Diagnostic performance of immunochromatography assay for rapid detection of IgM and IgG in coronavirus disease 2019.

Serologic assays have been developed to detect infection with coronavirus disease 2019 (COVID-19). This study was conducted to evaluate the diagnostic performance of an immunochromatography-based assay of human serum for COVID-19. The present study enrolled 149 subjects who had been tested by real-time reverse transcription-polymerase chain reaction (RT-PCR) for COVID-19 and were classified into two groups: 70 who were positive for COVID-19 and 79 who were negative for COVID-19 based on RT-PCR. An immunochromatography-based COVID-19 immunoglobulin G (IgG)/immunoglobulin M (IgM) rapid test on the sera of the study population was applied to measure the sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and receiver operating characteristic (ROC) curve compared to RT-PCR, with a 95% confidence interval (CI). IgM or IgG antibodies were detected in 65 subjects (92.9%) classified as positive for COVID-19 and in three subjects (3.8%) classified as negative for COVID-19. The sensitivity and specificity percentages for IgM or IgG antibodies were 92.9% (95% CI: 84.1-97.6) and 96.2% (95% CI: 89.3-99.2), respectively, with 95.6% PPV and 93.8% NPV. The PPV rapidly improved with increasing disease prevalence from 19.8% to 96.1% in the presence of either IgM or IgG, while the NPV remained high with a change from 99.9% to 93.1%. The area under the ROC curve was 0.945 (95% CI: 0.903-0.988) for subjects with either IgM or IgG positivity. In conclusion, the immunochromatography-based COVID-19 IgG/IgM rapid test is a useful and practical diagnostic assay for detection of COVID-19, especially in the presence of IgM or IgG antibodies.

Genetic Variant of Notch Regulator DTX1 Predicts Survival After Lung Cancer Surgery.

BACKGROUND: We evaluated the association between genetic variants in the Notch pathway and survival outcomes of patients with surgically resected NSCLC. METHODS: Sixty-four single nucleotide polymorphisms (SNPs) in the Notch pathway genes were evaluated in the discovery study (n = 354) and two sequential validation studies (n = 772 and n = 746, respectively). The association of genotype with overall survival (OS) and disease-free survival (DFS) was evaluated. RESULTS: Of the 64 SNPs analyzed in the discovery study, 9 were significantly associated with OS or DFS. Among them, the association remained significant only for Deltex-1 (DTX1) rs1732786A>G in the first validation study. The second validation study confirmed again the association between DTX1 rs1732786A>G and survival outcomes. In the combined analysis, rs1732786A>G was significantly associated with better OS and DFS (adjusted HR ·aHR· for OS, 0.75; 95% CI 0.64-0.87; P = 0.0002; aHR for DFS, 0.79; 95% CI 0.71-0.89; P = 0.0001). In vitro luciferase assay showed that the rs1732786G allele was associated with higher promoter activity compared to rs1732786A allele. Consistently, relative mRNA expression level of DTX1 showed significant positive correlation with rs1732786 A-to-G change (Ptrend = 0.02) in tumor tissues. CONCLUSIONS: These results suggest that DTX1 rs1732786 is a potential prognostic factor that may have clinical utility in the management of early stage NSCLC.

Durvalumab Consolidation After Chemoradiotherapy in Elderly Patients With Unresectable Stage III NSCLC: A Real-World Multicenter Study.

BACKGROUND: The PACIFIC trial demonstrated survival benefit of durvalumab after concurrent chemoradiotherapy (CCRT) in unresectable stage III non-small-cell lung cancer. Data on the effectiveness and safety of durvalumab in elderly patients is lacking. METHODS: This retrospective study was conducted between September 2017 and September 2022. Progression-free survival (PFS), overall survival (OS), recurrence patterns, first subsequent treatment after recurrence, factors associated with survival outcomes, and adverse events (AEs) were compared. RESULTS: Of the 286 patients, 120 (42.0%) were ≥ 70 years and 166 (58.0%) were < 70 years. The median PFS (17.7 vs. 19.4 months; P = .43) and median OS (35.7 months vs. not reached; P = .13) were similar between 2 groups. Proportion of patients who completed durvalumab was lower in elderly patients (27.5% vs. 39.2%; P = .040). In elderly patients, ECOG PS 0 or 1 was associated with better PFS, and being male and having received a cisplatin-based regimen during CCRT were factors associated with better and worse OS, respectively. In patients aged < 70 years, a PD-L1 ≥ 50% was associated with improved PFS and OS. Elderly patients experienced more treatment-related AEs, grade 3/4 AEs, permanent discontinuation of durvalumab, and treatment-related deaths. Among the AEs leading to permanent discontinuation or death, pulmonary AE was significantly more common in elderly patients. CONCLUSION: Durvalumab demonstrated similar outcomes in elderly compared to younger patients. However, AEs were more common in elderly patients. Thus, judicious selection of patients and chemotherapy regimens, coupled with careful AE monitoring, are important factors for ensuring optimal durvalumab treatment.

Real-world outcome of crizotinib for anaplastic lymphoma kinase-positive lung cancer: Multicenter retrospective analysis in South Korea.

BACKGROUND: About 3%-5% of non-small cell lung cancer (NSCLC) presents positive anaplastic lymphoma kinase (ALK). Recently, several target agents have been approved as a treatment for ALK-positive NSCLC. This study aimed to analyze the real-world efficacy and outcome when administered crizotinib, the first approved target agent for ALK-positive NSCLC, according to first- or late-line treatment. METHODS: A total of 290 patients with ALK-positive advanced NSCLC who were treated with crizotinib in 15 institutions in South Korea from January 2009 to December 2018 were enrolled. RESULTS: The median age of patients was 57.0 years, and 50.3% were male. The median follow-up duration was 29.3 months. Among them, 113 patients received crizotinib as first-line therapy. The objective response rate (ORR) was 60.1% (57.0% for first-line recipients, 61.8% for second-/later-line). Median (95% CI) progression-free survival (PFS) was 13.7 (11.6-17.0) months. For first-line recipients, overall survival (OS) was 26.3 (17.6-35.0) months. No significant difference in ORR, PFS and OS, according to the setting of crizotinib initiation, was observed. In a multivariate Cox regression analysis, old age, male gender, initially metastatic, and number of metastatic organs were associated with poor PFS and OS. The most common adverse events were nausea and vomiting, and severe adverse event leading to dose adjustment was hepatotoxicity. CONCLUSIONS: ORR, PFS, OS, and adverse event profiles were comparable to previous clinical trials. Our findings could aid in the efficient management of ALK-positive lung cancer patients.

Impact of a Psychiatric Consultation Program on COVID-19 Patients: An Experimental Study.

OBJECTIVE: Following the coronavirus disease-2019 (COVID-19) outbreak, the importance of addressing acute stress induced by psychological burdens of diseases became apparent. This study attempted to evaluate the effectiveness of a new mode of psychiatric intervention designed to target similar psychological crises. METHODS: Participants included 32 out of 114 COVID inpatients at a hospital in Daegu, Korea, who were assessed between March 30 and April 7, 2020. Multiple scales for screening psychological difficulties such as depressed mood, anxiety, insomnia, acute stress, and suicidality were done. Psychological problem evaluations and interventions were conducted in the form of consultations to alleviate participants' psychological challenges via telepsychiatry. The interventions' effects, as well as clinical improvements before and after the intervention, were analyzed. RESULTS: As a result of screening, 21 patients were experiencing psychological difficulties beyond clinical thresholds after COVID-19 infection (screening positive group). The remaining 11 were screening negative groups. The two groups differed significantly in past psychiatric histories (p=0.034), with the former having a higher number of diagnoses. The effect of the intervention was analyzed, and clinical improvement before and after the intervention was observed. Our intervention was found to be effective in reducing the overall emotional difficulties. CONCLUSION: This study highlighted the usefulness of new interventions required in the context of healthcare following the COVID-19 pandemic.

Five-Year Overall Survival and Prognostic Factors in Patients with Lung Cancer: Results from the Korean Association of Lung Cancer Registry (KALC-R) 2015.

PURPOSE: This study aimed to provide the clinical characteristics, prognostic factors, and 5-year relative survival rates of lung cancer diagnosed in 2015. MATERIALS AND METHODS: The demographic risk factors of lung cancer were calculated using the KALC-R (Korean Association of Lung Cancer Registry) cohort in 2015, with survival follow-up until December 31, 2020. The 5-year relative survival rates were estimated using Ederer II methods, and the general population data used the death rate adjusted for sex and age published by the Korea Statistical Information Service from 2015 to 2020. RESULTS: We enrolled 2,657 patients with lung cancer who were diagnosed in South Korea in 2015. Of all patients, 2,098 (79.0%) were diagnosed with non-small cell lung cancer (NSCLC) and 345 (13.0%) were diagnosed with small cell lung cancer (SCLC), respectively. Old age, poor performance status, and advanced clinical stage were independent risk factors for both NSCLC and SCLC. In addition, the 5-year relative survival rate declined with advanced stage in both NSCLC (82%, 59%, 16%, 10% as the stage progressed) and SCLC (16%, 4% as the stage progressed). In patients with stage IV adenocarcinoma, the 5-year relative survival rate was higher in the presence of epidermal growth factor receptor (EGFR) mutation (19% vs. 11%) or anaplastic lymphoma kinase (ALK) translocation (38% vs. 11%). CONCLUSION: In this Korean nationwide survey, the 5-year relative survival rates of NSCLC were 82% at stage I, 59% at stage II, 16% at stage III, and 10% at stage IV, and the 5-year relative survival rates of SCLC were 16% in cases with limited disease, and 4% in cases with extensive disease.

Real-world first-line afatinib for advanced EGFR mutation-positive non-small cell lung cancer in Korea: updated survival data.

Background: Data from clinical trials and real-world studies show that afatinib is effective in treating non-small cell lung cancer (NSCLC) harboring activating mutations in the epidermal growth factor receptor (EGFR) gene. A previous analysis of patients enrolled in the Korean Academy of Tuberculosis and Respiratory Disease (KATRD) EGFR cohort showed that first-line afatinib was well tolerated and effectiveness results were encouraging. At the time of the previous analysis, survival data were not mature. Here we briefly present updated survival data from the cohort. Methods: The study was a retrospective, multicenter (15 sites) review of electronic records of Korean adult patients (aged >20 years) with advanced EGFR mutation-positive NSCLC who initiated first-line afatinib (N=421). Progression-free survival (PFS) and overall survival (OS) were evaluated using Kaplan-Meier survival curves. Results: Overall, median PFS was 20.2 months and median OS was 48.6 months. OS rates at 36 and 60 months were 60.1% and 42.3%, respectively. Presence vs. absence of baseline brain metastases was associated with significantly reduced median PFS (14.9 vs. 28.0 months; P<0.001) and median OS (32.2 vs. 65.6 months; P<0.001). The presence of common baseline EGFR mutations (Del19, L858R) was associated with significantly prolonged median OS (49.6 vs. 30.1 months; P=0.017). In patients stratified by the presence/absence of T790M EGFR mutation, the T790M mutation was associated with significantly reduced median PFS (P=0.0005) but there was no significant difference between groups in survival (P=0.263). There were no significant differences in PFS or OS for patients stratified by afatinib dose reduction or by age group (<70 vs. ≥70 years). Conclusions: Afatinib was effective in Korean patients with EGFR mutation-positive NSCLC with median OS over 4 years. The presence of baseline brain metastases and/or uncommon EGFR mutations were associated with reduced survival. In the absence of baseline brain metastases, median OS was more than 5 years.

Bacterial etiology and pneumococcal urinary antigen in moderate exacerbation of chronic obstructive pulmonary disease.

Background: This study aimed to establish nationwide data for the distributions of typical and atypical bacterial pathogens in Korean patients with moderate acute exacerbations of chronic obstructive pulmonary disease (AECOPD) and evaluate the clinical usefulness of a urinary antigen test (UAT) to detect Streptococcus pneumoniae. Methods: This study was a post hoc analysis of a randomized controlled trial designed to compare oral zabofloxacin with moxifloxacin for treating outpatients with moderate AECOPD. From clinics across South Korea, 342 subjects with AECOPD were enrolled, and their blood, sputum, and urine samples were collected at baseline. A serologic test, sputum culture and polymerase chain reaction (PCR), and UAT were performed to identify bacterial pathogens. Bacterial prevalence and regional distributions were analyzed. The patients' characteristics and clinical response between UAT-positive and UAT-negative groups were compared, as were the Streptococcus pneumoniae detection rates using conventional sputum culture and PCR versus UAT. Results: The most commonly isolated pathogen was Haemophilus influenzae (30.3%), followed by Streptococcus pneumoniae (24.7%) and Pseudomonas aeruginosa (14.0%), with no significant regional differences in bacterial distribution. Patients with positive UAT for Streptococcus pneumoniae showed no clinical failure when treated with respiratory quinolone (0.0%), whereas 11.8% of patients with negative UAT showed clinical failure (P=0.037). UAT showed moderate agreement with sputum culture by kappa coefficient (κ=0.476). Conclusions: The bacterial prevalence in patients with moderate AECOPD in South Korea showed correlations with the global prevalence, without significant regional differences. In outpatient settings, UAT has the potential to be used as a supplemental tool with sputum culture as a guide for determining the suspicion of bacterial exacerbation.

Unraveling COVID-19: A Large-Scale Characterization of 4.5 Million COVID-19 Cases Using CHARYBDIS.

Purpose: Routinely collected real world data (RWD) have great utility in aiding the novel coronavirus disease (COVID-19) pandemic response. Here we present the international Observational Health Data Sciences and Informatics (OHDSI) Characterizing Health Associated Risks and Your Baseline Disease In SARS-COV-2 (CHARYBDIS) framework for standardisation and analysis of COVID-19 RWD. Patients and Methods: We conducted a descriptive retrospective database study using a federated network of data partners in the United States, Europe (the Netherlands, Spain, the UK, Germany, France and Italy) and Asia (South Korea and China). The study protocol and analytical package were released on 11th June 2020 and are iteratively updated via GitHub. We identified three non-mutually exclusive cohorts of 4,537,153 individuals with a clinical COVID-19 diagnosis or positive test, 886,193 hospitalized with COVID-19, and 113,627 hospitalized with COVID-19 requiring intensive services. Results: We aggregated over 22,000 unique characteristics describing patients with COVID-19. All comorbidities, symptoms, medications, and outcomes are described by cohort in aggregate counts and are readily available online. Globally, we observed similarities in the USA and Europe: more women diagnosed than men but more men hospitalized than women, most diagnosed cases between 25 and 60 years of age versus most hospitalized cases between 60 and 80 years of age. South Korea differed with more women than men hospitalized. Common comorbidities included type 2 diabetes, hypertension, chronic kidney disease and heart disease. Common presenting symptoms were dyspnea, cough and fever. Symptom data availability was more common in hospitalized cohorts than diagnosed. Conclusion: We constructed a global, multi-centre view to describe trends in COVID-19 progression, management and evolution over time. By characterising baseline variability in patients and geography, our work provides critical context that may otherwise be misconstrued as data quality issues. This is important as we perform studies on adverse events of special interest in COVID-19 vaccine surveillance.

Anti-glomerular basement membrane disease associated with thin basement membrane nephropathy: A case report.

RATIONALE: Simultaneous occurrence of anti-glomerular basement membrane (anti-GBM) disease and thin basement membrane nephropathy (TBMN), both of which invade the type IV collagen subunits, is very rare. Here, we present the case of a 20-year-old male patient diagnosed with both anti-GBM disease and TBMN upon presenting dyspnea and hemoptysis. PATIENT CONCERNS: No laboratory abnormalities, except arterial hypoxemia (PaO275.4 mmHg) and microscopic hematuria, were present. Chest computed tomography revealed bilateral infiltrations in the lower lung fields; thus, administration of empirical antibiotics was initiated. Gross hemoptysis persisted nonetheless, and bronchoscopy revealed diffuse pulmonary hemorrhage with no endobronchial lesions. Broncho-alveolar lavage excluded bacterial pneumonia, tuberculosis, and fungal infection. DIAGNOSIS: Enzyme-linked immunosorbent assay of his serum was positive for anti-GBM antibody (95.1 U/mL). Human leukocyte antigen (HLA) test was positive for both HLA-DR15/-DR04. Other than diffuse thinning of the GBM (average thickness, 220 nm), index kidney biopsy did not demonstrate any specific abnormalities such as crescent formation. INTERVENTIONS: Methylprednisolone was administered intravenously for 7 consecutive days (500 mg/day), followed by the daily dose of oral prednisolone (80 mg). Cyclophosphamide was also orally administered every day for 3 months (250 mg/day). Following 6 sessions of plasmapheresis, the anti-GBM antibody in serum became negative. OUTCOMES: There was no clinical evidence suggesting recurrence of pulmonary hemorrhage or azotemia during hospitalization and 12-month follow-up period. Twelve months after hospital discharge, oral prednisolone was discontinued. LESSONS: The patients with concurrent anti-GBM disease and TBMN will have a favorable prognosis after proper therapy. However, further research is needed to elucidate the pathogenesis and long-term outcome of the comorbidity of these 2 diseases.

Lopinavir-ritonavir versus hydroxychloroquine for viral clearance and clinical improvement in patients with mild to moderate coronavirus disease 2019.

BACKGROUND/AIMS: The efficacies of lopinavir-ritonavir or hydroxychloroquine remain to be determined in patients with coronavirus disease 2019 (COVID-19). To compare the virological and clinical responses to lopinavir-ritonavir and hydroxychloroquine treatment in COVID-19 patients. METHODS: This retrospective cohort study included patients with COVID-19 treated with lopinavir-ritonavir or hydroxychloroquine at a single center in Korea from February 17 to March 31, 2020. Patients treated with lopinavir-ritonavir and hydroxychloroquine concurrently and those treated with lopinavir-ritonavir or hydroxychloroquine for less than 7 days were excluded. Time to negative conversion of viral RNA, time to clinical improvement, and safety outcomes were assessed after 6 weeks of follow-up. RESULTS: Of 65 patients (mean age, 64.3 years; 25 men [38.5%]), 31 were treated with lopinavir-ritonavir and 34 were treated with hydroxychloroquine. The median duration of symptoms before treatment was 7 days and 26 patients (40%) required oxygen support at baseline. Patients treated with lopinavir-ritonavir had a significantly shorter time to negative conversion of viral RNA than those treated with hydroxychloroquine (median, 21 days vs. 28 days). Treatment with lopinavir-ritonavir (adjusted hazard ratio [aHR], 2.28; 95% confidence interval [CI], 1.24 to 4.21) and younger age (aHR, 2.64; 95% CI 1.43 to 4.87) was associated with negative conversion of viral RNA. There was no significant difference in time to clinical improvement between lopinavir-ritonavir- and hydroxychloroquine-treated patients (median, 18 days vs. 21 days). Lymphopenia and hyperbilirubinemia were more frequent in lopinavir-ritonavir-treated patients compared with hydroxychloroquine-treated patients. CONCLUSION: Lopinavir-ritonavir was associated with more rapid viral clearance than hydroxychloroquine in mild to moderate COVID-19, despite comparable clinical responses. These findings should be confirmed in randomized, controlled trials.

Impact of Computed Tomography-Quantified Emphysema Score on Clinical Outcome in Patients with COVID-19.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is considered a risk factor for poor outcomes in patients with coronavirus disease 2019 (COVID-19). However, data on the prognostic impact of radiological emphysema extent on patients with COVID-19 are limited. Thus, this study aimed to examine whether computed tomography (CT)-quantified emphysema score is associated with a worse clinical outcome in patients with COVID-19. METHODS: Volumetric quantitative analyses of CT images were performed to obtain emphysema scores in COVID-19 patients admitted to four tertiary referral hospitals in Daegu, South Korea, between February 18 and March 25, 2020. Patients were divided into three groups according to emphysema score (emphysema score ≤1%, 1%< emphysema score ≤5%, and emphysema score >5%). RESULTS: A total of 146 patients with confirmed SARS-CoV-2 infection were included. The median emphysema score was 1.0% (interquartile range, 0.5-1.8%). Eight patients (6%) had a previous COPD diagnosis. Eighty (55%), 55 (38%), and 11 (8%) patients had emphysema scores ≤1%, between 1% and 5%, and >5%, respectively. The number of patients who received oxygen therapy two weeks after admission was significantly higher in the group with emphysema scores >5% than in other groups (p=0.025). The frequency of deaths was three (27%) in the group with emphysema scores >5% and tended to be higher than that in other groups. Multivariate analysis revealed that age, COPD, and serum lactate dehydrogenase levels were associated with a greater risk of in-hospital mortality in patients with COVID-19. CONCLUSION: The current study demonstrated that patients with CT-quantified emphysema scores >5% tended to progress to severe disease over time; however, they did not exhibit an increased risk of mortality in our COVID-19 cohort. Further studies with consideration of both emphysema extent and airflow limitation degree are warranted.

Prognostic Implication of Baseline Sarcopenia for Length of Hospital Stay and Survival in Patients With Coronavirus Disease 2019.

BACKGROUND: The impact of sarcopenia on clinical outcomes of coronavirus disease 2019 (COVID-19) is not clearly determined yet. We aimed to investigate the association between baseline sarcopenia and clinical outcomes in patients with COVID-19. METHODS: All hospitalized adult patients with COVID-19 who had baseline chest computed tomography (CT) scans at a Korean university hospital from February 2020 to May 2020 were included. The main outcome was time from hospital admission to discharge. Death was considered as a competing risk for discharge. Baseline skeletal muscle cross-sectional area at the level of the 12th thoracic vertebra was measured from chest CT scans. The lowest quartile of skeletal muscle index (skeletal muscle cross-sectional area divided by height-squared) was defined as sarcopenia. RESULTS: Of 121 patients (median age, 62 years; 44 men; 29 sarcopenic), 7 patients died and 86 patients were discharged during the 60-day follow-up. Patients with sarcopenia showed a longer time to discharge (median, 55 vs 28 days; p < .001) and a higher incidence of death (17.2% vs 2.2%; p = .004) than those without sarcopenia. Baseline sarcopenia was an independent predictor of delayed hospital discharge (adjusted hazard ratio [aHR], 0.47; 95% confidence interval [95% CI], 0.23-0.96), but was not independently associated with mortality in patients with COVID-19 (aHR, 3.80; 95% CI, 0.48-30.26). The association between baseline sarcopenia and delayed hospital discharge was consistent in subgroups stratified by age, sex, comorbidities, and severity of COVID-19. CONCLUSIONS: Baseline sarcopenia was independently associated with a prolonged hospital stay in patients with COVID-19. Sarcopenia could be a prognostic marker in COVID-19.

Clinical impact of rebiopsy among patients with epidermal growth factor receptor-mutant lung adenocarcinoma in a real-world clinical setting.

BACKGROUND: In this study, we investigated the risk factors of acquired T790M mutation among patients with lung adenocarcinoma with epidermal growth factor receptor (EGFR) tyrosine mutation who were treated with EGFR-tyrosine kinase inhibitors (TKIs). The aim was to identify the clinical impact of rebiopsy. METHODS: This multicenter, retrospective cohort study was conducted in South Korea from January 2007 to June 2017. Patients with adenocarcinoma with EGFR mutation who underwent rebiopsy and were treated with EGFR-TKIs were included. RESULTS: Of a total of 352 patients, T790M mutation was identified in 156 (41.9%) at the time of rebiopsy. The median duration from initial biopsy to rebiopsy was 17 months. Univariate logistic regression analysis revealed associations of exon 19 deletion (odds ratio [OR], 1.643; p = 0.026), absence of L858R (OR, 0.627; p = 0.042), and previous EGFR-TKI treatment duration (OR, 1.039; p < 0.001) with T790M mutation. Previous EGFR-TKI treatment duration (OR, 3.580; p < 0.001) was independently associated with T790M mutation. A multivariate Cox proportional hazard model revealed that brain metastasis at initial diagnosis (hazard ratio, 1.390; p = 0.050) tended to be associated with T790M mutation. Among the patients with T790M mutation at rebiopsy, the osimertinib user group (n = 90) had a better one-year survival (68.7 vs. 58.3%, p = 0.048) than the osimertinib nonuser group (n = 66). CONCLUSIONS: Rebiopsy might affect the clinical course of patients with EGFR-mutant adenocarcinoma who receive EGFR-TKIs.

Real-world experience of afatinib as first-line therapy for advanced EGFR mutation-positive non-small cell lung cancer in Korea.

BACKGROUND: We investigated the clinical characteristics and treatment outcomes of Korean patients receiving first-line afatinib for advanced epidermal growth factor receptor mutation-positive (EGFRm+) non-small cell lung cancer (NSCLC) in a real-world setting. METHODS: Electronic case reports were retrospectively reviewed from patients across 15 sites in South Korea. Outcome measures included baseline characteristics, overall response rate (ORR), time-to-treatment discontinuation (TTD), and overall survival (OS). Subgroups were: presence/absence of brain metastases at baseline, dose reductions, and baseline EGFR mutation category. RESULTS: Among 422 patients, 39.8% had brain metastases and 59.0%/25.1%/10.0%/5.0% had Del19/L858R/compound/uncommon EGFR mutations at baseline. ORR was 62.6% overall; responses were observed across all EGFR mutation categories, including against compound mutations. Median TTD was 17.8 months; median OS was not reached (NR). Median TTD and OS were longer in patients without versus with brain metastases (TTD: 22.9 vs. 14.8 months, P=0.001; OS: NR vs. 40.3 months, P=0.0009) and patients with versus without dose reductions (TTD: 22.2 vs. 14.2 months, P=0.0004; OS: NR vs. 40.3 months, P=0.0117). Median OS was 30.5/37.7 months in patients receiving chemotherapy/osimertinib as subsequent therapy. The most common treatment-related adverse events (TRAEs; any grade/grade ≥3) were diarrhea (31.3%/8.5%) and rash (23.0%/8.1%). Overall, 34 patients (8.1%) discontinued afatinib due to AEs. CONCLUSIONS: Afatinib was well tolerated with no new safety signals, and efficacy was encouraging in Korean patients with EGFRm+ NSCLC, including those with baseline brain metastases and/or uncommon EGFR mutations. AE management with dose reductions facilitated a long TTD, prolonging the chemotherapy-free period for many patients.

Unraveling COVID-19: a large-scale characterization of 4.5 million COVID-19 cases using CHARYBDIS.

Background: Routinely collected real world data (RWD) have great utility in aiding the novel coronavirus disease (COVID-19) pandemic response [1,2]. Here we present the international Observational Health Data Sciences and Informatics (OHDSI) [3] Characterizing Health Associated Risks, and Your Baseline Disease In SARS-COV-2 (CHARYBDIS) framework for standardisation and analysis of COVID-19 RWD. Methods: We conducted a descriptive cohort study using a federated network of data partners in the United States, Europe (the Netherlands, Spain, the UK, Germany, France and Italy) and Asia (South Korea and China). The study protocol and analytical package were released on 11 th June 2020 and are iteratively updated via GitHub [4]. Findings: We identified three non-mutually exclusive cohorts of 4,537,153 individuals with a clinical COVID-19 diagnosis or positive test, 886,193 hospitalized with COVID-19 , and 113,627 hospitalized with COVID-19 requiring intensive services . All comorbidities, symptoms, medications, and outcomes are described by cohort in aggregate counts, and are available in an interactive website: https://data.ohdsi.org/Covid19CharacterizationCharybdis/. Interpretation: CHARYBDIS findings provide benchmarks that contribute to our understanding of COVID-19 progression, management and evolution over time. This can enable timely assessment of real-world outcomes of preventative and therapeutic options as they are introduced in clinical practice.

Experience of percutaneous tracheostomy in critically ill COVID-19 patients.

BACKGROUND: Coronavirus disease 2019 (COVID-19) is a highly contagious disease that causes respiratory failure. Tracheostomy is an essential procedure in critically ill COVID-19 patients; however, it is an aerosol-generating technique and thus carries the risk of infection transmission. We report our experience with percutaneous tracheostomy and its safety in a real medical setting. METHODS: During the COVID-19 outbreak, 13 critically ill patients were admitted to the intensive care unit (ICU) at Daegu Catholic University Medical Center between February 24 and April 30, 2020. Seven of these patients underwent percutaneous tracheostomy using Ciaglia Blue Rhino. The medical environment, percutaneous tracheostomy method, and COVID-19 reverse transcriptase-polymerase chain reaction (RT-PCR) results were retrospectively reviewed. After treatment, the COVID-19 infection status of healthcare personnel was investigated by RT-PCR. RESULTS: The ICU contained negative pressure cohort areas and isolation rooms, and healthcare personnel wore a powered air-purifying respirator system. We performed seven cases of percutaneous tracheostomy in the same way as in patients without COVID-19. Five patients (71.4%) tested positive for COVID-19 by RT-PCR at the time of tracheostomy. The median cycle threshold value for the RNA-dependent RNA polymerase was 30.60 (interquartile range [IQR], 25.50-36.56) in the upper respiratory tract and 35.04 (IQR, 28.40-36.74) in the lower respiratory tract. All healthcare personnel tested negative for COVID-19 by RT-PCR. CONCLUSIONS: Percutaneous tracheostomy was performed with conventional methods in the negative pressure cohort area. It was safe to perform percutaneous tracheostomy in an environment of COVID-19 infection.

Characteristics of female lung cancer in Korea: analysis of Korean National Lung Cancer Registry.

BACKGROUNDS: The present study evaluated Korean women with lung cancer and compared the clinical characteristics of ever-smoker and never-smoker groups using the National Lung Cancer Registry. METHODS: In affiliation with the Korean Central Cancer Registry, the Korean Association for Lung Cancer constructed a registry into which 10% of the lung cancer cases in Korea were registered. Female lung cancer patients with valid smoking history were evaluated. RESULTS: Among 735 female lung cancer patients, 643 (87.5%) were never-smokers and 92 (12.5%) were smokers. The median survival was significantly longer in the never-smoker group (28 vs. 14 months; P<0.001). Among 683 patients with non-small cell lung cancer (NSCLC), the never-smoker group showed significantly longer median survival (29 vs. 14 months; P=0.002) and a higher proportion of stage I cancer (40.3% vs. 25.7%; P<0.001). Survival analysis of the NSCLC patients showed that smoking status, receiving only supportive care, EGFR mutation status, lung cancer stage, and forced vital capacity (FVC) (%) were significantly associated with mortality in the multivariate analysis (P=0.025, HR 2.39, 95% CI: 1.12-5.11; P=0.017, HR 3.14, 95% CI: 1.22-8.06; P=0.033, HR 0.63, 95% CI: 0.41-0.96; P<0.001, HR 11.88, 95% CI: 5.79-24.38; P=0.002, HR 0.98, 95% CI: 0.96-0.99, respectively). CONCLUSIONS: In Korean women with NSCLC, smoking status, not receiving active anticancer treatment, EGFR mutation status, lung cancer stage, and pulmonary function were significantly associated with mortality.

The Clinical Characteristics and Outcomes of Patients with Moderate-to-Severe Coronavirus Disease 2019 Infection and Diabetes in Daegu, South Korea.

BACKGROUND: Coronavirus disease 2019 (COVID-19) is a global pandemic that had affected more than eight million people worldwide by June 2020. Given the importance of the presence of diabetes mellitus (DM) for host immunity, we retrospectively evaluated the clinical characteristics and outcomes of moderate-to-severe COVID-19 in patients with diabetes. METHODS: We conducted a multi-center observational study of 1,082 adult inpatients (aged ≥18 years) who were admitted to one of five university hospitals in Daegu because of the severity of their COVID-19-related disease. The demographic, laboratory, and radiologic findings, and the mortality, prevalence of severe disease, and duration of quarantine were compared between patients with and without DM. In addition, 1:1 propensity score (PS)-matching was conducted with the DM group. RESULTS: Compared with the non-DM group (n=847), patients with DM (n=235) were older, exhibited higher mortality, and required more intensive care. Even after PS-matching, patients with DM exhibited more severe disease, and DM remained a prognostic factor for higher mortality (hazard ratio, 2.40; 95% confidence interval, 1.38 to 4.15). Subgroup analysis revealed that the presence of DM was associated with higher mortality, especially in older people (≥70 years old). Prior use of a dipeptidyl peptidase-4 inhibitor or a renin-angiotensin system inhibitor did not affect mortality or the clinical severity of the disease. CONCLUSION: DM is a significant risk factor for COVID-19 severity and mortality. Our findings imply that COVID-19 patients with DM, especially if elderly, require special attention and prompt intensive care.

Deep phenotyping of 34,128 adult patients hospitalised with COVID-19 in an international network study.

Comorbid conditions appear to be common among individuals hospitalised with coronavirus disease 2019 (COVID-19) but estimates of prevalence vary and little is known about the prior medication use of patients. Here, we describe the characteristics of adults hospitalised with COVID-19 and compare them with influenza patients. We include 34,128 (US: 8362, South Korea: 7341, Spain: 18,425) COVID-19 patients, summarising between 4811 and 11,643 unique aggregate characteristics. COVID-19 patients have been majority male in the US and Spain, but predominantly female in South Korea. Age profiles vary across data sources. Compared to 84,585 individuals hospitalised with influenza in 2014-19, COVID-19 patients have more typically been male, younger, and with fewer comorbidities and lower medication use. While protecting groups vulnerable to influenza is likely a useful starting point in the response to COVID-19, strategies will likely need to be broadened to reflect the particular characteristics of individuals being hospitalised with COVID-19.