Real-world study of lazertinib as second-line or greater treatment in advanced non-small cell lung cancer.

BACKGROUND: Lazertinib is an oral, third-generation EGFR-TKI, which specifically targets the EGFR T790M mutation along with activating mutations Ex19del and L858R. More real-world data are needed to evaluate its efficacy and safety in treating locally advanced and metastatic non-small cell lung cancer (NSCLC) following prior EGFR TKI treatment. METHODS: This multicenter retrospective study was conducted at seven university hospitals affiliated to the Catholic Medical Center (CMC) in Korea. A clinical data warehouse (CDW) platform was used to access and extract information. RESULTS: A total of 48 patients were assessed. The majority were female (75%) and diagnosed with adenocarcinoma (95.8%). All patients had the EGFR mutation at diagnosis, 27 (56.3%) had the exon 19 deletion, 20 (41.7%) had the L858R mutation, and one (2.0%) had the exon 18 mutation. The median progression-free survival (PFS) was 15.4 months. At 6, 12, and 18 months, PFS rates were 79.1%, 53.6%, and 27.3%, respectively. When PFS was analyzed by prior TKI duration (<18 months vs. >18 months), significant differences were noted at the 6 and 9-month mark (p = 0.013 and p = 0.010, respectively). In multivariate analysis for PFS, only prior TKI duration and ECOG score showed statistical significance (p = 0.026 and p = 0.049, respectively). In the multivariate analysis for OS, ECOG score showed statistical significance (p = 0.006). Among 48 patients, 34 (70.8%) experienced adverse events (AEs) related to lazertinib. The most frequent AEs were skin reaction (29.8%), diarrhea (21.3%), and peripheral neuropathy (20.8%). CONCLUSIONS: The results suggest that lazertinib is effective in second or more line settings, with tolerable safety profile. More patient data are necessary to find possible prognostic markers associated with patient outcome.

High-quality chromosome-level genome assembly of Nicotiana benthamiana.

Nicotiana benthamiana is a fundamental model organism in plant research. Recent advancements in genomic sequencing have revealed significant intraspecific genetic variations. This study addresses the pressing need for a precise genome sequence specific to its geographic origin by presenting a comprehensive genome assembly of the N. benthamiana LAB strain from the Republic of Korea (NbKLAB). We compare this assembly with the widely used NbLAB360 strain, shedding light on essential genomic differences between them. The outcome is a high-quality, chromosome-level genome assembly comprising 19 chromosomes, spanning 2,762 Mb, with an N50 of 142.6 Mb. Comparative analyses revealed notable variations, including 46,215 protein-coding genes, with an impressive 99.5% BUSCO completeness score. Furthermore, the NbKLAB assembly substantially improved the QV from 33% for NbLAB360 to 49%. This refined chromosomal genome assembly for N. benthamiana, in conjunction with comparative insights, provides a valuable resource for genomics research and molecular biology. This accomplishment forms a strong foundation for in-depth exploration into the intricacies of plant genetics and genomics, improved precision, and a comparative framework.

Population pharmacokinetic model of rifampicin for personalized tuberculosis pharmacotherapy: Effects of SLCO1B1 polymorphisms on drug exposure.

BACKGROUND: Rifampicin (RIF) exhibits high pharmacokinetic (PK) variability among individuals; a low plasma concentration might result in unfavorable treatment outcomes and drug resistance. This study evaluated the contributions of non- and genetic factors to the interindividual variability of RIF exposure, then suggested initial doses for patients with different weight bands. METHODS: This multicenter prospective cohort study in Korea analyzed demographic and clinical data, the solute carrier organic anion transporter family member 1B1 (SLCO1B1) genotypes, and RIF concentrations. Population PK modeling and simulations were conducted using nonlinear mixed-effect modeling. RESULTS: In total, 879 tuberculosis (TB) patients were divided into a training dataset (510 patients) and a test dataset (359 patients). A one-compartment model with allometric scaling for effect of body size best described the RIF PKs. The apparent clearance (CL/F) was 16.6% higher among patients in the SLCO1B1 rs4149056 wild-type group than among patients in variant group, significantly decreasing RIF exposure in the wild-type group. The developed model showed better predictive performance compared with previously reported models. We also suggested that patients with body weights of <40 kg, 40-55 kg, 55-70 kg, and >70 kg patients receive RIF doses of 450, 600, 750, and 1050 mg/day, respectively. CONCLUSIONS: Total body weight and SLCO1B1 rs4149056 genotypes were the most significant covariates that affected RIF CL/F variability in Korean TB patients. We suggest initial doses of RIF based on World Health Organization weight-band classifications. The model may be implemented in treatment monitoring for TB patients.

Enhanced binding and inhibition of SARS-CoV-2 by a plant-derived ACE2 protein containing a fused mu tailpiece.

Infectious diseases such as Coronavirus disease 2019 (COVID-19) and Middle East respiratory syndrome (MERS) present an increasingly persistent crisis in many parts of the world. COVID-19 is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The angiotensin-converting enzyme 2 (ACE2) is a crucial cellular receptor for SARS-CoV-2 infection. Inhibition of the interaction between SARS-CoV-2 and ACE2 has been proposed as a target for the prevention and treatment of COVID-19. We produced four recombinant plant-derived ACE2 isoforms with or without the mu tailpiece (µ-tp) of immunoglobulin M (IgM) and the KDEL endoplasmic reticulum retention motif in a plant expression system. The plant-derived ACE2 isoforms bound whole SARS-CoV-2 virus and the isolated receptor binding domains of SARS-CoV-2 Alpha, Beta, Gamma, Delta, and Omicron variants. Fusion of µ-tp and KDEL to the ACE2 protein (ACE2 µK) had enhanced binding activity with SARS-CoV-2 in comparison with unmodified ACE2 protein derived from CHO cells. Furthermore, the plant-derived ACE2 µK protein exhibited no cytotoxic effects on Vero E6 cells and effectively inhibited SARS-CoV-2 infection. The efficient and rapid scalability of plant-derived ACE2 µK protein offers potential for the development of preventive and therapeutic agents in the early response to future viral outbreaks.

Two long read-based genome assembly and annotation of polyploidy woody plants, Hibiscus syriacus L. using PacBio and Nanopore platforms.

Improvements in long read DNA sequencing and related techniques facilitated the generation of complex eukaryotic genomes. Despite these advances, the quality of constructed plant reference genomes remains relatively poor due to the large size of genomes, high content of repetitive sequences, and wide variety of ploidy. Here, we developed the de novo sequencing and assembly of high polyploid plant genome, Hibiscus syriacus, a flowering plant species of the Malvaceae family, using the Oxford Nanopore Technologies and Pacific Biosciences Sequel sequencing platforms. We investigated an efficient combination of high-quality and high-molecular-weight DNA isolation procedure and suitable assembler to achieve optimal results using long read sequencing data. We found that abundant ultra-long reads allow for large and complex polyploid plant genome assemblies with great recovery of repetitive sequences and error correction even at relatively low depth Nanopore sequencing data and polishing compared to previous studies. Collectively, our combination provides cost effective methods to improve genome continuity and quality compared to the previously reported reference genome by accessing highly repetitive regions. The application of this combination may enable genetic research and breeding of polyploid crops, thus leading to improvements in crop production.

Construction of deep learning-based disease detection model in plants.

Accurately detecting disease occurrences of crops in early stage is essential for quality and yield of crops through the decision of an appropriate treatments. However, detection of disease needs specialized knowledge and long-term experiences in plant pathology. Thus, an automated system for disease detecting in crops will play an important role in agriculture by constructing early detection system of disease. To develop this system, construction of a stepwise disease detection model using images of diseased-healthy plant pairs and a CNN algorithm consisting of five pre-trained models. The disease detection model consists of three step classification models, crop classification, disease detection, and disease classification. The 'unknown' is added into categories to generalize the model for wide application. In the validation test, the disease detection model classified crops and disease types with high accuracy (97.09%). The low accuracy of non-model crops was improved by adding these crops to the training dataset implicating expendability of the model. Our model has the potential to apply to smart farming of Solanaceae crops and will be widely used by adding more various crops as training dataset.

High-quality genome assembly and genetic mapping reveal a gene regulating flesh color in watermelon (Citrullus lanatus).

The unique color and type characteristics of watermelon fruits are regulated by many molecular mechanisms. However, it still needs to be combined with more abundant genetic data to fine-tune the positioning. We assembled genomes of two Korean inbred watermelon lines (cv. 242-1 and 159-1) with unique color and fruit-type characteristics and identified 23,921 and 24,451 protein-coding genes in the two genomes, respectively. To obtain more precise results for further study, we resequenced one individual of each parental line and an F2 population composed of 87 individuals. This identified 1,539 single-nucleotide polymorphisms (SNPs) and 80 InDel markers that provided a high-density genetic linkage map with a total length of 3,036.9 cM. Quantitative trait locus mapping identified 15 QTLs for watermelon fruit quality-related traits, including ß-carotene and lycopene content in fruit flesh, fruit shape index, skin thickness, flesh color, and rind color. By investigating the mapping intervals, we identified 33 candidate genes containing variants in the coding sequence. Among them, Cla97C01G008760 was annotated as a phytoene synthase with a single-nucleotide variant (A → G) in the first exon at 9,539,129 bp of chromosome 1 that resulted in the conversion of a lysine to glutamic acid, indicating that this gene might regulate flesh color changes at the protein level. These findings not only prove the importance of a phytoene synthase gene in pigmentation but also explain an important reason for the color change of watermelon flesh.

The complete chloroplast genome of Hibiscus syriacus using long-read sequencing: Comparative analysis to examine the evolution of the tribe Hibisceae.

Hibiscus syriacus, a member of the tribe Hibisceae, is considered an important ornamental and medicinal plant in east Asian countries. Here, we sequenced and assembled the complete chloroplast genome of H. syriacus var. Baekdansim using the PacBio long-read sequencing platform. A quadripartite structure with 161,026 base pairs was obtained, consisting of a pair of inverted repeats (IRA and IRB) with 25,745 base pairs, separated by a large single-copy region of 89,705 base pairs and a short single-copy region of 19,831 base pairs. This chloroplast genome had 79 protein-coding genes, 30 transfer RNA genes, 4 ribosomal RNA genes, and 109 simple sequence repeat regions. Among them, ndhD and rpoC1, containing traces of RNA-editing events associated with adaptive evolution, were identified by analysis of putative RNA-editing sites. Codon usage analysis revealed a preference for A/U-terminated codons. Furthermore, the codon usage pattern had a clustering tendency similar to that of the phylogenetic analysis of the tribe Hibisceae. This study provides clues for understanding the relationships and refining the taxonomy of the tribe Hibisceae.

The association between clinical parameters and resectability in stage III non-small cell lung cancer, and a combination of N2 lymph node burden and lung immune prognostic index score as a potential biomarker.

Background: Surgery is important treatment option for stage III non-small cell lung cancer (NSCLC) because of its curative potential. We investigated the characteristics of resectable patients, and compared the outcomes according to treatment modalities. Methods: Among 1,092 patients with NSCLC diagnosed between 2008 to 2020 from 7 university hospitals of Catholic Medical Center, we retrospectively analyzed 252 patients with clinical or pathological stage III. We compared survival outcomes among the groups according to resectability, first-line treatments, and the lung immune prognostic index (LIPI) score. Clinical N2 subgroup was analyzed using multi-parameter scoring system. Results: The resectable group consisted of less smokers, showed better pulmonary function and lower inflammatory markers, and tended to be diagnosed as earlier cancer stage than the unresectable group. The resectable group showed better progression-free survival (PFS) and overall survival (OS) than the unresectable group (P<0.001 and P<0.001, respectively). Regarding the first-line treatment, surgery showed the longest median PFS (33.70 months) and the highest 12-month OS rate (91.6%) than the other treatment modalities. OS was significantly different depending on the LIPI score in whole population, as well as in the unresectable group (P=0.004 and P=0.003, respectively). LIPI 0 group exhibited better OS than LIPI 1 and 2 in both populations. Eastern Cooperative Oncology Group (ECOG) 2-4, LIPI 1-2, and first-line treatment were independent prognostic factors for OS. Smoking, forced expiratory volume in the first second (FEV1) and more advanced cancer stage were associated with unresectability. In subgroup analysis of N2 disease, we attempted to create new scoring system combining lymph node (LN) status and LIPI score. This scoring system showed significant association with OS. Conclusions: The patients with resectable stage III NSCLC showed better PFS and OS than the patients with unresectable tumor. LIPI score exhibited possibility to be used as potential biomarker in stage III NSCLC. The multi-parameter scoring system using LN status and LIPI score was predictive of OS in the N2 subgroup.

Genome sequence and characterization of a novel fabavirus infecting Cirsium setidens (gondre) in South Korea.

The complete nucleotide sequence of a novel gondre (Cirsium setidens)-infecting virus, provisionally named "cirsium virus A" (CiVA), was determined by high-throughput and Sanger sequencing, revealing a genome organization typical of fabaviruses. RNA1 and RNA2 are 5,828 and 3,478 nucleotides long, excluding the 3'-terminal poly(A) tails, each containing a single open reading frame. The highest sequence identity values for the CiVA coat protein and proteinase-polymerase, compared with known fabavirus sequences, were 59.09% and 69.68%, respectively, falling below the current thresholds for Fabavirus species demarcation. Our findings support classifying CiVA as a novel putative member of the genus Fabavirus, subfamily Comovirinae, family Secoviridae.

Complete genome sequence of Stellaria aquatica virus B, a novel polerovirus that infects Stellaria aquatica.

The complete genome sequence of Stellaria aquatica virus B (StAVB), a new member of the genus Polerovirus that infects Stellaria aquatica, was determined using high-throughput RNA sequencing with confirmation by Sanger sequencing. The complete StAVB genome (GenBank accession no. OP389993) is 5,900 nucleotide (nt) long with seven open reading frames (ORF0-5 and ORF3a) that encode putative proteins (P0-P5 and P3a) in a similar configuration to that of other typical poleroviruses. Pairwise sequence comparisons with other poleroviruses showed 38-50% nt sequence identity in the complete genome and 13-24%, 36-45%, 7-68%, and 6-50% amino acid sequence identity in (aa), for the P0, P1-2, P3, and P4 protein, respectively. These data, together with the results of phylogenetic analysis, indicate that StAVB should be classified as a new member of the genus Polerovirus, family Solemoviridae.

Complete genome sequence and genome characterization of a novel potyvirus from Lamprocapnos spectabilis.

The genome of a new potyvirus from a Lamprocapnos spectabilis plant in South Korea was sequenced by high-throughput sequencing and confirmed by Sanger sequencing. The new potyvirus was tentatively named "lamprocapnos virus A" (LaVA); its complete genome contains 9,745 nucleotides, excluding the 3'-terminal poly(A) tail. The LaVA genome structure is similar to that of members of the genus Potyvirus and contains an open reading frame encoding a large putative polyprotein of 3,120 amino acids (aa) with conserved motifs. The complete genome shared 48%-56% nucleotide sequence identity and the polyprotein shared 41%-52% aa sequence identity with those of other potyviruses. These values are below the standard thresholds for potyvirus species demarcation. Phylogenetic analysis based on polyprotein sequences showed that LaVA belongs to the genus Potyvirus. To our knowledge, this is the first report of the complete genome sequence and genome characterization of a potyvirus infecting Lamprocapnos spectabilis.

Investigation of poor predictive factors in extensive stage small cell lung cancer under etoposide-platinum-atezolizumab treatment.

BACKGROUND: The phase III trial IMpower133 showed that platinum and etoposide plus atezolizumab was associated with improved overall survival (OS) and progression free-survival (PFS) when compared to the placebo group in treatment-naïve extensive stage (ES) small cell lung cancer (SCLC). Due to superiority in clinical outcomes, combination immunotherapy plus chemotherapy have become mainstay treatment modalities as first-line treatment in ES-SCLC. Nevertheless, real-world data are still lacking and the search for potential biomarkers is essential. This study aimed to evaluate potential predictive biomarkers applicable in ES-SCLC under combination therapy. METHODS: Patients with ES-SCLC under etoposide-platinum-atezolizumab enrolled from seven university hospitals affiliated to the Catholic University of Korea were evaluated. Pretreatment clinical parameters were evaluated for association with OS and PFS. Adverse events (AEs) during induction and maintenance phases were also evaluated. p-values below 0.05 were considered statistically significant. RESULTS: A total of 41 patients were evaluated. Six-month survival was 68.6%. As best response to treatment, 26 (63.4%) showed partial response, nine (22.0%) showed stable disease, and four (9.8%) showed progressive disease. During the induction phase, grade I-II AEs occurred in 22 (53.7%) patients, and grade III-IV AEs occurred in 26 (63.4%) patients. During the maintenance phase, nine out of 25 (36.0%) patients experienced any grade AEs. In multivariate analysis for OS, lactate dehydrogenase (LDH), c-reactive protein (CRP), and forced vital capacity (%) were significant factors. In multivariate analysis for PFS, sex, and LDH were significant. CONCLUSION: In ES-SCLC under etoposide-platinum-atezolizumab, pretreatment CRP, LDH and FVC (%) were independent predictive factors.

The cascade of care for latent tuberculosis infection in congregate settings: A national cohort analysis, Korea, 2017-2018.

Background: In 2017, Korea implemented a nationwide project to screen and treat latent tuberculosis infection (LTBI) in high-risk for transmission public congregate settings. We aimed to assess programme success using a cascade of care framework. Materials and methods: We undertook a cohort study of people from three congregate settings screened between March 2017 and December 2018: (1) first-grade high school students, (2) employees of educational institutions, (3) employees of social welfare facilities. We report percentages of participants with LTBI completing each step in the cascade of care model. Poisson regression models were used to determine factors associated with not visiting clinics, not initiating treatment, and not completing treatment. Results: Among the 96,439 participants who had a positive interferon-gamma release assay result, the percentage visiting clinics for further assessment, to initiate treatment, and who then completed treatment were 50.7, 34.7, and 28.9%, respectively. Compared to those aged 20-34 years, individuals aged < 20 years and aged ≥ 65 years were less likely to visit clinics, though more likely to complete treatment once initiated. Using public health centres rather than private hospitals was associated with people "not initiating treatment" (adjusted risk ratio [aRR], 3.72; 95% confidence interval [CI], 3.95-3.86). Nine-month isoniazid monotherapy therapy was associated with "not completing treatment," compared to 3-month isoniazid and rifampin therapy (aRR, 1.28; 95% CI, 1.16-1.41). Conclusion: Among participants with LTBI from three congregate settings, less than one third completed treatment. Age, treatment centre, and initial regimen were important determinants of losses to care through the cascade.

Complete nucleotide sequence of hemisteptia virus A, a polero-like virus.

The complete genomic nucleotide sequence of hemisteptia virus A (HemVA) from a Hemisteptia lyrata Bunge plant in South Korea was identified by high-throughput sequencing. The HemVA genome consists of 6,122 nucleotides and contains seven putative open reading frames, ORF0-5 and ORF3a, encoding the putative proteins P0-P5 and P3a, respectively. Pairwise amino acid sequence analysis shows that the HemVA P1-P5 proteins have the highest sequence identity (23.68%-54.15%) to the corresponding proteins of members of the families Solemoviridae and Tombusviridae. Phylogenetic analysis of the P1-P2 and P3 amino acid sequences indicated that HemVA should be classified as a member of a distinct species in the genus Polerovirus.

Hidden loss to follow-up among tuberculosis patients managed by public-private mix institutions in South Korea.

In South Korea, public-private mix (PPM) was launched in 2011. This retrospective cohort study sought to determine the rate of loss to follow-up (LTFU) among drug-susceptible tuberculosis (DS-TB) patients in all nationwide PPM institutions, and the risk factors for LTFU. National notification data for DS-TB patients diagnosed between August 2011 and July 2014 in PPM institutions were analysed. Determination of LTFU included detection of instances where patients were transferred out, but when they did not attend at other TB centres in the following two months. Univariable and multivariable competing risk models were used to determine risk factors for LTFU. 73,046 patients with 78,485 records were enrolled. Nominally, 3426 (4.4%) of records were LTFU. However, after linking the multiple records in each patient, the percentage of LTFU was 12.3% (9004/73,046). Risk factors for LTFU were: being foreign-born (3.13 (95% CI 2.77-3.53)), prior LTFU (2.31 (2.06-2.59)) and greater distance between the patient's home and the TB centre (4.27 (4.03-4.53)). 'Transfer-out' was a risk factor in patients managed by treatment centres close to home (1.65 (1.49-1.83)), but protective for those attending centres further (0.77 (0.66-0.89)) or far-away (0.52 (0.46-0.59)) from home. By considering the complete picture of a patient's interactions with healthcare, we identified a much higher level of LTFU than previously documented. This has implications for how outcomes of treatment are reported and argues for a joined-up national approach for the management and surveillance of TB patients, in nations with similar healthcare systems.

Natural History of Contralateral Bullae/Blebs After Ipsilateral Video-Assisted Thoracoscopic Surgery for Primary Spontaneous Pneumothorax: A Retrospective Cohort Study.

BACKGROUND: Contralateral bullae/blebs are frequently found in patients who are scheduled to undergo ipsilateral video-assisted thoracoscopic surgery (VATS) for primary spontaneous pneumothorax (PSP). RESEARCH QUESTION: Should visible contralateral bullae/blebs be simultaneously resected when ipsilateral VATS bullectomy is performed? STUDY DESIGN AND METHODS: In this single-center, retrospective cohort study, we included patients aged ≤ 30 years who underwent ipsilateral VATS for PSP from April 2009 to December 2019. Electronic medical records, radiograph images, and preoperative high-resolution CT images were reviewed. The primary end point was recurrence-free survival (no contralateral pneumothorax) after discharge of ipsilateral VATS for PSP, determined via Kaplan-Meier analysis. Recurrence was compared between the group with and that without contralateral bullae/blebs by using the log-rank test. A multivariable Cox proportional hazards model was constructed to investigate risk factors for contralateral pneumothorax. RESULTS: Among 567 patients, contralateral pneumothorax occurred in 86 of them after ipsilateral VATS (15.2%) during a median follow-up period of 51.3 (interquartile range, 67.2) months. The 1-, 5-, and 10-year recurrence-free survival rates were 92.2%, 83.7%, and 79.9%, respectively. Contralateral recurrence was higher in the group with (82/455, 18.0%) than in that without (4/112, 3.6%) contralateral bullae/blebs (P < .001). Age (hazard ratio [HR], 0.701; 95% CI, 0.629-0.780; P < .001), current smoking (HR, 2.106; 95% CI, 1.158-3.831; P = .015), and the presence of bullae/blebs (increasing with size, HR, 4.818-8.980; all P < .05) were independent risk factors for contralateral pneumothorax. The annual rates of contralateral pneumothorax in the group with (4.0%) and in that without (0.7%) contralateral bullae/blebs declined over time. INTERPRETATION: Although contralateral bullae/blebs were common in patients who underwent ipsilateral VATS for PSP and were statistically significantly associated with future pneumothorax, the annual rate of pneumothorax was 4.0% in such patients, and it decreased over time. Therefore, a conservative approach on unruptured contralateral bullae/blebs is recommended.

Latent Tuberculosis Cascade of Care Among Healthcare Workers: A Nationwide Cohort Analysis in Korea Between 2017 and 2018.

BACKGROUND: In 2017, Korea implemented nationwide latent tuberculosis infection (LTBI) project targeting healthcare workers (HCWs). We aimed to assess its performance using the cascade of care model. METHODS: We included 45,503 employees of medical institutions with positive interferon-gamma release assay result who participated between March 2017 and December 2018. We described percentages of LTBI participants completing each step in the cascade of care. Poisson regression model was conducted to assess individual characteristics and factors associated with not-visiting clinics for further care, not-initiating LTBI treatment, and not-completing treatment. RESULTS: Proportions of visiting clinics and initiating and completing treatment in HCWs were 54.9%, 38.5%, and 32.0%, respectively. Despite of less likelihood of visiting clinics and initiating LTBI treatment, older age ≥ 65 years were more likely to complete treatment (adjusted relative risk [aRR], 0.80; 95% confidence interval [CI], 0.64-0.99), compared to young age < 35 years. Compared to nurses, doctors were less likely to visit clinic; however, were more likely to initiate treatment (aRR, 0.88; 95% CI, 0.81-0.96). Those who visited public health centers were associated with not-initiating treatment (aRR, 1.34; 95% CI, 1.29-1.40). When treated at private hospitals, 9-month isoniazid monotherapy was less likely to complete treatment, compared to 3-month isoniazid and rifampicin combination therapy (aRR, 1.33; 95% CI, 1.16-1.53). CONCLUSION: Among employees of medical institutions with LTBI, only one third completed treatment. Age, occupation, treatment center, and initial regimen were significantly related to LTBI treatment performance indicators. Rifampicin-based short treatment regimens were effective under standard of care.

Investigating the appropriate adenosine deaminase cutoff value for the diagnosis of tuberculous pleural effusion in a country with decreasing TB burden.

As the burden of tuberculosis (TB) in South Korea decreases while that of malignancy increases with an aging society, the composition of etiology for pleural effusion is changing. The aim of this study was to investigate the diagnostic value of adenosine deaminase (ADA) for diagnosis of tuberculous pleural effusion (TPE) in this circumstance. Medical records of patients who underwent medical thoracoscopy from May 2015 to September 2020 in Incheon St. Mary Hospital, Korea were retrospectively reviewed. TPE was diagnosed if one of the following criteria was met: (1) granuloma in pleura, (2) positive TB polymerase chain reaction or culture in pleural fluid or tissue with non-specific pathologic findings in pleura, or (3) bacteriologically confirmed pulmonary TB with non-specific pathologic findings in pleura. A total of 292 patients, including 156 with malignant pleural effusion (MPE), 52 with TPE, and 84 with other benign effusion, were analyzed. Among 206 patients with lymphocyte dominant pleural effusion, the area under receiver characteristic curve of ADA for diagnosis of TPE was 0.971. The sensitivity and specificity of a current cutoff value of 40 IU/L were 1.00 and 0.61, respectively, whereas those of a raised cutoff value of 70 IU/L were 0.93 and 0.93, respectively. Among 54 patients with ADA levels of 40-70 IU/L, 30 (55.6%) patients were diagnosed as MPE, 21 (38.9%) as other benign effusion, and only 3 (5.6%) as TPE. Caution is needed in clinical diagnosis of TPE with current ADA cutoff value in countries with decreasing TB incidence, due to many false positive cases.