Phase II Efficacy and Safety of 80 mg Osimertinib in Patients With Leptomeningeal Metastases Associated With Epidermal Growth Factor Receptor Mutation-Positive Non-Small Cell Lung Cancer (BLOSSOM).

PURPOSE: Leptomeningeal metastases (LMs) exhibit a high incidence in patients with epidermal growth factor receptor (EGFR)-mutated non-small cell lung cancer (NSCLC) post-treatment with first- or second-generation EGFR tyrosine kinase inhibitors (TKIs). This investigation evaluates the efficacy, safety, and pharmacokinetics of 80 mg once daily osimertinib in patients with LMs resistant to prior first- or second-generation EGFR TKIs. MATERIALS AND METHODS: In this phase II multicenter, open-label, single-arm study, 80 mg osimertinib was administered to patients with EGFR-mutated NSCLC who had developed LMs subsequent to treatment with prior EGFR TKIs. The primary end point was overall survival (OS), assessed alongside objective response rate by the blinded independent central review (BICR) and a pharmacokinetic analysis of plasma and cerebrospinal fluid (CSF) on the first day of cycles 3 and 6. RESULTS: A total of 73 patients diagnosed with LM were treated with osimertinib, including 64 patients evaluable for the LM efficacy set-T790M negative (n = 62) and T790M positive (n = 2). The median OS in the full-analysis set was 15.6 months (95% CI, 11.5 to 20.2). The objective response rate for LM was 51.6%, including a 15.6% complete response, and the disease control rate was 81.3% by BICR in the LM efficacy evaluable set. The median LM progression-free survival by BICR was 11.2 months (95% CI, 7.7 to 15.3), the duration of response was 12.6 months (95% CI, 7.6 to 17.7), and OS was 15.0 months (95% CI, 11.3 to 18.7). Pharmacokinetic analysis showed that the CSF to free plasma osimertinib ratio was 22%. Most safety profiles were grade 1 and 2. CONCLUSION: The study demonstrates significant intracranial efficacy and survival benefits of 80 mg once daily osimertinib in NSCLC patients with LMs. The data support considering daily 80 mg of osimertinib as a treatment option for EGFR-mutated NSCLC patients with LMs, irrespective of T790M mutation status.

Comprehensive multiomics analysis reveals distinct differences between pediatric choroid plexus papilloma and carcinoma.

Choroid plexus tumors (CPTs) are intraventricular tumors derived from the choroid plexus epithelium and occur frequently in children. The aim of this study was to investigate the genomic and epigenomic characteristics of CPT and identify the differences between choroid plexus papilloma (CPP) and choroid plexus carcinoma (CPC). We conducted multiomics analyses of 20 CPT patients including CPP and CPC. Multiomics analysis included whole-genome sequencing, whole-transcriptome sequencing, and methylation sequencing. Mutually exclusive TP53 and EPHA7 point mutations, coupled with the amplification of chromosome 1, were exclusively identified in CPC. In contrast, amplification of chromosome 9 was specific to CPP. Differential gene expression analysis uncovered a significant overexpression of genes related to cell cycle regulation and epithelial-mesenchymal transition pathways in CPC compared to CPP. Overexpression of genes associated with tumor metastasis and progression was observed in the CPC subgroup with leptomeningeal dissemination. Furthermore, methylation profiling unveiled hypomethylation in major repeat regions, including long interspersed nuclear elements, short interspersed nuclear elements, long terminal repeats, and retrotransposons in CPC compared to CPP, implying that the loss of epigenetic silencing of transposable elements may play a role in tumorigenesis of CPC. Finally, the differential expression of AK1, regulated by both genomic and epigenomic factors, emerged as a potential contributing factor to the histological difference of CPP against CPC. Our results suggest pronounced genomic and epigenomic disparities between CPP and CPC, providing insights into the pathogenesis of CPT at the molecular level.

Nomogram for radiation-induced lymphopenia in patients receiving intensity-modulated radiotherapy based-chemoradiation therapy for newly diagnosed glioblastoma: A multi-institutional study.

Purpose: Severe lymphopenia (SLP) has emerged as a significant prognostic factor in glioblastoma. Intensity-modulated radiation therapy (IMRT)-based radiation therapy (RT) is suggested to minimize the risk of SLP. This study aimed to evaluate SLP incidence based on multi-institutional database in patients with GBM treated with IMRT and develop a predictive nomogram. Patients and methods: This retrospective study reviewed data from 348 patients treated with IMRT-based concurrent chemoradiation therapy (CCRT) at two major hospitals from 2016 to 2021. After multivariate regression analysis, a nomogram was developed and internally validated to predict SLP risk. Results: During treatment course, 21.0% of patients developed SLP and SLP was associated with poor overall survival outcomes in patients with GBM. A newly developed nomogram, incorporating gender, pre-CCRT absolute lymphocyte count, and brain mean dose, demonstrated fair predictive accuracy (AUC 0.723). Conclusions: This study provides the first nomogram for predicting SLP in patients with GBM treated with IMRT-based CCRT, with acceptable predictive accuracy. The findings underscore the need for dose optimization and radiation planning to minimize SLP risk. Further external validation is crucial for adopting this nomogram in clinical practice.

A 70% Ethanol Neorhodomela munita Extract Attenuates RANKL-Induced Osteoclast Activation and H2O2-Induced Osteoblast Apoptosis In Vitro.

The rapid aging of the population worldwide presents a significant social and economic challenge, particularly due to osteoporotic fractures, primarily resulting from an imbalance between osteoclast-mediated bone resorption and osteoblast-mediated bone formation. While conventional therapies offer benefits, they also present limitations and a range of adverse effects. This study explores the protective impact of Neorhodomela munita ethanol extract (EN) on osteoporosis by modulating critical pathways in osteoclastogenesis and apoptosis. Raw264.7 cells and Saos-2 cells were used for in vitro osteoclast and osteoblast models, respectively. By utilizing various in vitro methods to detect osteoclast differentiation/activation and osteoblast death, it was demonstrated that the EN's potential to inhibit RANKL induced osteoclast formation and activation by targeting the MAPKs-NFATc1/c-Fos pathway and reducing H2O2-induced cell death through the downregulation of apoptotic signals. This study highlights the potential benefits of EN for osteoporosis and suggests that EN is a promising natural alternative to traditional treatments.

Exploring Cardiac Exosomal RNAs of Acute Myocardial Infarction.

BACKGROUND: Myocardial infarction (MI), often a frequent symptom of coronary artery disease (CAD), is a leading cause of death and disability worldwide. Acute myocardial infarction (AMI), a major form of cardiovascular disease, necessitates a deep understanding of its complex pathophysiology to develop innovative therapeutic strategies. Exosomal RNAs (exoRNA), particularly microRNAs (miRNAs) within cardiac tissues, play a critical role in intercellular communication and pathophysiological processes of AMI. METHODS: This study aimed to delineate the exoRNA landscape, focusing especially on miRNAs in animal models using high-throughput sequencing. The approach included sequencing analysis to identify significant miRNAs in AMI, followed by validation of the functions of selected miRNAs through in vitro studies involving primary cardiomyocytes and fibroblasts. RESULTS: Numerous differentially expressed miRNAs in AMI were identified using five mice per group. The functions of 20 selected miRNAs were validated through in vitro studies with primary cardiomyocytes and fibroblasts. CONCLUSIONS: This research enhances understanding of post-AMI molecular changes in cardiac tissues and investigates the potential of exoRNAs as biomarkers or therapeutic targets. These findings offer new insights into the molecular mechanisms of AMIs, paving the way for RNA-based diagnostics and therapeutics and therapies and contributing to the advancement of cardiovascular medicine.

Effects of Melatonin, GM-CSF, IGF-1, and LIF in Culture Media on Embryonic Development: Potential Benefits of Individualization.

The implantation of good-quality embryos to the receptive endometrium is essential for successful live birth through in vitro fertilization (IVF). The higher the quality of embryos, the higher the live birth rate per cycle, and so efforts have been made to obtain as many high-quality embryos as possible after fertilization. In addition to an effective controlled ovarian stimulation process to obtain high-quality embryos, the composition of the embryo culture medium in direct contact with embryos in vitro is also important. During embryonic development, under the control of female sex hormones, the fallopian tubes and endometrium create a microenvironment that supplies the nutrients and substances necessary for embryos at each stage. During this process, the development of the embryo is finely regulated by signaling molecules, such as growth factors and cytokines secreted from the epithelial cells of the fallopian tube and uterine endometrium. The development of embryo culture media has continued since the first successful human birth through IVF in 1978. However, there are still limitations to mimicking a microenvironment similar to the reproductive organs of women suitable for embryo development in vitro. Efforts have been made to overcome the harsh in vitro culture environment and obtain high-quality embryos by adding various supplements, such as antioxidants and growth factors, to the embryo culture medium. Recently, there has been an increase in the number of studies on the effect of supplementation in different clinical situations such as old age, recurrent implantation failure (RIF), and unexplained infertility; in addition, anticipation of the potential benefits from individuation is rising. This article reviews the effects of representative supplements in culture media on embryo development.

Enhanced Osteocyte Differentiation: Cathepsin D and L Secretion by Human Adipose-Derived Mesenchymal Stem Cells.

Adipose-derived mesenchymal stem cells (ASCs) have the potential to differentiate into bone, cartilage, fat, and neural cells and promote tissue regeneration and healing. It is known that they can have variable responses to hypoxic conditions. In the present study, we aimed to explore diverse changes in the cells and secretome of ASCs under a hypoxic environment over time and to present the possibility of ASCs as therapeutic agents from a different perspective. The expression differences of proteins between normoxic and hypoxic conditions (6, 12, or 24 h) were specifically investigated in human ASCs using 2-DE combined with MALDI-TOF MS analysis, and secreted proteins in ASC-derived conditioned media (ASC-derived CM) were examined by an adipokine array. In addition, genetic and/or proteomic interactions were assessed using a DAVID and miRNet functional annotation bioinformatics analysis. We found that 64 and 5 proteins were differentially expressed in hypoxic ASCs and in hypoxic ASC-derived CM, respectively. Moreover, 7 proteins among the 64 markedly changed spots in hypoxic ASCs were associated with bone-related diseases. We found that two proteins, cathepsin D (CTSD) and cathepsin L (CTSL), identified through an adipokine array independently exhibited significant efficacy in promoting osteocyte differentiation in bone-marrow-derived mesenchymal stem cells (BM-MSCs). This finding introduces a promising avenue for utilizing hypoxia-preconditioned ASC-derived CM as a potential therapeutic approach for bone-related diseases.

Impact of boost sequence in concurrent chemo-radiotherapy on newly diagnosed IDH-wildtype glioblastoma multiforme.

BACKGROUND: The standard of care for glioblastoma multiforme (GBM) is maximal surgical resection followed by conventional fractionated concurrent chemoradiotherapy (CCRT) with a total dose of 60 Gy. However, there is currently no consensus on the optimal boost technique for CCRT in GBM. METHODS: We conducted a retrospective review of 398 patients treated with CCRT between 2016 and 2021, using data from two institutional databases. Patients were divided into two groups: those receiving sequential boost (SEB, N = 119) and those receiving simultaneous integrated boost (SIB, N = 279). The primary endpoint was overall survival (OS). To minimize differences between the SIB and SEB groups, we conducted propensity score matching (PSM) analysis. RESULTS: The median follow-up period was 18.6 months. Before PSM, SEB showed better OS compared to SIB (2-year, 55.6% vs. 44.5%, p = 0.014). However, after PSM, there was no significant difference between two groups (2-year, 55.6% vs. 51.5%, p = 0.300). The boost sequence was not associated with inferior OS before and after PSM (all p-values > 0.05). Additionally, the rates of symptomatic pseudo-progression were similar between the two groups (odds ratio: 1.75, p = 0.055). CONCLUSIONS: This study found no significant difference in OS between SEB and SIB for GBM patients treated with CCRT. Further research is needed to validate these findings and to determine the optimal boost techniques for this patient population.

Development and derivation of bacteremia prediction model in patients with hepatobiliary infection.

INTRODUCTION: Hepatobiliary infections are common in the emergency department (ED), and the mortality rate for this condition is high. A suitable bacteremia prediction model would support prompt identification of bacteremia and appropriate management of hepatobiliary infections in the ED. Therefore, we attempted to produce a bacteremia prediction model with both internal and external validation for hepatobiliary infections in the ED. METHODS: Patients with hepatobiliary infection were extracted from retrospective cohort databases of two tertiary hospitals from January 2018 to December 2019 and from January 2016 to December 2019, respectively. Independent risk factors were determined using multivariable logistic regression in a developmental cohort. We assigned a weighted value to predictive factors and developed a prediction model, which was validated both internally and externally. We assessed discrimination using the area under the receiver operating characteristics curve (AUC). RESULTS: One hospital cohort of 1568 patients was randomly divided into a developmental group of 927 patients (60%) and an internal validation group of 641 patients (40%), and 736 people from the other hospital cohort were used for external validation. Bacteremia rates were 20.5%, 18.1%, and 23.1% in the developmental, internal, and external validation cohorts, respectively. Nine significant factors were used for predicting bacteremia, including age, three vital signs, and five laboratory tests. After applying our bacteremia prediction rule to the validation cohort, 56.5% and 53.8% of the internal and external validation groups were classified as low-risk bacteremia groups (bacteremia rates: 8.6% and 13.9%, respectively). The AUCs were 0.727 (95% confidence interval [CI]: 0.686-0.767), 0.730 (95% CI: 0.679-0.781), and 0.715 (95% CI: 0.672-0.758) for the developmental, internal, and external validation cohorts, respectively. The sensitivity and specificity for internal validation/external validation was 73.2%/67.6% and 63.0%/60.2%, respectively. CONCLUSION: A bacteremia prediction model for hepatobiliary infection might be useful to predict the risk of bacteremia. It might also reduce the need for blood culture in low-risk patients.

The Korean Society for Neuro-Oncology (KSNO) Guideline for the Management of Brain Tumor Patients During the Crisis Period: A Consensus Recommendation Using the Delphi Method (Version 2023.1).

BACKGROUND: During the coronavirus disease 2019 (COVID-19) pandemic, the need for appropriate treatment guidelines for patients with brain tumors was indispensable due to the lack and limitations of medical resources. Thus, the Korean Society for Neuro-Oncology (KSNO), a multidisciplinary academic society, has undertaken efforts to develop a guideline that is tailored to the domestic situation and that can be used in similar crisis situations in the future. METHODS: The KSNO Guideline Working Group was composed of 22 multidisciplinary experts on neuro-oncology in Korea. In order to reach consensus among the experts, the Delphi method was used to build up the final recommendations. RESULTS: All participating experts completed the series of surveys, and the results of final survey were used to draft the current consensus recommendations. Priority levels of surgery and radiotherapy during crises were proposed using appropriate time window-based criteria for management outcome. The highest priority for surgery is assigned to patients who are life-threatening or have a risk of significant impact on a patient's prognosis unless immediate intervention is given within 24-48 hours. As for the radiotherapy, patients who are at risk of compromising their overall survival or neurological status within 4-6 weeks are assigned to the highest priority. Curative-intent chemotherapy has the highest priority, followed by neoadjuvant/adjuvant and palliative chemotherapy during a crisis period. Telemedicine should be actively considered as a management tool for brain tumor patients during the mass infection crises such as the COVID-19 pandemic. CONCLUSION: It is crucial that adequate medical care for patients with brain tumors is maintained and provided, even during times of crisis. This guideline will serve as a valuable resource, assisting in the delivery of treatment to brain tumor patients in the event of any future crisis.

The Korean Society for Neuro-Oncology (KSNO) Guideline for the Management of Brain Tumor Patients During the Crisis Period: A Consensus Survey About Specific Clinical Scenarios (Version 2023.1).

BACKGROUND: During the coronavirus disease 2019 (COVID-19) pandemic, there was a shortage of medical resources and the need for proper treatment guidelines for brain tumor patients became more pressing. Thus, the Korean Society for Neuro-Oncology (KSNO), a multidisciplinary academic society, has undertaken efforts to develop a guideline that is tailored to the domestic situation and that can be used in similar crisis situations in the future. As part II of the guideline, this consensus survey is to suggest management options in specific clinical scenarios during the crisis period. METHODS: The KSNO Guideline Working Group consisted of 22 multidisciplinary experts on neuro-oncology in Korea. In order to confirm a consensus reached by the experts, opinions on 5 specific clinical scenarios about the management of brain tumor patients during the crisis period were devised and asked. To build-up the consensus process, Delphi method was employed. RESULTS: The summary of the final consensus from each scenario are as follows. For patients with newly diagnosed astrocytoma with isocitrate dehydrogenase (IDH)-mutant and oligodendroglioma with IDH-mutant/1p19q codeleted, observation was preferred for patients with low-risk, World Health Organization (WHO) grade 2, and Karnofsky Performance Scale (KPS) ≥60, while adjuvant radiotherapy alone was preferred for patients with high-risk, WHO grade 2, and KPS ≥60. For newly diagnosed patients with glioblastoma, the most preferred adjuvant treatment strategy after surgery was radiotherapy plus temozolomide except for patients aged ≥70 years with KPS of 60 and unmethylated MGMT promoters. In patients with symptomatic brain metastasis, the preferred treatment differed according to the number of brain metastasis and performance status. For patients with newly diagnosed atypical meningioma, adjuvant radiation was deferred in patients with older age, poor performance status, complete resection, or low mitotic count. CONCLUSION: It is imperative that proper medical care for brain tumor patients be sustained and provided, even during the crisis period. The findings of this consensus survey will be a useful reference in determining appropriate treatment options for brain tumor patients in the specific clinical scenarios covered by the survey during the future crisis.

Prediction of disease comorbidity using explainable artificial intelligence and machine learning techniques: A systematic review.

OBJECTIVE: Disease comorbidity is a major challenge in healthcare affecting the patient's quality of life and costs. AI-based prediction of comorbidities can overcome this issue by improving precision medicine and providing holistic care. The objective of this systematic literature review was to identify and summarise existing machine learning (ML) methods for comorbidity prediction and evaluate the interpretability and explainability of the models. MATERIALS AND METHODS: The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) framework was used to identify articles in three databases: Ovid Medline, Web of Science and PubMed. The literature search covered a broad range of terms for the prediction of disease comorbidity and ML, including traditional predictive modelling. RESULTS: Of 829 unique articles, 58 full-text papers were assessed for eligibility. A final set of 22 articles with 61 ML models was included in this review. Of the identified ML models, 33 models achieved relatively high accuracy (80-95%) and AUC (0.80-0.89). Overall, 72% of studies had high or unclear concerns regarding the risk of bias. DISCUSSION: This systematic review is the first to examine the use of ML and explainable artificial intelligence (XAI) methods for comorbidity prediction. The chosen studies focused on a limited scope of comorbidities ranging from 1 to 34 (mean = 6), and no novel comorbidities were found due to limited phenotypic and genetic data. The lack of standard evaluation for XAI hinders fair comparisons. CONCLUSION: A broad range of ML methods has been used to predict the comorbidities of various disorders. With further development of explainable ML capacity in the field of comorbidity prediction, there is a significant possibility of identifying unmet health needs by highlighting comorbidities in patient groups that were not previously recognised to be at risk for particular comorbidities.

A Low Concentration of Citreoviridin Prevents Both Intracellular Calcium Deposition in Vascular Smooth Muscle Cell and Osteoclast Activation In Vitro.

Vascular calcification (VC) and osteoporosis are age-related diseases and significant risk factors for the mortality of elderly. VC and osteoporosis may share common risk factors such as renin-angiotensin system (RAS)-related hypertension. In fact, inhibitors of RAS pathway, such as angiotensin type 1 receptor blockers (ARBs), improved both vascular calcification and hip fracture in elderly. However, a sex-dependent discrepancy in the responsiveness to ARB treatment in hip fracture was observed, possibly due to the estrogen deficiency in older women, suggesting that blocking the angiotensin signaling pathway may not be effective to suppress bone resorption, especially if an individual has underlying osteoclast activating conditions such as estrogen deficiency. Therefore, it has its own significance to find alternative modality for inhibiting both vascular calcification and osteoporosis by directly targeting osteoclast activation to circumvent the shortcoming of ARBs in preventing bone resorption in estrogen deficient individuals. In the present study, a natural compound library was screened to find chemical agents that are effective in preventing both calcium deposition in vascular smooth muscle cells (vSMCs) and activation of osteoclast using experimental methods such as Alizarin red staining and Tartrate-resistant acid phosphatase staining. According to our data, citreoviridin (CIT) has both an anti-VC effect and anti-osteoclastic effect in vSMCs and in Raw 264.7 cells, respectively, suggesting its potential as an effective therapeutic agent for both VC and osteoporosis.

Effect of Bevacizumab Treatment in Cerebral Radiation Necrosis : Investigation of Response Predictors in a Single-Center Experience.

OBJECTIVE: Bevacizumab is a feasible option for treating cerebral radiation necrosis (RN). We investigated the clinical outcome of RN after treatment with bevacizumab and factors related to the initial response and the sustained effect. METHODS: Clinical data of 45 patients treated for symptomatic RN between September 2019 and February 2021 were retrospectively collected. Bevacizumab (7.5 mg/kg) was administered at 3-week intervals with a maximum four-cycle schedule. Changes in the lesions magnetic resonance image (MRI) scans were examined for the response evaluation. The subgroup analysis was performed based on the initial response and the long-term maintenance of the effect. RESULTS: Of the 45 patients, 36 patients (80.0%) showed an initial response, and eight patients (17.8%) showed delayed worsening of the corresponding lesion. The non-responders showed a significantly higher incidence of diffusion restriction on MRI than the responders (100.0% vs. 25.0%, p<0.001). The delayed worsening group showed a significantly higher proportion of glioma pathology than the maintenance group (87.5% vs. 28.6%, p=0.005). Cumulative survival rates with sustained effect were significantly higher in the groups with non-glioma pathology (p=0.019) and the absence of diffusion restriction (p<0.001). Pathology of glioma and diffusion restriction in MRI were the independent risk factors for non-response or delayed worsening after initial response. CONCLUSION: The initial response of RN to bevacizumab was favorable, with improvement in four-fifths of the patients. However, a certain proportion of patients showed non-responsiveness or delayed exacerbations. Bevacizumab may be more effective in treating RN in patients with non-glioma pathology and without diffusion restriction in the MRI.

Clinical Outcomes of Moderately Hypofractionated Concurrent Chemoradiotherapy for Newly Diagnosed Glioblastoma.

PURPOSE: Hypofractionated radiotherapy (HypoRT) has recently been implemented in patients with glioblastoma (GBM) receiving concurrent temozolomide. Lymphopenia during treatment (LDT) is considered an important prognostic factor of clinical outcomes for GBM. We aimed to investigate the outcomes of HypoRT. MATERIALS AND METHODS: Among 223 patients with GBM, 145 and 78 were treated with conventionally fractionated RT (ConvRT, 60 Gy in 30 fractions) and HypoRT (58.5 Gy in 25 fractions), respectively. To balance characteristics between the two groups, propensity score matching (PSM) was performed. RESULTS: Patients in the HypoRT group were older and had smaller tumors than those in the ConvRT group (p<0.05). Furthermore, dose distributions to the brain were significantly lower in HypoRT than in ConvRT (p<0.001). Changes in absolute lymphocyte counts (ALC) during treatment were significantly lower after HypoRT than after ConvRT (p=0.018). With a median follow-up of 16.9 months, HypoRT showed comparable progression-free survival (9.9 months vs. 10.5 months) and overall survival (27.2 months vs. 26.6 months) to ConvRT (all p>0.05). Multivariable analysis before PSM revealed that ≥grade 2 LDT at 6 months was associated with inferior outcomes. Subsequent analysis demonstrated that HypoRT significantly reduced the rate of ≥grade 2 LDT at 6 months post-RT before and after PSM. CONCLUSION: HypoRT with 58.5 Gy in 25 fractions could provide comparable oncologic outcomes and significantly reduce the ALC changes. In addition, HypoRT decreased the LDT. Further investigation should be warranted to suggest the significance of reduced LDT through HypoRT affecting survival outcomes.

Impact of Postural Changes on Sinonasal Pressure After Endoscopic Endonasal Surgery.

BACKGROUND: Postoperative management following endoscopic endonasal surgery (EES) is important to prevent cerebrospinal fluid leak and preserve the integrity of the nasoseptal flap. No consensus regarding an optimal posture in the postoperative period has been established. We hypothesized that sinonasal pressure (SNP) can represent intracranial pressure affecting the sellar floor in the absence of the sellar bone after surgery. This study provides evidence for the effect of postural changes and recommends optimal posture to reduce SNP following EES. METHODS: The authors conducted a retrospective analysis of 50 patients who underwent reconstruction for skull base defects with nasoseptal flap after EES for resection of suprasellar tumor between March 2020 and August 2020. The Spiegelberg intracranial pressure probe was placed through the nostril over the nasoseptal flap. SNPs were measured in Fowler' (45° tilt) and supine positions, respectively, daily for the first 3 days immediately after EES. RESULTS: For the first 3 days after surgery, the mean SNP in Fowler' position (24.82 mmHg; standard deviation, 12.23 mmHg) was lower than that in the supine position (28.42 mmHg; standard deviation, 12.33 mmHg) (P < 0.01). There were no significant differences in mean SNP for age, sex, tumor size, presence of hydrocephalus, and body mass index. CONCLUSIONS: There was a significant correlation between Fowler' position and a decrease in SNP measurements. Placing a patient in Fowler' position after surgery can decrease the SNP. We recommend that patients should be placed in a Fowler' position as an optimal position after surgery.

High Mean Platelet Volume Is Associated with Cerebral White Matter Hyperintensities in Non-Stroke Individuals.

PURPOSE: The mean platelet volume (MPV) is regarded as a marker for thrombosis, atherosclerosis, and inflammation in various vascular diseases. However, it still remains unclear whether plasma MPV is associated with cerebral white matter hyperintensities (WMH) and cerebral microvascular pathology in the elderly population. MATERIALS AND METHODS: We examined whether MPV level is associated with the presence of cerebral WMH on brain magnetic resonance imaging from 870 non-stroke outpatient subjects. The subjects were divided into three groups according to the consecutive level of MPV (low T1, middle T2, and high T3 MPV tertile groups). To determine the association of MPV levels with the WMH, logistic regression and receiver operating characteristic curve analyses were conducted. RESULTS: Subjects with higher MPV level were older and more likely to have hypertension, diabetes mellitus, and low renal function. Cerebral WMH were more prevalent in subjects with higher MPV level. After adjusting for confounding factors, moderate to severe cerebral WMH were significantly associated with high MPV tertile level. This association remained significant after adjusting for other cerebral vascular pathologies. T2 [odds ratio (OR): 1.49, 95% confidence interval (CI): 1.03-2.15] and T3 MPV tertile groups (OR: 1.51, 95%CI: 1.04-2.20) had more cerebral WMH lesions compared to T1 MPV tertile group. In addition, the subjects with higher Fazekas scores showed higher MPV level (p=0.020). CONCLUSION: We found that high MPV level is independently associated with cerebral WMH. This result suggests that platelet activation plays a role in the development of cerebral WMH.

Treatment Outcomes after Dose-Escalated Moderately Hypofractionated Radiotherapy for Frail Patients with High-Grade Glioma.

For high-grade glioma (HGG) patients with old age or poor performance status, hypofractionated radiotherapy (hypoRT) in 10-15 fractions is recommended. Also, limited data exist on the impact of salvage treatment after progression in frail patients. We retrospectively analyzed the outcomes of dose-escalated hypoRT in 40 frail HGG patients who were treated with hypoRT between 2013 and 2021. With a median biologically effective dose of 71.7 Gy, a total dose of 56 Gy in 20 fractions was the most frequently used regimen (53.7%). The median age and Karnofsky Performance Status of patients were 74 years and 70, respectively. Most patients (n = 31, 77.5%) were diagnosed with glioblastoma, IDH-wildtype, CNS WHO grade 4. Only 10 (25.0%) patients underwent surgical resection, and 28 (70.0%) patients received concurrent temozolomide during hypoRT. With a median follow-up of 9.7 months, the median overall survival (OS) was 12.2 months. Of the 30 (75.0%) patients with disease progression, only 12 patients received salvage treatment. The OS after progression differed significantly depending on salvage treatment (median OS, 9.6 vs. 4.6 months, p = 0.032). Dose-escalated hypoRT in 20 fractions produced survival outcomes outperforming historical data for frail patients.

Clinical outcomes of patients with multiple courses of radiosurgery for brain metastases from non-small cell lung cancer.

We investigated the long-term clinical outcomes of patients who underwent multiple courses (≥ 5) of gamma knife radiosurgery (GKRS) due to recurrent brain metastases (BM) from non-small cell lung cancer (NSCLC). Between December 2001 and July 2019, consecutive 2571 patients underwent GKRS for BM from NSCLC. Clinical and radiological outcomes were investigated in 76 patients who underwent GKRS ≥ 5 times. The median follow-up period after the diagnosis of NSCLC was 54.6 months (range 14.5-159.1 months). The median number of GKRS procedures per patient was six (range 5-15). Actuarial post-GKRS survival rates at 1, 2, 3, 4, and 5 years following initial GKRS were 88.1%, 79.5%, 65.3%, 51.4%, and 37.3%, respectively. No significant difference in overall survival was observed between patients (n = 22) with whole-brain radiotherapy (WBRT) and patients (n = 54) without WBRT (p = 0.076). The incidence of radiation-induced leukoencephalopathy was 64% and 18% in patients with and without WBRT, respectively (p < 0.0001). Multiple courses of SRS are a tolerable and effective treatment option for recurrent BM from NSCLC. Repeat SRS may be an alternative treatment option to avoid or delay WBRT.