Comparison of Metabolic Changes after 6 Months of High-Carbohydrate Diet or High-Fat Diet with Low Dose Streptozotocin Injection in Rats.

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.

Bexarotene-induced hypothyroidism and dyslipidemia; a nation-wide study.

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.

Effects of Body Mass Index on Hypertriglyceridemia Associated with Oral Bexarotene Therapy: A Post Hoc Analysis of an Open-Label Comparative Clinical Study of Combined Bexarotene and Phototherapy Versus Bexarotene Monotherapy for Japanese Patients with Cutaneous T-Cell Lymphoma.

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/m2 and ≥23 kg/m2). RESULTS: No statistically significant association was observed between patients with BMI ≥23 kg/m2 and severe hypertriglyceridemia; however, there was a significant association between BMI ≥23 kg/m2 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.

5-Fluorouracil Induced Hypertriglyceridemia During the Colorectal Cancer Treatment in a Patient With Multifactorial Chylomicronemia Syndrome: A Case Report.

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.

Sirolimus-induced Hypertriglyceridemia Leads to Acute Pancreatitis and Diabetic Ketoacidosis Post Stem Cell Transplant for Sickle Cell Disease.

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.

5-Fluorouracil-associated severe hypertriglyceridaemia with positive rechallenge.

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.

Risk factors for abnormal glucose metabolism during antipsychotic treatment: A prospective cohort study.

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.

Indications for omega-3 fatty acid supplementation in prevention of cardiovascular disease: From fish to pharmaceuticals.

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.

The effects of ART on the dynamics of lipid profiles in Chinese Han HIV-infected patients: comparison between NRTI/NNRTI and NRTI/INSTI.

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.

APOC3 inhibition with volanesorsen reduces hepatic steatosis in patients with severe hypertriglyceridemia.

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.

Propofol-Associated Hypertriglyceridemia in Adults With Acute Respiratory Distress Syndrome on Extracorporeal Membrane Oxygenation.

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.

Phase I trial of intravenous fenretinide (4-HPR) plus safingol in advanced malignancies.

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/m2 24-h infusion on Day 1 of a 21-day cycle followed by 900 mg/m2/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/m2, 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).

Impact of body mass index on the severity of bexarotene-associated hypertriglyceridemia: A post hoc analysis of an open-labeled clinical study of combined bexarotene and phototherapy in Japanese patients with cutaneous T-cell lymphoma.

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/m2 group) and overweight and obese (BMI ≥25 kg/m2 group) patients. The overall incidence of hypertriglyceridemia was 81.3% (13/16) in the BMI <25 kg/m2 group and 88.9% (8/9) in the BMI ≥25 kg/m2 group. The incidence of grade ≥3 hypertriglyceridemia (≥500 mg/dL) was 7.7% (1/13) in the BMI <25 kg/m2 group and 7/8 (87.5%) in the BMI ≥25 kg/m2 group (P < 0.001). Consequently, dose reduction in the BMI ≥25 kg/m2 group was larger than that in the BMI <25 kg/m2 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/m2 , the sensitivity and specificity for identifying grade ≥3 hypertriglyceridemia were 0.875 and 0.882, respectively. The present findings suggest that BMI ≥25 kg/m2 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.

Tocilizumab-related hypertriglyceridemia is independent of key molecules regulating lipid metabolism.

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.

Incidence and risk factors of hypertriglyceridemia in males with human immunodeficiency virus who are treated with combination antiretroviral therapy: a retrospective cohort study.

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/m2 (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.

Prevalence of adverse events varies with the different oral isotretinoin brands in acne treatment: a retrospective observational study.

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.

Acute pancreatitis secondary to tamoxifen-associated hypertriglyceridemia: A clinical update.

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.

Triglyceride Concentrations and Their Relationship to Sedation Choice and Outcomes in Mechanically Ventilated Patients Receiving Propofol.

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.