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Chikako Ichikawa,1 Sho Tanaka,2,3 Masahiro Takubo,1,3 Masaru Kushimoto,3 Jin Ikeda,3 Katsuhiko Ogawa,3,4 Ichiro Tsujino,3,5 Yutaka Suzuki,3,4 Masanori Abe,2 Hisamitsu Ishihara,1 Midori Fujishiro1,3 1Division of Diabetes and Metabolic Diseases, Department of Internal Medicine, Nihon University School of Medicine, Tokyo, Japan; 2Division of Nephrology, Hypertension and Endocrinology, Department of Internal Medicine, Nihon University School of Medicine, Tokyo, Japan; 3Department of Internal Medicine, Nihon University Hospital, Tokyo, Japan; 4Division of Neurology, Department of Medicine, Nihon University School of Medicine, Tokyo, Japan; 5Division of Respiratory Medicine, Department of Internal Medicine, Nihon University School of Medicine, Tokyo, JapanCorrespondence: Sho TanakaDivision of Nephrology, Hypertension and Endocrinology, Department of Internal Medicine, Nihon University School of Medicine, 30-1 Oyaguchi Kami-cho, Itabashi-ku, Tokyo, 173-8610, JapanTel +81-3-3972-8111Fax +81-3-3972-8311Email tanakasho13@gmail.comMidori FujishiroDivision of Diabetes and Metabolic Diseases Department of Internal Medicine, Nihon University School of Medicine, 30-1 Oyaguchi Kami-cho, Itabashi-ku, Tokyo, 173-8610, JapanTel +81-3-3972-8111Fax +81-3-3972-8199Email fujishiro.midori@nihon-u.ac.jpAbstract: The standard six-month tuberculosis (TB) treatment comprises an intensive phase lasting two months, followed by a continuation phase lasting four months. Meanwhile, the nine-month regimen, which has a prolonged continuation phase, is indicated for patients with complicated diabetes mellitus (DM) because of their poor response to treatment. A 61-year-old Japanese man with poorly controlled DM for five years presented with bilateral scrotal swelling noticed two weeks ago. He had a history of pleuritis, pericarditis, and peritonitis two years ago. These symptoms led to the diagnosis of culture-negative extrapulmonary TB. He received the nine-month chemotherapy regimen (isoniazid, rifampin, pyrazinamide, and ethambutol for two months, followed by isoniazid and rifampin for seven months), and his symptoms significantly improved. The swollen scrotum was accompanied by mild tenderness and pus discharge from a fistula. Imaging study revealed bilaterally diffusely enlarged epididymis. However, the acid-fast bacilli smear and culture and polymerase chain reaction using urine and pus discharge tested negative. Bilateral epididymectomy was performed. Although the acid-fast bacilli smear was negative, the pathology demonstrated granuloma formation and acid-fast bacilli tissue culture confirmed multi-drug resistant Mycobacterium tuberculosis. The optimal treatment regimen and duration for extrapulmonary TB with unknown drug susceptibility are debatable. The nine-month regimen can be insufficient in some cases. Thus, detailed follow-up is essential, and TB relapse should be thoroughly monitored.Keywords: chemotherapy, diabetes mellitus, tuberculosis, epididymitis

Introduction: The pathogenesis and clinical profiles of patients with pulmonary hypertension (PH) associated with interstitial lung disease (ILD-PH) are poorly understood. Whether and to what extent pulmonary arterial hypertension (PAH)-specific therapy improves hemodynamic and outcome in ILD-PH are also unknown., Study Objective: This study aims to clarify the characteristics, clinical course and response to PAH-specific therapy of ILD and/or PH by enrolling three unique subsets: PAH, ILD-PH, and ILD., Methods: The proposed study is a retrospective and prospective, multi-centre, observational cohort study of patients treated at any of three university hospitals in the Hokkaido region of Japan who have any one of the following: PAH; ILD-PH with or without PAH features; or ILD without PH. We aim to enrol 250 patients in total. For the retrospective observation period, data obtained after 1 January 2010, will be analysed, and the prospective observation period will be 1 year. We will compare the clinical data of patients with ILD-PH with those of patients with PAH and those of patients with ILD without PH in the real-world clinical setting. In addition, within the cohort of patients with ILD-PH, we will explore the subset with "ILD-PH with PAH features" and compare the response to PAH-specific therapy with that of PAH. The primary outcome will be the change in pulmonary vascular resistance from first treatment to follow-up in patients with PAH and ILD-PH with PAH features (excluding ILD-PH without PAH feature and ILD-no-PH for the primary outcome). The exploratory outcomes will include analyses of PH-associated biomarkers, right ventricular function and patient-reported outcomes., Results: This is a protocol article and the results will be presented after data collection is completed., Conclusion: The POPLAR study will provide data that help better understand the pathophysiology of ILD-PH and improve the quality of life and outcome of patients with PH and/or ILD., Trial Registration: Japan Registry of Clinical Trials: jRCT1010230018., (© 2024. The Author(s).)

Background: The contemporary outcome of balloon pulmonary angioplasty (BPA) and pulmonary endarterectomy (PEA) in patients with chronic thromboembolic pulmonary hypertension (CTEPH) are unclear., Objectives: This study aimed to clarify the characteristics and outcomes of CTEPH patients treated with BPA and PEA in Japan., Methods: Among 1,270 participants enrolled between 2018 and 2023 in the CTEPH AC (Chronic Thromboembolic Pulmonary Hypertension Anticoagulant) registry, a Japanese nationwide CTEPH registry, 369 treatment-naive patients (BPA strategy: n = 313; PEA strategy: n = 56) and 690 on-treatment patients (BPA strategy: n = 561; PEA strategy: n = 129) were classified according to the presence of prior reperfusion therapy. Morbidity and mortality events (all-cause death, rescue mechanical reperfusion therapy, and/or initiation of parenteral pulmonary vasodilators), pulmonary hemodynamics, exercise tolerance, and relevant laboratory test results were evaluated., Results: The BPA strategy was chosen in older patients than the PEA strategy (mean age, BPA vs PEA: 66.5 ± 12.6 years vs 62.5 ± 11.8 years; P  = 0.028). Median follow-up period was 615 (Q1-Q3: 311-997) days in treatment-naive patients and 1,136 (Q1-Q3: 684-1,300) days in on-treatment patients. BPA strategy had as acceptable morbidity and mortality as PEA strategy (5-year morbidity and mortality event rate, BPA vs PEA: 10.2% [95% CI: 5.2%-19.5%] vs 16.1% [95% CI: 4.3%-50.6%] in treatment-naive patients; 9.7% [95% CI: 6.7%-13.8%] vs 6.9% [95% CI: 2.7%-17.3%] in on-treatment patients), with greater improvement of renal function; glomerular filtration rate in propensity score-matched population (difference between change: 4.9 [95% CI: 0.5-9.3] mL/min/1.73 m 2 ; P  = 0.030)., Conclusions: BPA strategy was more frequently chosen in older patients compared with PEA strategy and showed acceptable outcomes for efficacy with greater advantage for improvement in renal function. (Multicenter registry of chronic thromboembolic pulmonary hypertension in Japan; UMIN000033784)., Competing Interests: This study is supported by the Japan Agency for Medical Research and Development (grant numbers JP20ek0109371, JP19lk0201102, JP22lk0201125, and JP19lk1601003), JSPS KAKENHI (grant number JP20286266), and grant from Konica Minolta based on a contract. The funding body had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; or decision to submit the manuscript for publication. Dr Hosokawa has received grants from Konica Minolta; and personal fees from Bayer Yakuhin, Nippon Shinyaku, Janssen Pharmaceutical, Pfizer, and Konica Minolta, outside the submitted work. Dr Taniguchi has received grants from Nippon Shinyaku and Janssen Pharmaceutical; and personal fees from Nippon Shinyaku, Janssen Pharmaceutical, and Bayer Yakuhin, outside the submitted work. Dr Inami has received personal fees from Janssen Pharmaceutical and Bayer Yakuhin, outside the submitted work. Dr Yamashita has received a grant from Abbott Vascular Japan; and personal fees from Kaneka Medix, Boston Scientific Japan, Nihon Kohden, Philips Japan, Janssen Pharmaceutical, and Bayer Yakuhin, outside the submitted work. Dr Ogino has received consulting fees from Terumo, Japan Lifeline, and Century Medical; and personal fees from Bayer Yakuhin, Daiichi-Sankyo, Pfizer, and Nippon Shinyaku, outside the submitted work. Dr Tsujino has received personal fees from Nippon Shinyaku and Janssen Pharmaceutical; and affiliation with the division supported by endowments from Nippon Shinyaku, Nippon Boehringer Ingelheim, Mochida Pharmaceutical, Kaneka Medix, Takeyama, and Medical System Network, outside the submitted work. Dr Hatano has received personal fees from Bayer Yakuhin and Janssen Pharmaceutical, outside the submitted work. Dr Yaoita has received personal fees from Bayer Yakuhin and Konica Minolta, outside the submitted work. Dr Ikeda has received personal fees from Janssen Pharmaceutical, Bayer Yakuhin, Nippon Shinyaku, Daiichi -Sankyo, and Bristol Myers Squibb, outside the submitted work. Dr Shimokawahara has received a grant from Bayer Yakuhin; and personal fees from Bayer Yakuhin and Nippon Shinyaku, outside the submitted work. Dr Tanabe has received personal fees from Janssen Pharmaceutical, Bayer Yakuhin, and Nippon Shinyaku, outside the submitted work. Dr Kubota has received personal fees from Janssen Pharmaceutical and Nippon Shinyaku, outside the submitted work. Dr Ogihara has received grants from Bayer Yakuhin; and personal fees from Janssen Pharmaceutical, Bayer Yakuhin, Nippon Shinyaku, Daiichi-Sankyo, and Bristol Myers Squibb, outside the submitted work. Dr Kawakami has received personal fees from Kaneka Medix and Abbott Medical Japan, and consulting fees from ACIST Japan, outside the submitted work. Dr Tamura has received grants from Bayer Yakuhin, Nippon Shinyaku, and Mochida Pharmaceutical; and personal fees from Bayer Yakuhin, Nippon Shinyaku, Daiichi-Sankyo, and Janssen Pharmaceutical, outside the submitted work. Dr Abe has received a grant from Konica Minolta and Daiichi-Sankyo, outside the submitted work. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (© 2024 The Authors.)

Objectives: Pulmonary arterial hypertension associated with systemic sclerosis (PAH-SSc) sometimes accompanies pulmonary veno-occlusive disease (PVOD). We aimed to reveal the relationship between clinical signs of PVOD and severity of pulmonary vasculopathy in SSc., Methods: This study included 52 consecutive SSc patients who had pulmonary haemodynamic abnormalities [mean pulmonary arterial pressure (mPAP) >20 mmHg, pulmonary vascular resistance >2 WU or pulmonary artery wedge pressure (PAWP) >15 mmHg]. A chest CT scan was evaluated in all patients. Patients were divided into two groups, the 0-1 group and the 2-3 group, according to the number of chest CT signs for PVOD, including mediastinal lymph node enlargement, thickened interlobular septal wall and ground glass opacity. Pulmonary haemodynamics, echocardiography and MRI-based cardiac function, pulmonary function and serum biomarkers were compared between the two groups., Results: Mediastinal lymph node enlargement, thickened interlobular septal wall and ground glass opacity were observed in 11 (21%), 32 (62%) and 11 (21%) patients, respectively. The 2-3 group (n = 15) had higher mPAP (P = 0.02) but lower diffusing capacity of carbon monoxide (DLCO)/alveolar volume (P = 0.02) compared with the 0-1 group (n = 37). Other parameters, including PAWP, cardiac output, left ventricular ejection fraction, left atrial diameter, forced vital capacity, brain natriuretic peptide and Krebs von den Lunge-6 were not different between the two groups., Conclusions: The CT signs for PVOD had a positive correlation with mPAP but a negative correlation with DLCO in SSc patients, indicating that PAH-SSc may reflect a spectrum of pulmonary vascular disease that ranges from the pulmonary artery to the vein., (© The Author(s) 2023. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

The aim of this study was to examine the association of insulin resistance (evaluated by the short insulin tolerance test [SITT]) with parameters related to obesity and insulin resistance. We prospectively recruited controls and patients with type 2 diabetes mellitus (T2DM), subjected them to the SITT, and calculated the K indices of the intravenous insulin tolerance test (KITT(iv)) and the subcutaneous insulin tolerance test (KITT(sc)). We compared KITT(iv) results between the volunteers and patients and examined its correlation with KITT(sc). We also examined the association of KITT(iv) with obesity, insulin resistance-related parameters, and the insulin dose required for glycemic control. A total of 24 participants (seven controls and 17 patients with T2DM) were studied. The mean KITT(iv) was significantly lower in patients with T2DM than in the controls (2.5%±2.1% vs. 4.5%±1.8%). In all participants, KITT(iv) was significantly correlated with the homeostasis model assessment for insulin resistance (HOMA-IR) values (r = -0.601, p<0.05) but not with KITT(sc) (p = 0.62). KITT(iv) was correlated positively with the serum adiponectin concentration, but negatively with the visceral fat area and serum concentrations of tumor necrosis factor-α and branched-chain amino acids. In patients with T2DM, KITT(iv) and HOMA-IR values were significantly correlated with the total insulin dose required for glycemic control. Insulin resistance evaluated using KITT(iv) was correlated with the HOMA-IR values, but not with the resistance evaluated using KITT(sc). The degree of insulin resistance was associated with biomarkers, such as adiponectin, tumor necrosis factor-α, branched-chain amino acids, the visceral fat area, and the dose of insulin required for glycemic control., Competing Interests: I have read the journal’s policy and the authors of this manuscript have the following competing interests: Taku Watanabe received lecture fees from Sumitomo Pharma co. Ltd. Ichizo Tsujino receives funding from Janssen Pharmaceutical K.K. for a Joint Research; and funding from Nippon Shinyaku Co Ltd, Mochida Pharmaceuticals Co Ltd, Boehringer Ingelheim Japan Co Ltd, Takeyama Co Ltd, Kaneka Co Ltd, and Medical System Network Co Ltd for endowed department. Isao Yokota reports grants from KAKENHI, AMED, and Health, Labour and Welfare Policy Research Grants, research fund by Nihon Medi-Physics, and speaker fees from Chugai Pharmaceutical Co, AstraZeneca, and Pfizer outside the submitted work. This does not alter our adherence to PLOS ONE policies on sharing data and materials., (Copyright: © 2024 Hayashishita et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Right ventricular (RV) diastolic stiffness is an independent predictor of survival and is strongly associated with disease severity in patients with precapillary pulmonary hypertension (PH). Therefore, a fully validated echocardiographic method for assessing RV diastolic stiffness needs to be established. This study aimed to compare echocardiography-derived RV diastolic stiffness and invasively measured pressure-volume loop-derived RV diastolic stiffness in patients with precapillary PH. We studied 50 consecutive patients with suspected or confirmed precapillary PH who underwent cardiac catheterization, magnetic resonance imaging, and echocardiography within a 1-week interval. Single-beat RV pressure-volume analysis was performed to determine the gold standard for RV diastolic stiffness. Elevated RV end-diastolic pressure (RVEDP) was defined as RVEDP ≥ 8 mmHg. Using continuous-wave Doppler and M-mode echocardiography, an echocardiographic index of RV diastolic stiffness was calculated as the ratio of the atrial-systolic descent of the pulmonary artery-RV pressure gradient derived from pulmonary regurgitant velocity (PRPGD AC ) to the tricuspid annular plane movement during atrial contraction (TAPM AC ). PRPGD AC /TAPM AC showed significant correlation with β (r = 0.54, p < 0.001) and RVEDP (r = 0.61, p < 0.001). A cut-off value of 0.74 mmHg/mm for PRPGD AC /TAPM AC showed 83% sensitivity and 93% specificity for identifying elevated RVEDP. Multivariate analyses indicated that PRPGD AC /TAPM AC was independently associated with disease severity in patients with precapillary PH, including substantial PH symptoms, stroke volume index, right atrial size, and pressure. PRPGD AC /TAPM AC , based on pulmonary regurgitation velocity waveform analysis, is useful for the noninvasive assessment of RV diastolic stiffness and is associated with prognostic risk factors in precapillary PH., (© 2024. The Author(s), under exclusive licence to Springer Nature B.V.)

Pulmonary arterial hypertension (PAH) remains a significant challenge in cardiology, necessitating advancements in treatment strategies. This study explores the safety and efficacy of transitioning patients from beraprost to selexipag, a novel selective prostacyclin receptor agonist, within a Japanese cohort. Employing a multicenter, open-label, prospective design, 25 PAH patients inadequately managed on beraprost were switched to selexipag. Key inclusion criteria included ongoing beraprost therapy for ≥3 months, a diagnosis of PAH confirmed by mean pulmonary artery pressure (mPAP) ≥ 25 mmHg, and current treatment with endothelin receptor antagonists and/or phosphodiesterase type 5 inhibitors. Outcomes assessed were changes in hemodynamic parameters (mPAP, cardiac index, pulmonary vascular resistance) and the 6 min walk distance (6-MWD) over 3-6 months. The study found no statistically significant changes in these parameters post-switch. However, a subset of patients, defined as responders, demonstrated improvements in all measured hemodynamic parameters, suggesting a potential benefit in carefully selected patients. The transition was generally well-tolerated with no serious adverse events reported. This investigation underscores the importance of personalized treatment strategies in PAH, highlighting that certain patients may benefit from switching to selexipag, particularly those previously on higher doses of beraprost. Further research is needed to elucidate the predictors of positive response to selexipag and optimize treatment regimens for this complex condition.

Echocardiography is a widely used modality for the assessment of right ventricular (RV) function; however, few studies have comprehensively compared the accuracy of echocardiographic parameters using invasively obtained reference values. Therefore, this exploratory study aimed to compare the accuracy of echocardiographic parameters of RV function and RV-pulmonary artery (PA) coupling. We calculated four indices of RV function (end-systolic elastance [Ees] for systolic function [contractility], τ for relaxation, and β and end-diastolic elastance [Eed] for stiffness), and an index of RV-PA coupling (Ees/arterial elastance [Ea]), using pressure catheterization, cardiac magnetic resonance imaging, and a single-beat method. We then compared the correlations of RV indices with echocardiographic parameters. In 63 participants (54 with pulmonary hypertension (PH) and nine without PH), Ees and τ correlated with several echocardiographic parameters, such as RV diameter and area, but the correlations were moderate (|correlation coefficients ( ρ )| < 0.5 for all parameters). The correlations of β and Eed with echocardiographic parameters were weak, with | ρ | < 0.4. In contrast, Ees/Ea closely correlated with RV free wall longitudinal strain (RVFW-LS)/estimated systolic PA pressure (eSPAP) ( ρ  = -0.72). Ees/Ea also correlated with tricuspid annular plane systolic excursion/eSPAP, RV diameter, and RV end-systolic area, with | ρ  | >0.65. In addition, RVFW-LS/eSPAP yielded high sensitivity (0.84) and specificity (0.75) for detecting reduced Ees/Ea. The present study indicated a limited accuracy of echocardiographic parameters in assessing RV systolic and diastolic function. In contrast to RV function, they showed high accuracy for assessing RV-PA coupling, with RVFW-LS/eSPAP exhibiting the highest accuracy., Competing Interests: Ichizo Tsujino and Satoshi Konno received funding from Janssen Pharmaceutical K.K. Ichizo Tsujino, Takahiro Sato, and Satoshi Konno received funding from Nippon Shinyaku Co Ltd, Mochida Pharmaceuticals Co Ltd, Boehringer Ingelheim Japan Co Ltd, Takeyama Co Ltd, Kaneka Ltd, and Medical System Network Co Ltd. Isao Yokota received grants from KAKENHI, AMED, and Health, Labor and Welfare Policy research grants, research funds from Nihon Medi‐Physics, and speakers' bureau fees from Chugai Pharmaceutical Co. and AstraZeneca, all for work outside the submitted work., (© 2024 The Authors. Pulmonary Circulation published by John Wiley & Sons Ltd on behalf of Pulmonary Vascular Research Institute.)

Background: Precapillary pulmonary hypertension (PH) is characterized by a sustained increase in right ventricular (RV) afterload, impairing systolic function. Two-dimensional (2D) echocardiography is the most performed cardiac imaging tool to assess RV systolic function; however, an accurate evaluation requires expertise. We aimed to develop a fully automated deep learning (DL)-based tool to estimate the RV ejection fraction (RVEF) from 2D echocardiographic videos of apical four-chamber views in patients with precapillary PH., Methods: We identified 85 patients with suspected precapillary PH who underwent cardiac magnetic resonance imaging (MRI) and echocardiography. The data was divided into training (80%) and testing (20%) datasets, and a regression model was constructed using 3D-ResNet50. Accuracy was assessed using five-fold cross validation., Results: The DL model predicted the cardiac MRI-derived RVEF with a mean absolute error of 7.67%. The DL model identified severe RV systolic dysfunction (defined as cardiac MRI-derived RVEF < 37%) with an area under the curve (AUC) of .84, which was comparable to the AUC of RV fractional area change (FAC) and tricuspid annular plane systolic excursion (TAPSE) measured by experienced sonographers (.87 and .72, respectively). To detect mild RV systolic dysfunction (defined as RVEF ≤ 45%), the AUC from the DL-predicted RVEF also demonstrated a high discriminatory power of .87, comparable to that of FAC (.90), and significantly higher than that of TAPSE (.67)., Conclusion: The fully automated DL-based tool using 2D echocardiography could accurately estimate RVEF and exhibited a diagnostic performance for RV systolic dysfunction comparable to that of human readers., (© 2024 Wiley Periodicals LLC.)

Background: Recent guidelines discourage the use of pulmonary arterial hypertension (PAH)-targeted therapies in patients with pulmonary hypertension (PH) associated with respiratory diseases. Therefore, stratifications of the effectiveness of PAH-targeted therapies are important for this group., Objectives: The authors aimed to identify phenotypes that might benefit from initial PAH-targeted therapies in patients with PH associated with interstitial pneumonia and combined pulmonary fibrosis and emphysema., Methods: We categorized 270 patients with precapillary PH (192 interstitial pneumonia, 78 combined pulmonary fibrosis and emphysema) into severe and mild PH using a pulmonary vascular resistance of 5 WU. We investigated the prognostic factors and compared the prognoses of initial (within 2 months after diagnosis) and noninitial treatment groups, as well as responders (improvements in World Health Organization functional class, pulmonary vascular resistance, and 6-minute walk distance) and nonresponders., Results: Among 239 treatment-naive patients, 46.0% had severe PH, 51.8% had mild ventilatory impairment (VI), and 40.6% received initial treatment. In the severe PH with mild VI subgroup, the initial treatment group had a favorable prognosis compared with the noninitial treatment group. The response rate in this group was significantly higher than the others (48.2% vs 21.8%, ratio 2.21 [95% CI: 1.17-4.16]). In multivariate analysis, initial treatment was a better prognostic factor for severe PH but not for mild PH. Within the severe PH subgroup, responders had a favorable prognosis., Conclusions: This study demonstrated an increased number of responders to initial PAH-targeted therapy, with a favorable prognosis in severe PH cases with mild VI. A survival benefit was not observed in mild PH cases. (Multi-institutional Prospective Registry in Pulmonary Hypertension associated with Respiratory Disease; UMIN000011541)., Competing Interests: This study was supported by grants from Grant-in-Aid for Scientific Research (20FC1027, 23FC1031) from the Ministry of Health, Labour and Welfare of Japan, the Medical Research Fund of the Japan Medical Association (No. 16ek0109127h0002 and No. JP18lk1601003h0001), and the Nonprofit Organization Japan PH registry. Dr Tanabe has received remuneration from Nippon Shinyaku, Janssen Pharmaceutical K.K., and Bayer Yakuhin, and belongs to a department endowed by Nippon Shinyaku. Dr Kumamaru has received consultation fees from Mitsubishi-Tanabe Pharma Corp, and EPS Corp; speaker fee from Chugai Pharmaceutical Co, Ltd; and a research grant from Pfizer Japan Inc. Drs Kumamaru, Kinukawa, and Miyata are affiliated with the Department of Health Quality Assessment at the University of Tokyo, a social collaboration department supported by the National Clinical Database, Johnson & Johnson K.K., Nipro Corp, and Intuitive Surgical Sàrl. Dr Nishiyama has received remuneration from Nippon Shinyaku, Janssen Pharmaceutical K.K., and Boehringer Ingelheim. Dr Tsujino has received remuneration from Nippon Shinyaku and Janssen Pharmaceutical K.K., and belongs to a department endowed by Nippon Shinyaku, Mochida Pharmaceutical Co Ltd, Boehringer Ingelheim, Takeyama Co, Ltd, Kaneka Medics Co, and Medical System Network Co Ltd. Dr Inoue has received remuneration from Boehringer Ingelheim. Dr Hirata has received a research grant from Janssen Pharmaceutical K.K. Dr Kuwana has received remuneration from Nippon Shinyaku. Dr Handa has received a research grant from Fujifilm Corp and belongs to a department endowed by Teijin Pharma Ltd. Dr Taniguchi has received a research grant from Janssen Pharmaceutical K.K. Dr Matsubara has received remuneration from Nippon Shinyaku, Janssen Pharmaceutical K.K., Bayer Yakuhin, Mochida Pharmaceutical. Co Ltd, and Kaneka Medics Co; and research grants from Nippon Shinyaku, Janssen Pharmaceutical K.K., Mochida Pharmaceutical Co Ltd, and Insmed Incorporated. Dr Tatsumi has received remuneration from Janssen Pharmaceutical K.K. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (© 2024 The Authors.)

Objectives: The potential benefit of routine prophylactic anticoagulation for all hospitalized patients with clinically stable coronavirus disease 2019 (COVID-19) is still controversial. Method: The CLOT-COVID Study was a multicenter observational study enrolling 2894 consecutive hospitalized patients with COVID-19. The current study population consisted of 1738 hospitalized patients with mild COVID-19 at admission not requiring oxygen administration, who were divided into 2 groups: patients with prophylactic anticoagulation (n = 326) and those without (n = 1412). Results: Patients with prophylactic anticoagulation had more severe status of the worst severity of COVID-19 during hospitalization compared with those without (mild: 38% versus 82%, moderate: 55% versus 17%, and severe or death at discharge: 6.4% versus 0.7%, P <0.001). During hospitalization, 8 patients (0.5%) developed thrombosis, and the incidences of thrombosis were numerically higher in patients with more severe status of worst severity of COVID-19 during hospitalization (mild: 0.2%, moderate: 1.2%, and severe or death at discharge: 3.2%). Conclusions: Among hospitalized patients with clinically stable COVID-19 at admission, patients who did not worsen in COVID-19 severity after admission rarely developed thrombosis, although patients with worsening of COVID-19 severity after admission more often received prophylactic anticoagulation and might have a higher risk of thrombosis., (@ 2024 The Editorial Committee of Annals of Vascular Diseases.)

Competing Interests: Disclosures Dr Hosokawa reports personal fees from Janssen Pharmaceutical, Bayer Yakuhin, Nippon Shinyaku, and Pfizer, outside the submitted work. Dr Taniguchi reports grants from Janssen Pharmaceutical and Nippon Shinyaku; and personal fees from Janssen Pharmaceutical and Nippon Shinyaku, outside the submitted work. Dr Ikeda reports personal fees from Daiichi-Sankyo, Bayer Yakuhin, and Bristol-Myers Squibb, outside the submitted work. Dr Inami reports personal fees from Janssen Pharmaceutical and Bayer Yakuhin, outside the submitted work. Dr Murohara reports a grant and personal fees from Daiichi Sankyo, outside the submitted work. Dr Hatano reports a grant from Japan Agency for Medical Research and Development and personal fees from Janssen Pharmaceutical and Bayer Yakuhin, outside the submitted work. Dr Tamura reports grants from Bayer Yakuhin, Nippon Shinyaku, and Mochida Pharmaceutical; and personal fees from Bayer Yakuhin, Nippon Shinyaku, Daiichi Sankyo, and Janssen Pharmaceutical, outside the submitted work. Dr Yamashita reports a grant from Abbott Vascular Japan; and personal fees from Kaneka Medix, Boston Scientific Japan, Nihon Kohden, Philips Japan, Janssen Pharmaceutical, and Bayer Yakuhin, outside the submitted work. Dr Tsujino reports personal fees from Janssen Pharmaceutical and Nippon Shinyaku; and affiliation with the division supported by endowments from Nippon Shinyaku, Nippon Boehringer Ingelheim, and Mochida Pharmaceutical, outside the submitted work. Dr Yaoita reports personal fees from Bayer Yakuhin and Konica Minolta, outside the submitted work. Dr Minatsuki reports a grant from Fukuda Foundation for Medical Technology, outside the submitted work. Dr Todaka reports a grant from Mochida Pharmaceutical; and personal fee from Bayer Yakuhin, outside the submitted work. Dr Fukuda reports grants from Bayer Yakuhin, Daiichi Sankyo, Nippon Boehringer Ingelheim, Pfizer, Eisai, Janssen Pharmaceutical, Nippon Shinyaku, GlaxoSmithKline, and Mochida Pharmaceutical; and personal fees from Bayer Yakuhin, Daiichi Sankyo, Nippon Boehringer Ingelheim, Pfizer, Eisai, Janssen Pharmaceutical, Nippon Shinyaku, GlaxoSmithKline, and Mochida Pharmaceutical, outside the submitted work. Dr Tsutsui reports grants from Mitsubishi Tanabe Pharma, IQVIA Services Japan, MEDINET, Medical Innovation Kyushu, Kowa, Daiichi Sankyo, Johnson & Johnson, NEC, and Nippon Boehringer Ingelheim; personal fees from Novartis Pharma, Ono Pharmaceutical, Nippon Boehringer Ingelheim, Bayer Yakuhin, Kowa, Teijin Pharma, Mitsubishi Tanabe Pharma, Pfizer Japan, Daiichi Sankyo, Novartis Pharma, Janssen Pharmaceutical, Pfizer Japan, Bayer Yakuhin, Otsuka Pharmaceutical, AstraZeneca, and Nippon Rinsho; and is Chairman of Japan Heart Failure Society, outside the submitted work. Dr Abe reports a grant from Konica Minolta and Daiichi Sankyo, outside the submitted work. Drs Watanabe, Yasuda, Kobayakawa, Adachi, and Tatsumi report no conflicts of interest.

The possibility of stratifying patients according to differences in ROS proto-oncogene 1 (ROS1) fusion partners has been discussed. This study aimed to clarify the clinicopathological differences between two SDC4::ROS1 positive NSCLC cases who had different responses to crizotinib. Cytology and pathology samples from two NSCLC cases with SDC4::ROS1 who were diagnosed and treated with crizotinib at Nihon University Itabashi Hospital were obtained. Case 1 has been well-controlled with crizotinib for over 5 years, but case 2 was worse and overall survival was 19 months. Sequencing analysis of ROS1 fusion genes was performed by reverse-transcription-PCR and Sanger's sequencing methods. In addition, thyroid transcription factor (TTF)-1, ROS-1, Ki67, and phosphorylated extracellular signal-regulated kinase (pERK)1/2 expression were investigated using immunohistochemistry. Sequencing analysis showed SDC4 exon2::ROS1 exon 32 (exon33 deleted) in case 1, and coexistence of SDC4 exon2::ROS1 exon 34 and SDC4 exon2::ROS1 exon35 in case 2. The Ki67 index was not different, but ROS1 and pERK1/2 expression levels tended to be higher in the tumor cells of case 2 than in case 1. Therapeutic response to crizotinib and patients' prognosis in ROS1 rearranged NSCLC may be related to the activation of ROS1 signaling, depending on ROS1 and pERK1/2 overexpression status, even if the ROS1 fusion partner is the same., (© 2023 The Authors. Thoracic Cancer published by China Lung Oncology Group and John Wiley & Sons Australia, Ltd.)