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by Teruo Nakamura, Tomohiro Shibata, Ken-ichi Ito
Anaplastic thyroid cancer (ATC) is a rare but highly aggressive malignancy with a dismal prognosis. Although recent advances in targeted therapies have modestly improved survival, the molecular mechanisms driving ATC progression remain incompletely elucidated. Epithelial cell adhesion molecule (EpCAM), a multifunctional cell-surface protein, is implicated in proliferation, migration, and stemness in various cancers. However, its role in thyroid cancer progression remains unclear. In this study, we investigated the function of EpCAM in thyroid cancer cell lines of varying differentiation status. EpCAM expression was significantly elevated in ATC cell lines compared with differentiated thyroid cancer (DTC) lines. EpCAM knockdown by siRNA suppressed proliferation, adhesion, motility, and invasion in ATC cells, but had minimal effects on DTC cells. Morphological analyses revealed that EpCAM silencing induced differentiation features, including follicle-like structure formation and increased expression of thyroid differentiation markers such as thyroglobulin and PAX8 in ATC cells. Furthermore, EpCAM inhibition decreased mesenchymal marker expression, reduced filopodia formation, and suppressed extravasation of cancer cells into the lung in an in vivo mouse model. Mechanistically, EpCAM knockdown attenuated epithelial–mesenchymal transition (EMT)-related pathways but did not affect major proliferation signaling cascades in ATC cells. These findings suggest that EpCAM promotes dedifferentiation and metastatic potential in ATC through EMT modulation. Our results provide new insights into the role of EpCAM in thyroid cancer biology and highlight its potential as a therapeutic target in ATC. Further studies are warranted to elucidate the mechanisms linking EpCAM to anaplastic transformation and to explore the therapeutic efficacy of EpCAM-targeting strategies in aggressive thyroid cancers.
by Caio R. Monteiro, Victor Augusto de Oliveira, Rabeche Schmith, João Pedro A. Rezende, Tales L. Resende, João A. Negrão, Marina A. C. Danés
This study aimed to evaluate the effects of rumen-protected methionine (RPM) supplementation on productive and physiological responses of primiparous Holstein cows during summer. We hypothesized that RPM supplementation would maintain or improve milk yield and composition due to beneficial physiological, redox, and inflammatory responses in cows exposed to summer heat. The trial was conducted in a randomized block design during nine weeks in Brazil using 80 primiparous cows (182 ± 64 DIM; 42.9 ± 4.7 kg/d milk). Cows were blocked by milk yield and DIM and assigned to a control diet (CON; no added RPM) or the same diet supplemented with RPM (Mepron®, Evonik) at 0.75 g/kg diet dry matter, targeting 20 g/cow/day (product contains 62% metabolizable methionine) to the average cow. Milk yield and composition, vaginal temperature, respiratory rate, and plasma samples were collected in weeks 3, 6, and 9. Data were analyzed using mixed models including treatment, week, and their interaction as fixed effects, and block and cow as random effects. Cows were maintained under naturally occurring summer conditions. Environmental monitoring during weeks 3, 6, and 9 indicated elevated temperature–humidity index (THI) values, with values remaining above the heat-stress threshold (THI > 68) for 68.3% of the monitored hours (mean THI = 70.6; range 61.0–84.4). Overall (least squares mean across weeks 3, 6, and 9), RPM increased milk yield by 2.0 kg/d (44.9 vs. 42.9 kg/d), protein yield by 50 g/d (1,464 vs. 1,414 g/d), lactose yield by 108 g/d (2,109 vs. 2,001 g/d), and total solids yield by 176 g/d (5,331 vs. 5,155 g/d). Lactose concentration was lower in RPM (4.71 vs. 4.76%). Fat yield was unaffected, but a treatment × week interaction was observed for fat content. Milk fatty acid (FA) profile was unchanged, although treatment × week interactions were observed for individual fatty acids (C16:0, C18:0, C18:1, and preformed FA). Plasma glucose was lower, and insulin was higher in RPM than in CON cows (39.3 vs. 43.2 mg/dL and 0.52 vs. 0.35 ng/mL, respectively). Antioxidant capacity improved, with RPM cows having greater ferric reducing antioxidant power (32.9 vs. 28.5 µM) and lower malondialdehyde (2.48 vs. 2.78 nmol/mL). Other biochemical, inflammatory, and immune markers were unaffected. Respiratory rate was slightly higher in RPM than in CON cows (55 vs. 50 breaths/min). Mean vaginal temperature did not differ between treatments; however, a treatment × time × hour interaction was observed. Supplementation with RPM improved milk and solids yield, and enhanced antioxidant capacity and insulin levels, supporting its use to improve metabolic resilience under warm conditions.
by Masanori Nishi, Yasushi Yoshikawa, Yuki Usui, Hajime Nishida, Shota Nakamura, Koichiro Tashiro, Yoshifumi Kudo
The purpose of this study was to investigate the correlation between femoral morphological indices from anteroposterior hip radiographs and dual-energy X-ray absorptiometry-assessed bone mineral density in postmenopausal female patients undergoing primary total hip arthroplasty for hip osteoarthritis. We also evaluated the impact of hip deformity on these correlations and the diagnostic cut-off values for osteoporosis. This retrospective study, conducted at a single institute (February 2018 to July 2024), reviewed the data of postmenopausal patients (>50 years old) with hip osteoarthritis who underwent total hip arthroplasty. Patients with a history of hip surgical procedures, infection, metabolic bone disease, or inadequate imaging findings were excluded. Dual-energy X-ray absorptiometry was used to assess bone mineral density at the femoral neck, total hip, lumbar spine, and distal radius. Five femoral indices were measured: the canal-to-calcar ratio, canal flare index, cortical thickness index, canal diaphysis ratio, and canal bone area ratio. Analyses included Pearson’s correlation and receiver operating characteristic curve analysis. Moderate correlations were observed between total hip bone mineral density and indices in 95 hip osteoarthritic joints (all Tönnis grade 3) and 86 normal joints. The canal bone area ratio had the strongest correlation (hip osteoarthritis: r = −0.61; normal: r = −0.62; p
by Aditya Sri Listyoko, Ryota Okazaki, Tomoya Harada, Genki Inui, Hiroki Kohno, Miyu Nishigami, Miki Takata, Masato Morita, Akira Yamasaki
BackgroundThe interaction between viral components and type 1 or type 2 cytokines during asthma exacerbations in the airway epithelium may contribute to worsening inflammation. However, these interactions in the small airway epithelium—particularly those involving alarmins (TSLP, IL-25, and IL-33) and IL-8—remain unclear. Dupilumab, a biologic agent used in severe asthma, blocks IL-4 receptor alpha (IL-4Rα) and may offer therapeutic benefits in virus-induced asthma exacerbations. In this study, we evaluate the effects of double-stranded RNA (dsRNA), in combination with various cytokines and dupilumab, on the Human Small Airway Epithelial Cells (HSAECs) line.
MethodsPrimary HSAECs were preincubated with dsRNA to induce the gene and protein expression of alarmins and IL-8. To evaluate the effects of cytokines on dsRNA-induced alarmin and IL-8 expression, various type 1 and type 2 cytokines were co-stimulated with dsRNA. Dupilumab was used as a pretreatment prior to co-stimulation with dsRNA and IL-4 or IL-13. Gene expression of TSLP, IL-25, IL-33, and IL-8 was assessed by quantitative PCR, and protein expression was evaluated by Western Blotting.
ResultsdsRNA significantly increased the expression of TSLP and IL-8. IL-4 and IL-13 further enhanced dsRNA-induced TSLP and IL-8 gene and protein expression. In contrast, TNF-α reduced dsRNA-induced TSLP expression but enhanced IL-8 gene and protein expression. Dupilumab attenuated the expression of TSLP and IL-8 induced by co-stimulation with dsRNA and IL-4 or IL-13 in HSAECs.
ConclusionIn the microenvironment of small airway epithelial cells, particularly during viral infections, the presence of IL-4 or IL-13 may enhance the expression of TSLP and IL-8. Dupilumab attenuates this expression, potentially offering additional benefits in the treatment of asthma, especially during virus-induced asthma exacerbations.
by Ryosuke Segawa, Makiko Yagisawa, Chihiro Miyata, Noriyasu Hirasawa
Thymic stromal lymphopoietin (TSLP) is an epithelial-derived cytokine that induces type 2 immune responses through dendritic cell activation, and its aberrant regulation is implicated in TSLP-associated inflammatory disorders including atopic dermatitis. We previously demonstrated that hypoxia-inducible factor (HIF) suppresses TSLP expression in human keratinocyte cells; however, the underlying mechanism remained unclear. In this study, we aimed to explore the suppressive mechanism of enarodustat, an HIF-prolyl hydroxylase inhibitor. Enarodustat selectively suppressed TSLP expression induced by the fibroblast-stimulating lipopeptide (FSL-1), a toll like receptor 2/6 agonist in HaCaT, a human keratinocyte cell line. Although both the nuclear factor-κB (NF-κB) and activator protein (AP)-1 contributed to FSL-1-induced TSLP induction, enarodustat preferentially attenuated AP-1 signaling by reducing c-Jun N-terminal kinase (JNK) phosphorylation. This JNK dephosphorylation required both HIF1α and HIF2α and was accompanied by increased expression of dual-specificity phosphatases (DUSPs), which target JNK for dephosphorylation. Collectively, our findings identify a previously uncharacterized HIF–DUSP–JNK axis that negatively regulates TSLP expression. This study provides mechanistic insight into how HIF activation shapes epithelial cytokine responses, offering a basis for understanding the pathogenesis of TSLP-associated diseases such as atopic dermatitis.
by Yasutaka Tanaka, Daiki Mizushima, Yoshimitsu Izawa, Tomohiro Matsumura, Chikara Yonekawa, Hirotomo Kato, Takashi Mato
BackgroundIn tropical to subtropical regions, centipede bites may prompt medical attention, with manifestations largely reflecting venom-related discomfort, although infections, including rare fatal necrotizing soft tissue infection (NSTI), have been reported. However, no reports are available on the commensal bacteria on centipede forcipules.
ObjectivesThis study aimed to investigate bacterial species residing on and in centipede forcipules and their potential role in post-bite infections.
MethodsNine Scolopendra mutilans, three Scolopendra japonica, and two Bothropolys rugosus were collected from three regions in Japan. The bacterial composition of their forcipules was analyzed using 16S ribosomal ribonucleic acid gene sequencing and microbiome analysis.
FindingsA diverse bacterial community was observed on the centipede forcipules. Among the NSTI-associated genera examined (Escherichia, Staphylococcus, and Streptococcus), only Staphylococcus was identified as a minor population.
ConclusionThis study provides the first evidence that some bacteria found on centipede forcipules have been previously isolated from centipede bite infections. The risk of infection from bacteria on centipede forcipules during a centipede bite appears low. However, the presence of diverse bacterial species emphasizes the importance of thoroughly cleaning centipede bite wounds to prevent secondary infection.
by Yuto Kimura, Takahiro Kozuka
This study examined the association between event-related disclosure and posttraumatic growth (PTG). Specifically, it targeted the Japanese adult, assessed attitudes toward event-related disclosure, and examined event-related rumination as a mediating variable. A cross-sectional online survey was conducted among Japanese adults aged 20–59. Participants completed measures of demographic characteristics, stressful life events attributes, attitudes toward disclosure, event-related rumination, and PTG. Analysis of data from 480 individuals revealed that neither willingness to disclose nor resistance to disclose was directly associated with PTG. However, both willingness to disclose and resistance to disclose were positively associated with PTG through deliberate rumination and negatively associated with PTG through intrusive rumination. The effect sizes for willingness to disclose were approximately three times greater than those for resistance to disclose. These findings suggest that event-related disclosure may enhance PTG by promoting deliberate meaning-making processes, while also potentially hindering it by reinforcing involuntary negative thinking. Furthermore, these effects may be stronger when individuals are more proactive and disclose more frequently. These results have important implications for interventions aimed at enhancing PTG through event-related disclosure.
by Petar Stanimirović, Tea Borozan, Katarina Petrović, Dragan Bjelica, Zorica Mitrović, Marko Mihić, Dejan Petrović, Anđelija Đorđević Tomić
Young people often face uncertainty during the transition from education to work, along with high unemployment and job dissatisfaction, which is addressed in the EU Youth Strategy, highlighting the need for better career support. This study aimed to identify main factors influencing youth career decisions and to develop a decision-making model. Five core constructs were defined through literature review: Dealing with Uncertainty, Risk Preference, Adaptability and Resilience, Education and Support, and Life Satisfaction. Data were collected from 673 engineering students. Regression analysis was used to test the proposed model and hypotheses, while Mann-Whitney and Kruskal-Wallis tests examined group differences. The developed model accounts for 46.2% (R² = 0.462) of the variability in students’ career choices. Adaptability and resilience emerged as the most influential factor (β = 0.557). Certain differences, for specific constructs, were also observed in relation to different groups of family income, gender and extracurricular activity engagement. The model supports more informed career decisions and provides insights that may help improve career guidance and educational policy. The findings also may contribute to bridging theory and practice in career development research. The study is limited by its sample, which included only engineering students from the Republic of Serbia, potentially restricting the generalizability of the results.
by Emily Dunlap, Yanbing Zhou, Manny M.Y. Kwok, Billy C.L. So, Hirofumi Tanaka
ObjectiveTo evaluate the effects of aquatic exercise compared with non-exercise controls and land-based exercise on arterial stiffness and endothelial function.
DesignSystematic review and meta-analyses of randomized controlled trials assessed using the Cochrane risk-of-bias tool and Grading of Recommendations Assessment, Development and Evaluation.
Data sourcesPubMed/MEDLINE, CINAHL Plus, SPORTDiscus, and reference lists, searched from database inception to April 16, 2025.
Eligibility criteriaStudies evaluating chronic aquatic exercise (multi-session interventions) compared with land-based exercise or non-exercise comparison groups in adults, measuring arterial stiffness via pulse wave velocity (PWV) or endothelial function via flow-mediated dilation (FMD).
ResultsThis review includes 18 randomized controlled trials with 845 participants (mean age 65 ± 7 years). Studies compared aquatic exercise with non-exercise controls (8 studies), land-based exercise (6 studies), or both (4 studies). Exercise sessions averaged 50 minutes, 3 times weekly for 11 weeks. Most studies (17 out of 18) implemented moderate-to-vigorous intensity protocols. Aquatic exercise resulted in improvements in arterial stiffness compared with non-exercise controls (7 studies; SMD = –2.37, 95% CI: –4.46 to –0.29; I2 = 98%: low certainty), with most evidence reflecting systemic and peripheral PWV. Changes in arterial stiffness did not differ from those observed after land-based exercise (6 studies; SMD = –0.07, 95% CI: –0.34 to 0.20; I2 = 0%, moderate certainty). For endothelial function, aquatic exercise may improve outcomes versus non-exercise controls (6 studies; SMD = 0.91, 95% CI: 0.39 to 1.43; I2 = 68%; low certainty) and may lead to greater improvements than land-based exercise (7 studies; SMD = 0.55, 95% CI: 0.05 to 1.06; I2 = 75%; low certainty).
ConclusionAquatic exercise improves systemic and peripheral arterial stiffness as well as endothelial function compared with non-exercising controls. Changes in arterial stiffness do not differ from those observed after land-based exercise. Aquatic exercise may provide greater improvement in endothelial function than land-based exercise, though this is supported by low-certainty evidence, and substantial heterogeneity limits confidence in the generalizability of this finding.
PROSPERO registrationCRD42025642087.
by Azusa Kubota, Kentaro Kojima, Shinnosuke Koketsu, Takayuki Kannon, Takehiro Sato, Kazuyoshi Hosomichi, Yoshiaki Shinohara, Atsushi Tajima
Brain asymmetry is a fundamental feature of neural organization. However, the molecular basis of hippocampal lateralization in response to environmental stimuli remains poorly understood. Here, we examined the transcriptomic profiles of the left and right hippocampal CA1 regions in rats reared under isolated or enriched housing conditions to elucidate hemisphere-specific responses and shared molecular adaptations. RNA-sequencing analysis revealed lateralized differences in the number and identity of differentially expressed genes, accompanied by distinct biological themes, as indicated by overrepresentation and gene set enrichment analysis. The left CA1 region was prominently engaged in pathways related to synaptic organization and mitochondrial function, whereas the right CA1 region exhibited enrichment in transcriptional regulation and RNA metabolic processes. Despite these asymmetries, co-expression and protein–protein interaction network analyses revealed shared molecular architectures. Immediate early genes formed consistent central hubs across both hemispheres, and a common Mecp2–Grin2b–Cdkl5–Tet3 protein interaction cluster was identified as a potential integrative regulatory module. Additional enrichment analysis of differentially expressed genes shared between hemispheres further highlighted conserved responses, particularly in synaptic plasticity and cell–cell communication. Together, these findings demonstrate that the left and right CA1 regions employ distinct yet partially convergent transcriptional programs to adapt to environmental stimuli. This coordinated molecular asymmetry provides novel insights into hippocampal lateralization and its role in experience-dependent brain plasticity.
by Thomas Buyinza, Edward Buzigi, Joshua Kitimbo, Gabriel Ssabika, Mary Mbuliro, Julius Kiwanuka, Justine Bukenya, David Guwatudde, Rawlance Ndejjo
IntroductionAdolescents and young adults (AYAs) worldwide display poor dietary behaviors, including high consumption of sugar-sweetened beverages and insufficient intake of fruits and vegetables. These issues are more pronounced in Sub-Saharan Africa, such as rural Eastern Uganda, where 45.3% of adolescents eat low-diversity diets high in refined grains and fats. Such diets raise the risk of malnutrition and diet-related non-communicable diseases (NCDs). However, there is limited contextual evidence on the multi-level factors influencing AYAs’ dietary behaviors in rural Uganda. This study examined socio-ecological factors shaping dietary behaviors among AYAs in this setting.
MethodsA qualitative study guided by the socio-ecological model (SEM) was conducted in Mayuge District, Eastern Uganda. Focus group discussions (FGDs) were held with AYAs, including male and female, aged 10–14, 15–19, and 20–24 years. To have a nuanced understanding of how AYAs’ dietary behaviours are shaped, additional FGDs were conducted with parents or guardians and teachers, and key informant interviews with the district education officer, nutrition focal person, civil society staff, and food vendors. Data were analyzed in ATLAS.ti using both inductive and deductive thematic approaches: data-driven sub-themes were first identified inductively, then deductively mapped onto pre-determined themes of the SEM.
ResultsDietary behaviors were shaped by satiety, energy needs, sensory appeal, and nutrition knowledge at the individual level. Peer influence, parental control, and food’s perceived link to attractiveness acted interpersonally, while community factors included gendered cultural taboos, norms, and health worker advice. At the societal level, cultural identity, ancestral restrictions, and media exposure strongly influenced choices.
ConclusionsThis study contributes novel rural-specific evidence from rural Uganda, where AYAs’ diets are uniquely constrained by satiety demands, parental dominance, cultural taboos, and seasonal scarcity; contrasting with urban contexts where convenience, autonomy, and wider food environments prevail. Multi-level interventions integrating nutrition education, family and peer engagement, cultural dialogue, and household food security support are essential for promoting healthier diets in resource-limited rural settings.
by Temitope Ruth Folorunso, Gabriel Silva, Marilis E. Girón, Tess Lindow, Micah Persyn, Lori Eckhardt, Janna R. Willoughby
Effective culturing and DNA extraction protocols are essential for advancing research on fungal pathogens of brown spot needle blight (BSNB) that infect loblolly pine (Pinus taeda) and other Pinus species. We evaluated the performance of four widely used fungal media, including Sabouraud dextrose, malt extract, potato dextrose, and yeast extract peptone dextrose, in both solid (agar) and liquid (broth) formats, quantifying fungal growth through colony diameter and biomass accumulation over a three-week period. Sabouraud dextrose agar and broth consistently supported the most rapid and extensive growth in both formats, while potato dextrose underperformed across these metrics. To identify an optimal protocol for downstream molecular applications, we also compared four DNA extraction methods, three of which were modified variants of the CTAB (cetyl-trimethyl-ammonium bromide) chemistry as well as the Qiagen DNeasy kit following the yeast DNA extraction protocol. DNA yield, quantified by fluorometry, was highest for the high-salt CTAB polyvinylpyrrolidone (PVP) protocol and DNA purity (assessed by 260/280 absorbance ratio) was optimal for both PVP and Qiagen extractions. From these comparisons, we suggest that Sabouraud dextrose culturing combined with CTAB PVP extraction for use as a robust and accessible pipeline for generating high-quality fungal DNA.
by Kenichi Shibuya, Rie Ibusuki, Daisaku Nishimoto, Shiroh Tanoue, Chihaya Koriyama, Shuhei Niiyama, Yasuyuki Kakihana, Toshiro Takezaki, Megumi Hara, Yuichiro Nishida, Sadao Suzuki, Takeshi Nishiyama, Mako Nagayoshi, Takashi Tamura, Yudai Tamada, Rieko Okada, Teruhide Koyama, Satomi Tomida, Kiyonori Kuriki, Jun Otonari, Hiroaki Ikezaki, Asahi Hishida, Masashi Ishizu, Sakurako Katsuura-Kamano, Kenji Wakai, Keitaro Matsuo, for the J-MICC Study group
Although the clinical importance of serum albumin and gamma gap levels is well established, it is unclear how these levels are associated with health risks in the general population. This cohort study aimed to clarify the association between serum albumin and gamma gap levels, and their combined effect, and mortality risk in a Japanese population. The participants totaled 35,746 (17,160 men and 18,586 women) aged 35–69 years from the Japan Multi-Institutional Collaborative Cohort (J-MICC) Study. The mean follow-up period was 11.8 years, with 1,529 deaths and 1,907 censoring. The Cox proportional hazards model was used to estimate hazard ratios (HRs) and 95% confidence intervals after adjusting for related factors. Increased HRs of low albumin and high gamma gap levels were respectively observed for deaths from all-causes, cancer, cardiovascular diseases, respiratory system diseases without pneumonia, and other-causes; and the HR was the highest on respiratory system diseases without pneumonia (HR = 7.31, 4.15–12.9). Low albumin and low gamma gap levels were strongly associated for pneumonia death (HR = 12.4, 3.98–38.5). The interaction between albumin and gamma gap levels was significant for deaths from all-causes, pneumonia and other-causes. The dose relationship for each association was dose-dependent in albumin and threshold-type in gamma gap, except for other-causes. This study suggests that albumin and gamma gap levels are independent indicators of an increased risk of mortality in a Japanese population. Combined effect was apparent for mortality from all-causes, pneumonia, and other-causes.
by Sadahiro Hijikata, Norihiko Inoue, Kiyohide Fushimi, Tetsuo Sasano
Takotsubo cardiomyopathy is characterized by temporary ballooning of the left ventricle and may lead to thrombosis, necessitating anticoagulation therapy in high-risk patients. However, no previous studies have compared anticoagulation therapies for this population. We aimed to compare the clinical outcomes of patients treated with direct oral anticoagulants (DOACs) and those treated with heparin. This retrospective study included patients with Takotsubo cardiomyopathy receiving DOACs or heparin within the first 2 days of admission between April 2012 and March 2021, identified from a nationwide in-hospital database in Japan. The primary outcome was in-hospital mortality. The secondary outcomes were ischemic and bleeding events, hospitalization costs, and length of hospital stay. After adjustment with propensity score-based inverse probability weighting, the risks of outcomes were estimated using Poisson regression models. Among 4,813 patients, 530 received DOACs and 4,283 received heparin. The DOAC group was older than the heparin group (mean [standard deviation] 78.1 [9.4] vs. 74.4 [11.2] years). After covariate adjustment, in-hospital mortality (4.0% vs. 3.8%; p = 0.87), ischemic events (1.1% vs. 2.8%; p = 0.067), and bleeding events (0.2% vs. 0.3%; p = 0.67) did not significantly differ between the DOAC and heparin groups. In contrast, the DOAC group had shorter hospital stays (median, 11 days vs. 13 days; p
by Sophie Lekkerkerker, Karin A. H. Kaasjager, Saskia Haitjema, Cornelia Hulsbergen-Veelken, Karin H. Herbschleb, Marianne C. Verhaar, Meriem Khairoun, Gurbey Ocak
BackgroundAlthough immune checkpoint inhibitors improve survival in patients with malignancies, a substantial number of patients treated with these agents experience immune-related adverse events. It is unknown whether inflammation-related hematological ratios are associated with immune-related adverse events or mortality.
ObjectiveWe aimed to investigate the association between pretreatment inflammation-related hematological ratios and the occurrence of immune-related adverse events and mortality in patients receiving checkpoint inhibitors.
MethodsPatients treated with checkpoint inhibitors within a tertiary hospital in the Netherlands were studied using routine care data between January 2013 and May 2020. Cox regression analysis was performed to assess the association between neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), neutrophil-to-lymphocytes and platelets ratio (NLPR), and systemic immune-inflammation index (SII) and outcomes (immune-related adverse events or mortality).
ResultsAmong 664 patients treated with checkpoint inhibitors, 397 (59.8%) patients developed an immune-related adverse event and 363 (54.7%) patients died during a median follow-up period of 17 months (interquartile range 7–30 months). Hematological ratios were not associated with immune-related adverse events. However, highest tertiles as compared with lowest tertiles of all hematological ratios were independently associated with mortality (NLR: adjusted hazard ratio (HR) 2.23, 95% CI 1.69–2.95; PLR: adjusted HR 1.88, 95% CI 1.43–2.47; NLPR: adjusted 1.59, 95% CI 1.22–2.06; SII: adjusted HR 2.33, 95% CI 1.77–3.08).
ConclusionIn this study, pretreatment inflammation-based hematological ratios were not associated with future immune-related adverse events in patients treated with checkpoint inhibitors. However, elevated hematological ratios were associated with an increased mortality risk.
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