Recommendations for Adult Immunization by the Korean Society of Infectious Diseases, 2023: Minor Revisions to the 3rd Edition.

The Korean Society of Infectious Diseases has been regularly developing guidelines for adult immunization since 2007. In 2023, the guidelines for the following seven vaccines were revised: influenza, herpes zoster, pneumococcal, tetanus-diphtheria-pertussis (Tdap), human papillomavirus (HPV), meningococcal, and rabies vaccines. For the influenza vaccine, a recommendation for enhanced vaccines for the elderly was added. For the herpes zoster vaccine, a recommendation for the recombinant zoster vaccine was added. For the pneumococcal vaccine, the current status of the 15-valent pneumococcal conjugate vaccine and 20-valent PCV was described. For the Tdap vaccine, the possibility of using Tdap instead of tetanus-diphtheria vaccine was described. For the HPV vaccine, the expansion of the eligible age for vaccination was described. For the meningococcal vaccine, a recommendation for the meningococcal B vaccine was added. For the rabies vaccine, the number of pre-exposure prophylaxis doses was changed. This manuscript documents the summary and rationale of the revisions for the seven vaccines. For the vaccines not mentioned in this manuscript, the recommendations in the 3rd edition of the Vaccinations for Adults textbook shall remain in effect.

Physical Activity and the incidence of sepsis: A 10-year observational study among 4 million adults.

BACKGROUND: As the group at high risk for sepsis is increasing with the aging of the population, physical activity (PA), which has beneficial effects on various diseases, needs to be considered as a personalized prevention strategy for sepsis without direct anti-sepsis drug. PURPOSE: To examine the association between the amount of PA (based on intensity, duration, and frequency) and the incidence rates of sepsis and mortality after sepsis. METHODS: This was a large-scale, retrospective, longitudinal cohort study using data from the Korean National Health Insurance Service and the biennial general health screening program. The amount of PA self-reported at the time of the health screening was categorized as non-PA, mild (<500 metabolic equivalents [METs]-Min/Week), moderate (500-1000), severe (1000-1500), and extreme (≥1500). The multivariable regression model was adjusted for age, sex, income, body mass index, smoking, alcohol consumption, diabetes, hypertension, dyslipidemia, and chronic diseases. RESULTS: From 4,234,415 individuals who underwent a health screening in 2009, 3,929,165 subjects were selected after exclusion for wash-out period and a 1-year lag period, and then observed for the event of sepsis or all-cause death until December 2020. During a median 10.3 years of follow-up, 83,011 incidents of sepsis were detected. The moderate-PA group showed the lowest incidence (1.56/1000 person-years) and risk for sepsis, with an adjusted hazard ratio (aHR) of 0.73 (95% CI, 0.72-0.75, P < 0.001) compared with the non-PA group. The occurrence of sepsis among people aged ≥65 years and ex-smokers were significantly lower in the moderate-PA group (aHR; 0.77, 95% CI; 0.74-0.79; and 0.68, 0.64-0.71, respectively, Ps < 0.001). The long-term all-cause mortality after sepsis was significantly lower in the PA group than in the non-PA group (overall P = 0.003). CONCLUSIONS: Physical activity is associated with a lower risk of sepsis, especially in elderly people who have the highest incidence of sepsis. The protective effects of aerobic PA on sepsis might need to be incorporated with other interventions in sepsis guidelines through the accumulation of future studies.

The Relation Between Cigarette Smoking and Development of Sepsis: A 10-Year Follow-Up Study of Four Million Adults from the National Health Screening Program.

BACKGROUND: Sepsis remains a growing global health concern with soaring mortality and no direct anti-sepsis drug. Although smoking has distinct deleterious effects on chronic inflammatory illnesses and can impair immune function, a comprehensive analysis of the connection between sepsis and smoking is lacking. METHODS: This large-scale longitudinal cohort study retrospectively assessed adults aged ≥ 20 years who underwent national health checkups under the Korean National Health Insurance Service between January and December 2009 (N = 4,234,415) and were followed up for 10 years. Sepsis was identified based on the International Classification of Diseases, 10th Revision codes, and smoking status, including accumulated amount, was collected through a self-administered questionnaire. The Cox proportional hazard regression model was used, adjusting for age, sex, household income, body mass index, drinking, exercise, diabetes, hypertension, dyslipidemia, and chronic renal disease. RESULTS: After excluding cases with sepsis occurring before follow-up or after ≤ 1 year of follow-up, 3,881,958 participants, including non-smokers (N = 2,342,841), former smokers (N = 539,850), and active smokers (N = 999,267), were included. Compared to non-smokers, all active smokers (adjust hazard ratio: 1.41, 95% confidence interval 1.38-1.44) and former smokers (1.10, 1.07-1.14) with ≥ 20 pack-years exhibited a significantly higher risk of sepsis (p < 0.001). Smoking of ≥ 30 pack-years in former and active smokers groups significantly increased sepsis incidence (adjust hazard ratio [95% confidence interval] 1.34 [1.31-1.38], p < 0.001). CONCLUSIONS: Smoking is closely associated with the incidence of sepsis. Smoking cessation may help in the primary prevention of sepsis.

Discovery and Characterization of Selective, First-in-Class Inhibitors of Citron Kinase.

Citron kinase (CITK) is an AGC-family serine/threonine kinase that regulates cytokinesis. Despite knockdown experiments implicating CITK as an anticancer target, no selective CITK inhibitors exist. We transformed a previously reported kinase inhibitor with weak off-target CITK activity into a first-in-class CITK chemical probe, C3TD879. C3TD879 is a Type I kinase inhibitor which potently inhibits CITK catalytic activity (biochemical IC50 = 12 nM), binds directly to full-length human CITK in cells (NanoBRET Kd < 10 nM), and demonstrates favorable DMPK properties for in vivo evaluation. We engineered exquisite selectivity for CITK (>17-fold versus 373 other human kinases), making C3TD879 the first chemical probe suitable for interrogating the complex biology of CITK. Our small-molecule CITK inhibitors could not phenocopy the effects of CITK knockdown in cell proliferation, cell cycle progression, or cytokinesis assays, providing preliminary evidence that the structural roles of CITK may be more important than its kinase activity.

Prevalence of carbapenemase producing Enterobacterales colonization and risk factor of clinical infection.

BACKGROUND: Carbapenemase-producing Enterobacterales (CPE) are global concerns in infection control, and the number of CPE outbreaks in hospitals is increasing despite the strengthening of contact precautions. This study aimed to confirm the prevalence and transition rate of CPE infection from stool surveillance culture and to identify the acquisition pathway of CPE. METHODS: This is a longitudinal review of patients with stool surveillance cultures at a tertiary center in Seoul, South Korea, from July 2018 to June 2020. Pulsed-field gel electrophoresis, multi-locus sequence typing, and whole genome sequencing were performed for carbapenemase-producing Klebsiella pneumoniae and Escherichia coli strains. RESULTS: Among 1620 patients who had undergone stool CPE surveillance cultures, only 7.1% of active surveillance at the Emergency Room (ER) and 4.4% of universal surveillance in the Intensive Care Unit (ICU) were stool CPE positive. The transition rates from stool carriers to clinical CPE infections were 29.4% in the ER and 31.3% in the ICU. However, it was significantly high (55.0%) in the initial stool CPE-negative ICU patients. Among the initial stool CPE-positive patients, hypertension (61% vs. 92.3%, P = 0.004), malignancy (28.8% vs. 53.8%, P = 0.027), and mechanical ventilation (25.4% vs. 53.8%, P = 0.011) were significant risk factors for clinical CPE infection. Molecular typing revealed that sequence type (ST) 307 and ST 395 were dominant in K. pneumoniae, and ST 410 was dominant in E. coli isolates. CONCLUSIONS: Active surveillance showed a higher detection rate than universal stool CPE screening, and one-third of positive stool CPE specimens ultimately developed subsquent clinical CPE infection. According to the molecular typing of the identified CPE strains, in-hospital spread prevailed over external inflow, and the transition rate to clinical CPE was particularly high in the ICU. Therefore, in order to control CPE propagation, not only active surveillance to block inflow from outside, but also continuous ICU monitoring within the hospital is necessary.

A multicenter, open-label study for efficacy and safety evaluation of anagrelide in patients with treatment-naïve, high-risk essential thrombocythemia as a primary treatment.

As the discussion of first-line anagrelide treatment is ongoing, we aimed to prospectively examine the efficacy and safety of anagrelide in cytoreduction therapy-naïve high risk essential thrombocythemia (ET) patients in Korea. Seventy patients from 12 centers were treated with anagrelide monotherapy for up to 8 weeks, followed up until 24 months. At week 8, 50.0% of the patients were able to achieve platelet < 600 x 109/L, and by 12 months, 55/70 (78.6%) patients stayed on anagrelide, and 40.0% patients showed platelet normalization. 14 patients required additional hydroxyurea (HU) for cytoreduction. The median daily dose of needed HU was 500mg (range 250mg - 1500mg). The efficacy was independent of the somatic mutation status. There were 4 thromboembolic events and 7 bleeding events during the follow-up period. The most common adverse events associated with anagrelide use were headache, followed by palpitation/chest discomfort, edema and generalized weakness/fatigue. 7 patients wished to discontinue anagrelide treatment due to adverse events (3 due to headache; 2 due to edema; 1 due to palpitation and 1 due to skin eruption). All in all, first-line anagrelide treatment showed a favorable response with tolerable safety profiles regardless of somatic mutation status.

Antiviral activity of canine interferon lambda 3 expressed using a recombinant adenovirus against canine coronavirus, canine parvovirus, and canine distemper virus.

Canine coronavirus (CCoV), canine parvovirus (CPV), and canine distemper virus (CDV) are highly contagious canine pathogens; dogs with these diseases are difficult to treat. In a previous study, we developed a recombinant adenovirus expressing canine interferon lambda 3 (Ad-caIFNλ3) in canine epithelial cells. In this study, we aimed to investigate the antiviral activity of Ad-caIFNλ3 against CCoV, CPV, and CDV in two canine cell lines, A72 and MDCK. Ad-caIFNλ3 transduction suppressed replication of these viruses without cytotoxicity. Our results suggest that Ad-caIFNλ3 may be a therapeutic candidate for canine viral diseases.

Association of cytomegalovirus diseases with newly developed myocardial infarction and congestive heart failure: data from a national population-based cohort.

Introduction: Anti-cytomegalovirus (CMV) IgG seropositive and/or titer are associated with a higher risk of cardiovascular diseases (CVD). However, it is not clear whether CMV end-organ disease may have a relation with development of CVD or chronic heart diseases. Material and methods: In matched cohort study, the National Health Insurance Database covering 50 million people was used to identify 667 patients with CMV diseases and aged ≥ 20 years between 2010 and 2014. 6,670 control subjects without CMV diseases were matched by age, sex, type 2 diabetes mellitus (DM), hypertension, dyslipidemia, and cohort entry year. Data on CMV disease and heart disease events of myocardial infarction (MI), congestive heart failure (CHF), and atrial fibrillation (AF) were retrieved. Previous events before CMV disease or cohort entry were excluded until January 2006. Subjects were followed until December 2015 in subjects without events and until date of events in subjects with events. Results: The multivariate regression model adjusted by age, sex, low-income status, type 2 DM, hypertension, dyslipidemia, solid organ transplantation, and hematopoietic stem cell transplantation showed a significantly higher incidence rate of MI (odds ratio (OR) = 2.1, 95% confidence intervals (CI): 1.0-4.5) and CHF (OR = 3.8, 95% CI: 2.1-6.8) but not AF (OR = 1.9, 95% CI: 0.9-4.0) in patients with CMV disease. The age group of 40-64 years with CMV disease had the highest risk for new-onset CHF in this regression model (OR = 9.4, 95% CI: 4.12-21.44, p = 0.029). Conclusions: Symptomatic CMV tissue-invasive diseases were associated with a higher risk of new-onset MI and CHF.

Clinical Implication of Candida Score in Multidrug-Resistant Pneumonia with Airway Candida Colonization.

BACKGROUND: The growth of Candida in respiratory secretions is usually considered colonization, and antifungal therapy is rarely required. The role of Candida colonization in the progression of bacterial pneumonia remains controversial. The aim of this study was to identify the clinical implication of Candida score by analyzinge the relationship with multidrug-resistant (MDR) pneumonia and prognosis in patients with airway Candida colonization. MATERIALS AND METHODS: This study was a retrospective review of patients with airway Candida colonization by bronchial washing or bronchoalveolar lavage. The Candida score was calculated according to the four factors (severe sepsis, surgery at baseline, total parenteral nutrition, and multifocal Candida colonization). Pneumonia related mortality or hopeless discharge expecting death was defined as a poor outcome. RESULTS: A total of 148 patients were enrolled in the study. In a multivariate analysis model, Candida score was identified as an independent predictor of poor outcomes (odds ratio 2.23; 95% confidential interval 1.57 - 3.17; P <0.001) in pneumonia patients with airway Candida colonization. With a Candida score of three or higher compared with low score group, it was associated with bacterial pneumonia, especially methicillin-resistant Staphylococcus aureus (MRSA) infection (0.0% vs. 15.2%, P = 0.004). In addition, patients with a high Candida score had a longer hospital stay (13 vs. 38 days, P <0.001), longer duration of intensive care (7 vs. 18 days, P <0.001), and higher pneumonia-related mortality (0.0% vs. 45.5%, P <0.001) as compared to the low Candida score group. The Candida score showed a positive correlation with other pneumonia severity scales such as CURB-65 (Confusion, Urea, Respiratory rate, Blood pressure, and age ≥65 years) (r = 0.461, P <0.001), Pneumonia Severity Index (r = 0.397, P <0.001), and predisposition, insult, response, and organ dysfunction (PIRO) score (r = 0.425, P <0.001). CONCLUSION: This study revealed that Candida is no longer a bystander of airway colonization, and that it affects the progression of bacterial pneumonia, including multidrug-resistant pathogens, particularly MRSA infection. Also Candida score can be used to predict the prognosis of patients with pneumonia.

Human MicroRNAs Attenuate the Expression of Immediate Early Proteins and HCMV Replication during Lytic and Latent Infection in Connection with Enhancement of Phosphorylated RelA/p65 (Serine 536) That Binds to MIEP.

Attenuating the expression of immediate early (IE) proteins is essential for controlling the lytic replication of human cytomegalovirus (HCMV). The human microRNAs (hsa-miRs), miR-200b-3p and miR-200c-3p, have been identified to bind the 3'-untranslated region (3'-UTR) of the mRNA encoding IE proteins. However, whether hsa-miRs can reduce IE72 expression and HCMV viral load or exhibit a crosstalk with the host cellular signaling machinery, most importantly the NF-κB cascade, has not been evaluated. In this study, argonaute-crosslinking and immunoprecipitation-seq revealed that miR-200b-3p and miR-200c-3p bind the 3'-UTR of UL123, which is a gene that encodes IE72. The binding of these miRNAs to the 3'-UTR of UL123 was verified in transfected cells stably expressing GFP. We used miR-200b-3p/miR-200c-3p mimics to counteract the downregulation of these miRNA after acute HCMV infection. This resulted in reduced IE72/IE86 expression and HCMV VL during lytic infection. We determined that IE72/IE86 alone can inhibit the phosphorylation of RelA/p65 at the Ser536 residue and that p-Ser536 RelA/p65 binds to the major IE promoter/enhancer (MIEP). The upregulation of miR-200b-3p and miR-200c-3p resulted in the phosphorylation of RelA/p65 at Ser536 through the downregulation of IE, and the binding of the resultant p-Ser536 RelA/p65 to MIEP resulted in a decreased production of pro-inflammatory cytokines. Overall, miR-200b-3p and miR-200c-3p-together with p-Ser536 RelA/p65-can prevent lytic HCMV replication during acute and latent infection.

Pulmonary Tuberculosis and Risk of Lung Cancer: A Systematic Review and Meta-Analysis.

Pulmonary tuberculosis (TB) is a known risk factor for lung cancer. However, a detailed analysis of lung cancer type, age, sex, smoking, and TB burden associated with geographic and socioeconomic status has not been performed previously. We systematically appraised relevant observational studies reporting an association between pulmonary TB and lung cancer. All studies were included in the primary analysis, and studies that used robust TB diagnostic methods, such as validated medical diagnostic codes, were included in the secondary analysis. Thirty-two articles were included. The association between the history of pulmonary TB and diagnosis of lung cancer was statistically significant (OR 2.09, 95% CI: 1.62-2.69, p < 0.001). There was a high heterogeneity (I2 = 95%), without any publication bias. The analysis indicated a high association in advanced articles describing stringent pulmonary TB diagnosis (OR 2.26, 95% CI: 1.29-3.94, p = 0.004). The subgroup analyses suggested a significant association in countries with medium or high TB burdens, from East Asia and the Pacific region, and upper-middle income countries. Heterogeneity within the subgroups remained high in a majority of the subgroup analyses. A meta-regression analysis revealed that younger patients showed a significantly higher association between TB and lung cancer (regression coefficient = 0.949, p < 0.001). The history of pulmonary TB is an independent risk factor for lung cancer, especially in younger patients diagnosed with pulmonary TB. Clinicians should be aware of this association while treating young patients with a history of pulmonary TB.

Structure-Based Optimization of ML300-Derived, Noncovalent Inhibitors Targeting the Severe Acute Respiratory Syndrome Coronavirus 3CL Protease (SARS-CoV-2 3CLpro).

Starting from the MLPCN probe compound ML300, a structure-based optimization campaign was initiated against the recent severe acute respiratory syndrome coronavirus (SARS-CoV-2) main protease (3CLpro). X-ray structures of SARS-CoV-1 and SARS-CoV-2 3CLpro enzymes in complex with multiple ML300-based inhibitors, including the original probe ML300, were obtained and proved instrumental in guiding chemistry toward probe compound 41 (CCF0058981). The disclosed inhibitors utilize a noncovalent mode of action and complex in a noncanonical binding mode not observed by peptidic 3CLpro inhibitors. In vitro DMPK profiling highlights key areas where further optimization in the series is required to obtain useful in vivo probes. Antiviral activity was established using a SARS-CoV-2-infected Vero E6 cell viability assay and a plaque formation assay. Compound 41 demonstrates nanomolar activity in these respective assays, comparable in potency to remdesivir. These findings have implications for antiviral development to combat current and future SARS-like zoonotic coronavirus outbreaks.

Epidemiological changes in cytomegalovirus end-organ diseases in a developed country: A nationwide, general-population-based study.

BACKGROUND: Cytomegalovirus (CMV) can cause tissue-invasive diseases in various organs after primary infection or through reactivation of latent-to-lytic switch over a lifetime. The number of individuals who are at risk of CMV diseases, such as elderly or immunocompromised patients, is constantly increasing; however, recent epidemiological changes associated with CMV disease have not been fully evaluated. METHODS: We used claims data of about 50 million individuals between 2010 and 2015 from the Korean Health Insurance Review and Assessment Service nationwide database. The code for CMV end-organ diseases in the 'Relieved Co-payment Policy' program matches the ICD-10 code of B25, except for congenital CMV infection and mononucleosis. A 628 cases of CMV and 3140 controls (without CMV disease), matched for age and sex, were selected from this dataset in order to evaluate the effect of adult CMV diseases on all-cause death. RESULTS: The overall unadjusted incidence rate (IR) of CMV end-organ diseases was 0.52/100,000 individuals. The standardized IR, adjusted for age and sex, have continuously increased from 0.32/100,000 in 2010 to 0.75/100,000 in 2015. The overall unadjusted IR in adult population was highest in 70-79 years for six years (0.96/100,000). In the model adjusted for age, sex, immunocompromised status including solid-organ or hematopoietic stem cell transplant recipients, hematologic malignancies, and human immunodeficiency virus diseases, the hazard ratio of case group was 5.2 (95% confidence interval, 3.6-7.4) for all-cause mortality. CONCLUSION: Nationwide data indicates that CMV end-organ disease has steadily increased in the past six years and is associated with higher mortality.

Incidence rate of active tuberculosis in solid organ transplant recipients: Data from a nationwide population cohort in a high-endemic country.

BACKGROUND: The management of active tuberculosis (TB) in solid organ transplantation (SOT) recipients is challenging given the pharmacological interaction and the potential delays in diagnosis due to atypical presentation. The incidence rates (IRs) of post-SOT TB from the whole recipients' cohort in a high-endemic country have not been evaluated. METHODS: We established a SOT cohort (n = 15 598) and confirmed cases of TB between 2011 and 2015 from the Korean National Health Insurance Database using ICD-10 codes. After excluding 1302 and 180 SOT-recipients due to age (<18 years) and presence of pre-SOT TB and/or treatment for latent TB during wash-out period between 2006 and cohort entry, we analyzed 14 116 SOT recipients and 70 580 individuals with no history of SOT matched by age and sex. The hazard ratios (HRs) of IRs were adjusted for age, sex, low-income status, diabetes mellitus, chronic co-morbidities, and anti-TNF-α therapy. RESULTS: The IR of TB was significantly higher (adjusted HR [aHR]: 6.1, 95% confidence interval [CI]: 4.5-7.6) in SOT recipients (4.9/1000 person-years) than in non-SOT individuals (0.8/1000 person-years). Of the transplanted organs, the pancreas (pancreas alone and simultaneous pancreas-kidney) and lung had the highest IR (aHR: 16.3 [6.1-42.2] and 16.1 [5.9-43.8], respectively). The use of anti-thymocyte globulin and azathioprine was associated with a higher IR (aHR: 1.53 [1.01-2.43] and 3.92 [1.21-12.47], respectively), but basiliximab was associated with a lower IR (aHR: 0.67 [0.48-0.98]). CONCLUSION: The IR of TB in SOT recipients, especially in the pancreas and lung, was significantly higher than that in the non-SOT population.

The Incidence and Effect of Cytomegalovirus Disease on Mortality in Transplant Recipients and General Population: Real-world Nationwide Cohort Data.

Background: In addition to the conventional opportunistic infections in solid organ transplantation (SOT) and hematopoietic stem cell transplantation (HSCT) recipients, cytomegalovirus (CMV) infection is associated with various chronic inflammatory diseases or poor outcomes in non-immunocompromised critically ill patients. To evaluate the burden or outcome of CMV replication in non-transplant individuals, we compared the incidence rates (IRs) for CMV disease and all-cause mortality between SOT recipients, HSCT recipients, and non-transplant population. Methods: The SOT (N=16,368) and HSCT (N=10,206) cohorts between 2010 and 2015 were established using the WHO ICD-10 from the whole population-based large database of the Health Insurance Review & Assessment Service (HIRA). CMV cases, defined as symptomatic disease with isolation of virus, DNA, pp65 antigen, and pathology except CMV syndrome, were extracted with the unique codes for relief of medical costs of HIRA in the same dataset. Cox's proportional hazard regression analyses and log-rank test in the Kaplan-Meier curves were performed to compare all-cause mortality between the three groups. Results: The CMV IRs adjusted by age and sex were significantly higher in the SOT (adjusted IR [95% confidence intervals], 33.1 [28.8-38.0] per 1,000 person-years) and HSCT recipients (5.1 [4.6-6.1] per 1,000 person-years) than in the whole population (0.58 [0.49-0.67] per 100,000 person-years). However, SOT recipients with CMV (18/283, 6.4%) had significantly lower all-cause mortality than non-transplant individuals with CMV (207/1,258, 16.5%) (adjusted hazard ratio [95% CI], 0.42 [0.25-0.67], log-rank P < 0.001). Conclusion: These data suggest that CMV disease in patients without transplants is associated with poor outcomes.

Induction of IFN-ß through TLR-3- and RIG-I-Mediated Signaling Pathways in Canine Respiratory Epithelial Cells Infected with H3N2 Canine Influenza Virus.

Canine influenza virus (CIV) induces acute respiratory disease in dogs. In this study, we aimed to determine the signaling pathways leading to the induction of IFN-ß in a canine respiratory epithelial cell line (KU-CBE) infected with the H3N2 subtype of CIV. Small interfering RNAs (siRNAs) specific to pattern recognition receptors (PRRs) and transcription factors were used to block the IFN-ß induction signals in H3N2 CIV-infected KU-CBE cells. Among the PRRs, only the TLR3 and RIG-I expression levels significantly (p < 0.001) increased in CIV-infected cells. Following transfection with siRNA specific to TLR3 (siTLR3) or RIG-I (siRIG-I), the mRNA expression levels of IFN-ß significantly (p < 0.001) decreased, and the protein expression of IFN-ß also decreased in infected cells. In addition, co-transfection with both siTLR3 and siRIG-I significantly reduced IRF3 (p < 0.001) and IFN-ß (p < 0.001) mRNA levels. Moreover, the protein concentration of IFN-ß was significantly (p < 0.01) lower in cells co-transfected with both siTLR3 and siRIG-I than in cells transfected with either siTLR3 or siRIGI alone. Also, the antiviral protein MX1 was only expressed in KU-CBE cells infected with CIV or treated with IFN-ß or IFN-α. Thus, we speculate that IFN-ß further induces MX1 expression, which might suppress CIV replication. Taken together, these data indicate that TLR3 and RIG-I synergistically induce IFN-ß expression via the activation of IRF3, and the produced IFN-ß further induces the production of MX1, which would suppress CIV replication in CIV-infected cells.

Lenalidomide for anemia correction in lower-risk del(5q) myelodysplastic syndrome patients of Asian ethnicity.

BACKGROUND: To estimate real-world outcomes in East Asian populations, we conducted a nationwide retrospective analysis of the efficacy and safety of lenalidomide for del(5q) myelodysplastic syndrome (MDS) patients with transfusion-dependent anemia in Korea. METHODS: Patients aged ≥19 years who had received lenalidomide for the treatment of lower-risk, red blood cell (RBC) transfusion-dependent del(5q) MDS were selected. A filled case report form (CRF) with information from electronic medical records was requested from members of the acute myeloid leukemia (AML)/MDS Working Party of the Korean Society of Hematology. All the CRFs were gathered and analyzed. RESULTS: A total of 31 patients were included in this study. Of 28 evaluable patients, 19 (67.9%) achieved RBC transfusion independence (RBC-TI). Female sex and the development of thrombocytopenia during treatment were associated with achieving RBC-TI. The most common non-hematologic toxicities were pruritus, fatigue, and rashes. All non-hematologic toxicities of grades ≥3 were limited to rash (12.9%) and pruritus (6.5%). Dose reduction was required in 15 of the 19 responders (78.9%). The most common final stable dosing schedule for the responders was 5 mg once every other day (31.6%). CONCLUSION: Lenalidomide efficacy and tolerability were similar in the Asian del(5q) MDS patients and western patients. Dose reduction during treatment was common, but it was not associated with inferior outcomes.

A novel synthetic microtubule inhibitor exerts antiproliferative effects in multidrug resistant cancer cells and cancer stem cells.

The success of cancer chemotherapy is limited by multidrug resistance (MDR), which is mainly caused by P-glycoprotein (P-gp) overexpression. In the present study, we describe a novel microtubule inhibitor, 5-(N-methylmaleimid-3-yl)-chromone (SPC-160002), that can be used to overcome MDR. A synthetic chromone derivative, SPC-160002, showed a broad spectrum of anti-proliferative effects on various human cancer cells without affecting P-gp expression and its drug efflux function. Treatment with SPC-160002 arrested the cell cycle at the M phase, as evidenced using fluorescence-activated cell sorting analysis, and increased the levels of mitotic marker proteins, including cyclin B, pS10-H3, and chromosomal passenger complex. This mitotic arrest by SPC-160002 was mediated by promoting and stabilizing microtubule polymerization, similar to the mechanism observed in case of taxane-based drugs. Furthermore, SPC-160002 suppressed the growth and sphere-forming activity of cancer stem cells. Our data herein strongly suggest that SPC-160002, a novel microtubule inhibitor, can be used to overcome MDR and can serve as an attractive candidate for anticancer drugs.

Characteristics of community-acquired respiratory viruses infections except seasonal influenza in transplant recipients and non-transplant critically ill patients.

BACKGROUND/PURPOSE: Transplant recipients are vulnerable to life-threatening community-acquired respiratory viruses (CA-RVs) infection (CA-RVI). Even if non-transplant critically ill patients in intensive care unit (ICU) have serious CA-RVI, comparison between these groups remains unclear. We aimed to evaluate clinical characteristics and mortality of CA-RVI except seasonal influenza A/B in transplant recipients and non-transplant critically ill patients in ICU. METHODS: We collected 37,777 CA-RVs multiplex real-time reverse transcription-polymerase chain reaction test results of individuals aged ≥18 years from November 2012 to November 2017. The CA-RVs tests included adenovirus, coronavirus 229E/NL63/OC43, human bocavirus, human metapneumovirus, parainfluenza virus 1/2/3, rhinovirus, and respiratory syncytial virus A/B. RESULTS: We found 286 CA-RVI cases, including 85 solid organ transplantation recipients (G1), 61 hematopoietic stem cell transplantation recipients (G2), and 140 non-transplant critically ill patients in ICU (G3), excluding those with repeated isolation within 30 days. Adenovirus positive rate and infection cases were most prominent in G2 (p < 0.001). The median time interval between transplantation and CA-RVI was 30 and 20 months in G1 and G2, respectively. All-cause in-hospital mortality was significantly higher in G3 than in G1 or G2 (51.4% vs. 28.2% or 39.3%, p = 0.002, respectively). The mechanical ventilation (MV) was the independent risk factor associated with all-cause in-hospital mortality in all three groups (hazard ratio, 3.37, 95% confidence interval, 2.04-5.56, p < 0.001). CONCLUSIONS: This study highlights the importance of CA-RVs diagnosis in transplant recipients even in long-term posttransplant period, and in non-transplant critically ill patients in ICU with MV.