Newly Diagnosed Multifocal GBM: A Monocentric Experience and Literature Review

Simple SummaryGlioblastoma is an aggressive brain tumor with a dismal prognosis. In a minority of cases, it presents with multiple lesions already at the time of diagnosis, affecting patients’ survival and treatment. Our retrospective study aims to increase the current understanding and define a treatment for this sub-entity, to improve patient survival. Chemoradiotherapy is a also safe and efficacy treatment in patients with multiple lesions. Survival advantages from extensive resection remain unclear.AbstractGlioblastomas with multiple foci at presentation (mGBMs) account for 2–35% of all GBMs. mGBMs have limited existing data and no standardized treatment. This study aims to determine their incidence, demographic and clinical features, outcome, and prognostic factors in terms of overall survival. We performed a monocentric retrospective study, reviewing patients treated at the Istituto Oncologico Veneto. Inclusion criteria were: new diagnosis of GBM and presence of multiple lesions on pre-treatment MRI. ECOG PS was used to evaluate clinical condition, RANO criteria for radiological assessment, and CTCAE v5.0 for treatment-related adverse events. The incidence of newly diagnosed mGBM was 7.2% and the study population consisted of 98 patients. Median age was 63 years, M:F ratio of 1.8:1, and a surgical approach was undertaken in 73 patients (mostly partial resection). MGMT was methylated in 47.5%, and 82 patients received active oncological treatment (65.9% radiotherapy plus temozolomide (RT + TMZ)). The disease control rate with RT + TMZ was 63%. Median OS of the entire study population was 10.2 months (95% CI 6.6–13.8), and median PFS was 4.2 months (95% CI 3.2–5.2). The ECOG PS, the extent of resection, and the RT + TMZ were significant prognostic factors in the univariate analysis for OS, but only the RT + TMZ was a significant independent OS predictor in the multivariate analysis (HR = 3.1, 95% IC 1.3–7.7, p = 0.014). The incidence of mGBM is not rare. RT + TMZ is confirmed to be an independent prognostic factor for survival and a safe and effective treatment. When feasible, RT + TMZ should be considered as a possible first-line treatment. The role of the extent of resection is still unclear.     

Effect of oral CDP-choline on visual function in young amblyopic patients

Purpose The purpose of the study was to evaluate the effect on visual function of orally administered CDP-choline in addition to patching for the treatment of amblyopia in children. Methods This was an open label parallel group study comparing patching plus oral CDP-choline with patching alone. Sixty-one participants (aged between 5 and 10 years) suffering from anisometropic or strabismic amblyopia were divided at random into two groups: Group A, 800 or 1,200 mg (according to the body weight) of orally administered CDP-choline and 2-h patching a day; Group B, 2-h patching a day. Both groups were treated for 30 consecutive days. A follow-up visit was set 60 days after the treatment was discontinued. The main outcome measure was the change in visual acuity of amblyopic eyes as measured by Snellen’s E charts. The secondary outcome measures were changes in the visual acuity of amblyopic eye as measured by isolated letters (Snellen’s E) and changes in the contrast sensitivity of amblyopic eyes. Results The addition of CDP-choline to patching therapy was not found to be more effective than patching alone after 30-day treatment. The present results showed that adding CDP-choline to patching stabilised the effects obtained during the treatment period. In fact, whereas the participants treated only with patching showed a decrease in visual acuity at 90 days, these receiving CDP-choline and patching combined appeared to maintain the results obtained (two-way ANOVA: P = 0.0042). Similar results were obtained when measuring visual acuity by isolated Snellen’s E letters. Conclusions In amblyopic patients, CDP-choline combined with patching contributes to obtaining more stable effects than patching alone. Fabio De Gregorio works as an advisor for Tubilux Pharma S.p.A. The authors have full control of all primary data and they agree to allow Graefe’s Archives for Clinical and Experimental Ophthalmology to review their data if requested.     

Metronidazole-induced hepatotoxicity in a patient with xeroderma pigmentosum: A case report

Rationale:Whereas metronidazole-induced hepatotoxicity is quite rare in the general population, in individuals carrying a nucleotide excision repair disorder, namely Cockayne syndrome, there is a high risk of developing this complication.Patient concerns:We report the case of a 44-year-old man, affected by xeroderma pigmentosum, who was admitted to the hospital presenting aspiration pneumoniae caused by worsening dysphagia and with severe hepatotoxicity during the hospitalization.Diagnoses:Acute hepatitis, which was leading to acute liver failure, occurred during antibiotic treatment with metronidazole and ceftazidime with an elevation of liver enzymes consistent with hepatocellular damage pattern.Interventions:Hydration with glucose 5% solution, pantoprazole and vitamin K were administered, meanwhile other causes of hepatitis were ruled out and the ongoing antibiotic treatment was stopped suspecting a drug-induced liver injury.Outcomes:Liver function nearly completely recovered 1 month later with a first rapid improvement, within few days, of aminotransferases and coagulation studies, and slower of cholestatic enzymes.Lessons:We describe the first case available in the literature of hepatotoxicity associated with metronidazole treatment in a xeroderma pigmentosum patient. Clinicians therefore, based on this report and according to the possible underlying mechanism shared by other genetic diseases characterized by alterations in the pathway of DNA-repair, should consider such adverse event also in patients affected by this rare disease.     

Feto-maternal safety of intracervical sodium nitroprusside application in sheep

The feto-maternal safety of sodium nitroprusside (SNP) administration in the cervix of pregnant sheep is evaluated. Chronically catheterized pregnant sheep at approximately 0.9 gestation were divided into 2 groups that received 0.1 mg/kg maternal body weight of SNP gel (2%) or placebo into the internal cervical os. SNP or placebo gel was administered at 9 AM with both maternal and fetal blood gas/pH, and cardiovascular parameters were monitored for 6 hours. Except for a slight transient decrease of maternal oxygen and meta-hemoglobin content, and fetal oxygen content in the SNP group, no other significant changes were observed. However, such changes are minimal and unlikely to be of any clinical significance. Moreover, nitric oxide metabolites were unchanged in both maternal and fetal circulations.These data demonstrate few, if any, effects of intrauterine SNP administration on both cellular oxygenation and cardiovascular indexes. Thus, SNP treatment, once applied into the cervix, could be considered a safe procedure.     

Antiproliferative oleanane saponins from Meryta denhamii

Eight new oleanane saponins (1- 8) together with four know saponins (9-12) were isolated from the aerial parts of Meryta denhamii. Their structures were elucidated by 1D and 2D NMR experiments including 1D TOCSY, DQF-COSY, ROESY, HSQC, and HMBC spectroscopy, as well as ESIMS analysis. The antiproliferative activity of all compounds was evaluated using three murine and human cancer cell lines: J774.A1, HEK-293, and WEHI-164.     

Molecular analysis of the β-catenin gene in patients with the Mayer-Rokitansky-Küster-Hauser syndrome

Purpose

To study the β-catenin gene in a group of Mayer-Rokitansky-Küster-Hauser patients.

Methods

Twelve patients with the Mayer-Rokitansky-Küster-Hauser syndrome were included in this study. DNA was extracted from peripheral blood and the region codifying β-catenin GSK-3β phosphorylation sites on exon 3 was amplified. PCR products were purified and directly sequenced.

Results

No mutations were found in the GSK-3β phosphorylation sites on exon 3 of β-catenin gene in this group of patients with the MRKH syndrome.

Conclusions

β-catenin gene mutations are an unlikely cause of the MRKH syndrome.