In the era of precision medicine, pharmacogenetics has substantial potential for addressing inter-individual variability in drug responses. Although pharmacogenetics has been a research focus for many years, resulting in the establishment of several formal guidelines, its clinical implementation remains limited to several gene–drug combinations in most countries, including Korea. The main causes of delayed implementation are technical challenges in genotyping and knowledge gaps among healthcare providers; therefore, clinical laboratories play a critical role in the timely implementation of pharmacogenetics. This paper presents an update of the Clinical Pharmacogenetic Testing and Application guidelines issued by the Korean Society for Laboratory Medicine and aims to provide the necessary information for clinical laboratories planning to implement or expand their pharmacogenetic testing. Current knowledge regarding nomenclature, gene–drug relationships, genotyping technologies, testing strategies, methods for clinically relevant information delivery, QC, and reimbursements has been curated and described in this guideline.

Purpose: This study aimed to report the results from an early-phase study of rivoceranib, an oral tyrosine kinase inhibitor highly selective for vascular endothelial growth factor receptor 2, in patients with advanced solid tumors. Materials and Methods: In this open-label, single-arm, dose-escalating, multicenter three-part phase 1/2a trial, patients had advanced solid tumors refractory to conventional therapy. Part 1 evaluated the safety and pharmacokinetics of five ascending once-daily doses of rivoceranib from 81 mg to 685 mg. Part 2 evaluated the safety and antitumor activity of once-daily rivoceranib 685 mg. Part 3 was conducted later, due to lack of maximum tolerated dose determination in part 1, to evaluate the safety and preliminary efficacy of once-daily rivoceranib 805 mg in patients with unresectable or advanced gastric cancer. Results: A total of 61 patients were enrolled in parts 1 (n=25), 2 (n=30), and 3 (n=6). In parts 1 and 2, patients were white (45.5%) or Asian (54.5%), and 65.6% were male. The most common grade ≥ 3 adverse events were hypertension (32.7%), hyponatremia (10.9%), and hypophosphatemia (10.9%). The objective response rate (ORR) was 15.2%. In part 3, dose-limiting toxicities occurred in two out of six patients: grade 3 febrile neutropenia decreased appetite, and fatigue. The ORR was 33%. Conclusion The recommended phase 2 dose of rivoceranib was determined to be 685 mg once daily, which showed adequate efficacy with a manageable safety profile (NCT01497704 and NCT02711969).

Background: Accurate measurement of glycated hemoglobin (HbA1c) is crucial for a diabetes diagnosis and subsequent patient management. The detection method and presence of variant Hb can interfere with HbA1c measurements. We evaluated the HbA1c-measuring performance of the DxC 700 AU (Beckman Coulter, Brea, CA, USA) immunoassay-based device in comparison with another immunoassay device and the reference method. Methods: A total of 120 normal and 14 variant Hb samples were analyzed using the Cobas c 513 (Roche Diagnostics, Mannheim, Germany) and DxC 700 AU analyzers. Variant Hb samples were also analyzed using the reference method, along with 20 normal samples. The accuracy, precision, linearity, and carryover were determined. Results: DxC 700 AU results strongly correlated with those of Cobas c 513 and exhibited accuracy in comparison with the reference method. The within-run, between-run, between-day, and total imprecision (%CV) values for the low- and high-concentration control materials were below 2%. The results of DxC 700 AU were linear over a wide HbA1c range (3.39%–18.30%). Although DxC 700 AU performed well in the presence of variant Hb, the HbA1c concentration was underestimated in the presence of fetal Hb. The possibility of interference from a high HbH proportion could not be ruled out. Conclusions The overall analytical performance of DxC 700 AU was acceptable. The device is accurate, precise, and linear over a wide HbA1c concentration range. Although DxC 700 AU results highly correlated with those of Cobas c 513, caution should be exercised in cases of high HbF and HbH concentrations.

Purpose: Specialty choice in residency training has a significant impact on an individual’s career and satisfaction, as well as the supply-demand imbalance in the healthcare system. The current study aimed to investigate the quality of life (QOL), stress, self-confidence, and job satisfaction of residents, and to explore factors associated with such variables, including postgraduate year, sex, and especially specialty, through a cross-sectional survey. Methods: An online survey was administered to residents at 2 affiliated teaching hospitals. The survey had a total of 46 items encompassing overall residency life such as workload, QOL, stress, confidence, relationship, harassment, and satisfaction. Related survey items were then reconstructed into 4 key categories through exploratory factor analysis for comparison according to group classification. Results: The weekly work hours of residents in vital and other specialties were similar, but residents in vital specialties had significantly more on-call days per month. Residents in vital specialties had significantly lower scores for QOL and satisfaction. Specifically, vital-surgical residents had significantly lower QOL scores and higher stress scores than the other specialty groups. Satisfaction scores were also lowest among vital-surgical residents, with a marginal difference from vital-medical, and a significant difference from other-surgical residents. Female residents had significantly lower satisfaction scores than their male counterparts. Conclusion Residents in vital specialties, particularly vital-surgical specialties, experience significantly worse working conditions across multiple dimensions. It is necessary to improve not only the quantity but also the quality of the system in terms of resource allocation and prioritization.

Diabetic foot wounds have a significant effect on the health-related quality of life of patients. As diabetic foot wounds are usually chronic and recurrent, it is possible that they can lead to skin malignancies. Several factors can make it difficult to make an early and accurate diagnosis of skin malignancies of the foot in patients with diabetes mellitus. Even though the prevalence of diabetes mellitus and diabetic foot wounds is increasing, currently there are no guidelines for the biopsy of diabetic foot wounds. We have evolved a criterion for the above based on six cases of diabetic foot wounds with concomitant skin malignancies. We recommend that clinicians should broadly consider implementing this criterion when managing patients with diabetic foot wounds.

Background: The coronavirus disease 2019 (COVID-19) pandemic has caused significant changes. This study aimed to investigate the impact of COVID-19 on patients with chronic pain. Methods: Patients with chronic pain from 23 university hospitals in South Korea participated in this study. The anonymous survey questionnaire consisted of 25 questions regarding the following: demographic data, diagnosis, hospital visit frequency, exercise duration, time outside, sleep duration, weight change, nervousness and anxiety, depression, interest or pleasure, fatigue, daily life difficulties, and self-harm thoughts. Depression severity was evaluated using the Patient Health Questionnaire-9 (PHQ-9). Logistic regression analysis was used to investigate the relationship between increased pain and patient factors. Results: A total of 914 patients completed the survey, 35.9% of whom had decreased their number of visits to the hospital, mostly due to COVID-19. The pain level of 200 patients has worsened since the COVID-19 outbreak, which was more prominent in complex regional pain syndrome (CRPS). Noticeable post-COVID-19 changes such as exercise duration, time spent outside, sleep patterns, mood, and weight affected patients with chronic pain. Depression severity was more significant in patients with CRPS. The total PHQ-9 average score of patients with CRPS was 15.5, corresponding to major depressive orders. The patients’ decreased exercise duration, decreased sleep duration, and increased depression were significantly associated with increased pain. Conclusions COVID-19 has caused several changes in patients with chronic pain.During the pandemic, decreased exercise and sleep duration and increased depression were associated with patients’ increasing pain.

Methods: In this retrospective study, 43 consecutive patients who underwent SI joint fusion between August 2017 and February 2020 were enrolled; 60 SI joints were fused. The patients’ fusion was documented on computed tomography or X-rays, and Visual Analog Scale (VAS) scores were used to determine patient subjective clinical outcomes. Results: A total of 60 joints were fused, including 26 joints fused using robotic guidance and 34 joints fused using the Stealth Navigation System. Student t-test was used to compare the mean preoperative VAS score (7.52±1.3) with the mean postoperative VAS score at the 12-month follow-up (1.43±1.22) (p<0.05). The SI joint fusion rate using this technique was 61% at 6 months, 96.4% at 12 months, and 100% at 18 months. Conclusions The use of navigation guidance or robotic assistance enables accurate percutaneous screw placement across the SI joint. The use of bone morphogenetic protein in the screw bore hastens fusion across the joint, improving patient-perceived pain.

Background: Recent studies have successfully implemented next-generation sequencing (NGS) in HLA typing. We performed HLA NGS in a Korean population to estimate HLA-A, -B, -C, and -DRB1 allele and haplotype frequencies up to an 8-digit resolution, which might be useful for an extended application of HLA results. Methods: A total of 128 samples collected from healthy unrelated Korean adults, previously subjected to Sanger sequencing for 6-digit HLA analysis, were used. NGS was performed for HLA-A, -B, -C, and -DRB1 using the AllType NGS kit (One Lambda, West Hills, CA, USA), Ion Torrent S5 platform (Thermo Fisher Scientific, Waltham, MA, USA), and Type Steam Visual NGS analysis software (One Lambda). Results: Eight HLA alleles showed frequencies of ≥ 10% in the Korean population, namely, A*24:02:01:01 (19.5%), A*33:03:01 (15.6%), A*02:01:01:01 (14.5%), A*11:01:01:01 (13.3%), B*15:01:01:01 (10.2%), C*01:02:01 (19.9%), C*03:04:01:02 (11.3%), and DRB1*09:01:02 (10.2%). Nine previous 6-digit HLA alleles were further identified as two or more 8-digit HLA alleles. Of these, eight alleles (A*24:02:01, B*35:01:01, B*40:01:02, B*55:02:01, B*58:01:01, C*03:02:02, C*07:02:01, and DRB1*07:01:01) were identified as two 8-digit HLA alleles, and one allele (B*51:01:01) was identified as three 8-digit HLA alleles. The most frequent four-loci haplotype was HLA-A*33:03:01-B*44:03:01:01-C*14:03-DRB1*13:02:01. Conclusions We identified 8-digit HLA-A, -B, -C, and -DRB1 allele and haplotype frequencies in a healthy Korean population using NGS. These new data can be used as a representative Korean data for further disease-related HLA type analysis.

Background: We previously elucidated the protective mechanism of Korean red ginseng oil (RGO) against Brucella abortus infection, and our phytochemical analysis revealed that palmitic acid (PA) was an abundant component of RGO. Consequently, we investigated the contribution of PA against B. abortus. Objectives: We aimed to investigate the efficacy of PA against B. abortus. infection using a murine cell line and a murine model. Methods: Cell viability, bactericidal, internalization, and intracellular replication, western blot, nitric oxide (NO), and superoxide (O2 - ) analyses and flow cytometry were performed to determine the effects of PA on the progression of B. abortus. infection in macrophages. Flow cytometry for cytokine analysis of serum samples and bacterial counts from the spleens were performed to determine the effect of PA in a mouse model. Results: PA did not affect the growth of B. abortus.. PA treatment in macrophages did not change B. abortus. uptake but it did attenuate the intracellular survivability of B. abortus.. Incubation of cells with PA resulted in a modest increase in sirtuin 1 (SIRT1) expression.Compared to control cells, reduced nitrite accumulation, augmented O2 - , and enhanced pro-inflammatory cytokine production were observed in PA-treated B. abortus.-infected cells.Mice orally treated with PA displayed a decreased serum interleukin-10 level and enhanced bacterial resistance. Conclusions Our results suggest that PA participates in the control of B. abortus. within murine macrophages, and the in vivo study results confirm its efficacy against the infection. However, further investigations are encouraged to completely characterize the mechanisms involved in the inhibition of B. abortus. infection by fatty acids.