This study evaluated abnormal electrocardiogram (ECG) types and frequencies and their associations with disease severity in patients with scrub typhus and normal age-matched subjects. Demographic characteristics and ECG and laboratory findings of patients with scrub typhus admitted to Chosun University Hospital and normal subjects visiting the hospital for health check-ups from January 2008 to December 2012 were retrospectively studied. ECG abnormalities at admission were observed in 76 (43.2%) of 176 patients with confirmed scrub typhus. The following ECG abnormalities were observed: long QT interval (34 cases, 19.3%); ischemia, including ST-segment changes, abnormal Q waves, and poor R progression (26 cases, 14.8%); arrhythmia (22 cases, 12.5%; this group included atrial fibrillation [Af] [16 cases, 9.1%], atrial premature contraction [5 cases, 2.8%] and premature ventricular complex [1 case, 0.6%]); and conduction changes, including atrioventricular (AV) block, right bundle branch block (RBBB), and left bundle branch block (LBBB) (12 cases; 6.8%). Compared with the age- and sex-matched control group, ECG abnormalities were significantly more common among scrub typhus patients (43.6% vs. 13.9%, P < 0.001). Abnormal laboratory findings were significantly more common in patients with scrub typhus in the abnormal ECG group, which showed a significantly higher severity score than the normal ECG group (6.47 vs. 5.05, P = 0.001); abnormal ECG findings were also correlated with increased disease severity. ECG abnormalities were more common in patients with scrub typhus than in the general population and were associated with more severe disease. As QT prolongation occurs in ~20% of patients with scrub typhus, clinicians should pay additional attention to drugs that affect QT prolongation. All authors: No reported disclosures.
Abstract Funding Acknowledgements Type of funding sources: Public grant(s) – National budget only. Main funding source(s): the National Research Foundation of Korea (NRF) grants funded by the Korea government (MSIT), the Korean Fund for Regenerative Medicine (KFRM) grant funded by the Korea government Background Functional mutations in the PITX2 (Paired-like homeodomain transcription factor 2) gene cause genetically inherited atrial fibrillation (AF). PITX2 is known to plays a pivotal role in regulating the expression of distinct ion channels, beta-adrenergic stimulation, cell-cell coupling and resulting in AF due to abnormal calcium abnormalities and electrical remodeling. However, the pathophysiological mechanisms linking impaired PITX2 with AF are still to be explored. This study was performed to generate PITX2c knockout human iPSC atrial cardiomyocytes (hiPSC-atrial CM), which are useful tools for arrhythmia modeling, and evaluate the mechanism of PITX2 deficiency leading to AF. Methods We generated a PITX2 knock-out iPSC line using a CRISPR/Cas9-based genome editing system. hiPSCs were electroporated with Cas9/sgRNA ribonucleoprotein (RNP) complexes. PITX2c knock-out hiPSC-CMs differentiated into atrial cardiomyocytes based on the manipulation of retinoic acid signaling. For the three-dimensional (3D) culture model, cells were plated in the spherical plate 5D. Electrophysiological properties and oxidative stress were assessed in PITX2c-deficient cardiomyocytes. Proarrhythmic effects of the PITX2c knock-out were quantified with AP morphology, AP duration (APD) restitution, wavelength (WL) and conduction velocity (CV) restitution using microelectrode arrays (MEA). Results We demonstrated that atrial-specific differentiated hiPSC-CMs expressed atrial-specific genes and the properties of action potentials were like those of human atrial cardiomyocytes. In addition, both 2D and 3D PITX2c knock-out atrial hiPSC-CMs showed signs of APD shortening and reduced wavelength (WL) and increased conduction velocity (CV) restitution (P<0.05). Next, a functional assessment of calcium homeostasis has shown that PITX2c causes atrial arrhythmias by impairing calcium handling genes (SERCA2a, RyR2, PLN). We then demonstrated that miR-374a-5p and miR-374b-5p could be involved in pathophysiological functions as therapeutic candidates when affinity for PITX2 was based on the upper context score percentile (> 99). Conclusions This study provides an understanding of electrical remodeling by PITX2c loss-of-function mutations and suggests the potential therapeutic candidates by miR-374a-5p and miR-374b-5p, thus helping to understand the mechanism of PITX2 deficiency leading to atrial fibrillation.
Submitted 18 June 2008, Accepted 12 August 2008 Correspondence : Jong Hoon Chung, M.D. Department of Internal Medicine, Chosun University College of Medicine 588 Seosuk-dong, Dong-gu, Gwangju, 501-717, Korea Tel : +82-62-220-3016, Fax : +82-62-234-9653 E-mail : jhchung@mail.chosun.ac.kr 용되어 왔다. 그러나 1997년 이후부터 베트남, 타지키스탄, 영국, 인도 등에서 quinolones 항균제의 모체인 nalidixic acid 내성 균(nalidixic acid-resistant Salmonella Typhi, NARST)에 의한 감염 증례가 보고되었다(2). NARST에 감염된 환자에서 항생제 감수성 검사상 fluoroquinolone에 감수성임에도 불구하고 임상적으로 quinolones으로 치료 시 치료 반응이 지연되거나 치료 실패가 초래될 수 있다(3). 이러한 NARST 감염에 대한 치료법은 고용량의 fluoroquinolone을 오래 투여하거나, 3세대 cephalosporin이나 azithromycin을 단독 투여하는 방법, 그리고 두 가지 약제 의 병합 투여를 고려해 볼 수 있다(4). 그러나 아직까지 이 러한 항생제의 병합요법의 효과에 대한 연구는 시행된 바 없다. 저자 등은 최근 인도 여행 후 발열이 지속되어 장티 원 저
Abstract Background As only few studies have analyzed viral kinetics between the incubation and symptomatic periods of COVID-19 patients, we investigated the viral kinetics and compared viral loads between patients with mild and severe COVID-19. Methods We determined the viral kinetics of 10 patients diagnosed with COVID-19 at Chosun University Hospital. Six patients were classified into the “mild” group and 4 into the “severe” group according to supplemental oxygen use during admission. Samples were collected via nasopharyngeal swabs and sputum specimens. SARS-CoV-2 was detected using real-time reverse transcription-polymerase chain reaction (RT-PCR). Chest radiograph scores during hospitalization were obtained Results Ct values of the upper respiratory tract specimens were low during the early stages after symptom onset but gradually increased over time in both groups. The severe group had lower Ct values than the mild group. The Ct values of the RdRP and E genes on day 6 after symptom onset were significantly lower in the severe group than in the mild group (p < 0.05). Three of 6 patients had positive results on RT-PCR even before symptom onset; 2 of them had the lowest Ct values. The chest radiograph scores were higher in the severe group than in the mild group, and the score in the severe group was the highest at approximately 3 weeks after symptom onset. Ct values when the RdRP gene and E gene were targeted to detect SARS-CoV-2 on the basis of the days after symptom onset in all the patients Conclusion Viral load and chest radiograph scores were significantly different between the severe and mild groups of COVID-19 patients. Disclosures All Authors: No reported disclosures
Rickettsial diseases associated with the spotted fever group constitute a growing number of newly identified Rickettsia pathogens and their tick vectors in various parts of the world. At least 15 distinct tick species belonging to six genera have shown the presence of Rickettsia raoultii. Herein, we report the detection of R. raoultii in ticks from the Republic of Korea (ROK).Thirty-five ticks were collected from 29 patients with tick bites in Gwangju Metropolitan City, Jeollanam Province, ROK. The ticks were identified using molecular, morphological, and taxonomic characteristics. All samples were screened for presence of Rickettsia species using nested polymerase chain reactions of their outer membrane protein (ompA) and citrate synthase (gltA) genes. The amplified products were sequenced for subsequent phylogenetic analyses.Sequencing data showed the DNA sequences of R. raoultii in three Haemaphysalis longicornis ticks. All three tick samples were 99.4-100% similar to previously reported partial sequences of ompA of R. raoultii strains CP019435 and MF002523, which formed a single clade with the reference strains.We provide the first description and molecular identification of R. raoultii detected in H. longicornis ticks in the ROK. This observation extends the geographical distribution of R. raoultii. Screening of human samples for this pathogen will provide information about the prevalence of rickettsial infections in this region.
Background Thromboembolic events are a well-recognized cause of in-hospital deaths of patients with infectious diseases. However, thromboembolic events in patients with scrub typhus, caused by Orientia tsutsugamushi have rarely been reported. This study aimed to assess risk factors associated with thromboembolic events in patients with scrub typhus. Methods All 93 scrub typhus patients’ diagnoses were confirmed serologically or by positive nested polymerase chain reaction (PCR). The clinical and laboratory findings from 12 scrub typhus patients with thromboembolic events and 81 scrub typhus patients with nonthromboembolic events were retrospectively studied. To determine the factors implicated in thromboembolic events, we performed multivariate logistic regression analysis using the six independent factors identified by the univariate analysis. Findings The mean age of the patients in the thromboembolic group was 76.4 years (median, 76 years), and in nonthromboembolic group it was 64.6 years (median, 65 years) ( P <0·001). Thromboembolic events were observed in 12 patients. These events included acute coronary syndrome (n = 5), acute limb ischemia (n = 4), ischemic stroke (n = 1), deep vein thrombosis combined with pulmonary thromboembolism (n = 1), and left common iliac artery aneurysm with a thrombus (n = 1). According to multivariate analysis, the following four factors were significantly associated with the thromboembolic events: 1) treatment with rifampin (OR = 57.63; P = 0.039; CI 1.230–2700.27)., 2) Taguchi genotype (OR = 41.5; P = 0.028; CI 1.5–1154.6), 3) atrial fibrillation (OR = 9.4; P = 0.034; CI 1.2–74.0), and 4) age (OR = 1.1; P = 0.046; CI 1.0–1.3). Conclusions Our study suggests that clinicians should be cautious when managing patients with scrub typhus to avoid the development of thromboembolic events, especially in patients with risk factors such as treatment with rifampin, Taguchi genotype, atrial fibrillation, and advanced age.
Hemorrhagic fever with renal syndrome (HFRS) is caused by hantaviruses. Data of 34 patients with HFRS hospitalized at Chosun University Hospital, South Korea, between 2010 and 2021 were retrospectively analyzed. Nested reverse transcription polymerase chain reaction (RT-nPCR) targeting the L segment of hantavirus and sequencing were used for diagnosis. Most cases occurred in men and during the months of October through December. Common symptoms were fever, chills, gastrointestinal symptoms, and myalgia. The common laboratory abnormalities were thrombocytopenia, proteinuria, and elevated levels of serum creatinine, aspartate transaminase, alanine transaminase, and lactate dehydrogenase. Approximately 91.2% of patients had the Hantaan virus with a new genotype cluster, whereas 8.8% had the Seoul virus. Seropositivity based on IgM titer >1:32 on admission was noted in 20.6%, and a 4-fold increase in IgG titer of 1:512 was observed in 11.8%. This study demonstrated that RT-nPCR targeting the L segment of hantaviruses is a more reliable diagnostic method compared to serological testing.
Serum tumor necrosis factor-α (TNF-α) was evaluated in Vibrio vulnificus-infected patients at admission. The median TNF-α concentration in the non-survivor group was determined to be 261.0 pg/mL, in contrast to 69.5 pg/mL in the survivor group (P = 0.001). Hence, serum TNF-α concentration may potentially be an early predictor of the mortality in patients with Vibrio septicemia.
We aimed to develop a simple scoring system to predict risk for methicillin resistance in community-onset Staphylococcus aureus bacteremia (CO-SAB) by identifying the clinical and epidemiological risk factors for community-onset methicillin-resistant S. aureus (MRSA).We retrospectively analyzed data from three multicenter cohort studies in Korea in which patient information was prospectively collected and risk factors for methicillin resistance in CO-SAB were identified. We then developed and validated a risk-scoring system.To analyze the 1,802 cases of CO-SAB, we included the four most powerful predictors of methicillin resistance that we identified in the scoring system: underlying hematologic disease (-1 point), endovascular infection as the primary site of infection (-1 point), history of hospitalization or surgery in ≤1 year (+0.5 points), and previous isolation of MRSA in ≤6 months (+1.5 points). With this scoring system, cases were classified into low (less than -0.5), intermediate (-0.5-1.5), and high (≥1.5) risk groups. The proportions of MRSA cases in each group were 24.7% (22/89), 39.0% (607/1,557), and 78.8% (123/156), respectively, and 16.7% (1/6), 33.8% (112/331), and 76.9% (10/13) in a validation set.This risk-scoring system for methicillin resistance in CO-SAB may help physicians select appropriate empirical antibiotics more quickly.
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