BACKGROUND: Immune checkpoint inhibitors (ICIs), including those targeting PD-1, are currently used in a wide range of tumors, but only 20-40% of patients achieve clinical benefit. The objective of our study was to find predictive peripheral blood-based biomarkers for ICI treatment. METHODS: In 41 patients with advanced malignant melanoma (MM) and NSCLC treated with PD-1 inhibitors, we analyzed peripheral blood-based immune subsets by flow cytometry before treatment initialization and the second therapy dose. Specifically, we assessed basic blood differential count, overall T cells and their subgroups, B cells, and myeloid-derived suppressor cells (MDSC). In detail, CD4 + and CD8 + T cells were assessed according to their subtypes, such as central memory T cells (TCM), effector memory T cells (TEM), and naïve T cells (TN). Furthermore, we also evaluated the predictive value of CD28 and ICOS/CD278 co-expression on T cells. RESULTS: Patients who achieved disease control on ICIs had a significantly lower baseline proportion of CD4 + TEM (p = 0.013) and tended to have a higher baseline proportion of CD4 + TCM (p = 0.059). ICI therapy-induced increase in Treg count (p = 0.012) and the proportion of CD4 + TN (p = 0.008) and CD28 + ICOS- T cells (p = 0.012) was associated with disease control. Patients with a high baseline proportion of CD4 + TCM and a low baseline proportion of CD4 + TEM showed significantly longer PFS (p = 0.011, HR 2.6 and p ˂ 0.001, HR 0.23, respectively) and longer OS (p = 0.002, HR 3.75 and p ˂ 0.001, HR 0.15, respectively). Before the second dose, the high proportion of CD28 + ICOS- T cells after ICI therapy initiation was significantly associated with prolonged PFS (p = 0.017, HR 2.51) and OS (p = 0.030, HR 2.69). Also, a high Treg count after 2 weeks of ICI treatment was associated with significantly prolonged PFS (p = 0.016, HR 2.33). CONCLUSION: In summary, our findings suggest that CD4 + TEM and TCM baselines and an early increase in the Treg count induced by PD-1 inhibitors and the proportion of CD28 + ICOS- T cells may be useful in predicting the response in NSCLC and MM patients.

• MeSH
• antigeny CD278 metabolismus   MeSH
• antigeny CD279 antagonisté a inhibitory   MeSH
• antigeny CD28 MeSH
• CD8-pozitivní T-lymfocyty imunologie   účinky léků   metabolismus   MeSH
• dospělí MeSH
• inhibitory kontrolních bodů * terapeutické užití   farmakologie   MeSH
• lidé středního věku MeSH
• lidé MeSH
• melanom * farmakoterapie   imunologie   krev   patologie   MeSH
• nádory plic * farmakoterapie   imunologie   krev   patologie   MeSH
• nemalobuněčný karcinom plic * farmakoterapie   imunologie   krev   patologie   MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

INTRODUCTION: Meningiomas are usually slow-growing tumours, constituting about one third of all primary intracranial tumours. They occur more frequently in women. Clinical manifestation of meningiomas depends on their location, tumour size and growth rate. In most cases, surgical treatment is the procedure of choice. The success of this treatment is, however, associated with the radicality of the resection. Radiotherapy represents an additional or alternative treatment modality. Gamma knife surgery is another notable treatment method, especially in small and/or slow-growing tumours in eloquent areas or in elderly patients. MATERIAL AND METHODS: Authors describe their experience with the diagnosis, treatment and outcome of the patients with meningioma (n = 857). Furthermore, they also assess the postoperative morbidity/mortality and recurrence rate. RESULTS AND CONCLUSIONS: In view of the benign histology of meningiomas, the success of the treatment largely depends (besides the tumour grading) on the radicality of the resection. The emphasis is also put on appropriate follow-up of the patients. In certain patients, the watch and wait strategy should be also considered as a suitable treatment method.

• MeSH
• lidé MeSH
• lokální recidiva nádoru chirurgie   MeSH
• meningeální nádory * chirurgie   MeSH
• meningeom * chirurgie   patologie   MeSH
• mikrochirurgie MeSH
• neurochirurgické výkony metody   MeSH
• retrospektivní studie MeSH
• senioři MeSH
• výsledek terapie MeSH
• Check Tag
• lidé MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

BACKGROUND: Ring 18 chromosome is a rare chromosomal aberration associated with a wide range of symptoms affecting all organ systems. One possible symptom associated with this condition is an orofacial cleft. However, to date, there are very few reported cases where the cleft has been surgically treated. CASE DESCRIPTION: In our case study, we present a female patient with Ring 18 chromosome who underwent cleft palate surgery at 14 months of age. Subsequently, a reoperation of the palate was necessary due to wound dehiscence. For the secondary reconstruction of the palate, the acellular dermal matrix (ADM) MatriDerm® was used to improve healing. The cleft palate surgery progressively improved her ability to take in food, allowing a transition from nasogastric tube feeding to oral intake. RESULTS: This is only the fourth reported case of a child with Ring 18 chromosome undergoing surgical correction of an orofacial cleft. Additionally, it is one of the first cases where an ADM MatriDerm® was used in the surgical correction of a cleft palate. In this study, we also present a comprehensive literature review, providing an overview of the various symptoms associated with this syndrome. CONCLUSION: Cleft palate surgery had a very positive effect on improving food intake in the patient with Ring 18 chromosome. The use of an acellular dermal matrix during the secondary cleft palate surgery led to improved healing and a good outcome.

• MeSH
• kojenec MeSH
• kruhové chromozomy * MeSH
• lidé MeSH
• lidské chromozomy, pár 18 genetika   MeSH
• rozštěp patra * genetika   chirurgie   MeSH
• Check Tag
• kojenec MeSH
• lidé MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• kazuistiky MeSH
• přehledy MeSH

BACKGROUND: Myasthenia gravis (MG) is a rare autoimmune disorder with significant clinical implications, including life-threatening myasthenic crises and exacerbations. Understanding real-world treatment patterns, especially associated direct medical costs, is essential for the effective management of healthcare delivery. METHODS: We conducted a descriptive cohort study using health administrative claims data from the Czech Republic covering more than 1,500 prevalent MG patients. Data were analysed for healthcare resource utilization, medication costs, and hospitalization rates related to MG and its complications. RESULTS: Acetylcholine inhibitors and corticosteroids were widely prescribed, with 91.1% and 75.2% of patients receiving them at least once, respectively. Immunosuppressive therapy was given to 45.2% of patients. Myasthenic crises occurred in 2% of patients, with a mean hospitalization cost of 21,020 EUR, while exacerbations occurred in 9.2% of patients, with lower costs (5,951 EUR per hospitalization). Outpatient intravenous immunoglobulin and plasma exchange therapies incurred additional costs of 20,700 EUR and 18,206 EUR per person-year, respectively. The mean total cost per patient-year was 1,271 EUR, with significant cost differences among patients with different treatment patterns. CONCLUSION: This study offers real-world insights into the treatment patterns and associated direct medical costs of MG in the Czech Republic. Myasthenic crises and exacerbations pose considerable cost burdens, while outpatient therapies and common pharmacotherapies are less costly. These findings are vital for healthcare planning, economic evaluation, and resource allocation, potentially leading to enhanced patient care and outcomes.

• MeSH
• dospělí MeSH
• hospitalizace ekonomika   MeSH
• kohortové studie MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• myasthenia gravis * ekonomika   terapie   farmakoterapie   MeSH
• náklady na zdravotní péči MeSH
• senioři MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Geografické názvy
• Česká republika MeSH

BACKGROUND: Telerehabilitation is a practical option for individuals with multiple sclerosis (MS) to engage in sustained physical activity without -visiting a rehabilitation facility. The aim of this systematic review was to evaluate the feasibility, effectiveness, safety, and adherence of exercise-based telerehabilitation as compared with usual care for MS patients. METHODS: A comprehensive literature search adhering to PRISMA guidelines was conducted, focusing on studies published in English since 2000. The systematic review protocol was registered in PROSPERO. The selection process involved strict criteria, including studies focusing on people with MS, telerehabilitation centred on regular exercise, a control group receiving usual care, valid exercise testing, and adherence to randomized controlled trial principles. Methodological quality was assessed using the TESTEX tool, ensuring rigour in study design and reporting. RESULTS: Among the 281 records screened, 10 studies met the criteria. Telerehabilitation interventions varied in format and outcomes were assessed using diverse exercise tests and questionnaires. Despite variations, the studies collectively demonstrated promising feasibility and safety, with minimal withdrawals and minor adverse events. Effectiveness varied, with 5 out of 10 studies showing significant improvements in the intervention group. Adherence rates ranged from 38% to 100%. CONCLUSION: In most of the assessed aspects, telerehabilitation is comparable to regular centre-based rehabilitation.

• MeSH
• adherence pacienta MeSH
• cvičení * MeSH
• lidé MeSH
• roztroušená skleróza * rehabilitace   MeSH
• telerehabilitace * MeSH
• terapie cvičením * metody   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• systematický přehled MeSH

BACKGROUND: Although cystic fibrosis (CF) standards of care have been produced and regularly updated, they are not specifically targeting at the adult population. The ECFS Standards of Care Project established an international task force of experts to identify quality standards for adults with CF and assess their adherence. METHODS: This study was composed of two phases. In the first one, a task force of international experts derived from published guidelines and graded ten quality standards for adult CF care using a modified Delphi methodology. In the second phase, an international audit was conducted among adult CF centers to retrospectively validate the quality statements and monitor adherence. RESULTS: The task force identified 10 quality standards specific to the care of adults with CF, mainly based on the 2018 ECFS standards of care. 14 adult CF centers participated in the audit, which showed that most quality standards for the management of CF in adults are met across Europe. Heterogeneity in adherence to standards was found across centers according to geographical setting and centers' characteristics. CONCLUSIONS: The identification of quality standards is a valuable resource for the standardization and monitoring of care delivery across centers taking care of adults with CF.

• MeSH
• cystická fibróza * terapie   MeSH
• delfská metoda MeSH
• dodržování směrnic MeSH
• dospělí MeSH
• lidé MeSH
• management nemoci MeSH
• poradní výbory MeSH
• retrospektivní studie MeSH
• směrnice pro lékařskou praxi jako téma MeSH
• standardní péče MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• Geografické názvy
• Evropa MeSH

BACKGROUND: Anaplastic Large Cell Lymphoma (ALCL) is a rare and aggressive T-cell lymphoma, classified into ALK-positive and ALK-negative subtypes, based on the presence of chromosomal translocations involving the ALK gene. The current standard of treatment for ALCL is polychemotherapy, with a high overall survival rate. However, a subset of patients does not respond to or develops resistance to these therapies, posing a serious challenge for clinicians. Recent targeted treatments such as ALK kinase inhibitors and anti-CD30 antibody-drug conjugates have shown promise but, for a fraction of patients, the prognosis is still unsatisfactory. METHODS: We investigated the genetic landscape of ALK + ALCL by whole-exome sequencing; recurring mutations were characterized in vitro and in vivo using transduced ALCL cellular models. RESULTS: Recurrent mutations in FAT family genes and the transcription factor RUNX1T1 were found. These mutations induced changes in ALCL cells morphology, growth, and migration, shedding light on potential factors contributing to treatment resistance. In particular, FAT4 silencing in ALCL cells activated the β-catenin and YAP1 pathways, which play crucial roles in tumor growth, and conferred resistance to chemotherapy. Furthermore, STAT1 and STAT3 were hyper-activated in these cells. Gene expression profiling showed global changes in pathways related to cell adhesion, cytoskeletal organization, and oncogenic signaling. Notably, FAT mutations associated with poor outcome in patients. CONCLUSIONS: These findings provide novel insights into the molecular portrait of ALCL, that could help improve treatment strategies and the prognosis for ALCL patients.

• MeSH
• anaplastický velkobuněčný lymfom * genetika   patologie   farmakoterapie   MeSH
• fenotyp MeSH
• kadheriny * genetika   MeSH
• lidé MeSH
• mutace * MeSH
• myši MeSH
• nádorové buněčné linie MeSH
• prognóza MeSH
• sekvenování exomu MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH

OBJECTIVES: This study evaluated maxillary growth and dental arch relationships at 5 and 10 years of age in patients with unilateral cleft lip and palate (UCLP) who underwent early cleft lip and palate surgery. METHODS: 28 patients with UCLP who underwent cleft lip surgery in neonatal age and cleft palate surgery at average age of 7 months without orthodontic treatment (intervention group) were measured for intercanine and intermolar distances and for dental arch length. These measurements were compared with those of 30 healthy participants in a control group. Dental arch relationships in the intervention group were evaluated by 5-YO index at 5 years and the GOSLON Yardstick score at 10 years of patients' age. RESULTS: Patients in the intervention group had significantly shorter mean intercanine distance and arch length than control patients at both 5 and 10 years of age (p<.001 for all). There were no significant differences in intermolar distance at both 5 (p = .945) and 10 years (p = .105) of patients' age. The average 5YO index increased from 2.46 to an average GOSLON 10-year score of 2.89 in intervention group. CONCLUSION: Intercanine distance and dental arch length of patients with UCLP are significantly reduced at 5 and 10 years after early cleft lip and palate surgeries compared to the healthy population. Dental arch relationships at 5 and 10 years of patients with UCLP show comparable outcomes to those reported by other cleft centers. CLINICAL SIGNIFICANCE: This study evaluates maxillary growth in UCLP patients 5 and 10 years of age who underwent early primary lip and palate surgery.

• MeSH
• dítě MeSH
• lidé MeSH
• maxila * chirurgie   růst a vývoj   MeSH
• maxilofaciální vývoj MeSH
• předškolní dítě MeSH
• průřezové studie MeSH
• rozštěp patra * chirurgie   MeSH
• rozštěp rtu * chirurgie   MeSH
• studie případů a kontrol MeSH
• zubní oblouk * růst a vývoj   patologie   chirurgie   MeSH
• Check Tag
• dítě MeSH
• lidé MeSH
• mužské pohlaví MeSH
• předškolní dítě MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

INTRODUCTION: Dynamic indices of fluid responsiveness (FR) such as pulse pressure variation (PPV) and stroke volume variation (SVV) differ among hemodynamic monitors, which use proprietary algorithms, and vary even over a short period of time. We aimed to compare the baseline values, fluctuation and predictive value for FR of PPV and SVV measured by three minimally invasive monitors. PATIENTS AND METHODS: Twenty patients undergoing high-risk abdominal surgery were included and 45 fluid challenges were analysed. The patients were simultaneously monitored using Carescape B650, LiDCO Rapid and FloTrac/Vigileo system. Cardiac output (CO), PPV and SVV were recorded before and after the fluid challenge of 500 ml of balanced crystalloid solution. An increase in CO ≥ 15 % defined fluid responders. Concurrently recorded arterial waveform was used for offline calculation of PPV. RESULTS: Mean baseline values of the indices ranged between 8.6 % and 13.4 %. LiDCO showed higher fluctuation of indices compared to the other monitors. Area under the receiver operating characteristic curve (AUROC) ranged from 0.71 to 0.76 with optimal cut-off value between 7.5 % and 13.9 %. AUROC increased for all indices when FR was defined as an increase in stroke volume. Furthermore, a decrease in PPV or SVV after fluid challenge (ΔPPV, ΔSVV) proved a better marker of FR (AUROC 0.82-0.93) than baseline values with a uniform threshold of approximately -3%. CONCLUSIONS: Although a significant range of baselines variations and optimal cut-off values was observed, the predictive value of PPV and SVV from all the monitors was only moderate and comparable. Nevertheless, ΔPPV and ΔSVV appear to be a reliable and device-independent markers of FR.

• Publikační typ
• časopisecké články MeSH

BACKGROUND AND IMPORTANCE: Extracranial-intracranial bypass remains an enduring procedure for a select group of patients suffering from steno-occlusive cerebrovascular disease. Although the superficial temporal artery (STA) to middle cerebral artery (MCA) bypass is most familiar among neurosurgeons, particular circumstances preclude the use of an STA donor. In such cases, alternative revascularization strategies must be pursued. CLINICAL PRESENTATION: A 63-year-old female presented with symptoms of hemodynamic insufficiency and was found to have left common carotid artery occlusion at the origin. She experienced progressive watershed ischemia and pressure-dependent fluctuations in her neurological examination despite maximum medical therapy. The ipsilateral STA was unsuitable for use as a donor vessel. We performed an extracranial vertebral artery (VA) to MCA bypass with a radial artery interposition graft. CONCLUSION: This technical case description and accompanying surgical video review the relevant anatomy and surgical technique for a VA-MCA bypass. The patient was ultimately discharged home at her preoperative neurological baseline with patency of the bypass. The VA can serve as a useful donor vessel for cerebral revascularization procedures in pathologies ranging from malignancies of the head and neck to cerebral aneurysms and cerebrovascular steno-occlusive disease.

• MeSH
• arteria carotis interna chirurgie   MeSH
• arteria cerebri media diagnostické zobrazování   chirurgie   MeSH
• arteria vertebralis diagnostické zobrazování   chirurgie   MeSH
• cerebrovaskulární poruchy * chirurgie   MeSH
• lidé středního věku MeSH
• lidé MeSH
• revaskularizace mozku * metody   MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• kazuistiky MeSH