BACKGROUND: Cardiac magnetic resonance (CMR) plays a major diagnostic role in acute myocarditis (AM) in children as biopsy is rarely performed in this age group. Contribution of standard echocardiography (ECHO) is limited in AM, but speckle tracking echocardiography (STE) quantitatively characterizes myocardial function, with good sensitivity for detecting subclinical left ventricular (LV) dysfunction and regional kinetics disorders beyond the site of inflammation. This work aimed to evaluate the diagnostic potential of STE as compared with CMR findings in pediatric patients with AM. METHODS: The study was conducted during 2022-2023. Troponin, electrocardiography, ECHO with STE, and CMR with early and late enhancement were performed on each patient. Affected heart segments were analyzed by both STE and CMR, and the correlation of the two methods was assessed. RESULTS: During the study period, 20 children were diagnosed with AM [14 boys, 6 girls; mean age 12 years (median 14)]. On ECHO, three patients had a deviation in LV biometry, and four patients had a mild systolic function disorder. STE showed at least one affected cardiac segment in all patients, most often the inferolateral segment (16/20; 80%). Of the 20 patients, STE showed a reduction in LV global longitudinal strain in 13 (65%) patients. In all patients, CMR identified an inflammatory focus, most frequently inferolateral (15/20; 75%). The strongest accordance between STE and CMR was observed for the involvement of anterolateral segments (k = 0.88) and the weakest for inferoseptal damage (k = 0.4). CONCLUSIONS: STE can provide important diagnostic information in pediatric patients with AM. This modality supports the detection of early regional edema and subclinical myocardial dysfunction and can determine the impairment severity. STE is non-invasive and repeatable without the need for special patient preparation or for general anesthesia.

• Publikační typ
• časopisecké články MeSH

There is a well-established link between abnormal sperm chromatin states and poor motility, however, how these two processes are interdependent is unknown. Here, we identified a possible mechanistic insight by showing that Protamine 2, a nuclear DNA packaging protein in sperm, directly interacts with cytoskeletal protein Septin 12, which is associated with sperm motility. Septin 12 has several isoforms, and we show, that in the Prm2-/- sperm, the short one (Mw 36 kDa) is mis-localized, while two long isoforms (Mw 40 and 41 kDa) are unexpectedly lost in Prm2-/- sperm chromatin-bound protein fractions. Septin 12 co-immunoprecipitated with Protamine 2 in the testicular cell lysate of WT mice and with Lamin B1/2/3 in co-transfected HEK cells despite we did not observe changes in Lamin B2/B3 proteins or SUN4 expression in Prm2-/- testes. Furthermore, the Prm2-/- sperm have on average a smaller sperm nucleus and aberrant acrosome biogenesis. In humans, patients with low sperm motility (asthenozoospermia) have imbalanced histone-protamine 1/2 ratio, modified levels of cytoskeletal proteins and we detected retained Septin 12 isoforms (Mw 40 and 41 kDa) in the sperm membrane, chromatin-bound and tubulin/mitochondria protein fractions. In conclusion, our findings present potential interaction between Septin 12 and Protamine 2 or Lamin B2/3 and describe a new connection between their expression and localization, contributing likely to low sperm motility and morphological abnormalities.

• Publikační typ
• časopisecké články MeSH

BACKGROUND: Quercetin is a promising phytochemical in treating abnormalities associated with metabolic syndrome (MetS). This study aimed to explore the morphometric, metabolic, transcriptomic, and nutrigenetic responses to quercetin supplementation using two genetically distinct MetS models that only differ in the variant of the MetS-related Zbtb16 gene (Zinc Finger And BTB Domain Containing 16). RESULTS: Quercetin supplementation led to a significant reduction in the relative weight of retroperitoneal adipose tissue in both investigated strains. A decrease in visceral (epididymal) fat mass, accompanied by an increase in brown fat mass after quercetin treatment, was observed exclusively in the SHR strain. While the levels of serum triglycerides decreased within both strains, the free fatty acids levels decreased in SHR-Zbtb16-Q rats only. The total serum cholesterol levels were not affected by quercetin in either of the two tested strains. While there were no significant changes in brown adipose tissue transcriptome, quercetin supplementation led to a pronounced gene expression shift in white retroperitoneal adipose tissue, particularly in SHR-Zbtb16-Q. CONCLUSION: Quercetin administration ameliorates certain MetS-related features; however, the efficacy of the treatment exhibits subtle variations depending on the specific variant of the Zbtb16 gene.

• Publikační typ
• časopisecké články MeSH

The intestinal epithelium, a rapidly renewing tissue, is characterized by a continuous cell turnover that occurs through a well-coordinated process of cell proliferation and differentiation. This dynamic is crucial for the long-term function of the gastrointestinal tract. Disruption of this process can lead to colorectal carcinoma, a common malignancy worldwide. The first part of the review focuses on the cellular composition of the epithelium and the molecular mechanisms that control its functions, and describes the pathways that lead to epithelial transformation and tumor progression. This forms the basis for understanding the development and progression of advanced colorectal cancer. The second part deals with current therapeutic approaches and presents the latest treatment options, ongoing clinical trials and new drugs. In addition, the biological and medical perspectives of the adverse effects of therapies and models of regeneration of the intestinal epithelium are highlighted and, finally, future treatment options are discussed.

• MeSH
• kolorektální nádory * terapie   patologie   MeSH
• lidé MeSH
• nádorová transformace buněk MeSH
• onkologové MeSH
• střevní sliznice patologie   účinky léků   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH

OBJECTIVES: This study aimed to investigate relationships between cholesterol profile, brain volumetric MRI, and clinical measures in a large observational cohort of multiple sclerosis (MS) patients. MATERIALS AND METHODS: We included 1.505 patients with 4.966 time points including complete lipid, clinical, and imaging data. The time among lipid, brain MRI and clinical measures was under 90 days. Cross-sectional statistical analysis at baseline was performed using an adjusted linear regression and analysis of longitudinal lipid and MRI measures data was performed using adjusted linear mixed models. RESULTS: We found associations between higher high-density lipoprotein cholesterol (HDL-C) and lower brain parenchymal fraction (BPF) at cross-sectional analysis at baseline (B = -0.43, CI 95%: -0.73, -0.12, p = 0.005), as well as in longitudinal analysis over follow-up (B = -0.32 ± 0.072, χ2 = 36.6; p = < 0.001). Higher HDL-C was also associated with higher T2-lesion volume in longitudinal analysis (B = 0.11 ± 0.023; χ2 = 23.04; p = < 0.001). We observed a weak negative association between low-density lipoprotein cholesterol (LDL-C) levels and BPF at baseline (B = -0.26, CI 95%: -0.4, -0.11, p = < 0.001) as well as in longitudinal analysis (B = -0.06 ± 0.03, χ2 = 4.46; p = 0.03). T2-LV did not show an association with LDL-C. We did not find any association between lipid measures and disability. The effect of lipid levels on MRI measures and disability was minimal (Cohen f2 < 0.02). CONCLUSIONS: Our results contradict the previously described exclusively positive effect of HDL-C on brain atrophy in patients with MS. Higher LDL-C was weakly associated with higher brain atrophy but not with higher lesion burden.

• MeSH
• cholesterol krev   MeSH
• dospělí MeSH
• HDL-cholesterol * krev   MeSH
• kohortové studie MeSH
• LDL-cholesterol krev   MeSH
• lidé středního věku MeSH
• lidé MeSH
• longitudinální studie MeSH
• magnetická rezonanční tomografie * MeSH
• mozek * diagnostické zobrazování   patologie   MeSH
• průřezové studie MeSH
• roztroušená skleróza * diagnostické zobrazování   krev   patologie   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• pozorovací studie MeSH

Buprenorfin patří mezi silné opioidy. Zároveň je řazen i mezi tzv atypické opioidy. Ty působí ještě i na jiném než p opioidním mechanismu. Buprenorfin je parciální agonista na p opioidních receptorech, antagonista na k a 6 receptorech a agonista na ORLI (opioid receptor-like 1). Buprenorfin má minimum nežádoucích účinků. Aplikační místa se doporučuje pr

Buprenorphine belongs between very strong opioids. At the same time, it is categorized among atypical opioids. They besides effect on something else then p opioid mechanism. Buprenorphine is a partial agonist on m opioid receptors, antagonist on k and 6 receptors and agonist on ORLI (opioid receptor-like 1). In case of local reaction is recommended to use dexpanthenol on application area as a precaution, it is advisable to do so after application as well. In case of adverse reaction, we treat the skin with local corticosteroids. It could be used preventively as well.

Prognóza nemocných s neresekovatelným či metastazujícím karcinomem prsu s pozitivitou receptoru 2 pro lidský epidermální růstový faktor (human epidermal growth factor receptor 2, HER2) se významně zlepšila zavedením nových anti-HER2 přípravků. Současným léčebným standardem 1. linie je kombinace taxanů s pertuzumabem a trastuzumabem. Možnosti terapie pokročilého HER2 pozitivního karcinomu prsu se stále rozvíjejí, k dispozici v dalších liniích léčby jsou konjugáty cytostatika s protilátkou a malé molekuly tyrozinkinázových inhibitorů. Zásadní zlepšení léčebných výsledků přináší především trastuzumab deruxtekan (T-DXd), který prokázal výjimečnou účinnost u pacientek s HER2 pozitivním metastazujícím karcinomem prsu v klinických studiích DESTINY-Breast01 a DESTINY-Breast03. Předkládaná kazuistika dokládá vysokou účinnost tohoto přípravku ve 3. linii léčby nemocné s prognosticky nepříznivým HER2 pozitivním karcinomem prsu.

The prognosis of patients with unresectable or metastatic breast cancer with positive human epidermal growth factor receptor 2 (HER2) has significantly improved with the introduction of new anti-HER2 agents. The current first-line treatment standard is a combination of taxanes with pertuzumab and trastuzumab. Treatment options for advanced HER2-positive breast cancer continue to evolve, with antibody-drug conjugates and small molecule tyrosine kinase inhibitors available in subsequent lines of therapy. A significant improvement in treatment outcomes is primarily brought by trastuzumab deruxtecan, which has demonstrated exceptional efficacy in patients with HER2-positive metastatic breast cancer in the clinical studies DESTINY-BreastOI and DESTINY-Breast03. The presented case report confirms the high efficacy of this drug in the third-line treatment of a patient with a prognostically unfavorable HER2-positive breast cancer.

Selperkatinib je nový cílený inhibitor tyrozinkinázy receptoru RET indikovaný původně k léčbě nádorů štítné žlázy a plic s alteracemi RET a recentně schválený i k léčbě pokročilých stadií ostatních solidních nádorů s pozitivitou RET fúze. V kazuistice popisujeme případ nemocného s pokročilým papilárním karcinomem štítné žlázy léčeným v první linii lenvatinibem, v druhé linii pro progresi a přítomnost RET fúze selperkatinibem, s následnou progresí v důsledku vzniku sekundární mutace. Další léčba multikinázovým inhibitorem kabozantinibem byla neúčinná.

Selpercatinib is a novel targeted RET receptor tyrozinkinase inhibitor indicated primarily for the treatment of thyroid and lung tumors with RET alterations and recently approved also for the treatment of advanced stages of other solid tumors with RET fusion positivity. In the case report, we describe the case of a patient with advanced papillary thyroid cancer treated in the first line with lenvatinib, in the second line for progression and the presence of RET fusion selpercatinib with subsequent progression due to secondary mutation. Further treatment with the multikinase inhibitor cabozantinib was ineffective.

Polycytemia vera je klinickou podjednotkou Ph-negativních myeloproliferací. Polycytemie má sice lepší prognózu než primární myelofibróza, ale zhoršuje významně kvalitu života, zvyšuje infekční a onkologické riziko a pacienty ohrožuje zejména závažnými trombotickými komplikacemi: například hlubokou žilní trombózou, plicní embolií, trombózami v abdominální oblasti, trombózou portální žíly, linenálních či hepatálních žil (Buddův-Chiariho syndrom) a trombózou žilních splavů v centrálním nervovém systému. Tyto trombotické příhody mohou být fatální. U rizikových pacientů je tedy nutné včas zahájit cytoredukční terapii s cílem minimalizovat symptomy onemocnění, zabránit progresi onemocnění, snížit riziko trombotických komplikací a transformaci do primární myelofibrózy či akutní hemoblastózy. Léčba interferony dokáže podle výsledků dosavadních studií ovlivnit podstatu onemocnění snížením alelické nálože mutace JAK2 V617F. Tato kazuistika demonstruje úspěšnou a velmi dobře tolerovanou Léčbu ropeginterferonem aLfa-2b s dosažením hematologické remise bez nutnosti hemodiluce, bez trombotických komplikací, a umožňující i po určité době snížení dávek ropeginterferonu a lfa -2 b vlivem snížení aktivity onemocnění.

Polycythemia vera is a clinical subset of Ph negative myeloproliferations. Polycythemia vera has a relatively good prognosis, in contrast to primary myelofibrosis. However, it worsens the quality of life, increases the risk of infection and oncology, and especially threatens patients with serious thrombotic complications: for example, deep vein thrombosis, pulmonary embolism, thrombosis in the abdominal area, thrombosis venae portae lienal or hepatic veins (Budd-Chiary syndrome) thrombosis of venous vessels in the central nervous system. These thrombotic events can be fatal. In patients at risk, it is therefore necessary to initiate cytoreductive therapy early to minimize the symptoms of the disease, prevent the progression of the disease, reduce the risk of thrombotic complications, progression to primary myelofibrosis or acute hemoblastosis. Treatment with interferons according to the results of studies to date, the essence of the disease can be influenced by reducing the mutational findings of the JAK2 V617F mutation. This case report demonstrates a successful and very well tolerated treatment with ropeginterferon alfa-2b with the establishment of hematological remission without the need for hemodilution and the possibility by reducing doses due to a reduction in disease activity.

Myelodysplastický syndrom je klonální onemocnění hemopoezy. U nemocných s nízkým rizikem progrese choroby či přechodu do akutní myeloidní leukemie je dominantním problémem cytopenie, a to především anemie. Ta se vyskytuje až u 90 % nemocných. Hlubší anemie zvláště u nemocných závislých na transfuzích významně snižuje kvalitu života, zvyšuje morbiditu i mortalitu. Dosud jsme byli odkázáni u většiny nemocných (s výjimkou nemocných s 5q-syndromem, kteří jsou výbornými respondenty na terapii lenalidomidem) na transfuze či podání erytropoetinů. Erytropoetiny ale nejsou příliš účinné právě u nemocných s již vyvinutou závislostí na transfuzích. Proto je velkým přínosem v léčbě těchto nemocných nový přípravek luspatercept, inhibitor dráhy transformujícího růstového faktoru β (transforming growth factor β, TGF – β), který vede až u 50 % nemocných k eliminaci transfuzní potřeby, výraznému zlepšení kvality života, a jak bylo recentně prokázáno, i k prodloužení přežívání. Prezentujeme zde kazuistiku nemocné, kde byl tento přípravek úspěšně použit v kombinaci s erytropoetinem a v dlouhodobé léčbě vysokou dávkou.

Myelodysplastic syndrome (MDS) is a clonal disease of the hemopoesis. In patients with a low risk of disease progression or transition to acute myeloid leukemia, cytopenia, especially anemia, is the dominant problem. It occurs in up to 90% of patients. Deeper anemia, especially in transfusion-dependent patients, significantly reduces quality of life, increases morbidity and mortality. So far, we could use as a treatment only transfusions or erythropoetins for most patients (except for patients with 5q-syndrome, who are excellent responders to lenalidomide therapy). However, erythropoetins are not very effective in patients with already developed transfusion dependence. Therefore, the new drug luspatercept,an inhibitor of the transforming growth factor p pathway, is of great benefit in the treatment of these patients, resulting in the elimination of the need for transfusions in up to 50% of patients, a significant improvement in quality of life and, as recently demonstrated, prolonged survival. We present a case report of a patient where this agent was successfully used in combination with erythropoietin and in long-term high-dose therapy.