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The human T-cell leukemia virus type 1 (HTLV-1), a retrovirus, integrates into host DNA and causes adult T-cell leukemia/lymphoma (ATL) in some individuals. Two types of defective proviruses, Type 1 and Type 2, are often observed in ATL cells. Here, we developed a 3-plex digital PCR (dPCR) method to detect HTLV-1 proviral deletions by comparing the ratios of copy numbers quantified using specific primer-probes for the LTR, pol, and pX regions. We analyzed HTLV-1-positive asymptomatic carriers (ACs) and AC samples at high risk for developing ATL due to high proviral load (ATL high-risk (HR) ACs) using dPCR. Deletions were identified in 11.8 % (4/34, all Type 1) of ACs and 33.3 % (7/21, Type 1:1, Type 2:6) of ATL HR ACs. dPCR analysis revealed that in three ATL samples, all exhibited Type 1 defective characteristics, and two showed extremely low ratios in the pol region. Clonality analysis of these two samples revealed high monoclonality, indicating monoclonal expansion of ATL cells with defective proviruses. These findings demonstrate that our method effectively detects defective proviruses in both ACs and ATL, providing a valuable tool for understanding the genomic characteristics of proviruses in these conditions., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: This study aimed to evaluate the impact of image enhancement techniques on the interobserver reliability of tear break-up time (TBUT), tear meniscus height (TMH), corneal fluorescein staining (CFS) scoring, and conjunctivochalasis detection using the Smart Eye Camera (SEC), a portable device for anterior segment examination., Methods: A retrospective analysis was conducted on video recordings captured by the SEC from 46 patients with dry eye disease (DED). Separate sets of images were created for each level of enhancement: unenhanced (G0), mildly enhanced (G3), and strongly enhanced (G7). These sets were not intermixed, ensuring that each enhancement level was assessed independently. Three observers-two DED specialists and one general ophthalmologist-assessed TBUT, TMH, CFS scores, and conjunctivochalasis. Interobserver reliability was evaluated using intraclass correlation coefficients (ICCs) for each image set., Results: Interobserver reliability for CFS scores significantly improved with G3, yielding an ICC of 0.8413. In contrast, G7 improved reliability for TBUT measurements (ICC = 0.7381), but led to a notable decrease in reliability for both CFS scoring (ICC = 0.2259) and conjunctivochalasis detection (ICC = 0.0786). Furthermore, the assessment of TMH demonstrated a progressive decline in accuracy with increasing levels of image enhancement., Conclusions: Image enhancement using the SEC improved the diagnostic consistency of dry eye specialists and general ophthalmologists, especially for TBUT and CFS assessments. However, excessive enhancement may obscure key diagnostic features, indicating the need for careful optimization of image processing techniques depending on the diagnostic focus.

Introduction: Cow's milk (CM) is one of the most common food allergens in Japan. The oral food challenge (OFC) of CM is important for the definite diagnosis of children with CM allergy and it is recommended to be actively and safely performed in individuals with low CM-sIgE levels. This study aimed to investigate the safety of low-dose CM-OFC in individuals with low CM-sIgE levels and discuss the prognostic factors and appropriate approaches for assessing the starting doses of CM-OFC in these individuals., Methods: We retrospectively analyzed 6,929 OFC tests conducted between January 1, 2017 and December 31, 2021; of which, 1,390 were CM-OFC tests. The characteristics, OFC-positive rates, CM loading, and related factors were analyzed in 138 cases involving low CM-sIgE levels. Stepwise OFC tests were conducted according to the FA guidelines in Japan using an open and unblinded method., Results: Among 138 individuals with low CM-sIgE levels, 110 (79.7%) passed the OFC test without any symptoms. Among the cases with OFC-positive status, 50.0% (14/28) cases showed symptoms with low-dose OFC (30-105 mg CM protein). Moreover, complete CM elimination was associated with a significantly high OFC-positive rate, and 60.0% (12/20) of the cases involving complete CM elimination showed symptoms with low-dose OFC., Conclusion: Eighty percent of the patients with low CM-sIgE levels safely completed the OFC test. Nevertheless, careful observation is essential during low-dose OFC test in cases with low CM-sIgE levels, especially in the cases with complete elimination. The starting dose of the OFC test should be re-evaluated and modified using baked milk or a lower dose of CM to ensure safety and early outgrowth of CM allergy., (S. Karger AG, Basel.)

Purpose of Review: This review evaluates the emerging role of the pullback pressure gradient (PPG) as a standardized metric for assessing coronary artery disease (CAD) patterns and its implications for clinical decision-making when managing patients undergoing percutaneous coronary interventions (PCIs). By integrating PPG with existing physiological assessments, this review highlights the potential benefits of PPG in predicting treatment outcomes and refining therapeutic strategies for CAD., Recent Findings: Recent studies, particularly the PPG Global study have demonstrated a strong correlation between PPG values and post-PCI outcomes, revealing that focal disease is associated with improved fractional flow reserve (FFR) and lower rates of adverse events than vessels with diffuse disease (low PPG). Additionally, PPG has been linked to specific atherosclerotic plaque characteristics, indicating its utility in identifying high-risk plaques. The integration of PPG with advanced imaging techniques further enhances the understanding of CAD patterns and their implications for treatment planning., Summary: The PPG represents a significant advancement in the management of CAD, providing a reproducible and objective assessment of coronary artery disease patterns that can inform clinical decision-making. As research continues to explore the relationship among PPG, atherosclerotic characteristics, and patient outcomes, its integration into routine practice is expected to improve the effectiveness of PCI and optimize patient management strategies. Future studies are warranted to establish specific PPG thresholds and further investigate its potential in identifying vulnerable plaques and guiding treatment decisions., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.)

Background: Angiography-derived fractional flow reserve (virtual FFR) has shown excellent diagnostic performance compared with wire-based FFR. However, virtual FFR pullback curves have not been validated yet., Objectives: To validate the accuracy of virtual FFR pullback curves compared to wire-based FFR pullbacks and to assess their clinical utility using patient-reported outcomes., Methods: Pooled analysis of two prospective studies, including patients with hemodynamically significant (FFR ≤ 0.80) coronary artery disease (CAD). Virtual and wire-based FFR pullbacks were compared to assess the accuracy of virtual pullbacks to characterize CAD as focal or diffuse. Pullbacks were analyzed visually and quantitatively using the pullback pressure gradient (PPG). Patients underwent PCI, and the Seattle Angina Questionnaire (SAQ) was administered at 3-month follow-up., Results: A total of 298 patients (300 vessels) with both virtual and wire-based pullbacks who underwent PCI were included in the analysis. The mean age was 61.8 ± 8.8, and 15% were female. The agreement on the visual adjudication of the CAD pattern was fair (Cohen's Kappa: 0.31, 95% confidence interval: 0.18-0.45). The mean PPG were 0.65 ± 0.18 from virtual pullbacks and 0.65 ± 0.13 from wire-based pullbacks (r = 0.68, mean difference 0, limits of agreement -0.27 to 0.28). At follow-up, patients with high virtual PPG (>0.67) had higher SAQ angina frequency scores (i.e., less angina) than those with low virtual PPG (SAQ scores 92.0 ± 14.3 vs. 85.5 ± 23.1, p = 0.022)., Conclusion: Virtual FFR pullback curves showed moderate agreement with wire-based FFR pullbacks. Nonetheless, patients with focal disease based on virtual PPG reported greater improvement in angina after PCI., (© 2024 Wiley Periodicals LLC.)

Multiple system atrophy (MSA) is a progressive neurodegenerative disease that often causes vocal cord paralysis (VCP), Parkinsonism, cerebellar ataxia, and autonomic dysfunction. VCP is the most fatal symptom that affects the prognosis of patients with MSA. Coronavirus disease 2019 (COVID-19) is often associated with neurological complications and it has recently been reported to induce VCP in patients without neurodegenerative diseases. We herein present two cases of patients with MSA in whom VCP worsened after COVID-19 and this led to the need to perform emergency tracheostomies. As VCP may deteriorate after COVID-19 in patients with MSA, it is important to prevent COVID-19 in these patients and closely monitor such patients for any signs of VCP deterioration post-infection to improve their prognosis.

Background: Recent studies suggest that the presence of calcified nodules (CN) is associated with worse prognosis in patients with acute coronary syndrome (ACS). We investigated clinical predictors of optical coherence tomography (OCT)-defined CN in ACS patients in a prospective multicenter registry., Methods and Results: We investigated 695 patients enrolled in the TACTICS registry who underwent OCT assessment of the culprit lesion during primary percutaneous coronary intervention. OCT-CN was defined as calcific nodules erupting into the lumen with disruption of the fibrous cap and an underlying calcified plate. Compared with patients without OCT-CN, patients with OCT-CN (n=28) were older (mean [±SD] age 75.0±11.3 vs. 65.7±12.7 years; P<0.001), had a higher prevalence of diabetes (50.0% vs. 29.4%; P=0.034), hemodialysis (21.4% vs. 1.6%; P<0.001), and Killip Class III/IV heart failure (21.4% vs. 5.7%; P=0.003), and a higher preprocedural SYNTAX score (median [interquartile range] score 15 [11-25] vs. 11 [7-19]; P=0.003). On multivariable analysis, age (odds ratio [OR] 1.072; P<0.001), hemodialysis (OR 16.571; P<0.001), and Killip Class III/IV (OR 4.466; P=0.004) were significantly associated with the presence of OCT-CN. In non-dialysis patients (n=678), age (OR 1.081; P<0.001), diabetes (OR 3.046; P=0.014), and Killip Class III/IV (OR 4.414; P=0.009) were significantly associated with the presence of OCT-CN., Conclusions: The TACTICS registry shows that OCT-CN is associated with lesion severity and poor clinical background, which may worsen prognosis.

Introduction: Stepwise oral food challenge (OFC) tests begin with low doses of allergens and progress to full doses. We previously reported the safety and efficacy of stepwise OFC for reintroducing hen eggs. In this study, we discuss its application for cow's milk (CM) allergy., Methods: We included 927 children (median age, 3.2 years) who underwent CM-OFC between 2017 and 2021. The target challenge dose was classified as low (&lt;10 mL), middle (≥10 mL but &lt;100 mL), or full. When participants reacted to the low dose, they underwent a very low-dose OFC using baked milk or &lt;1 mL of CM., Results: Positive reactions occurred in 210 cases (22.7%), including 69 anaphylactic reactions (7.4%). A lower target dose resulted in more positive OFC results (p &lt; 0.001) and anaphylaxis (p = 0.001). The lower dose group included more children with complete elimination of CM (p &lt; 0.001), with numerous histories of anaphylaxis induced by CM (p &lt; 0.001), and higher levels of total IgE (p = 0.033) and CM-sIgE (p &lt; 0.001). A multivariate analysis indicated that in the low-dose-OFC group, higher CM-sIgE levels (p = 0.034), younger age (p = 0.005), and complete elimination of CM (p = 0.002) were associated with positive OFC results., Conclusion: The stepwise OFC could reintroduce small amounts of CM, even in cases with high CM-sIgE levels or a history of anaphylaxis. Performing CM-OFC at younger ages, specifically from infancy, with very low doses, might facilitate the safe reintroduction of CM., (© 2024 S. Karger AG, Basel.)

Background/Objective: It is not uncommon for elderly patients to experience difficulties with feeding and swallowing. In the simple suspension method, tablets are dissolved and suspended in warm water without prior crushing or decapsulation, and then administered via a tube. Despite the prevalence of this method, the pharmacokinetics of suspended tablet dosage forms remain poorly understood. Methods: Verapamil was employed in dissolution tests following both the simple suspension and crushing methods. A pharmacokinetics study was conducted on healthy adult males. Results : The resultant dissolution profiles from the two methods exhibited notable dissimilarities. Drug release from the crushed product commenced earlier than that from the simple suspension and intact tablet. Furthermore, the area under the curve for verapamil during the initial 24 h period was 1.7 and 1.3 times greater in the crushed and simple suspension groups, respectively, than in the tablet group. Conclusions : The crushing and simple suspension methods are safe techniques for administering medications to patients with dysphagia, thereby preventing aspiration. Nevertheless, the processing of medications may result in an increased frequency of adverse effects. It is recommended that the processing of medicines prior to administration be avoided.

Background: Continuous intracoronary thermodilution with saline allows for the accurate measurement of volumetric blood flow (Q) and absolute microvascular resistance (R μ ). However, this requires repositioning of the temperature sensor by the operator to measure the entry temperature of the saline infusate, denoted as T i ., Aims: We evaluated whether Ti could be predicted based on known parameters without compromising the accuracy of calculated Q. This would significantly simplify the technique and render it completely operator independent., Methods: In a derivation cohort of 371 patients with Q measured both at rest and during hyperaemia, multivariate linear regression was used to derive an equation for the prediction of T i . Agreement between standard Q (calculated with measured T i ) and simplified Q (calculated with predicted T i ) was assessed in a validation cohort of 120 patients that underwent repeat Q measurements. The accuracy of simplified Q was assessed in a second validation cohort of 23 patients with [ 15 O]H 2 O positron emission tomography (PET)-derived Q measurements., Results: Simplified Q exhibited strong agreement with standard Q (r=0.94, confidence interval [CI]: 0.93-0.95; intraclass correlation coefficient [ICC] 0.94, CI: 0.92-0.95; both p<0.001). Simplified Q exhibited excellent agreement with PET-derived Q (r=0.86, CI: 0.75-0.92; ICC=0.84, CI: 0.72-0.91; both p<0.001). Compared with standard Q, there were no statistically significant differences between correlation coefficients (p=0.29) or standard deviations of absolute differences with PET-derived Q (p=0.85)., Conclusions: Predicting T i resulted in an excellent agreement with measured T i for the assessment of coronary blood flow. It significantly simplifies continuous intracoronary thermodilution and renders absolute coronary flow measurements completely operator independent.

Coronary computed tomography angiography (CCTA) provides 3D information on obstructive coronary artery disease, but cannot fully visualize high-resolution features within the vessel wall. Intravascular imaging, in contrast, can spatially resolve atherosclerotic in cross sectional slices, but is limited in capturing 3D relationships between each slice. Co-registering CCTA and intravascular images enables a variety of clinical research applications but is time consuming and user-dependent. This is due to intravascular images suffering from non-rigid distortions arising from irregularities in the imaging catheter path. To address these issues, we present a morphology-based framework for the rigid and non-rigid matching of intravascular images to CCTA images. To do this, we find the optimal virtual catheter path that samples the coronary artery in CCTA image space to recapitulate the coronary artery morphology observed in the intravascular image. We validate our framework on a multi-center cohort of 40 patients using bifurcation landmarks as ground truth for longitudinal and rotational registration. Our registration approach significantly outperforms other approaches for bifurcation alignment. By providing a differentiable framework for multi-modal vascular co-registration, our framework reduces the manual effort required to conduct large-scale multi-modal clinical studies and enables the development of machine learning-based co-registration approaches.

The widespread adoption of smartphones due to advances in information and communication technology(ICT)has enabled the use of software for data collection in clinical trials. In March 2021, revisions to the"Ethical Guidelines for Medical and Biological Research Involving Human Subjects"expanded the methods for obtaining consent using electronic means, further broadening the approaches to conducting clinical trials. However, nutrition impact symptoms in cancer patients remain inadequately defined. The authors aim to define these symptoms through the WASHOKU trial, utilizing smartphones for data collection related to nutrition. Through the WASHOKU trial, many challenges such as patient awareness, recruitment for research, smartphone ownership rates, and the technical proficiency of patients and users utilizing digital devices have come to light. Such trials serve as litmus tests, raising expectations for further clinical trials leveraging ICT.

Background: Vulnerable plaque presents prognostic implications in addition to functional significance., Objectives: The aim of this study was to identify relevant features of vulnerable plaque in functionally significant lesions., Methods: In this multicenter, prospective study conducted across 5 countries, including patients who had invasive fractional flow reserve (FFR) ≤0.80, a total of 95 patients with available pullback pressure gradient (PPG) and plaque analysis on coronary computed tomographic angiography and optical coherence tomography were analyzed. Vulnerable plaque was defined as the presence of plaque rupture or thin-cap fibroatheroma on optical coherence tomography. Among the 25 clinical characteristics, invasive angiographic findings, physiological indexes, and coronary computed tomographic angiographic findings, significant predictors of vulnerable plaque were identified., Results: Mean percentage diameter stenosis, FFR, and PPG were 77.8% ± 14.6%, 0.66 ± 0.13, and 0.65 ± 0.13, respectively. Vulnerable plaque was present in 53 lesions (55.8%). PPG and FFR were identified as significant predictors of vulnerable plaque (P < 0.05 for all). PPG >0.65 and FFR ≤0.70 were significantly related to a higher probability of vulnerable plaque after adjustment for each other (OR: 6.75 [95% CI: 2.39-19.1]; P < 0.001] for PPG >0.65; OR: 4.61 [95% CI: 1.66-12.8]; P = 0.003 for FFR ≤0.70). When categorizing lesions according to combined PPG >0.65 and FFR ≤0.70, the prevalence of vulnerable plaque was 20.0%, 57.1%, 66.7%, and 88.2% in the order of PPG ≤0.65 and FFR >0.70, PPG ≤0.65 and FFR ≤0.70, PPG >0.65 and FFR >0.70, and PPG >0.65 and FFR ≤0.70 (P for trend < 0.001), respectively., Conclusions: Among low-FFR lesions, the presence of vulnerable plaque can be predicted by PPG combined with FFR without additional anatomical or plaque characteristics. (Precise Percutaneous Coronary Intervention Plan [P3] Study; NCT03782688)., Competing Interests: Funding Support and Author Disclosures This study received funding from HeartFlow and was also supported by grants from the Patient-Centered Clinical Research Coordinating Center (HI19C0481 and HC19C0305) funded by the Ministry of Health and Welfare and from the Ministry of Food and Drug Safety (RS-2023-00215667), Republic of Korea. Dr Mizukami has received consulting fees from Zeon Medical and HeartFlow; and has received speaker fees from Abbott Vascular. Dr Leipsic is a consultant for and holds stock options in Circle CVI and HeartFlow; has received a research grant from GE; and has received modest speaker fees from GE and Philips. Drs Sonck and Munhoz have received research grants provided by the Cardiopath PhD program. Dr Nørgaard has received unrestricted institutional research grants from Siemens and HeartFlow. Dr Otake has received research grants from Abbott Vascular; and has received speaker fees from HeartFlow and Abbott Vascular. Dr Ko has received consulting fees from Canon Medical, Abbott, and Medtronic. Dr Koo has received institutional research grants from HeartFlow. Dr Maeng has received advisory board and lecture fees from AstraZeneca, Bayer, Boehringer Ingelheim, Bristol Myers Squibb, Boston Scientific, and Novo Nordics; and has received institutional research grants from Bayer, Philips Healthcare, and Novo Nordisk. Dr Jensen has received unrestricted institutional research grants from Siemens and HeartFlow. Dr Andreini has received research grants from GE Healthcare and Bracco. Dr Shinke has received research grants from Boston Scientific and Abbott Vascular. Dr Barbato has received speaker fees from Boston Scientific, Abbott Vascular, and GE. Dr De Bruyne has received consulting fees from Boston Scientific and Abbott Vascular; has received research grants from Coroventis Research, Pie Medical Imaging, CathWorks, Boston Scientific, Siemens, HeartFlow, and Abbott Vascular; and owns equity in Siemens, GE, Philips, HeartFlow, Edwards Lifesciences, Bayer, Sanofi, and Celyad. Dr Collet has received research grants from Biosensor, Coroventis Research, Medis Medical Imaging, Pie Medical Imaging, CathWorks, Boston Scientific, Siemens, HeartFlow, and Abbott Vascular; and has received consulting fees from HeartFlow, OpSens, Abbott Vascular, and Philips Volcano. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2024 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Objectives: We explored the connection between varicose vein and edema, by investigating extracellular water ratio (E/T) using bioelectrical impedance analysis., Methods: In a prospective cohort study 120 patients underwent varicose vein surgery with extracellular fluid to total body water ratio (E/T) and E/T postop divided by E/Tpreop (E/T ratio) measured using a body composition analyzer. Edema was defined as E/T ≥0.390. Seventy-nine patients received unilateral treatment, while 41 underwent bilateral. p < .05 is statistically significant., Results: Preoperatively, patients exhibited edema (E/T) in the treated leg (0.394 ± 0.009), untreated leg (0.392 ± 0.009), trunk (0.390 ± 0.007), and whole body (0.391 ± 0.007). Postoperatively, E/T decreased across body ( p < .05). The lowest E/T ratio was observed in the treated leg (0.991 ± 0.012), followed by the untreated leg (0.994 ± 0.012), the trunk (0.995 ± 0.009), and the whole body (0.994 ± 0.009). E/T ratio of bilateral group were lower than unilateral group ( p < .05)., Conclusion: Varicose vein contributes to generalized edema, and treatment alleviates edema in the treated leg and the entire body., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: Approximately half of the patients with angina and nonobstructive coronary artery disease (ANOCA) have evidence of coronary microvascular dysfunction (CMD)., Objectives: This study aims to characterize patients with ANOCA by measuring their minimal microvascular resistance and to examine the pattern of vascular remodeling associated with these measurements., Methods: The authors prospectively included patients with ANOCA undergoing continuous thermodilution assessment. Lumen volume and vessel-specific myocardial mass were quantified using coronary computed tomography angiography (CTA). CMD was defined as coronary flow reserve <2.5 and high minimal microvascular resistance as >470 WU., Results: A total of 153 patients were evaluated; 68 had CMD, and 22 of them showed high microvascular resistance. In patients with CMD, coronary flow reserve was 1.9 ± 0.38 vs 3.2 ± 0.81 in controls (P < 0.001). Lumen volume was significantly correlated with minimal microvascular resistance (r = -0.59 [95% CI: -0.45 to -0.71]; P < 0.001). In patients with CMD and high microvascular resistance, lumen volume was 40% smaller than in controls (512.8 ± 130.3 mm 3 vs 853.2 ± 341.2 mm 3 ; P < 0.001). Epicardial lumen volume assessed by coronary CTA was independently associated with minimal microvascular resistance (P < 0.001). The predictive capacity of lumen volume from coronary CTA for detecting high microvascular resistance showed an area under the curve of 0.79 (95% CI: 0.69-0.88)., Conclusions: Patients with CMD and high minimal microvascular resistance have smaller epicardial vessels than those without CMD. Coronary CTA detected high minimal microvascular resistance with very good diagnostic capacity. Coronary CTA could potentially aid in the diagnostic pathway for patients with ANOCA., Competing Interests: Funding Support and Author Disclosures Dr Collet has received research grants from Biosensor, Coroventis Research, Medis Medical Imaging, Pie Medical Imaging, CathWorks, Boston Scientific, Siemens, HeartFlow Inc, and Abbott Vascular; and consultancy fees from HeartFlow Inc, OpSens, Abbott Vascular, and Philips Volcano. Dr Mizukami has received consultancy fees from Zeon Medical Inc, research grants from Boston Scientific, and speaker fees from Abbott Vascular, Cath works, and Boston Scientific. Drs Buytaert and Munhoz have received research grants provided by the Cardiopath PhD program. Dr De Bruyne has received consultancy fees from Boston Scientific and Abbott Vascular; research grants from Coroventis Research, Pie Medical Imaging, CathWorks, Boston Scientific, Siemens, HeartFlow Inc, and Abbott Vascular; and owns equity in Siemens, GE, Philips, HeartFlow Inc, Edwards Life Sciences, Bayer, Sanofi, and Celyad. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2024 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Purpose: In this study, we aimed to evaluate and compare the effects of intravitreal aflibercept (IVA) and intravitreal faricimab (IVF) injections on the blood flow of retinal vessels in the peripapillary region and optic nerve head (ONH) in eyes with diabetic macular edema (DME) using laser speckle flowgraphy (LSFG)., Patients and Methods: This study included 20 eyes of 18 patients treated with IVA and 15 eyes of 11 patients treated with IVF for DME. The mean blur rate (MBR) of the ONH and retinal artery and vein of the peripapillary region were measured using LSFG at baseline and 1 month after injection. Central retinal thickness (CRT) and best-corrected visual acuity (BCVA) were measured for all patients., Results: CRT decreased significantly in both IVA-treated ( p = 0.0003) and IVF-treated groups ( p = 0.0004). Some of the MBR-related parameters of the ONH, such as MBR of all areas (MA), MBR of vascular areas (MV), and MBR of tissue areas (MT), decreased significantly 1 month after IVA and IVF compared to baseline values (MA of IVA, p < 0.0001; MT of IVA, p = 0.0220; MA of IVF, p = 0.0002; MT of IVF, p = 0.0461). MBR of the retinal artery (MBR-A) and vein (MBR-V) also decreased significantly 1 month after IVA and IVF compared with baseline values (MBR-A of IVA, p = 0.0002; MBR-V of IVA, p = 0.0010; MBR-A of IVF, p = 0.0368). No significant difference in ocular perfusion was observed between the IVA-treated and IVF-treated groups., Conclusion: Intravitreal injection led to a reduction in ocular blood flow in both retinal peripapillary vessels and the ONH in both IVA-treated and IVF-treated groups. No significant difference was observed in MBR reduction between the IVA-treated and IVF-treated groups. Our findings warrant further long-term investigations to reveal differences between aflibercept and faricimab., Competing Interests: The authors report no conflicts of interest in this work., (© 2024 Mizukami et al.)

Aims: Left atrial (LA) volume index (LAVI) in chronic heart failure (HF) predicts cardiovascular outcomes. However, the association between LAVI reduction during acute decompensated HF (ADHF) and its prognostic potential is limited. We hypothesized that LA reverse remodelling (LARR) after ADHF therapy would be associated with better clinical outcomes., Methods: This retrospective study analysed clinical outcomes and the LAVI reduction rate of 363 out of 861 patients hospitalized for ADHF who underwent two-point echocardiography at admission and discharge between January 2015 and December 2019. The mean age was 74.3 ± 13.6 years, and the mean ejection fraction (EF) was 38.9 ± 15.2%. The follow-up echocardiogram was performed 13.0 [9.5, 20] days after admission. As the median LAVI reduction rate was 7.02%, the LARR was defined as an LAVI reduction rate >7%., Results: During the 34.0 ± 20.2 months of follow-up, 117 patients (32.2%) reached the primary endpoint defined as cardiovascular death and rehospitalization for ADHF. Kaplan-Meier survival analysis showed that patients with LARR had a better prognosis. Multivariate analysis indicated that LARR was an independent predictor of cardiovascular events. Similar findings were observed in the subgroup analyses of patients with persistent/permanent atrial fibrillation and those with non-HF with reduced EF. Among patients who were brain natriuretic peptide (BNP) responders, defined as a relative reduction of >70% in BNP from admission to discharge, non-LARR was observed in 41.6%. BNP responders without LARR experienced worse prognoses., Conclusions: LARR in the early vulnerable phase after hospitalization for ADHF was associated with better long-term clinical outcomes., (© 2024 The Author(s). ESC Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)

Sweet's syndrome (SS), also known as acute febrile neutrophilic dermatosis, manifests as tender, erythematous skin lesions such as papules, nodules, and plaques that may appear vesicular or pustular. The condition is characterized by widespread infiltrates mainly consisting of mature neutrophils, usually in the upper dermis. Erythema nodosum (EN) is a form of septal panniculitis marked by tender, erythematous lesions primarily appearing on the lower legs. Additionally, subcutaneous Sweet's syndrome (SSS) is a rare variant of SS that mainly involves the subcutaneous adipose tissue. Skin lesions in SSS generally present as tender, erythematous subepidermal nodules on the extremities, morphologically resembling EN. Both EN and SS can present with fever, malaise, gastrointestinal disturbances, lymphadenopathy, arthralgia, increased white blood cell (WBC) count with neutrophilia, elevated C-reactive protein (CRP), and elevated erythrocyte sedimentation rate (ESR), making differentiation between them often challenging. Therefore, histopathologic evaluation is necessary for an accurate diagnosis. In our case, the patient exhibited a very painful plaque measuring 20 cm in diameter on the upper thigh without significant neutrophil infiltration in the dermis, but with subcutaneous septal neutrophil infiltration. Generally, SS shows stronger leukocytosis with neutrophilia than EN does. Considering the clinical symptoms, laboratory results, and clinical progression, the clinicopathological findings aligned more closely with SSS than EN. This article describes a rare case of SSS presenting with a single cutaneous lesion on the thigh, which mimicked the histopathological features of EN., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Youh et al.)

Background: Diffuse coronary artery disease affects the safety and efficacy of percutaneous coronary intervention (PCI). Pathophysiologic coronary artery disease patterns can be quantified using fractional flow reserve (FFR) pullbacks incorporating the pullback pressure gradient (PPG) calculation. This study aimed to establish the capacity of PPG to predict optimal revascularization and procedural outcomes., Methods: This prospective, investigator-initiated, single-arm, multicenter study enrolled patients with at least one epicardial lesion with an FFR ≤0.80 scheduled for PCI. Manual FFR pullbacks were used to calculate PPG. The primary outcome of optimal revascularization was defined as an FFR ≥0.88 after PCI., Results: A total of 993 patients with 1044 vessels were included. The mean FFR was 0.68±0.12, PPG 0.62±0.17, and the post-PCI FFR was 0.87±0.07. PPG was significantly correlated with the change in FFR after PCI (r=0.65 [95% CI, 0.61-0.69]; P <0.001) and demonstrated excellent predictive capacity for optimal revascularization (area under the receiver operating characteristic curve, 0.82 [95% CI, 0.79-0.84]; P <0.001). FFR alone did not predict revascularization outcomes (area under the receiver operating characteristic curve, 0.54 [95% CI, 0.50-0.57]). PPG influenced treatment decisions in 14% of patients, redirecting them from PCI to alternative treatment modalities. Periprocedural myocardial infarction occurred more frequently in patients with low PPG (<0.62) compared with those with focal disease (odds ratio, 1.71 [95% CI, 1.00-2.97])., Conclusions: Pathophysiologic coronary artery disease patterns distinctly affect the safety and effectiveness of PCI. PPG showed an excellent predictive capacity for optimal revascularization and demonstrated added value compared with an FFR measurement., Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT04789317., Competing Interests: Dr Collet reports receiving research grants from Biosensors, Coroventis Research, Medis Medical Imaging, Pie Medical Imaging, CathWorks, Boston Scientific, Siemens, HeartFlow, and Abbott Vascular; consultancy fees from HeartFlow, OpSens Medical, Abbott Vascular, and Philips Volcano; and has patents pending on diagnostic methods for coronary artery disease. Dr Munhoz reports a research grant provided by the CardioPath PhD programme and speaker fees from Abbott Vascular. Dr Mizukami reports receiving research grants from Boston Scientific and speaker fees from Abbott Vascular, CathWorks, and Boston Scientific. Dr Matsuo has received consulting fees from Kaneka and Zeon and speaker’s fees from Abbott Medical Japan, Boston Scientific, Philips, and Amgen. Dr Ko has received consulting fees from Canon Medical, Abbott, and Medtronic. Dr Biscaglia received research grants provided by Sahajanand Medical Technologies, Medis Medical Imaging, Eukon Srl, Siemens Healthineers, General Electric Healthcare, and Insight Lifetech. Dr Engstrøm reports speaker and advisory board fees from Abbott, Boston Scientific, and Novo Nordisk. Dr Leone reports receiving consultancy fees from Abbott and honoraria for sponsored symposia from Abbott, Medtronic, and Abiomed. Dr Fearon receives institutional research support from Abbott, Boston Scientific, and Medtronic and has consulting relationships with CathWorks and Siemens and stock options from HeartFlow. Dr Christiansen has received consulting fees from Abbott Medical Denmark A/S. Dr Yong has received minor honoraria from Abbott Vascular and research grants from Abbott Vascular and Philips. Dr Escaned is supported by the Intensification of Research Activity project INT22/00088 from the Spanish Instituto de Salud Carlos III and received speaker and advisory board member fees from Abbott and Philips. Dr Storozhenko reports a grant provided by the EAPCI Fellowship Programme. Dr West is an employee of Abbott Vascular. Dr De Potter is a paid consultant for Biosense Webster and receives grant support (institutional) and consultancy fees (institutional) from Abbott. Dr Berry receives research funding from the British Heart Foundation (grants RE/18/6134217, BHF/FS/17/26/32744, and PG/19/28/34310) and is employed by the University of Glasgow, which holds consultancy and research agreements for his work with Abbott Vascular, AstraZeneca, Boehringer Ingelheim, Coroventis Research, GlaxoSmithKline, HeartFlow, Menarini, Novartis, Servier, Siemens Healthcare, and Valo Health. Dr Collison has received consulting fees from Abbott. Dr Johnson has received consultancy or speaker fees from Abbott Vascular, Boston Scientific, Medtronic, Shockwave, and Terumo, and research grants from Abbott Vascular. Dr Amano reports receiving lecture fees from Astellas Pharma, Astra Zeneca, Bayer, Daiichi Sankyo, and Bristol Myers Squibb. Dr Perera has received research grant support from Abbott Vascular, HeartFlow, and Philips. Dr Jeremias has received consulting fees from Canon Medical, Artrya Medical, and Boston Scientific. Dr Ali reports institutional grant support from Abbott, Abiomed, Acist, Amgen, Boston Scientific, CathWorks, Canon Medical, Conavi, HeartFlow, Inari, Medtronic, the US National Institutes of Health, Nipro, OpSens Medical, Medis, Philips, Shockwave, Siemens, SpectraWAVE, and Teleflex; consulting fees from Abiomed, Astra Zeneca, Boston Scientific, CathWorks, OpSens Medical, Philips, and Shockwave; and equity in Elucid, Lifelink, SpectraWAVE, Shockwave, and VitalConnect. Dr Pijls has received research grants from Abbott and Hexacath; consultancy fees from Abbott, GE, Philips, and HeartFlow; and has equity in General Electric, Philips, and HeartFlow. Dr De Bruyne reports receiving consultancy fees from Boston Scientific and Abbott and research grants from Coroventis Research, Pie Medical Imaging, CathWorks, Boston Scientific, Siemens, HeartFlow, and Abbott Vascular. Dr Johnson received internal funding from the Weatherhead PET Center for Preventing and Reversing Atherosclerosis; has received significant institutional research support from St Jude Medical (CONTRAST [Can Contrast Injection Better Approximate FFR Compared to Pure Resting Physiology?; URL: https://www.clinicaltrials.gov; Unique identifier: NCT02184117]) and Philips Volcano (DEFINE-FLOW [Combined Pressure and Flow Measurements to Guide Treatment of Coronary Stenoses; URL: https://www.clinicaltrials.gov; Unique identifier: NCT02328820]) for other studies using intracoronary pressure and flow sensors; has an institutional licensing agreement with Boston Scientific for the smart-minimum FFR algorithm (now commercialized under 510[k] K191008); and has patents pending on diagnostic methods for quantifying aortic stenosis and TAVI physiology and on methods to correct pressure tracings from fluid-filled catheters.

Angiography-derived fractional flow reserve (FFR) has emerged as a non-invasive technique to assess the functional significance of coronary artery stenoses. The clinical applications of angiography-derived FFR span a wide range of scenarios, including assessing intermediate coronary lesions and guiding revascularization decisions. This review paper aims to provide an overview of angiography-derived FFR, including its principles, clinical applications, and evidence supporting its accuracy and utility. Lastly, the review discusses future directions and ongoing research in the field, including the integration of angiography-derived FFR into routine clinical practice., Competing Interests: Declaration of competing interest None., (Copyright © 2024. Published by Elsevier Inc.)

Background/Objectives : The use of food thickeners with ciprofloxacin tablets may result in a gelatinous appearance and experience delayed dissolution, which presents a challenge for the drug's efficacy, creating a healthcare economic issue. However, the pharmacokinetic impact of this compound in humans remains uncertain. Therefore, a comparative pharmacokinetic study of ciprofloxacin was conducted on healthy adult Japanese males. Methods : We compared the effects of administering tablets with water or thickened water and crushed tablets mixed with thickened water. The maximum blood concentration (C max ) of ciprofloxacin determines the drug's efficacy. Results : There were variations in drug absorption across different administration methods. The group who took the tablets immersed in thickened water exhibited different results in the area under the blood drug concentration-time curve (AUC) and C max compared to the group who took the tablets in regular water. Notably, the group that consumed the crushed tablets mixed with thickened water demonstrated equivalent results for both AUC and C max . Conclusions : Administering crushed tablets in thickened water may yield pharmacokinetics comparable to those of tablets taken with water. However, the process of crushing tablets may result in the loss of active ingredients and compromise the formulation, necessitating a comprehensive assessment before administration.

Purpose: Panel-based comprehensive genomic profiling (CGP) is used in clinical practice worldwide; however, large real-world data (RWD) of patients with advanced small intestine cancer have not been characterized. We investigated differences in the prevalence of clinically relevant alterations across molecularly defined or age-stratified subgroups., Patients and Methods: This was a collaborative biomarker study of RWD from CGP testing (Foundation Medicine, Inc). Hybrid capture was conducted on at least 324 cancer-related genes and select introns from up to 31 genes frequently rearranged in cancer. Overall, 1,364 patients with advanced small intestine cancer were available for analyses and were stratified by age (≥40 years/<40 years), microsatellite instability (MSI) status, tumor mutational burden (TMB) status (high ≥10/low <10 Muts/Mb), and select gene alterations. The frequency of alterations was analyzed using a chi-square test with Yate's correction., Results: Genes with frequent alterations included TP53 (59.8%), KRAS (54.8%), APC (27.7%), and CDKN2A (22.4%). Frequent genes with amplifications were MYC (6.7%), MDM2 (5.9%), GATA6 (5.5%), and CCND1 (3.4%). Patients younger than 40 years had significantly lower frequency of APC mutations than those 40 years and older (10.4% v 28.7%; P = .0008). Druggable genomic alterations were detected in 22.3% of patients: BRAF V600E (1.2%), BRCA1 (1.8%), BRCA2 (3.2%), ERBB2 amplification (3.2%), KRAS G12C (3.3%), NTRK1/2/3 fusion (0.07%), MSI-high (7.0%), and TMB-high (12.2%), with no significant differences in the frequency according to age (<40 years v ≥40 years; 22.1% v 22.3%). TMB of 10-20 Mut/Mb was observed in 4.8% of patients, and TMB ≥20 Mut/Mb was seen in 7.3% of the cohort., Conclusion: RWD from clinical panel testing revealed the genomic landscape in small intestine cancer by subgroup. These findings provide insights for the future development of treatments in advanced small intestine cancer.

Background: Simian T-cell leukemia virus type 1 (STLV-1) is a retrovirus closely related to human T-cell leukemia virus type 1 (HTLV-1), the causative agent of adult T-cell leukemia (ATL). It has been shown that Japanese macaques (Macaca fuscata, JMs) are one of the main hosts of STLV-1 and that a high percentage of JMs (up to 60%) are infected with STLV-1; however, the molecular epidemiology of STLV-1 in JMs has not been examined., Methods: In this study, we analyzed full-length STLV-1 genome sequences obtained from 5 independent troops including a total of 68 JMs., Results: The overall nucleotide heterogeneity was 4.7%, and the heterogeneity among the troops was 2.1%, irrespective of the formation of distinct subclusters in each troop. Moreover, the heterogeneity within each troop was extremely low (>99% genome homology) compared with cases of STLV-1 in African non-human primates as well as humans. It was previously reported that frequent G-to-A single-nucleotide variants (SNVs) occur in HTLV-1 proviral genomes in both ATL patients and HTLV-1 carriers, and that a G-to-A hypermutation is associated with the cellular antiviral restriction factor, Apobec3G. Surprisingly, these SNVs were scarcely observed in the STLV-1 genomes in JMs., Conclusions: Taken together, these results indicate that STLV-1 genomes in JMs are highly homologous, at least in part due to the lack of Apobec3G-dependent G-to-A hypermutation., (© 2024. The Author(s).)

Background and Objectives : In this study, our objective was to assess and compare the changes in visual and structural outcomes among patients with neovascular age-related macular degeneration (nAMD) who were switched from intravitreal aflibercept (IVA) to either intravitreal brolucizumab (IVBr) or intravitreal faricimab (IVF) injections in a clinical setting. Materials and Methods : This observational clinical study included 20 eyes of 20 patients switched to brolucizumab and 15 eyes of 14 patients switched to faricimab from aflibercept in eyes with nAMD. We measured the structural outcome (central macular thickness (CMT)) and the visual outcome (best-corrected visual acuity (BCVA); logMAR) as follows: just before the most recent IVA injection (B0), one month after the most recent IVA injection (B1), just before the first IVBr or IVF injection (A0), one month after (A1) and three months after (A3) the first IVBr or IVF injection. Results : BCVA showed significant improvement at A1 (0.25 ± 0.34) and at A3 (0.19 ± 0.24) compared to A0 (0.38 ± 0.35) in the IVBr group ( p = 0.0156, p = 0.0166, respectively). CMT (μm) was significantly thinner at A1 (IVBr: 240.55 ± 51.82, IVF: 234.91 ± 47.29) and at A3 (IVBr: 243.21 ± 76.15, IVF: 250.50 ± 72.61) compared to at A0 (IVBr: 303.55 ± 79.18, IVF: 270.33 ± 77.62) in the IVBr group (A1: p = 0.0093, A3: p = 0.0026) and in the IVF group (A1: p = 0.0161, A3: p = 0.0093). There was no significant difference in BCVA and CMT improvement observed between two groups at any time point ( p > 0.05 for all). Conclusions : Switching from aflibercept to either brolucizumab or faricimab has a significant anatomical effect in eyes with nAMD and both treatments appear to be effective short-term treatment options. There is a trend towards greater visual improvements and reductions in CMT with brolucizumab.

Mucosa-associated lymphoid tissue (MALT) lymphoma arising from the tongue is a rare pathologic condition for which a standard treatment mode has not been established. This disease represents a low-grade lymphoma frequently found in the stomach but rarely in the lymphoid tissue of the tongue. Only six cases that have been reported could be retrieved. We present the case of a 79-year-old woman who manifested with a mass on her tongue. A biopsy of the mass confirmed a diagnosis of MALT lymphoma. Radiation therapy of 30.6 Gy in 17 fractions was performed, and a complete metabolic response was achieved., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Tobikawa et al.)

Background: The commercial availability of anamorelin, Japan's first therapeutic agent for cancer cachexia in 2021, led to an investigation into its prescription patterns at Toyama University Hospital. Objective: We aimed to analyze anamorelin prescription trends and outcomes among cancer cachexia patients. Methods: A retrospective study from July 2021 to December 2022 examined 88 cases, assessing demographics, cancer types, prescription locations, and meal intake changes. Results: Anamorelin usage was predominant during chemotherapy, especially for pancreatic cancer in outpatient settings. Approximately 30% experienced increased meal intake. Chemotherapy-initiated cases had a longer median duration (55 days) compared with best supportive care only cases (12 days). Conclusion: Anamorelin demonstrated significant prescription patterns, particularly during chemotherapy for pancreatic cancer in outpatient settings, suggesting potential efficacy enhancements when administered with chemotherapy in cancer cachexia management. The study underscores the importance of tailored approaches to optimize anamorelin's therapeutic benefits.

Background: Coronary CT angiography (CCTA) is well-established for diagnosis and stratification of coronary artery disease (CAD). Its usefulness in guiding percutaneous coronary interventions (PCI) and stent sizing is unknown., Methods: This is a sub-analysis of the Precise Percutaneous Coronary Intervention Plan (P3) study (NCT03782688). We analyzed 65 vessels with matched CCTA and pre-PCI optical coherence tomography (OCT) assessment. The CCTA-guided stent size was defined by the mean distal reference lumen diameter rounded up to the nearest stent diameter. The OCT lumen-guided stent size was the mean distal reference lumen diameter rounded to the closest stent diameter. The agreement on stent diameters was determined with Kappa statistics, Passing-Bablok regression analysis, and the Bland-Altman method., Results: The distal reference lumen diameter by CCTA and OCT were 2.75 ​± ​0.53 ​mm and 2.72 ​± ​0.55 ​mm (mean difference 0.06, limits of agreement -0.7 to 0.82). There were no proportional or systematic differences (coefficient A 1.06, 95% CI 0.84 to 1.3 and coefficient B -0.22, 95% CI -0.83 to 0.36) between methods. The agreement between the CCTA and OCT stent size was substantial (Cohen's weighted Kappa 0.74, 95% CI 0.64 to 0.85). Compared to OCT stent diameter, CCTA stent size was concordant in 52.3% of the cases; CCTA overestimated stent size in 20.0% and underestimated in 27.7%., Conclusion: CCTA accurately assessed the reference vessel diameter used for stent sizing. CCTA-based stent sizing showed a substantial agreement with OCT. CCTA allows for PCI planning and may aid in selecting stent diameter., Competing Interests: Declaration of competing interest TM reports receiving consulting fees from Zeon Medical and HeartFlow Inc, and speaker fees from Abbott Vascular. BLN has received an unrestricted institutional research grant from HeartFlow Inc. MM is supported by a grant from the Novo Nordisk Foundation (grant NNF22OC0074083). BKK received an Institutional Research Grant from Abbott Vascular, Boston Scientific Corporation, and Philips. BDB reports receiving consultancy fees from Boston Scientific and Abbott Vascular, research grants from Coroventis Research, Pie Medical Imaging, CathWorks, Boston Scientific, Siemens, HeartFlow Inc, and Abbott Vascular, and owning equity in Siemens, GE, Philips, HeartFlow Inc, Edwards Life Sciences, Bayer, Sanofi, Celyad. CC reports receiving research grants from Biosensor, Coroventis Research, Medis Medical Imaging, Pie Medical Imaging, CathWorks, Boston Scientific, Siemens, HeartFlow Inc, Abbott Vascular, and consultancy fees from HeartFlow Inc, OpSens, Abbott Vascular, and Philips Volcano. The other authors have no further disclosures., (Copyright © 2024 Society of Cardiovascular Computed Tomography. Published by Elsevier Inc. All rights reserved.)

Familial episodic pain syndrome (FEPS) is an early childhood onset disorder of severe episodic limb pain caused mainly by pathogenic variants of SCN11A , SCN10A , and SCN9A , which encode three voltage-gated sodium channels (VGSCs) expressed as key determinants of nociceptor excitability in primary sensory neurons. There may still be many undiagnosed patients with FEPS. A better understanding of the associated pathogenesis, epidemiology, and clinical characteristics is needed to provide appropriate diagnosis and care. For this study, nationwide recruitment of Japanese patients was conducted using provisional clinical diagnostic criteria, followed by genetic testing for SCN11A , SCN10A , and SCN9A . In the cohort of 212 recruited patients, genetic testing revealed that 64 patients (30.2%) harbored pathogenic or likely pathogenic variants of these genes, consisting of 42 (19.8%), 14 (6.60%), and 8 (3.77%) patients with variants of SCN11A , SCN10A , and SCN9A , respectively. Meanwhile, the proportions of patients meeting the tentative clinical criteria were 89.1%, 52.0%, and 54.5% among patients with pathogenic or likely pathogenic variants of each of the three genes, suggesting the validity of these clinical criteria, especially for patients with SCN11A variants. These clinical diagnostic criteria of FEPS will accelerate the recruitment of patients with underlying pathogenic variants who are unexpectedly prevalent in Japan.

Aim: This study aimed to report initial results of hypofractionated carbon-ion radiotherapy (C-ion RT) for inoperable upper tract ureteral cancer., Methods: Retrospective chart review was performed for five consecutive patients with medically inoperable ureter cancer that was treated with radical C-ion RT between December 2013 and December 2014. The median age of the patients was 80 years (range, 68-84 years). The reasons for inoperability were advanced age, post-contralateral nephrectomy, alcoholic cirrhosis, both advanced age and contralateral renal function degeneracy, and pneumonia. The median size of tumor was 2.8 cm (range, 2.2-4.0 cm). Diagnostic imaging did not identify lymph node metastases or distant metastases in any case. All patients underwent C-ion RT (52.8 Gy relative biological effectiveness; 12 fractions in 3 weeks). The clinical target volume encompassed the growth tumor volume with a 5-mm margin bilaterally; there was a 40-mm margin craniocaudally but the clinical target volume did not encompass the whole ureter., Results: Within a median follow-up time of 32.9 months (range, 24-36 months), two patients died and three remained alive. Neither local recurrence nor regional lymph node metastases were observed. Secondary bladder tumor was observed in four patients, and one patient had a liver metastasis. Grade 1 hematuria was observed in two patients, and Grade 3 pyelonephritis was observed in one patient as acute toxicity. Ureteral obstruction was observed in two patients., Conclusion: C-ion RT might be a useful treatment option for inoperable ureter cancer., (© 2023 The Authors. Asia‐Pacific Journal of Clinical Oncology published by John Wiley & Sons Australia, Ltd.)

Background: The aim of this study is to examine the outcomes of an accelerated fractionated irradiation for N0 glottic carcinoma., Methods: In this retrospective analysis, 29 patients with N0 glottic carcinoma treated by radiation therapy were enrolled. Thirteen patients had T1a disease, six had T1b disease, and ten had T2 disease. A fractional dose of 2.1 Gy was administered to seven patients. The total doses were 65.1 and 67.2 Gy in four and three patients, respectively. A fractional dose of 2.25 Gy was administered to 22 patients. The total doses were 63 and 67.5 Gy in 21 patients and 1 patient with T2 disease, respectively. Additionally, 13 patients underwent the use of TS-1 (80-100 mg per day)., Results: The median follow-up period was 33 months, and the 3-year local control rate was 95.6%. No patient had a lymph node or distant recurrence. As acute adverse events, grades 2 and 3 dermatitis were observed in 18 patients and 1 patient, and grades 2 and 3 mucositis were observed in 15 patients and 1 patient. As a late adverse event, one patient required tracheotomy because of laryngeal edema occurring., Conclusions: Accelerated fractionated irradiation may be an option in the radiation therapy of N0 glottic carcinoma because of its ability to shorten the treatment time.

Background: Two invasive methods are available to estimate microvascular resistance: bolus and continuous thermodilution. Comparative studies have revealed a lack of concordance between measurements of microvascular resistance obtained through these techniques., Aims: This study aimed to examine the influence of vessel volume on bolus thermodilution measurements., Methods: We prospectively included patients with angina with non-obstructive coronary arteries (ANOCA) undergoing bolus and continuous thermodilution assessments. All patients underwent coronary CT angiography to extract vessel volume. Coronary microvascular dysfunction was defined as coronary flow reserve (CFR) < 2.0. Measurements of absolute microvascular resistance (in Woods units) and index of microvascular resistance (IMR) were compared before and after volumetric adjustment., Results: Overall, 94 patients with ANOCA were included in this study. The mean age was 64.7 ± 10.8 years, 48% were female, and 19% had diabetes. The prevalence of CMD was 16% based on bolus thermodilution, while continuous thermodilution yielded a prevalence of 27% (Cohen's Kappa 0.44, 95% CI 0.23-0.65). There was no correlation in microvascular resistance between techniques (r = 0.17, 95% CI -0.04 to 0.36, p = 0.104). The adjustment of IMR by vessel volume significantly increased the agreement with absolute microvascular resistance derived from continuous thermodilution (r = 0.48, 95% CI 0.31-0.63, p < 0.001)., Conclusions: In patients with ANOCA, invasive methods based on coronary thermodilution yielded conflicting results for the assessment of CMD. Adjusting IMR with vessel volume improved the agreement with continuous thermodilution for the assessment of microvascular resistance. These findings strongly suggest the importance of considering vessel volume when interpreting bolus thermodilution assessment., (© 2024 Wiley Periodicals LLC.)

Background: Panel-based comprehensive genomic profiling is used in clinical practice worldwide; however, large real-world datasets of patients with advanced gastric cancer are not well known., Objective: We investigated what differences exist in clinically relevant alterations for molecularly defined or age-stratified subgroups., Methods: This was a collaborative biomarker study of a real-world dataset from comprehensive genomic profiling testing (Foundation Medicine, Inc.). Hybrid capture was carried out on at least 324 cancer-related genes and select introns from 31 genes frequently rearranged in cancer. Overall, 4634 patients were available for analyses and were stratified by age (≥ 40/< 40 years), microsatellite instability status, tumor mutational burden status (high 10 ≥ /low < 10 Muts/Mb), Epstein-Barr virus status, and select gene alterations. We analyzed the frequency of alterations with a chi-square test with Yate's correction., Results: Genes with frequent alterations included TP53 (60.1%), ARID1A (19.6%), CDKN2A (18.2%), KRAS (16.6%), and CDH1 (15.8%). Differences in comprehensive genomic profiling were observed according to molecularly defined or age-stratified subgroups. Druggable genomic alterations were detected in 31.4% of patients; ATM (4.4%), BRAF V600E (0.4%), BRCA1 (1.5%), BRCA2 (2.9%), ERBB2 amplification (9.2%), IDH1 (0.2%), KRAS G12C (0.7%), microsatellite instability-high (4.8%), NTRK1/2/3 fusion (0.13%), PIK3CA mutation (11.4%), and tumor mutational burden-high (9.4%). CDH1 alterations and MET amplification were significantly more frequent in patients aged < 40 years (27.7 and 6.2%) than in those aged ≥ 40 years (14.7 and 4.0%)., Conclusions: Real-world datasets from clinical panel testing revealed the genomic landscape in gastric cancer by subgroup. These findings provide insights for the current therapeutic strategies and future development of treatments in gastric cancer., (© 2024. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Coronary microvascular dysfunction (CMD) can cause myocardial ischemia in patients presenting with angina without obstructive coronary artery disease (ANOCA). Evaluating for CMD by using the thermodilution technique offers a widely accessible means of assessing microvascular resistance. Through this technique, 2 validated indices, namely coronary flow reserve and the index of microcirculatory resistance, can be computed, facilitating investigation of the coronary microcirculation. The index of microcirculatory resistance specifically estimates minimum achievable microvascular resistance within the coronary microcirculation. We aim to review the bolus thermodilution method, outlining the fundamental steps for conducting measurements and introducing an algorithmic approach (CATH CMD) to systematically evaluate the coronary microcirculation. Embracing a standardized approach, exemplified by the CATH CMD algorithm, will facilitate adoption of this technique and streamline the diagnosis of CMD., (© 2024 The Author(s).)

Background: Long-term anti-EGFR antibody treatment increases the risk of severe dermatologic toxicities. This single-arm, phase II trial aimed to investigate the strategy of switching from cetuximab to bevacizumab in combination with FOLFIRI based on early tumor shrinkage (ETS) in patients with RAS wild-type metastatic colorectal cancer (mCRC)., Methods: Radiologic assessment was performed to evaluate ETS, defined as ≥20% reduction in the sum of the largest diameters of target lesions 8 weeks after the introduction of FOLFIRI plus cetuximab. ETS-negative patients switched to FOLFIRI plus bevacizumab, whereas ETS-positive patients continued FOLFIRI plus cetuximab for eight more weeks, with a switch to FOLFIRI plus bevacizumab thereafter. The primary endpoint was progression-free survival., Results: This trial was prematurely terminated due to poor accrual after a total enrollment of 30 patients. In 29 eligible patients, 7 were ETS-negative and 22 were ETS-positive. Two ETS-negative patients and 17 ETS-positive patients switched to FOLFIRI plus bevacizumab 8 weeks and 16 weeks after initial FOLFIRI plus cetuximab, respectively. Median progression-free and overall survival durations were 13.4 and 34.7 months, respectively. Six (20%) patients experienced grade ≥3 paronychia, which improved to grade ≤2 by 18 weeks. Grade ≥3 acneiform rash, dry skin, and pruritus were not observed in any patients., Conclusions: Our novel treatment strategy delivered acceptable survival outcomes and reduced severe dermatologic toxicities., (© 2024 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

Objective: To assess the accuracy of a virtual stenting tool based on coronary CT angiography (CCTA) and fractional flow reserve (FFR) derived from CCTA (FFR CT Planner) across different levels of image quality., Materials and Methods: Prospective, multicenter, single-arm study of patients with chronic coronary syndromes and lesions with FFR ≤ 0.80. All patients underwent CCTA performed with recent-generation scanners. CCTA image quality was adjudicated using the four-point Likert scale at a per-vessel level by an independent committee blinded to the FFR CT Planner. Patient- and technical-related factors that could affect the FFR CT Planner accuracy were evaluated. The FFR CT Planner was applied mirroring percutaneous coronary intervention (PCI) to determine the agreement with invasively measured post-PCI FFR., Results: Overall, 120 patients (123 vessels) were included. Invasive post-PCI FFR was 0.88 ± 0.06 and Planner FFR CT was 0.86 ± 0.06 (mean difference 0.02 FFR units, the lower limit of agreement (LLA) - 0.12, upper limit of agreement (ULA) 0.15). CCTA image quality was assessed as excellent (Likert score 4) in 48.3%, good (Likert score 3) in 45%, and sufficient (Likert score 2) in 6.7% of patients. The FFR CT Planner was accurate across different levels of image quality with a mean difference between FFR CT Planner and invasive post-PCI FFR of 0.02 ± 0.07 in Likert score 4, 0.02 ± 0.07 in Likert score 3 and 0.03 ± 0.08 in Likert score 2, p = 0.695. Nitrate dose ≥ 0.8mg was the only independent factor associated with the accuracy of the FFR CT Planner (95%CI - 0.06 to - 0.001, p = 0.040)., Conclusion: The FFR CT Planner was accurate in predicting post-PCI FFR independent of CCTA image quality., Clinical Relevance Statement: Being accurate in predicting post-PCI FFR across a wide spectrum of CT image quality, the FFR CT Planner could potentially enhance and guide the invasive treatment. Adequate vasodilation during CT acquisition is relevant to improve the accuracy of the FFR CT Planner., Key Points: • The fractional flow reserve derived from coronary CT angiography (FFR CT ) Planner is a novel tool able to accurately predict fractional flow reserve after percutaneous coronary intervention. • The accuracy of the FFR CT Planner was confirmed across a wide spectrum of CT image quality. Nitrates dose at CT acquisition was the only independent predictor of its accuracy. • The FFR CT Planner could potentially enhance and guide the invasive treatment., (© 2023. The Author(s), under exclusive licence to European Society of Radiology.)

Vascular calcification is a hallmark of atherosclerosis and adds considerable challenges for percutaneous coronary intervention (PCI). This review underscores the critical role of coronary computed tomography (CT) angiography in assessing and quantifying vascular calcification for optimal PCI planning. Severe calcification significantly impacts procedural outcomes, necessitating accurate preprocedural evaluation. We describe the potential of coronary CT for calcium assessment and how CT may enhance precision in device selection and procedural strategy. These advancements, along with the ongoing Precise Procedural and PCI Plan study, represent a transformative shift toward personalized PCI interventions, ultimately improving patient outcomes in the challenging landscape of calcified coronary lesions., (© 2024 The Author(s).)

Background and Aims: Coronary hemodynamics impact coronary plaque progression and destabilization. The aim of the present study was to establish the association between focal vs. diffuse intracoronary pressure gradients and wall shear stress (WSS) patterns with atherosclerotic plaque composition., Methods: Prospective, international, single-arm study of patients with chronic coronary syndromes and hemodynamic significant lesions (fractional flow reserve [FFR] ≤ 0.80). Motorized FFR pullback pressure gradient (PPG), optical coherence tomography (OCT), and time-average WSS (TAWSS) and topological shear variation index (TSVI) derived from three-dimensional angiography were obtained., Results: One hundred five vessels (median FFR 0.70 [Interquartile range (IQR) 0.56-0.77]) had combined PPG and WSS analyses. TSVI was correlated with PPG (r = 0.47, [95% Confidence Interval (95% CI) 0.30-0.65], p < 0.001). Vessels with a focal CAD (PPG above the median value of 0.67) had significantly higher TAWSS (14.8 [IQR 8.6-24.3] vs. 7.03 [4.8-11.7] Pa, p < 0.001) and TSVI (163.9 [117.6-249.2] vs. 76.8 [23.1-140.9] m -1 , p < 0.001). In the 51 vessels with baseline OCT, TSVI was associated with plaque rupture (OR 1.01 [1.00-1.02], p = 0.024), PPG with the extension of lipids (OR 7.78 [6.19-9.77], p = 0.003), with the presence of thin-cap fibroatheroma (OR 2.85 [1.11-7.83], p = 0.024) and plaque rupture (OR 4.94 [1.82 to 13.47], p = 0.002)., Conclusions: Focal and diffuse coronary artery disease, defined using coronary physiology, are associated with differential WSS profiles. Pullback pressure gradients and WSS profiles are associated with atherosclerotic plaque phenotypes. Focal disease (as identified by high PPG) and high TSVI are associated with high-risk plaque features., Clinical Trial Registration: https://clinicaltrials,gov/ct2/show/NCT03782688., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Background: Following percutaneous coronary intervention (PCI), optical coherence tomography provides prognosis information. The pullback pressure gradient is a novel index that discriminates focal from diffuse coronary artery disease based on fractional flow reserve pullbacks. We sought to investigate the association between coronary artery disease patterns, defined by coronary physiology, and optical coherence tomography after stent implantation in stable patients undergoing PCI., Methods and Results: This multicenter, prospective, single-arm study was conducted in 5 countries (NCT03782688). Subjects underwent motorized fractional flow reserve pullbacks evaluation followed by optical coherence tomography-guided PCI. Post-PCI optical coherence tomography minimum stent area, stent expansion, and the presence of suboptimal findings such as incomplete stent apposition, stent edge dissection, and irregular tissue protrusion were compared between patients with focal versus diffuse disease. Overall, 102 patients (105 vessels) were included. Fractional flow reserve before PCI was 0.65±0.14, pullback pressure gradient was 0.66±0.14, and post-PCI fractional flow reserve was 0.88±0.06. The mean minimum stent area was 5.69±1.99 mm 2 and was significantly larger in vessels with focal disease (6.18±2.12 mm 2 versus 5.19±1.72 mm 2 , P =0.01). After PCI, incomplete stent apposition, stent edge dissection, and irregular tissue protrusion were observed in 27.6%, 10.5%, and 51.4% of the cases, respectively. Vessels with focal disease at baseline had a lower prevalence of incomplete stent apposition (11.3% versus 44.2%, P =0.002) and more irregular tissue protrusion (69.8% versus 32.7%, P <0.001)., Conclusions: Baseline coronary pathophysiological patterns are associated with suboptimal imaging findings after PCI. Patients with focal disease had larger minimum stent area and a higher incidence of tissue protrusion, whereas stent malapposition was more frequent in patients with diffuse disease.

We describe humans with rare biallelic loss-of-function PTCRA variants impairing pre-α T cell receptor (pre-TCRα) expression. Low circulating naive αβ T cell counts at birth persisted over time, with normal memory αβ and high γδ T cell counts. Their TCRα repertoire was biased, which suggests that noncanonical thymic differentiation pathways can rescue αβ T cell development. Only a minority of these individuals were sick, with infection, lymphoproliferation, and/or autoimmunity. We also report that 1 in 4000 individuals from the Middle East and South Asia are homozygous for a common hypomorphic PTCRA variant. They had normal circulating naive αβ T cell counts but high γδ T cell counts. Although residual pre-TCRα expression drove the differentiation of more αβ T cells, autoimmune conditions were more frequent in these patients compared with the general population.

Objective: CHARGE syndrome is a congenital malformation syndrome caused by heterozygous mutations in the CHD7 gene. Severe combined immunodeficiency (SCID) arises from congenital athymia called CHARGE/complete DiGeorge syndrome. While cultured thymus tissue implantation (CTTI) provides an immunological cure, hematopoietic cell transplantation (HCT) is an alternative option for immuno-reconstitution of affected infants. We aimed to clarify the clinical outcomes of patients with athymic CHARGE syndrome after HCT., Methods: We studied the immunological reconstitution and outcomes of four patients who received non-conditioned unrelated donor cord blood transplantation (CBT) at Kyushu University Hospital from 2007 to 2022. The posttransplant outcomes were compared with the outcomes of eight reported patients., Results: Four index cases received CBT 70-144 days after birth and had no higher than grade II acute graft-versus-host disease. One infant was the first newborn-screened athymic case in Japan. They achieved more than 500/μL naïve T cells with balanced repertoire 1 month post transplant, and survived more than 12 months with home care. Twelve patients including the index cases received HCT at a median 106 days after birth (range: 70-195 days). One-year overall survival rate was significantly higher in patients who underwent non-conditioned HCT than in those who received conditioned HCT (100% vs. 37.5%, p = .02). Nine patients died, and the major cause of death was cardiopulmonary failure., Conclusions: Athymic infants achieved a prompt reconstitution of non-skewing naïve T cells after non-conditioned CBT that led to home care in infancy without significant infections. Non-conditioned CBT is a useful bridging therapy for newborn-screened cases toward an immunological cure by CTTI., (© 2023 Wiley Periodicals LLC.)

Diagnosing coronary microvascular dysfunction remains challenging, primarily due to the lack of direct measurements of absolute coronary blood flow (Q) and microvascular resistance (R μ ). However, there has been recent progress with the development and validation of continuous intracoronary thermodilution, which offers a simplified and validated approach for clinical use. This technique enables direct quantification of Q and R μ , leading to precise and accurate evaluation of the coronary microcirculation. To ensure consistent and reliable results, it is crucial to follow a standardized protocol when performing continuous intracoronary thermodilution measurements. This document aims to summarize the principles of thermodilution-derived absolute coronary flow measurements and propose a standardized method for conducting these assessments. The proposed standardization serves as a guide to ensure the best practice of the method, enhancing the clinical assessment of the coronary microcirculation., Competing Interests: Funding Support and Author Disclosures Drs Belmonte, Bertolone, and Viscusi are supported by a research grant from the CardioPaTh PhD Program. Dr Pijls has received institutional research grants from Abbott; has consulting relationships with and receives fees from Abbott and Coroventis; has equity in ASML, General Electric, HeartFlow, and Philips; is a member of the Scientific Advisory Board of Heartflow; and has patents pending in the field of the coronary microcirculation and aortic valve stenosis. Dr Mizukami has received consulting fees from Zeon Medical and HeartFlow; and has received speaker fees from Abbott Vascular. Dr Barbato has received speaker fees from Abbott Vascular, Boston Scientific, and GE. Dr Dannab has received grants from Philips, Abbott, and AstraZeneca; and has received consulting fees from Philips. Dr Keeble has received honoraria and institutional research funding from Abbott Vascular, Medtronic, Terumo, Zoll, and Shockwave; has received consulting fees from BD; has received speaker fees from Cardionovum, Abbott Vascular, and AstraZeneca; is on the steering group for the ORBITA-2 trial; and is on the committee for the National Institute for Health and Care Research Invention for Innovation (i4i), British Cardiovascular Intervention Society and Resuscitation Council. Dr Kern is a speaker for Abbott Vascular, Boston Scientific, Acist, Opsens, and Zoll. Dr Fearon has received institutional research support from Abbott, Boston Scientific, and Medtronic; has a consulting relationship with CathWorks and Siemens; and has stock options with HeartFlow. Dr Collet has received research grants from Biosensors, HeartFlow, and Abbott Vascular; and has received consultancy fees from HeartFlow, Abbott Vascular, Boston Scientific, Opsens, and Philips Volcano. Dr De Bruyne has consulting relationships with Boston Scientific, Abbott Vascular, CathWorks, Siemens, and Coroventis Research; has received research grants from Abbott Vascular, Coroventis Research, Cathworks, and Boston Scientific; and holds minor equities in Philips Volcano, Siemens, GE Healthcare, Edwards Lifesciences, HeartFlow, Opsens, Sanofi, and Celiad. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2024 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

The Eighth Asian National Control Laboratory (NCL) Network meeting, entitled "Biological Products Quality Control and Self-Sufficiency Strategy focusing on plasma-derived medicinal products (PDMPs)" was held in Seoul on 31 August 2023. The participants were NCL experts from Indonesia, Japan, Malaysia, the Philippines, Vietnam, and the Republic of Korea. Special lectures included the PDMPs self-sufficiency strategies of the World Health Organization (WHO) and Indonesian Food and Drug Authority, and a case study on Global Benchmarking Tool (GBT) assessment for vaccines by the Korea Ministry of Food and Drug Safety. The NCL delegates shared their current experiences with national lot releases and biological standardisation. The meeting contributed to a mutual understanding of the progress of the PDMPs self-sufficiency among Asian countries, the WHO's support strategies, and the NCL's plan for the preparation of the WHO GBT assessment. In the panel discussion, all participants agreed that building capacity in blood safety in the Asian region and harmonisation of relevant international regulatory requirements will support appropriate emergency preparedness, particularly source materials in the region, and will build the foundation for resolving the PDMPs supply insecurity that has worsened after the COVID-19 pandemic in some countries., (Copyright © 2024. Published by Elsevier Ltd.)