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Ujemna korelacja między utratą masy ciała spowodowaną przyjmowaniem tirzepatydu, a stężeniem wolnej trójjodotyroniny
Ruxolitinib for the treatment of secondary myelofibrosis following polycythemia vera in an elderly patient: a case report
U pacjentki w podeszłym wieku z czerwienicą prawdziwą potwierdzono transformację do włóknienia szpiku. Zastosowanie ruksolitynibu pozwoliło uzyskać poprawę kliniczną i laboratoryjną, przy zachowaniu bezpieczeństwa terapii.In an elderly female patient diagnosed with polycythemia vera, transformation to myelofibrosis was confirmed. Initiation of ruxolitinib therapy was associated with both clinical and laboratory improvement, while the treatment’s safety profile remained acceptable throughout therapy
Poprawa jakości życia podczas leczenia asciminibem u pacjenta z wcześniejszym niepowodzeniem i nietolerancją poprzednich linii leczenia
Wprowadzenie: Wraz ze wzrostem oczekiwanej długości życia pacjentów chorujących na przewlekłą białaczkę szpikową (CML), nowym wyzwaniem w leczeniu tej choroby stało się poprawienie jakości życia chorych. Najczęściej zgłaszanym działaniem niepożądanym terapii inhibitorami kinazy tyrozynowej jest zmęczenie, które znacząco wpływa na codzienne funkcjonowanie pacjentów. Asciminib, dzięki odmiennemu mechanizmowi działania, wykazuje skuteczność po niepowodzeniu leczenia innymi inhibitorami i charakteryzuje się korzystnym profilem bezpieczeństwa. Opis przypadku: W opisywanym przypadku pacjent, pomimo dobrej odpowiedzi na leczenie imatynibem, nie doświadczył poprawy w zakresie redukcji zmęczenia. Terapia dazatynibem została szybko przerwana z powodu nietolerancji leczenia. Dopiero asciminib nie tylko pogłębił i ustabilizował odpowiedź molekularną, lecz także poprawił jakość życia pacjenta
Asciminib jako skuteczna terapia czwartej linii u pacjenta z przewlekłą białaczką szpikową nietolerującego wielu inhibitorów kinazy tyrozynowej — opis przypadku
Wprowadzenie: Przewlekła białaczka szpikowa (CML) jest nowotworem mieloproliferacyjnym układu krwiotwórczego. Istotą choroby jest klonalny rozrost komórki macierzystej zawierającej nieprawidłowy gen fuzyjny BCR/ABL1 na chromosomie Filadelfia. Standardem leczenia CML jest stosowanie inhibitorów kinazy tyrozynowej (TKI). Jest to heterogenna grupa leków, różniąca się profilem bezpieczeństwa, częstością działań niepożądanych oraz wskazaniami rejestracyjnymi. Asciminib jako pierwszy TKI o odmiennym punkcie uchwytu — ukierunkowany na kieszeń mirystilową ABL — wykazuje korzystniejszy profil bezpieczeństwa i mniejszy zakres działań niepożądanych. Opis przypadku: W niniejszej pracy przedstawiono opis przypadku starszego pacjenta z licznymi chorobami współistniejącymi, u którego rozpoznano CML. Liczne działania niepożądane związane z wcześniejszymi TKI były na tyle nasilone, że prowadziły do przerw w terapii, co negatywnie wpływało na skuteczność leczenia i skutkowało niepowodzeniem trzech pierwszych linii terapii. Dopiero zastosowanie terapii czwartej linii — asciminibu — umożliwiło zachowanie równowagi pomiędzy skutecznością a bezpieczeństwem leczenia. Dzięki temu pacjent kontynuował terapię przez ponad dwa lata bez powikłań, utrzymując przy tym optymalną odpowiedź molekularną
A recombinase polymerase amplification-coupled Cas12a for detection of Salmonella Typhi — a preliminary report
Introduction. Typhoid fever, a disease resulting from an infection with Salmonella Typhi (S. Typhi) remains widespread in economically disadvantaged regions, where it continues to be a critical public health concern. As the symptoms and signs are non-specific, they are difficult to diagnose directly based on the clinical picture. Therefore, laboratory examinations are essential for diagnosis. Material and methods. This research introduces a fast and equipment-independent approach for detecting S. Typhi by employing CRISPR/Cas12a-based technology. The optimized CRISPR/Cas12a system achieved a detection limit of 103 copies/μL of S. Typhi DNA per reaction, with the entire assay completed within 60 min. Results. Four clinical isolates cultured from patients with typhoid fever were collected and evaluated using our CRISPR/Cas12a-based detection system. The assay results demonstrated that all four samples were accurately identified as positive. Conclusions. We showed that the developed CRISPR/Cas12a-based detection method provides a promising alternative for the on-site and simple detection of S. Typhi
Molecular landscape of the mouse adrenal gland and adjacent adipose tissue by spatial transcriptomics
Introduction. The adrenal glands are central regulators of endocrine homeostasis and stress adaptation. Despite decades of research, the molecular mechanisms governing adrenal zonation and cortical renewal remain incompletely understood. Material and methods. Here, the 10x Genomics Visium CytAssist platform was applied to generate a high-resolution atlas of the adult CD1 IGS male mouse adrenal gland. The study employed a range of analytical approaches, including unsupervised clustering, differential gene expression analysis, pathway and Gene Ontology enrichment, cell-type deconvolution, and pseudotime trajectory inference. These approaches collectively facilitated the comprehensive characterization of transcriptional signatures across the primary adrenal cortical zones and the medulla. Results. Herein transcriptional signatures of distinct compartments were identified, including zona glomerulosa/adrenal capsule (ZG/capsule), outer and inner zona fasciculata (oZF, iZF), medulla, connective tissue, and surrounding brown and white adipose depots. Deconvolution analysis further delineated contributions from stromal, immune, endothelial, and erythrocyte populations, highlighting the complexity of adrenal and periadrenal tissues. Pseudotime trajectory analysis validated the centripetal differentiation model of the adrenal cortex, demonstrating a continuum of transcriptional states from capsule and ZG/capsule through oZF to iZF, consistent with progressive acquisition of steroidogenic functions. Functional enrichment confirmed zone-specific pathways, including WNT and steroid biosynthesis in the cortex and neuroendocrine pathways in the medulla. Conclusions. Together, this study provides the first spatially resolved transcriptomic reference map of the adult male mouse adrenal gland, revealing the cellular and molecular framework underlying zonation, renewal, and inter-compartment interactions. This atlas constitutes a valuable resource for advancing the understanding of adrenal physiology and pathology
Hypoxia and human papillomavirus status in head and neck squamous cell carcinoma — biological insights and implications for personalized treatment
Hypoxia is a central feature of the tumor microenvironment in head and neck squamous cell carcinoma (HNSCC). It profoundly affects tumor biology, progression, treatment response, and patient prognosis. Oxygen deprivation activates complex adaptive pathways, largely driven by hypoxia-inducible factors (HIFs). These pathways reprogramme cellular metabolism, stimulate angiogenesis, promote epithelial–mesenchymal transition, induce genomic instability, and shape the immune response. Collectively, these processes drive the development of a more aggressive phenotype, characterized by increased resistance to radiotherapy, chemotherapy, and immunotherapy. Growing evidence highlights that HPV-positive and HPV-negative tumors exhibit distinct biological responses to hypoxia. The former often retain greater radiosensitivity, whereas in HPV-negative tumors hypoxia more often triggers resistance mechanisms. Incorporating hypoxia biomarkers such as imaging modalities, gene expression signatures, and molecular markers into clinical practice could allow more accurate patient stratification. This, in turn, would enable better tailoring of treatment intensity and modality to the tumor’s biological profile. In recent years, several therapeutic strategies targeting hypoxia have been developed. These include hypoxia-activated prodrugs, HIF inhibitors, angiogenesis modulators, metabolic therapies, and immunotherapeutic approaches, some of which are already in clinical trials. This article reviews current knowledge on the role of hypoxia in HNSCC, its relationship with HPV biology, and its influence on treatment response. It also highlights potential therapeutic directions in which the integration of hypoxia assessment with HPV status could support the optimization of treatment strategies
Analysis of adverse events associated with VEGFR-TKIs and their impact on prognosis in patients with mRCC — narrative review
Vascular endothelial growth factor receptor tyrosine kinase inhibitors (VEGFR-TKIs) remain a cornerstone in the treatment of metastatic renal cell carcinoma (mRCC), particularly in favorable-risk patients, in cases where immunotherapy is contraindicated, and in subsequent lines of therapy after progression or toxicity. Differences in drug profiles, adverse events (AEs) spectra, and pharmacokinetics among VEGFR-TKIs enable treatment individualization. Proper management of AEs may contribute to increased treatment tolerance and improved outcomes. This narrative review summarizes key differences in AEs among VEGFR-TKIs, evaluates their impact on prognosis, and discusses risk factors and predictive relevance, including implications for clinical practice in the context of sequential therapy after immune checkpoint inhibitors.
A review of expenditure, outcomes, access to oncology medicines and oncology health systems in ten European countries
Introduction. Substantial variation exists across Europe in cancer outcomes, health spending, and access to oncology medicines. The study aimed to collect and compare epidemiological indicators and data on oncological care in 10 selected European countries.
Material and methods. A cross-national, targeted review of oncological data was undertaken to characterize key epidemiological and healthcare profiles in Poland, Czechia, Estonia, Germany, Spain, Slovenia, Netherlands, United Kingdom, Italy, and Finland. Data on health expenditure, site-standardized relative survival, and access to medicine were drawn from international sources (OECD, ECIS, EFPIA Wait Report and IHE Report).
Summary of findings. In all the countries studied, the 2 leading causes of death were lung and colorectal cancer. Both incidence (537–690 cases per 100,000 population) and mortality rates (241–326 cases per 100,000 population) vary substantially in the selected countries. National cancer plans incorporating most of the elements stipulated in Europe’s Beating Cancer Plan have been implemented in every country. Among the selected countries in 2023, spending on cancer care accounted from 4% of total healthcare spending in Finland, to 8% in Germany and Poland. Poland shows the lowest levels of cancer screening, with breast cancer screening reaching only 37% of women (vs. 82% in Finland) and cervical cancer screening was as low as 11% (compared with 77% in Czechia).
Conclusions. Improving oncology system performance requires strategic resource allocation and is crucial to the impact analysis on population outcomes. The access granted to health services without a long-term strategy in implementation and prospective evaluation to value-based cancer care should be in compliance according to the Beating Cancer Plan. The level of integration, equity in access also at a regional level, not only on the country level is crucial to shaping health care in Europe
Comparative validation of prognostic indices in brain metastases receiving cranial radiotherapy
Introduction. This study aimed to externally validate widely used prognostic indices in patients with brain metastases (BM) treated with cranial radiotherapy and to evaluate the combined prognostic impact of clinical variables at the time of BM diagnosis and treatment-related factors on overall survival (OS).
Material and methods. A total of 116 patients who received cranial radiotherapy for BM between 2020 and 2024 were retrospectively analyzed. OS was estimated using the Kaplan–Meier method. Univariate and multivariate Cox regression analyses were performed separately for clinical variables at the time of BM diagnosis and treatment-related factors, followed by a combined analysis including all significant predictors. The prognostic performance of four indices — Recursive Partitioning Analysis (RPA), Graded Prognostic Assessment (GPA), Diagnosis-Specific GPA (ds-GPA), and Basic Score For Brain Metastases (BSBM) — was assessed using receiver operating characteristic (ROC) curves and area under the curve (AUC) values.
Results. The median OS was 9.0 months, with 6- and 12-month survival rates of 63.8% and 34.5%, respectively. In the final multivariate analysis, higher performance status [Karnofsky Performance Score (KPS) ≥ 70], lung primary, lower extracranial metastasis burden, receipt of chemotherapy, and surgical resection were independent predictors of improved survival, while radiotherapy modality (sterotactic radiosurgery vs. whole brain radiotherapy) showed no significant difference. All four indices effectively stratified OS, with ds-GPA and BSBM demonstrating the highest predictive accuracy (AUC = 0.931 and 0.899).
Conclusions. This study confirms the validity of established prognostic indices and highlights that achieving the survival predicted at the time of BM diagnosis largely depends on the effective delivery of systemic and local therapies. These findings underscore the importance of individualized and multidisciplinary management in optimizing real-world outcomes