Treatment and Survival Outcome of BRAF-Mutated Metastatic Colorectal Cancer: A Retrospective Matched Case-Control Study

Background

Somatic v-Raf murine sarcoma viral oncogene homolog B (BRAF) mutation, present in approximately 10% of metastatic colorectal cancer (mCRC) cases, is associated with poor prognosis. Patient outcome outside of clinical trials has only been reported in small series. We report real-world data on treatment and survival for BRAF-mutated (MT) patients at a single tertiary center, compared with a matched BRAF wild type (WT) control group.

The role of exosomes and miRNAs in drug‐resistance of cancer cells

Chemotherapy, one of the principal approaches for cancer patients, plays a crucial role in controlling tumor progression. Clinically, tumors reveal a satisfactory response following the first exposure to the chemotherapeutic drugs in treatment. However, most tumors sooner or later become resistant to even chemically unrelated anticancer agents after repeated treatment. The reduced drug accumulation in tumor cells is considered one of the significant mechanisms by decreasing drug permeability and/or increasing active efflux (pumping out) of the drugs across the cell membrane. The mechanisms of treatment failure of chemotherapeutic drugs have been investigated, including drug efflux, which is mediated by extracellular vesicles (EVs). Exosomes, a subset of EVs with a size range of 40–150 nm and a lipid bilayer membrane, can be released by all cell types. They mediate specific cell‐to‐cell interactions and activate signaling pathways in cells they either fuse with or interact with, including cancer cells. Exosomal RNAs are heterogeneous in size but enriched in small RNAs, such as miRNAs. In the primary tumor microenvironment, cancer‐secreted exosomes and miRNAs can be internalized by other cell types. MiRNAs loaded in these exosomes might be transferred to recipient niche cells to exert genome‐wide regulation of gene expression. How exosomal miRNAs contribute to the development of drug resistance in the context of the tumor microenvironment has not been fully described. In this review, we will highlight recent studies regarding EV‐mediated microRNA delivery in formatting drug resistance. We also suggest the use of EVs as an advancing method in antiresistance treatment.     

The association between the serum vitamin D levels and the stroke lesion size,functional ability,and cognition in elderly Korean ischemic stroke patients

The purpose of this study was to confirm the association between the serum vitamin D levels and ischemic stroke lesion size, functional ability, and cognitive function in elderly ischemic stroke patients. This study included Korean ischemic stroke patients aged 65 to 85 years. The size of the lesion was measured in brain images taken within 24 hours of hospitalization. The level of 25-(OH) Vitamin D (ng/mL), a metabolite of vitamin D, in the serum collected within 48 hours of hospitalization, and the modified Barthel index (MBI), gait performance, the muscle power of hip and knee extensors on the hemiplegic side, and mini-mental status examination (MMSE) were recorded within 1 week of the onset of the disease. Each factor was compared through correlation analysis, and the significance was confirmed using the Spearman correlation coefficient method. The association between the serum vitamin D levels and the size of the ischemic stroke lesion, the MBI, gait performance, the muscle power of hip and knee extensors on the hemiplegic side, and the MMSE were analyzed. It was confirmed that there was a significant correlation between all the factors (P < .005). In patients with serum vitamin D levels of ≥ 30 ng/mL, both the functional ability and cognitive functions were better than in patients lower than 30 ng/mL. We confirmed the lower the level of serum vitamin D levels, the larger the size of the ischemic stroke lesion when it occurred in elderly Koreans. And we confirmed that serum vitamin D levels affected the functional ability and cognitive function. And we recommend that elderly Koreans should maintain their blood vitamin D level above 30 ng/mL. We believe that this will help preserve the functional ability and cognitive function when ischemic stroke occurred.     

Outcomes of lipectomy in patients with advanced unilateral upper extremity lymphedema with regard to the difference in time required for indocyanine green to reach the axilla: A retrospective cohort study in a single center

This study aimed to compare and analyze the prognosis after lipectomy with respect to the difference in time required for indocyanine green (ICG) to reach the axilla in patients with advanced unilateral upper extremity lymphedema. The study population was divided into 2 groups, according to the time required by ICG to reach the axilla after injection, that is, <1 hour (<1 hour; n = 9) and over 1 hour (>1 hour; n = 8). The patient’s arm volume was examined before surgery and up to 12 months after surgery. The volume difference between the 2 groups was compared using the excess volume ratio. Statistically significant differences were not observed before surgery (P = .847) and 1 month (P = .336), 3 months (P = .630), and 6 months after surgery (P = .124) between the excess volume ratio values of the < 1 hour and > 1 hour groups. A statistically significant difference was confirmed 12 months after surgery (P = .034). The difference in the time when ICG reached the axilla in patients with lymphedema was associated with prognosis after lipectomy. The difference in time could possibly be used as a variable to classify the progress of lymphedema in the future.     

Performance of Remsima® Monitor Drug Level versus RIDASCREEN IFX Monitoring in therapeutic drug monitoring of infliximab in patients with inflammatory bowel disease: A study of diagnostic accuracy

Therapeutic drug monitoring (TDM) is effective in optimizing the efficacy of infliximab in patients with inflammatory bowel disease (IBD). An affordable way of monitoring is in high demand. This study evaluated the analytical and clinical performances of the newly available Remsima monitor kits and compared them with the established enzyme-linked immunosorbent assay kits. The trough level of infliximab in patients with IBD treated with an infliximab originator (Remicade) or biosimilar compounds (Remsima and Remaloce) was measured using a Remsima® Monitor Drug Level (Remsima) kit at the Samsung Medical Center, Seoul, Korea. Twenty-six plasma samples were collected immediately before the infusion of infliximab from 18 patients with IBD (Remicade, n = 8; Remsima, n = 6; and Remaloce, n = 4). The intra-assay intraclass correlation coefficient (ICC) of the RIDA and Remsima kits was 0.951 (95% CI = 0.908–0.976) and 0.990 (95% CI = 0.981–0.995). The inter-assay ICC of infliximab trough level between the RIDA and Remsima kits was very high (R = 0.971; 95% CI = 0.935–0.987), and the mean difference between the kits was 1.458 (95% limits of agreement = −3.302 to 6.219). The intra- and inter-assay reliabilities of all types of infliximab did not show significant differences. Qualitative stratification revealed substantial similarities between the kits (weighted kappa = 0.798). This study indicated that the Remsima kit was reproducible and highly correlated with the RIDA kit.     

Association of renal function with muscle strength in Korean adults: A population-based study using the Korea National Health and Nutrition Examination Surveys (KNHANES) from 2014 to 2018

Hand grip strength (HGS), a simple measure of upper limb muscle function, can be used to assess overall muscular strength, and reduced HGS in patients with poor renal functions has been observed. This study examined the associations between renal function and HGS, a surrogate marker of muscular strength, among a stratified sample of Korean adults. This study obtained data from the Korea National Health and Nutrition Examination Survey from 2014 to 2018, a cross-sectional and nationally representative survey conducted by the Korea Centers for Diseases Control and Prevention. In men, low muscle strength (LMS) and normal muscle strength (NMS) were defined as HGS < 28.9 kg and HGS ≥ 28.9 kg, respectively. In women, LMS and NMS were considered as HGS < 16.8 kg and HGS ≥ 16.8 kg, respectively. Of the 25,746 subjects in this study, there were 3603 (14.0%) and 22,143 (86.0%) subjects who displayed LMS and NMS, respectively. Subjects with estimated glomerular filtration rate (eGFR) < 60 mL/min/1.73 m² had a higher risk of developing LMS than those with eGFR ≥ 60 mL/min/1.73 m² after adjusting for age (odds ratio, 1.772; 95% CI, 1.498–2.096); the significant differences remained after adjusting for other factors including age. Similar tendencies were shown in men and women when analyzed according to gender; however, the risk of developing LMS was higher in men than in women. Results showed that decreased renal function was likely to contribute to an increased prevalence of LMS based on HGS. This association may assist in developing better strategies to estimate renal function in clinical or public health practice.     

Clinical Characteristics of Korean Patients with Elderly-Onset Crohn’s Disease: Results from the Prospective CONNECT Study

The clinical course and prognosis of patients with elderly-onset Crohn’s disease (CD) remain unclear. This study aimed to analyze the clinical characteristics and outcomes of elderly-onset CD patients from the prospective CONNECT study cohort, a nationwide, multicenter cohort study of patients with CD in Korea. Among a total of 1,175 patients in the prospective CONNECT study cohort, 94 patients (Montreal age A3) were included and divided into two groups according to their age at diagnosis: the elderly-onset group (diagnosed with CD after 60 years of age, n=26, 67.54±6.7 years) and late adult-onset group (diagnosed as CD at age 41 to 59 years, n=68, 48.06±5.1 years). The elderly-onset group was characterized by a lower Crohn’s disease activity index at diagnosis (124.89±101.9 vs 189.55±128.6, p=0.023) and higher rates of previous anti-tuberculosis treatment (34.6% vs 4.4%, p<0.001) than the late adult-onset group. Compared with the late adult-onset group, the elderly-onset group showed a significantly less use of thiopurines (p=0.003), as well as anti-tumor necrosis factor-alpha agents (p=0.047). Additionally, the elderly-onset group was less likely to require bowel resection than the late adult-onset group (p=0.067), suggesting that elderly-onset CD patients in Korea appear to have more favorable clinical outcomes than late adult-onset CD patients. (Gut Liver 2022;16:-1000)     

Epidemiological Trends of Pediatric Inflammatory Bowel Disease in Korea: A Multicenter Study of the Last 3 Years Including the COVID-19 Era

BackgroundStudies on how the coronavirus pandemic has affected pediatric inflammatory bowel disease (PIBD) are lacking. We aimed to investigate the trends in epidemiology, characteristics, initial management, and short-term outcomes of PIBD in South Korea over the recent three years including the era of coronavirus disease 2019 (COVID-19).MethodsThis multicenter study retrospectively investigated temporal trends in the epidemiology of PIBD in Korea. Annual occurrences, disease phenotypes, and initial management at diagnosis were analyzed from January 2018 to June 2021.ResultsA total of 486 patients from 17 institutions were included in this epidemiological evaluation. Analysis of the occurrence trend confirmed a significant increase in PIBD, regardless of the COVID-19 pandemic. In Crohn’s disease, patients with post-coronavirus outbreaks had significantly higher fecal calprotectin levels than those with previous onset (1,339.4 ± 717.04 vs. 1,595.5 ± 703.94, P = 0.001). Patients with post-coronavirus-onset ulcerative colitis had significantly higher Pediatric Ulcerative Colitis Activity Index scores than those with previous outbreaks (48 ± 17 vs. 36 ± 15, P = 0.004). In the initial treatment of Crohn’s disease, the use of 5-aminosalicylic acid (5-ASA) and steroids significantly decreased (P = 0.006 and 0.001, respectively), and enteral nutrition and the use of infliximab increased significantly (P = 0.045 and 0.009, respectively). There was a significant increase in azathioprine use during the initial treatment of ulcerative colitis (P = 0.020).ConclusionRegardless of the COVID-19 pandemic, the number of patients with PIBD is increasing significantly annually in Korea. The initial management trends for PIBD have also changed. More research is needed to establish appropriate treatment guidelines considering the epidemiological and clinical characteristics of Korean PIBD.     

Relative Effectiveness of COVID-19 Vaccination in Healthcare Workers: 3-Dose Versus 2-Dose Vaccination

The omicron variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is known to have high infectivity and is more likely to evade vaccine immunity. However, booster vaccination is expected to strengthen cross-reactive immunity, thereby increasing the vaccine effectiveness (VE). This study aimed to evaluate the relative VE of the 3-dose (booster) vaccination compared with the 2-dose primary series vaccination in healthcare workers during omicron variant-dominant periods. During the omicron-dominant period from February 1, 2022 to February 28, 2022, a 1:1 matched case-control study was conducted. Healthcare workers with positive SARS-CoV-2 test results were classified as positive cases, whereas those with negative results served as controls. Compared with the 2-dose primary series vaccination, booster vaccination with mRNA vaccine showed moderate VE (53.1%). However, in multivariate analysis including the time elapsed after vaccination, the significant VE disappeared, reflecting the impact of recent vaccination rather than the third dose itself.