Pathogenic alterations, namely, fusions and amplifications, of the GLI1 gene have been identified in various mesenchymal tumors, including pericytoma with t(7;12), plexiform fibromyxoma, gastroblastoma, and other malignant mesenchymal neoplasms arising in the soft tissues, as well as in various visceral organs. However, only three cases of GLI1-rearranged renal tumors have been reported to date, comprising two low-grade spindle cell tumors with GLI1::FOXO4 fusion along with one GLI1-rearranged case with an unknown fusion partner. In this study, we analyzed three cases with GLI1::FOXO4 fusion and overlapping morphology. One of the cases was reported previously, but an extended clinical and immunohistochemical information is provided. The studied cases occurred in 2 female and 1 male patients aged 35, 55, and 62 years (mean 51 years). All three tumors affected the renal parenchyma and grew as unencapsulated but well-circumscribed solid masses containing occasional entrapped and dilated renal tubules. The tumor cells were organized in cords, nests, or fascicles, had a round to spindled shape, and exhibited only mild nuclear atypia and minimal mitotic activity. They had a sparse eosinophilic to clear cytoplasm and were embedded in myxocollagenous stroma. Immunohistochemically, all cases expressed GLI1 (albeit with variable intensity) and harbored GLI1::FOXO4 fusion. All three patients were treated solely by complete surgical excision. Case 1 was alive with unknown disease status, case 2 was alive without evidence of disease, and case 3 died of unrelated causes. Our study doubles the number of reported cases with GLI1::FOXO4 fusion. The so far absolute predilection of this fusion for renal tumors, coupled with the absence of reports of other GLI1 fusions in tumors of the kidney, might indicate the potential existence of a distinct renal subtype with morphological features similar to other GLI1-altered tumors. All four reported cases had an uneventful follow-up which, together with their low-grade morphological features, suggests that these tumors might have a favorable prognosis.

• Klíčová slova
• GLI1::FOXO4 fusion, GLI1-altered tumors, Kidney, Soft tissue,
• MeSH
• dospělí MeSH
• forkhead transkripční faktory * genetika   MeSH
• genová přestavba * MeSH
• imunohistochemie MeSH
• lidé středního věku MeSH
• lidé MeSH
• nádorové biomarkery * genetika   analýza   MeSH
• nádory ledvin * genetika   patologie   MeSH
• protein Gli1 * genetika   MeSH
• proteiny buněčného cyklu * genetika   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• kazuistiky MeSH
• Názvy látek
• forkhead transkripční faktory * MeSH
• FOXO4 protein, human MeSH Prohlížeč
• GLI1 protein, human MeSH Prohlížeč
• nádorové biomarkery * MeSH
• protein Gli1 * MeSH
• proteiny buněčného cyklu * MeSH

AIMS: CIC-rearranged sarcomas (CRS) are clinically aggressive undifferentiated round cell sarcomas (URCS), commonly driven by CIC::DUX4. Due to the repetitive nature of DUX4 and the variability of the fusion breakpoints, CIC::DUX4 fusion may be missed by molecular testing. Immunohistochemical (IHC) stains have been studied as surrogates for the CIC::DUX4 fusion. We aim to assess the performance of DUX4 IHC in the work-up of CRS and its expression in non-CRS round cell or epithelioid neoplasms. METHODS AND RESULTS: Cases of molecularly confirmed CRS (n = 48) and non-CRS (n = 105) were included. CRS cases consisted of 35 females and 13 males, with ages ranging from less than 1 year to 67 years (median = 41 years). Among the molecularly confirmed non-CRS cases, C-terminal DUX4 expression was investigated in Ewing sarcomas (38 cases), alveolar rhabdomyosarcomas (18 cases), desmoplastic small round cell tumours (12 cases) and synovial sarcomas (n = five), as well as in non-mesenchymal neoplasms such as SMARCA4/SMARCB1-deficient tumours (n = five), carcinomas of unknown primary (n = three) and haematolymphoid neoplasms (four cases). DUX4 IHC was considered positive when strong nuclear expression was detected in more than 50% of neoplastic cells. When used as a surrogate for the diagnosis of CRS, the sensitivity and specificity of DUX4 IHC was 98 and 100%, respectively. Only one CRS case was negative for DUX4 IHC and harboured a CIC::FOXO4 fusion. CONCLUSIONS: DUX4 IHC is a highly sensitive and specific surrogate marker for the presence of CIC::DUX4 fusion, demonstrating its utility in establishing a diagnosis of CRS.

• Klíčová slova
• CIC::DUX4, CIC‐rearranged sarcomas, immunohistochemistry, round cell sarcoma, small round cell tumours,
• MeSH
• dítě MeSH
• dospělí MeSH
• fúzní onkogenní proteiny * genetika   MeSH
• genová přestavba MeSH
• homeodoménové proteiny * metabolismus   genetika   MeSH
• imunohistochemie * MeSH
• kojenec MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• nádorové biomarkery * metabolismus   analýza   genetika   MeSH
• nádory měkkých tkání diagnóza   patologie   genetika   metabolismus   MeSH
• předškolní dítě MeSH
• sarkom * diagnóza   patologie   genetika   metabolismus   MeSH
• senioři MeSH
• senzitivita a specificita MeSH
• Check Tag
• dítě MeSH
• dospělí MeSH
• kojenec MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• předškolní dítě MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• CIC-DUX4 fusion protein, human MeSH Prohlížeč
• DUX4L1 protein, human MeSH Prohlížeč
• fúzní onkogenní proteiny * MeSH
• homeodoménové proteiny * MeSH
• nádorové biomarkery * MeSH

We aimed to determine the persisting effects of various exercise modalities and intensities on functional capacity after periods of training cessation in older adults. A comprehensive search was conducted across the Cochrane Library, PubMed/MEDLINE, Scopus, and Web of Science Core Collection up to March 2024 for randomized controlled trials examining residual effects of physical exercise on functional capacity in older adults ≥ 60 years. The analysis encompassed 15 studies and 21 intervention arms, involving 787 participants. The exercise and training cessation periods ranged from 8 to 43 weeks and 4 to 36 weeks, respectively. Meta-analyses were performed using change scores from before the physical exercise to after the training cessation. The effect sizes (ES) were calculated as the standardized mean differences between the intervention and control groups' change scores. Subgroup analyses and meta-regressions explored the influence of participant characteristics, the magnitude of the effect produced by the initial training program, various exercise modalities (resistance and multicomponent training) and intensities (high and low), and subdomains of functional capacity (agility, balance, standing ability, walking ability, and stair walking). The findings revealed that exercise interventions had a significant effect on preserving functional capacity after training cessation (ES = 0.87; p < 0.01). This protective effect was consistent across various exercise modalities and intensities (ES ≥ 0.67; p ≤ 0.04). The benefits obtained during the training program were positively associated with the residual effects observed after training cessation (β = 0.73; p < 0.01), while age negatively influenced the persisting adaptations (β = -0.07; p < 0.01). Current evidence suggests that exercise-based interventions, irrespective of modality and intensity, are highly effective in preventing functional declines after training cessation among older adults.

• Klíčová slova
• deconditioning, functional impairments, long‐term effects, physical inactivity,
• MeSH
• cvičení * fyziologie   MeSH
• lidé středního věku MeSH
• lidé MeSH
• odporový trénink metody   MeSH
• posturální rovnováha fyziologie   MeSH
• randomizované kontrolované studie jako téma MeSH
• senioři MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• senioři MeSH
• Publikační typ
• časopisecké články MeSH
• metaanalýza MeSH
• přehledy MeSH
• systematický přehled MeSH

Mucocele of the appendix and pseudomyxoma peritonei are rare diseases. The clinical findings are nonspecific in the early stages of the disease. The sequelae of appendiceal mucocele, its perforation, and extensive peritoneal involvement via pseudomyxoma peritonei (jelly belly) are repeatedly described in the literature. We present the typical findings in the natural history of the disease.

• Klíčová slova
• HIPEC, cytoreductive surgery, jelly belly, mucocele, pseudomyxoma peritonei,
• Publikační typ
• časopisecké články MeSH

PURPOSE: The aim of the study is to capture the difference between the groups in direct relation to the type of electrode array insertion during cochlear implantation (CI). The robotic insertion is expected to be a more gently option. As recent studies have shown, there is a difference in perception of visual vertical (SVV) and postural control related to the CI. We assume that there can be differences in postural control and space perception outcomes depending on the type of the surgical method. METHODS: In total, 37 (24 females, mean age ± SD was 42.9 ± 13.0) candidates for CI underwent an assessment. In 14 cases, the insertion of the electrode array was performed by a robotic system (RobOtol, Colin, France) and 23 were performed conventionally. In all of these patients, we performed the same examination before the surgery, the first day, and 3 weeks after the surgery. The protocol consists of static posturography and perception of visual vertical. RESULTS: The both groups, RobOtol and conventional, responded to the procedure similarly despite the dissimilar electrode insertion. There was no difference between two groups in the dynamic of perception SVV and postural parameters. Patients in both groups were statistically significantly affected by the surgical procedure, SVV deviation appeared in the opposite direction from the implanted ear: 0.90° ± 1.25; - 1.67° ± 3.05 and - 0.19° ± 1.78 PRE and POST surgery (p < 0.001). And this deviation was spontaneously adjusted in FOLLOW-UP after 3 weeks (p < 0.01) in the both groups. We did not find a significant difference in postural parameters between the RobOtol and conventional group, even over time. CONCLUSION: Although the robotic system RobOtol allows a substantial reduction in the speed of insertion of the electrode array into the inner ear, our data did not demonstrate a postoperative effect on vestibular functions (SVV and posturography), which have the same character and dynamics as in the group with standard manual insertion. REGISTRATION NUMBER: The project is registered on clinicaltrials.gov (registration number: NCT05547113).

• Klíčová slova
• Adults, Cochlear implantation, Hearing loss, Posturography, Robot-assisted surgery, Subjective visual vertical,
• MeSH
• dospělí MeSH
• kochleární implantace * metody   MeSH
• kochleární implantáty MeSH
• lidé středního věku MeSH
• lidé MeSH
• posturální rovnováha * fyziologie   MeSH
• roboticky asistované výkony * metody   MeSH
• vnímání prostoru * fyziologie   MeSH
• výsledek terapie MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• srovnávací studie MeSH

A syndromic association between a subset of testicular/paratesticular neoplasms is well established. Such examples include Carney complex and large cell calcifying Sertoli cell tumor, Peutz-Jeghers syndrome and intratubular large cell hyalinizing Sertoli cell neoplasia, and VHL syndrome and clear cell papillary cystadenoma of the epididymis.However, recent studies proposed potential novel links between some testicular and paratesticular neoplasms with certain tumor syndromes. While more studies are still needed to solidify these associations, recent research suggests that a subset of Leydig cell tumors may arise in patients with hereditary leiomyomatosis and renal cell carcinoma syndrome or that some seminomas may occur in Lynch syndrome patients. Additionally, an association between testicular sex cord stromal tumors and paratesticular sarcomas with Familial adenomatous polyposis syndrome and DICER1 syndrome, respectively, has been proposed as well. This review provides a comprehensive overview of the intricate relationship between familial syndromes and associated testicular and paratesticular tumors, shedding light on their clinicopathological and molecular characteristics.

• Klíčová slova
• Association, Familial syndromes, Paratestis, Testis, Tumors,
• MeSH
• dědičné nádorové syndromy * patologie   genetika   MeSH
• genetická predispozice k nemoci MeSH
• lidé MeSH
• nádory mužských pohlavních orgánů patologie   genetika   MeSH
• testikulární nádory * genetika   patologie   MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH

OBJECTIVES: We describe age-specific survival in thyroid cancer (TC) from Denmark, Finland, Norway, and Sweden over a 50-year period. DESIGN: Population-based survival study. METHODS: Relative 5-year survival data were obtained from the NORDCAN database for the years 1972-2021. RESULTS: In the first period 1972-1976, 5-year survival in TC in Finland, Norway, and Sweden was 90% or higher, but a strong negative step-wise age gradient was observed, which was worse for men than women. Over time, survival increased, and in the final period, 2017-2021, survival for all women and Danish men up to age 69 years was about 90% or higher and, for men from the other countries, only marginally lower. Even for older women survival reached 80%, for older men somewhat less. CONCLUSIONS: Age disadvantage in TC survival was for the most part corrected over the 50-year period, and the remaining task is to boost survival for the oldest patients.

• Klíčová slova
• anaplastic cancer, metastasis, prognosis, relative survival, trends,
• MeSH
• incidence MeSH
• lidé MeSH
• míra přežití MeSH
• nádory štítné žlázy * terapie   MeSH
• registrace MeSH
• rizikové faktory MeSH
• senioři MeSH
• věkové rozložení MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Geografické názvy
• Dánsko epidemiologie   MeSH
• Finsko epidemiologie   MeSH
• Norsko epidemiologie   MeSH
• Skandinávie a severské státy epidemiologie   MeSH
• Švédsko epidemiologie   MeSH

BACKGROUND: Biological aging is a physiological process that can be altered by various factors. The presence of a chronic metabolic disease can accelerate aging and increase the risk of further chronic diseases. The aim of the study was to determine whether the presence of metabolic syndrome (MetS) affects levels of markers that are associated with, among other things, aging. MATERIAL AND METHODS: A total of 169 subjects (58 with MetS, and 111 without metabolic syndrome, i.e., non-MetS) participated in the study. Levels of telomerase, GDF11/15, sirtuin 1, follistatin, NLRP3, AGEs, klotho, DNA/RNA damage, NAD+, vitamin D, and blood lipids were assessed from blood samples using specific enzyme-linked immunosorbent assay (ELISA) kits. RESULTS: Telomerase (p < 0.01), DNA/RNA damage (p < 0.006) and GDF15 (p < 0.02) were higher in MetS group compared to non-MetS group. Only vitamin D levels were higher in the non-MetS group (p < 0.0002). Differences between MetS and non-MetS persons were also detected in groups divided according to age: in under 35-year-olds and those aged 35-50 years. CONCLUSIONS: Our results show that people with MetS compared to those without MetS have higher levels of some of the measured markers of biological aging. Thus, the presence of MetS may accelerate biological aging, which may be associated with an increased risk of chronic comorbidities that accompany MetS (cardiovascular, inflammatory, autoimmune, neurodegenerative, metabolic, or cancer diseases) and risk of premature death from all causes.

• Klíčová slova
• AGEs, DNA/RNA damage GDF11/15, NAD+, NLRP3, aging, follistatin, klotho, metabolic syndrome, sirtuin 1, telomerase, vitamin D,
• Publikační typ
• časopisecké články MeSH

Background and Objectives: Insulinoma is a rare tumor of the Langerhans islets of the pancreas. It produces insulin and causes severe hypoglycemia with neuroglycopenic symptoms. The incidence is low, at about 1-2 per 1 million inhabitants per year. The diagnosis is based on the presence of Whipple's triad and the result of a fasting test. Surgery is the treatment of choice. Objectives: A retrospective observational study of patients operated on for insulinoma in our hospital focused on the diagnosis, the type of surgery, and complications. Materials and Methods: We retrospectively reviewed patients operated on due to insulinoma. There were 116 surgeries between 2000 and 2022. There were 79 females and 37 males in this group. A fasting test and a CT examination were performed on all the patients. Results: The average duration of the fasting test was 18 h. Insulinoma was found in the body and tail of the pancreas in more than half of the patients. Enucleation was the most frequent type of surgery. Complications that were Clavien Dindo grade III or more occurred in 18% of the patients. The most frequent complications were abscesses and pancreatic fistula. Five patients had malignant insulinoma. Conclusions: Surgery is the treatment of choice in the case of insulinomas. The enucleation of the tumor is a sufficient treatment for benign insulinomas, which are not in contact with the main pancreatic duct. Due to the low incidence of the condition, the centralization of patients is recommended.

• Klíčová slova
• Whipple’s triad, hypoglycemia, insulinoma, pancreas,
• MeSH
• hypoglykemie * etiologie   MeSH
• inzulinom * diagnóza   chirurgie   MeSH
• lidé MeSH
• nádory slinivky břišní * diagnóza   chirurgie   MeSH
• pankreas MeSH
• retrospektivní studie MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• pozorovací studie MeSH

PURPOSE: The treatment options for metastatic soft tissue sarcomas (STSs) are limited. In most cases, immunotherapy with immune checkpoint inhibitors has not been successful so far. Macrophages dominate the immune landscape of STSs; thus, combinatorial strategies aiming at both tumor-infiltrating lymphocytes and macrophages may represent a particularly relevant treatment approach for metastatic or recurrent STSs. METHODS: In this cohort study, 66 patients who underwent surgery for STSs were enrolled. Tumor cells and tumor-infiltrating immune cells were analyzed using flow cytometry and immunohistochemistry. In cell suspensions obtained from surgical resections, human T cells were activated by superparamagnetic polymer beads and cultured at a concentration of 0.3 × 106/µl in the absence or presence of therapeutic monoclonal antibodies (anti-PD-1, anti-CD47, and anti-PD-1 + anti-CD47). Supernatants from cell suspensions were analyzed using multiplex Luminex cytokine bead-based immunoassays. RESULTS: The most profound response to anti-CD47 therapy was observed in an undifferentiated pleiomorphic sarcoma which also displayed high expression of CD47 in the tumor microenvironment. Both anti-PD-1 and anti-CD47 therapies drastically increased the production of pro-inflammatory cytokines in the tumor microenvironment of STSs, but co-administration of both agents did not further increase cytokine secretion. Furthermore, all patient samples treated with a combination of both anti-PD-1 and anti-CD47 antibodies showed a dramatic reduction in cytokine secretion. CONCLUSION: Our findings suggest that anti-PD-1 and anti-CD47 therapies do not enhance each other, and the combined application of anti-PD-1 and anti-CD47 agents in vitro limits rather than potentiates their efficacy.

• Klíčová slova
• Combined immunotherapy, Don’t eat me signal, Immune checkpoint inhibitor sarcoma, Leiomyosarcoma, Undifferentiated pleiomorphic sarcoma,
• MeSH
• cytokiny metabolismus   MeSH
• imunoterapie * MeSH
• kohortové studie MeSH
• lidé MeSH
• nádorové mikroprostředí MeSH
• sarkom * farmakoterapie   MeSH
• suspenze MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• cytokiny MeSH
• suspenze MeSH