BACKGROUND: Skeletal muscle alterations are associated with higher mortality and morbidity in patients with liver cirrhosis. Assessing these changes seems to be a promising method for identifying patients at a high risk of poor outcomes following liver transplantation (LT). This is particularly important given the current global shortage of organ donors. However, evidence of the impact of these alterations on the prognosis of patients undergoing LT is inconclusive. The aim of our prospective study was to evaluate the impact of skeletal muscle changes, reflected in sarcopenia, myosteatosis and metabolic changes in the calf muscles, on perioperative outcomes and long-term survival after LT. We also sought to determine the posttransplant evolution of the resting muscle metabolism. METHODS: We examined 134 adult LT candidates. Of these, 105 underwent LT. Sarcopenia and myosteatosis were diagnosed by measuring the skeletal muscle index and mean psoas muscle radiation attenuation, respectively, which were obtained from computed tomography (CT) scans taken during pretransplant assessment. Additionally, patients underwent 31P MR spectroscopy (MRS) of the calf muscles at rest before LT and 6, 12 and 24 months thereafter. The median follow-up was 6 years. RESULTS: Patients with abnormal 31P MRS results and CT-diagnosed myosteatosis prior to LT had significantly worse long-term survival after LT (hazard ratio (HR), 3.36; 95% confidence interval (CI), 1.48-7.60; p = 0.0021 and HR, 2.58; 95% CI, 1.06-6.29; p = 0.03, respectively). Multivariable analysis showed that abnormal 31P MR spectra (HR, 3.40; 95% CI, 1.50-7.71; p = 0.003) were a better predictor of worse long-term survival after LT than myosteatosis (HR, 2.78; 95% CI, 1.14-6.78; p = 0.025). Patients with abnormal 31P MR spectra had higher blood loss during LT (p = 0.038), required a higher number of red blood cell transfusions (p = 0.006) and stayed longer in ICU (p = 0.041) and hospital (p = 0.007). Myosteatosis was associated with more revision surgeries following LT (p = 0.038) and a higher number of received red blood cell transfusion units (p = 0.002). Sarcopenia had no significant effect on posttransplant patient survival. An improvement in the resting metabolism of the calf muscles was observed at 12 and 24 months after LT. CONCLUSIONS: Abnormal 31P MRS results of calf muscles were superior to CT-based diagnosis of myosteatosis and sarcopenia in predicting perioperative complications and long-term survival after LT. Resting muscle metabolism normalized 1 year after LT in most recipients.
- MeSH
- Adult MeSH
- Muscle, Skeletal * diagnostic imaging metabolism MeSH
- Middle Aged MeSH
- Humans MeSH
- Magnetic Resonance Spectroscopy * methods MeSH
- Tomography, X-Ray Computed * methods MeSH
- Prognosis MeSH
- Prospective Studies MeSH
- Sarcopenia etiology metabolism MeSH
- Aged MeSH
- Liver Transplantation * MeSH
- Check Tag
- Adult MeSH
- Middle Aged MeSH
- Humans MeSH
- Male MeSH
- Aged MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
Stravovací režim je faktorem, který ovlivňuje výsledky léčby každého onkologického pacienta nehledě na charakter onemocnění. Dle odhadů zemře v důsledku malnutrice 10–20 % onkologických pacientů. Významným faktorem nadměrné mortality je také nádorová kachexie, která postihuje až polovinu pacientů s pokročilým nádorovým onemocněním. Systematické hodnocení nutričního stavu a příjmu nutrientů je jedním z nejlevnějších diagnostických nástrojů, které má současná medicína k dispozici, a ze kterého pak vyplývají podpůrné terapeutické postupy v rámci onkologické léčby. Nejpozději od zjištění Oty Warburga o „závislosti“ nádorových buněk na glykolytickém metabolismu byly v nutriční onkologii zkoumány a zkušebně využívány i ketogenní režimy. Ketogenní režimy patří v současné době mezi široce popularizovanou dietní intervenci hlavně ve vztahu k metabolickým chorobám a udržování zdravé délky života. Povědomí veřejnosti o možné prospěšnosti ketogenních režimů se bez ohledu na vědeckou evidenci může projevovat v přístupech ke stravování při nádorovém onemocnění. Článek poskytne čtenáři právě přehled odborných doporučení pro onkologickou péči, definici ketogenních režimů a širších kontextů a limitací nutričního výzkumu.
Diet is a factor that influences the treatment outcome of every cancer patient, regardless of the nature of the disease. According to estimates, 10 to 20 % of cancer patients die as a result of malnutrition. Up to half of patients with advanced cancer meet the criteria for cachexia. Systematic assessment of nutritional status and nutritional status is one of the most cost-effective diagnostic tools that are available to modern medicine, and from which supportive therapeutic procedures can arise in cancer treatment. At least since Oto Warburg's findings on the "dependence" of cancer cells on glycolytic metabolism, the ketogenic regimens have been investigated and trialled. Ketogenic regimens are currently broadly popular especially in relation to metabolic diseases and the maintenance of a healthy life expectancy. Public awareness of the potential benefits and harms related to ketogenic regimens doesn’t reflect the certainty of scientific evidence. Article will provide the reader with an overview of expert recommendations for cancer care, a definition of ketogenic regimens, a broader correlation to the clinic, and an overview of some of the fundamental limitations of nutritional research.
Hormón grelín bol objavený pomerne nedávno (r. 1999). Dnes ho vnímame najmä ako jeden z dôležitých regulátorov príjmu potravy. Okrem svojej primárnej funkcie (zvyšovanie hladiny rastového hormónu) je výrazne pleiotropný: navodzuje pocit hladu, resp. chuti do jedla, participuje na vnímaní chutí, organizmus pripravuje na príjem potravy (zvyšuje motilitu a sekréciu žalúdka), má mnohé metabolické účinky – znižuje sekréciu inzulínu, brzdí lipolýzu, indukuje lipogenézu atď. Biologický polčas grelínu je krátky, preto v prípade liečebného používania prichádzajú do úvahy skôr jeho syntetické analógy – agonisty. Aktuálne sa grelín, jeho agonisty ani antagonisty v liečbe rutinne nepoužívajú (okrem anamorelínu – analógu grelínu v Japonsku), hoci s nimi prebiehajú klinické štúdie. Na základe už existujúcich poznatkov sa dá odôvodnene predpokladať, že by mohli byť efektívne pri liečbe viacerých významných patológií, ako sú sarkopénia, kachexia, obezita, Alzheimerova a Parkinsonova choroba, koronárna artériová a chronická obličková choroba a ďalšie patologické stavy s vysokou prevalenciou v séniu. V našom písomníctve zatiaľ neboli publikované informácie, ktoré by sa špecifickejšie týkali vzťahu grelínu a veku. V tomto článku ponúkame jeden z možných pohľadov na túto oblasť.
The hormone ghrelin was discovered relatively recently (in 1999). Today, we perceive it mainly as one of the important regulators of food intake. In addition to its primary function (increasing the level of growth hormone), it is significantly pleiotropic: it induces a feeling of hunger, or rather appetite, participates in the perception of tastes, prepares the body for food intake (increases motility and secretion of the stomach), has many metabolic effects – reduces insulin secretion, inhibits lipolysis, induces lipogenesis, etc. The biological half-life of ghrelin is short, therefore, in the case of therapeutic use, its synthetic analogues – agonists are more likely to be considered. Currently, ghrelin, its agonists or antagonists are not routinely used in treatment (except for anamorelin – a ghrelin analogue in Japan), although clinical trials are underway with them. Based on existing knowledge, it can be reasonably assumed that they could be effective in the treatment of several important pathologies, such as sarcopenia, cachexia, obesity, Alzheimer’s and Parkinson’s diseases, coronary artery and chronic kidney disease and other pathological conditions with a high prevalence in elderly. In our literature, there has not yet been published information that would specifically relate to the relationship between ghrelin and age. In this article, we offer one possible insight into this area.
BACKGROUND: Preservation of mobility independence is a primary goal in older adults with physical frailty and sarcopenia (PF&S). Interventions based on the combination of physical activity (PA) and nutritional counselling have been indicated as strategies for the management of this condition, although their effectiveness is not confirmed in all investigations. A possible explanation for this uncertain scenario relies in the impact of the adherence to PA interventions. Hence, the present study investigated the impact of the adherence to PA sessions on the incidence of mobility disability in older adults with PF&S. METHODS: This is a secondary analysis of an evaluator blinded, randomised controlled trial, developed in 16 clinical sites across 11 European countries, from January 2016 to 31 October 2019. Participants were community-dwelling older adults (70+ years) with PF&S enrolled in the SPRINTT trial (NCT02582138). PF&S was operationalised as having a total score from 3 to 9 on the short physical performance battery (SPPB), low appendicular lean mass and ability to complete the 400-m walk test in < 15 min. Data from participants allocated to a multicomponent intervention (PA with technological support plus nutritional counselling) and a healthy ageing lifestyle education programme (control group) were analysed. Adherence to PA was assessed based on the number of weekly sessions attended. According to recommendations of the American College of Sports Medicine, adherence was categorised as below recommendations (< 2 sessions/week, BR), meeting recommendations (2-3 sessions/week, MR), and above recommendations (> 3 sessions/week, AR). The primary outcome was incident mobility disability, operationalised as incident inability to complete the 400-m walk test in < 15 min during up to 36 months of follow-up. RESULTS: Data of 1444 participants (mean age 79.3 years, 72.6% women) were analysed. In those with SPPB scores of 3-7, MR and AR groups had lower risk of mobility disability compared with controls [MR HR (95% CI): 0.57 (0.41-0.78), p = 0.001; AR HR (95% CI): 0.33 (0.23-0.46), p < 0.001] and BR groups [MR: HR (95% CI): 0.48 (0.34-0.69), p < 0.001; AR: HR (95% CI): 0.27 (0.18-0.38), p < 0.001] in a dose-dependent manner. In those with SPPB scores of 8 or 9, the BR group had a higher risk of mobility disability than controls. MR and AR groups had a lower risk of mobility disability than the BR group. CONCLUSIONS: In older adults with PF&S, adherence to PA recommendations is associated with lower incidence of mobility disability. This benefit depends on the degree of adherence as well as baseline physical performance. TRIAL REGISTRATION: ClinicalTrials.gov NCT02582138.
- MeSH
- Exercise * physiology MeSH
- Humans MeSH
- Mobility Limitation * MeSH
- Persons with Disabilities MeSH
- Sarcopenia * physiopathology therapy MeSH
- Aged, 80 and over MeSH
- Aged MeSH
- Check Tag
- Humans MeSH
- Male MeSH
- Aged, 80 and over MeSH
- Aged MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Multicenter Study MeSH
- Randomized Controlled Trial MeSH
BACKGROUND: Neuromuscular diseases (NMDs) are rare disorders characterized by progressive muscle fibre loss, leading to replacement by fibrotic and fatty tissue, muscle weakness and disability. Early diagnosis is critical for therapeutic decisions, care planning and genetic counselling. Muscle magnetic resonance imaging (MRI) has emerged as a valuable diagnostic tool by identifying characteristic patterns of muscle involvement. However, the increasing complexity of these patterns complicates their interpretation, limiting their clinical utility. Additionally, multi-study data aggregation introduces heterogeneity challenges. This study presents a novel multi-study harmonization pipeline for muscle MRI and an AI-driven diagnostic tool to assist clinicians in identifying disease-specific muscle involvement patterns. METHODS: We developed a preprocessing pipeline to standardize MRI fat content across datasets, minimizing source bias. An ensemble of XGBoost models was trained to classify patients based on intramuscular fat replacement, age at MRI and sex. The SHapley Additive exPlanations (SHAP) framework was adapted to analyse model predictions and identify disease-specific muscle involvement patterns. To address class imbalance, training and evaluation were conducted using class-balanced metrics. The model's performance was compared against four expert clinicians using 14 previously unseen MRI scans. RESULTS: Using our harmonization approach, we curated a dataset of 2961 MRI samples from genetically confirmed cases of 20 paediatric and adult NMDs. The model achieved a balanced accuracy of 64.8% ± 3.4%, with a weighted top-3 accuracy of 84.7% ± 1.8% and top-5 accuracy of 90.2% ± 2.4%. It also identified key features relevant for differential diagnosis, aiding clinical decision-making. Compared to four expert clinicians, the model obtained the highest top-3 accuracy (75.0% ± 4.8%). The diagnostic tool has been implemented as a free web platform, providing global access to the medical community. CONCLUSIONS: The application of AI in muscle MRI for NMD diagnosis remains underexplored due to data scarcity. This study introduces a framework for dataset harmonization, enabling advanced computational techniques. Our findings demonstrate the potential of AI-based approaches to enhance differential diagnosis by identifying disease-specific muscle involvement patterns. The developed tool surpasses expert performance in diagnostic ranking and is accessible to clinicians worldwide via the Myo-Guide online platform.
- MeSH
- Adult MeSH
- Internet MeSH
- Middle Aged MeSH
- Humans MeSH
- Magnetic Resonance Imaging * methods MeSH
- Neuromuscular Diseases * diagnosis diagnostic imaging MeSH
- Machine Learning * MeSH
- Check Tag
- Adult MeSH
- Middle Aged MeSH
- Humans MeSH
- Male MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
BACKGROUND: Growth differentiation factor (GDF)-15 is a pleiotropic cytokine that is associated with appetite-suppressing effects and weight loss in patients with malignancy. OBJECTIVES: This study aims to investigate the relationships between GDF-15 levels, anorexia, cachexia, and clinical outcomes in patients with advanced heart failure with reduced ejection fraction (HFrEF). METHODS: In this observational, retrospective analysis, a total of 344 patients with advanced HFrEF (age 58 ± 10 years, 85% male, 67% NYHA functional class III), underwent clinical and echocardiographic examination, body composition evaluation by skinfolds and dual-energy x-ray absorptiometry, circulating metabolite assessment, Minnesota Living with Heart Failure Questionnaire, and right heart catheterization. RESULTS: The median GDF-15 level was 1,503 ng/L (Q1-Q3: 955-2,332 ng/L) (reference range: <1,200 ng/L). Higher GDF-15 levels were associated with more prevalent anorexia and cachexia. Patients with higher GDF-15 had increased circulating free fatty acids and beta-hydroxybutyrate, lower albumin, cholesterol, and insulin/glucagon ratio, consistent with a catabolic state. Patients with higher GDF-15 had worse congestion and more severe right ventricular dysfunction. In multivariable Cox analysis, elevated GDF-15 was independently associated with risk of the combined endpoint of death, urgent transplantation, or left ventricular assist device implantation, even after adjusting for coexisting anorexia and cachexia (T3 vs T1 HR: 2.31 [95% CI: 1.47-3.66]; P < 0.001). CONCLUSIONS: In patients with advanced HFrEF, elevated circulating GDF-15 levels are associated with a higher prevalence of anorexia and cachexia, right ventricular dysfunction, and congestion, as well as an independently increased risk of adverse events. Further studies are warranted to determine whether therapies altering GDF-15 signaling pathways can affect metabolic status and clinical outcomes in advanced HFrEF.
- MeSH
- Weight Loss * MeSH
- Cachexia * etiology MeSH
- Middle Aged MeSH
- Humans MeSH
- Anorexia * etiology MeSH
- Retrospective Studies MeSH
- Growth Differentiation Factor 15 * blood MeSH
- Aged MeSH
- Heart Failure * complications physiopathology blood MeSH
- Stroke Volume physiology MeSH
- Check Tag
- Middle Aged MeSH
- Humans MeSH
- Male MeSH
- Aged MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Observational Study MeSH
Febrility majú mnoho príčin. Najčastejšou je infekcia. Môžu sa vyskytovať aj pri onkologických ochoreniach. Febrility spôsobené priamo malignitou sa nazývajú paraneoplastické. Ich diagnostika môže byť niekedy veľmi zložitá a zdĺhavá a pred- stavuje terapeutickú výzvu aj pre skúseného lekára, pretože predstavujú nezanedbateľné percento horúčok neznámeho pôvodu. Nápomocný môže byť tzv. naproxénový test. Hladiny zápalových parametrov môžu byť niekedy zavádzajúce – pri aktívnej malignite môžu byť výrazne zvýšené. Okrem toho sa febrility u onkologického pacienta môžu vyskytovať aj z príčin infekcie, ktorá vznikne v dôsledku malígnej kachexie alebo pri febrilnej neutropénii, ktorá vzniká ako nežiaduci účinok chemoterapie, ďalej iatrogénne (po ožiari alebo po podaní chemoterapeutík), pri postihnutí centrálneho nervového systému primárnou malignitou alebo metastázami, v rámci adrenálnej krízy pri liečbe glukokortikoidmi alebo po podaní transfúzie.
Fevers have many causes. The most common is infection. They can also occur in oncological diseases. Fevers caused directly by malignancy are called paraneoplastic. Their diagnosis can sometimes be very complex and lengthy and represents a therapeutic challenge even for an experienced physician; therefore they represent a non-negligible percentage of fevers of unknown origin. The so-called can be helpful naproxen test. Levels of inflammatory parameters can sometimes be misleading - they can be significantly elevated in active malignancy. In addition, febrility in an oncology patient can also occur due to infection, which arises as a result of malignant cachexia or febrile neutropenia, which arises as an adverse effect of chemotherapy, further iatrogenically (after radiation or after the administration of chemotherapeutic drugs), when the central nervous system is affected by primary malignancy or metastases, as part of an adrenal crisis during glucocorticoid treatment or after transfusion.
Závěrečná zpráva o řešení grantu Agentury pro zdravotnický výzkum MZ ČR
nestr.
Karcinom pankreatu (KP), jehož incidence je v západních zemích na vzestupu, patří mezi nádory s nejhorší prognózou. KP je již v časných stadiích provázen nádorovou kachexií, systémovým postižením, které vede k vyčerpání hostitelových substrátových rezerv. Cílem projektu je identifikovat klíčové metabolické dráhy nádoru a tukové tkáně asociované s nádorovou kachexií. Pacienti s KP budou charakterizováni (antropometrie, inzulínová citlivost a sekrece, substrátová utilizace, zánětlivé parametry) s cílem komplexní metabolické diagnostiky nádorové kachexie. Primární kultury z nádoru budou podrobeny metabolomické analýze, zejména ve vztahu k metabolizmu glutaminu a aminokyselin s větveným řetězcem, a interferenci jejich degradačních drah. Ve vzorku peripankreatického tuku bude analyzována lipolytická a sekreční aktivita. U diferencovaných adipocytů bude sledována schopnost inzulín-senzitizujících látek omezit uvolňování lipidů vyvolané nádorovým médiem. Výsledky umožní popsat substrátový cross-talk hostitele a nádoru a identifikovat její potenciální léčebné cíle kachexie u KP.; Pancreatic cancer (PC), whose incidence is increasing in the Western countries, ranks among tumours with the worst prognosis. PC is associated with early development of cancer cachexia, a systemic condition leading to the depletion of host substrate reserves. The project aims to identify key metabolic pathways of the tumour and adipose tissue related to cancer cachexia. Patients with PC will be characterized (anthropometry, insulin sensitivity and secretion, substrate utilization, inflammatory parameters) to describe complex metabolic phenotype. Primary cultures of the tumour will be subjected to metabolomics analyses, specifically related to glutamine and branched chain amino acid metabolism and interference of their degradation pathways. Peripancreatic fat will be analysed for its lipolytic and secretory activity. In differentiated adipocytes, the ability of insulin sensitizing drugs to ameliorate lipolysis induced by tumour medium will be assessed. Results will enable to describe host-tumour substrate cross-talk and to identify potential treatment targets of PC induced cachexia.
- Keywords
- Karcinom pankreatu, Pancreatic cancer, inzulínová rezistence, insulin resistance, glutaminolýza, glutaminolysis, nádorová kachexie, cancer cachexia, Lipolýza, BCAA, Lipolysis, BCAA,
- NML Publication type
- závěrečné zprávy o řešení grantu AZV MZ ČR
- MeSH
- Diagnostic Techniques, Cardiovascular MeSH
- Health Care Economics and Organizations MeSH
- Cachexia etiology MeSH
- Cardio-Renal Syndrome etiology MeSH
- Contraindications, Procedure MeSH
- Humans MeSH
- Heart-Assist Devices MeSH
- Disease Progression * MeSH
- Ventricular Remodeling MeSH
- Liver Failure etiology MeSH
- Heart Failure * complications MeSH
- Histocompatibility Testing methods MeSH
- Heart Transplantation methods MeSH
- Check Tag
- Humans MeSH
- Publication type
- Review MeSH
- MeSH
- Geriatric Assessment methods MeSH
- Cachexia etiology physiopathology MeSH
- Frail Elderly MeSH
- Kwashiorkor etiology physiopathology prevention & control MeSH
- Humans MeSH
- Protein-Energy Malnutrition etiology physiopathology prevention & control psychology MeSH
- Sarcopenia * etiology physiopathology prevention & control MeSH
- Aged, 80 and over MeSH
- Aged MeSH
- Muscular Disorders, Atrophic etiology physiopathology MeSH
- Check Tag
- Humans MeSH
- Aged, 80 and over MeSH
- Aged MeSH
- Publication type
- Review MeSH