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1.
A maintained absolute lymphocyte count predicts the overall survival benefit from eribulin therapy, including eribulin re-administration, in HER2-negative advanced breast cancer patients: a single-institutional experience.
Watanabe, J, Saito, M, Horimoto, Y, Nakamoto, S
Breast cancer research and treatment. 2020;(1):211-220
Abstract
PURPOSE Eribulin methylate (eribulin) improved the overall survival (OS) of HER2-negative advanced breast cancer (HER2-ABC) patients; however, the mechanism underlying the OS improvement has not been clarified. Several reports suggest that eribulin promotes antitumor immunity via tumor micro-environment conditioning. Recently, a maintained baseline lymphocyte count was proposed as predictive marker for eribulin therapy in HER2-ABC patients; however, no associations with the OS have been noted. We retrospectively investigated the neutrophil-to-lymphocyte ratio and absolute lymphocyte count (ALC) in HER2-ABC patients receiving eribulin and assessed the utility of eribulin re-administration for further OS improvement. METHODS HER2-ABC patients who received eribulin therapy at Shizuoka Cancer Center between November 2011 and December 2018 were retrospectively analyzed. RESULTS A total of 144 HER2-ABC (108 estrogen receptor-positive [ER+], 36 ER-) patients were identified, and 32 patients (28 ER+ , 4 ER-) were re-administered with eribulin. In the ER+ subgroup, a multivariate analysis showed that an ALC ≥ 1000/μL and re-administration were significantly associated with the OS (hazard ratio [HR] 0.503; P = 0.034 and HR 0.366; P < 0.0001, respectively), and an ALC ≥ 1000/μL was also identified as the only predictive factor for re-administration (HR 0.329; P = 0.033). In contrast, a multivariate analysis in the ER- subgroup identified no predictive markers. CONCLUSION In HER2-ER + ABC patients, ALC was identified as a predictive marker for eribulin therapy, and the re-administration of eribulin is considered a valid therapeutic option for further improvement of the OS.
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Immunoregulatory Sensory Circuits in Group 3 Innate Lymphoid Cell (ILC3) Function and Tissue Homeostasis.
Domingues, RG, Hepworth, MR
Frontiers in immunology. 2020;:116
Abstract
Recent years have seen a revolution in our understanding of how cells of the immune system are modulated and regulated not only via complex interactions with other immune cells, but also through a range of potent inputs derived from diverse and varied biological systems. Within complex tissue environments, such as the gastrointestinal tract and lung, these systems act to orchestrate and temporally align immune responses, regulate cellular function, and ensure tissue homeostasis and protective immunity. Group 3 Innate Lymphoid Cells (ILC3s) are key sentinels of barrier tissue homeostasis and critical regulators of host-commensal mutualism-and respond rapidly to damage, inflammation and infection to restore tissue health. Recent findings place ILC3s as strategic integrators of environmental signals. As a consequence, ILC3s are ideally positioned to detect perturbations in cues derived from the environment-such as the diet and microbiota-as well as signals produced by the host nervous, endocrine and circadian systems. Together these cues act in concert to induce ILC3 effector function, and form critical sensory circuits that continually function to reinforce tissue homeostasis. In this review we will take a holistic, organismal view of ILC3 biology and explore the tissue sensory circuits that regulate ILC3 function and align ILC3 responses with changes within the intestinal environment.
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Neutrophil-lymphocyte ratio and nutritional status are clinically useful in predicting prognosis in colorectal cancer patients.
Silva, TH, Schilithz, AOC, Peres, WAF, Murad, LB
Nutrition and cancer. 2020;(8):1345-1354
Abstract
Background: Neutrophil-lymphocyte ratio (NLR) and nutritional status may provide a prognostic value in colorectal cancer (CRC). Thus, aim of this study was to evaluate the prognostic value of nutritional status and NLR in CRC patients.Methods: A retrospective analysis was conducted in CRC patients. The independent variables were body mass index (BMI), weight loss (WL) and NLR. Logistic regression was used to estimate the odds chance of low NLR. Kaplan-Meier curves and Cox regression were used to evaluate the overall survival at 5 years old.Results: In the 148 patients evaluated, the most prevalent nutritional status was overweight/obesity (43.2%) and 27.0% had severe WL. Sixty-seven subjects (45.3%) had NLR ≥ 3 that was associated with the lower OS (P < 0.001). There was a higher OS for overweight/obese patients (P = 0.002) and a lower among subjects with severe WL (P = 0.009). The NLR ≥3 (HR: 3.639; 95% CI, 1.708-7.771) was an independent poor prognostic factor for OS. Patients without WL (HR: 0.367, 95% CI, 0.141-0.954) and classified as overweight/obesity (HR: 0.260; 95% CI, 0.106-0.639) presented better prognostic.Conclusion: NLR, WL, BMI assessments are promising prognostic indicators in the CRC.
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Prognostic value of pre-treatment Naples prognostic score (NPS) in patients with osteosarcoma.
Yang, Q, Chen, T, Yao, Z, Zhang, X
World journal of surgical oncology. 2020;(1):24
Abstract
BACKGROUND This study aimed to evaluate the clinical significance of pre-treatment Naples prognostic score (NPS) in patients with osteosarcoma. METHODS The clinical data of 133 osteosarcoma patients between January 2011 and February 2018 in our hospital was retrospectively collected and analyzed. NPS was calculated from four parameters, including serum albumin level, serum total cholesterol (TC), lymphocyte-to-monocyte ratio (LMR), and neutrophil-to-lymphocyte ratio (NLR). Patients were divided into three groups (group 1-3) based on NPS. The relationships between NPS and clinical features, overall survival (OS), and progression-free survival (PFS) were analyzed. Two prediction models based on NPS and clinical parameters were developed: clinical parameters model (model A), and the combined model of NPS and clinical parameters (model B). Their predictive performances were further evaluated and compared. RESULTS The median follow-up time of this cohort was 46.0 (range, 5-75) months, while the median OS and PFS was 40 (range, 5-75) months and 36 (range, 5-71) months, respectively. NPS was significantly correlated with gender, tumor location, Enneking stage, pathological fracture, local recurrence, and metastasis (all P < 0.05). Variables of NPS, Enneking stage, local recurrence, metastasis, and NLR were confirmed as independent prognostic factors for OS and PFS by univariate and multivariate Cox analysis. Prediction model B obtained larger AUCs for OS and PFS and showed better consistency between nomogram-predicted and actual survival than that of model A at the follow-up time of 1-, 3-, and 5-year. CONCLUSIONS NPS was a novel, reliable, and multidimensional prognostic scoring system with favorable predictive performance for patients with osteosarcoma.
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Neutrophil-to-lymphocyte ratio and histological type might predict clinical responses to eriburin-based treatment in patients with metastatic breast cancer.
Myojin, M, Horimoto, Y, Ito, M, Kitano, S, Ishizuka, Y, Sasaki, R, Uomori, T, Himuro, T, Murakami, F, Nakai, K, et al
Breast cancer (Tokyo, Japan). 2020;(4):732-738
Abstract
BACKGROUND Metastatic breast cancer (MBC) is generally considered to be incurable. Although many options are available for treating MBC, physicians often encounter difficulties in choosing the most appropriate treatment because the MBCs of individual patients respond differently even to the same treatments. Thus, predictive markers for therapeutic efficacy are urgently needed. Neutrophil- and platelet-to-lymphocyte ratios (NLR and PLR, respectively), have been studied and established as prognostic markers for breast cancer patients but whether either or both of these markers are predictive of treatment responses is still unclear. Herein, we investigated predictive markers for eribulin-based treatment responsiveness in patients with MBC, by examining clinicopathological features, including several markers of immunocompetent cells in peripheral blood. METHODS Clinicopathological features of the 104 patients with metastatic/Stage IV breast cancer given eribulin-based regimens were investigated in relation to clinical responses to eribulin-based treatments and progression-free-survival (PFS). RESULTS Special histological types and high NLR at baseline were independently related to poor clinical responses to the treatments (p = 0.023 and 0.039, respectively). The Cox hazard model revealed that patients with oestrogen receptor (ER)-negative tumours and high NLR, monocyte-to-lymphocyte ratio (MLR) and PLR showed significantly shorter PFS (p = 0.021, 0.005, 0.008 and 0.030, respectively). On multivariate analysis, only ER status and NLR remained independent factors related to PFS (p = 0.011 and 0.003, respectively). CONCLUSIONS Our data revealed that special histological types and high NLR might be factors related to low responsiveness to eribulin-based regimens in patients with MBC.
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Iron metabolism and lymphocyte characterisation during Covid-19 infection in ICU patients: an observational cohort study.
Bolondi, G, Russo, E, Gamberini, E, Circelli, A, Meca, MCC, Brogi, E, Viola, L, Bissoni, L, Poletti, V, Agnoletti, V
World journal of emergency surgery : WJES. 2020;(1):41
Abstract
BACKGROUND Iron metabolism and immune response to SARS-CoV-2 have not been described yet in intensive care patients, although they are likely involved in Covid-19 pathogenesis. METHODS We performed an observational study during the peak of pandemic in our intensive care unit, dosing D-dimer, C-reactive protein, troponin T, lactate dehydrogenase, ferritin, serum iron, transferrin, transferrin saturation, transferrin soluble receptor, lymphocyte count and NK, CD3, CD4, CD8 and B subgroups of 31 patients during the first 2 weeks of their ICU stay. Correlation with mortality and severity at the time of admission was tested with the Spearman coefficient and Mann-Whitney test. Trends over time were tested with the Kruskal-Wallis analysis. RESULTS Lymphopenia is severe and constant, with a nadir on day 2 of ICU stay (median 0.555 109/L; interquartile range (IQR) 0.450 109/L); all lymphocytic subgroups are dramatically reduced in critically ill patients, while CD4/CD8 ratio remains normal. Neither ferritin nor lymphocyte count follows significant trends in ICU patients. Transferrin saturation is extremely reduced at ICU admission (median 9%; IQR 7%), then significantly increases at days 3 to 6 (median 33%, IQR 26.5%, p value 0.026). The same trend is observed with serum iron levels (median 25.5 μg/L, IQR 69 μg/L at admission; median 73 μg/L, IQR 56 μg/L on days 3 to 6) without reaching statistical significance. Hyperferritinemia is constant during intensive care stay: however, its dosage might be helpful in individuating patients developing haemophagocytic lymphohistiocytosis. D-dimer is elevated and progressively increases from admission (median 1319 μg/L; IQR 1285 μg/L) to days 3 to 6 (median 6820 μg/L; IQR 6619 μg/L), despite not reaching significant results. We describe trends of all the abovementioned parameters during ICU stay. CONCLUSIONS The description of iron metabolism and lymphocyte count in Covid-19 patients admitted to the intensive care unit provided with this paper might allow a wider understanding of SARS-CoV-2 pathophysiology.
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High absolute lymphocyte counts are associated with longer overall survival in patients with metastatic breast cancer treated with eribulin-but not with treatment of physician's choice-in the EMBRACE study.
Miyoshi, Y, Yoshimura, Y, Saito, K, Muramoto, K, Sugawara, M, Alexis, K, Nomoto, K, Nakamura, S, Saeki, T, Watanabe, J, et al
Breast cancer (Tokyo, Japan). 2020;(4):706-715
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Abstract
BACKGROUND Eribulin, a nontaxane synthetic inhibitor of microtubule dynamics, is widely used to manage locally advanced or metastatic breast cancer (MBC). Eribulin has demonstrated immunomodulatory activity on the tumour microenvironment. Baseline neutrophil-to-lymphocyte ratio (NLR), a marker of immune status, may predict progression-free survival in eribulin treatment. This post hoc analysis assessed predictors for overall survival (OS). METHODS The phase 3 open-label study (EMBRACE) of eribulin versus treatment of physician's choice (TPC) in patients with MBC provided source data. Baseline absolute lymphocyte counts (ALCs) and NLR were evaluable in 751 and 713 patients, respectively. RESULTS Eribulin prolonged OS versus TPC in patients with baseline ALC ≥ 1500/µl (hazard ratio [HR] 0.586; 95% confidence interval [CI] 0.437-0.784; P < 0.001). There was no significant difference by treatment for ALC < 1500/µl (HR 1.002; 95% CI 0.800-1.253; P = 0.989). Univariate and multivariate analyses were performed and identified baseline ALC as a potential predictor of OS in eribulin-treated patients. Interaction analysis of OS supported 1500/µl as a potentially differential cutoff value. NLR at a cutoff value of 3 was associated with prolonged OS (eribulin group). However, similar results were also observed in the TPC group, without apparent interaction effect, suggesting that NLR may be a general prognostic marker rather than a specific predictor of OS for eribulin. DISCUSSION This hypothesis-generating study speculates that baseline ALC may be an independent predictor for longer OS in eribulin-treated MBC patients and could be clinically impactful because it can be evaluated without the need for additional invasive procedures. TRIAL REGISTRATION www.ClinicalTrials.gov code: NCT00388726.
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Lymphocyte-to-C-reactive protein ratio and score are clinically feasible nutrition-inflammation markers of outcome in patients with gastric cancer.
Okugawa, Y, Toiyama, Y, Yamamoto, A, Shigemori, T, Ichikawa, T, Yin, C, Suzuki, A, Fujikawa, H, Yasuda, H, Hiro, J, et al
Clinical nutrition (Edinburgh, Scotland). 2020;(4):1209-1217
Abstract
BACKGROUNDS Systemic inflammation arising from complex host-tumour interactions is considered the seventh hallmark of cancer. The aim of this study was to assess the clinical feasibility of our newly developed 'lymphocyte-to-C-reactive protein (CRP) ratio' (LCR) and 'lymphocyte CRP score' (LCS) for predicting short- and long-term outcomes in patients with gastric cancer (GC). METHODS In this observational study, we retrospectively analysed pre-operative LCRs and LCSs from 551 GC patients to elucidate these prognostic value for overall survival (OS) and disease free survival (DFS) and to clarify these predictive value for peri-operative risk of surgical site infection (SSI) in GC patients. RESULTS Reduced pre-operative LCRs significantly correlated with all of the well-established clinicopathological factors for disease development, including advanced T stage, venous and lymphatic vessel invasion, lymph node/hepatic/peritoneal metastasis, distant metastasis, and advanced tumour-node-metastasis stage. In the short-term outcome, low pre-operative LCR was an independent predictive factor for post-operative SSI. In the long-term outcome, low pre-operative LCR was an independent prognostic factor for OS and DFS, and prognostic impact of pre-operative LCR were verified in patients with metastatic and non-metastatic gastric cancer. Furthermore, our developed scoring system using lymphocyte and CRP (Lymphocyte-CRP Score; LCS) could also demonstrate all of clinical significance in GC patients, and both of LCR and LCS were significantly correlated with various representative nutrition markers, including BMI, PNI, and albumin, in GC patients. CONCLUSIONS Pre-operative LCR and LCS are clinically feasible nutrition-inflammation markers in GC patients. Assessment of lymphocytes and CRP could aid physicians in determining surgical risk and oncological risk, thus facilitating appropriate peri-operative and post-operative management of patients with GC.
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Neutrophil to lymphocyte ratio and cancer prognosis: an umbrella review of systematic reviews and meta-analyses of observational studies.
Cupp, MA, Cariolou, M, Tzoulaki, I, Aune, D, Evangelou, E, Berlanga-Taylor, AJ
BMC medicine. 2020;(1):360
Abstract
BACKGROUND Although neutrophils have been linked to the progression of cancer, uncertainty exists around their association with cancer outcomes, depending on the site, outcome and treatments considered. We aimed to evaluate the strength and validity of evidence on the association between either the neutrophil to lymphocyte ratio (NLR) or tumour-associated neutrophils (TAN) and cancer prognosis. METHODS We searched MEDLINE, Embase and Cochrane Database of Systematic Reviews from inception to 29 May 2020 for systematic reviews and meta-analyses of observational studies on neutrophil counts (here NLR or TAN) and specific cancer outcomes related to disease progression or survival. The available evidence was graded as strong, highly suggestive, suggestive, weak or uncertain through the application of pre-set GRADE criteria. RESULTS A total of 204 meta-analyses from 86 studies investigating the association between either NLR or TAN and cancer outcomes met the criteria for inclusion. All but one meta-analyses found a hazard ratio (HR) which increased risk (HR > 1). We did not find sufficient meta-analyses to evaluate TAN and cancer outcomes (N = 9). When assessed for magnitude of effect, significance and bias related to heterogeneity and small study effects, 18 (9%) associations between NLR and outcomes in composite cancer endpoints (combined analysis), cancers treated with immunotherapy and some site specific cancers (urinary, nasopharyngeal, gastric, breast, endometrial, soft tissue sarcoma and hepatocellular cancers) were supported by strong evidence. CONCLUSION In total, 60 (29%) meta-analyses presented strong or highly suggestive evidence. Although the NLR and TAN hold clinical promise in their association with poor cancer prognosis, further research is required to provide robust evidence, assess causality and test clinical utility. TRIAL REGISTRATION PROSPERO CRD42017069131 .
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Preceding exercise and postprandial hypertriglyceridemia: effects on lymphocyte cell DNA damage and vascular inflammation.
Brown, M, McClean, CM, Davison, GW, Brown, JCW, Murphy, MH
Lipids in health and disease. 2019;(1):125
Abstract
BACKGROUND Exercise has proved effective in attenuating the unfavourable response normally associated with postprandial hypertriglyceridemia (PHTG) and accompanying oxidative stress. Yet, the acute effects of prior exercise and PHTG on DNA damage remains unknown. The purpose of this study was to examine if walking alters PHTG-induced oxidative damage and the interrelated inflammatory mechanisms. METHODS Twelve apparently healthy, recreationally active, male participants (22.4 ± 4.1 years; 179.2 ± 6 cm; 84.2 ± 14.7 kg; 51.3 ± 8.6 ml·kg- 1·min- 1) completed a randomised, crossover study consisting of two trials: (1) a high-fat meal alone (resting control) or (2) a high-fat meal immediately following 1 h of moderate exercise (65% maximal heart rate). Venous blood samples were collected at baseline, immediately post-exercise or rest, as well as at 2, 4 and 6 h post-meal. Biomarkers of oxidative damage (DNA single-strand breaks, lipid peroxidation and free radical metabolism) and inflammation were determined using conventional biochemistry techniques. RESULTS DNA damage, lipid peroxidation, free radical metabolism and triglycerides increased postprandially (main effect for time, p < 0.05), regardless of completing 1 h of preceding moderate intensity exercise. Plasma antioxidants (α-tocopherol and γ-tocopherol) also mobilised in response to the high-fat meal (main effect for time, p < 0.05), but no changes were detected for retinol-binding protein-4. CONCLUSION The ingestion of a high fat meal induces postprandial oxidative stress, inflammation and a rise in DNA damage that remains unaltered by one hour of preceding exercise.