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This study investigated natal factors influencing developmental defects of enamel (DDE) in premature infants using a newly refined preterm developmental defects of enamel (PDDE) index. Dental examinations were conducted on a cohort of 118 preterm infants (average age 3.5 ± 1.4 years) to record PDDE scores, while reviewing their medical records to examine natal factors. According to the logistic regression analysis, factors related to DDE prevalence were advanced maternal age, gestational age < 28 weeks, birth weight < 1000 g, 1 min APGAR score < 7, and hospitalization period > 2 months, which were significantly higher by 2.91, 5.53, 7.63, 10.02, and 4.0 times, respectively. According to regression analysis with generalized linear models, the PDDE scores were approximately 7.65, 4.96, and 15.0 points higher in premature children diagnosed with bronchopulmonary dysplasia, intraventricular hemorrhage, and necrotizing enterocolitis, respectively. When endotracheal intubation was performed, the PDDE score was 5.06 points higher. The prevalence of PDDE was primarily observed bilaterally in the maxillary anterior teeth. Extremely preterm infants showed significantly delayed tooth eruption, suggesting that the influence of gestational age on dental development rates. Identifying the factors related to DDE in premature children can inform early dental interventions to support the oral health of high-risk children. [ABSTRACT FROM AUTHOR]

Purpose: This study aimed to analyze pharyngeal reflux episodes in patients with suspected LPR versus healthy subjects using 24-h MII-pH monitoring. Methods: One hundred twenty-one patients who visited our clinic with a chief complaint of LPR-related symptoms and underwent 24-h MII-pH monitoring were enrolled prospectively. Also, 27 healthy subjects were enrolled and underwent 24-h MII-pH monitoring during the same period. We analyzed sensitivity, specificity, and accuracy comprehensively to determine appropriate cut-off values of pharyngeal reflux episodes in 24-h MII-pH monitoring to diagnose patients with LPR. Results: Twenty-nine of 121 patients with suspected LPR showed no pharyngeal reflux episodes, while 92 showed more than one pharyngeal reflux event. In contrast, the 22 healthy subjects showed no pharyngeal reflux episodes, three showed one reflux event, and two showed two reflux events. A cut-off value of ≥ 1 showed best accuracy reflected by combined sensitivity and specificity values, while ≥ 2 demonstrated better specificity with slight loss of sensitivity and slightly lower overall accuracy, suggesting cut-off value of ≥ 1 pharyngeal reflux episodes is a good clinical indicator. Conclusion: A cut-off value of ≥ 1 in pharyngeal reflux episodes on 24-h MII-pH monitoring in patients with suspected LPR might be an acceptable diagnostic tool for LPR. [ABSTRACT FROM AUTHOR]

Objective: To estimate the risk of developing autoimmune disease in patients diagnosed having recurrent aphthous stomatitis (RAS) through a nationwide population‐based cohort study. Methods: This study included two group of patients who had three or more episodes with aphthae diagnosed from their physician (RAS group) and a similar matched group of patients without aphthae (control group). Both groups were collected within the period of 2005–2007 from the Korean National Health Insurances claims database. Non‐RAS cohort was matched after frequency matching. The final enrolled subjects were observed during a follow‐up period from 2008 to 2015 and those who received autoimmune diseases diagnoses during follow‐up were identified. The hazard ratio (HR) for developing autoimmune diseases was estimated. Results: A total of 4,637 patients with RAS and 4,637 controls were included. The risk of overall autoimmune diseases was significantly increased in the RAS group (adjusted HR [aHR)], 1.19). With regard to each disease entity, patients with RAS showed an increased risk of Behcet's disease (31.16), systemic lupus erythematous (SLE) (1.74), ankylosing spondylitis (AS) (1.47), gout (1.47), Hashimoto thyroiditis (1.42), Graves' disease (1.37), and rheumatoid arthritis (RA) (1.19). Conclusion: RAS‐like lesion may be an early sign of systemic autoimmune disease, as it was associated with an increased risk of Graves' disease, Hashimoto thyroiditis, SLE, AS, gout, RA, and Behcet's disease from real‐world data. [ABSTRACT FROM AUTHOR]

Background Obesity and metabolic syndrome (MetS) are prevalent among chronic kidney disease (CKD) patients. However, it is unclear whether obesity without MetS is associated with a higher risk of adverse clinical outcomes in CKD patients. Methods We searched the National Health Insurance Service database of Korea for patients who underwent national health screenings in 2009–11 and identified 59 725 CKD patients. Obesity was defined as a body mass index ≥25 kg/m2. MetS was defined as the presence of three or more metabolic risks. Results The cumulative event rate of cardiovascular (CV) events, progression to end-stage kidney disease (ESKD) and all-cause mortality was the lowest among obese patients without MetS (all P  < .001). In multivariable analysis, obese (versus non-obese) patients without MetS were not at increased risks of CV events [adjusted hazard ratio (HR) 1.02 (95% confidence interval 0.94–1.11)] or progression to ESKD [0.92 (0.77–1.09)]. Their risk of all-cause mortality was significantly decreased [0.82 (0.75–0.90)]. These findings were consistently observed in overweight, obese and morbidly obese patients without MetS. Moreover, despite a linear increase in HR for each additional metabolic abnormality in both obese and non-obese patients, the slope of HR increase for CV events was significantly slower in obese patients (P for interaction = .038). Conclusions Obesity without MetS did not increase the risk of CV complications or progression to ESKD. The healthy effect of obesity on all-cause mortality risk and its weakening effect on the association between metabolic hazards and CV risk should be considered in CKD patients. [ABSTRACT FROM AUTHOR]

Comparing to data in patients with severe coronavirus diseases 2019 (COVID-19), there are few studies on the prevalence anxiety and/or depression in patients with asymptomatic or mildly symptomatic COVID-19. We investigated the clinical characteristics and the prevalence of anxiety and/or depression among asymptomatic or mildly symptomatic patients with COVID-19 and monitored their mental health using an online assessment. An online survey for monitoring and assessing the mental health of patients with COVID-19 using a mobile phone was conducted. We used the Hospital Anxiety and Depression Scale to measure anxiety and/or depression levels. Of the 234 patients, 66 patients were asymptomatic (28.2%), while the remaining 168 patients were mildly symptomatic. The prevalence of anosmia (p = 0.001) and ageusia (p = 0.008) significantly decreased with the increasing age. In addition, 19.8% and 14.0% patients had anxiety and/or depression in the first survey, and one week after the first survey, respectively. Compared to patients without anxiety and/or depression, those with anxiety and/or depression had a longer quarantine duration. We found that anomia and ageusia were relatively common in the young age group. Furthermore, one-fifth asymptomatic or mildly symptomatic patients with COVID-19 had anxiety and/or depression. [ABSTRACT FROM AUTHOR]

Although alcohol consumption is known to affect the incidence of diabetes mellitus (DM), reports on the effects of moderate alcohol consumption on DM incidence have been inconsistent. This community-based prospective cohort study was performed to investigate the incidence of DM in male Korean moderate alcohol drinkers. The Ansan and Ansung cohort was used for the analysis. The study population included a total of 3,492 men with no history of DM. The subjects were classified as mild (1–14 g/d), moderate (15–29 g/d), and heavy (≥30 g/d) drinkers based on their amount of alcohol consumption. The incidence rates of DM in the three groups were compared and analyzed over a 10 year follow-up period. The hazard ratios (HRs) for DM incidence were 25.12 (95% confidence interval [CI], 21.73–28.90) per 1,000 person years (PY) in mild drinkers, 31.13 (26.11–36.83) per 1,000 PY in moderate drinkers, and 31.68 (26.81–37.18) per 1,000 PY in heavy drinkers (p for trend, p = 0.043). Multivariate regression analysis showed that the HRs (95% CI) for DM were 1.25 (0.97–1.61, p = 0.086) in moderate drinkers and 1.30 (1.01–1.68, p = 0.045) in heavy drinkers compared to mild drinkers. The changes in pancreatic insulin secretion were more remarkable than those in insulin resistance in all three groups. The incidence of DM in male Korean moderate drinkers did not increase significantly over the observation period. However, the incidence of DM tended to increase with increasing alcohol consumption. Pancreatic insulin secretion may play a more important role than insulin resistance in the relationship between alcohol and incidence of DM. [ABSTRACT FROM AUTHOR]

• Late-onset PCP after routine prophylaxis post-LT remains a lethal infection. • Old age, CMV infection, steroid pulse, and lymphopenia were associated with PCP. • HCC recurrence was additionally found to be a risk factor for PCP in LT recipients. • Targeted prophylaxis could improve the prevention of this lethal complication. The risk factors for late-onset Pneumocystis jirovecii pneumonia (PCP) after liver transplantation (LT) have not been well studied. We aimed to analyze the clinical features preceding PCP in LT recipients that would guide individualized prophylaxis. Among 742 patients who underwent LT and routine PCP prophylaxis from January 2009 through December 2019 at Severance Hospital, 27 patients developed PCP. We conducted a retrospective case-control study matching each patient with four controls and analyzed the risk factors for late-onset PCP. After 6 months, post-transplant PCP cases increased steadily with an overall incidence of 6.36 cases per 1000 patient-year. The PCP-related mortality was 37.0%. In the multivariate analyses, age at LT ≥65 years (odds ratio [OR], 13.305; 95% confidence interval [CI], 2.507-70.618; P = 0.002), cytomegalovirus infection (OR, 5.390; 95% CI, 1.602-18.132; P = 0.006), steroid pulse therapy (OR, 6.564; 95% CI, 1.984-21.719; P = 0.002), hepatocellular carcinoma recurrence (OR, 18.180; 95% CI, 3.420-96.636; P = 0.001), and lymphocytopenia (OR, 3.758; 95% CI, 1.176-12.013; P = 0.026) were independently associated with PCP. Late-onset PCP after routine prophylaxis after LT remains a lethal infection and is associated with age ≥65 years at LT, cytomegalovirus infection, steroid pulse therapy, hepatocellular carcinoma recurrence, and lymphocytopenia. Targeted prophylaxis considering these risk factors could improve the prevention of this potentially lethal complication. [Display omitted] [ABSTRACT FROM AUTHOR]

Aim To evaluate the relationship between human cytomegalovirus ( HCMV) antibody status, and hypertension and functional status among elderly Koreans. Methods Patients aged ≥65 years were prospectively enrolled from March 2011 to February 2012 at a 2000-bed university hospital. We collected data including CD4+ and CD8+ T-lymphocyte count, and functional status by measuring basic activities of daily living and instrumental activities of daily living for all patients. In addition, HCMV immunoglobulin G levels were analyzed using enzyme-linked fluorescent assay. Results During the study period, 103 patients (51 men), who were admitted for treatment of infections or other diseases, were enrolled. Multivariate analysis showed that body mass index and HCMV immunoglobulin G antibody titers were independent factors associated with hypertension in elderly patients ( OR 1.347, 95% CI 1.113-1.630, P = 0.002; OR 1.023, 95% CI 1.001-1.047, P = 0.042, respectively). In univariate linear correlations, HCMV antibody levels were positively correlated with systolic blood pressure levels ( r = 0.303, P = 0.002), CD8+ T-lymphocyte count ( r = 0.313, P = 0.001) and instrumental activities of daily living scores ( r = 0.217, P = 0.028). In addition, HCMV immunoglobulin G titers were inversely associated with estimated glomerular filtration rate ( r = −0.268, P = 0.006). These four variables remained independently significant in multivariate correlation analysis. Conclusion These findings could provide insight into the important role of HCMV in the pathogenesis of essential hypertension and decreased functional status in the elderly. Geriatr Gerontol Int 2016; 16: 21-27. [ABSTRACT FROM AUTHOR]

Invasive mucormycosis is an uncommon but increasing life-threatening fungal infection. The present study investigated clinical characteristics and mortality among patients diagnosed as invasive mucormycosis infection. We retrospectively reviewed a total of 24 histologically proven cases of invasive mucormycosis at two tertiary care referral hospitals between November 2005 and February 2014. Overall survival was 50% ( n = 12). The time between onset of symptom and diagnostic procedure proved to be associated with mortality ( P = 0.009). In addition, preexisting renal failure and thrombocytopenia demonstrated trends toward a poor outcome in our study ( P = 0.089 and 0.065, respectively). On multivariate regression analysis, delayed diagnostic procedure (more than 16 days after the onset of symptoms) was an independent predictor of mortality (OR= 12.34, 95% CI, 1.43-10.64; P = 0.022). Mucormycosis is a destructive fungal infection that is associated with high mortality rates, ranging from 40% to 100% depending on the form of disease. When a clinician suspects invasive mucormycosis infection, an early diagnostic procedure performed within 16 days from the onset of symptom and early initiation of antifungal therapy will lead to successful management of this highly fatal disease. [ABSTRACT FROM AUTHOR]

Background Recent studies have implicated human cytomegalovirus (HCMV) infection as a possible etiological factor in cardiovascular disease. We assessed whether anti-HCMV antibody levels are associated with carotid atherosclerosis and inflammatory cytokine production in elderly Koreans. Methods Participants (age, ≥ 65 years) were prospectively enrolled from September 2012 to July 2013 at a 2000-bed university hospital. During the study period, 71 participants (29 males) were prospectively enrolled, and thirty-five (49.3%) of these individuals were in the group designated as high intima–media thickness (IMT). Results Multivariate logistic regression analysis revealed three independent risk factors of high IMT: higher levels of anti-HCMV antibody (odds ratio [OR] 1.04, p = 0.003), Framingham score (OR 1.14, p = 0.018), and levels of IL-1β (OR 2.96, p = 0.013). Anti-HCMV antibody levels had a significantly positive correlation with max-IMT ( r = 0.523, p < 0.001), free T 4 levels ( r = 0.315, p = 0.021), and Log(TNF-α) ( r = 0.562, p < 0.001) in multivariate correlation analysis. Conclusions These findings may provide insight into the role of HCMV in the pathogenesis of atherosclerosis and chronic inflammation in elderly individuals. [ABSTRACT FROM AUTHOR]

The incidence of carbapenem-resistant Pseudomonas aeruginosa (CRPA) bacteremia has increased in recent years, and infections caused by CRPA result in higher mortality than those caused by susceptible strains. This study was performed to evaluate the risk factors for mortality and to study the impact of virulence factors and bacterial strains on clinical outcomes in patients with CRPA bacteremia. Data on 63 episodes of CRPA bacteremia that have occurred between January 1, 2007, and December 31, 2009, in a teaching hospital (2000 beds) in Seoul, Korea, were analyzed. The Acute Physiology and Chronic Health Evaluation II (APACHE II) score at the time of CRPA bacteremia and the capacity of CRPA to form biofilm were independent predictive factors for mortality in patients with CRPA bacteremia. In addition, the biofilm-forming ability and elastase activity of strains were correlated with APACHE II scores to measure the severity of disease and estimate predicted mortality in the patients. [ABSTRACT FROM AUTHOR]

Abstract: The clinical significance of humoral immune response to nosocomial pathogens and functional status in elderly patients with sepsis is not clear. We evaluated the humoral immune to nosocomial pathogens and the effect of functional dependencies on clinical outcomes among elderly patients with sepsis. This study prospectively enrolled patients aged ≥65 years with sepsis from September 2011 to May 2012 at a 2000-bed university hospital. The data including CD4 and CD8 T-cell count, functional status by measuring basic activities of daily living (ADL) and instrumental activities of daily living (IADL) were collected for all patients. In addition, the collected blood samples were analyzed for serum antibody levels against nosocomial pathogens using an ELISA. During the study period, 72 patients (38 males) treated with sepsis were enrolled. The all-cause in-hospital mortality rate was 16.7% (12/72). The mean CD4/CD8 T-cell ratio was significantly lower in nonsurvivors than in survivors (1.08±0.72 vs. 1.93±1.42, P =0.003). Serum antibody titers to Acinetobacter baumannii, Klebsiella pneumonia, Stenotrophomonas maltophilia, and Enterococcus faecalis were statistically higher in nonsurvivors than in survivors. On multivariate analysis, the IADL score was independently predictive of mortality in elderly patients with sepsis (odds ratio 1.410, 95% confidence interval 1.007–1.975, P =0.046). These results suggest that IADL scores could be used as predictors to identify elderly patients with a poor prognosis of nosocomial infections. [Copyright &y& Elsevier]

Background: Surgical site infection (SSI) is a potentially morbid and costly complication of surgery. We conducted a multicentre case-control study to determine the risk factors for SSI in patients undergoing gastric surgery and to establish strategies to reduce the risk of SSI. Methods: Between January 2007 and December 2008, 121 patients who developed an SSI after gastric surgery were matched with controls who had undergone surgery on the dates closest to those of the cases, at 13 centres in Korea. Results: The results of multivariate analyses showed that the independent risk factors for SSI after gastric surgery were older age ( p = 0.016), higher body mass index (BMI) ( p = 0.033), male gender ( p = 0.047), and longer duration of prophylactic antibiotic use ( p < 0.001). Conclusion: Older age, higher BMI, male gender, and longer duration of prophylactic antibiotic use were independently associated with significant increases in the risk of SSI. Additional prospective randomized studies are required to confirm these results. [ABSTRACT FROM AUTHOR]

Abstract: Objective: Combined antiretroviral therapy (cART) has significantly improved the survival rate and quality of life for HIV-infected subjects, but it contributes to the development of metabolic complications including coronary artery disease (CAD). Recent studies have reported that high plasma levels of the soluble receptor for advanced glycation end products (sRAGE) were associated with a lower incidence of CAD in non-HIV infected patients. However, there has been no report of an association of sRAGE and subclinical carotid atherosclerosis in HIV-infected patients receiving cART. Methods: We examined the association of circulating sRAGE in HIV-infected patients with carotid intima–media thickness (IMT) and other metabolic variables. We prospectively enrolled 76 HIV-infected patients receiving cART for ≥6 months. Results: sRAGE had a significantly negative correlation with body mass index (r =−0.324, p =0.005), waist-to-hip ratio (r =−0.335, p =0.003), systolic blood pressure (BP) (r =−0.359, p =0.002), diastolic BP (r =−0.343, p =0.004), total cholesterol (r =−0.240, p =0.037), low-density lipoprotein-cholesterol (r =−0.284, p =0.024), log(homeostasis model assessment of insulin resistance [HOMA-IR]) (r =−0.380, p =0.002) and carotid IMT including max-IMT and mean-IMT (r =−0.358, p =0.001 and r =−0.329, p =0.004, respectively). By the use of multiple stepwise regression analyses, systolic BP (p =0.001) and log[HOMA-IR] (p =0.001) remained significant independently. Conclusions: These results suggest that sRAGE may have a protective effect against subclinical atherosclerosis by preventing inflammatory responses mediated by the activation of cell surface RAGE in HIV-infected patients receiving cART. [Copyright &y& Elsevier]

Background: Among Jamaican women, cervical cancer is the second leading cause of cancer mortality but factors that facilitate follow-up of women receiving abnormal Pap smear results are not known. We examined whether socio-demographic factors, factors reported by the women, and assistance received for follow-up facilitate adequate follow-up of abnormal Pap smears.Methods: One hundred and twenty-one women who had abnormal Pap results during June 1998-September 2005 in Portland, Jamaica were interviewed to identify determinants of adequate follow-up. Chi-square, t-test and multivariable logistic regression analysis were used to identify determinants.Results: Only half of the women in this sample sought adequate follow-up. These women had a lower number of surviving children, higher monthly income, and perceived the cost of services to be inexpensive. Advice about the timing of the follow-up activity and the next step to take by the healthcare workers were significant determinants of adequate follow-up. Women who received advice on the timing of follow-up were almost six times (adjusted OR: 5.99, 95% CI: 1.17, 30.66, p<0.05) more likely to seek adequate follow-up after adjusting for other factors.Conclusions: Perceived low cost of services as well as assistance provided by healthcare workers regarding follow-up action helps to facilitate adequate follow-up of abnormal Pap smear results. [ABSTRACT FROM AUTHOR]

Infection is a major cause of mortality in patients with systemic lupus erythematosus (SLE). This study describes infectious complications in SLE patients and analyzes the risk factors for infection at the time of SLE diagnosis and during the course of SLE in a case-control study. Of 110 patients enrolled, 42 (38%) had at least 1 episode of infectious disease. The incidence of infectious disease was 4.4/100 patient-years (py) with a total follow-up duration of 954 y. In multivariate analysis, independent predictors of infection at the time of SLE diagnosis were an SLE disease activity index (SLEDAI) > 12 (p = 0.01), C3 levels < 90 mg/dl (p = 0.01) and positive anti-ds DNA antibodies (p < 0.01). Frequent flare-ups (p = 0.04) and follow-up duration ≥8 y (p = 0.023) were also significant risk factors for infectious diseases. It is mandatory to closely observe SLE patients with risk factors for developing infectious diseases. [ABSTRACT FROM AUTHOR]

Abstract: Cells change their gene expression profile dynamically in various conditions. By taking the advantage of ChIP, we examined the transcription profile of Saccharomyces cerevisiae genes in response to DNA damaging agents such as MMS or 4NQO. Gene expression profiles of different groups of genes roughly correlated with that revealed by Northern blot assay or microarray method. Damage-inducible genes showed increased cross-linking signals of RNA polymerase II, TFIIH, and TFIIF, meanwhile damage repressible genes decreased them, which means that gene expression is mainly regulated at the level of transcription. Interestingly, the characteristic occupancy pattern of TFIIH and polymerase with phosphorylated carboxy-terminal domain (CTD) in promoter or in coding regions was not changed by the presence of DNA damaging agents in both non-inducible and inducible genes. ChIP data showed that the extent of phosphorylation of CTD per elongating polymerase complex was still maintained. These findings suggest that overall increase in CTD phosphorylation in response to DNA damage is attributed to the global shift of gene expression profile rather than modification of specific polymerase function. [Copyright &y& Elsevier]

Background: Little is known about the risk factors and frequency of metronidazole-associated neurological adverse events. Objective: To investigate the risk factors and frequency of metronidazole-associated neurological adverse events. Design: This retrospective study contained two parts. First, we investigated metronidazole treatment-associated neurologic adverse events by performing a population-based cohort study using the Korea Adverse Event Reporting System (KAERS) database from January 2011 to December 2020. Second, we conducted a matched case-control study based on a retrospective cohort of patients treated with metronidazole between January 2006 and July 2021 at a tertiary hospital in South Korea. The data analysis was performed from August 2021 to April 2022. Participants: In the case-control study, case patients were defined as those diagnosed with metronidazole-associated encephalopathy or peripheral neuropathy during the study period with causal assessment based on the clinical diagnoses and findings from associated tests. In a ratio of 1:3, case patients were compared to a control group of patients prescribed metronidazole without neurologic adverse events matched for age and cumulative dose of metronidazole. Main Measures: Frequency and risk factors for metronidazole-associated neurological adverse events. Key Results: Overall, 2,309 cases of neurologic adverse events were reported to the KAERS from 2011 to 2020, and the number of reported neurological adverse events showed an increasing trend. Further, 92,838 patients were prescribed metronidazole during the study period at the Severance Hospital; 54 patients were diagnosed with metronidazole-associated encephalopathy or peripheral neuropathy, 40 with central and 28 with peripheral nervous system adverse events. Liver cirrhosis, chronic kidney disease, intravenous administration, and lower body weight were identified as risk factors for these adverse events. Conclusions: The number of reported metronidazole-associated neurological adverse events are increasing. Prolonged metronidazole treatment in patients with the aforementioned factors requires careful examination for neurological adverse events. [ABSTRACT FROM AUTHOR]

Recently, sarcopenia was identified as a risk factor for non-alcoholic fatty liver disease (NAFLD) in adults. We here investigated the association between skeletal muscle mass (SMM) and NAFLD in non-obese children and adolescents. A retrospective medical chart review was performed for individuals aged 9–15 years diagnosed with NAFLD. Healthy volunteers aged 9–15 years were recruited as controls. Participants were subject to laboratory tests, abdominal sonography, and multi-frequency bioelectrical impedance analysis. SMM data were calculated as the skeletal muscle-to-body fat ratio (MFR), and the diagnosis of fatty liver was established by abdominal sonography. The control and NAFLD groups included 73 and 53 individuals, respectively. No significant difference was observed in gender and body mass index (BMI) distribution between the groups. Mean MFR was significantly lower in individuals with NAFLD than in those without (0.83 vs. 1.04, p = 0.005). After adjusting for age, sex, BMI, and serum glucose, the risk of having NAFLD was significantly associated with a decreased MFR (p = 0.016). NAFLD is significantly associated with relatively low SMM in non-obese children and adolescents. Increasing SMM, such as weight training, can be suggested as one of the treatment strategies in pediatric NAFLD without obesity. [ABSTRACT FROM AUTHOR]

Background: The coronavirus disease (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has become a major global public health issue. SARS-CoV-2 infection is confirmed by the detection of viral RNA using reverse transcription polymerase chain reaction (RT-PCR). Prolonged viral shedding has been reported in patients with SARS-CoV-2 infection, but the presence of viral RNA does not always correlate with infectivity. Therefore, the present study aimed to confirm the presence of viable virus in asymptomatic or mildly symptomatic patients in the later phase of the disease, more than two weeks after diagnosis. Method: Asymptomatic or mildly symptomatic COVID-19 patients who had been diagnosed with the disease at least two weeks previously and admitted to a community treatment center (CTC) from 15 March to 10 April 2020 were enrolled in this study. Nasopharyngeal and salivary swab specimens were collected from each patient. Using these specimens, RT-PCR assay and viral culture were performed. Result: In total, 48 patients were enrolled in this study. There were no significant differences in baseline characteristics between the asymptomatic and mildly symptomatic patient groups. RT-PCR assay and viral culture of SARS-CoV-2 were performed using nasopharyngeal and salivary swabs. The results of RT-PCR performed using salivary swab specimens, in terms of cycle threshold (Ct) values, were similar to those of RT-PCR using nasopharyngeal swab specimens. In addition, no viable virus could be cultured from swab specimens collected from the late-phase COVID-19 patients with prolonged viral RNA shedding. Conclusions: In conclusion, our study suggests that even if viral shedding is sustained in asymptomatic or mildly symptomatic patients with later phase of COVID-19, it can be expected that the transmission risk of the virus is low. In addition, saliva can be used as a reliable specimen for the diagnosis of SARS-CoV-2 infection. [ABSTRACT FROM AUTHOR]

Background. Imbalance of the gut microbiome and decrease in the number of short-chain fatty acid (SCFA)-producing bacteria often affect human health by altering intestinal and immune homeostasis. The use of probiotics has been shown to be an attractive method to modulate gut microbiota to prevent or treat intestinal dysbiosis. Likewise, this study aimed to determine whether the oral consumption of heat-treated Lactiplantibacillus plantarum nF1 (HLp-nF1) induces changes in the gut environment in healthy infants by measuring changes in fecal SCFAs. Methods. The study enrolled 43 infants aged under 2 months, with 30 infants in the HLp-nF1 group receiving HLp-nF1 orally (2.5 × 1010 cells/g/pack, daily dose of two packs) for 8 weeks. The fecal samples were collected and the questionnaires were administered at weeks 0 and 8. Results. The concentrations of the total SCFAs, acetate, propionate, and butyrate significantly increased following HLp-nF1 supplementation (P < 0.0001 , P < 0.0001 , P < 0.0001 , and P = 0.028 , respectively). Conclusions. Supplementation of HLp-nF1 has a positive effect on SCFA production and could be a potentially useful and straightforward method to manipulate SCFA formation. [ABSTRACT FROM AUTHOR]

One of the most important factors for calculating the accumulated degree days (ADD), which is used to estimate the postmortem interval (PMI) is the accurate estimation of the scene temperature after death. As the estimation method used up to now, they applied to the linear regression analysis using the temperature of the nearest weather station, but the prediction error becomes larger in the case that the ambient temperature do not follow the temperature of the station. In the present study applied we have more accurate methods such as the quadratic regression model and support vector machine (SVM) and have included weather factors such as wind capacity, wind speed and humidity, and regression method. Also, we investigate the optimal statistical method for estimating the ambient temperature in indoor and outdoor locations in Korea. [ABSTRACT FROM AUTHOR]

Genome-wide methylation profiling is used in breast cancer (BC) studies, because DNA methylation is a crucial epigenetic regulator of gene expression, involved in many diseases including BC. We investigated genome-wide methylation profiles in both canine mammary tumor (CMT) tissues and peripheral blood mononuclear cells (PBMCs) using reduced representation bisulfite sequencing (RRBS) and found unique CMT-enriched methylation signatures. A total of 2.2–4.2 million cytosine–phosphate–guanine (CpG) sites were analyzed in both CMT tissues and PBMCs, which included 40,000 and 28,000 differentially methylated regions (DMRs) associated with 341 and 247 promoters of differentially methylated genes (DMGs) in CMT tissues and PBMCs, respectively. Genes related to apoptosis and ion transmembrane transport were hypermethylated, but cell proliferation and oncogene were hypomethylated in tumor tissues. Gene ontology analysis using DMGs in PBMCs revealed significant methylation changes in the subset of immune cells and host defense system-related genes, especially chemokine signaling pathway-related genes. Moreover, a number of CMT tissue-enriched DMRs were identified from the promoter regions of various microRNAs (miRNAs), including cfa-mir-96 and cfa-mir-149, which were reported as cancer-associated miRNAs in humans. We also identified novel miRNAs associated with CMT which can be candidates for new miRNAs associated with human BC. This study may provide new insight for a better understanding of aberrant methylation associated with both human BC and CMT, as well as possible targets for methylation-based BC diagnostic markers. [ABSTRACT FROM AUTHOR]

Atopic dermatitis (AD) is associated with allergic comorbidities, such as asthma, allergic rhinitis (AR), and allergic contact dermatitis (ACD). The etiology of keloid is largely unknown; however, AD and keloid share inflammatory pathways characterized by T-helper cell 2 cytokines and increased dermal fibroblast activity. The prevalence of keloids has been reported to increase in patients with AD, but it remains controversial. This study aimed to estimate the prevalence of keloids in patients with AD, and compare it with the prevalence of other comorbidities of AD. We assessed the Korean National Health Information Database and medical records including coexisting asthma, AR, and ACD. Single and multiple logistic regression models were created for keloids and each allergic disease. The prevalence of keloids was higher in the AD group than in the control group. Among patients with AD, adolescents and adults had a higher prevalence of keloids than infants and children. The risk of keloids was high with AD alone, and coexisting asthma significantly increased the risk. Similarly, the risk of keloids was higher in AR associated with AD and ACD associated with AD than in AD alone. Thus, among Koreans, patients with AD have a higher risk of keloid development, with coexisting allergic diseases increasing the risk. [ABSTRACT FROM AUTHOR]

The treatment approach to type 2 diabetes (T2D) should begin with an assessment of atherosclerotic cardiovascular disease (ASCVD). Sodium-glucose cotransporter-2 inhibitors (SGLT2i) should be considered in T2D with established ASCVD or heart failure (HF). In this study, we analyzed the prescription patterns of ant-diabetic treatment in T2D with ASCVD or HF in real-world clinical practice. During 1-year period (2018), we reviewed 1553 consecutive T2D patients with ASCVD or HF visiting an endocrinology outpatient clinic from four teaching hospitals in Seoul Capital Area after excluding patients aged ≥85 years or estimated glomerular filtration rate (eGFR) ≤30 ml/min/1.73m2. Mean age was 65 years, duration of diabetes 11 years, and duration of ASCVD 7 years; HbA1C 7.5%, eGFR 80 ml/min/1.73m2, and body mass index (BMI) 25.6 kg/m2. ASCVD characteristics were stroke 27%, coronary artery disease (CAD) 59%, stroke+CAD 5%, peripheral arterial occlusive disease 1%, and heart failure 8%. Over four years, the initiation of SGLT2i has increased (2015=9% vs. 2018=42%). Compared with SGLT2i non-users (80%, n=1249), SGLT2i users (20%, n=304) tended to be younger (60 vs. 67) and with significantly lower stroke (16% vs. 30%). They also had higher BMI (27 vs. 25), worse HbA1C levels (8.1 vs. 7.4), and higher eGFR (88 vs. 78). Non-users with HbA1C 8 ∼9% (n=245) who might be eligible for switching to SGLT2i showed a longer duration of diabetes (14 vs. 11 years) or ASCVD (7.4 vs. 6.5 years) compared to users. The most common prescription pattern in non-users was triple oral glucose-lowering drugs (OGLD) followed by dual OGLD while in users, dual OGLD followed by triple OGLD. Interestingly, 0.5% were on GLP-1RA in this study. In contrast to clinical guidelines, a small proportion of T2D with ASCVD or HF is currently treated with SGLT2i in real-world clinical practice. The limiting factors for failing to initiate SGLT2i are age, stoke, eGFR, and clinical inertia. Disclosure: S. Jeong: None. I. Park: None. S. Lee: None. D. Shin: None. K. Kim: None. [ABSTRACT FROM AUTHOR]

Inhaled corticosteroids are known to be relatively safe for long-term use in inflammatory respiratory diseases and it has been repurposed as one of the potential therapies for outpatients with coronavirus disease 2019 (COVID-19). However, inhaled corticosteroids have not been accepted for COVID-19 as a standard therapy because of its lack of proven benefits. Therefore, this study aimed to evaluate the effectiveness of inhaled corticosteroids in patients with COVID-19. Randomized controlled trials comparing the efficacy of inhaled corticosteroid treatment in patients with COVID-19 were identified through literature electronic database searches up to March 10, 2023. Meta-analyses were conducted for predefined outcomes, and the certainty of evidence was graded using the grading of recommendations, assessment, development, and evaluation approach. Overall, seven trials (eight articles) were included in this systematic review. Compared with usual care, inhaled corticosteroids was associated with significantly improved clinical recovery at 7 and 14 days in patients with COVID-19. In subgroup analysis, only budesonide showed significant efficacy in clinical recovery, whereas no significant benefit was observed for ciclesonide. Moreover, inhaled corticosteroids use was not significantly associated with all-cause hospitalization, all-cause mortality, admission to intensive care unit, or the use of mechanical ventilation. Our systematic review used evidence with very low to moderate certainty. Although based on limited evidence, our results suggest that inhaled corticosteroids treatment, especially budesonide, improves the clinical recovery of patients with COVID-19. More trials and meta-analyses are needed to assess the efficacy of inhaled corticosteroids for COVID-19 treatment. [ABSTRACT FROM AUTHOR]

Background: Interest in complications and sequelae following Coronavirus disease 2019 (COVID-19) is increasing. Several articles have reported COVID-19-associated autoimmune diseases and the association between autoantibodies and the severity of COVID-19. Thromboembolic complications are frequent in patients with COVID-19, and the anti-phospholipid antibodies (aPL) is frequently detected. We conducted this study to investigate the prevalence, clinical significance, and persistence of anti-nuclear antibodies (ANA) and aPLs in COVID-19. Methods: We enrolled patients diagnosed with COVID-19 with oxygen demand and admitted to a tertiary hospital in South Korea between July 2020 and March 2022. ANA and aPLs levels were assessed using an immunoassay kit. Results: A total of 248 patients were enrolled in the study. Among them, five patients were ANA-positive, and 41 were aPL-positive (IgM anti-cardiolipin (aCL) antibody in seven patients, IgG aCL in seven patients, IgM anti-β2Glycoprotein1 antibody (aβ2-GPI) in 32 patients, and IgG aβ2-GPI in one patient). Two of five ANA-positive patients, 13 of 32 IgM aβ2-GPI-positive patients, 5 of 7 IgM aCL-positive patients, and 2 of 7 IgG aCL-positive patients were eligible for follow-up analysis, and 100%, 69.2%, 40%, and 50% of the patients remained autoantibody-positive, respectively. There were no differences in clinical outcomes between the autoantibody-positive and autoantibody-negative groups, except for the IgG aCL group showing a tendency for worse outcomes. Conclusion: A significant proportion of COVID-19 patients with oxygen demand were autoantibody-positive, and autoantibodies persisted for several months after symptom onset. Whether these autoantibodies are related to long-term sequelae in COVID-19 patients requires further investigation. [ABSTRACT FROM AUTHOR]

Progressive multifocal leukoencephalopathy (PML) is a rare but fatal opportunistic infection and mainly occurs in patients with immunosuppressive conditions. Despite the increasing number of patients receiving immunosuppressive treatments, studies on PML are still lacking due to its low prevalence and incidence. We retrospectively reviewed patients diagnosed with PML in two tertiary hospitals in South Korea from 1999 to 2021. Total of 47 PML patients were included. Of 27 patients (57.4%) were diagnosed with human immunodeficiency virus (HIV). Median last follow-up modified Rankin Scale (mRS) score was higher in the non-HIV PML group than that in the HIV group (5 vs. 4, p = 0.020). Median survival duration was lower in the non-HIV group (184 vs. 1,564 days). The 1-year and overall mortality rates of PML patients were significantly higher in the non-HIV group than that in HIV group (60.0% vs. 25.9%, p = 0.019; 80.0% vs. 40.7%, p = 0.007). Initial mRS score (HR 1.685, p = 0.038) and highly active antiretroviral therapy (HAART) in HIV patients (HR 0.374, p = 0.013) had a significant effect on overall mortality. Our findings suggest that early detection of PML with low mRS score and early initiation of HAART in patients with HIV may improve prognosis. [ABSTRACT FROM AUTHOR]

Background: Interest in complications and sequelae following Coronavirus disease 2019 (COVID-19) is increasing. Several articles have reported COVID-19-associated autoimmune diseases and the association between autoantibodies and the severity of COVID-19. Thromboembolic complications are frequent in patients with COVID-19, and the anti-phospholipid antibodies (aPL) is frequently detected. We conducted this study to investigate the prevalence, clinical significance, and persistence of anti-nuclear antibodies (ANA) and aPLs in COVID-19. Methods: We enrolled patients diagnosed with COVID-19 with oxygen demand and admitted to a tertiary hospital in South Korea between July 2020 and March 2022. ANA and aPLs levels were assessed using an immunoassay kit. Results: A total of 248 patients were enrolled in the study. Among them, five patients were ANA-positive, and 41 were aPL-positive (IgM anti-cardiolipin (aCL) antibody in seven patients, IgG aCL in seven patients, IgM anti-β2Glycoprotein1 antibody (aβ2-GPI) in 32 patients, and IgG aβ2-GPI in one patient). Two of five ANA-positive patients, 13 of 32 IgM aβ2-GPI-positive patients, 5 of 7 IgM aCL-positive patients, and 2 of 7 IgG aCL-positive patients were eligible for follow-up analysis, and 100%, 69.2%, 40%, and 50% of the patients remained autoantibody-positive, respectively. There were no differences in clinical outcomes between the autoantibody-positive and autoantibody-negative groups, except for the IgG aCL group showing a tendency for worse outcomes. Conclusion: A significant proportion of COVID-19 patients with oxygen demand were autoantibody-positive, and autoantibodies persisted for several months after symptom onset. Whether these autoantibodies are related to long-term sequelae in COVID-19 patients requires further investigation. [ABSTRACT FROM AUTHOR]

The utility of α-defensin (AD), leukocyte esterase (LE) levels, and metagenomics sequencing as diagnostic tools for prosthetic joint infection (PJI) has been suggested, but there are few studies among the Asian population. This study aimed to evaluate the diagnostic performance of various biomarkers for PJI and the role of the microbiome in the synovial fluid of patients with prostheses. Patients with suspected knee PJI were enrolled, and their blood and synovial fluid were collected. The cases were classified into the PJI and non-PJI groups. Significant differences between the two groups were observed in the levels of AD (4698 µg/L vs. 296 µg/L, p < 0.001) and positivity for LE (62.5% vs. 21.1%, p = 0.01). AD had 94.4% sensitivity and 89.5% specificity for diagnosing PJI, whereas LE had 37.5% sensitivity and 100% specificity. Microbiome taxonomic profiling showed high sensitivity. The number of operational taxonomic units and the richness of the microbiome in the synovial fluid were higher in the non-PJI than in the PJI group. AD has shown encouraging results in the Asian population as a diagnostic biomarker for PJI, and LE can be used as a diagnostic adjunct. The bacterial richness of the synovial fluid is likely associated with infections. [ABSTRACT FROM AUTHOR]

Progressive multifocal leukoencephalopathy (PML) is a rare but fatal opportunistic infection and mainly occurs in patients with immunosuppressive conditions. Despite the increasing number of patients receiving immunosuppressive treatments, studies on PML are still lacking due to its low prevalence and incidence. We retrospectively reviewed patients diagnosed with PML in two tertiary hospitals in South Korea from 1999 to 2021. Total of 47 PML patients were included. Of 27 patients (57.4%) were diagnosed with human immunodeficiency virus (HIV). Median last follow-up modified Rankin Scale (mRS) score was higher in the non-HIV PML group than that in the HIV group (5 vs. 4, p = 0.020). Median survival duration was lower in the non-HIV group (184 vs. 1,564 days). The 1-year and overall mortality rates of PML patients were significantly higher in the non-HIV group than that in HIV group (60.0% vs. 25.9%, p = 0.019; 80.0% vs. 40.7%, p = 0.007). Initial mRS score (HR 1.685, p = 0.038) and highly active antiretroviral therapy (HAART) in HIV patients (HR 0.374, p = 0.013) had a significant effect on overall mortality. Our findings suggest that early detection of PML with low mRS score and early initiation of HAART in patients with HIV may improve prognosis. [ABSTRACT FROM AUTHOR]

Background We evaluated the clinical accuracy and utility of whole-genome sequencing (WGS) of plasma microbial cell-free DNA (cfDNA) as a novel noninvasive method in diagnosing invasive aspergillosis (IA) in patients with hematologic malignancy (HM) or coronavirus disease 2019 (COVID-19). Methods Adults with HM or COVID-19 and suspected IA were recruited. IA cases were retrospectively diagnosed according to EORTC/MSG definitions and ECMM/ISHAM criteria for HM and COVID-19 patients, respectively. The results of cfDNA WGS were compared with the conventional diagnosis. Results Microbial cfDNA WGS was performed 53 times from 41 participants (19 from HM, 16 from COVID-19, and 7 from the control group). In participants with HM, Aspergillus cfDNA was detected in 100% of proven IA and 91.7% of probable IA cases. In participants with COVID-19, 50.0% of probable IA were positive for Aspergillus in cfDNA WGS. Concordance between Aspergillus cfDNA detection and proven/probable IA conventional diagnosis was significantly higher in participants with HM than in those with COVID-19. IA diagnosed using EORTC/MGS definitions showed significantly high concordance between Aspergillus cfDNA detection and proven/probable IA. Conclusions Aspergillus cfDNA detection strongly correlated with proven/probable IA diagnosed using EORTC/MSG definitions and could be used as an additional diagnostic tool for IA. [ABSTRACT FROM AUTHOR]

Background: During the novel coronavirus disease-2019 pandemic, a considerable number of pneumothorax (PNX)/pneumomediastinum (PNM) associated with COVID-19 have been reported, and the incidence is higher in critically ill patients. Despite using a protective ventilation strategy, PNX/PNM still occurs in patients on invasive mechanical ventilation (IMV). This matched case–control study aims to identify the risk factors and clinical characteristics of PNX/PNM in COVID-19. Methods: This retrospective study enrolled adult patients with COVID-19, admitted to a critical care unit from March 1, 2020, to January 31, 2022. COVID-19 patients with PNX/PNM were compared, in a 1–2 ratio, to COVID-19 patients without PNX/PNM, matched for age, gender, and worst National Institute of Allergy and Infectious Diseases ordinal scale. Conditional logistic regression analysis was performed to assess the risk factors for PNX/PNM in COVID-19. Results: 427 patients with COVID-19 were admitted during the period, and 24 patients were diagnosed with PNX/PNM. Body mass index (BMI) was significantly lower in the case group (22.8 kg/m2 and 24.7 kg/m2; P = 0.048). BMI was statistically significant risk factor for PNX/PNM in univariate conditional logistic regression analysis [odds ratio (OR), 0.85; confidence interval (CI), 0.72–0.996; P = 0.044]. For patients on IMV support, univariate conditional logistic regression analysis showed the statistical significance of the duration from symptom onset to intubation (OR, 1.14; CI, 1.006–1.293; P = 0.041). Conclusions: Higher BMI tended to show a protective effect against PNX/PNM due to COVID-19 and delayed application of IMV might be a contributive factor for this complication. [ABSTRACT FROM AUTHOR]

With the introduction of combination antiretroviral therapy (cART), the prevalence of human immunodeficiency virus (HIV)-associated nontuberculous mycobacteria (NTM) disease has declined. However, NTM diseases still occur in people living with HIV/acquired immunodeficiency syndrome (AIDS) (PLWHA). We analysed the clinical and microbiological features of NTM diseases in PLWHA in South Korea. PLWHA who were diagnosed with NTM diseases between January 2000 and March 2021 were retrospectively enrolled from five different hospitals in South Korea. Data on baseline demographics, HIV status, CD4+ T cell counts, viral load, past and current cART regimens, isolated NTM species, results of antimicrobial susceptibility tests, treatment regimens, and outcomes were collected by reviewing medical records. A total of 34 cases of NTM in PLWHA were included. Pulmonary and extrapulmonary NTM diseases accounted for 58.8% (n = 20) and 41.2% (n = 14), respectively. The lymph node was the most common site of extrapulmonary NTM disease (64.3%). The age at the time of NTM disease diagnosis was younger in the extrapulmonary NTM group than in the pulmonary NTM group (37.0 vs. 49.0 years). Mean CD4+ T cell counts at the time of NTM disease diagnosis was 186.6 cells/μL (range: 1–1394). Nine patients (26.5%) had fully suppressed viral loads at the time of NTM disease diagnosis. Mycobacterium avium complex (MAC) was the most common species found, followed by M. intracellulare and M. kansasii. MAC isolates were all susceptible to clarithromycin, but the rates of non-susceptibility to moxifloxacin, linezolid, ethambutol, and rifampin were 75%, 37.5%, 12.5%, and 12.5%, respectively. The average duration of treatment was 17 months and the mortality rate was 8.8%. NTM diseases may occur in PLWHA, even with completely suppressed viral loads. The identified clinical features of NTM diseases are essential for its clinical management in South Korea. [ABSTRACT FROM AUTHOR]

Dehydroepiandrosterone (DHEA) is an adrenal steroid converted to potent androgens. This study aimed to discover the association between serum DHEA levels and immunologic response in people with HIV/AIDS (PLWHA). We enrolled patients aged ≥ 18 years who were treated with combination antiretroviral therapy (cART). We measured CD4+ and CD8+ T-cell counts, HIV-RNA titres, and serum DHEA levels. We assigned each patient to a good- or poor-responder group depending on their CD4+ T-cell counts at study enrolment. Participants with CD4+ T-cell counts > 200/µL were assigned to the good-responder group, whilst those with CD4+ T-cell counts < 200/µL were assigned to the poor-responder group. The participants were followed up for 2 years. The poor-responder group showed lower CD4+ T-cell counts and higher HIV PCR titres at their initial HIV diagnosis and in their 2-year follow-up data. Serum DHEA level was lower in the poor-responder group. Multivariable logistic analysis showed that BMI, initial CD4+ T-cell counts, and serum DHEA level were clinical factors associated with poor immunologic responsiveness to cART in PLWHA. Therefore, DHEA may be used as an indicator of the immunological recovery of PLWHA. [ABSTRACT FROM AUTHOR]

Extracorporeal membrane oxygenation (ECMO) provides hemodynamic and oxygenation support to critically ill patients. Due to multiple catheter cannulations, patients on ECMO are vulnerable to bloodstream infections (BSIs). We aimed to investigate the incidence, clinical characteristics, risk factors, and microorganisms associated with BSIs during ECMO. This single-center retrospective cohort study was conducted between January 2015 and May 2021. Patients aged 18 years or older with an ECMO duration of > 48 h for cardiogenic or respiratory support were included in the study. Patients who developed bacteremia or candidemia from 12 h after ECMO cannulation to 7 days after de-cannulation were included. The clinical factors between non-BSI and BSI were compared, along with an analysis of the risk factors associated with BSI during ECMO. A total of 480 patients underwent ECMO for cardiogenic shock (n = 267, 55.6%) or respiratory failure (n = 213, 44.4%) during the study period. The incidence was 20.0 episodes per 1000 ECMO-days. Approximately 20.2% (97/480) and 5.4% (26/480) of the patients developed bacteremia and candidemia, respectively. The median numbers of days of BSI development were 8.00 days for bacteremia and 11.0 days for candidemia. The most common pathogens were methicillin-resistant coagulase-negative staphylococci (n = 24), followed by vancomycin-resistant Enterococcus (n = 21). Multivariable logistic analysis demonstrated that hemodialysis (odds ratio [OR] 2.647, p < 0.001), veno-arterial-venous mode (OR 1.911, p = 0.030), and total ECMO duration (OR 1.030, p = 0.007) were significant risk factors for bacteremia. The total ECMO duration was the only risk factor associated with candidemia (OR 1.035, p = 0.010). The mortality rate was significantly higher in the bacteremia (57.7%) and candidemia (69.2%) groups than that in the non-BSI group (43.6%). BSI is a common complication of patients receiving ECMO support and is associated with poor clinical outcomes. Determining the type of frequently isolated organisms and the median onset time of BSI would help in the selection of appropriate prophylactic antibiotics or antifungal agents. [ABSTRACT FROM AUTHOR]

There is an error in affiliation of authors. The correct affiliation is: Division of Infectious Diseases, Department of Internal Medicine and AIDS Research Institute, Yonsei University College of Medicine, Seoul, South Korea.By Se Ju Lee; Yae Jee Baek; Jin Nam Kim; Ki Hyun Lee; Eun Hwa Lee; Joon Sup Yeom; Jun Yong Choi; Nam Su Ku; Jin Young Ahn; Jung Ho Kim and Su Jin JeongReported by Author; Author; Author; Author; Author; Author; Author; Author; Author; Author; Author [Extracted from the article]

Objectives: To investigate the rate of antineutrophil cytoplasmic antibody (ANCA) positivity and its clinical significance in patients infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Methods: This study included 178 patients infected with SARS-CoV-2 who were enrolled in a cohort at a single centre. Myeloperoxidase (MPO)-ANCA and proteinase 3 (PR3)-ANCA levels in stored blood sera were measured using immunoassay kits. Mortality, mechanical ventilator care, and severe infection were assessed as three poor outcomes. The 2022 American College of Rheumatology and the European Alliance of Associations for Rheumatology (ACR/EULAR) classification criteria for the three subtypes of AAV were applied only to patients who had MPO-ANCA or PR3-ANCA among study subjects. Results: The detection rate of ANCA positivity was 18.5%. MPO-ANCA and PR3-ANCA were found in 22 (12.4%) and 14 (7.9%) patients, respectively. However, neither MPO-ANCA nor PR3-ANCA affected the three poor outcomes. According to the new criteria, 12 (6.7%) and 21 (11.8%) patients were classified as having granulomatosis with polyangiitis (GPA) and microscopic polyangiitis (MPA), respectively. Conclusions: SARS-CoV-2 infection may increase the rate of ANCA positivity. Although it might not affect poor outcomes, it might contribute to the classification of GPA and MPA despite uncertain clinical significance. [ABSTRACT FROM AUTHOR]

Introduction: Infective endocarditis (IE) is a severe and fatal infection with high in-hospital and overall mortality rates of approximately up to 30%. Valve culture positivity was associated with in-hospital mortality and postoperative complications; however, few studies have analyzed the relationship between valve cultures and overall mortality over a long observation period. This study aimed to compare the association of valve culture positivity with overall mortality in patients with IE who underwent valve surgery. Methods: A total of 416 IE patients admitted to a tertiary hospital in South Korea from November 2005 to August 2017 were retrospectively reviewed. A total of 202 IE patients who underwent valve surgery and valve culture were enrolled. The primary endpoint was long-term overall mortality. Kaplan–Meier curve and Cox proportional hazards model were used for survival analysis. Results: The median follow-up duration was 63 (interquartile range, 38–104) months. Valve cultures were positive in 22 (10.9%) patients. The overall mortality rate was 15.8% (32/202) and was significantly higher in valve culture-positive patients (36.4%, p = 0.011). Positive valve culture [hazard ratio (HR) 3.921, p = 0.002], Charlson Comorbidity Index (HR 1.181, p = 0.004), Coagulase-negative staphylococci (HR 4.233, p = 0.001), new-onset central nervous system complications (HR 3.689, p < 0.001), and new-onset heart failure (HR 4.331, p = 0.001) were significant risk factors for overall mortality. Conclusions: Valve culture positivity is a significant risk factor for long-term overall mortality in IE patients who underwent valve surgery. The importance of valve culture positivity needs to be re-evaluated, as the valve culture positivity rate increases with increasing early surgical intervention. [ABSTRACT FROM AUTHOR]

Background and Aims: Little is known about the association between non‐alcoholic fatty liver disease (NAFLD) and dementia. Given that hepatic steatosis is linked to abnormal fat metabolism, and fat dysregulation in the brain is related to dementia, we aimed to investigate whether NAFLD is associated with an increased risk of dementia. Methods: We conducted a nationwide cohort study involving 4 031 948 subjects aged 40–69 years who underwent ≥2 health check‐ups provided by the National Health Insurance Service in Korea between January 2004 and December 2007. Based on the hepatic steatosis index (HSI), subjects were categorized into non‐NAFLD (HSI <30 at all check‐ups) and NAFLD (HSI >36 at one or more check‐ups). Dementia defined by ICD‐10 codes with prescription data was followed up until December 2017. Cox proportional hazards regression models analysed the dementia risk. Results: At baseline, 31.3% had NAFLD. During the median follow‐up of 9.5 years, 138 424 in NAFLD group and 69 982 in non‐NAFLD group developed dementia. NAFLD group was associated with a higher risk of dementia than non‐NAFLD group on multivariable‐adjusted analysis (hazard ratio [HR], 1.05; p <.001), competing risk analysis (HR, 1.08; p <.001) and propensity‐score matched analysis (HR, 1.09; p <.001). The association between NAFLD and dementia risk was more prominent among females (HR, 1.16; p <.001). The association was stronger among non‐obese NAFLD subjects (BMI <25 kg/m2, HR, 1.09; p <.001) than obese NAFLD subjects. Conclusions: This nationwide study found that NAFLD is associated with an increased risk of dementia. The association was prominent among females and non‐obese NAFLD subjects. [ABSTRACT FROM AUTHOR]

Infections caused by Fusobacterium species are rare; however serious infections with complications or mortality may occur occasionally. We conducted a retrospective study to investigate the clinical features of patients with Fusobacterium infections and the differences between infections caused by the species F. necrophorum, F. nucleatum, and F. varium. Additionally, we attempted to identify risk factors for Fusobacterium-associated mortality. This study included all patients at a large tertiary care teaching hospital in South Korea with Fusobacterium infections from January 2006 to April 2021. Demographic, clinical, laboratory, and outcome data were analyzed. Multiple logistic regression analysis was performed to assess the risk factors for in-hospital mortality associated with F. nucleatum and F. varium infections. We identified 272 patients with Fusobacterium infections during the study period. The number of Fusobacterium cases has increased recently, with F. varium infections markedly increasing since 2016 and causing a significant proportion of infections. Patients with F. varium infections were older and had a higher proportion of nosocomial infections than the other groups. The F. nucleatum and F. varium groups showed higher in-hospital mortality than the F. necrophorum group. Through logistic regression analysis, APACHE II score and serum albumin level were considered risk factors for in-hospital mortality. APACHE II score was positively correlated with age, red cell distribution width, and serum blood urea nitrogen, and negatively correlated with serum albumin level. Infections caused by Fusobacterium species are increasing. F. varium causes a significant proportion of severe infections. [ABSTRACT FROM AUTHOR]

Background: The photosynthetic microorganism Chlamydomonas reinhardtii has been approved as generally recognized as safe (GRAS) recently, this can excessively produce carotenoid pigments and fatty acids. Zeaxanthin epoxidase (ZEP), which converts zeaxanthin to violaxanthin, and ADP-glucose pyrophosphorylase (AGP). These are key regulating genes for the xanthophyll and starch pathways in C. reinhardtii respectively. In this study, to produce macular pigment-enriched microalgal oil, we attempted to edit the AGP gene as an additional knock-out target in the zep mutant as a parental strain. Results: Using a sequential CRISPR-Cas9 RNP-mediated knock-out method, we generated double knock-out mutants (dZAs), in which both the ZEP and AGP genes were deleted. In dZA1, lutein (2.93 ± 0.22 mg g−1 DCW: dried cell weight), zeaxanthin (3.12 ± 0.30 mg g−1 DCW), and lipids (450.09 ± 25.48 mg g−1 DCW) were highly accumulated in N-deprivation condition. Optimization of the culture medium and process made it possible to produce pigments and oil via one-step cultivation. This optimization process enabled dZAs to achieve 81% higher oil productivity along with similar macular pigment productivity, than the conventional two-step process. The hexane/isopropanol extraction method was developed for the use of macular pigment-enriched microalgal oil for food. As a result, 196 ± 20.1 mg g−1 DCW of edible microalgal oil containing 8.42 ± 0.92 mg g−1 lutein of oil and 7.69 ± 1.03 mg g−1 zeaxanthin of oil was produced. Conclusion: Our research showed that lipids and pigments are simultaneously induced in the dZA strain. Since dZAs are generated by introducing pre-assembled sgRNA and Cas9-protein into cells, antibiotic resistance genes or selective markers are not inserted into the genome of dZA, which is advantageous for applying dZA mutant to food. Therefore, the enriched macular pigment oil extracted from improved strains (dZAs) can be further applied to various food products and nutraceuticals. [ABSTRACT FROM AUTHOR]

Before NTAP treatment, a spherical spore surrounded by a bright visible wall was observed in the RCM image; after NTAP treatment, cell wall disruption and fungal hyphae breakage were observed (Figure 1). Although the effect may be weak as a single treatment, we suggest that irradiating onychomycosis with NTAP prior to topical antifungal or laser treatment could enhance the therapeutic effect. A pilot study of semiquantitative treatment evaluation following nonthermal atmospheric-pressure plasma administration for onychomycosis. [Extracted from the article]

Background: Multidrug-resistant organisms (MDROs) such as vancomycin-resistant enterococci (VRE) and carbapenemase-producing Enterobacteriaceae (CPE) are associated with prolonged hospitalisation, increased medical costs, and severe infections. Faecal microbiota transplantation (FMT) has emerged as an important strategy for decolonisation. This study aimed to evaluate the genetic response of MDROs to FMT. Methods: A single-centre prospective study was conducted on patients infected with VRE, CPE, or VRE/CPE who underwent FMT between May 2018 and April 2019. Genetic response was assessed as the change in the expression of the resistance genes VanA, blaKPC, blaNDM, and blaOXA on days 1, 7, 14, and 28 by real-time reverse-transcription polymerase chain reaction. Results: Twenty-nine patients received FMT, of which 26 (59.3%) were infected with VRE, 5 (11.1%) with CPE, and 8 (29.6%) with VRE/CPE. The mean duration of MDRO carriage before FMT was 71 days. Seventeen patients (63.0%) used antibiotics within a week of FMT. In a culture-dependent method, the expression of VanA and overall genes significantly decreased (p = 0.011 and p = 0.003 respectively). In a culture-independent method, VanA, blaNDM, and overall gene expression significantly decreased over time after FMT (p = 0.047, p = 0.048, p = 0.002, respectively). Similar results were confirmed following comparison between each time point in both the culture-dependent and -independent methods. Regression analysis did not reveal important factors underlying the genetic response after FMT. No adverse events were observed. Conclusion: FMT in patients infected with MDROs downregulates the expression of resistance genes, especially VanA, and facilitates MDRO decolonisation. [ABSTRACT FROM AUTHOR]

Background: Despite advances in therapy, sepsis still has a high mortality rate. To improve the treatment outcome, early diagnosis and treatment is essential, as reflected in many publications about biomarkers for sepsis. Recent models of automatic cell analyzers provide the delta neutrophil index (DN), which corresponds to the fraction of immature granulocytes in circulating blood. This study investigated DN as a prognostic marker in patients with bacteraemia. Methods: We retrospectively collected data on adult patients with bacteraemia admitted to an urban hospital between November 2009 and April 2010. The DN was measured at the onset of bacteraemia and at 24 and 72 h later. Factors associated with 28-day mortality were assessed using logistic regression. Results: A total of 102 patients were included in the analysis, and 24 patients died within 28 days. In the univariate analysis, appropriate antibiotic treatment, multidrug-resistant bacterial infection, history of intensive care unit (ICU) stay before the onset of bacteraemia, healthcare-associated infection, DN at 72 h after the onset of bacteraemia (DN-72 h), and platelet count at the onset of bacteraemia were significantly associated with survival. In multivariate analysis, DN-72 h (odds ratio (OR) 1.246, 95% confidence interval (CI) 1.030-1.508; p = 0.023), platelet count at the onset of bacteraemia (OR 0.986, 95% CI 0.977-0.995; p = 0.003), and history of ICU stay before the onset of bacteraemia (OR 4.907, 95% CI 1.045-23.051; p = 0.044) were the independent factors associated with survival. Conclusion: DN at 72 h after bacteraemia may be valuable to assess the prognosis of patients with bacteraemia. [ABSTRACT FROM AUTHOR]

Background: Pharmacokinetic-pharmacodynamic (PK/PD) targets of vancomycin therapy have been recognized for methicillin-resistant Staphylococcus aureus infections but not for other gram-positive bacterial infections. Therefore, we investigated whether vancomycin concentration targets such as the trough level and ratio of the area under the curve to minimum inhibitory concentration (AUC/MIC) are associated with the treatment outcome in enterococcal bacteremia.Methods: A retrospective cohort analysis enrolled patients with bacteremia caused by vancomycin-susceptible Enterococcus faecium and Enterococcus faecalis who were treated with vancomycin from January 2007 to December 2017 at a tertiary hospital located in Seoul, South Korea. Patients without vancomycin concentrations were excluded from the study. The primary outcome was 28-day all-cause mortality.Results: A total of 37 patients were enrolled-26 with E. faecium infection and 11 with E. faecalis infection. The 28-day all-cause mortality rate was 21.6 %. In univariate analysis, vancomycin trough level (≤ 15 µg/mL; p = 0.042), age (p = 0.044), and septic shock (p = 0.049) were associated with 28-day mortality but not AUC24/MIC (> 389; p = 0.479). In multivariate analysis, vancomycin trough concentration (≤ 15 µg/mL; p = 0.041) and younger age (p = 0.031) were associated with 28-day mortality in patients with enterococcal bacteremia.Conclusions: In this study, a vancomycin trough level of 15 µg/mL or lower was associated with 28-day mortality in enterococcal bacteremia. However, relatively large prospective studies are needed to examine the efficacy of vancomycin PK/PD parameters in patients with enterococcal bacteremia. [ABSTRACT FROM AUTHOR]

Objectives: We aim to compare the trends of non‐communicable diseases (NCDs) and death among people living with HIV (PLWH) and uninfected controls in South Korea. Methods: We identified PLWH from a nationwide database of all Korean citizens enrolled from 1 January 2004 to 31 December 2016. A control cohort was randomly selected for PLWH by frequency matching for age and sex in a 20:1 ratio. To compare NCD trends between the groups, adjusted incidence rate ratios for outcomes across ages, calendar years and times after HIV diagnosis were calculated. Results: We included 14 134 PLWH and 282 039 controls in this study; 58.5% of PLWH and 36.4% of the controls were diagnosed with at least one NCD. The incidence rates of cancers, chronic kidney disease, depression, osteoporosis, diabetes and dyslipidaemia were higher in PLWH than in the controls, whereas those of cardiovascular disease, heart failure, ischaemic stroke and hypertension were lower in PLWH. Relative risks (RRs) for NCDs in PLWH were higher than controls in younger age groups. Trends in the RRs of NCDs tended to increase with the calendar year for PLWH vs. controls and either stabilized or decreased with time after HIV diagnosis. The RR of death from PLWH has decreased with the calendar year, but showed a tendency to rise again after 2014 and was significant at the early stage of HIV diagnosis. Conclusions: Although the RR of each NCD in PLWH showed variable trends compared with that in controls, NCDs in PLWH have been increasingly prevalent. [ABSTRACT FROM AUTHOR]

Background: Brain abscess can be life-threatening and manifest various neurological findings, although the mortality rate has decreased recently. We investigated the risk factors for unfavorable outcomes of patients with brain abscess. Methods: A retrospective cohort study examined patients with brain abscess seen from May 2005 to December 2018 in a tertiary care hospital in Seoul, South Korea. We reviewed the medical records for clinical findings, therapeutic modalities, and prognostic factors of brain abscess. Unfavorable clinical outcomes were defined as death, moderate to severe disability with neurological deficits, or vegetative state at 1 year or at the time of discharge from outpatient follow-up. Results: The study enrolled 135 patients: 65.2% were males; the mean age was 56 years. 35.6% had unfavorable outcomes. In multivariate analysis, higher Sequential Organ Failure Assessment (SOFA) (p < 0.001), pre-existing hemiplegia (p = 0.049), and higher Charlson comorbidity index (CCI) (p = 0.028) were independently associated with unfavorable outcomes. Conclusions: Higher SOFA, pre-existing hemiplegia and higher Charlson comorbidity index were significant risk factors for unfavorable clinical outcomes in patients with brain abscess. [ABSTRACT FROM AUTHOR]

Abstract: Acanthoic, continentalic and kaurenoic acids are bioactive diterpenoids that are structural isomers isolated from Acanthopanax species. Due to the interest in their potent biological activity, an analytical method of diterpenoids was developed for the quality control and the classification of Acanthopanax species. Capillary electrophoresis was used to separate and quantify the isomers. The three compounds were successfully separated from each other and from the matrices in the extracts of leaves, stems and roots of Acanthopanax species. The contents of acanthoic, continentalic and kaurenoic acids showed taxonomical differences in Acanthopanax species. Relatively higher concentrations of diterpenoids were found from A. koreanum and A. trifoliatus, while only trace amounts were found from the four other species tested: A. senticosus, A. senticosus f. inermis, A. chiisanensis, and A. divaricatus var. albeofructus. The contents of diterpenoids in association with lignans and triterpenoids in the Acanthopanax species could provide a chemotaxonomical index able to be used in the classification and discrimination of the species. [Copyright &y& Elsevier]

Background Spinal tuberculosis (TB) remains an important concern. Although spinal TB often has sequelae such as myelopathy after treatment, the predictive factors affecting such unfavorable outcomes are not yet known. Therefore, we investigated the clinical manifestations and predictors of unfavorable treatment outcomes in patients with spinal TB. Methods We performed a multi-center retrospective cohort study of patients with spinal TB. The clinical features, comorbidities, laboratory data, imaging findings and treatment outcomes of the patients were analyzed. The unfavorable outcome was defined according to previous studies. The prognostic factors for unfavorable outcomes as the primary outcome were determined using multivariate logistic regression analysis and a linear mixed model were used to compare time course of inflammatory markers during treatment. Results A total of 185 patients (85 males and 100 females) were included. The mean age of the patients was 57.2 years. Of them, 115 underwent surgery during treatment, with a median treatment duration of 12 months. Fifty-nine patients had unfavorable outcomes. In multivariate regression analysis, the factors associated with unfavorable outcome were old age (odds ratio [OR], 2.51; P = 0.034), acid-fast bacilli (AFB) smear positivity in specimens obtained through biopsy (OR, 3.05; P = 0.039), and elevated erythrocyte sedimentation rate (ESR) at the end of treatment (OR, 3.85; P = 0.002). Patients with unfavorable outcomes had a significant trend toward higher ESR during treatment compared with patients with favorable outcome (P = 0.009). Duration of anti-TB and surgical treatment did not affect prognosis. Conclusion Elevated ESR at the end of treatment could be used as a marker to identify spinal TB patients with a poor prognosis. Patients whose ESR are not normalized during treatment, as well as those with old age and AFB smear positivity, should be aware of unfavorable outcomes. Disclosures All authors: No reported disclosures. [ABSTRACT FROM AUTHOR]