Post-diagnosis serum 25-hydroxyvitamin D concentrations in women treated for breast cancer participating in a lifestyle trial in Italy.

OBJECTIVE: To report cross-sectionally serum levels of 25-hydroxyvitamin D [25(OH)D] in women living in Italy within 12 months from breast cancer (BC) diagnosis. METHODS: Baseline data were obtained from 394 women diagnosed with primary BC, enrolled from 2016 to 2019 in a lifestyle trial conducted in Italy. Subjects' characteristics were compared between two 25(OH)D concentrations (hypovitaminosis D<20 and ≥20 ng/mL) with the Chi-squared test or Fisher's exact test for small-expected counts. Using multiple logistic regression-adjusted models, we estimated odds ratios (ORs) of hypovitaminosis D with 95% confidence intervals (CIs) in the total sample and in the unsupplemented subgroup. RESULTS: Hypovitaminosis D was found in 39% of all subjects, 60% in unsupplemented subjects, and 10% in supplemented subjects. Increasing ORs of hypovitaminosis D were found with increasing body mass index, 25-30, >30, and ≥35 versus <25 kg/m2 (ORs: 2.50, 4.64, and 5.81, respectively, in the total cohort and ORs: 2.68, 5.38, and 7.08 in the unsupplemented); living in the most southern Italian region (OR 2.50, 95%CI 1.22-5.13); and with hypertriglyceridemia (OR 2.46; 95%CI 1.16-5.22), chemotherapy history (OR 1.86, 95%CI 1.03-3.38), and inversely with anti-estrogenic therapy (OR 0.43, 95%CI 0.24-0.75) in the total sample. CONCLUSIONS: Hypovitaminosis D in women recently diagnosed with BC and participating in a lifestyle trial in Italy was widespread and highest with obesity, hypertriglyceridemia, and chemotherapy use. Considering that hypovitaminosis D is a risk factor for lower efficacy of bone density treatments and possibly BC mortality, our results suggest the need to promptly address and treat vitamin D deficiency.

Metabolic and other morbid complications in congenital generalized lipodystrophy type 4.

Morbidity and mortality rates in patients with autosomal recessive, congenital generalized lipodystrophy type 4 (CGL4), an ultra-rare disorder, remain unclear. We report on 30 females and 16 males from 10 countries with biallelic null variants in CAVIN1 gene (mean age, 12 years; range, 2 months to 41 years). Hypertriglyceridemia was seen in 79% (34/43), hepatic steatosis in 82% (27/33) but diabetes mellitus in only 21% (8/44). Myopathy with elevated serum creatine kinase levels (346-3325 IU/L) affected all of them (38/38). 39% had scoliosis (10/26) and 57% had atlantoaxial instability (8/14). Cardiac arrhythmias were detected in 57% (20/35) and 46% had ventricular tachycardia (16/35). Congenital pyloric stenosis was diagnosed in 39% (18/46), 9 had esophageal dysmotility and 19 had intestinal dysmotility. Four patients suffered from intestinal perforations. Seven patients died at mean age of 17 years (range: 2 months to 39 years). The cause of death in four patients was cardiac arrhythmia and sudden death, while others died of prematurity, gastrointestinal perforation, and infected foot ulcers leading to sepsis. Our study highlights high prevalence of myopathy, metabolic abnormalities, cardiac, and gastrointestinal problems in patients with CGL4. CGL4 patients are at high risk of early death mainly caused by cardiac arrhythmias.

Update About the Management of Low-Density Lipoprotein Cholesterol and Hypertriglyceridemia in Lower Extremity Peripheral Artery Disease Patients: Consensus of the French Society of Vascular Medicine and the French Society for Vascular and Endovascular Surgery.

BACKGROUND: A French intersociety consensus on behalf the Société Française de Médecine Vasculaire and the Société de Chirurgie Vasculaire et Endovasculaire was proposed in 2021 for the management of patients with lower extremity peripheral artery disease (LEAD). Recent studies have been published and an update of this consensus about the management of low-density lipoprotein cholesterol (LDLc) and hypertriglyceridemia was required. METHODS: A steering committee of 12 vascular physicians and surgeons defined questions of interest about LDLc and hypertriglyceridemia management. A French expert panel voted the proposals. Consensus was considered to have been achieved if more than 80% of the responses corresponded to either "Agreement" or "Disagreement". RESULTS: Among the 56 experts who were asked to participate, 46 (82%) accepted. After the first round of the Delphi procedure, the 4 proposals reached consensus. The following suggestions and recommendations were approved: 1. For LEAD patients treated by the highest tolerated statin dose ± ezetimibe and who have an LDLc ≥0.70 g/L, we recommend adding a proprotein convertase subtilisin/kexin type 9 inhibitor. 2. For LEAD patients treated by statin and who have elevated triglyceride level between ≥150 mg/dL and ≤500 mg/dL, we suggest adding Icosapent Ethyl. 3. Before adding Icosapent Ethyl in LEAD patients treated with statin, we suggest looking for symptoms that may suggest atrial fibrillation. 4. For LEAD patients treated by Icosapent Ethyl and who have symptoms that suggest atrial fibrillation, we recommend performing an electrocardiogram. CONCLUSIONS: This update will help clinicians to improve LEAD patient management.

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.

Fish Oil Derivatives in Hypertriglyceridemia: Mechanism and Cardiovascular Prevention: What Do Studies Say?

Hypertriglyceridemia is a type of dyslipidemia characterized by high triglyceride levels in the blood and increases the risk of cardiovascular disease. Conventional management includes antilipidemic medications such as statins, lowering LDL and triglyceride levels as well as raising HDL levels. However, the treatment may be stratified using omega-3 fatty acid supplements such as eicosatetraenoic acid (EPA) and docosahexaenoic acid (DHA), aka fish oil derivatives. Studies have shown that fish oil supplements reduce the risk of cardiovascular diseases; however, the underlying mechanism and the extent of reduction in CVD need more clarification. Our paper aims to review the clinical trials and observational studies in the current literature, investigating the use of fish oil and its benefits on the cardiovascular system as well as the proposed underlying mechanism.

Association between periodontal disease and hypertriglyceridemia: Propensity score matching analysis using the 7th Korea National Health and Nutrition Examination Survey.

The prevalence of periodontitis and dyslipidemia continues to increase, and several studies have reported an association between the 2. Therefore, we assessed the relationship between periodontitis and hypertriglyceridemia using propensity score matching to efficiently address confounding factors, as well as complex sample analysis with data from Korea National Health and Nutrition Examination Survey VII (2016-2018). To match the 1:1 ratio between the groups with and without periodontitis, the propensity scores of covariates, such as age, sex, education, income, smoking, drinking, obesity, and diabetes mellitus, were calculated using logistic regression. Both results of logistic regression analysis using complex sample design for whole and matched sample after propensity score matching demonstrated a significant association between hypertriglyceridemia and periodontitis, of which the adjusted odds ratio was 1.28 (95% confidence interval = 1.10-1.50) and 1.29 (95% confidence interval = 1.09-1.52), respectively. Our findings suggest that dental healthcare workers can help raise awareness among patients with periodontitis regarding the association between periodontitis and hypertriglyceridemia, which may help them manage the condition and receive treatment.

Future risk of metabolic syndrome after recurrent pregnancy loss: a cohort study using UK Biobank.

OBJECTIVE: To evaluate the risk of metabolic syndrome (MS) after recurrent pregnancy loss (RPL) using UK Biobank data. A history of pregnancy loss is associated with the development of cardiovascular diseases in the future. However, the association between RPL and subsequent MS is poorly understood. Therefore, we aimed to check the risk of MS after RPL. DESIGN: The study population was divided into 2 groups according to reproductive history: women with a history of RPL and women without a history of RPL. Recurrent pregnancy loss was defined as 2 or more spontaneous miscarriages, and MS was defined as at least 3 of the following: abdominal obesity, hypertriglyceridemia, low high-density lipoprotein cholesterol levels, high-blood pressure, and hyperglycemia. SETTING: UK Biobank resource. PATIENTS: The UK Biobank is a prospective cohort study that enrolled individuals aged between 40 and 69 years whose medical and reproductive histories were retrieved at enrollment. In this cohort, only women with a history of at least one pregnancy were selected. INTERVENTIONS: Recurrent pregnancy loss. MAIN OUTCOME MEASURES: The primary outcome was the prevalence of MS. The secondary outcomes were 5 diagnostic components of MS. RESULTS: We analyzed 228,674 women, including 15,702 with a history of RPL and 212,972 without a history of RPL. Women with a history of RPL have a higher prevalence of MS between the ages of 40 and 60 years (33.0% vs. 31.5%). After adjusting for covariates (age, race, number of live births, early menopause, smoking, alcohol consumption, and physical activity), the increased risk of MS after RPL remained significant (adjusted odds ratio, 1.10; 95% confidence interval, 1.06-1.15). Furthermore, in the analysis of the 5 diagnostic components of MS, a history of RPL significantly increased the risk of abdominal obesity, hypertriglyceridemia, low high-density lipoprotein cholesterol levels, and hyperglycemia. CONCLUSION: Middle-aged women with a history of RPL have an increased risk of MS.

Very severe hypertriglyceridemia complicating pediatric acute lymphoblastic leukemia treatment: a call for management guidelines.

OBJECTIVES: Severe and very severe hypertriglyceridemia although rare within the pediatric population occur more often among oncology patients, secondary to chemotherapeutic agents. Currently there exists minimal literature to guide management of severe hypertriglyceridemia among pediatric patients. Very-low-fat dietary restriction should be considered over nil per os (NPO) for initial management of severe hypertriglyceridemia in stable pediatric patients. Pediatricians caring for oncology patients must consider chylomicronemia as a potential etiology for presenting symptoms. Pediatric severe hypertriglyceridemia management guidelines are needed as pediatricians must currently rely on anecdotal experiences for management decisions. CASE PRESENTATION: Three children receiving treatment for acute lymphoblastic leukemia required hospitalization for very severe hypertriglyceridemia. Management varied among the cases but included: NPO or very-low-fat diet, insulin, intravenous fluids, fibrates, and omega-3 fatty acids. CONCLUSIONS: These cases suggest that pediatric severe hypertriglyceridemia management, in the absence of pancreatitis should allow a very-low-fat diet initially rather than NPO followed by pharmacologic therapies.

Recurrence rates and risk factors for recurrence after first episode of acute pancreatitis: A systematic review and meta-analysis.

BACKGROUND: There are a certain number of acute pancreatitis (AP) patients who may suffer from multiple episodes and develop recurrent acute pancreatitis (RAP), but recurrence rates and associated risk factors for RAP vary significantly in the published literature. METHODS: We searched PubMed, Web of Science, Scopus, and Embase databases to identify all publications reporting AP recurrence until October 20th, 2022. Meta-analysis and meta-regression were performed to calculate the pooled estimates using the random-effects model. RESULTS: A total of 36 studies met the inclusion criteria and all were used in pooled analyses. The overall rate of recurrence after first-time AP was 21% (95% CI, 18%- 24%), and pooled rates in biliary, alcoholic, idiopathic, and hypertriglyceridemia etiology patients were 12%, 30%, 25%, and 30%, respectively. After managing underlying causes post-discharge, the recurrence rate decreased (14% versus 4% for biliary, 30% versus 6% for alcoholic, and 30% versus 22% for hypertriglyceridemia AP). An increased risk of recurrence was reported in patients with a smoking history (odds ratio [OR] = 1.99), alcoholic etiology (OR = 1.72), male sex (hazard ratio [HR] = 1.63), and local complications (HR = 3.40), while biliary etiology was associated with lower recurrence rates (OR = 0.38). CONCLUSION: More than one-fifth of AP patients experienced recurrence after discharge, with the highest recurrence rate in alcoholic and hypertriglyceridemia etiologies, and managing underlying causes post-discharge was related to decreased incidence. In addition, smoking history, alcoholic etiology, male gender, and presence of local complications were independent risks for the recurrence.

Inhibition of TRAF6 improves hyperlipidemic acute pancreatitis by alleviating pyroptosis in vitro and in vivo rat models.

OBJECTIVE: Hypertriglyceridemia (HTG) is one of the common causes of acute pancreatitis (AP). Hyperlipidemic acute pancreatitis (HTG-AP) is associated with higher mortality owing to its tendency for greater severity and rapid progression. The purpose of this study was to explore the mechanism of involvement of tumor necrosis factor receptor-related factor 6 (TRAF6) in pyroptosis during HTG-AP. METHODS: The HTG environment was simulated with palmitic acid treatment in vitro and a high-fat diet in vivo. Cerulein was used to establish the HTG-AP model, followed by genetic and pharmacological inhibition of TRAF6. Pyroptosis activation, inflammatory reaction, and the interaction between TRAF6 and pyroptosis in HTG-AP were assessed. RESULTS: HTG was found to aggravate the development of pancreatitis, accompanied by increased pyroptosis and enhanced inflammatory response in HTG-AP models. Mechanistically, TRAF6 downregulation decreased the activation of pyroptosis in cerulein-induced HTG-AP. CONCLUSION: Collectively, inhibition of TRAF6 improved HTG-AP and the associated inflammation by alleviating pyroptosis.

Correlation between pancreatic cancer and metabolic syndrome: A systematic review and meta-analysis.

Objective: Pancreatic cancer is a globally frequent cause of death, which can be caused by many factors. This meta-analysis was performed to assess the correlation between pancreatic cancer and metabolic syndrome (MetS). Methods: Publications were identified by searching PubMed, EMBASE, and the Cochrane Library for studies published until November 2022. Case-control and cohort studies published in English that provided information on the odds ratio (OR), relative risk (RR), or hazard ratio (HR) of metabolic syndrome and pancreatic cancer were included in the meta-analysis. Two researchers separately retrieved the core data from the included Random effects meta-analysis was conducted to summarize the findings. Results were presented as relative risk (RR) and 95% confidence interval (CI). Results: MetS showed a strong association with an increased risk of developing pancreatic cancer (RR1.34, 95% CI1.23-1.46, P<0.001), and gender differences were also observed (men: RR 1.26, 95% CI 1.03-1.54, P=0.022; women: RR 1.64, 95% CI 1.41-1.90, P< 0.001). Moreover, an increased risk of developing pancreatic cancer was strongly linked to hypertension, poor high-density lipoprotein cholesterol, and hyperglycemia (hypertension: RR 1.10 CI 1.01-1.19, P=0.027; low high-density lipoprotein cholesterol: RR 1.24 CI 1.11-1.38, P<0.001; hyperglycemia: RR 1.55, CI 1.42-1.70, P< 0.001). However, pancreatic cancer was independent of obesity and hypertriglyceridemia (obesity: RR 1.13 CI 0.96-1.32, P=0.151, hypertriglyceridemia: RR 0.96, CI 0.87-1.07, P=0.486). Conclusions: Although further prospective studies are required for confirmation, this meta-analysis indicated a strong relationship between MetS and pancreatic cancer. Regardless of gender, a greater risk of pancreatic cancer existed in people with MetS. Patients with MetS were more likely to develop pancreatic cancer, regardless of gender. Hypertension, hyperglycemia, and low HDL-c levels may largely account for this association. Further, the prevalence of pancreatic cancer was independent of obesity and hypertriglyceridemia. Systematic review registration: https://www.crd.york.ac.uk/prospero/, identifier CRD42022368980.

[Honokiol reduces oxidative stress by activating the SIRT3-MnSOD2 pathway to alleviate hypertriglyceridemia-induced acute pancreatitis in rats].

OBJECTIVE: To determine how honokiol affects the sirtuin-3 (SIRT3)-MnSOD2 pathway and oxidative stress in rats with hypertriglyceridemia-induced acute pancreatitis (HTGP). METHODS: Thirty 4-week-old male SD rats were randomly divided into two groups for normal feeding and high-fat feeding for 4 weeks, after which the rats with normal feeding were randomized into control group and acute pancreatitis (AP) group (n=6), and those with high-fat feeding were divided into hypertriglyceridemia group, HTGP group, and honokiol treatment group (n=6). In AP, HTGP, and honokiol groups, AP models were established by intraperitoneal injection of cerulean; in honokiol group, the rats received an intraperitoneal injection of 5 mg/kg honokiol 15 min after cerulean injection. Serum TG, IL-6, and TNF-α levels were measured 24 h after the treatments, and pathological changes in the pancreas were observed with HE staining; The levels of reactive oxygen species (ROS), malondialdehyde (MDA), and glutathione peroxidase (GSH) were measured, and SIRT3 and manganese superoxide dismutase (MnSOD2) expressions were detected using Western blotting and immunohistochemistry. Transmission electron microscopy was used to examine the ultrastructure of pancreatic acinar cells and mitochondria. RESULTS: Compared with the those with normal feeding, the rats with high-fat feeding had significantly elevated serum TG level (P < 0.05). The rat models of AP showed significantly increased serum levels of IL-6, TNF-α, and MDA and decreased GSH level and expressions of SIRT3 and MnSOD2, with obvious edema and inflammatory cell infiltration and enhanced ROS fluorescence intensity in the pancreas and ultrastructural damages of the acinar cells and mitochondria. In rats with HTGP, honokiol treatment significantly decreased serum levels of IL-6, TNF-α, and MDA, increased GSH level and SIRT3 and MnSOD2 expressions, reduced ROS production, and alleviated ultrastructural damage of the acinar cells and mitochondria in the pancreas. CONCLUSION: Honokiol reduce oxidative stress and alleviates pancreatic injuries in HTGP rats possibly by activating the SIRT3-MnSOD2 pathway.

Delayed Presentation of Berardinelli-Siep Lipodystrophy in an Adolescent Female.

Berardinelli-Siep syndrome (BSS) is a form of congenital generalized lipodystrophy that disrupts the pathways of lipid metabolism. It presents with physical exam findings, including muscular hypertrophy and lipoatrophy as well as serious metabolic consequences such as diabetes mellitus, hypertriglyceridemia, acute pancreatitis, hepatomegaly, and hepatic steatosis. Diagnosis generally occurs soon after birth or in childhood. The case presented is significant for a delayed diagnosis of suspected BSS Type 1 which is rather uncommon in a developed country. Due to the detrimental complications of BSS, such as hypertrophic cardiomyopathy, pancreatitis, and liver disease, early diagnosis and intervention are crucial. Pediatric providers must be knowledgeable about physical features of BSS and common presentations such as new onset diabetes, hypertriglyceridemia, or pancreatitis throughout early childhood and adolescence in order to avoid delayed diagnoses.

Overexpression of NgBR inhibits high-fat diet-induced atherosclerosis in ApoE-deficiency mice.

BACKGROUND: Hyperlipidemia (hypercholesterolemia and/or hypertriglyceridemia) is a risk factor for atherosclerosis. Nogo-B receptor (NgBR) plays important roles in hepatic steatosis and cholesterol transport. However, the effect of NgBR overexpression on atherosclerosis remains unknown. MATERIALS AND METHODS: Apolipoprotein E deficient (ApoE-/-) mice infected with adeno-associated virus (AAV)-NgBR expression vector were fed a high-fat diet for 12 weeks, followed by determination of atherosclerosis and the involved mechanisms. RESULTS: We determined that high expression of NgBR by AAV injection mainly occurs in the liver and it can substantially inhibit en face and aortic root sinus lesions. NgBR overexpression also reduced levels of inflammatory factors in the aortic root and serum, and levels of cholesterol, triglyceride, and free fatty acids in the liver and serum. Mechanistically, NgBR overexpression increased the expression of scavenger receptor type BI and the genes for bile acid synthesis, and decreased the expression of cholesterol synthesis genes by reducing sterol regulatory element-binding protein 2 maturation in the liver, thereby reducing hypercholesterolemia. In addition, NgBR overexpression activated AMP-activated protein kinase α via the Ca2+ signaling pathway, which inhibited fat synthesis and improved hypertriglyceridemia. CONCLUSIONS: Taken together, our study demonstrates that overexpression of NgBR enhanced cholesterol metabolism and inhibited cholesterol/fatty acid synthesis to reduce hyperlipidemia, and reduced vascular inflammation, thereby inhibiting atherosclerosis in ApoE-/- mice. Our study indicates that NgBR might be a potential target for atherosclerosis treatment.

Clinical features of generalized lipodystrophy in Turkey: A cohort analysis.

AIM: To describe the Turkish generalized lipodystrophy (GL) cohort with the frequency of each complication and the death rate during the period of the follow-up. METHODS: This study reports on 72 patients with GL (47 families) registered at different centres in Turkey that cover all regions of the country. The mean ± SD follow-up was 86 ± 78 months. RESULTS: The Kaplan-Meier estimate of the median time to diagnosis of diabetes and/or prediabetes was 16 years. Hyperglycaemia was not controlled in 37 of 45 patients (82.2%) with diabetes. Hypertriglyceridaemia developed in 65 patients (90.3%). The Kaplan-Meier estimate of the median time to diagnosis of hypertriglyceridaemia was 14 years. Hypertriglyceridaemia was severe (≥ 500 mg/dl) in 38 patients (52.8%). Seven (9.7%) patients suffered from pancreatitis. The Kaplan-Meier estimate of the median time to diagnosis of hepatic steatosis was 15 years. Liver disease progressed to cirrhosis in nine patients (12.5%). Liver disease was more severe in congenital lipodystrophy type 2 (CGL2). Proteinuric chronic kidney disease (CKD) developed in 32 patients (44.4%) and cardiac disease in 23 patients (31.9%). Kaplan-Meier estimates of the median time to diagnosis of CKD and cardiac disease were 25 and 45 years, respectively. Females appeared to have a more severe metabolic disease, with an earlier onset of metabolic abnormalities. Ten patients died during the follow-up period. Causes of death were end-stage renal disease, sepsis (because of recurrent intestinal perforations, coronavirus disease, diabetic foot infection and following coronary artery bypass graft surgery), myocardial infarction, heart failure because of dilated cardiomyopathy, stroke, liver complications and angiosarcoma. CONCLUSIONS: Standard treatment approaches have only a limited impact and do not prevent the development of severe metabolic abnormalities and early onset of organ complications in GL.

Hypertriglyceridemia is associated with decline of estimated glomerular filtration rate and risk of end-stage kidney disease in a real-word Italian cohort: Evidence from the TG-RENAL Study.

BACKGROUND: This analysis investigated the role of hypertriglyceridemia on renal function decline and development of end-stage kidney disease (ESKD) in a real-world clinical setting. METHODS: A retrospective analysis using administrative databases of 3 Italian Local Health Units was performed searching patients with at least one plasma triglyceride (TG) measurement between 2013 and June 2020, followed-up until June 2021. Outcome measures included reduction in estimated glomerular filtration rate (eGFR) ≥30% from baseline and ESKD onset. Subjects with normal (normal-TG), high (HTG) and very high TG levels (vHTG) (respectively <150 mg/dL, 150-500 mg/dL and >500 mg/dL) were comparatively evaluated. RESULTS: Overall 45,000 subjects (39,935 normal-TGs, 5,029 HTG and 36 vHTG) with baseline eGFR of 96.0 ± 66.4 mL/min were considered. The incidence of eGFR reduction was 27.1 and 31.1 and 35.1 per 1000 person-years, in normal-TG, HTG and vHTG subjects, respectively (P<0.01). The incidence of ESKD was 0.7 and 0.9 per 1000 person-years, in normal-TG and HTG/vHTG subjects, respectively (P<0.01). Univariate and multivariate analyses revealed that HTG subjects had a risk of eGFR reduction or ESKD occurrence (composite endpoint) increased by 48% compared to normal-TG subjects (adjusted OR:1.485, 95%CI 1.300-1.696; P<0.001). Moreover, each 50 mg/dL increase in TG levels resulted in significantly greater risk of eGFR reduction (OR:1.062, 95%CI 1.039-1.086 P<0.001) and ESKD (OR:1.174, 95%CI 1.070-1.289, P = 0.001). CONCLUSIONS: This real-word analysis in a large cohort of individuals with low-to-moderate cardiovascular risk suggests that moderate-to-severe elevation of plasma TG levels is associated with a significantly increased risk of long-term kidney function deterioration.

Genetic determinants of pancreatitis: relevance in severe hypertriglyceridemia.

PURPOSE OF REVIEW: Not all patients with severe hypertriglyceridemia develop acute pancreatitis. We surveyed recent literature on inter-individual genetic variation in susceptibility to pancreatitis. RECENT FINDINGS: Genetic determinants of pancreatitis include: rare Mendelian disorders caused by highly penetrant pathogenic variants in genes involved in trypsinogen activation; uncommon susceptibility variants in genes involved in trypsinogen activation, protein misfolding as well as calcium metabolism and cystic fibrosis, that have variable penetrance and show a range of odds ratios for pancreatitis; and common polymorphisms in many of the same genes that have only a small effect on risk. The role of these genetic variants in modulating pancreatitis risk in hypertriglyceridemia is unclear. However, among genetic determinants of plasma triglycerides, those predisposing to more severe hypertriglyceridemia associated with chylomicronemia appear to have higher pancreatitis risk. SUMMARY: Currently, among patients with severe hypertriglyceridemia, the most consistent predictor of pancreatitis risk is the triglyceride level. Furthermore, pancreatitis risk appears to be modulated by a higher genetic burden of factors associated with greater magnitude of triglyceride elevation. The role of common and rare genetic determinants of pancreatitis itself in this metabolic context is unclear.

Metabolic syndrome and its components predict the biochemical recurrence and adverse pathological features of patients following radical prostatectomy: a propensity score matching study.

BACKGROUND: To investigate the predictive value of metabolic syndrome (MetS) and its components in biochemical recurrence (BCR) and adverse pathological features of patients with prostate cancer (PCa) after radical prostatectomy (RP). METHODS: A total of 525 PCa patients who underwent RP between 2010 and 2019 at Peking University Third Hospital were analyzed retrospectively. The Kaplan-Meier method was performed to assess BCR-free survival (BCRFS). Univariate and multivariate Cox regression models and multivariate logistic regression models were conducted to identify the predictive factors of BCRFS and adverse pathological features respectively before and after propensity score matching (PSM). RESULTS: Enrolled patients were allocated into MetS group (n = 136) and non-MetS group (n = 389) according to the presence or absence of MetS, and 127 new matched pairs were identified to balance the baseline characteristics after 1:1 PSM. In propensity matched patients, the Kaplan-Meier analysis revealed that MetS (P = 0.020), hyperglycemia (P = 0.015) and hypertriglyceridemia (P = 0.001) were significantly associated with worse BCRFS; the results of multivariate Cox analyses showed that hyperglycemia (P = 0.040), hypertriglyceridemia (P = 0.017), percentage of positive biopsy cores (P = 0.041) and prostate specific antigen (P = 0.019) were identified as independent prognostic factors for BCRFS. In addition, hypertriglyceridemia was independently associated with non-organ confined disease (NOCD) (P = 0.010), extra-capsular extension (ECE) (P = 0.010) and upgrading (P = 0.017) in the multivariate logistic analyses. CONCLUSIONS: Hyperglycemia and hypertriglyceridemia are the two effective MetS components both identified as independent risk factors for worse BCRFS after RP, while hypertriglyceridemia was independently associated with NOCD, ECE and upgrading as well.

Severe hypertriglyceridemia in an infant on chronic hemodialysis.

Severe hyperlipidemia is a risk factor for cardiovascular disease. Children with chronic kidney disease and end stage renal disease are at risk for development of hyperlipidemia. In this report, we describe a 7-month-old male infant with Denys-Drash syndrome who was found to have a "milky-layer" floating on the deaerator of the hemodialysis machine. Investigations showed severe hypertriglyceridemia of >1000 mg/dl. The patient had been on chronic continuous manual peritoneal dialysis until 6 months of age and recently had been switched to hemodialysis. Management included lowering of caloric intake and addition of medium chain triglyceride with reduction of the serum triglyceride levels to 300-400 mg/dl. Close monitoring of serum lipids and timely intervention is important to prevent serious complications associated with dyslipidemia. Observation of the "milky layer" in the deaerator of the hemodialysis machine may be an interesting visual clue of underlying severe hypertriglyceridemia.