Secondary hemophagocytic lymphohistiocytosis in pediatric patients with visceral leishmaniasis and Epstein-Barr virus infection.

Visceral leishmaniasis-associated hemophagocytic lymphohistiocytosis (VL-HLH) is indistinguishable from those of HLH of other etiologies due to the overlap symptoms, posing a serious threat to life. In this study, we aimed to provide insights for early diagnosis and improve outcomes in pediatric patients with VL-HLH. We retrospectively analyzed the clinical and laboratory data of 10 pediatric patients with VL-HLH and 58 pediatric patients with Epstein-Barr virus-associated hemophagocytic lymphohistiocytosis (EBV-HLH). The median time from symptom onset to cytopenia in patients with VL-HLH and EBV-HLH was 11 days (interquartile range, 7-15 days) and five days (interquartile range, 3.75-9.25 days) (P = 0.005). Both groups showed liver injury and increased lactate dehydrogenase levels; however the levels of aspartate aminotransferase, alanine aminotransferase, direct bilirubin, and lactate dehydrogenase in patients with VL-HLH were significantly lower than those in patients with EBV-HLH (P < 0.05). The fibrinogen and triglyceride levels were almost normal in VL-HLH patients but were significantly altered in EBV-HLH cases ( P < 0.05). The positive rate of first bone marrow microscopy examination, anti-rK39 IgG detection, and blood metagenomic next-generation sequencing was 50%, 100%, and 100%, respectively. After VL diagnosis, eight patients were treated with sodium stibogluconate and two were treated with liposomal amphotericin B. All the patients with VL-HLH recovered. Our study demonstrates that regular triglyceride and fibrinogen levels in pediatric patients with VL-HLH may help in differential diagnosis from EBV-HLH. VL-HLH is milder than EBV-HLH, with less severe liver injury and inflammatory responses, and timely treatment with antileishmanial agents is essential to improve the outcomes of pediatric patients with VL-HLH.

Umbrella Review: Association Between Antipsychotic Drugs and Metabolic Syndrome Hallmarks in Children and Adolescents.

OBJECTIVE: To summarize the available evidence on metabolic parameters indicating metabolic adverse effects and risk of metabolic syndrome in children and adolescents treated with antipsychotics, following a pre-specified protocol (PROSPERO ID 252336). METHOD: We searched PubMed, Embase and PsycINFO until May 14, 2021, to identify systematic reviews (SR), meta-analyses (MA) and network meta-analyses (NMA) examining symptoms associated to metabolic syndrome in patients <18 years of age who required treatment with oral antipsychotic drugs. Evidence from quantitative analyses for all outcomes related to anthropometric, glyco-metabolic, and blood pressure parameters (measured from baseline to intervention-end and/or follow-up, in subjects exposed to antipsychotics and placebo) was reported on the basis of their metrics (median difference [medianD], mean difference [MD], standardized mean difference [SMD], odds ratio [OR], risk ratio ([RR]). A qualitative synthesis was also made. A formal quality assessment of the included studies was carried out by using the AMSTAR 2. We also provided a hierarchical stratification of the evidence from meta-analyses based on the class of evidence. RESULTS: A total of 23 articles (13 MA, 4 NMA and 6 SR) were included for review. As compared with placebo, an increase in triglyceride levels was associated with olanzapine (medianD [95% CI]: 37 [12.27, 61.74] mg/dL; MD [95% CI]: 38.57 [21.44, 55.77] mg/dL) and quetiapine (medianD [95% CI]: 21.58 [95% CI]: 4.27, 38.31 mg/dL; MD [95% CI]: 34.87 [20.08, 49.67] mg/dL; SMD [95% CI]: 0.37 [0.06, 0.068]), whereas decreased triglyceride levels were found for lurasidone. Increased total cholesterol level was associated with asenapine (medianD [95% CI]: 9.1 [1.73, 16.44] mg/dL), quetiapine (medianD [95% CI]: 15.60 [7.30, 24.05] mg/dL; olanzapine (MD [95% CI] from 3.67 [1.43, 5.92] mg/dL to 20.47 [13.97, 26.94] mg/dL]; and lurasidone (medianD [95% CI]: 8.94 [1.27, 16.90] mg/dL). Change in glucose levels did not differ among antipsychotics or placebo. Lurasidone, molindone, and ziprasidone were the best tolerated in terms of weight gain. According to the AMSTAR 2 scoring system, 13 (56.5%) reviews were rated as very low quality. According to classes of evidence, most MA were level 4, especially because of their limited total sample size. CONCLUSION: By collating meta-analyses assessing biochemical markers of metabolic syndrome in antipsychotic-treated children, we conclude that olanzapine should not be the antipsychotic of choice in patients at risk for hypertriglyceridemia or hypercholesterolemia. Aripiprazole and lurasidone appear to be better tolerated in terms of metabolic adverse events. Insufficient meta-analytic data are available to provide a precise risk estimate of metabolic syndrome, and, overall, the quality of evidence is low. STUDY REGISTRATION INFORMATION: Association between the use of antipsychotic drugs and alterations of the parameters defining the Metabolic Syndrome (MetS) in children and adolescents: an umbrella review; https://www.crd.york.ac.uk/prospero/; CRD42021252336.

Residual cardiovascular risk: When should we treat it?

Cardiovascular disease (CVD) still being the most common cause of death in worldwide. In spite of development of new lipid-lowering therapies which optimize low-density lipoprotein cholesterol (LDL-c) levels, recurrence of CVD events implies addressing factors related with residual cardiovascular (CV) risk. The key determinants of residual CV risk include triglyceride-rich lipoproteins (TRLs) and remnant cholesterol (RC), lipoprotein(a) [Lp(a)] and inflammation including its biochemical markers such as high sensitivity C reactive protein (hs-CRP). On the other hand, unhealthy lifestyle habits, environmental pollution, residual thrombotic risk and the residual metabolic risk determined by obesity and type 2 diabetes (T2D) have a specific weight in the residual CV risk. New pharmacologic therapies and pathways are being explored such as inhibition of apolipoprotein C-III (apoC-III) and angiopoietin-related protein 3 (ANGPTL3) in order to explore if a reduction in TRLs and RC reduce CVD events. Therapeutic target of inflammation plays an attractive way to reduce the atherosclerotic process and to date, approved therapies as colchicine plays a beneficial effect in chronic inflammation and residual CV risk. Lp(a) constitutes one of the most residual CV risk factor due to linkage with CVD and aortic valve stenosis. New and hopeful treatments including antisense oligonucleotides (ASO) and small-interfering ribonucleic acid (siRNA) which interfere in LP(a) codification have been developed to achieve an adequate control in Lp(a) levels. This review points out the paradigms of residual CV risk, discus how we should manage their features and summarize the different therapies targeting each residual CV risk factor.

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.

[Systemic lupus erythematosus associated macrophage activation syndrome with neuropsychiatric symptoms: A report of 2 cases].

Systemic lupus erythematosus (SLE) associated macrophage activation syndrome (MAS) is clinically severe, with a high mortality rate and rare neuropsychiatric symptoms. In the course of diagnosis and treatment, it is necessary to actively determine whether the neuropsychiatric symptoms in patients are caused by neuropsychiatric systemic lupus erythematosus (NPSLE) or macrophage activation syndrome. This paper retrospectively analyzed the clinical data of 2 cases of SLE associated MAS with neuropsychiatric lesions, Case 1: A 30-year-old female had obvious alopecia in 2019, accompanied by emaciation, fatigue and dry mouth. In March 2021, she felt weak legs and fell down, followed by fever and chills without obvious causes. After completing relevant examinations, she was diagnosed with SLE and given symptomatic treatments such as hormones and anti-infection, but the patient still had fever. The relevant examinations showed moderate anemia, elevated ferritin, elevated triglycerides, decreased NK cell activity, and a perforin positivity rate of 4.27%, which led to the diagnosis of "pre-hemophagocytic syndrome (HPS)". In May 2021, the patient showed mental trance and babble, and was diagnosed with "SLE-associated MAS"after completing relevant examinations. After treatment with methylprednisolone, anti-infection and psychotropic drugs, the patient's temperature was normal and mental symptoms improved. Case 2: A 30-year-old female patient developed butterfly erythema on both sides of the nose on her face and several erythema on her neck in June 2019, accompanied by alopecia, oral ulcers, and fever. She was diagnosed with "SLE" after completing relevant examinations, and her condition was relieved after treatment with methylprednisolone and human immunoglobulin. In October 2019, the patient showed apathy, no lethargy, and fever again, accompanied by dizziness and vomiting. The relevant examination indicated moderate anemia, decreased NK cell activity, elevated triglycerides, and elevated ferritin. The patient was considered to be diagnosed with "SLE, NPSLE, and SLE-associated MAS". After treatment with hormones, human immunoglobulin, anti-infection, rituximab (Mabthera), the patient's condition improved and was discharged from the hospital. After discharge, the patient regularly took methylprednisolone tablets (Medrol), and her psychiatric symptoms were still intermittent. In November 2019, she developed symptoms of fever, mania, and delirium, and later turned to an apathetic state, and was given methylprednisolone intravenous drip and olanzapine tablets (Zyprexa) orally. After the mental symptoms improved, she was treated with rituximab (Mabthera). Later, due to repeated infections, she was replaced with Belizumab (Benlysta), and she was recovered from her psychiatric anomalies in March 2021. Through the analysis of clinical symptoms, imaging examination, laboratory examination, treatment course and effect, it is speculated that the neuropsychiatric symptoms of case 1 are more likely to be caused by MAS, and that of case 2 is more likely to be caused by SLE. At present, there is no direct laboratory basis for the identification of the two neuropsychiatric symptoms. The etiology of neuropsychiatric symptoms can be determined by clinical manifestations, imaging manifestations, cerebrospinal fluid detection, and the patient's response to treatment. Early diagnosis is of great significance for guiding clinical treatment, monitoring the condition and judging the prognosis. The good prognosis of the two cases in this paper is closely related to the early diagnosis, treatment and intervention of the disease.

Effect of Grape Seed Procyanidins Combined with Allicin on Lipid Levels in Hyperlipidemic Rats.

OBJECTIVES: To study the effects of grape seed proanthocyanidins (GSP) combined with allicin on serum lipids level and vascular damage in a rat model of hyperlipidemia. MATERIALS AND METHODS: SD rats(male, 170-220 gn= 40) were randomized into five groups (n = 8/group): modelhigh fat and cholesterol diet; controlnormal diet; model+low-dose (GSP+allicin )(GSP 45mg/kg, allicin 30mg/kg, orally); model+high-dose (GSP+allicin) (GSP180mg/kg, allicin 90mg/kg, orally) and positive control (model+simvastatin (4 mg/kg)). Normal control group was fed conventionally, and remaining four groups were fed high cholesterol and fat food to replicate the high fat model. After 9 weeks, the normal control group continued to receive regular feeding, while the other groups continued to receive high-fat feeding. At the same time, model and normal control groups were given equal volume of physiological saline by gavage, and the other treatment groups began to receive corresponding drugs by gavage once a day. After 4 weeks, serum levels of total cholesterol (TC), triglyceride (TG), low density lipoprotein cholesterol (LDL-C) as well as high-density lipoprotein cholesterol (HDL-C) in rats were determined. And the body weight of rat, total antioxidant capacity (T-AOC), superoxide dismutase (SOD) and malondialdehyde (MDA)in serum were identified. The level of endothelin-1(ET-1) was quantitative analysis by ELISA assay. RESULTS: In comparison to normal controls, the model group displayed a marked rise in body weight, an increment in serum concentrations of LDL-C, TG and TC, as well as a decline in HDL (P<0.01), demonstrating successful model replication; All doses of GSP in combination with allicin resulted in a reduction in TG, LDL-C, and TC and an enhancement in HDL-C in contrast to the model control (all P<0.05). High-dose (GSP+allicin ) decreased MDA, and increased T-AOC and SOD activity(all P<0.01). All doses of GSP combined with allicin decreased ET-1 (all P<0.05). In addition, the protective effect of GSP combined with allicin was dose-dependent. CONCLUSIONS: Studies have shown that GSP combined with allicin can significantly improve blood lipids in hyperlipidemic rats, and this mechanism may be related to antioxidants and reduced endothelial damage.

Worms and welfare: Behavioural and physiological changes associated with gastrointestinal nematode parasitism in lambs.

Parasitism with gastrointestinal nematodes (GIN) is a worldwide issue impacting negatively on animal production, health, and welfare. Therefore, early diagnostic signs of parasitism are required to allow for timely interventions. The objective of this study was to evaluate the behavioural and physiological changes in lambs associated with GIN infection. We used 30, 8-month-old Romney-cross wethers, that were administered anthelmintics until faecal egg counts (FEC) were zero and housed in an indoor facility. The study lasted 9 weeks, which comprised a 3-week pre-treatment, and a 6-week treatment phase. Lambs were randomly assigned to one of two treatments (n = 15/treatment) trickle-dosed with: 1) 1500 infective third stage larvae (L3) three days/week for 6 weeks (27,000 total L3; challenged), or 2) water 3 days/week for 6 weeks (control). Within each pen there were 5 pairs of lambs (balanced for liveweight), with each pair comprising a challenged and control lamb. Blood, faecal, and saliva samples were collected 1 week pre-treatment and weekly for 6 weeks of treatment. Behaviour was observed (e.g., feeding, lying, standing) from video-camera recordings using scan sampling every 5 min for 8 h, 1 day pre-treatment and on the day immediately prior to physiological sampling across the 6-week treatment phase (7 days in total). Accelerometers were attached to each lamb to continuously monitor behaviour from 3 weeks pre-treatment and for the remainder of the study. Liveweight, body condition, faecal soiling and faecal consistency scoring were performed weekly as was lipidomic analysis of plasma samples. From week 2 of treatment, challenged lambs spent less time feeding and more time lying than control lambs until week 5 of treatment (P ≤ 0.01). At week 3 of treatment, elevated lipids (mainly triglycerides and phospholipids), loose faeces and faecal soiling around the anus were observed in challenged lambs compared with controls (P ≤ 0.05). From week 4 of treatment, FEC were elevated in the challenged compared to control lambs (P ≤ 0.05). There was also lower liveweight gain at 4 and 5 weeks of treatment in the challenged lambs compared with control lambs (P ≤ 0.05). These results show a clear timeline of changes in behaviour (e.g., feeding and lying), lipids such as triglycerides, and digestive function (e.g., faecal soiling) suggestive of GIN subclinical disease, which show promise for use in future studies on early identification of subclinical GIN parasitism in lambs.

Metabolic Dysfunction, Triglyceride-Glucose Index, and Risk of Severe Asthma Exacerbation.

BACKGROUND: Metabolic conditions may worsen asthma. There is a need to define a composite biomarker of metabolic dysfunction that has relevance to asthma outcomes. OBJECTIVE: To determine the association of the triglyceride-glucose index (TyG), a biomarker of metabolic syndrome and insulin resistance, with risk of severe asthma exacerbation. METHODS: A 5-year retrospective cohort of patients with asthma receiving health care from the US Veterans Health Administration from January 1, 2015, to December 31, 2019, was constructed. Fasting TyG values were extracted. Patients were followed for a severe asthma exacerbation, defined as an asthma-related corticosteroid prescription fill or an emergency encounter or hospitalization for asthma. Adjusted models estimated the relative hazard of exacerbation associated with elevated TyG, accounting for known exacerbation risk factors. RESULTS: A total of 108,219 patients fulfilled study criteria. Over 286,343 person-years of follow-up, 21,467 exacerbations were identified, corresponding to a crude rate of 7.5 exacerbations/100 person-years. In exploratory analysis, we found a threshold effect at a TyG of 8.3, which was defined as elevated. In a fully adjusted model, patients with an elevated TyG had a 6% (95% CI, 3%-10%) higher hazard for severe asthma exacerbation, independent of eosinophil count, smoking, obesity, and asthma treatment intensity. CONCLUSIONS: Elevated TyG is a risk factor for severe asthma exacerbation independent of conventional predictors. Elevated TyG may identify patients who warrant more intensive asthma treatment and who are candidates for future clinical trials of metabolic intervention for purposes of improving asthma morbidity.

Differential effects on renal function and glucose metabolism of renal dependent bezafibrate and non-renal dependent pemafibrate in patients with hypertriglyceridemia.

OBJECTIVE: Among fibrates as triglyceride-lowering agents, bezafibrate and fenofibrate are predominantly renally excreted, while pemafibrate is mainly hepatically metabolized and biliary excreted. To elucidate possible different properties among fibrates, this retrospective observational study examined the changes in clinical laboratory parameters, including indices of renal function and glucose metabolism, in cases of switching from bezafibrate to pemafibrate. MATERIALS AND METHODS: In 93 patients with hypertriglyceridemia, the average values of laboratory parameters including serum creatinine, estimated glomerular filtration rate (eGFR), plasma glucose, and hemoglobin A1c on respective two occasions before and after switching from bezafibrate to pemafibrate were evaluated. RESULTS: Triglycerides, low-density and high-density lipoprotein cholesterol, creatine kinase, and uric acid did not change before and after switching from bezafibrate to pemafibrate. Serum creatinine significantly decreased and eGFR significantly increased after switching from bezafibrate to pemafibrate (p < 0.001, respectively). Plasma glucose tended to increase (p = 0.070) and hemoglobin A1c significantly increased (p < 0.001) after switching to pemafibrate. The degrees of changes in creatinine, eGFR, glucose, and hemoglobin A1c before and after drug switching were not affected by the presence or absence of coexisting disease, and with or without drug treatment including statin and renin-angiotensin system inhibitor. CONCLUSION: Our findings indicate that switching from bezafibrate to pemafibrate produces a significant decrease in serum creatinine and increases in eGFR and hemoglobin A1c in patients with hypertriglyceridemia, suggesting that the effects on renal function and glucose metabolism differ among fibrates.

Successful Treatment of Cirrhotic Chylous Ascites using Orlistat and Dietary Modifications: A Case Study and Literature Review.

BACKGROUND Chylous ascites (chyloperitoneum), a condition arising from lymphatic leakage in the peritoneal cavity, is rare in liver cirrhosis patients, accounting for less than 1% of cases. Treatment typically involves therapeutic paracentesis, dietary modifications, a low-fat, high-protein diet, and medium-chain triglyceride (MCT) supplementation. Orlistat, a fat absorption inhibitor, has been reported to show potential efficacy in treating chylous ascites. CASE REPORT We detail the case of a 59-year-old male patient admitted for decompensated liver disease and worsening ascites. Diagnostic paracentesis identified chylous ascites, indicated by a 3.5 mmol/L triglyceride level. Despite administering therapeutic paracentesis, dietary modifications, MCT supplementation, Spironolactone, and Terlipressin for a presumed hepatorenal syndrome, the patient's ascites remained chylous for two weeks. On administering orlistat, a significant reduction in ascites volume and chylous content was observed, with triglyceride levels dropping to 0.7 mmol/L. CONCLUSIONS Our case illustrates the potential of orlistat in managing chylous ascites in liver cirrhosis patients, marking only the second such case reported in the existing literature. It encourages further exploration of orlistat's therapeutic potential in treating chylous ascites.

Medical management of hypertriglyceridemia in pancreatitis.

PURPOSE OF REVIEW: Hypertriglyceridemia-induced acute pancreatitis (HTG-AP) should be considered in all cases of acute pancreatitis and triglyceride levels measured early, so that appropriate early and long-term treatment can be initiated. RECENT FINDINGS: In most cases of HTG-AP, conservative management (nothing by mouth, intravenous fluid resuscitation and analgesia) is sufficient to achieve triglyceride levels less than 500 mg/dl. Intravenous insulin and plasmapheresis are sometimes used, although prospective studies showing clinical benefits are lacking. Pharmacological management of hypertriglyceridemia (HTG) should start early and target triglyceride levels of less than 500 mg/dl to reduce the risk or recurrent acute pancreatitis. In addition to currently used fenofibrate and omega-3 fatty acids, several novel agents are being studied for long-term treatment of HTG. These emerging therapies focus mainly on modifying the action of lipoprotein lipase (LPL) through inhibition of apolipoprotein CIII and angiopoietin-like protein 3. Dietary modifications and avoidance of secondary factors that worsen triglyceride levels should also be pursued. In some cases of HTG-AP, genetic testing may help personalize management and improve outcomes. SUMMARY: Patients with HTG-AP require acute and long-term management of HTG with the goal of reducing and maintaining triglyceride levels to less than 500 mg/dl.

Triheptanoin for the treatment of long-chain fatty acid oxidation disorders: Final results of an open-label, long-term extension study.

Long-chain fatty acid oxidation disorders (LC-FAODs) result in life-threatening energy metabolism deficiencies/energy source depletion. Triheptanoin is an odd-carbon, medium chain triglyceride (that is an anaplerotic substrate of calories and fatty acids) for treating pediatric and adult patients with LC-FAODs. Study CL202 (NCT02214160), an open-label extension study of study CL201 (NCT01886378), evaluated the long-term safety/efficacy of triheptanoin in patients with LC-FAODs (N = 94), including cohorts who were triheptanoin naïve (n = 33) or had received triheptanoin in study CL201 (n = 24) or in investigator-sponsored trials/expanded access programs (IST/EAPs; n = 37). Primary endpoint was the annualized rate of LC-FAOD major clinical events (MCEs; rhabdomyolysis, hypoglycemia, cardiomyopathy). Mean ± standard deviation (SD) triheptanoin treatment durations were 27.4 ± 19.9, 46.9 ± 13.6, and 49.6 ± 21.4 months for the triheptanoin-naïve, CL201 rollover, and IST/EAP cohorts, respectively. In the triheptanoin-naïve cohort, median (interquartile range [IQR]) MCE rate significantly decreased from 2.00 (0.67-3.33) events/patient/year pre-triheptanoin to 0.28 (0.00-1.43) events/patient/year with triheptanoin (p = 0.0343), a reduction of 86%. In the CL201 rollover cohort, mean ± SD MCE rate significantly decreased from 1.76 ± 1.64 events/patient/year pre-triheptanoin to 1.00 ± 1.00 events/patient/year with triheptanoin (p = 0.0347), a reduction of 43%. In the IST/EAP cohort, mean ± SD MCE rate was 1.40 ± 2.37 (median [IQR] 0.57 [0.00-1.67]) events/patient/year with triheptanoin. Safety data were consistent with previous observations. Treatment-related treatment-emergent adverse events (TEAEs) occurred in 68.1% of patients and were mostly mild/moderate in severity. Five patients had seven serious treatment-related TEAEs; all resolved. Our results confirm the long-term efficacy of triheptanoin for patients with LC-FAOD.

Hypertriglyceridemic pancreatitis managed with heparin and insulin: a case report.

BACKGROUND: Alcohol and gall stones are common causes of pancreatitis. Other causes of pancreatitis include hypertriglyceridemia, trauma, congenital anomalies, and medications. Hypertriglyceridemic pancreatitis is distinguished, as it is more severe and complicated. The management of hypertriglyceridemic pancreatitis, other than the basic care given to other pancreatitis patients, is to decrease the serum triglyceride level to less than 500 mg/dl as soon as possible. Plasmapheresis, hemofiltration, and other modalities have been proven effective therapies, but, are expensive and not easily accessible. Insulin and heparin which are cheaper alternatives for treatment, have been reported in case reports along with one randomized controlled trial. The number of patients in these reports was small, so, the therapy is not well established. For most African countries like ours, the only option for management is heparin and insulin. Despite this fact, there has not been any publication regarding this issue on our continent. CASE REPORT: We report the case of a 24 years old Ethiopian male who presented with severe central abdominal pain, easy fatiguability, and vomiting of one-day duration. He was tachycardic and tachypneic with diffuse abdominal tenderness, and had tendon xanthomas. His plasma was lactescent with a serum triglyceride level of 4775 mg/dl. His abdominal CT scan showed diffuse pancreatic swelling with a peripancreatic fluid collection, and his serum lipase was elevated. With a diagnosis of hypertriglyceridemic pancreatitis, he was managed with intravenous insulin infusion along with subcutaneous heparin. His random blood sugar was checked hourly with three episodes of hypoglycemia during therapy. His serum triglyceride level dropped to less than 500 mg/dl in three days, and he was discharged with no complications. CONCLUSION: Since our findings are consistent with a prior randomized controlled trial and compilation of case reports, it would strengthen the evidence for safety and efficacy of insulin and heparin therapy. This therapy, which is the only available therapy in most countries of our continent, would decrease most of the complications of hypertriglyceridemic pancreatitis that we face. We believe, our report would be a wake-up call for researchers and clinicians in our continent to change their practice and strengthen the evidence for the treatment.

The Effects of Medium Chain Triglyceride for Alzheimer's Disease Related Cognitive Impairment: A Systematic Review and Meta-Analysis.

BACKGROUND: The current lack of effective drug therapies for Alzheimer's disease (AD) has prompted researchers to seek alternative nutritional therapies, such as medium chain triglycerides (MCTs). However, results are inconclusive. OBJECTIVE: This systematic review and meta-analysis aims to summarize current evidence on the effect of MCT on cognitive function in patients with mild cognitive impairment (MCI) or AD. METHODS: A systematic search was conducted up until December 16, 2022, to identify human interventions reporting the effects of MCT on cognitive functioning of MCI or AD patients. 995 non-duplicated publications were identified, of which nine (n = 10 studies) met the inclusion criteria. RESULTS: Meta-analysis showed cognitive improvements in general (SMD = 0.64; 95% CI [0.05, 1.24]), but not in memory, language, and attention domains after oral MCT administration, compared to placebo. The effect of MCT was greater among APOEɛ4 (-) subjects than APOEɛ4 (+) subjects (SMD = 1.87; 95% CI [0.35, 3.40]). CONCLUSION: This review provides some evidence that treatment with MCT could improve general cognitive function in APOEɛ4 (-) cognitive impaired patients. Better characterized clinical studies are warranted before making a definitive conclusion on the use of MCT for MCI and AD management.

The association between platelet reactivity and lipoprotein levels in Framingham Heart Study participants.

BACKGROUND: Hypertriglyceridemia is an independent risk factor for major adverse cardiovascular events, though the mechanisms linking triglycerides and platelet function with thrombosis, remain elusive. The aim of this study was to assess the association between platelet function and triglyceride levels. METHODS: We included participants from the Framingham Heart Study Third Generation cohort, OMNI, and New Offspring Spouse cohort who attended the third examination cycle (2016-2019). Eligible participants were categorized into four triglyceride subgroups. RESULTS: The study comprised a total of 1897 (55.53 %) participants with normal TG levels; 883 (25.85 %) participants with high-normal TGs; 378 (11.07 %) with borderline high TGs; and 258 (7.55 %) participants with hypertriglyceridemia. After adjusting for age, sex, alcohol consumption, aspirin, statin and P2Y12 inhibitors, the levels of ADP-induced platelet aggregation were inversely associated with total cholesterol levels (P < 0.0001). Platelet disaggregation was associated with low-density lipoprotein and high-density lipoprotein cholesterol levels (P < 0.0001). Lastly, in a shear-stress chamber assay mimicking arterial flow velocities, TG levels in the normal-high group were associated with increased levels of collagen-dependent thrombogenicity (ß = 24.16, SE = 6.65, P < 0.0001). CONCLUSION: Triglyceride levels are associated with altered platelet activation and aggregation. Furthermore, increased platelet-driven thrombogenicity is directly associated with triglyceride levels after adjusting for medications and other covariates.

Successful management of rhabdomyolysis with triheptanoin in a child with severe long-chain 3-hydroxyacyl-coenzyme A dehydrogenase (LCHAD) deficiency.

Early-onset long-chain 3-hydroxyacyl-coenzyme A dehydrogenase (LCHAD) deficiency is a fatty acid ß-oxidation disorder with a poor prognosis. Triheptanoin, an anaplerotic oil with odd-chain fatty acids can improve the disease course. The female patient presented here was diagnosed at the age of 4 months, and treatment was started as fat restriction, frequent feeding, and standard medium-chain triglyceride supplementation. In follow-up, she had frequent rhabdomyolysis episodes (∼8 per year). At the age of six, she had 13 episodes in 6 months, and triheptanoin was started as part of a compassionate use program. Following unrelated hospital stays due to multisystem inflammatory syndrome in children and a bloodstream infection, she had only 3 rhabdomyolysis episodes, and hospitalized days decreased from 73 to 11 during her first year with triheptanoin. Triheptanoin drastically decreased the frequency and severity of rhabdomyolysis, but progression of retinopathy was not altered.

Long-term changes in serum levels of lipoproteins in children and adolescents with attention-deficit/hyperactivity disorder (ADHD).

Attention-deficit/hyperactivity disorder (ADHD) is a neurodevelopmental disorder affecting approximately 5% of children worldwide. The causal mechanisms of ADHD remain unclear as the aetiology of this disorder seems to be multifactorial. One research field addresses the impact on lipid metabolism and particularly serum lipid fractions on the development of ADHD symptoms. This post hoc analysis aimed to investigate long-term changes in serum levels of lipoproteins in children and adolescents with ADHD and controls. Data of German children and adolescents from the nationwide and representative "Kinder- und Jugendgesundheitssurvey (KiGGS)" study were analysed at baseline and at a ten-year follow-up. At the two time points, participants in the control group were compared with those in the ADHD group, both before and after propensity score matching. Differences in total cholesterol, low-density lipoproteins (LDL), high-density lipoproteins (HDL) and triglycerides were assessed between matched children with and without ADHD. In addition, subgroups with versus without methylphenidate use were compared at both time points. At baseline before matching, there were no significant differences for lipid parameters between participants in the ADHD group (n = 1,219) and the control group (n = 9,741): total cholesterol (Exp(ß) = 0.999, 95%-CI 0.911-1.094, p = .979), LDL (Exp(ß) = 0.967, 95%-CI 0.872-1.071, p = .525), HDL (Exp(ß) = 1.095, 95%-CI 0.899-1.331, p = .366) and triglycerides (Exp(ß) = 1.038, 95%-CI 0.948-1.133, p = .412). Propensity score matching confirmed the non-significant differences between the ADHD and non-ADHD group at baseline. At the 10-year follow-up, n = 571 participants fulfilled complete inclusion criteria, among them 268 subjects were classified as ADHD. The two groups did not significantly differ in lipid fractions, neither cross-sectionally nor with regard to long-term changes. There was also no significant difference between methylphenidate subgroups. In this sample of children and adolescents we could not reveal any significant associations between serum lipid fractions and the diagnosis of ADHD, neither cross-sectionally nor longitudinally; even when methylphenidate use was considered. Thus, further studies using larger sample sizes are required to investigate putative long-term changes in serum lipid fractions related to ADHD.

Longitudinal comparison of insulin resistance and dyslipidemia in children with and without perinatal HIV infection in South Africa.

INTRODUCTION: HIV infection is associated with insulin resistance and dyslipidaemia driven by HIV-associated immune dysregulation and antiretroviral therapy (ART). Children living with perinatally acquired HIV (CHIV) face many decades of exposure to these factors. We evaluated the longitudinal trajectory of insulin resistance and dyslipidaemia in CHIV and HIV-exposed uninfected children (CHEU), compared with children HIV-unexposed (CHU). METHODS: Four hundred and eighty-five children (141 CHIV, 169 CHEU, 175 CHU) aged 5-16 years, previously part of CHER and P1060 trials, were followed annually at Tygerberg Children's Hospital, South Africa. The primary outcome was Homeostatic Model Assessment of Insulin Resistance (HOMA-IR). Secondary outcomes included low-density lipoprotein (LDL) cholesterol, triglyceride-to-HDL ratio, android fat mass and SBP. Outcomes were evaluated using linear mixed effects models, adjusting for potential confounders. RESULTS: CHIV had 73% greater HOMA-IR than CHU in ages 6-8 years (95% CI 15.9-158.2%, P < 0.001), and 24.7% greater HOMA-IR than CHU in ages 9-10 years (0.3-55.1%, P = 0.04). By 10-11 years, the difference was not significant (P = 0.161). Longitudinally, triglyceride-to-HDL was 47.94% (34.50-62.73%, P < 0.001) higher in CHIV vs. CHU; LDL was 0.25 mmol/l (0.10-0.39, P = 0.001) higher in CHIV vs. CHU; android fat mass was 11.57% (-21.11 to -0.87%, P = 0.035) lower in CHIV than CHU. No significant difference in SBP was found. CHEU and CHU had similar outcomes. CONCLUSION: Early-treated CHIV have elevated insulin resistance, which resolves with time. Triglyceride-to-HDL ratio and LDL cholesterol were elevated into puberty. CHIV should be monitored for insulin resistance, dyslipidaemia and subclinical cardiovascular disease.

Effect of clevidipine on intracranial pressure in pediatric neurosurgical patients: a single-center retrospective review.

OBJECTIVE: Hemodynamic management in pediatric neurosurgical patients is essential for maintaining cerebral perfusion pressure (CPP), avoiding hemorrhage, and preventing secondary neurological injury. Antihypertensive infusions approved for pediatrics are not widely studied in the pediatric neurosurgical population and may have adverse effects on intracranial pressure (ICP), contributing to reduced CPP. Clevidipine is an ultra-rapid-acting intravenous antihypertensive agent used for hemodynamic control in adult surgical patients. In pediatric patients, clevidipine is safe and effective in controlling blood pressure in the perioperative period, although studies evaluating its effect on ICP in neurosurgical patients are lacking. The objective of this research was to evaluate the effect of clevidipine on ICP in pediatric neurosurgical patients. METHODS: This single-center retrospective study involved patients admitted to the pediatric ICU between January 1, 2017, and December 31, 2020. Patients eligible for inclusion had ICP monitoring devices and received clevidipine infusion for a minimum of 6 hours postoperatively, with at least one ICP measurement pre- and postinfusion. Excluded patients had an elevated preinfusion ICP > 20 mm Hg. The primary outcome was the average change in ICP from preinfusion baseline to hours 6 to < 12, 12 to < 24, and 24 to < 48 of clevidipine infusion. Secondary outcomes included frequency of ICP measurements > 20 mm Hg, CPP measurements < 50 mm Hg, treatment failure defined by a need for concurrent antihypertensive infusion, and frequency of elevated serum triglycerides > 200 mg/dL. Descriptive data were expressed as frequency with percentage or median with interquartile range as appropriate. Analysis of continuous outcome variable data involved Mann-Whitney U-tests with an alpha significance of 0.05. RESULTS: Data from 47 patients were included in the analysis. The average change in ICP from preinfusion baseline to 48 hours was < 1 mm Hg. Of 3025 total postinfusion ICP measurements in 47 patients, 67 measurements (2.2%) in 13 patients (28%) were > 20 mm Hg. CPP measurements < 50 mm Hg occurred in 16 of 45 patients (36%). Three patients (6.4%) required use of a secondary antihypertensive medication infusion, and 5 of 14 patients (36%) had serum triglycerides > 200 mg/dL. CONCLUSIONS: Use of clevidipine had minimal effect on ICP. The results of this study suggest that clevidipine is effective at safely maintaining ICP and CPP measurements without detrimental adverse effects in pediatric neurosurgical patients.

Treatment of Hypertriglyceridemia: A Review of Therapies in the Pipeline.

BackgroundThe 2018 American College of Cardiology/American Heart Association (ACC/AHA) guidelines and 2021 ACC Expert Consensus Decision Pathway recommend nonpharmacological interventions and initiation of statin therapy for patients with moderate hypertriglyceridemia and addition of fibrates or omega-3 fatty acids in severe hypertriglyceridemia. Although the association between triglyceride (TG) lowering and atherosclerotic cardiovascular disease (ASCVD) risk reduction remains controversial, patients with hypertriglyceridemia may represent a subgroup that require additional therapy to further reduce residual ASCVD risk. Moreover, medications that target novel pathways could provide alternative options for patients who are intolerant of existing therapies or doses needed to provide adequate triglyceride lowering. Objective: Assess recent evidence for TG-lowering agents including omega-3 fatty acid-based therapies, PPARα modulators, apoC-III mRNA antisense inhibitors, angiopoietin-like 3 (ANGPTL3) antibodies, and herbal supplements. Methods: A literature search was performed using PubMed with hypertriglyceridemia specified as a MeSH term or included in the title or abstract of the article along with each individual agent. For inclusion, trials needed to have a primary or secondary outcome of TG levels or TG lowering. Conclusion: Currently, the only US Food and Drug Administration approved medication for CV risk reduction in patients with hypertriglyceridemia is icosapent ethyl. Results from phase 3 trials for CaPre, pemafibrate, and volanesorsen as well as additional evidence for pipeline pharmacotherapies with novel mechanisms of action (e.g., ApoC-III mRNA antisense inhibitors and ANGPTL3 antibodies) will help to guide future pharmacotherapy considerations for patients with hypertriglyceridemia.