Clustering and multiple-spreading events of nosocomial severe acute respiratory syndrome coronavirus 2 infection.

BACKGROUND: There is growing evidence that super-spreading events (SSEs) and multiple-spreading events (MSEs) are a characteristic feature of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. However, data regarding the possibility of SSEs or MSEs in healthcare settings are limited. METHODS: This study was performed at a tertiary-care hospital in Korea. We analysed the nosocomial COVID-19 cases that occurred in healthcare workers and inpatients and their caregivers between January and 20th December 2020. Cases with two to four secondary cases were defined as MSEs and those with five or more secondary cases as SSEs. FINDINGS: We identified 21 nosocomial events (single-case events, N = 12 (57%); MSE + SSE, N = 9 (43%)) involving 65 individuals with COVID-19. Of these 65 individuals, 21 (32%) were infectors. The infectors tended to have a longer duration between symptom onset and diagnostic confirmation than did the non-infectors (median two days vs zero days, P=0.08). Importantly, 12 (18%) individuals were responsible for MSEs and one (2%) for an SSE, which collectively generated 35 (54%) secondary cases. CONCLUSION: In a hospital with thorough infection-control measures, approximately 70% of the nosocomial cases of COVID-19 did not generate secondary cases, and one-fifth of the infectors were responsible for SSEs and MSEs, which accounted for approximately half of the total cases. Early case identification, isolation, and extensive contact tracing are important for the prevention of transmission and SSEs.

Outbreak of carbapenemase-producing Enterobacteriaceae associated with a contaminated water dispenser and sink drains in the cardiology units of a Korean hospital.

BACKGROUND: Concerns are growing over the importance of the hospital water environment for the transmission of carbapenemase-producing Enterobacteriaceae (CPE). AIM: To report a large outbreak in the cardiology units involving intensive care units (ICUs) and wards at a tertiary-care hospital. METHODS: This was a contact tracing, case-control study to find the risk factors for acquisition of CPE and environmental sampling was performed during a CPE outbreak between July and December 2018. FINDINGS: A total of 87 patients with CPE infection or colonization were identified in the cardiology units of the Asan Medical Centre. Diverse organisms were identified containing blakpc, blaNDM-1, blaVIM or blaIMP, blaOXA-48, and co-producing organisms. A case-control study indicated that using the sinks in the ward patient room bathroom for teeth brushing was associated with CPE acquisition (83% vs 30%; P=0.03). The environment was cultured and Klebsiella pneumoniae carbapenemase (KPC)-producing Escherichia coli was isolated from a water dispenser and New Delhi metallo-beta-lactamase (NDM) 1-producing Citrobacter freundii and Enterobacter cloacae from sinks in patient rooms. Pulsed-field gel electrophoresis (PFGE) analysis of KPC-producing E. coli from patients and the water dispenser in ICU and NDM-1-producing E. cloacae from the patient and sink drain showed the same pulsotypes. CONCLUSIONS: The water dispenser and sink drain were suspected as possible reservoirs of CPE in this outbreak. Close contacts with contaminated water such as tooth brushing were identified as risk factors for CPE acquisition. Education for the adequate use of the water environment system as well as the control of the hospital water environment should be implemented to prevent the CPE outbreaks.

Protective role of γδ T cells in cigarette smoke and influenza infection.

Airborne pathogens commonly trigger severe respiratory failure or death in smokers with lung disease. Cigarette smoking compromises the effectiveness of innate immunity against infections but the underlying mechanisms responsible for defective acquired immune responses in smokers remains less clear. We found that mice exposed to chronic cigarette smoke recovered poorly from primary Influenza A pneumonia with reduced type I and II interferons (IFNs) and viral-specific immunoglobulins, but recruited γδ T cells to the lungs that predominantly expressed interleukin 17A (IL-17A). Il-17a-/- mice exposed to smoke and infected with Influenza A also recruited γδ T cells to the lungs, but in contrast to wild-type mice, expressed increased IFNs, made protective influenza-specific antibodies, and recovered from infection. Depletion of IL-17A with blocking antibodies significantly increased T-bet expression in γδ T cells and improved recovery from acute Influenza A infection in air, but not smoke-exposed mice. In contrast, when exposed to smoke, γδ T cell deficient mice failed to mount an effective immune response to Influenza A and showed increased mortality. Our findings demonstrate a protective role for γδ T cells in smokers and suggest that smoke-induced increase in IL-17A inhibits the transcriptional programs required for their optimal anti-viral responses. Cigarette smoke induces IL-17A expression in the lungs and inhibits γδ T-cell-mediated protective anti-viral immune responses.

A prospective study on symptom generation according to spicy food intake and TRPV1 genotypes in functional dyspepsia patients.

BACKGROUND: Capsaicin is an ingredient of red peppers that binds to transient receptor potential vanilloid subtype 1 (TRPV1), and Koreans eat more capsaicin-rich food than do Japanese. This study aimed to compare symptom generation according to TRPV1 genotypes and the intake of spicy foods. METHODS: Consecutive functional dyspepsia (FD) patients who were evaluated at Konkuk University Medical Centre (Korea) and Keio University Hospital (Japan) were included. Questionnaires on spicy food intake, patient assessment of gastrointestinal symptoms (PAGI-SYM), patient assessment of quality of life, and hospital anxiety and depression scale were provided. Blood was sampled for the detection of TRPV1 polymorphisms, and upper gastrointestinal endoscopy was performed with biopsies. KEY RESULTS: Of 121 included subjects, 35 and 28 carried the TRPV1 CC and GG genotypes, respectively, with the prevalence rates not differing between Japan and Korea. The prevalence of FD subtypes did not differ with the spicy food intake, TRPV1 genotypes, or Helicobacter pylori infection. Neither TRPV1 polymorphisms nor H. pylori infections were related to scores on the PAGI-SYM questionnaires, but spicy food intake was positively correlated with the scores for stomach fullness (p = 0.001) and retching (p = 0.001). Using the linear regression analysis, stomach fullness was associated with spicy food intake (p = 0.007), whereas retching was related to younger age (p < 0.001) and female gender (p = 0.014). CONCLUSIONS & INFERENCES: Upper gastrointestinal symptoms are more common in subjects with a higher consumption of spicy foods, younger age and female gender, regardless of TRPV1 genotypes and the H. pylori infection status. Capsaicin-rich foods may induce stomach fullness.

Spinal Accessory Nerve: Ultrasound Findings and Correlations with Neck Lymph Node Levels.

Purpose: To evaluate the ultrasound characteristics of the spinal accessory nerve (SAN) and correlate nerve location with neck lymph node level. Materials and Methods: 50 participants with 100 SANs were enrolled in this study. The SAN was traced from the trapezius muscle to the upper neck and was identified by a hypoechoic linear structure without color Doppler flow. The ultrasound characteristics of the SAN, such as visibility, diameter, relationship with adjacent structures, and its correlation with lymph node levels, were evaluated. Results: The SAN was identified in 96 %-100 % of segments. The mean diameter of the SAN was 0.54 ±â€Š0.09 mm. The SANs was located between the trapezius and levator scapulae muscles and 90.8 % were traced into the trapezius muscle. In the upper neck, the SAN passed deep into the sternocleidomastoid (SCM) muscle in 38 % of cases and between the two heads of the SCM muscle in 62 % of cases. The SAN was found at neck lymph node levels II, III, IV, and V, but not I or VI. Conclusion: Continuous ultrasound monitoring of the SAN and its correlation with lymph node levels is possible in most patients. Our current findings may assist in the future prevention of SAN injury during ultrasound-guided procedures.

A genetic variation in microRNA target site of KRT81 gene is associated with survival in early-stage non-small-cell lung cancer.

BACKGROUND: MicroRNAs (miRNAs) have a key role in carcinogenesis through negative regulation of their target genes. Therefore, genetic variations in miRNAs or their target sites may affect miRNA-mRNA interactions, thereby result in altered expression of target genes. This study was conducted to investigate the associations between single-nucleotide polymorphisms (SNP) located in the miRNA target sites (poly-miRTSs) and survival of patients with early-stage non-small-cell lung cancer (NSCLC). METHODS: Using public SNP database and miRNA target sites prediction program, 354 poly-miRTSs were selected for genotyping. Among these, 154 SNPs applicable to Sequenom's MassARRAY platform were investigated in 357 patients. A replication study was carried out on an independent patient population (n = 479). Renilla luciferase assay and reverse transcription-polymerase chain reaction were conducted to examine functional relevance of potentially functional poly-miRTSs. RESULTS: Of the 154 SNPs analyzed in a discovery set, 14 SNPs were significantly associated with survival outcomes. Among these, KRT81 rs3660G>C was found to be associated with survival outcomes in the validation cohort. In the combined analysis, patients with the rs3660 GC + CC genotype had a significantly better overall survival compared with those with GG genotype [adjusted hazard ratio (aHR) for OS, 0.65; 95% confidence interval (CI) 0.50-0.85; P = 0.001]. An increased expression of the reporter gene for the C allele of rs3660 compared with the G allele was observed by luciferase assay. Consistently, the C allele was associated with higher relative expression level of KRT81 in tumor tissues. CONCLUSION: The rs3660G>C affects KRT81 expression and thus influences survival in early-stage NSCLC. The analysis of the rs3660G>C polymorphism may be useful to identify patients at high risk of a poor disease outcome.

Activation of C3a receptor is required in cigarette smoke-mediated emphysema.

Exposure to cigarette smoke can initiate sterile inflammatory responses in the lung and activate myeloid dendritic cells (mDCs) that induce differentiation of T helper type 1 (Th1) and Th17 cells in the emphysematous lungs. Consumption of complement proteins increases in acute inflammation, but the contribution of complement protein 3 (C3) to chronic cigarette smoke-induced immune responses in the lung is not clear. Here, we show that following chronic exposure to cigarette smoke, C3-deficient (C3(-/-)) mice develop less emphysema and have fewer CD11b(+)CD11c(+) mDCs infiltrating the lungs as compared with wild-type mice. Proteolytic cleavage of C3 by neutrophil elastase releases C3a, which in turn increases the expression of its receptor (C3aR) on lung mDCs. Mice deficient in the C3aR (C3ar(-/-)) partially phenocopy the attenuated responses to chronic smoke observed in C3(-/-) mice. Consistent with a role for C3 in emphysema, C3 and its active fragments are deposited on the lung tissue of smokers with emphysema, and smoke-exposed mice. Together, these findings suggest a critical role for C3a through autocrine/paracrine induction of C3aR in the pathogenesis of cigarette smoke-induced sterile inflammation and provide new therapeutic targets for the treatment of emphysema.

Comparison of the clinical characteristics and imaging findings of acute cholangitis with and without biliary dilatation.

OBJECTIVE: To evaluate the causes of acute cholangitis without biliary dilatation and to compare the clinical characteristics and the imaging findings between patients with acute cholangitis with and without biliary dilatation. METHODS: 93 patients diagnosed with acute cholangitis underwent contrast-enhanced CT. Among them, 17 patients were classified as not having biliary dilatation (Group 1) and 76 patients were classified as having biliary dilatation (Group 2). The causes of acute cholangitis were evaluated in both groups. Clinical characteristics and imaging findings were compared between the two groups. RESULTS: The causes of acute cholangitis without biliary dilatation included common bile duct (CBD) stones (n=11), CBD sludge (n=3), a passed stone (n=1) and unknown causes (n=2). The total bilirubin levels of Group 1 were significantly lower than those of Group 2 (p=0.001). By contrast, Group 1 had higher median alanine aminotransferase (ALT) levels than Group 2 (p=0.04). The length of hospital stay was significantly longer in Group 2 than in Group 1 patients (p<0.001). In the imaging findings, the extent of transient hepatic attenuation differences (THADs) (p=0.003) were significantly smaller in Group 1 than in Group 2. CONCLUSION: CBD stones and sludge were the most common causes of acute cholangitis in patients without biliary dilatation. These patients showed lower levels of bilirubin and higher levels of ALT than those with acute cholangitis with biliary dilatation, and had a shorter duration of hospital stay. The extent of THADs was the only discriminative CT finding between the two groups. ADVANCES IN KNOWLEDGE: Acute cholangitis can present without biliary dilatation on imaging, and the most common causes are CBD stones and sludge. The patients with acute cholangitis without biliary dilatation have different clinical characteristics and imaging findings compared with those with acute cholangitis presenting with biliary dilatation.

Diagnostic performance of multidetector CT for acute cholangitis: evaluation of a CT scoring method.

OBJECTIVE: The aim of this study was to retrospectively assess the diagnostic performance of multidetector CT (MDCT) for the diagnosis of acute cholangitis using a new scoring method. METHODS: Of 80 patients with suspected biliary disease who underwent biphasic CT and endoscopic retrograde cholangiography, 39 were diagnosed as having acute cholangitis (Group 1) and 41 patients were classified as suspected biliary disease (Group 2). 100 age-matched patients without evidence of biliary disease were selected randomly as a control group (Group 3). Each patient's axial scan was scored by two independent radiologists for the extent of transient hepatic attenuation difference, the presence of biliary dilatation and identification of a biliary obstructive lesion. The difference in the scores among the three groups was evaluated and the optimal cut-off score for the diagnosis of acute cholangitis was determined. Interobserver agreement was also evaluated. RESULTS: The total scores (mean ± standard deviation) for Groups 1, 2 and 3 were 7.0 ± 2.0, 4.4 ± 2.4 and 0.9 ± 1.2, respectively, for Reviewer 1 and 7.2 ± 2.7 and 0.7 ± 1.1, respectively, for Reviewer 2. Significant differences were found for the subscores and the total scores among the three groups (p < 0.001). Using a cut-off score of ≥ 5, the sensitivity and specificity for diagnosing acute cholangitis were 84.6% and 83.7%, respectively, for Reviewer 1 and 89.7% and 83.7%, respectively, for Reviewer 2. Agreement for the subscores between readers was good to excellent (κ = 0.74-0.86). CONCLUSION: Based on dynamic MDCT and the described CT scoring method, the diagnosis of acute choangitis can be made with high sensitivity and specificity.

Food insecurity is associated with dietary intake and body size of Korean children from low-income families in urban areas.

OBJECTIVE: This study examined household food insecurity of urban low-income families in Korea and the associations of the food insecurity with children's dietary intake and body size. DESIGN: Cross-sectional study. SETTING: Low-income neighborhoods in large cities. SUBJECTS: Included 370 children aged 4-12 y, who had all records on dietary intake and anthropometry as well as household food insecurity measures. RESULTS: Using the 10-item Radimer/Cornell Scale, 62.7% of the households showed some degree of food insecurity (8.6% for food insecure for family, 28.4% for food insecure for adults and 25.7% for child hunger households). Food insecurity was linearly and negatively associated with household economic conditions as well as the caretaker's use of nutrition knowledge. There were also significant associations of food insecurity with the children's dietary intakes, indicating the largest amount of nutrients for the children from the household food insecure, followed by those from the food secure, adult food insecure and child hunger groups. The household food insecure children were fatter than the food secure children. The fatter condition of the former children appeared to be related to more frequent intakes of low-quality foods. CONCLUSION: This study reports curvilinear associations between the status of household food insecurity and children's food intakes and fatness. SPONSORSHIP: This work was funded by a grant of the 2001 Korea Health Promotion Research Program, the Ministry of Health & Welfare, Republic of Korea.

Relationship between dobutamine echocardiography and the elevation of cardiac troponin I in patients with acute coronary syndromes.

An elevated cardiac troponin I (cTnI) and a positive dobutamine echocardiography are powerful predictors for future cardiac events in patients with coronary artery disease. Investigating their correlation also should be helpful in understanding their clinical usefulness in evaluating patients with acute coronary syndromes (ACS). Dobutamine echocardiography and a blood sampling for cTnI were performed on 117 patients with ACS 70 +/- 2 hours after arriving at the hospital. CTnI was considered elevated when its value was greater than 2.0 ng/ml. Dobutamine echocardiography was positive in 86 (73.5%) patients, and cTnI was elevated in 37 (31.6%). The occurrence of positive dobutamine echocardiography in patients with elevated cTnI was significantly higher than in those with normal cTnI (86.5% vs. 67.5%, P = 0.042). More patients in the elevated cTnI group developed myocardial ischemia before or at the stage of dobutamine 20 microg/kg/min (43.2% vs. 15%, P = 0.002). When compared with patients with normal cTnI, patients with elevated cTnI had a lower ischemic threshold during dobutamine echocardiography, and more frequently had baseline echocardiographic wall-motion abnormalities, a history of myocardial infarction, and a positive dobutamine echocardiography. Using multivariate analysis, we found that only a lower dobutamine echocardiography ischemic threshold (P = 0.0008) and baseline wall-motion abnormalities (P = 0.0004) were associated independently with the elevation of cTnI. Our results suggest that in patients with ACS, dobutamine echocardiography can offer information regarding wall-motion abnormalities and ischemic threshold, which are suggested to have a clinical value similar to elevated cTnI.

Aberrant development of thymocytes in mice lacking laminin-2.

In previous in vitro studies, we proposed a role for the extracellular matrix component, laminin-2, and its integrin receptor, VLA-6, in thymocyte development. The characterization of two dystrophic mouse strains with different defects in laminin-2 allowed us to examine this proposal in vivo. Mice deficient in laminin-2, dy/dy, show a significant reduction in thymus size and number of thymocytes compared to normal littermates. These mice also exhibited apparent alterations of thymic architecture. Examination of the CD4/CD8 populations in dy/dy thymi showed large relative increases in the DN (CD4- CD8-) and SP (CD4+ CD8-, CD4- CD8+) populations and a significant decrease in the DP (CD4+ CD8+) population. Further examination of the DN population for CD44 and CD25 expression showed a remarkable decrease in the more mature pre-T cell populations. Analysis of apoptosis in situ, and by flow cytometry, in dy/dy thymi revealed a significant increase in apoptotic DN thymocytes in the capsule and subcapsular regions. Interestingly, thymocyte development appeared to proceed normally in dystrophic mice expressing a mutant form of laminin-2, dy2J, as well as, in fetal and neonatal dy/dy mice. We propose that laminin-2 plays an active role in thymocyte development by delivering cell survival and differentiation signals at specific stages of development in young adult mice.

Expression of a novel integrin beta 1 chain epitope and anti-beta 1 antibody-mediated enhancement of fibronectin binding are dependent on the stage of T cell differentiation.

Beta 1 integrins are a family of alpha beta heterodimers that serve as cell surface receptors for extracellular matrix proteins. We demonstrate that the anti-mouse integrin beta 1 chain mAb KMI6 selectively recognizes a beta 1 epitope that is constitutively expressed by certain immature thymocytes and is induced only slightly on mature thymocytes and peripheral T cells by activation with Con A. Because virtually all cells examined expressed beta 1 integrins on their surface, expression of the KMI6 epitope is T cell differentiation stage specific. Most CD3-4-8- thymocytes were KMI6+, with the lowest level of staining observed on the earliest CD44+IL-2R- cells within this subset. Expression was down-regulated during the CD3-4-8- to CD3-4-8+ transition, and lost by the CD4+8+ stage. Mature single positive thymocytes and resting peripheral T cells were also KMI6-. In contrast with the loss of the epitope before TCR expression by other thymocytes, most CD3+4-8- and certain CD8+ gamma delta TCR+ thymocytes were KMI6+ Addition of KMI6 to cell adhesion assays enhanced CD4-8- thymocyte, but not activated mature thymocyte or peripheral T cell, binding to fibronectin (via alpha 4 beta 1 and alpha 5 beta 1), whereas laminin binding (via alpha 6 beta 1) was unaffected. These properties distinguish the KMI6 epitope from other epitopes involved in beta 1 integrin activation in mice and other species. The unique selectivity of KMI6 recognition of beta 1 integrins, and its selective enhancement of ligand binding suggest that beta 1 integrin structure and factors that regulate beta 1 integrin binding are correlated with the stage of T cell differentiation.

Alpha 3 beta 1 and alpha 6 beta 1 integrins mediate laminin/merosin binding and function as costimulatory molecules for human thymocyte proliferation.

Integrins comprise a superfamily of alpha beta heterodimers that serve as cell signaling as well as adhesion molecules. We demonstrate that the alpha 3 beta 1 and alpha 6 beta 1 integrins are laminin/merosin receptors expressed in human thymocytes. By reverse transcriptase-PCR analysis, we determined that the alpha 3A beta 1, but not the alpha 3B beta 1, cytoplasmic structural variant of alpha 3 beta 1 is expressed in thymocytes. In contrast, both alpha 6A beta 1 and alpha 6B beta 1 cytoplasmic structural variants of alpha 6 beta 1 are expressed. A small percentage (10 to 15%) of human thymocytes bind to immobilized laminin, and even fewer (3 to 5%) bind to merosin, the laminin isoform normally present in the thymus. This binding, however, can be increased to 39 to 41% after activation of thymocytes with Mn2+ (or PMA). Binding to either laminin or merosin is completely inhibited by anti-beta 1 mAb or by a mixture of anti-alpha 3 and anti-alpha 6 mAbs, indicating that both alpha 3 beta 1 and alpha 6 beta 1 participate in thymocyte adhesion to the laminin family of extracellular matrix proteins. The protein kinase C inhibitors, calphostin C and staurosporine, inhibit Mn(2+)-enhanced thymocyte binding, suggesting that protein kinase C activity is crucial for the binding. Furthermore, the data indicate that at least two divalent cation binding sites serve to regulate integrin binding activity. Finally, we show that both immobilized laminin and merosin have costimulatory function for anti-CD3-induced thymocyte proliferation, and both anti-alpha 3 and anti-alpha 6 mAbs can block this proliferative response. The cooperative function of alpha 3 beta 1 and alpha 6 beta 1 evidenced in the laminin/merosin binding and proliferation assays suggests that thymocyte-merosin interactions may play an important role in thymic T cell development.

Isolated left coronary ostial stenosis--a case report.

A patient with isolated left coronary ostial stenosis proved by coronary angiography is presented. Isolated left coronary ostial stenosis is a rare condition of unknown etiology. Unique clinical and angiographic profiles are discussed in detail with a review of the literature, along with a suggestion of a natural history distinct from that usually seen in atherosclerotic coronary diseases.