Acute Pancreatitis With Normal Amylase and Lipase: A Diagnostic Dilemma.

Acute pancreatitis is a common and potentially life-threatening condition. It is characterized by inflammation of the pancreas, most often leading to elevated levels of pancreatic enzymes in the blood. In a subset of patients, however, conventional biomarker levels may remain within the reference range. Such instances have the potential to create a diagnostic challenge for healthcare professionals and can lead to misdiagnosis or delayed treatment. This article presents the intriguing clinical scenario of acute pancreatitis with normal amylase and lipase, discusses factors that may lead to normoenzymatic presentation, and reminds clinicians of the diagnostic criteria for acute pancreatitis, which does not necessarily require elevated pancreatic enzymes.

Pseudo-Hypobicarbonatemia in Patients With Hypertriglyceridemia.

Hypobicarbonatemia with an elevated anion gap on a metabolic panel is frequently the initial marker of a life-threatening condition such as diabetic ketoacidosis in a patient with epigastric pain. The two commonly used means of measuring bicarbonate levels are direct measurement from a metabolic panel and calculated measurement from arterial blood gas. In this case report, we would like to highlight a potentially serious deficiency in one of these two means and how it may lead to a dangerous misdiagnosis and subsequent mismanagement. We also shine a light on potential measures to counteract or prevent this undesirable outcome.

Unusual Manifestation of Dermatomyositis: Exacerbation of Hypertriglyceridemia.

Systemic lupus erythematosus is known to cause autoimmune hyperlipidemia. We present a case in which hypertriglyceridemia was exacerbated by dermatomyositis. A 53-year-old woman with a medical history of undertreated hypertriglyceridemia complained of dyspnea and arthralgia. Despite the treatment, her triglyceride levels increased concurrently with the onset of arthralgia. She had characteristic skin manifestations and tested positive for anti-Jo-1 autoantibodies, leading to a diagnosis of dermatomyositis. Chronic inflammation may result in elevated triglyceride levels. When dermatomyositis is diagnosed, evaluating lipid abnormalities is important.

Multidisciplinary diagnosis and treatment of severe acute pancreatitis associated with hypertriglyceridemia in pregnancy: a case report.

Background: Hypertriglyceridemia (HTG) is an important cause of acute pancreatitis (AP) in pregnant women. Due to the variable clinical features of acute pancreatitis, it is difficult to make a differential diagnosis when abdominal pain occurs in late pregnancy. Severe HTG induced acute pancreatitis during pregnancy is rare, but may be a fatal threat to both mothers and fetuses during the peripartum period, and can increase maternal and fetal mortality. If emotional disorder combined, difficulty of treatment increased. So, multidisciplinary diagnosis combination of psychiatric treatment could improve the diagnosis rate and cure rate of acute pancreatitis during pregnancy. Case Description: We present the case of a 27-year-old Chinese woman in her first pregnancy, who was admitted to the hospital in the planned delivery period, but then developed progressive abdominal pain and whose biochemistry parameters were high enough to underwent a cesarean section as a result of AP a few hours after admission. The patient developed organ failure after a successful labor, which rapidly evolved to multi-organ failure, accompanied by depressive symptoms. Afterwards She appeared such as agitated, uneasy, and sad, and did not comply with the treatment, according to the classification of symptoms and course of disease, postpartum depression (PPD) was highly suspected. The patient benefited from multidisciplinary treatments that combined and integrated traditional Chinese medicine (TCM) with Western medicine therapies. The patient was discharged 35 days after her admission. Conclusions: This case highlights the importance of monitoring and managing excess dyslipidemia during pregnancy. A proactive strategy should be encouraged in the management of the patients with high risk of pancreatitis to improve the outcomes of patients. Our case report elucidates the possible long-term effects of HTG and reminds us of the need for long-term management of those affected.

Nomogram for Predicting Persistent Organ Failure With Acute Pancreatitis in Pregnancy.

Background: Acute pancreatitis in pregnancy (APIP) with persistent organ failure (POF) poses a high risk of death for mother and fetus. This study sought to create a nomogram model for early prediction of POF with APIP patients. Methods: We conducted a cross-sectional study on APIP patients with organ failure (OF) between January 2012 and March 2021. 131 patients were collected. Their clinical courses and pregnancy outcomes were obtained. Risk factors for POF were identified by univariate and multivariate logistic regression analysis. Prediction models with POF were built and nomogram was plotted. The performance of the nomogram was evaluated by using a bootstrapped-concordance index and calibration plots. Results: Hypertriglyceridemia was the most common etiology in this group of APIP patients, which accounted for 50% of transient organ failure (TOF) and 72.3% of POF. All in-hospital maternal death was in the POF group (P<0.05), which also had a significantly higher perinatal mortality rate than the TOF group (P<0.05). Univariate and multivariate logistic regression analysis determined that lactate dehydrogenase, triglycerides, serum creatinine, and procalcitonin were independent risk factors for predicting POF in APIP. A nomogram for POF was created by using the four indicators. The area under the curve was 0.875 (95%CI: 0.80-0.95). The nomogram had a bootstrapped-concordance index of 0.85 and was well-calibrated. Conclusions: Hypertriglyceridemia was the leading cause of organ failure-related APIP. Lactate dehydrogenase, triglycerides, serum creatinine, and procalcitonin were the independent risk factors of POF in APIP. Our nomogram model showed an effective prediction of POF with the four indicators in APIP patients.

Inflammatory Links Between Hypertriglyceridemia and Atherogenesis.

PURPOSE OF REVIEW: Recent studies indicate an association between hypertriglyceridemia (HTG) and atherosclerotic cardiovascular disease (ASCVD). The purpose of this review is to discuss the potential mechanism connecting HTG and ASCVD risk and the potential efficacy of HTG-targeting therapies in ASCVD prevention. RECENT FINDINGS: HTG, with elevations in triglyceride-rich lipoproteins (TGRL) and their remnants, are causal ASCVD risk factors. The mechanisms whereby HTG increases ASCVD risk are not well understood but may include multiple factors. Inflammation plays a crucial role in atherosclerosis. TGRL compared to low-density lipoproteins (LDL) correlate better with inflammation. TGRL remnants can penetrate endothelium and interact with macrophages leading to foam cell formation and inflammation in arterial walls, thereby contributing to atherogenesis. In addition, circulating monocytes can take up TGRL and become lipid-laden foamy monocytes, which infiltrate the arterial wall and may also contribute to atherogenesis. Novel therapies targeting HTG or inflammation are in development and have potential of reducing residual ASCVD risk associated with HTG. Clinical and preclinical studies show a causal role of HTG in promoting ASCVD, in which inflammation plays a vital role. Novel therapies targeting HTG or inflammation have potential of reducing residual ASCVD risk.

The Effect of Plasma Triglyceride-Lowering Therapy on the Evolution of Organ Function in Early Hypertriglyceridemia-Induced Acute Pancreatitis Patients With Worrisome Features (PERFORM Study): Rationale and Design of a Multicenter, Prospective, Observational, Cohort Study.

Background: Acute pancreatitis (AP) is a potentially life-threatening inflammatory disease with multiple etiologies. The prevalence of hypertriglyceridemia-induced acute pancreatitis (HTG-AP) has been increasing in recent years. It is reported that early triglyceride (TG) levels were associated with the severity of the disease, and TG- lowering therapies, including medical treatment and blood purification, may impact the clinical outcomes. However, there is no consensus regarding the optimal TG-lowering therapy, and clinical practice varies greatly among different centers. Our objective is to evaluate the TG-lowering effects of different therapies and their impact on clinical outcomes in HTG-AP patients with worrisome features. Methods: This is a multicenter, observational, prospective cohort study. A total of approximately 300 patients with HTG-AP with worrisome features are planned to be enrolled. The primary objective of the study is to evaluate the relationship between TG decline and the evolution of organ failure, and patients will be dichotomized depending on the rate of TG decline. The primary outcome is organ failure (OF) free days to 14 days after enrollment. Secondary outcomes include new-onset organ failure, new-onset multiple-organ failure (MOF), new-onset persistent organ failure (POF), new receipt of organ support, requirement of ICU admission, ICU free days to day 14, hospital free days to day 14, 60-day mortality, AP severity grade (Based on the Revised Atlanta Classification), and incidence of systemic and local complications. Generalized linear model (GLM), Fine and Gray competing risk regression, and propensity score matching will be used for statistical analysis. Discussion: Results of this study will reveal the current practice of TG-lowering therapy in HTG-AP and provide necessary data for future trials.

A Case of Glycogen Storage Disease Type 1a Mimicking Familial Chylomicronemia Syndrome.

Glycogen storage disease type 1a (GSD1a) is an autosomal recessively inherited inborn error of metabolism caused by a mutation in the G6PC gene, which encodes the catalytic subunit of glucose-6-phosphatase-α (G6Pase-α) enzyme. This enzyme plays a role in the final step of gluconeogenesis and glycogenolysis. Patients carrying GSD1a show growth retardation, hypoglycemia, hepatomegaly, hepatic steatosis, hyperlipidemia, hyperuricemia and lactic acidemia. Long-term symptoms include gouty arthritis and uric acid stones, osteoporosis, renal failure, intestinal impairment, cirrhosis and hepatic adenomas, and eventually, hepatocellular carcinoma. Hyperlipidemia is the indicator of poor metabolic control in GSD1a. Patients with variable levels of triglycerides (TGs) have been reported in the literature. We present a case of GSD1a that presented with severe hypertriglyceridemia (HTG) mimicking familial chylomicronemia syndrome.

Ancestry-specific profiles of genetic determinants of severe hypertriglyceridemia.

BACKGROUND: Susceptibility to severe hypertriglyceridemia (HTG), defined as plasma triglyceride (TG) levels ≥10 mmol/L (880 mg/dL), is conferred by both heterozygous rare variants in five genes involved in TG metabolism and numerous common single-nucleotide polymorphisms (SNPs) associated with TG levels. OBJECTIVE: To date, these genetic susceptibility factors have been comprehensively assessed primarily in severe HTG patients of European ancestry. Here, we expand our analysis to HTG patients of East Asian and Hispanic ancestry. METHODS: The genomic DNA of 336, 63 and 199 severe HTG patients of European, East Asian and Hispanic ancestry, respectively, was evaluated using a targeted next-generation sequencing panel to screen for: 1) rare variants in LPL, APOA5, APOC2, GPIHBP1 and LMF1; 2) common, small-to-moderate effect SNPs, quantified using a polygenic score; and 3) common, large-effect polymorphisms, APOA5 p.G185C and p.S19W. RESULTS: While the proportion of individuals with high polygenic scores was similar, frequency of rare variant carriers varied across ancestries. Compared with ancestry-matched controls, Hispanic patients were the most likely to have a rare variant (OR = 5.02; 95% CI 3.07-8.21; p < 0.001), while European patients were the least likely (OR = 2.56; 95% CI 1.58-4.13; p < 0.001). The APOA5 p.G185C polymorphism, exclusive to East Asians, was significantly enriched in patients compared with controls (OR = 10.1; 95% CI 5.6-18.3; p < 0.001), showing the highest enrichment among the measured genetic factors. CONCLUSION: While TG-associated rare variants and common SNPs are both found in statistical excess in severe HTG patients of different ancestral backgrounds, the overall genetic profiles of each ancestry group were distinct.

The polygenic nature of mild-to-moderate hypertriglyceridemia.

BACKGROUND: Patients with mild-to-moderate hypertriglyceridemia (HTG) are thought to share specific genetic susceptibility factors that are also present in patients with severe HTG, but no data have been reported on this issue. OBJECTIVE: The objective of this study was to characterize genetic profiles of patients with mild-to-moderate HTG and compare them to patients with severe HTG. METHODS: DNA from patients with mild-to-moderate HTG was sequenced using our targeted sequencing panel, "LipidSeq". For each patient, we assessed 1) rare variants disrupting five TG metabolism genes and 2) the accumulation of 16 common single-nucleotide polymorphisms (SNPs) using a polygenic risk score. The genetic profiles for these patients were then compared with normolipidemic controls from the 1000 Genomes Project and with patients with severe HTG. RESULTS: Across 134 patients with mild-to-moderate HTG, 9.0% carried heterozygous rare variants and 26.9% had an excess accumulation of common SNPs. Patients with mild-to-moderate HTG were 2.38 times (95% CI [1.13-4.99]; P = .021) more likely to carry a rare variant and 3.26 times (95% CI [2.02-5.26]; P < .0001) more likely to have an extreme polygenic risk score compared with the 1000 Genomes Project. In addition, patients with severe HTG were 1.86 times (95% CI [0.98-3.51]; P = .032) more likely to carry a rare variant and 1.63 times (95% CI [1.07-2.48]; P = .013) more likely to have an extreme polygenic risk score than patients with mild-to-moderate HTG. CONCLUSIONS: We report an increased prevalence of genetic determinants in patients with an increased severity of the HTG phenotype when considering either rare variants disrupting TG metabolism genes or an excess accumulation of common SNPs. As well, the findings confirm that the most prevalent genetic contributor to HTG, regardless of severity, is polygenic SNP accumulation.

Severe hypertriglyceridemia is primarily polygenic.

BACKGROUND: Hypertriglyceridemia (HTG) is a complex trait defined by elevated plasma triglyceride levels. Genetic determinants of HTG have so far been examined in a piecemeal manner; understanding of its molecular basis, both monogenic and polygenic, is thus incomplete. OBJECTIVE: The objective of this study was to characterize genetic profiles of patients with severe HTG, and quantify the genetic determinants and molecular contributors. METHODS: We concurrently assessed rare and common variants in two independent cohorts of 251 and 312 Caucasian patients with severe HTG. DNA was subjected to targeted next-generation sequencing of 73 genes and 185 SNPs associated with dyslipidemia. LPL, APOC2, GPIHBP1, APOA5, and LMF1 genes were screened for rare variants, and a polygenic risk score was used to assess the accumulation of common variants. RESULTS: As there were no significant differences in the prevalence of genetic determinants between cohorts, data were combined for all 563 patients: 1.1% had biallelic (homozygous or compound heterozygous) rare variants, 14.4% had heterozygous rare variants, 32.0% had an extreme accumulation of common variants (ie, high polygenic risk), and 52.6% remained genetically undefined. Patients with HTG were 5.77 times (95% CI [4.26-7.82]; P < .0001) more likely to carry one of these types of genetic susceptibility compared with controls. CONCLUSIONS: We report the most in-depth, systematic evaluation of genetic determinants of severe HTG to date. The predominant feature was an extreme accumulation of common variants (high polygenic risk score), whereas a substantial proportion of patients also carried heterozygous rare variants. Overall, 46.3% of patients had polygenic HTG, whereas only 1.1% had biallelic or homozygous monogenic HTG.