Objective: Anti-programmed cell death ligand 1 (PD-L1) and anti-programmed cell death 1 (PD-1) therapy in cancer treatment cause immune-related adverse events (irAEs), such as hypothyroidism. We investigated the potential of quantitative computed tomography (CT) for early diagnosis and severity assessment of overt hypothyroidism induced by PD-L1/PD-1 treatment.

Methods: Sixty-six patients were enrolled in this study. Patients were divided into two groups: those who developed immune checkpoint inhibitor (ICI) -related hypothyroidism (n=32) and those without thyroid-irAEs (n=34). Using non-contrast CT images, the mean attenuation value of a polygonal region-of-interest delineating the right and left lobes of the thyroid gland was obtained. Longitudinal changes in CT attenuation values of the thyroid gland before and after ICI administration were calculated. Using non-contrast and contrast CT images, the maximum width, length, and anterior-posterior diameter pre- and post-ICI administration were measured to approximate thyroid volume and assess atrophy. Thyrotropin (TSH) levels and levothyroxine doses were analyzed.

Results: The CT attenuation values were significantly decreased in the thyroid-irAE group during or before the TSH levels increase (p＜0.0001). CT attenuation values decreased 43 days before TSH levels increased. High TSH levels and levothyroxine doses were associated with atrophy (r=-0.69, p＜0.0001 and r=-0.52, p=0.01, respectively).

Conclusion: Thyroid CT attenuation values decrease before TSH levels increase in overt hypothyroidism induced by ICIs, which may facilitate early diagnosis of hypothyroidism. Maximum width, length, and anteroposterior diameter measurement can reliably detect thyroid atrophy, which is associated with hypothyroidism severity.

The immune checkpoint blockade is a promising strategy for cancer immunotherapy. Expression of programmed death protein ligand 1 (PD-L1) is often upregulated in tumors with high genomic instability. Cytoplasmic DNA results from genomic instability and stimulates the transcription of type I interferon (IFN) via the cyclic GMP-AMP synthase (cGAS) - stimulator of interferon genes (STING) pathway. Type I IFN stimulates the JAK-STAT pathway, leading to the transcription of IFN-stimulated genes and PD-L1. Hence, the cGAS-STING pathway is a potential therapeutic target. However, its precise regulatory mechanism remains elusive. Here, we showed that BI-D1870, an inhibitor of ribosomal S6 kinases (RSKs), attenuated PD-L1 transcription by inhibiting TBK1 activation in cGAS-STING signaling triggered by cytoplasmic DNA. BI-D1870 strongly downregulated PD-L1; therefore, it could be a potential therapeutic drug for impaired tumor immune escape.

Objective: We investigated the correlation between the distance walked in the first 4 steps, 6-m walking speed test and 6-m walking speed, and 5-times sit-to-stand test to establish an alternative method for evaluating walking speed, a criterion for diagnosing sarcopenia.

Methods: We included in this study 50 patients who underwent elective abdominal surgery between October 2023 and May 2024 at our department. The main analyses were measurements of distance traveled over the first 4 steps taken at the start of the test, 6-m walking speed, 5-times sit-to-stand test, and correlations of 4-step walking distance with 6-m walking speed and with 5-times sit-to-stand test.

Results: The mean (range) 6-m walking speed was 1.224 (0.636-2.073) m/sec, and the mean 4-step walking distance was 2.485 (1.88-3.68) m, which showed a significant positive correlation with a correlation coefficient of 0.72 (95% confidence interval [CI]: 0.5559-0.8332, p＜0.0001) . Based on the receiver operating characteristic curve derived from logistic regression analysis, the cut-off value for the 4-step walking distance was 2.24 m when the 6-m walking speed was＜1.0 m/sec. The mean value of the 5-times sit-to-stand test was 9.55 s. The 4-step walking distance and the 5-times sit-to-stand test time were significantly correlated (correlation coefficient: -0.32, 95% CI: -0.5484 — -0.0442, p=0.0241).

Conclusion: There was a correlation between the 6-m walking speed and the distance walked over the first 4 steps, suggesting that a 4-step walking distance of less than 2.24 m may indicate a decline in physical function.

Background: Previous studies have established low Left Ventricular Ejection Fraction (LVEF) as a significant predictor of poor prognosis across various cardiac conditions. However, the prognostic implications of low LVEF and its postoperative improvement in patients undergoing Transcatheter Aortic Valve Implantation (TAVI) remain unclear.

Methods and Results: We reviewed consecutive patients with severe aortic stenosis (AS) who underwent TAVI between January 2016 and October 2022. Patients were categorized into three groups based on LVEF: preserved LVEF (≥50%), mildly reduced LVEF (40-49%), and reduced LVEF (＜40%). The primary outcome was a composite of all-cause mortality and heart failure rehospitalization, with subgroup analysis on rapid LVEF improvement (≥10% increase at discharge). A total of 909 patients were included: 769 with preserved LVEF, 69 with mildly reduced LVEF, and 71 with reduced LVEF. Kaplan-Meier analysis showed that LVEF pattern significantly predicted composite outcomes (log-rank p＜0.001), with reduced LVEF indicating the poorest prognosis. Rapid LVEF improvement was observed in 39.7% of patients with reduced LVEF. Logistic regression identified low pressure gradient as independently associated with the absence of significant LVEF improvement post-TAVI.

Conclusion: Reduced LVEF is a predictor of poor prognosis in TAVI patients. Although LVEF can improve postoperatively, this improvement does not necessarily lead to better outcomes. Careful patient selection and consideration of myocardial fibrosis are essential in managing these patients.

Background: In patients with chronic heart failure and coronary artery disease (CAD) with residual myocardial viability, percutaneous coronary intervention (PCI) makes no difference in mortality and heart failure (HF) hospitalization compared with medical therapy. However, studies specifically focusing on the prognosis following PCI in patients hospitalized HF with concomitant CAD are limited.

Method and Results: A retrospective study of patients admitted for acute HF from April 1, 2017 to March 31, 2021 was conducted. Of a total of 649 patients who presented with acute decompensated HF, 92 had CAD with significant stenosis. A total of 60 patients were enrolled in the study, and the outcomes of the PCI group (n=28) and the medical therapy group (n=32) were compared. The primary endpoint was a composite of all-cause mortality, rehospitalization for HF, and acute coronary syndrome at one year. Clinical outcomes in the PCI and medical therapy groups were comparable, with no significant difference in the primary composite endpoint (log-rank test p=0.94). Chronic kidney disease (CKD) on admission was an independent predictor of clinical outcomes at one year (HR: 3.20, 95% CI: 1.12-9.16, p=0.03).

Conclusion: PCI did not improve clinical outcomes over medical therapy in patients hospitalized for HF with concomitant CAD. This study showed that, especially in patients with CKD, the cardiac team needs to address the precise clinical implications and prognostic benefits of the procedure in individual patients.

Certain breast cancer treatments are ineffective and develop drug resistance in some cases. In various cancers, the c-Myc protein plays a critical role in cell proliferation regulation and cell cycle control, promoting carcinogenesis and treatment resistance. High c-Myc protein expression is in 30—50% of high-grade breast tumors. This study focused on examining the relationship between c-Myc protein expression and c-myc gene amplification in triple-negative breast cancer (TNBC) compared with other invasive ductal carcinomas. We performed c-Myc immunohistochemistry and c-myc fluorescence in situ hybridization on 108 invasive ductal carcinoma cases, which had not received preoperative treatment and were resected between January 2019 and December 2021. The proportion of TNBC increased in the group with high c-Myc expression within invasive ductal carcinoma. Fluorescence in situ hybridization divided cases with high c-Myc protein expression into those with and without c-myc gene amplification, suggesting that c-Myc protein expression in breast cancer is induced by c-myc gene amplification. Additionally, cases of high c-Myc protein expression might result from tumor cell polyploidization and epigenomic factors. Given that c-Myc protein is associated with breast cancer malignancy and treatment resistance, determining gene amplification presence or absence can be crucial in developing breast cancer prognostic and treatment strategies.

Objective: Surgical treatment is invasive, and complications may be more likely in individual patients based on their physical reserve, nutritional status, and underlying disease. We developed a surgical risk score (SRS) to calculate the limits of surgical invasiveness during gastrointestinal procedures and created a versatile preoperative predictor of these limits based on patient characteristics.

Methods: We conducted a retrospective study of 1537 subjects who underwent gastrointestinal surgery at our hospital during the three-year period from January 2020 to December 2022. Subjects were classified into the complication group and the complication-free group based on the presence of postoperative complications classified as Clavien-Dindo grade III or greater. Risk prediction formulas were also calculated using risk factors determined by multivariate logistic analysis.

Results: The significant factors independently related to onset of complications were sex (odds ratio [OR]: 1.922; 95% confidence interval [CI]: 1.251-2.953; p=0.0021), gait status (OR: 2.11; 95% CI: 1.165-3.822; p=0.0163), serum albumin level (OR: 1.707; 95% CI: 1.223-2.369; p=0.0019), and extent of surgical invasion (OR: 4.679; 95% CI: 3.077-7.115; p＜0.0001). The predictive equation derived by including duration of surgery with these surgical risk factors was SRS=-1.808+0.731×(0.807+0.656×sex-0.664×gait status-0.565×serum albumin-1.568×invasiveness)+0.004×duration of surgery. The cutoff value from the ROC curve for the surgical risk of the onset of complications of Clavien-Dindo III or greater was -2.1238.

Conclusion: Retrograde extrapolation using the surgical risk prediction cutoff value allows us to estimate the time limits placed on surgery to avoid postoperative complications in individual cases. We consider this prediction formula, which allows preoperative calculation of an acceptable duration of surgery for individual cases using factors that can be easily evaluated, to be a useful score for reducing the rate of perioperative complications.

Background: An atrial septal defect (ASD) is a common congenital heart disease in adults. Signs or symptoms such as shortness of breath, especially when exercising, leg fatigue, heart palpitations, stroke, or heart murmur can be detected. However, some patients with ASD present with uncommon symptoms such as dyspnoea with upright position.

Case Summary: We report the case of a patient with ASD who complained of dyspnoea with upright position. Dyspnoea and desaturation were observed immediately after sitting upright. The patient was diagnosed as having platypnoea—orthodeoxia syndrome. We performed transcatheter ASD closure with no compliments, and the desaturation in the upright position was resolved.

Discussion: Patients with ASD present with different symptoms including dyspnoea with upright position. Therefore, dyspnoea in the upright position should not be overlooked in such patients.