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.

There are geographical, regional, and ethnic differences in the phenotypes and endotypes of patients with drug hypersensitivity reactions (DHRs) in different parts of the world. In Asia, aspects of drug hypersensitivity of regional importance include IgE-mediated allergies and T-cell-mediated reactions, including severe cutaneous adverse reactions (SCARs), to beta-lactam antibiotics, antituberculous drugs, nonsteroidal anti-inflammatory drugs (NSAIDs) and radiocontrast agents. Delabeling of low-risk penicillin allergy using direct oral provocation tests without skin tests have been found to be useful where the drug plausibility of the index reaction is low. Genetic risk associations of relevance to Asia include human leucocyte antigen (HLA)-B*1502 with carbamazepine SCAR, and HLA-B*5801 with allopurinol SCAR in some Asian ethnic groups. There remains a lack of safe and accurate diagnostic tests for antituberculous drug allergy, other than relatively high-risk desensitization regimes to first-line antituberculous therapy. NSAID hypersensitivity is common among both adults and children in Asia, with regional differences in phenotype especially among adults. Low dose aspirin desensitization is an important therapeutic modality in individuals with cross-reactive NSAID hypersensitivity and coronary artery disease following percutaneous coronary intervention. Skin testing allows patients with radiocontrast media hypersensitivity to confirm the suspected agent and test for alternatives, especially when contrasted scans are needed for future monitoring of disease relapse or progression, especially cancers.
Adult ; Allopurinol ; Anaphylaxis ; Anti-Bacterial Agents ; Asia ; Asian Continental Ancestry Group ; Aspirin ; Asthma ; Carbamazepine ; Child ; Cicatrix ; Contrast Media ; Coronary Artery Disease ; Diagnostic Tests, Routine ; Drug Hypersensitivity ; Ethnic Groups ; Humans ; Hypersensitivity ; Penicillins ; Percutaneous Coronary Intervention ; Phenotype ; Recurrence ; Skin Tests

PURPOSE: Standard treatment for cases of non-small cell lung cancer (NSCLC) exhibiting acquired drug resistance includes tumor rebiopsy, epidermal growth factor receptor (EGFR) mutation testing (e.g., for T790M mutations), and the subsequent administration of third-generation EGFR-tyrosine kinase inhibitors (EGFR-TKIs). However, rebiopsies are typically invasive, costly, and occasionally not feasible. Therefore, the present study aimed to assess rebiopsy procedures by analyzing real-world data collected by the ASTRIS study of patients with resistant NSCLC. MATERIALS AND METHODS: The present study used statistical models to evaluate data collected by the ASTRIS trial (NCT02474355) conducted at Yonsei Cancer Center, including the rebiopsy success rate, incidence of T790M mutations in collected tissue and plasma samples, and association of administered osimertinib treatment efficacy. RESULTS: In a total of 188 screened patients, 112 underwent rebiopsy. An adequate tumor specimen was obtained in 95 of these patients, the greatest majority of whom (43.8%) were subjected to bronchoscopy. T790M mutations were detected in 53.3% of successfully EGFR-tested rebiopsy samples. A total of 88 patients received osimertinib treatment, and the objective response rate and median progression-free survival time was 44.3% and 32.7 weeks, respectively, among the treated patients overall, but 57.8% and 45.0 weeks, and 35.2% and 20.4 weeks among patients who exhibited T790M-positive tissue (n=45) and plasma (n=54) samples, respectively. CONCLUSION: Approximately 60% of patients in the analyzed real-world cohort were eligible for tissue rebiopsy upon NSCLC progression. Osimertinib activity was higher in patients in whom T790M mutations were detected in tissues rather than in plasma samples.
Bronchoscopy ; Carcinoma, Non-Small-Cell Lung ; Cohort Studies ; Disease-Free Survival ; Drug Resistance ; Humans ; Incidence ; Models, Statistical ; Phosphotransferases ; Plasma ; Receptor, Epidermal Growth Factor ; Treatment Outcome

A 12-year-old spayed female Pomeranian (weighing 2.4 kg) was referred with primary complaints of acute dyspnea, cough, and lethargy. Diagnostic imaging studies found degenerative mitral valve cusps, chordae tendinae rupture, severe mitral regurgitation (5.45 m/s of peak velocity), and marked left atrial and ventricular dilation. The dog was diagnosed as having degenerative mitral valve disease (DMVD) with ISACHC stage IIIa heart failure. Her clinical condition was stabilized after administration of cardiac medication (e.g. diuretics and pimobendan). Ten months later, the dog was referred back to the clinic due to a sudden worsening of clinical signs. Echocardiographic study found pulmonary hypertension in addition to DMVD. After medication was adjusted, clinical signs were stabilized in 2 weeks. The patient was returned after 4 months for cardiac recheck and there was no obvious worsening of clinical signs. Incidental finding of a left-to-right atrial septal defect from rupture of the atrial septum secondary to marked left atrial dilation by DMVD was noted by echocardiography. To diminish left atrial volume overload, the frequencies of both furosemide and pimobendan were increased (i.e. from q 12 hr to q 8 hr) in addition to adding spironolactone (1 mg/kg q 12 hr). Based on diagnostic findings, this case was re-diagnosed as acquired atrial septal defect secondary to rupture of the atrial septum with advanced stage DMVD. The dog was then stabilized and is currently being regularly monitored.
Animals ; Atrial Septum* ; Child ; Cough ; Diagnostic Imaging ; Diuretics ; Dogs* ; Dyspnea ; Echocardiography ; Female ; Furosemide ; Heart Failure ; Heart Septal Defects, Atrial ; Humans ; Hypertension, Pulmonary ; Incidental Findings ; Lethargy ; Mitral Valve Insufficiency ; Mitral Valve* ; Rupture* ; Spironolactone

PURPOSE: The purpose of this study was to examine the effects of a stress-management program on stress coping methods, interpersonal relations and quality of life in patients with chronic mental illness. METHODS: A nonequivalent control group pre-posttest design was used for this quasi-experimental study. The study was conducted from May 1 to December 30, 2010. The 41 participants in this study were selected from patients with chronic mental illness (20 for the experimental group and 21 for the control group). Datas were analyzed chi2-test, t-test, paired t-test, and one-way ANCOVA with the SPSS/WIN 15.0 program. RESULTS: There were significant changes in stress coping methods scores, interpersonal relations scores and quality of life scores in the experimental group before and after treatment, which were significantly different from those in the control group. CONCLUSION: The results of the study indicate that the stress-management program resulted in significant improvement in stress coping methods, interpersonal relations and quality of life for patients with chronic mental illness. Therefore, this study shows stress-management programs are useful in clinical practice as effective nursing interventions in patients with chronic mental illness.
Humans ; Interpersonal Relations* ; Nursing ; Quality of Life*

BACKGROUND: Sleep is an essential restorative physiologic phenomenon. Impaired sleep results in significant negative effect to the health. Symptoms like sleep initiation difficulty, frequent awakening, severe snoring have related to poor sleep quality. We studied frequency and compared the characteristics of common sleep disorders at family practice. METHODS: We surveyed patients over 18 years of age and their guardians who visited 16 familial practices for 6 days. We investigated sleep characteristics, frequency of sleep disorder and associated factors by questionnaires and analyzed by frequency analysis, Spearman's correlation coefficient, multiple logistic regression. RESULTS: We enrolled 1,117 participants. Older participants were more likely to report early sleep onset and off time, short sleep duration. Mean number of awakening during a typical night is 1.69. Female complained difficulties in initiation and maintenance of sleep more than male. A total of 32.5% had these insomnia symptoms and related to hypertension, stroke, stress, arthralgia, depression, urological disorder. 31.1% had excessive daytime sleepiness, related to stress, arthralgia, depression. Loud snoring and gasp for breath showed positive correlation between male, high BMI. Disrupted sleep over 3 times was related to old age, female, diabetes, hypertension, stroke, stress, arthralgia, depression. Restless leg syndrome were high in elderly, high BMI, stress, arthralgia and depression. CONCLUSION: About one in three who visit in primary medical practice have sleep disorder symptoms like insomnia, daytime fatigue, snoring. 3% of them have gasp for breath, 8% have restless leg syndrome.
Aged ; Arthralgia ; Depression ; Family Practice ; Fatigue ; Female ; Humans ; Hypertension ; Leg ; Male ; Prevalence ; Sleep Wake Disorders ; Sleep Initiation and Maintenance Disorders ; Snoring ; Stroke

The etiology and pathogenesis of type 2 diabetes mellitus (T2DM) are not completely understood although it is often associated with other conditions such as obesity, hypertension, and dyslipidemia. Lipoprotein lipase (LPL) is a key enzyme in human lipid metabolism that facilitates the removal of triglyceride-rich lipoproteins from the bloodstream. LPL hydrolyzes the core of triglyceride-rich lipoproteins (chylomicrons and very low density lipoprotein) into free fatty acids and monoacylglycerol. To gain insight into the possible role of LPL in T2DM, nine single nucleotide polymorphisms (SNPs) of LPL were analyzed for the association with T2DM using 944 unrelated Koreans, including 474 T2DM subjects and 470 normal healthy controls. Of the nine LPL SNPs we analyzed, a significant association with multiple tests by the false discovery rate (FDR) was observed between T2DM and SNP rs343 (+13836C>A in intron 3). SNP rs343 was also marginally associated with some of T2DM-related phenotypes including total cholesterol, high density lipoprotein cholesterol (HDLc), and log transformed glycosylated hemoglobin in 470 normal controls, although no significant association was detected by multiple tests. In total, our results suggest that the control of lipid level by LPL in the bloodstream might be an important factor in T2DM pathogenesis in the Korean population.
Aged ; Asian Continental Ancestry Group ; Cohort Studies ; Databases, Genetic ; Diabetes Mellitus, Type 2/*genetics ; Female ; Gene Frequency ; Genetic Predisposition to Disease ; Genotype ; Humans ; Lipoprotein Lipase/*genetics ; Male ; Middle Aged ; *Polymorphism, Single Nucleotide

We sequenced 1,841 BAC clones by terminal sequencing, and 1,830 of these clones were characterized with regard to their human chromosomal location and gene content using Korean BAC library constructed at the Korean Science (KCGS). Sequence analyses of the 1,830 BAC clones was performed for chromosomal assignment: 1,144 clones were assigned to a single chromosome, 190 clones apparently assigned to more than one chromosome, and 496 clones to no chromosome. Evaluating gene content of the 1,144 BAC clones, we found that 706 clones represented 1,069 genes of which 415 genes existed in the BAC clones covering the full sequence of the gene, 180 genes covering a 50%~99%, and 474 genes covering less than 50% of the gene coverage. The estimated covering size of the KBAC clones was 73,379 kilobases (kb), in total corresponding to 2.3% of haploid human genome sequence. The identified BAC clones will be a public genomic resource for mapped clones for diagnostic and functional studies by Korean scientists and investigators worldwide.
Clone Cells* ; Genome ; Genome, Human ; Haploidy ; Humans ; Research Personnel ; Sequence Analysis

PURPOSE: It has been postulated that dopamine release in the striatum underlies the reinforcing properties of nicotine. Substantial evidence in the animal studies demonstrates that nicotine interacts with dopaminergic neuron and regulates the activation of the dopaminergic system. The aim of this study was to visualize the dopamine release by smoking in human brain using PET scan with [11C]raclopride. MATERIALS AND METHODS: Five male non-smokers or ex-smokers with an abstinence period longer than 1 year (mean age of 24.4+/-1.7 years) were enrolled in this study. [11C]raclopride, a dopamine D2 receptor radioligand, was administrated with bolus-plus- constant infusion. Dynamic PET was performed during 120 minutes (3x20s, 2x60s, 2x120s, 1x180s and 22x300s). Following the 50 minute-scanning, subjects smoked a cigarette containing 1 mg of nicotine while in the scanner. Blood samples for the measurement of plasma nicotine level were collected at 0, 5, 10, 15, 20, 25, 30, 45, 60, and 90 minute after smoking. Regions for striatal structures were drawn on the coronal summed PET images guided with co-registered MRI. Binding potential, calculated as (striatal-cerebellar) /cerebellar activity, was measured under equilibrium condition at baseline and smoking session. RESULTS: The mean decrease in binding potential of [11C]raclopride between the baseline and smoking in caudate head, anterior putamen and ventral striatum was 4.7 %, 4.0 % and 7.8 %, respectively. This indicated the striatal dopamine release by smoking. Of these, the reduction in binding potential in the ventral striatum was significantly correlated with the cumulated plasma level of the nicotine (Spearman's rho=0.9, p=0.04). CONCLUSION: These data demonstrate that in vivo imaging with [11C]raclopride PET could measure nicotine-induced dopamine release in the human brain, which has a significant positive correlation with the amount of nicotine administered by smoking.
Animals ; Basal Ganglia ; Brain ; Dopamine* ; Dopaminergic Neurons ; Head ; Humans ; Magnetic Resonance Imaging ; Male ; Nicotine ; Plasma ; Positron-Emission Tomography ; Putamen ; Receptors, Dopamine D2 ; Smoke ; Smoking ; Tobacco Products