Case of new-onset fulminant type 1 diabetes mellitus accompanied by autoimmune thyroid disease after SARS-CoV-2 infection.

There is growing evidence suggesting an association between severe acute respiratory coronavirus syndrome coronavirus 2 (SARS-CoV-2) infection and various extrapulmonary diseases since the advent of coronavirus disease 2019 (COVID-19) pandemic. However, case reports of fulminant type 1 diabetes mellitus (FT1D) following SARS-CoV-2 infection are limited. We encountered a 44-year-old Japanese woman who developed FT1D accompanied by subclinical thyrotoxicosis caused by autoimmune thyroid disease (AITD) approximately one week after SARS-CoV-2 infection. The patient developed fever and flu-like symptom 4 days before transportation and tested positive then for the SARS-CoV-2 antigen self-test. She subsequently developed sudden thirst, polyuria, and fatigue of 1 day duration and was urgently brought to our emergency room. Laboratory findings indicated diabetic ketoacidosis (DKA) without marked elevation of serum glycated hemoglobin (HbA1c) levels (glucose, 930 mg/dL; HbA1c, 7.4%). Her insulin secretory capacity was almost completely depleted, and islet-specific autoantibodies were negative. Endocrine examinations revealed subclinical thyrotoxicosis, which was positive for thyroid stimulation hormone receptor antibodies. Based on these results, the patient was diagnosed with FT1D accompanied by AITD and immediately started on intensive insulin therapy with a basal-bolus subcutaneous insulin regimen. Human leukocyte antigen analysis revealed haplotypes, indicating susceptibility to both FT1D and AITD. Further studies are required to elucidate the causal relationship between SARS-CoV-2 infection, FT1D, and AITD. However, clinicians must be vigilant about possible development of FT1D and AITD to enable accurate diagnosis and treatment of patients with DKA during the COVID-19 pandemic.

Combination of transbronchoscopic oxygen insufflation and a digital chest drainage system in endobronchial occlusion: a hybrid technique for localization of fistula in intractable pneumothorax.

BACKGROUND: The management of intractable secondary pneumothorax poses a considerable challenge as it is often not indicated for surgery owing to the presence of underlying disease and poor general condition. While endobronchial occlusion has been employed as a non-surgical treatment for intractable secondary pneumothorax, its effectiveness is limited by the difficulty of locating the bronchus leading to the fistula using conventional techniques. This report details a case treated with endobronchial occlusion where the combined use of transbronchoscopic oxygen insufflation and a digital chest drainage system enabled location of the bronchus responsible for a prolonged air leak, leading to the successful treatment of intractable secondary pneumothorax. CASE PRESENTATION: An 83-year-old male, previously diagnosed with chronic hypersensitivity pneumonitis and treated with long-term oxygen therapy and oral corticosteroid, was admitted due to a pneumothorax emergency. Owing to a prolonged air leak after thoracic drainage, the patient was deemed at risk of developing an intractable secondary pneumothorax. Due to his poor respiratory condition, endobronchial occlusion with silicone spigots was performed instead of surgery. The location of the bronchus leading to the fistula was unclear on CT imaging. When the bronchoscope was wedged into each subsegmental bronchus and low-flow oxygen was insufflated, a digital chest drainage system detected a significant increase of the air leak only in B5a and B5b, thus identifying the specific location of the bronchus leading to the fistula. With the occlusion of those bronchi using silicone spigots, the air leakage decreased from 200 mL/min to 20 mL/min, and the addition of an autologous blood patch enabled successful removal of the drainage tube. CONCLUSION: The combination of transbronchoscopic oxygen insufflation with a digital chest drainage system can enhance the therapeutic efficacy of endobronchial occlusion by addressing the problems encountered in conventional techniques, where the ability to identify the leaking bronchus is dependent on factors such as the amount of escaping air and the location of the fistula.

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.

A Case of Successful Removal of a Foreign Body Located in the Peripheral Airway Using Flexible Bronchoscopy with Virtual Bronchoscopy Navigation.

A case in which a foreign body located in the peripheral airway of the lung was removed by flexible bronchoscopy using a virtual bronchoscopy navigation (VBN) system has been reported. The patient was a 60-year-old man. Chest radiography revealed an incidental foreign body in the left lower lung. Chest computed tomography with 1.0-mm slices was used to create a VBN system and confirm the foreign body in left B9biiαy, which was removed by flexible bronchoscopy. Thus, peripheral foreign bodies can be safely removed using flexible bronchoscopy by creating a VBN system in advance.

Glymphatic system impairment in sleep disruption: diffusion tensor image analysis along the perivascular space (DTI-ALPS).

PURPOSE: This study aimed to evaluate the relationship between sleep quality as assessed using the Pittsburgh Sleep Quality Index (PSQI) and the index of diffusivity along the perivascular space (ALPS index), a possible indirect indicator of glymphatic system activity. MATERIALS AND METHODS: This study included the diffusion magnetic resonance imaging (MRI) data of 317 people with sleep disruption and 515 healthy controls (HCs) from the Human Connectome Project (WU-MINN HCP 1200). The ALPS index was calculated automatically based on diffusion tensor image analysis (DTI)-ALPS of diffusion MRI. The ALPS index of the sleep disruption and HC groups was compared using general linear model (GLM) analysis with covariates, such as age, sex, level of education, and intracranial volume. In addition, to confirm the relationship between sleep quality and the ALPS index in the sleep disruption group as well as evaluate the effect of each PSQI component on the ALPS index, correlation analyses between the ALPS indices and PSQI scores of all the components and between the ALPS index and each PSQI component was performed using GLM analysis with the abovementioned covariates, respectively. RESULTS: The ALPS index was significantly lower in the sleep disruption group than in the HC group (p = 0.001). Moreover, the ALPS indices showed significant negative correlations with the PSQI scores of all the components (false discovery rate [FDR]-corrected p < 0.001). Two significant negative correlations were also found between the ALPS index and PSQI component 2 (sleep latency, FDR-corrected p < 0.001) and 6 (the use of sleep medication, FDR-corrected p < 0.001). CONCLUSION: Our findings suggest that glymphatic system impairment contributes to sleep disruption in young adults.

Diagnostic Utility and Safety of Non-Intubated Cryobiopsy Technique Using a Novel Ultrathin Cryoprobe in Addition to Conventional Biopsy Techniques for Peripheral Pulmonary Lesions.

BACKGROUND: Transbronchial cryobiopsy enables high-quality sample collection around the probe tip. Meanwhile, existing cryoprobes have less flexibility and a higher risk of bleeding. The ultrathin cryoprobe with a 1.1-mm diameter addresses these problems and allows specimens to be directly retrieved through the working channel of a thin bronchoscope. OBJECTIVE: This study evaluated the diagnostic utility and safety of non-intubated cryobiopsy using an ultrathin cryoprobe added to conventional biopsy for diagnosing peripheral pulmonary lesions (PPLs). METHODS: The data of patients who underwent conventional biopsy followed by non-intubated cryobiopsy to retrieve specimens through the thin bronchoscope's working channel for diagnosing PPLs at Osaka Metropolitan University Hospital from July 2021 to June 2022 were retrospectively collected. They were analyzed to evaluate the diagnostic utility and safety of adding non-intubated cryobiopsy to conventional biopsy for PPLs. The characteristics of PPLs that obtain additional diagnostic benefits from cryobiopsy over conventional biopsy were also investigated. RESULTS: The analysis included 113 patients. The diagnostic yields of conventional biopsy and non-intubated cryobiopsy were 70.8% and 82.3%, respectively (p = 0.009). The total diagnostic yield was 85.8%, higher than conventional biopsy alone (p < 0.001). Although one moderate bleeding occurred, no severe complications developed. The additional diagnostic benefits of non-intubated cryobiopsy over conventional biopsy were demonstrated when the radial endobronchial ultrasound (R-EBUS) showed "adjacent to" (60.3% vs. 82.8%, p = 0.017). CONCLUSIONS: Non-intubated cryobiopsy using an ultrathin cryoprobe has high diagnostic utility and safety for diagnosing PPLs, with additional diagnostic benefits over conventional biopsy depending on the R-EBUS image.

Glymphatic system impairment in corticobasal syndrome: diffusion tensor image analysis along the perivascular space (DTI-ALPS).

PURPOSE: This study aimed to evaluate the along the perivascular space (ALPS) index based on the diffusion tensor image ALPS (DTI-ALPS) in corticobasal degeneration with corticobasal syndrome (CBD-CBS) and investigate its correlation with motor and cognitive functions. MATERIALS AND METHODS: The data of 21 patients with CBD-CBS and 17 healthy controls (HCs) were obtained from the 4-Repeat Tauopathy Neuroimaging Initiative and the Frontotemporal Lobar Degeneration Neuroimaging Initiative databases. Diffusion magnetic resonance imaging was performed using a 3-Tesla MRI scanner. The ALPS index based on DTI-ALPS was automatically calculated after preprocessing. The ALPS index was compared between the CBD-CBS and HC groups via a general linear model analysis, with covariates such as age, sex, years of education, and intracranial volume (ICV). Furthermore, to confirm the relation between the ALPS index and the motor and cognitive score in CBD-CBS, the partial Spearman's rank correlation coefficient was calculated with covariates such as age, sex, years of education, and ICV. A p value of < 0.05 was considered as statistically significant in all statistical analyses. RESULTS: The ALPS index of CBD-CBS was significantly lower than that of HC (Cohen's d = - 1.53, p < 0.005). Moreover, the ALPS index had a significant positive correlation with the mini mental state evaluation score (rs = 0.65, p < 0.005) and a significant negative correlation with the unified Parkinson's Disease Rating Scale III score (rs = - 0.75, p < 0.001). CONCLUSION: The ALPS index of patients with CBD-CBS, which is significantly lower than that of HCs, is significantly associated with motor and cognitive functions.

Reproducibility of automated calculation technique for diffusion tensor image analysis along the perivascular space.

PURPOSE: The method of diffusion tensor image analysis along the perivascular space (DTI-ALPS) was gathering attention to evaluate the brain's glymphatic function or interstitial fluid dynamics. However, to the best knowledge, no study was conducted on the reproducibility of these automated methods for ALPS index values. Therefore, the current study evaluated the ALPS index reproducibility based on DTI-ALPS using two major automated calculation techniques in scan and rescan of the same subject on the same day. MATERIALS AND METHODS: This study included 23 participants, including 2 with Alzheimer's disease, 15 with mild cognitive impairment, and 6 with cognitive normals. Scan and rescan data of diffusion magnetic resonance images were obtained, as well as automatically index for ALPS (ALPS index) and ALPS index maintaining tensor vector orientation information (vALPS index) with region of interest on the template fractional anisotropy map calculated by FSL software.These ALPS indices were compared in terms of scan and rescan reproducibility. RESULTS: The absolute difference in ALPS-index values between scan and rescan was larger in the ALPS index than in the vALPS index by approximately 0.6% as the relative difference. Cohen's d for the left and right ALPS indices between methods were 0.121 and 0.159, respectively. CONCLUSION: The vALPS index based on DTI-ALPS maintaining tensor vector orientation information has higher reproducibility than the ALPS index. This result encourages a multisite study on the ALPS index with a large sample size and helps detect a subtle pathological change in the ALPS index.

Distinct contributions of muscle mass and strength stratified by nutritional status to physical activity in patients with chronic obstructive pulmonary disease.

BACKGROUND: Physical activity is one of the most important prognostic factors for patients with chronic obstructive pulmonary disease (COPD). Physical activity correlates significantly with skeletal muscle mass and strength. Pulmonary rehabilitation has been conducted to improve physical activity, but its effectiveness has been inconsistent. Nutritional status is also related to physical activity in patients with COPD. The relationships between skeletal muscle mass, strength, and nutritional status evaluated using the Mini Nutritional Assessment Short Form (MNA-SF) were investigated. How nutritional status alters the relationships between physical activity, exercise capacity, skeletal muscle mass, and strength was also investigated. METHODS: This retrospective, cross-sectional study enrolled 81 outpatients with COPD. In all patients, physical activity, exercise capacity, body composition assessment, and MNA-SF were assessed. The relationships between physical activity, exercise capacity, skeletal muscle mass, and strength were examined according to the MNA-SF. RESULTS: The MNA-SF high group had significantly higher skeletal muscle mass than the MNA-SF low group when skeletal muscle strength was the covariate. In the MNA-SF low group, physical activity positively correlated with skeletal muscle mass. In the MNA-SF high group, physical activity positively correlated with skeletal muscle strength. CONCLUSIONS: This study showed that the nutritional status of patients with COPD alters the relationship between physical activity and skeletal muscle mass or strength. Optimizing rehabilitation with nutrition interventions according to nutritional status might improve physical activity in patients with COPD.

Feasibility of Quantitative MRI Using 3D-QALAS for Discriminating Immunohistochemical Status in Invasive Ductal Carcinoma of the Breast.

BACKGROUND: Two-dimensional synthetic MRI of the breast has limited spatial coverage. Three-dimensional (3D) synthetic MRI could provide volumetric quantitative parameters that may reflect the immunohistochemical (IHC) status in invasive ductal carcinoma (IDC) of the breast. PURPOSE: To evaluate the feasibility of 3D synthetic MRI using an interleaved Look-Locker acquisition sequence with a T2 preparation pulse (QALAS) for discriminating the IHC status, including hormone receptor (HR), human epidermal growth factor receptor 2 (HER 2), and Ki-67 expression in IDC. STUDY TYPE: Prospective observational study. POPULATION: A total of 33 females with IDC of the breast (mean, 52.3 years). FIELD STRENGTH/SEQUENCE: A 3-T, 3D-QALAS gradient-echo and fat-suppressed T1-weighted 3D fast spoiled gradient-echo sequences. ASSESSMENT: Two radiologists semiautomatically delineated 3D regions of interest (ROIs) of the whole tumors on the dynamic MRI that was registered to the synthetic T1-weighted images acquired from 3D-QALAS. The mean T1 and T2 were measured for each IDC. STATISTICAL TESTS: Intraclass correlation coefficient for assessing interobserver agreement. Mann-Whitney U test to determine the relationship between the mean T1 or T2 and the IHC status. Multivariate logistic regression analysis followed by receiver operating characteristics (ROC) analysis for discriminating IHC status. A P value <0.05 was considered statistically significant. RESULTS: The interobserver agreement was good to excellent. There was a significant difference in the mean T1 between HR-positive and HR-negative lesions, while the mean T2 value differed between HR-positive and HR-negative lesions, between the triple-negative and HR-positive or HER2-positive lesions, and between the Ki-67 level > 14% and ≤ 14%. Multivariate analysis showed that the mean T2 was higher in HR-negative IDC than in HR-positive IDC. ROC analysis revealed that the mean T2 was predictive for discriminating HR status, triple-negative status, and Ki-67 level. DATA CONCLUSION: 3D synthetic MRI using QALAS may be useful for discriminating IHC status in IDC of the breast. EVIDENCE LEVEL: 1. TECHNICAL EFFICACY: Stage 2.

COVID-19 vaccination benefits in preventing severe disease in mild-to-moderate cases: An analysis in the first specialized hospital for COVID-19 in Japan.

BACKGROUND: In Japan, the fourth round of coronavirus disease (COVID-19) vaccination is ongoing and is targeted at medical staff and nursing home workers, individuals aged ≥60 years, and those with comorbidities or other high-risk factors, including body mass index (BMI) ≥30 kg/m2. The incidence of severe COVID-19 decreased markedly after widespread COVID-19 vaccination drives, and our hospital experienced a similar trend. We, therefore, examined the characteristics of our patients to clarify who benefited the most from vaccination. METHODS: We retrospectively investigated all patients hospitalized for COVID-19 in Osaka City Juso Hospital between March 1, 2021, and June 30, 2022. Using multivariable logistic analysis, we calculated the adjusted odds ratios (aORs) for severe disease after vaccination in the whole dataset and in subsets stratified by age, sex, BMI, smoking history, pre-hospitalization location, and comorbidities. RESULTS: The analysis included 1041 patients. Multivariable logistic analysis showed that vaccination was associated with a low risk of severe disease, with an aOR of 0.21 (95% confidence interval: 0.12-0.36, p < 0.001). On stratifying the analysis according to background characteristics, lower aORs for severe COVID-19 were found for patients aged ≥60 years and for those with diabetes or hypertension. Notably, patients with BMI >30 kg/m2 and those with BMI ≥18 kg/m2 and ≤30 kg/m2 benefited from vaccination. CONCLUSIONS: Individuals with diabetes or hypertension and those of age ≥60 years benefited more from vaccination than did their counterparts. We recommend extending the fourth round of vaccinations to individuals with a BMI of 18-30 kg/m2.

Automation of a Rule-based Workflow to Estimate Age from Brain MR Imaging of Infants and Children Up to 2 Years Old Using Stacked Deep Learning.

PURPOSE: Myelination-related MR signal changes in white matter are helpful for assessing normal development in infants and children. A rule-based myelination evaluation workflow regarding signal changes on T1-weighted images (T1WIs) and T2-weighted images (T2WIs) has been widely used in radiology. This study aimed to simulate a rule-based workflow using a stacked deep learning model and evaluate age estimation accuracy. METHODS: The age estimation system involved two stacked neural networks: a target network-to extract five myelination-related images from the whole brain, and an age estimation network from extracted T1- and T2WIs separately. A dataset was constructed from 119 children aged below 2 years with two MRI systems. A four-fold cross-validation method was adopted. The correlation coefficient (CC), mean absolute error (MAE), and root mean squared error (RMSE) of the corrected chronological age of full-term birth, as well as the mean difference and the upper and lower limits of 95% agreement, were measured. Generalization performance was assessed using datasets acquired from different MR images. Age estimation was performed in Sturge-Weber syndrome (SWS) cases. RESULTS: There was a strong correlation between estimated age and corrected chronological age (MAE: 0.98 months; RMSE: 1.27 months; and CC: 0.99). The mean difference and standard deviation (SD) were -0.15 and 1.26, respectively, and the upper and lower limits of 95% agreement were 2.33 and -2.63 months. Regarding generalization performance, the performance values on the external dataset were MAE of 1.85 months, RMSE of 2.59 months, and CC of 0.93. Among 13 SWS cases, 7 exceeded the limits of 95% agreement, and a proportional bias of age estimation based on myelination acceleration was exhibited below 12 months of age (P = 0.03). CONCLUSION: Stacked deep learning models automated the rule-based workflow in radiology and achieved highly accurate age estimation in infants and children up to 2 years of age.

Effect of Temporal Sampling Rate on Estimates of the Perfusion Parameters for Patients with Moyamoya Disease Assessed with Simultaneous Multislice Dynamic Susceptibility Contrast-enhanced MR Imaging.

PURPOSE: The effect of temporal sampling rate (TSR) on perfusion parameters has not been fully investigated in Moyamoya disease (MMD); therefore, this study evaluated the influence of different TSRs on perfusion parameters quantitatively and qualitatively by applying simultaneous multi-slice (SMS) dynamic susceptibility contrast-enhanced MR imaging (DSC-MRI). METHODS: DSC-MRI datasets were acquired from 28 patients with MMD with a TSR of 0.5 s. Cerebral blood flow (CBF), cerebral blood volume (CBV), mean transit time (MTT), time to peak (TTP), and time to maximum tissue residue function (Tmax) were calculated for eight TSRs ranging from 0.5 to 4.0 s in 0.5-s increments that were subsampled from a TSR of 0.5 s datasets. Perfusion measurements and volume for chronic ischemic (Tmax ≥ 2 s) and non-ischemic (Tmax < 2 s) areas for each TSR were compared to measurements with a TSR of 0.5 s, as was visual perfusion map analysis. RESULTS: CBF, CBV, and Tmax values tended to be underestimated, whereas MTT and TTP values were less influenced, with a longer TSR. Although Tmax values were overestimated in the TSR of 1.0 s in non-ischemic areas, differences in perfusion measurements between the TSRs of 0.5 and 1.0 s were generally minimal. The volumes of the chronic ischemic areas with a TSR ≥ 3.0 s were significantly underestimated. In CBF and CBV maps, no significant deterioration was noted in image quality up to 3.0 and 2.5 s, respectively. The image quality of MTT, TTP, and Tmax maps for the TSR of 1.0 s was similar to that for the TSR of 0.5 s but was significantly deteriorated for the TSRs of ≥ 1.5 s. CONCLUSION: In the assessment of MMD by SMS DSC-MRI, application of TSRs of ≥ 1.5 s may lead to deterioration of the perfusion measurements; however, that was less influenced in TSRs of ≤ 1.0 s.

Idiopathic Obliterative Bronchiolitis in a Young Woman: A Rare Case of a Transbronchial Lung Biopsy Contributing to the Diagnosis.

Idiopathic obliterative bronchiolitis (OB) is a rare disease that usually requires a surgical lung biopsy. A 25-year-old woman with progressive exertional dyspnea for several months showed a severe mixed restrictive and obstructive pattern on spirometry. Chest computed tomography showed a mosaic pattern, and pulmonary ventilation-perfusion scintigraphy showed a matched defect. The bronchoscopic specimens obtained from both the alveolar and bronchiolar regions of the predicted lesion area contributed to the diagnosis of OB. She had no underlying causes of secondary OB, and she was diagnosed with idiopathic OB. Since lung transplantation was indicated, she was referred to a lung transplantation-certified hospital.

Safety profile and risk factors for bleeding in transbronchial cryobiopsy using a two-scope technique for peripheral pulmonary lesions.

BACKGROUND: A balloon occlusion technique is suggested for use in cryobiopsy for interstitial lung diseases because of the bleeding risk. However, it may interfere with selection of the involved bronchus for peripheral pulmonary lesions (PPLs). A two-scope technique, in which two scopes are prepared and hemostasis is started using the second scope immediately after cryobiopsy, has also been reported. This study aimed to evaluate the safety and diagnostic utility of transbronchial cryobiopsy using the two-scope technique for PPLs. METHODS: Data of patients who underwent conventional biopsy followed by cryobiopsy using the two-scope technique for PPLs from November 2019 to March 2021 were collected. The incidence of complications and risk factors for clinically significant bleeding (moderate to life-threatening) were investigated. Diagnostic yields were also compared among conventional biopsy, cryobiopsy, and the combination of them. RESULTS: A total of 139 patients were analyzed. Moderate bleeding occurred in 25 (18.0%) patients without severe/life-threatening bleeding. Although five cases required transbronchial instillation of thrombin, all bleeding was completely controlled using the two-scope technique. Other complications included two pneumothoraces and one asthmatic attack. On multivariable analysis, only ground-glass features (P < 0.001, odds ratio: 9.30) were associated with clinically significant bleeding. The diagnostic yields of conventional biopsy and cryobiopsy were 76.3% and 81.3%, respectively (P = 0.28). The total diagnostic yield was 89.9%, significantly higher than conventional biopsy alone (P < 0.001). CONCLUSIONS: The two-scope technique provides useful hemostasis for safe cryobiopsy for PPLs, with a careful decision needed for ground-glass lesions.

Genomic characterization of triple-carbapenemase-producing Acinetobacter baumannii.

OBJECTIVES: To characterize Acinetobacter baumannii OCU_Ac16a, a clinical isolate co-harbouring three acquired carbapenemase genes, bla NDM-1, bla TMB-1, and bla OXA-58, and assess the clinical significance of so-called multiple-carbapenemase producers. METHODS: OCU_Ac16a and its close relative, OCU_Ac16b, which lacks the bla NDM-1, were isolated from sputum cultures of a patient at Osaka City University Hospital. We subjected these strains to whole-genome analysis, particularly focusing on the genetic context of each carbapenemase gene. The transmissibility and functionality of each carbapenemase gene were analysed by conjugation and transformation experiments and antimicrobial susceptibility tests. RESULTS: bla TMB-1 was located in a class 1 integron on the chromosome, whereas bla NDM-1 and bla OXA-58 were found on plasmids named pOCU_Ac16a_2 and pOCU_Ac16a_3, respectively. pOCU_Ac16a_2 (which exhibited highly efficient self-transmissibility) and pOCU_Ac16a_3 (which did not show transmissibility but could be introduced into another A. baumannii strain via electroporation) could both confer carbapenem resistance (MICs ≥512 and ≥32 mg/L, respectively) on the recipient strain. The functionality of bla TMB-1 was evident from the high resistance of OCU_Ac16b to ceftazidime and cefepime (MICs ≥256 and 48 mg/L, respectively), and the high resistance of OCU_Ac16a to cefiderocol (MIC 32 mg/L) could be explained by the additive effect of bla NDM-1 and bla TMB-1. CONCLUSIONS: Our data revealed the genomic organization of OCU_Ac16a and demonstrated that all the carbapenemase genes are functional, each contributing to the extremely high broad-spectrum resistance of OCU_Ac16a to ß-lactams. As multiple-carbapenemase producers can be serious health threats as drug-resistant pathogens and disseminators of carbapenemase genes, close attention should be paid to their emergence.

The Fermented Soy Product ImmuBalanceTM Suppresses Airway Inflammation in a Murine Model of Asthma.

The fermented soy product ImmuBalance contains many active ingredients and its beneficial effects on some allergic diseases have been reported. We hypothesized that ImmuBalance could have potential effects on airway inflammation in a murine model of asthma. Mice sensitized and challenged with ovalbumin developed airway inflammation. Bronchoalveolar lavage fluid was assessed for inflammatory cell counts and levels of cytokines. Lung tissues were examined for cell infiltration and mucus hypersecretion. Oral administration of ImmuBalance significantly inhibited ovalbumin-induced eosinophilic inflammation and decreased Th2 cytokine levels in bronchoalveolar lavage fluid (p < 0.05). In addition, lung histological analysis showed that ImmuBalance inhibited inflammatory cell infiltration and airway mucus production. Our findings suggest that supplementation with ImmuBalance may provide a novel strategy for the prevention or treatment of allergic airway inflammation.

Deep Learning-Based Functional Independence Measure Score Prediction After Stroke in Kaifukuki (Convalescent) Rehabilitation Ward Annexed to Acute Care Hospital.

Introduction Prediction models of functional independent measure (FIM) score after kaifukuki (convalescent) rehabilitation ward (KRW) are needed to decide the treatment strategies and save medical resources. Statistical models were reported, but their accuracies were not satisfactory. We made such prediction models using the deep learning (DL) framework, Prediction One (Sony Network Communications Inc., Tokyo, Japan). Methods Of the 559 consecutive stroke patients, 122 patients were transferred to our KRW. We divided our 122 patients' data randomly into halves of training and validation datasets. Prediction One made three prediction models from the training dataset using (1) variables at the acute care ward admission, (2) those at the KRW admission, and (3) those combined (1) and (2). The models' determination coefficients (R2), correlation coefficients (rs), and residuals were calculated using the validation dataset. Results Of the 122 patients, the median age was 71, length of stay (LOS) in acute care ward 23 (17-30) days, LOS in KRW 53 days, total FIM scores at the admission of KRW 85, those at discharge 108. The mean FIM gain and FIM efficiency were 19 and 0.417. All patients were discharged home. Model (1), (2), and (3)'s R2 were 0.794, 0.970, and 0.972. Their mean residuals between the predicted and actual total FIM scores were -1.56±24.6, -4.49±17.1, and -2.69±15.7. Conclusion Our FIM gain and efficiency were better than national averages of FIM gain 17.1 and FIM efficiency 0.187. We made DL-based total FIM score prediction models, and their accuracies were superior to those of previous statistically calculated ones. The DL-based FIM score prediction models would save medical costs and perform efficient stroke and rehabilitation medicine.

Ternary Complexes of pDNA, Neuron-Binding Peptide, and PEGylated Polyethyleneimine for Brain Delivery with Nano-Bubbles and Ultrasound.

In brain-targeted delivery, the transport of drugs or genes across the blood-brain barrier (BBB) is a major obstacle. Recent reports found that focused ultrasound (FUS) with microbubbles enables transient BBB opening and improvement of drug or gene delivery. We previously developed nano-sized bubbles (NBs), which were prepared based on polyethylene glycol (PEG)-modified liposomes containing echo-contrast gas, and showed that our NBs with FUS could also induce BBB opening. The aim of this study was to enhance the efficiency of delivery of pDNA into neuronal cells following transportation across the BBB using neuron-binding peptides. This study used the RVG-R9 peptide, which is a chimeric peptide synthesized by peptides derived from rabies virus glycoprotein and nonamer arginine residues. The RVG peptide is known to interact specifically with the nicotinic acetylcholine receptor in neuronal cells. To enhance the stability of the RVG-R9/pDNA complex in vivo, PEGylated polyethyleneimine (PEG-PEI) was also used. The ternary complexes composed of RVG-R9, PEG-PEI, and pDNA could interact with mouse neuroblastoma cells and deliver pDNA into the cells. Furthermore, for the in vivo experiments using NBs and FUS, gene expression was observed in the FUS-exposed brain hemispheres. These results suggest that this systemic gene delivery system could be useful for gene delivery across the BBB.