether COVID-19 peak restrictions were associated with increased hospital visits for alcohol use or withdrawal. Secondary objectives were to describe differences based on age, sex and race, and to examine alcohol-related complication incidence. DESIGN: Multi-center, retrospective, pre-post study. SETTING: New York City health system with five participating hospitals. PARTICIPANTS: Adult emergency department encounters for alcohol use, alcoholic gastritis or pancreatitis or hepatitis, alcohol withdrawal syndrome, withdrawal seizure or delirium tremens. MEASUREMENTS: Age, sex, race, site and encounter diagnosis. Encounters were compared between 2019 and 2020 for 1 March to 31 May. FINDINGS: There were 2790 alcohol-related visits during the 2019 study period and 1793 in 2020, with a decrease in total hospital visits. Of 4583 alcohol-related visits, median age was 47 years, with 22.3% females. In 2020 there was an increase in percentage of visits for alcohol withdrawal [adjusted odds ratio (aOR) = 1.34, 95% confidence interval (CI) = 1.07-1.67] and withdrawal with complications (aOR = 1.40, 95% CI = 1.14-1.72), and a decline in percentage of hospital visits for alcohol use (aOR = 0.70, 95% CI = 0.59-0.85) and use with complications (aOR = 0.71, 95% CI = 0.58-0.88). It is unknown whether use visit changes mirror declines in other chief complaints. The age groups 18-29 and 60-69 years were associated with increased visits for use and decreased visits for withdrawal, as were non-white race groups. Sex was not associated with alcohol-related visit changes despite male predominance. CONCLUSIONS: In New York City during the initial COVID-19 peak (1 March to 31 May 2020), hospital visits for alcohol withdrawal increased while those for alcohol use decreased.

Natural Recovery by the Liver and Other Organs after Chronic Alcohol Use.

Chronic, heavy alcohol consumption disrupts normal organ function and causes structural damage in virtually every tissue of the body. Current diagnostic terminology states that a person who drinks alcohol excessively has alcohol use disorder. The liver is especially susceptible to alcohol-induced damage. This review summarizes and describes the effects of chronic alcohol use not only on the liver, but also on other selected organs and systems affected by continual heavy drinking-including the gastrointestinal tract, pancreas, heart, and bone. Most significantly, the recovery process after cessation of alcohol consumption (abstinence) is explored. Depending on the organ and whether there is relapse, functional recovery is possible. Even after years of heavy alcohol use, the liver has a remarkable regenerative capacity and, following alcohol removal, can recover a significant portion of its original mass and function. Other organs show recovery after abstinence as well. Data on studies of both heavy alcohol use among humans and animal models of chronic ethanol feeding are discussed. This review describes how (or whether) each organ/tissue metabolizes ethanol, as metabolism influences the organ's degree of injury. Damage sustained by the organ/tissue is reviewed, and evidence for recovery during abstinence is presented.

Takotsubo cardiomyopathy complicating acute pancreatitis: a case report.

BACKGROUND: Acute pancreatitis as a trigger of Takotsubo cardiomyopathy has been infrequently described in the literature. Misdiagnosis of this phenomenon can often occur due to overlap in symptomology, particularly in those outside of the usual patient demographic. CASE PRESENTATION: A 27-year-old man with a history of alcohol abuse presented with epigastric and chest pain. Electrocardiography showed ischemic changes, and laboratory workup revealed elevated lipase and troponin. He was diagnosed with acute pancreatitis and managed presumptively as acute coronary syndrome. Subsequent coronary angiography was negative for obstructive coronary artery disease, and left ventriculography demonstrated basal hyperkinesis and apical akinesis, characteristic of Takotsubo cardiomyopathy. CONCLUSIONS: Takotsubo cardiomyopathy is a rare complication of acute pancreatitis. Increased awareness of this phenomenon is required to prevent delays in diagnosis and avoid unnecessary interventions and complications.

Differential cytotoxicity, ER/oxidative stress, dysregulated AMPKα signaling, and mitochondrial stress by ethanol and its metabolites in human pancreatic acinar cells.

BACKGROUND: Alcoholic chronic pancreatitis (ACP) is a serious inflammatory disorder of the exocrine pancreatic gland. A previous study from this laboratory showed that ethanol (EtOH) causes cytotoxicity, dysregulates AMPKα and ER/oxidative stress signaling, and induces inflammatory responses in primary human pancreatic acinar cells (hPACs). Here we examined the differential cytotoxicity of EtOH and its oxidative (acetaldehyde) and nonoxidative (fatty acid ethyl esters; FAEEs) metabolites in hPACs was examined to understand the metabolic basis and mechanism of ACP. METHODS: We evaluated concentration-dependent cytotoxicity, AMPKα inactivation, ER/oxidative stress, and inflammatory responses in hPACs by incubating them for 6 h with EtOH, acetaldehyde, or FAEEs at clinically relevant concentrations reported in alcoholic subjects using conventional methods. Cellular bioenergetics (mitochondrial stress and a real-time ATP production rate) were determined using Seahorse XFp Extracellular Flux Analyzer in AR42J cells treated with acetaldehyde or FAEEs. RESULTS: We observed concentration-dependent increases in LDH release, inactivation of AMPKα along with upregulation of ACC1 and FAS (key lipogenic proteins), downregulation of p-LKB1 (an oxidative stress-sensitive upstream kinase regulating AMPKα) and CPT1A (involved in ß-oxidation of fatty acids) in hPACs treated with EtOH, acetaldehyde, or FAEEs. Concentration-dependent increases in oxidative stress and ER stress as measured by GRP78, unspliced XBP1, p-eIF2α, and CHOP along with activation of p-JNK1/2, p-ERK1/2, and p-P38MAPK were present in cells treated with EtOH, acetaldehyde, or FAEEs, respectively. Furthermore, a significant decrease was observed in the total ATP production rate with subsequent mitochondrial stress in AR42J cells treated with acetaldehyde and FAEEs. CONCLUSIONS: EtOH and its metabolites, acetaldehyde and FAEEs, caused cytotoxicity, ER/oxidative and mitochondrial stress, and dysregulated AMPKα signaling, suggesting a key role of EtOH metabolism in the etiopathogenesis of ACP. Because oxidative EtOH metabolism is negligible in the exocrine pancreas, the pathogenesis of ACP could be attributable to the formation of FAEEs and related pancreatic acinar cell injury.