Acto3D: an open-source user-friendly volume rendering software for high-resolution 3D fluorescence imaging in biology.

Advances in fluorescence microscopy and tissue-clearing have revolutionised 3D imaging of fluorescently labelled tissues, organs and embryos. However, the complexity and high cost of existing software and computing solutions limit their widespread adoption, especially by researchers with limited resources. Here, we present Acto3D, an open-source software, designed to streamline the generation and analysis of high-resolution 3D images of targets labelled with multiple fluorescent probes. Acto3D provides an intuitive interface for easy 3D data import and visualisation. Although Acto3D offers straightforward 3D viewing, it performs all computations explicitly, giving users detailed control over the displayed images. Leveraging an integrated graphics processing unit, Acto3D deploys all pixel data to system memory, reducing visualisation latency. This approach facilitates accurate image reconstruction and efficient data processing in 3D, eliminating the need for expensive high-performance computers and dedicated graphics processing units. We have also introduced a method for efficiently extracting lumen structures in 3D. We have validated Acto3D by imaging mouse embryonic structures and by performing 3D reconstruction of pharyngeal arch arteries while preserving fluorescence information. Acto3D is a cost-effective and efficient platform for biological research.

Standardized reporting for Head CT Scans in patients suspected of traumatic brain injury (TBI): An international expert endeavor.

BACKGROUND AND PURPOSE: Traumatic brain injury (TBI) is a major source of health loss and disability worldwide. Accurate and timely diagnosis of TBI is critical for appropriate treatment and management of the condition. Neuroimaging plays a crucial role in the diagnosis and characterization of TBI. Computed tomography (CT) is the first-line diagnostic imaging modality typically utilized in patients with suspected acute mild, moderate and severe TBI. Radiology reports play a crucial role in the diagnostic process, providing critical information about the location and extent of brain injury, as well as factors that could prevent secondary injury. However, the complexity and variability of radiology reports can make it challenging for healthcare providers to extract the necessary information for diagnosis and treatment planning. METHODS/RESULTS/CONCLUSION: In this article, we report the efforts of an international group of TBI imaging experts to develop a clinical radiology report template for CT scans obtained in patients suspected of TBI and consisting of fourteen different subdivisions (CT technique, mechanism of injury or clinical history, presence of scalp injuries, fractures, potential vascular injuries, potential injuries involving the extra-axial spaces, brain parenchymal injuries, potential injuries involving the cerebrospinal fluid spaces and the ventricular system, mass effect, secondary injuries, prior or coexisting pathology).

AJICAP Second Generation: Improved Chemical Site-Specific Conjugation Technology for Antibody-Drug Conjugate Production.

The site-directed chemical conjugation of antibodies remains an area of great interest and active efforts within the antibody-drug conjugate (ADC) community. We previously reported a unique site modification using a class of immunoglobulin-G (IgG) Fc-affinity reagents to establish a versatile, streamlined, and site-selective conjugation of native antibodies to enhance the therapeutic index of the resultant ADCs. This methodology, termed "AJICAP", successfully modified Lys248 of native antibodies to produce site-specific ADC with a wider therapeutic index than the Food and Drug Administration-approved ADC, Kadcyla. However, the long reaction sequences, including the reduction-oxidation (redox) treatment, increased the aggregation level. In this manuscript, we aimed to present an updated Fc-affinity-mediated site-specific conjugation technology named "AJICAP second generation" without redox treatment utilizing a "one-pot" antibody modification reaction. The stability of Fc affinity reagents was improved owing to structural optimization, enabling the production of various ADCs without aggregation. In addition to Lys248 conjugation, Lys288 conjugated ADCs with homogeneous drug-to-antibody ratio of 2 were produced using different Fc affinity peptide reagent possessing a proper spacer linkage. These two conjugation technologies were used to produce over 20 ADCs from several combinations of antibodies and drug linkers. The in vivo profile of Lys248 and Lys288 conjugated ADCs was also compared. Furthermore, nontraditional ADC production, such as antibody-protein conjugates and antibody-oligonucleotide conjugates, were achieved. These results strongly indicate that this Fc affinity conjugation approach is a promising strategy for manufacturing site-specific antibody conjugates without antibody engineering.

Incidence and changes in endometrial-leiomyoma fistula following uterine artery embolization: a single-center retrospective analysis.

OBJECTIVES: To investigate whether the number and size of endometrial-leiomyoma fistulas (ELFs) change following uterine artery embolization (UAE) for leiomyoma and the correlation between ELFs and vaginal discharge (VD). MATERIALS & METHODS: This study was a retrospective analysis of 100 patients who underwent UAE at a single institution between May 2016 and March 2021. They all underwent MRI at baseline, 4 months, and 1 year after UAE. The number and size of the ELFs were compared with the MRI images each time. The ELF tumor characteristics and the correlation between the ELFs and VD were assessed. Additional gynecologic interventions due to VD associated with ELFs were evaluated. RESULTS: No ELF was observed at baseline. Ten ELFs were noted in nine patients at 4 months, and 35 ELFs were noted in 32 patients 1 year after UAE. The ELFs significantly increased over time (p = 0.004, baseline vs. 4 months; p < 0.001, 4 months vs. 1 year). The ELF size did not significantly change over time (p = 0.941). The tumors developing ELFs after UAE were mainly located at the submucosal or intramural area contacting the endometrium at baseline, with a mean size of 7.1 (2.6) cm. Nineteen patients (19%) had VD 1 year after UAE. There was no significant correlation between VD and the number of ELFs (p = 0.80). No patients underwent additional gynecologic interventions due to VD associated with ELFs. CONCLUSION: ELFs increased in number and did not disappear over time after UAE in most tumors. CLINICAL RELEVANCE STATEMENT: Despite the MR imaging findings, within the limited data of this study, ELFs were not seemingly associated with clinical symptoms, including VD. KEY POINTS: • Endometrial-leiomyoma fistula (ELF) is a complication of uterine artery embolization (UAE). • ELFs increased in number over time after UAE and did not disappear in most tumors. • Most tumors developing ELFs after UAE were located near/contacted the endometrium and were larger.

Frequency and Risk Factors for Air Embolism in Computed Tomography Fluoroscopy-Guided Biopsy of Lung Tumor With the Use of Noncoaxial Automatic Needle.

PURPOSE: The aim of the study is to analyze incidence and risk factors for air embolism during computed tomography (CT) fluoroscopy-guided lung biopsies using noncoaxial automatic needle. MATERIALS AND METHODS: Between February 2014 and December 2019, 204 CT fluoroscopy-guided lung biopsies (127 men; mean age, 70.6 years) using noncoaxial automatic needle under inspiratory breath holding were performed. We retrospectively evaluated the incidence of air embolism as presence of air in the systemic circulation on whole-chest CT images obtained immediately after biopsy. Risk factors of the patient, tumor and procedural factors (size, location and type of nodule, distance from the pleura, the level of the lesion relative to the left atrium, emphysema, patient position, penetration of a pulmonary vein, etc) were analyzed. RESULTS: The technical success rate was 97.1%. Air embolism was radiologically identified in 8 cases (3.92%, 7 males; size, 21.6 ± 18.2 mm; distance to pleura, 11.9 ± 14.5 mm). Two patients showed overt symptoms and the others were asymptomatic. Independent risk factors were needle penetration of the pulmonary vein ( P = 0.0478) and higher location relative to left atrium ( P = 0.0353). Size, location and type of nodule, distance from the pleura, emphysema, patient position, and other variables were not significant risk factors. As other complications, pneumothorax and alveolar hemorrhage were observed in 57.4% and 77.5%, respectively. CONCLUSIONS: In CT fluoroscopy-guided lung biopsy using the noncoaxial automatic needles, radiological incidence of air embolism was 3.92%. Given the frequency of air embolism, it is necessary to incorporate this into postprocedure imaging and clinical evaluation.

Deep learning-based prediction model for postoperative complications of cervical posterior longitudinal ligament ossification.

PURPOSE: Postoperative complication prediction helps surgeons to inform and manage patient expectations. Deep learning, a model that finds patterns in large samples of data, outperform traditional statistical methods in making predictions. This study aimed to create a deep learning-based model (DLM) to predict postoperative complications in patients with cervical ossification of the posterior longitudinal ligament (OPLL). METHODS: This prospective multicenter study was conducted by the 28 institutions, and 478 patients were included in the analysis. Deep learning was used to create two predictive models of the overall postoperative complications and neurological complications, one of the major complications. These models were constructed by learning the patient's preoperative background, clinical symptoms, surgical procedures, and imaging findings. These logistic regression models were also created, and these accuracies were compared with those of the DLM. RESULTS: Overall complications were observed in 127 cases (26.6%). The accuracy of the DLM was 74.6 ± 3.7% for predicting the overall occurrence of complications, which was comparable to that of the logistic regression (74.1%). Neurological complications were observed in 48 cases (10.0%), and the accuracy of the DLM was 91.7 ± 3.5%, which was higher than that of the logistic regression (90.1%). CONCLUSION: A new algorithm using deep learning was able to predict complications after cervical OPLL surgery. This model was well calibrated, with prediction accuracy comparable to that of regression models. The accuracy remained high even for predicting only neurological complications, for which the case number is limited compared to conventional statistical methods.

Impact of spinal surgery on locomotive syndrome in patients with lumbar spinal stenosis in clinical decision limit stage 3: a retrospective study.

BACKGROUND: Locomotive syndrome (LS) is characterized by reduced mobility. Clinical decision limit (CDL) stage 3 in LS indicates physical frailty. Lumbar spinal canal stenosis (LSS) is one of the causes of LS, for which lumbar surgery is considered to improve the CDL stage. This study aimed to investigate the efficacy of lumbar surgery and independent factors for improving the CDL stage in patients with LSS. METHODS: This retrospective study was conducted at the Department of Orthopaedic Surgery at our University Hospital. A total of 157 patients aged ≥ 65 years with LSS underwent lumbar surgery. The 25-Question Geriatric Locomotive Function scale (GLFS-25) was used to test for LS, and the Timed Up and Go test (TUG) was used to evaluate functional ability. Lower limb pain was evaluated using a visual analog scale. Patients with at least one improvement in the CDL stage following lumbar surgery were included in the improvement group. Differences in lower limb pain intensity between the groups were evaluated using the Wilcoxon rank-sum test. The Spearman's rank correlation coefficient was used to determine correlations between Δ lower limb pain and Δ GLFS-25. Logistic regression analysis was used to identify factors associated with improvement in LS. RESULTS: The proportion of patients with improved CDL stage was 45.1% (improvement/non-improvement: 32/39). Δ Lower limb pain was significantly reduced in the improvement group compared with that in the non-improvement group (51.0 [36.3-71.0] vs 40.0 [4.0-53.5]; p = 0.0107). Δ GLFS-25 was significantly correlated with Δ lower limb pain (r = 0.3774, p = 0.0031). Multiple logistic regression analysis revealed that TUG and age were significantly associated with improvement in LS (odds ratio, 1.22; 95% confidence interval: 1.07-1.47). CONCLUSIONS: Lumbar surgery effectively improved the CDL stage in patients with LSS. In addition, TUG was an independent factor associated with improvement in the CDL.

Intradural extramedullary tumor location in the axial view affects the alert timing of intraoperative neurophysiologic monitoring.

OBJECTIVE: Intraoperative neurophysiologic monitoring (IONM) reportedly helps prevent postoperative neurological complications following high-risk spinal cord surgeries. There are negative and positive reports about using IONM for intradural extramedullary (IDEM) tumors. We investigated factors affecting alerts of IONM in IDEM tumor surgery. METHODS: We analyzed 39 patients with IDEM tumors who underwent surgery using IONM at our hospital between January 2014 and March 2021. Neurological symptoms were evaluated pre- and postoperatively using the manual muscle test (MMT). All patients were evaluated to ascertain the tumor level and location in the axial view, the operative time, intraoperative bleeding volume, and histological type. Additionally, the intraoperative procedure associated with significant IONM changes in transcranial electrical stimulation muscle-evoked potential was investigated. RESULTS: There were 11 false-positive and 16 true-negative cases. There was one true-positive case and one false-negative case; the monitoring accuracy achieved a sensitivity of 50%, a specificity of 59%, a positive predictive value of 8%, and a negative predictive value of 94%. In the 22 alert cases, if the tumor was located anterolateral in the axial view, alerts were triggered with a significant difference (p = 0.02) during tumor resection. Alerts were generated for fifteen patients during tumor resection; nine (60%) showed waveform improvement by intervention and were classified as rescue cases. CONCLUSION: Alert is probably triggered during tumor resection for anterolaterally located tumors. Alerts during tumor resection procedures were more likely to be rescued than other procedures in IDEM tumor surgery.

Artificial intelligence trained with integration of multiparametric MR-US imaging data and fusion biopsy trajectory-proven pathology data for 3D prediction of prostate cancer: A proof-of-concept study.

BACKGROUND: We aimed to develop an artificial intelligence (AI) algorithm that predicts the volume and location of clinically significant cancer (CSCa) using convolutional neural network (CNN) trained with integration of multiparametric MR-US image data and MRI-US fusion prostate biopsy (MRI-US PBx) trajectory-proven pathology data. METHODS: Twenty consecutive patients prospectively underwent MRI-US PBx, followed by robot-assisted radical prostatectomy (RARP). The AI algorithm was trained with the integration of MR-US image data with a MRI-US PBx trajectory-proven pathology. The relationship with the 3D-cancer-mapping of RARP specimens was compared between AI system-suggested 3D-CSCa mapping and an experienced radiologist's suggested 3D-CSCa mapping on MRI alone according to the Prostate Imaging Reporting and Data System (PI-RADS) version 2. The characteristics of detected and undetected tumors at AI were compared in 22,968 image data. The relationships between CSCa volumes and volumes predicted by AI as well as the radiologist's reading based on PI-RADS were analyzed. RESULTS: The concordance of the CSCa center with that in RARP specimens was significantly higher in the AI prediction than the radiologist' reading (83% vs. 54%, p = 0.036). CSCa volumes predicted with AI were more accurate (r = 0.90, p < 0.001) than the radiologist's reading. The limitations include that the elastic fusion technology has its own registration error. CONCLUSIONS: We presented a novel pilot AI algorithm for 3D prediction of PCa. AI was trained by integration of multiparametric MR-US image data and fusion biopsy trajectory-proven pathology data. This deep learning AI model may more precisely predict the 3D mapping of CSCa in its volume and center location than a radiologist's reading based on PI-RADS version 2, and has potential in the planning of focal therapy.

Does cerebrospinal fluid pulsation affect diffusion-weighted imaging thermometry? A study in healthy volunteers.

Diffusion-weighted imaging (DWI)-based thermometry offers potential as a noninvasive method for measuring temperatures deep inside the human brain. However, DWI might be influenced by the pulsatile flow of cerebrospinal fluid (CSF). This study aimed to investigate the influence of such pulsations on DWI thermometry in healthy individuals. A total of 104 participants (50 men, 54 women; mean [± standard deviation] age, 44.2 ± 14.3 years; range 21-69 years) were investigated. DWI-based brain temperature (TDWI ) was acquired at three speeds (maximum and minimum speeds of ascending flow and random timing at the cerebral aqueduct) of CSF pulsation using a 3-T magnetic resonance imaging scanner. Magnetic resonance spectroscopy (MRS)-based temperature (TMRS ) at the thalamus was also obtained as a reference standard for brain temperature. The three different CSF pulsatile flows were monitored by heart rate during the scan. The difference between reference temperature and brain temperature (ΔT = TDWI - TMRS ) along with the three CSF speeds were statistically compared using Student's matched pair t-test. No significant difference in ΔT was evident among CSF speeds (p > 0.05). No significant linear correlation between ΔT and CSF flow speed at the cerebral aqueduct was observed. Using DWI thermometry with clinical acquisition settings, which utilizes mean values within thresholds, no effect of CSF pulsation speed was observed in the estimation of ΔT.

The diffusion MRI signature index is highly correlated with immunohistochemical status and molecular subtype of invasive breast carcinoma.

OBJECTIVES: To evaluate the relationship of the signature index (S-index), an advanced diffusion MRI marker, and the immunohistochemical (IHC) status, proliferation rate, and molecular subtype of invasive breast cancers. METHODS: A retrospective study of patients with invasive carcinoma was conducted between 2017 and 2021. All patients underwent dynamic contrast-enhanced MRI and DWI using a 3-T system. For DWI, three b values (0, 200, and 1500 s/mm2) were used to derive the S-index. Three-dimensional ROIs were manually placed over the whole tumor on DWI. Mean and 85th percentile S-index values were compared to the IHC status, proliferation rate, and molecular subtypes of lesions. RESULTS: The study included 153 patients (mean age, 60 ± 13 years) with 160 invasive carcinomas. S-index values were significantly higher in estrogen receptor-positive (mean, p = .005; 85th percentile, p < .001) and progesterone receptor-positive (mean, p = .003; 85th percentile, p < .001) tumors, and significantly lower in human epidermal growth factor receptor 2 (HER2) - positive tumors (mean, p = .023; 85th percentile, p < .001). Mean and 85th percentile S-index values were significantly different among breast cancer subtypes (mean, p = .015; 85th percentile, p = .002), and the AUC of these values for the prediction of IHC status were 0.64 and 0.66 for HER2, and 0.70 and 0.74 for hormone receptors, respectively. CONCLUSIONS: The DWI S-index showed significantly higher values in invasive carcinomas with immunohistochemical status associated with good prognosis, suggesting its usefulness as a noninvasive imaging biomarker to estimate IHC status and orient treatment. KEY POINTS: • The signature index, an advanced diffusion MRI marker, showed good discrimination of immunohistochemical status in invasive breast carcinomas. • The signature index has the potential to differentiate noninvasively invasive breast carcinoma subtypes and appears as an imaging biomarker of prognostic factors and molecular phenotypes.

DWI-based MR thermometry: could it discriminate Alzheimer's disease from mild cognitive impairment and healthy subjects?

PURPOSE: The aim of this study is to compare lateral ventricular cerebrospinal fluid (CSF) temperature of the patients with Alzheimer's disease (AD), mild cognitive impairment (MCI), and healthy subjects (HS) using diffusion-weighted imaging (DWI)-based magnetic resonance (MR) thermometry. METHODS: Seventy-two patients (37 AD, 19 MCI, 16 HS) who underwent 3-T MR examination from September 2018 to August 2019 were included in this study. Smoking habits, education level, disease duration, and comorbidity status were recorded. Patients were assessed using Mini-Mental State Examination (MMSE) and the Clinical Dementia Rating (CDR) score. Brain temperatures were measured using DWI-based MR thermometry. Group comparisons of brain temperature were performed using the Pearson chi-square, Mann-Whitney, and Kruskal-Wallis tests. Further analysis was performed using the post hoc Bonferroni test. Receiver operating characteristic (ROC) analysis was also used. RESULTS: A CDR score of 0.5, 1, and 2 was 2 (5.4%), 14 (37.8%), and 21 (56.8%) in AD, respectively. The median MMSE score had significant differences among groups and also in pairwise comparisons. The median CSF temperature (°C) values showed statistically significant difference among groups (HS: 38.5 °C, MCI: 38.17 °C, AD: 38.0 °C). The post hoc Mann-Whitney U test indicated a significant difference between AD patients and HS (p = 0.009). There were no significant CSF temperature differences in other pairwise comparisons. CONCLUSION: Lower CSF temperatures were observed in AD patients than in HS, probably due to decreased brain metabolism in AD. DWI-based MR thermometry as a noninvasive imaging method enabling the measurement of CSF temperatures may contribute to the diagnosis of AD.

The impact of sarcopenia on low back pain and quality of life in patients with osteoporosis.

PURPOSE: Osteoporosis combined with sarcopenia contributes to a high risk of falling, fracture, and even mortality. However, sarcopenia's impact on low back pain and quality of life (QOL) in patients with osteoporosis is still unknown. The purpose of this study is to investigate low back pain and QOL in osteoporosis patients with sarcopenia. METHODS: We assessed 100 ambulatory patients who came to our hospital for osteoporosis treatment. Low back pain was evaluated using the Visual Analogue Scale (VAS) with 100 being an extreme amount of pain and 0 no pain. The Japanese Orthopaedic Association Back Pain Evaluation Questionnaire (JOABPEQ) score was used to assess QOL after adjustment for age, history of vertebral fracture, and adult spinal deformity. Differences in low back pain intensity assessed by VAS between groups were evaluated by the Willcoxon rank-sum test. Covariance analysis was used to assess QOL. All data are expressed as either median, interquartile range, or average, standard error. RESULTS: Patients were classified into the sarcopenia group (n = 32) and the non-sarcopenia group (n = 68). Low back pain intensity assessed by VAS was significantly higher in the sarcopenia group than in the non-sarcopenia group (33.0 [0-46.6] vs. 8.5 [0-40.0]; p < 0.05). The subscales of the JOABPEQ for low back pain were significantly lower in the sarcopenia group than in the non-sarcopenia group (65.0 ± 4.63 vs. 84.0 ± 3.1; p < 0.05). CONCLUSION: In this cross-sectional study, sarcopenia affected low back pain and QOL in ambulatory patients with osteoporosis. Sarcopenia may exacerbate low back pain and QOL.

Rational Design of Silicon-Based Zinc Ionophores.

Ionophores transport ions across biological membranes and have wide-ranging applications, but a platform for their rapid development does not exist. We report a platform for developing ionophores from metal-ion chelators, which are readily available with wide-ranging affinities and specificities, and structural data that can aid rational design. Specifically, we fine-tuned the binding affinity and lipophilicity of a ZnII -chelating ligand by introducing silyl groups proximal to the ZnII -binding pocket, which generated ionophores that performed better than most of the currently known ZnII ionophores. Furthermore, these silicon-based ionophores were specific for ZnII over other metals and exhibited better antibacterial activity and less toxicity to mammalian cells than several known ZnII ionophores, including pyrithione. These studies establish rational design principles for the rapid development of potent and specific ionophores and a new class of antibacterial agents.

Chemical Site-Specific Conjugation Platform to Improve the Pharmacokinetics and Therapeutic Index of Antibody-Drug Conjugates.

To overcome a lack of selectivity during the chemical modification of native non-engineered antibodies, we have developed a technology platform termed "AJICAP" for the site-specific chemical conjugation of antibodies through the use of a class of IgG Fc-affinity reagents. To date, a limited number of antibody-drug conjugates (ADCs) have been synthesized via this approach, and no toxicological study was reported. Herein, we describe the compatibility and robustness of AJICAP technology, which enabled the synthesis of a wide variety of ADCs. A stability assessment of a thiol-modified antibody synthesized by AJICAP technology indicated no appreciable increase in aggregation or decomposition upon prolonged storage, indicating that the unexpectedly stable thiol intermediate has a great potential intermediate for payload or linker screening or large-scale manufacturing. Payload conjugation with this stable thiol intermediate generated several AJICAP-ADCs. In vivo xenograft studies indicated that the AJICAP-ADCs displayed significant tumor inhibition comparable to benchmark ADC Kadcyla. Furthermore, a rat pharmacokinetic analysis and toxicology study indicated an increase in the maximum tolerated dose, demonstrating an expansion of the AJICAP-ADC therapeutic index, compared with stochastic conjugation technology. This is the first report of the therapeutic index estimation of site-specific ADCs produced by utilizing Fc affinity reagent conjugation. The described site-specific conjugation technology is a powerful platform to enable next-generation ADCs through reduced heterogeneity and enhanced therapeutic index.

Thermal Ablation, Embolization, and Selective Internal Radiation Therapy Combined with Checkpoint Inhibitor Cancer Immunotherapy: Safety Analysis.

PURPOSE: To describe interventional oncology therapies combined with immune checkpoint inhibitor (ICI) therapy targeting the programmed death 1 pathway in patients with different neoplasms. MATERIALS AND METHODS: This was a retrospective cohort study of patients who underwent tumor-directed thermal ablation, embolization, or selective internal radiation therapy (SIRT) between January 1, 2011, and May 1, 2019, and received anti-programmed death 1/PD-L1 agents ≤ 90 days before or ≤ 30 days after the interventional procedure. Immune-related adverse events (irAEs) and procedural complications ≤ 90 days after the procedure were graded according to the Common Terminology Criteria for Adverse Events version 5.0. The study included 65 eligible patients (49% female; age 63 years ± 11.1). The most common tumors were metastatic melanoma (n = 28) and non-small cell lung cancer (NSCLC) (n = 12). Patients underwent 78 procedures (12 patients underwent > 1 procedure), most frequently SIRT (35.9%) and cryoablation (28.2%). The most common target organs were liver (46.2%), bone (24.4%), and lung (9.0%). Most patients received ICI monotherapy with pembrolizumab (n = 30), nivolumab (n = 22), and atezolizumab (n = 6); 7 patients received ipilimumab and nivolumab. RESULTS: Seven (10.8%) patients experienced an irAE (71.4% grade 1-2), mostly affecting the skin. Median time to irAE was 33 days (interquartile range, 19-38 days). Five irAEs occurred in patients with melanoma, and no irAEs occurred in patients with NSCLC. Management required corticosteroids (n = 3) and immunotherapy discontinuation (n = 1); all irAEs resolved to grade ≤ 1. There were 4 intraprocedural and 32 postprocedural complications (77.8% grade < 3). No grade 5 irAEs and/or procedural complications occurred. CONCLUSIONS: No unmanageable or unanticipated toxicities occurred within 90 days after interventional oncology therapies combined with ICIs.

A 10-year longitudinal study of deep white matter lesions on magnetic resonance imaging.

PURPOSE: Deep white matter lesions (DWMLs), T2 high-intensity areas in the subcortical white matter on magnetic resonance imaging (MRI), are a clinical phenotype of cerebral small vessel disease. Factors such as age and hypertension have been reported to significantly contribute to the presence and severity of DWMLs in cross-sectional studies. We herein report a 10-year longitudinal study on DWMLs in elderly Japanese subjects to reveal the clinical variables contributing to the progression of DWMLs. METHODS: A total of 469 Japanese subjects were invited to participate in the study. Of the participants at baseline, 259 subjects completed the revisit MRI study 10 years later. In those 259 subjects, we evaluated the correlation between the progression of DWMLs and clinical variables, such as the gender, age, and overt vascular risk factors. To clarify the role of hypertension, 200 subjects with grade 1 DWMLs at baseline were categorized into three groups according to their status of hypertension and its treatment. RESULTS: Of the 200 subjects with grade 1 DWMLs, 47 subjects (23.5%) showed progression of DWMLs (progression group). In the progression group, the percentage of subjects with hypertension and the systolic blood pressure values were higher than in the non-progression group. In addition, subjects ≥ 60 years old at baseline tended to show deterioration of DWMLs in the group with hypertension without antihypertensive treatment. CONCLUSION: The results of this 10-year longitudinal study imply a positive correlation between long-standing hypertension and the progression of DWMLs.

Radiologic-pathologic association of tumor-like lesions with inflammation in cerebral white matter: Comparison of two cases with distinct clinical outcomes.

Here, we report two cases showing tumor-like white matter lesions; one case was diagnosed as having inflammatory disease, and the other was diagnosed as having astrocytoma. Their outcomes were completely distinct despite similar pathology. Prior to biopsy, perfusion computed tomography (CT) and magnetic resonance imaging (MRI) were conducted. The two mass-forming lesions were distinct in edema level and vascularity patterns on CT and MRI. However, pathological examination of brain biopsy specimens revealed commonalities, including (1) proliferation of glial cells, (2) perivascular lymphocytic infiltration, and (3) appearance of numerous macrophages. Although atypical astrocytes proliferated in both cases, nuclear atypia was more distinct in case 2 than in case 1. The immunohistochemical results were the same for both cases: isocitrate dehydrogenase 1 (IDH1) R132H mutation was negative, and alpha thalassaemia mental retardation X-linked (ATRX) was retained. Faint immunoreactivity for p53 was observed in a few glial cells, and Ki-67 immunoreactive cells were markedly reduced in numbers (< 1%). Inflammatory reactions were evident in both cases: T cells dominantly infiltrated over B cells in the perivascular area in case 1, whereas both T and B cells infiltrated in case 2. Molecular analysis revealed wild-type IDH1 and IDH2 in both cases. However, a telomerase reverse transcriptase (TERT) sequence mutation was detected in case 2 but not in case 1. Eventually, case 1 was diagnosed as having inflammatory lesions, whereas case 2 was diagnosed as having diffuse astrocytoma associated with inflammatory reactions. The prognosis was favorable for case 1, whereas case 2 died 10 months following biopsy. These data indicated the diagnostic value of molecular analysis, for example, a TERT mutation, in association with the radiological findings. Although in case 2, histopathological evidence did not suggest high-grade glioma, the case met the new diagnostic criteria: "diffuse astrocytic glioma, IDH wild-type, with molecular features of glioblastoma, World Health Organization (WHO) grade IV," according to cIMPACT-NOW, update 3. Thus, interdisciplinary approaches are essential for accurate diagnosis of newly categorized white matter diseases.

Low-grade IVH in preterm infants causes cerebellar damage, motor, and cognitive impairment.

BACKGROUND: Few studies have examined the effect of low-grade intraventricular hemorrhage (IVH) on the white matter in the cerebellum and its association with neurodevelopment. We evaluated cerebellar white matter at term-equivalent age (TEA) in preterm infants with low-grade IVH. Furthermore, we assessed neurodevelopmental outcomes at 3 years of age to examine the influence of low-grade IVH on neurodevelopment. METHODS: Thirteen infants with low-grade IVH and 26 without IVH, born at <30 weeks' postmenstrual age (PMA), were enrolled in this study. Diffusion tensor imaging (DTI) parameters, including fractional anisotropy (FA) and apparent diffusion coefficient (ADC) in the middle and superior cerebellar peduncles (SCP), were measured. Neurodevelopmental outcomes at three years of age were assessed and the correlation between DTI parameters and developmental quotient (DQ) was analyzed. RESULTS: Preterm infants with IVH showed lower FA values (P < 0.01) and higher ADC values (P < 0.05) in the SCP at TEA than the no-IVH group. Lower Postural-Motor and Cognitive-Adaptive DQ at 3 years of age were observed in the IVH compared to the no-IVH group. A significant correlation between the FA values in the SCP at TEA and the Posture-Motor DQ was observed at three years of age (P = 0.043, r = 0.50). CONCLUSIONS: These data suggest that low-grade IVH in preterm infants affects the SCP at TEA and that impaired cerebellar white matter correlates with poor motor development at three years of age.

Understanding the effect of non-surgical factors in a transcranial motor-evoked potential alert: A retrospective cohort study.

BACKGROUND: Intraoperative neuromonitoring (IONM) is important for detecting neurological dysfunction, allowing for intervention and reversal of neurological deficits before they become permanent. Of the several IONM modalities, transcranial electrical stimulation of motor-evoked potential (TES-MEP) can help monitor the activity in the pyramidal tract. Surgery- and non-surgery-related factors could result in a TES-MEP alert during surgery. Once the alert occurs, the surgeon should immediately intervene to prevent a neurological complication. However, TES-MEP monitoring does not provide sufficient data to identify the non-surgery-related factors. Therefore, this study aimed to identify and describe these factors among TES-MEP alert cases. METHODS: In this multicenter study, data from 1934 patients who underwent various spinal surgeries for spinal deformities, spinal cord tumors, and ossification of the posterior longitudinal ligament of the spine from 2017 to 2019 were collected. A 70% amplitude reduction was set as the TES-MEP alarm threshold. All surgeries with alerts were categorized into true-positive (TP) and false-positive (FP) cases according to the assessment of immediate postoperative neurological deficits. RESULTS: In total, TES-MEP alerts were observed in 251 cases during surgery: 62 TP and 189 FP IONM cases. Overall, 158 cases were related to non-surgery-related factors. We observed 22 (35.5%) TP cases and 136 (72%) FP cases, which indicated cases associated with non-surgery-related factors. A significant difference was observed between the two groups regarding factors associated with TES-MEP alerts (p < 0.01). The ratio of TP and FP cases (related to non-surgery-related factors) associated with TES-MEP alerts was 13.9% (22/158 cases) and 86.1% (136/158 cases), respectively. CONCLUSIONS: Non-surgery-related factors are proportionally higher in FP than in TP cases. Although the surgeon should examine surgical procedures immediately after a TES-MEP alert, surgical intervention may not always be the best approach according to the results of this study.