WNT10A variants: following the pattern of inheritance in tooth agenesis and self-reported family history of cancer.

OBJECTIVES: The aim of this study was the analysis of WNT10A variants in seven families of probands with various forms of tooth agenesis and self-reported family history of cancer. MATERIALS AND METHODS: We enrolled 60 young subjects (aged 13 to 17) from the Czech Republic with various forms of tooth agenesis. Dental phenotypes were assessed using Planmeca ProMax 3D (Planmeca Oy, Finland) with Planmeca Romexis software (version 2.9.2) together with oral examinations. After screening PAX9, MSX1, EDA, EDAR, AXIN2 and WNT10A genes on the Illumina MiSeq platform (Illumina, USA), we further analyzed the evolutionarily highly conserved WNT10A gene by capillary sequencing in the seven families. RESULTS: All the detected variants were heterozygous or compound heterozygous with various levels of phenotypic expression. The most severe phenotype (oligodontia) was found in a proband who was compound heterozygous for the previously identified WNT10A variant p.Phe228Ile and a newly discovered c.748G > A variant (p.Gly250Arg) of WNT10A. The newly identified variant causes substitution of hydrophobic glycine for hydrophilic arginine. CONCLUSIONS: We suggest that the amino acid changes in otherwise highly conserved sequences significantly affect the dental phenotype. No relationship between the presence of WNT10A variants and a risk of cancer has been found. CLINICAL RELEVANCE: Screening of PAX9, MSX1, EDA, EDAR, AXIN2 and WNT10A genes in hope to elucidate the pattern of inheritance in families.

An association of neovascular age-related macular degeneration with polymorphisms of CFH, ARMS2, HTRA1 and C3 genes in Czech population.

PURPOSE: We investigated associations between neovascular age-related macular degeneration (AMD) and rs10490924 polymorphism of ARMS2 gene (age-related maculopathy susceptibility 2), rs1061170 polymorphism of gene for complement factor H (CFH), rs2230199 polymorphism of gene for complement component C3 and rs11200638 polymorphism of gene for serine protease high-temperature requirement A1 (HTRA1) in the Czech population. METHODS: We analysed samples of DNA from 307 patients diagnosed with neovascular form of late AMD (average age: 73.7 ± 7.7 years) and 191 control subjects, recruited from patients awaiting cataract surgery (average age, 73.6 ± 8.7 years). RESULTS: HTRA1, CFH and ARMS2 genes polymorphisms were found to be related to neovascular AMD in the Czech population. All analysed polymorphisms were statistically significantly associated with neovascular AMD, with stronger associations in females than in males. In whole group, CC genotype of CFH gene polymorphism, TT genotype of ARMS2 gene polymorphism and AA genotype of HTRA1 gene polymorphism showed the greatest risk for neovascular AMD with odds ratios equal to 8.43, 10.07, 9.83, respectively (p < 0.0001). Only CG polymorphism of C3 gene showed statistically significant risk for neovascular AMD. In addition, we observed an association between waist circumference and neovascular AMD in both sexes, which further suggests the significance of excessive abdominal fat as a risk factor of AMD. We found a statistically significant association between polymorphisms in HTRA1, CFH and ARMS2 genes and neovascular AMS in the Czech population. The association was stronger in females than in males. CONCLUSION: We demonstrated a relationship between neovascular AMD and genes for HTRA1, CFH, ARMS2 and C3 in Czech population. To our knowledge, the relationship between these polymorphisms and neovascular AMD in Czech population has never been investigated before.

Reoperations after surgery for acute subdural hematoma: reasons, risk factors, and effects.

PURPOSE: To analyze the reasons and patient-related and injury-related risk factors for reoperation after surgery for acute subdural hematoma (SDH) and the effects of reoperation on treatment outcome. METHODS: Among adult patients operated on for acute SDH between 2013 and 2017, patients reoperated within 14 days after the primary surgery were identified. In all patients, parameters were identified that related to the patient (age, anticoagulation, antiplatelet, and antiepileptic treatment, and alcohol intoxication), trauma (Glasgow Coma Score, SDH thickness, midline shift, midline shift /hematoma thickness rate, other surgical lesion, primary surgery-trephination, craniotomy, or decompressive craniotomy), and Glasgow Outcome Score (GOS). The reasons for reoperation and intervals between primary surgery and reoperation were studied. RESULTS: Of 86 investigated patients, 24 patients were reoperated (27.9%), with a median interval of 2 days between primary surgery and reoperation. No significant differences in patients and injury-related factors were found between reoperated and non-reoperated patients. The rate of primary craniectomies was higher in non-reoperated patients (P = 0.066). The main indications for reoperation were recurrent /significant residual SDH (10 patients), contralateral SDH (5 patients), and expansive intracerebral hematoma or contusion (5 patients). The final median GOS was 3 in non-reoperated and 1.5 in reoperated patients, with good outcomes in 41.2% of non-reoperated and 16.7% of reoperated patients. CONCLUSIONS: Reoperation after acute SDH surgery is associated with a significantly worse prognosis. Recurrent /significant residual SDH and contralateral SDH are the most frequently found reasons for reoperation. None of the analyzed parameters were significant reoperation predictors.

Single-center long-term results of vagus nerve stimulation for epilepsy: A 10-17 year follow-up study.

PURPOSE: The paper presents a long-term follow-up study of VNS patients, analyzing seizure outcome, medication changes, and surgical problems. METHOD: 74 adults with VNS for 10 to 17 years were evaluated yearly as: non-responder - NR (seizure frequency reduction <50%), responder - R (reduction ≥ 50% and <90%), and 90% responder - 90R (reduction ≥ 90%). Delayed R or 90R (≥ 4 years after surgery), patients with antiepileptic medication changes and battery or complete system replacement were identified. Statistical analysis of potential outcome predictors (age, seizure duration, MRI, seizure type) was performed. RESULTS: The rates of R and 90R related to the patients with outcome data available for the study years 1, 2, 10, and 17 were for R 38.4%, 51.4%, 63.6%, and 77.8%, and for 90R 1.4%, 5.6%, 15.1%, and 11.1%. The absolute numbers of R and 90R increased until years 2 and 6. Antiepileptic therapy was changed in 62 patients (87.9%). There were 11 delayed R and four delayed 90R, with medication changes in the majority. At least one battery replacement was performed in 51 patients (68.9%), 49 of whom R or 90R. VNS system was completely replaced in 7 patients (9.5%) and explanted in 7 NR (9.5%). No significant predictor of VNS outcome was found. CONCLUSIONS: After an initial increase, the rate of R and 90R remains stable in long-term follow-up. The changes of antiepileptic treatment in most patients potentially influence the outcome. Battery replacements or malfunctioning system exchange reflect the patient's satisfaction and correlate with good outcomes.

The Results of Neuroendoscopic Surgery in Patients with Posttraumatic and Posthemorrhagic Hydrocephalus.

BACKGROUND: Posttraumatic hydrocephalus (PTH) and posthemorrhagic hydrocephalus (PHH) were previously considered not suitable for neuroendoscopic treatment. New hydrocephalus theories support possible successful neuroendoscopy in such patients. METHODS: This study presents the results of neuroendoscopy in PTH and PHH with a background analysis. From 130 hydrocephalic patients after neuroendoscopic surgeries, 35 cases with PTH (n = 11) or PHH (n = 24; acute: n = 9, subacute: n = 10, chronic: n = 5) were found. The success rate (Glasgow Outcome Scale [GOS] score 4 or 5 without shunt) and clinical outcome (GOS score) of endoscopic third ventriculostomy (ETV) were analyzed. During the study period, 34 patients had ventriculoperitoneal shunts implanted, including 2 PTH and 5 PHH patients (all chronic). RESULTS: The success rate of ETV in PTH was 54.5%. In acute PHH, the success rate was 33.3%, 42.8% after excluding devastating hematomas. A post-ETV shunt was implanted in 1 patient (massive subarachnoid hemorrhage [SAH]) with final GOS score of 5. In subacute cases, the ETV success rate was 40% (no post-ETV shunts). In chronic PHH, only 1 patient with a GOS score of 5 was shunt-free (20%). The cause of ETV failure was massive SAH. Low final GOS score was caused by the extent of intracerebral bleeding or extracranial problems. The main indications for primary shunt implantation in PTH and PHH were infectious complications. The rate of good outcomes was 0% in PTH and 40% in PHH. CONCLUSIONS: The best results of neuroendoscopy were achieved in PTH and acute PHH. ETV failures were associated with massive SAH; arachnoid cistern blockage and scarring precludes ETV success.

CD36 gene is associated with intraocular pressure elevation after intravitreal application of anti-VEGF agents in patients with age-related macular degeneration: Implications for the safety of the therapy.

BACKGROUND: The wet form of age-related macular degeneration (AMD) is characterized by pathological vascularization of the outer retinal layers. The condition responds to treatment with antibodies against vascular endothelial growth factor (VEGF), but the patients receiving such anti-VEGF therapy sometimes show undesirable acute short-term increases in the intraocular pressure (IOP). The cause of this adverse effect is unknown, and here, we are testing a hypothesis that it is related to CD36 gene polymorphisms. MATERIALS AND METHODS: A group of 134 patients with AMD were given three therapeutic doses of anti-VEGF antibody (ranibizumab) at monthly intervals. Their IOP was measured immediately before and 30 min after each injection. Patients' DNA was analyzed, and the changes in IOP were matched against seven polymorphisms of the CD36 gene. RESULTS: Three polymorphisms were found to be associated with increases in IOP: rs1049673 (p = 0.006), rs3211931 (p = 0.01), and rs1761667 (p = 0.043) at the time of the third injection only. Pronounced elevations (IOP > 25 mmHg) were associated with rs1049673 polymorphism: GC genotype (p < 0.01) and CC genotype (p < 0.05); both increasing the risk 2.6-fold, the presence of C-allele conferring a 1.5-fold greater risk and with rs3211931 polymorphism: AG genotype (p < 0.01) and GG genotype (p < 0.05); increasing the risk 2.6-fold (AG) and 2.7-fold (GG). CONCLUSIONS: CD36 receptor may be involved in mediating the effects of VEGF on IOP. The findings will help to identify the patients at risk of acutely elevated IOP following the anti-VEGF therapy.