A Case Report on Initial Experience of Lattice Radiation Therapy for Managing Massive Non-small Cell Lung Cancer and Renal Pelvic Cancer.

Lattice radiation therapy (LRT) is an advanced treatment approach specifically designed for massive tumors. It aims to deliver high-dose regions within tumors while ensuring the safety of the surrounding dose-limiting organs at risk (OAR). This case report introduces two unique clinical cases: a 63-year-old male diagnosed with a massive non-small cell lung cancer (NSCLC) tumor and a 61-year-old male with an inoperable recurrent left-sided adrenal mass intricately surrounded by dose-limiting bowel structures. Both patients underwent LRT to enhance tumor control and maintain less toxicity. Notably, both patients displayed a significant tumor volume reduction accompanied by minimal adverse effects during the 12-month follow-up period. While these initial results suggest that LRT may be effective and safe for treating large tumors, further investigation through exhaustive research and multicenter trials is necessary to fully understand and determine the specifics of lattice radiation therapy techniques.

Neurosurgery activity levels in the United Kingdom and republic of Ireland during the first wave of the covid-19 pandemic - a retrospective cross-sectional cohort study.

The impact of Covid-19 on surgical patients worldwide has been substantial. In the United Kingdom (UK) and the Republic of Ireland (RoI), the first wave of the pandemic occurred in March 2020. The aims of this study were to: (1) evaluate the volume of neurosurgical operative activity levels, Covid-19 infection rate and mortality rate in April 2020 with a retrospective cross-sectional cohort study conducted across 16 UK and RoI neurosurgical centres, and (2) compare patient outcomes in a single institution in April-June 2020 with a comparative cohort in 2019. Across the UK and RoI, 818 patients were included. There were 594 emergency and 224 elective operations. The incidence rate of Covid-19 infection was 2.6% (21/818). The overall mortality rate in patients with a Covid-19 infection was 28.6% (6/21). In the single centre cohort analysis, an overall reduction in neurosurgical operative activity by 65% was observed between 2020 (n = 304) and 2019 (n = 868). The current and future impact on UK neurosurgical operative activity has implications for service delivery and neurosurgical training.

Management of aneurysmal subarachnoid haemorrhage 17 years after the ISAT trial: a survey of current practice in the UK and Ireland.

Introduction: In the last two decades and driven by the International Subarachnoid Aneurysm Trial (ISAT), the management of aneurysmal subarachnoid haemorrhage (aSAH) has undergone extensive change from predominantly neurosurgical (clipping) to predominantly neuroradiological (coiling) treatment. In 2013, the UK's national Confidential Enquiry into Patient Outcome and Death (NCEPOD) recommended aSAH to be definitively treated within 48h of ictus. The aim of this survey was to assess how this recommendation is being followed across the UK and Ireland 17 years after ISAT and 6 years after the NCEPOD.Methods: An online survey consisting of 9 questions was electronically distributed to neurosurgical consultants and trainees. Missing or ambivalent data was collected or verified by emailing consultant neurosurgeons to ensure the coverage of all 32 neurosurgical units in the UK and Ireland.Results: Only 9 (28%) of units provide 7 days a week interventional neuroradiology service, but all 32 (100%) units have established networks with other neuroradiology centres to provide aSAH treatment within 48h of ictus assuming no delays in patient transfer. For aSAH patients requiring neurosurgical clipping, 27 (84%) of units provide (locally or through networks) aneurysm repair within 48h of ictus, whereas 5 (16%) units may breach this recommendation by keeping the aSAH patients that present after 5PM on Fridays and delaying their clipping to the subsequent Monday.Conclusion: Assuming no delays in patient transfer, 32 (100%) neurosurgical centres in the UK and Ireland meet the <48h ictus-to-treatment target for endovascular coiling and 27 (84%) units for neurosurgical clipping of aSAH.

Management of Concomitant Moyamoya Disease, Arterial Venous Malformation, and Intracranial Aneurysm: Case Illustration, Literature Review, and Management Algorithm.

BACKGROUND: Moyamoya disease (MMD), arterial venous malformations (AVMs), and intracranial aneurysms are distinct cerebrovascular disease processes that most commonly occur in isolation. The literature on the treatment algorithm of each individual condition is well established. An association between MMD and intracranial aneurysms is also known, but MMD in association with AVM is rare. CASE DESCRIPTIONS: The authors discuss various dilemmas in the multimodality management of these conditions when they coexist with an illustrative case of a 46-year-old woman who presented following a stroke, with 1) left-sided MMD, 2) left-sided frontal AVM, and 3) an aneurysm arising from the A1 segment of the right anterior cerebral artery. These were managed respectively by 1) the left external carotid artery to M2 segment of middle cerebral artery bypass using an autologous radial artery graft and left indirect superior temporal artery-encephaloduroarteriosynangiosis, 2) stereotactic radiosurgery, and 3) endovascular coiling of the aneurysm. Three years following intervention, cerebral angiography showed a patent bypass, complete obliteration of the AVM, and no residual filling of the coiled aneurysm. CONCLUSIONS: Our strategy of surgical revascularization for MMD, radiosurgery for AVM, and endovascular coiling for aneurysm resulted in a positive long-term clinical outcome. In view of the rarity of the condition, the authors propose a management algorithm for such patients.

Characterization of IDH1 p.R132H Mutant Clones Using Mutation-specific Antibody in Myeloid Neoplasms.

Isocitrate dehydrogenase 1 (IDH1) and IDH2 mutations occur in a variety of myeloid neoplasms. Immunohistochemistry (IHC)-based direct visualization of mutant clones of hematopoietic cells can be useful for rapid diagnostic screening and for monitoring treatment response. In this study, we first evaluated the sensitivity and specificity of the IDH1 p.R132H mutation-specific antibody by IHC. All IDH1 wild type cases (n=11) and IDH1 mutant cases with a non-p.R132H mutation (n=30) were negative by IHC, demonstrating 100% antibody specificity. All the initial diagnostic specimens with IDH1 p.R132H mutation including acute myeloid leukemia (n=30), myelodysplastic syndromes (MDS) (n=10), MDS/myeloproliferative neoplasms (MPN) (n=4), and MPN (n=5) were positive by IHC, demonstrating 100% antibody sensitivity. Both immature and mature myeloid cells showed immunoreactivity. Erythroid precursors, lymphoid cells, endothelial cells, and osteoblasts were consistently negative by IHC. We then evaluated the follow-up specimens with a known IDH1 mutation status including acute myeloid leukemia (n=23), MDS (n=2), MDS/MPN (n=2), and MPN (n=2). Thirty-three IDH1 p.R132H mutant cases were positive by IHC and 12 IDH1 mutation negative cases were negative by IHC. However, IHC reactivity in up to 25% of bone marrow cells was noted in 8 of 20 polymerase chain reaction-negative cases, all from patients with a known history of IDH1 p.R132H mutation indicating sampling error or a sensitivity issue with molecular tests. These data indicate that IHC is a highly specific and sensitive tool to detect IDH1 p.R132H mutation in bone marrow involved by myeloid neoplasms. In addition, IDH1 p.R132H IHC also allows localization and assessment of the maturation stage of the clones carrying the mutation.

Diagnostic, Prognostic, and Predictive Utility of Recurrent Somatic Mutations in Myeloid Neoplasms.

The classification and risk stratification of myeloid neoplasms, including acute myeloid leukemia, myelodysplastic syndromes, myelodysplastic syndromes/myeloproliferative neoplasms, and myeloproliferative neoplasms, have increasingly been guided by molecular genetic abnormalities. Gene expression analysis and next-generation sequencing have led to the ever increasing discovery of somatic gene mutations in myeloid neoplasms. Mutations have been identified in genes involved in epigenetic modification, RNA splicing, transcription factors, DNA repair, and the cohesin complex. These new somatic/acquired gene mutations have refined the classification of myeloid neoplasms and have been incorporated into the 2016 update of the World Health Organization (WHO) classification and the National Comprehensive Cancer Network guidelines. They have also been helpful in the development of new targeted therapeutic agents. In the present review, we describe the clinical utility of recently identified, clinically important gene mutations in myeloid neoplasms, including those incorporated in the 2016 update of the WHO classification.

Cervical cord decompression following embolisation of a giant cervical vertebro-vertebral arteriovenous fistula.

Arteriovenous fistulation between the vertebral arteries to extradural (epidural) veins, termed vertebro-vertebral arteriovenous fistulae, are uncommon diagnoses without established diagnostic algorithms or treatment options. Minimal evidence exists describing the management of this pathology. Endovascular treatment was performed under general anaesthesia by coil occlusion of the vertebral artery from the point of the fistula to the mid-vertebral artery. Repeat magnetic resonance angiographic imaging one week following the procedure confirmed an 80% reduction in the size of the epidural vein and decompression of the cervical spinal cord. At four-week follow-up there was significant qualitative improvement in the myelopathic symptoms including walking distance and pain. Normal physiological filling of the collapsed extradural vein was observed on follow-up digital subtraction angiography at five months. Catheter angiography by an experienced interventional neuro-radiologist is critical in defining the anatomy and providing minimally invasive treatment.

Intracerebral Masson's Tumor-Slow-Filling Vascular Lesion Demonstrated by Indocyanine Green Video Angiography.

BACKGROUND: Intravascular papillary endothelial hyperplasia, or Masson's tumors, are benign vascular lesions that are rarely seen intracranially. The vascular characteristics of these lesions are also unknown. CASE DESCRIPTION: We report the case of a 24-year-old male patient with a 3-year history of headache and dizziness. Neuroradiologic imaging showed a slow-growing lesion consistent with a low-grade glioma. Intraoperative appearance was of a vascular lesion that was slow filling as demonstrated with indocyanine green video angiography. Histologic analysis following resection revealed intravascular papillary endothelial hyperplasia (Masson's tumor). CONCLUSION: Masson's tumors are slow-filling vascular lesions. The preoperative diagnosis of this lesion is difficult as it can mimic a neoplastic lesion. Conservative and surgical treatment options should therefore be carefully considered. Patients with subtotal resection must undergo long-term follow-up surveillance imaging as recurrence is a possibility.

Do Studies Evaluating QT/QTc Interval Prolongation with Dietary Supplements Meet FDA Standards: A Systematic Review.

PURPOSE: Dietary supplement use is continuously increasing, but the safety evaluation of these products remains partial. While dietary supplements have no mandate for assessing cardiovascular safety, all new drug entities (NDE) are required to undergo a thorough QT/corrected QT (QTc) assessment to determine their propensity to impact cardiac repolarization. Independent investigators and manufacturers of dietary supplements voluntarily initiate safety studies; however, the quality of these studies is controversial. We sought to compare studies evaluating the QT/QTc effects of dietary supplements based on the International Conference of Harmonization (ICH)-E14 recommendations for NDE. CASE SUMMARY: Twenty-six published dietary supplement studies assessed QT/QTc interval prolongation. Sample sizes ranged from nine subjects to 206 among the 15 crossover studies, six parallel design studies, and five observational studies. A plan to account for electrocardiogram (ECG) morphological abnormalities was included in 10 studies, and two studies reported cardiovascular adverse events. Eight studies found a significant change in QT/QTc intervals. CONCLUSIONS: The majority of studies included in this review contained many of the critical elements recommended by the ICH E14, which includes the U.S. Food and Drug Administration guidance document for QT/QTc interval assessment. Compared with the thorough QT (TQT) standards, studies are typically well performed but can be bolstered by some study design changes. More than 30% of the included studies showed some degree of ECG changes, suggesting the need for continued cardiovascular safety assessment of dietary supplements.

Acute myeloid leukemia with t(4;12)(q12;p13): A morphological dilemma.

Cytogenetics has a pivotal role in risk stratification of acute myeloid leukemia (AML). We report a case of AML with a t(4;12)(q12;p13). To the best of our knowledge, there are about 24 cases of t(4;12) reported in AML which are usually misdiagnosed as lymphoproliferative disorders on morphological assessment. This case showed specific clinical, morphological, and immunophenotypic features such as (1) pseudo lymphoid morphology, (2) dysplasia in granulocytic series, (3) an immature immunophenotype with positivity for CD34 and CD117, and (4) poor treatment response.

Electron ionization of open/closed chain isocarbonic molecules relevant in plasma processing: theoretical cross sections.

In this paper, we report theoretical electron impact ionization cross sections from threshold to 2000 eV for isocarbonic open chain molecules C4H6, C4H8, C4F6 including their isomers, and closed chain molecules c-C4H8 and c-C4F8. Theoretical formalism employed presently, viz., Complex Scattering Potential-ionization contribution method has been used successfully for a variety of polyatomic molecules. The present ionization calculations are very important since results available for the studied targets are either scarce or none. Our work affords comparison of C4 containing hydrocarbon versus fluorocarbon molecules. Comparisons of the present ionization cross sections are made wherever possible, and new ionization data are also presented.

Advance statement of consent from patients with primary CNS tumours to organ donation and elective ventilation.

A deficit in the number of organs available for transplantation persists even with an increase in donation rates. One possible choice of donor for organs that appears under-referred and/or unaccepted is patients with primary brain tumours. In spite of advances in the treatment of high-grade primary central nervous system (CNS) tumours, the prognosis remains dire. A working group on organs from donors with primary CNS tumours showed that the risk of transmission is small and outweighs the benefits of waiting for a normal donor, in survival and organ life-years, with caveats. This paper explores the possibility that, if information on organ donation were made available to patients and their families with knowledge of their inevitable fate, perhaps some will choose to donate. It would be explained that to achieve this, elective ventilation would be performed in their final moments. This would obviate the consent question because of an advance statement. It is accepted that these are sensitive matters and there will be logistic issues. This will need discussion with the public and other professionals, but it could increase the number of donors and can be extrapolated to encompass other primary CNS tumours.

Formulation of thermoresponsive and buccal adhesive in situ gel for treatment of oral thrush containing poorly water soluble drug bifonazole.

The aim of the present work is to formulate and evaluate in situ oral topical gels of poorly water soluble drug Bifonazole based on temperature induced systems for the treatment of oral candidiasis. Bifonazole is poorly water soluble and low permeable drug means it's belongs to BCS Class IV. Due to its poor water solubility, it necessary to enhance solubility in water by make complex with Beta- Cyclodextrin (Drug to ßCyclo Dextrine ratio is 1:1). After in situ gel preparation done by using Poloxamer (10% and 15%w/w) along with carbopol 934 (0.2 to 1.0% w/w) and Bifonazole - ß CD complex (1%w/w). The formulations were evaluated for physiochemical parameter, gelation Temperature, viscosity, gel strength, content uniformity mucoadhesive force, Diffusion Study.

Assessing quality of life in an ambulatory medicare population.

OBJECTIVE: Medicare beneficiaries have unique health-related challenges causing significant impact on quality of life. This study examined the overall health-related quality of life (HRQOL) and differences in HRQOL between subgroups of an ambulatory Medicare beneficiary population. METHODS: Nine outreach events were held during the 2011 Medicare Part D prescription drug open-enrollment period, in which 397 beneficiaries were assisted with Part D plan evaluation and comprehensive medication therapy review. Demographic data were collected, and the SF-36v2 was administered to measure beneficiaries' self-reported HRQOL. Correlations were assessed between the mental component summary (MCS) or physical component summary (PCS) scores of the SF-36v2, prescription utilization, number of chronic conditions, and whether beneficiaries were government subsidy recipients. RESULTS: Mean Å standard deviation of PCS and MCS scores were 43.3 Å 11.4 and 52.2 Å 11.7, respectively. Both PCS and MCS scores were negatively correlated with the number of prescription medications and number of self-reported chronic conditions. Both PCS and MCS scores related to sociodemographics were significantly lower (P < 0.05) in subsidy and least-educated recipients. CONCLUSIONS: HRQOL can vary widely as a result of sociodemographic, drug, or disease differences in an ambulatory Medicare beneficiary population.

Computational hemodynamics in cerebral aneurysms: the effects of modeled versus measured boundary conditions.

Modeling of flow in intracranial aneurysms (IAs) requires flow information at the model boundaries. In absence of patient-specific measurements, typical or modeled boundary conditions (BCs) are often used. This study investigates the effects of modeled versus patient-specific BCs on modeled hemodynamics within IAs. Computational fluid dynamics (CFD) models of five IAs were reconstructed from three-dimensional rotational angiography (3DRA). BCs were applied using in turn patient-specific phase-contrast-MR (pc-MR) measurements, a 1D-circulation model, and a physiologically coherent method based on local WSS at inlets. The Navier-Stokes equations were solved using the Ansys®-CFX™ software. Wall shear stress (WSS), oscillatory shear index (OSI), and other hemodynamic indices were computed. Differences in the values obtained with the three methods were analyzed using boxplot diagrams. Qualitative similarities were observed in the flow fields obtained with the three approaches. The quantitative comparison showed smaller discrepancies between pc-MR and 1D-model data, than those observed between pc-MR and WSS-scaled data. Discrepancies were reduced when indices were normalized to mean hemodynamic aneurysmal data. The strong similarities observed for the three BCs models suggest that vessel and aneurysm geometry have the strongest influence on aneurysmal hemodynamics. In absence of patient-specific BCs, a distributed circulation model may represent the best option when CFD is used for large cohort studies.