Integration of circulating tumor cell and neutrophil-lymphocyte ratio to identify high-risk metastatic castration-resistant prostate cancer patients.

BACKGROUND: The neutrophil-lymphocyte ratio (NLR), platelet-lymphocyte ratio (PLR), and circulating tumor cells (CTCs) have been associated with survival in castration-resistant prostate cancer (CRPC). However, no study has examined the prognostic value of NLR and PLR in the context of CTCs. METHODS: Baseline CTCs from mCRPC patients were enumerated using the CellSearch System. Baseline NLR and PLR values were calculated using the data from routine complete blood counts. The associations of CTC, NLR, and PLR values, individually and jointly, with progression-free survival (PFS) and overall survival (OS), were evaluated using Kaplan-Meier analysis, as well as univariate and multivariate Cox models. RESULTS: CTCs were detected in 37 (58.7%) of 63 mCRPC patients, and among them, 16 (25.4%) had ≥5 CTCs. The presence of CTCs was significantly associated with a 4.02-fold increased risk for progression and a 3.72-fold increased risk of death during a median follow-up of 17.6 months. OS was shorter among patients with high levels of NLR or PLR than those with low levels (log-rank P = 0.023 and 0.077). Neither NLR nor PLR was individually associated with PFS. Among the 37 patients with detectable CTCs, those with a high NLR had significantly shorter OS (log-rank P = 0.024); however, among the 26 patients without CTCs, the OS difference between high- and low-NLR groups was not statistically significant. Compared to the patients with CTCs and low NLR, those with CTCs and high levels of NLR had a 3.79-fold risk of death (P = 0.036). This association remained significant after adjusting for covariates (P = 0.031). Combination analyses of CTC and PLR did not yield significant results. CONCLUSION: Among patients with detectable CTCs, the use of NLR could further classify patients into different risk groups, suggesting a complementary role for NLR in CTC-based prognostic stratification in mCRPC

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ABSTRACT. Objective. To explore the potential role of Dickkopf-1 (DKK-1) in rheumatoid arthritis (RA) and to evaluate the effect of a tumor necrosis factor-a (TNF-a) inhibitor (infliximab) and an interleukin 1 receptor antagonist (IL-1Ra; anakinra) on DKK-1 secretion in patients with RA. Methods. Serum samples were collected from 100 patients with RA, 100 patients with other rheumatic diseases (e.g., osteoarthritis and ankylosing spondylitis), and 40 healthy controls. DKK-1 and osteoprotegerin (OPG) levels in serum were detected by ELISA. Serum C-reactive protein (CRP) levels, erythrocyte sedimentation rates (ESR), rheumatoid factor (RF) titers, and anti-cyclic citrullinated peptide antibody were also measured in patients with RA. Results. The serum level of DKK-1 was significantly higher in patients with RA than in healthy controls and those with other rheumatic diseases (p < 0.01); the serum DKK-1 level was correlated with levels of CRP (r = 0.488, p = 0.003) and ESR (r = 0.458, p = 2.4 x 10 -4 ) and the Sharp score of radiologic change (r = 0.449, p = 0.001) in RA. In contrast to the increasing level of OPG, DKK-1 was significantly decreased in RA patients treated with TNF-a inhibitor (p < 0.01). DKK-1 was significantly decreased in RA patients treated with IL-1Ra (p < 0.01). Conclusion. DKK-1, as an important mediator, was correlated with bone erosion and inflammation in RA. Rheumatoid arthritis (RA) is a chronic autoimmune inflammatory disease that primarily attacks synovial joints, leading to articular destruction and functional disability. It typically presents as symmetric peripheral polyarthritis and most commonly involves the small joints of the hands and feet 1,2 . One of the hallmarks of RA is progressive bone erosion. Research on the mechanisms by which RA induces osteolysis has focused on the osteoclast's roles in shifting the normal balance between bone formation and resorption. This imbalance is generated by key molecules that regulate osteoclast differentiation, such as cross-talk between receptor activators of nuclear factor-kB ligand (RANKL) and Wingless (Wnt) signaling pathway, which is important for the growth and differentiation of osteoblasts 3,4 . Dickkopf-1 (DKK-1) is an endogenous, secreted inhibitory factor in the canonical Wnt signaling by binding the Wnt coreceptor LRP5/6 5 . Studies have demonstrated that activation of the Wnt signaling pathway in mature osteoblasts upregulates osteoprotegerin (OPG), which blocks RANKL-induced osteoclastogenesis and results in the inhibition of bone resorption Cytokines play a pivotal role in RA pathogenesis. Tumor necrosis factor-a (TNF-a) contributes substantially to the pathology of RA. Interestingly, studies have shown that upregulation of DKK-1 could activate TNF receptor-1 (TNFR1) in cultivated articular mesenchymal cells 11 . TNF-a inhibitor could downregulate DKK-1 in ankylosing spondylitis (AS) 12 . Moreover, interleukin 1 (IL-1) can modulate the RANKL/OPG pathway, and may also affect the ability of the osteoblast to repair bone at sites of articular erosio

Infant Feeding Regimens and Gastrointestinal Tolerance: A Multicenter, Prospective, Observational Cohort Study in China

To study feeding tolerance in infants fed formula with increased sn -2 palmitate and oligofructose ( sn -2+OF) in a real-world setting, healthy Chinese infants were enrolled in this 48-day observational study on their current feeding regimens: exclusively breastfed (BF; n = 147), exclusively sn -2+OF formula-fed (FF; n = 150), or mixed-fed with breast milk and sn -2+OF formula (MF; n = 163). Throughout the study, incidence (90% confidence interval) of hard stools was ≤2.1% (0.0-5.3) in FF and 0.8% (0.0-3.5) in MF, with no hard stools in BF. Incidence of watery stools was ≤5.0% (1.0-9.2) in FF and ≥5.1% (2.4-9.3) in MF and BF. Gastrointestinal tolerance scores, although low in all groups (lower scores indicating better tolerance), were slightly higher ( P ≥ .03) in FF (17.5 ± 4.8) and MF (18.2 ± 5.0) versus BF (16.3 ± 3.2) at mid-study; this difference disappeared at study end. Overall, low incidences of hard and watery stools and good feeding tolerance were observed in infants fed sn -2+OF formula

The Value of Dual-Energy Computed Tomography-Based Radiomics in the Evaluation of Interstitial Fibers of Clear Cell Renal Carcinoma

Objective We investigated the potential of dual-energy computed tomography (DECT) radiomics in assessing cancer-associated fibroblasts in clear cell renal carcinoma (ccRCC). Methods A retrospective analysis was conducted on 132 patients with ccRCC. The arterial and venous phase iodine-based material decomposition images (IMDIs), virtual non-contrast images, 70 keV, 100 keV, and 150 keV virtual monoenergetic images, and mixed energy images (MEIs) were obtained from the DECT datasets. On the Radcloud platform, radiomics feature extraction, feature selection, and model establishment were performed. Seven radiomics models were established using the support vector machine. The predictive performance was evaluated by utilizing receiver operating characteristic and the area under the curve (AUC) was calculated. Nomograms were constructed. Results The combined model demonstrated high efficiency in evaluating pseudocapsule thickness with AUC, specificity, and sensitivity of 0.833, 0.870, and 0.750, respectively in the validation set, surpassing those of other models. The precision, F1-score, and Youden index were also higher for the combined model. For evaluating the number of collagen fibers, the combined model exhibited the highest AUC (0.741) among all models, with a specificity of 0.830 and a sensitivity of 0.330. The AUC in the 150 kv model and IMDI model were slightly lower than those in the combined model (0.728 and 0.710, respectively), with corresponding sensitivity and specificity of 0.560/0.780 and 0.670/0.830. The nomogram exhibited that Rad-score had good prediction efficiency. Conclusion DECT radiomics features have significant value in evaluating the interstitial fibers of ccRCC. The combined model of IMDI + MEI exhibits superior performance in assessing the thickness of the pseudocapsule, while the combined, 150 keV, and IMDI models demonstrate higher efficacy in evaluating collagen fiber number. Radiomics, combined with imaging features and clinical features, has excellent predictive performance. These findings offer crucial support for the clinical diagnosis, treatment, and prognosis of ccRCC and provide valuable insights into the application of DECT

Effects of Managing Cancer and Living Meaningfully on Cancer-Related Fatigue and Cytokine Levels in Gastrointestinal Cancer Patients

Objective: To evaluate the effects of managing cancer and living meaningfully (CALM), a psychological intervention with semi-structured interviews, on cancer-related fatigue (CRF), quality of life (QOL), and sleep quality in patients with gastrointestinal (GI) cancer, which may be accompanied by changes in cytokine levels. Methods: A total of 152 GI cancer patients with CRF were enrolled in the study during treatment. Patients were randomly assigned to CALM or usual care (UC) groups. Patients in the CALM group received 12 weeks of CALM plus usual care, and patients in the UC group received usual care plus usual health education. All study participants were evaluated at baseline and at 12 weeks using the Revised Piper Fatigue Scale, the European Organization for Research and Treatment of Cancer-Quality of Life Questionnaire-Core 30, and the Pittsburgh Sleep Quality Index scale, while cytokine levels were measured. Results: At 12 weeks, the differences in total CRF, QOL, sleep quality, IL-6, IL-4, and TNF-α levels were statistically significant not only in the CALM group compared to patients in the UC group ( t  = −7.902, t  = 2.163, t  = −2.187, t  = 3.313, t  = −4.120, t  = −3.853, respectively; P  < .05), but also in the CALM group compared to baseline ( t  = 11.331, t  = −5.492, t  = 5.450, t  = −2.418, t  = 2.186, t  = 2.699, respectively; P  < .05). Additionally, the total CRF at 12 weeks was correlated with IL-4, IL-6, and TNF-α levels ( r  = −.30, r  = .31, r  = .32, respectively; P  < .001). Conclusions: CALM alleviated CRF and improved QOL and sleep quality in patients with GI cancer, and these improvements were accompanied by changes in IL-4, IL-6, and TNF-α levels