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The precise physiological functions and mechanisms regulating RNase Regnase-2 (Reg-2/ZC3H12B/MCPIP2) activity remain enigmatic. We found that Reg-2 actively modulates neuroinflammation in nontransformed cells, including primary astrocytes. Downregulation of Reg-2 in these cells results in increased mRNA levels of proinflammatory cytokines IL-1ß and IL-6. In primary astrocytes, Reg-2 also regulates the mRNA level of Regnase-1 (Reg-1/ZC3H12A/MCPIP1). Reg-2 is expressed at high levels in the healthy brain, but its expression is reduced during neuroinflammation as well as glioblastoma progression. This process is associated with the upregulation of Reg-1. Conversely, overexpression of Reg-2 is accompanied by the downregulation of Reg-1 in glioma cells in a nucleolytic NYN/PIN domain-dependent manner. Interestingly, low levels of Reg-2 and high levels of Reg-1 correlate with poor-glioblastoma patients' prognoses. While Reg-2 restricts the basal levels of proinflammatory cytokines in resting astrocytes, its expression is reduced in IL-1ß-activated astrocytes. Following IL-1ß exposure, Reg-2 is phosphorylated, ubiquitinated, and degraded by proteasomes. Simultaneously, the Reg-2 transcript is destabilized by tristetraprolin (TTP) and Reg-1 through the AREs elements and conservative stem-loop structure present in its 3'UTR. Thus, the peer-control loop, of Reg-1 and Reg-2 opposing each other, exists. The involvement of TTP in Reg-2 mRNA turnover is confirmed by the observation that high TTP levels correlate with the downregulation of the Reg-2 expression in high-grade human gliomas. Additionally, obtained results reveal the importance of Reg-2 in inhibiting human and mouse glioma cell proliferation. Our current studies identify Reg-2 as a critical regulator of homeostasis in the brain.
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Glioblastoma , Doenças Neuroinflamatórias , Animais , Humanos , Camundongos , Citocinas/metabolismo , Regulação para Baixo , RNA Mensageiro/genética , RNA Mensageiro/metabolismoRESUMO
PURPOSE: To compare quantitative tortuosity descriptors of Internal Carotid Artery (ICA) on aneurysmal and non-aneurysmal side before and after embolization of aneurysm and to determine possible factors associated with its change. MATERIAL AND METHODS: An analysis of 52 patients with intracranial aneurysm, treated with endovascular procedure, was performed. Based on their Digital Subtraction Angiography images, obtained prior to the procedure and after first follow-up examination, tortuosity of ICA, both on the side of embolization and on the other side was analysed. For each patient tortuosity descriptors were calculated: Relative Length, Sum of Angle Metrics, Triangular Index, Product of Angle Distance, and Inflection Count Metric. To represent changes in tortuosity, for each descriptor delta value (Δ) was defined as value of the descriptor prior to embolization - value of the descriptor on follow-up examination. RESULTS: In the follow-up We found no statistically significant changes in tortuosity on non-embolized side. On the embolized side SOAM (2.89±0.92 vs. 2.38±0.94;p<0.001), PAD (5.01±1.83 vs. 3.95±1.72 ;p<0.001) and ICM (12.18±4.55 vs. 9.76±4.04 vs.;p = 0.006) was significantly higher after embolization than before embolization. Mean ΔRelative Length (-0.02 [-0.045--0.002] vs. -0.01 [-0.02-0.003];p - 0.003),ΔProduct of Angle Distance (0.84 [0.30 - 1.82] vs. 0.10 [-0.001 - 1.10];p<0.001) and ΔInflection Count Metric (2.05 [0.42 - 3.50] vs. 0.27 [0.02 - 2.16];p = 0.004) were significantly higher on the embolized side. CONCLUSION: Following study showed that embolization may increase the tortuosity of ICA.
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Intracranial aneurysms (IAs) are a significant public health concern because they have the potential to cause deva-stating consequences, including death and disability. Despite advances in diagnostic and treatment modalities, the outcomes for patients with aneurysmal subarachnoid haemorrhage (aSAH) remain poor, with high rates of rebleeding, vasospasm, and cerebral ischaemia. IAs are a significant risk factor for aSAH, and it is estimated that up to 3% of the general population have IAs. Recent studies using novel imaging modalities have shown that the prevalence of IAs may be much higher, with 6.6% of adults aged 40-84 years having intradural saccular IAs ≥ 2 mm. The risk of rupture for IAs is difficult to predict, and the decision to treat them invasively is based on a balance between the estimated rupture risk and the procedural risks of the treatment. However, the mortality and morbidity rates among patients treated for IAs can be as high as 5%. There is a need for clear guidelines on the treatment of IAs, and this review aims to provide an update on recent findings in this area. To achieve this goal, the authors identified and summarized recent, high-impact studies on IAs. The review focuses on the diagnostic and treatment options for IAs, as well as the risks associated with these interventions. The authors also provide an overview of the natural history of IAs and discuss the challenges and uncertainties in managing these patients.
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PURPOSE: Although lumbar discectomy is the most common procedure in spine surgery, reports about anatomical relations between discs and prevertebral vessels are limited. Aim of this research was to investigate morphometric of the lumbar region and the relations between intervertebral discs (IVDs) and abdominal aorta. METHODS: 557 abdominal computed tomography scans were assessed. For each spinal column level from Th12/L1 down to L4/L5, we investigated: intervertebral disc's and vertebra's height, width, length, and distance from aorta or common iliac artery (CIA). Those arteries were also measured in two dimensions and classified based on location. RESULTS: 54.58% of patients were male. There was a significant difference in arterial-disc distances (ADDs) between genders at the levels: L1/L2 (1.32 ± 1.97 vs. 0.96 ± 1.78 mm; p = 0.0194), L2/L3 (1.97 ± 2.16 vs. 1.15 ± 2.01 mm; p < 0.0001), L3/L4 (2.54 ± 2.78 vs. 1.71 ± 2.61 mm; p = 0.0012), also for both CIAs (left CIA 3.64 ± 3.63 vs. 2.6 ± 3.06 mm; p = 0.0004 and right CIA: 7.96 ± 5.06 vs. 5.8 ± 4.57 mm; p < 0.001)-those ADDs were higher in men at all levels. The length and width of IVD increased alongside with disc level with the maximum at L4/L5. CONCLUSION: Bifurcations of the aorta in most cases occurred at the L4 level. Collected data suggest that at the highest lumbar levels, there is a greater possibility to cause injury of the aorta due to its close anatomical relationship with discs. Females have limited, in comparison to males, ADD at L1/L2, L2/L3, and L3/L4 levels what should be taken into consideration during preoperative planning of surgical intervention.
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Disco Intervertebral , Vértebras Lombares , Aorta Abdominal/diagnóstico por imagem , Feminino , Humanos , Disco Intervertebral/diagnóstico por imagem , Vértebras Lombares/cirurgia , Região Lombossacral , Masculino , Tomografia Computadorizada por Raios XRESUMO
OBJECTIVE: To determine the frequency and consequences of intra- and postoperative adverse events in awake craniotomy for intrinsic supratentorial brain tumors. Despite the growing prevalence of awake craniotomy intra- and postoperative, adverse events related to this surgery are poorly discussed. METHODS: We studied 25 patients undergoing awake craniotomy with maximum safe resection of intrinsic supratentorial brain tumors in the awake-asleep-awake protocol. RESULTS: Surgery-related inconveniences occurred in 23 patients (92%), while postoperative adverse events were observed in 17 cases (68%). Seven patients suffered from more than one postoperative complication. The most common surgery-related inconvenience was intraoperative hypertension (8 cases, 32%), followed by discomfort (7 cases, 28%), pain during surgery (5 cases, 20%), and tachycardia (3 cases, 12%). The most common postoperative adverse event was a new language deficit that occurred in 10 cases (40%) and remained permanent in one case (4%). Motor deficits occurred in 36% of cases and were permanent in one case (1%). Seizures were observed in 4 cases (16%) intra- and in 2 cases (8%) postoperatively. Seizures appeared more frequently in patients with multilobar insular-involving gliomas and in patients without prophylactic antiepileptic drug therapy. CONCLUSIONS: Surgery-related inconveniences and postoperative adverse events occur in most awake craniotomies. The most common intraoperative adverse event is hypertension, pain, and tachycardia. The most frequent postoperative adverse events are new language deficits and new motor deficits.
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Neoplasias Encefálicas , Craniotomia , Glioma , Mapeamento Encefálico , Neoplasias Encefálicas/cirurgia , Craniotomia/efeitos adversos , Glioma/cirurgia , Humanos , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Convulsões/epidemiologia , Convulsões/etiologia , VigíliaRESUMO
Iatrogenic brain aneurysms are rare and are usually a result of direct trauma to the arterial wall during various neurosurgical or endovascular procedures. Single cases of pericallosal posttraumatic and postsurgical aneurysms were previously reported. Herein, we report the first confirmed case of iatrogenic pericallosal artery aneurysm caused by an arterial wall injury during the endovascular treatment of another aneurysm. A 50-year-old woman with ruptured anterior communicating artery aneurysm was initially treated with balloon-assisted coiling. During the procedure the tip of a microwire inserted into balloon catheter placed in the pericallosal artery caused a local injury of the inner layer of the vessel wall and vasoconstriction, without bleeding, dissection, or flow disturbances visible in digital subtraction angiography (DSA). Control examination revealed dissecting pericallosal aneurysm. After standard dual-antiplatelet oral preparation, stent-assisted coiling of the pericallosal artery aneurysm was performed with residual contrast filling of the base of the aneurysm sac in control angiography (RROC III). After 6 months the control DSA examination showed entirely cured pericallosal aneurysm (RROC I) and reconstruction of the parent artery. Successful endovascular treatment of an iatrogenic pericallosal aneurysm was previously reported, and this method seems to be the first-choice treatment. In our case, endovascular stent-assisted coiling also allowed for safe exclusion from circulation of pericallosal dissecting aneurysm, and the implanted stent caused reconstruction of the parent artery, restoring the normal lumen diameter. The second endovascular treatment option considered was implantation of a flow-diverted stent into the pericallosal artery.
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OBJECTIVES: We analysed tortuosity of basilar artery (BA) to determine its relationship with the presence of aneurysm. METHODS: We retrospectively analysed 71 patients with BA aneurysms along with 71 age- and risk factors-matched control patients without BA aneurysm. From patients' medical records, we obtained their history including previous and current diseases and medications. For each patient, we calculated relative length (RL), sum of angle metrics (SOAM), triangular index (TI), product of angle distance (PAD) and inflexion count metrics (ICM). We used t-test and Mann-Whitney U test for continuous variables and χ2 test for dichotomised variables. To find independent predictors of BA aneurysm, we employed logistic regression analysis. RESULTS: We found significant positive correlation between age and SOAM (R = 0.195, p = 0.02) and PAD (R = 0.199, p = 0.018). Our study also showed that patients with BA aneurysm had significantly higher SOAM (0.21 ± 0.16 vs. 0.11 ± 0.08; p < 0.01), PAD (0.30 ± 0.19 vs. 0.18 ± 0.11; p < 0.01), TI (0.23 ± 0.23 vs. 0.10 ± 0.16; p < 0.01) and ICM (0.20 ± 0.16 vs. 0.15 ± 0.11; p = 0.045). In multivariate logistic regression analysis, after adjustment for all possible confounders, SOAM (OR = 1.086; 95% CI 1.046-1.136; p < 0.01) and TI (OR = 1.004; 95%C: 1.002-1.006; p < 0.01) remained independently associated with higher risk of BA aneurysm. CONCLUSIONS: Increased tortuosity of BA is associated with higher risk of its aneurysm development. KEY POINTS: ⢠Basilar artery sum of angle metrics and product of angle distance are correlated with age. ⢠Basilar artery tortuosity is independently associated with higher risk of its aneurysm development. ⢠Basilar artery tortuosity is positively correlated with its diameter and bifurcation angle.
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Artéria Basilar/anatomia & histologia , Artéria Basilar/fisiopatologia , Aneurisma Intracraniano/etiologia , Adulto , Idoso , Angiografia Cerebral , Feminino , Hospitalização , Humanos , Aneurisma Intracraniano/fisiopatologia , Masculino , Pessoa de Meia-Idade , Análise de Regressão , Estudos Retrospectivos , Fatores de RiscoRESUMO
PURPOSE: Despite a growing range of therapeutic possibilities, including various intravascular methods, treating cerebral aneurysms can be still a therapeutic challenge. A growing number of patients previously treated with older techniques require additional therapy. Treatment options as well as their efficiency may be influenced by previous procedures. CASE REPORT: We report a rare case of a giant treatment-resistant aneurysm in a 65-year-old woman. The aneurysm was first diagnosed due to visual disturbances in the right eye. Computed tomography angiography showed large (20 × 18 mm) wide neck aneurysm of the right internal carotid artery. The patient was subsequently treated with several methods including coiling with regular stent implantation, two flow diverter stent implantations, and hybrid neurosurgery. Full occlusion was not achieved after any of those procedures. After the last procedure (hybrid neurosurgery) the patient, in vegetative state, was transferred to the intensive care unit and then to the Health and Care Centre. CONCLUSIONS: Discussion focuses on endovascular treatment options after failure of previous treatment such as "stent in stent" technique. We conclude that three subsequent stent implantations are technically possible; however, subsequent procedures are associated with technical difficulties and their effectiveness is questionable. Ventriculoperitoneal shunt may influence the outcome of flow diversion therapy.
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PURPOSE: The middle cerebral artery (MCA) is the second most common location of intracerebral aneurysms. Traditionally, they are treated by microsurgical clipping, but with the development of new techniques and devices endovascular embolisation is gaining more importance. The aim of this study was to summarise six years of experience of our department in endovascular treatment of MCA aneurysms. MATERIAL AND METHODS: Forty patients with 41 MCA aneurysms treated in a single centre were included in this study. Data on patients' comorbidities, aneurysm morphology, and treatment course were collected, with special emphasis on complications. RESULTS: There were no statistically significant differences in terms of aneurysm morphology between males and females and between ruptured and unruptured aneurysms. None of the diseases analysed in the current study were linked with significantly increased risk of SAH. Unruptured aneurysms were significantly more frequently treated by stent-assisted coiling (30.4% vs. 5.6%, p = 0.0388) than were ruptured aneurysms, while ruptured aneurysms were treated more frequently by coiling alone (77.8% vs. 34.8%, p = 0.0062). After an initial course of treatment 63.4% (n = 26) of patients had class I in Raymond-Roy occlusion classification, 22% (n = 9) had class II, and 14.6% (n = 6) had class III. Complications of the procedure were observed in 17.5% (n = 7) of patients: 22.2% (n = 4) with ruptured and 13.6% (n = 3) with unruptured aneurysms. CONCLUSIONS: Endovascular treatment of MCA aneurysms is feasible, and our results are convergent with other studies. Ruptured MCA aneurysms may be treated endovascularly with similar effects as unruptured MCA aneurysms. The complication rate of such treatment is low.
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OBJECTIVES: We decided to perform computer-aided analysis of the anterior cerebral artery (ACA) to check for a potential correlation with anterior communicating artery (ACoA) aneurysm presence and growth. METHODS: We retrospectively analyzed the ACA anatomy of 121 patients with ACoA aneurysms along with 121 age, risk factors, and vessel side-matched control patients without an ACoA aneurysm. We obtained their medical history and digital subtraction angiography (DSA) data from their medical records. For each patient's DSA, we extracted curve representing the course of their ACA and calculated its relative length (RL), sum of angle metrics (SOAM), triangular index (TI), product of angle distance (PAD), and inflection count metrics (ICM). RESULTS: Patients with ACoA aneurysm had significantly higher RL (0.64 ± 0.23 vs. 0.56 ± 0.22; p < 0.01), SOAM (0.27 ± 0.19 vs. 0.18 ± 0.15; p < 0.01), PAD (0.12 ± 0.13 vs. 0.09 ± 0.11; p = 0.02), and TI (0.57 ± 0.14 vs. 0.44 ± 0.15; p < 0.01). In multivariate logistic regression analysis, after adjustment for possible confounders, SOAM (OR, 1.34; 95% CI, 1.12-1.63; p < 0.01) and TI (OR, 1.84; 95% CI, 1.47-2.35; p < 0.01) remained independently associated with higher risk of ACoA aneurysm. Additionally, we found significant negative correlations between TI and aneurysm dome size (R = - 0.194; p = 0.047). CONCLUSIONS: Increased tortuosity of ACA might increase the risk of ACoA aneurysm development and decrease the risk of aneurysm growth. KEY POINTS: ⢠Anterior cerebral artery's sum of angle metrics is associated with hypertension as well as with history of ischemic stroke and myocardial infarction. ⢠Increased tortuosity of anterior cerebral artery might be associated with anterior communicating artery aneurysm development. ⢠Tortuosity of anterior cerebral artery is negatively correlated with anterior communicating artery aneurysm dome size.
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Artéria Cerebral Anterior/anatomia & histologia , Aneurisma Intracraniano/patologia , Adulto , Idoso , Algoritmos , Angiografia Digital/métodos , Artéria Cerebral Anterior/diagnóstico por imagem , Estudos de Casos e Controles , Angiografia Cerebral/métodos , Feminino , Humanos , Aneurisma Intracraniano/diagnóstico por imagem , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de RiscoRESUMO
OBJECTIVE: Female sex is associated with a greater prevalence of cerebral aneurysms. However, it also might be linked to the location and size of the aneurysm. The aim of this study was to find the link between female sex and aneurysm characteristics. METHODS: Our study group consisted of 357 patients admitted to the hospital with both unruptured and ruptured aneurysms confirmed by Digital Subtraction Angiography or Computed Tomography Angiography and aneurysmal subarachnoid haemorrhage confirmed by head CT. Patients' medical records were analyzed for necessary information including, but not limited to medical history, blood test results, and aneurysm prevalence, size and location. RESULTS: Women constituted 232 (64.98%) of all patients. In this group, compared to males, we observed a more common occurrence of multiple aneurysms (1.35 ± 0.67 vs. 1.2 ± 0.57; p = .046) and left internal carotid artery aneurysms (25.88% vs. 13.93%; p < .01). Anterior communicating artery aneurysms were less common (17.11% vs. 31.15%; p < .01). Women also had lower dome-to-neck ratios (2.16 ± 0.82 vs. 2.82 ± 1.92; p < .01), were less likely to be smokers (53.6% vs. 33.19%; p < .01) and smoked fewer cigarettes per day (15.09 ± 6.62 vs. 21.09 ± 11.08; p < 0.01). CONCLUSIONS: Female patients have a greater risk of multiple aneurysms and left internal carotid artery aneurysms, but a lower risk of anterior communicating artery aneurysms.
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Aneurisma Intracraniano/epidemiologia , Adulto , Idoso , Aneurisma Roto/epidemiologia , Angiografia Digital , Doenças das Artérias Carótidas/diagnóstico por imagem , Doenças das Artérias Carótidas/epidemiologia , Feminino , Humanos , Aneurisma Intracraniano/diagnóstico por imagem , Masculino , Pessoa de Meia-Idade , Prevalência , Estudos Retrospectivos , Fatores de Risco , Fatores Sexuais , Fumar/epidemiologia , Tomografia Computadorizada por Raios XRESUMO
INTRODUCTION: Acute subdural hematoma (aSDH) removal is one of the most commonly performed procedure in neurosurgery. Complications of those surgeries which require reoperation are associated with higher risk of poor treatment outcome. Therefore we decided to analyse potential factors which might be associated with risk of early reoperation among patients who underwent aSDH surgery. MATERIALS AND METHODS: We retrospectively analysed 328 patients treated due to aSDH. From their medical records we obtained detailed medical history. Early reoperation was de ned as reoperation during the same hospital stay. To determine the potential predictors of early reoperation we used univariate and multivariate logistic regression analyses. RESULTS: A total of 20 (6.09%) patients required early reoperation. Those patients had significantly higher International Normalized Ratio (INR) upon admission (1.96 ± 2.55 vs. 1.26 ± 0.50; p <0.01) and significantly higher Prothrombin Time (PT) upon admission (21.84 ± 27.10 vs. 13.40 ± 3.45; p <0.01). In multivariate logistic regression analysis a er adjustment for all possible confounders higher INR (OR: 1.762; 95% CI: 1.017-22.840; p = 0.045) remained independently associated with higher risk of early reoperation among patients with aSDH. CONCLUSIONS: Patients with higher INR and PT upon admission are at higher risk of early reoperation. Higher INR is independently associated with higher risk of early reoperation among patients with aSDH.
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Hematoma Subdural Agudo/epidemiologia , Hematoma Subdural Agudo/cirurgia , Procedimentos Neurocirúrgicos/estatística & dados numéricos , Complicações Pós-Operatórias/epidemiologia , Reoperação/estatística & dados numéricos , Idoso , Feminino , Humanos , Coeficiente Internacional Normatizado , Masculino , Pessoa de Meia-Idade , Admissão do Paciente/estatística & dados numéricos , Recidiva , Estudos RetrospectivosRESUMO
INTRODUCTION: Complications occurring after neurosurgical procedures which lead to reoperations are associated with poor treatment outcomes. The aim of our study was to establish predictive factors of unplanned early reoperations after intracranial meningioma removal. MATERIALS AND METHODS: We retrospectively analyzed 177 patients who underwent craniotomy due to an intracranial meningioma. Early reoperation was de ned as reoperation during the same hospital stay. We used a χ2 test for proportional values and t-test and Mann-Whitney U tests as appropriate for continuous variables. To determine the potential predictors of early reoperation we used univariate and multivariate logistic regression analyses. RESULTS: A total of 13 (7.34%) patients underwent unplanned early reoperation. These patients underwent retrosigmoid craniotomies (25.00% vs. 6.40%; p = 0.047), suffered from ischemic heart disease (66.67% vs. 6.64%; p <0.01) and atrial fibrillation (60.00% vs. 6.25%; p <0.01), were receiving heparin (50.00% vs. 6.74%; p <0.01) and anticoagulants (66.67% vs. 6.21%; p <0.01) significantly more often than the general study population. In multivariate logistic regression analysis anticoagulant use (OR: 31.463; 95% CI: 1.139-868.604; p = 0.04) and retrosigmoid craniotomy (OR: 6.642; 95% CI: 1.139-38.73; p = 0.034) remained independently associated with a higher risk of early reoperation. CONCLUSIONS: Patients who underwent retrosigmoid craniotomy, those with a history of ischemic heart disease or atrial fibrillation and those who take heparin or anticoagulants are more likely to require early reoperation. Retrosigmoid craniotomy and anticoagulant use are independent risk factors for early reoperation.
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Neoplasias Meníngeas/cirurgia , Meningioma/cirurgia , Recidiva Local de Neoplasia/cirurgia , Procedimentos Neurocirúrgicos/estatística & dados numéricos , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Reoperação , Estudos Retrospectivos , Resultado do TratamentoRESUMO
BACKGROUND: The aim of this study was to evaluate morphometrically the pituitary adenomas immunoexpression. METHODS: The cases of 72 patients were analyzed, who underwent transsphenoidal surgery for pituitary adenomas. Subsequently, the immunohistochemical pituitary hormone panel was applied including alpha- subunit of the glycoprotein hormones. Immunohistochemical sections were analyzed quantitatively with the help of morphometric grid. The percentage rate of the immunoexpression was calculated separately for every single hormone. RESULTS: As a result, 22 monohormonal adenomas (30.56%), 21 plurihormonal adenomas (29.17%), 21 immunonegative adenomas (29.17%) and 8 unreliable cases (11.11%) were recognized. The immunopositivity for particular hormones was found as follows: PRL and GH (25% each), α-SU (22.22%), ACTH (13.89%), LH and FSH (12.5% each), and TSH (5.56%). An average percentage of immunoexpression in each positive staining groups occurred as follows: for PRL - 59.98%, for GH - 53.97%, for ACTH - 39.21%, for TSH - 25.05%, for LH - 37.3%, for FSH - 54.66%, for α-SU - 45.71. CONCLUSION: The morphometrical method utilizing the immunoexpression index introduced in this study provided a very precise recognition of pituitary adenomas pathology. This method may limit the subjectivity of a single researcher and enable better comparison of the studies. The plurihormonality is a common phenomenon, and immunohistochemical staining for all adenohypophyseal hormones is obligatory in order to classify pituitary adenomas correctly. The awareness of an operating neurosurgeon of the importance of meticulous collecting histopathological material, especially in microadenoma cases, has essential impact on further neuropathological evaluation and possibility of immunohistochemical staining.
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Adenoma/metabolismo , Hormônio do Crescimento Humano/metabolismo , Neoplasias Hipofisárias/metabolismo , Adenoma/cirurgia , Hormônio Adrenocorticotrópico/análise , Feminino , Hormônio Foliculoestimulante/análise , Humanos , Imuno-Histoquímica , Antígeno Ki-67/análise , Antígeno Ki-67/metabolismo , Masculino , Pessoa de Meia-Idade , Neoplasias Hipofisárias/cirurgia , Tireotropina/análiseRESUMO
Regnase-2 (Reg-2/MCPIP2/ZC3H12B) is uniquely expressed at a high level in the healthy brain and down-regulated in samples from patients with glioma, reaching the lowest level in high-grade glioblastoma multiforme (GBM). This RNase is involved in the regulation of neuroinflammation through the degradation of IL-6 and IL-1 mRNAs, key pro-inflammatory cytokines for GBM pathology. Reg-2 is a strong inhibitor of the proliferation of human glioblastoma cell lines and blocks their potential to form colonies. Here, we describe that overexpression of Reg-2 stalls glioblastoma cells in the G1 phase of the cell cycle and reduces the level of transcripts implicated in cell cycle progression. These newly identified targets include CCND1, CCNE1, CCNE2, CCNA2, CCNB1, and CCNB2, encoding the cyclins as well as AURKA and PLK1, encoding two important mitosis regulators. By RNA immunoprecipitation we confirmed the direct interaction of Reg-2 with the investigated transcripts. We also tested mRNA regions involved in their interaction with Reg-2 on the example of CCNE2. Reg-2 interacts with the 3'UTR of CCNE2 in a dose-dependent manner. In conclusion, our results indicate that Reg-2 controls key elements in GBM biology by restricting neuroinflammation and inhibiting cancer cell proliferation.
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Neoplasias Encefálicas , Glioblastoma , Humanos , Glioblastoma/patologia , Doenças Neuroinflamatórias , Linhagem Celular Tumoral , Neoplasias Encefálicas/patologia , Proliferação de Células/genética , Regulação Neoplásica da Expressão GênicaRESUMO
AIM: Hypertension is a risk factor for intracranial aneurysm rupture. We analyzed whether the intake of drugs from specific classes of anti-hypertensive medications affects hemodynamic parameters of intracranial aneurysm dome. METHODS AND RESULTS: We recorded medical history including medications and the in-hospital blood pressure values. We then obtained 3D reconstruction of each patients' aneurysm dome and the feeding artery. Using OpenFOAM software we performed Computational Fluid Dynamics analysis of blood flow through the modeled structures. Blood was modeled as Newtonian fluid, using the incompressible transient solver. As the inlet boundary condition we used the patient-specific Internal Carotid Artery blood velocity waves obtained with Doppler ultrasound. We calculated haemodynamic parameters of the aneurysm dome. All presented analyses are cross-sectional.We included 72 patients with a total of 91 unruptured intracranial aneurysms. The history of ß-blocker intake significantly influenced hemodynamic parameters of aneurysm dome. The patients on ß-blockers had significantly smaller aneurysm domes (5.09 ± 2.11 mm vs. 7.41 ± 5.89 mm; p = 0.03) and did not have aneurysms larger than 10 mm (0% vs 17.0%; p = 0.01). In the Computational Fluid Dynamics analysis, walls of aneurysms in patients who took ß-blockers were characterized by lower Wall Shear Stress Gradient (1.67 ± 1.85 Pa vs. 4.3 ± 6.06 Pa; p = 0.03), Oscillatory Shear Index (0.03 ± 0.02 vs. 0.07 ± 0.10; p = 0.04) and Surface Vortex Fraction (16.2% ± 5.2% vs. 20.0% ± 6.8%; p<0.01). After controlling for covariates, we demonstrated difference of Surface Vortex Fraction (F[1, 48] = 4.36; p = 0.04) and Oscillatory Shear Index (F[1, 48] = 6.51; p = 0.01) between patients taking and not taking ß-blockers, respectively. CONCLUSION: Intake of ß-blockers might contribute to more favorable hemodynamics inside aneurysmal sac. Other antihypertensive medication classes were not associated with differences in intracranial aneurysm parameters.
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BACKGROUND: The gut microbiota has been implicated in Parkinson's disease (PD), with alterations observed in microbial composition and reduced microbial species richness, which may influence gastrointestinal symptoms in PD patients. It remains to be determined whether the severity of gastrointestinal symptoms correlates with microbiota variations in PD patients treated pharmacologically or with subthalamic nucleus deep brain stimulation (STN-DBS) therapy. This study aims to explore how these treatments affect gut microbiota and gastrointestinal symptoms in PD, identifying specific microbial differences associated with each treatment modality. METHODS: A total of 42 individuals diagnosed with PD, along with 38 age-matched household control participants, contributed stool samples for microbiota characterization. Differences in the gut microbiota across various groups of PD patients and their households were identified through comprehensive sequencing of the 16S rRNA gene amplicon sequencing. KEY RESULTS: Differences in microbial communities were observed between PD patients and controls, as well as between PD patients receiving pharmacological treatment and those with STN-DBS. Pharmacologically treated advanced PD patients have higher gastrointestinal dysfunctions. Gut microbiota profile linked to STN-DBS and reduced levodopa consumption, characterized by its anti-inflammatory properties, might play a role in diminishing gastrointestinal dysfunction relative to only pharmacological treatments. CONCLUSIONS & INFERENCES: Advanced PD patients on medication exhibit more gastrointestinal issues, despite relatively stable microbial diversity, indicating a complex interaction between gut microbiota, PD progression, and treatment effects. An imbalanced gut-brain axis, particularly due to reduced butyrate production, may lead to constipation by affecting the enteric nervous system, which emphasizes the need to incorporate gut microbiome insights into treatment strategies.
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Estimulação Encefálica Profunda , Microbioma Gastrointestinal , Doença de Parkinson , Humanos , Doença de Parkinson/microbiologia , Doença de Parkinson/terapia , Microbioma Gastrointestinal/efeitos dos fármacos , Microbioma Gastrointestinal/fisiologia , Masculino , Feminino , Pessoa de Meia-Idade , Idoso , Antiparkinsonianos/uso terapêutico , Levodopa/uso terapêutico , Levodopa/farmacologia , Gastroenteropatias/microbiologia , Núcleo SubtalâmicoRESUMO
INTRODUCTION: Aneurysmal subarachnoid hemorrhage is a devastating type of stroke, associated with high mortality and morbidity. One of modifiable risk factors of aneurysm rupture is hypertension, however, it is still not clear whether any particular antihypertensive drugs play a significant role in the prevention of aneurysm rupture. OBJECTIVES: We decided to investigate whether there is any association between acetylsalicylic acid, α-blockers, ßblockers, angiotensinconverting enzyme inhibitors, angiotensin II receptor blockers, calcium channel blockers, diuretics, statins, and anticoagulants and a risk of intracranial aneurysm rupture. PATIENTS AND METHODS: We retrospectively analyzed 334 patients with ruptured and unruptured intracranial aneurysm. Based on logistic regression models, we obtained unadjusted and adjusted odds ratios (ORs) of subarachnoid hemorrhage associated with the use of vasoactive medications and with indices of tortuosity. RESULTS: We found that ßblocker intake was significantly related to higher tortuosity of the cerebral arteries. Also, the intake of ßblockers (OR, 0.41; 95% CI, 0.21-0.77; P = 0.01) and statins (OR, 0.23; 95% CI, 0.05-0.68; P = 0.01) significantly decreased the risk of aneurysm rupture, a result driven by a decreased rupture risk of anterior circulation aneurysms. No such association was found for the posterior part of the cerebral circulation. CONCLUSIONS: Aneurysm located in the anterior cerebral circulation might be less likely to rupture if patients receive ßblockers or statins.
Assuntos
Aneurisma Roto , Inibidores de Hidroximetilglutaril-CoA Redutases , Aneurisma Intracraniano , Hemorragia Subaracnóidea , Humanos , Aneurisma Intracraniano/complicações , Estudos Retrospectivos , Inibidores de Hidroximetilglutaril-CoA Redutases/efeitos adversos , Hemorragia Subaracnóidea/complicações , Fatores de Risco , Aneurisma Roto/complicações , Antagonistas Adrenérgicos beta/efeitos adversosRESUMO
PURPOSE: Intracerebral hemorrhage is the deadliest form of stroke. This study aimed to enhance the prediction of 30-day mortality in intracerebral hemorrhage patients by integrating computational parameters. METHODS: This study retrospectively analyzed 435 patients with spontaneous intracerebral hemorrhage (ICH). Utilizing the acquired computed tomography (CT) images, we extracted the contour and visual representation of ICH. For the extracted contour, the analysis encompassed factors including compactness, fractal dimension, Fourier factor, and circle factor. For the images depicting ICH, we calculated various factors related to density distribution including mean, coefficient of variance, skewness and kurtosis, as well as texture parameters, such as energy, entropy, contrast and homogeneity. To assess the impact of surgical treatment on 30-day mortality, logistic regression analysis was used. RESULTS: A total of 126 patients (29.09%) died within 30 days. A total of 62 (14.25%) patients underwent surgical treatment. Multivariate logistic regression analysis revealed that surgical treatment was independently associated with a lower risk of 30-day mortality (odds ratio, OR 0.226, 95% confidence interval, CI 0.049-0.85; pâ¯= 0.039). Based on the moderated analysis, we found that the volume of ICH (OR 0.905, 95% CI 0.902-0.908; pâ¯< 0.001) and ICH energy (OR 1.389, 95%CI 0.884-0.988; pâ¯= 0.010) had positive moderating effect on such associations while the presence of intraventricular blood had negative moderating effect (OR 1.154, 95% CI 1.034-1.628; pâ¯= 0.010). CONCLUSION: Patients exhibiting a higher volume and energy of ICH might benefit from surgical treatment; however, this efficacy was found to be diminished in cases involving the presence of intraventricular blood.
Assuntos
Hemorragia Cerebral , Tomografia Computadorizada por Raios X , Humanos , Hemorragia Cerebral/diagnóstico por imagem , Hemorragia Cerebral/mortalidade , Hemorragia Cerebral/cirurgia , Masculino , Feminino , Estudos Retrospectivos , Pessoa de Meia-Idade , Idoso , Tomografia Computadorizada por Raios X/métodos , Resultado do TratamentoRESUMO
PURPOSE: Intraoperative cerebral aneurysm rupture (IOR) is a common phenomenon with a frequency of around 19%. Research regarding IOR lacks an analysis of its predictors. METHODS: We retrospectively examined all saccular aneurysms, in 198 patients with subarachnoid hemorrhage, surgically treated from 2013 to 2019. Operative reports, patient histories, blood test results, discharge summaries, and radiological data were reviewed. IOR was defined as any bleeding from the aneurysm during surgery, preceding putting a clip on its neck, regardless of how trivial. RESULTS: The frequency of IOR was 20.20%. Patients with IOR had higher aneurysm dome size (9.43 ± 8.39 mm vs. 4.96 ± 2.57 mm; p < 0.01). The presence of blood clot on the aneurysm dome was significantly associated with IOR (12.50% vs. 2.53%; p < 0.01). We also associated lamina terminalis fenestration during surgery (7.50% vs. 21.52%; p = 0.04) and multiple aneurysms (5.00% vs. 18.35%; p = 0.038) with a lower risk of IOR. Glucose blood levels were also elevated in patients with IOR (7.47 ± 2.78 mmol/l vs. 6.90 ± 2.22 mmol/l; p = 0.04). Multivariate analysis associated that urea blood levels (OR 0.55, 0.33 to 0.81, p < 0.01) and multiple aneurysms (OR 0.04, 0.00 to 0.37, p = 0.014) were protective factors against the occurrence of IOR. CONCLUSION: Large dome size of an aneurysm, a blood clot on the aneurysm dome and elevated glucose blood levels can be IOR predictive. Lamina terminalis fenestration, the appearance of multiple aneurysms, and high urea blood levels may be associated with a lower risk of such an event.