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Combination products, amalgamating drugs, biologics, and medical devices, have revolutionized the healthcare landscape with their potential for innovative therapies. However, the intersection of diverse components within these products presents a complex regulatory environment, demanding rigorous attention to safety and efficacy. This article delves into the intricate landscape of regulatory considerations, safety, and efficacy assessments pertaining to combination products-a category at the intersection of drugs, devices, and biologics. The regulatory framework, primarily governed by the U.S. Food and Drug Administration (FDA), necessitates a nuanced classification determining the regulatory pathway. Collaboration between diverse regulatory centers, such as the Center for Drug Evaluation and Research (CDER) and the Center for Devices and Radiological Health (CDRH), underscores the integrated approach required for these innovative healthcare solutions. Safety considerations unravel the potential risks and adverse events associated with combining diverse components, emphasizing the need for robust risk assessment and mitigation strategies. The evaluation of efficacy involves sophisticated methodologies, clinical trials, and post-market surveillance, with recent advancements incorporating digital technologies. This comprehensive exploration aims to contribute to the evolving understanding and best practices in the regulatory and scientific realms, fostering collaboration and innovation in the development and assessment of combination products.
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Visual field loss due to glaucoma is a severe and concerning problem, leading to limited visual range and poor quality vision. The progression of this loss begins with a para-central arcuate scotoma which eventually advances to a ring scotoma and constricted visual fields in later stages. Currently, no animal model is available for screening this pattern of vision loss. However, we have successfully developed two mazes to evaluate visual field loss - the visual field-testing maze (VFTZ) for peripheral vision loss and the vision maze (VM) for central vision loss. Our studies involved inducing glaucoma in Wistar and Sprague Dawley rats using lipopolysaccharide (LPS) and testing them in VFTZ and VM. We used Latanoprost and dorzolamide eye drops as standard drug candidates during the study. We evaluated the animals for intraocular pressure, retinal vasculature imaging, and anxiety using tonometry, ophthalmoscopy, and light and dark model techniques. Furthermore, we quantified the antioxidant parameters of the retina using UV spectroscopy. Our findings showed that animals with peripheral visual field loss in VFTZ took significantly more time to reach the goal and spent more time within the maze compared to normal or drug-treated animals (P < 0.001). Additionally, animals with compromised central visual field in VM spent more time in a particular arm and changed arms less frequently (P < 0.001) compared to normal or drug-treated animals. Moreover, we observed that glaucomatous rats exhibited elevated anxiety levels and impaired performance in the mazes, emphasizing the impact of vision loss on anxiety. Finally, the antioxidant and ATPase alterations in the retinal layers verified the glaucomatous changes in the experimental animals. Based on our remarkable findings, we strongly recommend the use of VFTZ and VM to evaluate visual field loss in animals.
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Glaucoma de Ângulo Aberto , Glaucoma , Animais , Ratos , Campos Visuais , Glaucoma de Ângulo Aberto/diagnóstico , Antioxidantes , Ratos Wistar , Ratos Sprague-Dawley , Transtornos da Visão/diagnóstico , Glaucoma/induzido quimicamente , Glaucoma/diagnósticoRESUMO
CONTEXT: Pituitary apoplexy (PA) has been traditionally considered a neurosurgical emergency, yet retrospective single-institution studies suggest similar outcomes among patients managed medically. OBJECTIVE: We established a multicenter, international prospective registry to compare presentation and outcomes in PA patients treated with surgery or medical management alone. METHODS: A centralized database captured demographics, comorbidities, clinical presentation, visual findings, hormonal status, and imaging features at admission. Treatment was determined independently by each site. Key outcomes included visual, oculomotor, and hormonal recovery, complications, and hospital length of stay. Outcomes were also compared based on time from symptom onset to surgery, and from admission or transfer to the treating center. Statistical testing compared treatment groups based on 2-sided hypotheses and P less than .05. RESULTS: A total of 100 consecutive PA patients from 12 hospitals were enrolled, and 97 (67 surgical and 30 medical) were evaluable. Demographics, clinical features, presenting symptoms, hormonal deficits, and imaging findings were similar between groups. Severe temporal visual field deficit was more common in surgical patients. At 3 and 6 months, hormonal, visual, and oculomotor outcomes were similar. Stratifying based on severity of visual fields demonstrated no difference in any outcome at 3 months. Timing of surgery did not affect outcomes. CONCLUSION: We found that medical and surgical management of PA yield similar 3-month outcomes. Although patients undergoing surgery had more severe visual field deficits, we could not clearly demonstrate that surgery led to better outcomes. Even without surgery, apoplectic tumor volumes regress substantially within 2 to 3 months, indicating that surgery is not always needed to reduce mass effect.
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Adenoma , Apoplexia Hipofisária , Neoplasias Hipofisárias , Humanos , Adenoma/patologia , Apoplexia Hipofisária/etiologia , Apoplexia Hipofisária/cirurgia , Neoplasias Hipofisárias/cirurgia , Neoplasias Hipofisárias/complicações , Resultado do Tratamento , Estudos ProspectivosRESUMO
Only a limited number of studies have focused on the results of the Endoscopic Endonasal Approach (EEA) for treatment of prolactinomas. We sought to assess the effectiveness of EEA for prolactinoma surgery, identify factors for disease remission, and present our approach for the management of persistent disease. Forty-seven prolactinomas operated over 10 years, with a mean follow-up of 59.9 months, were included. The primary endpoints were early disease remission and remission at last follow-up. Resistance/intolerance to DA were surgical indications in 76.7%. Disease remission was achieved in 80% of microprolactinomas and 100% of microprolactinomas enclosed by the pituitary. Early disease remission was correlated with female gender (p=0.03), lower preoperative PRL levels (p=0.014), microadenoma (p=0.001), lack of radiological hemorrhage (p=0.001), absence of cavernous sinus (CS) invasion (p<0.001), and extent of resection (EOR) (p<0.001). Persistent disease was reported in 48.9% of patients, with 47% of them achieving remission at last follow-up with DA therapy alone. Repeat EEA and/or radiotherapy were utilized in 6 patients, with 66.7% achieving remission. Last follow-up remission was achieved in 76.6%, with symptomatic improvement in 95.8%. Factors predicting last follow-up remission were no previous operation (p=0.001), absence of CS invasion (p=0.01), and EOR (p<0.001). Surgery is effective for disease control in microprolactinomas. In giant and invasive tumors, it may significantly reduce the tumor volume. A multidisciplinary approach may lead to long-term disease control in three-quarters of patients, with symptomatic improvement in an even greater proportion.
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Neoplasias Hipofisárias , Prolactinoma , Humanos , Feminino , Prolactinoma/cirurgia , Prolactinoma/patologia , Neoplasias Hipofisárias/cirurgia , Neoplasias Hipofisárias/patologia , Prognóstico , Resultado do Tratamento , Estudos RetrospectivosRESUMO
OBJECTIVE: To characterize and classify the location of recurrence in surgically resected World Health Organization (WHO) grade 2 intracranial meningiomas that did not receive adjuvant radiation and compare the recurrence pattern of those who underwent gross total resection (GTR) versus subtotal resection (STR). METHODS: We performed a retrospective review of patients who underwent surgical resection of a newly diagnosed WHO grade 2 meningioma at our institution between 1996 and 2019. Patients who were observed postoperatively without adjuvant radiation and subsequently developed a recurrence were included in the study. All patients who received adjuvant therapy were excluded. Recurrence was defined as any evidence of radiographic progression on postoperative surveillance magnetic resonance imaging. Location of recurrence was categorized as follows: 1) central-growth observed inside the area of the previously resected tumor more than 1 cm inside the original tumor margin; 2) marginal-growth observed within 1 cm (inside or outside) of the original tumor margin; and 3) remote-growth observed >1 cm outside the original tumor margin. Patterns of recurrence were evaluated by 2 observers after coregistering preoperative and postoperative magnetic resonance imaging, and any differences were reconciled by discussion. RESULTS: A total of 22 patients matched the inclusion criteria. Twelve (55%) underwent GTR, and 10 (45%) underwent STR. In 12 patients in whom GTR was achieved, the mean preoperative tumor volume was 50.6 cm3, with 5 (41.7%) in a skull base location. The average time to recurrence for these tumors was 22.7 months, with a mean recurrent tumor volume of 9.0 cm3. Ten patients (83.3%) had central recurrence, 11 patients (91.7%) had marginal recurrence, and only 4 patients (33.3%) had remote recurrence. In 10 patients in whom STR was achieved, mean preoperative tumor volume was 44.8 cm3, with 7 (70.0%) in a skull base location. The average time to recurrence for these tumors was 23.0 months, with a mean recurrent tumor volume of 21.8 cm3. Of these 10 patients, 9 (90.0%) had central recurrence, all 10 (100.0%) had marginal recurrence, and only 4 (40.0%) patients had remote recurrence. CONCLUSIONS: The present study evaluating patterns of recurrence for WHO grade 2 meningiomas after surgical resection (GTR or STR) showed that recurrence occurred centrally and/or at the original tumor margin, with only a few recurring >1 cm outside the original tumor margin. The results of this study suggest that treatment, whether initial surgical resection or adjuvant radiation, may benefit from including at least a 1-cm dural margin when safe, to optimize tumor control, but further clinical study is needed.
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OBJECTIVE: Surgery is the primary treatment for craniopharyngioma with the preservation of hypothalamic function of paramount importance. Infundibular preservation is debated, as maximal resection decreases recurrence rates but causes hypopituitarism. A triphasic response of diabetes insipidus (DI), syndrome of inappropriate antidiuretic hormone secretion (SIADH), and recurrent DI has been described after pituitary surgery, but the impact of infundibular preservation on the triphasic response following craniopharyngioma resection has not been well established. The authors' objective was to assess postoperative fluid and sodium balance and differences in ADH imbalance management following endonasal craniopharyngioma resection based on infundibular transection status. METHODS: This is a retrospective cohort study of 19 patients with craniopharyngioma treated with endoscopic endonasal resection between 2014 and 2021. Resection was dichotomized into infundibular transection or preservation. Postoperative triphasic response, time to DI, and time to ADH replacement were compared using Fisher's exact test and Kaplan-Meier analysis. RESULTS: Based on surgeon impression, 10 patients had infundibular transection and 9 had infundibular preservation. Overall, 16 patients experienced DI, 12 experienced persistent DI, and 6 experienced SIADH. A postoperative triphasic response occurred in 40% (n = 4) of transection patients without preoperative DI and 11% (n = 1) of preservation patients without preoperative DI. The median time to postoperative DI (0.5 vs 18.0 hours, p = 0.022) and median time to ADH replacement therapy (4.5 vs 24 hours, p = 0.0004) were significantly shorter in the transection group than in the preservation group. CONCLUSIONS: Following endonasal craniopharyngioma resection, the triphasic response occurs in nearly half of infundibular transection cases. DI begins earlier with infundibular transection. On the basis of the study findings in which no patients met the criteria for SIADH or were endocrinologically unstable after postoperative day 6, it is reasonable to suggest that otherwise stable patients can be discharged at or before postoperative day 6 when ADH fluctuations have normalized and endocrinopathy is appropriately managed with oral desmopressin. Infundibular transection status may impact postoperative hormonal replacement strategies, but additional studies should evaluate their efficacies.
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Craniofaringioma , Diabetes Insípido , Síndrome de Secreção Inadequada de HAD , Neoplasias Hipofisárias , Humanos , Craniofaringioma/cirurgia , Craniofaringioma/complicações , Síndrome de Secreção Inadequada de HAD/complicações , Estudos Retrospectivos , Neoplasias Hipofisárias/cirurgia , Neoplasias Hipofisárias/complicações , Hipófise/cirurgia , Diabetes Insípido/etiologia , Complicações Pós-Operatórias/etiologiaRESUMO
OBJECTIVE: In 2017, the United States opioid epidemic was declared a public health emergency. Increased efforts have been made to understand and reduce patient opioid use in neurosurgery. However, the factors associated with postoperative opioid use remain understudied in endoscopic endonasal skull base surgery (EESBS). We identified the demographic and surgical factors associated with postoperative opioid use in EESBS. METHODS: A retrospective review was conducted of patients who underwent elective EESBS between January 2015 and December 2020. Patient demographics, relevant clinical history, and operative data were collected and analyzed. Total opioid use was calculated 24, 48, and 72 hours postoperatively. Multivariable linear regression analyses were performed to identify factors associated with opioid use. RESULTS: There were 454 patients included. A history of anxiety/depression and younger patient age were associated with a significant increase in opioid use at 24 (28.2 MME, p < 0.001), 48 (53.4 MME, p < 0.001), and 72 (89.4 MME, p < 0.001) hours after surgery. Nasoseptal flap use was significantly associated with increased opioid use at 24 (12.8 MME, p < 0.49) and 48 (19.6 MME, p < 0.048) h postoperatively while controlling for intraoperative variables and surgical approach (trans-sellar vs. expanded). No significant association was observed for patient sex, history of migraines, preoperative opioid use, length of surgery, or surgical approach. CONCLUSION: In patients undergoing EESBS, patient history of anxiety/depression, younger patient age, and nasoseptal flap use are associated with increased postoperative opioid use. Knowledge of these risk factors may guide perioperative prescribing patterns to both adequately control postoperative pain and reduce opioid use. LEVEL OF EVIDENCE: 4 Laryngoscope, 133:494-499, 2023.
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Analgésicos Opioides , Transtornos Relacionados ao Uso de Opioides , Humanos , Analgésicos Opioides/uso terapêutico , Base do Crânio/cirurgia , Endoscopia/efeitos adversos , Retalhos Cirúrgicos , Dor Pós-Operatória/tratamento farmacológico , Dor Pós-Operatória/etiologia , Estudos Retrospectivos , Transtornos Relacionados ao Uso de Opioides/etiologiaRESUMO
BACKGROUND: Solitary fibrous tumor/hemangiopericytoma (SFT/HPCT) is a rare tumor characterized by high recurrence rate and metastatic potential, even after surgical resection. We report on the clinical outcomes and risk factors for metastasis and progression-free survival (PFS) of patients diagnosed with SFT/HPCT. METHODS: We retrospectively identified patients with intracranial or spinal SFT/HPCT who underwent surgical resection and/or radiation therapy at our institution between 1995 and 2021. Baseline demographics, tumor characteristics, and outcome data were collected, and factors associated with PFS and metastasis were analyzed. RESULTS: Thirty-four subjects (mean age, 46.4 years; 44% female) with a histopathologically proven diagnosis of SFT/HPCT were included; the median follow-up was 89.7 months. Twenty-two tumors were supratentorial (67%), 6 (18%) were infratentorial, and 5 (15%) were spinal. Eleven patients had documented occurrence of metastasis (32%). Detailed preoperative and postoperative data were available for 25 patients (74%) who received treatment at our institution after their initial diagnosis. Of those, 20 (80%) underwent gross total resection (GTR), and 12 (48%) received either adjuvant or salvage radiotherapy. Univariate analyses revealed that males had a shorter mean PFS compared with females (25 months vs. 78 months; P = 0.01), and that patients who underwent GTR had a longer mean PFS compared with those who underwent subtotal resection (54 months vs. 23 months; P = 0.02). Male sex was the sole risk factor for metastasis (odds ratio, 6.75; 95% confidence interval, 1.19-38.02). CONCLUSIONS: Our data demonstrate a strong association between male sex and the outcomes of shorter PFS and higher risk for metastases. Further research is warranted to understand the clinical characteristics and outcomes of this rare tumor.
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Hemangiopericitoma , Tumores Fibrosos Solitários , Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Estudos Retrospectivos , Prognóstico , Hemangiopericitoma/radioterapia , Hemangiopericitoma/cirurgia , Hemangiopericitoma/diagnóstico , Tumores Fibrosos Solitários/patologia , Intervalo Livre de Progressão , Recidiva Local de NeoplasiaRESUMO
BACKGROUND: Cancer is a deadly disease responsible for worldwide mortality; usually, middle- and low-income countries have been more affected by cancer and are responsible for 70% of deaths. The present study was performed with the aim to design silver nanoparticles using three species of Curcuma, i.e., Curcuma longa, Curcuma aromatica, and Curcuma caesia. METHODS: The rhizomes of different plants were extracted with ethanol. The rhizome extracts were used to prepare silver nanoparticles. It was optimized at different pH, silver ion concentrations, and concentrations of plant extracts. The anticancer activity of prepared nanoparticles of C. longa, C. aromatica, and C. caesia was evaluated on a human colon cancer cell line (HT-29) using sulforhodamine B (SRB) assay. RESULTS: The percentage yield of C. longa, C. aromatica, and C. caesia was 11.34 g, 15.45 g, and 12.67 g, respectively. The results exhibited that the prepared nanoparticles were smooth and spherical. All the nanoparticles of rhizome extracts rescued the viability of HT-29 cells in a different extent. HT-29 cells were sensitive to prepared nanoparticles that induce more cytotoxicity towards cancer cells. CONCLUSION: Thus, the prepared silver nanoparticle of Curcuma species through green synthesis may help treat cancer with low toxicity.
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Neoplasias do Colo , Nanopartículas Metálicas , Humanos , Células HT29 , Curcuma/química , Nanopartículas Metálicas/uso terapêutico , Prata/farmacologia , Extratos Vegetais/farmacologia , Extratos Vegetais/química , Neoplasias do Colo/tratamento farmacológicoRESUMO
Objective In 2017, the United States officially declared opioid overuse a public health emergency. Due to a paucity of published benchmark data in skull base neurosurgery, we quantified postoperative opioid use in patients undergoing skull base craniotomies and identified factors that influence postoperative opioid use. Setting Tertiary academic medical center. Participants Patients who underwent elective craniotomies by two skull base neurosurgeons between January 2015 and May 2020. Main Outcome Measures Demographic and perioperative data were retrospectively extracted from the electronic medical record. Surgical approaches were categorized as having either "significant" or "minimal" muscle dissection. Univariate and multivariate linear regression analyses were performed to identify predictors of postoperative opioid use at 24, 48, and 72 hours. Results We included 300 craniotomies, 206 were supratentorial and 94 were infratentorial. This included 195 women and 105 men, with a mean age of 54.9 years. In multivariable analysis, a history of anxiety or depression, preoperative opioid use, and a history of migraines independently predicted a significantly greater opioid use at 24, 48, and 72 hours. Increased age and minimal muscle dissection independently predicted lower opioid consumption. Sex, infratentorial versus supratentorial approach, length of surgery, and postoperative steroid use did not impact total opioid use. Conclusion Younger age, history of anxiety or depression, preoperative opioid consumption, preexisting history of migraines, and significant intraoperative muscle dissection were associated with higher postoperative opioid consumption. These risk factors provide insight on potential targets for minimizing postoperative opioids in craniotomies.
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Interviews are critical to the neurosurgery resident application process. The COVID-19 pandemic forced residency interview activities are conducted virtually. To maintain a degree of control during a period of uncertainty, our department implemented a standardized survey for interviewers to evaluate the noncognitive attributes and program compatibility of applicants. Our objective was to assess the reliability and biases associated with our standardized interviewer survey implemented in neurosurgical residency interviews. A 5-question interviewer survey to assess applicant interview performance and program compatibility was implemented during the 2020 to 2021 interview season. After the application cycle, survey metrics were retrospectively reviewed. Multiple cohort analyses were performed by dividing interviewers into cohorts based on status (faculty or resident) and sex. Applicant scores were assessed within sex subgroups for each aforementioned interviewer cohort. Intraclass correlation coefficients (ICCs) were calculated to assess survey reliability. Fifteen interviewers (8 faculty and 7 residents) and 35 applicants were included. Female applicants (17%) and interviewers (20%) comprised the minority. There were no differences between resident and faculty reviewer scores; however, female reviewers gave higher overall scores than male reviewers ( P = .003). There was no difference in total scores between female and male applicants when evaluating all reviewers or subgroups of faculty, residents, females, or males. ICC analysis demonstrated good (ICC 0.75-0.90) or excellent (ICC > 0.90) reliability for all questions and overall score. The standardized interviewer survey was a feasible and reliable method for evaluating noncognitive attributes during neurosurgery residency interviews. There was no perceptible evidence of sex bias in our single-program experience.
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COVID-19 , Internato e Residência , Masculino , Feminino , Humanos , Reprodutibilidade dos Testes , Estudos Retrospectivos , Pandemias , COVID-19/epidemiologiaRESUMO
BACKGROUND: Minimally invasive surgery (MIS) for intracranial pathology minimizes surgical morbidity but can come at the cost of operator ergonomics and technical surgical success. Here, the authors present a case series to report the first use of a novel 15-mm tubular retraction system with integrated lighting and visualization capabilities for MIS access to intracranial lesions. OBJECTIVE: To demonstrate feasibility and effectiveness of the 15-mm Aurora Surgiscope (Integra Lifesciences) for intracranial MIS approaches. METHODS: The 15-mm Aurora Surgiscope facilitated MIS approach to gain access to intraparenchymal pathologies. The device consists of a tubular access system with integrated light source and a reusable control unit that modifies video parameters. The port was inserted along a preplanned trajectory through a mini-craniotomy. Bimanual access allowed the surgeon to comfortably dissect/resect lesional tissue using high-quality video. RESULTS: Four patients are presented. In cases 1 and 2, the authors evacuated acute intracerebral hemorrhages. Both had <15 cc hemorrhage with improved or stable neurological examination. In case 3, the authors performed gross total resection of a cerebellar pilocytic astrocytoma. In case 4, the authors resected a mesial posterior temporal cavernoma. No perioperative/technical complications were noted. CONCLUSION: The Aurora Surgiscope system is a novel integrated tubular retraction, lighting, and visualization system that allows access to a wide variety of pathologies using a MIS approach. The Surgiscope allows the surgeon to use bimanual dexterity through a small access port while limiting the need for additional equipment such as microscope, exoscope, or endoscope.
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Astrocitoma , Neoplasias Encefálicas , Astrocitoma/diagnóstico por imagem , Astrocitoma/cirurgia , Neoplasias Encefálicas/diagnóstico por imagem , Neoplasias Encefálicas/cirurgia , Craniotomia , Humanos , Microcirurgia , Procedimentos NeurocirúrgicosRESUMO
OBJECTIVE: Secretory meningioma (SM) is a rare subtype of World Health Organization (WHO) grade 1 meningioma, associated with significant peritumoral brain edema (PTBE). Because of this, SM may be mistaken preoperatively to be a WHO grade 2 meningioma (G2M). In this study, we identified radiographic features to differentiate these 2 tumor types preoperatively to help inform surgical decision-making. METHODS: We performed a retrospective review of all patients with histologically confirmed intracranial SM and G2M at a single institution from 2000 to 2019. Relevant clinic, demographic and radiographic data were collected. We performed a stepwise multivariable logistic regression to identify independent predictors of SM. RESULTS: A total of 43 SM and 140 G2M patients were included in this study. In multivariable analysis, severe PTBE, meaning edema size greater than tumor size (odds ratio [OR] 4.44, P = 0.01), tumor hyperintensity on fluid-attenuated inversion recovery (FLAIR) magnetic resonance imaging sequences (OR 7.80, P = 0.002), and higher normalized apparent diffusion coefficient (nADC) values (OR 1.54, P < 0.001) were strong predictors of SM. Conversely, larger tumor volume (OR 1.79 per 10 mL volume increase, P < 0.001) and cystic component (OR 12.50, P = 0.007) correlated with G2M. CONCLUSIONS: In this study, we found that preoperative FLAIR hyperintensity, severe PTBE, and higher nADC values correlated with SM pathology, and larger size and cystic component were associated with G2M. Accurate identification of SM on preoperative imaging may provide surgeons useful information in decision-making.
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Edema Encefálico , Neoplasias Meníngeas , Meningioma , Edema Encefálico/diagnóstico por imagem , Edema Encefálico/etiologia , Edema Encefálico/patologia , Criança , Imagem de Difusão por Ressonância Magnética/métodos , Humanos , Imageamento por Ressonância Magnética/métodos , Neoplasias Meníngeas/complicações , Neoplasias Meníngeas/diagnóstico por imagem , Neoplasias Meníngeas/cirurgia , Meningioma/complicações , Meningioma/diagnóstico por imagem , Meningioma/cirurgia , Estudos Retrospectivos , Organização Mundial da SaúdeRESUMO
OBJECTIVE: The objective of this paper was to describe the volumetric natural history of meningiomas in patients with neurofibromatosis type 2 (NF2). METHODS: The authors performed a retrospective descriptive study by reviewing NF2 patients with meningiomas at their institution between 2000 and 2019. Demographic data were collected from the electronic medical records. Tumor volume was collected using volumetric segmentation software. Imaging characteristics including peritumoral brain edema (PTBE) and tumor calcification were collected for each patient from their first to most recent MRI at the authors' institution. An increase of 15% or more per year from original tumor size was used as the cutoff to define growth. RESULTS: A total of 137 meningiomas from 48 patients were included in the analysis. The average number of tumors per person was 2.9. Ninety-nine (72.3%) tumors were in female patients. The median length of follow-up from first imaging to last imaging was 32 months (IQR 10.9, 68.3 months). Most tumors were located in the cerebral convexity (24.8%), followed by the falcine region (18.2%) and spine (10.2%). The median tumor growth was 0.12 cm3/yr (IQR 0.03, 0.52 cm3/yr). At the time of first imaging, 21.9% of tumors had calcifications, while 13.9% of meningiomas had PTBE. Of 137 tumors, 52 showed growth. Characteristics associated with tumor growth included PTBE (OR 9.12, 95% CI 1.48-56.4), tumor volume (per cm3) at first imaging (OR 0.91, 95% CI 0.83-0.99), and 10-year increased age at first imaging (OR 0.57, 95% CI 0.43-0.74). PTBE had the shortest median time to growth at 9.2 months. CONCLUSIONS: Although the majority of NF2-associated meningiomas do not grow in the short term, a wide range of growth patterns can be seen. Younger age at first imaging and presence of PTBE are associated with growth. Patients with these characteristics likely benefit from closer follow-up.
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Edema Encefálico , Neoplasias Meníngeas , Meningioma , Neurofibromatose 2 , Feminino , Humanos , Imageamento por Ressonância Magnética , Neoplasias Meníngeas/complicações , Neoplasias Meníngeas/diagnóstico por imagem , Neoplasias Meníngeas/patologia , Meningioma/complicações , Meningioma/diagnóstico por imagem , Meningioma/patologia , Neurofibromatose 2/complicações , Neurofibromatose 2/diagnóstico por imagem , Neurofibromatose 2/patologia , Estudos RetrospectivosRESUMO
BACKGROUND CONTEXT: Primary malignant non-osseous spinal tumors are relatively rare and this has led to a paucity of studies specifically examining the epidemiology of malignant spinal tumors. PURPOSE: To provide an updated and more comprehensive study examining the epidemiology and relative survival of these rare tumors. STUDY DESIGN/SETTING: Data was retrospectively acquired from the Central Brain Tumor Registry of the United States (CBTRUS). PATIENT SAMPLE: Primary malignant non-osseous spinal tumor cases diagnosed between 2000 and 2017 in the United States. OUTCOME MEASURES: Incidence rates (IRs), relative survival rates, and hazard ratios (HR) were measured. METHODS: IRs were calculated only for histologically-confirmed cases between 2000 and 2017. Relative survival estimates were calculated from survival information on malignant spinal tumors between 2001 and 2016 for death from any cause. Multivariable Cox proportional hazards regression models were constructed to control for age, sex, race, and ethnicity. RESULTS: From 2000 to 2017, approximately 587 new cases of malignant non-osseous spinal tumors were diagnosed every year in the United States. The overall IR was 0.178 per 100,000 persons. Ependymomas were the most commonly diagnosed tumor in all age groups. The 10-year relative survival rates were 94.1%, 62.1%, 62.0%, and 13.3% for ependymomas, lymphomas, diffuse astrocytomas, and high-grade astrocytomas, respectively. Females have a significantly lower risk of death as compared with males for ependymomas (HR: 0.74, p<.001) and diffuse astrocytomas (HR: 0.70, p=.005). African-Americans have a significantly higher risk of death compared with Caucasians when diagnosed with ependymomas (HR: 1.52, p=.009) or lymphomas (HR: 1.55, p=.009). CONCLUSION: Primary malignant non-osseous spinal tumors are primarily diagnosed in adulthood or late adulthood. Ependymal tumors are the most commonly diagnosed primary malignant non-osseous spinal tumors and have the highest 10-year relative survival rates. High-grade astrocytomas are rare and portend the worst prognosis.
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Astrocitoma , Ependimoma , Linfoma , Neoplasias da Medula Espinal , Neoplasias da Coluna Vertebral , Adulto , Astrocitoma/diagnóstico , Feminino , Humanos , Masculino , Estudos Retrospectivos , Neoplasias da Medula Espinal/patologia , Neoplasias da Coluna Vertebral/epidemiologia , Estados Unidos/epidemiologiaRESUMO
The present study was designed to determine protective effects of Coleus forskohlii hydroalcoholic leaf-extract along with its fractions against fructose-induced cataract rat model. The Coleus forskolii leaf extract was subjected to silica gel column chromatography and fractions were collected. A major high yielding fraction of the leaf extract, designated as fraction B6 was pharmacologically evaluated in Sprague Dawley albino rats at three doses 0.1, 1 and 10 mg/kg respectively. Compound B2; isolated from B6 fraction, identified as 'gallic acid' was also pharmacologically evaluated at three different doses. Cataract was induced by concurrent administration of fructose solution (10% w/v, per oral, dissolved in drinking water) for eight consecutive weeks. Mean arterial pressure, blood glucose level and lenticular opacity were determined. At the end of eight weeks, C. forskohlii leaf extract fraction and gallic acid reduced mean arterial pressure and glucose level in a dose dependent manner. In addition, C. forskohlii led to significant restoration of lens antioxidants enzyme level and reduced cataract formation in rats. These results showed the concentration dependent protective effect by C. forskohlii leaf extract against cataract formation due to restoration of oxidative stress markers.
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Catarata , Plectranthus , Animais , Catarata/induzido quimicamente , Catarata/tratamento farmacológico , Catarata/prevenção & controle , Frutose/toxicidade , Extratos Vegetais/farmacologia , Ratos , Ratos Sprague-DawleyRESUMO
OBJECTIVE: After gross-total resection (GTR) of a newly diagnosed WHO grade II meningioma, the decision to treat with radiation upfront or at initial recurrence remains controversial. A comparison of progression-free survival (PFS) between observation and adjuvant radiation fails to account for the potential success of salvage radiation, and a direct comparison of PFS between adjuvant and salvage radiation is hampered by strong selection bias against salvage radiation cohorts in which only more aggressive, recurrent tumors are included. To account for the limitations of traditional PFS measures, the authors evaluated radiation failure-free survival (RFFS) between two treatment strategies after GTR: adjuvant radiation versus observation with salvage radiation, if necessary. METHODS: The authors performed a retrospective review of patients who underwent GTR of newly diagnosed WHO grade II meningiomas at their institution between 1996 and 2019. They assessed traditional PFS in patients who underwent adjuvant radiation, postoperative observation, and salvage radiation. For RFFS, treatment failure was defined as time from initial surgery to failure of first radiation. To assess the association between treatment strategy and RFFS while accounting for potential confounders, a multivariable Cox regression analysis adjusted for the propensity score (PS) and inverse probability of treatment weighted (IPTW) Cox regression analysis were performed. RESULTS: A total of 160 patients underwent GTR and were included in this study. Of the 121 patients who underwent observation, 32 (26.4%) developed recurrence and required salvage radiation. PFS at 3, 5, and 10 years after observation was 75.1%, 65.6%, and 45.5%, respectively. PFS at 3 and 5 years after salvage radiation was 81.7% and 61.3%, respectively. Of 160 patients, 39 received adjuvant radiation, and 3- and 5-year PFS/RFFS rates were 86.1% and 59.2%, respectively. In patients who underwent observation with salvage radiation, if necessary, the 3-, 5-, and 10-year RFFS rates were 97.7%, 90.3%, and 87.9%, respectively. Both PS and IPTW Cox regression models demonstrated that patients who underwent observation with salvage radiation treatment, if necessary, had significantly longer RFFS (PS model: hazard ratio [HR] 0.21, p < 0.01; IPTW model: HR 0.21, p < 0.01). CONCLUSIONS: In this retrospective, nonrandomized study, adjuvant radiation after GTR of a WHO II meningioma did not add significant benefit over a strategy of observation and salvage radiation at initial recurrence, if necessary, but results must be considered in the context of the limitations of the study design.
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OBJECTIVE: The direct lateral approach is an alternative to the transoral or endonasal approaches to ventral epidural lesions at the lower craniocervical junction. In this study, the authors performed, to their knowledge, the first in vitro biomechanical evaluation of the craniovertebral junction after sequential unilateral C1 lateral mass resection. The authors hypothesized that partial resection of the lateral mass would not result in a significant increase in range of motion (ROM) and may not require internal stabilization. METHODS: The authors performed multidirectional in vitro ROM testing using a robotic spine testing system on 8 fresh cadaveric specimens. We evaluated ROM in 3 primary movements (axial rotation [AR], flexion/extension [FE], and lateral bending [LB]) and 4 coupled movements (AR+E, AR+F, LB + left AR, and LB + right AR). Testing was performed in the intact state, after C1 hemilaminectomy, and after sequential 25%, 50%, 75%, and 100% C1 lateral mass resection. RESULTS: There were no significant increases in occipital bone (Oc)-C1, C1-2, or Oc-C2 ROM after C1 hemilaminectomy and 25% lateral mass resection. After 50% resection, Oc-C1 AR ROM increased by 54.4% (p = 0.002), Oc LB ROM increased by 47.8% (p = 0.010), and Oc-C1 AR+E ROM increased by 65.8% (p < 0.001). Oc-C2 FE ROM increased by 7.2% (p = 0.016) after 50% resection; 75% and 100% lateral mass resection resulted in further increases in ROM. CONCLUSIONS: In this cadaveric biomechanical study, the authors found that unilateral C1 hemilaminectomy and 25% resection of the C1 lateral mass did not result in significant biomechanical instability at the occipitocervical junction, and 50% resection led to significant increases in Oc-C2 ROM. This is the first biomechanical study of lateral mass resection, and future studies can serve to validate these findings.
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OBJECTIVES: Cerebrospinal fluid (CSF) leaks and meningoencephaloceles originating in the lateral recess of the sphenoid sinus can be challenging. The traditional transpterygoid approach through the pterygopalatine fossa (PPF) is time consuming and places important structures at risk, which can lead to significant morbidity. We report a multi-institutional experience using a simplified, endoscopic modified transpterygoid approach (MTPA), which spares the PPF contents in the management of lateral sphenoid sinus meningoencephaloceles and CSF leaks. STUDY DESIGN: Multi-Institutional, Retrospective Case Series. METHODS: Patients with lateral sphenoid recess CSF leaks and meningoencephaloceles between 2014 and 2020 who underwent the MTPA at two academic medical centers were identified. Repair techniques and outcomes were evaluated. RESULTS: Thirty-three patients underwent the MTPA for management. Skull base reconstruction was performed using a free mucosal graft (24/33, 72.7%), nasoseptal flap (4/33, 12.1%), bone grafts (3/33, 9.1%), and abdominal fat grafts (2/33, 6.1%). Lumbar drains and perioperative intracranial pressure measurements were routinely employed. Postoperative complications were uncommon and included three patients (9.7%) with temporary V2 anesthesia, one patient (3.2%) with prolonged V2 anesthesia, and one patient (3.2%) with subjective dry eye, all of which resolved at 9 months postoperatively. There were no recurrent CSF leaks resulting in a 100% success rate. Average follow-up was 13 months. CONCLUSION: The MTPA reduces morbidity and greatly simplifies access to the lateral sphenoid sinus for the management of CSF leaks and meningoencephaloceles, without compromising exposure. This technique avoids the need for extensive PPF dissection and should be considered for the management of benign lesions involving the lateral sphenoid sinus. LEVEL OF EVIDENCE: 4 Laryngoscope, 131:2224-2230, 2021.
Assuntos
Vazamento de Líquido Cefalorraquidiano/cirurgia , Encefalocele/cirurgia , Endoscopia/métodos , Meningocele/cirurgia , Osso Esfenoide/cirurgia , Adulto , Idoso , Vazamento de Líquido Cefalorraquidiano/diagnóstico , Vazamento de Líquido Cefalorraquidiano/etiologia , Encefalocele/complicações , Encefalocele/diagnóstico , Encefalocele/patologia , Feminino , Seguimentos , Humanos , Masculino , Meningocele/complicações , Meningocele/diagnóstico , Meningocele/patologia , Pessoa de Meia-Idade , Estudos Retrospectivos , Osso Esfenoide/diagnóstico por imagem , Seio Esfenoidal/diagnóstico por imagem , Seio Esfenoidal/patologia , Seio Esfenoidal/cirurgia , Retalhos Cirúrgicos/transplante , Tomografia Computadorizada por Raios X , Resultado do TratamentoRESUMO
BACKGROUND: Meningoencephaloceles originating in the lateral recess of the sphenoid sinus can be difficult to access. Historically, the endoscopic transpterygoid approach was advocated, which carries additional morbidity given the dissection of the pterygopalatine fossa (PPF) contents to provide a direct line approach to the defect. Given our increased facility with angled endoscopes and instrumentation, we now approach this region in a less invasive manner. METHODS: We describe the endoscopic modified transpterygoid approach (MTPA), a quicker approach to the lateral sphenoid recess which preserves the PPF contents through a single nostril corridor. RESULTS: In the MTPA, the face of the sphenoid and anterior junction of the pterygoid plates are removed, allowing for mobilization of the PPF contents with the periosteum intact. Angled instrumentation is then used to resect the meningoencephalocele and repair the skull base defect in the lateral recess. If increased exposure is needed, this can be gained by sacrificing the sphenopalatine artery and even the vidian nerve, although this is rarely required. CONCLUSIONS: The MTPA obviates the need for PPF dissection and simplifies access to the lateral sphenoid recess while minimizing postoperative morbidity. This approach should be considered for accessing meningoencephaloceles and other benign lesions in this challenging location.