• Biomolecules & Therapeutics
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• 제30권1호
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• pp.19-27
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• 2022

Epidermal growth factor receptor (EGFR) is a receptor tyrosine kinase widely expressed in many cancers such as non-small cell lung cancer (NSCLC), pancreatic cancer, breast cancer, and head and neck cancer. Mutations such as L858R in exon 21, exon 19 truncation (Del19), exon 20 insertions, and others are responsible for aberrant activation of EGFR in NSCLC. First-generation EGFR tyrosine kinase inhibitors (TKIs) such as gefitinib and erlotinib have clinical benefits for EGFR-sensitive (L858R and Del19) NSCLC patients. However, after 10-12 months of treatment with these inhibitors, a secondary T790M mutation at the gatekeeper position in the kinase domain of EGFR was identified, which limited the clinical benefits. Second-generation EGFR irreversible inhibitors (afatinib and dacomitinib) were developed to overcome this T790M mutation. However, their lack of selectivity toward wild-type EGFR compromised their clinical benefits due to serious adverse events. Recently developed third-generation irreversible EGFR TKIs (osimertinib and lazertinib) are selective toward driving mutations and the T790M mutation, while sparing wild-type EGFR activity. The latest studies have concluded that their efficacy was also compromised by additional acquired mutations, including C797S, the key residue cysteine that forms covalent bonds with irreversible inhibitors. Because second- and third-generation EGFR TKIs are irreversible inhibitors, they are not effective against C797S containing EGFR triple mutations (Del19/T790M/C797S and L858R/T790M/C797S). Therefore, there is an urgent unmet medical need to develop next-generation EGFR TKIs that selectively inhibit EGFR triple mutations via a non-irreversible mechanism.

• 대한한방내과학회지
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• 제43권3호
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• pp.423-435
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• 2022

Purpose: The purpose of this study was to confirm the clinical efficacy of Gyeongok-go. Methods: Public/Publisher MEDLINE (PubMed), Cochrane Central Register of Controlled Trials (CENTRAL), Excerpta Medica dataBASE (EMBASE), Research Information Sharing Service (RISS), ScienceON, Korean Traditional Knowledge Portal (KTKP), and China National Knowledge Infrastructure (CNKI) were searched for randomized controlled clinical trials administering Gyeongok-go as an intervention, published from inception to December 31, 2021. The risk-of-bias of the included trials was assessed with the Cochrane risk-of-bias tool for randomized trials version 2. From the experimental and control groups of the selected trials, the mean value (or rate) of each outcome was extracted and statistically compared. Results: Statistically significant mean differences were in VO₂max (MD 6.82), post-exercise heart rate (MD -8.76 at 5 min, -11.58 at 30 min, -14.6 at 60 min), senescence scale (MD -6.52), Th1 cells and Th2 cells in pulmonary tuberculosis (MD 2.79 and -1.64), yin-deficient and qi-deficient score (MD -9.64 and -9.76), and phlegm-dampness score (MD 5.56). Overall risk-of-bias was 20% low risk, 80% some concerns, and 0% high risk. There were no reports of adverse events. Conclusions: Gyeongok-go is likely to have the effect of improving cardiorespiratory endurance, increasing fatigue recovery ability, reducing senescence, and enhancing immune function in tuberculosis patients. Also, it is more suitable for those who are yin-deficient or qi-deficient, and those with phlegm-dampness probably need caution.

• 대한한방내과학회지
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• 제43권3호
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• pp.375-386
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• 2022

Objectives: The purpose of this study was to summarize current clinical study trends and results regarding transcutaneous electrical nerve stimulation (TENS) treatment for xerostomia. Methods: Studies published from 2017 to 2022 were searched on domestic databases and PubMed. The included studies were analyzed according to the year, language, study design, diagnosis xerostomia method, and TENS treatment method. Results: Nine studies were included. There were three randomized controlled trials (RCTs), three case series, one case report, one case-control study, and one cross-sectional study. Conventional TENS was used in seven studies, and acupuncture-like TENS (ALTENS) was used in one study. The most common TENS attachment site was externally on the skin overlying the parotid gland region, and the setting of TENS was 50 Hz-250 μs the most. In all nine studies, TENS was effective for xerostomia as assessed by salivary flow rate or quality of life questionnaire. Additionally, no persistent adverse events were reported after TENS treatment. Conclusions: TENS treatment for xerostomia can be considered effective and safe, so it can be used in clinical practice.

• 사상체질의학회지
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• 제34권2호
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• pp.48-64
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• 2022

Objectives The purpose of this study was to review and evaluate the clinical evidence of the efficacy and safety of treatment based on Sasang constitutional medicine (SCM) for post-stroke patients by systematic review and meta-analysis. Methods Randomized controlled trials (RCTs), published in 10 electronic databases up to December 2020, were searched. For the included studies, Cochrane's risk of bias assessment was performed to analyze the methodological quality. The strength of evidence was evaluated using the grading of recommendations assessment, development, and evaluation system based on the results of analyses. All review processes were performed by two independent researchers. Results Five RCTs were finally included. All included RCTs were conducted for one month on post-stroke patients in 60-80s, four studies on Tae-Eum patients and one study on So-Yang patients. Four types of constitution-specific herbal medicine (Chungpyesagan-tang, Cheongsimsanyak-tang, Yeoldahanso-tang, and Yangkyuksanhwa-tang) and constitution-specific acupuncture therapy were identified as interventions. More than half of the included studies were evaluated as low quality due to the high-risk of bias in selection, performance, and detection. The combination of constitution-specific herbal medicine, acupuncture, and conventional treatment was more effective in improving the patients' motor impairment, dysphagia, aphasia, and depression than conventional treatment alone. No serious adverse events by SCM treatment were reported. Conclusions SCM treatment may improve the sequelae of post-stroke patients safely in combination with conventional treatment. Since the quality of clinical evidence included in this study was low, higher quality clinical evidence obtained in well-designed clinical studies will be needed.

• The Korean Journal of Pain
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• 제35권2호
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• pp.202-208
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• 2022

Background: Neurolytic celiac plexus block (NCPB) is a typical treatment for severe epigastric cancer pain, but the therapeutic effect is often affected by the variation of local anatomical structures induced by the tumor. Greater and lesser splanchnic nerve neurolysis (SNN) had similar effects to the NCPB, and was recently performed with a paravertebral approach under the image guidance, or with the transdiscal approach under the guidance of computed tomography. This study observed the feasibility and safety of SNN via a transdiscal approach under fluoroscopic guidance. Methods: The follow-up records of 34 patients with epigastric cancer pain who underwent the splanchnic nerve block via the T11-12 transdiscal approach under fluoroscopic guidance were investigated retrospectively. The numerical rating scale (NRS), the patient satisfaction scale (PSS) and quality of life (QOL) of the patient, the dose of morphine consumed, and the occurrence and severity of adverse events were recorded preoperatively and 1 day, 1 week, 1 month, and 2 months after surgery. Results: Compared with the preoperative scores, the NRS scores and daily morphine consumption decreased and the QOL and PSS scores increased at each postoperative time point (P < 0.001). No patients experienced serious complications. Conclusions: SNN via the transdiscal approach under flouroscopic guidance was an effective, safe, and easy operation for epigastric cancer pain, with fewer complications.

• Tuberculosis and Respiratory Diseases
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• 제85권1호
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• pp.25-36
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• 2022

Background: Only a few studies directly compared the therapeutic efficacy and safety of two pressurized metered-dose inhalers (pMDIs) in asthma. We analyzed the asthma treatment outcomes, safety, and patient preferences using formoterol/beclomethasone (FORM/BDP), a pMDI with extra-fine particles, compared with formoterol/budesonide (FORM/BUD), another pMDI with non-extra-fine particles. Methods: In this randomized, double-blind, double-dummy parallel group study, 40 adult asthmatics were randomized to FORM/BDP group (n=18; active FORM/BDP and placebo FORM/BUD) or FORM/BUD group (n=22; active FORM/BUD and placebo FORM/BDP). During the two visits (baseline and end of 8-week treatment), subjects were asked to answer questionnaires including asthma control test (ACT), asthma control questionnaires (ACQ), and Quality of Life Questionnaire for Adult Korean Asthmatics (QLQAKA). Lung function, compliance with inhaler, and inhaler-handling skills were also assessed. Results: Ten subjects in the FORM/BDP group and 14 in the FORM/BUD group completed follow-up visits. ACT, ACQ, QLQAKA (a primary outcome), and adverse events did not differ between two groups. We found that the increase in forced expiratory volume in 1 second/forced vital capacity and forced expiratory flow at 25% to 75% of the pulmonary volume in the FORM/BDP group was higher than in the FORM/BUD group. Regarding preference, subjects responded that the flume velocity of FORM/BDP was higher, but more adequate than that of FORM/BUD. They also answered that FORM/BDP reached the trachea and bronchus and irritated them significantly more than FORM/BUD. Conclusion: The use of pMDI with extra-fine particles may relieve small airway obstruction more than the one with non-extra-fine particles despite no significant differences in overall treatment outcomes. Some asthmatics have a misconception about the adequacy of high flume velocity of pMDIs.

• Molecules and Cells
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• 제45권7호
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• pp.479-494
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• 2022

Human mesenchymal stem cells (MSCs) are multipotent stem cells that have been intensively studied as therapeutic tools for a variety of disorders. To enhance the efficacy of MSCs, therapeutic genes are introduced using retroviral and lentiviral vectors. However, serious adverse events (SAEs) such as tumorigenesis can be induced by insertional mutagenesis. We generated lentiviral vectors encoding the wild-type herpes simplex virus thymidine kinase (HSV-TK) gene and a gene containing a point mutation that results in an alanine to histidine substitution at residue 168 (TK(A168H)) and transduced expression in MSCs (MSC-TK and MSC-TK(A168H)). Transduction of lentiviral vectors encoding the TK(A168H) mutant did not alter the proliferation capacity, mesodermal differentiation potential, or surface antigenicity of MSCs. The MSC-TK(A168H) cells were genetically stable, as shown by karyotyping. MSC-TK(A168H) responded to ganciclovir (GCV) with an half maximal inhibitory concentration (IC₅₀) value 10-fold less than that of MSC-TK. Because MSC-TK(A168H) cells were found to be non-tumorigenic, a U87-TK(A168H) subcutaneous tumor was used as a SAE-like condition and we evaluated the effect of valganciclovir (vGCV), an oral prodrug for GCV. U87-TK(A168H) tumors were more efficiently ablated by 200 mg/kg vGCV than U87-TK tumors. These results indicate that MSC-TK(A168H) cells appear to be pre-clinically safe for therapeutic use. We propose that genetic modification with HSV-TK(A168H) makes allogeneic MSC-based ex vivo therapy safer by eliminating transplanted cells during SAEs such as uncontrolled cell proliferation.

• Journal of Yeungnam Medical Science
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• 제39권3호
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• pp.223-229
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• 2022

Background: The first large coronavirus disease 2019 (COVID-19) outbreak outside China occurred in Daegu. In response, we developed infection prevention measures for surgical patients during the outbreak at our hospital and retrospectively reviewed the outcomes of COVID-19-related surgical patients. Methods: We reviewed the medical records of 118 COVID-19-related surgical patients and monitored their clinical outcomes until March 31, 2021. We also interviewed healthcare workers who participated in their perioperative care at Kyungpook National University Chilgok Hospital. The perioperative management guidelines for COVID-19-related patients were prepared through multidisciplinary discussions, including the infection control department, surgical departments, and anesthesiology department before and during the COVID-19 outbreak. Results: One standard operating room was temporarily converted to a negative-pressure room by increasing the exhaust air volume, creating a relative pressure of -11.3 Pa. The healthcare workers were equipped with personal protective equipment according to the patient's classification of the risk of COVID-19 transmission. The 118 COVID-19-related patients underwent emergent surgery in the negative-pressure room, including three COVID-19-confirmed patients and five COVID-19-exposed patients. Conclusion: All surgeries of the COVID-19-related patients were performed without specific adverse events or perioperative COVID-19 transmission. Our experience setting up a negative-pressure operating room and conservative perioperative protocol to prevent COVID-19 transmission will help plan and execute infection control measures in the future.

• 비만대사연구학술지
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• 제1권1호
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• pp.4-13
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• 2022

Currently, pharmacotherapy is becoming essential for obesity, owing to its expanding and increasing epidemiology. In this review, novel peptide-based drugs of four classes are covered: GLP-1 receptor agonist, GIP/GLP-1 receptor dual agonist, glucagon/GLP-1 receptor dual agonist, and a combination of amylin receptor agonist/GLP-1 receptor agonist. Semaglutide is a next-generation GLP-1 receptor agonist with a longer duration and stronger weight and glucose reduction effects than liraglutide and dulaglutide. In the STEP1 trial, semaglutide 2.4 mg reduced body weight by approximately 15% in people with obesity with similar or milder adverse events than liraglutide 3.0 mg. Tirzepatide, a GIP/GLP-1 receptor dual agonist, also has a long duration and strong weight- and glucose-lowering effect. According to SURPASS-2, 3, and 4, in patients with BMI≥25 kg/m² and type 2 diabetes mellitus (T2DM), tirzepatide 15 mg reduced the initial body weight by >13%. Cotadutide, a glucagon/GLP-1 receptor dual agonist, showed weaker weight-lowering effects than semaglutide and tirzepatide, while it was comparable to that of liraglutide in a phase 2 clinical trial for non-alcoholic fatty liver disease in patients with BMI≥25 kg/m² and T2DM. Additionally, its effect on the liver was noticeable. The long-acting amylin receptor agonist cargrilintide combined with semaglutide can be another effective option for obesity treatment. Even in a small phase 1 trial with a short study period of 20 weeks, cargrilintide 2.4 mg/semaglutide 2.4 mg reduced by 17% of initial body weight in people with BMI 27-39.9 kg/m². In coming several years, semaglutide, tirzepatide, and cargrilintide/semaglutide will become available for obesity treatment in Korea.

• 한국임상약학회지
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• 제32권3호
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• pp.166-177
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• 2022

Background: Recently clinical trials have expanded extensively in Korea; thus, ensuring the rights of subjects participating in clinical trials is imperative. Accordingly, national regulations on subject recruitment advertisement were enforced from October 25, 2018. In this study, the effect of this regulation was evaluated by analyzing the difference in the provision of information before and after enforcement of the regulation. Methods: Recruitment advertisements for clinical trial subjects 3 years before and after enforcement of the regulation were collated by the significance sampling approach. Print-based (newspapers, buses, and subways) and web-based (clinical trial center websites and online platforms) materials for recruitment in clinical trials of phase 1 to 4 for investigational drugs, medical devices, and oriental medicine were considered. Chi-square tests were conducted for inter-group comparisons. SPSS version 26 was employed for statistical analyses. Results: A total of 137 advertisements were collected comprising 60 pre- and 77 post-regulation enforcement. The overall rate of delivery of critical information in advertisements increased significantly from 47.5% before regulation to 93.2% after regulation enforcement. Particularly, details on expected adverse events augmented significantly (p<0.001). Benefits from participation in clinical trial reduced significantly from 88.3% to 70.1% (p<0.05). As the information provision amplified, the inclusion of professional terms increased. Conclusions: Enforcement of regulations has led to a surge in the amount of information and challenging terms contained in advertisements for recruiting subjects. Therefore, additional efforts are required by subjects to completely understand the information provided in the advertisements.