White Blood Cell Ratio Research Articles

PO-0951 Effects of COVID-19 during radio(chemo)therapy in head and neck cancer patients

Purpose or Objective To evaluate effects of COVID-19 during (chemo)radiation (RT) or quarantine on overall treatment time and outcome, as well as to determine prognostic parameters for COVID-19 related death in patients with head and neck cancer (HNC). Materials and Methods We have performed a retrospective review and identified patients with confirmed SARS-CoV-2 or quarantine during RT of HNC, who were treated in 3 radiotherapy departments from March 2020 till February 2021. The quarantine was imposed due to a close contact with COVID-19 positive person e.g. after hospitalisation in the same patient's room. Univariate analysis was performed using a Cox proportional hazards model for COVID-19 positive patients. The covariates included were age, co-morbidities, smoking, white blood cell (WBC) ratio measured on the day of positive COVID-19 test result divided by WBC count taken one week before, C-reactive protein (CRP) ratio, which was obtained analogically to WBC ratio. WBC-ratio and CRP-ratio were chosen to reflect dynamics of possible changes in inflammatory parameters. Results 36 patients (pts) were included in the analysis. Mean age yield 66 years (Range: 25-87). 92% of pts, were treated with curative intent. Two patients had induction chemotherapy and 9 pts got simultaneous chemoradiation. The median follow-up was 3.4 month (Range: 1-5.6). In total 7 patients died, 5 of them were categorised as COVID-19 related death. The time lapsed from a COVID-19 positive test result to death varied in these 5 pts from 8 to 17 days. 26 (72%) pts had SARS-CoV-2 infection confirmed and in the case of 10 pts RT was interrupted due to imposed quarantine. The median interruption time of RT yield 20 days (13-65) and 14 days (10-19) due to COVID-19 and quarantine, respectively. 36% patients did not continue RT due to various reasons including death (5 pts) and deterioration of performance status (3 pts). We did not observe a significant correlation between age, hypertension, performance status, intention to treat (primary vs adjuvant vs palliative), smoking, number of RT fractions before COVID-19 infection, ischaemic heart disease, pulmonary disease, uncontrolled diabetes and risk of COVID-19 related death on univariate Cox analysis. However, in a subgroup of patients (n=17) with available regular blood analysis data WBC-ratio correlated significantly with risk of COVID-19 related death (p=0.02). CRP-ratio did not show significance for risk of COVID-19 related death (p=0.12). By the time of 3 month follow-up one patient treated with palliative intention progressed and died. Conclusion COVID-19 infection extended overall treatment time in median for 20 days. From radiobiological point of view this is a substantial prolongation, thus these patients are at higher risk of recurrence and demand careful follow-up. In our subgroup of patients WBC-ratio was prognostic for risk of COVID-19 related death. Due to low number of patients this observation should be validated in a larger cohort of patients.

Acute and Chronic Hematologic Implications of Emergency and Elective Splenectomy

Thrombocytosis and leukocytosis are common after splenectomy. The potential effect of emergency surgery on these postoperative findings is unknown. We hypothesized that emergency splenectomy leads to a more profound and persistent hematologic change as compared to elective splenectomy. A retrospective review was conducted of patients who underwent elective or trauma splenectomy. Records were queried for platelet (PLT) and white blood cell (WBC) count prior to splenectomy, on postoperative days 1-5, and at day 14, 1 month, 3 months, 6 months, and 1 year. Complications, including thromboembolic events, infection, need for repeat operation, and readmission within 30 days of discharge, were recorded. 463 patients were identified as being eligible for the study, with 173 patients in the elective cohort and 145 patients in each of the isolated trauma splenectomy and polytrauma cohorts. Both cohorts had peak thrombocytosis at week 2 postoperatively. However, polytrauma patients had a significantly higher peak platelet count (P < 0.01). The PLT:WBC ratio was lower in both trauma cohorts pre-operatively and postoperative day 1. Trauma splenectomy had a higher PLT:WBC ratio on days 2 and 3 whereas polytrauma had a lower ratio on days 4 and 5. Emergency cases had greater reoperation and infection rates, whereas elective cases were more likely to require readmission. Postoperative thromboembolic events were only higher in the polytrauma cohort. While trauma splenectomy resulted in more profound postoperative leukocytosis and thrombocytosis, there was no correlation with timing of infection or risk of thromboembolic events. These findings suggest that thrombocytosis and leukocytosis may be associated with thrombotic and infectious events but their presence alone does not indicate direct risks of concomitant infection or thrombosis.

Acute and Chronic HPA Axis Stimulation Alters White Blood Cell Ratios but Not Inflammatory Markers or Oxidative Stress in Elephant Seals

Activation of the hypothalamic-pituitary-adrenal (HPA) axis regulates immune and inflammatory responses through modulation of cytokines, white blood cells (WBCs), and oxidative stress. However, little is known about the impact of HPA axis activation during extreme physiological conditions in marine mammals. We challenged 18 post-weaning (simultaneously fasting and developing) northern elephant seal pups with daily intra-muscular injections of slow-release adrenocorticotropin (ACTH), a glucocorticoid receptor (GR) antagonist (RU486), or a combination (ACTH+RU486) for four days. Animals were blood sampled at baseline, 2 hours (2h), and 4 days (4d) after the beginning of the treatment. ACTH and ACTH+RU486 elevated aldosterone and cortisol at 2h, with the effect diminishing at 4d. RU486 alone induced a compensatory increase in aldosterone, but not cortisol, at 4d. ACTH decreased neutrophils (N) at 2h while decreasing lymphocytes (L) and increasing N:L ratio at 4d. These effects were abolished by RU486. Despite alterations in WBCs, there was no effect of ACTH on TGF-b or IL6; however, both cytokines decreased across the fast (4d). Similarly, ACTH did not impact protein oxidation, lipid peroxidation, or antioxidant enzyme activities, but lipid peroxidation and catalase decreased while glutathione peroxidase increased with fasting progression. ACTH did not alter triglycerides or NEFA, although triglycerides did decrease with fasting progression. These data show that HPA axis activation has differential acute (2h) and chronic (4d) modulatory effects on WBCs and that the chronic effect is mediated, at least in part, by GR signaling. These results also underscore the robustness and tolerance of these elephant seals to repeated HPA activation.

Positive Correlation between Monocyte-to-Lymphocyte Ratio and C-Reactive Protein in Vitamin D Deficient Preterm Infants with Respiratory Distress Syndrome

INTRODUCTION: Respiratory distress syndrome (RDS) is one of the leading causes of preterm infant mortality. Vitamin D deficiency is known as a risk factor for RDS related to infants with immature lungs leading to inflammatory exacerbations. Therefore, early diagnosis is needed to prevent RDS. This study evaluated white blood cells (WBC) ratios and C-reactive protein (CRP) among vitamin D deficient preterm infants with RDS to identify simple and prompted inflammatory markers. MATERIALS AND METHODS: A cross-sectional study involving forty preterm infants (28 to 34-weeks gestational age) with low vitamin D levels (25(OH)D&lt;20 ng/dL) was conducted in a neonatal ward of a hospital in Bandung, Indonesia, from February to October 2018. Two consecutive blood collections (cord blood at birth and venous blood at first week) were performed to measure cord blood vitamin D (25(OH)D) levels, complete blood count (CBC), and CRP levels. White blood cell ratios (Monocyte-to-Lymphocyte ratio: MLR, Neutrophil-to-Lymphocyte ratio: NLR, and Platelet-to-Lymphocyte ratio: PLR) were calculated and analyzed. Association analysis was performed using Student’s t-test, Mann-Whitney U and Spearman correlation tests. RESULTS: The median of 25(OH)D levels were 9.96 (7.58-15.81) ng/dL. A significant positive correlation between MLR and CRP was found in the RDS group (r=0.576, p=0.004) and all the subjects (r=0.491, p=0.002); the WBC ratio and CRP levels showed insignificant higher trends when compared to the non[1]RDS group. CONCLUSION: There was a positive correlation between MLR and CRP among vitamin D deficient preterm infants with RDS.

Diagnostic value of serum amyloid A, procalcitonin and hypersensitive C-reactive protein for pulmonary tuberculosis complicated by pneumonia

To assess the value of serum amyloid A (SAA), procalcitonin (PCT) and high-sensitivity C-reactive protein (hs-CRP) in the diagnosis of pulmonary tuberculosis (PTB) complicated by pneumonia. We collected serum samples from patients with pneumonia, patients with PTB, patients with PTB complicated by pneumonia and patients with PTB complicated by sepsis hospitalized in our hospital between April, 2019 and April, 2020. Serum levels of SAA, PCT and hs-CRP were tested, and receiver- operating characteristic (ROC) curves were used to evaluate their efficacy for predicting PTB with concurrent pneumonia and the possibility of differentiating PTB cases with pneumonia from those with sepsis using these 3 parameters. We also tested serum levels of SAA, PCT and hs-CRP in patients with PTB and those with PTB complicated by pneumonia admitted from May to July in 2020 to verify the accuracy of these 3 parameters combined for predicting the complication of PTB by pneumonia. Compared with the patients with PTB, the patients with pneumonia had significantly higher SAA and hs-CRP levels; serum SAA, PCT and hs-CRP levels were all significantly elevated in patients with PTB complicated by pneumonia (all P < 0.05). The levels of hs-CRP, white blood cell, D-dimer, FIB, APTT and neutrophil ratio were positively correlated with serum SAA level (all P < 0.05). The areas under the ROC curve (AUC) for serum SAA, PCT, and hs-CRP were 0.762, 0.781, and 0.800, respectively, and their combined AUC was 0.849 (all P < 0.001). For predicting PTB complicated by pneumonia, SAA combined with PCT had the same sensitivity (53.85%) and specificity (90.48%) as SAA, PCT and hs-CRP all combined. Serum SAA and PCT levels were similar between PTB patients with pneumonia and those with sepsis. Combined detection of serum SAA and PCT levels can be helpful in the diagnosis of PTB complicated by pneumonia, but neither of them is capable of differentiating the complication of pneumonia from sepsis possibly due to influence by abnormal blood coagulation.

Health status evaluation of striped bass ( Morone saxatilis ) exposed to low temperature in sea cage culture during the grow‐out

Striped bass (Morone saxatilis) is a species with high production potential for human consumption. However, like any other cultured species, they are prone to be exposed to adverse climate conditions, compromising their health status until a certain degree compromises the success of reaching commercial size. It is proposed that haematological parameters testing during the whole growing out season represents a useful tool to assess the overall fish health status. Information on M. saxatilis haematology is limited. Therefore, the present study aimed was to provide the haematological and blood chemistry values for commercial striped bass grow-out. Fish from three different group sizes and under low sub-optimal temperature (16 to 18°C) were sampled in correlation to copepods (Peniculus sp.) present attached to the fins. Thirty fish from each group (sized 0.17, 0.54 and 1.17 kg, corresponding to different ages and batches) were all sampled (blood and external parasites count) during the spring (5 June, June 12 and June 16, 2019). The results show that differences in blood parameters were only observed according to the weight of striped bass such as the haematocrit (HCT), haemoglobin, mean corpuscular haemoglobin concentration (MCHC), white blood cells (WBC) count, total protein, globulin, ratio A/G, cholesterol, triglycerides and glucose. In contrast, the copepods present showed a preference for the caudal fin of the striped bass, followed by the first dorsal and pectoral fin. The smaller fish (0.179 kg) were the most susceptible to Peniculus sp., compared to the largest fish (1.174 kg). So far, it can be concluded that at this stage, the copepod does not show any adverse effect on the fish health since the condition factor and blood parameters were statistically similar along with the different copepod infestation levels (intensity ranged from 7 to 109). However, this new copepod, here registered for the first time in the Morone saxatilis, was registered during the sunset to increase environmental temperature. Even if no signs of a harmful relationship between parasites between young and old organisms, it will be necessary to be further monitored. The copepod incidence and the blood parameters should be analysed along the year (different temperatures), aiming to detect any correlation to the copepods present or, in any case, the overall health status or another parasite present under the seabass culture conditions.

Diagnostic Utility of C-Reactive Protein and Permutation Combination of Quantitative and Qualitative Haematological Parameters in Neonatal Sepsis

Introduction: Neonatal sepsis at times is subclinical and lacks specific symptoms. The C-Reactive Protein (CRP) which is an acute phase reactant protein is thought to be an alternative biomarker to blood culture. Haematological parameters of sepsis are indirect biomarkers of infection. Authors found it worthwhile to discern efficacy of haematological parameters obtained by such three part haematology analysers in diagnosis of neonatal sepsis, when used in their pure form or with peripheral blood smear or with CRP, in isolation or in their combinations. Aim: To find out the diagnostic utility of combinations of haematological parameters as obtained by three part differential automated haematology analyser and peripheral blood smear along with CRP in neonatal sepsis. Materials and Methods: This observational and analytical study of diagnostic test outcome was carried out over a period of 12 months from January-December 2016 in Rajarshi Chhatrapati Shahu Maharaj Medical College and Chhatrapati Pramilaraje Rugnalaya, Kolhapur, Maharashtra, India, with special reference to clinical profile, blood culture, qualitative and quantitative haematological parameters and CRP. The statistical analysis included calculating diagnostic utility of isolated and combination of parameters and performing Chi-square test to study difference in frequency of occurrence and significance of association. Results: There were 104 cases of neonatal sepsis out of which culture proven sepsis was seen in 73 (70.2%) cases while probable sepsis was seen in 31 (29.8%) cases. There were 32 (30.8%) fatalities. With parallel method with OR values, combination of haemoglobin, platelet parameters and White Blood Cells (WBC) parameters as obtained by analyser and peripheral blood smear exhibited sensitivity of 98.6%, specificity and Positive Predictive Value (PPV) of 100%, Negative Predictive Value (NPV) of 96.9% and Diagnostic Accuracy (DA) of 99%. This was surpassed by combination of CRP and all these parameters to attend values of 100%. Combination of all haematological parameters obtained purely by analyser showed these values to be 89%, 100%, 79.5% and 92.3%. Immature to Total WBC (I:T) ratio and platelet count influenced clinical outcome of fatality. Conclusion: The liberal use of combination of haematological parameters is rewarding in supporting diagnosis of neonatal sepsis. The same was obtained by purely using analyser which showed remarkable diagnostic utility suitable for resource poor settings.

Systemic Inflammatory Response Syndrome Combined with Pre- and Postoperative White Blood Cell Ratio Is a Better Criterion to Identify Septic Shock Patients After Flexible Ureteroscopic Lithotripsy.

Objective: To find out a better criterion to identify septic shock patients after flexible ureteroscopic lithotripsy (FUL). Materials and Methods: In total, 2364 patients who underwent the FUL procedure were enrolled in the study. The demographics and preoperative results of laboratory tests of the patients were collected. The postoperative white blood cell (WBC), systemic inflammatory response syndrome (SIRS), and quick sequential (sepsis-related) organ failure assessment score (qSOFA) were assessed 2 hours after FUL. The predictive efficacy was measured by sensitivity, specificity, positive and negative predictive value, and area under the receiver's operating characteristic curve (AUROC). Results: A total of 15 (0.63%) patients developed septic shock. There were 86 (3.64%) patients who were SIRS positive and 69 (2.92%) patients who were qSOFA positive. The pre- and postoperative WBC ratios in septic shock patients and normal patients were 2.50 ± 1.55 and 0.69 ± 0.24, respectively (p < 0.001). For sensitivity and negative predictive value, all reached 100%. For specificity, qSOFA was 97.70%, SIRS was 96.98%, and SIRS combining pre- and postoperative WBC ratio (the new criterion) was 99.79%. The new criterion had statistically significant higher specificity than SIRS or qSOFA (p < 0.001 for both), but when comparing SIRS and qSOFA, it had statistically insignificant specificity (p = 0.142). For positive predictive value, qSOFA was 21.73%, SIRS was 17.44%, and the new criterion was 75%. qSOFA and SIRS had similar AUROC (0.989 for qSOFA and 0.985 for SIRS), both lower than the new criterion (AUROC: 0.999). Conclusions: SIRS combined with pre- and postoperative WBC ratio has a much better specificity and positive predictive value than SIRS or qSOFA alone. It has 99.79% specificity and 75% positive predictive value, and as high as 100% sensitivity and negative predictive value.

Lymphocyte-White Cell Ratio Is a Novel Marker of Morbidity Following Colorectal Cancer Surgery

BackgroundA preoperative marker for morbidity in patients with colorectal cancer would help to risk stratify patients and allow for timely intervention to avert poor outcomes. We conducted this study to evaluate preoperative lymphocyte–white blood cell ratio (LWR) as a marker of postoperative morbidity. MethodsA prospective cohort of patients who underwent elective surgery for colorectal cancer was reviewed. Three morbidity-related outcomes were described—overall morbidity, multiple morbidities, and severe morbidity, defined as Clavien-Dindo Class ≥3. Univariable and multivariable analyses of presurgical predictors of these three outcomes were performed. Preoperative variables included hemoglobin levels, neoadjuvant therapy, albumin levels, white blood cell count, lymphocyte count, LWR, neutrophil-lymphocyte ratio, and prognostic nutritional index. ResultsOf 177 patients, 31.6% (56/177) suffered at least one morbidity, 15.3% (27/177) had multiple morbidities, 7.9% (14/177) suffered severe morbidity. On multivariate analysis, only LWR <0.180 (odds ratio [OR] 2.53, 95% confidence interval [CI] 1.15-5.55) and neoadjuvant therapy (OR 2.49, 95% CI 1.16-5.24) were associated with overall morbidity. For multiple morbidities and severe morbidity, only LWR <0.180 was significantly associated on multivariate analysis with an OR of 2.92 (95% CI 1.19-7.13) and 4.62 (95% CI 1.45-14.73), respectively. ConclusionsLWR is a preoperative marker which can be conveniently applied using standard preoperative blood tests. LWR is an independent risk factor for overall morbidity, multiple morbidities, as well as severe morbidity when used with a cut-off of LWR<1.80.

Value of blood ammonia on predicting the severity and prognosis of patients with sepsis: a prospective observation study

To investigate the value of arterial blood ammonia on predicting the severity and prognosis of patients with sepsis. A prospective observation study was conducted. A total of 169 patients with sepsis admitted to intensive care unit (ICU) of Jining First People's Hospital Affiliated to Jining Medical University from January 2018 to June 2019 were enrolled. Thirty-five healthy volunteers were served as controls. Demographics, acute physiology and chronic health evaluation II (APACHE II) score were recorded. At 6-8 hours after the diagnosis of sepsis, the serum levels of arteria blood ammonia and whole blood cell count were run. The septic patients were divided into the sepsis group and septic shock group according to the disease severity, and the septic patients were divided into survival group and death group according to the outcomes during 28-day hospitalization. The clinical data were compared. Spearman rank correlation was applied to determine the correlation between those variables. The predictive value of the parameters on 28-day mortality was evaluated with receiver operating characteristic (ROC) curve. Kaplan-Meier survival curve analysis was used to compare different blood ammonia levels of patients with 28-day cumulative survival rate. Among the 169 sepsis patients, after excluding 12 patients who did not meet the inclusion criteria and loss to follow-up, there were finally 157 patients enrolled in the analysis. Among the 157 septic patients, 71 of them were in the sepsis group, and 86 in the septic shock group. After 28-day follow-up, 115 patients survived and 42 died. No significant differences were found in age and gender among groups with different severity and clinical prognosis. Compared with the control group, the blood ammonia, counts of white blood cell (WBC) and neutrophils ratio (Neut%) in serum of sepsis patients were significantly higher [blood ammonia (μmol/L): 42.28±28.64 vs. 12.05±5.44, WBC (×109/L): 17.51±5.13 vs. 6.57±2.20, Neut%: 0.87 (0.82, 0.90) vs. 0.62 (0.59, 0.67), all P < 0.05]. Compared with the sepsis group, the APACHE II score, blood ammonia, WBC, Neut% and 28-day mortality in the septic shock group were significantly higher [APACHE II score: 24.49±6.22 vs. 14.31±3.32,blood ammonia (μmol/L): 52.93±34.11 vs. 29.38±10.37, WBC (×109/L): 20.21±3.77 vs. 14.02±4.23, Neut%: 0.89 (0.86, 0.92) vs. 0.82 (0.79, 0.89), 28-day mortality: 43.0% (37/86) vs 7.0% (5/71), all P < 0.05]. APACHE II score, blood ammonia, WBC and Neut% in the death group were significantly higher than those in the survival group [APACHE II score: 26.89±7.91 vs. 17.34±4.90, blood ammonia (μmol/L): 69.98±41.14 vs. 32.17±11.31, WBC (×109/L): 20.20±4.78 vs. 16.53±4.91, Neut%: 0.89 (0.87, 0.95) vs. 0.87 (0.82, 0.90), all P < 0.05]. Spearman rank correlation analysis showed that blood ammonia in patients with sepsis was correlated well with APACHE II score (r = 0.592, P < 0.01), and there was moderately positive correlation between blood ammonia and the counts of WBC (r = 0.343, P < 0.01). ROC curve analysis showed that the areas under ROC curve (AUC) of APACHE II score and blood ammonia for predicting 28-day mortality were 0.846 and 0.901, respectively, and there was no statistical significance (P = 0.187). The AUC of APACHE II score combined with blood ammonia was significantly higher than that of APACHE II score alone (0.913 vs. 0.846, P = 0.002), but was not higher than that of blood ammonia alone (0.913 vs. 0.901, P = 0.647). Using a blood ammonia cut-off value of > 36.50 μmol/L for predicting 28-day mortality, the sensitivity and specificity was 92.9% and 73.9%, respectively, and the positive and negative likelihood ratios were 3.56 and 0.10, respectively. Kaplan-Meier survival curve analysis indicated that the patients whose blood ammonia was higher than 36.50 μmol/L, had lower 28-day cumulative survival rate when compared with those patients with blood ammonia ≤ 36.50 μmol/L (Log-Rank test: χ2 = 9.620, P = 0.002). The level of arterial blood ammonia could somehow indicate the severity and prognosis of sepsis, which could provide evidence for the treatment.

Evaluation of Inflammatory Markers in Single-Port Laparoscopic and Vaginal Hysterectomies: A Retrospective Study in Kocaeli, Northwest Turkey

Objective: The authors in this study aimed to detect inflammatory marker changes in two natural orifice hysterectomies: single-port laparoscopic hysterectomy (SLH) and vaginal hysterectomy (VH). Materials and Methods: Between 2018 and 2019, data obtained from patients in the SLH and VH groups were reviewed retrospectively. The preoperative and postoperative hematocrit (HCT), hemoglobin (HB), white blood cell (WBC), platelet (PLR), and neutrophil-lymphocyte (NLR) ratios and values were compared as well as the demographic characteristics of the patients. This study was also registered in Registry of Clinical Trials; registration number: NCT04221308. Results: In the postoperative period, WBC, NLR, and PLR were statistically increased, and HB and HCT were decreased in all groups. However, the changes in inflammatory markers were similar in both groups. The changes in HB and HCT were less in the SLH group. Moreover, both the duration of the operation and the hospital stay were higher in the SLH group. Conclusions: Both natural orifice techniques provided low morbidity and good cosmetic results. The results regarding inflammatory markers indicate that both procedures are acceptable. As surgical experience in performing SLH increases, operation and hospital stay durations may decrease.

Role of Systemic Inflammatory Response Markers in Urothelial Carcinoma.

Urothelial carcinoma (UC) can occur in various parts of the urinary tract and occurs in different stages and grades. The disease recurs frequently and is monitored through a series of invasive tests, such as cystoscopy or ureteroscopy, over the lifetime of an individual. Although many researchers have attempted to stratify the risks of UC, with the majority being based on cancer characteristics and host factors such as performance status, a risk classification system has yet to be fully developed. Cancer affects various parts of the body through the systemic immune response, including changes in hormones, the number and ratio of white blood cells and platelets, and C-reactive protein (CRP) or albumin levels under the influence of neuroendocrine metabolism, hematopoietic function, and protein and energy metabolism, respectively. Herein, we reviewed various systemic inflammatory response markers (SIRs) related to UC, including CRP, albumin-globulin ratio, albumin, Glasgow prognostic score (GPS), modified GPS, neutrophil-lymphocyte ratio, and platelet-lymphocyte ratio. Our aim was to summarize the role of various SIRs in the treatment of patients with UC.

Adaptive therapy in early rehabilitation of the patients with industrial injuries as an indicator of the eff ectiveness of course programs

The results of determining adaptive responses to treatment of patients with industrial injuries in the early stages of rehabilitation are presented. Studies have shown that the preliminary determination of reactions by L.Kh. Garkavi allows you to individually plan the duration of stay, the nature of treatment procedures with their sequence for each patient.The aim of the study is to study the adaptation indicators according to L.Kh. Garkavi in patients with occupational injuries before treatment, during rehabilitation and aft er its completion.Patients with industrial injuries, aimed at early rehabilitation, were determined by L.Kh. Garkavi adaptation reaction using the blood formula with the ratio of white blood cells, eosinophils, rod-shaped neutrophils, segmentonuclear neutrophils, lymphocytes, monocytes three times — before treatment, fi ve days aft er the end of the program. Th e resulting adaptation system data was evaluated as “training”, “quiet activation”, “increased activation”, or “stress”.The application of the scheme for diff erent periods of treatment according to the response of individually adapting the patient to begin rehabilitation contributed to the full year program: disappeared pain syndrome, restored the functional ability of the respective injured body, help prevent development of disability, decreased period of disability.The highly informative adaptation response, determined by the blood formula, answers the question about the reserve capabilities of this patient, which ultimately provides a positive result in the form of recovery of working capacity in the case of a fl exible rehabilitation scheme.

Size Matters: Zoo Data Analysis Shows that the White Blood Cell Ratio Differs between Large and Small Felids.

The total number of white blood cells (WBCs) is related the immune system. In mammals, it is affected by the body mass, but it is unclear how the numbers of different WBC types correlate with this parameter. We analyzed the effect of body mass on WBC number and ratio in felids, where species are similar in diet (warm-blood vertebrates) and reproductive strategy (promiscuity). Based on zoo veterinary data (ZIMS database) we analyzed the effect of body mass on WBC number and neutrophils/lymphocytes ratio in 26 species of felids. The number of WBCs correlated with the body masses of animals: large cats had more WBC, which may be due to greater risks of infection associated with larger body surface, lifespan and home range size. For the first time we found obvious differences in the number of WBC types. Large cats also had more neutrophils and monocytes but fewer lymphocytes than smaller cats. The ratio of neutrophils to lymphocytes is greater in large felids. This phenomenon may be related to diet (relative prey size and kill utilization time), which suggests regular contact of large cats with bacterial and protozoal pathogens in contrast to the small cats.

Super-MSI: CfDNA-based pan-cancer microsatellite instability detection.

e13672 Background: Microsatellite instability (MSI) is a molecular subtype found in many cancers, which is often associated with the benefits of immunotherapy. However, the application of traditional testing strategies (such as PCR or IHC) is largely limited due to their dependencies on sufficient tumor tissues. Here, we introduced Super-MSI, a cfDNA-based pan-cancer MSI detection method using next-generation sequencing (NGS). Methods: 5500 detectable microsatellite loci from 250 white blood cells (WBCs) and 29 PCR-validated MSI-H tissue samples were sequenced and characterized, while the former represented for MSS pattern, and the later, for MSI-H. 91 microsatellite loci with the most variable motif repeat numbers between patterns were filtered and the Super-MSI method was established. Plasma samples were collected from 608 patients with known MSI status assessed by PCR (593 MSS and 15 MSI-H) to validate the method. All samples were sequenced with a 642-gene panel, and initial microsatellite reads count distributions were profiled by MSIsensor. Results: We characterized each microsatellite locus by REF alleles (MSI-H:WBC ratio less than 1) and ALT alleles (MSI-H:WBC ratio more than 20), then defined the sum of ALT alleles frequency in WBC group as the baseline for each candidate locus. For plasma samples with unknown MSI status, hypergeometric distribution and FDR calibration were employed to assess the difference of ALT alleles frequency between the WBC baseline and plasma samples. Locus with FDR adjusted p-value less than 0.05 was defined as an unstable locus based on prior knowledge, and negative log-transformed FDR-p was defined as MSscore for the locus. The plasma sample with both unstable microsatellite proportion larger than 20% and total MSscore larger than 270 was defined as MSI-H, and contrariwise, MSS. For all evaluable samples in the validation cohort, Super-MSI showed high sensitivity and specificity of 60% (9/15) and 100% (593/593) for an overall accuracy of 99.0% (602/608), superior to its kind bMSISEA (83.5%, 106/127) and Guardant360 (98.4%, 934/949). Within LOD of 0.5% maxAF (approximately 1% ctDNA fraction), Super-MSI was able to detect 81.8% (9/11) of MSI-H samples, demonstrating high concordance with tissue-based PCR tests. Conclusions: Super-MSI can genotype pan-cancer patients with blood cfDNA samples and give highly accurate MSI evaluation with 81.8% sensitivity and 100% specificity above 1% ctDNA fraction.

Mechanism of heparin-binding protein increasing vascular permeability in early burn

To investigate the effect of heparin-binding protein (HBP) on the damage of vascular permeability in early burn. (1) Clinical research: 12 patients with severe burns admitted to Suzhou Hospital of Nanjing Medical University from January 1st to August 30th in 2019 were enrolled. Eight patients with severe trauma admitted to the same hospital during the same period were also enrolled as controls to explain the specificity of burn injury. Whole blood samples were obtained within 0.5 hour after admission. The white blood cell count (WBC), absolute value and ratio of neutrophils, and serum HBP levels were measured. Serum samples of 12 patients with severe burn were collected within 9 days after admission, and enzyme-linked immunosorbent assay (ELISA) was used to detect the levels of metabolism products of glycocalyx including syndecan-1 and hyaluronic acid (HA). The correlation between HBP and neutrophils ratio, syndecan-1 and HA were analyzed by linear correlation. (2) Basic research: a 30% total body surface area (TBSA) III degree angle burn model of Sprague-Dawley (SD) rat aged 6-8 weeks was prepared. In low molecular weight heparin (LMWH) intervention group (n = 5), 200 U/kg LMWH was injected subcutaneously immediately and every 2 hours after injury for 4 times in total; the burn group (n = 5) was given the same amount of normal saline. No intervention was given to the normal control group (n = 5). The peripheral venous blood was collected at 0, 2, 4, and 8 hours after injury, and the serum levels of HBP, syndecan-1 and HA were measured; the injury of glycocalyx on pulmonary vascular endothelial cells was observed under transmission electron microscope. (1) Clinical research results: the WBC, neutrophils absolute value and ratio, and HBP levels were increased in 12 patients with severe burn and 8 patients with severe trauma. There was no significant difference in the WBC, absolute value and ratio of neutrophils between severe burn and severe trauma patients [WBC (×109/L): 14.5±6.1 vs. 10.8±3.6, the absolute value of neutrophils (×109/L): 12.0±5.9 vs. 9.0±4.0, the ratio of neutrophils: 0.81±0.10 vs. 0.79±0.14, all P > 0.05], but the HBP levels in the burn patients were significantly higher than those in the trauma patients (μg/L: 192.92±61.73 vs. 51.17±23.05, P < 0.01). Twelve patients with severe burns had a sharp increase in serum syndecan-1 and HA levels after burns, which continued to maintain high levels and peaked at the 9th day [syndecan-1 (μg/L): 16.02±0.39, HA (μg/L): 106.83±4.90]. The analysis showed that HBP was positively correlated with neutrophils ratio, syndecan-1 and HA in severe burn patients at the 1st day after admission (r values were 0.805, 0.732 and 0.900, respectively, all P < 0.01). It indicated that the sharp increase of neutrophils after the burn released a lot of HBP, and the glycocalyx of the vascular endothelium was severely damaged. (2) Basic research results: the levels of serum HBP, syndecan-1 and HA in the burn group were increased sharply as compared with the normal control group, and continued to increase with time, reaching a peak at 8 hours after burn. In the LMWH intervention group, the serum levels of HBP, syndecan-1 and HA were significantly lower than those in the burn group, and the difference was still statistically significant after 8 hours [HBP (μg/L): 6.47±0.25 vs. 12.48±0.08, syndecan-1 (μg/L): 19.06±1.48 vs. 25.92±3.34, HA (μg/L): 35.76±2.10 vs. 54.91±2.64, all P < 0.01]. The results of transmission electron microscopy showed that in the normal control group, the glycocalyx pulmonary vascular endothelial cells was continuous, evenly distributed and dense. The glycocalyx on pulmonary vascular endothelial cells of rats were significantly damaged and shed 2 hours after burn in the burn group, and no glycocalyx was observed at 8 hours. In the LMWH intervention group, the glycocalyx on pulmonary vascular endothelial cells was damaged and the phenomenon of shedding was significantly relieved, and the glycocalyx could be observed 8 hours after the injury. The massive exudation of body fluids and the significant increase of vascular permeability in patients in early burns may be related to the destruction of the glycocalyx on endothelial cells by HBP released from increased neutrophils.

A Lower Urine White Blood Cell Median Can be a Predictor of Undiscovered Urolithiasis in Patients with Acute Urinary Tract Symptoms

Purpose: Acute urinary tract infection (UTI) causes symptoms including urgency, frequency, dysuria, and pain in the lower urinary tract. However, these symptoms are not unique to infection. Urolithiasis, injury, neurological disease, and malignancy present with the same symptoms. We aimed to find predictors in urinalysis to detect underlying causes in patients with acute UTI symptoms. Materials and Methods: We recruited 192 patients who presented with acute UTI symptoms from a single institute between September 2012 and September 2018. Each patient received urinalysis, kidney–ureter–bladder X-ray, and kidney plus transabdominal bladder sonography as primary surveys. Patients with flank pain and hydronephrosis but without definitive radiopaque lesion received computed tomography (CT) scan as an advanced intervention. Cystoscopy was ordered by the physician if the patient had gross hematuria and was suspected to have intravesical lesion. We correlated the urine nitrate, the median of red blood cells (RBCs) and white blood cells (WBCs), and the ratio of red and WBCs with the finding on image studies, which included sonography, X-ray, and CT by statistical models. Results: In patients with urolithiasis detected by either X-ray or CT, logistic regression showed that higher urine RBC and lower urine WBC medians were predictors of urolithiasis. In the ROC analysis, WBC median lower than 7.75 per high power field (HPF) was a significant predicting factor for the positive finding of urolithiasis on a CT scan. Conclusion: When presenting with acute UTI symptoms, patients with a lower urine WBC median are correlated with a higher probability to have urolithiasis. In addition, WBC median lower than 7.75 per HPF in urinalysis is a predictor for urolithiasis found on CT in patients with flank pain or hydronephrosis.

A tale of two islands: evidence for impaired stress response and altered immune functions in an insular pit viper following ecological disturbance.

The frequency and intensity of ecological perturbations affecting wild animal populations is expected to increase in the future with animals facing numerous global threats. Seahorse Key is a continental island off mainland Florida that has historically been a major rookery for several species of waterbirds. As a result of an unknown disturbance, the entire rookery abandoned Seahorse Key in April 2015 and shifted nesting activities to nearby Snake Key, resulting in an influx of food resources in the form of fish carrion to resident Florida cottonmouth snakes (Agkistrodon conanti), while snakes on Seahorse Key experienced a drastic reduction in food resources. Our objective was to assess plasma corticosterone concentrations, corticosterone negative feedback using dexamethasone, blood glucose, body condition, packed cell volume, natural antibody agglutination, white blood cell counts and ratios and erythrocyte sedimentation rate to characterize the long-term effects of differential resource availability in these two snake populations 3years after this major ecological disturbance. We collected blood samples at three time points from cottonmouths on Seahorse Key (n = 6 individuals) and Snake Key (n = 13 individuals) in fall 2018. In due consideration of the small sample size, our study shows evidence that 3years after the shift in waterbird nesting Seahorse Key cottonmouths exhibit a dampened acute stress response and presumptive impaired innate immune functions relative to cottonmouths on Snake Key. These results highlight the context-dependent nature of biomarkers and implicate the significant decrease in food resources on Seahorse Key in altering hormonal stress responses and innate immune functions, possibly leading to unknown long-term downstream effects. This study assessed the response of a wild population of pit viper to ecological disturbance in situ with the aim to improve our understanding of how animals cope with such perturbations and improve our capacity to make informed decisions for conservation.

Dysregulation of Immune Response in Patients with COVID-19 in Wuhan, China

Background: In December 2019, a novel coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), emerged in Wuhan and rapidly spread throughout China. The immune response is likely to be highly involved in the pathological process of coronavirus disease 2019 (COVID-19). However, information on specific changes of immune response in COVID-19 are limited. Methods: Demographic and clinical data of all confirmed cases with COVID-19 on admission at Tongji Hospital from January 10 to February 12, 2020, were collected and analyzed. The expression of lymphocytes, lymphocyte subsets, infection related biomarkers and inflammatory cytokines were analyzed and compared between severe cases and non-severe patients. Findings: Of the 452 patients with COVID-19 recruited from January 10 to February 12, 2020, 286 were diagnosed as severe infection. The median age was 58 years and 235 were male. 201 patients had chronic diseases and a higher percentage in the severe cases. The most common symptoms were fever, shortness of breath, expectoration, and fatigue. Severe cases tend to have higher white blood cell and neutrophil lymphopenia ratio (NLR), as well as lower percentages of monocytes, eosinophils, and basophils. Most of severe cases demonstrated elevated levels of infection-related biomarkers, and inflammatory cytokines. The numbers of B cells, T cells and NK cells was significantly decreased in patients with COVID-19, and more severely decreased in the severe cases. T cells were shown to be most affected by SARS-CoV-2, and more hampered in severe cases. Both helper T cells and suppressor T cells in patients with COVID-19 were below normal levels. Helper T cells tend to be more affected in severe cases. The percentage of naïve helper T cells increased and memory helper T cells decreased in severe cases. Patients with COVID-19 have lower level of regulatory T cells, and more obviously damaged in severe cases. Interpretation: SARS-CoV-2 might mainly act on lymphocytes, especially T lymphocytes, and induce a cytokine storm in the body, generate a series of immune responses. Surveillance of NLR and lymphocyte subsets is helpful in the early screening of critical illness, diagnosis and treatment of COVID-19.Funding Statement: None.Declaration of Interests: All authors declare no competing interests.Ethics Approval Statement: The study was performed in accordance with Tongji Hospital Ethics Committee (IRB ID: TJ-C20200121). Written informed consent was waived by the Ethics Commission of the designated hospital for emerging infectious disease.

A Retrospective Analysis: A Novel Index Predicts Survival and Risk-Stratification for Bone Destruction in 419 Newly Diagnosed Multiple Myelomas.

ObjectiveMultiple myeloma (MM) patients with bone destruction are difficult to restore, so it is of great clinical significance to further explore the factors affecting MM bone destruction.Methods and resultsThis study retrospectively analyzed 419 cases with MM. Multiple linear regression analysis showed that those MM patients with a higher concentration of Ca2+ in serum, higher positive rate of CD138 immuno-phenotype and advanced in stage with 13q34 deletion in cytogenetics would be more prone to bone destruction, while total bile acid (TBA) and kappa chain isotope negatively correlated with bone destruction in MM patients. The Kaplan–Meier analysis indicated that Ca2+, serum β2-microglobulin (β2-MG), hemoglobin (HGB), creatinine (CREA), uric acid (UA) and age correlated with the survival of bone destruction in MM patients. Cox regression analysis further showed that the independent prognostic factors of β2-MG and CREA had a higher risk for early mortality in bone destruction patients. Moreover, an index was calculated based on β2-MG and globulin (GLB) to white blood cell (WBC) ratio to predict the poor survival of bone destruction patients.ConclusionWe provide a novel marker to predict the prognosis of myeloma patients using routine examination method instead of bone marrow aspiration, and provide a reference for clinical evaluation.