In recent years, next-generation sequencing (NGS)–based genetic testing has become crucial in cancer care. While its primary objective is to identify actionable genetic alterations to guide treatment decisions, its scope has broadened to encompass aiding in pathological diagnosis and exploring resistance mechanisms. With the ongoing expansion in NGS application and reliance, a compelling necessity arises for expert consensus on its application in solid cancers. To address this demand, the forthcoming recommendations not only provide pragmatic guidance for the clinical use of NGS but also systematically classify actionable genes based on specific cancer types. Additionally, these recommendations will incorporate expert perspectives on crucial biomarkers, ensuring informed decisions regarding circulating tumor DNA panel testing.

In recent years, next-generation sequencing (NGS)–based genetic testing has become crucial in cancer care. While its primary objective is to identify actionable genetic alterations to guide treatment decisions, its scope has broadened to encompass aiding in pathological diagnosis and exploring resistance mechanisms. With the ongoing expansion in NGS application and reliance, a compelling necessity arises for expert consensus on its application in solid cancers. To address this demand, the forthcoming recommendations not only provide pragmatic guidance for the clinical use of NGS but also systematically classify actionable genes based on specific cancer types. Additionally, these recommendations will incorporate expert perspectives on crucial biomarkers, ensuring informed decisions regarding circulating tumor DNA panel testing.

Purpose: Gastric cancer (GC) is among the most prevalent and fatal cancers worldwide.National cancer screening programs in countries with high incidences of this disease provide medical aid beneficiaries with free-of-charge screening involving upper endoscopy to detect early-stage GC. However, the coronavirus disease 2019 (COVID-19) pandemic has caused major disruptions to routine healthcare access. Thus, this study aimed to assess the impact of COVID-19 on the diagnosis, overall incidence, and stage distribution of GC. Materials and Methods: We identified patients in our hospital cancer registry who were diagnosed with GC between January 2018 and December 2021 and compared the cancer stage at diagnosis before and during the COVID-19 pandemic. Subgroup analyses were conducted according to age and sex. The years 2018 and 2019 were defined as the “before COVID” period, and the years 2020 and 2021 as the “during COVID” period. Results: Overall, 10,875 patients were evaluated; 6,535 and 4,340 patients were diagnosed before and during the COVID-19 period, respectively. The number of diagnoses was lower during the COVID-19 pandemic (189 patients/month vs. 264 patients/month) than before it.Notably, the proportion of patients with stages 3 or 4 GC in 2021 was higher among men and patients aged ≥40 years. Conclusions During the COVID-19 pandemic, the overall number of GC diagnoses decreased significantly in a single institute. Moreover, GCs were in more advanced stages at the time of diagnosis. Further studies are required to elucidate the relationship between the COVID-19 pandemic and the delay in the detection of GC worldwide.

Background/Aims: The aim of this study was to investigate long-term post-discontinuation outcomes in patients with rheumatoid arthritis (RA) who had been treated with tumor necrosis factor-α inhibitors (TNF-αi) which was then discontinued. Methods: Sixty Korean patients with RA who participated in a 5-year GO-BEFORE and GO-FORWARD extension trials were included in this retrospective study. Golimumab was deliberately discontinued after the extension study (baseline). Patients were then followed by their rheumatologists. We reviewed their medical records for 2 years (max 28 months) following golimumab discontinuation. Patients were divided into a maintained benefit (MB) group and a loss-of-benefit (LB) group based on treatment pattern after golimumab discontinuation. The LB group included patients whose conventional disease-modifying antirheumatic drug(s) were stepped-up or added/switched (SC) and those who restarted biologic therapy (RB). Results: The mean age of patients at baseline was 56.5 years and 55 (91.7%) were females. At the end of follow-up, 23 (38.3%) patients remained in the MB group. In the LB group, 75.7% and 24.3% were assigned into SC and RB subgroups, respectively. Fifty percent of patients lost MB after 23.3 months. Demographics and clinical variables at baseline were comparable between MB and LB groups except for age, C-reactive protein level, and corticosteroid use. Restarting biologic therapy was associated with swollen joint count (adjusted hazard ratio [HR], 1.90; 95% confidence interval [CI], 1.01 to 3.55) and disease duration (adjusted HR, 1.12; 95% CI, 1.02 to 1.23) at baseline. Conclusions Treatment strategies after discontinuing TNF-αi are needed to better maintain disease control and quality of life of patients with RA.

Background and Objectives: The association between chemosensory dysfunction (CSD) and coronavirus disease 2019 (COVID-19) remains unclear. The aim of the present study was to determine the incidence of olfactory and taste dysfunction in asymptomatic and mildly symptomatic patients with COVID-19 and to evaluate the symptoms associated with CSD in patients with COVID-19.Materials and Method: On March 9, 2020, 309 patients with asymptomatic or mildly symptomatic COVID-19 confirmed by real-time polymerase chain reaction (RT-PCR) were admitted to the No. 7 Community Treatment Center in Korea. An internet-based survey about symptomatology was administered to these patients, with responses obtained from 244 (79.0%). Subjects who completed the survey were enrolled in this study and were categorized into either a CSD group or a normal chemosensory group based on the presence or absence of CSD, respectively. Results: General symptoms, including fever, myalgia, and chills, were most common (29.1%), followed by upper respiratory tract infection (URI) symptoms (20.9%), CSD (20.5%), and nasal symptoms (13.5%). In patients with CSD (n=50), 10 (4.1%) reported no other symptoms. After adjustment for age, sex, past medical history, and other symptoms, general symptoms [odds ratio (OR), 3.63; confidence interval (CI), 1.70-7.76] and nasal symptoms (OR, 7.00; CI, 2.61-18.80) were significantly associated with CSD. Conclusion The incidence of CSD was relatively high (20.5%) in asymptomatic and mildly symptomatic patients with COVID-19. General symptoms were independent risk factors of CSD, suggesting a sensorineural mechanism for the observed olfactory and taste dysfunction.

BACKGROUND/AIMS: Phosphatase and tensin homolog (PTEN) is a known tumor suppressor gene that is downregulated in hepatocellular carcinoma (HCC). Here, we investigated the association between single nucleotide polymorphisms (SNPs) of PTEN and HCC development in patients with hepatitis B virus (HBV) infection. METHODS: Six SNPs of PTEN at positions rs1234221, rs1903860, rs1234220, rs1903858, rs2299941, and rs17431184 were analyzed in a development population (417 chronic HBV carriers without HCC and 281 chronic HBV carriers with HCC). PTEN rs1903858, rs1903860, and rs2299941 SNPs were further assessed for the development of HCC in a validation population of 200 patients with HBV-related liver cirrhosis. RESULTS: In the development population, PTEN rs1903860 C allele, rs1903858 G allele, and rs2299941 G allele were associated with a low risk of HCC. The haplotype A-T-A-A-A was associated with an increased risk of HCC (recessive model; odds ratio=2.277, 95% confidence interval [CI] =1.144-4.532, P=0.019). In the validation population, PTEN rs2299941 G allele was the only significant protective genetic polymorphism related to HCC development after adjustment for age and sex (hazard ratio=0.582, 95% CI =0.353–0.962, P=0.035). CONCLUSIONS: These findings suggest that genetic polymorphisms in PTEN may affect HCC development in patients with chronic HBV infection.
Alleles ; Carcinoma, Hepatocellular ; Genes, Tumor Suppressor ; Haplotypes ; Hepatitis B virus ; Hepatitis B ; Hepatitis ; Humans ; Liver Cirrhosis ; Polymorphism, Genetic ; Polymorphism, Single Nucleotide

BackgroundUntil now, various types of combined therapy with nucleotide analogs and pegylated interferon (Peg-INF) in patients with hepatitis B patients have been tried. However, studies regarding the benefits of de novo combination, late-add on, and sequential treatment are very limited. The objective of the current study was to identify the efficacy of sequential treatment of Peg-INF after short-term antiviral treatment.

MethodsBetween June 2010 and June 2015, hepatitis B e antigen (HBeAg)-positive patients (n = 162) received Peg-IFN for 48 weeks (mono-treatment group, n = 81) and entecavir (ETV) for 12 weeks with a 48-week course of Peg-IFN starting at week 5 of ETV therapy (sequential treatment group, n = 81). The primary endpoint was HBeAg seroconversion at the end of follow-up period after the 24-week treatment. The primary endpoint was analyzed using Chi-square test, Fisher's exact test, and regression analysis.

ResultsHBeAg seroconversion rate (18.2% vs. 18.2%, t = 0.03, P = 1.000) and seroclearance rate (19.7% vs. 19.7%, t = 0.03, P = 1.000) were same in both mono-treatment and sequential treatment groups. The rate of alanine aminotransferase (ALT) normalization (45.5% vs. 54.5%, t = 1.12, P = 0.296) and serum hepatitis B virus (HBV)-DNA <2000 U/L (28.8% vs. 28.8%, t = 0.10, P = 1.000) was not different in sequential and mono-treatment groups at 24 weeks of Peg-INF. Viral response rate (HBeAg seroconversion and serum HBV-DNA <2000 U/L) was not different in the two groups (12.1% vs. 16.7%, t = 1.83, P = 0.457). Baseline HBV-DNA level (7 logU/ml vs. 7.5 logU/ml, t = 1.70, P = 0.019) and hepatitis B surface antigen titer (3.6 logU/ml vs. 4.0 logU/ml, t = 2.19, P = 0.020) were lower and predictors of responder in mono-treatment and sequential treatment groups, respectively.

ConclusionsThe current study shows no differences in HBeAg seroconversion rate, ALT normalization, and HBV-DNA levels between mono-therapy and sequential therapy regimens.

Trial RegistrationClinicalTrials.gov, NCT01220596; https://clinicaltrials.gov/ct2/show/NCT01220596?term=NCT01220596&rank=1.

BACKGROUND AND OBJECTIVES: After the first acute myocardial infarction (AMI), a considerable proportion of patients are newly diagnosed with diabetes mellitus (DM). However, in AMI, controversy remains regarding the disparity in prognosis between previously diagnosed DM (known-DM) and newly diagnosed DM (new-DM). METHODS: The study included 10,455 patients with AMI (non-DM, 6,236; new-DM, 659; known-DM, 3,560) admitted to one of 15 participating centers in Korea between November 2011 and January 2016 (average follow-up, 523 days). We compared the characteristics and clinical course of patients with known-DM and those with new- or non-DM. RESULTS: Compared to patients with known-DM, those with new-DM or non-DM were younger, more likely to be male, and less likely to have hypertension, dyslipidemia, prior stroke, angina, or myocardial infarction. Compared to patients with new-DM or non-DM (reference), those with known-DM had higher risks of major adverse cardiac events (hazard ratio [HR], 1.20; 95% confidence interval [CI], 1.06–1.35; p=0.004), cardiac death (HR, 1.26; 95% CI, 1.01–1.57; p=0.042), and congestive heart failure (HR, 1.58; 95% CI, 1.20–2.08). Unlike known-DM, new-DM did not increase the risk of cardiac events (including death). CONCLUSIONS: Known-DM was associated with a significantly higher risk of cardiovascular events after AMI, while new-DM had a similar risk of cardiac events as that noted for non-DM. There were different cardiovascular outcomes according to diabetes status in patients with AMI.
Death ; Diabetes Mellitus ; Dyslipidemias ; Follow-Up Studies ; Heart Failure ; Humans ; Hypertension ; Korea ; Male ; Myocardial Infarction ; Prognosis ; Stroke

In the present study, we investigated whether tussilagone, a natural product derived from Tussilago farfara, significantly affects the production and gene expression of airway MUC5AC mucin. Confluent NCI-H292 cells were pretreated with tussilagone for 30 min and then stimulated with EGF (epidermal growth factor) or PMA (phorbol 12-myristate 13-acetate) for 24 h or the indicated periods. The MUC5AC mucin gene expression was measured by RT-PCR. Production of MUC5AC mucin protein was measured by ELISA. To elucidate the action mechanism of tussilagone, effect of tussilagone on PMA-induced NF-κB signaling pathway was investigated by western blot analysis. Tussilagone significantly inhibited the production of MUC5AC mucin protein and down-regulated the expression of MUC5AC mucin gene, induced by EGF or PMA. Tussilagone inhibited PMA-induced activation (phosphorylation) of inhibitory kappa B kinase (IKK), and thus phosphorylation and degradation of inhibitory kappa Ba (IκBα). Tussilagone inhibited PMA-induced phosphorylation and nuclear translocation of nuclear factor kappa B (NF-κB) p65. This, in turn, led to the down-regulation of MUC5AC protein production in NCI-H292 cells. These results suggest that tussilagone can regulate the production and gene expression of mucin by acting on airway epithelial cells through regulation of NF-κB signaling pathway.
Blotting, Western ; Down-Regulation ; Enzyme-Linked Immunosorbent Assay ; Epidermal Growth Factor ; Epithelial Cells* ; Epithelium ; Gene Expression* ; Mucins* ; NF-kappa B ; Phosphorylation ; Phosphotransferases ; Tussilago

BACKGROUND: To evaluate the therapeutic benefits of the treat-to-target (T2T) strategy for Asian patients with early rheumatoid arthritis (RA) in Korea. METHODS: In a 1-year, multicenter, open-label strategy trial, 346 patients with early RA were recruited from 20 institutions across Korea and stratified into 2 groups, depending on whether they were recruited by rheumatologists who have adopted the T2T strategy (T2T group) or by rheumatologists who provided usual care (non-T2T group). Data regarding demographics, rheumatoid factor titer, anti-cyclic citrullinated peptide antibody titer, disease activity score of 28 joints (DAS28), and Korean Health Assessment Questionnaire (KHAQ) score were obtained at baseline and after 1 year of treatment. In the T2T group, the prescription for disease-modifying antirheumatic drugs was tailored to the predefined treatment target in each patient, namely remission (DAS28 < 2.6) or low disease activity (LDA) (2.6 ≤ DAS28 < 3.2). RESULTS: Data were available for 163 T2T patients and 162 non-T2T patients. At the end of the study period, clinical outcomes were better in the T2T group than in the non-T2T group (LDA or remission, 59.5% vs. 35.8%; P < 0.001; remission, 43.6% vs. 19.8%; P < 0.001). Compared with non-T2T, T2T was also associated with higher rate of good European League Against Rheumatism response (63.0% vs. 39.8%; P < 0.001), improved KHAQ scores (−0.38 vs. −0.13; P = 0.008), and higher frequency of follow-up visits (5.0 vs. 2.0 visits/year; P < 0.001). CONCLUSION: In Asian patients with early RA, T2T improves disease activity and physical function. Setting a pre-defined treatment target in terms of DAS28 is recommended.
Antirheumatic Agents ; Arthritis, Rheumatoid* ; Asian Continental Ancestry Group* ; Demography ; Follow-Up Studies ; Humans ; Joints ; Korea* ; Multicenter Studies as Topic* ; Prescriptions ; Rheumatic Diseases ; Rheumatoid Factor ; Treatment Outcome