Safety assessment of high fructose corn syrup and fructose used as sweeteners in foods.

High Fructose Corn Syrup (HFCS) and Fructose (FR) are widely used sweeteners in many foods and beverages. This study aimed at investigating the cytotoxic effects of HFCS (5%-30%) and FR (62.5-2000 µg/mL) using MTT assay in Human Hepatocellular Carcinoma (HepG2) cells, and genotoxic effects of using Chromosome Aberrations (CAs), Sister Chromatid Exchanges (SCEs), Micronuclei (MN) and comet assays in human lymphocytes. HFCS significantly reduced the cell viability in HepG2 cells at between 7.5% and 30% for 24 and 48 h. 30% HFCS caused a very significant toxic effect. FR had a cytotoxic effect in HepG2 cells at all treatments. However, as fructose concentration decreased, the cell viability decreased. HFCS (10%-20%) and FR (250-2000 µg/mL) decreased the mitotic index at higher concentrations. IC50 value was found to be a 15% for 48 h. IC50 value of FR was detected as 62.5 µg/mL for 24 h and 48 h. HFCS significantly increased CAs frequency at 15% and 20%. FR significantly increased the frequency of CAs at 250, 1000, and 2000 µg/mL for 48 h. Both sweeteners increased the frequency of SCEs at all concentrations. HFCS (15% and 20%) and FR (250, 1000, and 2000 µg/mL) induced MN frequency at higher concentrations. HFCS caused DNA damage in comet assay at 10% -30%. FR increased tail intensity and moment at 125-2000 µg/mL and tail length at 62.5, 250 and 500 µg/mL. Therefore, HFCS and FR are clearly seen to be cytotoxic and genotoxic, especially at higher concentrations.

HFCS and FR exhibited cytotoxic effect at HepG2 and human lymphocytes at higher concentrations.Both sweeteners increased the frequencies of CAs and SCEs at higher concentrations.HFCS caused DNA damage at 10% -30% concentrations.HFCS (15% and 20%) and FR (250, 1000, and 2000 µg/mL) induced MN frequency.

Assessment of Intratumoural and Stromal Infiltrating Lymphocytes In The Various Subtypes of Breast Carcinoma Patients who have Received Neoadjuvant Chemotherapy.

BACKGROUND: Breast cancer comprises a highly heterogeneous subset of tumours that respond well to Neoadjuvant Chemotherapy (NAC). Tumour Infiltrating Lymphocytes (TIL) act as a means to an end by shedding light on the treatment response as well as predictive factors to the clinicopathological features for the same. Therefore, this article attempts to shift the attention to the relevance of TIL in the aforementioned aspects by bringing to notice the contrasting traits displayed by them in the different immunohistochemical subtypes of breast carcinoma. MATERIALS AND METHODS: 75 triple-negative breast cancer (TNBC) patients, 25 human epidermal growth factor receptor (HER2BC) positive patients and 77 hormone receptor (HRBC) positive breast cancer patients were included in this study who received NAC before surgical excision of the tumour which was then stained using routine Haematoxylin and Eosin techniques. Standardised guidelines were used to evaluate TIL in the stroma and the tumour. RESULTS: In TNBC, a significant association between Intratumoural (IT) TIL (p=0.0288) and Intrastromal (IS) TIL (p=0.0250) with pathological complete response (pCR). IS TIL and age at operation (p=0.0494) showed significant values but no correlation was found with IT TIL. In HER2BC, IS TIL revealed a significant association with the tumour response(p=0.0229). A strong association was found between IT TIL and the age of menopause(p=0.0441). In HRBC, no significant associations were found between IT and IS TIL scores and the clinicopathological features. CONCLUSION: The predictive factors of TIL and complete response post-neoadjuvant chemotherapy can be a strong indicative factor for immunohistochemical markers. It also helps throw light on further studies which can be carried out to determine the clinicopathological features and TIL correlation in the various subtypes of breast carcinoma.

Diagnostic Value of Inflammation-Related Indicators in Distinguishing Early Colon Cancer and Adenomatous Polyps.

BACKGROUND: There are few clinical symptoms in early colorectal cancer, so it is necessary to find a simple and economical tumor detection index for auxiliary diagnosis. This study aims to explore the diagnostic value of preoperative inflammation-related indicators, such as neutrophil, lymphocyte, platelet count, platelet to lymphocyte ratio (PLA), neutrophil to lymphocyte ratio (NLR), and systemic immune-inflammation index (SII), for early colorectal cancer, and determine whether inflammation-related indicators can provide more accurate diagnostic judgment for patients. METHODS: This study was a retrospective study. Patients who were first diagnosed with colorectal cancer or colorectal adenomatous polyp at Beijing Friendship Hospital from October 2016 to October 2017 were retrospectively collected. According to inclusion and exclusion criteria, a total of 342 patients were included, including 216 patients with colorectal cancer and 126 patients with colorectal adenomatous polyp. Fasting venous blood and other clinical features were collected to compare the differences between colorectal cancer and colorectal adenoma. RESULTS: There were statistically significant differences in age, carcinoembryonic antigen, albumin, hemoglobin, mean platelet volume, lymphocyte, monocyte, NLR, PLA, SII, and mean platelet volume to platelet count ratio between colorectal cancer group and colorectal adenoma group (P < .05), and a Nomogram model was established. Using inflammatory markers to differentiate colorectal and colorectal polyps produced greater AUC than using tumor markers alone (.846 vs .695). CONCLUSION: Inflammation-related indicators, such as lymphocyte, monocyte, and mean platelet volume, may serve as potential indicators to assist in the diagnosis of early colorectal cancer.

Novel prognostic indicator combining inflammatory indicators and tumor markers for gastric cancer.

BACKGROUND: Gastric cancer (GC) is one of the most common malignant tumors worldwide, and we hope to identify an economical but practical prognostic indicator. It has been reported that inflammatory indicators and tumor markers are associated with GC progression and are widely used to predict prognosis. However, existing prognostic models do not comprehensively analyze these predictors. METHODS: This study retrospectively reviewed 893 consecutive patients who underwent curative gastrectomy from January 1, 2012, to December 31, 2015, in the Second Hospital of Anhui Medical University. Prognostic factors predicting overall survival (OS) were analyzed using univariate and multivariate Cox regression analyses. Nomograms including independent prognostic factors were plotted for predicting survival. RESULTS: Ultimately, 425 patients were enrolled in this study. Multivariate analyses demonstrated that the neutrophil-to-lymphocyte ratio (NLR, total neutrophil count/lymphocyte count × 100%) and CA19-9 were independent prognostic factors for OS (p=0.001, p=0.016). The NLR-CA19-9 score (NCS) is constructed as the combination of the NLR and CA19-9. We defined NLR<2.46 and CA19-9≤37 U/ml as an NCS of 0, NLR≥2.46 or CA19-9>37 U/ml as an NCS 1, and NLR≥2.46 and CA19-9>37 U/ml as an NCS of 2. The results showed that higher NCS was significantly associated with worse clinicopathological characteristics and OS (p<0.05). Multivariate analyses revealed that the NCS was an independent prognostic factor for OS (NCS1: p<0.001, HR=3.172, 95% CI=2.120-4.745; NCS2: p<0.001, HR=3.052, 95% CI=1.928-4.832). Compared with traditional predictive indices, the NCS had the highest AUC for a 12-month survival, a 36-month survival, a 60-month survival, and OS (AUC= 0.654, 0.730, 0.811, 0.803, respectively). The nomogram had a higher Harrell's C-index than the TNM stage alone (0.788 vs. 0.743). CONCLUSIONS: The NCS provides more accurate predictions of the prognosis of GC patients, and its predictive value is significantly better than that of traditional inflammatory indicators or tumor markers. It is an effective complement to existing GC assessment systems.

The neutrophil-to-lymphocyte ratio: A low-cost antenatal indicator of placental chorioamnionitis in women who deliver preterm without clinical signs and symptoms of infection.

Chorioamnionitis is present in up to 70% of spontaneous preterm births and is associated with poor maternal, fetal and neonatal outcomes. OBJECTIVE: To explore the relationship between the neutrophil-to-lymphocyte ratio and histological chorioamnionitis in women who delivered preterm with no clinical signs or symptoms of infection. STUDY DESIGN: This was a retrospective analysis of a cohort of women who delivered spontaneously between 16 and 36+6 weeks at a tertiary UK hospital. Only women with placental histology and no signs of clinical infection were included. The neutrophil-to-lymphocyte ratio was calculated from a full blood count sample taken routinely within 24 h of delivery. The neutrophil-to-lymphocyte ratio was also calculated from first trimester booking bloods (<13 + 6 weeks) in a subgroup. Placental histopathology was categorised as either inflammatory (i.e. histologic chorioamnionitis, with or without evidence of fetal inflammatory response) or non-inflammatory (vascular pathology or a normal placenta). RESULTS: 169 women had available placental pathology and were included in the analysis. 70 % (118/169) had confirmed placental inflammation. The mean neutrophil-to-lymphocyte ratio was significantly raised in this group compared to those with normal (n = 24) or vascular (n = 27) pathology (inflammatory neutrophil-to-lymphocyte ratio 9.81 vs non-inflammatory neutrophil-to-lymphocyte ratio 6.53, p = 0.002. The delivery neutrophil-to-lymphocyte ratio had an area under the receiver operating characteristic curve of 0.69 (0.60 to 0.78) for predicting placental inflammation. A raised neutrophil-to-lymphocyte ratio (>6) was associated with an odds ratio of 5.2 (95 % CI 2.55 to 10.56) for histological chorioamnionitis, with a sensitivity of 80 % and negative predictive value of 86 %. A higher cut-off of 9 had a negative predictive value of 79 % for fetal inflammatory response. CONCLUSIONS: A raised neutrophil-to-lymphocyte ratio is associated with a 5-fold increased risk of histological chorioamnionitis in women who delivered early without signs or symptoms of infection. It was also raised at the time of preterm labour compared to the first trimester. A full blood count is an almost universal investigation in women admitted in preterm labour, often repeated, making this inexpensive and non-invasive ratio a useful additional antenatal biomarker in women admitted in spontaneous preterm labour at risk of subclinical chorioamnionitis and its associated poor outcomes.

Preoperative neutrophil-lymphocyte ratio/platelet-lymphocyte ratio: A potential and economical marker for renal cell carcinoma.

Background: Emerging evidences have elucidated the crucial role of inflammation in carcinogenesis and tumor progression. In the recent years, many inflammatory biomarkers showed promising prognostic factors in renal cell carcinoma (RCC). We intended to evaluate the significance of one such inflammatory factor which is potential, noninvasive, simple, as well as economical. The preoperative neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) in RCC patients have shown favorable results. Objective: The objective was to assess the prognostic role of NLR/PLR in the advanced stage and high-grade RCC. Subjects and Methods: This is a retrospective study. Ethical clearance was obtained from the institute ethics committee. One hundred and fifty histopathologically proven RCC cases during the period of January 2010-September 2018 were chosen from the pathology department and corresponding blood reports were obtained from the medical records department. We divided the cases based on their staging and grading. NLR/PLR values were calculated using formulas. Statistical Analysis: Statistical analysis was done using R software. Data were expressed as mean ± standard deviation, median, and percentage. Independent t-test, Mann-Whitney test, and Chi-square test were used. P < 0.05 was considered statistically significant. The receiver operating characteristic curve (ROC) was plotted to assess the sensitivity of NLR/PLR. Results: The elevated NLR/PLR values showed a significant relation with high-grade and advanced stage RCC. The ROC curve proved the accuracy of NLR/PLR in the advanced stage and high-grade RCC. Limitations: A multicentric, prospective study can be planned in the future. Follow-up studies are needed to assess their prognostic role. Conclusion: NLR/PLR values can become part of routine investigations for all RCC patients. The values may help to estimate pathological outcomes, chance of recovery, recurrence, and survival rates.

Prognostic assessment of C­reactive protein and neutrophil to lymphocyte ratio in patients with non-small cell lung cancer.

OBJECTIVE: To investigate the prognostic assessment of inflammatory factor serum C­reactive protein CRP and neutrophil to lymphocyte ratio NLR value in patients with non-small cell lung cancer NSCLC. METHODS: A retrospective analysis was conducted for 475 patients with NSCLC who visited our hospital with complete follow-up data from January 2017 to 1 January 2019. The changes of serum CRP, NLR levels in patients with NSCLC of different stages, as well as the changes in the levels of the two indexes before and after chemotherapy in patients with advanced stage were compared using t tests with SPSS19.0 software. Serum CRP and NLR were divided into low and high groups with median intercept values and the relationship between inflammation score index and tumor progression-free survival time (PFS) was analyzed retrospectively. Clinical factors that may affect disease prognosis were included in the proportional hazards (COX) regression model for multifactorial prognostic analysis. RESULTS: Pretreatment serum levels of NLR and CRP were significantly higher in non-operated patients relative to preoperative levels in surgical patients. Advanced patients had higher levels of both indexes than locally advanced patients. After chemotherapy, the levels of the two indexes reaching remission were significantly lower than those before chemotherapy. The levels of the two indexes in patients with stable disease after chemotherapy were not statistically significant compared with those before chemotherapy, and the levels of the two indexes in the group with progressive disease after chemotherapy were significantly higher than those before chemotherapy. The results of PFS survival analyses showed that PFS was prolonged in the low score CRP and the low score NLR group, compared with the high score group. Multifactorial prognostic analysis showed that smoking, CRP and NLR were risk factors for PFS prognosis in patients with NSCLC. CONCLUSION: Serum CRP and NLR are effective predictors of poor prognosis in patients with NSCLC.

Value Research of NLR, PLR, and RDW in Prognostic Assessment of Patients with Colorectal Cancer.

Objective: This study aimed to investigate the relevance of the study with the neutrophil count and lymphocyte count ratio (NLR), platelet count and lymphocyte count ratio (PLR), and red blood cell distribution width (RDW) in the prognostic evaluation of colorectal cancer patients. Methods: 143 patients with colorectal cancer from January 2016 to January 2019 were selected by our hospital, and then, other 143 cases of physical examiners as normal groups were selecting to proceed colonoscopic biopsy to diagnose 106 cases of precancerous diseases related to colorectal cancer. Among them were the inflammatory bowel group (n = 56) and the colorectal polyp group (n = 50). Analysis of the survival impact factors of patients with carcinoma of the rectum, preoperative NLR, ROW, PLR, and prognostic relationship, and comparison of NLR, PLR, and RDW diagnostic rate and expression were performed. Results: Tissue type, TNM stage, lymph node metastasis, NLR, RDW, and PLR had a predictive influence on patients with colorectal cancer (P0.05). There was no link between gender, age, aetiology, pathological type, and prognosis in patients with colorectal cancer (P > 0.05). Multiple variables in patients with colorectal cancer are affected by tissue categorization (poor differentiation), TNM stages (III, IV), lymph node metastases, NLR, ROW, and PLR (P0.05). When compared to solo NLR, Row, and PLR diagnostics, the combination diagnosis and malignancy rates were greater, and the differences were statistically significant (P0.05). Diagnostic sensitivity, specificity, and accuracy were greater when compared to single NLR, ROW, and PLR. When compared to the normal control group, NLR, ROW, and PLR have greater levels, and the differences are statistically significant (P0.05). The patient survival declines more slowly as PLR, NLR, and the severity of the condition rises. Conclusion: NLR, ROW, and PLR combined diagnosis has high accuracy in colorectal cancer diagnosis, and the prognosis of patients with NLR, ROW, and PLR levels has a tight association; so, clinically, the above signs should be identified, and the optimal treatment time is grasped.

Neutrophil-to-Lymphocyte Ratio and Ferritin as Measurable Tools for Disease Burden and B Symptoms in Pediatric Patients With Hodgkin Lymphoma.

BACKGROUND: Pediatric Hodgkin lymphoma (HL) has been treated successfully with risk-adapted and response-adapted therapy. While risk factors like Ann Arbor staging system, B symptoms, bulky disease, and erythrocyte sedimentation rate were measured objectively, B symptoms are subjective tools. We evaluated whether the neutrophil-to-lymphocyte ratio (NLR) and inflammatory marker levels correlated with B symptoms and disease burden. MATERIALS AND METHODS: We conducted a retrospective chart review of all children ≤14 years old with pathology-confirmed HL treated at our institution. Data included clinical and pathologic features, pretreatment erythrocyte sedimentation rate, ferritin levels; monocyte, neutrophil, and lymphocyte counts; and NLR. Optimum cutoffs of variables significantly associated with B symptoms were determined based on receiver operating characteristic curves. RESULTS: Sixty-four patients were included in the analysis. Sixteen patients (25%) had B symptoms. Patients with B symptoms had higher ferritin levels (P<0.0001), monocyte counts (P=0.0060), neutrophil counts (P=0.0003) and NLR (P<0.0001), and lower lymphocyte counts (P=0.0017). Multiple receiver operating characteristic curves were generated to identify the optimum cutoff. Sensitivities and specificities of NLR (cutoff, 3.5) and ferritin (cutoff, 173 ng/mL) were the highest (81.25% and 81.25% [P<0.0001] and 89.36% and 75% [P<0.0001], respectively). Patients with NLR >3.5 and ferritin >173 (ng/mL) had significantly higher stage, bulky disease, and B symptoms. NLR and ferritin are not predictive of worst outcome in the cohort analyzed. CONCLUSIONS: NLR and ferritin levels were associated with high disease burden and B symptoms. Therefore, these variables can be used as measurable tools for B symptoms that can help stratify patients with HL. Larger and prospective studies are needed to validate these findings.

Assessment of genetic damage induced by gadolinium-based radiocontrast agents.

BACKGROUND: Today, although gadolinium based contrast agents have been frequently used in the field of medicine, there is limited data available whether gadolinium based agents affect the genome. AIM: The present study aimed to investigate the genotoxic and cytotoxic potentials of gadoteric acid and gadoversetamide used as gadolinium-based contrast agents for magnetic resonance (MR) imaging. MATERIAL AND METHODS: The cytokinesis-block micronucleus assay was applied to human peripheral blood lymphocytes to assess the genotoxicity measured as micronucleus (MN), nucleoplasmic bridge (NPBs) and nuclear bud (NBUDs) frequencies. Furthermore, cytokinesis-block proliferation index (CBPI) was calculated to determine cytostasis. Lymphocytes were treated with gadoteric acid at concentrations of 1.0, 2.5, 5.0, and 25 mM and with gadoversetamide at concentrations of 0.25, 1.0, 2.5, and 5.0 mM for 48 h. RESULTS: Gadoteric acid did not cause significant increase in MN, NBPs and NBUDs frequencies and CBPI values at any concentration. Gadoversetamide induced significantly increase MN formation at concentration of 2.5 mM, NBP formation at concentrations of 1.0 and 2.5 mM, and NBUD formation at concentrations of 0.25, 1.0 and 2.5 mM. Additionally, gadoversetamide exposure resulted in statistically significant decrease in CBPI values compared to the control at concentrations of 2.5 and 5.0 mM. In addition, CBPI levels in response to concentrations of gadoversetamide was negatively and significantly associated with concentration. CONCLUSION: These findings show that gadoteric acid does not have genotoxic or cytotoxic potential, while gadoversetamide might have both genotoxic and cytotoxic potential on human peripheral blood lymphocytes. As a comparison, gadoversetamide was found more genotoxic and cytotoxic.

CXCL10 levels at hospital admission predict COVID-19 outcome: hierarchical assessment of 53 putative inflammatory biomarkers in an observational study.

BACKGROUND: Host inflammation contributes to determine whether SARS-CoV-2 infection causes mild or life-threatening disease. Tools are needed for early risk assessment. METHODS: We studied in 111 COVID-19 patients prospectively followed at a single reference Hospital fifty-three potential biomarkers including alarmins, cytokines, adipocytokines and growth factors, humoral innate immune and neuroendocrine molecules and regulators of iron metabolism. Biomarkers at hospital admission together with age, degree of hypoxia, neutrophil to lymphocyte ratio (NLR), lactate dehydrogenase (LDH), C-reactive protein (CRP) and creatinine were analysed within a data-driven approach to classify patients with respect to survival and ICU outcomes. Classification and regression tree (CART) models were used to identify prognostic biomarkers. RESULTS: Among the fifty-three potential biomarkers, the classification tree analysis selected CXCL10 at hospital admission, in combination with NLR and time from onset, as the best predictor of ICU transfer (AUC [95% CI] = 0.8374 [0.6233-0.8435]), while it was selected alone to predict death (AUC [95% CI] = 0.7334 [0.7547-0.9201]). CXCL10 concentration abated in COVID-19 survivors after healing and discharge from the hospital. CONCLUSIONS: CXCL10 results from a data-driven analysis, that accounts for presence of confounding factors, as the most robust predictive biomarker of patient outcome in COVID-19.

Healthy Tissue Damage Following Cancer Ion Therapy: A Radiobiological Database Predicting Lymphocyte Chromosome Aberrations Based on the BIANCA Biophysical Model.

Chromosome aberrations are widely considered among the best biomarkers of radiation health risk due to their relationship with late cancer incidence. In particular, aberrations in peripheral blood lymphocytes (PBL) can be regarded as indicators of hematologic toxicity, which is a major limiting factor of radiotherapy total dose. In this framework, a radiobiological database describing the induction of PBL dicentrics as a function of ion type and energy was developed by means of the BIANCA (BIophysical ANalysis of Cell death and chromosome Aberrations) biophysical model, which has been previously applied to predict the effectiveness of therapeutic-like ion beams at killing tumour cells. This database was then read by the FLUKA Monte Carlo transport code, thus allowing us to calculate the Relative Biological Effectiveness (RBE) for dicentric induction along therapeutic C-ion beams. A comparison with previous results showed that, while in the higher-dose regions (e.g., the Spread-Out Bragg Peak, SOBP), the RBE for dicentrics was lower than that for cell survival. In the lower-dose regions (e.g., the fragmentation tail), the opposite trend was observed. This work suggests that, at least for some irradiation scenarios, calculating the biological effectiveness of a hadrontherapy beam solely based on the RBE for cell survival may lead to an underestimation of the risk of (late) damage to healthy tissues. More generally, following this work, BIANCA has gained the capability of providing RBE predictions not only for cell killing, but also for healthy tissue damage.

Transfusion of γ-irradiated blood components to individuals does not compromise the cytogenetic dose assessment.

Most blood components for transfusions are irradiated ex vivo to prevent transfusion-associated graft-versus-host disease (TA-GvHD); this irradiation can potentially affect the cytogenetic dose assessment of patients showing acute radiation syndrome (ARS) with bone marrow suppression or acute anaemia. Whole blood samples from five donors were irradiated with 0, 10 or 25 Gy γ-rays. The mitotic activity of each cultured blood sample was measured by calculating the mitotic index. A dicentric chromosome assay was used to evaluate the chromosomal aberrations and absorbed dose of blood lymphocytes. Mitogenic activity and scorable metaphase spreads were significantly decreased in the blood samples irradiated with 10 and 25 Gy (p < 0.001). Moreover, a significant increase in the mean scores of all types of chromosomal aberrations in the 10 Gy γ-irradiated samples was observed, with the estimated dose being 11.3 Gy (95% CI: 10.67-11.95 Gy); however, we were unable to estimate the exposure dose in the 25 Gy γ-irradiated samples due to a limited number of scorable metaphase spreads. The mitotic index of the 25 Gy γ-irradiated whole blood samples was significantly suppressed by more than 4-log fold. Thus, in the present study, we evaluated the effects of recommended radiation doses in γ-irradiated transplantation blood components using cytogenetic dosimetry. These results suggest that the partial transfusion of blood components to patients with ARS or acute anaemia did not compromise the estimation of the exposure dose using cytogenetic dosimetry.

Circulating cell-free DNA, peripheral lymphocyte subsets alterations and neutrophil lymphocyte ratio in assessment of COVID-19 severity.

Cell destruction results in plasma accumulation of cell-free DNA (cfDNA). Dynamic changes in circulating lymphocytes are features of COVID-19. We aimed to investigate if cfDNA level can serve in stratification of COVID-19 patients, and if cfDNA level is associated with alterations in lymphocyte subsets and neutrophil-to-lymphocyte ratio (NLR). This cross-sectional comparative study enrolled 64 SARS-CoV-2-positive patients. Patients were subdivided to severe and non-severe groups. Plasma cfDNA concentration was determined by real-time quantitative PCR. Lymphocyte subsets were assessed by flow cytometry. There was significant increase in cfDNA among severe cases when compared with non-severe cases. cfDNA showed positive correlation with NLR and inverse correlation with T cell percentage. cfDNA positively correlated with ferritin and C-reactive protein. The output data of performed ROC curves to differentiate severe from non-severe cases revealed that cfDNA at cut-off ≥17.31 ng/µl and AUC of 0.96 yielded (93%) sensitivity and (73%) specificity. In summary, excessive release of cfDNA can serve as sensitive COVID-19 severity predictor. There is an association between cfDNA up-regulation and NLR up-regulation and T cell percentage down-regulation. cfDNA level can be used in stratification and personalized monitoring strategies in COVID-19 patients.

Peripheral Absolute Lymphocyte Count: An Economical and Clinical Available Immune-Related Prognostic Marker for Newly Diagnosed Multiple Myeloma.

BACKGROUND To find economical and clinically available immune-related prognostic markers that could predict the overall survival (OS) of newly diagnosed multiple myeloma (NDMM) in the new drug era. MATERIAL AND METHODS Absolute lymphocyte count (ALC) and absolute monocyte count (AMC) were measured in routine blood samples from 102 patients with NDMM, and the lymphocyte-monocyte ratio (LMR) was derived. All the patients were receiving bortezomib-based chemotherapy as induction treatment. Log-rank testing was used for comparing the differences between groups. Univariate and multivariate tests were used to identify prognostic markers. RESULTS The median ALC and LMR values at diagnosis were 1.43×109/L and 3.7, respectively, and served as the cutoff point. As prognostic factors, ALC, LMR, and a new staging system combining ALC and the ISS staging system (L-ISS) were expected to have a significant impact on predicting OS. Furthermore, multivariate analysis showed that ALC ≥1.43×109/L (hazard ratio [HR]: 0.223; 95% confidence interval [CI]: 0.071-0.705; P=0.011), LMR ≥3.7 (HR: 0.363; 95% CI: 0.139-0.947; P=0.038), and L-ISS late stage (HR: 1.619; 95% CI: 1.065-2.743; P=0.027) were independent predictors for OS. CONCLUSIONS ALC and LMR can serve as surrogate markers for patients' antitumor immunity at the initial diagnosis of multiple myeloma. A new immune-related staging system, L-ISS, which combines ALC and the ISS staging system, can predict clinical outcomes in patients who are receiving bortezomib-based chemotherapy.

Assessment of the genotoxic potential of a migraine-specific drug by comet and cytokinesis-block micronucleus assays.

Background: Eletriptan is a migraine-specific drug-containing the triptan group. In terms of drug safety, the present study aimed to investigate the genotoxic potential of eletriptan.Research design & methods: We conducted our study by using the cytokinesis-block micronucleus cytome (CBMN) assay, a comprehensive method for measuring micronucleus formation, and a sensitive method for detecting DNA-strand breaks. In the assay, cytokinesis-block proliferation index and the frequency of micronuclei were evaluated in lymphocytes treated with three different concentrations (1, 10 and 25 µg/ml) of eletriptan for 48 hours. In comet assays, DNA damage was evaluated in leucocytes treated with three different concentrations (1, 10 and 25 µg/ml) of eletriptan for an hour.Results: Eletriptan did not induce cytotoxicity nor any increased micronuclei frequencies. While the comet parameters % DNA in tail, tail moment, and the olive moment was found to be significantly increased at 10 and 25 µg/ml, the cytokinesis-block proliferation index values were not.Conclusion: These findings suggest that eletriptan is non-cytotoxic but potentially weakly genotoxic at higher concentrations (10 and 25 µg/ml).

Nutritional assessment and prognosis of oral cancer patients: a large-scale prospective study.

BACKGROUND: To evaluate and compare the prognostic performance of four nutritional indicators body mass index (BMI), serum albumin (ALB), prognostic nutritional index (PNI) and nutritional risk index (NRI) in oral cancer patients, and to predict the response to chemotherapy in patients with different nutritional status. METHODS: This prospective study which involved 1395 oral cancer patients was conducted in Fujian, China from September 2007 to November 2018. The BMI, PNI and NRI were calculated according to the following formulas: BMI = weight / height2 (kg/m2), PNI = albumin (g/l) + 0.005 × lymphocyte (count/µl) and NRI = (1.519 × albumin, g/l) + (41.7× present/ideal body weight), respectively. The univariate and multivariate Cox proportional hazards models were used to compare the prognostic value of BMI, ALB, PNI and NRI in overall survival (OS) in oral cancer. RESULTS: Patients with BMI < 18.5 kg/m2 (VS 18.5 kg/m2 ≤ BMI < 24 kg/m2) had a poor survival outcome (HR = 1.585; 95% CI: 1.207-2.082 ). ALB, PNI, NRI were inversely correlated with OS of oral cancer (HR = 0.716; 95% CI: 0.575-0.891; HR = 0.793; 95% CI: 0.633-0.992; HR = 0.588; 95% CI: 0.469-0.738, respectively). In addition, the prognostic predictive performance of NRI was superior to BMI or ALB or PNI. Interestingly, compared with patients with better nutritional status, chemotherapy was significantly associated with poorer OS in malnourished oral cancer patients. CONCLUSIONS: BMI, ALB, PNI and NRI are of prognostic value in patients with oral cancer and the prognostic performance of NRI was superior to BMI or ALB or PNI. Malnutrition (BMI < 18.5 kg/m2 or ALB< 40 g/l or PNI < 49.3 or NRI < 97.5) could predict an unfavorable response to chemotherapy in oral cancer patients.

Assessment of DNA damage by 53PB1 and pKu70 detection in peripheral blood lymphocytes by immunofluorescence and high-resolution transmission electron microscopy.

PURPOSE: 53BP1 foci detection in peripheral blood lymphocytes (PBLs) by immunofluorescence microscopy (IFM) is a sensitive and quantifiable DNA double-strand break (DSB) marker. In addition, high-resolution transmission electron microscopy (TEM) with immunogold labeling of 53BP1 and DSB-bound phosphorylated Ku70 (pKu70) can be used to determine the progression of the DNA repair process. To establish this TEM method in the PBLs of patients with cancer, we analyzed and characterized whether different modes of irradiation influence the formation of DSBs, and whether accompanying chemotherapy influences DSB formation. METHODS: We obtained 86 blood samples before and 0.1, 0.5, and 24 h after irradiation from patients (n = 9) with head and neck or rectal cancers receiving radiotherapy (RT; n = 4) or radiochemotherapy (RCT; n = 5). 53BP1 foci were quantified by IFM. In addition, TEM was used to quantify gold-labelled pKu70 dimers and 53BP1 clusters within euchromatin and heterochromatin of PBLs. RESULTS: IFM analyses showed that during radiation therapy, persistent 53BP1 foci in PBLs accumulated with increasing numbers of administered RT fractions. This 53BP1 foci accumulation was not influenced by the irradiation technique applied (3D conformal radiotherapy versus intensity-modulated radiotherapy), dose intensity per fraction, number of irradiation fields, or isodose volume. However, more 53BP1 foci were detected in PBLs of patients treated with accompanying chemotherapy. TEM analyses showed that DSBs, indicated by pKu70, were present for longer periods in PBLs of RCT patients than in PBLs of RT only patients. Moreover, not every residual 53BP1 focus was equivalent to a remaining DSB, since pKu70 was not present at every damage site. Persistent 53BP1 clusters, visualized by TEM, without colocalizing pKu70 likely indicate chromatin alterations after repair completion or, possibly, defective repair. CONCLUSION: IFM 53BP1 foci analyses alone are not adequate to determine individual repair capacity after irradiation of PBLs, as a DSB may be indicated by a 53BP1 focus but not every 53BP1 focus represents a DSB.

Lymphocytic thrombophilic arteritis and cutaneous polyarteritis nodosa: Clinicopathologic comparison with blinded histologic assessment.

BACKGROUND: Lymphocytic thrombophilic arteritis (LTA), or macular lymphocytic arteritis, is defined by a primary lymphocytic vasculitis. However, the nosology of LTA has been controversial, with speculation that it may represent an indolent non-nodule-forming variant of cutaneous polyarteritis nodosa (cPAN). OBJECTIVE: This study compares the clinicopathologic features of patients with LTA or cPAN to assess if these conditions should be considered distinct entities. METHODS: This is a cross-sectional study of all LTA and cPAN cases at a single tertiary center using prospectively collected clinical data and blinded histologic assessment. RESULTS: The study included 17 patients with LTA and 13 patients with cPAN. Clinically, cases of LTA were distinguished by a more widespread pattern of livedo racemosa, which was noninfiltrated and asymptomatic. In contrast, cPAN was associated with localized starburst livedo, purpura, and episodic features including nodules, pain, and large inflammatory ulcers. When patients were separated according to the presence (>5%) or paucity (≤5%) of neutrophils on blinded histology review, they had distinct clinical features and differences in disease course. LIMITATIONS: This was a single-center study. CONCLUSION: Our data support the classification of LTA and cPAN as separate entities rather than a spectrum of the same disorder and highlight the importance of clinicopathologic correlation in distinguishing these conditions.

Assessment of hypercoagulability using thromboelastography predicts advanced status in renal cell carcinoma.

BACKGROUND: Thromboelastography (TEG) has been established as a sensitive method to assess the whole coagulation process. The aim of the study was to evaluate the diagnosis significance of TEG on hypercoagulability in patients suffering renal mass. METHODS: A total of 478 patients were diagnosed with renal tumor by histolopathologic examination and were assigned to three groups. Group A: 79 patients with benign renal tumor; Group B: 317 patients with renal cell carcinoma (RCC, Fuhrman grades I and II); Group C: 82 patients with high-risk RCC (Fuhrman grades III and IV). Subgroup analysis was performed in malignant renal tumor patients according to the TMN classification. The clinical data, whole blood TEG, and conventional coagulation tests were reviewed. RESULTS: There was no statistically significant difference between subgroups in respect to conventional coagulation tests. Hypercoagulablity was marked in Group C according to the TEG parameters. The elevated platelets and fibrinogen is linked with hypercoagulability in renal tumor. The positive correlation was between fibrinogen and MA value (r = .663, P < .05). The pathologic tumor stages were also associated with the TEG parameters. CONCLUSION: Patients suffering advanced RCC are hypercoagulable which can be identified by TEG. MA value could be potential diagnosis indicators for detecting high-grade RCC.