Lazertinib versus Gefitinib as First-Line Treatment for EGFR-mutated Locally Advanced or Metastatic NSCLC: LASER301 Korean Subset / Journal of the Korean Cancer Association, 대한암학회지

Purpose@#This subgroup analysis of the Korean subset of patients in the phase 3 LASER301 trial evaluated the efficacy and safety of lazertinib versus gefitinib as first-line therapy for epidermal growth factor receptor mutated (EGFRm) non–small cell lung cancer (NSCLC). @*Materials and Methods@#Patients with locally advanced or metastatic EGFRm NSCLC were randomized 1:1 to lazertinib (240 mg/day) or gefitinib (250 mg/day). The primary endpoint was investigator-assessed progression-free survival (PFS). @*Results@#In total, 172 Korean patients were enrolled (lazertinib, n=87; gefitinib, n=85). Baseline characteristics were balanced between the treatment groups. One-third of patients had brain metastases (BM) at baseline. Median PFS was 20.8 months (95% confidence interval [CI], 16.7 to 26.1) for lazertinib and 9.6 months (95% CI, 8.2 to 12.3) for gefitinib (hazard ratio [HR], 0.41; 95% CI, 0.28 to 0.60). This was supported by PFS analysis based on blinded independent central review. Significant PFS benefit with lazertinib was consistently observed across predefined subgroups, including patients with BM (HR, 0.28; 95% CI, 0.15 to 0.53) and those with L858R mutations (HR, 0.36; 95% CI, 0.20 to 0.63). Lazertinib safety data were consistent with its previously reported safety profile. Common adverse events (AEs) in both groups included rash, pruritus, and diarrhoea. Numerically fewer severe AEs and severe treatment–related AEs occurred with lazertinib than gefitinib. @*Conclusion@#Consistent with results for the overall LASER301 population, this analysis showed significant PFS benefit with lazertinib versus gefitinib with comparable safety in Korean patients with untreated EGFRm NSCLC, supporting lazertinib as a new potential treatment option for this patient population.

Molecular and Treatment Characteristics of SMARCB1 or SMARCA4-Deficient Undifferentiated Tumor: Retrospective Case Series / Journal of the Korean Cancer Association, 대한암학회지

SMARCB1 or SMARCA4-deficient sinonasal carcinoma or thoracic undifferentiated tumor has aggressive nature with a poor prognosis. Patients with this disease were diagnosed by immunohistochemistry or next-generation sequencing. Those who were able to receive a surgery tended to be cured, while the others treated with chemotherapy, radiation therapy, or immune checkpoint inhibitor were often insensitive to these therapies. However, one having CD274 (PD-L1) amplification showed the response to immune checkpoint inhibitor and a good prognosis. We believed that this report could provide promising information for determining the optimal treatment option.

Analytical and Clinical Validation of a Highly Sensitive NGS-Based ctDNA Assay with Real-World Concordance in Non–Small Cell Lung Cancer / Journal of the Korean Cancer Association, 대한암학회지

Purpose@#There have been needs to improve the sensitivity of liquid biopsy. This report aims to report the analytical and clinical validation of a next-generation sequencing (NGS)–based circulating tumor DNA (ctDNA) assay. @*Materials and Methods@#Analytical validation was conducted in vitro by evaluating the limit of detection (LOD), precision, and specificity for various genomic aberrations. The real-world performance in non–small cell lung cancer (NSCLC) was assessed by comparing the results of AlphaLiquid100 to the tissue-based results. @*Results@#The LODs with 30 ng input DNA were 0.11%, 0.11%, 0.06%, 0.21%, and 2.13 copies for detecting single nucleotide variants, insertions, deletions, fusions, and copy number alterations (CNA), respectively. Quantitatively, single nucleotide variants/insertions and deletions, fusions, and CNAs showed a good correlation (R2=0.91, 0.40, and 0.65; y=0.95, 1.06, and 1.19) to the manufacturer’s values, and per-base specificities for all types of variants were near 100%. In real-world NSCLC (n=122), key actionable mutations in NSCLC were detected in 60.7% (74/122) with the ctDNA assay. Comparative analysis against the NGS-based tissue results for all key mutations showed positive percent agreement (PPA) of 85.3%. For individual genes, the PPA was as high as 95.7% for epidermal growth factor receptor (EGFR) mutations and 83.3% for ALK translocations. AlphaLiquid100 detected drug-sensitive EGFR mutation at a variant allele frequency as low as 0.02% and also identified an EGFR mutation in a case where tissue sample missed. Blood samples collected post-targeted therapies revealed additional acquired mutations. @*Conclusion@#The AlphaLiquid100 ctDNA assay demonstrates robust analytical validity, offering clinically important information for NSCLC patients.

Effects of Rehabilitation after Knee Arthroplasty by Home Care Pilot Program

Objective@#The nationwide rehabilitation at-home care pilot program aims to provide medical services such as education, counseling, and remote management to patients who require continuous medical management after surgery. This study aims to retrospectively analyze the medical records of patients who participated in the project after knee arthroplasty to investigate the effectiveness of rehabilitation education in home-based care. Method: Data for analysis were collected from the evaluation form which is completed by the physician immediately after surgery and outpatient follow-up. The collected data included the patient’s sex, age, pre-operative functional level, surgical site, and scores on the berg balance scale (BBS) and visual analogue scale (VAS) for evaluating pain. If patients were re-admitted to other medical institutions for rehabilitation, data on the duration of their stay were collected for further analysis. @*Results@#A total of 234 patients were selected and their data were analyzed. The average change in the BBS (ΔBBS) between immediately after surgery and outpatient follow-up was 43.34 ± 5.51, while the average change in the VAS (ΔVAS) was −0.77 ± 2.27. A significant positive correlation (p=0.001) was found between pre-operative functional level and ΔBBS or ΔVAS. However, no significant correlation (p=0.554) was observed between the duration of stay in other medical institutions and ΔBBS or ΔVAS. @*Conclusion@#The home care pilot program is effective in promoting functional recovery and pain relief after knee arthroplasty. It is expected that appropriate rehabilitation education, remote management, and follow-up observation for up to 6 months will sufficiently replace long-term inpatient treatment after knee arthroplasty.

Long-term Outcomes of Ampullary Adenoma According to Resected Margin Status after Endoscopic Papillectomy

Background/Aims@#Endoscopic papillectomy (EP) is increasingly used as an alternative to surgery for managing benign ampullary neoplasms. However, post-EP resection margins are often positive or indeterminate, and there is no consensus on the management of ampullary adenomas with positive or indeterminate margins after EP. This study was designed to compare the longterm outcomes between resected margin-negative (RMN) and resected margin-positive/indeterminate (RMPI) groups and to identify factors associated with clinical outcomes. @*Methods@#This retrospective analysis included patients with ampullary adenoma without evidence of adenocarcinoma who underwent EP between 2004 and 2016. The RMN and RMPI groups were compared for recurrence rates and recurrence-free duration during a mean followup duration of 71.7±39.8 months. Factors related to clinical outcomes were identified using multivariate analysis. @*Results@#Of the 129 patients who underwent EP, 82 were in the RMN group and 47 were in the RMPI group. The RMPI group exhibited a higher recurrence rate compared to the RMN group (14.6% vs 34.0%, p=0.019). However, the recurrence-free duration was not significantly different between the groups (34.7±32.6 months vs 36.2±27.4 months, p=0.900). Endoscopic treatment successfully managed recurrence in both groups (75% vs 75%). Submucosal injection was a significant risk factor for residual lesions (hazard ratio, 4.11; p=0.009) and recurrence (hazard ratio, 2.57; p=0.021). @*Conclusions@#Although ampullary adenomas with positive or indeterminate margins after EP showed a higher rate of recurrence at long-term follow-up, endoscopic treatment was effective with favorable long-term outcomes. Submucosal injection prior to resection was associated with increased risk of recurrence and residual lesions.

Emerging Concept of Intracranial Arterial Diseases: The Role of High Resolution Vessel Wall MRI / 대한뇌졸중학회지

Intracranial arterial disease (ICAD) is a heterogeneous condition characterized by distinct pathologies, including atherosclerosis. Advances in magnetic resonance technology have enabled the visualization of intracranial arteries using high-resolution vessel wall imaging (HR-VWI). This review summarizes the anatomical, embryological, and histological differences between the intracranial and extracranial arteries. Next, we review the heterogeneous pathophysiology of ICAD, including atherosclerosis, moyamoya or RNF213 spectrum disease, intracranial dissection, and vasculitis. We also discuss how advances in HR-VWI can be used to differentiate ICAD etiologies. We emphasize that one should consider clinical presentation and timing of imaging in the absence of pathology-radiology correlation data. Future research should focus on understanding the temporal profile of HR-VWI findings and developing quantitative interpretative approaches to improve the decision-making and management of ICAD.

Approaches to Consciousness Assessment in Neurocritically Ill Patients

The majority of neurocritically ill patients have disorders of consciousness. Both level and content of consciousness should be assessed repeatedly throughout the course of patient care. In this review, we describe the definition and diagnostic criteria for disorders of consciousness, and the neurological examination and standardized neurobehavioral assessment tools as methods of assessing consciousness. Next, we will discuss neurophysiological and neuroimaging tests as tools for assessing consciousness: automated quantitative pupillometry, electroencephalogram, evoked potentials, brain imaging, functional near-infrared spectroscopy, and biomarkers. We discuss the clinical utility of each assessment tool and the importance of a multimodal approach in the diagnosis, treatment, and prognostication of disorders of consciousness.

Relationship between midfacial fractures and maxillary sinus pathology

Background@#Midfacial fractures frequently involve the maxillary sinus, leading to maxillary sinus pathology. We aimed to examine the incidence and contributing factors of maxillary sinus pathology in patients who underwent open reduction and internal fixation (ORIF) for midfacial fractures. @*Methods@#A retrospective analysis was conducted on patients who underwent ORIF for midfacial fractures at our department over the past 10 years. The incidence of maxillary sinus pathology was identified clinically and/or by computed tomography findings. Factors that significantly influenced the groups with and without maxillary sinus pathology were examined. @*Results@#The incidence of maxillary sinus pathology in patients who underwent ORIF for midfacial fractures was found to be 11.27%, with sinusitis being the most common pathology. Maxillary sinus pathology was significantly associated with the presence of a blowout fracture involving both the medial and the inferior orbital walls. Factors such as sex, age, diabetes mellitus, hypertension, smoking, inflammatory disease, follow-up period, use of absorbable plates, and use of titanium plates did not have a significant impact on the development of maxillary sinus pathology. @*Conclusion@#The incidence of maxillary sinus pathology in patients who underwent ORIF for midfacial fractures was relatively low, and in most cases, it resolved without the need for specific treatment. Consequently, there may not be a significant need for concern regarding postoperative maxillary sinus pathology.

Survival Benefit of Adjuvant Chemotherapy in Patients with Pancreatic Ductal Adenocarcinoma Who Underwent Surgery Following Neoadjuvant FOLFIRINOX / Journal of the Korean Cancer Association, 대한암학회지

Purpose@#The benefit of adjuvant chemotherapy following curative-intent surgery in pancreatic ductal adenocarcinoma (PDAC) patients who had received neoadjuvant FOLFIRINOX is unclear. This study aimed to assess the survival benefit of adjuvant chemotherapy in this patient population. @*Materials and Methods@#This retrospective study included 218 patients with localized non-metastatic PDAC who received neoadjuvant FOLFIRINOX and underwent curative-intent surgery (R0 or R1) between January 2017 and December 2020. The association of adjuvant chemotherapy with disease-free survival (DFS) and overall survival (OS) was evaluated in overall patients and in the propensity score matched (PSM) cohort. Subgroup analysis was conducted according to the pathology-proven lymph node status. @*Results@#Adjuvant chemotherapy was administered to 149 patients (68.3%). In the overall cohort, the adjuvant chemotherapy group had significantly improved DFS and OS compared to the observation group (DFS: median, 13.8 months [95% confidence interval (CI), 11.0 to 19.1] vs. 8.2 months [95% CI, 6.5 to 12.0]; p < 0.001; and OS: median, 38.0 months [95% CI, 32.2 to not assessable] vs. 25.7 months [95% CI, 18.3 to not assessable]; p=0.005). In the PSM cohort of 57 matched pairs of patients, DFS and OS were better in the adjuvant chemotherapy group than in the observation group (p < 0.001 and p=0.038, respectively). In the multivariate analysis, adjuvant chemotherapy was a significant favorable prognostic factor (vs. observation; DFS: hazard ratio [HR], 0.51 [95% CI, 0.36 to 0.71; p < 0.001]; OS: HR, 0.45 [95% CI, 0.29 to 0.71; p < 0.001]). @*Conclusion@#Among PDAC patients who underwent surgery following neoadjuvant FOLFIRINOX, adjuvant chemotherapy may be associated with improved survival. Randomized studies should be conducted to validate this finding.

Targeting CD73 to Overcomes Resistance to First-Generation EGFR Tyrosine Kinase Inhibitors in Non–Small Cell Lung Cancer / Journal of the Korean Cancer Association, 대한암학회지

Purpose@#In patients with epidermal growth factor receptor (EGFR)-mutant non–small cell lung cancer (NSCLC), EGFR tyrosine kinase inhibitors (TKIs) improve response rate and survival. However, most patients eventually develop resistance. This study aimed to identify the role of CD73 in EGFR-mutant NSCLC and explore whether CD73 inhibition may serve as a therapeutic strategy in NSCLC patients with acquired resistance to EGFR-TKIs. @*Materials and Methods@#We evaluated the prognostic role of CD73 expression in EGFR-mutant NSCLC using tumor samples from a single institution. We silenced CD73 in EGFR-TKI–resistant cell lines using short hairpin RNA (shRNA) targeting CD73 and also transfected a vector alone as a negative control. Using these cell lines, cell proliferation and viability assays, immunoblot assays, cell cycle analysis, colony-forming assays, flow cytometry, and apoptosis analysis were performed. @*Results@#High expression of CD73 was associated with shorter survival in patients with metastatic EGFR-mutant NSCLC treated with first-generation EGFR-TKI. CD73 inhibition synergistically inhibited cell viability with first-generation EGFR-TKI treatment compared with the negative control. When CD73 inhibition and EGFR-TKI treatment were combined, G0/G1 cell cycle arrest was induced through the regulation of p21 and cyclin D1. In addition, the apoptosis rate was increased in CD73 shRNA-transfected cells treated with EGFR-TKI. @*Conclusion@#High expression of CD73 adversely affects the survival of patients with EGFR-mutant NSCLC. The study demonstrated that inhibiting CD73 in EGFR-TKI–resistant cell lines resulted in increased apoptosis and cell cycle arrest, which overcame the acquired resistance to first-generation EGFR-TKIs. Further research is needed to determine whether blocking CD73 plays a therapeutic role in EGFR-TKI–resistant patients with EGFR-mutant NSCLC.

Long-term Outcomes of Endoscopic Intraductal Radiofrequency Ablation for Ampullary Adenoma with Intraductal Extension after Endoscopic Snare Papillectomy

Background/Aims@#There are limitations in treating ampullary adenomas with intraductal extension using conventional endoscopic modalities. Endoscopic intraductal radiofrequency ablation (ID-RFA) may be useful for treating intraductal (common bile duct [CBD] and/or pancreatic duct [PD]) extensions of ampullary adenomas, but long-term data are lacking. We thus evaluated the long-term outcomes of endoscopic ID-RFA for managing ampullary adenomas with intraductal extension. @*Methods@#Prospectively collected endoscopic ID-RFA database at Asan Medical Center was reviewed to identify consecutive patients with ampullary adenoma who underwent ID-RFA for intraductal extension between January 2018 and August 2021. Technical success, short-term and long-term clinical success, and adverse events were evaluated. @*Results@#A total of 29 patients (14 CBD, 1 PD, and 14 CBD and PD) were analyzed. All patients had undergone endoscopic snare papillectomy prior to ID-RFA. A median of one session of IDRFA (range, 1 to 3) for residual or relapsed intraductal extension of ampullary adenoma were successfully performed (technical success=100%). Both biliary and pancreatic stenting were routinely performed after ID-RFA to prevent ductal stricture. After a median follow-up of 776 days (interquartile range, 470 to 984 days), the short-term and long-term clinical success rates were 93% and 76%, respectively. Seven patients experienced procedural adverse events and three patients developed ductal strictures. @*Conclusions@#Endoscopic ID-RFA showed good long-term outcomes in treating residual or relapsed ampullary adenomas with intraductal extension. Repeated ID-RFA may be considered as an option for managing recurrence. Further studies are needed to standardize the procedure.

Association between urinary chloride excretion and progression of coronary artery calcification in patients with nondialysis chronic kidney disease: results from the KNOW-CKD study

Urine chloride has recently been suggested as a biomarker of renal tubule function in patients with nondialysis chronic kidney disease (CKD), as low urinary chloride concentration is associated with an increased risk of CKD progression. We investigate the association between urinary chloride excretion and the progression of coronary artery calcification (CAC). Methods: A total of 1,065 patients with nondialysis CKD were divided into tertiles by spot urine chloride-to-creatinine ratios. The 1st, 2nd, and 3rd tertiles were defined as low, moderate, and high urinary chloride excretion, respectively. The study outcome was CAC progression, which was defined as an increase in coronary artery calcium score of more than 200 Agatston units during the 4-year follow-up period. Results: Compared to moderate urinary chloride excretion, high urinary chloride excretion was associated with decreased risk of CAC progression (adjusted odds ratio, 0.379; 95% confidence interval, 0.190–0.757), whereas low urinary chloride excretion was not associated with risk of CAC progression. Restricted cubic spine depicted an inverted J-shaped curve, with a significant reduction in the risk of CAC progression in subjects with high spot urine chloride-to-creatinine ratios. Conclusion: High urinary chloride excretion is associated with decreased risk of CAC progression in patients with nondialysis CKD.

A comparative study of rubber band ligation versus BANANA-Clip in grade 1 to 3 internal hemorrhoids

Purpose@#Rubber band ligation (RBL) for grade 1 to 3 internal hemorrhoids is a well-established modality of choice. But RBL is also a kind of surgical treatment; it is not free from complications (e.g., delayed bleeding [DB], rectal stenosis). This study aimed to investigate the results of the comparative treatment of RBL and BANANA-Clip (BC; Endovision). @*Methods@#Study participants were 632 consecutive patients with grade 1 to 3 internal hemorrhoids attended to Department of Colorectal Surgery at Wellness Hospital between January 2010 and May 2019. We retrospectively reviewed the incidence rate of complications, including DB between RBL and BC. @*Results@#There were 304 male and 328 female patients, whose ages ranged from 15 to 84 years, with a mean age of 45.7 years. The common symptom and cause of treatment was prolapse (70.1%). The number of ligated sites was 1.49±0.57 in the RBL group and 1.99±0.77 in the BC group. RBL showed a significantly higher incidence of DB (3.5%) compared to BC (0%) (P=0.001). The 1-year success rate was 95.9% in the RBL group and 99.7% in the BC group (P=0.005). @*Conclusion@#In our study, BC was more reliable in treating grade 1 to 3 internal hemorrhoids with higher success rates and less post-ligation complications, especially DB, compared to RBL.

Efficacy and Safety of Ceritinib 450 mg/day with Food and 750 mg/day in Fasted State in Treatment-Naïve Patients with ALK+ Non–Small Cell Lung Cancer: Results from the ASCEND-8 Asian Subgroup Analysis / Journal of the Korean Cancer Association, 대한암학회지

Purpose@#Previous report from the ASCEND-8 trial showed consistent efficacy with less gastrointestinal (GI) toxicity in patients with anaplastic lymphoma kinase-rearranged (ALK+) advanced/metastatic non–small cell lung cancer (NSCLC) treated with ceritinib 450-mg with food compared with 750-mg fasted. In this subgroup analysis, we report outcomes in Asian patients of the ASCEND-8 trial. @*Materials and Methods@#Key efficacy endpoints were blinded independent review committee (BIRC)–assessed overall response rate (ORR) and duration of response (DOR) evaluated per Response Evaluation Criteria in Solid Tumors v1.1. Other efficacy endpoints were investigator-assessed ORR and DOR; BIRC- and investigator-assessed progression-free survival (PFS) and disease control rate; overall survival (OS). Safety was evaluated by frequency and severity of adverse events. @*Results@#At final data cutoff (6 March 2020), 198 treatment-naïve patients were included in efficacy analysis, of which 74 (37%) comprised the Asian subset; 450-mg fed (n=29), 600-mg fed (n=19), and 750-mg fasted (n=26). Baseline characteristics were mostly comparable across study arms. At baseline, more patients in 450-mg fed arm (44.8%) had brain metastases than in 750-mg fasted arm (26.9%). Per BIRC, patients in the 450-mg fed arm had a numerically higher ORR, 24-month DOR rate and 24-month PFS rate than the 750-mg fasted arm. The 36-month OS rate was 93.1% in 450-mg fed arm and 70.9% in 750-mg fasted arm. Any-grade GI toxicity occurred in 82.8% and 96.2% of patients in the 450-mg fed and 750-mg fasted arms, respectively. @*Conclusion@#Asian patients with ALK+ advanced/metastatic NSCLC treated with ceritinib 450-mg fed showed numerically higher efficacy and lower GI toxicity than 750-mg fasted patients.

Comparison of dominant and nondominant C3 deposition in primary glomerulonephritis

Alternative complement pathway dysregulation plays a key role in glomerulonephritis (GN) and is associated with C3 deposition. Herein, we examined pathological and clinical differences between cases of primary GN with C3-dominant (C3D-GN) and nondominant (C3ND-GN) deposition. Methods: We extracted primary GN data from the Korean GlomeruloNEphritis sTudy (KoGNET). C3D-GN was defined as C3 staining two grades greater than C1q, C4, and immunoglobulin via immunofluorescence analysis. To overcome a large difference in the number of patients between the C3D-GN and C3ND-GN groups (31 vs. 9,689), permutation testing was used for analysis. Results: The C3D-GN group exhibited higher serum creatinine (p ≤ 0.001), a greater prevalence of estimated glomerular filtration rate of <60 mL/min/1.72 m2 (p ≤ 0.001), higher (but not significantly so) C-reactive protein level, and lower serum C3 level (p ≤ 0.001). Serum albumin, urine protein/creatinine ratio, number of patients who progressed to end-stage renal disease, and all-cause mortality were comparable between groups. Interstitial fibrosis and mesangial cellularity were greater in the C3D-GN group (p = 0.04 and p = 0.01, respectively) than in the C3ND-GN group. C3 deposition was dominant in the former group (p < 0.001), in parallel with increased subendothelial deposition (p ≤ 0.001). Conclusion: Greater progression of renal injury and higher mortality occurred in patients with C3D-GN than with C3ND-GN, along with pathologic differences in interstitial and mesangial changes.

Effect of Extra-Corporeal Shockwave Treatment in a Patient with Patellofemoral Pain Syndrome

Patellofemoral pain syndrome, one of the most common knee problems, is diagnosed by excluding other diseases that can cause similar pain or symptoms. The authors have been wondered about why patellofemoral pain syndrome can cause severe pain even when there are no structural abnormalities in the knee. For these reasons, if there are no structural abnormalities in the knee itself, the authors have strongly suspected referred pain due to injury of the surround structures, especially quadriceps femoris. Therefore, the authors want to report the successful experience in reducing knee pain and improving symptoms by performing extra-corporeal shockwave treatment in a patient who is concurred with diagnosis of patellofemoral pain syndrome and is suspected of having myofascial pain syndrome or chronic muscle injury of quadriceps femoris.

Effects of Telephone Hotline Counseling Program on Stroke Care / 보건행정학회지

Background@#This study focuses on the establishment and operation of a stroke patient hotline program to help patients and their caregivers determine when acute neurological changes require emergency attention.Method: The stroke hotline was established at the Gyeonggi Regional Cerebrovascular Center, Seoul National University Bundang Hospital, in June 2016. Patients diagnosed with stroke during admission or in outpatient clinics were registered and provided with stroke education. Consulting nurses managed hotline calls and made decisions about outpatient schedules or emergency room referrals, consulting physicians when necessary. The study analyzed consultation records from June 2016 to December 2020, assessing consultation volumes and types. Outcomes and hotline satisfaction were also evaluated. @*Results@#Over this period, 6,851 patients were registered, with 1,173 patients (18%) undergoing 3,356 hotline consultations. The average monthly consultation volume increased from 29.2 cases in 2016 to 92.3 cases in 2020. Common consultation types included stroke symptoms (22.3%), blood pressure/glucose inquiries (12.8%), and surgery/procedure questions (12.6%). Unexpected outpatient visits decreased from 103 cases before the hotline to 81 cases after. Among the 2,244 consultations between January 2019 and December 2020, 9.6% were recommended hospital visits, with two cases requiring intra-arterial thrombectomy. Patient satisfaction ratings of 9–10 points increased from 64% in 2019 to 69% in 2020. @*Conclusion@#The stroke hotline program effectively reduced unexpected outpatient visits and achieved high patient satisfaction.Expanding the program could enhance the management of stroke-related neurological symptoms and minimize unnecessary healthcare resource utilization.

Acquired Resistance Mechanism of EGFR Kinase Domain Duplication to EGFR TKIs in Non–Small Cell Lung Cancer / Journal of the Korean Cancer Association, 대한암학회지

Purpose@#Epidermal growth factor receptor kinase domain duplication (EGFR-KDD) is a rare and poorly understood oncogenic mutation in non–small cell lung cancer (NSCLC). We aimed to investigate the acquired resistance mechanism of EGFR-KDD against EGFR-TKIs. @*Materials and Methods@#We identified EGFR-KDD in tumor tissue obtained from a patient with stage IV lung adenocarcinoma and established the patient-derived cell line SNU-4784. We also established several EGFR-KDD Ba/F3 cell lines: EGFR-KDD wild type (EGFR-KDDWT), EGFR-KDD domain 1 T790M (EGFR-KDDD1T), EGFR-KDD domain 2 T790M (EGFR-KDDD2T), and EGFR-KDD both domain T790M (EGFR-KDDBDT). We treated the cells with EGFR tyrosine kinase inhibitors (TKIs) and performed cell viability assays, immunoblot assays, and ENU (N-ethyl-N-nitrosourea) mutagenesis screening. @*Results@#In cell viability assays, SNU-4784 cells and EGFR-KDDWT Ba/F3 cells were sensitive to 2nd generation and 3rd generation EGFR TKIs. In contrast, the T790M-positive EGFR-KDD Ba/F3 cell lines (EGFR-KDDT790M) were only sensitive to 3rd generation EGFR TKIs. In ENU mutagenesis screening, we identified the C797S mutation in kinase domain 2 of EGFR-KDDBDT Ba/F3 cells. Based on this finding, we established an EGFR-KDD domain 1 T790M/domain 2 cis-T790M+C797S (EGFR-KDDT/T+C) Ba/F3 model, which was resistant to EGFR TKIs and anti-EGFR monoclonal antibody combined with EGFR TKIs. @*Conclusion@#Our study reveals that the T790M mutation in EGFR-KDD confers resistance to 1st and 2nd generation EGFR TKIs, but is sensitive to 3rd generation EGFR TKIs. In addition, we identified that the C797S mutation in kinase domain 2 of EGFR-KDDT790M mediates a resistance mechanism against 3rd generation EGFR TKIs.

Prognosis and Clinical Characteristics of Patients with Pancreatic Ductal Adenocarcinoma Diagnosed by Endoscopic Ultrasonography but Indeterminate on Computed Tomography

Background/Aims@#Endoscopic ultrasonography (EUS) provides high-resolution images and is superior to computed tomography (CT) scan in diagnosing small pancreatic ductal adenocarcinoma (PDAC). As a result, the use of EUS for early detection of PDAC has attracted attention. This study aimed to identify the clinical and radiological characteristics of patients with PDAC diagnosed by EUS but not found on CT scan. @*Methods@#The medical records of patients diagnosed with PDAC at 12 tertiary referral centers in Korea from January 2003 to April 2019 were reviewed. This study included patients with pancreatic masses not clearly observed on CT scan but identified on EUS. The clinical characteristics and radiological features of the patients were analyzed, and survival analysis was performed. @*Results@#A total of 83 patients were enrolled. The most common abnormal CT findings other than a definite mass was pancreatic duct dilatation, which was identified in 61 patients (73.5%). All but four patients underwent surgery. The final pathologic stages were as follows: IA (n=31, 39.2%), IB (n=8, 10.1%), IIA (n=20, 25.3%), IIB (n=17, 21.5%), III (n=2, 2.5%), and IV (n=1, 1.4%). The 5-year survival rate of these patients was 50.6% (95% confidence interval, 38.8% to 66.7%). Elevated liver function testing and R1 resection emerged as significant predictors of mortality in the multivariable Cox regression analysis. @*Conclusions@#This multicenter study demonstrated favorable long-term prognosis in patients with PDAC diagnosed by EUS but indeterminate on CT scan. EUS should be considered for patients with suspected PDAC but indeterminate on CT scan.

Mediating effect of psychological resilience between perceived organizational support and presenteeism among medical staff in the prevention and control of COVID-19 / 中国职业医学

@#Objective （ ） To explore the influence of perceived organizational support POS and psychological resilience on （ - ）Methods presenteeism behavior in medical staff in the prevention and control of coronavirus disease COVID 19 . Doctors - - and nurses engaged in the front line work of prevention and control in the four designated hospitals for the treatment of COVID ， 19 in Guangdong Province Hunan Province and Jiangsu Province were selected as the research subjects using a random cluster ， - - sampling method. The Survey of Perceived Organizational Support Scale the 10 item Connor Davidson Resilience Scale and - ， Results Standford Presenteeism Scale 6 were used to investigate their POS psychological resilience and presenteeism. The ， （ ），（ ） （ ）， total scores of POS psychological resilience and presenteeism were 44.9±7.6 31.2±5.7 and 18.5±3.7 respectively. （ Both POS and psychological resilience had negative effect on presenteeism standardized regression coefficient were −0.59 ， P ） ［ and −0.38 both <0.01 . Psychological resilience played a partial mediating role between POS and presenteeism 95% （ - ）， ］ Conclusion confidence interval −0.22 −0.09 the mediating effect ratio was 23.4% . Both POS and psychological - ， resilience can directly affect the presenteeism behavior of medical staff in COVID 19 prevention and control and POS can also indirectly affect their presenteeism by affecting psychological resilience.