A case of coronary artery compression syndrome resulting from peri-valvular regurgitation and long-standing atrial fibrillation.

A man in his 70s with a history of mitral valve replacement (MVR) and long-standing persistent atrial fibrillation (AF) presented with effort angina. Coronary angiography revealed severe stenosis of the left main coronary artery (LMCA). As it was an emergent case, PCI (percutaneous coronary intervention) was selected for treatment. Intravascular ultrasonography revealed no atherosclerotic lesions in the LMCA. The LMCA was effectively dilated by the drug-eluting stent. No elevation in intracardiac pressure was observed in cardiac catheterization after PCI. Computed tomography scan indicated potential compression of the LMCA by the surrounding structures. In cases of long-standing persistent AF and an enlarged atrium after MVR, the possibility of LMCA stenosis due to anatomical changes should be considered. Learning Objectives: ◾Peri-valvular regurgitation and long-standing persistent atrial fibrillation can potentially cause atrial enlargement.◾Coronary artery stenosis without atherosclerosis can occur due to compression from surrounding structures or shifting of the coronary artery.◾Stent therapy provides a temporary solution and coronary artery bypass grafting or switching should be considered if re-stenosis occurs.

Pediatric-type high-grade gliomas with PDGFRA amplification in adult patients with Li-Fraumeni syndrome: clinical and molecular characterization of three cases.

Li-Fraumeni syndrome (LFS) is an autosomal dominant tumor predisposition syndrome caused by heterozygous germline mutations or deletions in the TP53 tumor suppressor gene. Central nervous system tumors, such as choroid plexus tumors, medulloblastomas, and diffuse gliomas, are frequently found in patients with LFS. Although molecular profiles of diffuse gliomas that develop in pediatric patients with LFS have been elucidated, those in adults are limited. Recently, diffuse gliomas have been divided into pediatric- and adult-type gliomas, based on their distinct molecular profiles. In the present study, we investigated the molecular profiles of high-grade gliomas in three adults with LFS. These tumors revealed characteristic histopathological findings of high-grade glioma or glioblastoma and harbored wild-type IDH1/2 according to whole exome sequencing (WES). However, these tumors did not exhibit the key molecular alterations of glioblastoma, IDH-wildtype such as TERT promoter mutation, EGFR amplification, or chromosome 7 gain and 10 loss. Although WES revealed no other characteristic gene mutations or copy number alterations in high-grade gliomas, such as those in histone H3 genes, PDGFRA amplification was found in all three cases together with uniparental disomy of chromosome 17p, where the TP53 gene is located. DNA methylation analyses revealed that all tumors exhibited DNA methylation profiles similar to those of pediatric-type high-grade glioma H3-wildtype and IDH-wildtype (pHGG H3-/IDH-wt), RTK1 subtype. These data suggest that high-grade gliomas developed in adult patients with LFS may be involved in pHGG H3-/IDH-wt. PDGFRA and homozygous alterations in TP53 may play pivotal roles in the development of this type of glioma in adult patients with LFS.

Stroke After Acute Type A Dissection Repair Using Right Axillary Cannulation First Approach.

BACKGROUND: This study sought to analyze the details of strokes after acute type A dissection repair (ATAD) using a right axillary artery (RAX) first approach. METHODS: A total of 356 consecutive ATAD repairs from 2005 to 2022 were analyzed on the basis of arterial cannulation site. Strokes were evaluated by head computed tomography. RESULTS: The rate of RAX cannulation was 82.6% (n = 294), with a 38.2% rate of antegrade cerebral perfusion use, both of which had increased over the years. The non-RAX group had more cardiogenic shock (RAX, 16.3% vs non-RAX, 37.1%; P < .001), cerebral malperfusion (8.8% vs 25.8%, respectively; P < .001), and innominate artery dissection (45.9% vs 69.2%, respectively; P = .007). Eight patients died before undergoing a full neurologic assessment. The overall stroke rate was 8.4% (n = 30), and it was lower in the RAX group (5.1% vs 24.2%; P < .001). All strokes were ischemic, with concomitant hemorrhagic strokes occurring in 6 patients. Strokes diagnosed immediately after surgery (perioperative stroke) accounted for 70% (n = 21 of 30) of cases. Strokes predominantly affected the right anterior circulation (right anterior, 80% vs left anterior, 46.7% vs left posterior, 26.7%; P = .013), independent of arterial cannulation site. The proposed mechanism of perioperative strokes was not uniform (embolism, 33.3%; hypoperfusion, 42.8%; embolism and hypoperfusion, 14.3%; lacunar infarct, 10%), whereas most postoperative strokes were embolic (77.8%). The mean National Institutes of Health Stroke Scale score was 20.6 ± 9.9, and the modified Rankin score at discharge was 4.1±2.2. CONCLUSIONS: Most strokes in ATAD occurred perioperatively from various mechanisms predominantly affecting the right anterior circulation irrespective of the arterial cannulation site. This complication is most likely the result of unstable hemodynamics and dissection of the innominate artery (IA) or its downstream vessels.

Predictive factors of post-operative apathy in patients with diffuse frontal gliomas undergoing awake brain mapping.

Patients with diffuse frontal gliomas often present with post-operative apathy after tumour removal. However, the association between apathy and tumour removal of gliomas from the frontal lobe remains unknown. This study aimed to investigate the factors influencing post-operative apathy after tumour removal in patients with diffuse frontal gliomas. We compared the demographics and clinical characteristics of patients with and without post-operative apathy in a cohort of 54 patients who underwent awake brain mapping for frontal gliomas. The frequency of clinical parameters such as left-sided involvement, high-grade tumour types (WHO grades III, IV), main tumour location in the anterior cingulate gyrus (ACC) and/or dorsolateral prefrontal cortex (DLPFC) and orbitofrontal cortex (OFC) was significantly greater in the apathetic group compared to the non-apathetic group. The apathetic group scored significantly lower on neuropsychological assessments such as the Letter Fluency Test among the Word Fluency Tests than the non-pathetic group (p = .000). Moreover, the scores of Parts 3, and 3-1 of the Stroop test were significantly lower in the apathetic group than those in the non-apathetic group (p = .023, .027, respectively). Multivariate model analysis revealed that the appearance of post-operative apathy was significantly related to side of the of lesion [left vs. right, hazard ratio (HR) = 8.00, 95% confidence interval (CI) = 1.36-46.96, p = .021], location of the main tumour in the frontal lobe (ACC/DLPFC/OFC vs. others, HR = 7.99, 95% CI = 2.16-29.59, p = .002), and the Letter Fluency Test (HR = .37, 95% CI = .15-.90, p = .028). Post-operative apathy is significantly associated with ACC and/or DLPFC and OFC in the left hemisphere of diffuse frontal gliomas. Apathy in frontal gliomas is correlated with a decline in the Letter Fluency Test scores. Therefore, this instrument is a potential predictor of post-operative apathy in patients with diffuse frontal gliomas undergoing awake brain mapping.

Minor Suture Fusion is Associated With Chiari Malformation in Nonsyndromic Craniosynostosis.

Here, we focused on the association between minor suture fusion and Chiari malformation (CM) occurrence in nonsyndromic craniosynostosis (NSC), and evaluated how the minor suture affects the posterior cranial fossa by measuring the posterior fossa deflection angle (PFA). In this retrospective study, the clinical records of 137 patients who underwent surgery for NSC at Aichi Children's Health and Medical Center between April 2010 and May 2022 were analyzed. Clinical data from Aichi Developmental Disability Center Central Hospital was collected for 23 patients as the external validation set. Among the 137 patients, 123 were diagnosed with NSC and the remaining 14 with syndromic craniosynostosis. Of the 123 NSC patients, 23 patients presented with CM. Multivariate analysis showed that occipito-mastoid fusion was the only significant risk factor for CM ( P =0.0218). Within the NSC group, CM patients had a significantly increased PFA (6.33±8.10 deg) compared with those without CM (2.76±3.29 deg, P =0.0487). Nonsyndromic craniosynostosis patients with occipito-mastoid suture fusion had a significantly increased PFA (6.50±7.60 deg) compared with those without occipito-mastoid fusion (2.60±3.23 deg, P =0.0164). In the validation cohort, occipito-mastoid suture fusion was validated as an independent risk factor for CM in univariate analysis. Minor suture fusion may cause CM associated with NSC. Chiari malformation could develop due to an increased PFA due to minor suture fusion, which causes growth disturbance in the affected side and compensatory dilation in the contralateral side within the posterior cranial fossa.

Evolutionary histories of breast cancer and related clones.

Recent studies have documented frequent evolution of clones carrying common cancer mutations in apparently normal tissues, which are implicated in cancer development1-3. However, our knowledge is still missing with regard to what additional driver events take place in what order, before one or more of these clones in normal tissues ultimately evolve to cancer. Here, using phylogenetic analyses of multiple microdissected samples from both cancer and non-cancer lesions, we show unique evolutionary histories of breast cancers harbouring der(1;16), a common driver alteration found in roughly 20% of breast cancers. The approximate timing of early evolutionary events was estimated from the mutation rate measured in normal epithelial cells. In der(1;16)(+) cancers, the derivative chromosome was acquired from early puberty to late adolescence, followed by the emergence of a common ancestor by the patient's early 30s, from which both cancer and non-cancer clones evolved. Replacing the pre-existing mammary epithelium in the following years, these clones occupied a large area within the premenopausal breast tissues by the time of cancer diagnosis. Evolution of multiple independent cancer founders from the non-cancer ancestors was common, contributing to intratumour heterogeneity. The number of driver events did not correlate with histology, suggesting the role of local microenvironments and/or epigenetic driver events. A similar evolutionary pattern was also observed in another case evolving from an AKT1-mutated founder. Taken together, our findings provide new insight into how breast cancer evolves.

Mutation detection of urinary cell-free DNA via catch-and-release isolation on nanowires for liquid biopsy.

Cell-free DNA (cfDNA) and extracellular vesicles (EVs) are molecular biomarkers in liquid biopsies that can be applied for cancer detection, which are known to carry information on the necessary conditions for oncogenesis and cancer cell-specific activities after oncogenesis, respectively. Analyses for both cfDNA and EVs from the same body fluid can provide insights into screening and identifying the molecular subtypes of cancer; however, a major bottleneck is the lack of efficient and standardized techniques for the isolation of cfDNA and EVs from clinical specimens. Here, we achieved catch-and-release isolation by hydrogen bond-mediated binding of cfDNA in urine to zinc oxide (ZnO) nanowires, which also capture EVs by surface charge, and subsequently we identified genetic mutations in urinary cfDNA. The binding strength of hydrogen bonds between single-crystal ZnO nanowires and DNA was found to be equal to or larger than that of conventional hydrophobic interactions, suggesting the possibility of isolating trace amounts of cfDNA. Our results demonstrated that nanowire-based cancer screening assay can screen cancer and can identify the molecular subtypes of cancer in urine from brain tumor patients through EV analysis and cfDNA mutation analysis. We anticipate our method to be a starting point for more sophisticated diagnostic models of cancer screening and identification.

Clinical characteristics and radiological features of glioblastoma, IDH-wildtype, grade 4 with histologically lower-grade gliomas.

The 2021 World Health Organization (WHO) classification of central nervous system tumors applied molecular criteria and further integrated histological and molecular diagnosis of gliomas. This classification allows for the diagnosis of isocitrate dehydrogenase wild-type (IDHwt) glioblastoma (GBM), and WHO grade 4 with histologically lower-grade gliomas (LrGGs), even in the absence of high-grade histopathologic features, such as necrosis and/or microvascular proliferation. They contain at least one of the following molecular features: epidermal growth factor receptor amplification, chromosome 7 gain/10 loss, or telomerase reverse transcriptase promoter mutation. In the imaging features at the time of histological diagnosis, a gliomatosis cerebri growth pattern was frequently observed in these tumors. Furthermore, this growth pattern was significantly higher in IDHwt GBM, WHO grade 4, with histological grade II gliomas. Although the exact prognosis of IDHwt GBM, WHO grade 4, with histologically LGGs remains unknown, its OS was approximately 1-2 years similar to that of histologically IDHwt GBM, WHO grade 4, despite histopathological features similar to IDHmut LrGGs. These findings reinforce the need for the analysis of molecular features, regardless of presenting similar clinical characteristics and imaging features to IDHmut LrGGs.

Efficacy and safety of bevacizumab, irinotecan, and temozolomide combination for relapsed or refractory pediatric central nervous system embryonal tumor: a single-institution study.

OBJECTIVE: This study aimed to evaluate the efficacy and safety of combination therapy with bevacizumab (Bev), irinotecan (CPT-11), and temozolomide (TMZ) in children with central nervous system (CNS) embryonal tumor relapse. METHODS: The authors retrospectively examined 13 consecutive pediatric patients with relapsed or refractory CNS embryonal tumors who received combination therapy comprising Bev, CPT-11, and TMZ. Specifically, 9 patients had medulloblastoma, 3 had atypical teratoid/rhabdoid tumor (AT/RT), and 1 had CNS embryonal tumor with rhabdoid features. Of the 9 medulloblastoma cases, 2 were categorized in the Sonic hedgehog subgroup and 6 in molecular subgroup 3 for medulloblastoma. RESULTS: The complete and partial objective response rates were 66.6% in patients with medulloblastoma and 75.0% in patients with AT/RT or CNS embryonal tumors with rhabdoid features. Furthermore, the 12- and 24-month progression-free survival rates were 69.2% and 51.9% for all patients with recurrent or refractory CNS embryonal tumors, respectively. In contrast, the 12- and 24-month overall survival rates were 67.1% and 58.7%, respectively, for all patients with relapsed or refractory CNS embryonal tumors. The authors observed grade 3 neutropenia, thrombocytopenia, proteinuria, hypertension, diarrhea, and constipation in 23.1%, 7.7%, 23.1%, 7.7%, 7.7%, and 7.7% of patients, respectively. Furthermore, grade 4 neutropenia was observed in 7.1% of patients. Nonhematological adverse effects, such as nausea and constipation, were mild and controlled with standard antiemetics. CONCLUSIONS: This study demonstrated favorable survival outcomes in patients with relapsed or refractory pediatric CNS embryonal tumors and thus helped to investigate the efficacy of combination therapy comprising Bev, CPT-11, and TMZ. Moreover, combination chemotherapy had high objective response rates, and all adverse events were tolerable. To date, data supporting the efficacy and safety of this regimen in the relapsed or refractory AT/RT population are limited. These findings suggest the potential efficacy and safety of combination chemotherapy in patients with relapsed or refractory pediatric CNS embryonal tumors.

Easy-to-use machine learning system for the prediction of IDH mutation and 1p/19q codeletion using MRI images of adult-type diffuse gliomas.

Adult-type diffuse gliomas are divided into Astrocytoma, IDH-mutant, Oligodendroglioma, IDH-mutant and 1p/19q-codeleted and Glioblastoma, IDH-wildtype based on the IDH mutation, and 1p/19q codeletion status. To determine the treatment strategy for these tumors, pre-operative prediction of IDH mutation and 1p/19q codeletion status might be effective. Computer-aided diagnosis (CADx) systems using machine learning have been noted as innovative diagnostic methods. However, it is difficult to promote the clinical application of machine learning systems at each institute because the support of various specialists is essential. In this study, we established an easy-to-use computer-aided diagnosis system using Microsoft Azure Machine Learning Studio (MAMLS) to predict these statuses. We constructed an analysis model using 258 adult-type diffuse glioma cases from The Cancer Genome Atlas (TCGA) cohort. Using MRI T2-weighted images, the overall accuracy, sensitivity, and specificity for the prediction of IDH mutation and 1p/19q codeletion were 86.9%, 80.9%, and 92.0%, and 94.7%, 94.1%, and 95.1%, respectively. We also constructed an reliable analysis model for the prediction of IDH mutation and 1p/19q codeletion using an independent Nagoya cohort including 202 cases. These analysis models were established within 30 min. This easy-to-use CADx system might be useful for the clinical application of CADx in various institutes.

Rapid detection of the MYD88 L265P mutation for pre- and intra-operative diagnosis of primary central nervous system lymphoma.

The myeloid differentiation primary response gene 88 (MYD88) L265P mutation is a disease-specific mutation of primary central nervous system lymphoma (PCNSL) among the central nervous system tumors. Accordingly, this mutation is considered a reliable diagnostic molecular marker of PCNSL. As the intra-operative diagnosis of PCNSL is sometimes difficult to achieve using histological examinations alone, intra-operative detection of the MYD88 L265P mutation could be effective for the accurate diagnosis of PCNSL. Herein, we aimed to develop a novel rapid genotyping system (GeneSoC) using real-time polymerase chain reaction (PCR) based on microfluidic thermal cycling technology. This real-time PCR system shortened the analysis time, which enabled the detection of the MYD88 L265P mutation within 15 min. Rapid detection of the MYD88 L265P mutation was performed intra-operatively using GeneSoC in 24 consecutive cases with suspected malignant brain tumors, including 10 cases with suspected PCNSL before surgery. The MYD88 L265P mutation was detected in eight cases in which tumors were pathologically diagnosed as PCNSL after the operation, while wild-type MYD88 was detected in 16 cases. Although two of the 16 cases with wild-type MYD88 were pathologically diagnosed as PCNSL after the operation, MYD88 L265P could be detected in all eight PCNSL cases harboring MYD88 L265P. The MYD88 L265P mutation could also be detected using cell-free DNA derived from the cerebrospinal fluid of two PCNSL cases. Detection of the MYD88 L265P mutation using GeneSoC might not only improve the accuracy of intra-operative diagnosis of PCNSL but also help the future pre-operative diagnosis through liquid biopsy of cerebrospinal fluid.

All-in-One Nanowire Assay System for Capture and Analysis of Extracellular Vesicles from an ex Vivo Brain Tumor Model.

Extracellular vesicles (EVs) have promising potential as biomarkers for early cancer diagnosis. The EVs have been widely studied as biological cargo containing essential biological information not only from inside vesicles such as nucleic acids and proteins but also from outside vesicles such as membrane proteins and glycolipids. Although various methods have been developed to isolate EVs with high yields such as captures based on density, size, and immunoaffinity, different measurement systems are needed to analyze EVs after isolation, and a platform that enables all-in-one analysis of EVs from capture to detection in multiple samples is desired. Since a nanowire-based approach has shown an effective capability for capturing EVs via surface charge interaction compared to other conventional methods, here, we upgraded the conventional well plate assay to an all-in-one nanowire-integrated well plate assay system (i.e., a nanowire assay system) that enables charge-based EV capture and EV analysis of membrane proteins. We applied the nanowire assay system to analyze EVs from brain tumor organoids in which tumor environments, including vascular formations, were reconstructed, and we found that the membrane protein expression ratio of CD31/CD63 was 1.42-fold higher in the tumor organoid-derived EVs with a p-value less than 0.05. Furthermore, this ratio for urine samples from glioblastoma patients was 2.25-fold higher than that from noncancer subjects with a p-value less than 0.05 as well. Our results demonstrated that the conventional well plate method integrated with the nanowire-based EV capture approach allows users not only to capture EVs effectively but also to analyze them in one assay system. We anticipate that the all-in-one nanowire assay system will be a powerful tool for elucidating EV-mediated tumor-microenvironment crosstalk.

Imaging features of localized IDH wild-type histologically diffuse astrocytomas: a single-institution case series.

Isocitrate dehydrogenase wild-type (IDHwt) diffuse astrocytomas feature highly infiltrative patterns, such as a gliomatosis cerebri growth pattern with widespread involvement. Among these tumors, localized IDHwt histologically diffuse astrocytomas are rarer than the infiltrative type. The aim of this study was to assess and describe the clinical, radiographic, histopathological, and molecular characteristics of this rare type of IDHwt histologically diffuse astrocytomas and thereby provide more information on how its features affect clinical prognoses and outcomes. We retrospectively analyzed the records of five patients with localized IDHwt histologically diffuse astrocytomas between July 2017 and January 2020. All patients were female, and their mean age at the time of the initial treatment was 55.0 years. All patients had focal disease that did not include gliomatosis cerebri or multifocal disease. All patients received a histopathological diagnosis of diffuse astrocytomas at the time of the initial treatment. For recurrent tumors, second surgeries were performed at a mean of 12.4 months after the initial surgery. A histopathological diagnosis of glioblastoma was made in four patients and one of gliosarcoma in one patient. The initial status of IDH1, IDH2, H3F3A, HIST1H3B, and BRAF was "wild-type" in all patients. TERT promoter mutations (C250T or C228T) were detected in four patients. No tumors harbored a 1p/19q codeletion, EGFR amplification, or chromosome 7 gain/10 loss (+ 7/ - 10). We assessed clinical cases of localized IDHwt histologically diffuse astrocytomas that resulted in malignant recurrence and a poor clinical prognosis similar to that of glioblastomas. Our case series suggests that even in patients with histologically diffuse astrocytomas and those who present with radiographic imaging findings suggestive of a localized tumor mass, physicians should consider the possibility of IDHwt histologically diffuse astrocytomas.

CD79B Y196 mutation is a potent predictive marker for favorable response to R-MPV in primary central nervous system lymphoma.

BACKGROUND: Rituximab, high-dose methotrexate (HD-MTX), procarbazine and vincristine (R-MPV), has significantly prolonged the survival of patients with primary central nervous system lymphoma (PCNSL), but predictive factors for response to R-MPV have not yet been investigated. Herein, we investigated the correlation of MYD88 L265P and CD79B Y196 mutations, which are the most frequently found molecular alterations in PCNSL, with prognosis of patients with PCNSL treated with R-MPV. METHODS: We investigated the long-term clinical course and status of MYD88 and CD79B genes in 85 patients with PCNSL treated with R-MPV or HD-MTX treatment, and the correlation of these genetic mutations with prognosis. RESULTS: R-MPV achieved an excellent tumor control rate (61.6% and 69.9% of 5-year progression-free and overall survival rates, respectively). While MYD88 L265P mutation had no significant effect on survival, patients with CD79B Y196 mutations exhibited prolonged survival (p < 0.05). However, the association of CD79B Y196 mutation with a better prognosis was not observed in the HD-MTX cohort, which indicated that CD79B Y196 mutation was a predictive marker for a favorable response to R-MPV. Furthermore, we established an all-in-one rapid genotyping system for these genetic mutations. CONCLUSIONS: In conclusion, CD79B Y196 mutation is a potent predictive marker for favorable response to R-MPV in PCNSL. The rapid identification of MYD88 L265P and CD79B Y196 mutations can be helpful not only for the accurate molecular diagnosis of PCNSL but also for the prediction of response to R-MPV.

Characteristic DNA methylation profiles of chorionic villi in recurrent miscarriage.

Dysregulation of transcriptional programs that are tightly regulated by DNA methylation during placental and fetal development at different gestational stages, may cause recurrent miscarriage. Here, we examined genome-wide DNA methylation in chorionic villi and decidual tissues from patients suffering RM and from healthy women who had undergone artificial abortion (n = 5 each). We found that 13,426 and 5816 CpG sites were differentially methylated in chorionic villi and decidua, respectively. DNA methylation profiles of chorionic villi, but not decidua, in RM patients was clearly distinct from AA controls. Among the differentially methylated genes, the enhancer region of SPATS2L was significantly more highly methylated in RM patients (n = 19) than AA controls (n = 19; mean methylation level, 52.0%-vs.-28.9%, P < 0.001), resulting in reduced expression of SPATS2L protein in the former. Functionally, depletion of SPATS2L in extravillous trophoblast cells decreased their invasion and migration abilities. Our data indicate that particularly the chorionic villi in RM patients exhibit distinct DNA methylation profiles compared with normal pregnancies and that this changed DNA methylation status may impede the progression of embryo development via the altered expression of genes such as SPATS2L in the villi.

Supratotal Resection of Gliomas With Awake Brain Mapping: Maximal Tumor Resection Preserving Motor, Language, and Neurocognitive Functions.

Gliomas are a category of infiltrating glial neoplasms that are often located within or near the eloquent areas involved in motor, language, and neurocognitive functions. Surgical resection being the first-line treatment for gliomas, plays a crucial role in patient outcome. The role of the extent of resection (EOR) was evaluated, and we reported significant correlations between a higher EOR and better clinical prognosis of gliomas. However, recurrence is inevitable, even after aggressive tumor removal. Thus, efforts have been made to achieve extended tumor resection beyond contrast-enhanced mass lesions in magnetic resonance imaging (MRI)-defined areas, a process known as supratotal resection. Since it has been reported that tumor cells invade beyond regions visible as abnormal areas on MRI, imaging underestimates the true spatial extent of tumors. Furthermore, tumor cells have the potential to spread 10-20 mm away from the MRI-verified tumor boundary. The primary goal of supratotal resection is to maximize EOR and prolong the progression-free and overall survival of patients with gliomas. The available data, as well as our own work, clearly show that supratotal resection of gliomas is a feasible technique that has improved with the aid of awake functional mapping using intraoperative direct electrical stimulation. Awake brain mapping has enabled neurosurgeons achieve supratotal resection with favorable motor, language, and neurocognitive outcomes, ensuring a better quality of life in patients with gliomas.

The landscape of genetic aberrations in myxofibrosarcoma.

Myxofibrosarcoma (MFS) is a rare subtype of sarcoma, whose genetic basis is poorly understood. We analyzed 69 MFS cases using whole-genome (WGS), whole-exome (WES) and/or targeted-sequencing (TS). Newly sequenced genomic data were combined with additional deposited 116 MFS samples. WGS identified a high number of structural variations (SVs) per tumor most frequently affecting the TP53 and RB1 loci, 40% of tumors showed a BRCAness-associated mutation signature, and evidence of chromothripsis was found in all cases. Most frequently mutated/copy number altered genes affected known disease drivers such as TP53 (56.2%), CDKN2A/B (29.7%), RB1 (27.0%), ATRX (19.5%) and HDLBP (18.9%). Several previously unappreciated genetic aberrations including MUC17, FLG and ZNF780A were identified in more than 20% of patients. Longitudinal analysis of paired diagnosis and relapse time points revealed a 1.2-fold mutation number increase accompanied with substantial changes in clonal composition over time. Our study highlights the genetic complexity underlying sarcomagenesis of MFS.

Reliability of IDH1-R132H and ATRX and/or p53 immunohistochemistry for molecular subclassification of Grade 2/3 gliomas.

Since the World Health Organization 2016 classification (2016 WHO), genetic status has been incorporated into the diagnosis of Grade 2/3 gliomas (lower-grade gliomas). Therefore, immunohistochemistry (IHC) of IDH1-R132H, ATRX, and p53 have been used in place of genetic status. We report the associations between histological findings, IHC, and genetic status. We performed IHC of IDH1-R132H, ATRX, and p53 in 76 lower-grade gliomas and discussed its validity based on the 2016 WHO and the upcoming 2021 WHO classification. The sensitivity and specificity of anti-ATRX, p53, and IDH1-R132H IHC were 40.9%/98.1%, 78.6%/85.4%, and 90.5%/84.6%, respectively. Among 21 IDH1-mutant gliomas without 1p/19q codeletion, two gliomas (9.5%) mimicked the so-called classic for oligodendroglioma (CFO) in their morphology. Of the 42 gliomas with 1p/19q codeletion, four cases were difficult to diagnose as oligodendroglioma through morphological examination. Moreover, there were three confusing cases with ATRX mutations but with retained ATRX-IHC positivity. The lessons learned from this study are as follows: (1) ATRX-IHC and p53-IHC should be supplementary to morphological diagnosis, (2) rare IDH mutations other than IDH1 R132H should be considered, and (3) there is no complete alternative test to detect molecular features of glioblastoma under the 2021 WHO classification.

Synthesis and structure of a phosphinoboronic ester in a fused bicyclic framework.

The first phosphinoboronic ester bearing a fused bicyclic framework was synthesised by either deprotonation and hydride abstraction or Rh-catalysed dehydrogenation of a hydrophosphineboronic ester. The phosphinoboronic ester reacted as a Lewis acid with KF/18-crown-6, pyridine and DMAP to give the corresponding adducts. Furthermore, its crystal structure shows a remarkably short P-B bond in comparison with other P-B bonded derivatives in spite of the trigonal pyramidal geometry of the phosphorus. Consistent with the phosphorus pyramidality, the π-type donor-acceptor interaction of the P-B bond is small as revealed by the DFT calculations. The P-B bond shared within the fused six-membered rings has to shorten because of the geometrical requirement and high s-character of the boron.