Cutoff of the reverse shock index multiplied by the Glasgow coma scale for predicting in-hospital mortality in adult patients with trauma: a retrospective cohort study.

BACKGROUND: Early identification of patients at risk of potential death and timely transfer to appropriate healthcare facilities are critical for reducing the number of preventable trauma deaths. This study aimed to establish a cutoff value to predict in-hospital mortality using the reverse shock index multiplied by the Glasgow Coma Scale (rSIG). METHODS: This multicenter retrospective cohort study used data from 23 emergency departments in South Korea between January 2011 and December 2020. The outcome variable was the in-hospital mortality. The relationship between rSIG and in-hospital mortality was plotted using the shape-restricted regression spline method. To set a cutoff for rSIG, we found the point on the curve where mortality started to increase and the point where the slope of the mortality curve changed the most. We also calculated the cutoff value for rSIG using Youden's index. RESULTS: A total of 318,506 adult patients with trauma were included. The shape-restricted regression spline curve showed that in-hospital mortality began to increase when the rSIG value was less than 18.86, and the slope of the graph increased the most at 12.57. The cutoff of 16.5, calculated using Youden's index, was closest to the target under-triage and over-triage rates, as suggested by the American College of Surgeons, when applied to patients with an rSIG of 20 or less. In addition, in patients with traumatic brain injury, when the rSIG value was over 25, in-hospital mortality tended to increase as the rSIG value increased. CONCLUSIONS: We propose an rSIG cutoff value of 16.5 as a predictor of in-hospital mortality in adult patients with trauma. However, in patients with traumatic brain injury, a high rSIG is also associated with in-hospital mortality. Appropriate cutoffs should be established for this group in the future.

Altered interictal serum histamine and immunoglobulin E but unchanged tryptase levels in individuals with episodic and chronic migraine.

BACKGROUND: Serum histamine, immunoglobulin E, and tryptase are markers of allergic diseases. Despite the reported association between migraine and allergic diseases, differences in these marker levels between episodic and chronic migraines remain unelucidated. METHODS: We investigated serum histamine, immunoglobulin E, and tryptase levels in 97 and 96 participants with episodic migraine and chronic migraine, respectively, and 56 controls according to the presence of allergic diseases. RESULTS: Serum histamine levels in episodic migraine (median and interquartile ranges, 0.78 [0.65-1.25] ng/mL, p < 0.001) and chronic migraine (0.89 [0.67-1.28] ng/mL, p < 0.001) participants were significantly lower than those in healthy controls (1.19 [0.81-2.08] ng/mL) among the 160 participants without allergic diseases. Serum immunoglobulin E levels in episodic migraine and chronic migraine participants with allergic diseases negatively correlated with headache frequency (correlation coefficient = -0.263, p = 0.017). Serum histamine levels in participants with allergic diseases and serum immunoglobulin E levels in participants without allergic diseases were not significantly different among episodic migraine, chronic migraine, and control groups. Serum tryptase levels did not significantly differ among episodic migraine, chronic migraine, and control participants with and without allergic diseases. CONCLUSIONS: Altered serum histamine and immunoglobulin E levels in episodic migraine and chronic migraine and different profiles concerning allergic diseases suggest the involvement of allergic mechanisms in migraine pathogenesis.

Respiratory Syncytial Virus Outbreak Without Influenza in the Second Year of the Coronavirus Disease 2019 Pandemic: A National Sentinel Surveillance in Korea, 2021-2022 Season.

BACKGROUND: This study aimed to investigate whether respiratory syncytial virus (RSV) and influenza virus (IFV) infections would occur in 2021-2022 as domestic nonpharmaceutical interventions (NPIs) are easing. METHODS: Data were collected from the Korean Influenza and Respiratory Virus Monitoring System database. The weekly positivity rates of respiratory viruses and number of hospitalizations for acute respiratory infections were evaluated (January 2016-2022). The period from February 2020 to January 2022 was considered the NPI period. The autoregressive integrated moving average model and Poisson analysis were used for data analysis. Data from 14 countries/regions that reported positivity rates of RSV and IFV were also investigated. RESULTS: Compared with the pre-NPI period, the positivity and hospitalization rates for IFV infection during 2021-2022 significantly decreased to 0.0% and 1.0%, respectively, at 0.0% and 1.2% of the predicted values, respectively. The RSV infection positivity rate in 2021-2022 was 1.8-fold higher than that in the pre-NPI period at 1.5-fold the predicted value. The hospitalization rate for RSV was 20.0% of that in the pre-NPI period at 17.6% of the predicted value. The re-emergence of RSV and IFV infections during 2020-2021 was observed in 13 and 4 countries, respectively. CONCLUSION: During 2021-2022, endemic transmission of the RSV, but not IFV, was observed in Korea.

Predictors of difficult intubation when using a videolaryngoscope with an intermediate-angled blade during the first attempt: a prospective observational study.

The curvature of a videolaryngoscope blade has been diversified from the standard macintosh-type to the hyperacute-angle-type, resulting in different performances. We aimed to determine the intubation success rate and identify predictors of difficult intubation when using an intermediate-angled videolaryngoscope in the first attempt of intubation under routine anaesthesia settings. We enrolled 808 patients between 19 and 79 years of age, scheduled for elective surgeries under general anaesthesia with orotracheal intubation from July 2017 to November 2018; patients who were candidates for awake intubation were excluded. We obtained patient demographic data and performed airway evaluation before induction of anaesthesia for elective surgeries. We used the UEScope for tracheal intubation with a hockey stick-shaped malleable stylet. The intubation time was defined as the total duration from the entry of the blade into the oropharynx to the detection of first end-tidal carbon dioxide capnogram; this duration was recorded along with the number of intubation attempts. Difficult intubation was defined as either > 60 s duration for tracheal intubation, or > 1 intubation attempt. The use of the UEScope demonstrated a 99.4% success rate for intubation; however, increased difficulties were observed in patients who were male, obese, had a short thyromental distance, limited mouth opening, and high upper-lip-bite test class. Despite the high intubation success rate using an intermediate-angled videolaryngoscope, we recommend preparing backup plans, considering the increased difficulty in patients with certain preoperative features.Clinical trial number and registry URL: Clinical Trials.gov Identifier: NCT03215823 (Date of registration: 12 July).

Chronological Trends of Breast Ductal Carcinoma In Situ: Clinical, Radiologic, and Pathologic Perspectives.

BACKGROUND: Because no prior studies have evaluated the chronological trends of ductal carcinoma in situ (DCIS) despite the increasing number of surgeries performed for DCIS, this study analyzed how the clinical, radiologic, and pathologic characteristics of DCIS changed during a 10-year period. METHODS: Of 7123 patients who underwent primary breast cancer surgery at a single institution from 2006 to 2015, 792 patients with pure DCIS were included in this study. The chronological trends of age, symptoms, method for detecting either mammography or ultrasonography, tumor size, nuclear grade, comedonecrosis, and molecular markers were calculated using Poisson regression for all patients and asymptomatic patients. RESULTS: During 10 years, DCIS surgery rates significantly increased (p < 0.001). Despite the high percentage of DCIS detected on mammography, the detection rate for DCIS by mammography significantly decreased (97.3% in 2006 to 67.6% in 2015; p = 0.025), whereas the detection rate by ultrasound significantly increased (2.7% to 31.0%; p < 0.001). Conservation surgery rates (odds ratio [OR], 1.058), low-to-intermediate nuclear grade rates (OR, 1.069), and the absence of comedonecrosis (OR, 1.104) significantly increased over time (all p < 0.05). Estrogen receptor (ER) negativity (OR, 0.935) and human epidermal growth factor receptor 2 (HER2) positivity rates (OR, 0.953) significantly decreased (all p < 0.05). The same trends were observed for the 613 asymptomatic patients. CONCLUSION: The rate of DCIS detected on ultrasound only significantly increased during 10 years. Low-to-intermediate nuclear grade rates significantly increased, whereas ER negativity and HER2 positivity rates significantly decreased during the same period. These findings suggest that DCIS detected on screening ultrasound is less aggressive than DCIS detected on mammography.

Effects of bisphosphonates on long-term kidney transplantation outcomes.

BACKGROUND: Bisphosphonates are administered to post-transplantation patients with mineral and bone disorders; however, the association between bisphosphonate therapy and long-term renal graft survival remains unclear. METHODS: This nested case-control study investigated the effects of bisphosphonates on long-term graft outcomes after kidney transplantation. We enrolled 3836 kidney transplant recipients treated from April 1979 to June 2016 and matched patients with graft failure to those without (controls). Annual post-transplant bone mineral density assessments were performed and recipients with osteopenia or osteoporosis received bisphosphonate therapy. The associations between bisphosphonate use and long-term graft outcomes and graft survival were analyzed using conditional logistic regression and landmark analyses, respectively. RESULTS: A landmark analysis demonstrated that death-censored graft survival was significantly higher in bisphosphonate users than in non-users in the entire cohort (log-rank test, P < 0.001). In the nested case-control matched cohort, bisphosphonate users had a significantly reduced risk of graft failure than did non-users (odds ratio = 0.38; 95% confidence interval 0.30-0.48). Bisphosphonate use, increased cumulative duration of bisphosphonate use >1 year and increased cumulative bisphosphonate dose above the first quartile were associated with a reduced risk of graft failure, after adjustments. CONCLUSIONS: Bisphosphonates may improve long-term graft survival in kidney transplant recipients.

Validity and reliability of the self-administered Visual Aura Rating Scale questionnaire for migraine with aura diagnosis: A prospective clinic-based study.

OBJECTIVE: To assess the validity and reliability of the self-administered Visual Aura Rating Scale (VARS) questionnaire using a hospital-based sample in a cross-sectional setting. BACKGROUND: Visual aura is the most common type of aura manifesting in 98%-99% of migraine with aura (MA). The VARS is a diagnostic rating scale used to quantify the cardinal characteristics of MA and has shown high sensitivity and specificity in the diagnosis of visual aura. METHODS: We translated the VARS into Korean and constructed a five-item self-administered questionnaire based on the VARS. We consecutively recruited first-visit patients with migraine at the neurology clinics of two university hospitals. The scoring of the self-administered VARS questionnaire was the same as that for the original VARS. We assessed criterion validity and internal consistency reliability. The diagnosis of migraine and aura was assigned by two headache neurologists based on a comprehensive clinical assessment using the International Classification of Headache Disorders, 3rd edition. RESULTS: A total of 240 participants with migraine were enrolled. Of these, 55 (22.9%) had MA. All participants with MA had visual aura. Receiver operating characteristic curve analysis revealed that a cutoff score of 3 provided the highest rate of correct identification of patients ([200/240], 83.3%), with a sensitivity of 96.4% (95% confidence interval [CI], 84.5%-99.6%) and specificity of 79.5% (95% CI, 72.9%-85.0%). Cronbach's alpha coefficient was 0.852. CONCLUSION: The self-administered VARS questionnaire is a valid and reliable instrument for the screening of visual aura in patients with migraine in neurology outpatient clinics.

Prediction model for bleeding after endoscopic submucosal dissection of gastric neoplasms from a high-volume center.

BACKGROUND AND AIM: Bleeding after endoscopic submucosal dissection (ESD) is a main adverse event. To date, although there have been several studies about risk factors for post-ESD bleeding, there has been few predictive model for post-ESD bleeding with large volume cases. We aimed to design a prediction model for post-ESD bleeding using a classification tree model. METHODS: We analyzed a prospectively established cohort of patients with gastric neoplasms treated with ESD from 2007 to 2016. Baseline characteristics were collected for a total of 5080 patients, and the bleeding risk was estimated using variable statistical methods such as logistic regression, AdaBoost, and random forest. To investigate how bleeding was affected by independent predictors, the classification and regression tree (CART) method was used. The prediction tree developed for the cohort was internally validated. RESULTS: Post-ESD bleeding occurred in 262 of 5080 patients (5.1%). In multivariate logistic regression, ongoing antithrombotic use during the procedure, cancer pathology, and piecemeal resection were significant risk factors for post-ESD bleeding. In the CART model, the decisive variables were ongoing antithrombotic agent use, resected specimen size ≥49 mm, and patient age <62 years. The CART model accuracy was 94.9%, and the cross-validation accuracy was 94.8%. CONCLUSIONS: We developed a simple and easy-to-apply predictive tree model based on three risk factors that could help endoscopists identify patients at a high risk of bleeding. This model will enable clinicians to establish precise management strategies for patients at a high risk of bleeding and to prevent post-ESD bleeding.

Validation of the CAMD Score in Patients With Chronic Hepatitis B Virus Infection Receiving Antiviral Therapy.

BACKGROUND & AIMS: Researchers previously developed a scoring system to determine the risk of hepatocellular carcinoma (HCC) in patients with chronic hepatitis B virus (HBV) infection, based on the presence of cirrhosis, patient age, male sex, and diabetes (called the CAMD scoring system). We validated the CAMD scoring system and compared its performance with that of other risk assessment models in an independent cohort. METHODS: We followed up 3277 patients with chronic HBV infection (mean age, 48.7 y; 62.6% male; 32.4% with cirrhosis) who were treated with entecavir (n = 1725) or tenofovir (n = 1552) as the first-line antiviral agent in 4 academic teaching hospitals in the Republic of Korea. The primary outcome was development of HCC. We evaluated the ability of the CAMD, PAGE-B, and mPAGE-B scoring systems to identify patients who would develop HCC using integrated area under the curve (iAUC) analysis. RESULTS: Over a median follow-up period of 58.2 months, 8.9% of the patients developed HCC. Patients who developed HCC were older, more likely to be male, and had higher proportions of cirrhosis and diabetes than patients who did not develop HCC (all P < .05). CAMD scores identified patients who developed HCC with an iAUC of 0.790, mPAGE-B scores with an iAUC of 0.769, and PAGE-B scores with an iAUC of 0.760. The 5-year cumulative risks of HCC were 1.3% in patients with low CAMD scores (<8), 8.0% in patients with intermediate CAMD scores (8-13), and 24.3% in patients with high CAMD scores (>13) (P < .001 for comparison of low- vs intermediate-score groups and between intermediate- vs high-score groups). The predicted and observed probabilities of HCC had excellent agreement. CONCLUSIONS: We validated the CAMD scoring system in determining the risk of HCC in patients with chronic HBV treatment receiving entecavir or tenofovir treatment. Validation was performed in a cohort of patients in the Republic of Korea, where most patients have genotype C2 HBV infection.

Retzius Sparing Robot-Assisted Radical Prostatectomy Conveys Early Regain of Continence over Conventional Robot-Assisted Radical Prostatectomy: A Propensity Score Matched Analysis of 1,863 Patients.

PURPOSE: We compared early continence recovery after surgical treatment of prostate cancer with Retzius sparing robot-assisted radical prostatectomy and conventional robot-assisted radical prostatectomy. MATERIALS AND METHODS: Robot-assisted radical prostatectomy was done by a single surgeon in 1,863 cases between October 2005 and May 2018 using the conventional and the Retzius sparing technique in 1,150 and 713, respectively. To compare continence outcomes between the groups propensity score matching was performed using 9 preoperative variables, including age, body mass index, prostate specific antigen, biopsy Gleason Grade Group, clinical T stage, prostate volume on transrectal ultrasound, and the I-PSS (International Prostate Symptom Score), I-PSS quality of life score and International Index of Erectile Function-5 scores. Continence was assessed by the pad count every month postoperatively until month 6 and was converted to a binary outcome. RESULTS: After propensity score matching 609 cases per group were matched with no significant difference in all 9 variables. The Kaplan-Meier curve analysis revealed that Retzius sparing robot-assisted radical prostatectomy was associated with a significantly better continence recovery rate than conventional robot-assisted radical prostatectomy during the 6-month study period (p <0.001). CONCLUSIONS: Based on propensity score matching with multiple variables and a large case series, Retzius sparing robot-assisted radical prostatectomy can be a candidate for future robot-assisted radical prostatectomy. It achieves better early continence recovery, a short operative time and early recovery compared to conventional robot-assisted radical prostatectomy.

Lipid Emulsion Restoration of Myocardial Contractions After Bupivacaine-Induced Asystole In Vitro: A Benefit of Long- and Medium-Chain Triglyceride Over Long-Chain Triglyceride.

BACKGROUND: The relative efficacies of a long- and medium-chain triglyceride (LCT/MCT) emulsion and an LCT emulsion for treatment of bupivacaine (BPV)-induced cardiac toxicity are poorly defined. METHODS: After inducing asystole by BPV, varied concentrations (1%-12%) of either LCT/MCT (Lipofundin; B. Braun, Melsungen, Germany) or LCT emulsion (Intralipid; Fresenius Kabi, Upsala, Sweden) were applied to observe the recovery of stimulated contractile responses and contractile forces in either a recirculating or washout condition for 60 minutes, using guinea pig papillary muscles. The recirculation condition was used to demonstrate BPV binding by lipid emulsion. The washout condition was used to determine whether the time-dependent recovery of contraction is due to their metabolic enhancement. Oxfenicine, an inhibitor of carnitine palmitoyltransferase I in heart mitochondria, was used to evaluate the effect of each lipid emulsion on mitochondrial metabolic inhibition by BPV. To examine the effect of the lipid emulsion alone on contractility, either lipid emulsion was examined. BPV concentrations in solution and myocardial tissues were measured. RESULTS: In the recirculating condition, LCT/MCT emulsions (2%-12%) restored regular stimulated contractile responses in all muscles. Eight percent and 12% LCT/MCT emulsions led to complete recovery of contractile forces after 30 minutes. Meanwhile, LCT emulsions (4%-12%) did not restore regular stimulated contractile responses in some muscles (6, 3, and 2 in 9 muscles each in 4%, 8%, and 12% emulsions, respectively). Partial recovery, approximately 60%, of contractile forces was observed with 8% and 12% LCT emulsions. In the washout experiments, after asystole, LCT/MCT emulsions (1%-12%) restored contractility to baseline levels earlier and greater than LCT emulsion. Partial recovery, approximately 60%, was observed with a high concentration of LCT emulsion (12%). In the oxfenicine-pretreated group, the contractile recovery was enhanced with LCT/MCT emulsion but showed no change with LCT emulsion. Contractile depression by 40% was observed with high concentrations of LCT emulsion alone (8% and 12%), whereas no depression or enhanced contraction was observed with LCT/MCT emulsion (1%-12%) alone. Both types of lipid emulsions (2%-12%) caused concentration-related reductions of tissue BPV levels; LCT/MCT emulsions reduced tissue BPV levels slightly greater than LCT emulsion in a recirculating condition. CONCLUSIONS: An LCT/MCT emulsion was more beneficial than an LCT emulsion in terms of local anesthetic-binding and metabolic enhancement for treating acute BPV toxicity. The metabolic benefit of MCT, combined with the local anesthetic-binding effect of LCT, in an LCT/MCT emulsion may improve contractile function better than an LCT emulsion in an isolated in vitro animal myocardium model.

Effect of hypertension duration and blood pressure level on ischaemic stroke risk in atrial fibrillation: nationwide data covering the entire Korean population.

AIMS: There are a paucity of data on the association of duration of hypertension and blood pressure (BP) level with risk of ischaemic stroke in patients with atrial fibrillation (AF). Our objective was to investigate the association between duration of hypertension and secondly, BP levels with risk of ischaemic stroke among patients with AF. METHODS AND RESULTS: A total of 246 459 oral anticoagulant-naïve non-valvular AF patients were enrolled from Korea National Health Insurance Service (NHIS) database (2005-2015). The risk of ischaemic stroke according to the duration of hypertension and systolic BP (SBP) levels were assessed. One-year increase of hypertension duration continuously increased the adjusted risk of ischaemic stroke (95% confidence interval 1.07-1.09) until 7 years, and reached a plateau with adjusted hazard ratio of 1.6. Risk of ischaemic stroke increased linearly with the increase of hypertension duration in patients younger than 65 years of age, whereas the risk reached a plateau in patients aged 65 years or older. In all baseline and pre-AF average SBP subgroups, longer duration of hypertension before AF was associated with higher ischaemic stroke risk than shorter duration of hypertension (all P-values for trends <0.01). However, the effect of long-term hypertension was not observed in patients with strictly well-controlled pre-AF average SBP of less than 120 mmHg. CONCLUSION: The increase of hypertension duration was associated with the increased risk of ischaemic stroke. However, this long-term effect of hypertension duration can be attenuated by long-term strict SBP control throughout the entire duration of hypertension.

A nomogram to preoperatively predict 1-year disease-specific survival in resected pancreatic cancer following neoadjuvant chemoradiation therapy.

OBJECTIVE: This study aimed to develop a nomogram to predict the 1-year survival of patients with pancreatic cancer who underwent pancreatectomy following neoadjuvant treatment with preoperatively detectable clinical parameters. Extended pancreatectomy is necessary to achieve complete tumor removal in borderline resectable and locally advanced pancreatic cancer. However, it increases postoperative morbidity and mortality rates, and should be balanced with potential benefit of long-term survival. METHODS: The medical records of patients who underwent pancreatectomy following neoadjuvant treatment from January 2005 to December 2016 at Severance Hospital were retrospectively reviewed. Medical records were collected from five international institutions from Japan and Singapore for external validation. RESULTS: A total of 113 patients were enrolled. The nomogram for predicting 1-year disease-specific survival was created based on 5 clinically detectable preoperative parameters as follows: age (year), symptom (no/yes), tumor size at initial diagnostic stage (cm), preoperative serum carbohydrate antigen (CA) 19-9 level after neoadjuvant treatment (<34/≥34 U/mL), and planned surgery [pancreaticoduodenectomy (PD) (pylorus-preserving PD)/distal pancreatectomy (DP)/total pancreatectomy]. Model performance was assessed for discrimination and calibration. The calibration plot showed good agreement between actual and predicted survival probabilities; the the Greenwood-Nam-D'Agostino (GND) goodness-of-fit test showed that the model was well calibrated (χ2=8.24, P=0.5099). A total of 84 patients were used for external validation. When correlating actual disease-specific survival and calculated 1-year disease-specific survival, there were significance differences according to the calculated probability of 1-year survival among the three groups (P=0.044). CONCLUSIONS: The developed nomogram had quite acceptable accuracy and clinical feasibility in the decision-making process for the management of pancreatic cancer.

Microsatellite Instability and Programmed Cell Death-Ligand 1 Expression in Stage II/III Gastric Cancer: Post Hoc Analysis of the CLASSIC Randomized Controlled study.

OBJECTIVE: We investigated microsatellite instability (MSI) status and programed cell death ligand 1 (PD-L1) expression as predictors of prognosis and responsiveness to chemotherapy for stage II/III gastric cancer. BACKGROUND: The clinical implications of MSI status and PD-L1 expression in gastric cancer have not been well-elucidated. METHODS: Tumor specimens and clinical information were collected from patients enrolled in the CLASSIC trial-a randomized controlled study of capecitabine plus oxaliplatin-based adjuvant chemotherapy. Five quasi-monomorphic mononucleotide markers were used to assess tumor MSI status. PD-L1 expressions of tumor and stromal immune cells were evaluated using immunohistochemistry. RESULTS: Of 592 patients, 40 (6.8%) had MSI-high (MSI-H) tumors. Among 582 patients available for immunohistochemistry evaluation, PD-L1 was positive in tumor cells (tPD-L1) of 16 patients (2.7%) and stromal immune cells (sPD-L1) of 165 patients (28.4%). Multivariable analysis of disease-free survival (DFS) showed that MSI-H and sPD-L1-positivity were independent prognostic factors [hazard ratio 0.301 (0.123-0.736), 0.714 (0.514-0.991); P = 0.008, 0.044), as were receiving chemotherapy, age, tumor grade, and TNM stage. Although adjuvant chemotherapy improved DFS in the microsatellite-stable (MSS) group (5-year DFS: 66.8% vs 54.1%; P = 0.002); no benefit was observed in the MSI-H group (5-year DFS: 83.9% vs 85.7%; P = 0.931). In the MSS group, sPD-L1-negative patients, but not sPD-L1-positive patients, had significant survival benefit from adjuvant chemotherapy compared with surgery only (5-year DFS: 66.1% vs 50.7%; P = 0.001). CONCLUSION: MSI status and PD-L1 expression are clinically actionable biomarkers for stratifying patients and predicting benefit from adjuvant chemotherapy after D2 gastrectomy for stage II/III gastric cancer.

Serum bilirubin level is associated with exercise capacity and quality of life in chronic obstructive pulmonary disease.

BACKGROUND: Bilirubin has antioxidant properties against chronic respiratory diseases. However, previous studies are limited by acquisition of serum bilirubin level at one time point and its analysis with clinical parameters. We evaluated the association of serum bilirubin levels with various clinical outcomes of chronic obstructive pulmonary disease (COPD) in Korean Obstructive Lung Disease (KOLD) cohort. METHODS: We included 535 patients with COPD from the KOLD cohort. Serum bilirubin levels and various clinical parameters, such as lung function, 6-min walking (6 MW) distance, quality of life (QoL), and exacerbation, were evaluated annually; their association was analyzed using generalized estimating equations and the linear mixed model. RESULTS: Among 535 patients, 345 (64.5%) and 190 (35.5%) were categorized into Global Initiative for Chronic Obstructive Lung Disease (GOLD) I-II and GOLD III-IV groups, respectively. 6 MW distance was positively associated with serum bilirubin levels, especially in the GOLD I-II group (estimated mean = 41.5). Among QoL indexes, the COPD assessment test score was negatively associated with serum bilirubin levels only in the GOLD I-II group (estimated mean = - 2.8). Higher serum bilirubin levels were independently associated with a higher number of acute exacerbation in the GOLD III-IV group (estimated mean = 0.45, P = 0.001). Multivariate analysis revealed that lung function and mortality were not associated with serum bilirubin levels. CONCLUSIONS: Higher serum bilirubin levels were associated with a longer 6 MW distance and better QoL, especially in the GOLD I-II group, whereas they were related to a higher risk of acute exacerbation, especially in the GOLD III-IV group. Bilirubin levels may represent various conditions in COPD.

Presepsin as a diagnostic marker of sepsis in children and adolescents: a systemic review and meta-analysis.

BACKGROUND: Early diagnosis of sepsis in pediatric patients is vital but remains a major challenge. Previous studies showed that presepsin is potentially a reliable diagnostic biomarker for sepsis in adult and neonates. However, there is no pooled analysis of its efficacy as a diagnostic biomarker for sepsis in children. The aims of the present meta-analysis were to assess the overall diagnostic accuracy of presepsin in pediatric sepsis and compare it to those for C-reactive protein (CRP) and procalcitonin (PCT). METHODS: A systematic literature search was performed in Medline/Pubmed, Embase, the Cochrane Library, and ISI Web of Science to identify relevant studies reporting the diagnostic accuracy of presepsin in patients with pediatric sepsis. Sensitivities and specificities were pooled by bivariate meta-analysis. Heterogeneity was evaluated by χ2 test. RESULTS: We identified 129 studies in total. Most were disqualified on the basis of their titles/abstracts and duplication. Four studies were included in the final analysis. They comprised 308 patients aged between 1 mo and 18 y. The pooled diagnostic sensitivity and specificity of presepsin were 0.94 (95% confidence interval [CI]: 0.74-0.99) and 0.71 (95% CI: 0.35-0.92), respectively. The pooled diagnostic odds ratio, positive likelihood ratio (LR), and negative LR of presepsin were 32.87 (95% CI: 2.12-510.09), 3.24 (95% CI, 1.14-12.38), and 0.08 (95% CI, 0.01-0.74), respectively. Heterogeneity was found in both sensitivity (χ2 = 11.17; P = 0.011) and specificity (χ2 = 65.78; P < 0.001). No threshold effect was identified among the studies (r = - 0.938). The pooled sensitivity of presepsin (0.94) was higher than that of CRP (0.51) and PCT (0.76), whereas the overall specificity of presepsin (0.71) was lower than that of CRP (0.81) and PCT (0.76). The AUC of presepsin (0.925) was higher than that of CRP (0.715) and PCT (0.820). CONCLUSION: Currently available evidence indicates that presepsin has higher sensitivity and diagnostic accuracy, but lower specificity, than PCT or CRP in detecting sepsis in children. However, these results must be carefully interpreted as the number of studies included was small and the studies were statistically heterogeneous.

Predictive test for chemotherapy response in resectable gastric cancer: a multi-cohort, retrospective analysis.

BACKGROUND: Adjuvant chemotherapy after surgery improves survival of patients with stage II-III, resectable gastric cancer. However, the overall survival benefit observed after adjuvant chemotherapy is moderate, suggesting that not all patients with resectable gastric cancer treated with adjuvant chemotherapy benefit from it. We aimed to develop and validate a predictive test for adjuvant chemotherapy response in patients with resectable, stage II-III gastric cancer. METHODS: In this multi-cohort, retrospective study, we developed through a multi-step strategy a predictive test consisting of two rule-based classifier algorithms with predictive value for adjuvant chemotherapy response and prognosis. Exploratory bioinformatics analyses identified biologically relevant candidate genes in gastric cancer transcriptome datasets. In the discovery analysis, a four-gene, real-time RT-PCR assay was developed and analytically validated in formalin-fixed, paraffin-embedded (FFPE) tumour tissues from an internal cohort of 307 patients with stage II-III gastric cancer treated at the Yonsei Cancer Center with D2 gastrectomy plus adjuvant fluorouracil-based chemotherapy (n=193) or surgery alone (n=114). The same internal cohort was used to evaluate the prognostic and chemotherapy response predictive value of the single patient classifier genes using associations with 5-year overall survival. The results were validated with a subset (n=625) of FFPE tumour samples from an independent cohort of patients treated in the CLASSIC trial (NCT00411229), who received D2 gastrectomy plus capecitabine and oxaliplatin chemotherapy (n=323) or surgery alone (n=302). The primary endpoint was 5-year overall survival. FINDINGS: We identified four classifier genes related to relevant gastric cancer features (GZMB, WARS, SFRP4, and CDX1) that formed the single patient classifier assay. In the validation cohort, the prognostic single patient classifier (based on the expression of GZMB, WARS, and SFRP4) identified 79 (13%) of 625 patients as low risk, 296 (47%) as intermediate risk, and 250 (40%) as high risk, and 5-year overall survival for these groups was 83·2% (95% CI 75·2-92·0), 74·8% (69·9-80·1), and 66·0% (60·1-72·4), respectively (p=0·012). The predictive single patient classifier (based on the expression of GZMB, WARS, and CDX1) assigned 281 (45%) of 625 patients in the validation cohort to the chemotherapy-benefit group and 344 (55%) to the no-benefit group. In the predicted chemotherapy-benefit group, 5-year overall survival was significantly improved in those patients who had received adjuvant chemotherapy after surgery compared with those who received surgery only (80% [95% CI 73·5-87·1] vs 64·5% [56·8-73·3]; univariate hazard ratio 0·47 [95% CI 0·30-0·75], p=0·0015), whereas no such improvement in 5-year overall survival was observed in the no-benefit group (72·9% [66·5-79·9] in patients who received chemotherapy plus surgery vs 72·5% [65·8-79·9] in patients who only had surgery; 0·93 [0·62-1·38], p=0·71). The predictive single patient classifier groups (chemotherapy benefit vs no-benefit) could predict adjuvant chemotherapy benefit in terms of 5-year overall survival in the validation cohort (pinteraction=0·036 in univariate analysis). Similar results were obtained in the internal evaluation cohort. INTERPRETATION: The single patient classifiers validated in this study provide clinically important prognostic information independent of standard risk-stratification methods and predicted chemotherapy response after surgery in two independent cohorts of patients with resectable, stage II-III gastric cancer. The single patient classifiers could complement TNM staging to optimise decision making in patients with resectable gastric cancer who are eligible for adjuvant chemotherapy after surgery. Further validation of these results in prospective studies is warranted. FUNDING: Ministry of ICT and Future Planning; Ministry of Trade, Industry, and Energy; and Ministry of Health and Welfare.

Association of serum bilirubin level with lung function decline: a Korean community-based cohort study.

BACKGROUND: Bilirubin has been reported to be associated with respiratory diseases due to its antioxidant action. We aimed to evaluate the relationship between serum bilirubin concentration and annual lung function decline in the Korean general population. METHODS: The study included 7986 subjects aged 40-69 years from the Ansung-Ansan cohort database I (2001-2002)-III (2005-2006). We analyzed the relationships between serum bilirubin level and forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC), FEV1/FVC, and mean forced expiratory flow between 25 and 75% of FVC (FEF25-75%) at baseline, as well as the annual average changes in these lung parameters. RESULTS: The FEV1, FVC, and FEF25-75% were significantly associated with serum bilirubin levels after adjustment for age, sex, body mass index (BMI), and smoking status (all P < 0.001). When stratified according to smoking status, these relationships were significant in never-smokers. Additionally, serum bilirubin level was negatively associated with the annual decline in FEV1 and FVC, and positively associated with the annual decline in FEV1/FVC after adjustment for age, sex, BMI, baseline lung function, and smoking status (all P < 0.001). CONCLUSIONS: We found significant associations of serum bilirubin levels with FEV1, FVC, and FEF25-75% in the general population, especially in never-smokers. Moreover, serum bilirubin levels were related with the annual decline in FEV1, FVC, and FEV1/FVC ratio.

Rectal Mucinous Adenocarcinoma: MR Imaging Assessment of Response to Concurrent Chemotherapy and Radiation Therapy-A Hypothesis-generating Study.

Purpose To develop a system for assessment of tumor regression grade (TRG) with magnetic resonance (MR) imaging that is applicable to rectal mucinous adenocarcinoma (RMAC) and to obtain a preliminary evaluation of the association of MR imaging assessment of TRG with response to preoperative concurrent chemotherapy and radiation therapy (CCRT). Materials and Methods This retrospective study was approved by the institutional review board, and informed consent was waived. Pre- and post-CCRT MR images of 59 patients with RMAC (median age, 59 years; range, 29-80 years; 42 men [median age, 59 years; range, 36-80 years] and 17 women [median age, 57 years; range, 29-79 years]) who underwent CCRT and subsequent elective resection from July 2005 to June 2015 were analyzed. Two experienced gastrointestinal radiologists independently analyzed imaging parameters such as T stage, mesorectal fascia status, extramural vascular invasion status, and TRG by using modified criteria developed for assessment of RMAC. Interobserver variability was calculated with weighted κ analysis, and disagreement was settled in consensus. MR imaging TRG results were compared with those from pathologic TRG analysis (Mandard grade). Logistic regression analyses were performed to evaluate associations between imaging parameters and pathologic TRG. Results There was moderate to substantial agreement for imaging parameters (post-CCRT T stage-weighted κ, 0.7134; post-CCRT mesorectal fascia status, 0.618; TRG, 0.5023). Modified MR imaging TRG results were significantly associated with pathologic responsiveness (responsive group, Mandard grade 1 or 2; nonresponsive group, Mandard grades 3-5; P = .023). Results of univariate and multivariate logistic regression analyses indicated that MR imaging TRG was the only factor significantly associated with CCRT responsiveness (univariate analysis, P = .023; multivariate analysis, P = .0261). Conclusion The modified MR imaging assessment of TRG was associated with treatment response to CCRT in patients with RMAC. © RSNA, 2017 Online supplemental material is available for this article.

Prediction model for non-curative resection of endoscopic submucosal dissection in patients with early gastric cancer.

BACKGROUND AND AIMS: Endoscopic submucosal dissection (ESD) is a useful method for complete resection of early gastric cancer (EGC). However, there are still some patients who undergo additional gastrectomy after ESD because of non-curative resection. There is no model that can accurately predict non-curative resection of ESD. We aimed to create a model for predicting non-curative resection of ESD in patients with EGC. PATIENTS AND METHODS: We reviewed the medical records, including all gross findings of EGC, of patients who underwent ESD for EGCs. We divided the patients into a non-curative resection group and a curative resection group. The clinicopathologic characteristics were compared between the groups to identify the risk factors for non-curative resection of ESD. We created a scoring system based on logistic regression modeling and bootstrap validation. RESULTS: Of 1639 patients who had undergone ESD for EGCs, 272 were identified as being treated non-curatively with ESD. A large tumor size (≥20 mm), tumor location in the upper body of the stomach, the presence of ulcer, fusion of gastric folds, the absence of mucosal nodularity, spontaneous bleeding, and undifferentiated tumor histology were associated with non-curative resection of ESD. Points of risk scores were assigned for these variables based on the ß coefficient as follows: tumor size (≥20 mm), 2 points; tumor location in the upper body of the stomach, 1 point; ulcer, 2 points; fusion of gastric folds, 2 points; absence of mucosal nodularity, 1 point; spontaneous bleeding, 1 point; and undifferentiated histology, 2 points. Our risk scoring model showed good discriminatory performance on internal validation (bootstrap-corrected area under the receiver operating characteristic curve, 0.7004; 95% confidence interval, 0.6655-0.7353). CONCLUSIONS: We developed a validated prediction model that can be used to identify patients who will undergo non-curative resection of ESD. Our prediction model can provide useful information for making decisions about the treatment of EGC before performing ESD.