Incidence of Clostridioides difficile Infections in Republic of Korea: A Prospective Study With Active Surveillance vs. National Data From Health Insurance Review & Assessment Service.

BACKGROUND: Since the emergence of hypervirulent strains of Clostridioides difficile, the incidence of C. difficile infections (CDI) has increased significantly. METHODS: To assess the incidence of CDI in Korea, we conducted a prospective multicentre observational study from October 2020 to October 2021. Additionally, we calculated the incidence of CDI from mass data obtained from the Health Insurance Review and Assessment Service (HIRA) from 2008 to 2020. RESULTS: In the prospective study with active surveillance, 30,212 patients had diarrhoea and 907 patients were diagnosed with CDI over 1,288,571 patient-days and 193,264 admissions in 18 participating hospitals during 3 months of study period; the CDI per 10,000 patient-days was 7.04 and the CDI per 1,000 admission was 4.69. The incidence of CDI was higher in general hospitals than in tertiary hospitals: 6.38 per 10,000 patient-days (range: 3.25-12.05) and 4.18 per 1,000 admissions (range: 1.92-8.59) in 11 tertiary hospitals, vs. 9.45 per 10,000 patient-days (range: 5.68-13.90) and 6.73 per 1,000 admissions (range: 3.18-15.85) in seven general hospitals. With regard to HIRA data, the incidence of CDI in all hospitals has been increasing over the 13-year-period: from 0.3 to 1.8 per 10,000 patient-days, 0.3 to 1.6 per 1,000 admissions, and 6.9 to 56.9 per 100,000 population, respectively. CONCLUSION: The incidence of CDI in Korea has been gradually increasing, and its recent value is as high as that in the United State and Europe. CDI is underestimated, particularly in general hospitals in Korea.

Immunogenicity and safety of concomitant bivalent COVID-19 and quadrivalent influenza vaccination: implications of immune imprinting and interference.

OBJECTIVES: Concomitant COVID-19 and influenza vaccination would be an efficient strategy. Although the co-administration of monovalent COVID-19 and influenza vaccinations showed acceptable immunogenicity, it remains unknown whether the bivalent COVID-19 vaccine could intensify immune interference. We aimed to evaluate the immunogenicity and safety of concomitant BA.5-based bivalent COVID-19 and influenza vaccination. METHODS: An open-label, nonrandomized clinical trial was conducted for 154 age-matched and sex-matched healthy adults between October 2022 and December 2022. Participants received either a concomitant bivalent COVID-19 mRNA booster and quadrivalent influenza vaccination (group C) or separate vaccinations (group S) at least 4 weeks apart. Solicited and unsolicited adverse events were reported up to 6 months postvaccination. Immunogenicity was evaluated by anti-spike (S) IgG electrochemiluminescence immunoassay, focus reduction neutralization test, and hemagglutination inhibition assay. RESULTS: Group C did not meet the noninferiority criteria for the seroconversion rates of anti-S IgG and neutralizing antibodies against the wild-type SARS-CoV-2 strain compared with group S (44.2% vs. 46.8%, difference of -2.6% [95% CI, -18 to 13.4]; 44.2% vs. 57.1%, difference of -13.0% [95% CI to -28.9 to 2.9]). However, group C showed a stronger postvaccination neutralizing antibody response against Omicron BA.5 (72.7% vs. 64.9%). Postvaccination geometric mean titers for SARS-CoV-2 and influenza strains were similar between groups, except for influenza B/Victoria. Most adverse events were mild and comparable between the study groups. DISCUSSION: Concomitant administration of bivalent COVID-19 mRNA and quadrivalent influenza vaccines showed tolerable safety profiles and sufficient immunogenicity, particularly attenuating immune imprinting induced by previous ancestral vaccine strains.

Assessment of quality of care for hospitalized non-COVID-19 older adult patients with pneumonia before and after the COVID-19 pandemic.

BACKGROUND: There is limited research into the clinical implications of the coronavirus disease 2019 (COVID-19) pandemic for non-COVID-19 pneumonia in older adults, as well as their quality of care or outcomes. This study aims to assess the process and outcome quality of care for hospitalized older adult patients with pneumonia before and after the pandemic. METHODS: A retrospective cohort of older adult patients (age ≥ 65) hospitalized for non-COVID pneumonia were recruited from five Korean hospitals (January 20, 2019, to January 19, 2021). The quality of care before and after the COVID-19 pandemic was evaluated. RESULTS: A total of 7356 hospitalization episodes of older adult pneumonia were identified, and 978 cases (552 pre-pandemic and 426 during the pandemic) were analyzed. The pneumonia severity score was higher during the pandemic, and the waiting time from the emergency room to admission was also longer. Furthermore, the pneumonia mortality rate during the pandemic was higher than that in the pre-pandemic period (in-hospital mortality: 10.1% vs. 18.1%; 90-day mortality: 11.6% vs. 22.3%). A significantly higher mortality risk was observed during the pandemic than in the period prior (adjusted odds ratio: 1.74, 95% confidence interval: 1.14-2.63). CONCLUSIONS: While the quality of care for hospitalized pneumonia has been maintained during the pandemic, there has been an increase in mortality rates. Further investigations are needed to understand the underlying causes of this increase.

Changes in proteinuria and the associated risks of ischemic heart disease, acute myocardial infarction, and angina pectoris in Korean population.

OBJECTIVES: Proteinuria is widely used to predict cardiovascular risk. However, there is insufficient evidence to predict how changes in proteinuria may affect the incidence of cardiovascular disease. METHODS: The study included 265,236 Korean adults who underwent health checkups in 2003-2004 and 2007-2008. They were categorized into 4 groups based on changes in proteinuria (negative: negative → negative; resolved: proteinuria ≥1+ → negative; incident: negative → proteinuria ≥1+; persistent: proteinuria ≥1+ → proteinuria ≥1+). We conducted 6 years of follow-up to identify the risks of developing ischemic heart disease (IHD), acute myocardial infarction (AMI), and angina pectoris according to changes in proteinuria. A multivariate Cox proportional-hazards model was used to calculate adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) for incident IHD, AMI, and angina pectoris. RESULTS: The IHD risk (expressed as HR [95% CI]) was the highest for persistent proteinuria, followed in descending order by incident and resolved proteinuria, compared with negative proteinuria (negative: reference, resolved: 1.211 [95% CI, 1.104 to 1.329], incident: 1.288 [95% CI, 1.184 to 1.400], and persistent: 1.578 [95% CI, 1.324 to 1.881]). The same pattern was associated with AMI (negative: reference, resolved: 1.401 [95% CI, 1.048 to 1.872], incident: 1.606 [95% CI, 1.268 to 2.035], and persistent: 2.069 [95% CI, 1.281 to 3.342]) and angina pectoris (negative: reference, resolved: 1.184 [95% CI, 1.065 to 1.316], incident: 1.275 [95% CI, 1.160 to 1.401], and persistent: 1.554 [95% CI, 1.272 to 1.899]). CONCLUSIONS: Experiencing proteinuria increased the risks of IHD, AMI, and angina pectoris even after proteinuria resolved.

Association between CYP2D6 phenotype and recurrence of Plasmodium vivax infection in south Korean patients.

BACKGROUND: Primaquine is activated by CYP2D6 in the hepatocytes. In Korea, primaquine is the only hypnozoitocidal agent used for patients with vivax malaria. Thus, patients with poor CYP2D6 activity could have an increased risk of primaquine failure and subsequent relapse. The study sought to identify the association between CYP2D6 phenotype and recurrence of malaria in Korean patients. METHODS: A total of 102 patients with vivax malaria were prospectively enrolled from eight institutions in Korea. An additional 38 blood samples from patients with recurred vivax malaria were provided by the Korea Disease Control and Prevention Agency. Malaria recurrence was defined as more than one episode of vivax malaria in the same or consecutive years. CYP2D6 star alleles, phenotypes, and activity scores were examined. RESULTS: Genotyping for CYP2D6 was successful in 101 of the prospectively enrolled patients and 38 samples from the Korea Disease Control and Prevention Agency, of which 91 were included in the no-recurrence group and 48 were included in the recurrence group. Reduced CYP2D6 activity (intermediate metabolizer) phenotype was more common in the recurrence group than in the no-recurrence group (OR, 2.33 (95% CI, 1.14-4.77); p = 0.02). Patients with lower CYP2D6 activity had a higher probability of recurrence (p = 0.029). CONCLUSION: This study suggests that CYP2D6 polymorphism may affect primaquine efficacy and thus Plasmodium vivax recurrence in Korea.

Four Times of Relapse of Plasmodium vivax Malaria Despite Primaquine Treatment in a Patient with Impaired Cytochrome P450 2D6 Function.

Plasmodium vivax exhibits dormant liver-stage parasites, called hypnozoites, which can cause relapse of malaria. The only drug currently used for eliminating hypnozoites is primaquine. The antimalarial properties of primaquine are dependent on the production of oxidized metabolites by the cytochrome P450 isoenzyme 2D6 (CYP2D6). Reduced primaquine metabolism may be related to P. vivax relapses. We describe a case of 4 episodes of recurrence of vivax malaria in a patient with decreased CYP2D6 function. The patient was 52-year-old male with body weight of 52 kg. He received total gastrectomy and splenectomy 7 months before the first episode and was under chemotherapy for the gastric cancer. The first episode occurred in March 2019 and each episode had intervals of 34, 41, and 97 days, respectively. At the first and second episodes, primaquine was administered as 15 mg for 14 days. The primaquine dose was increased with 30 mg for 14 days at the third and fourth episodes. Seven gene sequences of P. vivax were analyzed and revealed totally identical for all the 4 samples. The CYP2D6 genotype was analyzed and intermediate metabolizer phenotype with decreased function was identified.

Risk Scoring System of Mortality and Prediction Model of Hospital Stay for Critically Ill Patients Receiving Parenteral Nutrition.

Predicting the clinical progression of intensive care unit (ICU) patients is crucial for survival and prognosis. Therefore, this retrospective study aimed to develop the risk scoring system of mortality and the prediction model of ICU length of stay (LOS) among patients admitted to the ICU. Data from ICU patients aged at least 18 years who received parenteral nutrition support for ≥50% of the daily calorie requirement from February 2014 to January 2018 were collected. In-hospital mortality and log-transformed LOS were analyzed by logistic regression and linear regression, respectively. For calculating risk scores, each coefficient was obtained based on regression model. Of 445 patients, 97 patients died in the ICU; the observed mortality rate was 21.8%. Using logistic regression analysis, APACHE II score (15-29: 1 point, 30 or higher: 2 points), qSOFA score ≥ 2 (2 points), serum albumin level < 3.4 g/dL (1 point), and infectious or respiratory disease (1 point) were incorporated into risk scoring system for mortality; patients with 0, 1, 2-4, and 5-6 points had approximately 10%, 20%, 40%, and 65% risk of death. For LOS, linear regression analysis showed the following prediction equation: log(LOS) = 0.01 × (APACHE II) + 0.04 × (total bilirubin) - 0.09 × (admission diagnosis of gastrointestinal disease or injury, poisoning, or other external cause) + 0.970. Our study provides the mortality risk score and LOS prediction equation. It could help clinicians to identify those at risk and optimize ICU management.

Clinical application of next-generation sequencing for the management of desmoid tumors: A case report and literature review.

RATIONALE: Desmoid tumors are rare myofibroblastic neoplasms characterized by local invasiveness and high rates of recurrence, and sometimes mimic local recurrence of previously resected malignancies. Previous studies have suggested that molecular profiling may be useful for the diagnosis of the tumors and risk stratification. However, the clinical utility of next-generation sequencing (NGS) for the management of desmoid tumors has not been established. PATIENT CONCERNS: A 42-year-old man visited our clinic for routine follow-up 1 year after left upper lobe lingular segmentectomy for lung adenocarcinoma. DIAGNOSES: Chest computed tomography showed a pleural mass adherent to the thoracotomy site. Positron emission tomography revealed mildly increased metabolism with a maximal standardized uptake value of 2.7 within the tumor, suggesting local recurrence of the previous neoplasm. Exploratory thoracotomy and en bloc resection of the tumor revealed spindle cells in a massive collagenous tissue consistent with a desmoid tumor. INTERVENTIONS: NGS was performed to confirm the diagnosis and to identify any genetic alterations that might be relevant to the prognosis of this tumor. The tumor harbored an S45F mutation in CTNNB1, which has been correlated with a high recurrence rate. Therefore, we performed adjuvant radiotherapy on the resection bed at a dose of 56 Gy. OUTCOMES: The patients experienced no postoperative or radiotherapy-related complications. Periodic follow-up examinations using computed tomography were performed every 3 months, and no evidence of recurrence of either tumor was observed during the 38 months after the last surgery. LESSONS: To the best of our knowledge, this is the first case reporting the clinical application of NGS and aggressive treatment based on the genotyping results for the management of a desmoid tumor. Our case highlights the need to consider desmoid tumors among the differential diagnoses when a pleural mass is encountered at a previous thoracotomy site. More importantly, molecular profiling using NGS can be useful for the establishment of a treatment strategy for this tumor, although further investigations are required.

Retrosternal hematoma in sternal fracture for prediction of concomitant injury on chest CT.

BACKGROUND: Isolated sternal fracture, a benign injury, has been increasing in the pan-scan era, although one-third of patients with sternal fracture still has trouble with concomitant injury. The differentiation of these two entities is important to optimize patient management. PURPOSE: To evaluate correlation between retrosternal hematoma and concomitant injury in patients with sternal fracture and to identify predicting factors for concomitant injury in sternal fracture. MATERIAL AND METHODS: A total of 139 patients (84 men; mean age = 54.9 ± 15.3 years) with traumatic sternal fracture were enrolled in this study. We reviewed medical charts and multiplanar computed tomography (CT) images to evaluate cause, location, and degree of sternal fracture, retrosternal hematoma, and concomitant injury. Univariate and multivariate analysis were used to identify variables that were associated with concomitant injury. RESULTS: Concomitant injury on chest CT was observed in 85 patients with sternal fracture. Of the patients, 98 (70.5%) were accompanied by retrosternal hematoma. Multivariate analysis revealed that retrosternal hematoma (odds ratio [OR] = 5.350; P < 0.001), manubrium fracture (OR = 6.848; P = 0.015), and motor vehicle accident (OR = 0.342; P = 0.015) were significantly associated with sternal fracture with concomitant injury. CONCLUSION: Manubrium fracture and retrosternal hematoma portend a high risk of concomitant injury and indicate the need for further clinical and radiologic work-up.

Sex-dimorphic genetic effects and novel loci for fasting glucose and insulin variability.

Differences between sexes contribute to variation in the levels of fasting glucose and insulin. Epidemiological studies established a higher prevalence of impaired fasting glucose in men and impaired glucose tolerance in women, however, the genetic component underlying this phenomenon is not established. We assess sex-dimorphic (73,089/50,404 women and 67,506/47,806 men) and sex-combined (151,188/105,056 individuals) fasting glucose/fasting insulin genetic effects via genome-wide association study meta-analyses in individuals of European descent without diabetes. Here we report sex dimorphism in allelic effects on fasting insulin at IRS1 and ZNF12 loci, the latter showing higher RNA expression in whole blood in women compared to men. We also observe sex-homogeneous effects on fasting glucose at seven novel loci. Fasting insulin in women shows stronger genetic correlations than in men with waist-to-hip ratio and anorexia nervosa. Furthermore, waist-to-hip ratio is causally related to insulin resistance in women, but not in men. These results position dissection of metabolic and glycemic health sex dimorphism as a steppingstone for understanding differences in genetic effects between women and men in related phenotypes.

Comparison of antiviral effect for mild-to-moderate COVID-19 cases between lopinavir/ritonavir versus hydroxychloroquine: A nationwide propensity score-matched cohort study.

OBJECTIVES: We aimed to compare the antiviral effect of hydroxychloroquine (HCQ) and lopinavir/ritonavir (LPV/r) in patients with COVID-19. METHODS: Nationwide retrospective case-control study was conducted to compare the effect of HCQ and LPV/r on viral shedding duration among patients with mild-to-moderate COVID-19 using the reimbursement data of National Health Insurance Service. After propensity score matching (PSM), multivariate analysis was conducted to determine statistically significant risk factors associated with prolonged viral shedding. RESULTS: Overall, 4197 patients with mild-to-moderate COVID-19 were included. Patients were categorized into three groups: LPV/r (n = 1268), HCQ (n = 801), and standard care without HCQ or LPV/r (controls, n = 2128). The median viral shedding duration was 23 (IQR 17-32), 23 (IQR 16-32), and 18 (IQR 12-25) days in the LPV/r, HCQ, and control groups, respectively. Even after PSM, the viral shedding duration was not significantly different between LPV/r and HCQ groups: 23 (IQR, 17-32) days versus 23 (IQR, 16-32) days. On multivariate analysis, old age, malignancy, steroid use, and concomitant pneumonia were statistically significant risk factors for prolonged viral shedding. CONCLUSION: The viral shedding duration was similar between HCQ and LPV/r treatment groups. There was no benefit in improving viral clearance compared to the control group.

Case report of tracheobronchial injuries after acid ingestion: CT findings with serial follow-up: Airway complication after acid ingestion.

RATIONALE: Tracheobronchial injury from acid ingestion is a less reported clinical presentation than injury of the gastrointestinal tract, but it can occur due to direct exposure from acid aspiration and cause fatal complications. PATIENT CONCERNS: A 43-year-old man presented to the emergency department after ingesting nitric acid complaining of chest pain and dyspnea. DIAGNOSES: The initial chest computed tomography (CT) images revealed an acute lung injury related to acid aspiration. The follow-up chest CT showed acute and late tracheobronchial injures. INTERVENTIONS: Bronchoscopy showed deep caustic airway injuries consisting of hemorrhage, sloughing of the mucosa, and ulceration of the trachea and left-side bronchial tree. OUTCOMES: Progressive narrowing of the left main bronchus with total collapse of the left lung occurred as a late complication of acid ingestion. LESSONS: Tracheobronchial injury should be considered in cases of aspiration pneumonia after acid ingestion; chest CT can be used to detect and assess acute and late complications of tracheobronchial injuries.

Primary Resistance to Immune Checkpoint Blockade in an STK11/TP53/KRAS-Mutant Lung Adenocarcinoma with High PD-L1 Expression.

Several studies have shown that STK11 and TP53 mutations have different effects on the susceptibility to immune checkpoint blockade in KRAS-mutant non-small cell lung cancer (NSCLC). However, the impact of STK11/TP53 co-mutations on treatment outcomes in the same clinical setting has never been reported. We recently encountered a case of a 70-year-old man who was diagnosed with advanced lung adenocarcinoma with high-programmed death-ligand 1 (PD-L1) expression. He received pembrolizumab monotherapy as a frontline treatment; however, the tumor did not respond to this therapy and showed deleterious outcome. Next-generation sequencing revealed that the tumor harbored a rare STK11/TP53/KRAS triple mutation. Our case suggests that these compound mutations may constitute a distinct, aggressive subset that is resistant to immunotherapy even when the tumor strongly expresses PD-L1. In addition, this report highlights the importance of using molecular profiling to detect co-mutations that can be associated with primary resistance or disease progression to improve survival even in the immunotherapy setting.

Measurement accuracy of lung nodule volumetry in a phantom study: Effect of axial-volume scan and iterative reconstruction algorithm.

An axial-volume scan with adaptive statistical iterative reconstruction-V (ASIR-V) is newly developed. Our goal was to identify the influence of axial-volume scan and ASIR-V on accuracy of automated nodule volumetry.An "adult' chest phantom containing various nodules was scanned using both helical and axial-volume modes at different dose settings using 256-slice CT. All CT scans were reconstructed using 30% and 50% blending of ASIR-V and filtered back projection. Automated nodule volumetry was performed using commercial software. The image noise, contrast-to-noise ratio (CNR), and signal-to-noise ratio (SNR) were measured.The axial-volume scan reduced radiation dose by 19.7% compared with helical scan at all radiation dose settings without affecting the accuracy of nodule volumetric measurement (P = .375). Image noise, CNR, and SNR were not significantly different between two scan modes (all, P > .05).The use of axial-volume scan with ASIR-V achieved effective radiation dose reduction while preserving the accuracy of nodule volumetry.

Combined CT texture analysis and nodal axial ratio for detection of nodal metastasis in esophageal cancer.

OBJECTIVE: To assess the accuracy of a combination of CT texture analysis (CTTA) and nodal axial ratio to detect metastatic lymph nodes (LNs) in esophageal squamous cell carcinoma (ESCC). METHODS: The contrast-enhanced chest CT images of 78 LNs (40 metastasis, 38 benign) from 38 patients with ESCC were retrospectively analyzed. Nodal axial ratios (short-axis/long-axis diameter) were calculated. CCTA parameters (kurtosis, entropy, skewness) were extracted using commercial software (TexRAD) with fine, medium, and coarse spatial filters. Combinations of significant texture features and nodal axial ratios were entered as predictors in logistic regression models to differentiate metastatic from benign LNs, and the performance of the logistic regression models was analyzed using the area under the receiver operating characteristic curve (AUROC). RESULTS: The mean axial ratio of metastatic LNs was significantly higher than that of benign LNs (0.81 ± 0.2 vs 0.71 ± 0.1, p = 0.005; sensitivity 82.5%, specificity 47.4%); namely, significantly more round than benign. The mean values of the entropy (all filters) and kurtosis (fine and medium) of metastatic LNs were significantly higher than those of benign LNs (all, p < 0.05). Medium entropy showed the best performance in the AUROC analysis with 0.802 (p < 0.001; sensitivity 85.0%, specificity 63.2%). A binary logistic regression analysis combining the nodal axial ratio, fine entropy, and fine kurtosis identified metastatic LNs with 87.5% sensitivity and 65.8% specificity (AUROC = 0.855, p < 0.001). CONCLUSION: The combination of CTTA features and the axial ratio of LNs has the potential to differentiate metastatic from benign LNs and improves the sensitivity for detection of LN metastases in ESCC. ADVANCES IN KNOWLEDGE: The combination of CTTA and nodal axial ratio has improved CT sensitivity (up to 87.5%) for the diagnosis of metastatic LNs in esophageal cancer.

Coronary artery calcium severity grading on non-ECG-gated low-dose chest computed tomography: a multiple-observer study in a nationwide lung cancer screening registry.

OBJECTIVES: To identify the optimal method for evaluation of coronary artery calcium (CAC) severity on non-electrocardiogram-gated low-dose chest computed tomography (LDCT) in a nationwide lung cancer screening registry. METHODS: A total of 256 subjects were retrospectively enrolled from participants of the Korean Lung Cancer Screening (K-LUCAS) project (an LDCT lung cancer screening registry for high-risk individuals). Four board-certified cardiothoracic radiologists independently assessed CAC severity using four different scoring methods (visual assessment, artery-based grading, segment-involvement grading, and segment-based grading) and classified severity for each case using all four methods as none, mild, moderate, or severe. Agreements between the four observers for CAC category classification and between the four different scoring methods for the same observer were assessed by Fleiss kappa statistics. Evaluation time for CAC grading was compared between observers and between grading methods. RESULTS: Interobserver agreement was moderate for visual assessment (Fleiss kappa 0.451) and substantial for the other three methods (Fleiss kappa 0.673-0.704). Agreement between the four grading methods for the same observer was substantial for three observers (Fleiss kappa 0.610-0.705) and moderate for one (Fleiss kappa 0.578). Mean evaluation time differed significantly between methods (visual assessment, 14.3 ± 11.8 s; artery-based grading, 17.6 ± 22.3 s, segment-involvement grading, 19.2 ± 6.8 s; segment-based grading, 34.2 ± 37.4 s; p < 0.01). CONCLUSION: Artery-based grading could be appropriate with substantial interobserver agreement and an acceptable mean evaluation time. KEY POINTS: • CAC severity grading methods on LDCT show moderate to substantial agreements between grading methods and observers. • Artery-based grading could be appropriate with substantial interobserver agreement and a mean evaluation time of 17.6 s. • Visual assessment is disadvantaged by high interobserver variability despite having the shortest evaluation time.

Bayesian network analysis incorporating genetic anchors complements conventional Mendelian randomization approaches for exploratory analysis of causal relationships in complex data.

Mendelian randomization (MR) implemented through instrumental variables analysis is an increasingly popular causal inference tool used in genetic epidemiology. But it can have limitations for evaluating simultaneous causal relationships in complex data sets that include, for example, multiple genetic predictors and multiple potential risk factors associated with the same genetic variant. Here we use real and simulated data to investigate Bayesian network analysis (BN) with the incorporation of directed arcs, representing genetic anchors, as an alternative approach. A Bayesian network describes the conditional dependencies/independencies of variables using a graphical model (a directed acyclic graph) with an accompanying joint probability. In real data, we found BN could be used to infer simultaneous causal relationships that confirmed the individual causal relationships suggested by bi-directional MR, while allowing for the existence of potential horizontal pleiotropy (that would violate MR assumptions). In simulated data, BN with two directional anchors (mimicking genetic instruments) had greater power for a fixed type 1 error than bi-directional MR, while BN with a single directional anchor performed better than or as well as bi-directional MR. Both BN and MR could be adversely affected by violations of their underlying assumptions (such as genetic confounding due to unmeasured horizontal pleiotropy). BN with no directional anchor generated inference that was no better than by chance, emphasizing the importance of directional anchors in BN (as in MR). Under highly pleiotropic simulated scenarios, BN outperformed both MR (and its recent extensions) and two recently-proposed alternative approaches: a multi-SNP mediation intersection-union test (SMUT) and a latent causal variable (LCV) test. We conclude that BN incorporating genetic anchors is a useful complementary method to conventional MR for exploring causal relationships in complex data sets such as those generated from modern "omics" technologies.

Clinical Utility of Quantitative CT Analysis for Fissure Completeness in Bronchoscopic Lung Volume Reduction: Comparison between CT and Chartis™.

OBJECTIVE: The absence of collateral ventilation (CV) is crucial for effective bronchoscopic lung volume reduction (BLVR) with an endobronchial valve. Here, we assessed whether CT can predict the Chartis™ results. MATERIALS AND METHODS: This study included 69 patients (mean age: 70.9 ± 6.6 years; 66 [95.7%] males) who had undergone CT to assess BLVR eligibility. The Chartis™ system (Pulmonox Inc.) was used to check CV. Experienced thoracic radiologists independently determined the completeness of fissures on volumetric CT images. RESULTS: The comparison between the visual and quantitative analyses revealed that 5% defect criterion showed good agreement. The Chartis™ assessment was performed for 129 lobes; 11 (19.6%) of 56 lobes with complete fissures on CT showed positive CV, while this rate was significantly higher (40 of 49 lobes, i.e., 81.6%) for lobes with incomplete fissures. The size of the fissure defect did not affect the rate of CV. Of the patients who underwent BLVR, 22 of 24 patients (91.7%) with complete fissures and three of four patients with incomplete fissures (75%) achieved target lobe volume reduction (TLVR). CONCLUSION: The quantitative analysis of fissure shows that incomplete fissures increased the probability of CV on Chartis™, while the defect size did not affect the overall rates. TLVR could be achieved even in some patients with relatively large fissure defect, if they showed negative CV on Chartis™.