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Yusuke Suzuki,1 Yoshiaki Kitaguchi,1 Fumika Ueno,1 Yunden Droma,1 Norihiko Goto,1 Takumi Kinjo,1 Yosuke Wada,1 Masanori Yasuo,2 Masayuki Hanaoka1 1First Department of Internal Medicine, Shinshu University School of Medicine, Matsumoto, Nagano, Japan; 2Departments of Clinical Laboratory Sciences, Shinshu University School of Health Sciences, Matsumoto, Nagano, JapanCorrespondence: Yoshiaki Kitaguchi, First Department of Internal Medicine, Shinshu University School of Medicine, 3-1-1 Asahi, Matsumoto, Nagano, 390-8621, Japan, Tel +81-263-37-2631, Email kitaguti@shinshu-u.ac.jpPurpose: The associations between morphological phenotypes of COPD based on the chest computed tomography (CT) findings and clinical characteristics in surgically resected patients with COPD and concomitant lung cancer are unclear. The purpose of this study was to clarify the differences in clinical characteristics and prognosis among morphological phenotypes based on the chest CT findings in these patients.Patients and Methods: We retrospectively reviewed the medical records of 132 patients with COPD and concomitant lung cancer who had undergone pulmonary resection for primary lung cancer. According to the presence of emphysema and bronchial wall thickness on chest CT, patients were classified into three phenotypes: non-emphysema phenotype, emphysema phenotype, or mixed phenotype.Results: The mixed phenotype was associated with poorer performance status, higher score on the modified British Medical Research Council (mMRC) dyspnea scale, higher residual volume in pulmonary function, and higher proportion of squamous cell carcinoma than the other phenotypes. Univariate and multivariate Cox proportional hazards regression analyses showed that the extent of emphysema on chest CT, presented as a low attenuation area (LAA) score, was an independent determinant that predicted prognosis. In the Kaplan-Meier analysis, the Log rank test showed significant differences in survival between the non-emphysema and mixed phenotypes, and between the emphysema and mixed phenotypes.Conclusion: The cross-sectional pre-operative LAA score can predict the prognosis in surgically resected patients with COPD and concomitant lung cancer. The COPD phenotype with both emphysema and bronchial wall thickness on chest CT was associated with poorer performance status, greater extent of dyspnea, greater impairment of pulmonary function, and worse prognosis.Keywords: LAA, emphysema, CT, prognosis, mortality, surgery

Masanori Yasuo,* Yoshiaki Kitaguchi,* Yayoi Tokoro, Makoto Kosaka, Yosuke Wada, Takumi Kinjo, Atsuhito Ushiki, Hiroshi Yamamoto, Masayuki Hanaoka The First Department of Internal Medicine, Shinshu University School of Medicine, Matsumoto, Japan*These authors contributed equally to this workCorrespondence: Masanori YasuoThe First Department of Internal Medicine, Shinshu University School of Medicine, 3-1-1 Asahi, Matsumoto 390-8621, JapanTel +81 263 37 2631Fax +81 263 36 3722Email yasumasa@shinshu-u.ac.jpBackground: Obstructive ventilatory disturbances occur in both chronic obstructive pulmonary disease (COPD), a typical disease representative of peripheral airway obstruction, and central airway obstruction (CAO). Pulmonary function tests (PFTs), which depend on patient effort, are traditionally used to evaluate lung function. The forced oscillation technique (FOT) is an effort-independent method for examining lung function during tidal breathing. The FOT is used universally to assess respiratory function in patients with COPD. Several studies have measured FOT to assess ventilatory disturbances in CAO. The results showed that FOT measurements in patients with CAO were similar to those reported in patients with COPD. However, no studies have compared FOT measurements directly between CAO and COPD. The aim of this study was to identify differences in ventilatory disturbances between peripheral and central airway obstructions in COPD and CAO, before patients received pharmacological therapy or bronchoscopic interventions, respectively.Patients and Methods: We retrospectively included 16 patients with CAO (10 cases of tracheal obstruction and 6 cases of bronchial obstruction) and 75 treatment-naïve patients with COPD (60 cases in Global Initiative for Chronic Obstructive Lung Disease [GOLD] stage II and 15 cases in GOLD stage III) that were admitted from December 2013 to May 2017. Prior to treatment, patients were examined with the FOT and PFTs.Results: All parameters measured with the FOT in the inspiratory phase were significantly worse in patients with CAO than in patients with COPD. The PFTs showed that the CAO group had a significantly lower peak expiratory flow rate. In the airway wall thickening phenotype of COPD, a difference between the inspiratory and expiratory phases of the resonance frequency (ΔFres) was the best indicator for distinguishing between peripheral and central airway obstructions.Conclusion: This study compared differences between CAO and COPD (mainly GOLD stage II). We found that the FOT measurement, ΔFres, was the optimal indicator of the difference between the airway wall thickening COPD phenotype and CAO. Thus, the difference might be due to mechanical changes that occur in COPD with airway wall thickening.Keywords: forced oscillation technique, pulmonary function test, quality of life, central airway obstruction, COPD

Masanori Yasuo,1 Yunden Droma,1 Yoshiaki Kitaguchi,1 Michiko Ito,1 Hitomi Imamura,1 Masatomo Kawakubo,2 Masayuki Hanaoka11The First Department of Internal Medicine, Shinshu University School of Medicine, Matsumoto, Nagano, Japan; 2Department of Molecular Pathology, Shinshu University Graduate School of Medicine, Matsumoto, Nagano, JapanPurpose: Cigarette smoke produces a high level of acrolein, which is thought to be pathogenically involved in the development of chronic obstructive pulmonary disease (COPD). The present study investigated the pathological role of acrolein in the development of COPD.Patients and methods: Acrolein concentration was measured in plasmas obtained from 47 patients with COPD and 18 current smokers without COPD, and in supernatants of homogenized lung tissues obtained from 10 never-smokers, 8 current smokers, and 8 patients with COPD by high-performance liquid chromatography. Oxidant status and antioxidant activity were measured using derivatives of reactive oxygen metabolite (d-ROM) and bio-antioxidant power (BAP), respectively, in the Free Radical Elective Evaluation FRAS4 system. In addition, immunohistochemistry was used to evaluate the over-presentation of acrolein in lung tissues of patients with COPD.Results: Plasma concentrations of acrolein were significantly higher in the patients with COPD than the non-COPD smokers (P

Yosuke Wada,1 Yoshiaki Kitaguchi,1 Masanori Yasuo,1 Fumika Ueno,1 Satoshi Kawakami,2 Kiyoyasu Fukushima,3 Keisaku Fujimoto,4 Masayuki Hanaoka1 1First Department of Internal Medicine, Shinshu University School of Medicine, Matsumoto, Nagano, Japan; 2Department of Radiology, Shinshu University School of Medicine, Matsumoto, Nagano, Japan; 3Department of Respiratory Medicine, Japanese Red Cross Nagasaki Genbaku Isahaya Hospital, Isahaya, Nagasaki, Japan; 4Departments of Clinical Laboratory Sciences, Shinshu University School of Health Sciences, Matsumoto, Nagano, Japan Introduction: This study was conducted in order to investigate the diversity of respiratory physiology, including the respiratory impedance and reversibility of airway obstruction, based on quantitative computed tomography (CT) in patients with COPD. Patients and methods: Medical records of 174 stable COPD patients were retrospectively reviewed to obtain the patients’ clinical data, including the pulmonary function and imaging data. According to the software-based quantification of the degree of emphysema and airway wall thickness, the patients were classified into the “normal by CT” phenotype, the airway-dominant phenotype, the emphysema-dominant phenotype, and the mixed phenotype. The pulmonary function, including the respiratory impedance evaluated by using the forced oscillation technique (FOT) and the reversibility of airway obstruction in response to inhaled short-acting β2-agonists, was then compared among the four phenotypes. Results: The respiratory system resistance at 5 and 20 Hz (R5 and R20) was significantly higher, and the respiratory system reactance at 5 Hz (X5) was significantly more negative in the airway-dominant and mixed phenotypes than in the other phenotypes. The within-breath changes of X5 (ΔX5) were significantly greater in the mixed phenotype than in the “normal by CT” and emphysema-dominant phenotypes. The FOT parameters (R5, R20, and X5) were significantly correlated with indices of the degree of airway wall thickness and significantly but weakly correlated with the reversibility of airway obstruction. There was no significant correlation between the FOT parameters (R5, R20, and X5) and the degree of emphysema. Conclusion: There is a diversity of respiratory physiology, including the respiratory impedance and reversibility of airway obstruction, based on quantitative CT in patients with COPD. The FOT measurements may reflect the degree of airway disease and aid in detecting airway remodeling in patients with COPD. Keywords: FOT, respiratory impedance, MostGraph, AWT-Pi10

Keisaku Fujimoto,1 Haruna Yamazaki,2 Midori Ura,2 Yoshiaki Kitaguchi3 1Department of Clinical Laboratory Sciences, School of Health Sciences, 2Department of Biomedical Laboratory Science, Graduate School of Medicine, 3First Department of Internal Medicine, School of Medicine, Shinshu University, Matsumoto, Japan Background and objective: The difference in efficacy of long-acting muscarinic antagonists (LAMAs) and long-acting β2-agonists (LABAs) for dynamic lung hyperinflation (DLH) in COPD is unclear. The purpose of this study was to elucidate the difference in efficacy of LAMA and LABA alone and the combination thereof for DLH. Subjects and methods: Thirty stable patients were enrolled and randomly divided into two groups following baseline measurements. One group was treated with 5 µg tiotropium (Respimat inhaler) for 4 weeks following a 4-week treatment with 150 µg indacaterol, while the other group was treated with indacaterol for 4 weeks following a 4-week treatment with tiotropium. For both groups, these treatments were followed by a combination of the two drugs for 4 weeks. Pulmonary function tests, including DLH evaluated by metronome-paced incremental hyperventilation and exercise tolerance evaluated by the shuttle-walk test, were performed at the end of each treatment period. Results: In total, 23 patients completed this study. Both tiotropium and indacaterol alone significantly increased forced expiratory volume in 1 second, exercise tolerance, and improved health status. Tiotropium significantly improved DLH, but indacaterol did not. The combination therapy resulted in further improvements in lung function and exercise tolerance, but not in DLH. Conclusion: The efficacy of tiotropium in inhibiting DLH following metronome-paced incremental hyperventilation may be superior to that of 150 µg indacaterol, although the effects on airflow obstruction were the same, and the combination therapy showed further improvement in airflow obstruction, but not in DLH. Keywords: bronchodilator agents, clinical respiratory medicine, COPD, respiratory function tests, quality of life

Yoshiaki Kitaguchi, Masanori Yasuo, Masayuki Hanaoka First Department of Internal Medicine, Shinshu University School of Medicine, Matsumoto, Japan Background: This study was conducted in order to investigate the differences in the respiratory physiology of patients with chronic obstructive pulmonary disease (COPD), asthma-COPD overlap syndrome (ACOS), and asthma with airflow limitation (asthma FL+). Methods: The medical records for a series of all stable patients with persistent airflow limitation due to COPD, ACOS, or asthma were retrospectively reviewed and divided into the COPD group (n=118), the ACOS group (n=32), and the asthma FL+ group (n=27). All the patients underwent chest high-resolution computed tomography (HRCT) and pulmonary function tests, including respiratory impedance. Results: The low attenuation area score on chest HRCT was significantly higher in the COPD group than in the ACOS group (9.52±0.76 vs 5.09±1.16, P

Yoshiaki Kitaguchi,1,2 Keisaku Fujimoto,3 Masayuki Hanaoka,1 Takayuki Honda,4 Junichi Hotta,2 Jiro Hirayama2 1First Department of Internal Medicine, Shinshu University School of Medicine, Matsumoto, 2Department of Internal Medicine, Okaya City Hospital, Okaya, 3Department of Clinical Laboratory Sciences, 4Department of Laboratory Medicine, Shinshu University School of Medicine, Matsumoto, Japan Background: The syndrome of combined pulmonary fibrosis and emphysema (CPFE) is a recently described entity associating upper-lobe emphysema and lower-lobe fibrosis. We sought to evaluate differences in pulmonary function between CPFE patients with and without airflow obstruction. Subjects and methods: Thirty-one CPFE patients were divided into two groups according to the presence or absence of irreversible airflow obstruction based on spirometry (forced expiratory volume in 1 second/forced vital capacity

Yoshiyuki Kitaguchi, Shinsaku Yano, Fumi Gomi Department of Ophthalmology, Sumitomo Hospital, Osaka, Japan Abstract: Here we report a patient in whom there was a myopic shift after combined cataract surgery and pars plana vitrectomy against the epiretinal membrane, related to axial measurement estimation error caused by a hidden double-peak appearance on partial coherence interferometry measurement. A 52-year-old female presented with epiretinal membrane and underwent combined cataract surgery and pars plana vitrectomy. Axial length was measured with partial coherence interferometry. Although the signal curve in the summary display showed a single peak, a 1.6 diopter myopic shift occurred. Viewed retrospectively, six of 20 individual signal curves showed a double peak. Most of them showed a higher anterior peak, with only one having a higher posterior peak. The other 14 curves showed a single peak at a similar distance to an anterior peak. The anterior peak appeared to be derived from the epiretinal membrane. The possibility of a double peak should always be considered in patients with epiretinal membrane even if the summary display of the partial coherence interferometry measurement shows a single peak. Checking all signal curves would reduce the risk of missing a hidden double peak. Keywords: intraocular lens, master, double peak, epiretinal membrane

Yoshiaki Kitaguchi1,*, Yoshimichi Komatsu1,*, Keisaku Fujimoto2, Masayuki Hanaoka1, Keishi Kubo1 1First Department of Internal Medicine, Shinshu University School of Medicine, 2Department of Biomedical Laboratory Sciences, Shinshu University School of Health Sciences, Matsumoto, Japan *These authors contributed equally to this workBackground: Chronic obstructive pulmonary disease (COPD) and asthma may overlap and converge in older people (overlap syndrome). It was hypothesized that patients with overlap syndrome may have different clinical characteristics such as sputum eosinophilia, and better responsiveness to treatment with inhaled corticosteroid (ICS).Methods: Sixty-three patients with stable COPD (forced expiratory volume in 1 second [FEV1] ≤80%) underwent pulmonary function tests, including reversibility of airflow limitation, arterial blood gas analysis, analysis of inflammatory cells in induced sputum, and chest high-resolution computed tomography. The inclusion criteria for COPD patients with asthmatic symptoms included having asthmatic symptoms such as episodic breathlessness, wheezing, cough, and chest tightness worsening at night or in the early morning (COPD with asthma group). The clinical features of COPD patients with asthmatic symptoms were compared with those of COPD patients without asthmatic symptoms (COPD without asthma group).Results: The increases in FEV1 in response to treatment with ICS were significantly higher in the COPD with asthma group. The peripheral eosinophil counts and sputum eosinophil counts were significantly higher. The prevalence of patients with bronchial wall thickening on chest high-resolution computed tomography was significantly higher. A significant correlation was observed between the increases in FEV1 in response to treatment with ICS and sputum eosinophil counts, and between the increases in FEV1 in response to treatment with ICS and the grade of bronchial wall thickening. Receiver operating characteristic curve analysis revealed 82.4% sensitivity and 84.8% specificity of sputum eosinophil count for detecting COPD with asthma, using 2.5% as the cutoff value.Conclusion: COPD patients with asthmatic symptoms had some clinical features. ICS should be considered earlier as a potential treatment in such patients. High sputum eosinophil counts and bronchial wall thickening on chest high-resolution computed tomography might therefore be a good predictor of response to ICS.Keywords: COPD, asthma, HRCT, inhaled corticosteroid, pulmonary function

Keisaku Fujimoto1, Yoshiaki Kitaguchi2, Shintaro Kanda2, Kazuhisa Urushihata2, Masayuki Hanaoka2, Keishi Kubo21Department of Biomedical Laboratory Sciences, 2First Department of Internal Medicine, Shinshu University School of Medicine, Matsumoto, Nagano, JapanBackground: The purpose of this study was to clarify the association between morphological phenotypes according to the predominance of emphysema and efficacy of long-acting muscarinic antagonist and β2 agonist bronchodilators in patients with chronic obstructive pulmonary disease (COPD).Methods: Seventy-two patients with stable COPD treated with tiotropium (n = 41) or salmeterol (n = 31) were evaluated for pulmonary function, dynamic hyperinflation following metronome-paced incremental hyperventilation, six-minute walking distance, and St George’s Respiratory Questionnaire (SGRQ) before and 2–3 months following treatment with tiotropium or salmeterol. They were then visually divided into an emphysema dominant phenotype (n = 25 in the tiotropium-treated group and n = 22 in the salmeterol-treated group) and an emphysema nondominant phenotype on high-resolution computed tomography, and the efficacy of the two drugs in each phenotype was retrospectively analyzed.Results: Tiotropium significantly improved airflow limitation, oxygenation, and respiratory impedance in both the emphysema dominant and emphysema nondominant phenotypes, and improved dynamic hyperinflation, exercise capacity, and SGRQ in the emphysema dominant phenotype but not in the emphysema nondominant phenotype. Salmeterol significantly improved total score for SGRQ in the emphysema phenotype, but no significant effects on other parameters were found for either of the phenotypes.Conclusion: These findings suggest that tiotropium is more effective than salmeterol for airflow limitation regardless of emphysema dominance, and also can improve dynamic hyperinflation in the emphysema dominant phenotype, which results in further improvement of exercise capacity and health-related quality of life.Keywords: emphysema, dynamic hyperinflation, long-acting β2 agonist, long-acting muscarinic antagonist, exercise capacity, quality of life

A molecular junction of substituted benzene (chlorophenol) is fabricated and controlled by using a scanning tunneling microscope (STM). Prior to the junction formation, the bonding geometry of the molecule on the surface is characterized by STM and electron energy loss spectroscopy (EELS). EELS shows that the OH group of chlorophenol is dissociated on Cu(110) and that the molecule is bonded nearly flat to the surface via an O atom, with the Cl group intact. We demonstrate controlled contact of an STM tip to the "available" Cl group and lift-up of the molecule while it is anchored to the surface via an O atom. The asymmetric bonding motifs of the molecule to the electrodes allow for reversible control of the junction. [ABSTRACT FROM AUTHOR]

Adsorption of methanol and its dehydrogenation on Cu(110) were studied by using a scanning tunneling microscope (STM). Upon adsorption at 12 K, methanol preferentially forms clusters on the surface. The STM could induce dehydrogenation of methanol sequentially to methoxy and formaldehyde. This enabled us to study the binding structures of these products in a single-molecule limit. Methoxy was imaged as a pair of protrusion and depression along the [001] direction. This feature is fully consistent with the previous result that it adsorbs on the short-bridge site with the C-O axis tilted along the [001] direction. The axis was induced to flip back and forth by vibrational excitations with the STM. Two configurations were observed for formaldehyde, whose structures were proposed based on their characteristic images and motions. [ABSTRACT FROM AUTHOR]

Abstract Background The principal role of Toll-like receptor 4 (TLR4) is the induction of immune responses to lipopolysaccharides. Previously, mice deficient in the TLR4 gene exhibited up-regulation of the NADPH oxidase system in the lungs. This resulted in increased oxidant generation and elastolytic activity, which led to pulmonary emphysema. It was suggested that TLR4 might maintain constitutive lung integrity by modulating oxidant generation. We investigated whether single nucleotide polymorphisms (SNPs) in the TLR4 gene were associated with the emphysema phenotype in Japanese subjects with chronic obstructive pulmonary disease (COPD). Results Seven SNPs in the TLR4 gene (rs10759930, rs1927914, rs12377632, rs2149356, rs11536889, rs7037117, and rs7045953) were genotyped with allelic discrimination assays. The frequencies of SNPs were compared between 106 patients with the emphysema phenotype of COPD and 137 healthy smokers. We found that the positivity of the individuals with the major G allele of rs11536889 was significantly less in the emphysema group than the control group (p = 0.019). The frequencies of the minor C allele and the distribution of the CC genotype as well as the frequency of the major haplotype that carried the minor C allele of rs11536889 were all significantly higher in the emphysema group than the control group (p = 0.0083, 0.019, and 0.004, respectively). Furthermore, the strength of the association of the CC genotype with the emphysema phenotype was in an odds ratio of 2.60 with 95% confidence intervals from 1.17 to 5.78. However, these significances were not apparent after adjust for age and smoking history by logistic regression. No associations were observed between the rs11536889 and the low attenuation area score, the forced expiratory volume, and the carbon monoxide diffusion capacity in the emphysema group. Conclusions The minor C allele of the rs11536889 SNP in the TLR4 gene is likely associated with the risk of developing emphysema in the Japanese population.

Background: To describe a rare case of infiltrative optic neuropathy (ION) caused by vitreoretinal lymphoma (VRL) with hyperreflective deposits in the intraretinal and subretinal pigment epithelial (RPE) layers before the disease onset., Case Presentation: An 87-year-old Japanese female, previously treated for unexplained uveitis in the right eye, was referred for further evaluation. Despite the absence of intraocular inflammation or vitreous opacification (VO), yellowish-white deposits were noted in the macula, and OCT revealed hyperreflective deposits in the intraretinal and sub-RPE layers. One month later, she returned with acute visual deterioration. Optic disc swelling and disc hemorrhage were observed without VO or intraocular inflammation. Magnetic resonance imaging (MRI) showed no abnormalities. One week later, VO developed and we performed a 25-gauge vitrectomy. Cytology, flow cytometry, and gene rearrangement confirmed malignant B-cell lymphoma. The diagnosis of ION secondary to VRL was made, and intravitreal methotrexate injections were administered a total of 6 times. Six months postoperatively, VO and optic disc swelling resolved, and visual acuity improved to 20/50, with no recurrence on MRI., Conclusions: Although there were reports on VRL advanced from hyperreflective deposits in the intraretinal or sub-RPE layers, there have been no studies that these OCT findings has progressed to ION with VRL. When differentiating optic neuropathy, OCT may assist in the diagnosis by evaluating intraretinal and sub-RPE findings., Competing Interests: Declarations Ethics approval and consent to participate Not applicable. Consent for publication Written informed consent was obtained from the patient for publication of this case report and all accompanying images. A copy of the consent form is kept at our facility. Competing interests The authors declare no competing interests., (© 2024. The Author(s).)

Aim: To develop an artificial intelligence (AI) algorithm that diagnoses cataracts/corneal diseases from multiple conditions using smartphone images., Methods: This study included 6442 images that were captured using a slit-lamp microscope (6106 images) and smartphone (336 images). An AI algorithm was developed based on slit-lamp images to differentiate 36 major diseases (cataracts and corneal diseases) into 9 categories. To validate the AI model, smartphone images were used for the testing dataset. We evaluated AI performance that included sensitivity, specificity and receiver operating characteristic (ROC) curve for the diagnosis and triage of the diseases., Results: The AI algorithm achieved an area under the ROC curve of 0.998 (95% CI, 0.992 to 0.999) for normal eyes, 0.986 (95% CI, 0.978 to 0.997) for infectious keratitis, 0.960 (95% CI, 0.925 to 0.994) for immunological keratitis, 0.987 (95% CI, 0.978 to 0.996) for cornea scars, 0.997 (95% CI, 0.992 to 1.000) for ocular surface tumours, 0.993 (95% CI, 0.984 to 1.000) for corneal deposits, 1.000 (95% CI, 1.000 to 1.000) for acute angle-closure glaucoma, 0.992 (95% CI, 0.985 to 0.999) for cataracts and 0.993 (95% CI, 0.985 to 1.000) for bullous keratopathy. The triage of referral suggestion using the smartphone images exhibited high performance, in which the sensitivity and specificity were 1.00 (95% CI, 0.478 to 1.00) and 1.00 (95% CI, 0.976 to 1.000) for 'urgent', 0.867 (95% CI, 0.683 to 0.962) and 1.00 (95% CI, 0.971 to 1.000) for 'semi-urgent', 0.853 (95% CI, 0.689 to 0.950) and 0.983 (95% CI, 0.942 to 0.998) for 'routine' and 1.00 (95% CI, 0.958 to 1.00) and 0.896 (95% CI, 0.797 to 0.957) for 'observation', respectively., Conclusions: The AI system achieved promising performance in the diagnosis of cataracts and corneal diseases., Competing Interests: Competing interests: TY: Grants (Novartis Pharma); honoraria for lectures (Alcon Japan, HOYA, Novartis Pharma, AMO Japan, Santen Pharmaceuticals, Senju Pharmaceutical, Johnson & Johnson), MM: Grants (Novartis Pharma); honoraria for lectures (Bayer Yakuhin, Kowa Pharmaceutical, Alcon Japan, HOYA, Novartis Pharma, AMO Japan, Santen Pharmaceutical, Senju Pharmaceutical, Johnson & Johnson K.K., Japan Ophthalmic Instruments Association). MA: Grants (Novartis, Santen), honoraria for lectures (Novartis, Takeda, Senju, Chugai, Kowa), Support for attending meetings and travel (Wakamoto, Novartis), Endowed (NIDEK)., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

High-altitude pulmonary edema (HAPE) is a life-threatening, noncardiogenic pulmonary edema that occurs in unacclimatized individuals rapidly ascending to high altitudes above 2,500 m above sea level. Until the entity of HAPE was first identified in a case report published in Japan in 1966, the symptoms of severe dyspnea or coma occurring in climbers of the Japan Alps were incorrectly attributed to pneumonia or congestive heart failure. The Shinshu University Hospital serves as the central facility for rescuing and treating patients with HAPE in the region. Over the past 50 years, a series of studies have been conducted at Shinshu University to gain a better understanding of the characteristics of HAPE. This review summarizes the major achievements of these studies, including their clinical features, management, and pathogenesis of HAPE, particularly in the Japanese population.

CorneAI for iOS is an artificial intelligence (AI) application to classify the condition of the cornea and cataract into nine categories: normal, infectious keratitis, non-infection keratitis, scar, tumor, deposit, acute primary angle closure, lens opacity, and bullous keratopathy. We evaluated its performance to classify multiple conditions of the cornea and cataract of various races in images published in the Cornea journal. The positive predictive value (PPV) of the top classification with the highest predictive score was 0.75, and the PPV for the top three classifications exceeded 0.80. For individual diseases, the highest PPVs were 0.91, 0.73, 0.42, 0.72, 0.77, and 0.55 for infectious keratitis, normal, non-infection keratitis, scar, tumor, and deposit, respectively. CorneAI for iOS achieved an area under the receiver operating characteristic curve of 0.78 (95% confidence interval [CI] 0.5-1.0) for normal, 0.76 (95% CI 0.67-0.85) for infectious keratitis, 0.81 (95% CI 0.64-0.97) for non-infection keratitis, 0.55 (95% CI 0.41-0.69) for scar, 0.62 (95% CI 0.27-0.97) for tumor, and 0.71 (95% CI 0.53-0.89) for deposit. CorneAI performed well in classifying various conditions of the cornea and cataract when used to diagnose journal images, including those with variable imaging conditions, ethnicities, and rare cases., (© 2024. The Author(s).)