Risk Of Acute Pancreatitis Research Articles

How to Handle Elevated Triglycerides: Life after PROMINENT.

Hypertriglyceridaemia (HTG) is a common condition characterised by elevated levels of plasma triglycerides (TG), which are transported in the blood mainly by TG-rich lipoproteins (TRL). Elevated TG levels (150-400 mg/dL) are associated with increased cardiovascular risk. Severe HTG (>880 mg/dL) is associated with a risk of acute pancreatitis only. Randomised clinical trials investigating the clinical benefit of TG-lowering drugs in patients with elevated TG levels have provided conflicting results. Elevated TG levels are only one marker of altered lipid/lipoprotein metabolism and indeed reflect altered concentrations of one or more classes or subfractions of TRL, which in turn may have a different association with CV risk. Fibrates, the drugs most commonly used to treat HTG, provide cardiovascular benefits to only a specific subgroup of patients. The lack of clinical benefit from pemafibrate has emphasised the concept that lowering TG levels is not sufficient to reduce the CV risk unless it is accompanied by a reduction in the number of circulating atherogenic lipoproteins, which can be assessed by determining apolipoprotein B levels. Treatment with omega-3 fatty acids was also ineffective in reducing CV risk, with the exception of icosapent ethyl, which, however, appears to have beneficial effects beyond lipids. New drugs are currently being developed that aim to lower TG levels by targeting apolipoprotein C-III or angiopoietin-like-3, both of which are involved in the metabolism of TGs. TG reduction can be achieved by various drugs, but most of them are ineffective in reducing CV risk. The results of outcome studies on new TG-lowering drugs will clarify whether lowering apoB levels is critical to achieve clinical benefit.

Risk of pancreatitis and pancreatic carcinoma for anti-diabetic medications: findings from real-world safety data analysis and systematic review and meta-analysis of randomized controlled trials

ABSTRACT Background The existing evidence from pre- and post-marketing studies is conflicting on the risk of pancreatic events for anti-diabetic medications. Research design and methods A retrospective case/non-case study was conducted by using spontaneous reports on pancreatic events for anti-diabetic medications from the FDA Adverse Event Reporting System (FAERS) and VigiBase. Proportional Reporting Ratio (PRR), Reporting Odds Ratio (ROR), and Information Component (IC) were calculated by a disproportionality analysis. Furthermore, PubMed, Google Scholar, Scopus, and ClinicalTrials.gov were systematically searched for randomized controlled trials (RCTs) on anti-diabetic drugs with pancreatic outcomes. Results The FAERS data analysis found strong signals on incretin mimetics causing pancreatic events, with sitagliptin having the highest risk [PRR = 24.2, lower bound (LB) ROR = 24.4, IC025 = 4.4 for pancreatitis, and PRR = 15.4, LB ROR = 14.9, IC025 = 3.8 for pancreatic carcinoma]. Empagliflozin was the most pancreatitis-risk sodium-glucose co-transporter-2 inhibitor [PRR = 4.0, LB ROR = 3.5, IC025 = 1.8]. VigiBase reiterated these findings and identified some new signals for novel anti-diabetics. Meta-analysis revealed that the incidence of pancreatitis and pancreatic carcinoma with anti-diabetic medications was insignificant. However, compared to the placebo/active comparator, gliptins had a higher risk of acute pancreatitis (OR 1.44; 95% CI 1.03, 2.01; P = 0.03). Conclusion Evidence from the post-marketing safety data analysis identified a strong association between incretin mimetics and pancreatic events. Fewer events in RCTs may justify insignificant meta-analysis results.

Cardiometabolic Index (CMI), Lipid Accumulation Products (LAP), Waist Triglyceride Index (WTI) and the risk of acute pancreatitis: a prospective study in adults of North China

ObjectiveTo investigate the correlation between anthropometric indexes [cardiometabolic index (CMI), lipid accumulation products (LAP), waist triglyceride index (WTI), and body mass index (BMI)] and acute pancreatitis (AP) in a Chinese adult population.MethodologyThe present investigation consisted of a prospective group including 117,326 subjects who were enrolled in the Kailuan investigation. The individuals were categorized into quartiles based on their baseline levels of CMI, LAP, and WIT. BMI was categorized into three distinctive groups: normal weight group (BMI < 24 kg/m2), overweight group (BMI 24–28 kg /m2), and obesity group (BMI ≥ 28 kg/m2). The data were subjected to analysis in order to investigate the correlation between these anthropometric indexes and the incidence of AP. Cox regression models were employed to assess the relative risk of AP while accounting for known risk factors through appropriate adjustments.OutcomesOver the course of a median follow-up duration of 12.59 ± 0.98 years, we documented 401 incident AP cases. Incidence density and cumulative incidence rates of AP increased with the increase of CMI, LAP, and WTI. After multivariate adjustment, the fourth quartile of CMI, LAP, and WTI exhibited the greatest risk of AP [CMI: hazard ratio (HR) 1.93, 95% confidential interval (CI) (1.45–2.57); LAP: HR 2.00, 95% CI(1.49–2.68); WTI: HR 2.13,95% CI (1.59–2.83)]. In comparison to the normal weight group, the obesity group (BMI ≥ 28 kg/m2) had an elevated risk of AP (HR = 1.58, 95% CI: 1.21–2.05). Furthermore, the incremental effect of BMI combined with CMI on the prognostic value of AP was greater than that of BMI alone (the C statistics demonstrated a result of 0.607 versus 0.546; the integrated discrimination improvement revealed a result of 0.321%; net reclassification improvement was 1.975%).ConclusionWe found that CMI, LAP, and WTI were positively and independently connected to the risk of AP. Additionally, CMI demonstrates a superior prognostic capacity than other indexes in anticipating AP.

RBD5044 - a novel anti-ApoC3 GalNAc-siRNA drug resulted in sustained and profound reduction of triglycerides in mice and Rhesus monkeys

Abstract Introduction Hypertriglyceridemia leads to endothelial dysfunction and contributes to the onset and progression of atherosclerosis as well as an increased risk of acute pancreatitis. Inhibition of Apolipoprotein-CIII (APOC3) via the RNA interference mechanism is supposed to reduce plasma Triglycerides (TG) levels with durable and high efficacy. RBD5044, which targets APOC3 mRNA in the liver, is a chemically-modified double-stranded small interfering RNA (siRNA) conjugated with N-acetylgalactosamine (Ribo-GalSTAR). Purpose To investigate the preclinical efficacy and safety profile of RBD5044. Methods Rhesus monkeys with spontaneously developed hypertriglyceridemia were given a single subcutaneous (sc) injection of RBD5044. Humanized APOC3 transgenic mice were treated with a single dose or repeated doses (once every two weeks for three doses, Q2W×3) of RBD5044. Plasma was collected to quantify APOC3 and lipid biomarkers to evaluate preclinical efficacy of RBD5044. SD rats and cynomolgus monkeys were used to evaluate the preclinical toxicology for subcutaneously injected RBD5044, including single-dose toxicity studies and 4-week repeat-dose pivotal toxicology studies. Results In the rhesus monkeys with spontaneous hypertriglyceridemia, the maximum level of inhibition reached 61.2 % in APOC3 and resulted in a TG reduction by 53.3%. The levels of both APOC3 and TG were recovered to baseline till Day 85 after a single dose of 3 mg/kg RBD5044. In humanized APOC3 transgenic mice, RBD5044 achieved an average maximum inhibition level of over 90% for APOC3 and around 90% for TG after both single and repeated doses. The APOC3 and TG levels were recovered on Day 63 after a single dose of 3 mg/kg. On Day 63 after the last repeated dose at 3 mg/kg, the inhibition level remained at 41.6% for APOC3 and 49.4% for TG, hence did not recover to baseline within the study period. RBD5044 also showed reductions in total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) levels and elevations in high-density lipoprotein cholesterol (HDL-C) levels. Toxicology studies showed there is a sufficient therapeutic margin that supports the clinical development of RBD5044 with NOAEL of 40 mg/kg in rats and 300 mg/kg in monkeys. Conclusions RBD5044 shows high efficacy, long duration and a good safety profile in preclinical studies. The Phase I trial of RBD5044 injection in healthy volunteers has been initiated in Australia.Figure 1Figure 2

Risk of acute alcohol pancreatitis is not increased in patients with previous biliary pancreatitis in a long-term follow-up

Risk of acute alcohol pancreatitis is not increased in patients with previous biliary pancreatitis in a long-term follow-up

Social deprivation increases the risk of acute pancreatitis but does not impact on disease severity and mortality

Social deprivation increases the risk of acute pancreatitis but does not impact on disease severity and mortality

The joint contribution of the GGT1 gene and some haploand phenotypes to the development of acute biliary pancreatitis

He aim of the study was to determine the role of polymorphisms of the GGT1 gene and environmental risk factors in the acute biliary pancreatitis. The material of the study was DNA samples obtained from 84 patients with ABP and 573 healthy individuals. The disease was diagnosed using clinical guidelines (Russian Society of Surgeons). To assess the associations of alleles and genotypes of the gene with the risk of acute pancreatitis, the χ2 test and the odds ratio (OR) with 95% confidence intervals (CI) were used. Statistical analysis was carried out using the Statistica 10.0 program (StatSoft, USA) and the SNPStats program. Results. It was found that the A/A-G/G rs5760489 and A/A rs4820599 GGT1 genotypes have an increased risk of ABP. The H3 A-A-A-A haplotype is associated with a reduced risk of the disease, while the H6 A-G-A-A haplotype, on the contrary, increases the risk of developing the disease. The absence of exposure to alcohol abuse reduces the risk of ABP in carriers of the genotypes A/G-G/G rs5760489, A/G-G/G rs4820599, smoking -A/G-G/G rs4820599 and A/G-G/G rs5760489. The A/G-G/G rs4820599, G/A-A/A rs5751909 and A/G-G/G rs5760489 genotypes have a protective effect with sufficient consumption of fresh vegetables and fruits, the main suppliers of glutathione to the body. The presence of glutathione deficiency leads to the oxidative stress, and phenotypic changes we found: leukocytosis (allele A, rs5760489), peritonitis (allele A, rs5751909). Conclusion. The GGT1 gene can be used to predict the development and clinical course of acute biliary pancreatitis and its complications.

FRI092 Rationale And Design Of The Balance Study: A Randomized, Double-Blind, Placebo-Controlled, Phase 3 Study Of Olezarsen In Patients With Familial Chylomicronemia Syndrome

Abstract Disclosure: V. Alexander: Employee; Self; Ionis Pharmaceuticals Inc. E. Karwatowska-Prokopczuk: Employee; Self; Ionis Pharmaceuticals Inc. E.S. Stroes: Other; Self; Akcea Therapeutics, Ionis Pharmaceuticals Inc., Amgen Inc, Novo Nordisk, AstraZeneca, Esperion. C. Ballantyne: Speaker; Self; Ionis Pharmaceuticals Inc. H.N. Ginsberg: None. S. Xia: Employee; Self; Ionis Pharmaceuticals Inc. J. Witztum: Consulting Fee; Self; Ionis Pharmaceuticals Inc. S. Tsimikas: Employee; Self; Ionis Pharmaceuticals Inc. Background: Familial chylomicronemia syndrome (FCS) is a rare genetic cause of severe hypertriglyceridemia associated with an increased risk of acute pancreatitis (AP). Currently, there are no approved therapies for the treatment of FCS in the United States, and the absence of lipoprotein lipase (LPL) activity in FCS limits the effectiveness of current treatment options. Olezarsen, a ligand-conjugated antisense oligonucleotide (ASO), inhibits hepatic production of apolipoprotein (apo) C-III, a key regulator of LPL-mediated triglyceride (TG) lipolysis and non-LPL-mediated TG-rich lipoprotein hepatic uptake. In a phase 2 study of non-FCS patients with fasting serum TG levels of 200–500 mg/dL, olezarsen demonstrated reduction in fasting TG levels of up to 60% vs placebo (PBO). The Balance trial (NCT04568434) will evaluate the efficacy and safety of olezarsen as well as the rates of AP in patients with FCS. Methods: Balance is a phase 3, randomized, double-blind, PBO-controlled trial. Key inclusion criteria are genetic confirmation of FCS, fasting TG ≥ 880 mg/dL, and possible history of pancreatitis. Key exclusion criteria include clinically significant abnormalities in medical history such as major surgery within 3 mos of screening and active pancreatitis within 4 wks of screening. Patients will maintain ≤ 20 g daily fat intake and most will receive lipid-lowering medications per local standard of care. Results: Eligible patients (N=66) were enrolled at 29 sites (across 11 countries) and randomized 2:1 to receive one of two doses of olezarsen or PBO over a 53-wk treatment period, followed by post-treatment evaluation or entry into an open-label extension study. Enrollment was monitored to ensure that ≥ 65% of patients had history of pancreatitis within 10 yrs. Reported baseline parameters are preliminary. Of enrolled patients, mean age is 45±13.4 yrs, 58% of the population are female, and mean body mass index is 24.0 kg/m2; 83% had a history of hospitalization for AP, or severe abdominal pain episode, or symptoms suggestive of pancreatitis, with a mean of 2.4 episodes over the last 5 yrs and 5.1 over the last 10 yrs. Median fasting TG level is 2334.5 mg/dL. The primary efficacy endpoint of the study is percent change in fasting TG from baseline (BL) at 6 mos with olezarsen compared to PBO. Secondary endpoints (olezarsen vs PBO) include percent change in fasting TG from BL at 12 mos, achievement of ≥ 40% or ≥ 70% fasting TG reduction at 6 mos, patient proportions ≤ 500 mg/dL or ≤ 750 mg/dL at 6 mos, and adjudicated AP event rates. Exploratory assessments include patient-reported symptoms such as abdominal pain and health-related quality of life. Safety and tolerability assessments include adverse events and laboratory tests. Conclusion: Balance is designed to determine whether the apoC-III ASO olezarsen, added to standard of care, safely reduces TG levels and the rate of AP in patients with FCS. Presentation: Friday, June 16, 2023

The epidemiology and clinical features of pediatric acute pancreatitis in north of Guizhou, China.

The epidemiological data on distribution of pediatric acute pancreatitis was deficiency. And the purpose of this research was to investigate the epidemiology and clinical features of pediatric acute pancreatitis in the population in north of Guizhou, China. A retrospective case analysis was conducted to accomplish the aim. Patients who were under 18 years old with acute pancreatitis were recruited. Data were collected directly from Hospital Information System (HIS) after patients were discharged from the hospital. A total of 95 children aged from 3 to 17 years were collected, 49 patients were boys and 46 were girls. In addition, the percentage of acute pancreatitis occurring in girls aged 15-17 years was significantly higher than that of boys (54.3% vs 36.7%). Meanwhile, the percentage of severe patients over 12 years exceeded 90.0%. Moreover, the proportion of severe acute pancreatitis in girls was significantly higher than that in boys (26.1% vs 10.2%), and 64.7% of severe patients were from 12 to 14. What's more, more patients occurred in May, June, and December and on weekends, 47.1% (8/17) severe cases occurred in May, June, and July, and 47.1% (8/17) severe patients occurred on weekend. The length of hospitalization and hospitalization costs of severe patients were found higher compared to mild patients. Higher risk of pediatric acute pancreatitis, especially severe acute pancreatitis, in north of Guizhou, China occurred on weekend, during May and June, and among children aged 12-17 years, especially girls. Additionally, severe acute pancreatitis was associated with higher hospitalization costs and longer hospitalization length.

Akut pankreatitte şiddetin öngörülmesinde BUN/albümin oranı ile BISAP skorunun karşılaştırılması

Purpose: This study evaluated patients diagnosed with acute pancreatitis in the emergency department by comparing the BUN/Albumin Ratio (BAR) and BISAP scores to indicate disease severity and prognosis.&#x0D; Materials and Methods: 457 patients diagnosed with acute pancreatitis between 2016 and 2021 were included in this observational study, which was planned retrospectively. The laboratory data of the patients and the calculated BISAP scores were recorded. &#x0D; Results: Patients were categorized according to the BISAP score; 385 (84.2%) patients were at low risk for acute pancreatitis, while 72 (15.8%) were at high risk. The AUC for BAR values was 0.757 (75.7%), and this was statistically significant for determining cutoff values, with a cutoff value of &gt;4.60 (p

Unsolved mystery, the etiology of acute pancreatitis after liver resection: a case report and literature review

Link of Video Abstract: https://youtu.be/WQnJQwwYcHcIntroduction: After liver resection, pancreatitis is a well-known yet uncommon consequence. The actual cause is unclear, and the postoperative condition may mask the clinical symptoms. When a patient unexpectedly worsens after surgery, postoperative pancreatitis should always be taken into consideration due to its high fatality risk. After liver resection, we present our patient with acute pancreatitis. The paper was written using certain hypotheses. First, the surgeon should be aware of the possibility of pancreatitis following liver surgery, which is not included in the literature as a side effect of liver surgery. The second step is to increase our knowledge and develop measures to reduce the risk of acute pancreatitis following liver surgery. Case Description: We present here a case of acute pancreatitis following liver resection surgery from our institution, and we strongly suspect that the results of our postoperative white bile leak test contributed to this. According to the literature analysis, this test is risk-free and won't have a materially detrimental impact on the patient. Keep in mind the white test rule, which suggested things like focus and spooling following the test. Conclusion: The white test is effective for identifying bile leakage following liver resection, however, we do not advise frequent use of this test since there is a chance that it can trigger acute pancreatitis, which can have a substantial negative impact on the patient's morbidity or death. The precise process is still a mystery and will require further experimental research.

Therapeutic role of interleukin-1 receptor antagonist in pancreatic diseases: mendelian randomization study.

The interleukin-1 pathway has been linked to pancreatic diseases. We applied the Mendelian randomization approach to explore whether higher interleukin-1 receptor antagonist (IL-1RA) levels reduce the risk of acute and chronic pancreatitis and pancreatic cancer. Genetic variants associated with blood IL-1RA levels at the genome-wide significance level and located 5MB downstream or upstream of the IL1RN gene were extracted from a genome-wide meta-analysis of 21,758 participants. After pruning, genetic variants without linkage disequilibrium were used as genetic instrument for IL-1RA. Summary-level data on acute and chronic pancreatitis and pancreatic cancer were obtained from the UK Biobank and FinnGen studies. The associations were meta-analyzed for one outcome from two sources. Genetically predicted higher levels of IL-1RA were associated with a lower risk of acute and chronic pancreatitis and pancreatic cancer. In the meta-analysis of UK Biobank and FinnGen, the combined odds ratio was 0.87 (95% confidence interval [CI] 0.77-0.97, P=0.003) for acute pancreatitis, 0.73 (95% CI 0.65-0.82, P=2.93×10-8) for chronic pancreatitis, and 0.86 (95% CI 0.77-0.96, P=0.009) for pancreatic cancer per one standard deviation increment in genetically predicted levels of IL-1RA. This study suggests a protective role of IL-1RA in three major pancreatic diseases, which hints the therapeutic potentials of IL-1RA in pancreatic diseases.

Association of Apolipoprotein A5 Gene Variants with Hyperlipidemic Acute Pancreatitis in Southeastern China.

Background: Apolipoprotein A5 (APOA5) is involved in serum triglyceride (TG) regulation. Several studies have reported that the rs651821 locus in the APOA5 gene is associated with serum TG levels in the Chinese population. However, no research has been performed regarding the association between the variants of rs651821 and the risk of hyperlipidemic acute pancreatitis (HLAP). Methods: A case-control study was conducted and is reported following the STROBE guidelines. We enrolled a total of 88 participants in this study (60 HLAP patients and 28 controls). APOA5 was genotyped using PCR and Sanger sequencing. Logistic regression models were conducted to calculate odds ratios and a 95% confidence interval. Results: The genotype distribution of the rs651821 alleles in both groups follow the Hardy-Weinberg distribution. The frequency of the "C" allele in rs651821 was increased in HLAP patients compared to controls. In the recessive model, subjects with the "CC" genotype had an 8.217-fold higher risk for HLAP (OR = 8.217, 95% CI: 1.023-66.01, p = 0.046) than subjects with the "TC+TT" genotypes. After adjusting for sex, the association remained significant (OR = 9.898, 95% CI: 1.176-83.344, p = 0.035). Additionally, the "CC" genotype was related to an increased TG/apolipoprotein B (APOB) ratio and fasting plasma glucose (FPG) levels. Conclusions: Our findings suggest that the C allele of rs651821 in APOA5 increases the risk of HLAP in persons from Southeastern China.

Hypertriglyceridemia-Associated Pancreatitis: New Concepts and Potential Mechanisms.

Triglycerides are a major source of energy, while high plasma triglycerides are a risk factor for various diseases and premature death. Severely elevated plasma triglycerides are a well-established cause of acute pancreatitis with high mortality, likely due to the presence of elevated levels of chylomicrons and large very low-density lipoproteins in plasma. As markedly elevated levels of these very large lipoproteins are not generally found in mild to moderate hypertriglyceridemia, this was previously not regarded as a cause or marker of increased risk of acute pancreatitis. However, mild to moderate hypertriglyceridemia may identify individuals who at a later timepoint develop severe hypertriglyceridemia and acute pancreatitis. We describe measurement of plasma triglycerides and studies on plasma triglycerides and risk of acute pancreatitis. Further, we summarize current European and American guidelines for the prevention of acute pancreatitis and, finally, the potential for future prevention of acute pancreatitis through lowering of plasma triglycerides. Recent observational and genetic studies indicate that mild to moderate hypertriglyceridemia is causally related to increased risk of acute pancreatitis, most likely as a marker of future severe hypertriglyceridemia. Current guidelines do not mention individuals with mild to moderate hypertriglyceridemia, even though newer evidence suggests an unmet medical need. Treatment could include plasma triglyceride-lowering therapy targeting the pathway for lipoprotein lipase as the main triglyceride degrading enzyme in plasma. Angiopoietin-like 3 and apolipoproteinC-III are inhibitors of lipoprotein lipase, and blocking of these 2 inhibitors is showing promising results in relation to marked triglyceride-lowering and could perhaps be used to prevent acute pancreatitis in the future.

Hypertriglyceridaemic waist phenotype and waist circumference triglyceride index are associated with higher incidence of acute pancreatitis: a nationwide population-based retrospective cohort study

ObjectivesThe hypertriglyceridaemic waist (HTGW) phenotype, an indicator to assess metabolic syndrome, could be a useful predictive marker for the risk of acute pancreatitis. This study aimed to evaluate the association...

Enhancement pattern of the pancreatic parenchyma predicts postpancreatectomy acute pancreatitis after pancreaticoduodenectomy.

To assess the association between the enhancement pattern of the pancreatic parenchyma on preoperative multiphasic contrast-enhanced computed tomography (CECT) and the occurrence of postpancreatectomy acute pancreatitis (PPAP) after pancreaticoduodenectomy (PD). A total of 513 patients who underwent PD were retrospective enrolled. The CT attenuation values of the nonenhanced (N), arterial (A), portal venous (P), and late (L) phases in the pancreatic parenchyma were measured on preoperative multiphasic CECT. The enhancement pattern was quantized by the CT attenuation value ratios in each phase. Receiver operating characteristic (ROC) curve analyses were computed to evaluate predictive performance. Regression analyses were used to identify independent risk factors for PPAP. PPAP developed in 102 patients (19.9%) and was associated with increased morbidity and a worse postoperative course. The A/P ratio, P/L ratio, and A/L ratio were significantly higher in the PPAP group. On the ROC analysis, the A/L ratio and A/P ratio both performed well in predicting PPAP (A/L: AUC = 0.7579; A/P: AUC = 0.7497). On multivariate analyses, the A/L ratio > 1.29 (OR 4.30 95% CI: 2.62-7.06, p < 0.001) and A/P ratio > 1.13 (OR 5.02 95% CI: 2.98-8.45, p < 0.001) were both independent risk factors of PPAP in each model. The enhancement pattern of the pancreatic parenchyma on multiphasic preoperative CECT is a good predictor of the occurrence of PPAP after PD, which could help clinicians identify high-risk patients or enable selective enhance recovery protocols. Preoperative identification of patients at high risk for postpancreatectomy acute pancreatitis by enhancement patterns of the pancreatic parenchyma allows surgeons to tailor their perioperative management and take precautions. PPAP is associated with increased risk of postoperative complications and a worse postoperative course. A rapid-decrease enhancement pattern of the pancreatic parenchyma is related to the occurrence of PPAP. The A/L and A/P ratios were both independent risk factors of PPAP in each multivariate model.

Post-prandial analysis of fluctuations in the platelet count and platelet function in patients with the familial chylomicronemia syndrome

BackgroundThe familial chylomicronemia syndrome (FCS) is an ultra rare disease caused by lipoprotein lipase (LPL) deficiency associated with potentially lethal acute pancreatitis risk. Thrombocytopenia (platelet count < 150,000 × 109/L) has been reported in patients with FCS, treated or not with volanesorsen, a second generation APOC3 anti-sense oligonucleotide. Chylomicrons are the lipoproteins delivering fat after a meal and FCS thus has a post-prandial origin. Platelet count and function have not been studied post-prandially in FCS.ObjectiveTo evaluate post-prandial fluctuations in the platelet count (PLC) and functional defects of hemostasis in FCS.MethodsPLC, functional defects in hemostasis and hematologic variables were measured up-to 5 h after a meal in 6 homozygotes for FCS causing gene variants (HoLPL), 6 heterozygotes for LPL loss-of-function variants (HeLPL) and 7 normolipidemic controls.ResultsHourly post-prandial PLC was significantly lower in HoLPL than in controls (P < 0.009). Compared to the other groups, the PLC tended to decrease rapidly (in the first hour) post-meal in HoLPL (P = 0.03) and remained lower than baseline 5-h post-meal (P = 0.02) whereas it tended to slightly increase in normolipidemic controls (P = 0.02). Platelet function was not affected by the prandial status. In HoLPL, post-prandial fluctuations in the PLC positively correlated with the lymphocyte count (P = 0.005) and negatively with neutrophil/lymphocyte ratio (NLR).ConclusionThe PLC decreases post-prandially in FCS (HoLPL), is not associated with changes in functional defects of hemostasis and correlates with the NLR, a marker of acute pancreatitis severity.

Risks of Acute Cholecystitis, Acute Pancreatitis, and Acute Appendicitis in Patients with Dengue Fever: A Population-Based Cohort Study in Taiwan.

Although cases of acute cholecystitis, acute pancreatitis, and acute appendicitis following dengue virus infections have been documented, very few large-scale studies have investigated the postdengue risk of these acute abdominal conditions. This retrospective population-based cohort study included all patients with laboratory-confirmed dengue from 2002 to 2015 in Taiwan and 1:4 nondengue individuals matched by age, sex, area of residence, and symptom onset time. Multivariate Cox proportional hazards regression models were used to investigate the short-term (≤ 30days), medium-term (31-365days), and long-term (> 1year) risks of acute cholecystitis, pancreatitis, and appendicitis after dengue infection, adjusted for age, sex, area of residence, urbanization level, monthly income level, and comorbidities. Bonferroni correction was used for multiple testing; E-values were used to assess the robustness of the results to unmeasured confounding. This study included 65,694 individuals with dengue and 262,776 individuals without dengue. Patients with dengue had a significantly increased risk of acute cholecystitis (adjusted hazard ratio (aHR) 60.21; 95%CI 29.11-124.54; P < 0.0001, E-value = 119.92) and acute pancreatitis (aHR 17.13; 95%CI 7.66-38.29; P < 0.0001, E-value = 33.75) within the first 30days postinfection compared to those without dengue, but this increased risk was not present after that. The incidence rates of acute cholecystitis and pancreatitis in the first 30days were 18.79 and 5.27 per 10,000, respectively. No increased risk of acute appendicitis was observed among patients with acute dengue infection. This study was the first large epidemiological study to show a significantly increased risk of acute cholecystitis and pancreatitis among patients with dengue during the acute phase of dengue infection, while no such association was observed for acute appendicitis. Early identification of acute cholecystitis and pancreatitis in patients with dengue is crucial for preventing fatal complications.

CME: Hypertriglyceridemia

CME: Hypertriglyceridemia Abstract: The European Society of Cardiology defines hypertriglyceridaemia as fasting triglycerides >1,7mmol/l. Most patients are asymptomatic. Hypertriglyceridaemia is associated with an elevated risk of cardiovascular diseases and acute pancreatitis. Therapy consists mainly of lifestyle modifications, drug therapy plays a minor role.

Acute pancreatitis during valproic acid administration in a patient with vascular dementia, epileptic seizures, and psychiatric symptoms: a case report

BackgroundValproic acid (VPA) is a relatively safe drug widely used for the treatment of epileptic seizures and mania in bipolar disorder, as well as the prevention of migraine headaches. Here, we present a case of VPA-induced pancreatitis in a patient with vascular dementia, epileptic seizures, and psychiatric symptoms. He had no distinctive abdominal symptoms.Case presentationA 66-year-old Japanese man was treated with VPA for agitation and violent behavior due to vascular dementia, epileptic seizures, and psychiatric symptoms. During admission, he experienced a sudden decrease in consciousness and blood pressure. Abdominal findings were unremarkable; however, blood tests showed an inflammatory response and elevated amylase levels. Contrast-enhanced abdominal computed tomography showed diffuse pancreatic enlargement and inflammation extending to the subrenal pole. VPA-induced acute pancreatitis was diagnosed, VPA was discontinued, and high-dose infusions were administered. Acute pancreatitis resolved after treatment initiation.ConclusionsClinicians should be aware of this relatively rare side effect of VPA. Diagnosis may be challenging in elderly people and patients with dementia as they may present with non-specific symptoms. Clinicians should consider the risk of acute pancreatitis when using VPA in patients who cannot report spontaneous symptoms. Blood amylase and other parameters should be measured accordingly.