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Central hypothyroidism and dyslipidemia are well-known adverse events (AEs) of bexarotene therapy. Although hypothyroidism is known to cause dyslipidemia, no study has examined the association between hypothyroidism and dyslipidemia in patients undergoing bexarotene therapy. The aim of this study is to examine this association. A retrospective observational study was performed among 294 patients who initiated bexarotene therapy in Japan (nation-wide postmarketing complete surveillance). Jonckheere-Terpstra (one sided) test was performed to evaluate the effect of the bexarotene dose on lipid metabolisms, and regression analyses were performed to evaluate associations of bexarotene dose, free thyroxine (FT4), body mass index (BMI), and lipid metabolisms. Most patients developed hypothyroidism. Two-third of patients showed FT4 values below the lower limit at 1 week. Triglycerides (TG) increased in a bexarotene dose-dependent manner, and grade ≥3 AEs on hypertriglyceridemia was observed in 39% of the patients. Additionally, one-third of grade ≥3 AEs on hypertriglyceridemia occurred within 1 week. The delta_FT4 (difference in FT4 from baseline) negatively correlated with TG increase at 1 week (p = 0.012) but not with low density lipoprotein cholesterol (LDL-C) increase at any week. Bexarotene-induced hypothyroidism is almost inevitable and occurred quickly. Bexarotene-induced hypertriglyceridemia showed positive bexarotene dose dependency and negative delta_FT4 dependency. Prophylactic and appropriate thyroid hormone compensation therapy and starting bexarotene at low doses with subsequent titration while managing dyslipidemia may have a beneficial effect for the successful continuation of bexarotene therapy without severe endocrine and metabolic AEs.

We compared 2 models of metabolic syndrome in rats: high-fat diet (58% calories) with single streptozotocin injection at a dose of 25 mg/kg and replacement of water with 20% fructose solution. The model with fructose solution did not cause the main signs of metabolic syndrome over 24 weeks: concentrations of glucose, triglycerides, cholesterol, weight, and BP did not significantly differ from the control group (standard diet). At the same time, single streptozotocin administration was followed by the development of persistent hyperglycemia, hypertriglyceridemia, hypercholesterolemia, and signs of visceral obesity. High-fat diet combined with injection of streptozotocin in a low dose can be considered a more representative model of metabolic syndrome in humans., (© 2024. Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Bexarotene, which has been approved for use in Japan since 2016, is an effective drug for cutaneous T-cell lymphoma; however, careful management is imperative because of its adverse events. We previously demonstrated the severity of bexarotene-associated hypertriglyceridemia and the need for bexarotene dose reduction for patients with cutaneous T-cell lymphoma and high body mass index (BMI); however, high BMI does not affect the efficacy of combined bexarotene and phototherapy treatment., Objective: This study aimed to verify the effects of BMI on hypertriglyceridemia associated with oral bexarotene therapy., Methods: We conducted a post hoc analysis of data from a previous randomized, open-label clinical study that compared combined bexarotene-phototherapy treatment with bexarotene monotherapy for cutaneous T-cell lymphoma by dividing patients into two groups based on BMI (<23 kg/m 2 and ≥23 kg/m 2 )., Results: No statistically significant association was observed between patients with BMI ≥23 kg/m 2 and severe hypertriglyceridemia; however, there was a significant association between BMI ≥23 kg/m 2 and severe hypertriglyceridemia for patients who received bexarotene monotherapy, but not for those who received combined bexarotene-phototherapy treatment. The exact reasons for the discrepancies between the results of this thorough analysis and those of our past research are unclear. However, high BMI may be a risk factor for hypertriglyceridemia. Additional unidentified risk factors could also affect treatment outcomes., Conclusion: High BMI is the primary reason for hypertriglyceridemia-associated bexarotene dose reduction; however, unexplored risk factors other than high BMI could exist., (© 2024. The Author(s).)

Purpose: The case of a 47-year-old female patient who underwent sigmoidectomy for metastatic colorectal cancer is reported. Treatment with capecitabine and 5-fluorouracil induced severe hypertriglyceridemia repeatedly., Methods: Based on laboratory tests and clinical evaluations, treatment was suggested by specialists., Findings: After treatment with capecitabine, the patient's triglycerides increased from 19.7 mmol/L to 42 mmol/L. It was proposed that the patient had multifactorial chylomicronemia syndrome triggered by secondary factors. Statins, fenofibrate, ezetimib, and metformin were added to the therapy. After metastases appeared, FOLFIRI (leucovorin calcium [folinic acid], 5-fluorouracil, and irinotecan hydrochloride) chemotherapy and biological treatment (cetuximab) followed and triglycerides increased to 55.3 mmol/L., Implications: Monitoring triglyceride levels before and during therapy is suggested., Competing Interests: Declaration of competing interest None., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Sirolimus (mammalian target of rapamycin inhibitor) is a potent immunosuppressive agent, used in patients receiving hematopoietic stem cell transplant (HSCT) for Graft vs Host disease prophylaxis. Compared to calcineurin inhibitors, sirolimus has no neurotoxicity or nephrotoxicity, but sirolimus causes dose-dependent thrombocytopenia, leukopenia, delayed wound healing, hyperlipidemia, and hypertriglyceridemia. Here we report a case of acute pancreatitis and diabetic ketoacidosis in a patient with sickle cell disease post haploidentical family donor HSCT which was managed conservatively without plasmapheresis. Based on our review of the literature, this is the first reported case of developing acute pancreatitis as an adverse effect of sirolimus-induced hypertriglyceridemia leading to diabetic ketoacidosis in a recipient of HSCT., Competing Interests: The authors declare no conflict of interest., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Chemotherapy-induced hypertriglyceridaemia (HTG) is a potential serious adverse event. Severe HTG with triglycerides (TG) >11.3 mmol/L (1000 mg/dL) can cause acute pancreatitis in addition to cardiovascular diseases such as coronary artery disease. While the association of capecitabine (5-fluorouracil (5-FU) prodrug) with clinically relevant HTG is a well-known adverse reaction, 5-FU is not typically associated with HTG. We here report the case of a patient who developed 5-FU-associated grade 4 HTG with TG level raising up to 37.1 mmol/L (3286 mg/dL) occurring after the ninth cycle of adjuvant FOLFOX (Fluorouracil and Oxaliplatin) chemotherapy. Fenofibrate treatment and diet were started. Chemotherapy was postponed and then resumed for two additional cycles. However, severe HTG recurred shortly after. Chemotherapy was therefore permanently stopped. Approximately 8 weeks after chemotherapy discontinuation, TG fell back to range at 2.1 mmol/L (189 mg/dL) allowing interruption of fenofibrate without HTG recurrence at 3 months., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Antipsychotic medications increase the risk of abnormal glucose metabolism. However, in clinical practice, it is difficult to predict this risk because it is affected by medication-related and background factors. This study aimed to identify the risk factors for abnormal glucose metabolism during antipsychotic treatment. We conducted a multicenter, prospective, cohort study in patients with schizophrenia, schizoaffective disorder, or bipolar disorder. Of these patients, those with prediabetes or possible diabetes were excluded. Finally, 706 patients were included in the analysis. The hazard ratio (HR) for each factor was calculated for events of progression to hyperglycemia using time-dependent Cox regression analysis stratified according to facility type and adjusted for available background and drug-related factors. Treatments with olanzapine (HR = 2.06, 95% confidence interval [CI] = 1.05-4.05), clozapine (HR = 4.25, 95% CI = 1.56-11.60), and chlorpromazine (HR = 4.48, 95% CI = 1.21-16.57), overweight and obesity (HR = 1.57, 95% CI = 1.02-2.41), and hypertriglyceridemia (HR = 1.72, 95% CI = 1.02-2.88) were associated with a significantly higher occurrence of hyperglycemic progression. The number and daily dose of antipsychotics were not associated with their occurrence. Our study demonstrated that more careful monitoring is necessary during olanzapine, clozapine, and chlorpromazine treatment because of the higher occurrence of abnormalities in glucose metabolism. Furthermore, patients with obesity or hypertriglyceridemia warrant monitoring for the occurrence of abnormal glucose metabolism, regardless of the type of antipsychotic medication., Competing Interests: Declaration of competing interest The authors other than S.I., R.O., N.H. and I.K. declare no conflict of interest. S.I. has received personal fees from Janssen Pharmaceutical, Sumitomo Pharma, Eisai, Meiji Seika Pharma, Otsuka Pharmaceutical, Takeda Pharmaceutical, and Lundbeck and has received research/grant support from Eli Lilly. R.O. has received honoraria from Sumitomo Pharma, and Takeda Pharmaceutical. N.H. has received personal fees from Janssen Pharmaceutical, Yoshitomiyakuhin, Otsuka Pharmaceutical, Sumitomo Pharma, Novartis Pharma, and Meiji Seika Pharma. I.K. has received honoraria from Boehringer Ingelheim, Eisai, Eli Lilly, Janssen Pharmaceutical, Meiji Seika Pharma, Mochida Pharmaceutical, Novartis Pharma, Otsuka Pharmaceutical, Shionogi, Sumitomo Pharma, Takeda Pharmaceutical, Tsumura, Viatris, and Yoshitomiyakuhin and has received research and grant support from Asahi Kasei Pharma, Astellas, Daiichi Sankyo, Eisai, Eli Lilly, Mochida Pharmaceutical, Nihon Medi-Physics, Otsuka Pharmaceutical, Pfizer, Shionogi, Sumitomo Pharma, Takeda Pharmaceutical, and Tanabe Mitsubishi Pharma., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Competing Interests: The authors have no conflicts of interest to declare.

The incidence and risk factors for propofol-associated hypertriglyceridemia (HTG) in patients receiving extracorporeal membrane oxygenation (ECMO) have not been evaluated. The purpose of this study was to determine the incidence and risk factors for propofol-associated HTG in patients with acute respiratory distress syndrome (ARDS) on ECMO. This retrospective, cohort study included 167 adults admitted to a medical intensive care unit (ICU) from July 1, 2013 to September 1, 2021, who received 24 hours of concurrent propofol and ECMO therapy. The primary outcome was the incidence of propofol-associated HTG. Secondary outcomes included HTG risk factors, time to development and resolution of HTG, and incidence of pancreatitis. HTG occurred in 58 (34.7%) patients. Patients with HTG had longer durations of ECMO (19 vs. 13 days, p < 0.001), longer ICU length of stay (26.5 vs. 23 days, p = 0.002), and higher in-hospital mortality (51.7 vs. 34.9%, p = 0.047). Baseline sequential organ failure assessment score was associated with an increased risk of developing HTG (hazard ratio [HR] = 1.19, 95% confidence interval [CI] = 1.09-1.30; p < 0.001). Propofol-associated HTG occurred in one-third of patients receiving ECMO for ARDS. Higher baseline illness severity and ECMO duration were associated with an increased risk of propofol-associated HTG., Competing Interests: Disclosure: The authors have no conflicts of interest to report., (Copyright © ASAIO 2023.)

Introduction: Tocilizumab (TCZ) treatment is associated with dyslipidaemia, including a rise in triglycerides through a mechanism poorly understood. Three molecules play key roles in the regulation of triglyceride metabolism: apolipoprotein C-III (ApoC-III), angiopoietin-like protein 4(ANGPLT4) and lipoprotein lipase (LPL). The aim of this work was to analyse whether the changes in triglycerides shown by TCZ-treated RA patients could stem from the dysregulation that can occur in these regulatory molecules., Methods: Twenty-seven RA patients included in the TOCRIVAR study who received TCZ (8 mg/kg IV/q4w) were evaluated at baseline and at Weeks 12, 24 and 52 of treatment. ANGPTL4, ApoC-III and LPL, a complete lipid profile and RA disease activity, were analysed at baseline and at each visit. Multivariable linear mixed models were performed to study changes over time in lipids and regulatory molecules., Results: After 24 weeks of TCZ treatment, HDL cholesterol, apolipoprotein A1 and triglycerides increased, whereas lipoprotein (a) decreased significantly from baseline values. However, 1 year after TCZ, no significant differences in lipid pattern were observed with respect to baseline. Serum ANGPTL4 and Apo-CIII levels decreased gradually over time, both being significantly lower than baseline values at Week 52. LPL concentration did not change significantly during TCZ treatment. Remarkably, the elevation of triglycerides at Week 24 maintained its statistical significance after adjusting for the changes in ApoC-III, ANGPTL4 and LPL., Conclusion: In TCZ-treated RA patients basal serum levels of ANGPLT4 and ApoC-III, but not LPL, decreased significantly. However, the elevation of triglycerides after TCZ was not related to changes in these regulatory molecules., (© 2023 The Authors. European Journal of Clinical Investigation published by John Wiley & Sons Ltd on behalf of Stichting European Society for Clinical Investigation Journal Foundation.)

Purpose: Fenretinide (4-HPR) is a synthetic retinoid that induces cytotoxicity through dihydroceramide production. Safingol, a stereochemical-variant dihydroceramide precursor, exhibits synergistic effects when administered with fenretinide in preclinical studies. We conducted a phase 1 dose-escalation clinical trial of this combination., Methods: Fenretinide was administered as a 600 mg/m 2 24-h infusion on Day 1 of a 21-day cycle followed by 900 mg/m 2 /day on Days 2 and 3. Safingol was concurrently administered as a 48-h infusion on Day 1 and 2 using 3 + 3 dose escalation. Primary endpoints were safety and maximum tolerated dose (MTD). Secondary endpoints included pharmacokinetics and efficacy., Results: A total of 16 patients were enrolled (mean age 63 years, 50% female, median three prior lines of therapy), including 15 patients with refractory solid tumors and one with non-Hodgkin lymphoma. The median number of treatment cycles received was 2 (range 2-6). The most common adverse event (AE) was hypertriglyceridemia (88%; 38% ≥ Grade 3), attributed to the fenretinide intralipid infusion vehicle. Other treatment-related AEs occurring in ≥ 20% of patients included anemia, hypocalcemia, hypoalbuminemia, and hyponatremia. At safingol dose 420 mg/m 2 , one patient had a dose-limiting toxicity of grade 3 troponinemia and grade 4 myocarditis. Due to limited safingol supply, enrollment was halted at this dose level. Fenretinide and safingol pharmacokinetic profiles resembled those observed in monotherapy trials. Best radiographic response was stable disease (n = 2)., Conclusion: Combination fenretinide plus safingol commonly causes hypertriglyceridemia and may be associated with cardiac events at higher safingol levels. Minimal activity in refractory solid tumors was observed., Trial Registration Number: NCT01553071 (3.13.2012)., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Oral isotretinoin remains the most effective treatment for acne. The aim of this retrospective single-center cohort study was to estimate the prevalence of adverse events with the different oral isotretinoin brands used in acne treatment. The population consisted of all patients who consulted for acne between January 2015 and January 2020. The inclusion criterion was the initiation of treatment with oral isotretinoin. The exclusion criteria were the use of two or more brands during the same course of treatment and previous treatment with oral isotretinoin. Statistical analysis was carried out using Chi-square and Mann-Whitney tests. We analyzed 468 patients of whom 68.6% were female. The median age was 21 years. The median weight was 65 kg. The treatment was Roaccutane ® , Curacné ® , Acnotren ® , Isosupra ® , Contracné ® , or Acnogen ® in 44.2%, 28%, 14.5%, 10.5%, 1.7% and 0.4% of cases, respectively. Xerosis was the most frequently reported side effect regardless of the brand. The highest frequencies of hypercholesterolemia (25.6%) and eczema (13%) were noted with Roaccutane ® ; hypertriglyceridemia (16.8%), epistaxis (9.9%) and fatigue (3.1%) with Curacné ® ; excessive sweating (4.1%) and headache (4.1%) with Isosupra ® ; and abnormal liver function tests (11%) with Acnotren ® . We found a significant correlation mainly between abnormal ASAT and Acnotren ® (p = 0.009), hypercholesterolemia and Roaccutane ® [OR = 1.652 (95% CI 1.056-2.585)], hypertriglyceridemia and higher body weight (p = 0.004). Factors related to the drug brand and to characteristics of acne patients could explain the variability in the prevalence of some adverse events., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Bexarotene is an effective oral drug for the treatment of cutaneous T-cell lymphoma, but careful management is required due to its various side effects. In particular, hypertriglyceridemia often requires a reduction or even suspension of bexarotene therapy. The risk factors of bexarotene-associated severe hypertriglyceridemia are not clear. Here, we conducted a post hoc analysis of the data from our previous clinical trial, which confirmed the efficacy and safety of combined bexarotene and phototherapy, to evaluate the effect of body mass index on bexarotene-associated hypertriglyceridemia. Twenty-five subjects were divided into two subgroups: normal and underweight (body mass index [BMI] <25 kg/m 2 group) and overweight and obese (BMI ≥25 kg/m 2 group) patients. The overall incidence of hypertriglyceridemia was 81.3% (13/16) in the BMI <25 kg/m 2 group and 88.9% (8/9) in the BMI ≥25 kg/m 2 group. The incidence of grade ≥3 hypertriglyceridemia (≥500 mg/dL) was 7.7% (1/13) in the BMI <25 kg/m 2 group and 7/8 (87.5%) in the BMI ≥25 kg/m 2 group (P < 0.001). Consequently, dose reduction in the BMI ≥25 kg/m 2 group was larger than that in the BMI <25 kg/m 2 group. The bexarotene-induced change in the serum triglyceride concentration was significantly increased in cutaneous T-cell lymphoma patients with a higher body mass index (ρ = 0.508, P = 0.009). The area under the curve was 0.886 (95% confidence interval 0.748-1.000, P = 0.002). With a body mass index cut-off of 24.85 kg/m 2 , the sensitivity and specificity for identifying grade ≥3 hypertriglyceridemia were 0.875 and 0.882, respectively. The present findings suggest that BMI ≥25 kg/m 2 is a risk factor for bexarotene-associated severe hypertriglyceridemia, therefore overweight and obese patients treated with bexarotene should receive lipid-lowering drugs prophylactically. Further studies for optimizing the initial bexarotene dose in such patients are required., (© 2023 Japanese Dermatological Association.)

Objective: To explore the evidence for omega-3 fatty acid (O3FA) supplementation in primary and secondary prevention of cardiovascular disease (CVD)., Sources of Information: PubMed, Cochrane reviews, and Google Scholar were searched for meta-analyses and reviews related to O3FAs and CVD. Salient, recent randomized controlled trials referenced in these reviews were retrieved. Current lipid guidelines were reviewed., Main Message: Most O3FAs are derived from marine or aquatic microalgae, which are consumed by fish. The essential fatty acids eicosapentaenoic acid and docosahexaenoic acid are mainly sourced from fish, with a small fraction coming from plants. Omega-3 fatty acids modestly lower triglyceride levels, but the major impact on CVD is through a variety of other mechanisms related to cell membrane function, antioxidant properties, and reduction of atherogenic small low-density lipoprotein cholesterol particles. Guidelines continue to recommend eating 2 servings of fish per week. There is little evidence of benefit of O3FAs in primary prevention of CVD. Given that 40% of Canadians have insufficient levels and that these low levels may be associated with other chronic diseases over time, supplementation with O3FAs could be considered, particularly in those with hypertriglyceridemia, in those who eat no fish, or for vegetarians or vegans. Doses up to 1 g daily are considered safe. For secondary prevention after statin optimization, if triglyceride levels are between 1.5 and 5.6 mmol/L, guidelines recommend with level 1A evidence taking 2 g of icosapent ethyl twice a day. This is also recommended in primary prevention for patients with diabetes and hypertriglyceridemia and additional CVD risk factors. As fish stocks dwindle over time, preserving fisheries for developing countries and obtaining O3FA from microalgal or genetically modified plant sources may become important., Conclusion: All guidelines recommend at least 2 servings of oily fish per week, although benefit from O3FAs is mostly seen in secondary prevention. Fish oil and combination preparations of eicosapentaenoic acid and docosahexaenoic acid have failed to show benefit at any dose at any level of prevention in patients who are appropriately prescribed statins. High-dose eicosapentaenoic acid shows substantial benefit in selected patients taking statins who have high triglyceride levels., (Copyright © 2023 the College of Family Physicians of Canada.)

ApoC-III inhibits lipoprotein lipase and hepatic uptake of triglyceride-rich lipoproteins. It is unknown whether targeting apoC-III affects hepatic steatosis in patients with hypertriglyceridemia. We studied the effect of volanesorsen, a potent antisense oligonucleotide targeting APOC3 mRNA, on hepatic fat fraction (HFF) assessed by MRI in patients with severe hypertriglyceridemia (SHTG, triglycerides ≥500 mg/dL), familial partial lipodystrophy (FPL, triglycerides ≥200 mg/dL) and familial chylomicronemia syndrome (FCS, triglycerides ≥750 mg/dL). The data were evaluated individually in COMPASS (SHTG), APPROACH (FCS), and BROADEN (FPL) trials. The baseline absolute HFF were elevated in all three trials and ranged from 6.3-18.1%. In COMPASS, compared to placebo, volanesorsen significantly reduced the absolute HFF by -3.02% (95% CI, (-5.60, -0.60), p = 0.009) (placebo-adjusted % change from baseline -24.2%, p = 0.034) from baseline to 6 months. In APPROACH a non-significant absolute -1.0% (95% CI, -2.9, 0.0, p = 0.13) reduction in HFF was noted from baseline to 12 months (placebo-adjusted % change from baseline -37.1%, p = 0.20). In BROADEN volanesorsen significantly reduced the absolute HFF by -8.34% (95% CI, -13.01, -3.67, p = 0.001) from baseline to 12 months (placebo-adjusted % change from baseline -52.7%, p = 0.004). In all 3 trials individually, a strong inverse correlation was present between the baseline HFF and the change in HFF in the volanesorsen groups, but not in the placebo groups. In conclusion, apoC-III inhibition with volanesorsen has favorable effects in HFF in patients with different etiologies of hypertriglyceridemia., (Copyright © 2023. Published by Elsevier Inc.)

Introduction: This article aimed to compare the prevalence of dyslipidemia and determine risk factors associated with lipid levels in a cohort of HIV-infected patients receiving two different antiretroviral therapy (ART) regimens, nucleoside reverse transcriptase inhibitor/non-nucleoside reverse transcriptase inhibitor (NRTI/NNRTI) and nucleoside reverse transcriptase inhibitor/integrase strand transfer inhibitor (NRTI/INSTI)., Methods: This longitudinal study analyzed 633 HIV-infected patients with complete blood lipid profile records for at least 1 year at the ART clinic of Zhongnan Hospital of Wuhan University, China, from June 2018 to March 2021. Demographic and clinical data, including age, gender, body weight, height, current/former/non-smoker, current drinker, diabetes mellitus, hypertension, were extracted from electronic medical records. Laboratory tests included hematology, total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), Lipoprotein(a) and CD4 cell count. The observation duration of this study was a maximum of 33 months. Data comparisons were performed using the Chi-square test, Student's t -test and Mann-Whitney U test. Generalized linear mixed-effects model (GLMM) and value of p < 0.05 were used to determine factors associated with serum lipid profiles., Results: In this study, the effect of the NNRTIs group on the lipid profile over time was mainly an increase in TC and HDL-C, while a decrease in TC/HDL-C and LDL/HDL-C. However, the INSTIs group had higher mean TC and lower HDL-C compared to the NNRTIs group, with significantly increased levels of TC, TG, HDL-C, and LDL-C. In the analysis of dyslipidemia rates, there were significant differences in the prevalence of abnormal TG and TC/HDL-C in HIV-infected patients receiving two different ART regimen groups during different follow-up periods. Dyslipidemia, defined as hypercholesterolemia, hypertriglyceridemia, and low HDL-C, was more prevalent in the INSTIs group, with a higher risk of developing hypertriglyceridemia and a higher TC/HDL-C ratio compared to the NNRTIs group. GLMM analysis suggested significantly higher TG values in the INSTIs group (estimated 0.36[0.10, 0.63], SE 0.14, p  = 0.008) compared to the NNRTIs group, even after adjusting for other covariates. In addition, GLMM analysis also showed that age, gender, BMI, CD4 count, and ART duration were associated with dyslipidemia., Conclusion: In conclusion, treatment with both commonly-used ART regimens can increase the mean values of lipid profiles and the risk of dyslipidemia. The findings indicated that TG values were significantly higher in the INSTIs group than in HIV-infected patients receiving the NNRTIs regimens. Longitudinal TG values are independently associated with the clinical types of ART regimens. Clinical Trial Number : ChiCTR2200059861., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Liu, Wei, Liang, Chen, Deng, Zhao and Wan.)

Background: Hypertriglyceridemia is associated with subclinical atherosclerosis and vascular inflammation even when low-density lipoprotein cholesterol levels are normal. However, few cohort studies on hypertriglyceridemia have been conducted in males with higher susceptibility to human immunodeficiency virus (HIV)-related deterioration of arterial structure and function. Our objective was to investigate the incidence of hypertriglyceridemia during treatment with combination antiretroviral therapy (cART) in males with HIV and explore its related risk factors., Methods: In this retrospective study, we included 309 males living with HIV (median age 31 years [interquartile range 26-42.5]) who initiated cART treatment in our hospital from January 2013 to December 2018. We collected follow-up data on serum triglycerides and other related information as of June 31, 2021. A Cox proportional hazards regression model was used to analyze the related risk factors., Results: In 666.7 person-years, hypertriglyceridemia occurred in 140 patients (triglyceride ≥2.3 mmol/L [200 mg/dL]), and the incidence rate was 21.0 per 100 person-years (Patients who took the lamivudine [3TC] + tenofovir disoproxil fumarate [TDF] + efavirenz [EFV] regimen accounted for 77.0% of the total patients.). Multiple Cox regression analysis showed that baseline CD4/CD8 ratio < 0.20 (hazard ratio [HR], 2.705 [95% confidence interval (CI): 1.381-5.296]; P = 0.004}, body mass index (BMI) ≥ 24.0 kg/m 2 (HR, 1.768 [95% CI: 1.225-2.552]; P = 0.002), borderline high triglyceride at baseline (HR, 3.457 [95% CI: 2.162-5.527]; P < 0.001), and 3TC + zidovudine (AZT) + EFV regimen (HR, 2.702 [95% CI: 1.593-4.581]; P < 0.001), or 3TC + TDF + lopinavir/ritonavir (LPV/r) regimen (HR, 4.349 [95% CI: 2.664-7.102]; P < 0.001) were independent risk factors for hypertriglyceridemia., Conclusion: During the course of cART treatment, the incidence of hypertriglyceridemia in males with HIV was high. The main risk factors influencing its occurrence are a low baseline CD4/CD8 ratio, overweight and obesity, and the use of AZT or LPV/r in the cART regimen., (© 2023. The Author(s).)

Rationale: Propofol is a first-line sedative agent in the intensive care unit (ICU) but may be associated with hypertriglyceridemia and pancreatitis. To date, the relationship between propofol-induced hypertriglyceridemia and pancreatitis, as well as clinician responses to propofol-induced hypertriglyceridemia, have not been comprehensively studied. Objectives: To assess the incidence of hypertriglyceridemia and pancreatitis in patients receiving continuous propofol infusions in the ICU and to describe the association between hypertriglyceridemia and the use of nonpropofol continuous sedative infusions. Methods: This was a retrospective observational cohort study conducted at three urban academic hospitals within a single health system. Findings were additionally validated using the Medical Information Mart for Intensive Care-IV (MIMIC-IV) database containing data from a separate tertiary care hospital. Mechanically ventilated adult patients who received a continuous propofol infusion between 2016 and 2021 were included. The primary exposure was serum triglyceride concentration, and hypertriglyceridemia was defined as a triglyceride concentration greater than 400 mg/dl. Outcomes included new-onset pancreatitis as well as receipt of midazolam, dexmedetomidine, or ketamine after the triglyceride measurement. The incidence of pancreatitis was compared between groups using a Fisher's Exact test. Multivariable logistic regression was used to assess the association between dichotomized triglyceride concentration and alternative sedative use. Results: In the primary cohort of 7,037 patients, 1,724 (24.5%) had one or more triglyceride concentration measured. Of these, 1,365 (79.2%) had a maximum concentration of less than 400 mg/dl, and 359 (20.8%) had a maximum concentration of greater than 400 mg/dl. Compared with patients with low triglyceride concentrations, patients with high triglyceride concentrations were more likely to receive a continuous infusion of midazolam (37.0% vs. 16.4%; adjusted odds ratio [aOR], 3.1; 95% confidence interval [CI], 2.2-4.4; P  < 0.01), ketamine (22.8% vs. 6.9%; aOR, 3.5; 95% CI, 2.3-5.3; P  < 0.01), and dexmedetomidine (57.7% vs. 46.6%; aOR, 1.5; 95% CI, 1.1-2.0; P  < 0.01). Rates of midazolam infusion increased as triglyceride concentrations exceeded 500 mg/dl. Forty-four (0.6%) patients developed pancreatitis after propofol initiation, of which 4 (9.1%) were considered related to propofol-associated hypertriglyceridemia. Findings were similar in the MIMIC-IV cohort. Conclusions: Propofol-associated hypertriglyceridemia is relatively common in mechanically ventilated ICU patients who have triglycerides measured. Pancreatitis related to propofol-associated hypertriglyceridemia is rare. Patients who develop hypertriglyceridemia while receiving propofol are more likely to receive continuous infusions of other sedatives.

Introduction: Drug-induced pancreatitis has been increasingly recognized, but it is frequently encountered as an inconspicuous etiology. The underlying mechanisms of injury vary with different drugs. Tamoxifen is a frequently used anticancer drug that acts by selective modulation of the estrogen receptor in patients with breast cancer. Tamoxifen-induced hypertriglyceridemia is a relatively rare etiological factor for acute pancreatitis. However, acute pancreatitis secondary to this adverse effect remains an exceedingly important clinicopathologic entity., Case Report: We hereby delineate a rare case of acute pancreatitis secondary to hypertriglyceridemia in a patient who was on tamoxifen treatment for the past 3 years. Her serum lipase and triglyceride levels were markedly elevated at 14,285 IU/L and 20,344 mg/dL, respectively. The diagnosis was considered based on the findings of a standard diagnostic workup and exclusion of alternative causes of acute pancreatitis., Management and Outcome: The patient was instituted prompt treatment with intravenous insulin infusion and gemfibrozil. The clinical outcome was favorable with no complications. Tamoxifen was permanently discontinued and was replaced with letrozole., Discussion: This article illustrates that acute pancreatitis should be considered in the differential diagnoses of abdominal pain and elevated pancreatic enzymes in patients undergoing tamoxifen treatment. It also underscores the importance of pre- and post-tamoxifen lipid screening, especially in patients with a history of dyslipidemia and diabetes mellitus. It will facilitate an expedient detection of hypertriglyceridemia, potentially saving patients from associated morbidity and mortality.

Background: The antiarrhythmic drug amiodarone has noncardiac adverse effects, leading to restrictive therapeutic plasma ranges. Despite the significant positive correlation between triglyceride and amiodarone levels, the effect of fluctuations in amiodarone levels in patients with hypertriglyceridemia on amiodarone therapy has not been fully characterized. This study is the first to report on the effect of hypertriglyceridemia on the efficacy and safety of amiodarone therapy., Case Presentation: The first patient was a 58-year-old man with hypertriglyceridemia who was diagnosed with ventricular fibrillation (patient #1). The second patient with hypertriglyceridemia was a 72-year-old man with sustained ventricular tachycardia (patient #2). Both patients received implantable cardioverter-defibrillator therapy. During the study period, amiodarone and N-desethylamiodarone concentrations were measured 12 times in patient #1 and 26 times in patient #2. Triglyceride concentrations in patient #1 and patient #2 ranged from 102 to 765 mg/dL and from 125 to 752 mg/dL, respectively. For both patients, amiodarone dosage was maintained at 100 mg/day, and the administration of concomitant drugs that could affect amiodarone pharmacokinetics was neither initiated nor discontinued. However, amiodarone concentrations fluctuated (patient #1, 0.52 - 1.86 μg/mL; patient #2, 0.73 - 2.82 μg/mL). Although amiodarone concentrations fluctuated, neither of the patients had defibrillation shocks to stop the abnormal rhythm via an implantable cardioverter-defibrillator, and laboratory data showed that thyroid-stimulating hormone, free thyroxine, KL-6, and surfactant protein-D remained close to normal., Conclusion: In patients with hypertriglyceridemia, it may be necessary for clinicians to pay more attention to the clinical symptoms along with fluctuations in amiodarone levels and accordingly adjust amiodarone dosage.

Purpose: Brazil nuts ( Bertholletia excelsa ) are consumed world-wide and have become a new trend in weight loss supplementation. We present a unique case of severe hypertriglyceridemia-associated acute pancreatitis following daily usage of a Brazil nut supplement product., Summary: A Hispanic female presented with severe hypertriglyceridemia and acute pancreatitis several months after starting a Brazil nut weight loss supplement in the setting of poorly controlled Type 2 Diabetes Mellitus. Her initial triglyceride level was undetectably high >10,000 mg/dL but improved rapidly following euglycemic insulin infusion and supplement cessation. The patient was managed with supportive care, started on oral fibrate therapy after abdominal symptoms improved, and was discharged to home in stable condition., Conclusion: It is essential for pharmacists to maintain a high index of suspicion for patients taking complementary and alternative medications and supplements who present with acutely altered laboratory parameters or onset of acute disease. In this instance, a patient was found to have profound hypertriglyceridemia with onset of acute pancreatitis following usage of a Brazil nut weight loss supplement.

Aims: Pemafibrate, a novel selective peroxisome proliferator-activated receptor modulator, was shown to ameliorate lipid abnormalities in a phase III clinical trial of patients with type 2 diabetes mellitus (T2DM). However, its efficacy has not been demonstrated in real-world clinical practice in patients with T2DM., Methods: We performed a multi-center prospective observational study of the use of pemafibrate in patients with T2DM and hypertriglyceridemia versus conventional therapy, with or without a fibrate. The primary outcomes were the changes from baseline in fasting serum triglyceride (TG) and high-density lipoprotein-cholesterol (HDL-C) concentrations at week 52., Results: We recruited 650 patients, and data from 504 (252 per group) were analyzed after propensity score matching. In the pemafibrate group, both TG and HDL-C showed significant improvements (p < 0.001), and several indices reflecting TG-rich lipoproteins, low-density lipoprotein-cholesterol particle size, and liver enzyme elevations were significantly ameliorated compared with the control group, but there was no difference in glycemic control markers. One of the key secondary endpoints showed that switching from conventional fibrates to pemafibrate improved eGFR but increased uric acid concentration., Conclusions: In patients with T2DM, pemafibrate has superior effects on lipid profile as well as liver and renal dysfunction to conventional fibrates., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: The authors declare the following financial interests/personal relationships that may be considered as potential competing interests: Sakuma I, Nakamura A, Cho KY, Kameda H, Taneda S, Nagai S, Kurihara Y, Atsumi T, and Miyoshi H have received honoraria for lectures and research funding from the organizations listed below. The other authors declare no conflict of interest. Sakuma I has received research support from National Cerebral and Cardiovascular Center and Medical Informatics Study Group, Takeda Pharmaceutical Co. ltd., GlaxoSmithKline KK, AstraZeneca KK and Boehringer lngelheim Japan Inc.. Nakamura A has received research support from Mitsubishi Tanabe Pharma, Daiichi Sankyo, MSD, Novo Nordisk Pharma, Novartis Pharma, AstraZeneca, Life Scan Japan, and Taisho Pharmaceutical Co., ltd. Cho KY has received honoraria for lectures from Eli Lilly Japan K.K. Kameda H has received research support from Mitsubishi Tanabe Pharma. Taneda S has received honoraria for lectures from Eli Lilly Japan K.K. and Novo Nordisk Pharma. Nagai S has received honoraria for lectures from Sumitomo Pharma Co., ltd. and Eli Lilly Japan K.K. Kurihara Y has received honoraria for lectures from Astellas Pharma Inc., AstraZeneca, Mitsubishi Tanabe Pharma Co., MSD K.K., Ono Pharmaceutical Co., ltd., Sanofi, Shionogi & Co., ltd., Taisho Pharmaceutical Co., ltd., and Mitsubishi Tanabe Pharmaceutical Co., ltd. Atsumi T has received honoraria for lectures from Mitsubishi Tanabe Pharma Co., Chugai Pharmaceutical Co., ltd., Astellas Pharma Inc., Takeda Pharmaceutical Co., ltd., Pfizer Inc., AbbVie Inc., Eisai Co., ltd., Daiichi Sankyo Co., Bristol Myers Squibb Co., UCB Japan Co., ltd., and Eli Lilly Japan K.K.; and has received research funding from Astellas Pharma Inc., Takeda Pharmaceutical Co., ltd., Mitsubishi Tanabe Pharma Co., Chugai Pharmaceutical Co., ltd., Daiichi Sankyo Co., Otsuka Pharmaceutical Co., ltd., Pfizer Inc., and Alexion Inc. Miyoshi H has received honoraria for lectures from Astellas Pharma Inc., Sumitomo Pharma Co., ltd., Eli Lilly Japan K.K., Mitsubishi Tanabe Pharma Co., MSD K.K., Novo Nordisk Pharma ltd., Kowa Pharmaceutical Co., ltd., Nippon Boehringer Ingelheim Co., Ono Pharmaceutical Co., ltd., Taisho Pharmaceutical Co., ltd., and Sanofi; and has received research funding from Daiichi Sankyo Co., Sumitomo Pharma Co. ltd., Taisho Pharmaceutical Co. ltd., Mitsubishi Tanabe Pharma Co., Novo Nordisk Pharma, Kowa Pharmaceutical Co., ltd., Abbott Japan Co., Nippon Boehringer Ingelheim Co., ltd., Life Scan Japan Inc., and Ono Pharmaceutical Co., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Objectives: When using indirect ion-selective electrode (ISE) methods, hypertriglyceridemia leads to pseudohyponatremia due to water displacement artifacts. Multiple strategies exist to minimize this interference. Our objective was to create a patient-friendly one-tube-fits-all testing setup without compromising the method robustness., Methods: Four strategies were evaluated in a single patient with hypertriglyceridemia. Additionally, the interchangeability between the Cobas 8000 and ABL Flex was evaluated on samples (n = 2274) with different total protein (TP) concentrations. Finally, a proof-of-concept (n = 40) was performed by re-measuring the routine sample with the ABL90 Flex., Results: ABL90 flex results and calculated sodium did not suffer from the presence of high triglyceride levels. We did not observe any significant differences between the three groups (P > 0.05) of sample types (arterial vs. venous plasma vs. venous whole blood after mixing up) nor for the analysers (Roche vs. ABL90 Flex). Passing-Bablok and Bland-Altman tests revealed interchangeability., Conclusion: In future cases of hypertriglyceridemia, 1500 mg/dL will be used as a preliminary threshold for reliable sodium determination. Routine Li-heparin samples can be used for accurate sodium determination without any need for extra arterial or venous blood gas tubes, offering a patient-friendly test setup for similar cases.

Atherosclerotic cardiovascular disease (ASCVD) and its atherothrombotic complications impose a substantial disease burden in Europe, representing a cost of €210 billion per year for the European Union. Hypertriglyceridemia, a major risk factor for premature ASCVD, is present in more than 20% of the European population, and is a key feature of atherogenic dyslipidemia. Recent findings from the Progression of Early Subclinical Atherosclerosis (PESA) cohort in Spain showed that even in apparently healthy, middle-aged individuals without a history of cardiovascular (CV) risk, elevated triglyceride levels are associated with subclinical atherosclerosis and arterial inflammation. Emerging evidence from epidemiologic and genetic studies supports an independent causative role of triglycerides, triglyceride-rich lipoproteins, and their remnants in this pathology. Icosapent ethyl (IPE) is a highly purified, stable ethyl ester of eicosapentaenoic acid (EPA) that was initially approved by the United States Food and Drug Administration to treat severe hypertriglyceridemia, and subsequently received an expanded indication to reduce the risk of CV events in adult statin-treated patients. Approval was based on the pivotal, randomized, placebo-controlled, double-blind Reduction of Cardiovascular Events with Icosapent Ethyl-Intervention Trial (REDUCE-IT), which showed that high-dose IPE (4 g/day) significantly reduced the risk of primary and secondary composite endpoints comprising major CV events and CV death relative to placebo. In 2021, the European Medicines Agency (EMA) approved IPE to reduce the risk of CV events in adult statin-treated patients at high CV risk with elevated triglyceride levels (≥1.7 mmol/L [≥150 mg/dL]) and established CV disease, or diabetes and at least one other CV risk factor. Clinical studies in Europe, which included patients with acute myocardial infarction, coronary artery disease, and those undergoing cardiac rehabilitation, established that 12.5% to 23.3% of these high-risk populations may benefit from treatment with IPE. Such clinical benefit may in part result from the moderate triglyceride-lowering properties of IPE/EPA; equally however, concentrations of atherogenic remnant particle-cholesterol are markedly reduced. Furthermore, IPE/EPA exerts pleiotropic actions beyond its lipid-lowering properties, which include modulation of endothelial function, attenuation of intra-plaque inflammation and oxidative stress, and reduction in macrophage accumulation. Plasma phospholipids, into which EPA is primarily incorporated and transported, appear to serve as precursors for a series of anti-inflammatory metabolites involving the resolvins RvE1 to RvE3, a pathway which may confer cardioprotective benefits. In addition, plaque imaging data from the Effect of Icosapent Ethyl on Progression of Coronary Atherosclerosis in Patients With Elevated Triglycerides on Statin Therapy (EVAPORATE) and the Combination Therapy of Eicosapentaenoic Acid and Pitavastatin for Coronary Plaque Regression Evaluated by Integrated Backscatter Intravascular Ultrasonography (CHERRY) trials show that plaque stabilization may be favorably affected. These factors may act synergistically to stabilize atherosclerotic plaques and reduce CV risk. In addition to robust efficacy data, multiple cost-utility studies across several countries indicate that IPE/EPA is a cost-effective treatment option that is favorably situated relative to some common willingness-to-pay thresholds. This review will evaluate the relevance of hypertriglyceridemia to residual ASCVD burden in statin-treated dyslipidemic patients, the potential of IPE/EPA to reduce the risk of ASCVD and cardiovascular mortality in high-risk patient populations, and the mechanisms which may underlie these effects. Finally, the clinical implications of the EMA label for IPE will be critically appraised in light of the updated 2019 European Society of Cardiology/European Atherosclerosis Society guidelines on the management of dyslipidemia and the recent European Atherosclerosis Society consensus statement on triglyceride-rich lipoproteins and their remnants, together with considerations of its cost-effectiveness across several countries., Competing Interests: Declaration of Competing Interest M. John Chapman has received research grants, and/or undertaken consulting activities, and/or has been the recipient of speaker fees from Alexion, Amarin, Amgen, AstraZeneca, CSL, Daiichi Sankyo, Kowa Europe, MSD, Novartis, Pfizer, Sanofi, Regeneron, Servier, and Unilever. Jose L. Zamorano has received speaker honoraria from Bayer, Pfizer, and Daiichi Sankyo. Klaus G. Parhofer has received research funding and/or honoraria for consultancy and/or speaker's bureaus and/or DMC activity from Akcea, Amarin, Amgen, Boehringer-Ingelheim, Dr. Schär, Daiichi Sankyo, Ionis, MSD, Novartis, Pfizer, Regeneron, Sanofi, and Silence Therapeutics., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Saroglitazar, being a dual PPAR-α/γ agonist, has shown beneficial effect in diabetic dyslipidemia and hypertriglyceridemia. Fibrates are commonly used to treat severe hypertriglyceridemia. However, the effect of saroglitazar in patients with moderate to severe hypertriglyceridemia was not evaluated. We conducted a study to compare the efficacy and safety of saroglitazar (4 mg) with fenofibrate (160 mg) in patients with moderate to severe hypertriglyceridemia. This was a multicenter, randomized, double-blinded, double-dummy, active-control, and noninferiority trial in adult patients with fasting triglyceride (TG) levels of 500-1,500 mg/dl. The patients were randomized in a 1:1 ratio to receive daily dose of saroglitazar or fenofibrate for 12 weeks. The primary efficacy end point was the percent change in TG levels at week 12 relative to baseline. The study comprised of 41 patients in the saroglitazar group and 41 patients in the fenofibrate group. We found that the percent reduction from baseline in TG levels at week 12 was significantly higher in the saroglitazar group (least square mean = -55.3%; SE = 4.9) compared with the fenofibrate group (least square mean = -41.1%; SE = 4.9; P = 0.048). Overall, 37 treatment-emergent adverse events (AEs) were reported in 24 patients (saroglitazar: 13; fenofibrate: 11). No serious AEs were reported, and no patient discontinued the study because of AEs. We conclude that saroglitazar (4 mg) is noninferior to fenofibrate (160 mg) in reducing TG levels after 12 weeks of treatment, was safe, and well tolerated., Competing Interests: Conflict of interest The authors declare that they have no conflicts of interest with the contents of this article. D. P. was from Zydus Therapeutics, Inc.; F. S. was from Zydus Worldwide DMCC; R. R.-G. and J. G. G. are from the School of Medicine and University Hospital, Autonomous University of Nuevo León, Mexico. P. C.-L. is from the Avant Sante Research Center. Clinical trial registration: SARO.17.001.02.PROT., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: REDUCE-IT was a multinational, double-blind trial that randomized 8179 statin-treated patients with controlled low-density lipoprotein cholesterol and moderately elevated triglycerides to icosapent ethyl (IPE) or placebo. IPE was associated with a substantial reduction in the primary composite endpoint of death from cardiovascular causes, nonfatal myocardial infarction, nonfatal stroke, coronary revascularization, or unstable angina requiring hospitalization. Since the original publication of the trial, there have been a myriad of additional analyses confirming the benefit of IPE in various patient groups. Our objectives in this review are to summarize the key findings of the REDUCE-IT trial and its subsequent analyses as well as to call for the reevaluation and expansion of current guidelines to incorporate IPE as a therapy for patients at elevated cardiovascular risk with mild or moderate hypertriglyceridemia., (Copyright © 2022. Published by Elsevier Inc.)

Pegasparagase (PEG-Asparaginase) induced hypertriglyceridemia is rare in the treatment of lymphoblastic lymphoma in children. We present a case of PEG-asparaginase induced hypertriglyceridemia that was incidentally identified and suspicion of its interference with sodium measurement in the clinical laboratory. The use of a direct ion selective method clarified the presence of true hyponatremia. The patient was treated with an oral Fenofibrate therapy which resolved the hypertriglyceridemia. This case highlights that PEG-asparaginanse and Olazanpine can induce hypertriglyceridemia in acute lymphoblastic leukemia and it may be useful to obtain baseline triglyceride measurements for these patients., (Copyright © 2022. Published by Elsevier B.V.)

Objective: To investigate the impact of single nucleotide polymorphisms (SNPs) from APOA5, APOC3, CETP, ATP binding cassette transporter A1 and SIK3 genes in the development of hypertriglyceridemia in HIV patients under antiretroviral therapy., Material and Methods: A case-control study was developed. Leukocytic genomic DNA was extracted and genotyping for SNPs rs662799, rs964184, rs5128, rs2854116, rs2854117, rs3764261, rs4149310, rs4149267 and rs139961185 was performed by real time-PCR using TaqMan allelic discrimination assays, in Mexican mestizo patients with HIV infection, with hypertriglyceridemia (>1.7 mmol/L) under antiretroviral therapy. Genetic variants were also investigated in a control group of normolipidemic HIV patients (≤ 1.7 mmol/L). Haplotypes and gene interactions were analyzed., Results: A total of 602 HIV patients were genotyped (316 cases and 286 controls). Age and antiretroviral regimen based on protease inhibitors were associated with hypertriglyceridemia (P = 0.0001 and P = 0.0002. respectively). SNP rs964184 GG genotype in APOA5 gene exhibited the highest association with hypertriglyceridemia risk (OR, 3.2, 95% CI, 1.7-5.8, P = 0.0001); followed by SNP rs139961185 in SIK3 gene (OR = 2.3; (95% CI, 1.1-4.8; P = 0.03 for AA vs. AG genotype; and APOC3 rs5128 GG genotype, (OR, 2.2; 95% CI, 1.1-4.9; P = 0.04) under codominant models. These associations were maintained in the adjusted analysis by age and protease inhibitors based antiretroviral regimens., Conclusions: This study reveals an association between rs964184 in APOA5; rs5128 in APOC3 and rs139961185 in SIK3 and high triglyceride concentrations in Mexican HIV-patients receiving protease inhibitors. These genetic factors may influence the adverse effects related to antiretroviral therapy., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Introduction: The objective of this study was to investigate changes in serum lipids among HIV-infected patients switching from non-nucleoside-reverse transcriptase inhibitors (NNRTI) to protease inhibitor (PI)-based highly active antiretroviral therapy (HAART), and to determine if changes of lipid profiles impacted the monocyte subsets recovery., Methodology: Fifty-seven subjects who switched from NNRTIs to PI-based HAART (NNRTIs to PI group) and fifty-five subjects who initially started with PI-based HAART (initial PI group) were recruited. According to their baseline triglyceride (TG) levels, the NNRTIs to PI and initial PI groups were further divided into non-hypertriglyceridemia and hypertriglyceridemia subgroups, respectively. The effects of PI-based HAART on lipid profiles and monocyte subsets were analyzed., Results: At 48 weeks, the TG changes in the NNRTIs to PI group was higher than that of the initial PI group. The increases of serum TG levels in the initial PI non-hypertriglyceridemia group was greater than that of the NNRTIs to PI non-hypertriglyceridemia group. For the hypertriglyceridemia group at baseline, significant increment in TG levels were observed in the NNRTIs to PI hypertriglyceridemia group. The percentages of circulating CD14highCD16+ and CD14lowCD16+ subsets were elevated in the two groups. At 48 weeks, the proportion of CD14highCD16+ monocytes declined gradually, and the proportion of CD14lowCD16+ monocytes decreased independently of the TG level., Conclusions: For non-hypertriglyceridemia individuals at baseline, PI-based regimens increased the TG level in the initial PI group. For the NNRTIs to PI hypertriglyceridemia group, PI-based regimens reinforced HAART-related hypertriglyceridemia., Competing Interests: No Conflict of Interest is declared, (Copyright (c) 2022 Yu Zhang, Jiang Xiao, Wen Zhang, Ning Han, Di Yang, Wei Liu, Hui Zeng, Junyan Han, Hongxin Zhao.)

Objectives: We aimed to analyze the incidence rates of new-onset diabetes, hypertriglyceridemia, hypercholesterolemia, liver injury, and renal injury during antiretroviral therapy (ART) among people living with HIV (PLWH) and determine the associated risk factors., Methods: This study included PLWH enrolled from Beijing Ditan Hospital from November 11, 2004, to December 29, 2018. The incidence rates of new-onset diabetes, hypertriglyceridemia, hypercholesterolemia, liver injury, and renal injury were calculated and stratified based on ART regimen, CD4 count, and HIV-RNA. Risk factors were determined using Cox regression analysis., Results: Overall, 6747 participants were included. Moreover, 4.5%, 43.3%, 25.4%, 11.2%, and 6.2% of patients developed new-onset diabetes, hypertriglyceridemia, hypercholesterolemia, liver injury, and renal injury, respectively, with incidence rates of 1.7, 26.9, 10.2, 3.9, and 5.5 per 100 person-years, respectively. Longitudinally, the incidence rates and percentages of these outcomes were highest in the first year of ART. The percentage of dyslipidemia was significantly higher in protease inhibitor (PI)-based regimen than in non-nucleoside reverse transcriptase inhibitor (NNRTI)-based regimen. However, the percentage of liver injury was significantly higher in NNRTI-based regimen than in PI-based regimen. In multivariate Cox regression analysis, low CD4 count (<200 cells/µL, adjusted hazard ratio [aHR] = 1.34, 95% confidence interval [CI] 1.15-1.57) and high HIV-RNA (>10 5 copies/mL, aHR = 1.26, 95% CI 1.08-1.48) were risk factors for hypertriglyceridemia., Conclusions: Clinical outcomes, including new-onset diabetes, dyslipidemia, and liver and renal injuries, are common in PLWH. Regular glucose, lipid, liver, and renal function monitoring is required during ART, especially in high-risk patients., (© 2022 British HIV Association.)

Objective: There are no definitive treatment guidelines for hypertriglyceridemia (HTG)-induced acute pancreatitis (AP). The aim of this retrospective study was to evaluate the efficacy of insulin in decreasing triglyceride (TG) levels in patients with HTG-induced AP., Design: We included 17 cases of HTG-induced AP treated with continuous insulin aspart for 4 days., Patients: Fifteen patients were male, two were female. The mean TG level at admission was 56.53 ± 25.29 mmol/L. The mean APACHE II score was 10.2 ± 5.7, Ranson 4.2 ± 1.7 and Balthazar 6.5 ± 2.6, implying a severe form of the disease., Methods: In an 8-year period, 17 patients with a diagnosis of HTG-induced AP were treated with a continuous infusion of 5% dextrose and insulin aspart in an attempt to lower TG levels. TG levels were assessed on admission, the second and fourth day of therapy. The patient outcome, complications and recurrence of AP were monitored., Results: A significant reduction of TG levels was observed in all patients on Day 4. All patients survived, with one forming a giant pseudocyst as a disease complication, one needing haemodialyses treatment due to an acute kidney injury, and one developing acute respiratory distress syndrome that required mechanical ventilation for 4 days. All patients recovered completely., Conclusion: Our study showed that continuous insulin aspart infusion decreases TG levels in HTG-induced AP from a mean TG level of 56.53 mmol/L on Day 1 to 21.75 mmol/L on Day 2 and finally to 6.86 mmol/L on Day 4. We consider this therapy very efficient, safe, simple to administer and monitor., (© 2021 John Wiley & Sons Ltd.)

Background The association between fluoropyrimidines except for capecitabine and the risk of hypertriglyceridemia is unclear. Objective To investigate hypertriglyceridemia in patients receiving fluoropyrimidines. Method This observational study used anonymized patient data recorded in the open-access Japanese Adverse Drug Event Report database. All fluoropyrimidine and taxane users were investigated. Results We identified 29,451 fluoropyrimidine users and 21,266 taxane users. Disproportionality for both hypertriglyceridemia and an increase in serum triglyceride levels was observed in fluoropyrimidine users compared with in taxane users (reporting odds ratio, 6.74; 95% confidence interval [CI] 2.05-22.17; P < .001). Multivariate logistic analysis showed that both hypertriglyceridemia and an increase in serum triglyceride levels among fluoropyrimidines users were significantly associated with doxifluridine use (odds ratio [OR] 42.50; 95% CI 5.34-338.00; P < .001), tegafur use (OR 9.56; 95% CI 2.08-43.90; P < .001), capecitabine use (OR 12.30; 95% CI 2.67-56.80; P < .001), and breast cancer (OR 5.61; 95% CI 1.07-29.50; P = .042). Conclusion This study suggests that the use of tegafur and doxifluridine is associated with an increased risk of hypertriglyceridemia similar to that with the use of capecitabine; in particular, fluoropyrimidine users with breast cancer may have a high risk of hypertriglyceridemia., (© 2021. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Objective: We previously reported a case where S-1, containing tegafur, gimeracil, and oteracil potassium, induced severe hypertriglyceridemia. After the case, we regularly monitored serum lipid levels and surprisingly observed an additional 4 cases within 1.5 years. We here report the treatment process., Case Report: At least 3 patients exhibited hyperlipidemia at baseline; in 2 of them, this was caused by previous fluoropyrimidine treatment. One patient experienced grade 4 hypertriglyceridemia, and the other 3 grade 3 hypertriglyceridemia. One patient developed temporary serum triglyceride elevation during the S-1 administration period, and the 3 experienced persistent elevation. The severity of serum triglyceride level worsened with increasing administration and peaked in cycles 2 - 6. Fenofibrate 80 - 160 mg/day and S-1 dose reduction were effective, with some significantly and others gradually decreasing to grade 0 - 1., Discussion: The summarized clinical features are as follows: (1) Severe hypertriglyceridemia tends to appear after several treatment cycles and worsens with increasing administration. (2) It tends to occur in patients with hyperlipidemia at baseline. (3) Patients previously affected with fluoropyrimidines-induced hypertriglyceridemia can experience S-1 symptoms. (4) In some cases, it might decrease after the S-1 suspension period. (5) Fibrates and S-1 dose reductions were effective. As the final fluoropyrimidine product is fluorouracil, its presence or that of its metabolizing enzymes and the genetic background of the patients might have affected the results. We should be aware of the risk of temporal and asymptomatic occurrence of S-1-induced hypertriglyceridemia for early detection with appropriate treatment.

Inhibitors of mammalian target of rapamycin function to downregulate cell growth and proliferation and have off-label use in pediatrics for vascular malformations. Hypertriglyceridemia is a known side effect of mammalian target of rapamycin (mTOR) inhibitors. Further studies to better understand the incidence and treatment of hypertriglyceridemia in infants and neonates are warranted., (© 2021 Wiley Periodicals LLC.)

We present a case of a one-month-old female patient with severe hypertriglyceridaemia as a side effect of treating an ulcerating infantile hemangioma with systemic propranolol. The remarkedly rapid increase in triglyceride returned to normal 96 hours after the discontinuation of the medication, and further follow-up revealed normalisation of the lipid profile. Further research is necessary to unveil the association of systemic propranolol with hypertriglyceridaemia., (© 2021 Australasian College of Dermatologists.)

Competing Interests: Competing interests: None declared.

Background & Aims: Schizophrenia is a serious long-term disorder in which the metabolic complications and abnormalities of the brain-derived neurotrophic factor (BDNF) can be found. In this study, we conducted a systematic review of the relationship between BDNF, metabolic syndrome (MetS) and its components in schizophrenic patients., Methods: Data were collected mainly from PubMed, Google Scholar, Scopus, and ProQuest databases. The keywords related to the BDNF, MetS, schizophrenia were searched. Two reviewers independently screened 1061 abstracts. And eventually, a total of 7 studies (6 observational and 1 interventional) was included in the systematic reviews., Results: Four of the 7 study ascertained statistically significant inverse relationship between serum BDNF levels and MetS in schizophrenic patients. While in the other two studies, there was no inverse relationship. In the last selected study, the researchers found a weak association between the Val66Met polymorphism in BDNF Gene and clozapine-induced MetS., Conclusion: Although this relationship could not be determined but BDNF levels appear to be reduced in schizophrenic patients with MetS and factors such as sex and antipsychotic class differentiation, sampling and methodology and episodes of illness could play a role in the results and outcomes., (Copyright © 2021. Published by Elsevier Ltd.)

Introduction: S-1, a compounding agent of tegafur, gimeracil, and oteracil potassium, is one of the most effective chemotherapeutic agents for colorectal cancer. In this case, following S-1 administration, we observed predominant elevation of serum triglyceride., Case Report: A 49-year-old man with stage IV transverse colon adenocarcinoma received S-1 + irinotecan + bevacizumab. At the end of the S-1 administration period in every course, his serum triglyceride level was found to be elevated. Finally, it reached grade 4, without any symptoms of acute pancreatitis in the fifth course, and fenofibrate 80 mg once a day was administered. Management & outcome: Interestingly, the elevation spontaneously normalized without any pharmacotherapy 14 days after S-1 withdrawal, and this elevation did not occur when S-1 was not administered. Further, fenofibrate administration attenuated the hypertriglyceridemia to grades 1-3, with no complications., Discussion: S-1 administration induced hypertriglyceridemia owing to the elevated serum triglyceride; however, a contrasting result was observed in the S-1 withdrawal period and during the S-1-cessation cycle. Since dietary intake was poorer during the S-1 administration period, it is considered that S-1 might have disturbed lipid metabolism. Further, we know that capecitabine, which is a prodrug of fluorouracil, also induces hypertriglyceridemia. As the end product of these medicines is fluorouracil, the presence of fluorouracil or its metabolizing enzymes, the genetic background of the patient might have affected the results. We have to be aware of the risk of asymptomatic and temporal occurrence of hypertriglyceridemia by S-1 administration for the early detection with appropriate pre-emptive treatment.

Acute pancreatitis (AP) is a medical emergency associated with significant morbidity and mortality. Hypertriglyceridaemia is a well-established but often neglected cause of AP, associated with delayed diagnosis and worse outcome than other more common causes of AP. Although oestrogen-induced hypertriglyceridaemia is known to be a rare cause of AP in females, it is much less well-recognised in biological males. We report the case of a 52-year-old transgender woman receiving high-dose oral oestrogen therapy who was admitted with abdominal pain and found to have AP caused by severe hypertriglyceridaemia. We describe the features underlying the management of AP caused by hypertriglyceridaemia and review the link between oral oestrogen, hypertriglyceridaemia and AP.Given the growth in transgender medicine leading to increasing use of therapeutic high-dose oestrogens in biological males for gender reassignment, it is important that clinicians are alert to the phenomenon of oestrogen-induced-hypertriglyceridaemia and its associated risk of AP., (© Royal College of Physicians 2021. All rights reserved.)

A 43-year-old male with type 2 diabetes, under treatment with 5 mg/day of dapagliflozin, was referred to our hospital with upper left abdominal pain and marked hypertriglyceridemia (triglycerides [TGs], 5,960 mg/dl). He was also on a low-carbohydrate diet that promoted ketosis under sodium glucose cotransporter 2 (SGLT2) inhibitor administration. Polyacrylamide gel electrophoresis revealed a remarkable increase in very-low-den-sity lipoprotein, a TG-rich lipoprotein particle synthesized in the liver using free fatty acids derived from adi-pose tissue. Although SGLT2 inhibitors generally improve the lipid profile, under certain conditions such as a low-carbohydrate diet, they may adversely exacerbate the lipid profile via ketosis., Competing Interests: No potential conflict of interest relevant to this article was reported.

Scilla species are used as medicinal plants and contain lanosterol-type triterpene glycosides. The phytochemical investigation of the bulbs of Scilla peruviana led to the isolation of 17 compounds, including three new rearranged pentacyclic-lanosterol glycosides (1-3) and two new homoisoflavanone glycosides (12 and 13). The structures of the undescribed compounds were determined by extensive spectroscopic analyses, including two-dimensional (2D) NMR. Among the triterpene glycosides, 2, 3, and 6 showed significant pancreatic lipase inhibitory activity in a concentration-dependent manner in vitro. The oral administration of scillascilloside D-2 (6) reduced serum triglyceride levels in a dose-dependent manner in soybean oil-loaded mice., Competing Interests: The authors declare no conflict of interest.