Publications by authors named "Seong-Eun Kim"

283 Publications

Kinetic stability modulation of polymeric nanoparticles for enhanced detection of influenza virus penetration of viral fusion peptides.

J Mater Chem B 2021 Oct 14. Epub 2021 Oct 14.

Department of Chemical and Biomolecular Engineering, Yonsei University, Seoul 03722, Republic of Korea.

Specific interactions between viruses and host cells provide essential insights into material science-based strategies to combat emerging viral diseases. pH-triggered viral fusion is ubiquitous to multiple viral families and is important for understanding the viral infection cycle. Inspired by this process, virus detection has been achieved using nanomaterials with host-mimetic membranes, enabling interactions with amphiphilic hemagglutinin fusion peptides of viruses. Most research has been on designing functional nanoparticles with fusogenic capability for virus detection, and there has been little exploitation of the kinetic stability to alter the ability of nanoparticles to interact with viral membranes and improve their sensing performance. In this study, a homogeneous fluorescent assay using self-assembled polymeric nanoparticles (PNPs) with tunable responsiveness to external stimuli is developed for rapid and straightforward detection of an activated influenza A virus. Dissociation of PNPs induced by virus insertion can be readily controlled by varying the fraction of hydrophilic segments in copolymers constituting PNPs, giving rise to fluorescence signals within 30 min and detection of various influenza viruses, including H9N2, CA04(H1N1), H4N6, and H6N8. Therefore, the designs demonstrated in this study propose underlying approaches for utilizing engineered PNPs through modulation of their kinetic stability for direct and sensitive identification of infectious viruses.
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http://dx.doi.org/10.1039/d1tb01847gDOI Listing
October 2021

Medical Management of Constipation in Elderly Patients: Systematic Review.

J Neurogastroenterol Motil 2021 Oct;27(4):495-512

Department of Internal Medicine, Dankook University College of Medicine, Cheonan, Chungcheongnam-do, Korea.

Background/aims: Constipation is a common gastrointestinal problem in the elderly. Because of the limitations of life style modifications and the comorbidity, laxative use is also very common. Therefore, this study reviews the latest literature on the effect and safety of laxative in the elderly.

Methods: A systematic review of randomized controlled trials investigating the effectiveness and safety of laxatives for constipation in elderly patients over 65 years old were performed using the following databases: PubMed, EMBASE, and the Cochrane Library.

Results: Twenty-three randomized controlled trials were included in this review. Among the selected studies, 9 studies compared laxative with placebo and 5 studies compared laxatives of the same type. Four studies compared different types of laxatives or compared combination agents. Five studies compared novel medications such as prucalopride, lubiprostone, and elobixibat with placebo. Psyllium, calcium polycarbophil, lactulose syrup, lactitol, polyethylene glycol, magnesium hydroxide, stimulant laxative with or without fiber, and other medications were more effective than placebo in elderly constipation patients in short-term. Generally, the frequency and severity of adverse effects of laxative were similar between the arms of studies.

Conclusions: Bulk laxative, osmotic laxative, stimulant laxative with or without fiber, and other medications can be used in elderly patients in short-term within 3 months with reasonable safety. However, the quality of included studies was not high and most of studies was conducted in a small number of patients. Among these laxatives, polyethylene glycol seems to be safe and effective in long-term use of about 6 months in elderly patients.
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http://dx.doi.org/10.5056/jnm20210DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8521458PMC
October 2021

Colocalization with MMP-7 in the Distal Colon is Crucial for Syndecan-2 Shedding in Dextran Sulfate Sodium-Induced Colitis Mice.

J Inflamm Res 2021 29;14:4987-5000. Epub 2021 Sep 29.

Department of Life Sciences, Ewha Womans University, Seoul, South Korea.

Introduction: Syndecan-2 expression is elevated during chronic inflammation and cancer development, and its shedding is observed in cancer patients. However, it remained unknown whether inflammation triggers syndecan-2 shedding.

Methods: The colitis model was produced in C57BL/6 mice by oral administration of 2-3% dextran sulfate sodium (DSS) in the drinking water. Syndecan-2 and MMP-7 expression levels in tissues and cells were detected by real-time PCR, Western blotting, and immunohistochemistry. Shed syndecan-2 levels were detected by slot blotting. For tissue culture, colon tissues were divided into proximal, transverse, and distal parts, and incubated in culture media.

Results: In C57BL/6 mice with DSS-induced colitis, syndecan-2 shedding began to increase after week 12 of chronic inflammation and continued to increase at week 15. The level of shed syndecan-2 correlated with the colocalization of syndecan-2 and MMP-7 in distal colon tissues. The mRNA expression of IL-6 was increased specifically in trans-distal colon tissues from weeks 9 to 15. IL-6 induced syndecan-2 expression and shedding and MMP-7 expression in ex vivo-cultured distal colon tissues and adenoma cell lines derived from the distal colon. IL-6 treatment induced STAT3 phosphorylation and MMP-7 expression in DLD-1 cells. The application of MMP-7 to ex vivo-cultured colon tissues increased the shedding of syndecan-2 to the culture medium.

Conclusion: Our findings suggest that chronic inflammation induces syndecan-2 shedding via the site-specific colocalization of syndecan-2 with MMP-7 in the distal colon.
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http://dx.doi.org/10.2147/JIR.S329234DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8488046PMC
September 2021

Three-dimensional culture method enhances the therapeutic efficacies of tonsil-derived mesenchymal stem cells in murine chronic colitis model.

Sci Rep 2021 Oct 1;11(1):19589. Epub 2021 Oct 1.

Department of Internal Medicine, College of Medicine, Ewha Womans University, Seoul, South Korea.

Tonsil-derived mesenchymal stem cells (TMSCs) showed therapeutic effects on acute and chronic murine colitis models, owing to their immunomodulatory properties; therefore, we evaluated enhanced therapeutic effects of TMSCs on a murine colitis model using three-dimensional (3D) culture method. The expression of angiogenic factors, VEGF, and anti-inflammatory cytokines, IL-10, TSG-6, TGF-β, and IDO-1, was significantly higher in the 3D-TMSC-treated group than in the 2D-TMSC-treated group (P < 0.05). At days 18 and 30 after inducing chronic colitis, disease activity index scores were estimated to be significantly lower in the 3D-TMSC-treated group than in the colitis control (P < 0.001 and P < 0.001, respectively) and 2D-TMSC-treated groups (P = 0.022 and P = 0.004, respectively). Body weight loss was significantly lower in the 3D-TMSC-treated group than in the colitis control (P < 0.001) and 2D-TMSC-treated groups (P = 0.005). Colon length shortening was significantly recovered in the 3D-TMSC-treated group compared to that in the 2D-TMSC-treated group (P = 0.001). Histological scoring index was significantly lower in the 3D-TMSC-treated group than in the 2D-TMSC-treated group (P = 0.002). These results indicate that 3D-cultured TMSCs showed considerably higher therapeutic effects in a chronic murine colitis model than those of 2D-cultured TMSCs via increased anti-inflammatory cytokine expression.
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http://dx.doi.org/10.1038/s41598-021-98711-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8486762PMC
October 2021

Fasting Blood Glucose Variability and Unfavorable Trajectory Patterns Are Associated with the Risk of Colorectal Cancer.

Gut Liver 2021 Oct 1. Epub 2021 Oct 1.

Department of Internal Medicine, Seoul, Korea.

Background/aims: The relationship between fasting blood glucose (FBG) variability and colorectal cancer (CRC) remains ill-defined. This study aimed to evaluate the association of FBG variability with CRC risk in the healthy population without overt diabetes.

Methods: In the data from the Korean National Health Insurance Service-Health Screening Cohort, we included individuals examined by FBG testing at least 3 times between 2002 and 2007. FBG variability was calculated using standard deviation (SD) and coefficient of variation (CV).

Results: Regarding FBG variability, an increase in the quintile of SD or CV was independently associated with CRC risk (all p for trend <0.01). When the change in FBG was classified into six trajectory patterns, unfavorable trajectory patterns (high stable and upward) were significantly associated with increased CRC risk (hazard ratio [HR] 2.30, p=0.003; HR 1.19, p=0.007, respectively). In subgroup analyses according to the sex, a significant association between FBG variability (SD or CV) and CRC risk was observed in men but not in women. The high stable and upward pattern were also associated with CRC risk in men (HR 2.47, p=0.002; HR 1.21, p=0.012) but not in women.

Conclusions: This study identified that FBG variability and unfavorable trajectory patterns were significantly associated with increased CRC risk in the healthy population without overt diabetes. Our findings suggest that FBG variability as well as FBG itself may be a predictive factor for the development of CRC.
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http://dx.doi.org/10.5009/gnl210048DOI Listing
October 2021

Development of aldolase-based catalysts for the synthesis of organic chemicals.

Trends Biotechnol 2021 Aug 27. Epub 2021 Aug 27.

Department of Bioscience and Biotechnology, Konkuk University, Seoul 05029, Republic of Korea. Electronic address:

Aldol chemicals are synthesized by condensation reactions between the carbon units of ketones and aldehydes using aldolases. The efficient synthesis of diverse organic chemicals requires intrinsic modification of aldolases via engineering and design, as well as extrinsic modification through immobilization or combination with other catalysts. This review describes the development of aldolases, including their engineering and design, and the selection of desired aldolases using high-throughput screening, to enhance their catalytic properties and perform novel reactions. Aldolase-containing catalysts, which catalyze the aldol reaction combined with other enzymatic and/or chemical reactions, can efficiently synthesize diverse complex organic chemicals using inexpensive and simple materials as substrates. We also discuss the current challenges and emerging solutions for aldolase-based catalysts.
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http://dx.doi.org/10.1016/j.tibtech.2021.08.001DOI Listing
August 2021

[SARS-CoV-2 Vaccination for Adult Patients with Inflammatory Bowel Disease: Expert Consensus Statements by KASID].

Korean J Gastroenterol 2021 08;78(2):117-128

Department of Gastroenterology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.

Coronavirus disease 2019 (COVID-19), caused by the novel coronavirus, is threatening global health worldwide with unprecedented contagiousness and severity. The best strategy to overcome COVID-19 is a vaccine. Various vaccines are currently being developed, and mass vaccination is in progress. Despite the very encouraging clinical trial results of these vaccines, there is insufficient information on the safety and efficacy of vaccines for inflammatory bowel disease (IBD) patients facing various issues. After reviewing current evidence and international guidelines, the Korean Association for the Study of Intestinal Diseases (KASID) developed an expert consensus statement on COVID-19 vaccination issues for Korean IBD patients. This expert consensus statement emphasizes that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination be strongly recommended for IBD patients, and it is safe for IBD patients receiving immunomodulatory therapy.
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http://dx.doi.org/10.4166/kjg.2021.110DOI Listing
August 2021

[KASID Guidance for Clinical Practice Management of Adult Inflammatory Bowel Disease during the COVID-19 Pandemic: Expert Consensus Statement].

Korean J Gastroenterol 2021 08;78(2):105-116

Department of Gastroenterology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.

The coronavirus disease 2019 (COVID-19) pandemic has reduced the ability to prevent or control chronic disease due to the concerns about safety in accessing health care. Inflammatory bowel disease (IBD) is a chronic condition requiring long- term sustained treatment, which is difficult in the current panedemic situation. The Korean Association for the Study of Intestinal Diseases (KASID) has developed an expert consensus statement on the clinical practice management of adult inflammatory bowel disease during the COVID-19 pandemic. This expert consensus statement is based on guidelines and clinical reports from several countries around the world. It provides recommendations to deal with the risk of COVID-19 and medication use in IBD patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and emphasizes the importance of right treatment approach to avoid worsening of the disease condition in IBD patients.
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http://dx.doi.org/10.4166/kjg.2021.112DOI Listing
August 2021

Comparison of RT-PCR, RT-nested PCRs, and real-time PCR for diagnosis of severe fever with thrombocytopenia syndrome: a prospective study.

Sci Rep 2021 08 18;11(1):16764. Epub 2021 Aug 18.

Department of Internal Medicine, School of Medicine, Pusan National University, Pusan, Republic of Korea.

We designed a highly sensitive reverse transcription nested polymerase chain reaction targeting the M-segment (NPCR-M) of severe fever with thrombocytopenia syndrome (SFTS) virus. NPCR-M was performed in parallel with three other referenced PCR assays QPCR-S, PCR-M, and NPCR-S to assess their clinical usefulness as routine diagnostic techniques for SFTS. In this multi-centered prospective study, 122 blood samples from 38 laboratory-confirmed SFTS patients and 85 control samples were used. The results demonstrated that QPCR-S and NPCR-S had better sensitivity rate up to 21 days after symptom onset however, the PCR-M showed poor sensitivity after 7 days of symptom onset. Our designed NPCR-M had a higher detection rate up to 40 days from symptom onset and revealed the persistence of SFTSV RNA in the early convalescent phase. No false-positive results were seen for the control samples. Additionally, NPCR-M showed positive results for a sample that initially showed negative results from other PCRs and for many other samples collected in the convalescent phase of SFTS. Our designed nested PCR is suitable for SFTSV detection in patients' blood collected in the acute and early convalescent phase of SFTS, and shows better sensitivity and high specificity even up to 40 days after symptom onset.
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http://dx.doi.org/10.1038/s41598-021-96066-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8373928PMC
August 2021

Comparison of clinical outcome between incremental peritoneal dialysis and conventional peritoneal dialysis: a propensity score matching study.

Ren Fail 2021 Dec;43(1):1222-1228

Department of Internal Medicine, Dong-A University, Busan, Republic of Korea.

Background: Incremental peritoneal dialysis (iPD) can be useful in patients with residual renal function (RRF). RRF was well preserved and similar survival was shown in iPD compared to conventional PD (cPD) in previous study. However, the long-term survival of iPD remains unclear compared to cPD in diabetic patients. This study evaluated whether patient survival, hospitalization and peritonitis, and PD survival in iPD were lower than cPD or not.

Methods: We conducted a 12-year retrospective observational study of 303 PD patients (232 cPD and 71 iPD) using propensity score matching by age, gender, and diabetes mellitus (DM). Finally, 78 cPD patients and 39 iPD patients were included and 44 patients had DM. Incremental PD was defined as starting PD with two or three manual exchanges per day.

Results: The median duration of iPD was 24.1 months and iPD had higher RRF than cPD. Compared to cPD, the patient survival, PD survival and hospitalization benefits were not found in iPD but diabetic iPD patients had significantly longer survival and less hospitalization. Cumulative risk for peritonitis was lower iPD and PD duration of iPD was longer than those of cPD. The iPD was an independent factor associated with survival in patients with DM.

Conclusions: Incremental PD may be a safe PD modality to initiate and maintain PD in less uremic patients with tolerable RRF. Incremental PD would be a benefit for survival in diabetic patients. Further prospective studies are necessary to confirm the effectiveness of iPD in PD patients with similar RRF.
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http://dx.doi.org/10.1080/0886022X.2021.1960564DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8381909PMC
December 2021

Differentiation of symptomatic and asymptomatic carotid intraplaque hemorrhage using 3D high-resolution diffusion-weighted stack of stars imaging.

NMR Biomed 2021 11 23;34(11):e4582. Epub 2021 Jul 23.

Utah Center for Advanced Imaging Research, University of Utah, Salt Lake City, Utah, USA.

Ischemic events related to carotid disease are far more strongly associated with plaque instability than stenosis. 3D high-resolution diffusion-weighted (DW) imaging can provide quantitative diffusion measurements on carotid atherosclerosis and may improve detection of vulnerable intraplaque hemorrhage (IPH). The 3D DW-stack of stars (SOS) sequence was implemented with 3D SOS acquisition combined with DW preparation. After simulation of signals created from 3D DW-SOS, phantom studies were performed. Three healthy subjects and 20 patients with carotid disease were recruited. Apparent diffusion coefficient (ADC) values were statistically analyzed on three subgroups by using a two-group comparison Wilcoxon-Mann-Whitney U test with p values less than 0.05: symptomatic versus asymptomatic; IPH-positive versus IPH-negative; and IPH-positive symptomatic versus asymptomatic plaques to determine the relationship with plaque vulnerability. ADC values calculated by 3D DW-SOS provided values similar to those calculated from other techniques. Mean ADC of symptomatic plaque was significantly lower than asymptomatic plaque (0.68 ± 0.18 vs. 0.98 ± 0.16 x 10  mm /s, p < 0.001). ADC was also significantly lower in IPH-positive versus IPH-negative plaque (0.68 ± 0.13 vs. 1.04 ± 0.11 x 10  mm /s, p < 0.001). Additionally, ADC was significantly lower in symptomatic versus asymptomatic IPH-positive plaque (0.57 ± 0.09 vs. 0.75 ± 0.11 x 10  mm /s, p < 0.001). Our results provide strong evidence that ADC measurements from 3D DW-SOS correlate with the symptomatic status of extracranial internal carotid artery plaque. Further, ADC improved discrimination of symptomatic plaque in IPH. These data suggest that diffusion characteristics may improve detection of destabilized plaque leading to elevated stroke risk.
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http://dx.doi.org/10.1002/nbm.4582DOI Listing
November 2021

Circulating Plasmacytoid and Conventional Dendritic Cells Are Numerically and Functionally Deficient in Patients With Scrub Typhus.

Front Immunol 2021 1;12:700755. Epub 2021 Jul 1.

Department of Rheumatology, Chonnam National University Medical School and Hospital, Gwangju, South Korea.

Background: Dendritic cells (DCs) are specialized antigen-presenting cells known to bridge innate and adaptive immune reactions. However, the relationship between circulating DCs and infection is unclear. Therefore, this study aimed to examine the level and function of plasmacytoid DCs (pDCs) and conventional DCs (cDCs), two subsets of circulating DCs, in scrub typhus patients.

Methods: The study included 35 scrub typhus patients and 35 healthy controls (HCs). pDC and cDC levels, CD86 and CD274 expression, and cytokine levels were measured using flow cytometry.

Results: Circulating pDC and cDC levels were found to be significantly reduced in scrub typhus patients, which were correlated with disease severity. The patients displayed increased percentages of CD86 pDCs, CD274 pDCs, and CD274 cDCs in the peripheral blood. The alterations in the levels and surface phenotypes of pDCs and cDCs were recovered in the remission state. In addition, the production of interferon (IFN)-α and tumor necrosis factor (TNF)-α by circulating pDCs, and interleukin (IL)-12 and TNF-α by circulating cDCs was reduced in scrub typhus patients. Interestingly, our experiments showed that the percentages of CD86 pDCs, CD274 pDCs, and CD274 cDCs were increased in cultures treated with cytokines including IFN-γ, IL-12, and TNF-α.

Conclusions: This study demonstrates that circulating pDCs and cDCs are numerically deficient and functionally impaired in scrub typhus patients. In addition, alterations in the expression levels of surface phenotypes of pDCs and cDCs could be affected by pro-inflammatory cytokines.
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http://dx.doi.org/10.3389/fimmu.2021.700755DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8281928PMC
July 2021

Blood Pressure and Transient Postoperative Neurologic Deterioration, Following Superficial Temporal-to-Middle Cerebral Artery Anastomosis in Adult Patients with Moyamoya Disease: A Retrospective Cohort Study.

J Clin Med 2021 Jun 10;10(12). Epub 2021 Jun 10.

Department of Anesthesiology and Pain Medicine, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam 13620, Korea.

We investigated whether intraoperative systolic blood pressure (ISBP) is associated with the risk of transient neurologic deficits (TND) following superficial temporal-to-middle cerebral artery (STA-MCA) anastomosis in adult patients with moyamoya disease (MMD). In this retrospective observational study, data from adult patients with MMD who had undergone STA-MCA anastomosis at a single tertiary academic hospital during May 2003-April 2014 were examined. Data on patient characteristics were obtained from electronic medical records, including the details of comorbidities and laboratory findings. TND was the primary outcome of interest. Out of 192 patients (228 hemispheres), 66 (29%) hemispheres had TND after surgery. There were significant differences in ISBP between patients with and without TND. The lowest ISBP quartile was independently associated with TND (odds ratio: 5.50; 95% confidence interval: 1.96-15.46). Low ISBP might lead to TND after STA-MCA anastomosis in adult patients with MMD. In patients with poor perfusion status, low ISBP was associated with an increased risk of TND. Our findings suggest that strict ISBP control might be required to prevent TND after anastomosis in patients with MMD, in particular, in patients with poor perfusion status. Given limitations due to the retrospective design, further studies are needed to clarify these findings.
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http://dx.doi.org/10.3390/jcm10122567DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8227225PMC
June 2021

Novel enzymatic cross-linking-based hydrogel nanofilm caging system on pancreatic β cell spheroid for long-term blood glucose regulation.

Sci Adv 2021 Jun 23;7(26). Epub 2021 Jun 23.

School of Chemical and Biological Engineering, Institute of Chemical Processes, Seoul National University, Seoul 08826, Republic of Korea.

Pancreatic β cell therapy for type 1 diabetes is limited by low cell survival rate owing to physical stress and aggressive host immune response. In this study, we demonstrate a multilayer hydrogel nanofilm caging strategy capable of protecting cells from high shear stress and reducing immune response by interfering cell-cell interaction. Hydrogel nanofilm is fabricated by monophenol-modified glycol chitosan and hyaluronic acid that cross-link each other to form a nanothin hydrogel film on the cell surface via tyrosinase-mediated reactions. Furthermore, hydrogel nanofilm formation was conducted on mouse β cell spheroids for the islet transplantation application. The cytoprotective effect against physical stress and the immune protective effect were evaluated. Last, caged mouse β cell spheroids were transplanted into the type 1 diabetes mouse model and successfully regulated its blood glucose level. Overall, our enzymatic cross-linking-based hydrogel nanofilm caging method will provide a new platform for clinical applications of cell-based therapies.
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http://dx.doi.org/10.1126/sciadv.abf7832DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8221614PMC
June 2021

Small Bowel Necrosis Associated with Catastrophic Antiphospholipid Syndrome: A Case Report.

Korean J Gastroenterol 2021 06;77(6):294-299

Department of Internal Medicine, Ewha Womans University, College of Medicine, Seoul, Korea.

Catastrophic antiphospholipid syndrome is a highly fatal condition characterized by widespread thromboembolism subsequent to a triggering factor (e.g., infection, trauma, and neoplasia) in antiphospholipid antibody-positive patients. This paper reports a case of a 29-year-old male without the underlying disease who developed extensive mesenteric thromboembolism and jejunal necrosis during the treatment for acute enteritis. The patient's condition was improved with low-molecular-weight heparin and an intravenous Ig treatment with emergency surgery. The serum antiphospholipid (anticardiolipin IgM) and lupus anticoagulant antibody tests showed positive results. Acute infectious enterocolitis is generally considered a mild disease. On the other hand, aggressive evaluation and treatment should be considered if the clinical conditions do not improve and deteriorate rapidly despite appropriate antibiotic treatment because of the possibility of acute immunological complications, such as catastrophic antiphospholipid syndrome.
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http://dx.doi.org/10.4166/kjg.2021.014DOI Listing
June 2021

Source Analysis and Effective Control of a COVID-19 Outbreak in a University Teaching Hospital during a Period of Increasing Community Prevalence of COVID-19.

J Korean Med Sci 2021 Jun 21;36(24):e179. Epub 2021 Jun 21.

Department of Infectious Diseases, Chonnam National University Medical School, Gwangju, Korea.

Background: South Korea has been experiencing a third wave of coronavirus disease 2019 (COVID-19) since mid-November 2020. Our hospital in Gwangju metropolitan city experienced a healthcare-associated COVID-19 outbreak early in the third wave. The first confirmed COVID-19 patient was a symptomatic neurosurgery resident with high mobility throughout the hospital. We analyzed the transmission routes of nosocomial COVID-19 and discussed infection control strategies.

Methods: We retrospectively analyzed the severe acute respiratory syndrome coronavirus 2 reverse transcription-polymerase chain reaction (RT-PCR) testing results according to time point and evaluated transmission routes.

Results: Since COVID-19 was first confirmed in a healthcare worker (HCW) on 11/13/2020, we performed RT-PCR tests for all patients and caregivers and four complete enumeration surveys for all HCWs. We detected three clusters of nosocomial spread and several sporadic cases. The first cluster originated from the community outbreak spot, where an asymptomatic HCW visited, which led to a total of 22 cases. The second cluster, which included patient-to-patient transmission, originated from a COVID-19 positive caregiver before diagnosis and the third cluster involved a radiologist and a banker. We took measures to isolate Building 1 of the hospital for 17 days and controlled the outbreak during a period of increasing community COVID-19 prevalence. Universal screening of all inpatients upon admission and resident caregivers was made mandatory and hospital-related employees are now screened monthly.

Conclusion: Infection control strategies to prevent the nosocomial transmission of emerging infectious diseases must correspond with community disease prevalence. Our data reinforce the importance of multi-time point surveillance of asymptomatic HCWs and routine surveillance of patients and caregivers during an epidemic.
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http://dx.doi.org/10.3346/jkms.2021.36.e179DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8216991PMC
June 2021

Molecular insights into lipoxygenases for biocatalytic synthesis of diverse lipid mediators.

Prog Lipid Res 2021 07 16;83:101110. Epub 2021 Jun 16.

Department of Bioscience and Biotechnology, Konkuk University, Seoul 05029, Republic of Korea. Electronic address:

Oxylipins derived mainly from C20- and C22-polyunsaturated fatty acids (PUFAs), termed lipid mediators (LMs), are essential signalling messengers involved in human physiological responses associated with homeostasis and healing process for infection and inflammation. Some LMs involved in the resolution of inflammation and infection are termed specialized pro-resolving mediators (SPMs), which are generated by human M2 macrophages or polymorphonuclear leukocytes and have the potential to protect and treat hosts from bacterial and viral infections by phagocytosis activation. Lipoxygenases (LOXs) biosynthesize regio- and stereoselective LMs. Thus, understanding the regio- and stereoselectivities of LOXs for PUFAs at a molecular level is important for the biocatalytic synthesis of diverse LMs. Here, we elucidate the catalytic mechanisms and discuss regio- and stereoselectivities and their changes of LOXs determined by insertion direction and position of the substrate and oxygen at a molecular level for the biosynthesis of diverse human LMs. Recently, the biocatalytic synthesis of PUFAs to human LMs or analogues has been conducted using microbial LOXs. Such microbial LOXs involved in the biosynthesis of LMs are expected to exert significantly higher activity and stability than human LOXs. Diverse regio- and stereoselective LOXs can be obtained from microorganisms, which represent a wealth of genomic sources. We reconstruct the biosynthetic pathways of LOX-catalyzed LMs in humans and other organisms. Furthermore, we suggest the effective methods of biocatalytic synthesis of diverse human LMs from PUFAs or glucose by using microbial LOXs, increasing the stability and activity of LOXs, combining the reactions of LOXs, and constructing metabolic pathways.
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http://dx.doi.org/10.1016/j.plipres.2021.101110DOI Listing
July 2021

Fabrication of 2D and 3D Cell Cluster Arrays Using a Cell-Friendly Photoresist.

ACS Biomater Sci Eng 2021 07 14;7(7):3082-3087. Epub 2021 Jun 14.

Research Institute of Advanced Materials (RIAM), Seoul National University, 1, Gwanak-ro, Seoul 08826, South Korea.

Cells in 3D behave differently than cells in 2D. We develop a new method for the fabrication of 2D and 3D cell cluster arrays on an identical substrate using a cell-friendly photoresist, which enables comparative study between cells in 2D and 3D cell clusters. The fabricated cell cluster arrays maintain their structure up to 3 days with good viability. Using this method, 2D and 3D cancer cell clusters with comparable sizes are fabricated, and natural killer (NK) cell cytotoxicity assays are performed to assess how dimensionality of cancer cell clusters influence their susceptibility to immune cell-mediated killing.
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http://dx.doi.org/10.1021/acsbiomaterials.1c00655DOI Listing
July 2021

Retrospective study of the efficacy of vascularized tissue transfer for treating antibiotic-resistant bacteria-infected wound: Comparison with clean and antibiotic-sensitive bacteria-infected wound.

Medicine (Baltimore) 2021 Jun;100(23):e25907

Department of Plastic and Reconstructive Surgery, Kangnam Sacred Heart Hospital, Hallym University College of Medicine, Seoul.

Abstract: If wounds are infected with bacteria resistant to an empirical antibiotic regimen, effective wound treatment will be delayed. This can delay wound healing and lengthen hospital stays, increasing the costs to patients. Long-term antibiotic use can also result in minor and major complications, such as diarrhea, antibiotic resistance, or life-threatening leukopenia. Multidrug-resistant (MDR) bacteria make wound treatment even more difficult. Traditionally, surgeons thought that adequate infection control should be established before soft tissue coverage. However, wounds infected by MDR do not heal well with this traditional method and there are no optimal treatment guidelines for MDR bacteria-contaminated wounds.We reviewed 203 patients who underwent vascularized flap surgery from 2012 to 2019 to cover wounds. Class IV and I wounds were compared according to the Centers for Disease Control and Prevention classification. Class IV was further classified as antibiotic-resistant (ARB) and antibiotic-sensitive (ASB) bacteria. Wound size, mode, location, pathogens, healing time, and basic demographics were evaluated. Data were compared using Cramer's V and one-way ANOVA or independent t tests.The average healing time was longer in the ARB (19.7 [range 7-44] days) and ASB (17.9 [range 2-36] days) groups than in the Clean group (16.5 [range 7-28] days). Healing time differed in the 3 groups (P = .036). It was longer in the class IV group than in the class I group (P = .01). However, it was not statistically different between the ARB and ASB groups (P = .164).In our study the difference in healing time was small when vascularized tissue transfer was done in ARB-infected wound compared with ASB-infected and clean wound. It is necessary to perform surgery using vascularized tissue for the infected wound of antibiotic-resistant bacteria.
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http://dx.doi.org/10.1097/MD.0000000000025907DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8202535PMC
June 2021

Effect of pravastatin on erythrocyte membrane fatty acid contents in patients with chronic kidney disease.

Kidney Res Clin Pract 2021 Sep 26;40(3):392-400. Epub 2021 May 26.

Department of Internal Medicine, Dong-A University, Busan, Republic of Korea.

Background: Statin treatment has decreased the risk of cardiovascular events in patients with chronic kidney disease (CKD). Erythrocyte membrane oleic acid level is higher in patients with acute coronary syndrome. This study aimed to evaluate the effect of pravastatin on the erythrocyte membrane fatty acid (FA) contents in patients with CKD.

Methods: Sixty-two patients were enrolled from January 2017 to March 2019 (NCT02992548). Pravastatin was initially administered at a dose of 20 mg for 24 weeks. The pravastatin dose was increased to 40 mg after 12 weeks if it was necessary to control dyslipidemia. The primary outcome was change in erythrocyte membrane FA, including oleic acid, after pravastatin treatment for 24 weeks.

Results: Forty-five patients finished this study, and there was no adverse effect related to pravastatin. Compared with baseline, total cholesterol and low-density lipoprotein cholesterol levels were significantly decreased after pravastatin treatment. Compared with baseline, saturated FA, oleic acid, and arachidonic acid levels were significantly increased and polyunsaturated FA and linoleic acid (LA) levels were significantly decreased after pravastatin treatment. There was also a decrease in eicosapentaenoic acid after pravastatin treatment in CKD patients with estimated glomerular filtration rate <60 mL/min/1.73 m2.

Conclusion: Administration of pravastatin in patients with CKD leads to a decrease in FA known to be protective against the risk of CVD. Omega-3 FA or LA supplementation might be necessary to recover changes in erythrocyte membrane FA contents when pravastatin is used for treating dyslipidemia in patients with CKD.
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http://dx.doi.org/10.23876/j.krcp.20.247DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8476301PMC
September 2021

[How Should We Do Different Approach to Treat Inflammatory Bowel Disease by Gender Difference?]

Authors:
Seong-Eun Kim

Korean J Gastroenterol 2021 05;77(5):241-247

Department of Internal Medicine, Ewha Womans University College of Medicine, Seoul, Korea.

Although not as prominent, there are gender/sex differences in incidence/prevalence, clinical manifestation and disease course, comorbidities, therapeutic response, and patients coping strategy to the disease of inflammatory bowel disease (IBD). In this review, current knowledge about gender-specific differences in IBD would be provided and how to apply this in clinical practice be discussed.
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http://dx.doi.org/10.4166/kjg.2021.064DOI Listing
May 2021

A multilayered blood vessel/tumor tissue chip to investigate T cell infiltration into solid tumor tissues.

Lab Chip 2021 06;21(11):2142-2152

Department of Materials Science and Engineering, Research Institute of Advanced Materials (RIAM), Institute of Engineering Research, Bio-MAX Institute, Seoul National University, 1 Gwanak-ro, Gwanak-gu, Seoul 08826, Republic of Korea.

Cancer immunotherapies based on the ability of T cells to recognize and kill tumor cells (TCs), including immune checkpoint blockade (ICB) therapy and chimeric antigen receptor (CAR) T cell therapy, have been greatly successful recently, but they are applicable for only a fraction of patients. One of the main challenges in cancer immunotherapy is the improvement of T cell infiltration into solid tumor tissues, as T cells can exert cytotoxicity against TCs only when they are in contact with TCs. T cells in the bloodstream infiltrate into solid tumor tissues by following two steps known as extravasation and interstitial migration. Herein, we developed a multilayered blood vessel/tumor tissue chip (MBTC) that allows systematic investigation on T cell tumor infiltration. The MBTC is composed of a top fluidic chamber, a porous membrane covered with an endothelial cell (EC) monolayer, and a collagen gel block encapsulating TCs. The full sequence of T cell tumor infiltration, including extravasation and interstitial migration, required for TC killing is demonstrated in the MBTCs: T cells applied through the top fluidic chamber of the MBTCs exhibited dynamic interactions with ECs for extravasation, including intraluminal crawling and transendothelial migration (TEM). After extravasation, T cells migrate toward TCs located at the bottom of a collagen block to kill them. Key characteristics of T cell dynamics in tumor microenvironments are recapitulated in the MBTCs: the vascular endothelial growth factor (VEGF) produced by TCs suppressed EC activation by inflammatory cytokines, or induced EC anergy, thereby significantly reducing T cell extravasation, whereas chemokines produced by TCs triggered T cell chemotaxis toward TCs. Anti-VEGF treatment in the MBTCs reverts EC anergy and promotes T cell infiltration, similar to the clinical effects of anti-VEGF. The MBTC is a useful model for pre-clinical evaluation of immunotherapeutics and the fundamental study of tumor immunology.
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http://dx.doi.org/10.1039/d1lc00182eDOI Listing
June 2021

Risk Factors and a Scoring System to Predict ARDS in Patients with COVID-19 Pneumonia in Korea: A Multicenter Cohort Study.

Dis Markers 2021 9;2021:8821697. Epub 2021 Apr 9.

Department of Infectious Diseases, Chonnam National University Hospital, Gwangju, Republic of Korea.

Predictive studies of acute respiratory distress syndrome (ARDS) in patients with coronavirus disease 2019 (COVID-19) are limited. In this study, the predictors of ARDS were investigated and a score that can predict progression to ARDS in patients with COVID-19 pneumonia was developed. All patients who were diagnosed with COVID-19 pneumonia between February 1, 2020, and May 15, 2020, at five university hospitals in Korea were enrolled. Their demographic, clinical, and epidemiological characteristics and the outcomes were collected using the World Health Organization COVID-19 Case Report Form. A logistic regression analysis was performed to determine the predictors for ARDS. The receiver operating characteristic (ROC) curves were constructed for the scoring model. Of the 166 patients with COVID-19 pneumonia, 37 (22.3%) patients developed ARDS. The areas under the curves for the infiltration on a chest X-ray, C-reactive protein, neutrophil/lymphocyte ratio, and age, for prediction of ARDS were 0.91, 0.90, 0.87, and 0.80, respectively (all < 0.001). The COVID-19 ARDS Prediction Score (CAPS) was constructed using age (≥60 years old), C-reactive protein (≥5 mg/dL), and the infiltration on a chest X-ray (≥22%), with each predictor allocated 1 point. The area under the curve of COVID-19 ARDS prediction score (CAPS) for prediction of ARDS was 0.90 (95% CI 0.86-0.95; < 0.001). It provided 100% sensitivity and 75% specificity when the CAPS score cutoff value was 2 points. CAPS, which consists of age, C-reactive protein, and the area of infiltration on a chest X-ray, was predictive of the development of ARDS in patients with COVID-19 pneumonia.
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http://dx.doi.org/10.1155/2021/8821697DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8052177PMC
April 2021

Omega-3 Fatty Acids Upregulate SIRT1/3, Activate PGC-1α via Deacetylation, and Induce Nrf1 Production in 5/6 Nephrectomy Rat Model.

Mar Drugs 2021 Mar 26;19(4). Epub 2021 Mar 26.

Department of Internal Medicine, Dong-A University, Busan 49201, Korea.

Mitochondrial dysfunction contributes to the pathogenesis of kidney injury related with cardiovascular disease. Peroxisome proliferator-activated receptor gamma coactivator-1 alpha (PGC-1α) protects renal tubular cells by upregulating nuclear factor erythroid 2-related factor 2 (Nrf2). AMP-activated protein kinase (pAMPK)-mediated phosphorylation and sirtuin 1/3 (SIRT1/3)-mediated deacetylation are required for PGC-1α activation. In the present study, we aimed to investigate whether omega-3 fatty acids (FAs) regulate the expression of mediators of mitochondrial biogenesis in 5/6 nephrectomy (Nx) rats. Male Sprague-Dawley rats were assigned to the following groups: sham control, Nx, and Nx treated with omega-3 FA. The expression of PGC-1α, phosphorylated PGC-1α (pPGC-1α), acetylated PGC-1α, and factors related to mitochondrial biogenesis was examined through Western blot analysis. Compared to the control group, the expression of PGC-1α, pAMPK, SIRT1/3, Nrf1, mTOR, and Nrf2 was significantly downregulated, and that of Keap 1, acetylated PGC-1α, and FoxO1/3, was significantly upregulated in the Nx group. These changes in protein expression were rescued in the omega-3 FA group. However, the expression of pPGC-1α was similar among the three groups. Omega-3 FAs may involve mitochondrial biogenesis by upregulating Nrf1 and Nrf2. This protective mechanism might be attributed to the increased expression and deacetylation of PGC-1α, which was triggered by SIRT1/3.
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http://dx.doi.org/10.3390/md19040182DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8066610PMC
March 2021

Clinical and Virologic Effectiveness of Remdesivir Treatment for Severe Coronavirus Disease 2019 (COVID-19) in Korea: a Nationwide Multicenter Retrospective Cohort Study.

J Korean Med Sci 2021 Mar 22;36(11):e83. Epub 2021 Mar 22.

Division of Infectious Diseases, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.

Background: Remdesivir is widely used for the treatment of coronavirus disease 2019 (COVID-19), but controversies regarding its efficacy still remain.

Methods: A retrospective cohort study was conducted to evaluate the effect of remdesivir on clinical and virologic outcomes of severe COVID-19 patients from June to July 2020. Primary clinical endpoints included clinical recovery, additional mechanical ventilator (MV) support, and duration of oxygen or MV support. Viral load reduction by hospital day (HD) 15 was evaluated by calculating changes in cycle threshold (Ct) values.

Results: A total of 86 severe COVID-19 patients were evaluated including 48 remdesivir-treated patients. Baseline characteristics were not significantly different between the two groups. Remdesivir was administered an average of 7.42 days from symptom onset. The proportions of clinical recovery of the remdesivir and supportive care group at HD 14 (56.3% and 39.5%) and HD 28 (87.5% and 78.9%) were not statistically different. The proportion of patients requiring MV support by HD 28 was significantly lower in the remdesivir group than in the supportive care group (22.9% vs. 44.7%, = 0.032), and MV duration was significantly shorter in the remdesivir group (average, 1.97 vs. 5.37 days; = 0.017). Analysis of upper respiratory tract specimens demonstrated that increases of Ct value from HD 1-5 to 11-15 were significantly greater in the remdesivir group than the supportive care group (average, 10.19 vs. 5.36; = 0.007), and the slope of the Ct value increase was also significantly steeper in the remdesivir group (average, 5.10 vs. 2.68; = 0.007).

Conclusion: The remdesivir group showed clinical and virologic benefit in terms of MV requirement and viral load reduction, supporting remdesivir treatment for severe COVID-19.
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http://dx.doi.org/10.3346/jkms.2021.36.e83DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7985289PMC
March 2021

User-friendly image-activated microfluidic cell sorting technique using an optimized, fast deep learning algorithm.

Lab Chip 2021 05;21(9):1798-1810

Department of Mechanical Engineering, Pohang University of Science and Technology, Pohang (POSTECH), 77, Cheongam-ro, Nam-gu, Pohang, Gyeongbuk 37673, South Korea.

Image-activated cell sorting is an essential biomedical research technique for understanding the unique characteristics of single cells. Deep learning algorithms can be used to extract hidden cell features from high-content image information to enable the discrimination of cell-to-cell differences in image-activated cell sorters. However, such systems are challenging to implement from a technical perspective due to the advanced imaging and sorting requirements and the long processing times of deep learning algorithms. Here, we introduce a user-friendly image-activated microfluidic sorting technique based on a fast deep learning model under the TensorRT framework to enable sorting decisions within 3 ms. The proposed sorter employs a significantly simplified operational procedure based on the use of a syringe connected to a piezoelectric actuator. The sorter has a 2.5 ms latency. The utility of the sorter was demonstrated through real-time sorting of fluorescent polystyrene beads and cells. The sorter achieved 98.0%, 95.1%, and 94.2% sorting purities for 15 μm and 10 μm beads, HL-60 and Jurkat cells, and HL-60 and K562 cells, respectively, with a throughput of up to 82.8 events per second (eps).
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http://dx.doi.org/10.1039/d0lc00747aDOI Listing
May 2021

Simultaneous Synthesis and Consolidation of Nanostructured HfB₂-SiC Composite.

J Nanosci Nanotechnol 2021 Jul;21(7):4011-4015

Division of Advanced Materials Engineering, The Research Center of Hydrogen Fuel Cell, Jeonbuk National University, 567 Baekje-daero, Deokjin-gu, Jeonju-si, Jeollabuk-do 54896, Republic of Korea.

A dense nanostructured 2HfB₂-SiC composite was simultaneously synthesized and consolidated by the pulsed current activated sintering method in one step within very short time (two minutes) from mechanically activated 2Hf, B₄C and Si powders. Simultaneous combustion synthesis and consolidation were achieved through the combination of the effects of the pulsed current and mechanical pressure. A highly dense 2HfB₂-SiC composite with 97.5% relative density was achieved under the simultaneous application of a pressure of 80 MPa and the pulsed current. The fracture toughness of the 2HfB₂-SiC composite was higher than that of monolithic HfB₂.
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http://dx.doi.org/10.1166/jnn.2021.19243DOI Listing
July 2021

The Effect of Ball Milling on Properties and Sintering of Nanostructured TiB₂.

J Nanosci Nanotechnol 2021 Jul;21(7):3934-3937

Division of Advanced Materials Engineering and Research Center of Hydrogen Fuel Cell, Jeonbuk National University, Jeonju-si, Jeollabuk-do, 54896, Republic of Korea.

TiB₂ powder was milled in a high-energy ball mill (Pulverisette-5 planetary mill) at 250 rpm for various time periods (0, 1, 4, and 10 h) and consolidated by the high frequency induction heated sintering (HFIHS). The effect of milling on the sintering behavior and crystallite size of TiB₂ powders were investigated. A nanostructured dense TiB₂ specimen with a relative density of up to 98% was readily achieved within very short time (two min). The ball milling effectively refined the crystallite structure of TiB₂ powders and facilitated the subsequent consolidation. The sinter-onset temperature was reduced remarkably by the prior milling for 10 h. Accordingly, the relative density and mechanical properties of TiB₂ compact increased as the milling time increased.
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http://dx.doi.org/10.1166/jnn.2021.19246DOI Listing
July 2021

Mechanical Properties and Rapid Sintering of Nanostructured WC-Al₂O₃-Al Hard Materials.

J Nanosci Nanotechnol 2021 07;21(7):3929-3933

Division of Advanced Materials Engineering, The Research Center of Hydrogen Fuel Cell, Jeonbuk National University, 567 Baekje-daero, Deokjin-gu, Jeonju-si, Jeollabuk-do 54896, Republic of Korea.

Nanostructured WC-Al₂O₃-Al composites was sintered using rapid high-frequency induction heated sintering (HFIHS) and the mechanical properties such as hardness and fracture toughness with consolidation were investigated. The HFIHS method induced a very fast densification nearly at the level of theoretical density and successfully prohibited grain growth, resulting in nano-sized grains. The fracture toughness was improved due to the consolidation facilitated by adding Al to WC-Al₂O₃ matrix. The WC-Al₂O₃ composites added with 5 and 10 vol.% Al showed higher hardness and fracture toughness compared with that of WC-Al₂O₃.
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http://dx.doi.org/10.1166/jnn.2021.19244DOI Listing
July 2021

Effects of steroid therapy in patients with severe fever with Thrombocytopenia syndrome: A multicenter clinical cohort study.

PLoS Negl Trop Dis 2021 02 19;15(2):e0009128. Epub 2021 Feb 19.

Department of Internal Medicine, College of Medicine, Chosun University, Gwangju, Republic of Korea.

Background: Severe fever with thrombocytopenia syndrome (SFTS) is an acute, febrile, and potentially fatal tick-borne disease caused by the SFTS Phlebovirus. Here, we evaluated the effects of steroid therapy in Korean patients with SFTS.

Methods: A retrospective study was performed in a multicenter SFTS clinical cohort from 13 Korean university hospitals between 2013 and 2017. We performed survival analysis using propensity score matching of 142 patients with SFTS diagnosed by genetic or antibody tests.

Results: Overall fatality rate was 23.2%, with 39.7% among 58 patients who underwent steroid therapy. Complications were observed in 37/58 (63.8%) and 25/83 (30.1%) patients in the steroid and non-steroid groups, respectively (P < .001). Survival analysis after propensity score matching showed a significant difference in mean 30-day survival time between the non-steroid and steroid groups in patients with a mild condition [Acute Physiology and Chronic Health Evaluation II (APACHE II) score <14; 29.2 (95% CI 27.70-30.73] vs. 24.9 (95% CI 21.21-28.53], P = .022]. Survival times for the early steroid (≤5 days from the start of therapy after symptom onset), late steroid (>5 days), and non-steroid groups, were 18.4, 22.4, and 27.3 days, respectively (P = .005).

Conclusions: After steroid therapy, an increase in complications was observed among patients with SFTS. Steroid therapy should be used with caution, considering the possible negative effects of steroid therapy within 5 days of symptom onset or in patients with mild disease (APACHE II score <14).
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http://dx.doi.org/10.1371/journal.pntd.0009128DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7928499PMC
February 2021
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