Emergence and Potential Spread of Rust Disease on Wisteria floribunda and Corydalis incisa Influenced by Climate Change in Korea.

Global climate change influences the emergence, spread, and severity of rust diseases that affect crops and forests. In Korea, the rust diseases that affect Wisteria floribunda and its alternate host Corydalis incisa are rapidly spreading northwards. Through morphological, molecular, phylogenetic, and pathogenicity approaches, Neophysopella kraunhiae was identified as the causal agent, alternating between the two host plants to complete its life cycle. Using the maximum entropy model (Maxent) under shared socioeconomic pathways (SSPs), the results of this study suggest that by the 2050s, C. incisa is likely to extend its range into central Korea owing to climate shifts, whereas the distribution of W. floribunda is expected to remain unchanged nationwide. The generalized additive model revealed a significant positive correlation between the presence of C. incisa and the incidence of rust disease, highlighting the role that climate-driven expansion of this alternate host plays in the spread of N. kraunhiae. These findings highlight the profound influence of climate change on both the distribution of a specific plant and the disease a rust fungus causes, raising concerns about the potential emergence and spread of other rust pathogens with similar host dynamics.

Digitally designed and milled implant-retained maxillofacial prosthesis for velopharyngeal closure in a patient with a nonsurgically treated cleft palate: A clinical report.

An implant-retained maxillofacial overdenture with a pharyngeal speech aid prosthesis was fabricated for a patient with a nonsurgically treated cleft palate who was unable to achieve velopharyngeal closure. Computer-aided design and computer-aided manufacturing were used to fabricate a metal-reinforced prosthesis using the Ivotion Denture System and subtractive manufacturing with geographic guides. Magnetic attachments were incorporated to improve the retention and stability of the prosthesis. Masticatory function, deglutition, and esthetics were found to be improved at the 6-month follow-up.

ATF5-Mediated Mitochondrial Unfolded Protein Response (UPRmt) Protects Neurons Against Oxygen-Glucose Deprivation and Cerebral Ischemia.

BACKGROUND: The mitochondrial unfolded protein response (UPRmt) is an evolutionarily conserved mitochondrial response that is critical for maintaining mitochondrial and energetic homeostasis under cellular stress after tissue injury and disease. Here, we ask whether UPRmt may be a potential therapeutic target for ischemic stroke. METHODS: We performed the middle cerebral artery occlusion and oxygen-glucose deprivation models to mimic ischemic stroke in vivo and in vitro, respectively. Oligomycin and meclizine were used to trigger the UPRmt. We used 2,3,5-triphenyltetrazolium chloride staining, behavioral tests, and Nissl staining to evaluate cerebral injury in vivo. The Cell Counting Kit-8 assay and the Calcein AM Assay Kit were conducted to test cerebral injury in vitro. RESULTS: Inducing UPRmt with oligomycin protected neuronal cultures against oxygen-glucose deprivation. UPRmt could also be triggered with meclizine, and this Food and Drug Administration-approved drug also protected neurons against oxygen-glucose deprivation. Blocking UPRmt with siRNA against activating transcription factor 5 eliminated the neuroprotective effects of meclizine. In a mouse model of focal cerebral ischemia, pretreatment with meclizine was able to induce UPRmt in vivo, which reduced infarction and improved neurological outcomes. CONCLUSIONS: These findings suggest that the UPRmt is important in maintaining the survival of neurons facing ischemic/hypoxic stress. The UPRmt mechanism may provide a new therapeutic avenue for ischemic stroke.

Comprehensive Assessment of Multidrug-Resistant and Extraintestinal Pathogenic Escherichia coli in Wastewater Treatment Plant Effluents.

Multidrug-resistant (MDR) Escherichia coli poses a significant threat to public health, contributing to elevated rates of morbidity, mortality, and economic burden. This study focused on investigating the antibiotic resistance profiles, resistance and virulence gene distributions, biofilm formation capabilities, and sequence types of E. coli strains resistant to six or more antibiotic classes. Among 918 strains isolated from 33 wastewater treatment plants (WWTPs), 53.6% (492/918) demonstrated resistance, 32.5% (298/918) were MDR, and over 8% (74/918) were resistant to six or more antibiotic classes, exhibiting complete resistance to ampicillin and over 90% to sulfisoxazole, nalidixic acid, and tetracycline. Key resistance genes identified included sul2, blaTEM, tetA, strA, strB, and fimH as the predominant virulence genes linked to cell adhesion but limited biofilm formation; 69% showed no biofilm formation, and approximately 3% were strong producers. Antibiotic residue analysis detected ciprofloxacin, sulfamethoxazole, and trimethoprim in all 33 WWTPs. Multilocus sequence typing analysis identified 29 genotypes, predominantly ST131, ST1193, ST38, and ST69, as high-risk clones of extraintestinal pathogenic E. coli. This study provided a comprehensive analysis of antibiotic resistance in MDR E. coli isolated from WWTPs, emphasizing the need for ongoing surveillance and research to effectively manage antibiotic resistance.

Diagnostic Usefulness of p53 Immunostaining in Gastric Cancer and Dysplasia: A Real-world Clinical Experience.

BACKGROUND/AIM: Gastric cancer and its precancerous lesions represent a significant public health concern. A subset of gastric cancers exhibits mutations in the TP53 gene, often accompanying distinctive morphologic alterations. This study aimed to assess the diagnostic efficacy of p53 immunostaining in real-world clinical settings. PATIENTS AND METHODS: A retrospective analysis was conducted on 50 cases of gastric tumors and tumor-like lesions, wherein p53 immunostaining played a pivotal diagnostic role. The staining pattern of p53 was examined in conjunction with clinicopathologic parameters. RESULTS: Mutant p53 staining pattern demonstrated a significant association with high-grade nuclear atypia (p<0.001), high-grade dysplasia, and tubular adenocarcinoma (p<0.001), as well as microsatellite instability status (p=0.034). Furthermore, the diagnostic utility of p53 immunostaining was evident in scenarios where: 1) biopsy specimens contained few tumor cells, 2) pathologic evaluation of resection margins was limited by cauterization artifacts, and 3) distinction between low-grade and high-grade gastric dysplasia was challenging. CONCLUSION: P53 immunostaining can be helpful for the diagnosis of gastric tumor and tumor-like lesions, and accurate pathologic margin evaluation, particularly in lesions demonstrating intestinal-type differentiation and some degree of nuclear atypia.

Unraveling the Life Cycle of Nyssopsora cedrelae: A Study of Rust Diseases on Aralia elata and Toona sinensis.

Rust disease poses a major threat to global agriculture and forestry. It is caused by types of Pucciniales, which often require alternate hosts for their life cycles. Nyssopsora cedrelae was previously identified as a rust pathogen on Toona sinensis in East and Southeast Asia. Although this species had been reported to be autoecious, completing its life cycle solely on T. sinensis, we hypothesized that it has a heteroecious life cycle, requiring an alternate host, since the spermogonial and aecial stages on Aralia elata, a plant native to East Asia, are frequently observed around the same area where N. cedrelae causes rust disease on T. sinensis. Upon collecting rust samples from both A. elata and T. sinensis, we confirmed that the rust species from both tree species exhibited matching internal transcribed spacer (ITS), large subunit (LSU) rDNA, and cytochrome oxidase subunit III (CO3) mtDNA sequences. Through cross-inoculations, we verified that aeciospores from A. elata produced a uredinial stage on T. sinensis. This study is the first report to clarify A. elata as an alternate host for N. cedrelae, thus providing initial evidence that the Nyssopsora species exhibits a heteroecious life cycle.

Global perspectives on bipolar disorder treatment: in-depth comparative analysis of international guidelines for medication selection.

BACKGROUND: Bipolar disorder, a chronic mental health condition characterised by fluctuations in mood, energy and functionality, affects millions of individuals worldwide. Its management requires a comprehensive approach, and, as such, treatment guidelines have a pivotal role in guiding clinicians to alleviate symptoms, prevent relapse and enhance overall patient well-being. However, the treatment landscape is far from homogenous, with significant variations existing across different countries. AIMS: This study aimed to explore and compare treatment guidelines for bipolar disorder in various regions, shedding light on the factors that influence therapeutic approaches and thus offering insights that could contribute to the ongoing refinement of evidence-based practices in management. METHOD: The study explores various international treatment guidelines for bipolar disorder that have been updated after 2014. Guidelines from the UK, Canada, Australia/New Zealand, South Korea and the International College of Neuropsychopharmacology are scrutinised to identify factors contributing to the observed differences among them. RESULTS: The variations in recommended drugs across guidelines arise from the approaches employed in guideline development - whether relying on expert consensus or meta-analysis results. Timing disparities in conducting these analyses and the selection of studies also exert influence. Moreover, differences in metabolic enzymes among diverse races and the health policies implemented by individual nations play a significant part in shaping these differences. CONCLUSION: The primary hindrance to consistent treatment conclusions lies in the scarcity of high-quality research results, leading to variations in guidelines. Enhancing evidence-based recommendations necessitates the undertaking of large-scale studies dedicated to assessing treatments for bipolar disorder.

Mammalian adaptation risk in HPAI H5N8: a comprehensive model bridging experimental data with mathematical insights.

Understanding the mammalian pathogenesis and interspecies transmission of HPAI H5N8 virus hinges on mapping its adaptive markers. We used deep sequencing to track these markers over five passages in murine lung tissue. Subsequently, we evaluated the growth, selection, and RNA load of eight recombinant viruses with mammalian adaptive markers. By leveraging an integrated non-linear regression model, we quantitatively determined the influence of these markers on growth, adaptation, and RNA expression in mammalian hosts. Furthermore, our findings revealed that the interplay of these markers can lead to synergistic, additive, or antagonistic effects when combined. The elucidation distance method then transformed these results into distinct values, facilitating the derivation of a risk score for each marker. In vivo tests affirmed the accuracy of scores. As more mutations were incorporated, the overall risk score of virus heightened, and the optimal interplay between markers became essential for risk augmentation. Our study provides a robust model to assess risk from adaptive markers of HPAI H5N8, guiding strategies against future influenza threats.

Interaction between p21-activated kinase 4 and ß-catenin as a novel pathway for PTH-dependent osteoblast activation.

Parathyroid hormone (PTH) serves dual roles in bone metabolism, exhibiting both anabolic and catabolic effects. The anabolic properties of PTH have been utilized in the treatment of osteoporosis with proven efficacy in preventing fractures. Despite these benefits, PTH can be administered therapeutically for up to 2 years, and its use in patients with underlying malignancies remains a subject of ongoing debate. These considerations underscore the need for a more comprehensive understanding of the underlying mechanisms. p21-activated kinase 4 (PAK4) is involved in bone resorption and cancer-associated osteolysis; however, its role in osteoblast function and PTH action remains unknown. Therefore, in this study, we aimed to clarify the role of PAK4 in osteoblast function and its effects on PTH-induced anabolic activity. PAK4 enhanced MC3T3-E1 osteoblast viability and proliferation and upregulated cyclin D1 expression. PAK4 also augmented osteoblast differentiation, as indicated by increased mineralization found by alkaline phosphatase and Alizarin Red staining. Treatment with PTH (1-34), an active PTH fragment, stimulated PAK4 expression and phosphorylation in a protein kinase A-dependent manner. In addition, bone morphogenetic protein-2 (which is known to promote bone formation) increased phosphorylated PAK4 (p-PAK4) and PAK4 levels. PAK4 regulated the expression of both phosphorylated and total ß-catenin, which are critical for osteoblast proliferation and differentiation. Moreover, p-PAK4 directly interacted with ß-catenin, and disruption of ß-catenin's binding to T-cell factor impaired PAK4- and PTH-induced osteoblast differentiation. Our findings elucidate the effect of PAK4 on enhancing bone formation in osteoblasts and its pivotal role in the anabolic activity of PTH mediated through its interaction with ß-catenin. These insights improve the understanding of the mechanisms underlying PTH activity and should inform the development of more effective and safer osteoporosis treatments.

Evaluation metric of smile classification by peri-oral tissue segmentation for the automation of digital smile design.

OBJECTIVES: This study aimed to develop and validate evaluation metric for an automated smile classification model termed the "smile index." This innovative model uses computational methods to numerically classify and analyze conventional smile types. METHODS: The datasets used in this study consisted of 300 images to verify, 150 images to validate, and 9 images to test the evaluation metric. Images were annotated using Labelme. Computational techniques were used to calculate smile index values for the study datasets, and the resulting values were evaluated in three stages. RESULTS: The smile index successfully classified smile types using cutoff values of 0.0285 and 0.193. High accuracy (0.933) was achieved, along with an F1 score greater than 0.09. The smile index successfully reclassified smiles into six types (low, low-to-medium, medium, medium-to-high, high, and extremely high smiles), thereby providing a clear distinction among different smile characteristics. CONCLUSION: The smile index is a novel dimensionless parameter for classifying smile types. The index acts as a robust evaluation tool for artificial intelligence models that automatically classify smile types, thereby providing a scientific basis for largely subjective aesthetic elements. CLINICAL SIGNIFICANCE: The computational approach employed by the smile index enables quantitative numerical classification of smile types. This fosters the application of computerized methods in quantifying and analyzing real smile characteristics observed in clinical practice, paving the way for a more objective evidence-based approach to aesthetic dentistry.

Prognostic significance of tumour budding in noncolorectal gastrointestinal tract and pancreatobiliary tract: a systematic review and meta-analysis.

Tumour budding shows promise as a prognostic factor in various cancers, but its widespread application is hindered by the lack of large, validated studies and standardized criteria. This meta-analysis aims to review and examine the prognostic role of tumour budding specifically in noncolorectal gastrointestinal and pancreatobiliary tract cancers, broadening our perspective on its clinical relevance. The literature review was conducted through PubMed, Embase, and Web of Science from inception till 20 February 2023. Pooled odds ratio (OR) and hazard ratio (HR) with 95% confidence interval (CI) were calculated to assess the relation between tumour budding and clinicopathologic features, as well as overall survival. Each study was evaluated using the Newcastle-Ottawa Scale and both heterogeneity and publication bias were analysed. In this meta-analysis of 57 studies across various cancer types, multivariate HR revealed worse overall survival in oesophageal squamous cell carcinoma (HR 3.34 [95% CI 2.21-5.04]), gastric adenocarcinoma (2.03 [1.38-2.99]), pancreatic ductal adenocarcinoma (2.56 [2.02-3.25]), and biliary tract adenocarcinoma (3.11 [2.46-3.93]) with high-grade tumour budding. Additionally, high-grade tumour budding consistently correlated with adverse clinicopathological features, including lymph node metastasis, lymphovascular invasion, and distant metastasis without any observed inverse association. High heterogeneity was noted. Our study suggests that tumour budding is a valuable prognostic marker in various cancers. Nonetheless, standardized criteria tailored to specific organ types are necessary to enhance its clinical utility.

The Transposition of Insertion Sequences in Sigma-Factor- and LysR-Deficient Mutants of Deinococcus geothermalis.

Some insertion sequence (IS) elements were actively transposed using oxidative stress conditions, including gamma irradiation and hydrogen peroxide treatment, in Deinococcus geothermalis, a radiation-resistant bacterium. D. geothermalis wild-type (WT), sigma factor gene-disrupted (∆dgeo_0606), and LysR gene-disrupted (∆dgeo_1692) mutants were examined for IS induction that resulted in non-pigmented colonies after gamma irradiation (5 kGy) exposure. The loss of pigmentation occurred because dgeo_0524, which encodes a phytoene desaturase in the carotenoid pathway, was disrupted by the transposition of IS elements. The types and loci of the IS elements were identified as ISDge2 and ISDge6 in the ∆dgeo_0606 mutant and ISDge5 and ISDge7 in the ∆dgeo_1692 mutant, but were not identified in the WT strain. Furthermore, 80 and 100 mM H2O2 treatments induced different transpositions of IS elements in ∆dgeo_0606 (ISDge5, ISDge6, and ISDge7) and WT (ISDge6). However, no IS transposition was observed in the ∆dgeo_1692 mutant. The complementary strain of the ∆dgeo_0606 mutation showed recovery effects in the viability assay; however, the growth-delayed curve did not return because the neighboring gene dgeo_0607 was overexpressed, probably acting as an anti-sigma factor. The expression levels of certain transposases, recognized as pivotal contributors to IS transposition, did not precisely correlate with active transposition in varying oxidation environments. Nevertheless, these findings suggest that specific IS elements integrated into dgeo_0524 in a target-gene-deficient and oxidation-source-dependent manner.

First Report of Powdery Mildew Caused by Golovinomyces adenophorae on Adenophora triphylla var. japonica in Korea.

Adenophora triphylla var. japonica (Campanulaceae), known as Japanese lady bell, is native to East Asia. It has been used as a medicinal plant but is widely cultivated in Korea as an indigenous vegetable (Park et al. 2011). In the summer of 2020, about 100 plants in an experimental plot at the National Institute of Forest Science, Seoul, Korea, showed powdery mildew symptoms with a 100% disease incidence. Signs first appeared as white colonies, subsequently expanding over the leaves, stems, and inflorescences. Infected young shoots were elongated and became slender. Chasmothecia were found in late October. Voucher specimens were deposited in the Korea University Herbarium (KUS-F). Conidiophores arising from the lateral part of the hyphae were upright, 100 to 220 × 10 to 12 µm, and produced 2 to 5 immature conidia in chains with sinuate edge lines. Basal parts of foot-cells in conidiophores were curved. Conidia were barrel-shaped to ellipsoid, 26 to 40 × 14 to 20 µm, and produced germ tubes on the perihilar position of the conidia. Chasmothecia with short mycelioid appendages were gregarious, 144 to176 µm in diam., and contained 8 to 22 asci. Asci were clavate-saccate with short stalks, 60 to 82 × 28 to 42 µm, and contained two spores. Ascospores were broadly ellipsoid, cytoplasm-dense without vacuoles, colorless, and 22 to 28 × 12 to 18 µm. The structures and measurements were consistent with those of Golovinomyces adenophorae (R.Y. Zheng & G.Q. Chen) Heluta (Braun & Cook, 2012). To confirm the morphology-based identification, two herbarium specimens (KUS-F29252 and F31898) were sequenced for the internal transcribed spacer (ITS) and large subunit (LSU) regions with PM10/ITS4 and PM3/TW14 primers, respectively (Bradshaw and Tobin, 2020). A Blastn search revealed high similarities in the ITS and LSU sequences, with 99.81% (538/539 bp) and 99.86% (697/698 bp) to G. adenophorae sequences (AB077633 and AB077632), respectively. All resulting sequences were deposited in GenBank under accession numbers OR841069-70 for ITS and OR841071 for LSU. A pathogenicity test was performed through inoculation by gently dusting the conidia from a detached symptomatic leaf onto the leaves of five healthy plants. Five non-inoculated plants served as controls. Following inoculation, plants were covered with plastic film and maintained in a greenhouse (24 to 32°C) until symptoms developed. Powdery mildew colonies developed on the inoculated plants after twelve days, whereas the control plants remained symptomless. The inoculated pathogen was confirmed morphologically and molecularly by the sequence comparison aforementioned, fulfilling Koch's postulates. Based on morphological characteristics and the sequencing data, the powdery mildew was identified as G. adenophorae. The association of G. adenophorae and Adenophora spp. has been known in China, Japan, Kazakhstan, and the Far East of Russia (Farr and Rossman, 2023). This is the first report of powdery mildew caused by G. adenophorae on A. triphylla var. japonica in Korea. Since the commercial cultivation of this plant aims to harvest young shoots as one of the most popular vegetables in Korea, appropriate control measures for the powdery mildew should be considered.

The Effect of Sex on the Remimazolam Dosage Required for Successful i-gel Supraglottic Airway Insertion with Remifentanil in Non-Paralyzed Patients: An Up-and-Down Sequential Allocation Trial.

(1) Background: The physiological and pharmacological variations between men and women are known to influence drug efficacy. The objective of this study was to determine the 50% and 95% effective doses (ED50 and ED95) of remimazolam required for i-gel supraglottic airway (ISA) insertion under remifentanil infusion without neuromuscular blocking agents (NMBAs) in both males and females. (2) Methods: Patients aged 19-65 years, scheduled for general anesthesia using ISA, were enrolled in this study. Patients were divided into two groups based on their sex. The anesthesia process began with a remifentanil infusion targeting an effect-site concentration of 3.0 ng/mL, accompanied by a remimazolam injection. The initial remimazolam dose was 0.25 mg/kg, and it was adjusted with a step size of 0.05 mg/kg based on the outcome of ISA insertion in the preceding patient. (3) Results: The ED50 of remimazolam (mean ± standard error) was 0.28 ± 0.02 mg/kg in the male group and 0.18 ± 0.02 mg/kg in the female group (p < 0.001). Additionally, ED95, which was calculated using the isotonic regression method, was significantly comparable between the male and female groups (male: 0.35 mg/kg, 95% confidence interval [CI] = 0.34-0.35; female: 0.29 mg/kg, 95% CI = 0.25-0.30). (4) Conclusions: This study showed that both the ED50 and the ED95 of remimazolam for successful ISA insertion was higher for men than that for women. Therefore, while using remimazolam alongside remifentanil infusion without NMBAs for ISA insertion, one should consider the patient's sex for appropriate dosing.

Molecular Activity of Inflammation and Epithelial-Mesenchymal Transition in the Microenvironment of Ulcerative Colitis.

Background/Aims: : The genetic expression in the active inflammatory regions is increased in ulcerative colitis (UC) with endoscopic activity. The aim of this study was to investigate the molecular activity of inflammation and tissue remodeling markers in endoscopically inflamed and uninflamed regions of UC. Methods: : Patients with UC (n=47) and controls (n=20) were prospectively enrolled at the Seoul National University Bundang Hospital. Inflamed tissue was obtained at the most active lesion, and uninflamed tissue was collected from approximately 15 cm above the upper end of the active lesion via colonoscopic biopsies. The messenger RNA expression levels of transforming growth factor ß (TGF-ß), interleukin (IL)-1ß, IL-6, IL-17A, E-cadherin, olfactomedin-4 (OLFM4), leucine-rich repeat-containing G protein-coupled receptor 5 (LGR5), vimentin, fibroblast-specific protein-1 (FSP1), and α-smooth muscle actin (SMA) were evaluated. Mucosal healing (MH) was defined according to a Mayo endoscopic score of 0, 1 or non-MH (Mayo endoscopic score of 2 or 3). Results: : The messenger RNA expressions of TGF-ß, IL-1ß, OLFM4, FSP1, vimentin, and α-SMA were significantly higher, and that of E-cadherin was significantly lower in inflamed and uninflamed regions of patients with UC than those in controls. In the inflamed regions, patients in the non-MH group had significantly increased genetic expression of TGF-ß, FSP1, vimentin, and α-SMA compared to patients in the MH group. Similarly, the non-MH group had significantly higher genetic expression of TGF-ß, IL-1ß, IL-6, vimentin, and α-SMA than the MH group in the uninflamed regions. Conclusions: : Endoscopic activity in UC suggests inflammation and tissue remodeling of uninflamed regions similar to inflamed regions (ClinicalTrials.gov, NCT05653011).

Phase III, Randomized Study of Atezolizumab Plus Bevacizumab and Chemotherapy in Patients With EGFR- or ALK-Mutated Non-Small-Cell Lung Cancer (ATTLAS, KCSG-LU19-04).

PURPOSE: In the treatment of non-small-cell lung cancer (NSCLC) with a driver mutation, the role of anti-PD-(L)1 antibody after tyrosine kinase inhibitor (TKI) remains unclear. This randomized, open-label, multicenter, phase III study evaluates the efficacy of atezolizumab plus bevacizumab, paclitaxel, and carboplatin (ABCP ) in EGFR- or ALK-mutated NSCLC that progressed before TKI therapy. MATERIALS AND METHODS: We compared the clinical efficacy of ABCP followed by maintenance therapy with atezolizumab plus bevacizumab with pemetrexed plus carboplatin or cisplatin (PC) followed by pemetrexed maintenance. The primary end point was progression-free survival (PFS). RESULTS: A total of 228 patients with activating EGFR mutation (n = 215) or ALK translocation (n = 13) were enrolled from 16 sites in the Republic of Korea and randomly assigned at 2:1 ratio to either ABCP (n = 154) or PC arm (n = 74). The median follow-up duration was 26.1 months (95% CI, 24.7 to 28.2). Objective response rates (69.5% v 41.9%, P < .001) and median PFS (8.48 v 5.62 months, hazard ratio [HR], 0.62 [95% CI, 0.45 to 0.86]; P = .004) were significantly better in the ABCP than PC arm. PFS benefit increased as PD-L1 expression increased, with an HR of 0.47, 0.41, and 0.24 for PD-L1 ≥1%, ≥10%, and ≥50%, respectively. Overall survival was similar between ABCP and PC arm (20.63 v 20.27 months, HR, 1.01 [95% CI, 0.69 to 1.46]; P = .975). The safety profile of the ABCP arm was comparable with that previously reported, with no additional safety signals, but higher rates of treatment-related adverse events were observed compared with the PC arm. CONCLUSION: To our knowledge, this study is the first randomized phase III study to demonstrate the clinical benefit of anti-PD-L1 antibody in combination with bevacizumab and chemotherapy in patients with EGFR- or ALK-mutated NSCLC who have progressed on relevant targeted therapy.

Treatment Patterns and Prognosis of Palliative Chemotherapy Combined With Targeting Agents in Patients With Unresectable Metastatic Colorectal Cancer: CHOICE, A Multicenter Longitudinal Observational Study.

BACKGROUND/AIM: This study investigated the treatment patterns and prognosis of patients with metastatic or unresectable colorectal cancer (mCRC) treated with chemotherapy with targeting agents. PATIENTS AND METHODS: This longitudinal multicenter study included 963 patients with mCRC who were treated in Korea between 2016 and 2020. Treatment patterns and efficacy were compared according to the mutation status and clinical factors. RESULTS: As first-line therapy, most of the patients (83.5%) received FOLFOX plus bevacizumab (35.4%), followed by FOLFIRI plus bevacizumab (18.8%), FOLFIRI plus cetuximab (17.0%), and FOLFOX plus cetuximab (12.3%). Bevacizumab was the most frequent agent (78.8%) combined with chemotherapy in RAS-mutated CRC, while cetuximab (57.2%) in RAS wild-type CRC. Cetuximab was frequently combined with a doublet regimen in patients with left-sided CRC than in those with right-sided CRC (34.4% vs. 16%). As second-line therapy, most patients (63.4%) also received doublet regimens with bevacizumab, and FOLFIRI plus aflibercept was administered in 15.1%. The objective response rate with FOLFIRI plus cetuximab was significantly higher in patients with left-sided CRC than in those with right-sided CRC (59.2% vs. 30.8%, p=0.008) and marginally higher in patients with RAS wild-type CRC than in those with RAS-mutated CRC (55.6% vs. 0.0%, p=0.092). Progression-free survival (PFS) with FOLFOX plus bevacizumab was significantly shorter than that with FOLFIRI plus bevacizumab (p=0.030) in RAS-mutated CRC, whereas there were no significant differences between regimens in RAS wild-type CRC. CONCLUSION: In patients with unresectable metastatic colorectal cancer, doublet chemotherapy with targeting agents is the most common therapy and efficacy depends on the mutation status as well as clinical factors.

Feasibility of using red cell distribution width for prediction of postoperative mortality in severe burn patients: an association with acute kidney injury after surgery.

BACKGROUND: Severe burns cause pathophysiological processes that result in mortality. A laboratory biomarker, red cell distribution width (RDW), is known as a predictor of mortality in critically-ill patients. We examined the association between RDW and postoperative mortality in severe burn patients. METHODS: We retrospectively analyzed medical data of 731 severely burned patients who underwent surgery under general anesthesia. We evaluated whether preoperative RDW value can predict 3-month mortality after burn surgery using receiver operating characteristic (ROC) curve analysis, logistic regression, and Cox proportional-hazards regression analysis. Mortality was also analyzed according to preoperative RDW values and incidence of postoperative acute kidney injury (AKI). RESULTS: The 3-month mortality rate after burn surgery was 27.1% (198/731). The area under the ROC curve of preoperative RDW to predict mortality after burn surgery was 0.701 (95% confidence interval [CI], 0.667-0.734; P < 0.001) with a cut-off point of 12.9. The adjusted hazard ratio in patients with RDW > 12.9 was 1.238 (95% CI, 1.138-1.347; P < 0.001). Subgroup analysis showed that the survival rate was 88.8% for the non-AKI group with RDW ≤ 12.9 and 17.6% for the AKI group with RDW > 12.9. Preoperative RDW was considered an independent risk factor for mortality (odds ratio, 1.679; 95% CI, 1.378- 2.046; P < 0.001). CONCLUSIONS: Preoperative RDW may predict 3-month postoperative mortality in patients with severe burns, while preoperative RDW > 12.9 and postoperative AKI may further increase mortality after burn surgery.