PDGFRA, KIT, and KDR Gene Amplification in Glioblastoma: Heterogeneity and Clinical Significance.

Glioblastoma (GBM) is the most frequent tumor of the central nervous system, and its heterogeneity is a challenge in treatment. This study examined tumoral heterogeneity involving PDGFRA, KIT, and KDR gene amplification (GA) in 4q12 and its association with clinical parameters. Specimens from 22 GBM cases with GA for the 4q12 amplicon detected by FISH were investigated for homogeneous or heterogeneous coamplification patterns, diffuse or focal distribution of cells harboring GA throughout tumor sections, and pattern of clustering of fluorescence signals. Sixteen cases had homogenously amplification for all three genes (45.5%), for PDGFRA and KDR (22.7%), or only for PDGFRA (4.6%); six cases had heterogeneous GA patterns, with subpopulations including GA for all three genes and for two genes - PDGFRA and KDR (13.6%), or GA for all three and for only one gene - PDGFRA (9.1%) or KIT (4.6%). In 6 tumors (27.3%), GA was observed in focal tumor areas, while in the remaining 16 tumors (72.7%) it was diffusely distributed throughout the pathological specimen. Amplification was universally expressed as double minutes and homogenously stained regions. Coamplification of all three genes PDGFRA, KIT, and KDR, age ≥ 60 years, and total tumor resection were statistically associated with poor prognosis. FISH proved effective for detailed interpretation of molecular heterogeneity. The study uncovered an even more diverse range of amplification patterns involving the 4q12 oncogenes in GBM than previously described, thus highlighting a complex tumoral heterogeneity to be considered when devising more effective therapies.

Systematic Review of Platelet-Rich Plasma for Low Back Pain.

BACKGROUND: Low back pain (LBP) has a high economic burden and is strongly related to the degenerative process of the spine, especially in the intervertebral disc and of the facet joints. Numerous treatment modalities have been proposed for the management of LBP, and the use of platelet-rich plasma (PRP) has emerged as an innovative therapeutic option for degenerative disease of the spine. The present study aims to evaluate the efficacy of PRP injections in managing low back pain. METHODS: We conducted a systematic review in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) recommendations, a registered at PROSPERO Systematic Reviews Platform, under number CRD42021268491. The PubMed, Web of Science, and Scopus databases were searched to identify relevant articles, along with hand searching to identify gray literature articles, with no language restrictions. Randomized clinical trials (RCTs), nonrandomized trials (NRTs), and case series (CSs) with more than 10 patients were considered eligible. The quality assessment and the risk of bias of the randomized clinical trials were evaluated using the RoB II tool. An evaluation of the description of the preparation methods was performed using an adapted version of the MIBO checklist. RESULTS: An electronic database search resulted in 2324 articles, and after the exclusion of noneligible articles, 13 RCTs and 27 NRTs or CSs were analyzed. Of the 13 RCTs, 11 found favorable results in comparison to the control group in pain and disability, one showed no superiority to the control group, and one was discontinued because of the lack of therapeutic effect at eight-week evaluation. Description of the PRP preparation techniques were found in almost all papers. The overall risk of bias was considered high in 2 papers and low in 11. An adapted MIBO checklist showed a 72.7% compliance rate in the selected areas. CONCLUSIONS: In this systematic review, we analyzed articles from English, Spanish and Russian language, from large databases and grey literature. PRP was in general an effective and safe treatment for degenerative LPB. Positive results were found in almost studies, a small number of adverse events were related, the risk of bias of the RCTs was low. Based on the evaluation of the included studies, we graded as level II the quality of the evidence supporting the use of PRP in LBP. Large-scale, multicenter RCTs are still needed to confirm these findings.

Clinical and morphological profile of aneurysms of the anterior communicating artery treated at a neurosurgical service in Southern Brazil.

BACKGROUND: The aim of the study was to characterize the clinical profile of patients with anterior communicating artery (ACoA) aneurysms and examine potential correlations between clinical findings, aneurysm morphology, and outcome. METHODS: A review of medical records and diagnostic neuroimaging reports of patients treated at a neurosurgical service in Porto Alegre, Brazil, between August 2008 and January 2015 was performed. RESULTS: During the period, 100 patients underwent surgery for ACoA aneurysms. Fifteen had unruptured aneurysms and 85 had ruptured aneurysms. Ruptured aneurysms had a higher aspect ratio than unruptured ones (2.37 ± 0.71 vs. 1.93 ± 0.51, P = 0.02). Intraoperative rupture occurred in 3%, and temporary clipping was performed in 15%. Clinical vasospasm occurred in 43 patients with ruptured aneurysms (50.6%). Overall, mortality was 26%; 25 patients in the ruptured group (29.4%) and one in the unruptured group (6%). The Glasgow Outcome Scale (GOS) was favorable (GOS 4 or 5) in 54% of patients, significantly more so in those with unruptured aneurysms (P = 0.01). In patients with ruptured aneurysms, mortality was associated with preoperative Hunt and Hess (HH) score (P < 0.001), hydrocephalus (P < 0.001), and clinical complications (P < 0.001). Unfavorable outcomes were associated with HH score (P < 0.001), Fisher grade (P = 0.015), clinical vasospasm (P = 0.012), external ventricular drain (P = 0.015), hydrocephalus (P < 0.001), and presence of clinical complications (P = 0.001). In patients with unruptured aneurysms, presence of clinical complications was the only factor associated with mortality (P < 0.001). CONCLUSION: Despite advances in the management of subarachnoid hemorrhage and surgical treatment of aneurysms, mortality is still high, especially due to clinical complications.

Clinical and Molecular Characterization of Adult Glioblastomas in Southern Brazil.

We investigated 113 adult Brazilian patients with glioblastoma (GBM) for comparison with patients from distinct geographical areas and evaluation of suitability for novel targeted therapies. Patients were assessed for clinical features and tumor genomic characteristics such as ROS1 and NTRK1 rearrangements, KIT, PDGFRA, and KDR amplification, and RB1 deletion using multicolor fluorescence in situ hybridization. The majority of patients were male (53%), over 40 years (94%), with tumor located in single site (64%), in the right cerebral hemisphere (60%), and underwent partial resection (71%); 14% presented complications after surgery. The main clinical sign at diagnosis was focal abnormality (57%); frontal (31%); and temporal (20%) regions were most commonly affected. Median hospitalization time was 20 days, median survival was 175 days. One tumor was positive for rearrangement in NTRK1 and another in ROS1 (0.9% each). PDGFRA was amplified in 20% of cases, often co-amplified with KDR (>90%) and KIT (>60%). RB1 was deleted in 16% of patients. There was no association between these molecular abnormalities and patient survival. However, older age, complications after surgery, and right-sided tumors were independent variables associated with patient survival. This study contributes information on the molecular profile of glioblastomas in Latin America possibly supporting new target therapies.

Effect of N-acetylcysteine on vasospasm in subarachnoid hemorrhage.

Vasospasm remains an extremely serious complication that affects patients presenting with subarachnoid hemorrhage (SAH) due to ruptured intracranial aneurysms. The current therapeutic armamentarium is still insufficient in many cases, and the search for new therapies is necessary. In this study, we evaluated the effect of N-acetylcysteine (NAC) on cerebral arterial vasospasm using an experimental model. Twenty-four wistar rats were divided into 4 groups: [1] Control, [2] SAH, [3] SAH+NAC and [4] SAH+Placebo. The experimental model employed double subarachnoid injections of autologous blood. The proposed dose of NAC was 250 mg/kg intraperitoneally per day. We analyzed the inner area of the basilar artery to assess the action of NAC. The experimental model proved to be very adequate, with a mortality rate of 4%. The inner area of the basilar artery in the SAH group showed significant difference to the control group (p=0.009). The use of NAC significantly reduced vasospasm as compared to the untreated group (p=0.048) and established no significant difference to the control group (p=0.098). There was no significant improvement with the administration of placebo (p=0.97). The model of the dual hemorrhage proved to be very useful for vasospasm simulation, with overall low mortality. The administration of NAC significantly reduced vasospasm resulting from SAH, and may represent a new therapeutic alternative.

Peritumoral brain edema in intracranial meningiomas.

Occurrence of peritumoral brain edema (PBE) in meningiomas has been associated with several factors in recent years, although its pathophysiological mechanism has not yet been fully elucidated. The aim of this study was to analyze the correlation between the presence / degree of PBE and factors such as gender, age, size and histological subtype of tumor. We analyzed the MRI images of 74 patients operated on Hospital Beneficência Portuguesa de Porto Alegre for the presence / degree of PBE and data was statistically correlated with the parameters of the patient. PBE was present in 70.1% of patients. Tumors with higher volume had more PBE. Tumors of the olfactory groove showed more PBE than sphenoid wing and parassagittal tumors. Transitional subtype showed more PBE than fibroblastic and meningothelial subtypes.

Effect of N-acetylcysteine on vasospasm in subarachnoid hemorrhage / Efeito da N-acetilcisteína sobre o vasoespasmo na hemorragia subaracnóidea

Vasospasm remains an extremely serious complication that affects patients presenting with subarachnoid hemorrhage (SAH) due to ruptured intracranial aneurysms. The current therapeutic armamentarium is still insufficient in many cases, and the search for new therapies is necessary. In this study, we evaluated the effect of N-acetylcysteine (NAC) on cerebral arterial vasospasm using an experimental model. Twenty-four wistar rats were divided into 4 groups: [1] Control, [2] SAH, [3] SAH+NAC and [4] SAH+Placebo. The experimental model employed double subarachnoid injections of autologous blood. The proposed dose of NAC was 250 mg/kg intraperitoneally per day. We analyzed the inner area of the basilar artery to assess the action of NAC. The experimental model proved to be very adequate, with a mortality rate of 4 percent. The inner area of the basilar artery in the SAH group showed significant difference to the control group (p=0.009). The use of NAC significantly reduced vasospasm as compared to the untreated group (p=0.048) and established no significant difference to the control group (p=0.098). There was no significant improvement with the administration of placebo (p=0.97). The model of the dual hemorrhage proved to be very useful for vasospasm simulation, with overall low mortality. The administration of NAC significantly reduced vasospasm resulting from SAH, and may represent a new therapeutic alternative.

O vasoespasmo arterial encefálico continua sendo uma complicação extremamente grave que acomete pacientes com hemorragia subaracnóidea (HSA) por ruptura de aneurismas. O arsenal terapêutico atual ainda, em muitos casos, é insuficiente e a busca de novas alternativas terapêuticas torna-se necessária. Neste estudo, avaliamos a ação da N-acetilcisteína (NAC) sobre o vasoespasmo arterial encefálico em um modelo experimental. Foram utilizados 24 ratos wistar divididos em 4 grupos: [1] Controle, [2] HSA, [3] HSA+NAC e [4] HSA+Placebo. O modelo experimental utilizado foi o da dupla injeção subaracnóidea de sangue autólogo. A dose proposta da NAC foi de 250 mg/kg/dia por via intraperitoneal. Foi analisada a área interna da artéria basilar para avaliação da ação da NAC. O modelo experimental mostrou-se excelente com mortalidade de 4 por cento. A mensuração da área interna da artéria basilar do grupo HSA demonstrou diminuição significativa em relação ao grupo controle (p=0,009). A administração da NAC reduziu significativamente o vasoespasmo em relação ao grupo não tratado (p=0,048) e estabeleceu diferença não significativa em relação ao grupo controle (p=0,098). Não houve melhora significativa com administração de placebo (P=0,97). O modelo da dupla hemorragia mostrou-se bastante útil para reprodução do vasoespasmo, com baixos índices de mortalidade. A administração da NAC diminuiu significativamente o vasoespasmo decorrente da HSA, podendo representar uma nova alternativa terapêutica.

Peritumoral brain edema in intracranial meningiomas / Edema peritumoral em meningiomas intracranianos

Occurrence of peritumoral brain edema (PBE) in meningiomas has been associated with several factors in recent years, although its pathophysiological mechanism has not yet been fully elucidated. The aim of this study was to analyze the correlation between the presence / degree of PBE and factors such as gender, age, size and histological subtype of tumor. We analyzed the MRI images of 74 patients operated on Hospital Beneficência Portuguesa de Porto Alegre for the presence / degree of PBE and data was statistically correlated with the parameters of the patient. PBE was present in 70.1 percent of patients. Tumors with higher volume had more PBE. Tumors of the olfactory groove showed more PBE than sphenoid wing and parassagittal tumors. Transitional subtype showed more PBE than fibroblastic and meningothelial subtypes.

A presença de edema cerebral peritumoral (ECP) em meningiomas tem sido associada a diversos fatores nos últimos anos, embora o seu mecanismo fisiopatológico ainda não tenha sido inteiramente elucidado. O objetivo desse estudo foi analisar a correlação entre a presença/grau de ECP e fatores como sexo, idade, volume e subtipo histológico do tumor. Foram analisadas imagens de RM de 74 pacientes operados no Hospital Beneficência Portuguesa de Porto Alegre quanto à presença/grau de ECP e os dados correlacionados estatisticamente com os parâmetros do paciente. ECP estava presente em 70,1 por cento dos pacientes. Tumores com maior volume apresentaram mais ECP. Tumores da goteira olfatória apresentaram mais ECP que os da asa do esfenóide e que os parassagitais. Meningiomas transicionais apresentaram mais ECP que os fibroblásticos e que os meningoteliais.