Léze lícního nervu vede ve všech fázích onemocnění k celé řadě funkčních, motorických i psychických omezení. Akutní terapie má v neurologii a neurochirurgii již dlouhou dobu definované postupy na základech evidence based medicine. V navazující rehabilitační terapii jsou však postupy nekonzistentní, terapie jsou aplikovány dle empirických zkušeností, s malou oporou v evidenci. V současné době jsou již některé postupy ověřovány, ale stále buď na malém vzorku pacientů, nebo pouze v jednotlivých oblastech. Např. v oblasti elektroterapie jsou metodiky nejednotné, bez jednoznačně definovaných doporučení. K účinku relaxačních metod, masáží a manuální lymfatické drenáže neexistují rovněž žádná přesvědčivá data. Pozitivně se jeví využití zrcadlové terapie a virtuální terapie s biofeedbackem, ale i zde je potřebné sjednotit postup a doplnit evidenci.

Facial nerve lesions lead to a variety of functional, motor, and psychological limitations in all stages of the disease. Acute therapy in neurology and neurosurgery has long defined procedures based on evidence-based medicine. However, in follow-up, rehabilitation therapy procedures are inconsistent, with therapies applied according to empirical experience with little support from the evidence. Currently, some procedures are already being validated, but still either in a small sample of patients or only in individual areas. For example, in the field of electrotherapy, methodologies are inconsistent, without clearly defined recommendations. There are also no conclusive data on the effect of relaxation methods, massage, and manual lymphatic drainage. The use of mirror therapy and virtual therapy with biofeedback is positive, but here too, there appears a need for standardization of practice and the addition of evidence.

• MeSH
• faciální paralýza * diagnóza   rehabilitace   terapie   MeSH
• lidé MeSH
• nemoci lícního nervu diagnóza   rehabilitace   terapie   MeSH
• neurologické vyšetření metody   MeSH
• neurorehabilitace * metody   MeSH
• zrcadlová terapie v rehabilitaci MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• přehledy MeSH

Poly(ADP-ribose) polymerase (PARP) inhibitors (PARPis) are currently used to treat BRCA1/2 mutant cancers. Although PARPi sensitivity has been attributed to homologous recombination (HR) defects, other roles of HR factors have also been linked to response to PARPi, including replication fork protection. In this study, we investigated PARPi sensitivity in ovarian cancer patient-derived xenograft (PDX) models in relation to HR proficiency and replication fork protection. Analysis of BRCA1/2 status showed that in our cohort of 31 ovarian cancer PDX models 22.6% harbored a BRCA1/2 alteration (7/31), and 48.3% (15/31) were genomically unstable as measured by copy number alteration analysis. In vivo, PARPi olaparib response was measured in 15 selected PDX models. Functional assessment of HR using ex vivo irradiation-induced RAD51 foci formation identified all olaparib-sensitive PDX models, including four models without BRCA1/2 alterations. In contrast, replication fork protection or replication speed in ex vivo tumor tissue did not correlate with olaparib response. Targeted panel sequencing in olaparib-sensitive models lacking BRCA1/2 alterations revealed a MUS81 variant as a possible mechanism underlying PARPi sensitivity. Combined, we show that ex vivo RAD51 analysis effectively predicts in vivo olaparib response and revealed a subset of PARPi-sensitive, HR-deficient ovarian cancer PDX models, lacking a BRCA1/2 alteration.

• Publikační typ
• časopisecké články MeSH

Doporučené postupy klinické péče o nosiče patogenních variant v klinicky relevantních genech predisponujících ke vzniku Lynchova syndromu a karcinomu kolorekta definují kroky primární a sekundární prevence, která by měla být osobám ve vysokém riziku vzniku dědičných nádorů v ČR poskytnuta. Tvorba doporučených postupů byla organizována pracovní skupinou onkogenetiky Společnosti lékařské genetiky a genomiky při České lékařské společnosti J. E. Purkyně ve spolupráci se zástupci onkologie, onkogynekologie a gastroenterologie. Doporučené postupy vycházejí z aktuálních doporučení National Comprehensive Cancer Network (NCCN), Evropské společnosti pro klinickou onkologii (ESMO) a zohledňují kapacitní možnosti našeho zdravotnictví.

The guidelines for clinical practice for carriers of pathogenic variants in clinically relevant genes predisposing to Lynch syndrome and colorectal cancer define the steps of primary and secondary prevention that should be provided to the individuals at high risk of developing hereditary cancer in the Czech Republic. The drafting of the guidelines was organized by the Oncogenetics Working Group of the Society for Medical Genetics and Genomics of J. E. Purkyně Czech Medical Society, in cooperation with representatives of oncology, oncogynecology, and gastroenterology. The guidelines are based on the current recommendations of the National Comprehensive Cancer Network (NCCN), European Society of Medical Oncology (ESMO) and take into account the capacity of the Czech healthcare system.

• MeSH
• adhezní molekula epiteliálních buněk genetika   MeSH
• dědičné nepolypózní kolorektální nádory genetika   MeSH
• genetická predispozice k nemoci * genetika   MeSH
• kolorektální nádory * genetika   MeSH
• mismatch repair endonukleáza PMS2 genetika   MeSH
• MutL homolog 1 genetika   MeSH
• směrnice pro lékařskou praxi jako téma MeSH
• zárodečné mutace genetika   MeSH
• Publikační typ
• práce podpořená grantem MeSH
• přehledy MeSH
• Geografické názvy
• Česká republika MeSH

Background: The aim of our pilot study was to assess the feasibility and effectiveness of individual balance telerehabilitation for people with multiple sclerosis (MS). Methods: In this pilot study 20 individuals with MS with balance impairment were included (10 in experimental, 10 in control group). The experimental group underwent 12 weeks of individual telerehabilitation (with direct synchronous contact between the physiotherapist and the patient). The control group received conventional outpatient physiotherapy. The standardized tests of balance and functional mobility were assessed at baseline and after intervention. Results: Comparing the two groups, the experimental group achieved statistically significant improvement in balance: the BBS test (p=0.002), TUG (p=0.048), functional test standing on one limb (p=0.01), and subjectively perceived balance with the ABC Scale questionnaire (p=0.041). The substantive significance (Cohen's d) when comparing the two groups reached a large effect size in the BBS (d=0.83) and standing on one limb (d=1.06) and in the MSWS-12 (d=0.78) and ABC Scale questionnaire (d=0.78). Conclusion: Telerehabilitation interventions represent an increasing trend and our data suggest that individually delivered online telerehabilitation can be effective in the treatment of balance and functional mobility disorders in MS.

BACKGROUND: Monoallelic germline pathogenic variants (GPVs) in five Fanconi anemia (FA) genes (BRCA1/FANCS, BRCA2/FANCD1, PALB2/FANCN, BRIP1/FANCJ, and RAD51C/FANCO) confer an increased risk of breast (BC) and/or ovarian (OC) cancer, but the role of GPVs in 17 other FA genes remains unclear. METHODS: Here, we investigated the association of germline variants in FANCG/XRCC9 with BC and OC risk. RESULTS: The frequency of truncating GPVs in FANCG did not differ between BC (20/10,204; 0.20%) and OC (8/2966; 0.27%) patients compared to controls (6/3250; 0.18%). In addition, only one out of five tumor samples showed loss-of-heterozygosity of the wild-type FANCG allele. Finally, none of the nine functionally tested rare recurrent missense FANCG variants impaired DNA repair activities (FANCD2 monoubiquitination and FANCD2 foci formation) upon DNA damage, in contrast to all tested FANCG truncations. CONCLUSION: Our study suggests that heterozygous germline FANCG variants are unlikely to contribute to the development of BC or OC.

• MeSH
• dospělí MeSH
• genetická predispozice k nemoci * MeSH
• lidé středního věku MeSH
• lidé MeSH
• nádory prsu * genetika   MeSH
• nádory vaječníků * genetika   MeSH
• oprava DNA genetika   MeSH
• protein FANCG * genetika   MeSH
• senioři MeSH
• studie případů a kontrol MeSH
• zárodečné mutace * MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

Germline mutations in susceptibility genes predispose to approx. 10% of all breast cancer (BC) cases, but genetic factors cause much higher fraction of all BC cases. Recently, many rare single nucleotide polymorphisms (SNPs) were identified in genome-wide association studies (GWAS). These SNPs each account for a very low of risk, but when many risk variants are considered collectively, their predictive power is much greater. A combination of particular SNPs in an individual lead to their cumulative effect increasing the BC risk. Genotyping of these loci enables a calculation of polygenic risk score (PRS) for modification and individualization BC risk estimates. We will evaluate of a clinical utility of PRS for a stratification of BC risk in healthy carriers of mutation in predisposition genes, which could facilitate to assess a proper management and timing of preventive steps decreasing the BC risk. Another result is an estimation of a clinical value of PRS determination as an independent factor influencing risk of BC development in general population of women in the Czech Republic.

Zárodečné mutace v predispozičních genech se podílejí na vzniku přibližně 10% všech karcinomů prsu, ale podíl genetických faktorů na vzniku onemocnění je vyšší. V posledních letech byla díky celogenomovým asociačním (GWAS) studiím identifikována skupina častých jednonukleotidových polymorfismů (SNPs), které individuálně velmi málo, avšak signifikantně, modifikují riziko vzniku karcinomu prsu. Výskyt konkrétních SNP u jedince vede k jejich aditivnímu účinku na riziko vzniku karcinomu prsu. Genotypizace polymorfních lokusů umožňuje riziko onemocnění kvantifikovat a na základě tzv. skóre polygenního rizika (PRS) stratifikovat. Výsledkem studie bude zhodnocení klinického využití stanovení PRS pro stratifikaci rizika vzniku karcinomu prsu u nosiček mutací v predispozičních genech bez nádorového onemocnění, které by umožnilo určení vhodného postupu a načasování preventivních opatření snižujících riziko vzniku onemocnění. Sekundárním cílem je zhodnocení výpovědní hodnoty stanovení PRS jako nezávislého faktoru ovlivňujícího riziko vzniku karcinomu prsu v obecné populaci žen v ČR.

• Klíčová slova
• breast cancer, karcinom prsu, stratifikace rizika, risk stratification, PRS-polygenic risk score, PRS-polygenic risk score,

• NLK Publikační typ
• závěrečné zprávy o řešení grantu AZV MZ ČR

Doporučené postupy klinické péče o nosiče patogenních variant v klinicky relevantních nádorových predispozičních genech definují kroky primární a sekundární prevence, která by měla být těmto osobám ve vysokém riziku vzniku dědičných nádorů v ČR poskytnuta. Tvorba doporučení byla organizována pracovní skupinou onkogenetiky Společnosti lékařské genetiky a genomiky (SLG ČLS JEP) ve spolupráci se zástupci onkologie a onkogynekologie. Doporučené postupy vycházejí z aktuálních doporučení National Comprehensive Cancer Network (NCCN), European Society of Medical Oncology (ESMO) a zohledňují kapacitní možnosti našeho zdravotnictví.

The Guidelines for Clinical Practice for carriers of pathogenic variants in clinically relevant cancer predisposition genes define the steps of primary and secondary prevention that should be provided to these individuals at high risk of developing hereditary cancer in the Czech Republic. The drafting of the guidelines was organized by the Oncogenetics Working Group of the Society for Medical Genetics and Genomics of J. E. Purkyně Czech Medical Society (SLG ČLS JEP) in cooperation with the representatives of oncology and oncogynecology. The guidelines are based on the current recommendations of the National Comprehensive Cancer Network (NCCN), European Society of Medical Oncology (ESMO) and take into account the capacity of the Czech healthcare system.

• MeSH
• ATM protein genetika   MeSH
• checkpoint kinasa 2 genetika   MeSH
• genetická predispozice k nemoci * MeSH
• geny BRCA1 MeSH
• geny BRCA2 MeSH
• nádory prostaty diagnóza   genetika   prevence a kontrola   MeSH
• nádory prsu diagnóza   genetika   prevence a kontrola   MeSH
• nádory slinivky břišní diagnóza   genetika   prevence a kontrola   MeSH
• nádory vaječníků diagnóza   genetika   prevence a kontrola   MeSH
• primární prevence metody   MeSH
• protein FANCN genetika   MeSH
• sekundární prevence metody   MeSH
• směrnice pro lékařskou praxi jako téma MeSH
• zárodečné mutace MeSH

Background:Research in telerehabilitation (TR) in neurology tends to focus on patients with low to moderate disability. For neurology patients with severe mobility limitations, TR can help to enable rehabilitation for people whose mobility limitations make it difficult for them to access rehabilitation facilities. The aim of this study is to evaluate the interest of people with neurological disability caused by multiple sclerosis (MS) in TR services.Methods:This electronic survey targeted individuals with MS, specifically those with a higher level of disability.Results:A total of 355 patients with MS (155 with severe disabilities) participated in this study. There was no difference in interest in rehabilitation between people with mild-to-moderate and severe disabilities (p = 0.1258, confidence interval [CI] = 95%). However, we found a higher interest in upper limb exercises (p = 0.0006, CI = 95%) and balance training (p = 0.0000, CI = 95%) among people with higher disability.Conclusion:The results of this study may help to improve the planning and targeting of TR interventions, where a different focus of intervention is appropriate for patients with different levels of disability. This may enable TR to be maximally tailored to patient capabilities and current greatest limitations. For example, for people with severe disabilities, it is appropriate to focus on training the upper limb function to maintain self-sufficiency and implement interventions to prevent falls.

• MeSH
• lidé MeSH
• omezení pohyblivosti MeSH
• roztroušená skleróza * rehabilitace   MeSH
• telerehabilitace * metody   MeSH
• terapie cvičením metody   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• Geografické názvy
• Česká republika MeSH

The subset of ovarian cancer (OC) diagnosed ≤ 30yo represents a distinct subgroup exhibiting disparities from late-onset OC in many aspects, including indefinite germline cancer predisposition. We performed DNA/RNA-WES with HLA-typing, PRS assessment and survival analysis in 123 early-onset OC-patients compared to histology/stage-matched late-onset and unselected OC-patients, and population-matched controls. Only 6/123(4.9%) early-onset OC-patients carried a germline pathogenic variant (GPV) in high-penetrance OC-predisposition genes. Nevertheless, our comprehensive germline analysis of early-onset OC-patients revealed two divergent trajectories of potential germline susceptibility. Firstly, overrepresentation analysis highlighted a connection to breast cancer (BC) that was supported by the CHEK2 GPV enrichment in early-onset OC(p = 1.2 × 10-4), and the presumably BC-specific PRS313, which successfully stratified early-onset OC-patients from controls(p = 0.03). The second avenue pointed towards the impaired immune response, indicated by LY75-CD302 GPV(p = 8.3 × 10-4) and diminished HLA diversity compared with controls(p = 3 × 10-7). Furthermore, we found a significantly higher overall GPV burden in early-onset OC-patients compared to controls(p = 3.8 × 10-4). The genetic predisposition to early-onset OC appears to be a heterogeneous and complex process that goes beyond the traditional Mendelian monogenic understanding of hereditary cancer predisposition, with a significant role of the immune system. We speculate that rather a cumulative overall GPV burden than specific GPV may potentially increase OC risk, concomitantly with reduced HLA diversity.

• MeSH
• checkpoint kinasa 2 genetika   MeSH
• dospělí MeSH
• genetická predispozice k nemoci * MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladý dospělý MeSH
• nádory vaječníků * genetika   MeSH
• studie případů a kontrol MeSH
• věk při počátku nemoci * MeSH
• zárodečné mutace * MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladý dospělý MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH