Purpose: Developmental endothelial locus-1 (DEL-1) plays a role in regulating neutrophil migration within the periodontium. The objective of this study was to evaluate the levels of DEL-1 in saliva and gingival crevicular fluid (GCF), as well as the number of neutrophils in patients with periodontitis. Methods: Forty systemically healthy, non-smoking periodontitis patients participated in this study. Clinical periodontal parameters, including the plaque index, probing pocket depth (PPD), clinical attachment level, bleeding on probing, modified sulcular bleeding index, and marginal bone level, were measured. Levels of DEL-1, interleukin (IL)-1β, IL-6, and IL-8 in unstimulated saliva samples, as well as DEL-1 in the GCF of 3 teeth from each participant, were assessed. Neutrophil counts in oral rinse and GCF samples were recorded. Spearman correlation coefficients were used to examine the correlation between protein levels, clinical parameters, and neutrophil quantities. Participants were divided into 2 age groups (those under 50 years and those 50 years or older) in order to investigate potential age-related differences. Results: DEL-1 levels in the GCF showed a negative relationship with PPD (sum). Neutrophils in oral rinse samples were positively correlated with PPD, IL-8, and IL-1β levels. Neutrophils in GCF exhibited a positive correlation with PPD (sum). Salivary DEL-1 levels showed correlations with IL-8 and IL-1β, but not with the clinical parameters of periodontitis. Conclusions The negative relationship observed between PPD and GCF DEL-1 levels is consistent with the proposed protective role of DEL-1.

Purpose: Alectinib and brigatinib are second-generation anaplastic lymphoma receptor tyrosine kinases (ALKs) that are widely used as first-line therapy for treating ALK-positive advanced non–small cell lung cancer (NSCLC). Given the lack of a head-to-head comparison of these drugs as first-line therapies, this retrospective observational study aimed to compare the real-world efficacy and safety of alectinib and brigatinib. Materials and Methods: Patients who received alectinib or brigatinib as the first-line treatment for ALK-positive advanced NSCLC were evaluated for clinical outcomes of objective response rate (ORR), intracranial ORR, time to next treatment (TTNT), progression-free survival (PFS), overall survival (OS), and safety profiles. Results: Of 208 patients who received either alectinib or brigatinib as a first-line treatment, 176 received alectinib and 32 received brigatinib. At the data cutoff point, the median follow-up duration was 16.5 months (95% confidence interval [CI], 14.7 to 18.3) in the brigatinib group and 27.5 months (95% CI, 24.6 to 30.4) in the alectinib group. The ORR was 92.5% with alectinib and 93.8% for brigatinib. The intracranial ORR rates were 92.7% (38/41) and 100% (10/10), respectively. The rate of PFS at 12 months was comparable between the alectinib group and the brigatinib groups (84.4% vs. 84.1%, p=0.64), and the median TTNT, PFS, and OS were not reached in either group. Treatment-related adverse events were usually mild, and treatment discontinuation due to adverse events was rare (alectinib 4.5% vs. brigatinib 6.25%). Conclusion Alectinib and brigatinib had similar clinical benefits when used as the first-line treatment of NSCLC patients with ALK rearrangement in the real world.

Purpose: BRAF mutations are detected in 30%-80% of papillary thyroid cancer (PTC) cases. DaBRAFenib and trametinib showed promising antitumor activity in patients with BRAFV600E-mutated metastatic melanoma and non–small cell lung cancer. This study aimed to evaluate the efficacy and safety of daBRAFenib and trametinib in patients with metastatic BRAFV600E-mutated thyroid cancer. Materials and Methods: This was a retrospective study to evaluate the efficacy of daBRAFenib and trametinib in patients with metastatic BRAFV600E-mutated PTC. The patients received daBRAFenib 150 mg twice daily and trametinib 2 mg once daily at the Samsung Medical Center. This study evaluated the progression-free survival (PFS), objective response rate (ORR), disease control rate (DCR) overall survival (OS), and safety of daBRAFenib and trametinib. Results: Between December 2019 and January 2022, 27 PTC patients including eight patients with poorly differentiated or anaplastic transformation, received daBRAFenib and trametinib. The median age was 73.0 years, and the median follow-up period was 19.8 months. The majority (81.5%) had undergone thyroidectomy, while 8 patients had received prior systemic treatments. ORR was 73.1%, with 19 partial responses, and DCR was 92.3%. Median PFS was 21.7 months, and median OS was 21.7 months. Treatment-related adverse events included generalized weakness (29.6%), fever (25.9%), and gastrointestinal problems (22.2%). Dose reduction due to adverse events was required in 81.5% of the patients. Conclusion DaBRAFenib and trametinib demonstrated a high ORR with promising PFS; however, most patients with BRAFV600E-mutated metastatic PTC required a dose reduction.

Purpose: This study aimed to explore the existing literature on frailty experienced by patients with prostate cancer (PC) receiving androgen deprivation therapy (ADT). Materials and Methods: Database and manual searches were conducted to identify relevant studies published in English, with no limitation on the year of publication, according to the Preferred Reporting Items for Systematic reviews and Meta-Analyses extension for Scoping Reviews guidelines. Four databases—PubMed, Cochrane Library, EMBASE, and CINAHL—were used for database searches and reference lists, related journals, and Google Scholar were used for manual searches. Results: A total of 12 studies were analyzed for this scoping review. Of these, only 2 were intervention studies, and 1 was a randomized controlled trial. Among the two intervention studies, the multidisciplinary intervention program, including psychological counseling, nutritional coaching, and supervised group physical exercise did not show significant improvement in frailty. In contrast, high-dose vitamin D supplementation significantly decreased frailty. The conceptual and operational definitions of frailty used in each study varied, and the most used one was mainly focused on physical functions. As a result of analyzing the other health-related variables associated with frailty in patients with PC receiving ADT, age, metastases, comorbidities, and incident falls were related to a high frailty level. As for the physiological index, high levels of C-reactive protein, and interleukin-6, and fibrinogen, low levels of total testosterone, lymphocyte count, and creatinine were associated with a high level of frailty. A few studies explored the relationship between psychological and cognitive variables and frailty. Conclusions Further research related to frailty in patients with PC receiving ADT should be conducted, and effective interventions to manage frailty should be developed. Additionally, research that considers not only the physical domain of frailty but also the psychological, cognitive, and social domains needs to be conducted.

Overactive bladder (OAB) is prevalent in men and women and negatively impacts physical and psychological health. Fluid and caffeine intake modifications, which are lifestyle modification interventions, are simple methods to manage OAB. However, studies that synthesized both interventions and found scientific evidence are scarce. This review aimed to synthesize scientific evidence on whether fluid and caffeine intake modifications are effective for OAB symptoms. PubMed, CINAHL (Cumulative Index for Nursing and Allied Health Literature), Embase, Scopus, the Cochrane Library, KoreaMed, and RISS (Research Information Sharing Service) were used to search for studies and 8 studies were included. The Cochrane risk of bias tool (RoB 2.0) and ROBINS-I (Risk Of Bias In Non-randomized Studies - of Interventions) were used to assess the quality of selected studies. Due to the heterogeneous outcome variables, a meta-analysis was not conducted. Among the 8 included, 7 studies were randomized controlled trials and one was a quasi-experimental study. Four studies assessed urgency. Caffeine reduction was statistically effective for urgency symptoms, but increasing fluid intake was not. Frequency was assessed in 5 studies, which showed decreasing caffeine and fluid intake was effective in treating the symptoms. Urinary incontinence episodes were assessed in 6 studies, and nocturia in 2. Restricting caffeine intake was effective in treating these 2 symptoms, but restricting both caffeine and fluid intake was not. Quality of life (QoL) was examined in 5 studies, and modifying fluid and caffeine intake significantly improved QoL in 2. Although there were limited studies, our review provides scientific evidence that fluid and caffeine intake modification effectively manages OAB symptoms. Further research should examine acceptability and sustainability of interventions in the long-term and enable meta-analysis.

Purpose: Rearranged during transfection (RET) gene rearrangement is a well-known driver event in non–small cell lung cancer (NSCLC). Pralsetinib is a selective inhibitor of RET kinase and has shown efficacy in oncogenic RET-altered tumors. This study evaluated the efficacy and safety of expanded access program (EAP) use of pralsetinib in pretreated, advanced NSCLC patients with RET rearrangement. Materials and Methods: Patients who received pralsetinib as part of the EAP at Samsung Medical Center were evaluated through a retrospective chart review. The primary endpoint was overall response rate (ORR) per the Response Evaluation Criteria in Solid Tumors (RECIST) ver. 1.1 guidelines. Secondary endpoints were duration of response, progression-free survival (PFS), overall survival (OS), and safety profiles. Results: Between April 2020 and September 2021, 23 of 27 patients were enrolled in the EAP study. Two patients who were not analyzed due to brain metastasis and two patients whose expected survival was within 1 month were excluded from the analysis. After a median follow-up period of 15.6 months (95% confidence interval [CI], 10.0 to 21.2), ORR was 56.5%, the median PFS was 12.1 months (95% CI, 3.3 to 20.9), and the 12-month OS rate was 69.6%. The most frequent treatment-related adverse events (TRAEs) were edema (43.5%) and pneumonitis (39.1%). A total of 8.7% of patients experienced extra-pulmonary tuberculosis. TRAEs with a common grade of three or worse were neutropenia (43.5%) and anemia (34.8%). Dose reduction was required in nine patients (39.1%). Conclusion Pralsetinib presents a clinical benefit when used in patients with RET-rearranged NSCLC, consistent with a pivotal study.

Purpose: The optimal tumor mutational burden (TMB) value for predicting treatment response to programmed cell death-1 (PD-1) checkpoint inhibitors in advanced gastric cancer (AGC) remains unclear. We aimed to investigate the optimal TMB cutoff value that could predict the efficacy of PD-1 checkpoint inhibitors in AGC. Materials and Methods: Patients with AGC who received pembrolizumab or nivolumab between October 1, 2020, and July 27, 2021, at Samsung Medical Center in Korea were retrospectively analyzed. The TMB levels were measured using a next-generation sequencing assay. Based on receiver operating characteristic curve analysis, the TMB cutoff value was determined. Results: A total 53 patients were analyzed. The TMB cutoff value for predicting the overall response rate (ORR) to PD-1 checkpoint inhibitors was defined as 13.31 mutations per megabase (mt/Mb) with 56% sensitivity and 95% specificity. Based on this definition, 7 (13.2%) patients were TMB-high (TMB-H). The ORR differed between the TMB-low (TMB-L) and TMB-H (8.7% vs. 71.4%, P=0.001). The progression-free survival and overall survival (OS) for 53 patients were 1.93 (95% confidence interval [CI], 1.600–2.268) and 4.26 months (95% CI, 2.992–5.532). The median OS was longer in the TMB-H (20.8 months; 95% CI, 2.292–39.281) than in the TMB-L (3.31 months; 95% CI, 1.604–5.019; P=0.049). Conclusions The TMB cutoff value for predicting treatment response in AGC patients who received PD-1 checkpoint inhibitor monotherapy as salvage treatment was 13.31 mt/Mb.When applying the programmed death ligand-1 status to TMB-H, patients who would benefit from PD-1 checkpoint inhibitors can be selected.

Background: The depth of anesthesia is an essential factor in surgical prognosis. The neurotoxic effect of chemotherapeutic drugs affects the sensitivity to anesthetics. This study was conducted to determine whether the effect-site concentration (Ce) of propofol for loss of consciousness (LOC) differs in patients undergoing preoperative chemotherapy. Methods: A total of 60 patients scheduled for surgery for colorectal cancer under general anesthesia were included in this study. Patients who had received chemotherapy comprised the experimental (C) group, and those without a previous history of chemotherapy comprised the control (N) group. Propofol was administered as an effect-site target-controlled infusion, and the Modified Observer’s Assessment of Alertness/Sedation (MOAA/S) scores were evaluated. When the plasma concentration and Ce were similar, and if the MOAA/S score did not change, the target Ce was increased by 0.2 μg/ml; otherwise, the Ce was maintained for 2 min and then increased. Results: The Ce values of propofol for loss of verbal contact (LVC) in groups C and N were 2.40 ± 0.39 and 2.29 ± 0.39 μg/ml (P = 0.286), respectively, and those for LOC in groups C and N were 2.69 ± 0.43 and 2.50 ± 0.36 μg/ml (P = 0.069), respectively. No significant difference was observed in Ce values between the two groups. Conclusions Chemotherapy had no effect on the Ce of propofol for LVC and LOC in patients with colorectal cancer. We do not recommend reducing the dose of propofol for the induction of LOC in patients with colorectal cancer undergoing chemotherapy.

Purpose: The aims of this study were to examine the salivary microbiota in conditions of periodontal health and disease and to explore microbial changes following nonsurgical periodontal treatment. Methods: Non-stimulated saliva samples were collected from 4 periodontally healthy participants at baseline and from 8 patients with chronic periodontitis at baseline and 3 months following nonsurgical periodontal therapy. The V3 and V4 regions of the 16S rRNA gene from the DNA of saliva samples were amplified and sequenced. The salivary microbial compositions of the healthy participants and patients with periodontitis prior to and following nonsurgical treatment of periodontitis were compared based on the relative abundance of various taxa. Results: On average, 299 operational taxonomic units were identified in each sample. The phylogenetic diversity in patients with periodontitis was higher than that in healthy participants and decreased following treatment. The abundance of the phylum Spirochaetes and the genus Treponema in patients with periodontitis was 143- and 134-fold higher than in the healthy control group, respectively, but decreased significantly following treatment. The species that were overabundant in the saliva of patients with periodontitis included the Peptostreptococcus stomatis group, Porphyromonas gingivalis, the Fusobacterium nucleatum group, Parvimonas micra, Porphyromonas endodontalis, Filifactor alocis, and Tannerella forsythia. The phylum Actinobacteria, the genus Streptococcaceae_uc, and the species Streptococcus salivarius group were more abundant in healthy participants than in those with periodontitis. There was a trend toward a decrease in disease-associated taxa and an increase in health-associated taxa following treatment. Conclusions Our results revealed differences in the taxa of salivary microbiota between conditions of periodontal health and disease. The taxa found to be associated with health or disease have potential for use as salivary biomarkers for periodontal health or disease.

PURPOSE: The reaction of cells to a titanium implant depends on the surface characteristics of the implant which are affected by decontamination. The aim of this study was to evaluate the cytocompatibility of titanium disks treated with various decontamination methods, using salivary bacterial contamination with dental pellicle formation as an in vitro model. METHODS: Sand-blasted and acid-etched (SA) titanium disks were used. Three control groups (pristine SA disks [SA group]; salivary pellicle-coated SA disks [pellicle group]; and biofilm-coated, untreated SA disks [NT group]) were not subjected to any decontamination treatments. Decontamination of the biofilm-coated disks was performed by 14 methods, including ultrasonic instruments, rotating instruments, an air-powder abrasive system, a laser, and chemical agents. MG63 cells were cultured in the presence of the treated disks. Cell proliferation assays were performed on days 2 and 5 of cell culture, and cell morphology was analyzed by immunofluorescence and scanning electron microscopy (SEM). A vascular endothelial growth factor (VEGF) assay was performed on day 5 of culture. RESULTS: The cell proliferation assay revealed that all decontaminated disks, except for the 2 groups treated using a plastic tip, showed significantly less cell proliferation than the SA group. The immunofluorescence and SEM analyses revealed that most groups showed comparable cell density, with the exception of the NT group, in which the cell density was lower and bacterial residue was observed. Furthermore, the cells grown with tetracycline-treated titanium disks showed significantly lower VEGF production than those in the SA group. CONCLUSIONS: None of the decontamination methods resulted in cytocompatibility similar to that of pristine SA titanium. However, many methods caused improvement in the biocompatibility of the titanium disks in comparison with the biofilm-coated, untreated titanium disks. This suggests that decontamination is indispensable for the treatment of peri-implantitis, even if the original biocompatibility cannot be restored.
Biocompatible Materials ; Cell Count ; Cell Culture Techniques ; Cell Proliferation ; Decontamination ; Dental Implants ; Dental Pellicle ; Fluorescent Antibody Technique ; In Vitro Techniques ; Methods ; Microscopy, Electron, Scanning ; Peri-Implantitis ; Plastics ; Titanium ; Ultrasonics ; Vascular Endothelial Growth Factor A