Objective: Systemic administration of glucocorticoid steroids is the most common initial treatment for idiopathic sudden sensorineural hearing loss (ISSNHL); however, due to the prevalence of coronavirus disease, the indications for this treatment must be carefully determined. The aim of this study was to investigate the efficacy of intratympanic steroid therapy as an initial treatment for idiopathic SSNHL. Methods: Sixty-eight patients with idiopathic ISSNHL who were treated with intravenous or intratympanic steroids were included in this study. Patients were retrospectively evaluated regarding preoperative grade, type of additional treatment, outcome of treatment, and side effects of each treatment. Results: In 46 cases, patients received intravenous steroid therapy as the initial treatment, while 22 patients received intratympanic steroid therapy; 10 patients underwent salvage treatment due to inadequate improvement of symptoms. Regarding additional treatment, intravenous steroid monotherapy was used in 37 patients. The outcomes were similar after both treatments; 16 (43%) and 11 (52%) patients treated exclusively with intravenous and intratympanic steroids, respectively, were completely cured. There were no significant differences in the effects between the 2 treatments, indicating that they were almost equally effective. The side effects observed in patients treated with intravenous steroid therapy were increased blood pressure, acute gastric mucosal disorder, and insomnia. None of these side effects were observed in any of the patients treated with intratympanic steroids; however, 1 case of perforation of the tympanic membrane occurred due to the procedure. Conclusion: There were no significant differences in posttreatment outcomes between patients treated with either intratympanic or intravenous steroids. The therapeutic effects were comparable, and no severe side effects were observed; therefore, intratympanic steroid therapy may be considered useful as an initial treatment for ISSNHL in the context of widespread coronavirus disease.

Pulmonary hypertension (PH) is a progressive cardiopulmonary disease characterized by pulmonary arterial remodeling. Clonal somatic mutations including JAK2V617F, the most frequent driver mutation among myeloproliferative neoplasms, have recently been identified in healthy individuals without hematological disorders. Here, we reveal that clonal hematopoiesis with JAK2V617F exacerbates PH and pulmonary arterial remodeling in mice. JAK2V617F-expressing neutrophils specifically accumulate in pulmonary arterial regions, accompanied by increases in neutrophil-derived elastase activity and chemokines in chronic hypoxia-exposed JAK2V617F transgenic (JAK2V617F) mice, as well as recipient mice transplanted with JAK2V617F bone marrow cells. JAK2V617F progressively upregulates Acvrl1 (encoding ALK1) during the differentiation from bone marrow stem/progenitor cells peripherally into mature neutrophils of pulmonary arterial regions. JAK2V617F-mediated STAT3 phosphorylation upregulates ALK1-Smad1/5/8 signaling. ALK1/2 inhibition completely prevents the development of PH in JAK2V617F mice. Finally, our prospective clinical study identified JAK2V617F-positive clonal hematopoiesis is more common in PH patients than in healthy subjects. These findings indicate that clonal hematopoiesis with JAK2V617F causally leads to PH development associated with ALK1 upregulation.

Background: Sleep-disordered breathing (SDB) and blood pressure variability (BPV) are strongly associated with cardiovascular diseases. Recently, pulse transit time (PTT) has enabled the monitoring of beat-to-beat BP; however, little is known about its clinical utility. The present study aimed to clarify the impact of SDB on very short-term BPV determined by PTT-based BP monitoring (PTT-BP). Methods: We analyzed 242 patients with suspected SDB. PTT-BP was continuously recorded overnight together with a portable sleep monitor. PTT index was defined as the average number of transient rises in PTT-BP (≥12 mmHg) within 30 s/h. We compared PTT-BP values with each SDB parameter, and examined the association between BPV and subclinical organ damage. Results: Standard deviation (SD) of systolic, mean or diastolic PTT-BP, which indicates very short-term BPV, was significantly correlated with apnea--hypopnea index (AHI) and oxygen desaturation index (ODI). PTT index was positively associated with AHI, ODI, and minimal SpO2. Regression analyses showed that AHI and ODI were significant variables to determine systolic, mean, or diastolic PTT-BP SD and PTT index. Logistic regression analyses demonstrated that diastolic PTT-BP SD significantly influenced the presence of chronic kidney disease and left ventricular hypertrophy. Conclusion: SDB severity was closely associated with very short-term BP variability, and diastolic PTT-BP SD might be an important factor linked to subclinical organ damage. PTT-BP measurement may be useful to evaluate very short-term BPV during the night.

JAK2V617F is the most frequent driver mutation in myeloproliferative neoplasms (MPNs) and is associated with vascular complications. However, the impact of hematopoietic JAK2V617F on the aortic aneurysms (AAs) remains unknown. Our cross-sectional study indicated that 9 (23%) out of 39 MPN patients with JAK2V617F exhibited the presence of AAs. Next, to clarify whether the hematopoietic JAK2V617F contributes to the AAs, we applied a bone marrow transplantation (BMT) with the donor cells from Jak2V617F transgenic (JAK2V617F) mice or control wild-type (WT) mice into lethally irradiated apolipoprotein E-deficient mice. Five weeks after BMT, the JAK2V617F-BMT mice and WT-BMT mice were subjected to continuous angiotensin II infusion to induce AA formation. Four weeks after angiotensin II infusion, the abdominal aorta diameter in JAK2V617F-BMT mice was significantly enlarged compared to that in the WT-BMT mice. Additionally, the abdominal AA-free survival rate was significantly lower in the JAK2V617F-BMT mice. Hematopoietic JAK2V617F accelerated aortic elastic lamina degradation as well as activation of matrix metalloproteinase (MMP)-2 and MMP-9 in the abdominal aorta. The numbers of infiltrated macrophages were significantly upregulated in the abdominal aorta of the JAK2V617F-BMT mice accompanied by STAT3 phosphorylation. The accumulation of BM-derived hematopoietic cells carrying JAK2V617F in the abdominal aorta was confirmed by use of reporter GFP-transgene. BM-derived macrophages carrying JAK2V617F showed increases in mRNA expression levels of Mmp2, Mmp9, and Mmp13. Ruxolitinib decreased the abdominal aorta diameter and the incidence of abdominal AA in the JAK2V617F-BMT mice. Our findings provide a novel feature of vascular complications of AAs in MPNs with JAK2V617F.

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