Physiological Markers of Motor Improvement Following Five-month Sprint Training in Young Boys

The 11th International Symposium on Adaptive Motion of Animals and Machines. Kobe University, Japan. 2023-06-06/09. Adaptive Motion of Animals and Machines Organizing Committee.Poster Session P4

Update on Chemotherapeutic Approaches and Management of Bevacizumab Usage for Glioblastoma.

Glioblastoma, the most common primary brain tumor in adults, has one of the most dismal prognoses in cancer. In 2009, bevacizumab was approved for recurrent glioblastoma in the USA. To evaluate the clinical impact of bevacizumab as a first-line drug for glioblastoma, two randomized clinical trials, AVAglio and RTOG 0825, were performed. Bevacizumab was found to improve progression-free survival (PFS) and was reported to be beneficial for maintaining patient performance status as an initial treatment. These outcomes led to bevacizumab approval in Japan in 2013 as an insurance-covered first-line drug for glioblastoma concurrently with its second-line application. However, prolongation of overall survival was not evinced in these clinical trials; hence, the clinical benefit of bevacizumab for newly diagnosed glioblastomas remains controversial. A recent meta-analysis of randomized controlled trials of bevacizumab combined with temozolomide in recurrent glioblastoma also showed an effect only on PFS, and the benefit of bevacizumab even for recurrent glioblastoma is controversial. Here, we discuss the clinical impact of bevacizumab for glioblastoma treatment by reviewing previous clinical trials and real-world evidence by focusing on Japanese experiences. Moreover, the efficacy and safety of bevacizumab are summarized, and we provide suggestions for updating the approaches and management of bevacizumab

Pediatric Glioma: An Update of Diagnosis, Biology, and Treatment

Recent research has promoted elucidation of the diverse biological processes that occur in pediatric central nervous system (CNS) tumors. Molecular genetic analysis is essential not only for proper classification, but also for monitoring biological behavior and clinical management of tumors. Ever since the 2016 World Health Organization classification of CNS tumors, molecular profiling has become an indispensable step in the diagnosis, prediction of prognosis, and treatment of pediatric as well as adult CNS tumors. These molecular data are changing diagnosis, leading to new guidelines, and offering novel molecular targeted therapies. The Consortium to Inform Molecular and Practical Approaches to CNS Tumor Taxonomy (cIMPACT-NOW) makes practical recommendations using recent advances in CNS tumor classification, particularly in molecular discernment of these neoplasms as morphology-based classification of tumors is being replaced by molecular-based classification. In this article, we summarize recent knowledge to provide an overview of pediatric gliomas, which are major pediatric CNS tumors, and describe recent developments in strategies employed for their diagnosis and treatment

Pediatric Glioma: An Update of Diagnosis, Biology, and Treatment.

Recent research has promoted elucidation of the diverse biological processes that occur in pediatric central nervous system (CNS) tumors. Molecular genetic analysis is essential not only for proper classification, but also for monitoring biological behavior and clinical management of tumors. Ever since the 2016 World Health Organization classification of CNS tumors, molecular profiling has become an indispensable step in the diagnosis, prediction of prognosis, and treatment of pediatric as well as adult CNS tumors. These molecular data are changing diagnosis, leading to new guidelines, and offering novel molecular targeted therapies. The Consortium to Inform Molecular and Practical Approaches to CNS Tumor Taxonomy (cIMPACT-NOW) makes practical recommendations using recent advances in CNS tumor classification, particularly in molecular discernment of these neoplasms as morphology-based classification of tumors is being replaced by molecular-based classification. In this article, we summarize recent knowledge to provide an overview of pediatric gliomas, which are major pediatric CNS tumors, and describe recent developments in strategies employed for their diagnosis and treatment

Severe hypoglycemia during pneumocystis pneumonia treatment associated with trimethoprim–sulfamethoxazole use in a patient on peritoneal dialysis

Abstract Background Trimethoprim–sulfamethoxazole (TMP/SMX) is an essential antimicrobial agent for treating pneumocystis pneumonia (PCP). Furthermore, the risk of hypoglycemia is increased with the co-administration of sulfonylurea due to the presence of the same sulfanilamide structural group in SMX and sulfonylurea. However, hypoglycemia caused by a single administration of TMP/SMX is a rare adverse reaction, and not many cases have been reported. Renal failure is a risk factor for hypoglycemia with single TMP/SMX administration. Case presentation A 54-year-old Japanese woman on peritoneal dialysis (PD) for 10 years was admitted to our hospital for the suspicion of PCP. She underwent immunosuppressive treatment with oral prednisolone (3 mg/day) and a subcutaneous injection of adalimumab (40 mg) every 2 weeks for rheumatoid arthritis. We initiated the administration of a low-to-moderate dose of TMP/SMX (TMP equivalent to TMP/SMX, approximately 8 mg/kg/day) in the patient, considering that she was on PD. At 10 days after administration, the patient became unconscious, and blood test results showed that her blood glucose level was low (15 mg/dL). Unlike hypoglycemia, her serum insulin levels were abnormally high (69.4 μU/mL) at that time. Glucose injection was used for correcting the hypoglycemia, but it was refractory. Highly concentrated glucose infusion was needed to maintain her blood glucose level normal. Her serum insulin level was confirmed to have returned to normal (4.0 μU/mL) at 9 days after completing the TMP/SMX treatment. Conclusions We suspected that the refractory hypoglycemia in this case was caused by high levels of insulin secretion due to the accumulation of TMP/SMX. One of the risk factors in this patient was the low excretion rate of TMP/SMX into the PD fluid. Although hypoglycemia is a rare complication of TMP/SMX, we should consider this risk during TMP/SMX use in patients, especially those on PD

Effectiveness of psychological first aid in infectious disease pandemics: An overview of systematic reviews

Abstract There is insufficient research on the usefulness of psychological interventions, such as psychological first aid (PFA), during outbreaks. We searched for and critically appraised systematic reviews that examined the effectiveness of PFA during infectious disease outbreaks, such as the novel coronavirus disease (COVID‐19). Systematic reviews that examined the efficacy of PFA in the severe acute respiratory syndrome, Middle East respiratory syndrome coronavirus, Ebola virus disease, and COVID‐19 outbreaks were searched through PubMed on February 19, 2021. The three included systematic reviews were critically appraised and assessed using AMSTAR‐2. One review's overall confidence in its findings was evaluated as “high,” which suggested that PFA training had a favorable effect on healthcare personnel. Furthermore, the review also demonstrated that PFA was commonly used during outbreaks and could be delivered through multiple methods, such as a phone or video call. Although it was anticipated that PFA would improve subjective well‐being, reports showed no evidence of reduced depression or insomnia. Future studies should examine additional numbers of PFA recipients and conduct quasi‐experimental studies to better understand the effectiveness of PFA. Evidence on its effectiveness in infectious disease outbreaks is still lacking, along with research and evaluation methods. Quasi‐experimental studies, such as comparisons with other psychological interventions, are required to better understand the effectiveness of PFA

Current trend in treatment of glioblastoma in Japan: a national survey using the diagnostic procedure combination database (J-ASPECT study-glioblastoma).

BACKGROUND: In the treatment for glioblastoma (GBM), treatment modalities, such as bevacizumab (BEV) and carmustine wafers implants have been approved in Japan since 2013. However, it is unclear whether such a trend in treatment complexity can accelerate treatment centralization. The aim of this study was to reveal the current trend in the treatment of GBM in Japan. METHODS: We used diagnostic procedure combination (DPC) database to analyze the data of 1,774 patients from 305 institutions between April 2016 and March 2019. To analyze the situations associated with first-line BEV use during concurrent TMZ (temozolomide)-radiotherapy, we compared TMZ alone and TMZ-BEV groups. RESULTS: Of the 1,774 patients with GBM, tumor removal by craniotomy was performed in 1,572 (88.6%) patients, and stereotactic biopsy was performed in 156 (8.8%) patients. A total of 1,229 (69.3%) patients underwent radiotherapy, and 1,287 (72.5%) patients underwent chemotherapy. TMZ alone was administered to 878 (68.2%) and TMZ combined with BEV in 381 (29.6%) patients. In the TMZ-BEV group, as compared to the TMZ-alone group, the rate of discharge to home was significantly lower (P = 0.0044), and the rate of stereotactic biopsy was significantly higher (P < 0.0001). No significant difference was observed in the distribution of patients between the TMZ alone and TMZ-BEV groups depending on the scale of institution (P = 0.1240). CONCLUSION: First-line BEV administration seems to be selected properly regardless of the institutional scale. This Japan-wide study of GBM treatment revealed that high level and newly introduced treatments have been steadily generalized in Japanese institutions

Crystal growth, structure, and physical properties of Ln(Cu,Ga) 3-x(Ln=La-Nd, Eu; x≈0.2)

Single crystals of Ln(Cu,Ga) 13-x(Ln=La-Nd, Eu; x≈0.2) were grown using Ga flux and their structures determined by single-crystal X-ray diffraction. The Ln(Cu,Ga) 13-x (Ln=La-Nd, Eu; x≈0.2), adopting NaZn 13 structure type, crystallizes in the cubic Fm3̄c (No. 226) space group, with Z=8 and lattice parameters a≈11.8A° .Magnetic susceptibility and heat capacity measurements do not show any indication of long-range magnetic ordering down to 2 K for magnetic analogues. Metallic behavior is observed in the range of 2-300 K for each compound. A large positive magnetoresistance up to 154% at a field (μ )OH) of 9 T is also observed for Pr(Cu,Ga) 12.85(1). Most interestingly, the Pr analogue shows T 2 temperature-dependent resistivity and satisfies Kadowaki- Woods relation, which is indicative of heavy-fermion behavior. Here, we present the crystal structures and physical properties of Ln(Cu,Ga) 13-x (Ln=La-Nd, Eu; x≈0.2). © 2009 American Chemical Society

Molecular diagnosis of diffuse glioma using a chip-based digital PCR system to analyze IDH, TERT, and H3 mutations in the cerebrospinal fluid.

PURPOSE: Conventional genetic analyzers require surgically obtained tumor tissues to confirm the molecular diagnosis of diffuse glioma. Recent technical breakthroughs have enabled increased utilization of cell-free tumor DNA (ctDNA) in body fluids as a reliable resource for molecular diagnosis in various cancers. Here, we tested the application of a chip-based digital PCR system for the less invasive diagnosis (i.e., liquid biopsy) of diffuse glioma using the cerebrospinal fluid (CSF). METHODS: CSF samples from 34 patients with diffuse glioma were collected from the surgical field during craniotomy. Preoperative lumbar CSF collection was also performed in 11 patients. Extracted ctDNA was used to analyze diagnostic point mutations in IDH1 R132H, TERT promoter (C228T and C250T), and H3F3A (K27M) on the QuantStudio® 3D Digital PCR System. These results were compared with their corresponding tumor DNA samples. RESULTS: We detected either of the diagnostic mutations in tumor DNA samples from 28 of 34 patients. Among them, we achieved precise molecular diagnoses using intracranial CSF in 20 (71%). Univariate analyses revealed that the World Health Organization (WHO) grade (p = 0.0034), radiographic enhancement (p = 0.0006), and Mib1 index (p = 0.01) were significant predictors of precise CSF-based molecular diagnosis. We precisely diagnosed WHO grade III or IV diffuse gliomas using lumbar CSF obtained from 6 (87%) of 7 patients with tumors harboring any mutation. CONCLUSION: We established a novel, non-invasive molecular diagnostic method using a chip-based digital PCR system targeting ctDNA derived from CSF with high sensitivity and specificity, especially for high-grade gliomas

Supramaximal Resection Can Prolong the Survival of Patients with Cortical Glioblastoma: A Volumetric Study.

We aimed to retrospectively determine the resection rate of fluid-attenuated inversion recovery (FLAIR) lesions to evaluate the clinical effects of supramaximal resection (SMR) on the survival of patients with glioblastoma (GBM). Thirty-three adults with newly diagnosed GBM who underwent gross total tumor resection were enrolled. The tumors were classified into cortical and deep-seated groups according to their contact with the cortical gray matter. Pre- and postoperative FLAIR and gadolinium-enhanced T1-weighted imaging tumor volumes were measured using a three-dimensional imaging volume analyzer, and the resection rate was calculated. To evaluate the association between SMR rate and outcome, we subdivided patients whose tumors were totally resected into the SMR and non-SMR groups by moving the threshold value of SMR in 10% increments from 0% and compared their overall survival (OS) change. An improvement in OS was observed when the threshold value of SMR was 30% or more. In the cortical group (n = 23), SMR (n = 8) tended to prolong OS compared with gross total resection (GTR) (n = 15), with the median OS of 69.6 and 22.1 months, respectively (p = 0.0945). Contrastingly, in the deep-seated group (n = 10), SMR (n = 4) significantly shortened OS compared with GTR (n = 6), with median OS of 10.2 and 27.9 months, respectively (p = 0.0221). SMR could help prolong OS in patients with cortical GBM when 30% or more volume reduction is achieved in FLAIR lesions, although the impact of SMR for deep-seated GBM must be validated in larger cohorts