Quantitative Analysis of the MGMT Methylation Status of Glioblastomas in Light of the 2021 WHO Classification.

Background: Glioblastomas with methylation of the promoter region of the O(6)-methylguanine-DNA methyltransferase (MGMT) gene exhibit increased sensitivity to alkylating chemotherapy. Quantitative assessment of the MGMT promoter methylation status might provide additional prognostic information. The aim of our study was to determine a quantitative methylation threshold for better survival among patients with glioblastomas. Methods: We included consecutive patients ≥18 years treated at our department between 11/2010 and 08/2018 for a glioblastoma, IDH wildtype, undergoing quantitative MGMT promoter methylation analysis. The primary endpoint was overall survival. Results: A total of 321 patients were included. Median overall survival was 12.6 months. Kaplan−Meier and adjusted Cox regression analysis showed better survival for the groups with 16−30%, 31−60%, and 61−100% methylation. In contrast, survival in the group with 1−15% methylation was similar to those with unmethylated promoter regions. A secondary analysis confirmed this threshold. Conclusions: Better survival is observed in patients with glioblastomas with ≥16% methylation of the MGMT promoter region than with <16% methylation. Survival with tumors with 1−15% methylation is similar to with unmethylated tumors. Above 16% methylation, we found no additional benefit with increasing methylation.

Natural history of meningiomas: a serial volumetric analysis of 240 tumors.

OBJECTIVE: The management of asymptomatic intracranial meningiomas is controversial. Through the assessment of growth predictors, the authors aimed to create the basis for practicable clinical pathways for the management of these tumors. METHODS: The authors volumetrically analyzed meningiomas radiologically diagnosed at their institution between 2003 and 2015. The primary endpoint was growth of tumor volume. The authors used significant variables from the multivariable regression model to construct a decision tree based on the exhaustive Chi-Square Automatic Interaction Detection (CHAID) algorithm. RESULTS: Of 240 meningiomas, 159 (66.3%) demonstrated growth during a mean observation period of 46.9 months. On multivariable logistic regression analysis, older age (OR 0.979 [95% CI 0.958-1.000], p = 0.048) and presence of calcification (OR 0.442 [95% CI 0.224-0.872], p = 0.019) had a negative predictive value for tumor growth, while T2-signal iso-/hyperintensity (OR 4.415 [95% CI 2.056-9.479], p < 0.001) had a positive predictive value. A decision tree model yielded three growth risk groups based on T2 signal intensity and presence of calcifications. The median tumor volume doubling time (Td) was 185.7 months in the low-risk, 100.1 months in the intermediate-risk, and 51.7 months in the high-risk group (p < 0.001). Whereas 0% of meningiomas in the low- and intermediate-risk groups had a Td of ≤ 12 months, the percentage was 8.9% in the high-risk group (p = 0.021). CONCLUSIONS: Most meningiomas demonstrated growth during follow-up. The absence of calcifications and iso-/hyperintensity on T2-weighted imaging offer a practical way of stratifying meningiomas as low, intermediate, or high risk. Small tumors in the low- or intermediate-risk categories can be monitored with longer follow-up intervals.

Coverage of complex tissue defects following open cervicothoracic spine surgery with a lower trapezius island myocutaneous flap-an interdisciplinary approach.

The study design is a clinical case series. The objective of this study was to present the concept and efficacy of the lower trapezius island myocutaneous flap (LTIMF) for management of complex wound healing disorders following open cervicothoracic spine surgery. Wound healing disturbances with myocutaneous defects after open spine surgery at the cervical and upper thoracic spine are well-described complications. In severe cases, plastic reconstructive coverage is often required as a last resort. A review of all adult patients with deep wound dehiscence and tissue defects following open cervicothoracic spine surgery, who were managed with plastic surgery reconstruction using a LTIMF at our institution, was conducted. Synopses of these cases are presented. Seven patients with a mean age of 73 years ± 13 (range 50 to 89 years) were included in this case series. Six out of seven patients had instrumented posterior fusion added to their decompression. All patients were managed with a LTIMF for wound coverage. No spinal implants were removed prior to LTIMF surgery. The mean follow-up was 5.2 months (± 5.4 months). No major flap failure occurred, and all patients presented with satisfactory cosmetic results. The only minor complication was development of a sterile subcutaneous seroma in two patients, which were successfully managed by puncture and aspiration. The LTIMF is an effective and reliable salvage treatment option for spine surgery patients offering stable coverage of deep tissue defects resulting from complex wound healing disorders at the cervical and upper thoracic spine.

ACE-inhibitors: a preventive measure for bone flap resorption after autologous cranioplasty?

OBJECTIVEDecompressive craniectomy (DC) is an established treatment for refractory intracranial hypertension. It is usually followed by autologous cranioplasty (AC), the reinsertion of a patient's explanted bone flap. A frequent long-term complication of AC is bone flap resorption (BFR), which results in disfigurement as well as loss of the protective covering of the brain. This study investigates risk factors for BFR after AC, including medical conditions and antihypertensive drug therapies, with a focus on angiotensin-converting enzyme inhibitors (ACEIs), which have been associated with a beneficial effect on bone healing and bone preservation in orthopedic, osteoporosis, and endocrinology research.METHODSIn this single-center, retrospective study 183 consecutive cases were evaluated for bone flap resorption after AC. Information on patient demographics, medical conditions, antihypertensive therapy, and BFR-defined as an indication for revision surgery established by a neurosurgeon based on clinical or radiographic assessments-was collected. A Kaplan-Meier analysis of time from AC to diagnosis of BFR was performed, and factors associated with BFR were investigated using the log-rank test and Cox regression.RESULTSA total of 158 patients were considered eligible for inclusion in the data analysis. The median follow-up time for this group was 2.2 years (95% CI 1.9-2.5 years). BFR occurred in 47 patients (29.7%), with a median time to event of 3.7 years (95% CI 3.3-4.1 years). An ACEI prescription was recorded in 57 cases (36.1%). Univariate Kaplan-Meier analysis and the log-rank test revealed that ACEI therapy (2-year event free probability [EFP] 83.8% ± 6.1% standard error vs 63.9% ± 5.6%, p = 0.02) and ventriculoperitoneal (VP) shunt treatment (2-year EFP 86.9% ± 7.1% vs 66% ± 5.0%, p = 0.024) were associated with a lower probability of BFR. Multiple Cox regression analysis showed ACEI therapy (HR 0.29, p = 0.012), VP shunt treatment (HR 0.278, p = 0.009), and male sex (HR 0.500, p = 0.040) to be associated with a lower risk for BFR, whereas bone fragmentation (HR 1.92, p = 0.031) was associated with a higher risk for BFR.CONCLUSIONSHypertensive patients treated with ACEIs demonstrate a lower rate of BFR than patients treated with other hypertensive medications and nonhypertensive patients. Our results are in line with previous reports on the positive influence of ACEIs on bone healing and preservation. Further analysis of the association between ACEI treatment and BFR development is needed and will be evaluated in a multicenter prospective trial.