The objective of this study is to measure lymphocyte responses to metal antigens using MELISA (memory lymphocyte immunostimulation assay) test-modified lymphocyte transformation test (mLTT) and to evaluate metal sensitization in patients with and without the need of prosthetic surgery. This study is a case-control retrospective survey. We retrospectively analyzed all patients from 2013 to 2018 who were referred to the Institute of Dental Medicine, General University Hospital in Prague, and First Faculty of Medicine, Charles University, Prague, either following joint prosthesis-related complications or as a preoperative evaluation concerning metal hypersensitivity. For the control group, we selected healthy adults from our database. A group of 127 patients aged 25-81 years was chosen, 92 of which were female and 35 were male. The patients completed a special questionnaire aimed at information regarding their health status and history of metal exposure. After clinical examination, their peripheral blood samples were taken to perform mLTT. mLTT provided quantitative lymphocyte proliferation measurement, where a stimulation index of >2 indicated metal sensitivity. For statistical analysis, the Fisher's exact test, χ2 test, McNemar's exact test Student's paired t-test were used. By comparison of the study group and control group mLTT results, it can be stated that patients of the study group showed a higher level of lymphocyte reactivity to most of the tested metal antigens (Ag [silver], Cu [copper], Fe [iron], Mo [molybdenum], Pd [palladium], Pt [platinum], Ti [titanium], and Zn [zinc]) and an elevated incidence of metal hypersensitivity to Hg (mercury), Al (aluminum), Au (gold), Co (cobalt), Cr (chromium), Ni (nickel), and Sn (tin). The evaluation of the data obtained from patients in this study confirmed a significant clinical benefit of mLTT in diagnostics of metal hypersensitivity. Our study has revealed that the patients with the need of prosthetic surgery exhibited an elevated lymphocyte response to metal antigens. This result supports a metal-specific adaptive immune response and suggests involvement of metal exposure as a trigger for their health problems. This knowledge could be helpful in effectively enhancing the treatment of patients with need of orthopedic joint prosthesis.

• MeSH
• Lymphocyte Activation MeSH
• Hypersensitivity * etiology   diagnosis   immunology   MeSH
• Adult MeSH
• Metals * adverse effects   immunology   MeSH
• Middle Aged MeSH
• Humans MeSH
• Lymphocytes * immunology   MeSH
• Joint Prosthesis * adverse effects   MeSH
• Retrospective Studies MeSH
• Prosthesis Failure * MeSH
• Aged, 80 and over MeSH
• Aged MeSH
• Case-Control Studies MeSH
• Check Tag
• Adult MeSH
• Middle Aged MeSH
• Humans MeSH
• Male MeSH
• Aged, 80 and over MeSH
• Aged MeSH
• Female MeSH
• Publication type
• Journal Article 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.

• Publication type
• Journal Article MeSH

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
• Facial Paralysis * diagnosis   rehabilitation   therapy   MeSH
• Humans MeSH
• Facial Nerve Diseases diagnosis   rehabilitation   therapy   MeSH
• Neurologic Examination methods   MeSH
• Neurological Rehabilitation * methods   MeSH
• Mirror Movement Therapy MeSH
• Check Tag
• Humans MeSH
• Publication type
• Review 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
• Epithelial Cell Adhesion Molecule genetics   MeSH
• Colorectal Neoplasms, Hereditary Nonpolyposis genetics   MeSH
• Genetic Predisposition to Disease * genetics   MeSH
• Colorectal Neoplasms * genetics   MeSH
• Mismatch Repair Endonuclease PMS2 genetics   MeSH
• MutL Protein Homolog 1 genetics   MeSH
• Practice Guidelines as Topic MeSH
• Germ-Line Mutation genetics   MeSH
• Publication type
• Research Support, Non-U.S. Gov't MeSH
• Review MeSH
• Geographicals
• Czech Republic MeSH

• Keywords
• guselkumab,
• MeSH
• Acitretin administration & dosage   MeSH
• Biological Therapy methods   MeSH
• Adult MeSH
• Antibodies, Monoclonal, Humanized * administration & dosage   MeSH
• Humans MeSH
• Treatment Failure MeSH
• Obesity complications   MeSH
• Psoriasis * drug therapy   complications   pathology   MeSH
• Check Tag
• Adult MeSH
• Humans MeSH
• Male MeSH
• Publication type
• Case Reports 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
• Adult MeSH
• Genetic Predisposition to Disease * MeSH
• Middle Aged MeSH
• Humans MeSH
• Breast Neoplasms * genetics   MeSH
• Ovarian Neoplasms * genetics   MeSH
• DNA Repair genetics   MeSH
• Fanconi Anemia Complementation Group G Protein * genetics   MeSH
• Aged MeSH
• Case-Control Studies MeSH
• Germ-Line Mutation * MeSH
• Check Tag
• Adult MeSH
• Middle Aged MeSH
• Humans MeSH
• Aged MeSH
• Female MeSH
• Publication type
• Journal Article MeSH

• Keywords
• secukinumab, brodalumab,
• MeSH
• Antibodies, Monoclonal, Humanized pharmacology   therapeutic use   MeSH
• Middle Aged MeSH
• Humans MeSH
• Psoriasis * drug therapy   MeSH
• Check Tag
• Middle Aged MeSH
• Humans MeSH
• Female MeSH
• Publication type
• Case Reports MeSH

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.; 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.

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

• NML Publication type
• 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
• Ataxia Telangiectasia Mutated Proteins genetics   MeSH
• Checkpoint Kinase 2 genetics   MeSH
• Genetic Predisposition to Disease * MeSH
• Genes, BRCA1 MeSH
• Genes, BRCA2 MeSH
• Prostatic Neoplasms diagnosis   genetics   prevention & control   MeSH
• Breast Neoplasms diagnosis   genetics   prevention & control   MeSH
• Pancreatic Neoplasms diagnosis   genetics   prevention & control   MeSH
• Ovarian Neoplasms diagnosis   genetics   prevention & control   MeSH
• Primary Prevention methods   MeSH
• Fanconi Anemia Complementation Group N Protein genetics   MeSH
• Secondary Prevention methods   MeSH
• Practice Guidelines as Topic MeSH
• Germ-Line Mutation MeSH