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World Neurosurgery Dec 2020Bevacizumab, an anti-vascular endothelial growth factor (VEGF) antibody, is a new treatment approach for radionecrosis. In our study, we compared the prophylactic and... (Comparative Study)
Comparative Study
BACKGROUND
Bevacizumab, an anti-vascular endothelial growth factor (VEGF) antibody, is a new treatment approach for radionecrosis. In our study, we compared the prophylactic and therapeutic usage of a promising agent, ramipril (an angiotensin-converting enzyme inhibitor), with that of bevacizumab for reducing radiation-induced brain injury after high-dose stereotactic radiosurgery (SRS).
METHODS
A total of 60 Wistar rats were used. The rats were irradiated with a single dose of 50 Gy using a Leksell Gamma Knife device. Bevacizumab and ramipril were administered in the prophylactic protocol (starting the first day of SRS) and in the therapeutic protocol (starting the fourth week of SRS). Their usage was continued until 12 weeks, and the right frontal lobes of the rats were examined histologically (hematoxylin and eosin stain) and immunohistochemically (hypoxia-inducible factor [HIF]-1α, VEGF, and CD31 antibody expression).
RESULTS
The expression of VEGF, HIF-1α, and CD31 had significantly increased at 12 weeks after SRS compared with the control group. The addition of bevacizumab or ramipril to SRS significantly mitigated the histological severity of radiation injury and the expression of VEGF, HIF-1α, and CD31. However, the prophylactic use of bevacizumab and ramipril seemed to be more effective than therapeutic administration. Our results also revealed that the greatest benefit was achieved with the use of prophylactic administration of bevacizumab compared with other treatment protocols.
CONCLUSIONS
Ramipril might be a promising agent for patients with radionecrosis. Clinical studies are required to investigate the effective and safe doses of ramipril, which is an inexpensive, well-tolerated drug that can cross the blood-brain barrier.
Topics: Angiogenesis Inhibitors; Angiotensin-Converting Enzyme Inhibitors; Animals; Bevacizumab; Brain; Frontal Lobe; Hypoxia-Inducible Factor 1, alpha Subunit; Immunohistochemistry; Male; Necrosis; Platelet Endothelial Cell Adhesion Molecule-1; Radiation Injuries, Experimental; Radiosurgery; Ramipril; Rats; Rats, Wistar; Vascular Endothelial Growth Factor A
PubMed: 32822951
DOI: 10.1016/j.wneu.2020.08.081 -
Oral Oncology Mar 2021To investigate the incidence and clinical features of post-radiation nasopharyngeal necrosis (PRNN), and effectiveness of surgical intervention for its treatment.
PURPOSE
To investigate the incidence and clinical features of post-radiation nasopharyngeal necrosis (PRNN), and effectiveness of surgical intervention for its treatment.
MATERIALS AND METHODS
Retrospectively, we reviewed 380 NPC patients who underwent high dose radiotherapy (RT) (single RT in 355 and re-RT in 25) from January 2008 till December 2017 at the authors' institute, among who 22 developed Grade ≥ 3 PRNN. The management of PRNN was discussed through weekly multidisciplinary head and neck oncology conference, and surgical debridement was performed when feasible.
RESULTS
The incidence of PRNN was significantly higher following re-RT than in single RT (11/355, 3.1% vs. 11/25, 44.0%, p < 0.001). The PRNN patients in single RT group tended to be older and had more advanced initial tumor extents. The intervals from the latest RT start till PRNN assignment were similar between groups (7.3 vs. 6.6 months, p = 0.140). Nineteen patients underwent surgical debridement: two open; and 17 endoscopic approach, respectively. Endoscopic mucosal reconstruction was performed in eight patients. Resolution of PRNN was achieved in 11 patients (64.7%). The rates of 3-year overall survivals (OS) from the initial RT, latest RT (adjusting re-RT), and PRNN assignment were 84.4%, 70.9%, and 54.7%, respectively. Eight patients (36.4%) succumbed to death: NPC progression in three (13.6%); evidently PRNN-related events in two (9.1%), probably PRNN-related events in two (9.1%); and inter-current death in one (4.5%), respectively.
CONCLUSION
PRNN needs close collaboration among head and neck oncologists and could be successfully recovered, without compromising survival, following timely surgical intervention.
Topics: Adult; Aged; Female; Humans; Male; Middle Aged; Nasopharyngeal Carcinoma; Necrosis; Radiation Injuries; Treatment Outcome
PubMed: 33497910
DOI: 10.1016/j.oraloncology.2021.105180 -
La Clinica Terapeutica 2022Recently, there has been a worldwide rise in the popularity and abuse of synthetic cathinones. The spectrum of side effects caused by the intake of these drugs of abuse...
Recently, there has been a worldwide rise in the popularity and abuse of synthetic cathinones. The spectrum of side effects caused by the intake of these drugs of abuse is very wide since they act on different systems with various mechanisms of action, they appear to be involved in different cardiac events, including myocardial infarction and sudden cardiac death due to fatal arrhythmias. Overall, khat users have a higher risk of death, recurrent myocardial ischemia, cardiogenic shock, ventricular arrhythmia, and stroke compared with non-khat user.
Topics: Humans; Cardiotoxicity; Alkaloids; Arrhythmias, Cardiac; Myocardial Infarction
PubMed: 36373448
DOI: 10.7417/CT.2022.2475 -
International Journal of Radiation... Jan 2024Stereotactic radiosurgery (SRS) is the current standard of care in patients with brain metastases and controlled extracranial disease. Radiation necrosis (RN) is the...
PURPOSE
Stereotactic radiosurgery (SRS) is the current standard of care in patients with brain metastases and controlled extracranial disease. Radiation necrosis (RN) is the dose-limiting side effect of SRS, but the dose constraints especially for fractionated SRS remain poorly defined. We assessed the risk of RN after 3-fraction SRS with a goal to identify specific dose-volume constraints associated with grade 3 or higher RN (G3RN).
METHODS AND MATERIALS
A single-institutional retrospective review of patients treated with 3-fraction SRS was performed. The primary endpoint was G3RN, which was defined as severe symptoms with evidence of necrosis on magnetic resonance imaging with perfusion and/or biopsy confirmation. Tissue volume around each target lesion was contoured, and volumetric doses per lesion were recorded. Logistic regression models were used to estimate the relationship between RN and each volumetric dose, and normal tissue complication probability modeling was performed using a modified Lyman-Kutcher-Burman model.
RESULTS
From 2015 to 2021, 434 patients underwent 539 courses of linear accelerator-based SRS; 2518 lesions were treated. Median SRS dose was 24 Gy. Median follow-up after SRS was 7.9 months, and the median overall survival was 9 months. A total of 93 patients (17.2%) and 123 lesions (4.9%) developed any RN. Forty-two patients (7.8%) and 57 lesions (2.3%) developed G3RN. On logistic regression, V20 and V23 were best predictors of any grade RN and G3RN, respectively, with cutoff values of 4 cc, 10 cc, and 20 cc associated with <5%, <7.5%, and <10% risk of any RN, respectively, and V23 < 15 cc associated with <5% risk of G3RN. With constrained optimization of the normal tissue complication probability Lyman-Kutcher-Burman model for G3RN, we obtained a TD50 (uniform dose resulting in a 50% complication risk) of 31.4 Gy (95% CI, 27.8-35.1 Gy).
CONCLUSIONS
In patients receiving 3-fraction SRS, G3RN was seen in 7.8% of patients, and 2.3% of the lesions were treated. V20 and V23 were the most robust dosimetric parameters associated with RN. Further studies evaluating the outcomes and RN in patients treated with fractionated SRS compared with single-fraction SRS are warranted.
Topics: Humans; Radiosurgery; Brain Neoplasms; Brain; Probability; Radiation Injuries; Necrosis; Retrospective Studies
PubMed: 37574170
DOI: 10.1016/j.ijrobp.2023.07.040 -
Radiotherapy and Oncology : Journal of... Mar 2022The study aimed to develop and validate a novel nomogram to predict overall survival in head and neck cancer survivors following the diagnosis of radiation-induced brain... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND AND PURPOSE
The study aimed to develop and validate a novel nomogram to predict overall survival in head and neck cancer survivors following the diagnosis of radiation-induced brain necrosis (RN).
MATERIALS AND METHODS
We included head and neck cancer survivors with RN from a radiation complications registry study. A total of 495 eligible patients were 7:3 randomly allocated to a training cohort and an internal validation cohort. The Least Absolute Shrinkage and Selection Operator (LASSO) regression was applied to select significant predictors of post-RN survival in the training cohort, and a multivariable Cox model was used to develop the nomogram. The performance of the nomogram was assessed using the internal validation cohort and externally validated using additional 88 RN patients.
RESULTS
We identified five predictors of post-RN survival using the training data: age, tumor progression before RN, lower cranial nerves injury, bilateral necrosis, and history of stroke. The nomogram showed favorable performance in the internal validation cohort (C-index 0.761, 95% CI 0.676 to 0.847) and in the external validation cohort (C-index 0.795, 95% CI 0.717 to 0.874). The decision curve analysis indicated that the nomogram was clinically useful when the probabilities of death ranging from 1% to 48% at 1 year, from 3% to 50% at 3 years, and exceeding 2% at 5 years after being diagnosed with RN.
CONCLUSION
In this LASSO-Cox model-based nomogram study, we developed and validated an easily applied model to predict overall survival in head and neck cancer survivors following an RN diagnosis.
Topics: Brain; Head and Neck Neoplasms; Humans; Necrosis; Nomograms; Survivors
PubMed: 35121029
DOI: 10.1016/j.radonc.2022.01.033 -
Journal of Environmental Radioactivity Nov 2022This study has developed a relationship that categorized radiation protection and allows for a proper, clear, and concise review of the different classifications in... (Review)
Review
This study has developed a relationship that categorized radiation protection and allows for a proper, clear, and concise review of the different classifications in terms of principles of protection, dose criteria, categories, fundamental tools, exposure situations, applications and control measures. With the groundwork laid, advances of the linear no-threshold (LNT) model which has attracted attention in the field of radiobiology and epidemiology were examined in detail. Various plausible dose-response relationship scenarios were x-rayed under low-dose extrapolation. Intensive review of factors opposing the LNT model involving radiophobia (including misdiagnosis, alternative surgery/imaging, suppression of ionizing radiation (IR) research); radiobiology (including DNA damage repair, apoptosis/necrosis, senescence protection) and cost issues (including-high operating cost of LNT, incorrect prioritization, exaggeration of LNT impact, risk-to-benefit analysis) were performed. On the other hand, factors supporting the use of LNT were equally examined, they include regulatory bodies' endorsement, insufficient statistical significance, partial DNA repair, variability of irradiated bodies, different latency periods for cancer, dynamic nature of threshold and conflicting interests. After considering the gaps in the scientific investigations that either support or counter the scientific paradigm on the use of LNT model, further research and advocacy is recommended that will ultimately lead to the acceptance of an alternative paradigm by the international regulators.
Topics: Dose-Response Relationship, Radiation; Humans; Linear Models; Neoplasms, Radiation-Induced; Radiation Monitoring; Radiation Protection; Radiation, Ionizing; Risk Assessment
PubMed: 36057228
DOI: 10.1016/j.jenvrad.2022.106984 -
Environmental Science and Pollution... Jul 2022The strength and shape of the dose-response relationship between different types of noise and myocardial infarction (MI) remain unclear. Therefore, we aimed to summarize... (Meta-Analysis)
Meta-Analysis Review
The strength and shape of the dose-response relationship between different types of noise and myocardial infarction (MI) remain unclear. Therefore, we aimed to summarize the evidence of the association between various types of noise and MI incidence and mortality through a dose-response meta-analysis. We performed a systematic search of the PubMed, Embase, and Web of Science databases up to December 19, 2021. The generalized least-squares method and restricted cubic splines were used to assess the potential linear and nonlinear dose-response relationships between noise exposure and the risk of MI events. Twenty observational studies with 34 reports met the eligibility criteria. In the linear models, the pooled relative risk and corresponding 95% confidence interval (CI) for MI incidence was 1.04 (95% CI: 1.02 - 1.05), and the MI mortality was 1.02 (95% CI: 1.02 - 1.03) for each 10 dB(A) increase in noise exposure. In addition, we observed an approximately J-shaped dose-response relationship between noise and MI mortality (P = 0.0037), whereas the threshold for the statistical impact of noise on MI mortality may be 42 dB(A). Our findings support the notion that various types of noise exposure have a positive dose-response relationship with the risk of MI incidence and mortality.
Topics: Humans; Incidence; Myocardial Infarction; Noise; Risk
PubMed: 35504989
DOI: 10.1007/s11356-022-20377-w -
BMC Cancer Feb 2022Radiation-induced brainstem necrosis (RIBN) is a late life-threatening complication that can appear after treatment in patients with nasopharyngeal carcinoma (NPC)....
BACKGROUND
Radiation-induced brainstem necrosis (RIBN) is a late life-threatening complication that can appear after treatment in patients with nasopharyngeal carcinoma (NPC). However, the relationship between RIBN and radiation dose is not still well-defined.
METHODS
During January 2013 and December 2017, a total of 1063 patients with NPC were treated at Sichuan cancer hospital with IMRT. A total of 479 patients were eligible for dosimetric analysis. Dosimetric parameters of the RIBN, D(the maximum dose), D (maximum average dose delivered to a 0.1-cc volume), D, D, D, D, D and D (mean does) were evaluated and recorded. ROC curve was used to analyze the area under curve (AUC) and cutoff points. Logistic regression for screening dose-volume parameter and logistic dose response model were used to predict the incidence of brainstem necrosis.
RESULTS
Among the 479 patients with NPC, 6 patients were diagnosed with RIBN, the incidence of RIBN was 1.25% (6/479), and the median time to RIBN after treatment was 28.5 months (range 18-48 months). The dose of the brainstem in patients with RIBN were higher than that in patients without necrosis. ROC curve showed that the area under the curve (AUC) of D was the largest (0.987). Moreover, logistic stepwise regression indicated that D was the most important dose factor. The RIBN incidence at 5% over 5 years (TD) and 50% incidence over 5 years (TD) was 69.59 Gy and76.45 Gy, respectively.
CONCLUSIONS
Brainstem necrosis is associated with high dose irritation. D is the most significant predictive dosimetric factor for RIBN. D of brainstem should be considered as the dose limitation parameter. We suggest that the limitation dose for brainstem was D < 69.59 Gy.
Topics: Adult; Brain Injuries; Brain Stem; Female; Humans; Incidence; Logistic Models; Male; Middle Aged; Nasopharyngeal Carcinoma; Nasopharyngeal Neoplasms; Necrosis; ROC Curve; Radiation Injuries; Radiometry; Radiotherapy Dosage; Radiotherapy, Intensity-Modulated; Retrospective Studies
PubMed: 35177030
DOI: 10.1186/s12885-022-09213-z -
Journal of Visualized Experiments : JoVE Jul 2021This article describes the methods of measuring the toxicity of ultraviolet (UV) radiation and ocular toxins on primary (pHCEC) and immortalized (iHCEC) human corneal...
This article describes the methods of measuring the toxicity of ultraviolet (UV) radiation and ocular toxins on primary (pHCEC) and immortalized (iHCEC) human corneal epithelial cell cultures. Cells were exposed to UV radiation and toxic doses of benzalkonium chloride (BAK), hydrogen peroxide (H2O2), and sodium dodecyl sulfate (SDS). Metabolic activity was measured using a metabolic assay. The release of inflammatory cytokines was measured using a multi-plex interleukin (IL)-1β, IL-6, IL-8, and tumor necrosis factor-alpha (TNF-α) assay, and cells were evaluated for viability using fluorescent dyes. The damaging effects of UV on cell metabolic activity and cytokine release occurred at 5 min of UV exposure for iHCEC and 20 min for pHCEC. Similar percent drops in metabolic activity of the iHCEC and pHCEC occurred after exposure to BAK, H2O2, or SDS, and the most significant changes in cytokine release occurred for IL-6 and IL-8. Microscopy of fluorescently stained iHCEC and pHCEC BAK-exposed cells showed cell death at 0.005% BAK exposure, although the degree of ethidium staining was greater in the iHCECs than pHCECs. Utilizing multiple methods of assessing toxic effects using microscopy, assessments of metabolic activity, and cytokine production, the toxicity of UV radiation and chemical toxins could be determined for both primary and immortalized cell lines.
Topics: Benzalkonium Compounds; Epithelial Cells; Epithelium, Corneal; Humans; Hydrogen Peroxide; Ultraviolet Rays
PubMed: 34369925
DOI: 10.3791/62675 -
Brain Research Bulletin Aug 2022This study aims to investigate the impact of gamma-radiation on the cerebral- and cerebellar-cortex of rat's brain. Animals were whole-body exposed to 3 Gy, every 3...
This study aims to investigate the impact of gamma-radiation on the cerebral- and cerebellar-cortex of rat's brain. Animals were whole-body exposed to 3 Gy, every 3 days, up to 9 Gy, and sacrificed 1 h, 1, 3, 7 & 10 days post the last radiation-dose. Irradiation triggers oxidative stress. Superoxide dismutase, catalase, glutathione reductase decreased, malondialdehyde and protein carbonyl increased from the 1st hour till the 10th day in both tissues. Glutathione peroxidase and glutathione decreased from the 1st hour in the cerebral-cortex, and 3rd day in the cerebellar-cortex. Irradiation increased the inflammatory marker, tumor necrosis factor-alpha, and the apoptotic markers, cytochrome-c and caspase-3 from the 1st hour till the 10th day in both tissues. β-amyloid was observed the 7th and 10th day in cerebral-cortex and 3rd, 7th and 10th day in cerebellar-cortex. Irradiation change the level of neurotransmitters. Norepinephrine decreased from the 1st hour in both tissues, while dopamine, epinephrine, aspartic acid, glutamic acid decreased, and gamma amino butyric acid increased from the 1st hour in the cerebral-cortex and later on the 3rd day in the cerebellar-cortex. Electroencephalographic measurement (EEG) showed significant decreases in the frequencies of beta-(>12 Hz) alpha-(7-12 Hz), theta-(4-7 Hz), and delta-rhythms (1-4 Hz) from the 1st hour in both occipital and parietal areas of the brain. Gamma-irradiation triggers oxidative stress, change the level of neurotransmitters, increase inflammatory and apoptotic responses, enhance deposition of amyloid plaque in the cerebral- and cerebellar- cortex, and decrease brain electrical activity in occipital and parietal areas of the brain.
Topics: Animals; Brain; Cerebral Cortex; Gamma Rays; Male; Malondialdehyde; Oxidative Stress; Rats; Superoxide Dismutase
PubMed: 35636638
DOI: 10.1016/j.brainresbull.2022.05.011