bluuebunny/crossref_metadata_2025 huggingface dataset:
10137- ML-3 HIGH-DOSE CHEMOTHERAPY AND AUTOLOGOUS STEM-CELL TRANSPLANTATION (HDC-ASCT) FOR THE PATIENTS WITH PRIMARY CENTRAL NERVOUS SYSTEM LYMPHOMA (PCNSL)
Authors: Miyakita Yasuji , Yanagisawa Shunsuke , Ohno Makoto , Takeda Wataru , Fukuda Takahiro , Narita Yoshitaka
Published: November 2024

High-dose chemotherapy and autologous stem-cell transplantation (HDC-ASCT) for the patient with primary central nervous system lymphoma (PCNSL) has been used as treatment at relapse or as consolidation therapy. We report on the efficacy, safety, and future issues of HDC-ASCT. Sixteen patients with PCNSL (12 males and 4 females) underwent HDC-ASCT, ranging in age from 45 to 66 years (median 60 years) and KPS from 60 to 100 (median 90) at the time of HDC-ASCT. HDC-ASCT was performed at the time of consolidation therapy (without radiation) in 11 patients, at first recurrence in 3 (including 1 without radiation), and at second recurrence in 2. The main medical care was provided by the Department of Neurosurgery and Neuro-Oncology (NSNO) from PCNSL diagnosis to just before transplantation, HDC-ASCT by the Department of Hematopoietic Stem Cell Transplantation (HSCT), and after discharge by the Department of NSNO. The conditioning regimen consisted of busulfan 3.2mg/kg/day for 4 days and thiotepa 5mg/kg/day for the 2 following days, followed by ASCT. The observation period after HDC-ASCT ranged from 4.1 to 63.5 months (median 16.1 months), and the hospitalization period for HDC-ASCT ranged from 23 to 42 days (median 33 days), with no serious complications. All patients have returned to society and there have been no deaths to date, but one patient died and one patient relapsed afterwards. HDC-ASCT in PCNSL is an important option to improve outcomes. Sixteen patients who underwent HDC-ASCT at our hospital had good outcomes with no serious side effects. Therefore, it is important to have sufficient cooperation and communication among the departments from the biopsy of tumor diagnosis to the post-transplantation period, and it is essential to be fully aware of the roles of each department in the treatment.
10206- ML-10 CLINICAL SIGNIFICANCE OF CEREBROSPINAL FLUID IL-6 AND IL-10 IN PATIENTS WITH CENTRAL NERVOUS SYSTEM MALIGNANT LYMPHOMA
Authors: Sasayama Takashi , Yamanishi Syunsuke , Nagashima Hiroaki , Ikeuchi Yusuke , Tanaka Kazuhiro , Nishihara Masamitsu
Published: November 2024

INTRODUCTION

In primary central nervous system lymphoma (PCNSL), various cytokines and chemokines are known to be elevated in cerebrospinal fluid (CSF). In this study, we investigated the relationship between CSF IL-10 and IL-6 concentrations and prognosis.

METHODS

The patients with PCNSL who underwent treatment with MTX from 2008 to 2024 were analyzed. IL-10, IL-6, b2-microglobulin (MG), and sIL-2 receptor (sIL-2R) were measured preoperatively. we analyzed the relationship between CSF concentration d each cytokines and overall survival (OS) or progression-free survival (PFS).

RESULTS

A total of 67 patients (38 males, 29 females) were included, with an average age of 66 years and an average KPS of 72. Thirty-six patients received MTX + RT therapy, and 31 patients received R-MPV therapy. CSF IL-10, IL-6, b2-MG, and sIL-2R levels were 505±2133pg/ml, 20.5±40.4pg/ml, 4059±:1730ug/l, and 377±621U/ml, respectively. When the cutoff value for IL-6 was set at 8pg/ml, the PFS was significantly longer in the high CSF IL-6 group than in the low CSF group (p=0.026). When the cutoff value for IL-10 was set at 80pg/ml, the high CSF IL-10 group tended to have a longer PFS than the low CSF group (p=0.06). Multivariate analysis of PFS revealed that CSF IL-6 (p=0.0003), CD10 expression (p=0.0078), and pretreatment KPS (p=0.026) were significant prognostic factors. Multivariate analysis of OS revealed that CSF IL-6 (p=0.015), CD10 expression (p=0.043), and treatment (p=0.046) were significant prognostic factors, with CSF IL-6 being a significant prognostic factor for both OS and PFS.

CONCLUSION

Patients with high CSF IL-6 concentrations had significantly longer survival times, but CSF IL-10 was not. IL-6 is a proinflammatory cytokine with diverse effects, and PCNSL with high IL-6 levels may be more responsive to treatment.
10286- ML-16 RMPV REMISSION INDUCTION/MAINTENANCE THERAPY FOR ELDERLY PATIENTS WITH CENTRAL NERVOUS SYSTEM LYMPHOMA
Authors: Ehara Takuro , Shirahata Mitsuaki , Suzuki Tomonari , Takayanagi Syunsaku , Mishima Kazuhiko
Published: November 2024

OBJECTIVE

To evaluate the outcomes of RMPV (rituximab, methotrexate, procarbazine, vincristine) remission induction and maintenance therapy without whole brain irradiation for elderly patients with CNS lymphoma.

METHODS

CNS lymphoma patients aged 65 years or older who started treatment at our institution between November 2016 and November 2023 were included. Eight cycles of RMPV therapy were given every 2-4 weeks as remission induction, and in patients who reached remission, RMPV therapy was continued every 8 weeks for 2 years as maintenance therapy. Drug doses were reduced according to the adverse events according to the protocol. The endpoints were overall survival (OS), progression-free survival (PFS), adverse events (AE), Karnofsky Performance Status (KPS), Mini-Mental State Examination (MMSE), Best response.

RESULTS

43 patients (38 primary CNS lymphoma, 5 secondary CNS lymphoma), median age 73 years (66-84), median PFS 19.5 months, median OS 51.2 months, median KPS before treatment 60 (40-80), median after remission 80 (40-100), MMSE averaged 18 (8-27) before treatment and 25 (13-30) after treatment, and the best response was complete response in 31 patients (72.1%). AEs requiring reduction or discontinuation of treatment were drug eruption in 6 patients, renal dysfunction in 4, peripheral neuropathy in 7, hemopenia in 7, depression in 1, gastrointestinal bleeding in 1, and severe infection in 3.
10066- MET-7 RISK FACTORS FOR THE EPILEPSY IN PATIENTS WITH BRAIN METASTASES
Authors: Sasaki Takahiro , Nakai Yasuo , Fukai Junya , Nakao Naoyuki
Published: November 2024

In accordance with the progress of cancer treatment, there is a need for long-term control of epilepsy that develops in metastatic brain tumors. In this study, we examined risk factors for the development of epilepsy in metastatic brain tumors. We retrospectively analyzed 200 patients with metastatic brain tumors treated between January 2010 and December 2023 for clinical information such as tumor site, imaging features, genetic mutations, and treatment details. Overall, median age was 67 years, 112 (56%) were male, and the major primary sites were non-small cell lung cancer (55%), breast cancer (12.5%), and small cell lung cancer (11.5%). Epilepsy occurred in 42 patients (21%). In univariate analysis, maximum tumor size, peritumoral edema, intratumoral hemorrhage, surgical treatment, and nonuse of molecularly targeted drugs were significantly associated with the development of epilepsy. Current guidelines do not recommend prophylactic administration of antiepileptic drugs for metastatic brain tumors. However, with the availability of antiepileptic drugs that have fewer side effects and fewer interactions with chemotherapy, prophylactic administration of antiepileptic drugs in high-risk groups for the development of epilepsy may warrant reconsideration.
10099- MET-10 A PROPENSITY SCORE-MATCHED ANALYSIS OF STEREOTACTIC RADIOTHERAPY FOR METASTATIC BRAIN TUMORS USING THE LEKSELL GAMMA KNIFE ICON MASK SYSTEM: A SINGLE-CENTER RETROSPECTIVE COMPARATIVE STUDY OF CASES MEETING AND NOT MEETING THE JLGK0901 CRITERIA
Authors: Oi Yuta , Kawabe Takuya , Ogawa Takahiro , Taniyama Ichita , Yamanaka Takumi , Takahashi Yoshinobu , Sato Manabu , Hashimoto Naoya
Published: November 2024

OBJECTIVE

Stereotactic radiosurgery (SRS) for metastatic brain tumors (METs) has previously been considered to be indicated only for cases with a few lesions with small sizes. Expansion of the indication of SRS for METs is mainly due to the JLGK0901 study. Furthermore, since introduction of the Leksell Gamma knife Icon, both single irradiation and fractionated irradiation has become possible using a mask fixation system. The purpose of this study was to evaluate our own institutional experience in order to reexamine the limitations on the number and volume of lesions established in the JLGK0901 study.

METHODS

The study period was 6.5 years from the start of operations using the Leksell Gamma Knife Icon at Rakusai Shimizu Hospital (2017/09-2024/02). A retrospective study was conducted in 1043 patients who had undergone initial treatment with Gamma Knife Icon and had at least one post-treatment follow-up report. A comparison was made between cases that did (Group A) and did not (Group B, extended indication) meet JLGK0901 criteria. Propensity score matching was used to establish matched cases. Neurological death was the primary endpoint. Functional outcomes and imaging changes were secondary endpoints.

RESULTS

Of 1043 cases, 673 were in Group A and 370 were in Group B. The median survival time after Gamma Knife Icon radiotherapy was shorter in Group B (19.7 vs. 10.6 months, p<0.01), but the incidence of neurological death did not differ significantly between the two groups (p=0.635). There were also no significant differences in the rates of poor local control (p=0.381) and new intracranial lesions (p=0.925), or in neurological deterioration (p=0.738) and severe radiation-induced adverse events (p=0.994).

CONCLUSIONS

The results support expansion of the indication for Leksell Gamma Knife Icon for METs from that in JLGK0901 based on the absence of an influence of the number of metastases and tumor volume on outcomes.
10183- MET-14 SALVAGE SURGERY FOR LOCAL PROGRESSION AFTER RADIATION THERAPY OF BRAIN METASTASES
Authors: Arita Hideyuki , Umehara Toru , Takano Koji , Okita Yoshiko , Kinoshita Manabu
Published: November 2024

Recent advancement in cancer treatments have prolonged survival after the onset of brain metastases (BM), and this trend increases the risk of local progression (LP) after radiotherapy (RT)of BM. Salvage options include surgical resection, re-irradiation and medical therapies, but there is no standard management for this clinical setting. This study aimed to evaluate the outcome of salvage surgery. We performed surgical resection for intracranial metastases in 221 cases in a single institution between Apr 2014 and Mar 2024. Of those, the data of the cases underwent initial surgery after irradiation for BM were extracted. After excluding duplicated cases and those underwent surgery within one month after irradiation, we finally analyzed 49 cases. Overall survival (OS) and local progression free survival (LPFS) were evaluated by Kaplan Meier method. All but two cases had a history of stereotactic radiosurgery/radiotherapy for BM. Histopathological diagnosis of surgical specimens was tumor recurrence in 33 cases and radiation necrosis (RN) in 16 cases. RN cases showed longer duration between radiation and LP, when comparing with recurrent cases (median 42.3. vs. 9.3 months). OS was longer in RN cases than in tumor recurrent cases (median 68.5 vs. 26.9 months). In the recurrent cases, preoperative poor KPS (under 70), active state of extracranial lesions and RPA class were associated with shorter OS. Extent of resection, postoperative chemotherapy and local irradiation did not have significant impact on OS. Twenty cases experienced local recurrence after salvage surgery, and LPFS was 7.0 months. Any of extent of removal, postoperative chemotherapy and RT were not associated with LPFS. Relative long survival after salvage surgery for local failure of BM after irradiation was observed. Salvage surgery should be considered especially in patients with good extracranial control and performance status.
10093- MNG-4 PREDICTION MODEL FOR TUMOR GROWTH BY QUANTITATIVE IMAGE ANALYSIS FOR INCIDENTALLY DISCOVERED MENINGIOMAS
Authors: Oi Yuta , Taniyama Ichita , Minamoto Haruki , Fukuzawa Masayuki , Ogawa Takahiro , Yamanaka Takumi , Takahashi Yoshinobu , Hashimoto Naoya
Published: November 2024

PURPOSE

Most factors identified in prior studies on meningioma enlargement are qualitative, with limited quantitative evaluation. Predicting future tumor growth from initial imaging of incidentally discovered meningiomas could inform treatment decisions. This study quantitatively evaluates imaging data at diagnosis to identify characteristics associated with tumor enlargement.

METHODS

We compared MRI T2 features from the initial imaging of 10 patients in a clearly enlarged group with 10 in a non-enlarged group. Using 3D Slicer and Slicer Radiomics plug-ins, we created a program to set regions of interest (ROIs) in the tumor and calculate various features. Additional ROIs were placed in the outer tumor edge, brain, and white matter contralateral to the tumor. Inter-ROI ratios of features were calculated and compared using PyRadiomics software. We analyzed 107 features across seven classifications: one-dimensional statistics, shape features, Gray Level Co-occurrence Matrix, Gray Level Run Length Matrix, Gray Level Size Zone Matrix, Gray Level Dependence Matrix, and Neighbouring Gray Tone Difference Matrix. A t-test was conducted to identify significant predictors.

RESULTS

Twenty-four features showed significant differences (p<0.05), including 10 one-dimensional statistics, 1 shape feature, 5 Gray Level Co-occurrence Matrix, 6 Gray Level Run Length Matrix, 1 Gray Level Size Zone Matrix, and 1 Gray Level Dependence Matrix.

CONCLUSIONS

We identified potential quantitative predictors of incidentally discovered meningioma growth. Future analysis with a larger sample size will refine these predictors and support the development of a predictive formula and corresponding program.
10085- BT-4 MEDULLOBLASTOMA WITH INTRATUMORAL HEMORRHAGE
Authors: Yamaki Yusuke , Suzuki Tomonari , Sato Masaya , Fukuoka Masayoshi , Ehara Takuro , Takayanagi Shunsaku , Shirahata Mitsuaki , Fujimaki Takamitsu , Mishima Kazuhiko
Published: November 2024

INTRODUCTION

Medulloblastoma, a malignant pediatric brain tumor, is classified into four molecular subtypes: WNT, SHH, Group 3, and Group 4, according to the 2021 WHO classification. Reports indicate that WNT-type medulloblastomas have a higher incidence of intratumoral hemorrhage compared to other subtypes. This study investigates the correlation between intratumoral hemorrhage and molecular classification in medulloblastoma cases treated at our institution, supplemented by a literature review.

METHODS

We included patients diagnosed with medulloblastoma from January 2011 to July 2024. Intratumoral hemorrhage was identified using CT and MRI, and molecular diagnoses along with clinical findings were retrospectively reviewed and evaluated.

RESULTS

The study comprised 21 medulloblastoma cases with an average age of 12.2 years and a male-to-female ratio of 3:2. The molecular subtypes included 7 WNT, 5 SHH, 1 Group 3, and 7 Group 4. Intratumoral hemorrhage was observed in 3 cases, all of which were WNT-type. The average age of WNT-type cases was 10.1 years, with a male-to-female ratio of 4:3. There were no significant differences in treatment outcomes between hemorrhagic and non-hemorrhagic cases.

DISCUSSION

WNT-type medulloblastomas may cause blood-brain barrier dysfunction due to β-catenin mutations, leading to intratumoral hemorrhage. Our findings support previous reports showing a higher incidence of intratumoral hemorrhage in WNT-type medulloblastomas. Hemorrhagic medulloblastomas on imaging are likely WNT-type, making intratumoral hemorrhage an important factor in treatment strategy planning.

CONCLUSION

Our analysis of medulloblastoma cases at our institution confirmed a significantly higher incidence of intratumoral hemorrhage in WNT-type tumors. Intratumoral hemorrhage can aid in preoperative molecular diagnosis of medulloblastomas.
10210- CS-11 A CASE OF DIFFUSE HEMISPHERIC GLIOMA WITH H3 K27M MUTATION, NEC
Authors: Sumi Takuma , Uzuka Takeo , Matsuda Hadzki , Akutsu Hiroyoshi
Published: November 2024

Reports of diffuse glioma with H3 K27M mutation occurring in non-midline regions are rare. We report a case of diffuse hemispheric glioma with H3 K27M mutation (DHG) that infiltrated both temporal lobes without involvement of midline structures. The patient was a 50-year-old man who was found to have intracranial lesions during a brain checkup. MRI showed diffuse FLAIR high signal lesions in the right temporal lobe-hippocampus-insular cortex and the medial contralateral temporal lobe. A partial resection of the right temporal lobe was performed, and pathology showed moderately dense infiltrating atypical glial cells on HE staining. Immunostaining was positive for p53 and H3 K27M, negative for ATRX and H3K27me3, and Ki67 was 25.7% at a hot spot. Cancer panel test confirmed H3 K27M and TP53 mutations, as well as PDGFRA amplification. Based on these findings, the patient was diagnosed with diffuse hemispheric glioma, H3 K27M mutation, not elsewhere classified (NEC). The patient underwent postoperative radiation therapy (60 Gy/30 fractions) with concomitant and 12 courses of maintenance temozolomide therapy. At 18 months post-surgery, MRI showed progression of the FLAIR lesion and the appearance of some enhancing lesions, so gamma knife surgery was performed. The patient is currently under observation 21 months after surgery. Including this case, 12 cases of DHG, have been reported, with a median age of 44 years, older than diffuse midline glioma, H3 K27M mutant (DMG). Additionally, MAPK pathway alteration was observed in 42% of cases, and three patients had an overall survival of more than two years, indicating the presence of long-term survivors. Although the differences between DHG and DMG are unclear, DHG may exhibit clinical and molecular biological characteristics from DMG. Further accumulation of cases and studies is necessary to clarify these differences.
10048- COT-5 DEVELOPMENT OF A DIAGNOSTIC MODEL FOR GLIOMAS USING SERUM MICRO RNA
Authors: Osawa Sho , Ohno Makoto , Matsuzaki Juntaro , Mishima Kazuhiko , Nagane Motoo , Narita Yoshitaka
Published: November 2024

BACKGROUND

MicroRNAs (miRNAs) are non-coding RNAs consisting of approximately 20 base pairs. Several studies have reported the usefulness of serum miRNAs in the diagnosis of gliomas. However, the results differ among studies, and reproducibility remains an issue. In this study, we investigated the usefulness of serum miRNAs in the diagnosis of gliomas using prospectively collected samples with strictly defined procedures. Furthermore, we integrated the data set with retrospectively collected samples stored at the same temperature and constructed a diagnostic model.

MATERIALS AND METHODS

Fifty-eight gliomas and 273 healthy controls from prospective cohort, and 17 gliomas from retrospective cohort were included in the study. First, 58 gliomas from prospective cohort and 273 healthy subjects were divided into two groups: training set and validation set. Serum miRNAs were comprehensively analyzed, and a diagnostic model for gliomas was constructed. Second, 100 miRNAs useful for diagnosis of gliomas were extracted from both cohorts, and the diagnostic model was constructed based on the 45 miRNAs commonly extracted from both cohorts.

RESULTS

A diagnostic model for gliomas was generated using 24 miRNAs in the prospective cohort. The AUC was 0.818 and 0.925 for the prospective and retrospective cohorts, respectively. However, the miRNAs used in the model did not include miRNAs that have been reported to be useful in the diagnosis of gliomas. The expression profiles of miRNAs differed between the prospective and retrospective cohorts. The integrated analysis using both prospective and retrospective datasets constructed diagnostic model using seven miRNAs. The AUC was 0.810 for both datasets.

CONCLUSION

The serum miRNA profiles are greatly affected by conditions from sample collation to storage. Although interpretation of the results should be done with caution, the diagnostic model using miRNAs that are stably expressed under different conditions is expected to be useful for screening gliomas.
10123- COT-13 TREATMENT RESULTS OF TUMOR TREATING FIELD IN OUR HOSPITAL: EXAMINATION OF EARLY DROPOUT CAESE
Authors: Yamashita Shinji , Ogasawara Natsuki , Kawano Tomoki , Tamura Mitsuru , Okuyama Hironobu , Matsumoto Fumitaka , Ohta Hajime , Yokogami Kiyotaka , Okita Yoshiko
Published: November 2024

BACKGROUND/PURPOSE

Tumor treating field therapy (Novo-TTF) is a new treatment for glioblastoma that suppresses tumor growth by generating an alternating electric field in the brain. We have treated 21 cases since September 2019,and experienced a certain number of cases that dropped out of this treatment early. In this study, we examined TTF treatment at our hospital, with a particular focus on cases of early dropout.

SUBJECTS/METHODS

Nineteen patients with glioblastoma who underwent TTF at our hospital from September 2019 to July 2024 and were observed for at least 6 months. Patient information and outcome were analyzed retrospectively.

RESULTS

The median age of the patients was 64 years (33-72 years). Fourteen patients were males and five were females. The mean duration of TTF treatment was 9.9 months (0-55 months), and the mean usage rate was 41.0% (0-96.9%). Survival analyses showed that mPFS was 9 months and mOS was 23 months. Seven of 19 patients (37%) dropped out of treatment within 3 months (early dropout group). Compared to other patients (maintenance group), early dropout group included significantly more patients who had left cerebral lesions (71.4% vs. 16.7%, p=0.017) and fewer patients that KPS was 90 or higher (14.3% vs. 50.0%, p=0.144). Prognosis was significantly worse in the early dropout group compared to the maintenance group for both PFS and OS (p<0.01 for both PFS and OS), and multivariate analysis in PFS showed that early dropout was an independent poor prognostic factor (p=0.001).

CONCLUSION

In TTF treatment, the presence of patients who drop out early is a major factor that worsens the outcome of treatment. It is important to obtain the patient’s understanding and motivation for treatment in order to avoid early dropout. Tumor localization (left cerebellum) and low KPS may be potential disincentive factor for continue treatment.
10160- COT-18 DIFFERENCES IN 5-ALA FINDINGS AND BRIGHTNESS ON SECOND SURGERY
Authors: Kon Takashi , Kobayashi Yusuke , Sato Yosuke , Shimizu Katsuyoshi , Mizutani Tohru
Published: November 2024

We report cases of malignant brain tumor that underwent multiple surgeries, followed by postoperative radiation therapy and chemotherapy, and discuss the 5-ALA findings, changes in brightness, and factors that affect them. We report four cases, (case 1) anaplastic astrocytoma diagnosed by initial surgery, second surgery was done 18 months after, and the diagnosis was radiation necrosis. 5-ALA was negative at first surgery, and strongly positive at second surgery. (case 2) anapestic astrocytoma with 5-ALA negative findings at first surgery, and strongly positive at second surgery. histopathological findings were same. (case 3) Glioblastoma with 5-ALA strongly positive on both surgery, and they were histologically same. (case 4) breast cancer metastasis. 5-ALA brightness were strongly positive on initial and second surgery, and those were histopathologically same. We considered the malignant transformation of the tumor as the reason for the difference in 5-ALA findings, but one case was radiation necrosis, and three cases had the same pathological findings. It is possible that radiation, chemotherapy, etc. may have had some effect on the change in brightness, and we report here, together with a literature review, on factors that lead to differences in 5-ALA positive findings and brightness.
100310- COT-27 UNDERSTANDING THE BURDEN OF MIDH1/2 DIFFUSE GLIOMA AND THE COMPLEXITY OF NAVIGATING THE PATIENT PATHWAY: INSIGHTS FROM PATIENTS AND CAREGIVERS
Authors: Gatellier Laureline , Oliver Kathy , Burton Mary , Cardinal Craig , LaHay Shannon , Leon Bernard , Mallett Rebecca , Rogers Sarah , Tse Chris
Published: November 2024

Diffuse gliomas with mutations in isocitrate dehydrogenase 1/2 (mIDH1/2) are characterized by a slow-progressing, yet life-limiting, disease predominantly in young people. Herein, we report interim findings from a qualitative study to describe the mIDH1/2 diffuse glioma patient pathway, experience of the disease, and treatment approaches. Patients, caregivers, and patient-association group (PAG) representatives undertook individual interviews, with patients also completing standardized exercises as pre-work. Materials were developed in collaboration with the International Brain Tumour Alliance. Patients were aged ≥12 years with mIDH1/2 glioma, had their last resection ≥6 months before enrollment, and were either undergoing active observation or receiving chemotherapy/radiotherapy. Caregivers were living with the patient. PAG representatives were active members of a brain tumor PAG. From November 2023 to March 2024, 30 patients (Australia: n=10; China: n=6; France/UK: n=5 each; Canada/Japan: n=2 each), two caregivers (China/Australia: n=1 each) and one PAG (UK) participated. Median age of patients was 41.5 years. There were 17 astrocytoma and 13 oligodendroglioma diagnoses. Presentation symptoms, circumstances of diagnosis and treatment, access to care, and navigation in the healthcare system differed per patient and within countries. Surgical resection was perceived as a crucial stage, both feared and desired. A second opinion was more often sought for surgery than for subsequent treatment approaches. Patients undergoing chemotherapy/radiotherapy (n=17) or active observation (n=13) expressed substantial physical, socioeconomic, financial, and psychological burden. Patients receiving active observation experienced strong and ongoing anxiety, as the uncertainty of tumor recurrence took a toll on their emotional wellbeing in the long term. The experience of people living with mIDH1/2 diffuse glioma is heterogeneous regarding their pathway and complexity navigating the healthcare system, with a substantial psychological and socioeconomic impact. Improved education, as well as facilitating early navigation and prioritizing shared decision-making along the disease pathway, will better support people living with mIDH1/2 diffuse glioma.
IL-3 NOVEL SYNNOTCH-CAR-BASED T-CELL THERAPY FOR BRAIN TUMORS
Authors: Okada Hideho
Published: November 2024

The development of safe and effective chimeric antigen receptor (CAR)T therapy for malignant gliomas, such as glioblastoma (GBM), must overcome multiple challenges, including on-target off-tumor toxicity, heterogeneity of antigen expression, and exhaustion of CART cells. To this end, we adopted a novel synthetic Notch (synNotch) receptor system and developed innovative T cell circuits that recognize tumor cells based on the “prime-and-kill” strategy. In this system, the first antigen, which is expressed exclusively on GBM cells (e.g., EGFRvIII), primes the T cells to induce expression of a CAR that recognizes IL-13Rα2 and EphA2, thereby eradicating GBM cells expressing either EphA2 or IL-13Rα2. We reported that EGFRvIII-synNotch-primed EphA2/IL-13Rα2 CAR (E-SYNC) are effectively but restrictedly activated by EGFRvIII as the GBM-specific signal, thereby leading to complete eradication of orthotopic patient-derived xenografts with heterogeneous EGFRvIII expression, without attacking EphA2/IL-13Rα2-positive cells outside of the central nervous system (CNS) (Choe J, Watchmaker PB et al. Sci. Transl. Med 2021; PMID: 33910979). To extend the utility of synNotch-CART-cells to patients whose tumors do not express EGFRvIII, such as pediatric brain tumors, we developed a new concept of priming the synNotch-CAR circuit by antigens that are restrictedly expressed on CNS cells but not on cells of non-CNS systemic organs. This should be safe because, within the CNS, EphA2 and IL-13Rα2 are expressed only on tumor cells, but not normal CNS cells. Through screening, we have found Brevican (BCAN), a proteoglycan localized to the neuronal and glial cell surface, as the most promising priming antigen. A single IV infusion of T-cells engineered with the α-BCAN synNotch → CAR (B-SYNC) circuit showed complete remission in both PDX and immunocompetent mouse models without attacking CAR antigen-positive cells outside of CNS with superior efficacy and CNS-homing compared to conventional, constitutively expressed CART-cells (Simic M., Watchmaker PB, et al. Science in press). These synNotch-CART cells were more efficacious than conventional EphA2/IL-13Rα2 CART cells, associated with excellent persistence, and more juvenile in phenotype than conventional CART cells. We recently opened the phase I study evaluating the E-SYNC T-cells in patients with GBM (NCT06186401).
The Challenges of Constructing the Supreme Court by the Numbers: A Review Article
Authors: Gerhardt Michael J
Published: November 2024

This review article discusses the strengths and possible limitations of the new book, Making the Supreme Court: The Politics of Appointments, 1930–2020 by Charles M. Cameron and John P. Kastellec. The book, which provides the most extensive empirical analysis of the political construction of the Supreme Court yet written, including conventional and creative analyses of political influences shaping the Supreme Court. The book raises but does not resolve several important questions. While it illuminates some possible answers, a more nuanced analysis is needed in the future to capture the connection between the composition and direction of the Court, particularly in light of unforeseen developments in the law that challenge conventional notions of liberal and conservative jurists.
Death for the Minnows: Private Landlords and the Pendulum of Regulation
Authors: Mayfield Ben
Published: November 2024

Recent housing tragedies and scandals such as Grenfell Tower fire, and the death of a child in Rochdale due to mould, cast a long shadow over the provision of housing and have brought several deficiencies of the private rented sector into the light. Security of tenure and rent control in particular have become significant political issues that framed the housing policies of the two major parties at the last general election. This paper examines the history of key legislative interventions in the regulation of this sector to divine lessons for the present. This is a history of pendulum swings between free markets and market failure, with unintended consequences resulting from poorly developed laws that emerged from political overreactions to problems in the private rented sector. The paper notes the relative success of policy compromises and cooperation with private landlords. The tragic history of landlord and tenant law also provides an unrivalled opportunity to test the assertion of R. H Tawney, that ‘freedom for the pike is death for the minnows.’
Painful mycetoma: a study to understand the risk factors in patients visiting the Mycetoma Research Centre (MRC) in Khartoum, Sudan
Authors: El-Amin Saria O , El-Amin Rahba O , El-Sadig Sarah M , Fahal Ahmed Hassan , Musa Ahmed
Published: November 2024

Background

Mycetoma, a neglected tropical disease endemic to Sudan, is traditionally characterized as a painless condition. However, recent studies reporting painful mycetoma lesions have challenged this assumption. With limited reports in the medical literature regarding pain in mycetoma, this study was conducted to investigate the risk factors for painful mycetoma lesions in patients visiting the Mycetoma Research Centre (MRC) in Khartoum, Sudan.

Methods

This cross-sectional study aimed to identify the risk factors for painful mycetoma lesions. The study analyzed electronic records of 481 patients with confirmed mycetoma, seen between 1991 and 2020, using a systematic sampling approach.

Results

The study found that pain was more likely to occur in cases with bone destruction, secondary bacterial infection and actinomycete infection (OR=1.762, 1.815 and 1.259, respectively). Additionally, pain was more frequently observed in patients aged 45 y and older. Smaller mycetoma lesions, measuring less than 5 cm, were less likely to cause pain, and this was identified as a significant risk factor for painful mycetoma lesions (β coefficient=−1.294).

Conclusion

The findings suggested that pain in mycetoma is typically associated with the severity of the condition. Therefore, early initiation of appropriate treatment may help reduce pain. Furthermore, careful differentiation between actinomycetes and eumycetes is essential for the timely and accurate diagnosis of mycetoma.
Development and performance evaluation of a clinical prediction model for sepsis risk in burn patients
Authors: Luo Weiqing , Xiong Lei , Wang Jianshuo , Li Chen , Zhang Shaoheng
Published: November 2024

Sepsis is a common and severe complication in burn patients and remains one of the leading causes of mortality. This retrospective study aimed to develop a predictive model for the risk of in-hospital sepsis among burn patients treated at Guangzhou Red Cross Hospital between January 2022 and January 2024, with the goal of improving clinical outcomes through early prevention based on risk stratification. A total of 302 eligible patients were randomly divided into training and validation cohorts in a 7:3 ratio for model development and validation, respectively. Predictive factors were initially selected using LASSO regression, followed by logistic regression analysis to establish the prediction model and construct a nomogram. The final model incorporated 4 independent predictors: burn area (odds ratio [OR] = 1.043, 95% confidence interval [CI]: 1.026–1.062/1%), hemoglobin (OR = 0.968, 95% CI: 0.954–0.980/1 g/L), diabetes (OR = 10.91, 95% CI: 2.563–56.62), and potassium (OR = 3.091, 95% CI: 1.635–6.064/1 mmol/L). The areas under the receiver operating characteristic curve were 0.875 and 0.861 for the training and validation cohorts, with Youden indexes of 0.634 and 0.600, respectively. The calibration curve and decision curve analysis demonstrated good predictive accuracy and clinical utility of the model. These findings suggest that our developed model exhibits robust predictive performance for the risk of in-hospital sepsis in burn patients, and early prevention strategies based on risk stratification may potentially improve clinical outcomes.
Infective endocarditis causing recurrent cerebral infarction, cerebral hemorrhage and septic meningitis: A case report
Authors: Wang Huiliang , Fan Lingyan , Li Chenxi , Yu Haining , Han Jilan , Du Yeliang , Xing Guoping
Published: November 2024

Rationale:

We reported a rare case of recurrent cerebral infarction, intracerebral hemorrhage, and purulent meningitis, culminating in the diagnosis of a young patient with infective endocarditis who had been treated in 3 hospitals for a long course of illness for 8 months prior to diagnosis. It aims to enhance clinicians’ understanding of the neurological complications caused by infective endocarditis.

Patient concerns:

A 25-year-old male, student, was hospitalized for an 8-hour history of speech impairment and drooling with dysphagia. Magnetic resonance imaging (MRI) showed massive cerebral infarction in the right frontotemporal and insular lobes, and the first diagnosis was “cerebral infarction.” Later, the patient developed recurrent cerebral infarction, intracerebral hemorrhage, and purulent meningitis.

Diagnoses:

Recurrent cerebral infarction, intracerebral hemorrhage, and purulent meningitis were confirmed to be caused by infective endocarditis.

Interventions:

The patient was treated with antiplatelet drugs such as aspirin and clopidogrel, mannitol to reduce intracranial pressure, and ceftriaxone and vancomycin to fight infection, and the patient’s condition improved.

Outcomes:

The patient was diagnosed with infective endocarditis after 8 months without a clear diagnosis, and the patient was finally diagnosed with infective endocarditis during the final follow-up.

Lessons:

Febrile patients should be aware of infective endocarditis, particularly if the fever is persistent of unknown origin or structural changes in the heart with neurologic lesions. Cardiogenic neurological diseases are relatively more severe, have a worse prognosis, and have a higher recurrence rate than primary neurological diseases, so early diagnosis and treatment are more urgently needed.
Multitissue Multiomics Integration Reveals Tissue-Specific Pathways, Gene Networks, and Drug Candidates for Type 1 Diabetes
Authors: Blencowe Montgomery , Saleem Zara , Liu Ruoshui , Tseng I-Hsin , Wier Julian , Yang Xia
Published: November 2024

Aims/hypothesis

Although genome-wide association studies (GWAS) have identified loci associated with Type 1 diabetes (T1D), the specific pathways and regulatory networks linking these loci to disease pathology remain largely unknown. We hypothesized that T1D genetic risk factors disrupt tissue-specific biological pathways and gene networks that ultimately lead to beta cell loss.

Methods

We conducted a multitissue multiomics analysis that integrates human GWAS data for T1D with tissue-specific regulatory data on gene expression and gene network models across relevant tissues to highlight key pathways and key driver genes contributing to T1D pathogenesis. Key driver genes were validated using islet-specific gene expression and protein data from non-obese diabetic (NOD) mice compared to non-T1D mouse models. Drug repositioning predictions were generated using the L1000 and PharmOmics platforms.

Results

Our integrative genomics approach identified known immune pathways across multiple tissues, such as adaptive immune responses, cytokine-mediated inflammation, primary immunodeficiency, and interactions between lymphoid and non-lymphoid cells. Tissue-specific signals included genes related to type 2 diabetes in lymphocytes, viral response pathways in macrophages and monocytes, and Notch signaling in adipose and immune cells. In pancreatic islet analysis, we observed significant enrichment for T1D and type 2 diabetes gene sets alongside immune-related pathways, including antigen processing, systemic lupus erythematosus, and interferon signaling. Removing HLA genes from the analysis revealed additional immune pathways, such as RIG-I/MDA5 induction of interferons, along with melanogenesis, steroid hormone synthesis, and iron transport. Network modeling highlighted the autoimmune basis of disease with key drivers such as FYN, TAP1, WAS, and HLA-B/C/G, as well as further immunomodulatory genes such as LCK, LCP2, EMR1, and GC. These key drivers were further supported by gene and protein expression data from NOD mice. We additionally highlight various drug classes that target the T1D genetic networks and may be useful to delay T1D development.

Conclusions/interpretation

Our multitissue multiomics approach provides a detailed landscape of the tissue-specific genetic networks and regulators underlying T1D. This analysis confirms the roles of known immune pathways while uncovering additional regulatory elements and disease-associated networks, thus expanding our understanding of T1D pathogenesis. The identification of potential drug candidates through network analysis offers potential therapeutic strategies for targeting disease pathways and holds promise for delaying or preventing T1D progression.
DuckDerm: An Improved Water Infiltration Prevention Product for Long-Term Intravenous Therapy Patients
Authors: Fantini Dalia , Fisk Abigail , Leon-Vargas Andres , Lynch Emma , Scarlett Christine , Stafford Devon , Zegarra Marcos , Bielewicz Brady John
Published: November 2024

We propose an alternative to the widely implemented intravenous (IV) shower guard solution, AnchorDry, which we have coined DuckDerm. The AnchorDry is a rigid square of plastic with an adhesive border on the outer edge. This design does not adhere to the arm during the bathing period as it cannot withstand the range of motion (ROM) patients exert, leaving the Tegaderm and IV site vulnerable to water intrusion. Significant water intrusion compromises the IV site, leaving it susceptible to infection. By interviewing seasoned clinicians, nursing faculty, students, and patient care technicians (PCTs) we ascertained ineffective shower guard fit is an issue rooted in design and material selections. We have found that nurses and PCTs are often getting creative to modify or make their own IV shower guards.

After several design iterations and consultations with several University of Pittsburgh nursing faculty, we mass-manufactured our design. The DuckDerm body is composed of 1 mil polyethylene plastic, which is biocompatible and able to move with the skin, a hypoallergenic adhesive, and a foam barrier to envelop the Tegaderm. Based on this initial testing, we formulated our design specifications: (1) maintaining the patient’s ROM, (2) ease of use for both patients and clinicians, and (3) preventing water infiltration. We provided our manufactured design and interviewed nursing students and faculty (n=21) to address the following criteria: (1) the DuckDerm must be simple for clinicians to apply to not take away time from more essential tasks and to encourage patient self-application; (2) the DuckDerm must retain functionality without providing discomfort to the patient during use and removal. We also conducted functionality testing using our manufactured design to address the following criteria on volunteers (n=11): the DuckDerm must (1) contain all the IV components within the foam barrier, (2) not place unnecessary pressure on components to dislodge, and (3) fit securely on the patient’s arm. Additionally, the Duckderm must adhere to the skin while subjected to running water and movement, and the DuckDerm must be able to provide a sufficient range of motion about the antecubital space to allow for arm movements required while showering. The Duckderm outperformed the currently utilized solution in both verbal feedback and assessment by potential users (nurses and PCTs) and in functionality testing; therefore, we propose our novel design as an alternative to the currently employed AnchorDry.
Shared Clinical and Immunologic Features of mRNA Vaccines: Preliminary Results from a Comparative Clinical Study
Authors: Fierro Carlos , Sanchez-Crespo Nelia , Makrinos Daniel , Zhang Weijie , Sun Yanbo , Rohilla Poonam , Girard Bethany , Adeniji Abidemi , DiPiazza Anthony , Paris Robert
Published: November 2024

Introduction

Clinical trials do not typically assess underlying molecular mechanisms of vaccine immunogenicity or reactogenicity. We evaluated the reactogenicity and immunogenicity of 4 mRNA vaccines and potential contributing mechanisms and identified shared and unique clinical and immunologic features.

Methods

This ongoing open-label, phase 1 trial randomized healthy adults (18-75 years) to receive a single dose of mRNA-1273.222 (bivalent COVID-19), mRNA-1345 (RSV), mRNA-1010 (influenza), and FLUAD (active influenza comparator) or 2 or 3 doses of mRNA-1647 (CMV). The primary objective was to assess the safety and reactogenicity of each study vaccine, with humoral immunogenicity (neutralizing antibody [nAb] responses) as the secondary objective. This interim analysis reports safety and reactogenicity in all study vaccines and humoral immunogenicity in single-dose vaccines (mRNA-1273.222, mRNA-1345, mRNA-1010, and FLUAD). Exploratory objectives included antigen-specific T-cell responses after single-dose mRNA-1345 or mRNA-1273.222, and soluble mediators of inflammation and innate immunity following vaccination in single-dose vaccine groups and two doses of mRNA-1647.

Results

At the interim analysis data cutoff (February 1, 2023), 302 participants received 1 dose of the study vaccines. Reactogenicity exhibited a consistent trend across vaccine groups; most solicited local and systemic adverse reactions within 7 days were mild or moderate in severity. There were no deaths or serious, severe, or treatment-related adverse events leading to study discontinuation. At Day 29, nAb titers against vaccine-specific antigens increased 2- to 8-fold versus baseline for all single-dose vaccine groups. In an exploratory analysis, mRNA-1273.222 and mRNA-1345 induced antigen-specific Th1-biased CD4+and CD8+T-cell responses at Day 29. The cytokine response analysis showed increased levels of IFN-γ, IL-6, IL-2Ra, CXCL9, IP-10, MCP-2, and MIP-1β on Day 2 following vaccination, with generally greater increases observed with mRNA vaccines versus FLUAD. Regardless of age and across mRNA vaccine groups, peak serum levels of IL-1Ra and MCP-1/MCP-2 on Day 2 weakly correlated with systemic reactogenicity scores (correlation coefficient range: 0.15-0.27).

Conclusions

The 4 mRNA vaccines had acceptable reactogenicity, demonstrated changes in serum biomarkers of innate immune activation, and were immunogenic. This suggests that the observed reactogenicity of mRNA vaccines may be related to shared features of the mRNA platform (LNP platform).

Clinical Trial Registration

ClinicalTrials.govNCT05397223
H-MpoxNet: A Hybrid Deep Learning Framework for Mpox Detection from Image Data
Authors: Chakroborty Sajal
Published: November 2024

Infectious diseases can create significant global threats to public health and economic stability by creating pandemics. SARS-CoV-2 is a recent example. Early detection of infectious diseases is crucial to prevent global outbreaks. Mpox, a contagious viral disease first detected in humans in 1970, has experienced multiple outbreaks in recent decades, which emphasizes the development of tools for its early detection. In this paper, we develop a hybrid deep learning framework for Mpox detection. This framework allows us to construct hybrid deep learning models combining deep learning architectures as a feature extraction tool with Machine Learning classifiers and perform a comprehensive analysis of Mpox detection from image data. Our best-performing model consists of MobileNetV2 with LightGBM classifier, which achieves an accuracy of 91.49%, 91.87% weighted precision, 91.49% weighted recall, 91.51% weighted F1-score and Matthews Correlation Coefficient score of 0.83.
Sex and the Clock: Exploring Sex Differences in Chronotype and Circadian Preferences Among Cognitively Healthy Older Adults
Authors: Pandher Natalie S , Yack Leslie , Li Esther , Coppola Quentin , Cassaletto Kaitlin , Grinberg Lea T. , Neylan Thomas C , Kramer Joel H , Walsh Christine M
Published: November 2024

This study aimed to compare objective circadian rest-activity-rhythm (RAR) measures with self-reported circadian behavior and morning-evening preference in cognitively healthy older men and women. A total of 129 participants (ages 65-90) completed the Horne & Ostberg Morning-Eveningness Questionnaire (MEQ) and the Circadian Type Inventory (CTI) to assess their morning-evening preference and circadian traits, including rigidity, vigor, languidness, and flexibility. These subjective measures were compared to objective actigraphy data from a sub-cohort of 70 individuals who wore actigraphy watches for 24 hours a day over a 7-day period. Rest-activity rhythm variables were derived from the actigraphy data and analyzed. The results revealed sex differences in circadian behavior. Languid and flexible men (higher CTI scores) had significantly higher depression scores (GDS, p = 0.045) and showed more evening preference (MEQ, p = 0.007) compared to their vigorous and rigid counterparts, while no significant differences were found in women. Actigraphy data showed that men had less stable (interdaily stability, IS, p = 0.030) and more fragmented (interdaily variability, IV, p = 0.001) circadian rhythms than women. A significant association was found between acrophase time and CTI-FR scores (β = -0.406, p < 0.001), with earlier acrophase times linked to more rigid circadian rhythms. Additionally, earlier acrophase times and morningness preference were associated with faster information processing speeds (IPS, p = 0.018). These findings suggest that circadian behaviors and their impact on mood and cognition are more pronounced in older men than women, highlighting the value of actigraphy in assessing circadian profiles and sex differences in aging.