Venous Malformation in the Anterior Mediastinum.

Venous malformations (VMs) located in the anterior mediastinum are rare. Thus, diagnosis using imaging is often challenging, and they are typically diagnosed only after total tumor resection. Herein, we report a case of VM located in the anterior mediastinum diagnosed using computed tomography (CT) and magnetic resonance imaging (MRI). A 56-year-old woman presented for further evaluation of an anterior mediastinal mass observed during a chest CT. On CT, the mass was observed to have scattered calcifications and early and persistent enhancement with contrast material pooling dorsally in the delayed phase. On MRI, the mass was isointense on T1-weighted imaging and hyperintense on T2-weighted imaging without flow voids. From these images, we suspected the mass to be a VM, but the possibility of an arterial malformation/fistula could not be ruled out. Initially, a contrast material was injected via the arm, but to improve differentiation, it was also injected via the leg. The 4D-CT of the leg indicated no early enhancement of the mass; however, gradual enhancement was observed. This led to a definite diagnosis of VM. As she had no symptoms, we opted for a CT follow-up, and the mass remained stable for one year post-diagnosis. This case report underscores the usefulness of injecting contrast material through the leg in distinguishing VM from AVM/Fs in the anterior mediastinum.

Automatic Detection and Measurement of Renal Cysts in Ultrasound Images: A Deep Learning Approach.

Ultrasonography is widely used for diagnosis of diseases in internal organs because it is nonradioactive, noninvasive, real-time, and inexpensive. In ultrasonography, a set of measurement markers is placed at two points to measure organs and tumors, then the position and size of the target finding are measured on this basis. Among the measurement targets of abdominal ultrasonography, renal cysts occur in 20-50% of the population regardless of age. Therefore, the frequency of measurement of renal cysts in ultrasound images is high, and the effect of automating measurement would be high as well. The aim of this study was to develop a deep learning model that can automatically detect renal cysts in ultrasound images and predict the appropriate position of a pair of salient anatomical landmarks to measure their size. The deep learning model adopted fine-tuned YOLOv5 for detection of renal cysts and fine-tuned UNet++ for prediction of saliency maps, representing the position of salient landmarks. Ultrasound images were input to YOLOv5, and images cropped inside the bounding box and detected from the input image by YOLOv5 were input to UNet++. For comparison with human performance, three sonographers manually placed salient landmarks on 100 unseen items of the test data. These salient landmark positions annotated by a board-certified radiologist were used as the ground truth. We then evaluated and compared the accuracy of the sonographers and the deep learning model. Their performances were evaluated using precision-recall metrics and the measurement error. The evaluation results show that the precision and recall of our deep learning model for detection of renal cysts are comparable to standard radiologists; the positions of the salient landmarks were predicted with an accuracy close to that of the radiologists, and in a shorter time.

Acute Kidney Injury in Non-Intensive Care and Intensive Care Patients Treated with Vancomycin and Piperacillin-Tazobactam.

BACKGROUND: We investigated the incidence of acute kidney injury (AKI) and risk factors associated with vancomycin (VAN) and piperacillin-tazobactam (TZP) combination therapy in non-intensive care unit (ICU) and ICU settings. METHODS: In this single-center retrospective cohort study, adults who received VAN for ≥48 h during the period from 1 January 2016 through 31 December 2017 were included. The primary endpoint was incidence of AKI. RESULTS: Data from 593 adults were analyzed. The incidence of AKI was 10.6% overall, 8.0% in the non-TZP group, and 19.8% in the TZP group. In univariate analysis, the odds ratio (OR) for AKI was higher in the TZP group than in the non-TZP group (2.84, 95% CI = 1.64-4.90). In both the non-ICU and ICU settings, the OR for AKI was higher in the TZP group than in the non-TZP group (non-ICU: OR = 3.04, 95% CI = 1.52-6.09; ICU: OR = 2.51, 95% CI = 1.03-6.08). Furthermore, in propensity score analysis, the OR for AKI was higher in the TZP group than in the non-TZP group (OR = 2.81, 95% CI = 1.52-5.17). In both the non-ICU and ICU settings, the OR for AKI was higher in the TZP group than in the non-TZP group (non-ICU: OR = 2.57, 95% CI = 1.17-5.64; ICU: OR = 3.51, 95% CI = 1.05-11.6). CONCLUSIONS: Combined use of TZP in patients receiving VAN increased AKI incidence in non-ICU and ICU settings.

Malignancy Index Using Intraoperative Flow Cytometry is a Valuable Prognostic Factor for Glioblastoma Treated With Radiotherapy and Concomitant Temozolomide.

BACKGROUND: Intraoperative prediction of radiochemosensitivity is desirable for improving the clinical management of glioblastoma (GBM) patients. We have previously developed an original technique for intraoperative flow cytometry (iFC) and defined a malignancy index (MI). OBJECTIVE: To determine whether MI correlates with prognosis in GBM patients who underwent the standard treatment protocol of radiotherapy and temozolomide administration. METHODS: The current study included 102 patients with GBM that had been newly diagnosed from 2010 to 2015 who underwent our iFC analysis and received the standard treatment protocol. We evaluated MI values in each patient, then statistically analyzed the relationship between MI and prognosis using survival analysis that include other clinicopathological factors (age, sex, Karnofsky performance status [KPS], extent of resection, second-line bevacizumab, O6-methylguanine-DNA methyltransferase [MGMT] status, MIB-1 labeling index, and mutation of the isocitrate dehydrogenase 1 gene [IDH1]). RESULTS: Log-rank test revealed that age, KPS, extent of resection, MGMT status, IDH1 mutation, and high MI (≥26.3%) significantly correlated with overall survival. Multivariate analysis with Cox regression modeling identified MI as the most significant prognostic factor (hazard ratio = 2.246; 95% confidence interval = 1.347-3.800; P = .0019). MI showed strong correlation with IDH1 mutation status in chi-square test (P = .0023). In addition, log-rank test revealed that MI affects overall survival more strongly in patients with IDH1 wildtype than those with IDH1 mutant. CONCLUSION: MI from an iFC study may help predict the prognosis in patients with GBM who receive the standard treatment. Survival can be related to sensitivity to radio-chemotherapy.

Role of photodynamic therapy using talaporfin sodium and a semiconductor laser in patients with newly diagnosed glioblastoma.

OBJECTIVE: In this study on the effectiveness and safety of photodynamic therapy (PDT) using talaporfin sodium and a semiconductor laser, the long-term follow-up results of 11 patients with glioblastoma enrolled in the authors' previous phase II clinical trial (March 2009-2012) and the clinical results of 19 consecutive patients with newly diagnosed glioblastoma prospectively enrolled in a postmarket surveillance (March 2014-December 2016) were analyzed and compared with those of 164 patients treated without PDT during the same period. METHODS: The main outcome measures were the median overall survival (OS) and progression-free survival (PFS) times. Moreover, the adverse events and radiological changes after PDT, as well as the patterns of recurrence, were analyzed and compared between the groups. Kaplan-Meier curves were created to assess the differences in OS and PFS between the groups. Univariate and multivariate analyses were performed to identify the prognostic factors, including PDT, among patients with newly diagnosed glioblastoma. RESULTS: The median PFS times of the PDT and control groups were 19.6 and 9.0 months, with 6-month PFS rates of 86.3% and 64.9%, respectively (p = 0.016). The median OS times were 27.4 and 22.1 months, with 1-year OS rates of 95.7% and 72.5%, respectively (p = 0.0327). Multivariate analyses found PDT, preoperative Karnofsky Performance Scale score, and IDH mutation to be significant independent prognostic factors for both OS and PFS. Eighteen of 30 patients in the PDT group experienced tumor recurrence, including local recurrence, distant recurrence, and dissemination in 10, 3, and 4 patients, respectively. Conversely, 141 of 164 patients in the control group experienced tumor recurrence, including 101 cases of local recurrence. The rate of local recurrence tended to be lower in the PDT group (p = 0.06). CONCLUSIONS: The results of the present study suggest that PDT with talaporfin sodium and a semiconductor laser provides excellent local control, with few adverse effects even in cases of multiple laser irradiations, as well as potential survival benefits for patients with newly diagnosed glioblastoma.

A surgical strategy for lower grade gliomas using intraoperative molecular diagnosis.

Lower grade gliomas are both treated and diagnosed via surgical resection. Maximum tumor resection is currently the standard of care; however, this risks the loss of brain function. Glioma can be genetically subdivided into three different types, based on isocitrate dehydrogenase (IDH) mutation status and the presence of 1p/19q codeletion, which have radically different prognoses and responses to adjuvant therapies. Therefore, the means to identify the subtype and evaluate the surrounding tissues during surgery would be advantageous. In this study, we have developed a new surgical strategy for lower grade glioma based on the fourth edition of the World Health Organization Brain Tumor Classification, involving intraoperative molecular diagnosis. High-resolution melting analysis was used to evaluate IDH mutational status, while rapid immunohistochemistry of p53 and alpha-thalassemia/mental retardation syndrome X-linked (ATRX) was used to evaluate the 1p/19q codeletion status, allowing genetic classification during surgery. In addition, intraoperative flow cytometry was used to evaluate the surgical cavity for additional tumor lesions, allowing maximal resection while mitigating the risk of functional losses. This strategy allows the rapid intraoperative diagnosis and mapping of lower grade gliomas, and its clinical use could dramatically improve its prognosis.

Hydrogen Gas Inhalation Treatment in Acute Cerebral Infarction: A Randomized Controlled Clinical Study on Safety and Neuroprotection.

BACKGROUND: Molecular hydrogen (H2) acts as a therapeutic antioxidant. Inhalation of H2 gas (1-4%) was effective for the improvement of cerebral infarction in multiple animal experiments. Thus, for actual applications, a randomized controlled clinical study is desired to evaluate the effects of inhalation of H2 gas. Here, we evaluate the H2 treatment on acute cerebral infarction. METHODS: Through this randomized controlled clinical study, we assessed the safety and effectiveness of H2 treatment in patients with cerebral infarction in an acute stage with mild- to moderate-severity National Institute of Health Stroke Scale (NIHSS) scores (NIHSS = 2-6). We enrolled 50 patients (25 each in the H2 group and the control group) with a therapeutic time window of 6 to 24 hours. The H2 group inhaled 3% H2 gas (1 hour twice a day), and the control group received conventional intravenous medications for the initial 7 days. The evaluations included daily vital signs, NIHSS scores, physical therapy indices, weekly blood chemistry, and brain magnetic resonance imaging (MRI) scans over the 2-week study period. RESULTS: The H2 group showed no significant adverse effects with improvements in oxygen saturation. The following significant effects were found: the relative signal intensity of MRI, which indicated the severity of the infarction site, NIHSS scores for clinically quantifying stroke severity, and physical therapy evaluation, as judged by the Barthel Index. CONCLUSIONS: H2 treatment was safe and effective in patients with acute cerebral infarction. These results suggested a potential for widespread and general application of H2 gas.

Bevacizumab changes vascular structure and modulates the expression of angiogenic factors in recurrent malignant gliomas.

Bevacizumab (BV), a monoclonal antibody against vascular endothelial growth factor (VEGF), is currently used in the treatment of malignant glioma. To understand mechanisms of resistance to BV, we investigated morphological changes in tumor vessels and expression of angiogenic factors, such as VEGF, Flt-1, basic fibroblast growth factor (bFGF), and platelet-derived growth factor-BB (PDGF-BB), in four autopsied tumors after BV treatment. Three patients had glioblastomas; the fourth had a secondary glioblastoma that developed from a diffuse astrocytoma. BV was administered because of recurrence following the use of the Stupp regimen in these four patients. We compared the initial surgical specimen with that obtained after death following BV treatment. Immunohistochemical staining of the autopsied tumors showed that Flt-1 expression increased while VEGF expression was significantly reduced. Additionally, other angiogenic factors, particularly bFGF, were enhanced. Interestingly, the proliferation of endothelial cells was reduced, but remarkable proliferation of pericytes was observed. These results suggest that following BV treatment, glioblastomas can grow tumor vessels by expressing various angiogenic factors. These mechanisms might be important for rapid regrowth and blood brain barrier repair after BV treatment. Inhibition of multiple angiogenic factors will be required to control tumor vessels in glioblastoma.

Proposed therapeutic strategy for adult low-grade glioma based on aggressive tumor resection.

OBJECT There is no standard therapeutic strategy for low-grade glioma (LGG). The authors hypothesized that adjuvant therapy might not be necessary for LGG cases in which total radiological resection was achieved. Accordingly, they established a treatment strategy based on the extent of resection (EOR) and the MIB-1 index: patients with a high EOR and low MIB-1 index were observed without postoperative treatment, whereas those with a low EOR and/or high MIB-1 index received radiotherapy (RT) and/or chemotherapy. In the present retrospective study, the authors reviewed clinical data on patients with primarily diagnosed LGGs who had been treated according to the above-mentioned strategy, and they validated the treatment policy. Given their results, they will establish a new treatment strategy for LGGs stratified by EOR, histological subtype, and molecular status. METHODS One hundred fifty-three patients with diagnosed LGG who had undergone resection or biopsy at Tokyo Women's Medical University between January 2000 and August 2010 were analyzed. The patients consisted of 84 men and 69 women, all with ages ≥ 15 years. A total of 146 patients underwent surgical removal of the tumor, and 7 patients underwent biopsy. RESULTS Postoperative RT and nitrosourea-based chemotherapy were administered in 48 and 35 patients, respectively. Extent of resection was significantly associated with both overall survival (OS; p = 0.0096) and progression-free survival (PFS; p = 0.0007) in patients with diffuse astrocytoma but not in those with oligodendroglial subtypes. Chemotherapy significantly prolonged PFS, especially in patients with oligodendroglial subtypes (p = 0.0009). Patients with a mutant IDH1 gene had significantly longer OS (p = 0.034). Multivariate analysis did not identify MIB-1 index or RT as prognostic factors, but it did identify chemotherapy as a prognostic factor for PFS and EOR as a prognostic factor for OS and PFS. CONCLUSIONS The findings demonstrated that EOR was significantly correlated with patient survival; thus, one should aim for maximum tumor resection. In addition, patients with a higher EOR can be safely observed without adjuvant therapy. For patients with partial resection, postoperative chemotherapy should be administered for those with oligodendroglial subtypes, and repeat resection should be considered for those with astrocytic tumors. More aggressive treatment with RT and chemotherapy may be required for patients with a poor prognosis, such as those with diffuse astrocytoma, 1p/19q nondeleted tumors, or IDH1 wild-type oligodendroglial tumors with partial resection.

Intraoperative cortico-cortical evoked potentials for the evaluation of language function during brain tumor resection: initial experience with 13 cases.

OBJECTIVES: The objective in the present study was to evaluate the usefulness of cortico-cortical evoked potentials (CCEP) monitoring for the intraoperative assessment of speech function during resection of brain tumors. METHODS: Intraoperative monitoring of CCEP was applied in 13 patients (mean age 34 ± 14 years) during the removal of neoplasms located within or close to language-related structures in the dominant cerebral hemisphere. For this purpose strip electrodes were positioned above the frontal language area (FLA) and temporal language area (TLA), which were identified with direct cortical stimulation and/or preliminary mapping with the use of implanted chronic subdural grid electrodes. The CCEP response was defined as the highest observed negative peak in either direction of stimulation. In 12 cases the tumor was resected during awake craniotomy. RESULTS: An intraoperative CCEP response was not obtained in one case because of technical problems. In the other patients it was identified from the FLA during stimulation of the TLA (7 cases) and from the TLA during stimulation of the FLA (5 cases), with a mean peak latency of 83 ± 15 msec. During tumor resection the CCEP response was unchanged in 5 cases, decreased in 4, and disappeared in 3. Postoperatively, all 7 patients with a decreased or absent CCEP response after lesion removal experienced deterioration in speech function. In contrast, in 5 cases with an unchanged intraoperative CCEP response, speaking abilities after surgery were preserved at the preoperative level, except in one patient who experienced not dysphasia, but dysarthria due to pyramidal tract injury. This difference was statistically significant (p < 0.01). The time required to recover speech function was also significantly associated with the type of intraoperative change in CCEP recordings (p < 0.01) and was, on average, 1.8 ± 1.0, 5.5 ± 1.0, and 11.0 ± 3.6 months, respectively, if the response was unchanged, was decreased, or had disappeared. CONCLUSIONS: Monitoring CCEP is feasible during the resection of brain tumors affecting language-related cerebral structures. In the intraoperative evaluation of speech function, it can be a helpful adjunct or can be used in its direct assessment with cortical and subcortical mapping during awake craniotomy. It can also be used to predict the prognosis of language disorders after surgery and decide on the optimal resection of a neoplasm.

Updated therapeutic strategy for adult low-grade glioma stratified by resection and tumor subtype.

The importance of surgical resection for patients with supratentorial low-grade glioma (LGG) remains controversial. This retrospective study of patients (n = 153) treated between 2000 to 2010 at a single institution assessed whether increasing the extent of resection (EOR) was associated with improved progression-free survival (PFS) and overall survival (OS). Histological subtypes of World Health Organization grade II tumors were as follows: diffuse astrocytoma in 49 patients (32.0%), oligoastrocytoma in 45 patients (29.4%), and oligodendroglioma in 59 patients (38.6%). Median pre- and postoperative tumor volumes and median EOR were 29.0 cm(3) (range 0.7-162 cm(3)) and 1.7 cm(3) (range 0-135.7 cm(3)) and 95%, respectively. Five- and 10-year OS for all LGG patients were 95.1% and 85.4%, respectively. Eight-year OS for diffuse astrocytoma, oligoastrocytoma, and oligodendroglioma were 70.7%, 91.2%, and 98.3%, respectively. Five-year PFS for diffuse astrocytoma, oligoastrocytoma, and oligodendroglioma were 42.6%, 71.3%, and 62.7%, respectively. Patients were divided into two groups by EOR ≥90% and <90%, and OS and PFS were analyzed. Both OS and PFS were significantly longer in patients with ≥90% EOR. Increased EOR resulted in better PFS for diffuse astrocytoma but not for oligodendroglioma. Multivariate analysis identified age and EOR as parameters significantly associated with OS. The only parameter associated with PFS was EOR. Based on these findings, we established updated therapeutic strategies for LGG. If surgery resulted in EOR <90%, patients with astrocytoma will require second-look surgery, whereas patients with oligodendroglioma or oligoastrocytoma, which are sensitive to chemotherapy, will be treated with chemotherapy.

Complement inhibitor prevents disruption of sodium channel clusters in a rabbit model of Guillain-Barré syndrome.

Complement-mediated disruption of voltage-gated sodium channels at the nodes of Ranvier acts in the development of acute motor axonal neuropathy. Nafamostat mesilate, a synthetic serine protease inhibitor, used in clinical practice for more than 20 years, has anti-complement activity. Acute motor axonal neuropathy rabbits obtained by GM1 ganglioside sensitization were or were not given nafamostat mesilate intravenously. Complement deposition and sodium channel disruption in the spinal anterior roots were significantly less frequent in the treated rabbits than in the controls. Nafamostat mesilate inhibited complement deposition and prevented sodium channel disruption. This provided the rationale for a clinical trial.

Anti-GM1 antibodies cause complement-mediated disruption of sodium channel clusters in peripheral motor nerve fibers.

Voltage-gated Na+ (Na(v)) channels are highly concentrated at nodes of Ranvier in myelinated axons and facilitate rapid action potential conduction. Autoantibodies to gangliosides such as GM1 have been proposed to disrupt nodal Nav channels and lead to Guillain-Barré syndrome, an autoimmune neuropathy characterized by acute limb weakness. To test this hypothesis, we examined the molecular organization of nodes in a disease model caused by immunization with gangliosides. At the acute phase with progressing limb weakness, Na(v) channel clusters were disrupted or disappeared at abnormally lengthened nodes concomitant with deposition of IgG and complement products. Paranodal axoglial junctions, the nodal cytoskeleton, and Schwann cell microvilli, all of which stabilize Na(v) channel clusters, were also disrupted. The nodal molecules disappeared in lesions with complement deposition but no localization of macrophages. During recovery, complement deposition at nodes decreased, and Na(v) channels redistributed on both sides of affected nodes. These results suggest that Na(v) channel alterations occur as a consequence of complement-mediated disruption of interactions between axons and Schwann cells. Our findings support the idea that acute motor axonal neuropathy is a disease that specifically disrupts the nodes of Ranvier.