Clinical Characteristics and Predictors of Mortality in Patients with Combined Pulmonary Fibrosis and Emphysema Syndrome and Lung Cancer

Rationale: We performed this retrospective study to clarify the clinical characteristics, survival and mortality predictors in patients with combined pulmonary fibrosis and emphysema (CPFE) and lung cancer. Methods: We retrospectively reviewed the medical records of a total of 123 patients with lung cancer, as confirmed according to histological or cytological examinations. Based on the findings of chest CT, the patients were categorized into four groups: LC+normal (n=70); LC+emphysema (n=26); LC+fibrosis (n=10); LC+CPFE (n=17). The clinical characteristics and survival of the LC+CPFE group were compared with those of the other groups. In addition, mortality predictors were evaluated in the LC+CPFE group. Results: The proportion of females was significantly higher in the LC+normal group than in the LC+CPFE and LC+emphysema groups. Significantly more patients were diagnosed with squamous cell carcinoma in the LC+CPFE group than in the LC+normal group. The proportion of patients whose primary mass was located in “nonsubpleural” areas was significantly higher in patients with CPFE who also had lung cancer in the upper lobe than in those with CPFE who also had lung cancer in the other sites. There were significant differences in survival between the LC+normal group and the other groups, whereas there were no significant differences in survival among the LC+emphysema, LC+fibrosis and LC+CPFE groups. In the LC+CPFE group, the patients with a high level of serum KL-6 at diagnosis and upper lobe lung cancer demonstrated a high risk of death. A high level of serum KL-6 at diagnosis was also independently associated with a high risk of death. Conclusions: Patients with CPFE and lung cancer may have distinct clinical characteristics. Strict follow-up is required in patients with CPFE and lung cancer whose serum KL-6 level at diagnosis is higher than the normal range and/or the primary mass of lung cancer is located in the upper lobe.ArticleJournal of Pulmonary and Respiratory Medicine.5(3):263(2015)journal articl

Acute Exacerbation of Pulmonary Fibrosis in Syndrome of Combined Pulmonary Fibrosis and Emphysema Following Lung Surgery : A Report of Two Cases

We herein report two cases of an acute exacerbation of pulmonary fibrosis in the syndrome of combined pulmonary fibrosis and emphysema (CPFE) following lung surgery, and also review the relevant literature. One is a 76-year-old man, who had been diagnosed with CPFE and lung cancer and undergone lobectomy. He was admitted to our hospital because of aggravation of dyspnea 50 days after lung surgery. The other is a 69-yearold man who had been diagnosed with pulmonary bulla, pulmonary emphysema and idiopathic interstitial pneumonia at 53 years old and was complicated by lung cancer. He underwent right lower lobectomy and presented with slight fever and desaturation 18 days after lung surgery. In both cases, chest computed tomography showed diffuse bilateral ground-glass opacities superimposed on preceding reticular opacities in the lower lung field. They were diagnosed as acute exacerbation of pulmonary fibrosis in CPFE.A strict followup is required, because the prevalence of lung cancer may be higher, and acute exacerbation may occur following lung surgery in CPFE patients. HRCT plays an important role in evaluating the occurrence of lung cancer at an early stage and for determining whether there is an acute exacerbation of pulmonary fibrosis in CPFE patients.Article信州医学雑誌 60(3): 149-156(2012)journal articl

Cerebellar Ganglioglioma in Childhood: Histopathologic Implications for Management During Long-term Survival: A Case Report

We report the case of a 19-year-old female with cerebellar ganglioglioma that was diagnosed at 4 years of age. Despite treatment with partial resection, radiation, and chemotherapy, residual tumor slowly expanded into the brainstem and upper cervical cord, resulting in nocturnal hypopnea, progressive tetraparesis, and feeding difficulty during 8?10 years of age. Initiation of temozolomide and bevacizumab was effective in preventing further expansion of the tumor, and the patient has been treated at home and in school with noninvasive positive pressure ventilation and gastrostomy. Histopathologic examination of the resected tumor tissue revealed phospho-S6-positive tumor cells of either neuronal or astroglial appearance. This suggests that a higher proportion of cells of glial lineage could be linked to the progression of cerebellar ganglioglioma in childhood. Possible treatment options with mammalian target of rapamycin inhibitors are discussed

Electrical Storm in Idiopathic Ventricular Fibrillation Is Associated With Early Repolarization

ObjectivesThis study sought to characterize patients with idiopathic ventricular fibrillation (IVF) who develop electrical storms.BackgroundSome IVF patients develop ventricular fibrillation (VF) storms, but the characteristics of these patients are poorly known.MethodsNinety-one IVF patients (86% male) were selected after the exclusion of structural heart diseases, primary electrical diseases, and coronary spasm. Electrocardiogram features were compared between the patients with and without electrical storms. A VF storm was defined as VF occurring ≥3 times in 24 h and J waves >0.1 mV above the isoelectric line in contiguous leads.ResultsFourteen (15.4%) patients had VF storms occurring out-of-hospital at night or in the early morning. J waves were more closely associated with VF storms compared to patients without VF storms: 92.9% versus 36.4% (p < 0.0001). VF storms were controlled by intravenous isoproterenol, which attenuated the J-wave amplitude. After the subsidence of VF storms, the J waves decreased to the nondiagnostic level during the entire follow-up period. Implantable cardioverter-defibrillator therapy was administered to all patients during follow-up. Quinidine therapy was limited, but the patients on disopyramide (n = 3), bepridil (n = 1), or isoprenaline (n = 1) were free from VF recurrence, while VF recurred in 5 of the 9 patients who were not given antiarrhythmic drugs.ConclusionsThe VF storms in the IVF patients were highly associated with J waves that showed augmentation prior to the VF onset. Isoproterenol was effective in controlling VF and attenuated the J waves, which diminished to below the diagnostic level during follow-up. VF recurred in patients followed up without antiarrhythmic agents

Ex vivo reconstitution of fetal oocyte development in humans and cynomolgus monkeys

ヒト・サルの胎児卵巣から原始卵胞を体外で作出することに成功. 京都大学プレスリリース. 2022-08-01.New egg recipe to boost fertility research. 京都大学プレスリリース. 2022-08-14.In vitro oogenesis is key to elucidating the mechanism of human female germ-cell development and its anomalies. Accordingly, pluripotent stem cells have been induced into primordial germ cell-like cells and into oogonia with epigenetic reprogramming, yet further reconstitutions remain a challenge. Here, we demonstrate ex vivo reconstitution of fetal oocyte development in both humans and cynomolgus monkeys (Macaca fascicularis). With an optimized culture of fetal ovary reaggregates over three months, human and monkey oogonia enter and complete the first meiotic prophase to differentiate into diplotene oocytes that form primordial follicles, the source for oogenesis in adults. The cytological and transcriptomic progressions of fetal oocyte development in vitro closely recapitulate those in vivo. A comparison of single-cell transcriptomes among humans, monkeys, and mice unravels primate-specific and conserved programs driving fetal oocyte development, the former including a distinct transcriptomic transformation upon oogonia-to-oocyte transition and the latter including two active X chromosomes with little X-chromosome upregulation. Our study provides a critical step forward for realizing human in vitro oogenesis and uncovers salient characteristics of fetal oocyte development in primates

Pre-Angioplasty Instantaneous Wave-Free Ratio Pullback Predicts Hemodynamic Outcome In Humans With Coronary Artery Disease: Primary Results of the International Multicenter iFR GRADIENT Registry.

The authors sought to evaluate the accuracy of instantaneous wave-Free Ratio (iFR) pullback measurements to predict post-percutaneous coronary intervention (PCI) physiological outcomes, and to quantify how often iFR pullback alters PCI strategy in real-world clinical settings.This article is freely available via Open Access. Please click on the Additional Link above to access the full-text via the publisher's site

Enhancing rare variant interpretation in inherited arrhythmias through quantitative analysis of consortium disease cohorts and population controls.

PURPOSE: Stringent variant interpretation guidelines can lead to high rates of variants of uncertain significance (VUS) for genetically heterogeneous disease like long QT syndrome (LQTS) and Brugada syndrome (BrS). Quantitative and disease-specific customization of American College of Medical Genetics and Genomics/Association for Molecular Pathology (ACMG/AMP) guidelines can address this false negative rate. METHODS: We compared rare variant frequencies from 1847 LQTS (KCNQ1/KCNH2/SCN5A) and 3335 BrS (SCN5A) cases from the International LQTS/BrS Genetics Consortia to population-specific gnomAD data and developed disease-specific criteria for ACMG/AMP evidence classes-rarity (PM2/BS1 rules) and case enrichment of individual (PS4) and domain-specific (PM1) variants. RESULTS: Rare SCN5A variant prevalence differed between European (20.8%) and Japanese (8.9%) BrS patients (p = 5.7 × 10-18) and diagnosis with spontaneous (28.7%) versus induced (15.8%) Brugada type 1 electrocardiogram (ECG) (p = 1.3 × 10-13). Ion channel transmembrane regions and specific N-terminus (KCNH2) and C-terminus (KCNQ1/KCNH2) domains were characterized by high enrichment of case variants and >95% probability of pathogenicity. Applying the customized rules, 17.4% of European BrS and 74.8% of European LQTS cases had (likely) pathogenic variants, compared with estimated diagnostic yields (case excess over gnomAD) of 19.2%/82.1%, reducing VUS prevalence to close to background rare variant frequency. CONCLUSION: Large case-control data sets enable quantitative implementation of ACMG/AMP guidelines and increased sensitivity for inherited arrhythmia genetic testing