Cone-beam computed tomography (CBCT) dose optimization technique and image quality assessment scoring.

INTRODUCTION: Linear accelerator (LINAC) embedded with kV source-imager system is capable to do image-guided radiotherapy. The only disadvantage of cone-beam computed tomography image acquisition during treatment is the extra radiation dose to the patient. The aim of this study is to optimize the CBCT imaging doses likely to be received by the patient undergoing radiotherapy without affecting image quality. MATERIAL AND METHODS: The imaging dose to the patient was estimated on CTDI phantoms. The effect of additional filters of different materials (copper, brass, aluminum of thickness 0.1 mm each) was evaluated to find the optimized dose imaging technique. For the pelvis, a single imaging protocol available on the machine was used, whereas for the head and neck region, two protocols, high-quality head and standard-dose head were used. The image quality was assessed on CATPHAN-504 phantom using Owl CATPHAN® QA online tool. A new term "Image Assessment score" (IAS) was introduced to evaluate the image quality. RESULT: In the pelvis protocol, CBCT imaging doses with an additional 0.1-mm brass, copper, and aluminum filter were measured to be reduced by 7.1%, 4.7%, and 2.5%, respectively, whereas for high-quality head protocol, the dose reduction was 25.4% (with brass filter), 22% (with copper filter), and 3.1% (with aluminum filter). For the standard-dose head protocol, doses were reduced by 7.5%, 2.8%, and 2.1% with additional 0.1-mm brass copper and aluminum filters, respectively. Acceptable image quality was observed with all the filters. CONCLUSION: Although the reconstructed images were found somewhat noisier, they did not affect the purpose of imaging, that is, treatment position verification. It was observed that these extra filters further reduce the imaging dose without much affecting the image quality.

Challenges in commissioning the "TSET" technique: A new approach towards monitor unit calculation and beam profile measurements.

INTRODUCTION: Total skin electron beam therapy, commonly known as TSET, is a good choice of treatment for patients suffering from mycosis fungoides. The aim of this study was to introduce a new approach to the beam profile measurement using diodes and to calculate the monitor units required for the TSET treatment by the use of a simple setup of output measurement. Dosimetric measurements required for the treatment were taken to establish the Stanford technique in the department, and the measured data was compared with the published data. MATERIALS AND METHODS: High-energy Linear Accelerator Clinac-DHX, Varian medical system, Palo Alto, CA, was commissioned for TSET. The output of the machine was measured by the use of a Parallel-Plate Chamber (PPC40) as per the TRS 398 recommendation. Diode dosimeters (EDD2 and EDD5) were used for beam profile measurements due to easy setup and to reduce the measurement time. RESULTS: Homogeneous dose distribution within a field size of 80 cm x160 cm was observed with the variation of -5.0% on the horizontal axis and -5.4% on the vertical axis. The calculated monitor unit to deliver 200 cGy per fraction per field at the source to surface (SSD) of 416 cm was 489 MU. CONCLUSION: The technique described for the output measurements is simple and accurate. Results of the absorbed dose and MU measured were within good agreement compared to the published literature.

Radiosurgical Decompression of Trigeminal Nerve and Its Correlation with Functional Outcome in Tumor-Related Trigeminal Neuralgia.

BACKGROUND: Target selection during Gamma Knife radiosurgery (GKRS) in cases of tumor-related trigeminal neuralgia is always debatable. We analyzed the correlation of regression of tumor size and degree of release of the nerve with long-term pain control. METHODS: Between March 2012 and March 2023, 50 cases of tumor-related trigeminal neuralgia were treated with GKRS (tumor was targeted). Radiological findings after GKRS were categorized into 3 types: 1) tumor volume remained same or decreased, additional segment of nerve not seen; 2) tumor volume decreased, additional segment of trigeminal nerve seen, but tumor still adherent to the nerve; 3) tumor volume decreased, adjacent nerve seen completely separated from tumor. Pain score before and after GKRS (Barrow Neurological Institute I-III: good; Barrow Neurological Institute IV and V: poor) was correlated with these subgroups. RESULTS: At median follow-up of 46.5 months, 18 cases showed type 1 radiological response, 23 showed type 2 response, and 9 showed type 3 response. Good pain control was achieved in 10 (55.5%) patients with type 1, 15 (65.21%) with type 2, and 7 (77.8%) with type 3 responses. The outcome differences among these 3 groups were not statistically significant (P = 0.519). Five patients with type 3 radiological response were off medication, which was statistically better than type 1 and type 2 radiological responses, with 3 patients (P = 0.012) and 2 patients (P = 0.002), respectively, still receiving medication. CONCLUSIONS: Tumor volume reduction after GKRS may be associated with good pain control in tumor-related trigeminal neuralgia. Further, this allows visualization of additional segment of nerve that can be targeted in a second session for treating recurrent or failed cases.

Unlocking the Pharmacological Potential of Benzimidazole Derivatives: A Pathway to Drug Development.

Heterocyclic molecules have fascinated a massive interest in medicinal chemistry. They are heterocyclic compounds that have gained significance due to their diverse variety of pharmacological activities. Benzimidazole is a heterocyclic compound consisting of benzene and imidazole rings. The ease of synthesis and the structural versatility of benzimidazole make it a promising scaffold for drug development. Many biological actions of benzimidazole derivatives have been well documented, including antibacterial, antiviral, anticancer, anti-inflammatory, antitubercular, and anthelmintic properties. The mechanism of action of benzimidazole derivatives varies with their chemical structure and target enzyme. This review has explored numerous methods for producing benzimidazole derivatives as well as a broad range of pharmacological activities. SAR investigations are also discussed in this review as they provide crucial details regarding the essential structural qualities that benzimidazole derivatives must have in order to be biologically active, which could aid in the rational design of new drug candidates. Benzimidazole scaffold is an exclusive structure in drug design and discovery. Many new pharmaceutical drugs containing benzimidazole are anticipated to be available within the next ten years as a result of the extensive therapeutic applications of benzimidazole and its derivatives. This review inspired many researchers to develop more biologically active compounds bearing benzimidazole, expanding the scope of finding a remedy for other diseases. From this study, we concluded that 2-substituted benzimidazole was considered more extensively by researchers.

Simultaneous Integrated Boost (SIB) Versus Sequential Boost in Anal Cancer Patients: A Single-Center Experience.

PURPOSE: Concurrent chemoradiation is the standard of care for the treatment of anal cancer. Radiation can be delivered by sequential or simultaneous integrated boost (SIB) approach. The present study was conducted to compare the treatment outcomes and toxicity profile of patients with anal cancer treated with sequential boost and SIB approach. METHODS: A single-institution retrospective analysis of patients with squamous cell carcinoma of the anal canal treated between 2019 and 2022 with radical chemoradiation was performed. The sequential boost schedule consisted of 45 Gy in 25 fractions (1.8 Gy daily) to the gross tumor, nodes, and elective nodal volume, followed by a 9 Gy in five fractions boost to the gross disease. Patients receiving SIB were treated as per RTOG 0529 protocol. In both the groups, patients were treated with volumetric modulated arc therapy (VMAT). The two groups were compared in terms of overall survival (OS), colostomy-free survival (CFS), relapse-free survival (RFS), and acute toxicity profile. p-values < 0.05 were considered statistically significant. RESULTS: The patient and disease characteristics in both treatment arms were comparable. The only difference was a significantly longer overall treatment time of ≥ 50 days in the sequential arm (77.8% vs 43.8%, p = 0.04). The median follow-up was 18 months. The 2-year CFS was 80% in sequential vs 87.5% at 2 years for the SIB arm, 2-year OS 83.3% vs 58.6%, and 2-year RFS was 38.9% vs 41.7%, respectively. A total of 14 (77.8%) in sequential and 8 (50%) in the SIB arm had disease relapse. On univariate analysis, the involved pelvic lymph node significantly affected OS (HR 10.45, p = 0.03) while inguinal lymph node involvement adversely affected RFS (HR 6.16, p = 0.02). The most common acute toxicity was radiation-induced dermatitis, 15 (83.4%; 5 grade II, 10 grade III) in sequential vs 7 (43.8%; 3 each grade II and III) in the SIB group followed by hematological (61.1% vs 68.75%). However, the incidence of overall acute toxicities was significantly less in the SIB arm (p = 0.006). CONCLUSION: Our study showed that concurrent chemoradiation with the SIB-VMAT approach is well tolerated in patients of anal carcinoma and resulted in lesser treatment interruptions and comparable outcomes as compared to the sequential approach. Our results warrant further evaluation in a prospective study.

Addition of bioimpedance-derived body cell mass improves performance of serum creatinine-based GFR estimation in a chronic kidney disease cohort.

PURPOSE: Serum creatinine-based glomerular filtration rate (GFR) estimating equations are imprecise and systemic overestimate GFR in chronic kidney disease (CKD) populations with low muscle mass. Bioimpedance devices can measure body cell mass (BCM), a surrogate for muscle mass which has been included in a published GFR estimating equation. This BCM GFR equation is validated and compared with MDRD and CKD-EPI 2021 equations in an Indian CKD population. METHODS: Patients with stable CKD stages 1-5 and voluntary kidney donors underwent measurement of serum creatinine, DTPA GFR and bioimpedance on the same day. BCM GFR was tested for consistency, agreement and performance with respect to DTPA GFR. RESULTS: A total of 125 study participants were enrolled, including 106 patients with CKD (Stage 1: 8; stage 2: 32, stage 3: 42, stage 4: 20 and stage 5: 4 patients) and 19 voluntary kidney donors, with 66% males, and a mean age of 43.3 (± 16.5) years. The median bias of BCM GFR was 5.45 ml/min/1.73 m2 [95% confidence interval (CI) 4.2-8.3], absolute precision was 10.16 ml/min/1.73 m2 [95% CI 4.5-12.6], P30 was 59.1% [95% CI 50.0-67.7] and accuracy was 8.62% [95% CI 6.4-20.0]. Kappa measurement of agreement was the highest for BCM GFR-based staging (0.628 vs 0.545 for MDRD and 0.487 for CKD-EPI). CONCLUSION: BCM-based GFR estimating equation performed better than MDRD and CKD-EPI equations in this Indian CKD population, and BCM GFR-based KDIGO staging was associated with lesser misclassification than the MDRD and CKD-EPI equations. TRIAL REGISTRATION (PROSPECTIVE): Clinical Trials Registry of India (CTRI/2019/11/021850).

Early surgery versus conservative treatment in patients with traumatic intracerebral hematoma: a CENTER-TBI study.

PURPOSE: Evidence regarding the effect of surgery in traumatic intracerebral hematoma (t-ICH) is limited and relies on the STITCH(Trauma) trial. This study is aimed at comparing the effectiveness of early surgery to conservative treatment in patients with a t-ICH. METHODS: In a prospective cohort, we included patients with a large t-ICH (< 48 h of injury). Primary outcome was the Glasgow Outcome Scale Extended (GOSE) at 6 months, analyzed with multivariable proportional odds logistic regression. Subgroups included injury severity and isolated vs. non-isolated t-ICH. RESULTS: A total of 367 patients with a large t-ICH were included, of whom 160 received early surgery and 207 received conservative treatment. Patients receiving early surgery were younger (median age 54 vs. 58 years) and more severely injured (median Glasgow Coma Scale 7 vs. 10) compared to those treated conservatively. In the overall cohort, early surgery was not associated with better functional outcome (adjusted odds ratio (AOR) 1.1, (95% CI, 0.6-1.7)) compared to conservative treatment. Early surgery was associated with better outcome for patients with moderate TBI and isolated t-ICH (AOR 1.5 (95% CI, 1.1-2.0); P value for interaction 0.71, and AOR 1.8 (95% CI, 1.3-2.5); P value for interaction 0.004). Conversely, in mild TBI and those with a smaller t-ICH (< 33 cc), conservative treatment was associated with better outcome (AOR 0.6 (95% CI, 0.4-0.9); P value for interaction 0.71, and AOR 0.8 (95% CI, 0.5-1.0); P value for interaction 0.32). CONCLUSIONS: Early surgery in t-ICH might benefit those with moderate TBI and isolated t-ICH, comparable with results of the STITCH(Trauma) trial.

Comparative effectiveness of decompressive craniectomy versus craniotomy for traumatic acute subdural hematoma (CENTER-TBI): an observational cohort study.

Background: Limited evidence existed on the comparative effectiveness of decompressive craniectomy (DC) versus craniotomy for evacuation of traumatic acute subdural hematoma (ASDH) until the recently published randomised clinical trial RESCUE-ASDH. In this study, that ran concurrently, we aimed to determine current practice patterns and compare outcomes of primary DC versus craniotomy. Methods: We conducted an analysis of centre treatment preference within the prospective, multicentre, observational Collaborative European NeuroTrauma Effectiveness Research in Traumatic Brain Injury (known as CENTER-TBI) and NeuroTraumatology Quality Registry (known as Net-QuRe) studies, which enrolled patients throughout Europe and Israel (2014-2020). We included patients with an ASDH who underwent acute neurosurgical evacuation. Patients with severe pre-existing neurological disorders were excluded. In an instrumental variable analysis, we compared outcomes between centres according to treatment preference, measured by the case-mix adjusted proportion DC per centre. The primary outcome was functional outcome rated by the 6-months Glasgow Outcome Scale Extended, estimated with ordinal regression as a common odds ratio (OR), adjusted for prespecified confounders. Variation in centre preference was quantified with the median odds ratio (MOR). CENTER-TBI is registered with ClinicalTrials.gov, number NCT02210221, and the Resource Identification Portal (Research Resource Identifier SCR_015582). Findings: Between December 19, 2014 and December 17, 2017, 4559 patients with traumatic brain injury were enrolled in CENTER-TBI of whom 336 (7%) underwent acute surgery for ASDH evacuation; 91 (27%) underwent DC and 245 (63%) craniotomy. The proportion primary DC within total acute surgery cases ranged from 6 to 67% with an interquartile range (IQR) of 12-26% among 46 centres; the odds of receiving a DC for prognostically similar patients in one centre versus another randomly selected centre were trebled (adjusted median odds ratio 2.7, p < 0.0001). Higher centre preference for DC over craniotomy was not associated with better functional outcome (adjusted common odds ratio (OR) per 14% [IQR increase] more DC in a centre = 0.9 [95% CI 0.7-1.1], n = 200). Primary DC was associated with more follow-on surgeries and complications [secondary cranial surgery 27% vs. 18%; shunts 11 vs. 5%]; and similar odds of in-hospital mortality (adjusted OR per 14% IQR more primary DC 1.3 [95% CI (1.0-3.4), n = 200]). Interpretation: We found substantial practice variation in the employment of DC over craniotomy for ASDH. This variation in treatment strategy did not result in different functional outcome. These findings suggest that primary DC should be restricted to salvageable patients in whom immediate replacement of the bone flap is not possible due to intraoperative brain swelling. Funding: Hersenstichting Nederland for the Dutch NeuroTraumatology Quality Registry and the European Union Seventh Framework Program.

Dosimetric Comparison of Different Dose Calculation Algorithms in Postmastectomy Breast Cancer Patients Using Conformal Planning Techniques.

Background: The aim of the current study was to compare three different dose-calculating algorithms, i.e., superposition (SP), fast SP (FSP), and convolution (CV), for breast cancer patients treated with intensity-modulated radiotherapy (IMRT) and field-in-Field forward plan IMRT (FiF-FP-IMRT). Materials and Methods: The current retrospective study involved 100 postmastectomy breast cancer patients who were given radiotherapy using IMRT and FiF-FP-IMRT planning techniques. All the initially SP-calculated plans were recalculated with the same monitor units for FSP and CV algorithm without change in any of the other planning parameters. The isodose distribution and various plan evaluating parameters, for example, conformity index (CI), homogeneity index, and uniformity index target volume and normal structure doses were compared and analyzed for all the different algorithm calculated plans. Results: In the IMRT plans, all the target and normal structure dose-volume parameters showed a significant difference between all the three different algorithms with P < 0.05. In the FiF-FP-IMRT plans, CV algorithm showed a significant difference in most of the target and normal structure dose-volume parameters. Among quality indexes, only CI showed a significant difference between all the algorithms in both the planning techniques. R50 showed a significant difference with the CV algorithm in both the planning techniques. Conclusion: The change in the dose calculation algorithm resulted in dosimetric changes which must be evaluated by the medical physicists and oncologists while evaluating treatment plans. In the current study with breast patients, the results obtained for target and normal structure doses using the CV algorithm are overestimated as compared to SP and FSP algorithms, producing variable results in air and bony normal structures. However, the ipsilateral lung V5 parameter and the ipsilateral humeral head mean dose were found to be underestimated by the CV algorithm as compared to the SP and FSP algorithm in both the planning techniques.

A qualitative analysis of Black men's attitudes toward obesity and bariatric surgery.

BACKGROUND: Metabolic and bariatric surgery (MBS) is a safe and highly effective treatment for morbid obesity and related co-morbidities. While MBS access and insurance coverage have greatly improved, sex and racial disparities remain in utilization of MBS. OBJECTIVE: To identify novel intrinsic factors that may explain Black underutilization of surgical treatments for weight management. SETTING: This study was conducted in metropolitan communities of Western New York. METHODS: We conducted semistructured face-to-face interviews with 27 adult Black men with a history of obesity and at least 2 obesity-related conditions (diabetes, hypertension, and/or chronic kidney disease [CKD]), about their attitudes, beliefs, behaviors, and habits related to obesity and obesity management. Interview transcripts were reviewed using thematic analysis for patterns and themes. RESULTS: Most participants did not perceive obesity as a serious health condition and those who had weight-loss goals did not aim for a healthy body mass index (BMI). Trust and respectful communication with physician were very important in making healthcare decisions. MBS was perceived as extreme and dangerous option for weight loss, and only participants with severe symptoms such as chronic pain were open to discussing MBS with their providers. Participants acknowledged lack of role models of similar background who had successfully undergone MBS for obesity. CONCLUSIONS: This study identified misinformation about risks and benefits of MBS and lack of community role models as important factors contributing to Black men's unwillingness to consider MBS. Further research is needed to facilitate patient-provider communication about weight and improve provider's ability and motivation for weight management in primary care settings.

Mindful gratitude journaling: psychological distress, quality of life and suffering in advanced cancer: a randomised controlled trial.

CONTEXT: Numerous studies have shown that gratitude can reduce stress and improve quality of life. OBJECTIVE: Our study aimed to examine the effect of mindful gratitude journaling on suffering, psychological distress and quality of life of patients with advanced cancer. METHODS: We conducted a parallel-group, blinded, randomised controlled trial at the University of Malaya Medical Centre, Malaysia. Ninety-two adult patients with advanced cancer, and an overall suffering score ≥4/10 based on the Suffering Pictogram were recruited and randomly assigned to either a mindful gratitude journaling group (N=49) or a routine journaling group (N=43). RESULTS: After 1 week, there were significant reductions in the overall suffering score from the baseline in both the intervention group (mean difference in overall suffering score=-2.0, 95% CI=-2.7 to -1.4, t=-6.125, p=0.000) and the control group (mean difference in overall suffering score=-1.6, 95% CI=-2.3 to -0.8, t=-4.106, p=0.037). There were also significant improvements in the total Hospital Anxiety and Depression Scale score (mean difference=-3.4, 95% CI=-5.3 to -1.5, t=-3.525, p=0.000) and the total Functional Assessment of Chronic Illness Therapy-Spiritual Well-Being score (mean difference=7.3, 95% CI=1.5 to 13.1, t=2.460, p=0.014) in the intervention group after 7 days, but not in the control group. CONCLUSION: The results provide evidence that 7 days of mindful gratitude journaling could positively affect the state of suffering, psychological distress and quality of life of patients with advanced cancer. TRIAL REGISTRATION NUMBER: The trial was registered with the Australian and New Zealand Clinical Trials Registry (ACTRN1261800172191) and conducted in accordance with the Declaration of Helsinki.

Synthesis, in silico Studies and Pharmacological Evaluation of a New Series of Indanone Derivatives as Anti-Parkinsonian and Anti-Alzheimer's Agents.

OBJECTIVE: Parkinson's disease (PD) and Alzheimer's disease (AD) are the most common forms of neurodegenerative disorders. The aim of the current work is to study the potential of some new indanone derivatives for the treatment of these neurological disorders. METHODS: A new series of 4-(2-oxo-2-aminoethoxy)-2-benzylidene substituted indanone derivatives have been synthesized and studied for anti-Parkinsonian and anti-Alzheimer's effects. Substitution of different aminoalkyl functionalities at the para position of 2-benzylidene moiety of indanone ring resulted in the formation of potent anti-parkinsonian and anti-Alzheimer's agents (5-10). The neuroprotective effects of newly synthesized compounds were evaluated using perphenazine (PPZ)-induced catatonia in rats and LPS-induced cognitive deficits in mice models. Further, in silico molecular modelling studies of the new indanone derivatives were performed by docking against the 3D structures of various neuroinflammatory mediators, such as interleukin-1ß (IL-1ß), tumor necrosis factor-α (TNF-α) and monoamine oxidase-B (MAO-B), to gain the mechanistic insights of their anti-Alzheimer's and antiparkinsonian effects. RESULTS: The newly synthesized indanone analogues 5-10 were found effective against PPZinduced motor dysfunction and LPS-induced memory impairment in animal models. Among all the synthesized analogues, morpholine-substituted indanone 9 displayed maximum anti-parkinsonian activity, even better than the standard drug L-DOPA, while pyrrolidine and piperidine substituted analogues 5 and 6 were found to be the most potent anti-Alzheimer's agents. CONCLUSION: The new 2-arylidene-1-indanone analogues show good potential as promising leads for designing compounds against Parkinson's and Alzheimer's diseases.

Determination and validation of the initial beam parameters of Elekta Agility collimator head by Monte Carlo simulations.

The availability of geometrical, physical, and initial beam parameters for Monte Carlo (MC) simulations of the Elekta Agility collimator head has become very difficult due to the proprietary nature of this data. This study presents strategies to independently determine the geometrical and physical properties of the components and initial beam parameters of the Agility collimator head for full beam simulations and postulates a benchmarking process using the EGSnrc MC toolkit. Target material of W (90%) and Re (10%) of 0.09 cm thickness, flattening filter of 1.77 cm thick stainless steel placed on 0.5 cm Al disc, and primary and secondary collimators of Tungsten alloy have been found to best fit the Agility head. The initial beam energy of 6.0 MeV with a radial distribution given as full-width half maxima (FWHM) of 0.301 cm (crossline) × 0.201 cm (inline) for 6 MV beam with a mean angular spread of 1.34° has been found best fitting the model. Variations of 0.29% and 0.59% have been noted in the measured and calculated values of TPR20,10 and D10 respectively. More than 90% dose points for all simulations passed the 2D gamma criteria of 3% DD, 3 mm DTA. This MC model of the Agility head can be used for dose calculation and validation of advanced treatment techniques.

Diagnostic accuracy and inter-reader reliability of the MRI Liver Imaging Reporting and Data System (version 2018) risk stratification and management system.

Background: Hepatocellular carcinoma (HCC) can be diagnosed non-invasively, provided certain imaging criteria are met. However, the recent Liver Imaging Reporting and Data System (LI-RADS) version 2018 has not been widely validated. Objectives: This study aimed to evaluate the diagnostic accuracy and reader reliability of the LI-RADS version 2018 lexicon amongst fellowship trained radiologists compared with an expert consensus reference standard. Method: This retrospective study was conducted between 2018 and 2020. A total of 50 contrast enhanced liver magnetic resonance imaging (MRI) studies evaluating focal liver observations in patients with cirrhosis, hepatitis B virus (HBV) or prior HCC were acquired. The standard of reference was a consensus review by three fellowship-trained radiologists. Diagnostic accuracy including sensitivity, specificity, positive predictive value (PPV), negative predictive values (NPV) and area under the curve (AUC) values were calculated per LI-RADS category for each reader. Kappa statistics were used to measure reader agreement. Results: Readers demonstrated excellent specificities (88% - 100%) and NPVs (85% - 100%) across all LI-RADS categories. Sensitivities were variable, ranging from 67% to 83% for LI-RADS 1, 29% to 43% for LI-RADS 2, 100% for LI-RADS 3, 70% to 80% for LI-RADS 4 and 80% to 84% for LI-RADS 5. Readers showed excellent accuracy for differentiating benign and malignant liver lesions with AUC values > 0.90. Overall inter-reader agreement was 'good' (kappa = 0.76, p < 0.001). Pairwise inter-reader agreement was 'very good' (kappa ≥ 0.90, p < 0.001). Conclusion: The LI-RADS version 2018 demonstrates excellent specificity, NPV and AUC values for risk stratification of liver observations by radiologists. Liver Imaging Reporting and Data System can reliably differentiate benign from malignant lesions when used in conjunction with corresponding LI-RADS management recommendations.

Surgery versus conservative treatment for traumatic acute subdural haematoma: a prospective, multicentre, observational, comparative effectiveness study.

BACKGROUND: Despite being well established, acute surgery in traumatic acute subdural haematoma is based on low-grade evidence. We aimed to compare the effectiveness of a strategy preferring acute surgical evacuation with one preferring initial conservative treatment in acute subdural haematoma. METHODS: We did a prospective, observational, comparative effectiveness study using data from participants enrolled in the Collaborative European Neurotrauma Effectiveness Research in Traumatic Brain Injury (CENTER-TBI) cohort. We included patients with no pre-existing severe neurological disorders who presented with acute subdural haematoma within 24 h of traumatic brain injury. Using an instrumental variable analysis, we compared outcomes between centres according to treatment preference for acute subdural haematoma (acute surgical evacuation or initial conservative treatment), measured by the case-mix-adjusted percentage of acute surgery per centre. The primary endpoint was functional outcome at 6 months as rated with the Glasgow Outcome Scale Extended, which was estimated with ordinal regression as a common odds ratio (OR) and adjusted for prespecified confounders. Variation in centre preference was quantified with the median OR (MOR). CENTER-TBI is registered with ClinicalTrials.gov, number NCT02210221, and the Resource Identification Portal (Research Resource Identifier SCR_015582). FINDINGS: Between Dec 19, 2014 and Dec 17, 2017, 4559 patients with traumatic brain injury were enrolled in CENTER-TBI, of whom 1407 (31%) presented with acute subdural haematoma and were included in our study. Acute surgical evacuation was done in 336 (24%) patients, by craniotomy in 245 (73%) of those patients and by decompressive craniectomy in 91 (27%). Delayed decompressive craniectomy or craniotomy after initial conservative treatment (n=982) occurred in 107 (11%) patients. The percentage of patients who underwent acute surgery ranged from 5·6% to 51·5% (IQR 12·3-35·9) between centres, with a two-times higher probability of receiving acute surgery for an identical patient in one centre versus another centre at random (adjusted MOR for acute surgery 1·8; p<0·0001]). Centre preference for acute surgery over initial conservative treatment was not associated with improvements in functional outcome (common OR per 23·6% [IQR increase] more acute surgery in a centre 0·92, 95% CI 0·77-1·09). INTERPRETATION: Our findings show that treatment for patients with acute subdural haematoma with similar characteristics differed depending on the treating centre, because of variation in the preferred approach. A treatment strategy preferring an aggressive approach of acute surgical evacuation over initial conservative treatment was not associated with better functional outcome. Therefore, in a patient with acute subdural haematoma for whom a neurosurgeon sees no clear superiority for acute surgery over conservative treatment, initial conservative treatment might be considered. FUNDING: The Hersenstichting Nederland (also known as the Dutch Brain Foundation), the European Commission Seventh Framework Programme, the Hannelore Kohl Stiftung (Germany), OneMind (USA), Integra LifeSciences Corporation (USA), and NeuroTrauma Sciences (USA).

Managing brain tumors in pregnancy: The oncologist's struggle with maternal-fetal conflict.

The diagnosis of malignancy, particularly brain tumors, in pregnancy is uncommon but poses a complex dilemma for the management of both the patient and her fetus, as the interplay of disease with the physiological state of pregnancy affects both outcomes. The routine evaluations (symptomatology, imaging, and hormonal assessments) and treatments (surgery, radiation therapy, and chemotherapy) that are commonplace in brain tumor management may need to be omitted or modified keeping in mind the risk to offspring. Multidisciplinary care and extensive prenatal and perinatal counseling and monitoring are essential. In this review, we discuss the available data addressing these issues and factors which may affect considerations of therapeutic abortions, changes in surgical or medical practices, and outcomes thereof.

Randomized Evaluation of Surgery in Elderly with Traumatic Acute SubDural Hematoma (RESET-ASDH trial): study protocol for a pragmatic randomized controlled trial with multicenter parallel group design.

BACKGROUND: The rapidly increasing number of elderly (≥ 65 years old) with TBI is accompanied by substantial medical and economic consequences. An ASDH is the most common injury in elderly with TBI and the surgical versus conservative treatment of this patient group remains an important clinical dilemma. Current BTF guidelines are not based on high-quality evidence and compliance is low, allowing for large international treatment variation. The RESET-ASDH trial is an international multicenter RCT on the (cost-)effectiveness of early neurosurgical hematoma evacuation versus initial conservative treatment in elderly with a t-ASDH METHODS: In total, 300 patients will be recruited from 17 Belgian and Dutch trauma centers. Patients ≥ 65 years with at first presentation a GCS ≥ 9 and a t-ASDH > 10 mm or a t-ASDH < 10 mm and a midline shift > 5 mm, or a GCS < 9 with a traumatic ASDH < 10 mm and a midline shift < 5 mm without extracranial explanation for the comatose state, for whom clinical equipoise exists will be randomized to early surgical hematoma evacuation or initial conservative management with the possibility of delayed secondary surgery. When possible, patients or their legal representatives will be asked for consent before inclusion. When obtaining patient or proxy consent is impossible within the therapeutic time window, patients are enrolled using the deferred consent procedure. Medical-ethical approval was obtained in the Netherlands and Belgium. The choice of neurosurgical techniques will be left to the discretion of the neurosurgeon. Patients will be analyzed according to an intention-to-treat design. The primary endpoint will be functional outcome on the GOS-E after 1 year. Patient recruitment starts in 2022 with the exact timing depending on the current COVID-19 crisis and is expected to end in 2024. DISCUSSION: The study results will be implemented after publication and presented on international conferences. Depending on the trial results, the current Brain Trauma Foundation guidelines will either be substantiated by high-quality evidence or will have to be altered. TRIAL REGISTRATION: Nederlands Trial Register (NTR), Trial NL9012 . CLINICALTRIALS: gov, Trial NCT04648436 .

Development of video animations to encourage patient-driven deprescribing: A Team Alice Study.

OBJECTIVE: Patient-driven deprescribing initiatives aim to increase patient knowledge and strengthen self-advocacy skills. This article describes the development of three animated videos designed to educate older adults about unsafe prescribing and medication harm, based on the actionable lessons from the death, by polypharmacy, of an older adult in our community. METHODS: Using a community based participatory research approach (CBPR), members of three senior centers (n = 53) and the Deprescribing Partnership of Western New York (n = 30) were recruited and participated in two rounds of focus groups to guide the video development. RESULTS: Stakeholder input led to changes in content, wording, and visual presentation. The final versions of the videos emphasize the following messages (1) "New medications and what you should know about the risks", (2) "What you should do when a doctor tells you never to take a certain medication", (3) "What you should know about medications when you are in the hospital." CONCLUSION: The study highlights the successful process of using CBPR to develop a series of videos designed to provide information on the risks of polypharmacy, and empower older adults to advocate for themselves. PRACTICE IMPLICATIONS: Animated educational videos are a novel strategy to address medication harm in older adults. This research is a critical first step to increasing patient-led discussions that reduce the incidence of medication harm and inappropriate medication use among older adults.

16-Substituted steroids alleviate LPS-induced neurodegenerative disorders in rats.

The neuroprotective effects of some 16-substituted steroidal derivatives against the locomotive impairment and cognitive deficits in the lipopolysaccharide (LPS)-induced neuroinflammation model of rats have been investigated. The in vivo and in vitro evaluations include behavioural tests (actophotometer, block tests, Morris water maize and elevated plus maize), estimation of the biochemical parameters such as acetylcholinesterase, lipid peroxide, reactive oxygen, and nitric oxide species and molecular assays for the key proinflammatory mediators like Tumour Necrosis Factor alpha (TNF-α) and Interleukin 1 beta (IL- 1ß) after 21 days of the treatment with the steroids. Behavioural and biochemical studies indicated impairment in the locomotor activity and cognitive dysfunction in rats after LPS treatment. In addition, higher levels of TNF-α and IL-1ß in the blood serum of the rats were also noticed. However, significant alleviation of LPS-induced movement and memory disorders was observed in LPS-injected rats after treatment with 16-substituted steroidal derivatives 1-11. Furthermore the biochemical and molecular studies revealed suppression of oxidative and nitrosative stress, decreased acetylcholinesterase activity, and reduction of TNF-α and IL-1ß levels after treatment with compounds 1-11. Among all the 16-substituted steroidal derivatives, the compounds 8 and 11 were found to be the most active neuroprotective agents and produced effects marginally better than standard drug dexamethasone.

Delayed-onset white cord syndrome after anterior and posterior cervical decompression surgery for symptomatic ossification of spinal ligaments: illustrative cases.

BACKGROUND: White cord syndrome is an extremely rare complication of cervical decompressive surgery, characterized by serious postoperative neurological deficits in the absence of apparent surgical complications. It is named after the characteristic ischemic-edematous intramedullary T2-hyperintense signal on postoperative magnetic resonance imaging and is believed to be caused by ischemic-reperfusion injury. Neurological deficits typically manifest immediately after surgery, and delayed occurrence has been reported only once. OBSERVATIONS: The authors presented two cases of delayed white cord syndrome after anterior and posterior cervical decompression surgery for symptomatic ossification of the posterior longitudinal ligament and ligamentum flavum, respectively. Neurological deficits manifested on postoperative day 2 (case 1) and day 8 (case 2). The patients' conditions were managed with high-dose corticosteroids, mean arterial pressure augmentation, and early physical therapy, after which they showed partial neurological recovery at discharge, which improved further by the 3-month follow-up visit. LESSONS: The authors' aim was to raise awareness among spine surgeons about this rare but severe complication of cervical decompressive surgery and to emphasize the mainstays of treatment based on current best evidence: high-dose corticosteroids, mean arterial pressure augmentation, and early physical therapy.