Comparison of the diagnostic value of 3 T MRI after intratympanic injection of GBCA, electrocochleography, and the glycerol test in patients with Meniere's disease

Conclusion. 3 T MRI after intratympanic injection of gadolinium-based contrast agent (GBCA) is more useful for the diagnosis of endolymphatic hydrops compared with the glycerol test and electrocochleography (ECoG). Objective: To investigate the relationship between 3 T MRI after intratympanic injection of GBCA, the glycerol test, and ECoG in patients with Meniere's disease (MD). Methods: A total of 20 patients with MD were evaluated. Diluted gadodiamide (a gadolinium-based contrast agent) was administered to the bilateral tympanic cavity by injection through the tympanic membrane. After 24 h, the endolymphatic hydrops was evaluated by a 3.0 T MR scanner. To investigate cochlear hydrops, the glycerol test and ECoG were carried out in all patients. Results: A positive result was observed in 11 patients (55%) in the glycerol test and in 12 patients (60%) by ECoG. The incidence of positive findings when evaluating the same patients with both the glycerol test and ECoG increased to 75%. Nineteen of 20 (95%) patients showed positive results for 3 T MRI.ArticleACTA OTO-LARYNGOLOGICA. 132(2):141-145 (2012)journal articl

Pharmacological HIF-1 activation upregulates extracellular vesicle production synergistically with adiponectin through transcriptional induction and protein stabilization of T-cadherin

Fujii K., Fujishima Y., Kita S., et al. Pharmacological HIF-1 activation upregulates extracellular vesicle production synergistically with adiponectin through transcriptional induction and protein stabilization of T-cadherin. Scientific Reports 14, 3620 (2024); https://doi.org/10.1038/s41598-024-51935-6.Pharmacological activation of hypoxia-inducible factor 1 (HIF-1), a hypoxia-responsive transcription factor, has attracted increasing attention due to its efficacy not only in renal anemia but also in various disease models. Our study demonstrated that a HIF-1 activator enhanced extracellular vesicle (EV) production from cultured endothelial cells synergistically with adiponectin, an adipocyte-derived factor, through both transcriptional induction and posttranscriptional stabilization of an adiponectin binding partner, T-cadherin. Increased EV levels were observed in wild-type mice but not in T-cadherin null mice after consecutive administration of roxadustat. Adiponectin- and T-cadherin-dependent increased EV production may be involved in the pleiotropic effects of HIF-1 activators

Is the Importance of Achieving Stable Disease Different between Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitors and Cytotoxic Agents in the Second-Line Setting for Advanced Non-small Cell Lung Cancer?

BackgroundIt is controversial whether achieving stable disease leads to a survival benefit and whether the importance of achieving stable disease differs between cytotoxic agents and molecular targeted agents. To examine these questions, the authors retrospectively reviewed phase II and III studies in the second-line setting for advanced non-small cell lung cancer using epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) and cytotoxic agents separately.MethodsThe authors chose 45 trials for the chemotherapy group and nine for the EGFR TKI group by searching the PubMed database. All nine trials in the EGFR TKI group concern gefitinib and erlotinib.ResultsThe median survival time increased 0.0375 month with each 1% increase in stable disease rate (p = 0.039), and each 1% increase in response rate resulted in 0.0744 (p < 0.001) month of median survival time in the analysis combined with both cytotoxic agents and EGFR TKIs. Main and interaction terms for EGFR TKI treatment were not statistically significant. With respect to time to progression, only response rate showed a statistically significant relationship with survival.ConclusionsTo obtain response seems to be more important than to achieve stable disease for both cytotoxic agents and EGFR TKIs, although achieving stable disease is still valuable. The relationship between survival and response or stable disease appears similar for cytotoxic agents and EGFR TKIs

Soluble T-cadherin secretion from endothelial cells is regulated via insulin/PI3K/Akt signalling

Okita T., Kita S., Fukuda S., et al. Soluble T-cadherin secretion from endothelial cells is regulated via insulin/PI3K/Akt signalling. Biochemical and Biophysical Research Communications 732, 150403 (2024); https://doi.org/10.1016/j.bbrc.2024.150403.Aim and objective: Our recent report showed that soluble T-cadherin promotes pancreatic beta-cell proliferation. However, how and where the secretion of soluble T-cadherin is regulated remain unclear. Methods and results: Soluble T-cadherin levels significantly increased in leptin receptor-deficient db/db mice with hypoinsulinaemia or in wild-type mice treated with insulin receptor blockade by S961. Similar results were observed in human subjects; Diabetic ketoacidosis patients at the time of hospitalization had increased plasma soluble T-cadherin levels, which decreased after insulin infusion therapy. Patients with recurrent ovarian cancer who were administered a phosphatidylinositol-3 kinase (PI3K)-alpha inhibitor (a new anticancer drug) had increased plasma soluble T-cadherin and plasma C-peptide levels. Endothelial cell-specific T-cadherin knockout mice, but not skeletal muscle- or cardiac muscle-specific T-cadherin knockout mice, showed a 26 % reduction in plasma soluble T-cadherin levels and a significant increase in blood glucose levels in streptozocin-induced diabetes. The secretion of soluble T-cadherin from human endothelial cells was approximately 20 % decreased by insulin and this decrease was canceled by blockade of insulin receptor/Akt signalling, not Erk signalling. Conclusion: We conclude that insulin regulates soluble T-cadherin levels and soluble T-cadherin secretion from endothelial cells is positively regulated by insulin/insulin receptor/Akt signalling

Large Right Pulmonary Vein Is a Predictor of Atrial Fibrillation Recurrence after Pulmonary Vein Isolation in Patients with Persistent Atrial Fibrillation

Pulmonary vein isolation（PVI）is an effective treatment for atrial fibrillation（AF）. However, outcomes differ between paroxysmal AF and persistent AF. We analyzed the predictors of recurrence by examining the recurrence group after ablation. Of 372 consecutive patients with AF who underwent PVI between June 2016 and December 2018, we evaluated 250 patients（age, 67±12y, 65％ men）whose left atrium（LA）was constructed using the PENTARAY catheter（BioSense Webster, Los Angeles, CA）, a multipolar electrode catheter with a novel shape and excellent mapping capability. We measured the LA total volume（LATV）, right pulmonary vein＋antrum volume（RPAV）, left PV＋antrum volume（LPAV）, LA central volume（LACV）, and LA bipolar voltage. Of the 250 patients, 78 had persistent AF（recurrence, 20）and 172 had paroxysmal AF（recurrence, 16）. In all patients, LATV, LACV, RPAV, and LPAV were significantly larger in patients with persistent AF than those with paroxysmal AF. The mean LA bipolar voltage in patients with persistent AF was significantly lower than those with paroxysmal AF. In cases of persistent AF, RPAV was significantly larger in the recurrence group than that in the non-recurrence group（15.9±4.8 vs 13.4±5.4ml; P＜0.05）. In cases of paroxysmal AF, there were no differences in any volume between the recurrence and non-recurrence groups. In conclusion, larger right PV is a predictor of AF recurrence after PVI in patients with persistent AF. The right PV is close to the atrial septum and the septopulmonary bundle, and the expansion of RPAV reflects the disruption of these structures, which may be involved in this result

Alterations in ALK/ROS1/NTRK/MET drive a group of infantile hemispheric gliomas

© The Author(s) 2019. Open Access. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.Infant gliomas have paradoxical clinical behavior compared to those in children and adults: low-grade tumors have a higher mortality rate, while high-grade tumors have a better outcome. However, we have little understanding of their biology and therefore cannot explain this behavior nor what constitutes optimal clinical management. Here we report a comprehensive genetic analysis of an international cohort of clinically annotated infant gliomas, revealing 3 clinical subgroups. Group 1 tumors arise in the cerebral hemispheres and harbor alterations in the receptor tyrosine kinases ALK, ROS1, NTRK and MET. These are typically single-events and confer an intermediate outcome. Groups 2 and 3 gliomas harbor RAS/MAPK pathway mutations and arise in the hemispheres and midline, respectively. Group 2 tumors have excellent long-term survival, while group 3 tumors progress rapidly and do not respond well to chemoradiation. We conclude that infant gliomas comprise 3 subgroups, justifying the need for specialized therapeutic strategies.info:eu-repo/semantics/publishedVersio

Why Are Outcomes Different for Registry Patients Enrolled Prospectively and Retrospectively? Insights from the Global Anticoagulant Registry in the FIELD-Atrial Fibrillation (GARFIELD-AF).

Background: Retrospective and prospective observational studies are designed to reflect real-world evidence on clinical practice, but can yield conflicting results. The GARFIELD-AF Registry includes both methods of enrolment and allows analysis of differences in patient characteristics and outcomes that may result. Methods and Results: Patients with atrial fibrillation (AF) and ≥1 risk factor for stroke at diagnosis of AF were recruited either retrospectively (n = 5069) or prospectively (n = 5501) from 19 countries and then followed prospectively. The retrospectively enrolled cohort comprised patients with established AF (for a least 6, and up to 24 months before enrolment), who were identified retrospectively (and baseline and partial follow-up data were collected from the emedical records) and then followed prospectively between 0-18 months (such that the total time of follow-up was 24 months; data collection Dec-2009 and Oct-2010). In the prospectively enrolled cohort, patients with newly diagnosed AF (≤6 weeks after diagnosis) were recruited between Mar-2010 and Oct-2011 and were followed for 24 months after enrolment. Differences between the cohorts were observed in clinical characteristics, including type of AF, stroke prevention strategies, and event rates. More patients in the retrospectively identified cohort received vitamin K antagonists (62.1% vs. 53.2%) and fewer received non-vitamin K oral anticoagulants (1.8% vs . 4.2%). All-cause mortality rates per 100 person-years during the prospective follow-up (starting the first study visit up to 1 year) were significantly lower in the retrospective than prospectively identified cohort (3.04 [95% CI 2.51 to 3.67] vs . 4.05 [95% CI 3.53 to 4.63]; p = 0.016). Conclusions: Interpretations of data from registries that aim to evaluate the characteristics and outcomes of patients with AF must take account of differences in registry design and the impact of recall bias and survivorship bias that is incurred with retrospective enrolment. Clinical Trial Registration: - URL: http://www.clinicaltrials.gov . Unique identifier for GARFIELD-AF (NCT01090362)

Risk profiles and one-year outcomes of patients with newly diagnosed atrial fibrillation in India: Insights from the GARFIELD-AF Registry.

BACKGROUND: The Global Anticoagulant Registry in the FIELD-Atrial Fibrillation (GARFIELD-AF) is an ongoing prospective noninterventional registry, which is providing important information on the baseline characteristics, treatment patterns, and 1-year outcomes in patients with newly diagnosed non-valvular atrial fibrillation (NVAF). This report describes data from Indian patients recruited in this registry. METHODS AND RESULTS: A total of 52,014 patients with newly diagnosed AF were enrolled globally; of these, 1388 patients were recruited from 26 sites within India (2012-2016). In India, the mean age was 65.8 years at diagnosis of NVAF. Hypertension was the most prevalent risk factor for AF, present in 68.5% of patients from India and in 76.3% of patients globally (P < 0.001). Diabetes and coronary artery disease (CAD) were prevalent in 36.2% and 28.1% of patients as compared with global prevalence of 22.2% and 21.6%, respectively (P < 0.001 for both). Antiplatelet therapy was the most common antithrombotic treatment in India. With increasing stroke risk, however, patients were more likely to receive oral anticoagulant therapy [mainly vitamin K antagonist (VKA)], but average international normalized ratio (INR) was lower among Indian patients [median INR value 1.6 (interquartile range {IQR}: 1.3-2.3) versus 2.3 (IQR 1.8-2.8) (P < 0.001)]. Compared with other countries, patients from India had markedly higher rates of all-cause mortality [7.68 per 100 person-years (95% confidence interval 6.32-9.35) vs 4.34 (4.16-4.53), P < 0.0001], while rates of stroke/systemic embolism and major bleeding were lower after 1 year of follow-up. CONCLUSION: Compared to previously published registries from India, the GARFIELD-AF registry describes clinical profiles and outcomes in Indian patients with AF of a different etiology. The registry data show that compared to the rest of the world, Indian AF patients are younger in age and have more diabetes and CAD. Patients with a higher stroke risk are more likely to receive anticoagulation therapy with VKA but are underdosed compared with the global average in the GARFIELD-AF. CLINICAL TRIAL REGISTRATION-URL: http://www.clinicaltrials.gov. Unique identifier: NCT01090362

Bilateral delayed endolymphatic hydrops evaluated by bilateral intratympanic injection of gadodiamide with 3T-MRI.

The purpose of this study was to assess the diagnostic performance of 3T MRI after intratympanic injection of gadodiamide for delayed endolymphatic hydrops (DEH), and assess the relationship between endolymphatic hydrops (ELH) and vestibular function in patients diagnosed with DEH and confirmed by 3T MRI. Nineteen patients clinically diagnosed with DEH (11 ipsilateral DEH, 8 contralateral DEH) participated in this study. Diluted gadodiamide was administered to the bilateral tympanic cavity by injection through the tympanic membrane. At 24 hours post-injection, the ELH was evaluated by MRI. Patient vestibular functions were evaluated by caloric testing and cVEMP. ELH was observed in all patients (19/19: positive rate 100%). The distribution patterns of ELH varied between the cochlear or vestibular region. Vestibular ELH was observed in the affected ear in all ipsilateral DEH patients. In the contralateral DEH patients, however, there were individual differences in the distribution patterns of ELH. Six patients (1 ipsilateral DEH, 5 contralateral DEH) had bilateral ELH. No obvious relationships were observed between ELH and vestibular function. ELH distribution was complicated, particularly in the contralateral DEH cases. It was difficult to identify the existence of ELH by vestibular functional testing alone; therefore, 3T MRI is thought to be useful for identifying the affected ear. A significant number of cases had "bilateral" DEH, particularly among the contralateral DEH cases, indicating that we should pay careful attention to this pathology when treating DEH