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Fully vaccinated people remain at risk of Coronavirus Disease 2019 (COVID-19). We examined association between prior vaccination and clinical outcomes in patients with COVID-19. Overall, 387 patients with mild-to-severe COVID-19 were enrolled. Patients were considered fully vaccinated at least 14, 7, and 14 days after receiving the second dose of ChAdOx1 nCoV-19 or mRNA-1273, second dose of BNT162b2, or single dose of Ad26.COV2.S, respectively. The primary outcomes (risk of pneumonia, requirement of supplemental oxygen, and progression to respiratory failure) were compared between vaccinated and unvaccinated patients. Logistic regression analysis was performed to identify factors associated with the outcomes. There were 204 and 183 patients in the vaccinated and unvaccinated groups, respectively. The vaccinated group was significantly older and had more comorbidities than the unvaccinated group. Patients in the unvaccinated group were significantly more likely to develop pneumonia (65.6% vs. 36.8%) or require supplemental oxygen (29.0 vs. 15.7%) than the vaccinated group. The vaccinated group had a significantly shorter time from symptom onset to hospital discharge than the unvaccinated group (10 vs. 11 days; p

Background/Aims: There are few studies describing contemporary status of mechanical ventilation in Korea. We investigated changes in management and outcome of mechanical ventilation in Korea.Methods: International, prospective observational cohort studies have been conducted every 6 years since 1998. Korean intensive care units (ICUs) participated in 2010 and 2016 cohorts. We compared 2016 and 2010 Korean data.Results: Two hundred and twenty-six patients from 18 ICUs and 275 patients from 12 ICUs enrolled in 2016 and 2010, respectively. In 2016 compared to 2010, use of non-invasive ventilation outside ICU increased (10.2% vs. 2.5%, p = 0.001). Pressure-control ventilation was the most common mode in both groups. Initial tidal volume (7.1 mL/kg vs. 7.4 mL/kg, p = 0.372) and positive end-expiratory pressure (6 cmH2O vs. 6 cmH2O, p = 0.141) were similar, but peak pressure (22 cmH2O vs. 24 cmH2O, p = 0.011) was lower in 2016. More patients received sedatives (70.7% vs. 57.0%, p = 0.002) and analgesics (86.5% vs. 51.1%, p < 0.001) in 2016. The awakening (48.4% vs. 31.0%, p = 0.002) was more frequently attempted in 2016. The accidental extubation rate decreased to one tenth of what it was in 2010 (1.1% vs. 10.2%, p < 0.001). The ICU mortality did not change (31.4% 35.6%, p = 0.343) but ICU length of stay showed a decreasing trend (9 days vs. 10 days, p = 0.054) in 2016.Conclusions: There were temporal changes in care of patients on mechanical ventilation including better control of pain and agitation, and active attempt of awakening.

Human lung organoids (hLOs) are useful for disease modelling and drug screening. However, a lack of immune cells in hLOs limits the recapitulation of in vivo cellular physiology. Here, we generated hLOs containing alveolar macrophage (AMφ)-like cells derived from pluripotent stem cells (PSC). To bridge hLOs with advanced human lung high-resolution X-ray computed tomography (CT), we acquired quantitative micro-CT images. Three hLO types were observed during differentiation. Among them, alveolar hLOs highly expressed not only lung epithelial cell markers but also AMφ-specific markers. Furthermore, CD68

Patients with chronic diseases require ongoing treatment, and caregivers face financial burdens as well as psychological and physical difficulties. However, the current healthcare system does not provide adequate systems or services to address the difficulties that patients and caregivers face.The purpose of this study was to conduct an observational case study in order to evaluate and improve the application of an integrative healthcare service model developed for distress management and improved quality of life in breast cancer (BC) patients and caregivers.The integrative healthcare service model was intensively applied to a patient-caregiver pair in this observational study. This was followed by gathering feedback from participants and experts, as well as reflecting on the content of the feedback in order to improve the model further.This study will then modify and improve the program with feedback and provide integrative medical services to a BC patient and caregiver.This study used the BC patients' pain management and quality of life enhancement model, aiming to provide basic data for the establishment of a healthcare service system for patients suffering from chronic pain due to diseases such as BC by systematically integrating previously applied interventions into the current healthcare system and soliciting feedback from patients and caregivers.

Neuroinflammation is considered one of major factors in the pathogenesis of Alzheimer's disease (AD). In particular, inflammasome activation, including NLRP3 inflammasome in microglia, is regarded as fundamental for the pro-inflammatory response of immune cells. However, the precise molecular mechanism through which the NLRP3 inflammasome is associated with AD pathologies remains unclear. Here, we show that amyloid-β activates the NLRP3 inflammasome in microglia by activating Syk and inhibiting AMPK. Deactivated AMPK induces metabolic dysregulation, mitochondrial fragmentation, and reactive oxygen species formation, leading to the activation of the NLRP3 inflammasome. In addition, flufenamic acid (FA), a member of non-steroidal anti-inflammatory drugs, was found to effectively inhibit activation of the microglial NLRP3 inflammasome by regulating Syk and AMPK. Importantly, FA has marked therapeutic effects on major AD pathologies and memory function in vivo in microglia-dependent way. All together, these findings demonstrate the molecular mechanism of microglial NLRP3 inflammasome activation by amyloid-β, which acts as an important mediator of neuroinflammation. Also, we suggest that repurposing of FA for inhibiting microglial activation of the NLRP3 inflammasome is a potential treatment for AD.

There is a lack of evidence of genetic variation in the Helicobacter pylori cag-PAI in Thailand, a region with the low incidence of gastric cancer. To clarify this issue, variation in the H. pylori cag-PAI in strains detected in Thailand was characterized and simultaneously compared with strains isolated from a high-risk population in Korea. The presence of ten gene clusters within cag-PAI (cagA, cagE, cagG, cagH, cagL, cagM, cagT, orf13, virB11, and orf10) and IS605 was characterized in H. pylori strains detected from these two countries. The cagA genotypes and EPIYA motifs were analyzed by DNA sequencing. The overall proportion of the ten cag-PAI genes that were detected ranged between 66 and 79%; additionally, approximately 48% of the strains from Thai patients contained an intact cag-PAI structure, while a significantly higher proportion (80%) of the strains from Korean patients had an intact cag-PAI. A significantly higher proportion of IS605 was detected in strains from Thai patients (55%). Analysis of cagA genotypes and EPIYA motifs revealed a higher frequency of Western-type cagA in Thai patients (87%) relative to Korean patients (8%) who were predominately associated with the East Asian-type cagA (92%). Variations in the Western-type cagA in the Thai population, such as EPIYA-BC patterns and EPIYA-like sequences (EPIYT), were mainly detected as compared with the Korean population (p

In this study, we aimed to investigate the prevalence of bab genes (babA, babB, babC) at their three loci (loci A, B, and C) in Helicobacter pylori strains from varied clinical manifestations of Korean gastroduodenal patients. The overall prevalence of H. pylori Korean strains positive for babA and babB was 91.1% and 92.2%, respectively, but all strains were negative for bab C. H. pylori strains with two loci occupied (loci A and B) were the most prevalent in Korean patients (85.6%), compared to one locus occupied (14.4%) (locus A or B). Twelve bab genotypes were detected, additionally, the distribution of three bab genotypes was significantly associated with different clinical outcomes among Korean patients. The genotypes babA/babB/- and babA/babA+babB/- were significantly associated with peptic ulcer disease (PUD) (63.3%) and gastritis (GT) (33.3%) patients, respectively. In addition, we found that the babA+babB/babA+babB/- genotype was significantly associated with gastric cancer (GC) (36.7%) as compared to GT (6.7%) or PUD (6.7%) (p0.05) patients. This study provided evidence that the bab genotypes in H. pylori Korean strains were highly variable. Interestingly, three patterns of bab genotypes were significantly different among patients with different clinical outcomes in the population at high-risk for GC.

The Korean Obesity Index, which contains standard reference data (SRD) of obesity, was established in 2016 and revised in 2017 based on national health screening data to provide the distribution of the body mass index (BMI) of the whole population of Korea as a reference. This study aimed to investigate the effect of the SRD of obesity on the incidence of hypertension (HTN) and diabetes mellitus (DM).The percentile of BMI was calculated for each of the 864 subgroups by defined by gender, region, and age group according to the groupings in the SRD. Incident cases were defined as the presence of HTN and DM and medication prescription in the health care utilization database for a given individual in 2017, but not in 2015-2016. Logistic regression for the incidence of HTN and DM according to the relative distribution of BMI was performed. Gender, age, insurance type, insurance contribution, smoking, drinking, physical activity, blood pressure, waist circumference, fasting glucose, triglycerides, high-density lipoprotein cholesterol, the Charlson comorbidity index (2012-2014), and diagnosis and medication for HTN and DM (2015-2017) were adjusted in the analysis.The C-statistics of the fully adjusted model for HTN and DM were 0.799 and 0.852, respectively. The risks of HTN and DM increased by 1.007 and 1.011 times, respectively, for each 1-percentile increase in BMI.The results showed that BMI was associated with the incidence of HTN and DM according to the SRD. The relative distribution of BMI can be used to motivate self-care through providing more detailed information to individuals.

Background and Objectives: The effects of Ocimum tenuiflorum essential oil (OTEO) against gastric cancer remain unknown and merit investigation. Materials and Methods: In the present study, the anti-cancer activity of OTEO was examined in a human gastric cancer cell line (AGS). After OTEO treatment, AGS cell viability was determined by an MTT assay, and inhibition of metastasis was determined by cell migration and invasion assays. The expression of apoptosis-related genes in treated AGS cells was determined by qRT-PCR. Results: OTEO significantly decreased AGS cell viability in a dose-dependent manner (IC50 163.42 µg/mL) and effectively inhibited cell migration and invasion. Morphological examination demonstrated that OTEO induced cell shrinkage, chromatin condensation, and fragmentation, which are considered typical morphologies of apoptotic cell death. Pro-apoptotic genes (TP53, BAX, and BAK) were significantly up-regulated, while anti-apoptotic genes (BCL-2 and BCL-xL) were significantly down-regulated after treatment with OTEO. In addition, significantly increased gene expression was detected for CASP8, CASP9, and CASP3 in AGS cells exposed to OTEO. GC-MS analysis demonstrated that the major compound of OTEO was caryophyllene (25.85%) and α-pinene (11.66%). Conclusions: This in vitro study demonstrates for the first time that OTEO has potential anti-gastric cancer activity and may induce apoptosis in AGS cells through extrinsic and intrinsic pathways.

Background Triggering receptor expressed on myeloid cells 2 (TREM2) signaling is considered to regulate anti-inflammatory responses in macrophages, dendritic cell maturation, osteoclast development, induction of obesity, and Alzheimer’s disease pathogenesis. However, little is known regarding the effect of TREM2 on natural killer (NK) cells. Results Here, we demonstrated for the first time that CD3−CD122+NK1.1+ precursor NK (pNK) cells expressed TREM2 and their population increased in TREM2-overexpressing transgenic (TREM2-TG) mice compared with that in female C57BL/6 J wild type (WT) mice. Both NK cell-activating receptors and NK cell-associated genes were expressed at higher levels in various tissues of TREM2-TG mice than in WT mice. In addition, bone marrow-derived hematopoietic stem cells (HSCs) of TREM2-TG mice (TG-HSCs) successfully differentiated into NK cells in vitro, with a higher yield from TG-HSCs than from WT-HSCs. In contrast, TREM2 signaling inhibition by TREM2-Ig or a phosphatidylinositol 3-kinase (PI3K) inhibitor affected the expression of the NK cell receptor repertoire and decreased the expression levels of NK cell-associated genes, resulting in significant impairment of NK cell differentiation. Moreover, in melanoma-bearing WT mice, injection of bone marrow cells from TREM2-TG mice exerted greater antitumor effects than that with cells from WT control mice. Conclusions Collectively, our data clearly showed that TREM2 promoted NK cell development and tumor regression, suggesting TREM2 as a new candidate for cancer immunotherapy.

Triggering receptor expressed on myeloid cells 2 (TREM2) is a cell surface receptor expressed on macrophages, microglial cells, and pre-osteoclasts, and that participates in diverse cellular function, including inflammation, bone homeostasis, neurological development, and coagulation. In spite of the indispensable role of the TREM2 protein in the maintenance of immune homeostasis and osteoclast differentiation, the exact ligand for TREM2 has not yet been identified. Here, we report a putative TREM2 ligand which is secreted from MC38 cells and identified as a cyclophilin A (CypA). A specific interaction between CypA and TREM2 was shown at both protein and cellular levels. Exogenous CypA specifically interacted and co-localized with TREM2 in RAW264.7 cells, and the physical interactions were shown to regulate TREM2 signaling transduction. The Pro144 residue in the extracellular domain of TREM2 was found to be the specific binding site of CypA. When considered together, this provides evidence that CypA interacts specifically with TREM2 as a potent ligand.

Two virulence factors of

The general disease burden associated with the restrictive spirometric pattern (RSP) is substantial. However, the impact of RSP by its severity on general health problems and quality of life has not been well elucidated. This study aimed to analyse nutrition, physical activity, and quality of life in subjects who participated in the Korea National Health and Nutrition Examination Survey 2007–2016 according to severity of RSP. Participants were classified as subjects with normal spirometry, those with mild-to-moderate RSP, and those with severe RSP. Poor quality of life was defined as 25th percentile value on the EuroQoL five dimensions (Eq5D) questionnaire index, i.e., 0.90. This study included 23,615 subjects composed of 20,742 with normal spirometry, 2758 with mild-to-moderate RSP, and 115 with severe RSP. The subjects with severe RSP were more likely to have attained lower education levels, had a lower total caloric intake, had less physical activity, had experienced a higher prevalence of comorbidities, and poorer quality of life than those with normal spirometry (P

Background: This systematic review investigated the clinical effects of inhalation aromatherapy for the treatment of sleep problems such as insomnia. Methods: Studies on sleep problems and inhalation aromatherapy, published in Korean and international journals, were included in the meta-analysis. Five domestic and international databases, respectively each, were used for the literature search. Keywords included sleep disorder, sleep problems, insomnia, and aroma inhalation, and the related literature was further searched. After the screening, selected articles were assessed for their quality and conducted the risk of bias using RevMan 5.0, a systematic literature review was then conducted. A meta-analysis comparing the averages was conducted on studies that reported numerical values. Additionally, meta-analysis of variance and meta-regression analyses were performed. Results: Meta-analysis of the 34 studies using the random-effects model revealed that the use of aromatherapy was highly effective in improving sleep problems such as insomnia, including quantitative and qualitative sleep effects (95% confidence interval [CI], effect sizes = 0.6491). Subgroup analysis revealed that the secondary outcomes including stress, depression, anxiety, and fatigue were significantly effective. The single aroma inhalation method was more effective than the mixed aroma inhalation method. Among the single inhalation methods, the lavender inhalation effect was the greatest. Conclusion: Inhalation aromatherapy is effective in improving sleep problems such as insomnia. Therefore, it is essential to develop specific guidelines for the efficient inhalation of aromatherapy. Ethics and dissemination: Ethical approval is not required because individual patient data are not included. The findings of this systematic review were disseminated through peer-reviewed publications or conference presentations. PROSPERO registration number: CRD42020142120.

The increasing emergence of drug-resistant bacteria creates a requirement for new antibiotics and various types of antibiotic materials such as proteins, peptides, polymers, and chemical compounds. Among these, antimicrobial peptides (AMPs) are considered to be promising antibiotic candidates for clinical treatments. In this study, we have designed a novel series of peptides with repeated sequences of minimum membrane-active motif, ‘XWZX’ basic sequence (X: lysine or arginine, Z: leucine, tyrosine, valine, or glycine), and an α-helical secondary structure. Some peptides displayed a potent antibacterial activity via membranolytic action and high therapeutic index (toxic dose/minimum inhibitory concentration) in vitro. Furthermore, in vivo experiments using bacterial ear-skin infection models verified that these peptides have the potential to be powerful and safe antibiotics. The present study provides a lead sequence for designing peptide antibiotics against bacterial membranes and information for cell-selectivity of hydrophobic amino acids with aromatic side chains such as Trp and Tyr.

Axl receptor tyrosine kinase is involved in the tumorigenesis and metastasis of many cancers. Axl expression was markedly higher in human papilloma virus type 16E6 (HPV16E6)-overexpressing HeLa (HE6F) cells and lower in HPV16E6-suppressing CaSki (CE6R) cells than in the controls. SiRNA-mediated knockdown of E6 expression led to increased phosphatase and tensin homolog (PTEN) phosphorylation at Ser380 and attenuated AKT phosphorylation. Expression of membrane-associated guanylate kinase inverted-2 (MAGI-2), an E6-induced degradation target, was induced in E6-siRNA-transfected cells. Moreover, myeloid zinc finger protein 1 (MZF1) binds directly to the Axl promoter in HE6F cells. Axl expression was regulated by HPV16E6-mediated PTEN/AKT signalling pathway, and Axl promoter activity was regulated through MZF1 activation in cervical cancer, which promoted malignancy. Axl silencing suppressed the metastasis of Caski cells and enhanced the susceptibility to NK cell-mediated killing of HE6F cells. In addition, the expression of Axl and MZF1 was highly correlated with clinical stage of cervical cancer and HPV16/18 infection. Taken together, Axl expression was induced by HPV16E6 in cervical cancer cells, suggesting that blockade of Axl signalling might be an effective way to reduce the progression of cervical cancer.

Lipopolysaccharides (LPS) cause systemic inflammatory responses, which are characterized by high mortality and multiple signs, including metabolic disturbances, respiratory acidosis, hypotension, and vital organs disorder. Cytokines secretion and oxidative stress are the main features of the disease. Diagnosis and treatment of systemic inflammation (SI) remain a challenge. Korean Red Ginseng (RG) is one of medicinal herbs that showed a potent anti-oxidant effect. We aimed to study the protective effects of RG on systemic inflammatory response in rats and RAW 264.7 macrophage cells induced by LPS. The rats were treated with water and alcohol extracts of RG for four weeks to prevent the inflammatory response. The result showed that LPS toxin increased morbidity and mortality, and induced liver, kidney, and lung injuries manifested by deteriorated biomarkers. Hypotension, hypomagnesemia, acidosis, and oxidative stress were observed in septic rats. However, RG extracts attenuated liver, kidney, and lung enzymes and metabolites in treated groups via its anti-inflammatory and anti-oxidant properties. Furthermore, RG improved magnesium and blood pressure in the treated groups. RAW 264.7 macrophage cells exposed to LPS disturbance in translocation of p65 and MAPK/p38. Nevertheless, RG-pretreated cells did not significantly alter. In conclusion, RG reduced the rates of mortality and morbidity of treated rats — liver, kidney, and lung injuries were protected in the treated groups through the potentiation of anti-oxidant defense. RG was able to conserve mitochondrial function, inhibiting the activation of MAPK/p38 signaling and suppressing NF-[Formula: see text]B p65 cytoplasm-nucleus transport. Further studies are needed to examine the effects on chronic conditions in animal models and human.

Despite a substantial population of patients with a restrictive spirometric pattern, few studies have evaluated postoperative pulmonary complications (PPCs) after non-cardiothoracic surgery in these patients. We conducted a retrospective cohort study of 681 adults with a normal or restrictive spirometric pattern who were referred for preoperative evaluation of PPC risk before non-cardiothoracic surgery between March 2014 and January 2015. Overall, 8.7% (59/681) of study participants developed a PPC following non-cardiothoracic surgery. The occurrence of PPCs in patients with a restrictive spirometric pattern was higher than that in those with normal spirometry (12.4% [35/282] vs. 6.0% [24/399], P = 0.003). The occurrence of PPCs increased across the categories of restrictive spirometric pattern severity (6.0% with a normal spirometric pattern vs. 6.5% with a mild restrictive spirometric pattern [60 ≤ forced vital capacity (FVC) P for trend = 0.002) was longer, and all-cause mortality at 30 days (P for trend = 0.008) and 90 days (P for trend = 0.001) was higher across the restrictive spirometric pattern severity. In multivariable-adjusted analyses, a moderate-to-severe restrictive spirometric pattern was associated with a higher risk of PPCs compared with a normal spirometric pattern (adjusted odds ratio 2.64, 95% confidence interval 1.22–5.67). The incidence of PPCs in patients with a restrictive spirometric pattern was higher than that in those with a normal spirometric pattern, especially in patients with a moderate-to-severe restrictive spirometric pattern. Patients with a moderate-to-severe restrictive spirometric pattern should be regarded as high risk for developing PPCs following non-cardiothoracic surgery.

Background Severe centrum semiovale perivascular spaces (CSO-PVSs) are associated with the onset of brain atrophy and dementia. This study explored the relationship between severity of CSO-PVS and development of subdural fluid (SDF) in patients with mild traumatic brain injury (TBI), with the aim of investigating independent radiological risk factors for development of SDF. Methods The study cohort comprised 222 patients with a mean age of 51 years (64.0% men) who presented with mild TBI from January 2013 to November 2016. In this study, mild TBI was defined as a Glasgow Coma Scale (GCS) of ≥ 13, Post-Traumatic Amnesia (PTA) of

We analyzed the prognostic impact of retropharyngeal lymphadenopathy (RPL) in stage I node-positive HPV-associated oropharyngeal squamous cell carcinoma (OPSCC).We performed a centralized and blinded radiographic review of the pre-treatment images of 234 consecutive patients with AJCC 8th edition stage I cT1-2N1 HPV-associated OPSCC treated with definitive chemoradiation from 2006 to 2016. Five-year disease control and survival outcomes were reported. The prognostic significance of RPL was evaluated through multivariable analysis adjusting for age, smoking history (10 vs.10 pack-years), and systemic regimen received.Median follow-up for surviving patients was 49 months (range: 16-121). RPL was associated with increased locoregional recurrence (LRR) (17.0% v. 3.4%, p = 0.01) and distant metastasis (DM) (29.1% v. 5.9%, p = 0.001) and inferior progression-free survival (PFS) (55.6% v. 88.2%, p 0.001) and overall survival (OS) (60.6% v. 91.2%, p 0.001). In stage I patients who did not receive high-dose cisplatin (HDC), RPL was associated with worse LRR (p = 0.04), DM (p = 0.03), PFS (p 0.001), and OS (p 0.001), whereas in those who did receive HDC, RPL was only associated with increased DM (p = 0.002) and inferior PFS (p = 0.04).This study suggests that RPL portends a poor prognosis in stage I node-positive HPV-associated OPSCC. The negative impact on LRR may have been mitigated by receipt of HDC. Outcomes of stage I disease with RPL were comparable to historical reports of patients with more advanced-stage disease. Incorporation of RPL into future disease staging should be considered in order to optimize risk-stratification and exclude unsuitable candidates from treatment de-intensification efforts.

Hyung Koo Kang,1,2,* Kang Kim,1,* Hyun Lee,1 Byeong-Ho Jeong,1 Won-Jung Koh,1 Hye Yun Park1 1Division of Pulmonary and Critical Care Medicine, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, 2Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Ilsan Paik Hospital, Inje University School of Medicine, Goyang, Gyeonggi, South Korea *These authors contributed equally to this work Background: An eight-item questionnaire of the COPD assessment test (CAT) is widely used to quantify the impact of COPD on the patient’s health status. C-reactive protein (CRP) is associated with disease severity and adverse health outcomes of patients with COPD. This study aimed to evaluate the relationship between CAT score and serum CRP levels in stable COPD patients.Methods: We evaluated the medical records of 226 patients with CAT and serum CRP measured within a week at Samsung Medical Center between October 2013 and October 2015.Results: Serum CRP levels had a significantly positive relationship with CAT score (Spearman’s r=0.20, P=0.003). Patients with elevated serum CRP levels (>0.3 mg/dL) were significantly more likely to have CAT scores of ≥14. The adjusted odds ratio for elevated serum CRP levels in total CAT score was 1.06 (95% confidence interval, 1.02–1.09). Among CAT components, cough (adjusted P=0.005), phlegm (adjusted P=0.001), breathlessness going up hills/stairs (adjusted P=0.005), low confidence leaving home (adjusted P=0.002), and feeling low in energy (adjusted P=0.019) were independently associated with elevated serum CRP levels.Conclusion: In stable COPD patients, serum CRP levels were independently associated with total CAT score and CAT components related to respiratory symptoms, confidence leaving home, and energy. Keywords: chronic obstructive pulmonary disease assessment test, C-reactive protein, quality of life, inflammation

BACKGROUND The purpose of this study was to determine the shape of the distal femur of Korean women compared with the prostheses currently available in Korea. METHODS Morphometric data (5 parameters) were measured in 356 resected femurs of Korean women undergoing primary total knee arthroplasty (TKA) utilizing the LCS knee implant (DePuy). The data were then compared with 5 additional contemporary TKA implant systems. RESULTS Implant designs based on Caucasian population data do not ideally match the distal femoral morphology of Korean women. Overhang at the anterior mediolateral width was observed in 84.8% for the LCS while a gender-specific implant resulted in undercoverage of the bone in 86%. Posterior overhang was observed in up to 51.2%. Most implant designs have a narrower intercondylar notch than the morphologic data of Korean women. CONCLUSIONS Since there is some difference between the shape of distal femur of Korean women and that of the implants, surgeons should have this in mind when selecting an implant for a patient. These data may also be used as a guideline for future prosthetic design options for Korean women population.

BACKGROUND: Total lung capacity (TLC), forced expiratory flow between 25 and 75% (FEF25-75%), peak expiratory flow (PEF), or post-bronchodilator volume response is recommended to detect obstructive abnormalities in the lung. The present study was performed to evaluate the usefulness of these pulmonary function test (PFT) parameters to diagnose obstructive lung disease in subjects with a restrictive pattern of spirometry. METHODS: A retrospective study was conducted in 64 subjects with a restrictive pattern of spirometry (normal FEV1/FVC and low FVC) out of 3,030 patients who underwent all pre- and post-bronchodilator spirometry and lung volume measurement between April 2008 and December 2010. After subjects were clinically classified into those with obstructive lung disease, restrictive lung disease, and mixed lung disease, the agreements between the clinical diagnosis and PFT classification according to TLC, FEF25-75%, PEF, and post-bronchodilator response criteria were compared. RESULTS: Of 64 subjects, 18 (28.1%) were classified with obstructive lung disease, 39 (60.9%) had restrictive lung disease, 1 (1.6%) had mixed lung disease, and 6 (9.4%) had no clinical lung disease. Among the 58 subjects with clinical lung disease, 22 (37.9%), 37 (63.8%), 33 (56.9%), and 3 (5.2%) were classified as having obstructive pattern based on TLC, FEF25-75%, PEF, and post-bronchodilator response criteria, respectively. The kappa coefficients for the agreement between the clinical classification and PFT classification using TLC, FEF25-75%, PEF, and post-bronchodilator response criteria in 58 subjects were 0.59, 0.18, 0.17, and < 0.01, respectively. CONCLUSIONS: The additional measurement of TLC is more useful than FEF25-75%, PEF, and post-bronchodilator response for diagnosis of obstructive lung disease in subjects with a restrictive pattern of spirometry, when obstructive lung disease is clinically suspected.

Background: Mild neurocognitive disorder (mNCD) is one of the degenerative diseases that results in memory deficit, and can progress to dementia. The effectiveness of drug therapy for mNCD is still debatable, but treatment of this disease has important implications for postponing or preventing dementia. Jujadokseo-hwan (JDH) is a traditional herbal medicine formulation that exhibits improvement in cognitive abilities and neuroprotective effects. In this study, we will evaluate the safety and efficacy of JDH compared to placebo in mNCD patients. Methods and design: This is a randomized, double-blind, placebo-controlled, parallel-group, multicenter clinical trial. After obtaining informed consent from all participants and performing the screening process, the participants will be equally divided into an experimental group and a control group. Each participant will visit the trial center 7 times during the 12 weeks of intervention. The follow up study will be conducted 12 weeks after the intervention ends. The primary outcome is the variance in Seoul verbal learning test-elderly's version (SVLT-E) score from baseline to 12 weeks. Secondary outcomes include scores/values for the following variables: SVLT-E, Rey complex figure test, Digit span test, Korean-Boston naming test, calculation ability, controlled oral word association test, Korean-color word stroop test, digit symbol coding, Korean-trail making test-elderly's version, Korean version of mini mental state examination for dementia screening, euro-qol-5 dimension, pattern identifications tool for cognitive disorders, Korean version of Montreal cognitive assessment, Korean quality of life-Alzheimer disease, computerized tongue image analysis system, blood pressure pulse analyzer, bioelectrical impedance analyzer, wearable electroencephalogram device, functional near-infrared spectroscopy system, and cost analysis. Discussion: This is the first trial evaluating the efficacy of JDH for mNCD. We expect this trial will provide strong support for wide use of JDH for mNCD and lead to further research on herbal medicine treatments for mNCD. Trial registration number: KCT0003570 (Registered in Clinical Research Information Service of the Republic of Korea, https://cris.nih.go.kr/cris/search/search_result_st01.jsp?seq=12669).

Introduction: This systematic review protocol describes the methods that will be used to evaluate the efficacy and safety of mindfulness meditation and cognitive behavioral therapy programs as a psychological intervention for insomnia disorders. Methods and analysis: We will search the following 11 electronic databases without language or publication status restrictions: MEDLINE, the Cochrane Central Register of Controlled Trials, EMBASE, Allied and Complementary Medicine Database, Cumulative Index to Nursing and Allied Health Literature, and PsycARTICLES. Furthermore, we will also search 5 Korean-language databases (Oriental Medicine Advanced Searching Integrated System, Korean studies Information Service System, Research Information Service System, Korean Medical Database, and Korea Citation Index). The study selection and data extraction will be performed independently by 2 authors. The study quality assessment and evaluation of the quality of evidence for the main findings will be performed independently by 2 authors using the Cochrane tool for assessing risk of bias and predefined criteria (the Grading of Recommendations Assessment, Development, and Evaluation approach). Data synthesis and analysis will be performed using RevMan Version 5.3. Data will be synthesized by either a fixed effects or random effects model according to a heterogeneity test or the number of studies included in the meta-analysis. If any plan for documenting important protocol amendments changes, the researchers will have a revision agreement and then register the modification in the International Prospective Register of Systematic Reviews (PROSPERO). Ethics and dissemination: Ethical approval will not be required because individual patient data are not included and because this protocol is for a systematic review. The findings of this systematic review will be disseminated through conference presentations. PROSPERO registration number: CRD42018111217.

Background and Purpose:This study examined the psychometric properties of a 9-item Morisky Medication Adherence Scale (MMAS-9) adapted specifically for patients with HIV/AIDS.Methods:We used data from two randomized controlled trials investigating telephone-delivered interventions for improving adherence to antiretroviral therapy to assess reliability (Cronbach’s α and Pearson’s product correlation) and validity (convergent and concurrent) of the MMAS-9.Results:The internal consistency (Cronbach’s α) of the MMAS-9 was .66 (study 1) and .69 (study 2); 3-month test–retest reliability (Pearson’s correlation) ranged from .50 to .74. Validity was supported by associations with electronic event monitored adherence, social support, depressive symptoms, self-efficacy, stigma, regimen complexity, and impact of side effects in the hypothesized direction.Conclusions:The adapted MMAS-9 demonstrated good convergent validity but somewhat lower internal consistency reliability than other reports.

Background: The heart continuously transmits information to the cerebrum during each pulse, and influences information processing such as perception, cognition, and emotion, which are processed in the cerebrum. This is the basis for the theory of oriental medicine widely used in psychiatric medicine and clinical practice, so-called Simjushinji (heart and brain) theory, that the heart controls the mind. The present study aims to analyze the correlation between heart and brain function by 24-hour active electrocardiogram and quantitative electroencephalogram (EEG) measurement under meditation. Methods: This randomized, controlled, assessor-blinded, 2-armed, parallel, multicenter clinical trial will analyze a total of 50 subjects, including 25 each for the test group and the active control group. Subjects will be randomly allocated to the test group (performing resource mindfulness) and the control group (performing stress mindfulness) in a 1:1 ratio. The clinical trial consists of 3 stages. The first and third stages are stable states. The second stage is divided into the test and active comparator groups. Quantitative EEG (qEEG) measurements at stages 1 and 3 will be recorded for 10 minutes; measurements at stage 2 will be recorded for 20 minutes with the eyes closed. The 24-hour Holter Monitoring and heart rate variability will be evaluated at each stage. Before the beginning of stage 3, subjects will complete the questionnaires. The primary outcome will be analyzed by independent t tests of both groups. Discussion: Scientific studies based on clinical epistemology are expected to serve as a basis for sustainable medical services in the field of psychiatric medicine in Korea. HRV, blood pressure index, and biometric index in qEEG, as determined by 24-hour Holter monitoring, will complement quantitative biomarkers and be useful in various fields.

Few data are available regarding treatment outcomes in lung cancer patients with metastasis who initiated mechanical ventilation in the emergency department (ED). We aimed to evaluate 28-day mortality in lung cancer patients with metastasis who initiated mechanical ventilation in the ED. Patients with solid malignancy who initiated mechanical ventilation in the ED of a tertiary hospital were retrospectively identified and stratified into four groups according to the presence of lung cancer and metastasis. Among 212 included patients, the mortality rates by the 28th hospital day were as follows: 44.2% (19/43) in non-lung cancer patients without metastasis, 63.2% (43/68) in non-lung cancer patients with metastasis, 52.4% (11/21) in lung cancer patients without metastasis, and 66.2% (53/80) in lung cancer patients with metastasis. In multivariable analysis, lung cancer patients with metastasis had significantly higher odds ratio for 28-day mortality than non-lung cancer patients without metastasis (adjusted odds ratio [OR] = 7.17, 95% confidence interval [CI] = 2.14–24.01). Sepsis-related respiratory failure (adjusted OR = 2.60, 95% CI = 1.16–5.84) and cardiopulmonary resuscitation (adjusted OR = 13.34, 95% CI = 4.45–39.95) over respiratory failure without sepsis and acute organ dysfunction process measured by sequential organ failure assessment (SOFA) score (adjusted OR = 1.15, 95% CI = 1.05–12.6) were independently associated with an increase in mortality rate. In conclusion, the treatment outcomes in lung cancer patients with metastasis who initiated mechanical ventilation in the ED were poor. Aggressive resuscitation versus end-of-life care in advance of an unexpected medical crisis should be considered in lung cancer patients with metastasis via a multidisciplinary approach with a consideration of underlying comorbid illnesses in the acute organ dysfunction processes.

Background Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease that causes paralysis of limb, swallowing, and breathing muscles. Riluzole, the Food and Drug Administration-approved drug for ALS, provides minimal benefit, prolonging patient life by only 2–3 months. Previous studies have found a neuro-protective and anti-neuroinflammatory effect of Mecasin, with retrospective studies providing suggestive evidence for a beneficial effect of Mecasin. The aim of this study was to develop a protocol to determine the proper dosage of Mecasin. Methods This is a phase II-A, multi-center, randomized study with three arms. Thirty-six patients with ALS will be randomly assigned to one of three groups, each receiving the standard treatment with 100 mg of riluzole in addition to one of 1.6 g of Mecasin, 2.4 g of Mecasin, or a placebo. The Primary outcome is the Korean version of the Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised result after 12 weeks of treatment. Secondary outcomes include results of the Short Form Health Survey-8, Medical Research Council Scale, Visual Analogue Scale for Pain, Hamilton Rating Scale for Depression, Fatigue Severity Scale, Patient Global Impression of Change, pulmonary function test, forced expiratory volume in 1 s and its ratio to forced vital capacity, creatine kinase, and body weight. The frequencies of total adverse events and serious adverse events will be described and documented. The trial protocol has been approved by the Institutional Review Board of the Wonkwang University Gwangju and Sanbon Hospital (2016–5-4 and 2016–34-01, respectively). An Investigational New Drug status (30731) was granted by the Korea Food and Drug Administration. Discussion This trial will aim to identify the optimal dosage of Mecasin. Additionally, it will test the efficacy and safety of Mecasin in conjunction with standard treatment, riluzole, for alleviating the functional decline in patients with ALS. Trial registration Korean National Clinical Trial Registry CRIS; KCT0001984. Registered on 28 July 2016. Electronic supplementary material The online version of this article (10.1186/s13063-018-2557-z) contains supplementary material, which is available to authorized users.

Helicobacter pylori can persistently colonize the mucosa of the human stomach, resulting in gastric disorders. Endoscopic biopsy for rapid urease test and histopathologic examination are considered as the most accurate diagnostic methods for H. pylori infection. Serological methods are recommended for children because of invasiveness of the diagnosis mentioned above. Here, the cytotoxin-associated gene A protein (Cag A), as an immunodominant antigen, was subdivided to determine which regions harbor antigenicity for humans. CagA was divided into 17 overlapping fragments of ∼400 bp, which were used for the analysis of antigenic determinants. The partial proteins were subjected to immunoblot analysis using pooled serum samples from children with gastric symptoms. A partial recombinant CagA protein containing epitope regions (683-749 amino acids), which were identified in this study, was produced and used for the detection of anti-CagA antibodies and further investigated its serodiagnostic value for determination of H. pylori infection in children. The serum IgG reactivities from children with gastric symptoms were significantly three times more than that of serum samples from children with non-gastric symptoms (P

Moa Jeong,1 Hyung Koo Kang,1 Pamela Song,2 Hye Kyeong Park,1 Hoon Jung,1 Sung-Soon Lee,1 Hyeon-Kyoung Koo1 1Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, 2Department of Neurology, Ilsan Paik Hospital, Inje University College of Medicine, Goyang, Republic of Korea Purpose: Hand grip strength (HGS) is a simple way of predicting the risk of cardiovascular disease and all-cause mortality in the general population. However, the practical significance of grip strength in patients with COPD is uncertain. The aim of this study was to compare HGS between subjects with and without COPD and to evaluate its clinical relevance in patients with COPD by using a national survey.Methods: Data were collected from the Korean National Health and Nutrition Examination Survey. The study included 421 adults with COPD and 2,542 controls who completed questionnaires, spirometry, and a HGS test. HGS was compared between subjects with and without COPD, and the association between grip strength, lung function, and quality of life (QoL) was evaluated.Results: The mean HGS was 33.3±9.1 kg in the COPD group and 29.9±9.5 kg in the non-COPD group; adjusted HGS was 30.9±0.33 kg and 30.9±0.11 kg, respectively (P=0.99). HGS was not related to forced vital capacity (β=0.04, P=0.70) or forced expiratory volume in 1 second (β=0.11, P=0.24) in multivariable analysis. HGS was independently associated with the EQ-5D index, but the relationship was stronger in the COPD group (β=0.30, P

Background In patients with hemodialysis-associated pneumonia (HDAP), information on both microbiologic features and antimicrobial strategies is limited. The aim of this study is to investigate predictive factors of infection with multidrug-resistant (MDR) pathogens in HDAP patients. Methods This was a multicenter, retrospective, and observational study. Enrolled patients were classified into MDR or non-MDR pathogens groups according to culture results. We examined risk factors of infection with MDR pathogens and created a decision support tool using these risk factors. Results MDR pathogens were identified in 24 (22.8%) out of a total of 105 HDAP patients. The most common MDR pathogens were methicillin-resistant Staphylococcus aureus (10 patients, 9.5%) and the isolation rate of Pseudomonas aeruginosa was 6.6%. Logistic regression showed two variables were associated with the isolation of MDR pathogens: recent hospitalization (adjusted odds ratio [OR]: 2.951, 95% confidence interval [CI]: 1.022–8.518) and PSI (Pneumonia Severity Index) score (adjusted OR: 1.023, 95% CI: 1.005–1.041). The optimal cut-off value for PSI score using a receiver operating characteristic curve analysis was 147. According to the presence of 0, 1, or 2 of the identified risk factors, the prevalence of MDR pathogens was 7.6, 28.2 and 64.2%, respectively (p 147 are risk factors of infection with MDR pathogens in HDAP patients. This simple proposed tool would facilitate more accurate identification of MDR pathogens in these patients.

Pyogenic liver abscess (PLA) is a severe disease with considerable mortality and is often polymicrobial. Understanding the pathogens that cause PLA is the basis for PLA treatment. Here, we profiled the bacterial composition in PLA fluid by pyrosequencing the 16S ribosomal RNA (rRNA) gene based on next-generation sequencing (NGS) technology to identify etiological agents of PLA and to provide information of their 16S rRNA sequences for application to DNA-based techniques in the hospital. Twenty patients with PLA who underwent percutaneous catheter drainage, abscess culture, and blood culture for isolates were included. Genomic DNAs from abscess fluids were subjected to polymerase chain reaction and pyrosequencing of the 16S rRNA gene with a 454 GS Junior System. The abscess and blood cultures were positive in nine (45%) and four (20%) patients, respectively. Pyrosequencing of 16S rRNA gene showed that 90% of the PLA fluid samples contained single or multiple genera of known bacteria such as Klebsiella, Fusobacterium, Streptococcus, Bacteroides, Prevotella, Peptostreptococcus, unassigned Enterobacteriaceae, and Dialister. Klebsiella was predominantly found in the PLA fluid samples. All samples that carried unassigned bacteria had 26.8% reads on average. We demonstrated that the occurrence of PLA was associated with eight known bacterial genera as well as unassigned bacteria and that 16S rRNA gene sequencing was more useful than conventional culture methods for accurate identification of bacterial pathogens from PLA.

Corticotropin-releasing factor (CRF), a coordinator of the body's responses to stress, is found in various cancer tissues and cell lines. However, the exact abilities of CRF to manipulate natural killer (NK) cells during immune response have not been studied. NKG2D is an activating receptor that is expressed on most NK and CD8+ T cells. MHC class I-related chain A (MICA) and UL16-binding protein (ULBP) 1, 2 and 3 are well-known ligands for NKG2D. In the present study, we reported our findings regarding the role of CRF in cervical cancer cell survival. Human cervical cancer cell line, HeLa cells, had significantly higher intracellular expression of UL16-binding protein 2 (ULBP2) following CRF treatment but had only slightly increased surface expression of ULBP2. Notably, MMPi (pan-metalloproteases inhibitor) blocked the release of ULBP2 molecules from the surface of HeLa cells. Furthermore, incubating NK cells with culture supernatants from CRF-treated HeLa cells, which contained soluble NKG2D ligand, reduced NK cell activity by decreasing surface expression of NKG2D. Collectively, downregulation of NKG2D by CRF-induced soluble NKG2D ligand provides a potential mechanism by which cervical cancer cells escape NKG2D-mediated attack under stress conditions.

Intrathecal chemotherapy including methotrexate is well documented for neurotoxicity of diverse clinical manifestation. Acute or chronic leukoencephalopathy is the most common type of methotrexate-induced neurotoxicity, and subacute myelopathy is rare. Although its pathogenesis is not fully understood, it is postulated that direct damage of methotrexate to the central nervous system plays a major part and elevated levels of homocysteine and its excitatory amino acid neurotransmitter metabolites (homocysteic acid and cysteine sulfinic acid) could mediate, in part, MTX-associated neurotoxicity. On the while, subacute combined degeneration is a progressive degeneration of the dorsal and lateral columns of the spinal cord, mostly due to vitamin B12 deficiency. The authors report a case of a 15-year-old boy with Burkitt leukemia who developed progressive myelopathy after intrathecal triple therapy (methotrexate, cytarabine, and hydrocortisone) whose clinical and radiologic features were compatible with subacute combined degeneration. The pathogenic mechanism could be explained by biochemical alteration by methotrexate and a possible treatment strategy was discussed.

PurposeThe National Health Insurance Service (NHIS)-Senior was set up to provide high-quality longitudinal data that can be used to explore various aspects of changes in the socio-economical and health status of older adults, to predict risk factors and to investigate their health outcomes.ParticipantsThe NHIS-Senior cohort, a Korean nationwide retrospective administrative data cohort, is composed of older adults aged 60 years and over in 2002. It consists of 558 147 people selected by 10% simple random sampling method from a total of 5.5 million subjects aged 60+ in the National Health Information Database. The cohort was followed up through 2015 for all subjects, except for those who were deceased.Findings to dateThe healthcare utilisation and admission rates were the highest for acute upper respiratory infections and influenza (75.2%). The age-standardised (defined with reference to the world standard population) mortality rate for 10 years (through 2012) was 4333 per 100 000 person-years. Malignant neoplasms were the most common cause of death in both sexes (1032.1 per 100 000 person-years for men, 376.7 per 100 000 person-years for women). A total of 34 483 individuals applied for long-term care service in 2008, of whom 17.9% were assessed as grade 1, meaning that they were completely dependent on the help of another person to live daily life.Future plansThe data are provided for the purposes of policy and academic research under the Act on Promotion of the Provision and Use of Public Data in Korea. The NHIS-Senior cohort data are only available for Korean researchers at the moment, but it is possible for researchers outside the country to gain access to the data by conducting a joint study with a Korean researcher. The cohort will be maintained and continuously updated by the NHIS.

Few accurate analyses of clinically useful vertebral anatomy have been conducted, and most have focused on thoracic idiopathic scoliosis.To evaluate the different anatomic characteristics in scoliosis by disease type and level.Observational cohort study.Forty-eight patients with scoliosis were included in this study.Subjects underwent computed tomography (CT) of the whole spine.Forty-eight patients with scoliosis were included in this study: 15 adolescent idiopathic, 11 cerebral palsy (CP), 10 muscular dystrophy (MD), and 12 congenital (CG) scoliosis patients with similar demographics. Subjects underwent CT of the whole spine, preoperatively. Eight anatomic parameters were measured in multiplanar reconstructive CT images, and statistical analysis was performed to investigate differences.In general, values in the anatomic parameters were similar for the four diseases. Each parameter showed the unique change pattern according to the spinal level regardless of curvature shape, direction, or magnitude. In particular, chord length (CL) in MD and CG scoliosis was lower than in adolescent idiopathic scoliosis (AIS) and CP, and pedicle rib unit length was lower in CG scoliosis than in the other diseases (p.05). Comparisons of convex and concave anatomies in AIS showed that inner pedicle width (PWI) and outer pedicle width (PWO) were wider for convex side, CL, pedicle width, and transverse pedicle angle were greater for concave side (p.05), and differences were more significant at apices. However, in CP, PWI and PWO were similar between convex and concaves sides (p.05). Although PWI and PWO were wider for convex sides and CL and pedicle length were greater for concave sides in MD (p.05), differences were less significant at apices. Particularly, CG scoliosis showed severely deformed anatomy, with differences of seven parameters at apical vertebrae (p.05).Clinical anatomies of vertebrae in scoliosis were found to differ significantly at different levels and in terms of convexity and disease type.

Summary Eccrine angiomatous hamartoma (EAH) is a benign hamartomatous tumour characterized by a combination of proliferative eccrine and vascular elements. Papillary haemangioma (PH) is a distinct cutaneous haemangioma with predominantly intravascular capillary proliferation within dilated thin-walled blood vessels. EAHs have been reported in combination with various vascular components. We present the first case in the dermatological literature, to our knowledge, of a patient with congenital EAH with the histopathological features of a PH.

In this study, we have used computational fluid dynamics to investigate the blood flow in the stenosed blood vessels. The numerical simulation using commercial software ADINA 8.6 were solved about the stenosed blood vessel according to the percent of stenosis and Reynolds number. The blood flow in the normal and stenosed blood vessel was grasped for the validity of the model. The characteristic of the pulsatile flow changed through the steady state flow and analysis of the pulsatile flow according to the time was grasped. The computational model with the characteristics of the fluid-structure interaction is introduced to investigate the wall shear stress, pressure distribution and axial flow velocity. The results show that axial flow velocity and wall shear stress in the region of stenosis was increased by increasing percent of stenosis and Reynolds number. Also, we can know that in the stenosed blood vessel the possibility of the generation of the aneurysm was increased by increasing Reynolds number and percent of stenosis.

It is still uncertain whether total bilirubin per se is a risk factor for osteoporosis in postmenopausal women and no study has so far examined this important issue. This study was designed to assess the sheer effects of total bilirubin on the prevalence of osteoporosis in postmenopausal women without potential liver disease. In the present study, postmenopausal female subjects without potential liver disease (n = 918) who underwent measurement of bone mineral density were enrolled. Correlation and logistic regression analysis were used to assess the relationship between total bilirubin and other variables. As a result, subjects with osteoporosis had a significantly lower total bilirubin level (P = 0.005). A 0.1 mg/dl increase in total bilirubin was associated with reduced odds ratio of the risk by 38 % for osteoporosis [OR 0.62 (95 % CI 0.52–0.88), P = 0.012] after adjustment for several variables. Total bilirubin was independently associated with BMD [coefficient = 0.41, 95 % CI (0.35–0.47), P

Transplantation is often the only viable treatment for pediatric patients with end-stage liver disease. Making well-informed decisions on when to proceed with transplantation requires accurate predictors of transplant survival. The standard Cox proportional hazards (PH) model assumes that covariate effects are time-invariant on right-censored failure time; however, this assumption may not always hold. Gray’s piecewise constant time-varying coefficients (PC-TVC) model offers greater flexibility to capture the temporal changes of covariate effects without losing the mathematical simplicity of Cox PH model. In the present work, we examined the Cox PH and Gray PC-TVC models on the posttransplant survival analysis of 288 pediatric liver transplant patients diagnosed with cancer. We obtained potential predictors through univariable(P<0.15)and multivariable models with forward selection(P<0.05)for the Cox PH and Gray PC-TVC models, which coincide. While the Cox PH model provided reasonable average results in estimating covariate effects on posttransplant survival, the Gray model using piecewise constant penalized splines showed more details of how those effects change over time.

Human islet amyloid polypeptide (hIAPP), a major constituent of islet amyloid deposits, induces pancreatic β-cell apoptosis and eventually contributes to β-cell deficit in patients with type 2 diabetes mellitus (T2DM). In this study, Tat-mediated transduction of biliverdin reductase A (BLVRA) was investigated in INS-1 cells to examine whether exogenous supplementation of BLVRA prevented hIAPP-induced apoptosis and dysfunction in insulin secretion in β-cells. Tat-BLVRA fusion protein was efficiently delivered into INS-1 cells in a time- and dose-dependent manner. Exposure of cells to hIAPP induced apoptotic cell death, which was dose-dependently inhibited by pre-treatment with Tat-BLVRA for 1 h. Transduced Tat-BLVRA reduced hIAPP-evoked generation of reactive oxygen species, a crucial mediator of β-cell destruction. Immunoblot analysis showed that Tat-BLVRA suppressed hIAPP-induced increase in the levels of proteins involved in endoplasmic reticulum (ER) stress and apoptosis signaling. Transduced Tat-BLVRA also recovered hIAPP-induced dysfunction in basal and glucose-stimulated insulin secretions. These results suggested that transduced Tat-BLVRA enhanced the tolerance of β-cells against IAPP-induced cytotoxicity by alleviating oxidative stress and ER stress. Therefore, Tat-mediated transduction of BLVRA may provide a potential tool to ameliorate β-cell deficit in pancreas with T2DM.

Patients with pulmonary tuberculosis (TB) with acid-fast bacilli (AFB)-positive sputum smear at 5 months or later during treatment are considered to be cases of treatment failure according to World Health Organization guidelines. This study evaluated the proportion, clinical characteristics, and significance of positive sputum smears after ≥5 months of standard treatment in patients with drug-susceptible pulmonary TB. This was a retrospective cohort study of 1611 patients with culture-confirmed drug-susceptible pulmonary TB who received standard anti-TB treatment from January 2009 to February 2014. Forty-one patients (2.5%) who were smear-positive after ≥5 months of treatment and 123 age- and sex-matched control patients were evaluated. Among the 41 smear-positive patients, culture of the sputum specimens yielded Mycobacterium tuberculosis (MTB) in 1 patient (2.4%), nontuberculous mycobacteria (NTM) in 7 (17.1%), and no growth in the remaining 33 patients (80.5%). Treatment was successfully completed in 40 patients (97.6%) with prolongation of the continuation phase regimens without change to second-line anti-TB treatment. In patients with smear positivity after ≥5 months of treatment compared with controls, cavitation on chest radiographs (53.7% vs. 25.2%, P = 0.001), bilateral involvement (51.2% vs. 30.1%, P = 0.01) and combined pleural effusion (26.8% vs. 10.6%, P = 0.01) were found more frequently at the time of treatment initiation, and paradoxical response occurred more commonly (19.5% vs. 3.3%, P = 0.002) during treatment. Smear-positive sputum after ≥5 months of standard anti-TB treatment was mainly because of nonviable MTB bacilli or NTM in patients with drug-susceptible pulmonary TB. AFB smear alone should not be used to assess treatment failure and careful examination of microbiologic status, including culture and drug susceptibility testing, is needed before making changes to retreatment regimens or empirical second-line anti-TB regimens in these patients.

To find a simple enzymatic strategy for the efficient synthesis of the expensive 5′-hydroxyomeprazole sulfide, a recently identified minor human metabolite, from omeprazole sulfide, which is an inexpensive substrate. The practical synthetic strategy for the 5′-OH omeprazole sulfide was accomplished with a set of highly active CYP102A1 mutants, which were obtained by blue colony screening from CYP102A1 libraries with a high conversion yield. The mutant and even the wild-type enzyme of CYP102A1 catalyzed the high regioselective (98 %) C-H hydroxylation of omeprazole sulfide to 5′-OH omeprazole sulfide with a high conversion yield (85–90 %). A highly efficient synthesis of 5′-OH omeprazole sulfide was developed using CYP102A1 from Bacillus megaterium as a biocatalyst.

The association between airflow limitation severity and post-operative pulmonary complications (PPCs) among COPD patients undergoing extra-pulmonary surgery is unknown. We evaluated the association between forced expiratory volume in 1 s (FEVUsing prospective cohort of PPC evaluation for extra-pulmonary surgery, we identified 694 COPD patients who conducted PPC evaluation before extra-pulmonary surgery between March 2014 and January 2015 at a tertiary hospital, Seoul, Korea.The overall incidence of PPC was 24.4%. The incidence of PPC in quintiles 1-5 of FEVWe found a progressive and significant relationship between severity of airflow limitation and the incidence of PPC in COPD patients undergoing extra-pulmonary surgery. Furthermore, perioperative bronchodilator use was associated with a reduced risk of respiratory failure and post-operative exacerbations in patients with severe airflow limitation.

Post-intubation tracheal stenosis (PITS) and post-tracheostomy tracheal stenosis (PTTS) are serious complications in mechanically ventilated patients. Although the aetiologies and mechanisms of PITS and PTTS are quite different, little is known about the clinical impact of differentiating one from the other.We retrospectively conducted a chart review of 117 patients with PITS and 88 patients with PTTS who were treated with interventional bronchoscopy at Samsung Medical Center between January 2004 and December 2013.Compared to patients with PITS, patients with PTTS had a lower BMI, poorer performance status and more frequent neurological aetiologies, mid-to-lower tracheal lesions, total obstruction and mixed stenosis types. Although there were no differences in the number of patients who received silicone stents between the two groups, Montgomery T-tubes were more frequently used in the PTTS group than in the PITS group. The final success rate without surgery, mortality or tracheostomy in situ was higher in the PITS group than in the PTTS group (76.9% vs 63.6%, P = 0.043). Additionally, airway prosthesis removal was achieved in 46.2% of patients in the PITS group and in 33.0% of the PTTS group (P = 0.063).There were significant differences between PITS and PTTS in terms of patient and stenosis characteristics, treatment modalities and clinical outcomes. Therefore, PITS and PTTS should be considered two different entities.

Objective Most small-cell lung cancers (SCLCs) are located within the central aspect of the chest and manifest as a mediastinal or hilar lymphadenopathy. Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) makes it possible to perform mediastinal and hilar nodal examinations. The purpose of this study was to evaluate the performance of EBUS-TBNA in the diagnosis of SCLC. Methods The diagnostic performances of EBUS-TBNA and/or transesophageal bronchoscopic ultrasound-guided fine-needle aspiration (EUS-FNA-B/E) were calculated using the standard definitions. Patients The study consisted of a retrospective review of the medical records for all patients with histologically proven SCLC who previously underwent EBUS-TBNA and/or EUS-FNA-B/E from May 2009 to September 2014. Results The analysis was based on 161 patients and 299 aspirated specimens. The patient group included 144 males (89%); the median age was 66 years. EBUS-TBNA and/or EUS-FNA-B/E were performed in 239 mediastinal nodes, 39 hilar/interlobar nodes, and 21 lung parenchymal lesions. The median short diameter of the biopsied lesions was 17 mm. The overall sensitivity, specificity, negative predictive value, positive predictive value, and accuracy of EBUS-TBNA and/or EUS-FNA-B/E on a per-person basis were 97.4%, 100%, 60%, 100%, and 97.5%, respectively. The corresponding values on a per-lesion basis were 91.8%, 100%, 73.0%, 100%, and 93.3%, respectively. There were no serious complications related to EBUS-TBNA. Conclusion In our series of patients with SCLC, EBUS-TBNA had an excellent diagnostic yield in the evaluation of mediastinal, hilar and lung parenchymal lesions. Thus, EBUS-TBNA could be a useful and safe diagnostic method with which to evaluate patients with SCLC.

Background: The prognostic relevance of histologic differentiation in gastric carcinoma patients with curative resection is unclear. We analyzed the clinicopathologic features of gastric carcinoma patients with curative resection according to the histologic differentiation and evaluated surgical outcome. Materials And Methods: Of 1198 gastric carcinoma patients with curative resection (American joint committee on cancer, Stages I-III), 274 (22.9%) had well-differentiated, 331 (27.6%) had moderately differentiated and 593 (49.5%) had poorly differentiated gastric carcinomas. Results: Patients with the poorly differentiated type had more prominent serosal invasion, much more lymph node involvement and more advanced stage than patients with the well-differentiated type. The overall survival rate was higher for patients with a well-differentiated gastric carcinoma than for patients with a poorly differentiated type. Using Cox's proportional hazard regression model, histologic differentiation was found to be a statistically significant prognostic parameter (risk ratio, 1.41; 95% confidence interval, 1.028-1.922; P Conclusion: Our results suggest that patients with a well-differentiated gastric carcinoma have a good prognosis compared with those with a poorly differentiated type. Therefore, histologic differentiation can be used as a prognostic indicator in gastric carcinoma patients with curative resection.

Vascular calcification is a hallmark of cardiovascular disease. Interleukin-24 (IL-24) has been known to suppress tumor progression in a variety of human cancers. However, the role of IL-24 in the pathophysiology of diseases other than cancer is unclear. We investigated the role of IL-24 in vascular calcification. IL-24 was applied to a β-glycerophosphate (β-GP)-induced rat vascular smooth muscle cell (VSMC) calcification model. In this study, IL-24 significantly inhibited β-GP-induced VSMC calcification, as determined by von Kossa staining and calcium content. The inhibitory effect of IL-24 on VSMC calcification was due to the suppression of β-GP-induced apoptosis and expression of calcification and osteoblastic markers. In addition, IL-24 abrogated β-GP-induced activation of the Wnt/β-catenin pathway, which plays a key role in the pathogenesis of vascular calcification. The specificity of IL-24 for the inhibition of VSMC calcification was confirmed by using a neutralizing antibody to IL-24. Our results suggest that IL-24 inhibits β-GP-induced VSMC calcification by inhibiting apoptosis, the expression of calcification and osteoblastic markers, and the Wnt/ β-catenin pathway. Our study may provide a novel mechanism of action of IL-24 in cardiovascular disease and indicates that IL-24 is a potential therapeutic agent in VSMC calcification.