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Introduction: Drug-induced liver injury (DILI) associated with 5-aminosalicylic acid (5-ASA) is a rare but potentially life-threatening adverse event. Case Presentation: We report the case of a 58-year-old woman with ulcerative colitis who developed DILI after initiating maintenance therapy with the multimatrix system 5-ASA. The patient presented with grade 4 liver enzyme elevation on day 98 after initiating 5-ASA and was admitted to the hospital. Blood tests revealed the mixed liver injury, and imaging studies showed no abnormalities except for mild lymph node enlargement. Liver biopsy revealed acute lobular hepatitis with interfacial activity. The patient’s score on the International Autoimmune Hepatitis Group 1999 revised scoring system was a total score of 10, causing a suspicion for the diagnosis of autoimmune hepatitis. The DDW-J 2004 scale calculated a total score of six, indicating a high probability of DILI. We suspected DILI due to 5-ASA, and the 5-ASA formulations were discontinued. The patient was treated with ursodeoxycholic acid and neominophagen C, and her liver function gradually improved without steroid treatment. Finally, we definitively diagnosed DILI based on the pathological findings and clinical course after discontinuation of 5-ASA. Conclusion: This case highlights the importance of monitoring liver function in patients receiving 5-ASA therapy.

Abstract Background Recent developments in the field of companion diagnosis and molecular-targeting therapeutic agents have helped in developing treatments targeting human epidermal growth factor receptor 2 (HER2) in gastric cancer (GC) and esophagogastric junction cancer (EGJC), and the importance of accurate diagnosis of HER2 expression is increasing. However, the HER2-positivity rate significantly differs among reports in GC and EGJC, and factors that affect HER2-positivity require elucidation. Methods The present study retrospectively examined factors related to HER2-positivity in a single institution, including age, sex, body mass index, the American Society of Anesthesiologists physical status, tumor information, and surgery information, including time to specimen processing. Results Our study included 165 patients tested for HER2 using GC and EGJC surgery specimens among the 1,320 patients who underwent gastrectomy from January 2007 to June 2022. In total, 35 (21.2%) and 130 (78.8%) patients were HER2-positive and -negative, respectively. Multivariate analysis revealed that intestinal type (odds ratio [OR]: 3.41, 95% confidence interval [CI]: 1.44–8.09, p = 0.005), pM1 (OR: 3.99, 95% CI: 1.51–10.55, p = 0.005), and time to specimen processing of

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.

Abstract Pulmonary arterial hypertension (PAH), an intractable disease with a poor prognosis, is commonly treated using pulmonary vasodilators modulating the endothelin, cGMP, and prostacyclin pathway. Since the 2010s, drugs for treating pulmonary hypertension based on mechanisms other than pulmonary vasodilation have been actively developed. However, precision medicine is based on tailoring disease treatment to particular phenotypes by molecular‐targeted drugs. Since interleukin‐6 (IL‐6) is involved in the development of PAH in animal models, and some patients with PAH have elevated IL‐6 levels, the cytokine is expected to obtain potentials for therapeutic targeting. Accordingly, we identified a phenotype with elevated cytokine activity of the IL‐6 family in the PAH population by combining case data extracted from the Japan Pulmonary Hypertension Registry with a comprehensive analysis of 48 cytokines using artificial intelligence clustering techniques. Including an IL‐6 threshold ≥2.73 pg/mL as inclusion criteria for reducing the risk of insufficient efficacy, an investigator‐initiated clinical study using satralizumab, a recycling anti‐IL6 receptor monoclonal antibody, for patients with an immune‐responsive phenotype is underway. This study is intended to test whether use of patient biomarker profile can identify a phenotype responsive to anti‐IL6 therapy.

Histiocytic sarcoma (HS) is an extremely rare non-Langerhans histiocyte disorder of unknown origin. Recently, biomarkers for the confirmation of HS diagnosis have been reported. This report describes a case of primary HS of the central nervous system with description of the pathological anatomy. The patient was older than those in other such cases reported in the literature and presented with unspecific symptoms. This case highlights the difficulty in diagnosis and importance of suspicion of HS.

Abstract Inhaled iloprost is an established treatment for pulmonary arterial hypertension (PAH). However, the long‐term hemodynamic changes that inhaled iloprost induces are unclear. Here, we retrospectively enrolled 18 patients with PAH who received inhaled iloprost as add‐on to oral combination therapy from December 2016 to January 2021 at our institute in Japan. We then examined the changes in hemodynamic parameters induced by iloprost in these patients during right heart catheterization (RHC). To examine the long‐term effects of iloprost, we repeated the RHC examination at follow‐up (median time to follow‐up, 8.5 months). During both catheterization procedures, iloprost was administered by using an I‐neb AAD system (Philips NV). In a comparison of pre‐inhalation values at the first and follow‐up RHCs, inhaled iloprost significantly improved mean pulmonary artery pressure (mPAP; 39.9 ± 7.8 to 32.5 ± 7.2 mmHg, p = 0.016) and pulmonary vascular resistance (PVR; 588.5 ± 191.7 to 464.4 ± 188.5 dyn s cm−5, p = 0.047). During the follow‐up RHC, in a comparison of the pre‐inhalation and best recorded values out to 30 min after the end of iloprost inhalation, iloprost significantly decreased mPAP (32.5 ± 7.2 to 30.0 ± 6.6 mmHg, p = 0.007) and PVR (457.8 ± 181.4 to 386.2 ± 142.8 dyn s cm−5, p = 0.025) and significantly increased cardiac output (4.19 ± 0.91 to 4.64 ± 1.01 L/min, p = 0.035). Iloprost may have not only acute vasodilation effects but also long‐term hemodynamic benefits in PAH patients receiving combination therapy.

Abstract Pulmonary tumor thrombotic microangiopathy (PTTM) is a fatal disease associated with malignant tumors that progresses to pulmonary hypertension. Gastric cancer is the most common cause, followed by breast cancer and lung cancer, whereas PTTM due to thyroid cancer has not been reported. In addition to pulmonary obstruction by tumor embolism, tumor cells stimulate endothelial cells to release angiogenetic factors, which induce remodeling of pulmonary arteries and veins and lead to lymphatic obstruction. There is limited information on the relationship between thrombus and PTTM. We herein report an autopsy case with PTTM which was caused by diffuse sclerosing variant of thyroid papillary adenocarcinoma, in which differential diagnosis included the acute phase of chronic thromboembolic pulmonary hypertension.

The usefulness of the parameters of biventricular function simultaneously measured using enhanced multi-detector computed tomography (MDCT) pulmonary angiography in patients with chronic thromboembolic pulmonary hypertension (CTEPH) has not been clarified. This study aimed to verify the correlation between left and right ventricular (RV) parameters and pulmonary vascular resistance (PVR). Patients who underwent enhanced MDCT before diagnostic right heart catheterization at Nagoya University Hospital between October 2014 and April 2021 were enrolled. The correlation of biventricular function and volume parameters with PVR was assessed. Eighty patients were retrospectively analyzed. Patients’ mean age was 65 ± 13 years, mean PVR was 9.1 (range, 6.1–11.3) Wood units, and mean end-systolic eccentricity index (esEI) was 1.76 ± 0.50. RV end-systolic volume (ESV) (p = 0.007), RV cardiac output (CO) (p < 0.001), RV ejection fraction (p < 0.001), LV end-diastolic volume (EDV) (p < 0.001), left ventricular (LV) ESV (p = 0.006), LVCO (p < 0.001), end-diastolic EI (p < 0.001), and esEI (p < 0.001) were significantly correlated with PVR. The LVEDV (p = 0.001) and esEI (p < 0.009) were independent predictors of PVR. Systolic pulmonary arterial pressure (PAP) (p < 0.001), diastolic PAP (p < 0.001), mean PAP (p < 0.001), right atrial pressure (p < 0.023), and PVR (p < 0.001) were significantly higher in the high esEI group than in the low esEI group. The esEI was a simple predictor of CTEPH severity.

Endothelial dysfunction is important in the pathology of pulmonary hypertension, and circulating endothelial progenitor cells (EPCs) have been studied to evaluate endothelial dysfunction. In patients with chronic thromboembolic pulmonary hypertension (CTEPH), riociguat reportedly increases the number of circulating EPCs. However, the relationship between EPC numbers at baseline and changes in clinical parameters after riociguat administration has not been fully elucidated. Here, we evaluated 27 treatmentnaïve patients with CTEPH and analyzed the relationships between EPC number at diagnosis and clinical variables (age, hemodynamics, atrial blood gas parameters, brain natriuretic peptide, and exercise tolerance) before and after riociguat initiation. EPCs were defined as CD45dim CD34+ CD133+ cells and measured by flow cytometry. A low number of circulating EPCs at diagnosis was significantly correlated with increased reductions in mean pulmonary arterial pressure (mPAP) (correlation coefficient = 0.535, P = 0.004) and right atrial pressure (correlation coefficient = 0.618, P = 0.001) upon riociguat treatment. We then divided the study population into two groups according to the mPAP change: a weak-response group (a decrease in mPAP of 4 mmHg or less) and a strong-response group (a decrease in mPAP of more than 4 mmHg). The number of EPCs at diagnosis was significantly lower in the strong-response group than in the weak-response group (P = 0.022), but there were no significant differences in other clinical variables or in medication profiles. In conclusion, circulating EPC numbers could be a potential predictor of the therapeutic effect of riociguat in CTEPH patients. [ABSTRACT FROM AUTHOR]

Inhaled iloprost is an established treatment for pulmonary arterial hypertension (PAH). However, the long‐term hemodynamic changes that inhaled iloprost induces are unclear. Here, we retrospectively enrolled 18 patients with PAH who received inhaled iloprost as add‐on to oral combination therapy from December 2016 to January 2021 at our institute in Japan. We then examined the changes in hemodynamic parameters induced by iloprost in these patients during right heart catheterization (RHC). To examine the long‐term effects of iloprost, we repeated the RHC examination at follow‐up (median time to follow‐up, 8.5 months). During both catheterization procedures, iloprost was administered by using an Ineb AAD system (Philips NV). In a comparison of pre‐inhalation values at the first and follow‐up RHCs, inhaled iloprost significantly improved mean pulmonary artery pressure (mPAP; 39.9 ± 7.8 to 32.5 ± 7.2 mmHg, p = 0.016) and pulmonary vascular resistance (PVR; 588.5 ± 191.7 to 464.4 ± 188.5 dyn s cm−5, p = 0.047). During the follow‐up RHC, in a comparison of the pre‐inhalation and best recorded values out to 30 min after the end of iloprost inhalation, iloprost significantly decreased mPAP (32.5 ± 7.2 to 30.0 ± 6.6 mmHg, p = 0.007) and PVR (457.8 ± 181.4 to 386.2 ± 142.8 dyn s cm−5, p = 0.025) and significantly increased cardiac output (4.19 ± 0.91 to 4.64 ± 1.01 L/min, p = 0.035). Iloprost may have not only acute vasodilation effects but also long‐term hemodynamic benefits in PAH patients receiving combination therapy. [ABSTRACT FROM AUTHOR]