Dyslipidémie jsou většinou označovány za onemocnění hromadného výskytu. Existuje však i celá řada dyslipidémií vyskytujících se vzácně. Většina z nich je geneticky podmíněná. Vybrali jsme 3 onemocnění, pro která je dostupná nová terapie, jež zásadně mění prognózu pacientů. Homozygotní familiární hypercholesterolémie je spojená s extrémní elevací LDL cholesterolu, což vede k předčasné manifestaci aterosklerotického kardiovaskulárního onemocnění již v první dekádě života. Díky novým hypolipidemikům, jako jsou evinakumab a lomitapid, mají dnes pacienti daleko lepší prognózu. Lipodystrofie jsou heterogenní skupinou onemocnění, při kterých dochází k progresivnímu úbytku tukové tkáně a z toho plynoucím metabolickým abnormalitám. S příchodem kauzální terapie metreleptinem můžeme pacientům výrazně pomoci s ovlivněním těchto metabolických komplikací. Familiární chylomikronémie sice není spojená se zvýšeným rizikem aterosklerotického kardiovaskulárního onemocnění, ale je provázená extrémně vysokými koncentracemi triglyceridů, které vedou k častým atakám akutních pankreatitid, jež mohou být fatální. Terapie volanesorsenem snižuje hypertriglyceridémii a tím i riziko rozvoje akutní pankreatitidy. Byť se tato onemocnění vyskytují vzácně, je zapotřebí na ně myslet a diagnostikovat je včas. Mezioborová spolupráce je při vyhledávání a léčbě těchto pacientů esenciální.

Dyslipidemias are mostly considered to be diseases with mass incidence. However, there are also several dyslipidemias that occur within the framework of rare diseases. Most of them are genetically determined. In this review, we have focused on three selected diseases for which new therapy is available and significantly change prognosis of the patients. Homozygous familial hypercholesterolaemia is associated with extreme elevation of LDL cholesterol, leading to premature manifestation of atherosclerotic cardiovascular disease in the first decade of life. Thanks to new hypolipidemic drugs such as evinacumab and lomitapide, patients today have a much better prognosis than in the past. Lipodystrophies are a heterogeneous group of diseases characterized by progressive loss of adipose tissue leading to metabolic abnormalities. Due to new causal metreleptine therapy, we can help patients with managing these metabolic complications significantly. Familial chylomicronemia is not associated with an increased risk of atherosclerotic cardiovascular disease, but it is accompanied by extremely high levels of triglycerides, leading to frequent attacks of acute pancreatitis, which can be potentially fatal. Therapy with volanesorsen leads to a reduction of hypertriglyceridemia, thereby reducing the risk of developing acute pancreatitis. Although these diseases are rare, it is necessary to think about them and diagnose them early. Interdisciplinary cooperation is essential during search and treatment of these patients.

• Keywords
• familiární chylomikronémie, evinakumab, lomitapid,
• MeSH
• Benzimidazoles therapeutic use   MeSH
• Homozygous Familial Hypercholesterolemia * diagnosis   drug therapy   genetics   MeSH
• Humans MeSH
• Lipodystrophy diagnosis   drug therapy   genetics   MeSH
• Antibodies, Monoclonal therapeutic use   MeSH
• Mutation MeSH
• Hydroxymethylglutaryl-CoA Reductase Inhibitors therapeutic use   MeSH
• Rare Diseases MeSH
• Check Tag
• Humans MeSH
• Publication type
• Review MeSH

BACKGROUND: There are scarce data available on upadacitinib in children with Crohn's disease (CD). AIM: To evaluate the effectiveness and safety of upadacitinib as an induction therapy in paediatric CD. METHODS: This was a multicentre retrospective study between 2022 and 2024 of children treated with upadacitinib for induction of remission of active CD conducted in 30 centres worldwide affiliated with the IBD Interest and Porto group of the ESPGHAN. We recorded demographic, clinical and laboratory data and adverse events (AEs) at week 8 post-induction. The analysis of the primary outcome was based upon the intention-to-treat (ITT) principle. RESULTS: We included 100 children (median age 15.8 [interquartile range 14.3-17.2]). All were previously treated with biologic therapies including 89 with ≥ 2 biologics. At the end of the 8-week induction period, we observed clinical response, clinical remission and corticosteroid- and exclusive enteral nutrition-free clinical remission (CFR) in 75%, 56% and 52%, respectively. By the end of induction, 68% had achieved normalisation of C-reactive protein, and 58% had faecal calprotectin (FC) < 150 mcg/g. There was combined CFR and FC remission in 13/31 children with available data at 8 weeks (13% of the ITT population). AEs were recorded in 24 children; the most frequent was acne in 12. Two AEs (severe acne and hypertriglyceridemia) led to discontinuation of therapy. CONCLUSION: Upadacitinib is an effective induction therapy for refractory paediatric CD. Efficacy should be weighed against the potential risks of AEs.

• MeSH
• Crohn Disease * drug therapy   MeSH
• Child MeSH
• Heterocyclic Compounds, 3-Ring * therapeutic use   MeSH
• Remission Induction * methods   MeSH
• Humans MeSH
• Adolescent MeSH
• Retrospective Studies MeSH
• Treatment Outcome MeSH
• Check Tag
• Child MeSH
• Humans MeSH
• Adolescent MeSH
• Male MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Multicenter Study MeSH

Background: Hypertriglyceridemia has serious health risks such as cardiovascular disease, type 2 diabetes mellitus, nephropathy, and others. Fenofibrate is an effective hypolipidemic drug, but its benefits for ameliorating disorders associated with hypertriglyceridemia failed to be proven in clinical trials. Methods: To search for possible causes of this situation and possibilities of their favorable influence, we tested the effect of FF monotherapy and the combination of fenofibrate with silymarin on metabolic disorders in a unique model of hereditary hypertriglyceridemic rats (HHTg). Results: Fenofibrate treatment (100 mg/kg BW/day for four weeks) significantly decreased serum levels of triglyceride, (-77%) and free fatty acids (-29%), the hepatic accumulation of triglycerides, and the expression of genes encoding transcription factors involved in lipid metabolism (Srebf2, Nr1h4. Rxrα, and Slco1a1). In contrast, the hypertriglyceridemia-induced ectopic storage of lipids in muscles, the heart, and kidneys reduced glucose utilization in muscles and was not affected. In addition, fenofibrate reduced the activity of the antioxidant system, including Nrf2 expression (-35%) and increased lipoperoxidation in the liver and, to a lesser extent, in the kidneys and heart. Adding silymarin (micronized form, 600 mg/kg BW/day) to fenofibrate therapy increased the synthesis of glycogen in muscles, (+36%) and reduced hyperinsulinemia (-34%). In the liver, it increased the activity of the antioxidant system, including PON-1 activity and Nrf2 expression, and reduced the formation of lipoperoxides. The beneficial effect of combination therapy on the parameters of oxidative stress and lipoperoxidation was also observed, to a lesser extent, in the heart and kidneys. Conclusions: Our results suggest the potential beneficial use of the combination of FF with SLM in the treatment of hypertriglyceridemia-induced metabolic disorders.

• Publication type
• Journal Article MeSH

We investigated the sex-dependent effects of inflammatory responses in visceral adipose tissue (VAT) and perivascular adipose tissue (PVAT), as well as hematological status, in relation to cardiovascular disorders associated with prediabetes. Using male and female hereditary hypertriglyceridemic (HHTg) rats-a nonobese prediabetic model featuring dyslipidemia, hepatic steatosis, and insulin resistance-we found that HHTg females exhibited more pronounced hypertriglyceridemia than males, while HHTg males had higher non-fasting glucose levels. Additionally, HHTg females had higher platelet counts, larger platelet volumes, and lower antithrombin inhibitory activity. Regarding low-grade chronic inflammation, HHTg males exhibited increased serum leptin and leukocyte levels, while females had increased serum interleukin-6 (IL-6). Both sexes had increased circulating plasminogen activator inhibitor-1 (PAI-1), higher PAI-1 gene expression in VAT and PVAT, and elevated intercellular adhesion molecule-1 (ICAM-1) gene expression in the aorta, contributing to endothelial dysfunction in the HHTg strain. However, HHTg females had lower tumor necrosis factor alpha (TNFα) gene expression in the aorta. Severe dyslipidemia in this prediabetic model was associated with hypercoagulation and low-grade chronic inflammation. The increase in PAI-1 expression in both VAT and PVAT seems to indicate a link between inflammation and vascular dysfunction. Despite the more pronounced dyslipidemia and procoagulation status in females, their milder inflammatory response may reflect an association between reduced cardiovascular damage and prediabetes.

• MeSH
• Dyslipidemias * metabolism   pathology   genetics   MeSH
• Plasminogen Activator Inhibitor 1 * metabolism   genetics   MeSH
• Rats MeSH
• Disease Models, Animal * MeSH
• Vascular Diseases metabolism   pathology   etiology   genetics   MeSH
• Intra-Abdominal Fat * metabolism   pathology   MeSH
• Sex Characteristics MeSH
• Inflammation * metabolism   pathology   MeSH
• Animals MeSH
• Check Tag
• Rats MeSH
• Male MeSH
• Female MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH

• MeSH
• Hyperglycemia MeSH
• Hypertriglyceridemia MeSH
• Humans MeSH
• Metabolic Syndrome * epidemiology   complications   MeSH
• Obesity MeSH
• Pancreatitis * epidemiology   etiology   MeSH
• Risk Factors MeSH
• Check Tag
• Humans MeSH
• Publication type
• Research Support, Non-U.S. Gov't MeSH
• Review MeSH

• Keywords
• studie Bridge–TIMI 73, olezarsen,
• MeSH
• Hypertriglyceridemia * drug therapy   MeSH
• Humans MeSH
• Oligonucleotides pharmacology   therapeutic use   MeSH
• Randomized Controlled Trials as Topic MeSH
• Heart Disease Risk Factors MeSH
• Check Tag
• Humans MeSH

Abdominální katastrofa je závažný klinický stav, který obvykle vzniká jako komplikace při léčbě nitrobřišních netraumatických onemocnění anebo při poranění břicha. Kniha je odborným pojednáním, které vychází z dlouholetých zkušeností autorského kolektivu. Provází čtenáře všemi etapami léčby pacientů a pozornost věnuje jednotlivým úskalím léčby.

• Keywords
• Anesteziologie, resuscitace, emergency,
• MeSH
• Abdomen pathology   MeSH
• Comprehensive Health Care MeSH
• Digestive System Diseases therapy   MeSH
• Nutrition Therapy MeSH
• Critical Care MeSH
• Emergency Treatment MeSH
• Catastrophic Illness therapy   MeSH

• NML Fields
• gastroenterologie
• anesteziologie a intenzivní lékařství
• urgentní lékařství

Lipodystrofické syndromy jsou heterogenní skupinou vzácných onemocnění spojených se ztrátou podkožní tukové tkáně různého rozsahu, která vede k závažným metabolickým komplikacím – hypertriglyceridemii, steatóze jater a zejména inzulinové rezistenci. Tyto komplikace mohou zkracovat život. V důsledku chybění tukové tkáně dochází k deficitu adipokinů, zejména leptinu. V léčbě lipodystrofických syndromů se uplatňuje konvenční složka – standardní léčba metabolických komplikací, ale také nedávno zavedené podávání rekombinantního leptinu.(metreleptinu) který kompenzuje leptinový deficit. Jeho podávání významně zlepšuje klinický stav pacientů a jejich metabolické komplikace. Uplatňuje se v léčení jak generalizované, tak i parciální lipodystrofie.

Lipodystrophy syndromes represent a heterogeneous group of rare diseases characterized by various degree of adipose tissue loss that results in severe metabolic complications, including hypertriglyceridemia, steatohepatitis and particularly insulin resistance. These complications may increase the mortality rate. Adipokine deficiency, and especially leptin deficiency, is due to fat tissue loss. Therapy for lipodystrophy primarily consists of a conventional approach that involves standard treatments of metabolic abnormalities. Recently, recombinant leptin.(metreleptin) administration has been introduced to compensate for leptin deficiency. This therapy markedly improves the overall patients’ status and metabolic complications and was approved for the treatment of both generalized and partial lipodystrophy.

• MeSH
• Child MeSH
• Insulin Resistance genetics   MeSH
• Quality of Life MeSH
• Leptin pharmacology   classification   therapeutic use   MeSH
• Humans MeSH
• Lipodystrophy * diagnosis   drug therapy   classification   complications   congenital   MeSH
• Subcutaneous Fat metabolism   pathology   MeSH
• Adipocytes metabolism   pathology   MeSH
• Check Tag
• Child MeSH
• Humans MeSH
• Publication type
• Review MeSH

Druhá část cyklu o parenterální nutrici v neonatologii se zaměřuje na makronutrienty a energii. Makronutrienty poskytují primární nutriční zdroj energie a můžeme je rozdělit na bílkoviny (proteiny), tuky (lipidy) a cukry (sacharidy). V parenterální nutrici se bílkoviny dodávají ve formě aminokyselin, cukry ve formě glukózy a tuky jsou podávány v podobě intravenózních lipidových emulzí. Zhodnocení aktuálního stavu novorozence a biochemický monitoring přívodu makronutrientů jsou zásadní pro optimalizaci dodávky živin a prevenci závažných komplikací.

The second part of the neonatal parenteral nutrition series focuses on macronutrients and energy. Macronutrients provide the primary nutritional source of energy and can be classified into proteins, fats (lipids), and sugars (carbohydrates). In neonatal parenteral nutrition, proteins are provided in the form of amino acids, sugars in the form of glucose, and fats are administered in the form of intravenous lipid emulsions. Evaluating the condition of a newborn and biochemical monitoring of macronutrient intake are essential for optimizing nutrient delivery and preventing serious complications.

• MeSH
• Amino Acids administration & dosage   classification   MeSH
• Energy Intake MeSH
• Hypertriglyceridemia etiology   pathology   MeSH
• Blood Glucose analysis   MeSH
• Lipids physiology   therapeutic use   MeSH
• Infant, Newborn MeSH
• Parenteral Nutrition * methods   adverse effects   MeSH
• Glucose Metabolism Disorders etiology   MeSH
• Proteins therapeutic use   MeSH
• Parenteral Nutrition Solutions analysis   administration & dosage   pharmacology   MeSH
• Carbohydrates therapeutic use   MeSH
• Intestinal Failure diagnosis   etiology   drug therapy   MeSH
• Fat Emulsions, Intravenous administration & dosage   pharmacology   classification   MeSH
• Nutrients * administration & dosage   classification   MeSH
• Check Tag
• Infant, Newborn MeSH
• Publication type
• Review MeSH

Publikace se zaměřuje na různé typy abdominálních katastrof a na jejich komplexní léčbu. Určeno odborné veřejnosti.; Abdominální katastrofa je závažný klinický stav, který obvykle vzniká jako komplikace při léčbě nitrobřišních netraumatických onemocnění anebo při poranění břicha. Kniha je odborným pojednáním, které vychází z dlouholetých zkušeností autorského kolektivu. Provází čtenáře všemi etapami léčby pacientů a pozornost věnuje jednotlivým úskalím léčby.

• Keywords
• abdominální katastrofa, břišní katastrofa,
• MeSH
• Abdomen pathology   MeSH
• Comprehensive Health Care MeSH
• Digestive System Diseases therapy   MeSH
• Nutrition Therapy MeSH
• Critical Care MeSH
• Emergency Treatment MeSH
• Catastrophic Illness therapy   MeSH

• Conspectus
• Patologie. Klinická medicína
• NML Fields
• gastroenterologie
• anesteziologie a intenzivní lékařství
• urgentní lékařství
• NML Publication type
• kolektivní monografie