sv.
Práce je zaměřena na poruchy čichu u pacientů s olfaktoriálními meningiomy (OGM). Přesné klinické vyšetření pacientů s OGM, včetně pre- a pooperačního zhodnocení čichu, je nezbytné pro hodnocení provedené chirurgické resekce. Článek poskytuje základní přehled recentních sérií OGM světových autorů. Jen malý zlomek z nich však dokumentuje přesné vyšetření čichu. Standardní vyšetření čichu by mělo stanovit čichovou detekci, diskriminaci a identifikaci pomocí jednoho z užívaných testů (např. University of Pennsylvania Smell Identification Test [UPSIT], The Single Staircase Odor Detection Treshold Test, Sniffin’ Sticks Test). Metodami vyšetření čichu, které jsou zatím využívány pro výzkum, zůstávají elektro-olfaktogram, čichové evokované potenciály a funkční magnetická rezonance. Zlatým standardem léčby OGM je chirurgická resekce. Volba vhodného operačního přístupu je stále kontroverzní a mezi jednotlivými autory nepanuje shoda. Nejčastěji se používá frontolaterální a pterionální přístup. Alternativou je endoskopická resekce, jejíž indikace jsou však omezené. Pooperační zachování čichu představuje zatím obtížný úkol.
This review summarizes dysfunction of olfaction in patients with olfactory groove meningiomas (OGM). Clinical examination, including pre-operative and post-operative assessment of olfaction, is indispensable for the evaluation of the surgical outcome in patients with OGM. Review of a recent series of OGM documents showed a lack of the olfaction assessment in most of the studies. Psychophysical tests determining olfactory detection, discrimination and identification (e. g. University of Pennsylvania Smell Identification Test [UPSIT], The Single Staircase Odor Detection Threshold Test, Siffin’ Sticks Test) should be used to reveal olfactory dysfunction. Specialized examination techniques such as electro-olfactogram, olfactory evoked potentials and functional magnetic resonance imaging are being used in research. Standard treatment of OGM is a surgical resection. Controversy exists among the authors regarding the selection of a convenient surgical approach. Commonly, the uni-frontal and pterional approaches are being performed. Endoscopic resection, olfactory groove meningiomas, represents an alternative approach yet its indications are still limited. Postoperative olfaction preservation remains a difficult task even today.
- Klíčová slova
- olfaktoriální meningiom,
- MeSH
- baze lební chirurgie MeSH
- lidé MeSH
- lokální recidiva nádoru MeSH
- meningeální nádory diagnóza chirurgie patofyziologie MeSH
- meningeom * diagnóza chirurgie patofyziologie MeSH
- nemoci čichového nervu diagnóza etiologie MeSH
- nervus olfactorius MeSH
- neurochirurgické výkony * metody škodlivé účinky MeSH
- olfaktometrie MeSH
- pooperační komplikace MeSH
- poranění čichového nervu etiologie MeSH
- poruchy čichu * diagnóza etiologie chirurgie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- práce podpořená grantem MeSH
- přehledy MeSH
Acute lymphoblastic leukemia (ALL) is the most prevalent type of cancer occurring in children. ALL is characterized by structural and numeric genomic aberrations that strongly correlate with prognosis and clinical outcome. Usually, a combination of cyto- and molecular genetic methods (karyotyping, array-CGH, FISH, RT-PCR, RNA-Seq) is needed to identify all aberrations relevant for risk stratification. We investigated the feasibility of optical genome mapping (OGM), a DNA-based method, to detect these aberrations in an all-in-one approach. As proof of principle, twelve pediatric ALL samples were analyzed by OGM, and results were validated by comparing OGM data to results obtained from routine diagnostics. All genomic aberrations including translocations (e.g., dic(9;12)), aneuploidies (e.g., high hyperdiploidy) and copy number variations (e.g., IKZF1, PAX5) known from other techniques were also detected by OGM. Moreover, OGM was superior to well-established techniques for resolution of the more complex structure of a translocation t(12;21) and had a higher sensitivity for detection of copy number alterations. Importantly, a new and unknown gene fusion of JAK2 and NPAT due to a translocation t(9;11) was detected. We demonstrate the feasibility of OGM to detect well-established as well as new putative prognostic markers in an all-in-one approach in ALL. We hope that these limited results will be confirmed with testing of more samples in the future.
- Publikační typ
- časopisecké články MeSH
BACKGROUND: Stereotactic radiosurgery (SRS) is increasingly considered for selected olfactory groove meningiomas (OGMs). OBJECTIVE: To investigate the safety and efficacy of SRS for OGMs. METHODS: From 20 institutions participating in the International Radiosurgery Research Foundation, we pooled patients who underwent SRS for histologically confirmed or radiologically suspected WHO grade I OGMs and were followed for 6 mo or more after the SRS. RESULTS: In total, 278 (median age 57 yr) patients underwent SRS for histologically confirmed (29%) or radiologically suspected (71%) WHO grade I OGMs Median treatment volume was 4.60 cm3 (range: 0.12-27.3 cm3), median prescription dose was 12 Gy, and median dose to the olfactory nerve was 11.20 Gy. During median post-SRS imaging follow-up of 39 mo (range: 6-240 mo), 43% of patients had partial or marginal response, 54% of patients had stable disease, and 3% of patients experienced progression. During median post-SRS clinical follow-up of 51 mo (range: 6-240 mo), 36 (13%) patients experienced clinical and/or radiological adverse radiation events (AREs). Elevated risk of AREs was associated with larger OGM volume (P = .009) and pre-SRS peritumoral T2/fluid-attenuated inversion-recovery signal abnormalities (P < .001). After the SRS, olfaction remained stable, improved, or deteriorated in 90%, 8%, and 2% of patients, respectively. Complete post-SRS anosmia was predicted by partial/complete anosmia before the SRS (odds ratio [OR] = 83.125; 95% CI [24.589-281.01], P < .001) and prior resection of OGM (OR = 3.919; 95% CI [1.713-8.970], P = .001). CONCLUSION: SRS is associated with durable local control of the majority of OGM patients with acceptable safety profile. SRS allows preservation or improvement of olfactory function in the majority of OGM patients.
- MeSH
- lidé středního věku MeSH
- lidé MeSH
- meningeální nádory * diagnostické zobrazování radioterapie chirurgie MeSH
- meningeom * diagnostické zobrazování radioterapie chirurgie MeSH
- následné studie MeSH
- radiochirurgie * škodlivé účinky MeSH
- retrospektivní studie MeSH
- výsledek terapie MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- multicentrická studie MeSH
BACKGROUND: Fuchs endothelial corneal dystrophy (FECD) is the most common repeat-mediated disease in humans. It exclusively affects corneal endothelial cells (CECs), with ≤81% of cases associated with an intronic TCF4 triplet repeat (CTG18.1). Here, we utilise optical genome mapping (OGM) to investigate CTG18.1 tissue-specific instability to gain mechanistic insights. METHODS: We applied OGM to a diverse range of genomic DNAs (gDNAs) from patients with FECD and controls (n = 43); CECs, leukocytes and fibroblasts. A bioinformatics pipeline was developed to robustly interrogate CTG18.1-spanning DNA molecules. All results were compared with conventional polymerase chain reaction-based fragment analysis. FINDINGS: Analysis of bio-samples revealed that expanded CTG18.1 alleles behave dynamically, regardless of cell-type origin. However, clusters of CTG18.1 molecules, encompassing ∼1800-11,900 repeats, were exclusively detected in diseased CECs from expansion-positive cases. Additionally, both progenitor allele size and age were found to influence the level of leukocyte-specific CTG18.1 instability. INTERPRETATION: OGM is a powerful tool for analysing somatic instability of repeat loci and reveals here the extreme levels of CTG18.1 instability occurring within diseased CECs underpinning FECD pathophysiology, opening up new therapeutic avenues for FECD. Furthermore, these findings highlight the broader translational utility of FECD as a model for developing therapeutic strategies for rarer diseases similarly attributed to somatically unstable repeats. FUNDING: UK Research and Innovation, Moorfields Eye Charity, Fight for Sight, Medical Research Council, NIHR BRC at Moorfields Eye Hospital and UCL Institute of Ophthalmology, Grantová Agentura České Republiky, Univerzita Karlova v Praze, the National Brain Appeal's Innovation Fund and Rosetrees Trust.
- MeSH
- alely MeSH
- expanze trinukleotidových repetic MeSH
- Fuchsova endoteliální dystrofie * genetika patologie MeSH
- lidé středního věku MeSH
- lidé MeSH
- mapování chromozomů MeSH
- nestabilita genomu MeSH
- orgánová specificita genetika MeSH
- senioři MeSH
- transkripční faktor 4 * genetika metabolismus MeSH
- trinukleotidové repetice genetika MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
... -- BSPlayer 175 -- Instalace a prostředí programu 175 -- Přehrání zálohy AVI 176 -- Přehrání zálohy OGM ... ... 177 -- Vylepšení zálohy OGM pro BSPlayer 178 -- Nastavení programu 179 -- CAPITOLA 9 -- Alternativní ...
1.vyd. 202 s.
Quantitative genomic mapping of DNA damage may provide insights into the underlying mechanisms of damage and repair. Sequencing based approaches are bound to the limitations of PCR amplification bias and read length which hamper both the accurate quantitation of damage events and the ability to map them to structurally complex genomic regions. Optical Genome mapping in arrays of parallel nanochannels allows physical extension and genetic profiling of millions of long genomic DNA fragments, and has matured to clinical utility for characterization of complex structural aberrations in cancer genomes. Here we present a new mapping modality, Repair-Assisted Damage Detection - Optical Genome Mapping (RADD-OGM), a method for single-molecule level mapping of DNA damage on a genome-wide scale. Leveraging ultra-long reads to assemble the complex structure of a sarcoma cell-line genome, we mapped the genomic distribution of oxidative DNA damage, identifying regions more susceptible to DNA oxidation. We also investigated DNA repair by allowing cells to repair chemically induced DNA damage, pinpointing locations of concentrated repair activity, and highlighting variations in repair efficiency. Our results showcase the potential of the method for toxicogenomic studies, mapping the effect of DNA damaging agents such as drugs and radiation, as well as following specific DNA repair pathways by selective induction of DNA damage. The facile integration with optical genome mapping enables performing such analyses even in highly rearranged genomes such as those common in many cancers, a challenging task for sequencing-based approaches.
- MeSH
- bromičnany toxicita MeSH
- lidé MeSH
- mapování chromozomů * přístrojové vybavení metody MeSH
- mikrofluidní analytické techniky * přístrojové vybavení metody MeSH
- nádorové buněčné linie MeSH
- nanotechnologie * přístrojové vybavení metody MeSH
- oprava DNA genetika MeSH
- oxidační stres účinky léků genetika MeSH
- poškození DNA * genetika MeSH
- regulace genové exprese MeSH
- stanovení celkové genové exprese MeSH
- toxikogenetika * přístrojové vybavení metody MeSH
- variabilita počtu kopií segmentů DNA MeSH
- zobrazení jednotlivé molekuly * přístrojové vybavení metody MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
BACKGROUND: Clinical examination, including pre- and postoperative assessment of olfaction, is essential in evaluating surgical outcomes in patients with olfactory groove meningiomas (OGMs). A review of a recent series revealed a lack of assessment of olfaction in most of the studies. Tests determining olfactory detection should be used to reveal olfactory dysfunction. Specialized examination techniques (e.g., electro-olfactography, olfactory evoked potentials, and functional magnetic resonance imaging) are currently used in research. METHODS: Prospective analysis of 13 patients who underwent surgical resection of OGMs from December 2013 to December 2017 was performed. Data on clinical presentation, pre- and postoperative neurologic examinations, complications, recurrences, adjuvant treatment, and follow-up outpatient examinations were recorded. Olfactory function was assessed using the Sniffin' Sticks odor identification test preoperatively, postoperatively, and 1 year after surgery. RESULTS: All the meningiomas were resected via unilateral craniotomy, and gross total resection was achieved in all cases. Surgery-related permanent morbidity was 7.7% and overall mortality 0%. For the eight patients with preoperative normosmia, five remained normosmic (62.5%), one deteriorated to hyposmia (12.5%), and two deteriorated to anosmia (25%). For the two patients with preoperative hyposmia, one remained hyposmic and one deteriorated to anosmia. For the three anosmic patients, two remained anosmic, and one improved to hyposmia.The intact olfactory function preoperatively was associated with a better olfactory outcome. Overall, 62.5% of these patients remained normosmic, and none of the hyposmic or anosmic patients normalized their olfaction.Higher meningioma volume is associated with worse olfactory function before surgery (normosmia in 16.7% versus 100.0% in less voluminous) and following the surgery (normosmia in 16.7% versus 57.1% less voluminous).The unilateral surgical approach enabled the anatomical preservation of the contralateral olfactory nerve in 76.9% of our patients. Functional normosmia was achieved in 50% and hyposmia in 30% of these cases. CONCLUSIONS: Assessment of olfactory function is both vital in preoperative decision making (surgical approach, radicality of resection) and when evaluating surgical outcome. Preoperative normosmia seems to be the most important prognostic factor for functional olfactory outcome. In normosmic patients the olfaction was preserved in 62.5% of cases. Moreover, higher meningioma volume is associated with worse olfactory function before and following the surgery. The greatest advantage of the unilateral surgical approach is anatomical preservation of the contralateral olfactory nerve with a satisfactory functional outcome. These results support a proactive approach, with early surgical resection using a unilateral approach even in cases with less voluminous OGMs that enables the preservation of olfactory function in a significant proportion of patients.
- MeSH
- čich fyziologie MeSH
- dospělí MeSH
- kraniotomie škodlivé účinky MeSH
- lidé středního věku MeSH
- lidé MeSH
- magnetická rezonanční tomografie MeSH
- meningeální nádory diagnostické zobrazování patofyziologie chirurgie MeSH
- meningeom diagnostické zobrazování patofyziologie chirurgie MeSH
- pooperační komplikace etiologie patofyziologie MeSH
- pooperační období MeSH
- poruchy čichu etiologie patofyziologie MeSH
- prospektivní studie 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
