Linking between ambient pollution and metals concentration in blood. Nationwide study based on the national blood banking system.

This study was aimed to describe the chemical traces of air pollution in blood of residents and evaluate the association between ambient pollution and its dose absorbed internally by a human body. The national Magen David Adom Blood Services blood donation collection platform and the National Public Health Laboratory's testing services were utilized to conduct a human biomonitoring study among blood donors in Israel. The donors' residential addresses and donations sites' locations were geocoded and merged with the levels of pollutants recorded by the nearby monitoring stations. Pollutants included nitrogen dioxide (NO2), sulfate dioxide (SO2), ozone (O3), carbon monoxide (CO) and particulate matter of size <10 and 2.5 µm in diameter (PM10 & PM2.5). Metal concentrations were statistically analyzed by ratio t-test and a lognormal regression, and adjusted to age, gender and smoking (defined based on Cadmium values). The findings indicate an independent positive association between pollutants and metals' concentrations in blood. Specifically, an increase in interquartile range (IQR) of NO2 was associated with 9.5 % increase in As in blood. The increase in one IQR of PM10 and SO2 was associated with an increase in Pb, of 16.6 % and 12.4 %, respectively. SO2 was also adversely associated with Cd concentrations, by increasing its levels by 5.7 %. The donors' proximity to quarries was related to the Pb blood levels higher 1.47 times compared to donors without quarries close to their residence (p-value = 0.013). To conclude, ambient pollution levels are associated with internal metals' concentrations, reaffirming the link between the two in the pathological pathway from air pollution to morbidity.

National blood bank services as a platform for national human biomonitoring - A proof-of-concept study.

BACKGROUND: Human biomonitoring (HBM) is crucial for identifying potential risks to human health from exposure to environmental hazards. However, it is an expensive and labor-intensive endeavor. To save on samples' collection process we suggested using a national blood banking system as a platform for a national HBM program. For the case study, we used a comparison of blood donors from heavily industrialized Haifa Bay region, northern Israel, with donors from the rest of the country. METHODS: The study population comprised a random sample of blood donors donating blood all over Israel. Samples of whole blood were tested for arsenic (As), cadmium (Cd), chromium (Cr) and lead (Pb). Donors' donations sites and residential locations were geocoded. Smoking status was verified based on Cd levels, after calibrating their concentrations vs Cotinine in a sub-sample of 45 subjects. Metal concentrations were compared between regions using a lognormal regression, while controlling for age, gender, and predicted probability of smoking. RESULTS: During Mar 2020-Feb 2022, we collected 6230 and tested 911 samples. Concentrations of most of the metals were modified by age, gender, and smoking. Cr and Pb appeared to be 1.08-1.10 times higher among Haifa Bay residents than in the rest of the country (although with borderline significance of 0.069 for Cr). Cr and Pb were 1.13-1.15 times higher for those who donated blood in the Haifa Bay region, but not necessarily resided in the area. Donors from Haifa Bay had lower levels of As and Cd as compared to other donors in Israel. CONCLUSIONS: Using a national blood banking system for HBM proved to be feasible and efficient. Blood donors from Haifa Bay area were characterized by elevated levels of Cr and Pb and lower levels of As and Cd. An extensive investigation of industries in the area is warranted.

Cognitive and physical performance are well preserved following standard blood donation: A noninferiority, randomized clinical trial.

BACKGROUND: A walking blood bank (WBB) refers to the use of fellow combatants for battlefield blood donation. This requires pretesting combatants for infectious diseases and blood type. A fundamental prerequisite for this technique is that the donating soldier will suffer minimal physiological and mental impact. The purpose of the current study is to assess the effect of blood shedding on battlefield performance. METHODS: This is a double-blind randomized control trial. Forty Israel Defense Forces combatants volunteered for the study. Participants underwent baseline evaluation, including repeated measurement of vital signs, cognitive evaluation, physical evaluation, and a strenuous shooting test. Three weeks after the baseline evaluation, subjects were randomized to either blood donation or the control group. For blinding purposes, all subjects underwent venous catheterization for the duration of a blood donation. Repeated vital signs and function evaluation were then performed. RESULTS: Thirty-six patients were available for randomization. Baseline measurements were similar for both groups. Mean strenuous shooting score was 80.5 ± 9.5 for the control group and 82 ± 6.6 for the test group (p = 0.58). No clinically or statistically significant differences were found in tests designed to evaluate cognitive performance or physical functions. Vital signs taken multiple times were also similar between the test and control groups. CONCLUSIONS: Executive, cognitive, and physical functions were well preserved after blood donation. This study supports the hypothesis that a WBB does not decrease donor combat performance. The categorical prohibition of physical exercise following blood donation might need to be reconsidered in both military and civilian populations.

Human biologic monitoring based on blood donations to the National Blood Services.

BACKGROUND: The ambient exposure does not always reflect the internal levels of pollution absorbed in the body. While human biomonitoring (HBM) could provide a valid estimate of exposure extent, it is usually an expensive and a heavily manpowered enterprise. Using samples collected during blood donations for HMB may provide a more efficient platform for a routine biomonitoring. METHODS: The current study is aimed to explore the feasibility of using the national blood banking system for the purposes of HBM, to compare between residents of a suspected polluted area in northern Israel (Haifa Bay) to the rest of the country. Specifically, we will assemble a geographically representative sample of blood donors residing in the study area and of the general population, to test for four industry and traffic-related metals: lead (Pb), cadmium (Cd), arsenic (As) and chromium (Cr). Samples of whole blood from donors will be tested in the Laboratory of Public Health Services managed by the Ministry of Health. The information on donors' biomarkers levels will be further linked with the air pollution and meteorological data assessed at the location of the blood collection sites (short-term exposure) and donors' permanent address (long-term exposure), as recorded by the monitoring stations spread throughout Israel and the satellite-based exposure models. The association between biomarkers and ambient environmental exposures will be assessed. The samples' collection is planned for 2 years of 2020-2021. DISCUSSION: The information collected in this study could lead to environmental regulations within Haifa Bay area aimed to prevent exposure to high levels of hazardous chemicals.

[IS THERE STILL A PLACE TO USE ERYTHROCYTE SEDIMENTATION RATE IN THE 21ST CENTURY?]

INTRODUCTION: Erythrocyte sedimentation rate (ESR) is a simple test that is not without limitations but is still widely used. Dysfunction is used as a diagnostic test on the one hand and as a follow-up test on the other, where many physicians attribute normal results of this test to the absence of disease. Therefore, the question remains: Is there still room for continued ESR in the 21st century? And are there other tests with higher sensitivity and specificity that can replace the ESR? The purpose of the current review is to acquaint the reader with this test, its advantages and limitations, and to expand the scope of alternative tests and their effectiveness in comparison to ESR. It seems to us that the development of technology and research has strongly discouraged the use of ESR, but there are still quite a few instances where this test is still cost-effective. In most cases, especially during the diagnosis of life-threatening diseases, other tests are needed, or there is a need for a combination of the ESR with additional tests.

A cross-cultural perspective of medical clowning: comparison of its effectiveness in reducing pain and anxiety among hospitalized Bedouin and Jewish Israeli children.

PURPOSE: Medical clowning has proven effective for reducing pain, anxiety, and stress, however, its differential effects on children from different cultures have not yet been researched. This study evaluated the effects of medical-clowning intervention on anxiety and pain among Jewish and Bedouin children, and anxiety among their parents, in southern Israel. PATIENTS AND METHODS: The study was conducted in hospital pediatric departments and employed a pre-post design involving quantitative and qualitative methods. The study included 89 children whose ages ranged from 7.5 to 12 years (39 Jewish and 50 Bedouin) and 69 parents (19 Jewish and 50 Bedouin). Questionnaires assessing pain, anxiety, and demographics were used at the pre-intervention stage and pain, anxiety, and enjoyment of different aspects of the intervention were evaluated following the intervention. The intervention stage lasted for 8-10 minutes and included the use of word play, body language, and making faces, as well as the use of props brought by the clown. Semi-structured interviews were also conducted at the post-intervention stage. RESULTS: The intervention reduced pain and anxiety among both groups of children and reduced anxiety among both groups of parents. However, anxiety levels were reduced more significantly among Bedouin children. The nonverbal components of the clowns' humor were most central, but it was the verbal components that mediated the reduction in anxiety among the Bedouin children. CONCLUSION: This study underscored the effectiveness and importance of medical clowning in reducing pain and anxiety among children in different cultural contexts. Moreover, the issue of culturally appropriate humor was underscored and implications for intercultural clown training are discussed.

Neutropenia and eosinophilia among Ethiopian immigrants to Israel: Familial or environmental?

BACKGROUND: Due to trends of population movements, Israeli family physicians are treating increasing numbers of African immigrants from Ethiopia. These immigrants were found to have complete blood counts (CBC) that are different from other ethnic groups, with a higher prevalence of eosinophilia and neutropenia. OBJECTIVES: To evaluate haematological findings in an attempt to define whether they behave as familial (genetic) or environmental. METHODS: Retrospective chart review of 300 patients from a primary care clinic: 100 individuals of Ethiopian heritage born in Ethiopia (EE); 100 individuals of Ethiopian heritage born in Israel, whose parents were born in Ethiopia (EI), and a control group of 100 patients who were not of Ethiopian heritage (C). RESULTS: Absolute eosinophilia (greater than 500/dl) was found in 13% of the EE study group significantly higher than the two other groups (P < 0.05), with no difference between EI and C. neutropenia (defined as less than 1500/dl) was found in 32% of EE group, 20% of EI, and 1% of C (P < 0.01). CONCLUSION: On the one hand, findings point to a marked environmental influence on the eosinophilic response (most probably due to intestinal parasites present in immigrants from Ethiopia). On the other hand, a familial-genetic nature is probably the reason for the higher prevalence of neutropenia in this population, although some environmental influence may play a role. The knowledge of these findings may be useful for physicians treating people migrating from Africa.

A γ/δ T-cell receptor prolymphocytic leukemia and CD4-/CD8- double-negative immunophenotype in a pediatric patient.

T-cell prolymphocytic leukemia is a very rare neoplasm, peaking in the seventh decade. An extensive search failed to find any report of this malignancy in the pediatric population. The malignant cell is morphologically characterized by a high nucleocytopasmic ratio, condensed chromatin, a single nucleolus, and nongranular basophilic cytoplasm. Cells are usually positive for the α/ß and only rarely to the γ/δ T-cell receptors. Most patients follow an aggressive clinical course, only some respond to anti-CD52. We present a 6-year-old boy with T-cell prolymphocytic leukemia. The malignant cells expressed a postthymic immunophenotype (CD4/CD8) and positivity for the γ/δ T-cell receptors. The child died after 8 months despite aggressive chemotherapy, anti-CD52, and an allogeneic bone marrow transplant.

Clinical and laboratory parameter dynamics as markers of blood stream infections in pediatric oncology patients with fever and neutropenia.

BACKGROUND: Identifying markers associated with blood stream infection (BSI) in children with fever and neutropenia (FN) could lead to a substantial reduction in unnecessary treatment. STUDY OBJECTIVE: The aim of this study was to determine the association between clinical/laboratory parameters and BSI in pediatric oncology patients with FN. METHODS: This prospective study was conducted between 2007 and 2010 at the Pediatric oncology unit. Clinical and laboratory parameters were obtained from all hospitalized FN patients. Linear regression and trends were calculated to determine the association between clinical/laboratory parameters and BSI. RESULTS: Of the 195 FN episodes in 73 children, BSIs were identified in 38 (19%) episodes. Gram-positive bacteria, gram-negative bacteria, and fungi caused 47%, 43%, and 10% of all BSIs, respectively. Mean fever duration was longer in the BSI group (5 d) compared with the non-BSI group (2 d, P=0.01). Mean (±SD) monocyte count at admission was lower in the BSI group compared with the non-BSI group (0.06±0.1 vs. 0.14±0.33 cells/mm, respectively, P=0.05). Mean C-reactive protein (CRP) levels at hospitalization days 5 to 8 were higher in children with BSI (P<0.001). Increment trends of monocyte and platelet levels and decrement trend of CRP levels were noted in the BSI group but not in the non-BSI group (P<0.01 for all). CONCLUSIONS: Prolonged fever, lower monocyte count at admission, higher CRP levels between the fifth and the eighth hospitalization days, increment trends of monocyte and platelet levels, and CRP level decrement were associated with BSI. These factors may serve as markers for BSI in pediatric oncology patients with FN.

Unsupervised analysis of classical biomedical markers: robustness and medical relevance of patient clustering using bioinformatics tools.

MOTIVATION: It has been proposed that clustering clinical markers, such as blood test results, can be used to stratify patients. However, the robustness of clusters formed with this approach to data pre-processing and clustering algorithm choices has not been evaluated, nor has clustering reproducibility. Here, we made use of the NHANES survey to compare clusters generated with various combinations of pre-processing and clustering algorithms, and tested their reproducibility in two separate samples. METHOD: Values of 44 biomarkers and 19 health/life style traits were extracted from the National Health and Nutrition Examination Survey (NHANES). The 1999-2002 survey was used for training, while data from the 2003-2006 survey was tested as a validation set. Twelve combinations of pre-processing and clustering algorithms were applied to the training set. The quality of the resulting clusters was evaluated both by considering their properties and by comparative enrichment analysis. Cluster assignments were projected to the validation set (using an artificial neural network) and enrichment in health/life style traits in the resulting clusters was compared to the clusters generated from the original training set. RESULTS: The clusters obtained with different pre-processing and clustering combinations differed both in terms of cluster quality measures and in terms of reproducibility of enrichment with health/life style properties. Z-score normalization, for example, dramatically improved cluster quality and enrichments, as compared to unprocessed data, regardless of the clustering algorithm used. Clustering diabetes patients revealed a group of patients enriched with retinopathies. This could indicate that routine laboratory tests can be used to detect patients suffering from complications of diabetes, although other explanations for this observation should also be considered. CONCLUSIONS: Clustering according to classical clinical biomarkers is a robust process, which may help in patient stratification. However, optimization of the pre-processing and clustering process may be still required.

An osseous lesion in a 10-year-old boy with Hodgkin's lymphoma: a case report.

INTRODUCTION: Osseous involvement of Hodgkin's lymphoma is uncommon. When osteolytic lesions are seen on imaging it is important to evaluate potential other causes. CASE PRESENTATION: We report the case of a 10-year-old Caucasian boy who presented to our facility with a bony lesion of the right clavicle and enlarged cervical lymph nodes. A simultaneous biopsy of the lymph node and of the osteolytic process of his right proximal clavicle was performed and revealed two different kinds of lesions: a mixed cellularity Hodgkin's lymphoma and an osteochondroma. CONCLUSIONS: Since the latter is a common benign bone tumor, which should not interfere with the staging of the lymphoma, we emphasize the importance of ensuring that all efforts are made to acquire a diagnostic biopsy of all atypical lesions.

Normal hemoglobin at the age of 1 year does not protect infants from developing iron deficiency anemia in the second year of life.

BACKGROUND: Iron deficiency anemia (IDA) is the most common hematologic disorder worldwide. Measures to prevent IDA in infants have been successful with questionable sustainability. AIM: To evaluate the incidence of developing IDA in the second year of life, in infants who were nonanemic at the age of 1 year on routine blood test. METHODS: Blood samples were obtained from 193, 24-month-old toddlers, from 2 large clinics of both main sectors in Southern Israel, comparable for lower economic status. IDA was defined as hemoglobin < 11 gr% and microcytosis as mean corpuscular volume < 70 fL. RESULTS: IDA was detected in 8 of 118 Bedouins (5 males) and in 10 of 75 Jewish (6 males) infants (P < 0.01). The probability of a nonanemic child to develop IDA in the second year of life for the whole study population was 9.3% (18 of 193 infants) and significantly higher in the Jewish population (13.3.0% vs. 6.8%, P < 0.01). CONCLUSIONS: Given the difficulty of toddlers to maintain a non-IDA status, and the very low probability of iron overload, our results clearly support the need to continue iron supplementation into the second year.

Efficacy and safety of intravenous iron sucrose therapy in a group of children with iron deficiency anemia.

BACKGROUND: Iron deficiency is the most common single cause of anemia worldwide. Treatment consists of improved nutrition along with oral, intramuscular or intravenous iron administration. OBJECTIVES: To describe the efficacy and adverse effects of intravenous iron sucrose therapy in a group of children with iron deficiency anemia who did not respond to oral iron therapy. METHODS: We conducted a prospective investigation of 45 children, aged 11 months to 16 years, whose oral iron therapy had failed. The children attended the Pediatric Day Care Unit where they received intravenous iron sucrose infusion. RESULTS: Forty-four of the 45 patients were non-compliant. Nine had Helicobacter pylori gastritis and 16 patients suffered from intestinal malabsorption from different causes. Before treatment, the blood mean hemoglobin concentration was 7.43 g/dl (range 5-10.1 g/dl). Fourteen days after treatment it increased to 9.27 g/dl (SD 1.23) and 6 months later to 12.40 g/dl (SD 1.28). One patient demonstrated a severe side effect with temporary and reversible reduced blood pressure during treatment. CONCLUSIONS: These preliminary data suggest that administration of intravenous iron in pediatric patients is well tolerated and has a good clinical result, with minimal adverse reactions.

Flow cytometry and morphology analysis of bone marrow in a child with brucellosis and hematologic manifestations.

Constitutional symptoms and pancytopenia are occasionally the initial presentation of pediatric brucellosis. Therefore, in endemic areas, in children with pancytopenia, both brucellosis and malignancy should be included in the deferential diagnosis. We report here a child with pancytopenia and hepatosplenomegaly as manifestations of brucellosis in whom bone marrow morphology and flow cytometry data revealed hemophagocytosis, left shift in myeloid cells and activation changes in antigenic properties of T and B lymphocytes and monocytes. The patient had an uneventful and complete recovery after appropriate antibiotic therapy. Our report demonstrates that bone marrow and flow cytometry findings in children with brucellosis may include significant reactive changes in hematopoiesis.

The effects of guided written disclosure on psychological symptoms among parents of children with cancer.

This study examines whether structured writing about receiving a diagnosis and treatment for pediatric cancer reduces distress among highly distressed parents of children with cancer (PCWC). Eight PCWC completed measures of posttraumatic stress symptoms (PTSS) and depressive symptoms at two baselines, and again after writing, with 1-month gaps between assessments. Using a guided disclosure protocol (GDP), parents were asked to write about receiving the diagnosis first in a chronological manner, then to explicitly label their emotions at the time of diagnosis and explain the impact of the child's illness on their life. Finally, they were asked to reflect on current feelings, future coping ability, and personal growth. Although symptoms of distress did not change between baselines, significant reductions were found in PTSS from the first baseline to postwriting, but not in depression. This preliminary study suggests that the GDP may reduce PTSS in distressed PCWC.

Hypocholesterolemia in chronic anemias with increased erythropoietic activity.

Hypocholesterolemia of unknown etiology has been previously described in various chronic anemias. Few small studies also suggested that those patients have a lower incidence of atherosclerotic events. The aim of our study was to determine the extent of hypocholesterolemia in various types of anemias. We studied 59 patients with chronic anemias associated with high-erythropoietic activity (thalassemia intermedia, congenital dyserythropoietic anemia type I, congenital spherocytosis), 8 patients with low-erythropoietic activity anemias (acquired aplastic anemia, Fanconi anemia, and Diamond Blackfan anemia), and 20 healthy controls. Mean serum cholesterol, high-density lipoprotein (HDL) cholesterol, low-density lipoprotein (LDL) cholesterol, triglycerides, hemoglobin, serum ferritin, soluble transferrin receptor (STR), and serum erythropoietin levels were determined in each patient. All patients with chronic anemia and increased erythropoietic activity had hypocholesterolemia, whereas none of those with low erythropoietic activity was hypocholesterolemic. Mean serum cholesterol, HDL cholesterol, and LDL cholesterol levels were found to be significantly lower in the high-erythropoietic activity group (80+/-19 mg/dl; 31+/-10 mg/dl; 35+/-14 mg/dl, respectively) compared with the control group (P<0.001; 0.001; 0.001, respectively) and the low-erythropoietic activity group (P<0.001; 0.001; 0.01, respectively). Significant inverse correlation (R2=0.507) was observed between serum cholesterol and STR levels, which in the absence of iron deficiency reflect bone marrow activity. Taken together, our results imply that hypocholesterolemia accompanies anemias with high-erythropoietic activity. We suggest that the high-erythropoitic activity-associated hypocholesterolemia is due to increased cholesterol requirements by the proliferating erythoid cells. Further studies are needed to elucidate the exact mechanism and the possible clinical consequences of this phenomenon.

Imatinib resistant chronic myelogenous leukemia, BCR-ABL positive by chromosome and FISH analyses but negative by PCR, in a child progressing to acute basophilic leukemia: cytogenetic follow-up.

The case of an 11-year-old child with adult-type chronic myeloid leukemia, Philadelphia (BCR-ABL) positive, reverse transcription-polymerase chain reaction negative for the major, minor, and micro breakpoints is presented. In the course of 3 years, the child failed to respond to treatment with hydroxyurea, refused all therapy for 6 months, was intolerant to alpha-interferon and progressed, while on imatinib, to acute basophilic leukemia. Subsequently he underwent successful bone marrow transplantation. A secondary cytogenetic clonal evolution, i(17q), developed during hydroxyurea treatment and a tertiary clonal evolution, +8, was detected during imatinib treatment. It is not clear to what extent the several factors (undefined BCR-ABL breakpoint, treatment avoidance, and initial treatment choices, alone or in combination) played a role in the imatinib relapse and resistance and in the disease progression. We conclude that close follow-up with frequent bone marrow sampling is crucial in order to monitor such patients for early relapse and prompt referral for bone marrow transplant.