Uterine sarcomas with KAT6B/A::KANSL1 fusion represent a new entity characterized by bland morphology, commonly with hybrid features of low-grade endometrial stromal sarcoma (LG-ESS) and tumors with smooth muscle differentiation. In our study, we performed a detailed morphological, immunohistochemical, and molecular analysis of 9 cases of these tumors. Six of those had been originally diagnosed as LG-ESS, one as leiomyoma, one as leiomyosarcoma, and the remaining case as sarcoma with the KAT6B/A::KANSL1 fusion. Seven cases showed overlapping features between endometrial stromal and smooth muscle tumors, one case resembled cellular leiomyoma, and one case resembled high-grade endometrial stromal sarcoma. Immunohistochemically, the tumors showed a common expression of smooth muscle markers and endometrial stromal markers. Molecular findings showed the KAT6B/A::KANSL1 fusion in all cases (by NGS and FISH). In addition, mutations affecting genes such as TP53, PDGFRB, NF1, RB1, PTEN, ATM, RB1, FANCD2, and TSC1 were present in all 5 cases with aggressive behavior. One patient with no evidence of disease showed no additional mutations, while another harbored a mutation of a single gene (ERCC3). Of the 8 patients with available follow-up, two died of disease, 3 are currently alive with disease, and 3 have no evidence of disease. The correct recognition of tumors with the KAT6B/A::KANSL1 fusion is essential because despite the bland morphological features of most cases, these tumors have a propensity for aggressive behavior.
- MeSH
- Adult MeSH
- Sarcoma, Endometrial Stromal genetics pathology MeSH
- Oncogene Proteins, Fusion genetics MeSH
- Histone Acetyltransferases genetics MeSH
- Immunohistochemistry MeSH
- Middle Aged MeSH
- Humans MeSH
- Mutation MeSH
- Biomarkers, Tumor * genetics analysis MeSH
- Uterine Neoplasms * pathology genetics MeSH
- Sarcoma genetics pathology MeSH
- Aged MeSH
- Check Tag
- Adult MeSH
- Middle Aged MeSH
- Humans MeSH
- Aged MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
BACKGROUND: Proximal Femoral Focal Deficiency (PFFD) is the most proximal manifestation of a syndrome involving Congenitally Shortened lower Limbs (CSL), which also affects the fibula and midline metatarsals. This pattern of congenital human long bone deficiencies corresponds, in a time dependent manner, to the failed ingrowth pathways of new blood vessels of the growing embryonic limb. The distal femoral condyles are, in contrast, served by an alternative vascular supply from around the knee joint, and so remain resistant to the CSL deficiency. AIM: We hypothesize that embryonic vascular dysgenesis causes PFFD, as well as the cardinal features of the Femoral, Fibular and midline Metatarsal deficiencies (FFM) syndrome. RESULTS: Arteriography of CSL with PFFD reveals diminution or failed formation of the Femoral Artery (FA), which corresponds to downstream skeletal reductions. It may also reveal preservation of the primitive Axial Artery (AA) of the embryonic limb. The combination of missing and retained primitive vessels inform the time, place, and nature of the etiologic vascular events. This suggests that PFFD is the visible expression of a normally prefigured cartilaginous scaffold of the femur, which develops in conformity with the available pattern of blood vessels present. The teratogen thalidomide, known to affect the forming embryonic vasculature, also produces PFFD indistinguishable from the naturally occurring entity. CONCLUSION: The entire spectrum of PFFD, including phocomelia, fibular, and metatarsal dystrophisms, should thus be regarded as downstream skeletal results of embryonic arterial dysgeneses.
- MeSH
- Femoral Artery * abnormalities embryology MeSH
- Femur * abnormalities blood supply embryology MeSH
- Fibula abnormalities blood supply MeSH
- Humans MeSH
- Metatarsal Bones abnormalities MeSH
- Lower Extremity Deformities, Congenital * embryology MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
- Review MeSH
The establishment of the first JBI Affiliated group in Poland at Wroclaw Medical University marks a significant advancement in evidence-based healthcare (EBHC) nationally. This editorial explores the evolution of EBHC and the critical role of JBI in driving its progress. Founded in 1996 as a research institute at the Royal Adelaide Hospital in South Australia and now based at the University of Adelaide, JBI has emerged as an international leader in evidence synthesis, transfer and implementation. Its Feasibility, Appropriateness, Meaningfulness, and Effectiveness (FAME) framework highlights the feasibility, appropriateness, meaningfulness, and effectiveness of healthcare practices, ensuring that decisions are patient-centered and contextually relevant. JBI's global collaboration network encompasses over 85 entities, with 23 located in Europe, emphasizing the importance of cultural inclusivity and international partnerships. Recent initiatives include translating the JBI Model of into Polish, German and Czech, linking global knowledge to local contexts, and enhancing understanding for professionals and students alike. This editorial also underscores the collaborative achievements of JBI entities in Wroclaw, Brandenburg an der Havel, Prague, and Olomouc. These partnerships have propelled regional implementation, research and education, fostering a shared vision for elevating healthcare quality. Launching a new EBHC section in the Advances in Clinical and Experimental Medicine journal is a significant step forward, inviting global contributions and stimulating innovation and knowledge sharing in EBHC. The presence of a JBI Affiliated group at Wroclaw Medical University symbolizes a transformative commitment to excellence and collaboration. It sets new benchmarks for healthcare in Poland and beyond while reinforcing the global mission of evidence-based practice.
Genetika neurodegeneratívnych demencií je turbulentnou témou súčasnosti. Na jednej strane sa postupne zvyšuje množstvo génov zapojených do patogenézy neurodegeneratívnych procesov, na druhej strane vystupuje problém s interpretáciou dosiahnutých výsledkov. Alzheimerova choroba (AD) a demencia s Lewyho telieskami (DLB) predstavujú v súčasnosti dobre definované klinické jednotky. Alzheimerova choroba má jasne určené kauzálne gény (APP, PSEN1, PSEN2) a významný gén susceptibility (APOE). Popri nich sa postupne objavujú nové gény susceptibility, ktoré modifikujú klinický obraz, vek nástupu ochorenia a spolu s APOE vytvárajú komplikované genetické pozadie. Demencia s Lewyho telieskami je heterogénnejšou entitou ako Alzheimerova choroba z klinického aj genetického hľadiska. Génmi susceptibility DLB sú viaceré gény zdieľané s Alzheimerovou chorobou, Parkinsonovou chorobou (PD), frontotemporálnou demenciou (FTD) a inými neurodegeneráciami. V našom príspevku sa snažíme sumarizovať genetické pozadie AD a DLB, charakterizovať ich podobnosti a rozdiely a poukázať na komplexnosť neurodegeneratívneho ekosystému ("neurodegeneratómu").
The genetics of neurodegenerative dementias is a turbulent topic. On the one hand, the number of genes involved in the pathogenesis of neurodegenerative processes is gradually increasing, on the other hand, the problem of interpretation of the results is emerging. Alzheimer's disease (AD) and dementia with Lewy bodies (DLB) represent currently well-defined clinical entities. AD has clearly defined causal genes (APP, PSEN1, PSEN2) and a major susceptibility gene (APOE). In addition to these, new susceptibility genes are gradually emerging that modify the clinical picture, the age of onset and, together with APOE, create a complicated genetic background. Dementia with Lewy bodies (DLB) is a more heterogeneous entity than Alzheimer's disease, both clinically and genetically. DLB susceptibility genes are multiple genes shared with Alzheimer`s disease, Parkinson disease, frontotemporal dementia (FTD) and other neurodegenerations. In our paper, we aim to summarize the genetic background of both AD and DLB, to characterize their similarities and differences, and to highlight the complexity of the neurodegenerative ecosystem ("neurodegeneratome").
- MeSH
- Alzheimer Disease * diagnosis genetics MeSH
- Apolipoproteins metabolism MeSH
- Lewy Body Disease * diagnosis genetics MeSH
- Epigenomics classification MeSH
- Genetic Background MeSH
- Genetic Testing methods MeSH
- Humans MeSH
- Neurodegenerative Diseases diagnosis genetics MeSH
- Check Tag
- Humans MeSH
- Publication type
- Review MeSH
Metastatický kolorektální karcinom je heterogenní onemocnění, kde je léčba individuálně volena dle znalosti molekulárních vlastností nádoru. S přibývajícími poznatky o molekulární biologii onemocnění roste současně počet potenciálních cílů pro specifickou terapii. V posledních letech je novou možností pro pacienty s metastatickým kolorektálním karcinomem s prokázanou KRAS G12C mutací terapie KRAS G12C inhibitory. Cílem článku je poskytnout přehled současných možností léčby této jednotky.
Metastatic colorectal cancer is a heterogeneous disease where treatment is individually selected according to the knowledge of the molecular characteristics of the tumour. As the knowledge of the molecular biology of the disease increases, the number of potential targets for specific therapies increases. In recent years, KRAS G12C inhibitor therapy has become a new treatment option for patients with metastatic colorectal cancer with a proven KRAS G12C mutation. The aim of this article is to provide an overview of current treatment options for this entity.
- Keywords
- KRAS G12C,
- MeSH
- ErbB Receptors antagonists & inhibitors MeSH
- Clinical Studies as Topic MeSH
- Clinical Trials as Topic MeSH
- Colorectal Neoplasms * drug therapy MeSH
- Drug Therapy, Combination methods MeSH
- Humans MeSH
- Mutation MeSH
- Piperazines administration & dosage MeSH
- Antineoplastic Agents administration & dosage MeSH
- Pyrimidines administration & dosage MeSH
- ras Proteins antagonists & inhibitors genetics MeSH
- Check Tag
- Humans MeSH
- Publication type
- Review MeSH
Východiska: Solitární hepatocelulární karcinom (hepatocellular carcinoma – HCC) o průměru 3–5 cm představuje náročnou klinickou výzvu, zejména u pacientů, u kterých není kvůli komorbiditám vhodná chirurgická léčba. Případ: U 74letého muže s renálním karcinomem v anamnéze byla na MR zjištěna nová náhodná solitární léze jater o velikosti 5 cm. Po přezkoumání multidisciplinární komisí a vzhledem k věku a vysokému riziku pooperačních komplikací se léčebný plán skládal z perkutánní termické segmentektomie pomocí mikrovlnné ablace s balonkovou okluzí (baloon-occluded microwave abblation – b-MWA) a následné transarteriální chemoembolizace s balonkovou okluzí (balloon-occluded transarterial chemoembolization – b-TACE), přičemž došlo ke kompletní nekróze nádoru, jak ukázaly následných kontrolní snímky. Tento případ ukazuje, že b-MWA a b-TACE by mohly být bezpečnou a účinnou kombinovanou léčbou velkých neresekabilních lézí HCC, a to i u lézí s velikostí nad 3 cm. Závěr: Ačkoli se jedná o nepodložený případ, kterému přirozeně chybí srovnání nebo kontroly, zdůrazňuje potenciální hodnotu jednoho zákroku v podobě perkutánní termické segmentektomie pomocí b-MWA s následnou b-TACE při léčbě velkých neresekabilních solitárních lézí HCC.
Background: Solitary hepatocellular carcinoma (HCC) with a diameter of 3–5 cm represents a challenging clinical entity, especially for non-surgical candidates due to comorbidities. Case: A 74-year-old man with previous history of renal cell carcinoma presented with a new incidental solitary 5 cm liver lesion on MRI. Due to his age and a high risk for post-surgical complications, after multidisciplinary tumor board review the treatment plan consisted of percutaneous thermal segmentectomy using balloon-occluded microwave ablation (b-MWA) followed by balloon-occluded transarterial chemoembolization (b-TACE) with complete tumor necrosis, as evident in subsequent follow-up imaging. This case demonstrates that b-MWA plus b-TACE could be a safe and effective combined therapy for unresectable large HCC lesions, even for those exceeding 3 cm in size. Conclusion: Although the presented case is anecdotal and naturally without comparisons or control, it highlights the potential value of percutaneous thermal segmentectomy with a single session combined b-MWA followed by b-TACE for the treatment of large unresectable solitary HCC lesions.
CONTEXT: Noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP) was introduced as a new entity replacing the diagnosis of noninvasive encapsulated follicular variant of papillary thyroid carcinoma (PTC). Significant variability in the incidence of NIFTP diagnosed in different world regions has been reported. OBJECTIVE: To investigate the rate of adoption of NIFTP, change in practice patterns, and uniformity in applying diagnostic criteria among pathologists practicing in different regions. METHODS: Two surveys distributed to pathologists of the International Endocrine Pathology Discussion Group with multiple-choice questions on NIFTP adoption into pathology practice and whole slide images of 5 tumors to collect information on nuclear score and diagnosis. Forty-eight endocrine pathologists, including 24 from North America, 8 from Europe, and 16 from Asia/Oceania completed the first survey and 38 the second survey. RESULTS: A 94% adoption rate of NIFTP by the pathologists was found. Yet, the frequency of rendering NIFTP diagnosis was significantly higher in North America than in other regions (P = .009). While the highest concordance was found in diagnosing lesions with mildly or well-developed PTC-like nuclei, there was significant variability in nuclear scoring and diagnosing NIFTP for tumors with moderate nuclear changes (nuclear score 2) (case 2, P < .05). Pathologists practicing in North America and Europe showed a tendency for lower thresholds for PTC-like nuclei and NIFTP than those practicing in Asia/Oceania. CONCLUSION: Despite a high adoption rate of NIFTP across geographic regions, NIFTP is diagnosed more often by pathologists in North America. Significant differences remain in diagnosing intermediate PTC-like nuclei and respectively NIFTP, with more conservative nuclear scoring in Asia/Oceania, which may explain the geographic differences in NIFTP incidence.
- MeSH
- Cell Nucleus pathology MeSH
- Adenocarcinoma, Follicular * pathology epidemiology diagnosis MeSH
- Practice Patterns, Physicians' statistics & numerical data MeSH
- Humans MeSH
- Thyroid Neoplasms * epidemiology pathology diagnosis MeSH
- Thyroid Cancer, Papillary epidemiology pathology diagnosis MeSH
- Carcinoma, Papillary pathology epidemiology diagnosis MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
- Geographicals
- Asia MeSH
- Europe MeSH
- Oceania MeSH
- North America MeSH
Chronic heart failure (CHF) is a rare entity in children but carries a burden of high mortality and morbidity. Medical treatment of pediatric CHF is largely based on guidelines for the adult population. In contrast to adults, evidence for the efficacy of medications in treating CHF in children is sparse. This may be due to the difficulty of conducting high-powered studies in children or to true differences in the mechanisms of CHF pathophysiology. Recent observations suggest that CHF in children differs from adults at the molecular and cellular levels. Different pathways are involved, leading to less fibrosis and hypertrophy than in adults, with potential implications for therapy. The main pathophysiological goals of medical treatment of pediatric CHF due to systemic left ventricular dysfunction are discussed in this review. These include preload and afterload optimization, diminishing cardiomyocyte apoptosis and necrosis as well as interstitial fibrosis, and optimizing myocardial oxygen consumption. The pediatric myocardium should be provided with optimal conditions to achieve its regenerative potential. The cornerstones of medical CHF therapy are angiotensin converting enzyme inhibitors (ACEI), beta blockers and mineralocorticoid receptor antagonists. There are potential benefits of tissue ACEI and ?1-selective beta blockers in children. Angiotensin receptor blockers are an alternative to ACEI and their slightly different mechanism of action may confer certain advantages and disadvantages. Diuretics are employed to achieve a euvolemic state. Digoxin is used more frequently in children than in adults. Promising new drugs already routinely used in adults include angiotensin receptor-neprilysin inhibitors and sodium-glucose contransporter 2 inhibitors. Key words: Pediatric heart failure, Heart failure with reduced ejection fraction (HFrEF), ACE inhibitor, Beta blocker, Digoxin.
- MeSH
- Adrenergic beta-Antagonists therapeutic use MeSH
- Chronic Disease MeSH
- Child MeSH
- Angiotensin-Converting Enzyme Inhibitors therapeutic use MeSH
- Humans MeSH
- Heart Failure * drug therapy physiopathology MeSH
- Age Factors MeSH
- Check Tag
- Child MeSH
- Humans MeSH
- Publication type
- Journal Article MeSH
- Review MeSH
John Charles Steele (1934-2022) byl kanadský neurolog, který spolu s Richardsonem a Olszewskim popsal novou nozologickou jednotku, které byla původně pojmenována eponymně, časem se ale ujalo označení progresivní supranukleární paralýza. Později se věnoval epidemiologickému a klinickému výzkumu endemického onemocnění amyotrofická laterální skleróza - parkinsonismus - demence komplex z ostrova Guam, zdokumentoval jeho výskyt, fenotypy, klinickou manifestaci, dědičnost a klesající incidenci i prevalenci. Zabýval se taktéž patofyziologií tohoto onemocnění, a řadu let zastával názor, že se jedná o hereditární polygenní onemocnění; až ke konci života přijal hypotézu, která manifestaci nemoci přisuzovala chronické intoxikaci neurotoxickými sloučeninami obsaženými v cykasových plodech: beta-methylamino-L-alanin (BMAA) a metylazoxymetanol (MAM).
John Charles Steele (1934-2022) was a Canadian neurologist who, together with Richardson and Olszewski, described a new nosological entity that was originally named eponymously; however, over time, it became known as progressive supranuclear palsy. Later, he was concerned with epidemiological and clinical research on the endemic disease of amyotrophic lateral sclerosis-parkinsonism-dementia complex of Guam, documenting its occurrence, phenotypes, clinical manifestations, heredity, and decreasing incidence as well as prevalence. He also studied the pathophysiology of this disease, for years holding the view that it was a hereditary polygenic disease; it was only at the end of his life that he accepted the hypothesis which attributed the manifestation of the disease to chronic intoxication with neurotoxic compounds contained in cycad fruits: beta-methylamino-L-alanine (BMAA) and methylazoxymethanol (MAM).
- MeSH
- Humans MeSH
- Neurodegenerative Diseases history MeSH
- Neurology history MeSH
- Supranuclear Palsy, Progressive * history MeSH
- Famous Persons MeSH
- Check Tag
- Humans MeSH
- Publication type
- Biography MeSH
- About
- Steele, John C Authority
