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AbstractDiabetic foot wounds associated with oxidative stress are treated with hyperbaric oxygen (HBO), but that may also induce the stress itself; therefore, we studied the effect of HBO treatments on the oxidant–antioxidant balance in the venous blood of patients with diabetic foot syndrome. In addition, blood counts were also examined. 14 male patients (24–74 years), at risk of lower limb amputation were treated with 30 HBO procedures (60 min of the inhalation of pure oxygen at a pressure of 2.5 atm per day, 5 days a week). The control group consisted of 29 healthy male volunteers aged 25–69 years. No members of the group had been subjected to HBO therapy previously (ClinicalTrials.gov, no. NCT06401941). The analyzed redox parameters did not change during the experiment in the patients (p > 0.05). The concentration of thiobarbituric acid reactive substances (TBARS) in the plasma was higher in the patients before the first and after the thirtieth HBO treatments when compared to the control group. In contrast, the TBARS concentration in erythrocytes was lower in the patients after the first treatment vs. the controls. Moreover, the higher activity of catalase in the patients’ erythrocytes was noted before the therapy and after the first and last treatments compared to the controls. HBO therapy increased the percentage of monocytes and platelet volume, but it decreased the volume of platelets in the patients’ blood. HBO therapy does not affect the oxidant–antioxidant balance disturbed in diabetic foot patients. [ABSTRACT FROM AUTHOR]

Background: Blood counts and biochemical markers are among the most common tests performed in hospitals and most readily accepted by patients, and are widely regarded as reliable biomarkers in the literature. The aim of this study was to assess the causal relationship between blood counts, biochemical indicators and pulmonary arterial hypertension (PAH). Methods: A two-sample Mendelian randomization (MR) analysis was performed to assess the causal relationship between blood counts and biochemical indicators with PAH. The genome-wide association study (GWAS) for blood counts and biochemical indicators were obtained from the UK Biobank (UKBB), while the GWAS for PAH were sourced from the FinnGen Biobank. Inverse variance weighting (IVW) was used as the primary analysis method, supplemented by three sensitivity analyses to assess the robustness of the results. And we conducted an observational study using data from National Health and Nutrition Examination Survey (NHANES) 2003–2018 to verify the relationship. Results: The MR analysis primarily using the IVW method revealed genetic variants of platelet count (OR=2.51, 95% CI 1.56-4.22, P<0.001), platelet crit(OR=1.87, 95% CI1.17-7.65, P=0.022), direct bilirubin (DBIL)(OR=1.71, 95%CI 1.18-2.47,P=0.004), insulin-like growth factor (IGF-1)(OR=0.51, 95% CI 0.27-0.96, P=0.038), Lipoprotein A (Lp(a))(OR=0.66, 95% CI 0.45-0.98, P=0.037) and total bilirubin (TBIL)(OR=0.51, 95% CI 0.27-0.96, P=0.038) were significantly associated with PAH. In NHANES, multivariate logistic regression analyses revealed a significant positive correlation between platelet count and volume and the risk of PAH, and a significant negative correlation between total bilirubin and PAH. [ABSTRACT FROM AUTHOR]

BackgroundThe existing literature on the relationship of hyperparathyroidism with both blood counts and biochemical indicators primarily comprises observational studies, which have produced inconsistent findings. This study aimed to evaluate the causal relationship between hyperparathyroidism and blood counts and biochemical indicators.MethodsMendelian randomization (MR) analyses were conducted to investigate the associations between hyperparathyroidism and the identified 55 blood counts and biochemical indicators. The genome-wide association study (GWAS) for hyperparathyroidism data was obtained from FinnGen, while the GWASs for the blood counts and biochemical indicators were sourced from the UK Biobank (UKBB).ResultsThe MR analysis using the inverse-variance weighted (IVW) method revealed potential causality between genetically predicted hyperparathyroidism and seven out of 55 blood counts and biochemical indicators. These markers include “Platelet count” (Beta = -0.041; 95% CI: -0.066, -0.016; p = 0.001), “Platelet distribution width (PDW)” (Beta = 0.031; 95% CI: 0.006, 0.056; p = 0.016), “Mean platelet volume (MPV)” (Beta = 0.043; 95% CI: 0.010, 0.076; p = 0.011), “Vitamin D” (Beta = -0.038; 95% CI: -0.063, -0.013; p = 0.003), “Calcium (Ca2+)” (Beta = 0.266; 95% CI: 0.022, 0.509; p = 0.033), “Phosphate” (Beta = -0.114; 95% CI: -0.214, -0.014; p = 0.025), and “Alkaline phosphatase (ALP)” (Beta = 0.030; 95% CI: 0.010, 0.049; p = 0.003).ConclusionThe findings of our study revealed a suggestive causal relationship between hyperparathyroidism and blood cell count as well as biochemical markers. This presents a novel perspective for further investigating the etiology and pathological mechanisms underlying hyperparathyroidism.

Objectives: Stroke is the second-leading cause of death and the third-leading cause of death and disability combined in the world. We need to find easy, available, and reliable parameters on which we can depend to prevent stroke, predict outcome, and determine prognosis. This will help in stroke management in the future. Materials and Methods: We noted blood counts and serum homocysteine levels in acute stroke patients after the exclusion of confounding factors. Our team recorded the detailed demographic and blood parameters (blood counts and homocysteine) of acute stroke patients who got admitted to different departments of our hospital in 5 months. We later correlated or tried to find the association between these parameters and stroke severity (NIHSS), other clinical parameters such as dysarthria and stroke outcome (Modified Rankin Score (mRS) at discharge and at 3 months). The team also tried to find relationships, if any, with different stroke subtypes as per the Trial of ORG 10172 in Acute Stroke Treatment classification. Results: Out of 100 patients (34 females and 66 males), we had 28 patients with hyperhomocysteinemia (HHcy). The high neutrophil count and total leukocyte count correlated with stroke severity, dysarthria, and outcome at 3 months (poor mRS). While, it was the opposite in the case of lymphocyte count. Homocysteine level did not correlate with stroke severity or outcome but with dyslipidemia. HHcy was more prevalent among patients with large artery atherosclerotic disease. Conclusion: Findings of our study were agreeable to earlier studies on the relationship between blood counts and stroke prognosis. Although high homocysteine level was associated with stroke, its level was not found to be related to stroke severity or outcome. However, further study with a larger sample size is required to draw a confident conclusion.

Introduction: There are few reports on the effect of radiation alone on blood cells (without chemotherapy). We sought to develop a single source as a reference. Materials and Methods: For over 300 prostate cancer patients treated with radiation alone, we collected the baseline, end-of-treatment and three-month post-therapy complete blood counts (CBC). Results: The hemoglobin dropped by a mean of 1.00 g/dL (−7.1%), with an RBC count of 0.40 × 1012 (−8.6%) at the end of treatment and remained significantly (but 9), monocytes (−2.2%; −0.05 × 109) and platelets (−12.7%; −30.31 × 109) at the end of treatment, but all returned to baseline on follow-up. The neutrophils and basophils (the primary components of the granulocytes) suffered a significant decline but returned to baseline by the follow-up. The other granulocyte components, the eosinophils, did not decline significantly. The most dramatic decline was in the levels of lymphocytes −62.5% (−1.29 × 109), which were still significantly below baseline (−38%) after two years. Conclusion: The effect of radiation is mostly transitory, with some persistence in hemoglobin/erythrocyte levels (

Introduction: There are few reports on the effect of radiation alone on blood cells (without chemotherapy). We sought to develop a single source as a reference. Materials and Methods: For over 300 prostate cancer patients treated with radiation alone, we collected the baseline, end-oftreatment and three-month post-therapy complete blood counts (CBC). Results: The hemoglobin dropped by a mean of 1.00 g/dL (-7.1%), with an RBC count of 0.40 × 1012 (-8.6%) at the end of treatment and remained significantly (but <5%) below baseline at follow-up. Significant declines were seen in the levels of the granulocytes (-12.2%; -0.67 × 109), monocytes (-2.2%; -0.05 × 109) and platelets (-12.7%; -30.31 × 109) at the end of treatment, but all returned to baseline on follow-up. The neutrophils and basophils (the primary components of the granulocytes) suffered a significant decline but returned to baseline by the follow-up. The other granulocyte components, the eosinophils, did not decline significantly. The most dramatic decline was in the levels of lymphocytes -62.5% (-1.29 × 109), which were still significantly below baseline (-38%) after two years. Conclusion: The effect of radiation is mostly transitory, with some persistence in hemoglobin/erythrocyte levels (<5%). Lymphocytes are slower to recover, remaining significantly below baseline after two years. It is noteworthy that of the patients whose lymphocytes were in the normal range at the start of therapy, only 14% were below normal at follow-up. Radiation alone has negligible-to-modest long-term effects on blood counts. [ABSTRACT FROM AUTHOR]

Iodine deficiency in soil and water in many countries leads to its low content in plants and animal feed produced from them. The limited intake of this element in animals can lead to endemic diseases. The lack of iodine in animal feeding is most often compensated for by the use of additives with an inorganic form of iodine, which can be poorly absorbed by the body. Feed products with an organic form of iodine have a great biological effect. A study on the effect of iodine-containing additives on the physiological and biochemical parameters of the animal organism was carried out on two groups of 15 cows. The experimental group was fed an organic form of iodine as part of the additive, the control group received an inorganic form of iodine. For all animals during the experiment the biochemical parameters of blood, milk productivity and reproductive ability were studied. During the experiment, an increase in metabolic and redox processes in the body was noted in the experimental group. An increase in mineral metabolism, including iodine content, was found. Due to the sufficient intake of organic iodine in the animals of the experimental group, there was an increase in the activity of the main hepatic enzymes AST and ALT. An increase in the process of gluconeogenesis due to an increase in the glucose content in the blood of experimental cows was revealed. An increase in milk production and reproductive function of animals of the experimental group was established. Within 30 days after the termination of feeding the supplement with the organic form of iodine in the experimental group, a prolonging effect was observed, consisting in higher values of blood biochemical parameters, improved reproductive function and milk productivity relative to equivalent animals in the control. As a result, it was concluded that the use of an additive with an organic form of iodine in the amount of 1.5 g in feeding cows for 60 days increases the iodine content in the blood serum of animals and increases the performance of all types of metabolism, which may indicate the best stimulating effect of the organic form of iodine on thyroid activity glands. This in turn helps to improve the productive and reproductive qualities of animals. To recommend the studied drug as a means to replenish iodine deficiency in animals and to more accurately analyze its effect on the hormone-forming function of the thyroid gland, it is necessary to study the level of thyroid hormones in the blood.

Recent advances in sequencing technologies provide unprecedented opportunities for epigenetic biomarker development. Particularly the DNA methylation pattern—which is modified at specific sites in the genome during cellular differentiation, aging, and disease—holds high hopes for a wide variety of diagnostic applications. While many epigenetic biomarkers have been described, only very few of them have so far been successfully translated into clinical practice and almost exclusively in the field of oncology. This discrepancy might be attributed to the different demands of either publishing a new finding or establishing a standardized and approved diagnostic procedure. This is exemplified for epigenetic leukocyte counts and epigenetic age-predictions. To ease later clinical translation, the following hallmarks should already be taken into consideration when designing epigenetic biomarkers: 1) Identification of best genomic regions, 2) pre-analytical processing, 3) accuracy of DNA methylation measurements, 4) identification of confounding parameters, 5) accreditation as diagnostic procedure, 6) standardized data analysis, 7) turnaround time, and 8) costs and customer requirements. While the initial selection of relevant genomic regions is usually performed on genome wide DNA methylation profiles, it might be advantageous to subsequently establish targeted assays that focus on specific genomic regions. Development of an epigenetic biomarker for clinical application is a long and cumbersome process that is only initiated with the identification of an epigenetic signature.

Background: Magnetic field has being used in diagnostics for decades such as MRI. Sources of magnetic field were found in electronic devices and may emit extremely low intensity of magnetic field. Beside the daily use of electronic devices, there are some concerns regarding to side effects of magnetic field produces on living cells. Main Blood cells parameters were considered, and Red blood cells have targeted as the main and most affected by magnetic field. Concerns to blood, any abnormality in shape, aggregation, count may cause inflammations or chronic diseases such as anemia. Objective: In this review, we evaluated the previous works carried out to investigate the effect of static and time varying magnetic fields on rheological properties (blood parameters, viscosity and DNA strand break) of blood between periods from 1980-2019. We provided up-to-date state of research articles and the latest progress. Different intensities of magnetic fields (week, moderate and strong) were looked at. Result: Seventy two published research articles were reviewed. This shortened to thirty eight articles in respect to our goal. The chosen articles studied the biological effect of magnetic field on human and animal in vivo and in vitro experiments. A few theoretical studies were pointed to. Inconsistent results were compared. Conclusion: Magnetic fields can be static or time varying as frequency is not zero. Blood counts responded to external magnetic field with altering in counts, aggregations, change in viscosity and DNA strand break. RBCs aggregation increased as blood is affected by magnetic field. Whole blood viscosity enhanced the aggregation of red blood cells. Raise in aggregation changed the time flow of blood in microcirculations.

Background: Blood counts and biochemical markers are among the most common tests performed in hospitals and most readily accepted by patients, and are widely regarded as reliable biomarkers in the literature. The aim of this study was to assess the causal relationship between blood counts, biochemical indicators and pulmonary arterial hypertension (PAH)., Methods: A two-sample Mendelian randomization (MR) analysis was performed to assess the causal relationship between blood counts and biochemical indicators with PAH. The genome-wide association study (GWAS) for blood counts and biochemical indicators were obtained from the UK Biobank (UKBB), while the GWAS for PAH were sourced from the FinnGen Biobank. Inverse variance weighting (IVW) was used as the primary analysis method, supplemented by three sensitivity analyses to assess the robustness of the results. And we conducted an observational study using data from National Health and Nutrition Examination Survey (NHANES) 2003-2018 to verify the relationship., Results: The MR analysis primarily using the IVW method revealed genetic variants of platelet count (OR=2.51, 95% CI 1.56-4.22, P<0.001), platelet crit(OR=1.87, 95% CI1.17-7.65, P=0.022), direct bilirubin (DBIL)(OR=1.71, 95%CI 1.18-2.47,P=0.004), insulin-like growth factor (IGF-1)(OR=0.51, 95% CI 0.27-0.96, P=0.038), Lipoprotein A (Lp(a))(OR=0.66, 95% CI 0.45-0.98, P=0.037) and total bilirubin (TBIL)(OR=0.51, 95% CI 0.27-0.96, P=0.038) were significantly associated with PAH. In NHANES, multivariate logistic regression analyses revealed a significant positive correlation between platelet count and volume and the risk of PAH, and a significant negative correlation between total bilirubin and PAH., Conclusion: Our study reveals a causal relationship between blood counts, biochemical indicators and pulmonary arterial hypertension. These findings offer novel insights into the etiology and pathological mechanisms of PAH, and emphasizes the important value of these markers as potential targets for the prevention and treatment of PAH., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Liu, Fu, Yu, Ma and Yang.)

Variations in blood count parameters are potential mechanisms involved in the occurrence of cardiovascular events caused by particulate matter (PM) exposure. This study aims to estimate the effect of PM10 exposure on blood count parameters with potential to mediate a cardiovascular event. We used data from 2211 participants of the 1st Portuguese Health Examination Survey (INSEF, 2015) with available information on blood count parameters and living within a 30-km radius of at least one air quality monitoring station with available PM10 measurements. Generalised linear models were used to assess both short (3 days) and long-term effects (1 year) of PM10 exposure on blood count parameters. Both short and long-term PM10 effects on blood count parameters were found, with males and females affected in a different way. In the short-term scenario, we found a 2.76% (95% CI: 0.65–4.87) increase in white blood cells among females per each 10μg/m3 PM10 increment. Additionally, there was a 2.96% (95% CI: 0.80–5.12) increase in red cell distribution width (RDW), per each 10μg/m3 PM10 increment, among males, when considering the long-term scenario. In conclusion, we detected some sex-differential associations regarding the short and long-term effect of PM10 exposure on blood count parameters with potential to mediate a cardiovascular event, namely on the RDW parameter, that were never been described. It is uncertain whether changes in blood count parameters due to PM10 exposure constitute an adverse health outcome or it reflects only a normal immunity response. However, due to its potential to trigger cardiovascular events, it is essential to reduce PM10 levels exposure to protect the population's cardiovascular health. [ABSTRACT FROM AUTHOR]

This study was undertaken to investigate the influence of a homogenous and uniform static magnetic field (SMF) on the main blood cell counts in vitro experiment. Fresh blood samples were collected from albino rats and exposed to SMF (2.4, 6, 25, 50, 75, and 100 mT) versus 15–60 min. Results showed a significant change of blood counts under the low field effects. A 2.4 mT was a trend of white blood cells (WBCs) count increase non-linearly. However, a 6 mT exposure reduced WBCs with about 39%. Other variations fluctuated within 30%. The 25 mT decreased red blood cells (RBCs), hemoglobin, and hematocrit levels with 13% similarly. The lower exposure field, (2.4 and 6) mT, and effects on RBCs were 6% fluctuation. The 6 mT reduced platelet counts with half in comparison to control blood samples. About 20% increase obtained due to 50 mT exposure during all period. None of 75 and 100 mT exposures dominated blood counts alterations. The quiet magnetic field exposure for a certain time can be interesting to control blood cell count-related diseases.

Acute leukaemia represents uncontrolled malign, immature cell proliferations (called blasts) of the hematopoietic system. As opposed to chronic leukaemia, acute leukaemia occurs in a few weeks and determines the precocious occurrence of symptoms, severe in some situations, which renders its diagnosis and treatment extremely important. The diagnosis of acute leukaemia is established based on a blood exam: the complete blood count (CBC), the peripheral blood smear and the red marrow biopsy, highlighting leucocytes, leukemic blasts and thrombocytopenia; usually, anaemia and a haematocrit decrease are registered. It is worrying that the number of leukaemia cases has grown widely during the last years and it is increasingly harder to detect the causes of these genetic changes at cellular level. The purpose of the present study was to capture and highlight the importance of the changes that occurred in the examination of peripheral blood smears and of the automatic complete blood counts, before and after the intervention of the chemotherapy treatment, respectively in the high precision diagnosis of acute leukemias. Patients were monitored during the chemotherapy treatment, with 23 complete blood counts and peripheral blood smears being performed. The analysis and processing of complete blood counts was done following the changes that intensive chemotherapy induces at the level of haematological parameters and on the morphology of blood cells. It has been observed that depending on the individual and the time of diagnosis of acute leukemia, there are wide variations in blood parameters. The response to chemotherapy treatment is also variable over time. Chemotherapy caused the sudden decrease in the number of leukocytes and the complete destruction of leukemic blasts. The investigation of peripheral blood smears supported the results recorded in the processing of automatic complete blood counts for all patients. If the presence of leukemic blasts associated with leukocytosis or leukopenia was detected before chemotherapy, the chemotherapy treatment initially destroyed the leukemic blasts, and then they reappeared on the blood smears. The result indicates the need to consolidate the remission obtained following the first chemotherapy treatment by continuing the treatment until the complete release of the haematogenous bone marrow from the cancer cells, and by resuming the normal haematopoiesis of blood cells. [ABSTRACT FROM AUTHOR]

Background: The existing literature on the relationship of hyperparathyroidism with both blood counts and biochemical indicators primarily comprises observational studies, which have produced inconsistent findings. This study aimed to evaluate the causal relationship between hyperparathyroidism and blood counts and biochemical indicators., Methods: Mendelian randomization (MR) analyses were conducted to investigate the associations between hyperparathyroidism and the identified 55 blood counts and biochemical indicators. The genome-wide association study (GWAS) for hyperparathyroidism data was obtained from FinnGen, while the GWASs for the blood counts and biochemical indicators were sourced from the UK Biobank (UKBB)., Results: The MR analysis using the inverse-variance weighted (IVW) method revealed potential causality between genetically predicted hyperparathyroidism and seven out of 55 blood counts and biochemical indicators. These markers include "Platelet count" (Beta = -0.041; 95% CI: -0.066, -0.016; p = 0.001), "Platelet distribution width (PDW)" (Beta = 0.031; 95% CI: 0.006, 0.056; p = 0.016), "Mean platelet volume (MPV)" (Beta = 0.043; 95% CI: 0.010, 0.076; p = 0.011), "Vitamin D" (Beta = -0.038; 95% CI: -0.063, -0.013; p = 0.003), "Calcium (Ca 2+ )" (Beta = 0.266; 95% CI: 0.022, 0.509; p = 0.033), "Phosphate" (Beta = -0.114; 95% CI: -0.214, -0.014; p = 0.025), and "Alkaline phosphatase (ALP)" (Beta = 0.030; 95% CI: 0.010, 0.049; p = 0.003)., Conclusion: The findings of our study revealed a suggestive causal relationship between hyperparathyroidism and blood cell count as well as biochemical markers. This presents a novel perspective for further investigating the etiology and pathological mechanisms underlying hyperparathyroidism., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Jiang, Chen, Xu, Ding, Zhang, Bao, He and Li.)

This study aimed to indicate the influence of infection caused by genotype II African swine fever virus (ASFV)–isolate Pol18_28298_O111, currently circulating in Poland, on blood counts, biochemical parameters, as well as inflammatory and immune responses. Blood and sera collected from 21 domestic pigs infected intranasally with different doses of virulent ASFV were analysed. The infection led to variable changes in blood counts depending on the stage of the disease with a tendency towards leukopenia and thrombocytopenia. The elevated C-reactive protein (CRP) concentrations and microscopic lesions in organs confirmed the development of the inflammation process, which also resulted in an increased level of biochemical markers such as: Aspartate transaminase (AST), creatine kinase (CK), creatinine, and urea. Antibodies could be detected from 9 to 18 days post infection (dpi). Two survivors presented the highest titer of antibodies (>5 log10/mL) with a simultaneous increase in the lymphocyte T (CD3+) percentage–revealed by flow cytometry. Results confirmed a progressive inflammatory process occurring during the ASFV infection, which may lead to multiple organs failure and death of the majority of affected animals.

Objectives: We aimed to study the prevalence of CTCs in breast cancer (BC) patients undergoing neoadjuvant or palliative therapy with a label-free microfluidic platform (ClearCell FX), and its prognostic relevance in metastatic BC (mBC). Materials and methods: Peripheral blood samples were collected from 108 BC patients before starting a new line of treatment (“baseline”), majority of whom had mBC (76/108; 70.4%). CTCs were retrieved by dean flow fractionation that enriched for larger cells, and enumerated using immunofluorescence-based staining. Progression-free survival (PFS) in mBC patients was analysed using Kaplan-Meier method; cox proportional hazard models were used for univariable and multivariable analyses. Results: The detection rate of CTCs before starting a new line of treatment was 75.9% (n = 108; median: 8 CTCs/7.5 ml blood) at a cut off of ≥2 CTCs. PFS was inferior for mBC patients with baseline CTC count ≥5 CTCs/7.5 ml blood vs. those with < 5 CTCs/7.5 ml blood (median PFS: 4.3 vs. 7.0 months; p-value: 0.037). The prognostic relevance of CTCs was most significant in patients with HER2- mBC (median PFS: 4.1 vs. 8.3 months; p-value: 0.032), luminal (HR+HER2-) subtype (median PFS: 4.2 vs. 8.3 months; p-value: 0.048), and patients who had one or more prior treatments (median PFS: 4.2 vs. 7.0 months; p-value: 0.02). On multivariable analysis, baseline CTC level (hazard ratio (HR): 1.84, p-value: 0.02) and pre-treatment status (HR: 1.87, p-value: 0.05) were independent predictors of PFS. Conclusions: This work demonstrates the prognostic significance of CTCs in mBC detected using a label-free size-based enrichment platform. [ABSTRACT FROM AUTHOR]

Acute appendicitis is one of the major causes for emergency surgery in childhood and adolescence. Appendectomy is still the therapy of choice, but conservative strategies are increasingly being studied for uncomplicated inflammation. Diagnosis of acute appendicitis remains challenging, especially due to the frequently unspecific clinical picture. Inflammatory blood markers and imaging methods like ultrasound are limited as they have to be interpreted by experts and still do not offer sufficient diagnostic certainty. This study presents a method for automatic diagnosis of appendicitis as well as the differentiation between complicated and uncomplicated inflammation using values/parameters which are routinely and unbiasedly obtained for each patient with suspected appendicitis. We analyzed full blood counts, c-reactive protein (CRP) and appendiceal diameters in ultrasound investigations corresponding to children and adolescents aged 0–17 years from a hospital based population in Berlin, Germany. A total of 590 patients (473 patients with appendicitis in histopathology and 117 with negative histopathological findings) were analyzed retrospectively with modern algorithms from machine learning (ML) and artificial intelligence (AI). The discovery of informative parameters (biomarker signatures) and training of the classification model were done with a maximum of 35% of the patients. The remaining minimum 65% of patients were used for validation. At clinical relevant cut-off points the accuracy of the biomarker signature for diagnosis of appendicitis was 90% (93% sensitivity, 67% specificity), while the accuracy to correctly identify complicated inflammation was 51% (95% sensitivity, 33% specificity) on validation data. Such a test would be capable to prevent two out of three patients without appendicitis from useless surgery as well as one out of three patients with uncomplicated appendicitis. The presented method has the potential to change today’s therapeutic approach for appendicitis and demonstrates the capability of algorithms from AI and ML to significantly improve diagnostics even based on routine diagnostic parameters. [ABSTRACT FROM AUTHOR]

Objective: Blood transfusion is the most frequently used and life-saving therapeutic procedure today. Transmission of virus, bacteria and parasitic microorganisms may occur due to transfusion (Transfusion transmitted infections-TTIs). Hepatitis B and C, human immunodeficiency virus (HIV) and syphilis (Treponema pallidum) bear the risk of transmission by transfusion. Hepatitis B surface antigen (HBsAg), anti-HCV, anti-HIV½ and syphilis antibody (VDRL: Venereal Disease Research Laboratory) are routinely controlled in all donated blood samples. The aim of the present study was to analyze the seroprevalence rates of blood donors through screening test results according to duration, age range and gender. Material and methods: Data of all blood donors obtained from blood Centre of Marmara University Pendik Training and Research Hospital between January 2013 and October 2018 were analyzed retrospectively. Serum samples of the donors were analyzed for HBsAg, anti-HCV, anti-HIV½ and VDRL. Test results of 114.240 donors were scanned. Gender, age range and distribution by years of these donors were analyzed. According to age distribution of donors were divided into 4 groups. Results: There were 114.240 participants including 106.153 (92.9%) males and 8.087 (7.1%) females. The positivity rate of HBsAg was detected 0.4% (36/8087) in females and 0.5% (500/106.153) in males. The positivity rate of anti-HCV was detected 0.4% (32/8.087) in females and 0.3% (344/106.153) in males. The positivity rate of anti HIV½ was 0.1% (9/8.087) in females and 0.1% (92/106.153) in males whereas the positivity rate of VDRL was 0.5% (41/8.087) in females and 0.3% (362/ 106.153) in males. Positivity rate for HBsAg and HCV were lower in the cases between 18 and 30 years of age. The positivity rates for anti-HIV½ was not significantly different according to the age range. Positivity rate for VDRL was higher in the cases at 51 years of age and older. Conclusion: No difference was found between men and women in terms of HBsAg, anti-HCV and anti-HIV½positivity. However, VDRL test positivity was significantly higher in female participants. Furthermore, HBsAg, anti-HCV and VDRL positivity rates increased by age. [ABSTRACT FROM AUTHOR]

Introduction: The success of antiretroviral treatment (ART) programs can be compromised by high rates of patient loss to follow-up (LTFU). We assessed the incidence and risk factors of LTFU in a large cohort of HIV-infected children receiving ART in Thailand. Methods: All children participating in a multicenter cohort (NCT00433030) between 1999 and 2014 were included. The date of LTFU was 9 months after the last contact date. ART interruption was defined as ART discontinuation for more than 7 days followed by resumption of treatment. Baseline and time-dependent risk factors associated with LTFU were identified using Fine and Gray competing risk regression models with death or referral to another hospital as competing events. Results: Of 873 children who were followed during a median of 8.6 years (interquartile range 4.5–10.6), 196 were LTFU, 73 died, and 195 referred. The cumulative incidence of LTFU was 2.9% at 1 year, 7.3% at 5 years and 22.2% at 10 years. Children aged 13 years and more had a 3-fold higher risk (95% confidence interval 2.06–4.78) of LTFU than those younger. Children who had interrupted ART within the previous year had a 2.5-fold higher risk (1.12–5.91) than those who had not. The risk of LTFU was lower in children stunted (height-for-age Z-scores <-2 SD) (0.42–0.96) or underweight (weight-for-age Z-scores <-2 SD) (0.24–0.97). Conclusion: Adolescence, ART interruption and absence of growth deficit were associated with LTFU. These may be warnings that should draw clinicians’ attention and possibly trigger specific interventions. Children with no significant growth retardation may also be at risk of LTFU. [ABSTRACT FROM AUTHOR]

Capillaries are the prime location for oxygen and nutrient exchange in all tissues. Despite their fundamental role, our knowledge of perfusion and flow regulation in cortical capillary beds is still limited. Here, we use in vivo measurements and blood flow simulations in anatomically accurate microvascular network to investigate the impact of red blood cells (RBCs) on microvascular flow. Based on these in vivo and in silico experiments, we show that the impact of RBCs leads to a bias toward equation the values of the outflow velocities at divergent capillary bifurcations, for which we coin the term “well-balanced bifurcations”. Our simulation results further reveal that hematocrit heterogeneity is directly caused by the RBC dynamics, i.e. by their unequal partitioning at bifurcations and their effect on vessel resistance. These results provide the first in vivo evidence of the impact of RBC dynamics on the flow field in the cortical microvasculature. By structural and functional analyses of our blood flow simulations we show that capillary diameter changes locally alter flow and RBC distribution. A dilation of 10% along a vessel length of 100 μm increases the flow on average by 21% in the dilated vessel downstream a well-balanced bifurcation. The number of RBCs rises on average by 27%. Importantly, RBC up-regulation proves to be more effective the more balanced the outflow velocities at the upstream bifurcation are. Taken together, we conclude that diameter changes at capillary level bear potential to locally change the flow field and the RBC distribution. Moreover, our results suggest that the balancing of outflow velocities contributes to the robustness of perfusion. Based on our in silico results, we anticipate that the bi-phasic nature of blood and small-scale regulations are essential for a well-adjusted oxygen and energy substrate supply. [ABSTRACT FROM AUTHOR]

Chronic atherosclerosis may cause cerebral hypoperfusion and inadequate brain oxygenation, contributing to the progression of cognitive decline. In this study, we exploited two-photon phosphorescence lifetime microscopy to measure the absolute partial pressure of oxygen (PO2) in cortical tissue in both young and old LDLR-/-, hApoB100+/+ mice, spontaneously developing atherosclerosis with age. Capillary red-blood-cell (RBC) speed, flux, hematocrit and capillary diameter were also measured by two-photon imaging of FITC-labelled blood plasma. Our results show positive correlations between RBC speed, flux, diameter and capillary-adjacent tissue PO2. When compared to the young mice, we observed lower tissue PO2, lower RBC speed and flux, and smaller capillary diameter in the old atherosclerotic mice. The old mice also exhibited a higher spatial heterogeneity of tissue PO2, and RBC speed and flux, suggesting a less efficient oxygen extraction. [ABSTRACT FROM AUTHOR]

Background and aims: The revised Atlanta classification is widely used for the evaluation of acute pancreatitis (AP) severity. However, this classification cannot be used within 48 hours of AP onset. The aim of this study was to investigate the predictive factors of mortality in patients with AP on admission. Methods: We evaluated the association between AP mortality and clinical parameters at the time of admission in patients with AP from April 2013 to December 2017 at one university hospital and one tertiary care referral center. Results: A total of 203 consecutive patients were enrolled. Nine patients (4.4%) died despite multidisciplinary treatment. In a multivariable analysis, hematocrit ≥ 40% (odds ratio [OR], 1.07; 95% confidence interval [CI], 1.01–1.13; P = 0.021), blood urea nitrogen (BUN) ≥ 40 mg/dL (OR, 1.26; 95% CI, 1.11–1.42; P < 0.001), base excess < -3.0 mmol/L (OR, 1.15; 95% CI, 1.04–1.26; P = 0.004), and inflammation extending to the rectovesical excavation (OR, 1.19; 95% CI, 1.10–1.30; P < 0.001) on admission were significantly associated with mortality. Conclusion: Among the imaging findings, inflammation extending to the rectovesical excavation was the only independent predictive factor for mortality in AP. This simple finding, obtained on computed tomography without contrast agent on admission, might be a promising prognostic factor for AP. [ABSTRACT FROM AUTHOR]

Background: Although evidence of a disseminated intravascular coagulation (DIC)-like reaction has been identified in the lung parenchyma of patients with acute exacerbation of idiopathic pulmonary fibrosis (IPF), an association between DIC and IPF outcome has not been elucidated. Therefore, we retrospectively investigated the association between the Japanese Association for Acute Medicine (JAAM)-DIC score and mortality in patients with acute exacerbation of fibrosing idiopathic interstitial pneumonia (AE-fIIP). Methods: Between January 2008 and December 2016, consecutive patients with chronic fIIP who were admitted for the first time for AE-fIIP were recruited into the study. Associations between clinical data and JAAM-DIC score at the time of admission and mortality were examined. Results: During the study period, a total of 91 patients with fIIP (73.0±8.4 y.o.) were hospitalized for AE-fIIP for the first time. The 30-day and hospital mortality were 8.7% and 17.5%, respectively. A multivariate analysis showed that the JAAM-DIC score on admission was an independent predictor of 30-day mortality (odds ratio [OR] 2.57, 95% confidential interval [CI] 1.50–4.40, P = 0.0006). The APACHE II score (OR 1.29, 95% CI 1.01–1.63, P = 0.03) and the JAAM-DIC score (OR 3.47, 95% CI 1.73–6.94, P = 0.0004) were independent predictors of hospital mortality. Conclusions: The JAAM-DIC scoring system can predict survival in patients with AE-fIIP. The role of DIC in the pathogenesis of AE-fIIP merits further investigation. [ABSTRACT FROM AUTHOR]

Background: Extra-gastric manifestation of Helicobacter pylori infection involves systemic inflammation, which results in the production of several cytokines. Only a few clinical trials have investigated the effect of H. pylori eradication therapy on lipid metabolism in the infected patients with chronic gastritis. We aimed to evaluate the effect of H. pylori eradication therapy on lipid metabolism in a Japanese population with chronic gastritis. Methods: One hundred and sixty-three patients with H. pylori-associated chronic gastritis were enrolled in this study between June 2015 and March 2017. They underwent H. pylori eradication therapy; the effects of the therapy were assessed by the urea breath test performed at least 4 weeks after the therapy. After confirming H. pylori eradication, the health screening examination was repeated between May 2016 and August 2018. The clinical parameters were compared before and after the administration of the eradication therapy. Results: The mean age of the enrolled patients was 56.7 years, and the mean follow-up duration was 514.7 days. Weight, body mass index, and obesity index were significantly increased post-eradication therapy compared to those pre-eradication therapy. White blood cell and platelet counts were significantly decreased, and high density lipoprotein cholesterol (HDL) level was significantly increased (P = 0.001), while low density lipoprotein cholesterol (LDL), total cholesterol, and triglycerides levels were not altered significantly. Hence, the LDL/HDL ratio was significantly decreased. Conclusions: This study reported that H. pylori eradication therapy increase the HDL levels in the infected patients with chronic gastritis. Hence, the LDL/HDL ratio, which is used to evaluate the risk of atherosclerosis, was significantly decreased post-eradication therapy compared to that pre-eradication therapy. [ABSTRACT FROM AUTHOR]

Background: Relative blood volume (RBV) changes during hemodialysis (HD) are typically estimated based on online measurements of hematocrit, hemoglobin or total blood protein. The aim of this study was to assess changes in the above parameters during HD in order to compare the potential differences in the RBV changes estimated by individual methods. Methods: 25 anuric maintenance HD patients were monitored during a 1-week conventional HD treatment. Blood samples were collected from the arterial dialysis blood line at the beginning and at the end of each HD session. The analysis of blood samples was performed using the hematology analyzer Advia 2120 and clinical chemistry analyzer Advia 1800 (Siemens Healthcare). Results: During the analyzed 30 HD sessions with ultrafiltration in the range 0.7–4.0 L (2.5 ± 0.8 L) hematocrit (HCT) increased by 9.1 ± 7.0% (mean ± SD), hemoglobin (HGB) increased by 10.6 ± 6.3%, total plasma protein (TPP) increased by 15.6 ± 9.5%, total blood protein (TBP) increased by 10.4 ± 5.8%, red blood cell count (RBC) increased by 10.8 ± 7.1%, while mean corpuscular red cell volume (MCV) decreased by 1.5 ± 1.1% (all changes statistically significant, p < 0.001). HGB increased on average by 1.5% more than HCT (p < 0.001). The difference between HGB and TBP increase was insignificant (p = 0.16). Conclusions: Tracking HGB or TBP can be treated as equivalent for the purpose of estimating RBV changes during HD. Due to the reduction of MCV, the HCT-based estimate of RBV changes may underestimate the actual blood volume changes. [ABSTRACT FROM AUTHOR]

Aberrant DNA methylation patterns are common in cancers and environmental pollutant exposed subjects. Up to date, few studies have examined the aberrant DNA methylation patterns in benzene exposed workers. We recruited 141 benzene-exposed workers, including 83 benzene-exposed workers from a shoe factory in Wenzhou and 58 workers from a painting workshop in Wuhu, 35 workers in Wuhu were followed from 2009 to 2013, and 48 indoor workers as controls from Wenzhou. We used high-resolution melting (HRM) to quantitate human samples of DNA methylation in long interspersed nuclear element-1 (LINE-1), (6)-methylguanine-DNA methyltransferase (MGMT), and DNA mismatch repair gene human mutator L homologue 1 (hMLH1). AML-5 cells were treated with benzoquinone (BQ) and hydroquinone (HQ), and the promoter methylation of MGMT and hMLH1 was detected using the bisulfite sequencing PCR method. The degree of LINE-1 methylation in benzene-exposed workers was significantly lower than that of the controls (p<0.001), and the degree of MGMT (p<0.001) and hMLH1 (p = 0.01) methylation was significantly higher than that of the controls. The in vitro study validated the aberrant hypermethylation of hMLH1 after treatment with BQ. Among the cohort workers who were followed from 2009 to 2013, the LINE1 methylation elevated in 2013 than 2009 (p = 0.004), and premotor methylation in hMLH1 reduced in 2013 than 2009 (p = 0.045) with the reduction of the benzene exposure. This study provides evidence that benzene exposure can induce LINE-1 hypomethylation and DNA repair gene hypermethylation. [ABSTRACT FROM AUTHOR]

Objectives: To identify blood cell markers that predict the long-term outcomes of patients with colorectal cancer. Methods: Data from 892 stage II and III colorectal cancer patients who underwent R0 resection were included. We analyzed the correlations of the preoperative blood data, previously reported prognostic indices, and clinicopathologic factors with the long-term outcomes, such as relapse-free survival and overall survival, using univariate and multivariate analyses. Results: Multivariate analysis showed that tumor location, stage, mean corpuscular volume, neutrophil-to-lymphocyte ratio, and lymphocyte-to- monocyte ratio were significantly correlated with relapse-free survival. A mean corpuscular volume ≥80.5 fL, neutrophil-to-lymphocyte ratio ≥5.5, and lymphocyte-to- monocyte ratio <3.4 had hazard ratios for disease relapse between 1.39 and 1.93. The cumulative scores of these three factors were aggregated into a laboratory prognostic score, with a maximum score at 6. The relapse-free survival and overall survival were well stratified by a laboratory prognostic score between 0–3 and 4–6, respectively, independent of the stage. Conclusion: The mean corpuscular volume, neutrophil-to-lymphocyte ratio, and lymphocyte-to- monocyte ratio can serve as blood cell markers to predict the long-term outcomes of patients who underwent R0 resection for stage II/III colorectal cancer. [ABSTRACT FROM AUTHOR]

Background: Anemia is one of the common complications of pregnancy. Hemoglobin concentration, Hematocrit, and Red cell count are laboratory tests used to diagnose anemia. In are source poor setting, there is a practice of using three-fold converted Hematocrit. This study is designed to assess the association and acceptability of three-fold converted Hematocrit as compared to the standard Micro-hematocrit method, in pregnant women. Method: The cross-sectional study conducted from May 18 to June 12, 2018 involved 200 pregnant women who visited the Laboratory for a Hematocrit test. Three milliliter of venous blood was collected with EDTA tube to determine Hematocrit by the Micro-hematocrit method and Hemoglobin concentration measured by a HemoCue Hemoglobin B analyzer. A scatter plot, correlation coefficient, Bland and Altman plot, and Area under curve were employed to assess the agreement and acceptability of the calculated Hematocrit as compared to the standard Micro-hematocrit. Result: The correlation coefficient, Intraclass correlation coefficient and concordance correlation coefficient were 0.91, 0.94, and 0.89, respectively. The Bland and Altman plot showed a mean difference of 0.94 with the limit of agreement ranges from 0.6 to 1.3. The area under the receiver operating characteristics with cut-off point of Hematocrit <33% was 0.86. The sensitivity and specificity of the calculated method was 95.5% and 71.4%, respectively. Conclusion: Generally there is excellent association between the two methods. The two methods were identical within inherent imprecision of both methods. Hence, the Hematocrit value, threefold calculated from the Hemoglobin was found to be acceptable to diagnose anemia in pregnant women. [ABSTRACT FROM AUTHOR]

Background/Aim: No-reflow is a serious and frequent event during primary percutaneous coronary intervention (PPCI) for acute ST segment elevation myocardial infarction (STEMI). The aim of this study was to identify possible predictors for no-reflow. Patients and methods: We investigated 218 patients with acute anterior STEMI who underwent PPCI from December 2016 to December 2018. No-reflow was defined as a coronary TIMI flow grade of ≤ 2. TIMI flow grade 3 was defined as normal reflow. Results: In our study, the no-reflow phenomenon was observed in 39 patients (18%) during angiography. The patients of no-reflow group were found to be more older, diabetics, longer pain-to-balloon time, lower blood pressure, higher platelet counts and higher levels of D-Dimer and Cystatin C (Cys-C). In multivariate logistic regression analysis, only diabetes (OR = 0.371, 95% CI: 0.157–0.872, P = 0.023), longer pain-to-balloon time (OR = 1.147, 95% CI: 1.015–1.297, P = 0.028) and higher Cys-C level (OR = 10.07, 95% CI: 2.340–43.377, P = 0.002) were predictors for no-reflow. Conclusion: Cys-C might be a useful predictor for the no-reflow phenomenon after PPCI in STEMI patients. It might help to screen STEMI patients with high risk of no-reflow on admission. [ABSTRACT FROM AUTHOR]

Background: The mechanism by which Ethiopians adapt to altitude is quite unique compared to other Highlanders with respect to increased oxygen saturation of hemoglobin. Although the effects of altitude on cardiorespiratory and hematological quantities on athletics performances are well known, but there is little information about its underlying effect on chronotype orientations. Methods: In this cross-sectional study 60 male college students with mean age 20±1.3 years from high and low altitude regions living in a tropical setting in Ethiopia were included. The participants’ chronotype was determined using the self-administered Horne and Ostberg Morningness-Eveningness Questionnaires (MEQ). Measurements and estimations of hematological and cardiorespiratory parameters were performed from 7:00–9:00 AM, East African time zone, in order to minimize any variations that might occur in the course of the day. A multivariate binary logistic regression model was fitted to analyze the underlying chronotype predictors. Results: 28 (93.9%) of participants from high altitude were mainly intermediate type (I-type) dominant with (MEQ = 42–58). While, 16 (55.2%) of participants from low altitudes were morning type (M-type) dominant chronotype with (MEQ = 59–69). Our main finding confirmed that altitude is an independent predictor of chronotype orientations of the participants (p<0.015). Thus, the results of the multivariate analysis seem to indicate that, participants from low and high altitudes may be uniquely oriented towards either M-type or I-type chronotype respectively (adjusted odds ratio [AOR] 4.772, 95% CI = 3.748–4618458). However, no significant difference on cardiorespiratory and hematological quantities between I-type and M-type chronotype of students from low altitude living in the same setting was reported (p > 0.05). Conclusion: Our finding, reported for the first time that, the human chronotype varies according to the altitude, with no underlying effect of cardiorespiratory and hematological quantities. [ABSTRACT FROM AUTHOR]

This study investigated the effects of hydroxyurea (HU) on hematological, biochemical and inflammatory parameters in children with sickle cell anemia (SCA) in association with βS haplotype and α-thalassemia. We included 22 children with SCA who were followed for an average of 14.5 months. Laboratory parameters were assessed by electronic methods, and molecular analysis was investigated by PCR-RFLP and allele-specific PCR. Results showed significant increases in hemoglobin, HbF, hematocrit, MCV, MCH, glucose, HDL-C and albumin levels, as well as significant decreases in MCHC and AST levels, WBC, neutrophils, eosinophils, lymphocytes and reticulocytes, in children during HU therapy. HbF levels were positively correlated with hemoglobin, hematocrit, MCV and total protein, yet negatively correlated with MCHC, RDW, AAT and AST during HU therapy (p<0.05). Children who carried the Central African Republic haplotype, in response to HU therapy, presented significant increases in hemoglobin, hematocrit, triglycerides and uric acid levels, as well as significant decreases in MCHC, AST and direct bilirubin levels, WBC, neutrophils, eosinophils, lymphocytes and reticulocytes. Those with the Benin haplotype presented increases in HbF and albumin levels, and a reduction in platelet counts (p<0.05). Children with α-thalassemia presented decreased ALT during HU use, while those without this deletion presented increases in hemoglobin, hematocrit, MCV, MCH, HDL-C and albumin, as well as decreases in MCHC, neutrophils, lymphocytes, reticulocytes and AST (p<0.05). Hence, regardless of its use in association with βS haplotypes or α-thalassemia, HU seems to be linked to alterations in hemolytic, inflammatory, hepatic, lipid and glycemic profiles. [ABSTRACT FROM AUTHOR]

Background: Factors associated with hospital mortality are unclear in patients with acute exacerbation of COPD (AECOPD) requiring intensive care unit (ICU) admission. We aimed to characterize these patients and identify factors associated with hospital mortality. Patients and methods: We used a retrospective observational case-control design and recruited patients between January 2015 and March 2017. Of 146 patients enrolled, 24 (16.4%) died during their hospital stay, while 122 survived. Results: Multivariate logistic regression analyses revealed factors associated with hospital mortality: age (adjusted odds ratio [AOR] 1.12, 95% CI: 1.03–1.23), C-reactive protein (CRP) level >7.5 mg/dL at the emergency room (AOR 4.52, 95% CI: 1.27–16.04), peak eosinophil-to-neutrophil ratio (ENR)×102 on days 8–14 of treatment (AOR 0.22, 95% CI: 0.08–0.63), and in-hospital complications (AOR 4.23, 95% CI: 1.12–15.98) (all P<0.05). After receiver operating characteristic curve analyses, cutoff level for peak ENR×102 was 0.224. To examine the synergistic effects of CRP level and peak ENR, we divided patients into four groups: (G0, reference group) Peak ENR×102 >0.224 on days 8–14 and initial CRP <7.5 mg/dL; (G1) Peak ENR×102 >0.224 on days 8–14 and initial CRP >7.5 mg/dL; (G2) Peak ENR×102 <0.224 on days 8–14 and initial CRP <7.5 mg/dL; and (G3) Peak ENR×102 <0.224 on days 8–14 and initial CRP >7.5 mg/dL. For G2 and G3 patients, the AOR of mortality was significantly different from that of the reference group (G2: AOR 10.00, P = 0.020; G3: AOR 61.79, P<0.001). The relationship between 28-day mortality and the four groups was statistically significant (log-rank test, P<0.001). Conclusion: Older age, initial CRP >7.5 mg/dL, peak ENR on days 8–14, and in-hospital complications were associated with hospital mortality in patients with AECOPD requiring ICU admission. Patients with both biomarkers, initial CRP >7.5 mg/dL, and peak ENR×102 <0.224 on days 8–14 of treatment, had an increased risk of hospital mortality. [ABSTRACT FROM AUTHOR]

We investigate the personalisation and prediction accuracy of mathematical models for white blood cell (WBC) count dynamics during consolidation treatment using intermediate or high-dose cytarabine (Ara-C) in acute myeloid leukaemia (AML). Ara-C is the clinically most relevant cytotoxic agent for AML treatment. We extend a mathematical model of myelosuppression and a pharmacokinetic model of Ara-C with different hypotheses of Ara-C’s pharmacodynamic effects. We cross-validate the 12 model variations using dense WBC count measurements from 23 AML patients. Surprisingly, the prediction accuracy remains satisfactory in each of the models despite different modelling hypotheses. Therefore, we compare average clinical and calculated WBC recovery times for different Ara-C schedules as a successful methodology for model discrimination. As a result, a new hypothesis of a secondary pharmacodynamic effect on the proliferation rate seems plausible. Furthermore, we demonstrate the impact of treatment timing on subsequent nadir values based on personalised predictions as a possibility for influencing/controlling myelosuppression. [ABSTRACT FROM AUTHOR]

Steroid-resistant GvHD is one of the most significant causes of mortality following allogeneic Hematopoietic Stem Cell Transplantation (HSCT). Treatment with mesenchymal stromal cells (MSC) seems to be a promising solution, however the results from clinical studies are still equivocal. Better selection of candidate patients and improving monitoring of patients following MSC administration can increase treatment effectiveness. In order to determine which characteristics can be used to predict a good response and better monitoring of patients, blood samples were taken prior to therapy, one week and one month after therapy, from 26 allogeneic HSCT patients whom contracted GvHD and were treated with MSCs. Samples were examined for differential blood counts, bilirubin levels and cell surface markers. Serum cytokine levels were also measured. We found that the level of lymphocytes, in particular T and NK cells, may predict a good response to therapy. A better response was observed among patients who expressed low levels of IL-6 and IL-22, Th17 related cytokines, prior to therapy. Patients with high levels of bilirubin prior to therapy showed a poorer response. The results of this study may facilitate early prediction of success or failure of the treatment, and subsequently, will improve selection of patients for MSC therapy. [ABSTRACT FROM AUTHOR]

Background: Hepatitis E virus (HEV) has commonly been associated with large waterborne outbreaks of human jaundice in endemic areas but it has been increasingly recognised as a cause of sporadic human cases of jaundice in non-endemic areas, in individuals with no history of travel. Zoonotic exposure is widely hypothesized to be an important potential transmission route in these sporadic human cases. Serosurveys conducted to determine the frequency of HEV human exposure report wide ranges in prevalence across studies and locations. Our study objective was to compute meta-analysis summary estimates of human seroprevalence of HEV IgG within countries considered HEV non-endemic, where possible, and to determine whether this varied significantly across these countries, as well as investigating the role of potential HEV seroprevalence predictors such as population age structure. Materials and methods: A broad literature search was conducted in six electronic databases. Citations were appraised, and relevant data extracted using forms designed and pre-tested a priori. Meta-analysis and meta-regression were conducted in R, with HEV IgG seroprevalence in blood donors or the general population being the outcome of interest, and country, assay, population age and sex structure, and chronological time investigated as predictors of the outcome. Results: From 4163 unique citations initially captured, data were extracted from 135 studies investigating HEV serology in blood donors or the general population, of 31 countries among those categorised as ‘very high human development’ by the United Nations. Country of sampling and assay employed were consistently significant predictors of HEV IgG seroprevalence with chronological time being a non-significant predictor in the dataset of captured studies. Conclusions: While country of sampling and assay employed were significant predictors of HEV seroprevalence, comparison of HEV seroprevalence across non-endemic countries is hampered by the lack of a gold standard assay and uncertainty regarding residual bias across studies, as well as regional differences within some countries. [ABSTRACT FROM AUTHOR]

We sought to identify peripheral blood markers associated with two immune-related factors—programmed cell death-ligand-2 (PD-L2) and indoleamine 2,3-dioxygenase-1 (IDO1)—that are expressed on tumor cells in primary lung adenocarcinoma (AD) specimens. We randomly selected 448 patients (70%) from 640 consecutive patients with resected stage I–III primary lung AD, who had been treated at that point with surgery alone. Expression of PD-L2 and IDO1 in these patients was assessed by immunohistochemistry, and evaluated with respect to peripheral blood markers measured before surgery, including white blood cells, absolute neutrophil count, absolute lymphocyte count, absolute monocyte count (AMC), absolute eosinophil count (AEC), serum C-reactive protein, and serum lactate dehydrogenase levels. Membrane PD-L2 expression and cytoplasmic IDO1 expression were defined by tumor proportion score (TPS); samples with TPS < 1% were considered negative. Logistic regression models were used to identify variables associated with the immune-related factors. Advanced stage (P = 0.0090), higher AMC (P = 0.0195), and higher AEC (P = 0.0015) were independent predictors of IDO1 expression. PD-L2 expression was not associated with any tested peripheral blood markers. Peripheral blood markers, especially AMC and AEC, could potential predict IDO1 expression in lung AD. This study should be replicated in another cohort; further efforts to explore other biomarkers that predict PD-L2 or IDO1 expression are also warranted. [ABSTRACT FROM AUTHOR]

Objective: The aim of this study is to evaluate the performance of different platelet counting methods (optical, impedance, fluorescence and hand counting) applied in different analysers by comparing with the international flow cytometric reference method (IRM). Methods: A total of 333 blood samples from different subgroups (168 cases with thrombocytopenia, 136 cases with normal platelet counts and 29 cases with thrombocytosis) were tested. Regarding IRM as the gold standard, we compared the accuracy and precision of different platelet count methods; i.e. LH780 (impedance), BC-6000 Plus (optical (O) and impedance (I)), Sysmex XN-9000 (optical (O), impedance (I), fluorescence (F)), and hand counting. Results: Sysmex XN-9000-F (r = 0.988) had the best correlation with IRM for thrombocytopenic samples; BC-6000 Plus-I (r = 0.966) was more relevant to IRM than any other method for samples with normal platelet counts. Correlation between Sysmex XN-9000-I (r = 0.960) and IRM was the highest among these methods for samples with thrombocytosis. For bias evaluation, the average bias of Sysmex XN-9000-F was -1.5 × 109/L (95% LA = -9.4 to +6.4) for samples with thrombocytopenia, compared with IRM. BC-6000 Plus-I had a small mean difference with IRM for samples with normal platelet counts or thrombocytosis. Moreover, all evaluated methods had acceptable sensitivity, specificity, and concordance rates as compared with IRM in the diagnosis of thrombocytopenia and thrombocytosis. Conclusions: Platelet counting by Sysmex XN-9000-F is more accurate than other methods for thrombocytopenic samples. BC-6000 Plus-I has superior association and consistency for normal platelet counts. As for thrombocytosis patients, Sysmex XN-9000-I has the highest correlation with IRM while Sysmex XN-9000-O has the highest diagnosis efficacy. [ABSTRACT FROM AUTHOR]

Phospholipids, major constituents of bilayer cell membranes, are present in large amounts in pulmonary surfactant and play key roles in cell signaling. Here, we aim at finding clinically useful disease markers in community-acquired pneumonia (CAP) using comprehensive phospholipid profiling in blood and modeling of changes between sampling time points. Serum samples from 33 patients hospitalized with CAP were collected at admission, three hours after the start of intravenous antibiotics, Day 1 (at 12–24 h), Day 2 (at 36–48 h), and several weeks after recovery. A profile of 75 phospholipid species including quantification of the bioactive lysophosphatidylcholines (LPCs) was determined using liquid chromatography coupled to time-of-flight mass spectrometry. To control for possible enzymatic degradation of LPCs, serum autotaxin levels were examined. Twenty-two of the 33 patients with a clinical diagnosis of CAP received a laboratory-verified CAP diagnosis by microbial culture or microbial DNA detection by qPCR. All major phospholipid species, especially the LPCs, were pronouncedly decreased in the acute stage of illness. Total and individual LPC concentrations increased shortly after the initiation of antibiotic treatment, concentrations were at their lowest 3h after the initiation, and increased after Day 1. The total LPC concentration increased by a change ratio of 1.6–1.7 between acute illness and Day 2, and by a ratio of 3.7 between acute illness and full disease resolution. Autotaxin levels were low in acute illness and showed little changes over time, contradicting a hypothesis of enzymatic degradation causing the low levels of LPCs. In this sample of patients with CAP, the results demonstrate that LPC concentration changes in serum of patients with CAP closely mirrored the early transition from acute illness to recovery after the initiation of antibiotics. LPCs should be further explored as potential disease stage biomarkers in CAP and for their potential physiological role during recovery. [ABSTRACT FROM AUTHOR]

Many parameters treated as constants in traditional physiologically based pharmacokinetic models must be formulated as time-varying quantities when modeling pregnancy and gestation due to the dramatic physiological and anatomical changes that occur during this period. While several collections of empirical models for such parameters have been published, each has shortcomings. We sought to create a repository of empirical models for tissue volumes, blood flow rates, and other quantities that undergo substantial changes in a human mother and her fetus during the time between conception and birth, and to address deficiencies with similar, previously published repositories. We used maximum likelihood estimation to calibrate various models for the time-varying quantities of interest, and then used the Akaike information criterion to select an optimal model for each quantity. For quantities of interest for which time-course data were not available, we constructed composite models using percentages and/or models describing related quantities. In this way, we developed a comprehensive collection of formulae describing parameters essential for constructing a PBPK model of a human mother and her fetus throughout the approximately 40 weeks of pregnancy and gestation. We included models describing blood flow rates through various fetal blood routes that have no counterparts in adults. Our repository of mathematical models for anatomical and physiological quantities of interest provides a basis for PBPK models of human pregnancy and gestation, and as such, it can ultimately be used to support decision-making with respect to optimal pharmacological dosing and risk assessment for pregnant women and their developing fetuses. The views expressed in this article are those of the authors and do not necessarily represent the views or policies of the U.S. Environmental Protection Agency. [ABSTRACT FROM AUTHOR]

Introduction: The early identification of patients at risk of severe dengue infection (DI) is critical to guide clinical management. There is currently no validated laboratory test which can predict severe complications of DI. The Atypical lymphocyte count (ALC) is a research parameter generated at no extra cost when an automated Full Blood Count (FBC) is performed. The purpose of this study was to assess the association of ALC with the severity of DI. Methods: We prospectively collected data on patients admitted to Nawaloka Hospital Sri Lanka (NH) with DI between December 2016 and November 2017. DI was diagnosed based on a positive Non-structural antigen 1 (NS1) or dengue IgM antibody. ALC (absolute ALC and percentage) data were extracted from the Sysmex XS500i automated full blood count (FBC) analyzer (Sysmex Corporation Kobe, Japan). Clinical data was recorded from medical records and the computerized data base maintained by NH. Results: 530 patients were enrolled. Patients with clinical manifestations of severe dengue have a significantly higher AL % compared to dengue without warning signs. Patients who presented with respiratory compromise had statistically significantly higher AL% compared to those without. (AL%; 8.65±12.09 vs 2.17±4.25 [p = 0.01]). Similarly, patients who developed hypotension had higher AL% compared to those who did not suffered from shock (AL%; 8.40±1.26 vs 2.18±4.25 [p = 0.001]). The AL% of dengue patients presenting with bleeding, at 4.07%, is also higher than those without bleeding complications, at 2.15%. There was a significant negative association between platelet count and AL% (p = 0.04). Conclusions: Clinical manifestations of severe dengue have a significantly higher AL % compared to dengue without warning signs. AL % at presentation may be predictive of severe DI and future larger prospective longitudinal studies should be done to determine if AL % on admission is predictive of the complications of DI. [ABSTRACT FROM AUTHOR]

Background: The standard treatment of acute ischemic stroke patients is thrombolytic therapy within 60 minutes of a patient’s arrival in stroke center hospitals. Based on the policy of the Lampang Referral System Committee, blood samples of suspected stroke patients need to be collected before transfer to the stroke center (Lampang Hospital). It was still questionable as to whether these blood samples are valid for clinical use and the present study aimed to confirm or deny their validity. Methods: A diagnostic study was conducted from June 2015 to May 2016. After exclusion, 340 patients were deemed eligible for analysis. Blood samples were collected just before normal saline infusion at referring hospitals and stored in blood collecting tube boxes set during transportation. At the stroke center, informed consents was requested, blood samples were re-collected to serve as a ‘gold standard’. Prothrombin time (PT), international normalized ratio (INR), activated partial thromboplastin time (aPTT), platelet count, hemoglobin (Hb), hematocrit (Hct), blood urea nitrogen (BUN), and creatinine (Cr) were compared using paired t-tests. Binary regression was used to analyze for accuracy (%) to adjust for extraneous influences and was presented by modified Bland-Altman plots. Results: The laboratory results of referring hospitals vs. the stroke center were: PT, 12.4±3.2 vs. 12.5±3.0 sec; INR: 1.0±0.3 vs. 1.0±0.3; and platelet count: 239.8±77.1 vs. 239.8±74.8 (x103/μL). The adjusted accuracy of the PT, INR, and platelet counts were 96.8%, 96.8%, and 95.3% respectively. Conclusion: Laboratory tests from referring hospital were determined to be valid. Blood samples should thus be collected at referring hospitals in order to avoid unnecessary blood collection at the stroke center. [ABSTRACT FROM AUTHOR]

Background: Haematological reference values are necessary for accurate diagnosis of diseases, clinical decision-making, treatment monitoring and clinical research. Due to unavailability of pan-Nigerian reference values, local results interpretation is based on the use of Western values. Objective: This study aims to establish national reference values for some haematological parameters in apparently healthy young adult Nigerians. Methods: Seven Thousand, Seven Hundred and Ninety-Seven (7,797) volunteers aged 18 to 26 years participated in the study. Participants’ interviewer-administered questionnaires and blood samples were collected, analyzed and those with confounding factors (HIV infection, Hepatitis B sero-positivity, Malaria and Pregnancy) were excluded from statistical analysis. The 95-percentile reference range was determined for each haematological parameter using SPSS Version 16®. The result obtained was reviewed with reference to already established reference values in two West African and Western countries. Results: Blood specimens from 6153 (78.9%) participants [comprising 5915 (96.1%) males and 238 (3.9%) females] were analyzed after exclusion of 1,644 (21.1%) participants with confounding variables. Reference ranges among males and females varied and these were consistent with findings from two other West African countries. The median platelets count in this study was 218 x 109/l while commonly used Western value is 280 x 109/l. Other haematological parameters in the study were similar to Western values. Conclusion: The findings of this study will improve clinical and research decision-making. Considering that this study is limited to young adult participants, there is a need to conduct future pan-Nigerian studies that will include all age groups. [ABSTRACT FROM AUTHOR]

Objective: To determine pattern of basic hematological parameters in leukemias, thus highlighting their diagnostic significance. Material and method: This cross sectional descriptive study was done in Khyber Teaching Hospital, from January 2015 to July 2017. Cases of acute and chronic leukemias were included in the study by Non probability purposive sampling technique. Patients whose aspirates were inadequate were excluded from the study. Complete blood counts were done by Sysmex analyzer. CBC findings were recorded and results were drawn. Mean and standard deviation were used for quantitative data, while frequency and percentages were used for qualitative data. Results: Out of 117 cases of Leukemia, 8 cases were excluded due to inadequacy of their aspirate sample. Remaining 109 cases were included in the study. Mean age of study sample was 49 ± 19 years. Changes in blood counts were as increased TLC (in 52%, 66.6%, 87.5%, and 66.6% cases of ALL, AML,CML and CLL respectively), and low hemoglobin level (in 82%, 97.4%, 87.5%, and 100% cases of ALL, AML, CML and CLL). The platelet count was low (in 88%, 92.3%, and 58% cases of ALL, AML and CLL), but high in CML (in 62.5% cases). Conclusion: Anemia, raised white cell count and thrombocytopenia is characteristic in all leukemias, except chronic myeloid leukemia where platelet count is raised. Careful study of these parameters give idea about underlying leukemia. [ABSTRACT FROM AUTHOR]

Objectives: Imatinib has shown to be highly efficacious in the treatment of chronic myeloid leukemia (CML) but continuous dosing and patient adherence is essential treatment success. The study aimed to assess prevalence and reasons for non-adherence to Imatinib in newly diagnosed patients with CML in the first 3-months of treatment. Methods: The study was conducted from October 1, 2016 to November 30, 2017 at Tikur Anbessa Specialized Hospital, Addis Ababa, Ethiopia. A total of 147 newly diagnosed patients were followed and their adherence status was determined using the 8-items Morisky Medication Adherence Scale and reasons for their non-adherence were evaluated using semi-structured questionnaire. Descriptive statistics were used to summarize the data while multivariable logistic regression was employed to explore associations among variables of interest. Results: Participants’ median age at time of confirmed diagnosis was 36 years; with most of them in the age group of <40 years (64.6%). Males comprised 59.2%. Adherence rate was found to be 55.1%. Those who lived in rural area, had low income, adverse drug events and comorbidity were significantly associated with treatment non-adherence. Most (68.4%) patients missed their medication due to adverse drug events. Three patients were lost-to-follow-up. Among 144 patients who finished the 3-month follow-up, 91.7% of them achieved complete hematologic remission. Morisky high adherent (AOR = 8.6, 95%CI:4.32–11.1) was positively associated with complete hematologic remission. Conclusions: Overall treatment adherence is suboptimal. Thus, efforts should be made to improve adherence and further study is required to explore impact adherence on the cytogenetic and molecular responses of Ethiopian patients with CML. [ABSTRACT FROM AUTHOR]

Extracorporeal photopheresis (ECP) is an autologous immunomodulatory cell therapy that consists of the ex vivo collection of mononuclear cells (MNCs), which are irradiated with UVA in the presence of the photosensitizing agent 8-methoxypsoralen (8-MOP) to induce cell apoptosis. This photoactivated cell preparation is then reinfused into the patient. While the clinical benefits of ECP are well-demonstrated, no study has yet characterized the influence of variations in the composition of the cell preparation on the efficacy of ECP in vitro. Here, we describe a standardized methodology for the in vitro assessment of ECP that uses the human lymphoma T-cell line and mimics the clinical procedure. By quantifying cell apoptosis, inhibition of cell proliferation, and 8-MOP consumption, we used this approach to characterize the specific influence of key variables on the cellular response to ECP. We found that (i) increases in hematocrit and plasma concentrations attenuated the cellular response to ECP; (ii) plasma concentration was the only variable tested that influenced 8-MOP consumption; and (iii) the loss of efficacy due to variations in the concentration of certain blood components could be counteracted by modulating the UVA dose. This methodology may enable evaluation of other leukapheresis preparation protocols and better determination of the optimal working parameters for ECP. [ABSTRACT FROM AUTHOR]

Background: Early diagnosis and treatment has proven to be of utmost importance in the outcome of sepsis patients. We compared the accuracy of the neutrophil-lymphocyte count ratio (NLCR) to conventional inflammatory markers in patients admitted to the Intensive Care Unit (ICU). Methods: We performed a retrospective cohort study consisting of 276 ICU patients with sepsis and 388 ICU patients without sepsis. We compared the NLCR as well as C-reactive protein (CRP) level, procalcitonin (PCT) level, white blood cell (WBC) count, neutrophil count and lymphocyte count on ICU admission between sepsis and non-sepsis ICU patients. To evaluate the sensitivity and specificity, we constructed receiver operating characteristics (ROC) curves. Results: Significant differences in NLCR values were observed between sepsis and non-sepsis patients (15.3 [10.8–38.2] (median [interquartile range] vs. 9.3 [6.2–14.5]; P<0.001), as well as for CRP level, PCT level and lymphocyte count. The area under the ROC curve (AUROC) of the NLCR was 0.66 (95%CI = 0.62–0.71). AUROC was significantly higher for CRP and PCT level with AUROC’s of 0.89 (95%CI 0.87–0.92) and 0.88 (95%CI 0.86–0.91) respectively. Conclusions: The NLCR is less suitable than conventional inflammatory markers CRP and PCT to detect the presence of sepsis in ICU patients. Trial registration: ClinicalTrials.gov . [ABSTRACT FROM AUTHOR]

Introduction: In Ghana, initiation of Antiretroviral Therapy (ART) is recommended for all patients with an HIV diagnosis, regardless of CD4+ T-cell count. However, measurement of CD4 count remains an important metric for identifying patients with advanced HIV disease, and assessing a person’s overall immune status, which informs the decision to offer opportunistic infection screening and prophylaxis. Access to CD4+ T cell count in rural health facilities remains a major challenge in Ghana and other resource-limited settings. This study aimed to validate the accuracy of the BD FACSPresto near-patient device for measurement of CD4 count and hemoglobin concentration against the FACSCount (CD4) and Sysmex (hemoglobin) diagnostic machines when operated in both a district hospital and rural laboratory, serving a network of health posts in Ashanti Region, Ghana. Methodology: In the first phase of the study, patients were recruited from a district hospital, and both venous and capillary blood samples were tested using the FACSCount and Sysmex as reference tests and compared to results of the FACSPresto performed in the clinic laboratory at the district hospital. In the second phase, patients were recruited from both the hospital and from rural health clinics, and samples were tested using the FACSPresto at a rural laboratory. Sensitivity and specificity among samples categorized into different clinically relevant CD4 count ranges were calculated, along with correlation between the Presto and the reference measurements, and mean and relative bias with limits of agreement. Results: The FACSPresto was successfully operated in both clinical settings. A total of 59 samples in the first phase and 48 samples in the second phase were included. Positive bias was observed when comparing CD4 count measured by BD FACSPresto to FACSCount in the district hospital (bias = 44, LOA -72,160) and in the rural laboratory setting (bias = 74, LOA -96, 244). In addition, capillary blood samples were shown to give higher measures when compared to venous blood samples from the same participant. All results were statistically significant (p<0.05) apart from hemoglobin measurement in venous blood in the rural laboratory. Correlation coefficients were high for CD4 count measures and lower for hemoglobin measures. Conclusion: Overall, the Presto gave higher estimates of CD4 count compared to FACSCount, and hemoglobin measurements were higher than from Sysmex. Samples of capillary blood in turn gave higher results for both measurements compared to venous blood, consistent with previous analyses. These findings should be considered when selecting CD4 count machines for use at the point of care, especially in remote areas where capillary blood sampling may be preferable, but are likely balanced by device’s ease of use, portability, and ability to expand access to services. These results are some of the first to demonstrate the accuracy of the FACSPresto in West Africa and show that this device can be successfully operated in a very rural lab setting and may therefore assist to provide CD4 count and hemoglobin concentration measurement to populations in need. [ABSTRACT FROM AUTHOR]

Background: Quantitative assessments of the severity of bleeding in patients with bleeds within the gastrointestinal tract (GIB) are generally limited to blood tests like the hematocrit. The varied and irregular nature of the data collected during such observations makes it difficult in retrospective data analysis to characterize the complete course of bleeding. We intend to quantify the rate of blood loss over the course of an ICU stay, facilitating more precise analysis of retrospective data, and to use this quantification to examine questions about the effects of GIB. Methods and findings: A population of 2,445 intensive care admissions across 2,266 patients with a diagnosis of GIB was studied. Using statistical techniques for smoothing data and accepted medical approaches for calculating blood loss, we are able to convert collections of individual laboratory readings that are difficult to understand into a simple, interpretable overview of the patient’s bleeding status over time. To demonstrate this method, we compare patients’ standard vital signs while bleeding heavily to times when they are not bleeding, finding a 3.0 ± 0.5% increase in heart rate, a 1.3 ± 0.4% decrease in systolic blood pressure and a 0.9 ± 0.5% decrease in diastolic blood pressure. After considering the effect of bleeding on standard vital signs, we demonstrate that patients with upper GIB have significantly elevated blood urea nitrogen levels while bleeding heavily, with a mean increase of 11.7 ± 7.2%, while patients with lower GIB do not, with a mean increase of 4.2 ± 6.6%. Conclusions: This study introduces a novel method of processing retrospective laboratory data to characterize the course of bleeds within the gastrointestinal tract. This method is used to examine the direct effects of bleeding on a patient and can be deployed in future studies of bleeding using retrospective data. [ABSTRACT FROM AUTHOR]