PKM2-TMEM33 axis regulates lipid homeostasis in cancer cells by controlling SCAP stability.

The pyruvate kinase M2 isoform (PKM2) is preferentially expressed in cancer cells to regulate anabolic metabolism. Although PKM2 was recently reported to regulate lipid homeostasis, the molecular mechanism remains unclear. Herein, we discovered an ER transmembrane protein 33 (TMEM33) as a downstream effector of PKM2 that regulates activation of SREBPs and lipid metabolism. Loss of PKM2 leads to up-regulation of TMEM33, which recruits RNF5, an E3 ligase, to promote SREBP-cleavage activating protein (SCAP) degradation. TMEM33 is transcriptionally regulated by nuclear factor erythroid 2-like 1 (NRF1), whose cleavage and activation are controlled by PKM2 levels. Total plasma cholesterol levels are elevated by either treatment with PKM2 tetramer-promoting agent TEPP-46 or by global PKM2 knockout in mice, highlighting the essential function of PKM2 in lipid metabolism. Although depletion of PKM2 decreases cancer cell growth, global PKM2 knockout accelerates allografted tumor growth. Together, our findings reveal the cell-autonomous and systemic effects of PKM2 in lipid homeostasis and carcinogenesis, as well as TMEM33 as a bona fide regulator of lipid metabolism.

Dyslipidemia among adult people living with HIV on dolutegravir - based antiretroviral therapy at a private tertiary hospital in Kampala, Uganda: burden and determinants.

BACKGROUND: Understanding the burden of dyslipidemia and its associated factors among adult people living with HIV on dolutegravir (DTG) based anti-retroviral therapy (ART) is critical to provide clinical guidance and risk reduction strategies in our setting. METHODS: We conducted a cross-sectional study on adult people living with HIV on DTG based ART between July and August 2022 at Mengo Hospital, a private not for profit missionary hospital owned by the Church of Uganda. Dyslipidemia was defined as: Total cholesterol (TC) ≥ 5.2 mmol/l, or high-density lipoprotein (HDL) < 1 mmol/l for men and < 1.3 mmol/l for women, or triglycerides (TG) ≥ 1.7 mmol/l, and low-density lipoprotein (LDL) ≥ 3.4 mmol/l. A participant was considered to have dyslipidemia if they had any of the lipid profile parameters in the above ranges. Socio-demographic information, clinical data and behavioral characteristics were collected. Fasting lipid profile and fasting blood glucose levels were also measured. Bivariate and multivariate analyses were done using a generalized linear model regression of the Poisson family with a log link (modified Poisson) using robust standard errors since the prevalence of dyslipidemia was more than 10%. Adjusted prevalence ratios (PR) were reported with their 95% confidence intervals (CI). A p-value of less than 0.05 was considered statistically significant. RESULTS: A total of 341 participants were included. The prevalence of dyslipidemia was 78.0%, (95%CI:73.3-82.1). The highest prevalence was for low HDL (72.1%, 95%CI 67.1-76.7) followed by high TG (20.2%, 95%CI: 16.3-24.9), high TC (12.0%, 95%CI: 9.0-15.9) and high LDL (6.5%, 95%CI: 4.3-9.6). Female sex (aPR:1.55, 95%CI: 1.32-1.84, p < 0.001) and previous use of protease inhibitor (PI) based ART regimen (aPR:1.26, 95%CI: 1.04-1.53, p = 0.018) were significantly associated with dyslipidemia. CONCLUSION: We demonstrate that the prevalence of dyslipidemia is very high as it was present in more than three quarters of the study participants. Female sex and previous use of PI based ART regimen were significantly associated with dyslipidemia. Management of dyslipidemia should be integrated in the HIV treatment package and we recommend further inquiry into the temporal relationship between dyslipidemia and DTG among ART patients, if any.

Exploratory analysis of predictors of ventricular aneurysm in a cohort of 291 patients with acute myocardial infarction.

OBJECTIVE: In this study, we explored the determinants of ventricular aneurysm development following acute myocardial infarction (AMI), thereby prompting timely interventions to enhance patient prognosis. METHODS: In this retrospective cohort analysis, we evaluated 297 AMI patients admitted to the First People's Hospital of Changzhou. The study was structured as follows. Comprehensive baseline data collection included hematological evaluations, ECG, echocardiography, and coronary angiography upon admission. Within 3 months post-AMI, cardiac ultrasounds were administered to detect ventricular aneurysm development. Univariate and multivariate logistic regression analysis were employed to pinpoint the determinants of ventricular aneurysm formation. Subsequently, a predictive model was formulated for ventricular aneurysm post-AMI. Moreover, the diagnostic efficacy of this model was appraised using the ROC curves. RESULTS: In our analysis of 291 AMI patients, spanning an age range of 32-91 years, 247 were male (84.9%). At the conclusion of a 3-month observational period, the cohort bifurcated into two subsets: 278 patients without ventricular aneurysm and 13 with evident ventricular aneurysm. Distinguishing features of the ventricular aneurysm subgroup were markedly higher values for age, B-type natriuretic peptide(BNP), Left atrium(LA), Left ventricular end-diastolic dimension (LEVDD), left ventricular end systolic diameter (LVEWD), E-wave velocity (E), Left atrial volume (LAV), E/A ratio (E/A), E/e ratio (E/e), ECG with elevated adjacent four leads(4 ST-Elevation), and anterior wall myocardial infarction(AWMI) compared to their counterparts (p < 0.05). Among the singular predictive factors, total cholesterol (TC) emerged as the most significant predictor for ventricular aneurysm development, exhibiting an AUC of 0.704. However, upon crafting a multifactorial model that incorporated gender, TC, an elevated ST-segment in adjacent four leads, and anterior wall infarction, its diagnostic capability: notably surpassed that of the standalone TC, yielding an AUC of 0.883 (z = -9.405, p = 0.000) as opposed to 0.704. Multivariate predictive model included gender, total cholesterol, ST elevation in 4 adjacent leads, anterior myocardial infarction, the multivariate predictive model showed better diagnostic efficacy than single factor index TC (AUC: 0. 883 vs. 0.704,z =-9.405, p = 0.000), it also improved predictive power for correctly reclassifying ventricular aneurysm occurrence in patients with AMI, NRI = 28.42% (95% CI: 6.29-50.55%; p = 0.012). Decision curve analysis showed that the use of combination model had a positive net benefit. CONCLUSION: Lipid combined with ECG model after myocardial infarction could be used to predict the formation of ventricular aneurysm and aimed to optimize and adjust treatment strategies.

The effect of the modified Atkins diet and anti-seizure medications on lipid marker levels in adults with epilepsy.

OBJECTIVES: Some anti-seizure medications (ASMs) are known to induce liver enzymes and impact lipid values that include total cholesterol (TC), low density lipoprotein cholesterol (LDL), high density lipoprotein cholesterol (HDL), and triglyceride (TG). In addition, use of ketogenic diet therapies, including the modified Atkins diet (MAD), has also influenced lipids. Here, we explored the combined impact of enzyme inducing ASMs (EIASMs) and MAD on lipid values in adults with epilepsy. METHODS: Diet-naïve adults with epilepsy who began MAD were divided into three groups based on ASM use: EIASMs, non-EIASMs, and those on no ASMs. Demographic information, epilepsy-specific clinical history, anthropometrics and lipid values were obtained through retrospective chart review at baseline and after a minimum of 12 months of MAD use. RESULTS: Forty-two adults on MAD had baseline and follow up 12-month lipid outcomes. There was a significant increase in median levels of TC, LDL, non-HDL, and HDL after 12 months of MAD use. There was no change in median levels of TG. When separated according to ASM category, adults on non-EIASMs showed significant elevations in TC, HDL, and LDL after 12 months of MAD use. In contrast, adults on EIASMs only showed a significant increase in HDL after 12 months of MAD use. DISCUSSION: The increase in atherogenic cholesterol levels observed after 12 months of MAD use was most pronounced in adults with epilepsy on non-EIASMs and not observed in adults with epilepsy on EIASMs despite a higher proportion of abnormal cholesterol levels at baseline in those on EIASMs.

Dyslipidemia in adults with congenital heart disease: A systematic review and meta-analysis.

AIMS: Several particular characteristics of patients with congenital heart disease could affect lipid levels. The objectives of this study were: a) to analyze the prevalence of dyslipidemia in congenital heart disease patients; 2) to compare lipid levels between congenital heart disease patients and a control group. DATA SYNTHESIS: This systematic review and meta-analysis was performed according to PRISMA guidelines (PROSPERO CRD42023432041). A literature search was performed to detect studies that have reported lipid levels or the prevalence of dyslipidemia in congenital heart disease patients. We performed a qualitative analysis (studies that reported dyslipidemia prevalence) and quantitative analysis (studies that compared lipid values between congenital heart disease patients and controls). In total, 29 observational studies involving 22,914 patients with congenital heart disease and 641,086 controls were eligible for this review. The reported presence of "hyperlipidemia" or "dyslipidemia" ranged from 14.3% to 69.9%. When studies analyzed lipid variables dichotomously between congenital heart disease patients and controls, the results were conflicting. The quantitative analysis showed that patients with congenital heart disease have lower levels of total cholesterol (MD: -18.9 [95% CI: -22.2 to -15.7]; I2 = 93%), LDL-C (MD: -10.7 [95% CI: -13.1 to -8.3]; I2 = 90%) and HDL-C (MD: -6.3 [95% CI: -7.7 to -4.9]; I2 = 95%) compared to controls. CONCLUSIONS: The qualitative analysis showed some concerns, but the quantitative analysis indicates that congenital heart disease patients showed lower levels of total cholesterol, LDL-C, and HDL-C compared to controls. New research should be developed to clarify this relevant topic.

Dyslipidemia versus obesity as predictors of ischemic stroke prognosis: a multi-center study in China.

BACKGROUND: This multicenter observational study aimed to determine whether dyslipidemia or obesity contributes more significantly to unfavorable clinical outcomes in patients experiencing a first-ever ischemic stroke (IS). METHODS: The study employed a machine learning predictive model to investigate associations among body mass index (BMI), body fat percentage (BFP), high-density lipoprotein (HDL), triglycerides (TG), and total cholesterol (TC) with adverse outcomes in IS patients. Extensive real-world clinical data was utilized, and risk factors significantly linked to adverse outcomes were identified through multivariate analysis, propensity score matching (PSM), and regression discontinuity design (RDD) techniques. Furthermore, these findings were validated via a nationwide multicenter prospective cohort study. RESULTS: In the derived cohort, a total of 45,162 patients diagnosed with IS were assessed, with 522 experiencing adverse outcomes. A multifactorial analysis incorporating PSM and RDD methods identified TG (adjusted odds ratio (OR) = 1.110; 95% confidence interval (CI): 1.041-1.183; P <  0.01) and TC (adjusted OR = 1.139; 95%CI: 1.039-1.248; P <  0.01) as risk factors. However, BMI, BFP, and HDL showed no significant effect. In the validation cohort, 1410 controls and 941 patients were enrolled, confirming that lipid levels are more strongly correlated with the prognosis of IS patients compared to obesity (TC, OR = 1.369; 95%CI: 1.069-1.754; P <  0.05; TG, OR = 1.332; 95%CI: 1.097-1.618; P <  0.01). CONCLUSION: This study suggests that dyslipidemia has a more substantial impact on the prognosis of IS patients compared to obesity. This highlights the importance of prioritizing dyslipidemia management in the treatment and prevention of adverse outcomes in IS patients.

Lactate-to-albumin ratio and cholesterol levels predict neurological outcome in cardiac arrest survivors.

BACKGROUND: Out-of-hospital cardiac arrest (OHCA) increases lactate levels and reduces albumin levels on admission and tends to lead to a poor neurological prognosis. In our experience, reduced cholesterol levels predict poor neurological prognosis. However, the relationship between cholesterol levels and neurological prognosis in OHCA survivors remains unclear. METHODS: This retrospective observational study included data from January 2015 to June 2023 on 219 OHCA survivors at our intensive care unit. Patients were categorized into two groups based on cerebral functional classification (CPC) scores: Group A (CPC score of 1 or 2), including patients with a favorable neurological outcome, and Group B (CPC scores of 3 to 5), comprising those with a poor neurological outcome. We analyzed their lactate, albumin levels, and lipid profiles measured at 6 h after resuscitation. A model to predict the neurological prognosis of admission of OHCA survivors was developed. RESULTS: Approximately 40% of the patients had favorable neurological outcomes at the 30-day follow-up. The lactate-to-albumin ratio (LAR) was significantly lower in Group A than in Group B (3.1 vs. 5.0 mmol/dag, p < 0.001). However, the albumin, total cholesterol, and high-density lipoprotein (HDL) cholesterol levels were significantly higher in Group A than in Group B (3.6 vs. 2.9 g/dL, 166.1 vs. 131.4 mg/dL, and 38.8 vs. 29.7 mg/dL, respectively, p < 0.001). Favorable neurological outcome was indicated at the following thresholds: LAR < 3.7 mmol/dag, albumin level > 3.1 g/dL, total cholesterol level > 146.4 mg/dL, and HDL-cholesterol level > 31.9 mg/dL. These findings underscore the high sensitivity and negative predictive value of the biomarkers. Furthermore, the area under the curve values for LAR, albumin, total cholesterol, and HDL-cholesterol levels were 0.70, 0.75, 0.71, and 0.71, respectively. The corresponding odds ratios were 3.37, 7.08, 3.67, and 3.94, respectively. CONCLUSIONS: The LAR, albumin, total cholesterol, and HDL-cholesterol levels measured on admission may predict neurological prognosis in OHCA survivors. Thus, routine practice should include the measurement of these biomarkers at 6 h after resuscitation, especially in patients with a lactate level of > 5 mmol/L. TRIAL REGISTRATION: ClinicalTrials.gov ID: NCT02633358.

Prevalence and risk factors for subclinical hypothyroidism in older patients with major depressive disorder.

BACKGROUND: Subclinical hypothyroidism (SCH) is highly correlated with major depressive disorder (MDD). However, the prevalence and risk factors for SCH in older patients with MDD have rarely been reported in China. METHODS: This cross-sectional study included 266 older MDD patients with SCH was performed. Clinical and anthropometric, biochemical, and thyroid function data were collected. Depression, anxiety, and psychotic symptoms were assessed using the Hamilton Depression Scale, the Hamilton Anxiety Scale, and the Positive and Negative Syndrome Scale positive subscale, respectively. RESULTS: Among older patients with MDD, the prevalence of SCH was 64.7% (172/266). Compared to patients without SCH, older MDD patients with SCH had a longer disease course and higher TSH, A-TG, A-TPO, HDL-C, LDL-C, TC, FPG, and systolic pressure levels (all P ≤ 0.002). Furthermore, disease progression (OR 1.082, 95% CI 1.020-1.147, P = 0.009), A-TG (OR 1.005, 95% CI 1.001-1.009, P = 0.017), TC (OR 2.024, 95% CI 1.213-3.377, P = 0.007), FPG (OR 2.916, 95% CI 1.637-5.194, P < 0.001), systolic pressure (OR 1.053, 95% CI 1.008-1.100, P = 0.022) were independently associated with SCH, in older patients with MDD. CONCLUSIONS: Our findings suggest a high prevalence of SCH in older patients with MDD. Several demographic and clinical variables were independently associated with SCH in older patients with MDD.

Total cholesterol mediates the association between history of gestational diabetes mellitus and bone mineral density in US women aged 20-49 years.

OBJECTIVE: The aim of this study is to investigate the potential association between a history of gestational diabetes mellitus (GDM) and lumbar bone mineral density (BMD) among premenopausal women, with an additional examination of the mediating role of serum total cholesterol (TC). METHODS: In this cross-sectional study, 1809 women aged 20-49 years with at least one live birth between 2011 and 2018, drawn from the NHANES dataset, were analyzed. GDM history was identified through questionnaires. Using weighted multiple linear regression, we assessed the relationship between GDM history and lumbar BMD. Additionally, mediation analysis was performed to investigate the potential mediating role of TC. RESULTS: The fully adjusted linear regression model revealed a negative association between a history of GDM and lumbar BMD, indicating a reduction in lumbar BMD (ß = -0.023, 95% CI: -0.043, -0.003, P = 0.0275). Subgroup analysis highlighted a more pronounced trend in individuals aged ≥ 35 years and with a body mass index ≥ 30 kg/m². Furthermore, mediation analysis demonstrated a significant direct effect of a history of GDM on lumbar BMD (P < 0.0001), with serum TC playing a partial mediating role in this interaction (5.33%, P = 0.028). CONCLUSIONS: In women aged 20-49 years within the United States, a history of GDM was associated with diminished lumbar BMD, potentially mediated through serum TC.

Evaluating the Association of Anthropometric Indices With Total Cholesterol in a Large Population Using Data Mining Algorithms.

BACKGROUND: Unbalanced levels of serum total cholesterol (TC) and its subgroups are called dyslipidemia. Several anthropometric indices have been developed to provide a more accurate assessment of body shape and the health risks associated with obesity. In this study, we used the random forest model (RF), decision tree (DT), and logistic regression (LR) to predict total cholesterol based on new anthropometric indices in a sex-stratified analysis. METHOD: Our sample size was 9639 people in which anthropometric parameters were measured for the participants and data regarding the demographic and laboratory data were obtained. Aiding the machine learning, DT, LR, and RF were drawn to build a measurement prediction model. RESULTS: Anthropometric and other related variables were compared between both TC <200 and TC ≥200 groups. In both males and females, Lipid Accumulation Product (LAP) had the greatest effect on the risk of TC increase. According to results of the RF model, LAP and Visceral Adiposity Index (VAI) were significant variables for men. VAI also had a stronger correlation with HDL-C and triglyceride. We identified specific anthropometric thresholds based on DT analysis that could be used to classify individuals at high or low risk of elevated TC levels. The RF model determined that the most important variables for both genders were VAI and LAP. CONCLUSION: We tend to present a picture of the Persian population's anthropometric factors and their association with TC level and possible risk factors. Various anthropometric indices indicated different predictive power for TC levels in the Persian population.

Association between Dyslipidaemia and Cognitive Impairment: A Meta-Analysis of Cohort and Case-Control Studies.

BACKGROUND: This study explored the specific relationship between different lipid indicators and cognitive impairment and aimed to provide a reference for implementing targeted lipid regulation measures to prevent and alleviate cognitive impairment. METHODS: We searched three databases (PubMed, Embase, and Web of Science) for literature related to hyperlipidaemia, lipid levels, and cognitive impairment, and used the Newcastle-Ottawa Scale to evaluate the quality of the identified literature. A meta-analysis was performed using RevMan 5.4, and the combined effect size ratio using a random-effects model (odds ratio [OR] and 95% confidence interval [CI]) was used to evaluate the association between dyslipidaemia and cognitive impairment. RESULTS: Among initially identified 2247 papers, we ultimately included 18 studies involving a total of 758,074 patients. The results of the meta-analysis revealed that patients with hyperlipidaemia had a 1.23-fold higher risk of cognitive impairment than those with normal lipid levels (OR = 1.23, 95% CI: 1.04-1.47, p = 0.02). Further subgroup analysis showed that elevated total cholesterol (TC) levels increased the risk of cognitive impairment by 1.59-fold (OR = 1.59, 95% CI: 1.27-2.01, p < 0.0001) and were more significant in older or male patients. Moreover, elevated triglyceride levels were inversely correlated with cognitive disorders, whereas elevated low-density lipoprotein cholesterol levels were unrelated to cognitive impairment risk. CONCLUSIONS: Dyslipidaemia was strongly associated with cognitive impairment, and elevated TC levels were a risk factor for cognitive impairment. Furthermore, the damaging effects of elevated TC levels on cognition were more pronounced in older and male populations.

Body composition in second trimester is associated with dyslipidemia in third trimester.

OBJECTIVE: The aim of this study was to examine the correlation between maternal body composition during the second trimester and the occurrence of dyslipidemia in the third trimester. METHODS: A cohort of 1508 pregnant women who underwent antenatal testing at Shanghai Sixth People's Hospital, affiliated with Shanghai Jiao Tong University School of Medicine, were included in this study. Maternal body composition was assessed using bioimpedance analysis between 14 and 22 weeks of gestation. RESULTS: Among the 1508 participants, a total of 1420 individuals (94.2%) were diagnosed with dyslipidemia. Notably, there were significant differences in body composition between the normal lipid group and the dyslipidemia group. Logistic regression analysis revealed that various factors including BMI, total body water (TBW), intra-cellular water (ICW), extra-cellular water (ECW), percent body fat (PBF), visceral fat area (VFA), fat-free mass (FFM) and arm circumference (AC) during the second trimester were all found to be associated with dyslipidemia in the third trimester. CONCLUSION: The present study found that maternal body composition was associated with dyslipidemia. The BMI, TBW, ICW, ECW, PBF, VFA, FFM and AC in second trimester were associated with dyslipidemia in third trimester.

Relationship of serum total cholesterol and triglyceride with risk of mortality in maintenance hemodialysis patients: a multicenter prospective cohort study.

OBJECTIVE: The relationship between serum total cholesterol (TC) and triglyceride (TG) levels and mortality in maintenance hemodialysis (MHD) patients remains inconsistent. We aimed to explore the individual and combined association of TC and TG levels with the risk of mortality in Chinese MHD patients. METHODS: 1036 MHD patients were enrolled in this multicenter, prospective cohort study. The serum levels of total cholesterol and triglycerides were measured at baseline. The primary outcome was all-cause mortality and secondary outcome was cardiovascular disease (CVD) mortality. RESULTS: During a median follow-up duration of 4.4 years (IQR= 2.0-7.9 years), 549 (53.0%) patients died, and 297 (28.7%) deaths were attributed to CVD. Compared with patients with TC levels in the first three quartiles (<182.5 mg/dL), a significantly higher risk of all-cause mortality was found in participants with TC in the fourth quartile (hazard ratio [HR], 1.43; 95% confidence interval [CI], 1.17-1.76). However, a significantly lower risk of all-cause mortality was observed in participants with TG in the fourth quartile (≥193.9 mg/dL) (HR, 0.78; 95%CI: 0.63-0.98), compared with participants with TG in the first three quartiles. Similar trends were observed in CVD mortality. When analyzed jointly, patients with lower TC (<182.5 mg/dL) and higher TG (≥193.9 mg/dL) levels had the lowest risk of all-cause mortality and CVD mortality.Conclusions: In MHD patients in southern China, higher TC levels were associated with higher risk of mortality, while higher TG levels were related to lower risk of mortality. Patients with lower TC and higher TG levels had the best survival prognosis.

Psychotropic medication and hepatobiliary health: Ultrasound observations on patients with schizophrenia.

OBJECTIVE: This study sought to examine the association between antipsychotic drug use and hepatobiliary health based on serum markers and ultrasound observations on a sample of patients with schizophrenia compared to age and gender matched healthy controls. METHODS: The 120 patients with schizophrenia and 60 control subjects had their blood drawn to measure liver function tests and underwent hepatobiliary ultrasonography to determine hepatobiliary lesions. Liver function tests included total cholesterol (TC), triglycerides (TG), alanine aminotransferase (ALT), and aspartate aminotransferase (AST). Standardized cross-sectional images of the liver and kidneys were obtained from patients and controls, and analyses were stratified by length of taking psychotropic medication among those with schizophrenia. Liver echo attenuation coefficients, liver-kidney ratios, and liver fat content were determined. RESULTS: Psychotropic drug use was associated with greater liver burden and liver lesions in patients with schizophrenia compared to controls. The levels of TC, TG, ALT and AST in patients with schizophrenia were also all significantly higher among patients with schizophrenia. Long-term psychotropic medication was associated with increased levels of fatty liver in patients compared with controls. Levels of TC, TG, ALT and AST were all significantly higher in the long-term psychotropic medication use group than in the short-term group. Liver echo attenuation coefficient, liver-kidney ratio, and liver fat content were also higher in the long-term medication use group compared to the short-term group. CONCLUSION: Antipsychotic drug use, particularly long-term use, is associated with increased liver burden in patients with schizophrenia, impaired lipid metabolism, increased liver lesions and fat content.

Effect of isotretinoin treatment on inflammatory and hematological parameters in patients with acne vulgaris.

PURPOSE: Although the inflammatory and anti-inflammatory effects of isotretinoin (ISO) treatment in patients with acne vulgaris have been discussed in the literature in recent years, no sensitive and specific marker has been found in studies so far. Neutrophil/HDL (high-density lipoprotein) (NHR), lymphocyte/HD L(LHR), platelet/HDL (PHR), and lymphocyte/monocyte (LMR) are new biomarkers related to inflammation. Triglyceride/HDL (TG/HDL), LDL/HDL, and total cholesterol/HDL have been shown to be cardiometabolic risk factors predicting both cardiovascular disease risk and metabolic risk, rather than just a simple dyslipidemia scale. To our knowledge, the relationship between these parameters and ISO treatment has never been studied before. We aimed to evaluate the immuno-inflammatory response of ISO treatment in patients with acne vulgaris with NHR, LHR, PHR, LMR, TG/HDL, LDL/HDL, and total cholesterol/HDL parameters. MATERIALS AND METHODS: In this study, 153 patients who received oral ISO treatment for at least 3 months with a diagnosis of moderate-severe acne vulgaris were evaluated retrospectively. Patients were given oral isotretinoin at a dose of 0.5-1 mg/kg. Pre and post-treatment leukocyte (WBC), neutrophil (NE), lymphocyte (LY), platelet (PLT), red cell distribution width (RDW), plateletcrit (PCT), neutrophil/lymphocyte (NLR), platelet/lymphocyte (PLR), mean platelet volume (MPV), monocyte/lymphocyte (MLR), LMR, total cholesterol, LDL cholesterol, HDL cholesterol, triglyceride, MHR, NHR, LHR, PHR, TG/HDL, total cholesterol/HDL, LDL/HDL parameters were evaluated. RESULTS: It was found that post-treatment WBC and MPV values increased statistically significantly; NLR, neutrophil, and PCT values, on the other hand, decreased significantly (p < 0.05). No statistically significant change was detected in PLR, MLR, LMR, MHR, NHR, LHR, PHR, lymphocyte, monocyte, platelet, and RDW parameters (p > 0.05). It was determined that post-treatment total cholesterol, triglyceride, VLDL, and LDL levels increased statistically significantly; however, the HDL level decreased significantly (p < 0.05). Levels of total cholesterol/HDL, TG/HDL, and LDL/HDL were also found to increase statistically significantly (p < 0.05). CONCLUSION: Our study suggests that the MPV and NLR ratio as biomarkers can be used as indicators of atherosclerosis-related inflammation due to ISO treatment, but the MHR, NHR, LHR, PHR, MLR, LMR ratios cannot be used. Moreover, we believe that the ratios of TG/HDL, LDL/HDL, and total cholesterol/HDL offer a new contribution as indicators of cardiovascular risk and systemic inflammation related to ISO treatment.

Plasma total cholesterol concentration and risk of higher-grade prostate cancer: A nested case-control study and a dose-response meta-analysis.

Our previous publication found an increased risk of higher-grade (Gleason sum ≥7) prostate cancer for men with high total cholesterol concentration (≥200 mg/dl) in the Health Professionals Follow-up Study (HPFS). With additional 568 prostate cancer cases, we are now able to investigate this association in more detail. For the nested case-control study, we included 1260 men newly diagnosed with prostate cancer between 1993 and 2004, and 1328 controls. For the meta-analyses, 23 articles studied the relationship between total cholesterol level and prostate cancer incidence were included. Logistic regression models and dose-response meta-analysis were performed. An increased risk of higher-grade (Gleason sum ≥4 + 3) prostate cancer for high vs low quartile of total cholesterol level was observed in the HPFS (ORmultivariable = 1.56; 95% CI = 1.01-2.40). This finding was compatible with the association noted in the meta-analysis of highest vs lowest group of total cholesterol level, which suggested a moderately increased risk of higher-grade prostate cancer (Pooled RR =1.21; 95%CI: 1.11-1.32). Moreover, the dose-response meta-analysis indicated that an increased risk of higher-grade prostate cancer occurred primarily at total cholesterol levels ≥200 mg/dl, where the RR was 1.04 (95%CI: 1.01-1.08) per 20 mg/dl increase in total cholesterol level. However, total cholesterol concentration was not associated with the risk of prostate cancer overall either in the HPFS or in the meta-analysis. Our primary finding, as well as the result of the meta-analysis suggested a modest increased risk of higher-grade prostate cancer, at total cholesterol concentrations exceeding 200 mg/dl.

Total-, LDL-, and HDL-cholesterol, apolipoproteins, and triglycerides with risk of total and fatal prostate cancer in Black and White men in the ARIC study.

BACKGROUND: Cholesterol reduction is considered a mechanism through which cholesterol-lowering drugs including statins are associated with a reduced aggressive prostate cancer risk. While prior cohort studies found positive associations between total cholesterol and more advanced stage and grade in White men, whether associations for total cholesterol, low (LDL)- and high (HDL)-density lipoprotein cholesterol, apolipoprotein B (LDL particle) and A1 (HDL particle), and triglycerides are similar for fatal prostate cancer and in Black men, who experience a disproportionate burden of total and fatal prostate cancer, is unknown. METHODS: We conducted a prospective study of 1553 Black and 5071 White cancer-free men attending visit 1 (1987-1989) of the Atherosclerosis Risk in Communities Study. A total of 885 incident prostate cancer cases were ascertained through 2015, and 128 prostate cancer deaths through 2018. We estimated multivariable-adjusted hazard ratios (HRs) of total and fatal prostate cancer per 1-standard deviation increments and for tertiles (T1-T3) of time-updated lipid biomarkers overall and in Black and White men. RESULTS: Greater total cholesterol concentration (HR per-1 SD = 1.25; 95% CI = 1.00-1.58) and LDL cholesterol (HR per-1 SD = 1.26; 95% CI = 0.99-1.60) were associated with higher fatal prostate cancer risk in White men only. Apolipoprotein B was nonlinearly associated with fatal prostate cancer overall (T2 vs. T1: HR = 1.66; 95% CI = 1.05-2.64) and in Black men (HR = 3.59; 95% CI = 1.53-8.40) but not White men (HR = 1.13; 95% CI = 0.65-1.97). Tests for interaction by race were not statistically significant. CONCLUSIONS: These findings may improve the understanding of lipid metabolism in prostate carcinogenesis by disease aggressiveness, and by race while emphasizing the importance of cholesterol control.

Kinetics changes in total cholesterol predict HBeAg seroconversion in chronic hepatitis B patients treated with pegylated interferon-alfa.

There is no satisfactory standard for predicting HBeAg seroconversion during Pegylated interferon alpha (PegIFNα) treatment. Studies have shown that IFNα therapy in chronic hepatitis C patients could alter serum lipid profiles. However, there have been no studies on lipid changes that predict the outcome of PegIFNα monotherapy in treated-naive chronic hepatitis B (CHB) patients. This retrospective study included 130 treated-naive HBeAg-positive CHB patients receiving PegIFNα monotherapy. The relationship between serum lipid changes and HBeAg seroconversion was analysed. The TC-ALT-HBsAg-HBeAg-Genotype-Age (CASEGA) model was established to predict HBeAg seroconversion after PegIFN-α monotherapy. Among 130 patients, 33 achieved HBeAg seroconversion (SR) and 97 did not achieve HBeAg seroconversion (NR). The decrease in serum total cholesterol (TC) in the NR group was significantly higher than in the SR group at Week 24 (-9.59% vs. -0.31%, p < 0.001). Multivariate logistic regression analysis showed that the change in TC at Week 24 (odds ratio = 1.065, p = 0.009) was an independent predictor of HBeAg seroconversion. The area under the receiver operating characteristic curve for the CASEGA model was 0.883. The model score at the maximum Youden index was 90, and the specificity, sensitivity, positive predictive value and negative predictive value were 0.727, 0.794, 0.546 and 0.895, respectively. The HBeAg seroconversion rate at Week 72 in patients with scores >90 was significantly higher than that in patients with scores <90 (54.55% vs. 10.47%, p < 0.001). This study indicated that the change in the TC level at 24 weeks in CHB patients treated with PegIFNα was associated with HBeAg seroconversion. The CASEGA prediction model based on the TC change rate of 24 weeks has good predictive efficiency for HBeAg seroconversion.

The effect of lutein and Zeaxanthine on dyslipidemia: A meta-analysis study.

AIMS: The relationship between circulating Lutein and zeaxanthin (L/Z) concentrations, and plasma lipoproteins has been indicated by observational studies. However, the beneficial impact of L/Z administration on dyslipidemia are unclear. This meta-analysis aimed to investigate the effect of oral intake of L/Z on circulating total cholesterol (TC), low-density lipoprotein-cholesterol (LDL-C), as well as high-density lipoprotein-cholesterol (HDL-C) levels. METHODS: We electronically assessed all eligible interventional studies through different electronic databases, including PubMed, Scopus, ISI -Web of Science, and Cochrane library until Jun 2021. After identifying the quality of each included randomized controlled trials, they were evaluated by assessing the risk-difference between treatment and control groups by pooling available data on net change of serum LDL-C, HDL-C, and Cholesterol. RESULTS: L/Z supplementation has null effect on circulating levels of TC (WMD: -3.82 95% CI: -13.83, 6.18; I-square: 85.2%), and LDL-C (WMD: -4.54; 95% CI: -11.5, 2.48; I-square: 83.9%). In contrast, L/Z treatment could significantly increase HDL-C levels in older adults (WMD: 4.06; 95% CI: 0.64, 7.48; I-square: 50.7%). CONCLUSION: L/Z administration could be an effective treatment for improving circulating HDL-C concentration in elderly adults.

Clinical significance of dynamic variation of low cholesterol and its prognostic value in patients with pyogenic liver abscesses: a retrospective study.

BACKGROUND: Serum lipids variations are closely related to the sepsis progression; however, their value for patients with pyogenic liver abscesses (PLA) has rarely been studied. We investigated the serum lipid level variations in patients with PLA and its predictive value to the disease. METHODS: The study included 328 patients with PLA hospitalized in the First Affiliated Hospital of Nanjing Medical University from January 2017 to December 2021; 35 (10.67%) in the severe group (SG) and 293 (89.33%) in the non-severe group (nSG). Their clinical records were analyzed retrospectively, and dynamic curves were drawn to clarify the changes in different indicators during the course of the disease. RESULTS: High-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), and lipoprotein(a) (Lp(a)) in the SG were significantly lower than those in nSG (P < 0.001). Total cholesterol (TC) at baseline (OR = 0.184, P < 0.001) was an independent risk factor for severe patients and had the highest predictive value, with an area under the curve of 0.859 and a cut-off value of 2.70 mmol/L (sensitivity = 94.3%, specificity = 63.5%). For patients who met the criteria for drainage surgery, TC, HDL-C and LDL-C levels continued to decrease with antibiotic therapy alone before drainage and began to increase after the surgery. CONCLUSIONS: Low TC level on admission is an independent risk factor for the progression of severe illness in PLA patients, with the highest predictive value surpassing other routine clinical indices. Abscess drainage should be performed as soon as possible for patients whose TC continues to decline after medical treatment.