Dose-dependent incidence of agranulocytosis in patients treated with methimazole and propylthiouracil.

Agranulocytosis is a serious adverse effect of methimazole (MMI) and propylthiouracil (PTU), and although there have been reports suggesting a dose-dependent incidence in relation to both drugs, the evidence has not been conclusive. The objective of our study was to determine whether the incidences of agranulocytosis induced by MMI and PTU exhibit dose-dependency. The subjects were 27,784 patients with untreated Graves' disease, 22,993 of whom were on an antithyroid drug treatment regimen for more than 90 days. Within this subset, 18,259 patients had been treated with MMI, and 4,734 had been treated with PTU. The incidence of agranulocytosis according to dose in the MMI group was 0.13% at 10 mg/day, 0.20% at 15 mg/day, 0.32% at 20 mg/day, and 0.47% at 30 mg/day, revealing a significant dose-dependent increase. In the PTU group, there were 0 cases of agranulocytosis at doses of 125 mg/day and below, 0.33% at 150 mg/day, 0.31% at 200 mg/day, and 0.81% at 300 mg/day, also revealing a significant dose-dependent increase. The incidence of agranulocytosis at MMI 15 mg and PTU 300 mg, i.e., at the same potency in terms of hormone synthesis inhibition, was 0.20% and 0.81%, respectively, and significantly higher in the PTU group. Our findings confirm a dose-dependent increase in the incidence of agranulocytosis with both drugs, but that at comparable thyroid hormone synthesis inhibitory doses PTU has a considerably higher propensity to induce agranulocytosis than MMI does.

An Evaluation of the Efficacy of Machine Learning in Predicting Thyrotoxicosis and Hypothyroidism: A Comparative Assessment of Biochemical Test Parameters Used in Different Health Checkups.

Objective This study assessed the efficacy of machine learning in predicting thyrotoxicosis and hypothyroidism [thyroid-stimulating hormone (TSH) >10.0 mIU/L] by leveraging age and sex as variables and integrating biochemical test parameters used by the Japan Society of Health Evaluation and Promotion (JHEP) and the Japan Society of Ningen Dock (JND). Subjects and Methods Our study included 20,653 untreated patients with Graves' disease, 3,435 untreated patients with painless thyroiditis, 4,266 healthy individuals, and 18,937 untreated patients with Hashimoto's thyroiditis. Machine learning was conducted using Prediction One on three distinct datasets: the Ito dataset (age, sex, and 30 blood tests and biochemical test data), the JHEP dataset (age, sex, and TP, T-Bil, AST, ALT, γGTP, ALP, CRE, UA, and T-Cho test data), and the JND dataset (age, sex, and AST, ALT, γGTP, CRE, and UA test data). Results The results for distinguishing thyrotoxicosis patients from the healthy control group showed that the JHEP dataset yielded substantial discriminative capacity with an area under the curve (AUC) of 0.966, sensitivity of 92.2%, specificity of 89.1%, and accuracy of 91.7%. The JND dataset displayed similar robustness, with an AUC of 0.948, sensitivity of 92.0%, specificity of 81.3%, and accuracy of 90.4%. Differentiating hypothyroid patients from the healthy control group yielded similarly robust performances, with the JHEP dataset yielding AUC, sensitivity, specificity, and accuracy values of 0.864, 84.2%, 72.1%, and 77.4%, respectively, and the JND dataset yielding values of 0.840, 83.2%, 67.2%, and 74.3%, respectively. Conclusions Machine learning is a potent screening tool for thyrotoxicosis and hypothyroidism.

Effects of hybrid closed-loop system on glycemic control and psychological aspects in persons with type 1 diabetes treated with sensor-augmented pump: A prospective single-center observational study.

AIMS/INTRODUCTION: This study evaluated the effects of the Medtronic MiniMed 770G hybrid closed-loop system on glycemic control and psychological aspects in persons with type 1 diabetes mellitus. MATERIALS AND METHODS: This 3-month prospective observational study included 22 participants with type 1 diabetes mellitus who used the Medtronic MiniMed 640G predictive low-glucose suspend system and were switched to the 770G system. Time in the range of 70-180 mg/dL and glycated hemoglobin levels were evaluated; satisfaction, emotional distress and quality of life were assessed using self-reported questionnaires, including the Diabetes Treatment Satisfaction Questionnaire Status, Problem Area in Diabetes and Diabetes Therapy-Related Quality of Life. RESULTS: Time in the range of 70-180 mg/dL increased (63.5 ± 13.4 to 73.0 ± 10.9% [mean ± standard deviation], P = 0.0010), and time above the range of 181-250 mg/dL decreased (26.9 ± 8.9 to 19.6 ± 7.1%, P < 0.0005). Glycated hemoglobin levels decreased (7.7 ± 1.0 to 7.2 ± 0.8%, P = 0.0021). The percentage of participants with time below the range of 54-69 mg/dL <4% of readings increased from 91% to 100% (P < 0.0005). No significant changes were detected in the satisfaction, emotional distress and quality of life levels, but increased sensor calibration might be related to worsened emotional distress and quality of life. CONCLUSIONS: The hybrid closed-loop system decreased hyperglycemia and minimized hypoglycemia, but did not improve psychological aspects compared with the predictive low-glucose suspend system, probably because sensor calibration was increased.

Association of continuous positive airway pressure therapy on cardiac hypertrophy in patients with sleep apnea comorbid with type 2 diabetes mellitus.

Previous reports indicated the therapeutic effect of chronic continuous positive airway pressure (CPAP) therapy on cardiac hypertrophy due to sleep apnea syndrome. However, little is known for cases involving diabetic complications. This retrospective observational study examined the effects of CPAP therapy on left ventricular hypertrophy (LVH) in patients with obstructive sleep apnea syndrome (OSAS) and type 2 diabetes mellitus (T2DM). For all cases, the observation period was 3 years from the time when the patient was introduced to CPAP therapy. Overall, 123 patients were divided into a good CPAP group (CPAP ≥4 h/day, n = 63) and non-adherence group (CPAP <4 h/day, n = 60). The mean CPAP usage times were 5.58 ± 1.23 and 1.03 ± 1.17 h/day in the good CPAP and non-adherence groups, respectively. Regression tendencies of the thickness of the left ventricular posterior (-0.30 ± 1.19 mm) and interventricular septal walls (-0.48 ± 1.22 mm) were observed in the good CPAP group. Hypertrophic tendencies of the left ventricular posterior wall (+0.59 ± 1.44 mm) and interventricular septal wall thickness (+0.59 ± 1.43) were observed in the non-adherence group. Left ventricular posterior wall thickness (coefficient: -0.254, p = 0.0376) and interventricular septal wall thickness (coefficient: -0.426, p = 0.0006) were more likely to be greater in the non-adherence group than in the good CPAP group. Patients in the non-adherence group with an apnea hypopnea index ≥30 had increased left ventricular posterior wall thickness (coefficient: -0.263, p = 0.0673) and interventricular septal wall thickness (coefficient: -0.450, p = 0.0011). In conclusion, appropriate CPAP therapy is an effective treatment for LVH in patients with T2DM and OSAS, especially for severe cases.

The METRO study: a retrospective analysis of the efficacy of metformin for type 2 diabetes in Japan.

Metformin monotherapy as first-line treatment for patients with type 2 diabetes (T2D) has been shown to effectively improve blood glucose levels and motivation to undergo treatment and prevent complications. However, no studies have reported its effect when combined with other drugs or compared the effect based on administration time. This study aimed to investigate the effect of metformin administration in Japanese patients with T2D, examine how the introduction line impacts the effect of metformin, and examine the characteristics of patients demonstrating improved blood glucose levels. Data on characteristics of patients who were newly prescribed metformin with no shifting of hypoglycemic agents in the subsequent 24-week observation period, and their age [mean, 56.8 years], body mass index [mean, 27.5 kg/m2], glycated hemoglobin [HbA1c] [mean, 8.1%], and duration of diabetes [mean, 3.0 years] were obtained from the medical records of 201 patients. The changes in HbA1c by introduction line after 24 weeks were -1.59%, -0.91%, -0.89%, and -0.65% in the first, second, third, and fourth induction lines, respectively; earlier introduction more significantly improved blood glucose. The factors significantly associated with HbA1c changes were early introduction, high baseline HbA1c, high estimated glomerular filtration rate, decreased insulin secretion, short estimated duration of diabetes, and increased metformin dose. Furthermore, factors contributing to the largest HbA1c improvement by metformin were high baseline HbA1c and early administration. Metformin is expected to lower blood glucose levels in Japanese patients with T2D, even in those with decreased insulin secretion, due to its early introduction as a first-line drug.

Diagnostic accuracy of home sleep apnea testing using peripheral arterial tonometry for sleep apnea: A systematic review and meta-analysis.

This study aimed to evaluate the diagnostic accuracy of home sleep apnea testing using peripheral arterial tonometry for sleep apnea as an alternative to polysomnography. We conducted a systematic review and meta-analysis of observational studies, randomized controlled trials, and diagnostic case-control studies examining the diagnostic accuracy of peripheral arterial tonometry by searching the CENTRAL, MEDLINE, EMBASE, ICTRP and ClinicalTrials.gov databases on 5 October 2021. We assessed the risk of bias of the included studies using the Quality Assessment of Diagnostic Accuracy Studies-2 tool. A bivariate random-effects model was generated to derive the summary point estimates of sensitivity and specificity with 95% confidence intervals at different apnea-hypopnea index cutoffs. This meta-analysis included 13 studies (1227 participants, median prevalence of sleep apnea with apnea-hypopnea index ≥ 5 events per hr: 85%). The risk of bias in the included studies was low to moderate. The pooled sensitivity and specificity estimates were 96% (95% confidence interval: 93%-97%) and 44% (95% confidence interval: 32%-56%) at apnea-hypopnea index ≥ 5 events per hr, 88% (85%-91%) and 74% (63%-83%) at apnea-hypopnea index ≧ 15 events per hr, and 80% (66%-89%) and 90% (83%-95%) at apnea-hypopnea index ≧ 30 events per hr, respectively. Peripheral arterial tonometry resulted in a significant number of false negatives and false positives at any apnea-hypopnea index cutoff when applied to the median prevalence setting of the included studies. The inadequate sensitivity and specificity of peripheral arterial tonometry render it an unsuitable alternative to polysomnography for detecting sleep apnea for apnea-hypopnea index ≧ 5, 15 and 30 events per hr.

A comparative study of unpasteurized and pasteurized frozen whole hen eggs using size-exclusion chromatography and small-angle X-ray scattering.

Hen eggs are rich in proteins and are an important source of protein for humans. Pasteurized frozen whole hen eggs are widely used in cooking and confectionery and can be stored for long periods. However, processed eggs differ from raw eggs in properties such as viscosity, foaming ability, and thermal aggregation. To develop pasteurized frozen whole egg products with properties similar to those of unpasteurized whole eggs, it is necessary to establish a method that can differentiate between the two egg types with respect to the structures of their proteins. In this study, size-exclusion chromatography (SEC) and SEC coupled with small-angle X-ray scattering (SEC-SAXS) were successfully used to differentiate between the proteins in unpasteurized and pasteurized frozen whole eggs. We found that proteins in the plasma fraction of egg yolk, especially apovitellenins I and II, formed large aggregates in the pasteurized eggs, indicating that their structures are sensitive to temperature changes during pasteurization, freezing, and thawing. The results suggest that SEC and SEC-SAXS can be used to differentiate between unpasteurized and pasteurized frozen whole eggs. Additionally, they may be useful in determining molecular sizes and shapes of multiple components in various complex biological systems such as whole eggs.

Comparing the course and delivery outcomes of Japanese twin pregnancies with and without gestational diabetes mellitus: a single-center retrospective analysis.

Singleton pregnant women with gestational diabetes mellitus (GDM) are at an increased risk of adverse maternal and neonatal outcomes. Multiple pregnancies are associated with increased risks of perinatal complications; however, the impact of GDM on maternal and neonatal outcomes in multiple pregnancies is unknown, and there are currently few reports on GDM status in twin pregnancies. This study aimed to compare the background and perinatal outcomes between Japanese twin pregnancies with and without GDM at a perinatal center in Japan. Additionally, the clinical course of GDM was investigated. In this retrospective cohort study, women with twin pregnancies underwent GDM screening at Yokohama City University Medical Center from January 2011 to December 2016. Overall, 307 twin pregnancies were divided into GDM (47 cases, 15.3%) and non-GDM (260 cases, 84.7%) groups. GDM-associated pregnancy complications, GDM status, and pregnancy outcomes were ascertained. Women with GDM were older and had a higher pre-pregnancy body mass index than those without GDM. Glycemic control was good in all patients, and there was no difference in delivery outcomes between the two groups. Gestational weight gain was lower in pregnant women with GDM (+8.0 kg) than in those without GDM (+11.8 kg), suggesting the impact of strict nutritional guidance on twin pregnancies with GDM. In conclusion, twin pregnancies with GDM did not have different delivery outcomes compared to those without GDM. To manage twin pregnancies with GDM, this study suggests that it is important to monitor patients' weight and blood glucose levels.

Efficacy of education on injection technique for patients diagnosed with diabetes with lipohypertrophy: systematic review and meta-analysis.

OBJECTIVES: This study aimed to investigate the efficacy of providing education on injection technique to patients with diabetes with lipohypertrophy (LH). DESIGN: We conducted a systematic review and meta-analysis. METHODS: We included patients with diabetes who use insulin and have LH, and excluded patients without LH. We performed a literature search on CENTRAL, MEDLINE, EMBASE, ICTRP and ClinicalTrials.gov in November 2021 for randomised controlled trials (RCTs). We used the revised Cochrane Risk of Bias 2 tool to evaluate the risk of bias in each outcome in each study. We then pooled the data using a random-effects model and evaluated the certainty of evidence using the Grading of Recommendations, Assessment, Development and Evaluation approach. OUTCOME MEASURES: The primary endpoints were change in total daily dose (TDD) of insulin, change in HbA1c levels and prevalence of hypoglycaemia. RESULTS: We screened 580 records and included three RCTs (637 participants) in the meta-analysis. Education on injection technique may slightly increase the change of TDD of insulin (three studies, 637 participants: mean difference (MD) -6.26; 95% CI -9.42 to -3.10; p<0.001; I2=38%; low certainty of evidence) and may have little to no effect on change in HbA1c but the evidence is very uncertain compared with that in the control group (three studies, 637 participants: MD -0.59; 95% CI -1.71 to 0.54; p=0.31; I2=98%; very low certainty of evidence). Providing education about injection technique may have little to no effect on the prevalence of hypoglycaemia (three studies, 637 participants: risk ratio 0.44; 95% CI 0.06 to 3.13; p=0.41; I2=90%; very low certainty of evidence). CONCLUSIONS: The present meta-analysis suggests that injection technique education may result in a slight reduction in the TDD of insulin. However, the effect of education on HbA1c, hypoglycaemia and cured LH is uncertain. PROTOCOL REGISTRATION: DOI: dx.doi.org/10.17504/protocols.io.btiinkce.

Clinicopathological risk factors for a poor prognosis of primary central nervous system lymphoma in elderly patients in the Tohoku and Niigata area: a multicenter, retrospective, cohort study of the Tohoku Brain Tumor Study Group.

Clinicopathological risk factors for a poor prognosis were investigated in elderly patients with malignant lymphoma of the central nervous system. A total of 82 pathologically confirmed, CD20-positive, diffuse large B-cell lymphoma patients aged 71 years or older who underwent therapeutic intervention in the Tohoku and Niigata area in Japan were retrospectively reviewed. A univariate analysis was performed by the log-rank test using the Kaplan-Meier method. A Cox proportional hazards model was used for multivariate analysis of risk factors. Of the 82 patients, 39 were male and 43 were female, and their median age at onset was 75 years. At the end of the study, there were 34 relapse-free patients (41.5%), 48 relapse cases (58.5%), median progression-free survival was 18 months, and median overall survival (OS) was 26 months; there were 41 deaths and 41 survivors. Multivariate analysis of median OS showed that Karnofsky Performance Status less than 60% 3 months after treatment (p = 0.022, hazard ratio (HR) = 2.591) was the clinical risk factor, and double expressor lymphoma (p = 0.004, HR = 3.163), expression of programmed death-ligand 1 in tumor infiltrating lymphocytes or tumor-associated macrophages (p < 0.001, HR = 5.455), and Epstein-Barr virus infection (p = 0.031, HR = 5.304) were the pathological risk factors.

A cross-sectional study of the relationship between quality of life and sleep quality in Japanese patients with type 1 diabetes mellitus.

This study aimed to reveal the relationship between quality of life (QOL) and sleep quality in patients with type 1 diabetes mellitus (T1DM). Overall, 202 patients with T1DM were registered in our study, and 192 were eligible for analysis. Baseline characteristics and laboratory values were determined. Patients completed the Japanese versions of the Pittsburgh Sleep Quality Index (PSQI) and Diabetes Therapy-Related QOL (DTR-QOL) questionnaires. We investigated the relationship between the global PSQI and DTR-QOL total scores by using linear regression analysis. In univariate regression analysis, DTR-QOL total scores were associated with body mass index, alcohol consumption, hypertension, hemoglobin A1c (HbA1c), and global PSQI score (all p-value <0.05) but not with sleep duration. When the association between PSQI subscales and DTR-QOL total scores was examined, DTR-QOL total scores were significantly related to subjective sleep quality and daytime dysfunction. In a multivariate regression analysis, the global PSQI score was negatively related to DTR-QOL total scores. Patients with an HbA1c concentration ≥8.0% had significantly lower DTR-QOL total scores. We revealed a relationship between QOL and sleep quality in T1DM patients and showed that the relationship between QOL and PSQI subscales in T1DM patients may be different from that in patients with type 2 diabetes mellitus. Assessing and managing sleep quality may be necessary for patients with diabetes to improve QOL.

The Real-World status and risk factors for a poor prognosis in elderly patients with primary central nervous system malignant lymphomas: a multicenter, retrospective cohort study of the Tohoku Brain Tumor Study Group.

BACKGROUND: Elderly patients with primary central nervous system malignant lymphoma (EL-PCNSL) may not be given sufficient treatment due to their poor pre-treatment Karnofsky Performance Status (KPS) and comorbidities. Therefore, a retrospective, cohort study was performed to evaluate risk factors associated with a poor prognosis of EL-PCNSL in the Tohoku Brain Tumor Study Group. METHODS: Patients aged ≥ 71 years with PCNSL were enrolled from eight centers. Univariate analysis was performed with the log-rank test. A Cox proportional hazards model was used for multivariate analysis. RESULTS: Three of the total 142 cases received best supportive care (BSC). Treatment was given to 30 cases without a pathological diagnosis, 3 cases with cerebrospinal fluid (CSF) cytology, and 100 cases with a pathological diagnosis. After confirmation of no differences in progression-free survival (PFS) and overall survival (OS) between the group treated without pathology and the groups diagnosed by pathology or CSF cytology and between median age ≥ 76 years and < 76 years, a total of 133 patients were studied. The median pre-treatment KPS was 50%. Median PFS and median OS were 16 and 24 months, respectively. Risk factors associated with poor prognosis on Cox proportional hazards model analysis were pre-treatment cardiovascular disease and central nervous system disease comorbidities, post-treatment pneumonia and other infections, and the absence of radiotherapy or chemotherapy. CONCLUSIONS: Pre-treatment comorbidities and post-treatment complications would affect the prognosis. Radiation and chemotherapy were found to be effective, but no conclusions could be drawn regarding the appropriate content of chemotherapy and whether additional radiotherapy should be used.

Intraoperative transcranial facial motor evoked potential monitoring in surgery of cerebellopontine angle tumors predicts early and late postoperative facial nerve function.

OBJECTIVE: We propose a novel method that predicts facial nerve function (FNF) calculated from the drop and recovery of facial motor evoked potential (FMEP) amplitude ratio during the surgery of cerebellopontine angle tumors. METHODS: We enrolled 73 patients with cerebellopontine angle tumor, and used a biphasic, constant current, and suprathreshold stimulation (BCS) protocol to record FMEP of the orbicularis oris. We measured the intraoperative minimum-to-baseline amplitude ratio (MBR), the final-to-baseline amplitude ratio (FBR), and the recovery value (RV). RV was measured by subtracting MBR from FBR. Using those values, we evaluated FNF both at early postoperative (EP) and late postoperative (LP) periods. RESULTS: We successfully obtained 62 FMEP readings. Facial palsies occurred in 22 patients during the EP period, and 14 patients recovered during the LP period. Both MBR and FBR showed a significant correlation with FNF in the EP period. RV showed a good predictive power of FNF recovery during the LP period for the first time. CONCLUSIONS: RV is a new and useful predictor of FNF recovery. MBR can be an intraoperative predictor of FNF in the EP period. SIGNIFICANCE: FNF outcome in the early and late postoperative periods can be predicted by FMEP.

Molecular Features and Prognostic Factors of Pleomorphic Xanthoastrocytoma: A Collaborative Investigation of the Tohoku Brain Tumor Study Group.

Pleomorphic xanthoastrocytoma (PXA) is a rare glial tumor, however, its histological differentiation from high-grade gliomas is often difficult. Molecular characteristics may contribute to a better diagnostic discrimination. Prognostic factors of PXA are also important but few relevant reports have been published. This study investigated the molecular features and prognostic factors of PXAs. Seven university hospitals participated in this study by providing retrospective clinical data and tumor samples of PXA cases between 1993 and 2014. Tumor samples were analyzed for immunohistochemical (IHC) neuronal and glial markers along with Ki67. The status of the BRAF and TERT promoter (TERTp) mutation was also evaluated using the same samples, followed by feature extraction of PXA and survival analyses. In all, 19 primary cases (17 PXA and 2 anaplastic PXA) were included. IHC examination revealed the stable staining of nestin and the close association of synaptophysin to NFP. Of the PXA cases, 57% had the BRAF mutation and only 7% had the TERTp mutation. On univariate analysis, age (≥60 years), preoperative Karnofsky performance status (KPS) (≤80%), and marked peritumoral edema were significantly associated with progression-free survival (PFS). No independent factor was indicated by the multivariate analysis. In conclusion, PXA was characterized by positive nestin staining and a few TERTp mutations. The neuronal differential marker and BRAF status may help in diagnosis. Patient age, preoperative KPS, and marked perifocal edema were associated with PFS. The present study is limited because of small number of cases and its retrospective nature. Further clinical study is needed.

Impact of pH and protein hydrophobicity on norovirus inactivation by heat-denatured lysozyme.

Norovirus, the leading cause of non-bacterial food poisoning, is responsible for several outbreaks associated with bivalves and ready-to-eat food products worldwide. As norovirus is resistant to alcohol, which is commonly used in food manufacturing processes, sodium hypochlorite is used for its inactivation. However, sodium hypochlorite has two disadvantages: it cannot be added to foods, and its effect is significantly reduced in the presence of organic compounds. Thus, a novel disinfectant against norovirus is urgently required for food hygiene. Thermally denatured egg white lysozyme inactivates norovirus; however, the optimal inactivating conditions and the underlying mechanism are unclear. In the present study, the inactivating mechanism of heat-denatured lysozyme against norovirus was analyzed using murine norovirus strain 1 (MNV-1). We found that the inactivating effect was enhanced by adjusting the pH of the lysozyme solution before thermal denaturation to 6.5 or higher. The reaction of heat-denatured lysozyme and MNV-1 was irreversible, and norovirus was completely inactivated after exposure to heat-denatured lysozyme. Furthermore, it was found that lysozyme residues 5-39 contributed to the norovirus-inactivating effect. Notably, the hydrophobicity and positive charges in this region contributed to the norovirus-inactivating effect, as evidenced by the norovirus inactivation test using mutated residues 5-39. These findings are novel and highlight the possible application of heat-denatured lysozyme as a disinfectant against norovirus in a wide range of food processes.

Achievement of stable negative ion production with Cs-seeded for long pulse beam operation in the prototype of Cs-seeded negative ion source for JT-60SA.

Long pulse negative ion beams of 500 keV and 154 A/m2 for 118 s have been achieved for the first time, which exceeds the requirement of the JT-60SA negative ion source. In order to solve the issues of such long pulse beams, the fast cutoff system of the power supply aims to reduce the surge current and to extend the lifetime of filaments and the suppression method of excess cesium (Cs) accumulation on the plasma grid (PG) to achieve stable negative ion production. By developing the fast cutoff system using a field programmable gate array unit for the arc power supply, the cutoff time has been reduced to 1/10 that of the original system and the lifetime of the filament was extended by three times. In order to achieve stable negative ion production, incoming Cs on the PG surface has been reduced by keeping the chamber wall temperature below 40 °C. As a result, a stable beam current drift of <6% has been achieved for the 118 s duration.

Secondary brain tumors after cranial radiation therapy: A single-institution study.

AIM: To study the probability of developing secondary brain tumors after cranial radiotherapy.Background Patients treated with cranial radiotherapy are at risk for developing secondary brain tumors. PATIENTS AND METHODS: We planned an institutional survey for secondary brain tumors in survivors after cranial irradiation and reviewed the 30-year duration data. Event analysis and cumulative proportion curves were performed to generally estimate the cumulative proportion of developing secondary brain tumors, cavernoma and meningioma at different periods of time. RESULTS: Secondary brain tumors occurred in 21% of cases: 10% were cavernomas, 6% were meningiomas, 3% were skull osteomas, and 1% were anaplastic astrocytoma. The cumulative proportion of developing secondary brain tumor was 6% at 10 years and 20% at 20 years, while the cumulative proportion for developing cavernomas and meningiomas was 16% and 7% at 20 years, respectively. CONCLUSION: Our study shows that patients who received cranial irradiation were at risk of secondary brain tumors such as cavernomas and meningiomas. Thus, a meticulous follow-up of cancer survivors with history of cranial irradiation by an annual MRI scan is justifiable. This will help clinicians to detect secondary brain tumors early and make its management much easier.

Experimental investigation of the Cs behavior in the cesiated H- ion source during high power long beam operation.

The behavior of the Cesium (Cs) in Cs-seeded negative ion sources has been investigated experimentally under the beam accelerations of up to 0.5 MeV. The pulse length was extended to 100 s to catch the precise variations in the Cs D2 emission, discharge power, negative ion current, and temperatures in the ion source. The variations of the negative ions were estimated by the beam current and the heat loads in the accelerator. This experiment shows that the buildup of temperature in the chamber walls lead to the evaporation of deposited Cs to enter the plasma region and influenced H- ion production. The H- ion beams were stably sustained by reducing the temperature rise of the chamber wall below 50 °C. A stable long pulse beam could be achieved through the temperature control of the surfaces inside the source chamber walls.

Bevacizumab Therapy of Neurofibromatosis Type 2 Associated Vestibular Schwannoma in Japanese Patients.

We conducted a feasibility study to investigate the therapeutic effect of bevacizumab on vestibular schwannomas (VS) associated with neurofibromatosis type 2 (NF2) in a sample of Japanese patients. Ten NF2 patients were selected between 2013 and 2018: nine women and one man, with ages ranging from 12 to 45 years (mean: 29.4). Bevacizumab was administered intravenously in 5 mg/kg doses four times, with an inter-dose interval of 2 weeks. Seventeen tumors were followed for 3-72 months (mean: 39). A reduction from baseline tumor volume of at least 20% was considered a therapeutic radiologic response. Maximum reduction in tumor volume was identified in the 3rd month in 11 tumors, and in the 6th month in three tumors. Three tumors did not show any response to bevacizumab. A radiologic response was detected in seven tumors (41%). There was a significantly lower tumor volume mean in the 3rd month in comparison to the baseline for the entire sample. Tumors in patients aged 25 and above showed a significant reduction in volume in the 3rd month and significantly lower tumor-volume-to-baseline ratio than younger patients in both the 3rd and 6th months. The interaction between 'time' and 'age group' factors significantly affected the therapeutic outcome of bevacizumab on tumor volume. This study investigated the therapeutic effects of bevacizumab on NF2-associated vestibular schwannomas in Japanese patients. Bevacizumab appears to be a useful therapeutic choice in NF2 cases to control the growth of VS. Therefore, a randomised control trial to prove this assumption is necessary.