Pulmonary MRI with ultra-short TE using single- and dual-echo methods: comparison of capability for quantitative differentiation of non- or minimally invasive adenocarcinomas from other lung cancers with that of standard-dose thin-section CT.

OBJECTIVE: The purpose of this study was thus to compare capabilities for quantitative differentiation of non- and minimally invasive adenocarcinomas from other of pulmonary MRIs with ultra-short TE (UTE) obtained with single- and dual-echo techniques (UTE-MRISingle and UTE-MRIDual) and thin-section CT for stage IA lung cancer patients. METHODS: Ninety pathologically diagnosed stage IA lung cancer patients who underwent thin-section standard-dose CT, UTE-MRISingle, and UTE-MRIDual, surgical treatment and pathological examinations were included in this retrospective study. The largest dimension (Dlong), solid portion (solid Dlong), and consolidation/tumor (C/T) ratio of each nodule were assessed. Two-tailed Student's t-tests were performed to compare all indexes obtained with each method between non- and minimally invasive adenocarcinomas and other lung cancers. Receiver operating characteristic (ROC)-based positive tests were performed to determine all feasible threshold values for distinguishing non- or minimally invasive adenocarcinoma (MIA) from other lung cancers. Sensitivity, specificity, and accuracy were then compared by means of McNemar's test. RESULTS: Each index showed significant differences between the two groups (p < 0.0001). Specificities and accuracies of solid Dlong for UTE-MRIDual2nd echo and CTMediastinal were significantly higher than those of solid Dlong for UTE-MRISingle and UTE-MRIDual1st echo and all C/T ratios except CTMediastinal (p < 0.05). Moreover, the specificities and accuracies of solid Dlong and C/T ratio were significantly higher than those of Dlong for each method (p < 0.05). CONCLUSION: Pulmonary MRI with UTE is considered at least as valuable as thin-section CT for quantitative differentiation of non- and minimally invasive adenocarcinomas from other stage IA lung cancers. CLINICAL RELEVANCE STATEMENT: Pulmonary MRI with UTE's capability for quantitative differentiation of non- and minimally invasive adenocarcinomas from other lung cancers in stage IA lung cancer patients is equal or superior to that of thin-section CT. KEY POINTS: • Correlations were excellent for pathologically examined nodules with the largest dimensions (Dlong) and a solid component (solid Dlong) for all indexes (0.95 ≤ r ≤ 0.99, p < 0.0001). • Pathologically examined Dlong and solid Dlong obtained with all methods showed significant differences between non- and minimally invasive adenocarcinomas and other lung cancers (p < 0.0001). • Solid tumor components are most accurately measured by UTE-MRIDual2nd echo and CTMediastinal, whereas the ground-glass component is imaged by UTE-MRIDual1st echo and CTlung with high accuracy. UTE-MRIDual predicts tumor invasiveness with 100% sensitivity and 87.5% specificity at a C/T threshold of 0.5.

Comparison of the specimen quality of endobronchial ultrasound-guided intranodal forceps biopsy using standard-sized forceps versus mini forceps for lung cancer: A prospective study.

BACKGROUND AND OBJECTIVE: Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) is a diagnostic procedure with adequate performance; however, its ability to provide specimens of sufficient quality and quantity for treatment decision-making in advanced-stage lung cancer may be limited, primarily due to blood contamination. The use of a 0.96-mm miniforceps biopsy (MFB) permits true histological sampling, but the resulting small specimens are unsuitable for the intended applications. Therefore, we introduced a 1.9-mm standard-sized forceps biopsy (SFB) and compared its utility to that of MFB. METHODS: We prospectively enrolled patients from three institutions who presented with hilar/mediastinal lymphadenopathy and suspected advanced-stage lung cancer, or those who were already diagnosed but required additional tissue specimens for biomarker analysis. Each patient underwent MFB followed by SFB three or four times through the tract created by TBNA using a 22-gauge needle on the same lymph node (LN). Two pathologists assessed the quality and size of each specimen using a virtual slide system, and diagnostic performance was compared between the MFB and SFB groups. RESULTS: Among the 60 enrolled patients, 70.0% were diagnosed with adenocarcinoma. The most frequently targeted sites were the lower paratracheal LNs, followed by the interlobar LNs. The diagnostic yields of TBNA, MFB and SFB were 91.7%, 93.3% and 96.7%, respectively. The sampling rate of high-quality specimens was significantly higher in the SFB group. Moreover, the mean specimen size for SFB was three times larger than for MFB. CONCLUSION: SFB is useful for obtaining sufficient qualitative and quantitative specimens.

Chemical Exchange Saturation Transfer MRI: Capability for Predicting Therapeutic Effect of Chemoradiotherapy on Non-Small Cell Lung Cancer Patients.

BACKGROUND: Amide proton transfer (APT) weighted chemical exchange saturation transfer CEST (APTw/CEST) magnetic resonance imaging (MRI) has been suggested as having the potential for assessing the therapeutic effect of brain tumors or rectal cancer. Moreover, diffusion-weighted imaging (DWI) and positron emission tomography fused with computed tomography by means of 2-[fluorine-18]-fluoro-2-deoxy-D-glucose (FDG-PET/CT) have been suggested as useful in same setting. PURPOSE: To compare the capability of APTw/CEST imaging, DWI, and FDG-PET/CT for predicting therapeutic effect of chemoradiotherapy (CRT) on stage III non-small cell lung cancer (NSCLC) patients. STUDY TYPE: Prospective. POPULATION: Eighty-four consecutive patients with Stage III NSCLC, 45 men (age range, 62-75 years; mean age, 71 years) and 39 women (age range, 57-75 years; mean age, 70 years). All patients were then divided into two groups (Response Evaluation Criteria in Solid Tumors [RECIST] responders, consisting of the complete response and partial response groups, and RECIST non-responders, consisting of the stable disease and progressive disease groups). FIELD STRENGTH/SEQUENCE: 3 T, echo planar imaging or fast advanced spin-echo (FASE) sequences for DWI and 2D half Fourier FASE sequences with magnetization transfer pulses for CEST imaging. ASSESSMENT: Magnetization transfer ratio asymmetry (MTRasym ) at 3.5 ppm, apparent diffusion coefficient (ADC), and maximum standard uptake value (SUVmax, ) on PET/CT were assessed by means of region of interest (ROI) measurements at primary tumor. STATISTICAL TESTS: Kaplan-Meier method followed by log-rank test and Cox proportional hazards regression analysis with multivariate analysis. A P value <0.05 was considered statistically significant. RESULTS: Progression-free survival (PFS) and overall survival (OS) had significant difference between two groups. MTRasym at 3.5 ppm (hazard ratio [HR] = 0.70) and SUVmax (HR = 1.41) were identified as significant predictors for PFS. Tumor staging (HR = 0.57) was also significant predictors for OS. DATA CONCLUSION: APTw/CEST imaging showed potential performance as DWI and FDG-PET/CT for predicting the therapeutic effect of CRT on stage III NSCLC patients. LEVEL OF EVIDENCE: 2 TECHNICAL EFFICACY: Stage 1.

Computed DWI MRI Results in Superior Capability for N-Stage Assessment of Non-Small Cell Lung Cancer Than That of Actual DWI, STIR Imaging, and FDG-PET/CT.

BACKGROUND: Computed diffusion-weighted imaging (cDWI) is a mathematical computation technique that generates DWIs for any b-value by using actual DWI (aDWI) data with at least two different b-values and may improve differentiation of metastatic from nonmetastatic lymph nodes. PURPOSE: To determine the appropriate b-value for cDWI to achieve a better diagnostic capability for lymph node staging (N-staging) in non-small cell lung cancer (NSCLC) patients compared to aDWI, short inversion time (TI) inversion recovery (STIR) imaging, or positron emission tomography with 2-[fluorine-18] fluoro-2-deoxy-d-glucose combined with computed tomography (FDG-PET/CT). STUDY TYPE: Prospective. SUBJECTS: A total of 245 (127 males and 118 females; mean age 72 years) consecutive histopathologically confirmed NSCLC patients. FIELD STRENGTH/SEQUENCE: A 3 T, half-Fourier single-shot turbo spin-echo sequence, electrocardiogram (ECG)-triggered STIR fast advanced spin-echo (FASE) sequence with black blood and STIR acquisition and DWI obtained by FASE with b-values of 0 and 1000 sec/mm2 . ASSESSMENT: From aDWIs with b-values of 0 and 1000 (aDWI1000 ) sec/mm2 , cDWI using 400 (cDWI400 ), 600 (cDWI600 ), 800 (cDWI800 ), and 2000 (cDWI2000 ) sec/mm2 were generated. Then, 114 metastatic and 114 nonmetastatic nodes (mediastinal and hilar lymph nodes) were selected and evaluated with a contrast ratio (CR) for each cDWI and aDWI, apparent diffusion coefficient (ADC), lymph node-to-muscle ratio (LMR) on STIR, and maximum standard uptake value (SUVmax ). STATISTICAL TESTS: Receiver operating characteristic curve (ROC) analysis, Youden index, and McNemar's test. RESULTS: Area under the curve (AUC) of CR600 was significantly larger than the CR400 , CR800 , CR2000 , aCR1000 , and SUVmax . Comparison of N-staging accuracy showed that CR600 was significantly higher than CR400 , CR2000 , ADC, aCR1000 , and SUVmax , although there were no significant differences with CR800 (P = 0.99) and LMR (P = 0.99). DATA CONCLUSION: cDWI with b-value at 600 sec/mm2 may have potential to improve N-staging accuracy as compared with aDWI, STIR, and PET/CT. EVIDENCE LEVEL: 2 TECHNICAL EFFICACY: Stage 2.

Comparison of lung CT number and airway dimension evaluation capabilities of ultra-high-resolution CT, using different scan modes and reconstruction methods including deep learning reconstruction, with those of multi-detector CT in a QIBA phantom study.

OBJECTIVE: Ultra-high-resolution CT (UHR-CT), which can be applied normal resolution (NR), high-resolution (HR), and super-high-resolution (SHR) modes, has become available as in conjunction with multi-detector CT (MDCT). Moreover, deep learning reconstruction (DLR) method, as well as filtered back projection (FBP), hybrid-type iterative reconstruction (IR), and model-based IR methods, has been clinically used. The purpose of this study was to directly compare lung CT number and airway dimension evaluation capabilities of UHR-CT using different scan modes with those of MDCT with different reconstruction methods as investigated in a lung density and airway phantom design recommended by QIBA. MATERIALS AND METHODS: Lung CT number, inner diameter (ID), inner area (IA), and wall thickness (WT) were measured, and mean differences between measured CT number, ID, IA, WT, and standard reference were compared by means of Tukey's HSD test between all UHR-CT data and MDCT reconstructed with FBP as 1.0-mm section thickness. RESULTS: For each reconstruction method, mean differences in lung CT numbers and all airway parameters on 0.5-mm and 1-mm section thickness CTs obtained with SHR and HR modes showed significant differences with those obtained with the NR mode on UHR-CT and MDCT (p < 0.05). Moreover, the mean differences on all UHR-CTs obtained with SHR, HR, or NR modes were significantly different from those of 1.0-mm section thickness MDCTs reconstructed with FBP (p < 0.05). CONCLUSION: Scan modes and reconstruction methods used for UHR-CT were found to significantly affect lung CT number and airway dimension evaluations as did reconstruction methods used for MDCT. KEY POINTS: • Scan and reconstruction methods used for UHR-CT showed significantly higher CT numbers and smaller airway dimension evaluations as did those for MDCT in a QIBA phantom study (p < 0.05). • Mean differences in lung CT number for 0.25-mm, 0.5-mm, and 1.0-mm section thickness CT images obtained with SHR and HR modes were significantly larger than those for CT images at 1.0-mm section thickness obtained with MDCT and reconstructed with FBP (p < 0.05). • Mean differences in inner diameter (ID), inner area (IA), and wall thickness (WT) measured with SHR and HR modes on 0.5- and 1.0-mm section thickness CT images were significantly smaller than those obtained with NR mode on UHR-CT and MDCT (p < 0.05).

Substitution (CH3, Cl, or Br) effects of the imidazolate linker on benzene adsorption kinetics for the zeolitic imidazolate framework (ZIF)-8.

Herein, the time dependence of benzene adsorption uptake was examined for ZIF-8, Cl-ZIF-8, and Br-ZIF-8 and analysed using an intra-crystalline (Fick's) diffusion model, yielding the diffusion coefficient and saturated adsorption amount of benzene. The saturated adsorption amount of benzene decreased in the order of ZIF-8, Cl-ZIF-8, and Br-ZIF-8. Notably, ZIF-8, with an intermediate pore volume among the three specimens, accommodated the greatest number of molecules (5.5 molecules per micropore). The activation energy, Ea, and the pre-exponential factor, D0, for benzene diffusion increased in the order of ZIF-8, Cl-ZIF-8, and Br-ZIF-8. These findings suggest that the 2-methylimidazolate moiety forms an effective attraction interaction with benzene molecules. The D0 values also yielded the activation entropy, ΔS‡, in the transition state when a benzene molecule passed through a six-membered ring aperture. The ΔS‡ values at 303 K were negative, and their absolute values increased in the order of Br-ZIF-8, Cl-ZIF-8, and ZIF-8. Considering the degree of freedom of translation and rotation of the benzene molecule and the vibration and disorder of the linker, we found that the differences in ΔS‡ were caused by the dynamic local structure of the six-membered ring aperture among the ZIF-8 analogues. Furthermore, infrared spectroscopy revealed a low-wavenumber shift of the C-H stretching band in both the imidazolate moiety and adsorbed benzene molecules. A solid-state 13C-nuclear magnetic resonance spectrum presented a downfield shift of 13C resonance peaks in the imidazolate moiety, suggesting that CH/π interactions reasonably explain the intermolecular interaction between the imidazolate moiety (including the methyl group) and π-electrons of benzene.

Factors associated with mortality in patients with extremity necrotizing soft-tissue infections: a single academic center experience.

PURPOSE: Necrotizing soft-tissue infection (NSTI) is a surgical emergency associated with high mortality. This study primarily aimed to identify the factors associated with in-hospital mortality due to NSTI in the extremities at a single institution. Secondarily, we aimed to clarify the effectiveness of the optimal combination of hyperbaric oxygen therapy (HBOT) and surgery for NSTI treatment. STUDY DESIGN: Retrospective observational study. METHODS: This study included all patients newly diagnosed with NSTI in the extremity from 2003 to 2021 in our hospital. Factors associated with mortality, including patient's characteristics, duration from onset to hospitalization, NSTI type, and clinical data at the initial visit; acute disseminated intravascular coagulation (DIC), laboratory risk indicator for necrotizing fasciitis score, and sequential organ failure assessment score; treatment, initial surgery, surgery times, amputation, HBOT, combined surgery with HBOT, and clinical outcomes; amputation rate, mortality rate, and hospitalization duration were examined. RESULTS: A total of 37 cases were treated for NSTIs. The median age was 64 years (range: 22-86). Five cases (13.5%) died during hospitalization. Ten patients were diagnosed with DIC at the initial visit, of whom four died. HBOT combined with surgery was performed in 23 cases, and 16 cases underwent multiple surgeries. Factors associated with mortality included DIC (p = 0.015, 95% confidence interval [CI]: 0.015-0.633) and multiple surgeries combined with HBOT (p = 0.028, 95% CI: 1.302-95.418). CONCLUSION: This study demonstrates that DIC at the initial visit is associated with mortality in extremity NSTI. Additionally, HBOT might improve prognosis when combined with multiple surgeries.

Inhaled GM-CSF for Pulmonary Alveolar Proteinosis.

BACKGROUND: Pulmonary alveolar proteinosis is a disease characterized by abnormal accumulation of surfactant in the alveoli. Most cases are autoimmune and are associated with an autoantibody against granulocyte-macrophage colony-stimulating factor (GM-CSF) that prevents clearing of pulmonary surfactant by alveolar macrophages. An open-label, phase 2 study showed some therapeutic efficacy of inhaled recombinant human GM-CSF in patients with severe pulmonary alveolar proteinosis; however, the efficacy in patients with mild-to-moderate disease remains unclear. METHODS: We conducted a double-blind, placebo-controlled trial of daily inhaled recombinant human GM-CSF (sargramostim), at a dose of 125 µg twice daily for 7 days, every other week for 24 weeks, or placebo in 64 patients with autoimmune pulmonary alveolar proteinosis who had a partial pressure of arterial oxygen (Pao2) while breathing ambient air of less than 70 mm Hg (or <75 mm Hg in symptomatic patients). Patients with severe pulmonary alveolar proteinosis (Pao2 <50 mm Hg) were excluded to avoid possible exacerbation of the disease in patients who were assigned to receive placebo. The primary end point was the change in the alveolar-arterial oxygen gradient between baseline and week 25. RESULTS: The change in the mean (±SD) alveolar-arterial oxygen gradient was significantly better in the GM-CSF group (33 patients) than in the placebo group (30 patients) (mean change from baseline, -4.50±9.03 mm Hg vs. 0.17±10.50 mm Hg; P = 0.02). The change between baseline and week 25 in the density of the lung field on computed tomography was also better in the GM-CSF group (between-group difference, -36.08 Hounsfield units; 95% confidence interval, -61.58 to -6.99, calculated with the use of the Mann-Whitney U test and the Hodges-Lehmann estimate of confidence intervals for pseudo-medians). Serious adverse events developed in 6 patients in the GM-CSF group and in 3 patients in the placebo group. CONCLUSIONS: In this randomized, controlled trial, inhaled recombinant human GM-CSF was associated with a modest salutary effect on the laboratory outcome of arterial oxygen tension, and no clinical benefits were noted. (Funded by the Japan Agency for Medical Research and Development and the Ministry of Health, Labor, and Welfare of Japan; PAGE ClinicalTrials.gov number, NCT02835742; Japan Medical Association Center for Clinical Trials number, JMA-IIA00205.).

Deep Learning Reconstruction of Diffusion-weighted MRI Improves Image Quality for Prostatic Imaging.

Background Deep learning reconstruction (DLR) may improve image quality. However, its impact on diffusion-weighted imaging (DWI) of the prostate has yet to be assessed. Purpose To determine whether DLR can improve image quality of diffusion-weighted MRI at b values ranging from 1000 sec/mm2 to 5000 sec/mm2 in patients with prostate cancer. Materials and Methods In this retrospective study, images of the prostate obtained at DWI with a b value of 0 sec/mm2, DWI with a b value of 1000 sec/mm2 (DWI1000), DWI with a b value of 3000 sec/mm2 (DWI3000), and DWI with a b value of 5000 sec/mm2 (DWI5000) from consecutive patients with biopsy-proven cancer from January to June 2020 were reconstructed with and without DLR. Image quality was assessed using signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR) from region-of-interest analysis and qualitatively assessed using a five-point visual scoring system (1 [very poor] to 5 [excellent]) for each high-b-value DWI sequence with and without DLR. The SNR, CNR, and visual score for DWI with and without DLR were compared with the paired t test and the Wilcoxon signed rank test with Bonferroni correction, respectively. Apparent diffusion coefficients (ADCs) from DWI with and without DLR were also compared with the paired t test with Bonferroni correction. Results A total of 60 patients (mean age, 67 years; age range, 49-79 years) were analyzed. DWI with DLR showed significantly higher SNRs and CNRs than DWI without DLR (P < .001); for example, with DWI1000 the mean SNR was 38.7 ± 0.6 versus 17.8 ± 0.6, respectively (P < .001), and the mean CNR was 18.4 ± 5.6 versus 7.4 ± 5.6, respectively (P < .001). DWI with DLR also demonstrated higher qualitative image quality than DWI without DLR (mean score: 4.8 ± 0.4 vs 4.0 ± 0.7, respectively, with DWI1000 [P = .001], 3.8 ± 0.7 vs 3.0 ± 0.8 with DWI3000 [P = .002], and 3.1 ± 0.8 vs 2.0 ± 0.9 with DWI5000 [P < .001]). ADCs derived with and without DLR did not differ substantially (P > .99). Conclusion Deep learning reconstruction improves the image quality of diffusion-weighted MRI scans of prostate cancer with no impact on apparent diffusion coefficient quantitation with a 3.0-T MRI system. © RSNA, 2022 Online supplemental material is available for this article. See also the editorial by Turkbey in this issue.

Efficacy of Ultrashort Echo Time Pulmonary MRI for Lung Nodule Detection and Lung-RADS Classification.

Background Pulmonary MRI with ultrashort echo time (UTE) has been compared with chest CT for nodule detection and classification. However, direct comparisons of these methods' capabilities for Lung CT Screening Reporting and Data System (Lung-RADS) evaluation remain lacking. Purpose To compare the capabilities of pulmonary MRI with UTE with those of standard- or low-dose thin-section CT for Lung-RADS classification. Materials and Methods In this prospective study, standard- and low-dose chest CT (270 mA and 60 mA, respectively) and MRI with UTE were used to examine consecutive participants enrolled between January 2017 and December 2020 who met American College of Radiology Appropriateness Criteria for lung cancer screening with low-dose CT. Probability of nodule presence was assessed for all methods with a five-point visual scoring system by two board-certified radiologists. All nodules were then evaluated in terms of their Lung-RADS classification using each method. To compare nodule detection capability of the three methods, consensus for performances was rated by using jackknife free-response receiver operating characteristic analysis, and sensitivity was compared by means of the McNemar test. In addition, weighted κ statistics were used to determine the agreement between Lung-RADS classification obtained with each method and the reference standard generated from standard-dose CT evaluated by two radiologists who were not included in the image analysis session. Results A total of 205 participants (mean age: 64 years ± 7 [standard deviation], 106 men) with 1073 nodules were enrolled. Figure of merit (FOM) (P < .001) had significant differences among three modalities (standard-dose CT: FOM = 0.91, low-dose CT: FOM = 0.89, pulmonary MRI with UTE: FOM = 0.94), with no evidence of false-positive findings in participants with all modalities (P > .05). Agreements for Lung-RADS classification between all modalities and the reference standard were almost perfect (standard-dose CT: κ = 0.82, P < .001; low-dose CT: κ = 0.82, P < .001; pulmonary MRI with UTE: κ = 0.82, P < .001). Conclusion In a lung cancer screening population, ultrashort echo time pulmonary MRI was comparable to standard- or low-dose CT for Lung CT Screening Reporting and Data System classification. © RSNA, 2021 Online supplemental material is available for this article. See also the editorial by Wielpütz in this issue.

Comparison of utility of deep learning reconstruction on 3D MRCPs obtained with three different k-space data acquisitions in patients with IPMN.

OBJECTIVE: To compare the utility of deep learning reconstruction (DLR) for improving acquisition time, image quality, and intraductal papillary mucinous neoplasm (IPMN) evaluation for 3D MRCP obtained with parallel imaging (PI), multiple k-space data acquisition for each repetition time (TR) technique (Fast 3D mode multiple: Fast 3Dm) and compressed sensing (CS) with PI. MATERIALS AND METHODS: A total of 32 IPMN patients who had undergone 3D MRCPs obtained with PI, Fast 3Dm, and CS with PI and reconstructed with and without DLR were retrospectively included in this study. Acquisition time, signal-to-noise ratio (SNR), and contrast-to-noise ratio (CNR) obtained with all protocols were compared using Tukey's HSD test. Results of endoscopic ultrasound, ERCP, surgery, or pathological examination were determined as standard reference, and distribution classifications were compared among all 3D MRCP protocols by McNemar's test. RESULTS: Acquisition times of Fast 3Dm and CS with PI with and without DLR were significantly shorter than those of PI with and without DLR (p < 0.05). Each MRCP sequence with DLR showed significantly higher SNRs and CNRs than those without DLR (p < 0.05). IPMN distribution accuracy of PI with and without DLR and Fast 3Dm with DLR was significantly higher than that of Fast 3Dm without DLR and CS with PI without DLR (p < 0.05). CONCLUSION: DLR is useful for improving image quality and IPMN evaluation capability on 3D MRCP obtained with PI, Fast 3Dm, or CS with PI. Moreover, Fast 3Dm and CS with PI may play as substitution to PI for MRCP in patients with IPMN. KEY POINTS: • Mean examination times of multiple k-space data acquisitions for each TR and compressed sensing with parallel imaging were significantly shorter than that of parallel imaging (p < 0.0001). • When comparing image quality of 3D MRCPs with and without deep learning reconstruction, deep learning reconstruction significantly improved signal-to-noise ratio and contrast-to-noise ratio (p < 0.05). • IPMN distribution accuracies of parallel imaging with and without deep learning reconstruction (with vs. without: 88.0% vs. 88.0%) and multiple k-space data acquisitions for each TR with deep learning reconstruction (86.0%) were significantly higher than those of others (p < 0.05).

Fosphenytoin Alleviates Herpes Simplex Virus Infection-Induced Provoked and Spontaneous Pain-Like Behaviors in Mice.

In this study, we investigated the effects of fosphenytoin (fPHT), a water-soluble prodrug of phenytoin, on the pain responses of a mouse herpes zoster (HZ) pain model. Transdermal herpes simplex virus type 1 (HSV-1) inoculation induced mechanical allodynia and hyperalgesia of the hind paw and spontaneous pain-like behaviors, such as licking the affected skin. Intravenous injection of fPHT (15 and 30 mg/kg) alleviated HSV-1-induced provoked pain (allodynia and hyperalgesia). The suppressive effects of fPHT on provoked pain were weaker than those of diclofenac and pregabalin which were used as positive controls. fPHT, diclofenac, and pregabalin significantly suppressed HSV-1-induced spontaneous pain-like behaviors. Among them, high-dose fPHT (30 mg/kg) showed the strongest suppression. Intravenous fPHT may become a viable option for an acute HZ pain, especially for spontaneous pain.

Machine learning for lung texture analysis on thin-section CT: Capability for assessments of disease severity and therapeutic effect for connective tissue disease patients in comparison with expert panel evaluations.

BACKGROUND: The need for quantitative assessment of interstitial lung involvement on thin-section computed tomography (CT) has arisen in interstitial lung diseases including connective tissue disease (CTD). PURPOSE: To evaluate the capability of machine learning (ML)-based CT texture analysis for disease severity and treatment response assessments in comparison with qualitatively assessed thin-section CT for patients with CTD. MATERIAL AND METHODS: A total of 149 patients with CTD-related ILD (CTD-ILD) underwent initial and follow-up CT scans (total 364 paired serial CT examinations), pulmonary function tests, and serum KL-6 level tests. Based on all follow-up examination results, all paired serial CT examinations were assessed as "Stable" (n = 188), "Worse" (n = 98) and "Improved" (n = 78). Next, quantitative index changes were determined by software, and qualitative disease severity scores were assessed by consensus of two radiologists. To evaluate differences in each quantitative index as well as in disease severity score between paired serial CT examinations, Tukey's honestly significant difference (HSD) test was performed among the three statuses. Stepwise regression analyses were performed to determine changes in each pulmonary functional parameter and all quantitative indexes between paired serial CT scans. RESULTS: Δ% normal lung, Δ% consolidation, Δ% ground glass opacity, Δ% reticulation, and Δdisease severity score showed significant differences among the three statuses (P < 0.05). All differences in pulmonary functional parameters were significantly affected by Δ% normal lung, Δ% reticulation, and Δ% honeycomb (0.16 ≤r2 ≤0.42; P < 0.05). CONCLUSION: ML-based CT texture analysis has better potential than qualitatively assessed thin-section CT for disease severity assessment and treatment response evaluation for CTD-ILD.

Interstitial lung disease associated with adjuvant and neoadjuvant chemotherapy in early breast cancer.

BACKGROUND: Interstitial lung disease (ILD) is a rare adverse event in patients receiving adjuvant or neoadjuvant chemotherapy (NAC) for breast cancer. Few studies have reported the frequency of ILD in detail, and only small numbers of cases have been described in the literature. Given these previous findings concerning ILD, we retrospectively examined the clinicopathological characteristics of five cases of ILD who had received epirubicin and cyclophosphamide (EC) and compared their findings with non-ILD cases. METHODS: The present single-center retrospective study included breast cancer patients who underwent adjuvant chemotherapy or NAC at our hospital between January 2014 and January 2021. RESULTS: Thirty-nine patients who had received EC for operable breast cancer were enrolled in this study. ILD developed 5 out of 39 patients (12.8%). The incidence of ILD in patients with non-dose-dense (dd) or dd chemotherapy was statistically significantly different (p = 0.0149). ILD occurred in three patients during dd EC treatment and two during weekly paclitaxel (wPTX) after dd EC. ILD was detected in one patient with high Krebs von den Lungen-6 (KL-6) levels, in two patients with continuous pyrexia, and in two patients from computed tomography imaging, which was taken to estimate the efficacy of chemotherapy, in two patients. Three of the 5 ILD patients underwent bronchoalveolar lavage, and 2 of these patients were diagnosed with Pneumocystis jirovecii pneumonia (PCP). There were no cases of serious ILD that required steroid pulse therapy. CONCLUSIONS: Dd chemotherapy may be associated with an increased ILD frequency, which may reflect developing PCP. Careful monitoring and a timely diagnosis are useful for detecting early-stage ILD.

Adipose tissue-derived stem cells suppress coronary arteritis of Kawasaki disease in vivo.

BACKGROUND: Kawasaki disease (KD) is a systemic inflammatory disease resulting in an acute febrile syndrome commonly affecting children younger than 5 years. Coronary arteritis in KD is occasionally non-responsive to several treatments. Recently, adipose tissue-derived stem cells (ADSCs) have been shown to have anti-inflammatory, immunosuppressive, and tissue-repair characteristics and are considered a useful treatment for inflammatory disease. The present study aimed to elucidate whether the administration of ADSCs can suppress KD-associated vasculitis in vivo. METHODS: Candida albicans water-soluble fraction is often used to model KD via the induction of severe coronary arteritis. Kawasaki disease model mice were intravenously administered ADSCs and phosphate-buffered saline (PBS). On day 29, the mice were sacrificed and hearts from mice in each group were dissected. This was followed by serum collection. Cardiac tissue sections were subjected to histopathological examination to evaluate the inflammatory area. The levels of pro-inflammatory cytokines in the serum were analyzed at days 15 and 29. The survival rates of both groups were compared. RESULTS: The mean inflammatory area in coronary arteritis was significantly lower in the ADSC group compared to the PBS group (P < 0.01). Furthermore, the levels of pro-inflammatory cytokines, such as IL-1ß, IL-12, IL-17, RANTES, INF-γ, and TNF-α, in the ADSC group were significantly lower than those in the PBS group. Moreover, the ADSC group had a significantly higher survival rate than the PBS group. CONCLUSIONS: These findings highlight that ADSCs have anti-inflammatory and immune regulatory functions that could provide novel cell-based therapeutic strategies for severe KD.

Clinical and molecular characteristics of MEF2D fusion-positive B-cell precursor acute lymphoblastic leukemia in childhood, including a novel translocation resulting in MEF2D-HNRNPH1 gene fusion.

Fusion genes involving MEF2D have recently been identified in precursor B-cell acute lymphoblastic leukemia, mutually exclusive of the common risk stratifying genetic abnormalities, although their true incidence and associated clinical characteristics remain unknown. We identified 16 cases of acute lymphoblastic leukemia and 1 of lymphoma harboring MEF2D fusions, including MEF2D-BCL9 (n=10), MEF2D-HNRNPUL1 (n=6), and one novel MEF2D-HNRNPH1 fusion. The incidence of MEF2D fusions overall was 2.4% among consecutive precursor B-cell acute lymphoblastic leukemia patients enrolled onto a single clinical trial. They frequently showed a cytoplasmic µ chain-positive pre-B immunophenotype, and often expressed an aberrant CD5 antigen. Besides up- and down-regulation of HDAC9 and MEF2C, elevated GATA3 expression was also a characteristic feature of MEF2D fusion-positive patients. Mutations of PHF6, recurrent in T-cell acute lymphoblastic leukemia, also showed an unexpectedly high frequency (50%) in these patients. MEF2D fusion-positive patients were older (median age 9 years) with elevated WBC counts (median: 27,300/ml) at presentation and, as a result, were mostly classified as NCI high risk. Although they responded well to steroid treatment, MEF2D fusion-positive patients showed a significantly worse outcome, with 53.3% relapse and subsequent death. Stem cell transplantation was ineffective as salvage therapy. Interestingly, relapse was frequently associated with the presence of CDKN2A/CDKN2B gene deletions. Our observations indicate that MEF2D fusions comprise a distinct subgroup of precursor B-cell acute lymphoblastic leukemia with a characteristic immunophenotype and gene expression signature, associated with distinct clinical features.

A case of uterine lymphangioleiomyomatosis in a young woman that was identified via peritonitis.

Although lymphangioleiomyomatosis is often observed with tuberous sclerosis, uterine lymphangioleiomyomatosis is rare. Our patient was 36 years old (gravida 0, para 0). She had a history of tuberous sclerosis, and many myometrial cystic lesions were identified during assisted reproductive therapy. Although we administered a gonadotropin-releasing hormone analog, myometrial cystic lesions increased in size. Therefore, simple hysterectomy, bilateral salpingo-oophorectomy and pelvic lymph node biopsy were performed. Postoperative histology showed lymphangioleiomyomatosis and myometrial abscess. For uterine lesions in young women with tuberous sclerosis, the possibility of uterine lymphangioleiomyomatosis should also be considered.

Transition in Longgu Surface Associated with Decoction Process of Keishikaryukotsuboreito.

We aim to attain the sustainable use of longgu and have investigated the significance of longgu in Keishikaryukotsuboreito (KRB) decoction. We have already reported that longgu alters compound profiles in KRB decoction and hypothesized that it does so by adsorbing foreign organic compounds into its superficial pores. In the present study, we focused on the adsorbability of organic materials onto longgu surface as the cause of component profile alteration. We analyzed the physical changes in longgu through the decoction process by measuring the adsorbed water on longgu surface. 1H magic angle spinning NMR (1H-MASNMR) spectroscopic analysis revealed that raw longgu (R-raw) as well as decocted longgu [whether single (R-r) or KRB (R-krb) decoction] adsorbed water. However, the amount of adsorbed water in R-krb was smaller than that in R-raw and R-r. The nitrogen adsorption isotherms of longgu samples indicated that longgu was macroporous. The Brunauer-Emmett-Teller (BET) surface area of R-krb was smaller than that of R-raw and R-r. Further, thermogravimetric analysis of longgu samples showed that R-krb adsorbed matter that R-raw and R-r did not adsorb. The above findings and the 1H-MASNMR analysis of heated longgu samples suggested that longgu adsorbed organic compounds into the pores. We considered that longgu adsorbed organic compounds during KRB decoction into its superficial pores through the decoction process.

Photogeneration of Microporous Amorphous Coordination Polymers from Organometallic Ionic Liquids.

Ruthenium-containing organometallic ionic liquids with the B(CN)4 anion were developed that generate microporous amorphous coordination polymers upon UV irradiation. UV light irradiation of [Ru(C5 H5 )(C6 H5 R)][B(CN)4 ] (R=butyl, ethyl, octyl) quantitatively generated a yellow powder of a coordination polymer with the formula [Ru(C5 H5 ){B(CN)4 }]n . In this reaction, the arene ligand is eliminated by UV irradiation and coordination polymer is formed by coordination of the cyano groups of the anion to the Ru ion. The photogenerated solids exhibited nitrogen absorption properties due to their microporous structure. This paper proposes a method to fabricate functional coordination polymers by photoirradiation of liquids.