Type 2 diabetes patients requiring empagliflozin in Southeast of Iran: Frequency and guideline adherence (2022–2023) / Pacientes con diabetes tipo 2 que requieren empagliflozina en el sureste de Irán: frecuencia y cumplimiento de las directrices (2022-2023)

Introduction: Empagliflozin plays a beneficial role in individuals with type 2 diabetes at high risk of cardiovascular complications. This study aimed to assess the prevalence of individuals with type 2 diabetes who required empagliflozin based on clinical guidelines between the years 2022 and 2023. Material and methods: This study was a descriptive-analytical cross-sectional study conducted on a target population of patients with type 2 diabetes. Patient data, including demographic characteristics, smoking status, hypertension, hyperlipidemia, renal insufficiency, retinopathy, and proteinuria, were collected. The indication for prescribing empagliflozin was determined based on the risk of cardiovascular complications. Results: A total of 398 individuals with type 2 diabetes with a mean age of 58.4 years were examined. Overall, 87.4% of the patients had an indication for empagliflozin prescription. The indication for empagliflozin prescription was significantly higher in men, individuals with hyperlipidemia, those over 55 years of age, obese individuals, and smokers. The mean age, body mass index, and triglyceride levels were higher in candidates for empagliflozin prescription. Male candidates for empagliflozin had significantly higher rates of smoking and systolic blood pressure compared to females. Conclusions: The findings of this study demonstrated that a significant percentage of individuals with type 2 diabetes had an indication for empagliflozin prescription based on clinical and laboratory criteria. (AU)

Introducción: La empagliflozina tiene un papel beneficioso en las personas con diabetes tipo 2 con alto riesgo de complicaciones cardiovasculares. Este estudio tuvo como objetivo evaluar la prevalencia de pacientes con este padecimiento que requerían empagliflozina según las guías clínicas entre los años 2022 y 2023. Material y métodos: Se trata de un estudio transversal descriptivo-analítico realizado en una población objetivo de personas con diabetes tipo 2. Se recogieron los datos de los pacientes, incluyendo las características demográficas, el hábito tabáquico, la hipertensión, la hiperlipidemia, la insuficiencia renal, la retinopatía y la proteinuria. La indicación para prescribir empagliflozina se determinó en función del riesgo de complicaciones cardiovasculares. Resultados: Se examinaron un total de 398 individuos con diabetes tipo 2 con una edad media de 58,4 años. En general, 87,4% de estos tenía una indicación para la prescripción de empagliflozina, la cual fue significativamente mayor en los hombres, aquellos con hiperlipidemia, obesidad, los mayores de 55 años y los fumadores. La edad media, el índice de masa corporal y los niveles de triglicéridos fueron mayores en los candidatos a la prescripción de este medicamento. Los candidatos masculinos a este fármaco tenían tasas significativamente más altas de tabaquismo y presión arterial sistólica, en comparación con las mujeres. Conclusiones: Los resultados de este estudio demostraron que un porcentaje significativo de personas con diabetes tipo 2 tenía una indicación para la prescripción de empagliflozina según los criterios clínicos y de laboratorio. (AU)

La importancia de la genética en el estudio de la hipertrigliceridemia / The importance of genetics in the study of hypertriglyceridemia

La hipertrigliceridemia engloba un conjunto de trastornos lipídicos comunes en la práctica clínica, generalmente definidos como una concentración superior a 150mg/dL en ayunas. Existen diversas clasificaciones de la gravedad de la hipertrigliceridemia en función de sus valores séricos, considerándose por norma general moderada cuando los niveles son inferiores a 500mg/dL y severa cuando son mayores de 1.000mg/dL. Su importancia radica en su asociación con otras alteraciones del perfil lipídico, contribuyendo al aumento del riesgo cardiovascular y de pancreatitis aguda, fundamentalmente con concentraciones superiores a 500mg/dL.(AU)

Hypertriglyceridemia encompasses a set of lipid disorders common in clinical practice, generally defined as a fasting concentration above 150mg/dL. There are various classifications of the severity of hypertriglyceridaemia based on serum values, with levels generally considered moderate when below 500mg/dL and severe when above 1000mg/dL. Its importance lies in its association with other alterations in the lipid profile, contributing to increased cardiovascular risk and increased risk of acute pancreatitis, mainly with concentrations above 500mg/dL.(AU)

The association between rapid growth and lipid profile: a systematic review and meta-analysis.

Background & aims: Metabolic disease prevalence has increased in many regions, and is closely associated with dyslipidemia. Rapid growth refers to a significant increase in growth velocity above the normal range, particularly in infants and children, and is highly prevalent in congenital deficiency infants. But the association between dyslipidemia and rapid growth remains controversial. We performed this meta-analysis to investigate the lipid profile in subjects with and without postnatal rapid growth, and to determine what are the confounding factors. Methods: Medline, EMBASE, China National Knowledge Infrastructure Chinese citation database and WANFANG database were searched (last search in May 2021). Publication bias was examined by constructing funnel plots, Egger's linear regression test and Begg's rank correlation test. Results: The fixed effects model would be adopted if I2 is less than 25%, otherwise random effects model would be used. There were 11 articles involved with a total of 1148 participants (539 boys and 609 girls, mean age=7.4 years). Pooled analysis found that rapid growth was negatively associated with high-density lipoprotein cholesterol (HDL-C) (weighted mean difference=-0.068, 95%CI [-0.117, -0.020]), but not associated with triglycerides (TG), total cholesterol (TC), or low-density lipoprotein cholesterol (LDL-C). Stratified analysis suggested that increased TG were found in rapid growth subjects from developing countries. Higher TC was observed for rapid growth participants of follow-up age ≤8 years old, rapid growth duration ≤2 years, preterm, low birth weight, and from developing countries. But decreased TC was observed in small for gestational age (SGA) rapid growth subjects. Decreased LDL-C had been documented in rapid growth subjects of follow-up age >8 years old, from developed countries, and SGA. At last, rapid growth groups had lower HDL-C in infants of rapid growth duration >2 years and from developed countries. Conclusion: Rapid growth is associated with lipid profiles, particularly during early childhood, and this relationship is influenced by factors such as the duration of growth, the level of national development, and birth weight. These findings are significant for the development of strategies to prevent metabolic diseases.This review was registered in PROSPERO International Prospective Register of Systematic Reviews (www.crd.york.ac.uk/prospero/) with the registration number CRD42020154240.

Retrospective analysis of predictive factors for AVF dysfunction in patients undergoing MHD.

To construct an early clinical prediction model for AVF dysfunction in patients undergoing Maintenance Hemodialysis (MHD) and perform internal and external verifications. We retrospectively examined clinical data from 150 patients diagnosed with MHD at Hefei Third People's Hospital from January 2014 to June 2023. Depending on arteriovenous fistula (AVF) functionality, patients were categorized into dysfunctional (n = 62) and functional (n = 88) cohorts. Using the least absolute shrinkage and selection operator(LASSO) regression model, variables potentially influencing AVF functionality were filtered using selected variables that underwent multifactorial logistic regression analysis. The Nomogram model was constructed using the R software, and the Area Under Curve(AUC) value was calculated. The model's accuracy was appraised through the calibration curve and Hosmer-Lemeshow test, with the model undergoing internal validation using the bootstrap method. There were 11 factors exhibiting differences between the group of patients with AVF dysfunction and the group with normal AVF function, including age, sex, course of renal failure, diabetes, hyperlipidemia, Platelet count (PLT), Calcium (Ca), Phosphorus, D-dimer (D-D), Fibrinogen (Fib), and Anastomotic width. These identified factors are included as candidate predictive variables in the LASSO regression analysis. LASSO regression identified age, sex, diabetes, hyperlipidemia, anastomotic diameter, blood phosphorus, and serum D-D levels as 7 predictive factors. Unconditional binary logistic regression analysis revealed that advanced age (OR = 4.358, 95% CI: 1.454-13.062), diabetes (OR = 4.158, 95% CI: 1.243-13.907), hyperlipidemia (OR = 3.651, 95% CI: 1.066-12.499), D-D (OR = 1.311, 95% CI: 1.063-1.616), and hyperphosphatemia (OR = 4.986, 95% CI: 2.513-9.892) emerged as independent risk factors for AVF dysfunction in MHD patients. The AUC of the predictive model was 0.934 (95% CI: 0.897-0.971). The Hosmer-Lemeshow test showed high consistency between the model's predictive results and actual clinical observations (χ2 = 1.553, P = .092). Internal validation revealed an AUC of 0.911 (95% CI: 0.866-0.956), with the Calibration calibration curve nearing the ideal curve. Advanced age, coexisting diabetes, hyperlipidemia, blood D-D levels, and hyperphosphatemia are independent risk factors for AVF dysfunction in patients undergoing MHD.

Effects of moxibustion with wheat-grain size cone at "Zusanli" (ST 36) on vascular injury and oxidative stress in high-fat diet rats through mTOR/HIF-1α/VEGF signaling pathway. / 基于mTOR/HIF-1α/VEGF信号通路探讨麦粒灸"足三里"å¯¹é«˜è„‚é¥®é£Ÿå¤§é¼ è¡€ç®¡æŸä¼¤å’Œæ°§åŒ–åº”æ¿€çš„å½±å“.

OBJECTIVES: To explore the effect mechanism of moxibustion with wheat-grain size cone at "Zusanli" (ST 36) on vascular injury and oxidative stress in hyperlipidemia through mammalian target of rapamycin (mTOR)/hypoxia inducible factor-1α (HIF-1α)/vascular endothelial growth factor (VEGF) signaling pathway. METHODS: Forty healthy male SD rats with SPF grade were randomly divided into a normal group, a model group, a moxibustion group, and an inhibitor group, with 10 rats in each one. The hyperlipidemia model was established by feeding a high-fat diet for 8 weeks in rats of the model group, the moxibustion group and the inhibitor group. The moxibustion with wheat-grain size cone was delivered at bilateral "Zusanli" (ST 36) of each rat in the moxibustion group and the inhibitor group, with 3 cones on each acupoint in each intervention, once daily for 4 weeks. In the inhibitor group, before each intervention with moxibustion, rapamycin solution was injected intraperitoneally, 2.0 mg/kg. After modeling and intervention, using ELISA, the levels of total cholesterol (TC), triglyceride (TG), high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C) in the serum of rats were determined. After intervention, with HE staining and oil red O staining adopted, the abdominal aortic morphology and peripheral lipid deposition were observed. Separately, using WST-1, TBA and micro-plate method, the superoxide dismutase (SOD) activity and the levels of malondialdehyde (MDA) and nitric oxide (NO) in the serum were detected. The protein expression of mTOR, HIF-1α and VEGF in abdominal aorta were measured by Western blot method. RESULTS: Compared with those in the normal group, the levels of TC, TG and LDL-C increased (P<0.01) and HDL-C decreased (P<0.01) in the serum of the rats in the model group, the moxibustion group and the inhibitor group after model establishment. When compared with the normal group after intervention, in the model group, the serum levels of TC, TG, LDL-C and MDA increased (P<0.01), HDL-C level, SOD activity and NO level were reduced (P<0.01); the cell structure of the abdominal arota was abnormal, the peripheral lipids deposited seriously; and the protein expression of mTOR, HIF-1α and VEGF of abdominal aorta was elevated (P<0.01, P<0.05). In comparison with the model group, the levels of TC, TG, LDL-C and MDA were reduced (P<0.01), HDL-C levels, SOD activities and NO levels elevated (P<0.01, P<0.05), as well as the protein expression of mTOR, HIF-1α and VEGF of abdominal aorta (P<0.01, P<0.05) in the moxibustion group and the inhibitor group; besides, the vascular structure was ameliorated and the lipid deposition reduced in the moxibustion group, while, the vascular structure was still abnormal and the lipid deposition declined in the inhibitor group. When compared with the inhibitor group, the serum SOD activity and NO level increased (P<0.05) and MDA decreased (P<0.05); and the protein expression of mTOR, HIF-1α and VEGF of abdominal aorta was elevated (P<0.01, P<0.05) in the moxibustion group. CONCLUSIONS: The vascular injury due to hyperlipidemia is repaired by moxibustion with wheat-grain size cone at "Zusanli" (ST 36) through ameliorating oxidative stress, which is associated potentially with the modulation of mTOR/HIF-1α/VEGF signaling pathway.

[Research on mechanism of hypolipidemic effect of Massa Medicata Fermentata based on metabolomics].

This paper aims to study the therapeutic effect of Massa Medicata Fermentata on hyperlipidemia model rats and investigate its mechanism of hypolipidemic effect with the help of non-targeted metabolomics. The mixed hyperlipidemia model rats were constructed by giving high-fat chow. After successful modeling, the rats were divided into the model group, pravastatin sodium group(4.4 mg·kg~(-1)), lipotropic group(0.1 g·kg~(-1)), high-dose group(2.4 g·kg~(-1)), medium-dose group(1.2 g·kg~(-1)), and low-dose group(0.6 g·kg~(-1)) of Massa Medicata Fermentata, and they were administered for four weeks once daily. An equal volume of ultrapure water was given to the blank group and model group. Serum lipid level and liver hematoxylin-eosin(HE) staining were used as indicators to estimate the intervention effect of Massa Medicata Fermentata on mixed hyperlipidemia, and the changes in metabolites in plasma of mixed hyperlipidemia model rats were analyzed by non-targeted metabolomics. The mechanism of the hypolipidemic effect of Massa Medicata Fermentata was analyzed through metabolite pathway enrichment. The results showed that compared with the model group, the Massa Medicata Fermentata administration group, especially the high-dose group, could significantly reduce the content of total cholesterol(TC), triglyceride(TG), and low-density lipoprotein cholesterol(LDL-c)(P<0.05 or P<0.01), and liver HE staining revealed that the number of adipocytes in the high-dose group was reduced to some extent. The potential biomarkers obtained by non-targeted metabolomics screening included glycerol 3-phosphate, sphingomyelin, sphingosine 1-phosphate, and deoxyuridine, which were mainly involved in the sphingolipid metabolism process, glycerophospholipid metabolism process, glycerol ester metabolism pathway, and pyrimidine metabolism pathway, totaling four possible metabolic pathways related to lipid metabolism. This study provides a reference for an in-depth investigation of the hypolipidemic mechanism of Massa Medicata Fermentata, which is of great significance for further promoting the clinical application of Massa Medicata Fermentata and increasing the indications.

Effects of LP533401 on vascular and bone calcification in hyperlipidemic mice.

Peripheral serotonin levels are associated with cardiovascular disease risk. We previously found that serum serotonin levels are higher in hyperlipidemic mice than wild-type mice. Evidence also suggests that serotonin regulates biomineralization, in that serotonin treatment augments TNF-a-induced matrix calcification of aortic valve interstitial cells and that a selective inhibitor of peripheral serotonin, LP533401, rescues bone loss induced by ovariectomy in mice. Thus, in the present study, we examined the effects of LP533401 on both skeletal bone mineral density (BMD) and aortic calcification in both young and older hyperlipidemic mice susceptible to calcific atherosclerosis and bone loss. By serial in vivo microCT imaging, we assessed BMD and aortic calcification of Apoe-/- mice fed an atherogenic (high cholesterol) diet alone or mixed with LP533401. Results show that in the young mice, LP533401 blunted skeletal bone loss in lumbar vertebrae but not in femurs. LP533401 also blunted the initial development of aortic calcification but not its progression. Echocardiographic analysis showed that LP533401 blunted both hyperlipidemia-induced cardiac hypertrophy and left ventricular dysfunction. In the older mice, LP533401 increased the BMD of lumbar vertebrae but not of femurs. The aortic calcification progressed in both controls and LP533401-treated mice, but, at post-treatment, LP533401-treated mice had significantly less aortic calcification than the controls. These findings suggest that LP533401 mitigates adverse effects of hyperlipidemia on skeletal and vascular tissues in site- and stage-dependent manners.

Significant but partial lipoprotein lipase functional loss caused by a novel occurrence of rare LPL biallelic variants.

BACKGROUND: Lipoprotein lipase (LPL) plays a crucial role in triglyceride hydrolysis. Rare biallelic variants in the LPL gene leading to complete or near-complete loss of function cause autosomal recessive familial chylomicronemia syndrome. However, rare biallelic LPL variants resulting in significant but partial loss of function are rarely documented. This study reports a novel occurrence of such rare biallelic LPL variants in a Chinese patient with hypertriglyceridemia-induced acute pancreatitis (HTG-AP) during pregnancy and provides an in-depth functional characterization. METHODS: The complete coding sequences and adjacent intronic regions of the LPL, APOC2, APOA5, LMF1, and GPIHBP1 genes were analyzed by Sanger sequencing. The aim was to identify rare variants, including nonsense, frameshift, missense, small in-frame deletions or insertions, and canonical splice site mutations. The functional impact of identified LPL missense variants on protein expression, secretion, and activity was assessed in HEK293T cells through single and co-transfection experiments, with and without heparin treatment. RESULTS: Two rare LPL missense variants were identified in the patient: the previously reported c.809G > A (p.Arg270His) and a novel c.331G > C (p.Val111Leu). Genetic testing confirmed these variants were inherited biallelically. Functional analysis showed that the p.Arg270His variant resulted in a near-complete loss of LPL function due to effects on protein synthesis/stability, secretion, and enzymatic activity. In contrast, the p.Val111Leu variant retained approximately 32.3% of wild-type activity, without impacting protein synthesis, stability, or secretion. Co-transfection experiments indicated a combined activity level of 20.7%, suggesting no dominant negative interaction between the variants. The patient's post-heparin plasma LPL activity was about 35% of control levels. CONCLUSIONS: This study presents a novel case of partial but significant loss-of-function biallelic LPL variants in a patient with HTG-AP during pregnancy. Our findings enhance the understanding of the nuanced relationship between LPL genotypes and clinical phenotypes, highlighting the importance of residual LPL function in disease manifestation and severity. Additionally, our study underscores the challenges in classifying partial loss-of-function variants in classical Mendelian disease genes according to the American College of Medical Genetics and Genomics (ACMG)'s variant classification guidelines.

The effect of hyperlipidemia and body fat distribution on subclinical left ventricular function in obesity: a cardiovascular magnetic resonance study.

BACKGROUND: Obesity is often associated with multiple comorbidities. However, whether obese subjects with hyperlipidemia in the absence of other complications have worse cardiac indices than metabolically healthy obese subjects is unclear. Therefore, we aimed to determine the effect of hyperlipidemia on subclinical left ventricular (LV) function in obesity and to evaluate the association of cardiac parameters with body fat distribution. MATERIALS AND METHODS: Ninety-two adults were recruited and divided into 3 groups: obesity with hyperlipidemia (n = 24, 14 males), obesity without hyperlipidemia (n = 25, 13 males), and c ntrols (n = 43, 25 males). LV strain parameters (peak strain (PS), peak diastolic strain rate (PDSR), peak systolic strain rate) derived from cardiovascular magnetic resonance tissue tracking were measured and compared. Dual-energy X-ray absorptiometer was used to measure body fat distribution. Correlations of hyperlipidemia and body fat distribution with LV strain were assessed by multivariable linear regression. RESULTS: Obese individuals with preserved LV ejection fraction showed lower global LV longitudinal, circumferential, and radial PS and longitudinal and circumferential PDSR than controls (all P < 0.05). Among obese patients, those with hyperlipidemia had lower longitudinal PS and PDSR and circumferential PDSR than those without hyperlipidemia (- 12.8 ± 2.9% vs. - 14.2 ± 2.7%, 0.8 ± 0.1 s-1 vs. 0.9 ± 0.3 s-1, 1.2 ± 0.2 s-1 vs. 1.4 ± 0.2 s-1; all P < 0.05). Multivariable linear regression demonstrated that hyperlipidemia was independently associated with circumferential PDSR (ß = - 0.477, P < 0.05) in obesity after controlling for growth differences, other cardiovascular risk factors, and central fat distribution. In addition, android fat had an independently negative relationship with longitudinal and radial PS (ß = - 0.486 and ß = - 0.408, respectively; all P < 0.05); and visceral fat was negatively associated with longitudinal PDSR (ß = - 0.563, P < 0.05). Differently, gynoid fat was positively correlated with circumferential PS and PDSR and radial PDSR (ß = 0.490, ß = 0.481, and ß = 0.413, respectively; all P < 0.05). CONCLUSION: Hyperlipidemia is independently associated with subclinical LV diastolic dysfunction in obesity. Central fat distribution (android and visceral fat) has a negative association, while peripheral fat distribution (gynoid fat) has a positive association on subclinical LV function. These results suggest that appropriate management of hyperlipidemia may be beneficial for obese patients, and that the differentiation of fat distribution in different regions may facilitate the precise management of obese patients. Clinical trials registration Effect of lifestyle intervention on metabolism of obese patients based on smart phone software (ChiCTR1900026476).

A Comparative Analysis between Whole Chinese Yam and Peeled Chinese Yam: Their Hypolipidemic Effects via Modulation of Gut Microbiome in High-Fat Diet-Fed Mice.

Chinese yam is a "medicine food homology" food with medical properties, but little is known about its health benefits on hyperlipidemia. Furthermore, the effect of peeling processing on the efficacy of Chinese yam is still unclear. In this study, the improvement effects of whole Chinese yam (WY) and peeled Chinese yam (PY) on high-fat-diet (HFD)-induced hyperlipidemic mice were explored by evaluating the changes in physiological, biochemical, and histological parameters, and their modulatory effects on gut microbiota were further illustrated. The results show that both WY and PY could significantly attenuate the HFD-induced obesity phenotype, accompanied by the mitigative effect on epididymis adipose damage and hepatic tissue injury. Except for the ameliorative effect on TG, PY retained the beneficial effects of WY on hyperlipemia. Furthermore, 16S rRNA sequencing revealed that WY and PY reshaped the gut microbiota composition, especially the bloom of several beneficial bacterial strains (Akkermansia, Bifidobacterium, and Faecalibaculum) and the reduction in some HFD-dependent taxa (Mucispirillum, Coriobacteriaceae_UCG-002, and Candidatus_Saccharimonas). PICRUSt analysis showed that WY and PY could significantly regulate lipid transport and metabolism-related pathways. These findings suggest that Chinese yam can alleviate hyperlipidemia via the modulation of the gut microbiome, and peeling treatment had less of an effect on the lipid-lowering efficacy of yam.

Microbial Fermentation Enhances the Effect of Black Tea on Hyperlipidemia by Mediating Bile Acid Metabolism and Remodeling Intestinal Microbes.

Black tea (BT), the most consumed tea worldwide, can alleviate hyperlipidemia which is a serious threat to human health. However, the quality of summer BT is poor. It was improved by microbial fermentation in a previous study, but whether it affects hypolipidemic activity is unknown. Therefore, we compared the hypolipidemic activity of BT and microbially fermented black tea (EFT). The results demonstrated that BT inhibited weight gain and improved lipid and total bile acid (TBA) levels, and microbial fermentation reinforced this activity. Mechanistically, both BT and EFT mediate bile acid circulation to relieve hyperlipidemia. In addition, BT and EFT improve dyslipidemia by modifying the gut microbiota. Specifically, the increase in Lactobacillus johnsonii by BT, and the increase in Mucispirillum and Colidextribacter by EFT may also be potential causes for alleviation of hyperlipidemia. In summary, we demonstrated that microbial fermentation strengthened the hypolipidemic activity of BT and increased the added value of BT.

Pediatric hyperlipidemia.

The leading cause of mortality worldwide is atherosclerotic cardiovascular disease. Atherosclerotic plaques are well known to originate early in the childhood. Identifying hyperlipidemia in early childhood creates an opportunity to prevent major cardiovascular events in adults. Children with identified risk factors are at an increased risk of developing cardiovascular incidents in later life. This article emphasizes the diagnosis and management of pediatric hyperlipidemia with reference to the recent guidelines. In terms of etiology pediatric hyperlipidemia are divided into primary and secondary causes. The mainstay of management includes high-risk target screening, early risk factor identification and lifestyle modifications in vulnerable population. Drug therapy is recommended in primary hyperlipidemia and in children with no response to lifestyle changes.

Complicated Treatment Course of Severe Asymptomatic Hypertriglyceridemia: A Case Report and Literature Review.

BACKGROUND Close observation, statins, fibrate treatment, and lifestyle changes can safely manage asymptomatic individuals with severe hypertriglyceridemia (HTG) and minimal risk of symptom development. However, the risk of medication-induced liver injury in patients taking statin-fibrate makes management more challenging, and may require hospital admission and close monitoring with follow-up. CASE REPORT We present a rare case of a 43-year-old man with asymptomatic severe HTG exceeding 11.370 mg/dL with mixed hyperlipidemia, managed initially with high-intensity statins and fibrate. However, due to the concurrent use of statin and fibrates, the patient subsequently developed an acute liver injury. Hence, the oral medications had to be stopped, and the patient was admitted to the hospital for an insulin drip. Even during the hospital course, the patient's triglyceride (TG) levels showed resistance to the recommended dose of insulin and he required a higher insulin dose. He was discharged on fenofibrate and subcutaneous insulin to keep the TG level under 500. Fibrate was stopped, and high-intensity statin was used as primary prevention with lifestyle modifications. CONCLUSIONS This instance highlights the necessity of increased cognizance and cooperative endeavors in handling severe asymptomatic HTG. Our results highlight the significance of further research into the management of severe asymptomatic HTG in cases of injury to the liver. This work adds essential knowledge to the ongoing discussion about managing a rare case complicated by acute liver injury.

Effect of oesophagectomy on lipid profiles in patients with oesophageal cancer combined with hyperlipidaemia: a retrospective study.

BACKGROUND: Surgery is widely regarded as a pivotal therapeutic approach for treating oesophageal cancer, and clinical observations have revealed that many oesophageal cancer patients also present with concomitant hyperlipidaemia. It is surprising that few studies have been performed to determine how blood lipid levels are affected by oesophageal cancer resection. This research was designed to assess the influence of oesophageal cancer resection on lipid profiles among individuals diagnosed with both oesophageal cancer and hyperlipidaemia. METHODS: A retrospective analysis was carried out on 110 patients with hyperlipidaemia and oesophageal cancer who had undergone oesophagectomy at the 900th Hospital of the Joint Logistics Support Force of the Chinese People's Liberation Army. Preoperative and postoperative serological data were collected at seven-, thirty-, sixty-day-, and one-year-long intervals. Changes in lipid levels were compared, the remission of various types of hyperlipidaemia was statistically assessed, and Pearson correlation was used to analyse the association between lipid changes and preoperative body weight. The research sought to assess the reduction in body weight and the proportion of body weight lost one year following surgery. RESULTS: Noteworthy decreases were observed in total cholesterol (TC), triglyceride (TG), and low-density lipoprotein (LDL) levels, with TC decreasing from 6.20 mmol/L to 5.20 mmol/L, TG decreasing from 1.40 mmol/L to 1.20 mmol/L, and LDL decreasing from 4.50 mmol/L to 3.30 mmol/L. Conversely, there was a notable increase in high-density lipoprotein (HDL) levels, which increased from 1.20 mmol/L to 1.40 mmol/L (P < 0.05) compared to the preoperative levels. Notably, the remission rates for mixed hyperlipidaemia (60.9%) and high cholesterol (60.0%) were considerably greater than those for high triglycerides (16.2%). Alterations in TC at one year postoperatively correlated with preoperative weight and weight loss (r = 0.315, -0.216); changes in TG correlated with preoperative weight, percentage of total weight loss (TWL%), and weight reduction (r = -0.295, -0.246, 0.320); and changes in LDL correlated with preoperative weight, TWL%, and weight loss (r = 0.251, 0.186, and -0.207). Changes in non-high-density lipoprotein(non-HDL) were linked to preoperative weight (r = 0.300), and changes in TG/HDL were correlated with preoperative weight and TWL% (r = -0.424, -0.251). CONCLUSIONS: Oesophagectomy significantly improved lipid profiles in oesophageal cancer patients, potentially leading to a reduction in overall cardiovascular risk.

Discovery of Highly Potent Solute Carrier 13 Member 5 (SLC13A5) Inhibitors for the Treatment of Hyperlipidemia.

In the face of escalating metabolic disease prevalence, largely driven by modern lifestyle factors, this study addresses the critical need for novel therapeutic approaches. We have identified the sodium-coupled citrate transporter (NaCT or SLC13A5) as a target for intervention. Utilizing rational drug design, we developed a new class of SLC13A5 inhibitors, anchored by the hydroxysuccinic acid scaffold, refining the structure of PF-06649298. Among these, LBA-3 emerged as a standout compound, exhibiting remarkable potency with an IC50 value of 67 nM, significantly improving upon PF-06649298. In vitro assays demonstrated LBA-3's efficacy in reducing triglyceride levels in OPA-induced HepG2 cells. Moreover, LBA-3 displayed superior pharmacokinetic properties and effectively lowered triglyceride and total cholesterol levels in diverse mouse models (PCN-stimulated and starvation-induced), without detectable toxicity. These findings not only spotlight LBA-3 as a promising candidate for hyperlipidemia treatment but also exemplify the potential of targeted molecular design in advancing metabolic disorder therapeutics.

A Murine Model of Hyperlipidemia-Induced Heart Failure with Preserved Ejection Fraction.

The pathophysiology of heart failure with preserved ejection fraction (HFpEF) driven by lipotoxicity is incompletely understood. Given the urgent need for animal models that accurately mimic cardio-metabolic HFpEF, a hyperlipidemia-induced murine model was developed by reverse engineering phenotypes seen in HFpEF patients. This model aimed to investigate HFpEF, focusing on the interplay between lipotoxicity and metabolic syndrome. Hyperlipidemia was induced in wild-type (WT) mice on a 129J strain background through bi-weekly intraperitoneal injections of poloxamer-407 (P-407), a block co-polymer that blocks lipoprotein lipase, combined with a single intravenous injection of adeno-associated virus 9-cardiac troponin T-low-density lipoprotein receptor (AAV9-cTnT-LDLR). Extensive assessments were conducted between 4 and 8 weeks post-treatment, including echocardiography, blood pressure recording, whole-body plethysmography, echocardiography (ECG) telemetry, activity wheel monitoring (AWM), and biochemical and histological analyses. The LDLR/P-407 mice exhibited distinctive features at four weeks, including diastolic dysfunction, preserved ejection fraction, and increased left ventricular wall thickness. Notably, blood pressure and renal function remained within normal ranges. Additionally, ECG and AWM revealed heart blocks and reduced activity, respectively. Diastolic function deteriorated at eight weeks, accompanied by a significant decline in respiratory rates. Further investigation into the double treatment model revealed elevated fibrosis, wet/dry lung ratios, and heart weight/body weight ratios. The LDLR/P-407 mice exhibited xanthelasmas, ascites, and cardiac ischemia. Interestingly, sudden deaths occurred between 6 and 12 weeks post-treatment. The murine HFpEF model offers a valuable and promising experimental resource for elucidating the intricacies of metabolic syndrome contributing to diastolic dysfunction within the context of lipotoxicity-mediated HFpEF.

Comorbidities affecting re-admission and survival in COVID-19: Application of joint frailty model.

BACKGROUND: One of the common concerns of healthcare systems is the potential for re-admission of COVID-19 patients. In addition to adding costs to the healthcare system, re-admissions also endanger patient safety. Recognizing the factors that influence re-admission, can help provide appropriate and optimal health care. The aim of this study was to assess comorbidities that affect re-admission and survival in COVID-19 patients using a joint frailty model. METHODS: This historical cohort study was done using data of patients with COVID-19 who were re-hospitalized more than twice in a referral hospital in North of Iran. We used the joint frailty model to investigate prognostic factors of survival and recurrence, simultaneously using R version 3.5.1 (library "frailtypack"). P-values less than 0.05 were considered as statistically significant. RESULTS: A total of 112 patients with mean (SD) age of 63.76 (14.58) years old were recruited into the study. Forty-eight (42.9%) patients died in which 53.83% of them were re-admitted for a second time. Using adjusted joint model, the hazard of re-admission increased with cancer (Hazard ratio (HR) = 1.92) and hyperlipidemia (HR = 1.22). Furthermore, the hazard of death increased with hyperlipidemia (HR = 4.05) followed by age (HR = 1.76) and cancer (HR = 1.64). It Also decreased with lung disease (HR = 0.11), hypothyroidism (HR = 0.32), and hypertension (HR = 0.97). CONCLUSION: Considering the correlation between re-admission and mortality in the joint frailty model, malignancy and hyperlipidemia increased the risk of both re-admission and mortality. Moreover, lung disease probably due to the use of corticosteroids, was a protective factor against both mortality and re-admission.

Factors associated with post-hospitalization dialysis dependence in ECMO patients who required continuous renal replacement therapy.

OBJECTIVE: This single center retrospective study aimed to describe the variables associated with outpatient dialysis dependence in extracorporeal membrane oxygenation (ECMO) patients who needed continuous renal replacement therapy (CRRT) for acute kidney injury (AKI) during their hospitalization. METHODS: Retrospective study of patients who required ECMO-CRRT. RESULTS: Between the years of 2016 and 2022, 202 patients required ECMO-CRRT. One hundred and six patients (52.5%) survived their hospitalization and were followed up for a median of 391 [133, 1005] days. Eighty-one patients (76.5%) recovered kidney function and were dialysis-free before hospital discharge. Twenty-five patients (23.5%) were hemodialysis-dependent after hospitalization. On multivariate regression analysis, hyperlipidemia (odds ratio, OR 6.08 [1.67-22]) and CRRT duration (OR 1.09 [1.03-1.15]) were associated with the need for dialysis post-hospitalization. In this group, 16 patients eventually became dialysis-free, after a median of 49 [34.7, 78.5] days. These patients had a higher median baseline glomerular filtration rate (GFR) compared to those who never recovered renal function (93 mL/min/1.73 m2 [82.4, 104.3] vs. 63.8 mL/min/1.73 m2 [37.9, 83], p = .009). Their follow-up GFR was lower compared to those who recovered renal function before hospital discharge; (87 mL/min/1.73 m2 [68.2, 98.9] vs. 99 mL/min/1.73 m2 [79, 118], p = .07). CONCLUSIONS: AKI requiring CRRT was associated with high mortality in patients receiving ECMO. Nonetheless, most ECMO survivors became dialysis-free before hospital discharge. Variables associated with the need for outpatient dialysis included hyperlipidemia and prolonged need for CRRT during hospitalization.

Novel anthropometric indicators of visceral obesity predict the severity of hyperlipidemic acute pancreatitis.

BACKGROUND: Obesity substantially contributes to the onset of acute pancreatitis (AP) and influences its progression to severe AP. Although body mass index (BMI) is a widely used anthropometric parameter, it fails to delineate the distribution pattern of adipose tissue. To circumvent this shortcoming, the predictive efficacies of novel anthropometric indicators of visceral obesity, such as lipid accumulation products (LAP), cardiometabolic index (CMI), body roundness index (BRI), visceral adiposity index (VAI), A Body Shape Index (ABSI), and Chinese visceral adiposity index (CVAI) were examined to assess the severity of AP. METHOD: The body parameters and laboratory indices of 283 patients with hyperlipidemic acute pancreatitis (HLAP) were retrospectively analysed, and the six novel anthropometric indicators of visceral obesity were calculated. The severity of HLAP was determined using the revised Atlanta classification. The correlation between the six indicators and HLAP severity was evaluated, and the predictive efficacy of the indicators was assessed using area under the curve (AUC). The differences in diagnostic values of the six indicators were also compared using the DeLong test. RESULTS: Patients with moderate to severe AP had higher VAI, CMI, and LAP than patients with mild AP (all P < 0.001). The highest AUC in predicting HLAP severity was observed for VAI, with a value of 0.733 and 95% confidence interval of 0.678-0.784. CONCLUSIONS: This study demonstrated significant correlations between HLAP severity and VAI, CMI, and LAP indicators. These indicators, particularly VAI, which displayed the highest predictive power, were instrumental in forecasting and evaluating the severity of HLAP.