at many loci across the genome, 3 and that smoking-related changes in gene expression are epigenetically regulated. 4 Among EWAS-identified loci, the aryl-hydrocarbon receptor repressor (AHRR) gene has been noted as a promising candidate gene, with smoking-associated hypomethylation of AHRR CpG sites (e.g., cg05575921) detectable in DNA from peripheral lymphocytes and pulmonary macrophages. 5,6 AHRR encodes a transcription factor that can repress the aryl-hydrocarbon receptor pathway, which regulates the cytochrome P450 (CYP)-mediated catabolism of xenobiotics such as dioxin and polyaromatic hydrocarbons contained in tobacco smoke. 5 Although the exact relation-T obacco smoking is a leading preventable cause of morbidity and mortality in the world. Active smoking in adults increases the risk for a wide spectrum of chronic illness, such as cardiovascular and respiratory disease, and various forms of cancer. As self-reported smoking information is prone to inaccuracies due to recall bias and under-reporting, 1 an objective biomarker of longterm smoking behavior has been sought. Among current smokers, cotinine, a primary metabolite of nicotine, is a reliable measure of nicotine exposure, 2 but is not suited for the estimation of long-term smoking behavior due to its short half-life of 15-24 h.With the advent of epigenome-wide association studies (EWAS) in the last decade, it has become known that tobacco smoking has a broad effect on DNA methylation Editorial p ????

Objective In fever clinics screening coronavirus disease (COVID-19), there could be patients with life-threatening diseases that physicians should not overlook. We exploratorily investigated the final diagnosis among non-COVID-19 hospitalized patients who visited the fever clinic. Methods This was a retrospective, observational, and single-centered study conducted in the National Center for Global Health and Medicine (NCGM), Tokyo, Japan. We conducted a retrospective chart review of patients who visited the fever clinic in the NCGM from 11 March 2020 to 24 April 2020. Patients Patients who met the following clinical criteria visited the fever clinic in the NCGM: (1) body temperature >37.5℃, (2) any symptoms consistent with COVID-19 or (3) referral from local healthcare facilities. In the fever clinic, all patients who met the above criteria had severe acute respiratory syndrome coronavirus 2 polymerase chain reaction test with nasopharyngeal swab specimens. Patients with severe symptoms or an unstable condition were sent to an outpatient clinic for infectious diseases for further evaluation and treatment. Results Among 1,470 patients who visited the fever clinic, 84 patients were hospitalized, and 45 of them were diagnosed as having COVID-19. Among the remaining 39 non-COVID-19 patients, there were nine patients with life-threatening diseases. The life-threatening diseases included acute heart failure, septic shock, pneumocystis pneumonia, peritonsillar abscess, and necrotizing fasciitis. Conclusion Physicians should evaluate each patient carefully while considering other life-threatening conditions even in such a COVID-19 pandemic era.

Funding Acknowledgements Type of funding sources: None. Background Left atrial (LA) function is impaired in heart failure with preserved ejection fraction (HFpEF). However, the association between LA longitudinal strain and heart failure (HF) events in patients with HFpEF is still unknown. We evaluated whether LA strain measurements would be useful to predict hospitalizations for worsening HF in this study. Methods This study included 121 patients (Male 73, Female 48) with HFpEF who had echocardiogram at our institute (Age = 76 ± 14y, Left ventricular ejection fraction; LVEF = 63 ± 8%). Patients with atrial fibrillation were excluded. LA longitudinal strain was measured by speckle-tracking echocardiography, using TOMTEC imaging system. The endpoints were hospitalizations for worsening HF. Results During follow-up period of 319 ± 269 days, 33 patients (27%) experienced hospitalizations for worsening HF. LA strain was markedly lower in patients with HF events at 11.3 ± 5.6, whereas LA strain was higher at 20.3 ± 10.1 in patients without HF events. Kaplan-Meier analysis demonstrated a significant separation of survival curves stratified by median value of LA strain (Figure). Conclusions LA dysfunction in HFpEF is associated with a higher risk of HF hospitalization, and LA strain measurements would be useful to predict HF events. Abstract Figure

Pheochromocytoma is a rare catecholamine producing adrenal tumor. Pheochromocytoma crisis is a life-threatening condition inducing multiple organ failure and hemodynamic instability caused by too much catecholamines produced from pheochromocytoma. We report a 59-year-old woman with pheochromocytoma crisis rescued by veno-arterial extracorporeal membrane oxygenation (VA-ECMO), continuous renal replacement therapy (CRRT), and interval tumor resection. In June 2020, the patient was taken to our institution complaining of headache and left lower back pain. The patient developed cardiopulmonary arrest while at the emergency department. After extracorporeal cardiopulmonary resuscitation, the patient required VA-ECMO for hemodynamic support, and subsequently CRRT for catecholamine removal and acute kidney injury. After 1 month of hemodynamic management, the patient underwent left adrenalectomy. The postoperative course was uneventful and she was discharged on postoperative day 23. CRRT would be a safe and feasible option for catecholamine control in patients with acute kidney injury in pheochromocytoma crisis.