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Although CD4+CD25+FOXP3+ regulatory T (TREG) cells have been studied in patients with COVID-19, changes in the TREG cell population have not been longitudinally examined during the course of COVID-19. In this study, we longitudinally investigated the quantitative and qualitative changes in the TREG cell population in patients with COVID-19. We found that the frequencies of total TREG cells and CD45RA−FOXP3hi activated TREG cells were significantly increased 15–28 d postsymptom onset in severe patients, but not in mild patients. TREG cells from severe patients exhibited not only increased proliferation but also enhanced apoptosis, suggesting functional derangement of the TREG cell population during severe COVID-19. The suppressive functions of the TREG cell population did not differ between patients with severe versus mild COVID-19. The frequency of TREG cells inversely correlated with SARS-CoV-2–specific cytokine production by CD4+ T cells and their polyfunctionality in patients with mild disease, suggesting that TREG cells are major regulators of virus-specific CD4+ T cell responses during mild COVID-19. However, such correlations were not observed in patients with severe disease. Thus, in this study, we describe distinctive changes in the TREG cell population in patients with severe and mild COVID-19. Our study provides a deep understanding of host immune responses upon SARS-CoV-2 infection in regard to TREG cells.

We do not yet understand exactly how corticosteroids attenuate hyperinflammatory responses and alleviate high-risk coronavirus disease 2019 (COVID-19). We aimed to reveal the molecular mechanisms of hyperinflammation in COVID-19 and the anti-inflammatory effects of corticosteroids in patients with high-risk COVID-19. We performed single-cell RNA sequencing of peripheral blood mononuclear cells (PBMCs) from three independent COVID-19 cohorts: cohort 1 was used for comparative analysis of high-risk and low-risk COVID-19 (47 PBMC samples from 28 patients), cohort 2 for longitudinal analysis during COVID-19 (57 PBMC samples from 15 patients), and cohort 3 for investigating the effects of corticosteroid treatment in patients with high-risk COVID-19 (55 PBMC samples from 13 patients). PBMC samples from healthy donors (12 PBMC samples from 12 donors) were also included. Cohort 1 revealed a significant increase in the proportion of monocytes expressing the long noncoding RNAs NEAT1 and MALAT1 in high-risk patients. Cohort 2 showed that genes encoding inflammatory chemokines and their receptors were upregulated during aggravation, whereas genes related to angiogenesis were upregulated during improvement. Cohort 3 demonstrated downregulation of interferon-stimulated genes (ISGs), including STAT1, in monocytes after corticosteroid treatment. In particular, unphosphorylated STAT-dependent ISGs enriched in monocytes from lupus patients were selectively downregulated by corticosteroid treatment in patients with high-risk COVID-19. Corticosteroid treatment suppresses pathologic interferon responses in monocytes by downregulating STAT1 in patients with high-risk COVID-19. Our study provides insights into the mechanisms underlying COVID-19 aggravation and improvement and the effects of corticosteroid treatment.

Coronavirus disease 2019 (COVID-19) is an acute respiratory infection caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Other coronaviruses (CoVs) can also infect humans, although the majority cause only mild respiratory symptoms. Because early diagnosis of SARS-CoV-2 is critical for preventing further transmission events and improving clinical outcomes, it is important to be able to distinguish SARS-CoV-2 from other SARS-related CoVs in respiratory samples. Therefore, we developed and evaluated a novel reverse transcription quantitative polymerase chain reaction (RT-qPCR) assay targeting the genes encoding the spike (S) and membrane (M) proteins to enable the rapid identification of SARS-CoV-2, including several new circulating variants and other emerging SARS-like CoVs. By analysis of in vitro-transcribed mRNA, we established multiplex RT-qPCR assays capable of detecting 5 × 10° copies/reaction. Using RNA extracted from cell culture supernatants, our multiple simultaneous SARS-CoV-2 assays had a limit of detection of 1 × 10° TCID50/mL and showed no cross-reaction with human CoVs or other respiratory viruses. We also validated our method using human clinical samples from patients with COVID-19 and healthy individuals, including nasal swab and sputum samples. This novel one-step multiplex RT-qPCR assay can be used to improve the laboratory diagnosis of human-pathogenic CoVs, including SARS-CoV-2, and may be useful for the identification of other SARS-like CoVs of zoonotic origin.

Objectives We aimed to assess the longevity of spike-specific antibody responses and neutralizing activity in the plasma of recovered Middle East respiratory syndrome (MERS) patients. Methods We traced the antibody responses and neutralizing activity against MERS coronavirus (MERS-CoV) in peripheral blood samples collected from 70 recovered MERS patients for 5 years after the 2015 MERS outbreak in South Korea. We also measured the half-life of neutralizing antibody titres in the longitudinal specimens. Results The seropositivity rate persisted for up to 4 years (50.7–56.1%), especially in MERS patients who suffered from severe pneumonia, and then decreased (35.9%) in the fifth year. Although the spike-specific antibody responses decreased gradually, the neutralizing antibody titres decreased more rapidly (half-life: 20 months) in 19 participants without showing negative seroconversion during the study period. Only five (26.3%) participants had neutralizing antibody titres greater than 1/1000 of PRNT50, and a high neutralizing antibody titre over 1/5000 was not detected in the participants at five years after infection. Discussion The seropositivity rate of the recovered MERS patients persisted up to 4 years after infection and significantly dropped in the fifth year, whereas the neutralizing antibody titres against MERS-CoV decreased more rapidly and were significantly reduced at 4 years after infection.

IntroductionDespite of massive endeavors to characterize inflammation in COVID-19 patients, the core network of inflammatory mediators responsible for severe pneumonia stillremain remains elusive. MethodsHere, we performed quantitative and kinetic analysis of 191 inflammatory factors in 955 plasma samples from 80 normal controls (sample n = 80) and 347 confirmed COVID-19 pneumonia patients (sample n = 875), including 8 deceased patients. ResultsDifferential expression analysis showed that 76% of plasmaproteins (145 factors) were upregulated in severe COVID-19 patients comparedwith moderate patients, confirming overt inflammatory responses in severe COVID-19 pneumonia patients. Global correlation analysis of the plasma factorsrevealed two core inflammatory modules, core I and II, comprising mainly myeloid cell and lymphoid cell compartments, respectively, with enhanced impact in a severity-dependent manner. We observed elevated IFNA1 and suppressed IL12p40, presenting a robust inverse correlation in severe patients, which was strongly associated with persistent hyperinflammation in 8.3% of moderate pneumonia patients and 59.4% of severe patients. DiscussionAberrant persistence of pulmonary and systemic inflammation might be associated with long COVID-19 sequelae. Our comprehensive analysis of inflammatory mediators in plasmarevealed the complexity of pneumonic inflammation in COVID-19 patients anddefined critical modules responsible for severe pneumonic progression.

Although several antiviral agents have become available for coronavirus disease 2019 (COVID-19) treatment, oral drugs are still limited. Camostat mesylate, an orally bioavailable serine protease inhibitor, has been used to treat chronic pancreatitis in South Korea, and it has an in vitro inhibitory potential against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).

Vascular calcification is the heterotopic accumulation of calcium phosphate salts in the vascular tissue and is highly correlated with increased cardiovascular morbidity and mortality. In this study, we found that the expression of neuromedin B (NMB) and NMB receptor is upregulated in phosphate-induced calcification of vascular smooth muscle cells (VSMCs). Silencing of NMB or treatment with NMB receptor antagonist, PD168368, inhibited the phosphate-induced osteogenic differentiation of VSMCs by inhibiting Wnt/β-catenin signaling and VSMC apoptosis. PD168368 also attenuated the arterial calcification in cultured aortic rings and in a rat model of chronic kidney disease. The results of this study suggest that NMB-NMB receptor axis may have potential therapeutic value in the diagnosis and treatment of vascular calcification. [BMB Reports 2021; 54(11): 569-574].

Although nearly a fifth of symptomatic COVID-19 patients suffers from severe pulmonary inflammation, the mechanism of developing severe illness is not yet fully understood. To identify significantly altered genes in severe COVID-19, we generated messenger RNA and micro-RNA profiling data of peripheral blood mononuclear cells (PBMCs) from five COVID-19 patients (2 severe and 3 mild patients) and three healthy controls (HC). For further evaluation, two publicly available RNA-Seq datasets (GSE157103 and GSE152418) and one single-cell RNA-Seq dataset (GSE174072) were employed. Based on RNA-Seq datasets, thrombospondin 1 (THBS1) and interleukin-17 receptor A (IL17RA) were significantly upregulated in severe COVID-19 patients’ blood. From single-cell RNA-sequencing data, IL17RA level is increased in monocytes and neutrophils, whereas THBS1 level is mainly increased in the platelets. Moreover, we identified three differentially expressed microRNAs in severe COVID-19 using micro-RNA sequencings. Intriguingly, hsa-miR-29a-3p significantly downregulated in severe COVID-19 was predicted to bind the 3′-untranslated regions of both IL17RA and THBS1 mRNAs. Further validation analysis of our cohort (8 HC, 7 severe and 8 mild patients) showed that THBS1, but not IL17RA, was significantly upregulated, whereas hsa-miR-29a-3p was downregulated, in PBMCs from severe patients. These findings strongly suggest that dysregulated expression of THBS1, IL17RA, and hsa-miR-29a-3p involves severe COVID-19.

Background Although many deaths due to carbapenem-resistant Acinetobacter baumannii (CRAB) bacteremia occur within a few days after the onset of bacteremia, risk factors for early mortality (EM) have not been deeply investigated. We aimed to determine the risk factors for EM and the difference between risk factors associated with EM and late mortality (LM) in CRAB bacteremia. Methods All patients with CRAB bacteremia in 10 hospitals during a 1-year study period were identified. We prospectively collected patients’ clinical data, including microbiological and demographic data, underlying comorbidities, origin of bacteremia, severity of illness, antibiotic therapy, and mortality. Among the cases with mortality within 30 days, EM and LM were defined as death within 3 and more than 5 calendar days from the first positive blood culture, respectively. Results A total of 212 CRAB bacteremia cases were included in the analysis. Of 122 (57.5%) patients with 30-day mortality, EM was observed in 75 (61.5%) patients and LM in 39 (32.0%) patients. The proportion of severe sepsis or septic shock, Pitt score, and Sequential Organ Failure Assessment (SOFA) score were significantly higher in 30-day deaths than 30-day survivors. These factors of clinical severity were also significantly higher in patients with EM than those with LM. While urinary tract infection as the factor of site of infection and the severity of illness were independent predictors of LM, only factors representing the severity of illness were independent risk factors for EM. Appropriate empirical antibiotic therapy was associated with reduced risk of EM. Conclusion The difference between risk factors for EM and LM was identified in this study. Our data suggest that a large proportion of CRAB bacteremia with high severity progress to a rapidly fatal course, regardless of the underlying diseases or source of infection. Further studies might be needed to investigate the microbiological factors associated with CRAB and pathogen-host interaction in patients with EM. Disclosures All Authors: No reported disclosures.

PURPOSE: Neutralizing antibodies can reduce SARS-CoV-2 cellular entry, viral titers, and pathologic damage. CT-P59 (regdanvimab), a SARS-CoV-2 neutralizing monoclonal antibody, was examined in 2 randomized, double-blind, placebo-controlled, single ascending dose, Phase I studies. METHODS: In study 1.1, healthy adults were sequentially enrolled to receive CT-P59 10, 20, 40, or 80 mg/kg or placebo. In study 1.2, adult patients with mild SARS-CoV-2 infection were enrolled to receive CT-P59 20, 40, or 80 mg/kg or placebo. Primary objectives of both studies were safety and tolerability up to day 14 after infusion. Secondary end points included pharmacokinetic properties. Study 1.2 also measured virology and clinical efficacy. FINDINGS: Thirty-two individuals were randomized to study 1.1 (6 per CT-P59 dose cohort and 8 in the placebo cohort). By day 14 after infusion, adverse events (AEs) were reported in 2 individuals receiving CT-P59 20 mg/kg (headache and elevated C-reactive protein levels) and 1 receiving CT-P59 40 mg/kg (pyrexia) (all Common Terminology Criteria for Adverse Events grade 1). In study 1.2, 18 patients were randomized (5 per dose cohort and 3 in the placebo cohort). Sixteen AEs were reported in 10 patients receiving CT-P59. No AEs in either study led to study discontinuation. Greater reductions in viral titers were reported with CT-P59 than placebo in those with maximum titers >105 copies/mL. Mean time to recovery was 3.39 versus 5.25 days. IMPLICATIONS: CT-P59 exhibited a promising safety profile in healthy individuals and patients with mild SARS-CoV-2 infection, with potential antiviral and clinical efficacy in patients with mild SARS-CoV-2 infection. ClinicalTrials.gov identifier: NCT04525079 (study 1.1) and NCT04593641 (study 1.2).

It is highly important to sensitively measure the abundance of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on various surfaces. Here, we present a nucleic acid-based detection method consisting of a new sample preparation protocol that isolates only viruses, not the free RNA fragments already present on the surfaces of indoor human-inhabited environments, using a graphene oxide-coated microbead filter. Wet wipes (100 cm2), not cotton swabs, were used to collect viruses from environmental surfaces with large areas, and viruses were concentrated and separated with a graphene oxide-coated microbead filter. Viral RNA from virus was recovered 88.10 ± 8.03% from the surface and free RNA fragment was removed by 99.75 ± 0.19% from the final eluted solution. When we tested the developed method under laboratory conditions, a 10-fold higher viral detection sensitivity (Detection limit: 1 pfu/100 cm2) than the current commercial protocol was observed. Using our new sample preparation protocol, we also confirmed that the virus was effectively removed from surfaces after chemical disinfection; we were unable to measure the disinfection efficiency using the current commercial protocol because it cannot distinguish between viral RNA and free RNA fragments. Finally, we investigated the presence of SARS-CoV-2 and bacteria in 12 individual negative pressure wards in which patients with SARS-CoV-2 infection had been hospitalized. Bacteria (based on 16 S DNA) were found in all samples collected from patient rooms; however, SARS-CoV-2 was mainly detected in rooms shared by two patients. Supplementary Information The online version contains supplementary material available at 10.1186/s40580-021-00281-8.

Background/Aims: Coronavirus disease 2019 (COVID-19) is associated with acute respiratory syndrome. The mechanisms underlying the different degrees of pneumonia severity in patients with COVID-19 remain elusive. This study provides evidence that COVID-19 is associated with eosinophil-mediated inflammation.Methods: We performed a retrospective case series of three patients with laboratory and radiologically confirmed COVID-19 pneumonia admitted to Chosun University Hospital. Demographic and clinical data on inflammatory cell lung infiltration and cytokine levels in patients with COVID-19 were collected.Results: Cytological analysis of sputum, tracheal aspirates, and bronchoalveolar lavage fluid (BALF) samples from all three patients revealed massive infiltration of polymorphonuclear cells (PMNs), such as eosinophils and neutrophils. All sputum and BALF specimens contained high levels of eosinophil cationic proteins. The infiltration of PMNs into the lungs, together with elevated levels of natural killer T (NKT) cells in BALF and peripheral blood samples from patients with severe pneumonia in the acute phase was confirmed by flow cytometry.Conclusions: These results suggest that the lungs of COVID-19 patients can exhibit eosinophil-mediated inflammation, together with an elevated NKT cell response, which is associated with COVID-19 pneumonia.

The great challenge to global public health caused by the coronavirus pandemic has lasted for two years in Korea. However, Korean young adults seem less compliant with preventive health behaviors than older adults. This study aims to explore the relationship between risk perception variables of optimistic bias, hypochondriasis, and mass psychology, and preventive health behavior in relation to the coronavirus pandemic through a cross-sectional online survey. The participants are 91 Korean young adults aged 19–30. The results show that mass psychology has a positive relationship with preventive health behavior, whereas optimistic bias and hypochondriasis do not. In detail, people with high or middle levels of mass psychology displayed higher preventive health behavior compared with those who had low levels of mass psychology, and the highest compliance was for wearing a mask, followed by COVID-19 vaccination, whereas the lowest compliance was for influenza vaccination. These findings could be explained by the Korean culture of strong collectivism and the characteristics of COVID-19, which evoked extreme fear globally. The results of this study can be useful for policy establishment in the ongoing prevention of COVID-19 and suggest that mass psychology should be used effectively in planning preventive communication campaigns.

The socioeconomic and clinical burden of multidrug-resistant organisms (MDRO), including methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant enterococci (VRE), multidrug-resistant Acinetobacter baumannii (MRAB), multidrug-resistant Pseudomonas aeruginosa (MRPA), and carbapenem-resistant Enterobacteriaceae (CRE) have not yet been adequately addressed.We prospectively searched for MDRO bacteremia cases with matched controls from 10 hospitals across Korea during a 6-month period in 2017. Patients were classified into the MDRO, susceptible organism, and no-infection groups. The corresponding susceptible or no-infection controls had been selected according to predefined criteria. We collected clinical information and estimated the total additional medical cost due to MDRO infections using the multistate model.During the 6-month period, a total of 486 MDRO bacteremia cases (260, 87, 18, 20, and 101 cases of MRSA, MRAB, MRPA, CRE, and VRE, respectively) were identified. The 90-d mortality rates were 30.4%, 63.2%, 16.7%, 55.0%, and 47.5%, respectively. The additional costs caused by bacteremia were $15 768, $35 682, $39 908, $72 051, and $33 662 per MDRO type, respectively. Based on these 6-month data, the estimated annual number of bacteremia cases due to these five MDRO in Korea were 7979 (4070, 1396, 218, 461, and 1834 cases, respectively). Overall, this caused an estimated 3280 (1237, 882, 36, 254, and 871, respectively) deaths and cost $294 505 002 ($84 707 359, $74 387 364, $10 344 370, $45 850 215, and $79 215 694, respectively) (range $170,627,020-$416,094,679) in socioeconomic loss.A tremendous clinical and economic burden is caused by MDRO bacteremia compared with antibiotic-susceptible and no-infection groups. Substantial investment and efforts by related government agencies and medical staffs are needed.

The integrase strand transfer inhibitor dolutegravir has been indicated in Korea since 2014 for the treatment of human immunodeficiency virus type 1 (HIV-1) infection in combination with other antiretroviral agents. This regulatory post-marketing surveillance (PMS) study evaluated the real-life safety and effectiveness of dolutegravir in patients with HIV-1 in clinical practice in Korea.This open-label PMS study examined data from consecutive patients (aged ≥12 years) with HIV-1 infection receiving dolutegravir according to locally approved prescribing information; treatment-naïve and treatment-experienced patients were permitted. Data regarding patient demographics, medical history, clinical characteristics, medications (HIV-related and concomitant), and comorbidities were extracted from patient records over a 1-year treatment period. Outcomes included the safety of dolutegravir (primary endpoint) and real-life effectiveness according to the Physician Global Assessment (PGA) and the proportion of patients with plasma HIV-1 RNA count50 copies/mL at 48 weeks.Of 147 patients treated with dolutegravir at 18 centers in Korea (August 2014 - August 2020), 139 were eligible for the safety analyses and 75 for effectiveness analyses. Patients (mean age 47 years) were mostly male (92.8%) and received dolutegravir in combination with nucleoside reverse transcriptase inhibitor (70.5%) or protease inhibitors (21.6%). Adverse events (AEs) (n = 179 in total) were mostly mild in severity, with the most common being nasopharyngitis (5.0%), dyspepsia (5.0%), pruritus (4.3%), and rash (4.3%). Of 16 adverse drug reactions (ADRs), the most frequent were rash, diarrhea, headache, insomnia, and somnolence (1.4% each). Of 2 serious ADRs, only 1 (gastroenteritis) was unexpected, and both resolved. The risk of experiencing an AE while receiving dolutegravir appeared to be especially increased in patients receiving concomitant medications for other conditions. Dolutegravir effectively suppressed HIV-1 (93.3% of patients had plasma HIV-1 RNA50 copies/mL), and 100% of patients showed symptom improvement based on physician global assessment.Results of this PMS study showed that dolutegravir administered as highly active antiretroviral therapy was well tolerated and effective in patients with HIV-1 infection.

Vinpocetine induces anti-inflammatory effects in various inflammatory diseases via the inhibition of phosphodiesterase type-1-independent nuclear factor-κB signaling pathway and the release of inflammatory cytokines. In this study, we investigated the effect of vinpocetine on the proliferation of colon cancer cells and its underlying molecular mechanisms. Our data showed that vinpocetine inhibits the viability and proliferation of colon cancer cells. Vinpocetine treatment induced cell death in HCT116 cells, which the percentages of sub-G1 phase were significantly increased, and the apoptosis-related genes were regulated after HCT116 cells were treated with vinpocetine. In sum, our findings indicated that vinpocetine could be a therapeutically useful candidate in the treatment of colon cancer.

Numerous patients around the globe are dying from coronavirus disease 2019 (COVID-19). While age is a known risk factor, risk analysis in the young generation is lacking. The present study aimed to evaluate the clinical features and mortality risk factors in younger patients (≤ 50 years) with a critical case of COVID-19 in comparison with those among older patients (50 years) in Korea.We analyzed the data of adult patients only in critical condition (requiring high flow nasal cannula oxygen therapy or higher respiratory support) hospitalized with PCR-confirmed COVID-19 at 11 hospitals in Korea from July 1, 2021 to November 30, 2021 when the delta variant was a dominant strain. Patients' electronic medical records were reviewed to identify clinical characteristics.During the study period, 448 patients were enrolled. One hundred and forty-two were aged 50 years or younger (the younger group), while 306 were above 50 years of age (the older group). The most common pre-existing conditions in the younger group were diabetes mellitus and hypertension, and 69.7% of the patients had a body mass index (BMI)25 kg/m². Of 142 younger patients, 31 of 142 patients (21.8%, 19 women) did not have these pre-existing conditions. The overall case fatality rate among severity cases was 21.0%, and it differed according to age: 5.6% (n = 8/142) in the younger group, 28.1% in the older group, and 38% in the ≥ 65 years group. Age (odds ratio [OR], 7.902; 95% confidence interval [CI], 2.754-18.181), mechanical ventilation therapy (OR, 17.233; 95% CI, 8.439-35.192), highest creatinine1.5 mg/dL (OR, 17.631; 95% CI, 8.321-37.357), and combined blood stream infection (OR, 7.092; 95% CI, 1.061-18.181) were identified as independent predictors of mortality in total patients. Similar patterns were observed in age-specific analyses, but most results were statistically insignificant in multivariate analysis due to the low number of deaths in the younger group. The full vaccination rate was very low among study population (13.6%), and only three patients were fully vaccinated, with none of the patients who died having been fully vaccinated in the younger group. Seven of eight patients who died had a pre-existing condition or were obese (BMI25 kg/m²), and the one remaining patient died from a secondary infection.About 22% of the patients in the young critical group did not have an underlying disease or obesity, but the rate of obesity (BMI25 kg/m²) was high, with a fatality rate of 5.6%. The full vaccination rate was extremely low compared to the general population of the same age group, showing that non-vaccination has a grave impact on the progression of COVID-19 to a critical condition. The findings of this study highlight the need for measures to prevent critical progression of COVID-19, such as vaccinations and targeting young adults especially having risk factors.

Background Zoonotic coronaviruses have emerged as a global threat by causing fatal respiratory infections. Given the lack of specific antiviral therapies, application of human convalescent plasma retaining neutralizing activity could be a viable therapeutic option that can bridges this gap. Methods We traced antibody responses and memory B cells in peripheral blood collected from 70 recovered Middle East respiratory syndrome coronavirus (MERS-CoV) patients for 3 years after the 2015 outbreak in South Korea. We also used a mouse infection model to examine whether the neutralizing activity of collected sera could provide therapeutic benefit in vivo upon lethal MERS-CoV challenge. Results Anti-spike-specific IgG responses, including neutralizing activity and antibody-secreting memory B cells, persisted for up to 3 years, especially in MERS patients who suffered from severe pneumonia. Mean antibody titers gradually decreased annually by less than 2-fold. Levels of antibody responses were significantly correlated with fever duration, viral shedding periods, and maximum viral loads observed during infection periods. In a transgenic mice model challenged with lethal doses of MERS-CoV, a significant reduction in viral loads and enhanced survival was observed when therapeutically treated with human plasma retaining a high neutralizing titer (> 1/5000). However, this failed to reduce pulmonary pathogenesis, as revealed by pathological changes in lungs and initial weight loss. Conclusions High titers of neutralizing activity are required for suppressive effect on the viral replication but may not be sufficient to reduce inflammatory lesions upon fatal infection. Therefore, immune sera with high neutralizing activity must be carefully selected for plasma therapy of zoonotic coronavirus infection.

Background Simplified regimens for the treatment of human immunodeficiency virus type 1 (HIV-1) infection may increase patient satisfaction and facilitate adherence. Methods In this phase ...

BACKGROUND Staphylococcus aureus bacteremia (SAB) is a common and serious infection with a high mortality. Patients with chronic kidney disease (CKD) are vulnerable to SAB, but there have been few studies performed on the clinical characteristics and outcomes of SAB in CKD patients stratified by dialysis. We aimed to estimate the all-cause mortality and identify its predictors in patients with CKD. MATERIALS AND METHODS We conducted a retrospective study on the patients with SAB hospitalized in a tertiary care center in Korea between March 2014 and December 2018. Kaplan-Meier analysis was performed to compare all-cause mortality following SAB among patients with non-dialysis dependent CKD (ND-CKD), those receiving dialysis, and those without CKD (non-CKD). The predictors of mortality among CKD patients were analyzed by Cox proportional hazards regression. RESULTS As a total, 278 SAB of 43 ND-CKD (31 males), 58 dialysis (39 males), and 177 non-CKD (112 males) patients were included. The 30-day mortality was 39.5% in ND-CKD, 27.6% in dialysis, and 7.9% in non-CKD patients. The hazard ratio of all-cause mortality following SAB in ND-CKD was 2.335 (95% confidence interval, 1.203 - 4.531; P = 0.003), compared to non-CKD patients. For methicillin-resistant S. aureus bacteremia (MRSAB), the hazard ratio of all-cause mortality in ND-CKD was 2.628 (95% CI, 1.074 - 6.435; P = 0.011), compared to dialysis patients. Appropriate antibiotics

BackgroundDespite improved survival of patients with lupus nephritis (LN), some require kidney transplantation because of progression to end-stage renal disease (ESRD). However, the transplant outcomes of these patients and other recipients have not been thoroughly compared.MethodsIn total, 1848 Korean kidney recipients who underwent transplantation from 1998 to 2017 at two tertiary referral centers were evaluated retrospectively. Among them, 28 recipients with LN, and 50 control recipients matched by age, sex, and donor type, were compared with respect to graft and patient survival. We pooled our data with 17 previous cohort studies in which the graft survival of recipients with LN was described in detail.ResultsDuring the median follow-up period of 9.5 years (maximum 21 years), graft failure (GF) occurred in 10.7% and 16.0% of LN and control recipients, respectively. No differences were found in the rates of GF and death-censored graft failure or patient survival between the two groups. The risks of acute T cell-mediated and antibody-mediated rejection were also similar between the two groups. The pooled analysis showed similar 1- and 5-year graft survival rates between LN and control recipients.ConclusionsKidney transplantation is an acceptable option in patients with concurrent LN and ESRD.

We aimed to estimate the socioeconomic burden of pneumonia due to multidrug-resistant Acinetobacter baumannii (MRAB) and Pseudomonas aeruginosa (MRPA).We prospectively searched for MRAB and MRPA pneumonia cases and matched them with controls with susceptible-organism pneumonia and non-infected cases from ten hospitals over a 6-month period. The matching criteria were: same principal diagnosis, same surgery or intervention during hospitalization, age (years ± 10), sex, and admission date within 60 days. The total additional direct medical cost was estimated by the multistate model. A total of 108 cases of MRAB pneumonia [MRAB-P] and 28 cases of MRPA pneumonia [MRPA-P] were identified. The 90-day mortality rate was 37.0% and 39.3% for MRAB-P and MRPA-P, respectively. The additional medical costs were $42,203 and $35,556 for MRAB-P and MRPA-P, respectively. The estimated number of MRAB-P and MRPA-P cases were 1,309–2,483 and 339–644, respectively with estimated deaths being 485–920 and 133–253 in a year, respectively. The annual socioeconomic burden was $12,053,593–$22,898,271 and $15,241,883–$28,994,008, respectively. We estimated that MRAB-P and MRPA-P occurred in 1,648–3,172 patients, with 618–1,173 deaths, and caused $27,295,476–$51,892,279 in socioeconomic burden nationwide. It is time to investigate and invest in prevention of multidrug-resistant bacterial pneumonia.

We aimed to estimate the socioeconomic burden of pneumonia due to multidrug-resistant Acinetobacter baumannii (MRAB) and Pseudomonas aeruginosa (MRPA). We prospectively searched for MRAB and MRPA pneumonia cases and matched them with susceptible-organism pneumonia and non-infected patients from 10 hospitals. The matching criteria were: same principal diagnosis, same surgery or intervention during hospitalisation, age, sex, and admission date within 60 days. We calculated the economic burden by using the difference in hospital costs, the difference in caregiver costs, and the sum of productivity loss from an unexpected death. We identified 108 MRAB pneumonia [MRAB-P] and 28 MRPA pneumonia [MRPA-P] cases. The estimated number of annual MRAB-P and MRPA-P cases in South Korea were 1309-2483 and 339-644, with 485-920 and 133-253 deaths, respectively. The annual socioeconomic burden of MRAB-P and MRPA-P in South Korea was $64,549,723-122,533,585 and $15,241,883-28,994,008, respectively. The results revealed that MRAB-P and MRPA-P occurred in 1648-3127 patients, resulted in 618-1173 deaths, and caused a nationwide socioeconomic burden of $79,791,606-151,527,593. Multidrug-resistant organisms (MDRO) impose a great clinical and economic burden at a national level. Therefore, controlling the spread of MDRO will be an effective measure to reduce this burden.