Defining the need for blood and blood products transfusion following suicide bombing attacks on a civilian population: A level I single-centre experience

Introduction

Knowledge of patterns of blood use in the care of mass casualty settings is important for preparedness of medical centre resources and for maximising survival when blood supplies are limited. Our objectives were to review of our experience with the use of blood products and define the utilisation of blood transfusion following suicide bombing attacks.

Patients and methods

We conducted a retrospective analysis of blood and blood product transfusion following civilian bombing attacks at a level I trauma centre in Jerusalem, Israel from 2000 to 2005. The study group consisted of 137 patients who were admitted following 17 suicide bombing attacks which were carried out in Jerusalem during the 5-year period. Demographic data, number of units of blood and blood products transfused and the need for massive transfusions were recorded and analyzed.

Results

Fifty-three patients received blood transfusions (38.7%). There were 33 males (62.2%) with a median ISS of 13 (range 4–25). These 53 patients received 524 PRBC, 42 WB, and 449 FFP. The mean number of PRBC transfused/admitted patient was 3.82 units (range 0–59). Thirty patients (21.9%) received 236 PRBC (45% of total PRBC) at the first 2 h. The ratio of ordered to transfused blood was 946:524. The FFP:PRBC ratio for all transfused patients was 1:1.17. The number of PRBC transfused per attack correlated with the number of patients admitted per attack. The most commonly transfused blood type was A (52.3%). Only 18 units of uncrossed-matched blood were transfused (3.3% of total). 14 patients (10.2%) received massive transfusions. These patients received 399 PRBC (76.1% of total units transfused) and the average number of PRBC transfused was 28.5/patient (10–59).

Conclusions

More than 1/3 of casualties admitted following civilian bombing attacks received transfusions, most in the first 2 h. Large-scale attacks will require more blood and blood products than small-scale attacks. Twice the number of PRBC ordered than transfused reflects a known trend for over-triage during the initial assessment following bombing attacks. One tenth of patients received massive transfusion.     

Obstructive Sleep Apnea and Cardiovascular Comorbidities: A Large Epidemiologic Study

Obstructive sleep apnea (OSA) is a common disorder, characterized by cyclic cessation of airflow for 10 seconds or more. There is growing awareness that OSA is related to the development and progression of cardiovascular disease. However, only a few studies have associated OSA directly to major cardiovascular events. The aim of this study was to evaluate the relationship between OSA and cardiovascular morbidity in a well defined population of patients.The electronic database of the central district of a major health management organization was searched for all patients diagnosed with OSA in 2002–2010. For each patient identified, an age- and sex-matched patient was randomly selected from the members of the same health management organization who did not have OSA. Data on demographics, socioeconomic status, and relevant medical parameters were collected as well.The study population included 2797 patients, average age 58.1, in which 76.6% were males. There was a significant correlation between OSA and the presence of ischemic heart disease (P < 0.001), pulmonary hypertension (P < 0.001), congestive heart failure (P < 0.001), cardiomyopathy (P = 0.003), and arrhythmia (P < 0.001). OSA was also significantly correlated with low socioeconomic status (P < 0.001).OSA and cardiovascular disease were strongly correlated. As such, early diagnosis and treatment of OSA may change the course of both diseases. We suggest that sleep disordered breathing should be routinely assessed in patients with cardiovascular problems. An ear–nose–throat evaluation may also be important to rule out anatomic disorders that cause upper airway obstruction.     

Neuroimmunological function in parents of children suffering from cancer

The main aim of this study is to evaluate the relationship between depression and immunological function in parents of children with cancer. Thirty-two parents participated in the study. The parents completed the following assessments: a list of major stressful events in a Hemato-Oncology ward, beck depression inventory II (BDI-II), posttraumatic diagnostic scale (PDS) and quality of life (QOL) questionnaire. A single blood sample was drawn from parents for evaluation of cortisol levels and lymphocyte cell subgroups. The parents were divided into two groups: Those who suffered from depression as defined by BDI-II cutoff score of 14 (depressed parents (DP), n = 7), and non-depressed parents (non-DP, n = 25). In parents of children with cancer the DP group had statistically significantly higher stressful event scores, dysfunction scores (from the PDS) and CD8 percentage compared to the non-DP group. QOL, CD4 percentage and CD4/CD8 ratio were significantly lower in the DP group. The BDI scores significantly positively correlated with events and dysfunctional scores, and significantly negatively correlated with QOL scores and CD4/CD8 ratio. High psychiatric morbidity was found in parents of children with cancer. The findings of altered immunity in DP provide further evidence that the physiological response to stress and depression may alter immune functions.     

Correlation of serum and urinary matrix metalloproteases/tissue inhibitors of metalloproteases with subclinical allograft fibrosis in renal transplantation

Progressive interstitial fibrosis and tubular atrophy (IF/TA) is a leading cause of chronic allograft dysfunction. Increased extracellular matrix remodeling regulated by matrix metalloproteases (MMPs) and their inhibitors (TIMPs) has been implicated in the development of IF/TA. The aim of this study was to investigate whether urinary/serum MMPs/TIMPs correlate with subclinical IF/TA detected in surveillance biopsies within the first 6 months post-transplant. We measured eight different MMPs/TIMPs simultaneously in urine and serum samples from patients classified as normal histology (n = 15), IF/TA 1 (n = 15) and IF/TA 2–3 (n = 10). There was no difference in urinary MMPs/TIMPs among the three groups, and only 1/8 serum MMPs/TIMPs (i.e. MMP-1) was significantly elevated in biopsies with IF/TA 2–3 (p = 0.01). In addition, urinary/serum MMPs/TIMPs were not different between surveillance biopsies demonstrating an early development of IF/TA (i.e. delta IF/TA ≥ 1 compared to a previous biopsy obtained three months before; n = 11) and stable grade of IF/TA (i.e. delta IF/TA = 0; n = 20). Next, we investigated whether urinary/serum MMP/TIMP levels are elevated during acute subclinical tubulitis in surveillance biopsies obtained within the first 6 months post-transplant (n = 25). Compared to biopsies with normal histology, serum MMPs/TIMPs were not different; however, all urinary MMP/TIMP levels were numerically higher during subclinical tubulitis (MMP-1, MMP-7, TIMP-1 with p ≤ 0.04). We conclude that urinary/serum MMPs/TIMPs do hardly correlate with existing or early developing IF/TA in surveillance biopsies obtained within the first 6 months post-transplant. This could be explained by the dynamic process of extracellular matrix remodeling, which seems to be active during acute tubulo-interstitial injury/inflammation, but not in quiescent IF/TA.     

Epicutaneous sensitization in the development of food allergy: What is the evidence and how can this be prevented?

There is increasing evidence regarding the importance of allergic sensitization through the skin. In this review, we provide an overview of the atopic march and immune mechanism underlying the sensitization and effector phase of food allergy. We present experimental models and human data that support the concept of epicutaneous sensitization and how this forms one half of the dual-allergen exposure hypothesis. We discuss specific important elements in the skin (FLG and other skin barrier gene mutations, Langerhans cells, type 2 innate lymphoid cells, IL-33, TSLP) that have important roles in the development of allergic responses as well as the body of evidence on environmental allergen exposure and how this can sensitize an individual. Given the link between skin barrier impairment, atopic dermatitis, food allergy, allergic asthma, and allergic rhinitis, it is logical that restoring the skin barrier and prevention or treating atopic dermatitis would have beneficial effects on prevention of related allergic diseases, particularly food allergy. We present the experimental and human studies that have evaluated this approach and discuss various factors which may influence the success of these approaches, such as the type of emollient chosen for the intervention, the role of managing skin inflammation, and differences between primary and secondary prevention of atopic dermatitis to achieve the desired outcome.     

Hippocampus-specific deficiency in RNA editing of GluA2 in Alzheimer's disease

Adenosine to inosine (A-to-I) RNA editing is a base recoding process within precursor messenger RNA, catalyzed by members of the adenosine deaminase acting on RNA (ADAR) family. A notable example occurs at the Q/R site of the α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid glutamate receptor subunit GluA2. Abnormally, low editing at this site leads to excessive calcium influx and cell death. We studied hippocampus and caudate samples from Alzheimer's disease (AD) patients and age-matched healthy controls, using direct sequencing and a high accuracy primer-extension technique to assess RNA editing at the Q/R GluA2 site. Both techniques revealed lower, more variable RNA editing in AD, specific to the hippocampus and the GluA2 site. Deficient editing also characterized the hippocampus of apolipoprotein ε4 allele carriers, regardless of clinical diagnosis. In AD, messenger RNA expression of neuronal markers was decreased in the hippocampus, and expression of the Q/R-site editing enzyme ADAR2 was decreased in caudate. These findings provide a link between neurodegenerative processes and deficient RNA editing of the GluA2 Q/R site, and may contribute to both diagnosis and treatment of AD.     

Disturbed B and T cell homeostasis and neogenesis in patients with ataxia telangiectasia

Objective

Ataxia telangiectasia (AT) is a rare genetic, multi-system disorder characterized by neurodegeneration, chromosome instability, B and T cell immunodeficiency and a predisposition to cancer. We examined immunologic parameters reflecting cell development and proliferation and their relevancy to the clinical phenotype in affected individuals.

Patients and Methods

AT patients from the AT National Clinic in Israel underwent immunological investigation. Their T and B cell workup included lymphocyte subset counts, immunoglobulin levels, responses to mitogenic stimulations, TCR-Vβ families and BCR immunoglobulin heavy chain spectratyping, TCR rearrangement excision circles (TRECs) and Kappa-deleting recombination excision circles (KRECs).

Results

Thirty-seven AT patients (median age 12.7 years, range 4.2–25.1) were evaluated. CD20 B and CD3 T lymphocytes were decreased in 67 % and 64 % of the patients, respectively, while only 33 % of the patients had reduced lymphoproliferative responses. Almost all AT patients displayed extremely low TRECs and KRECs levels, irrespective of their age. Those levels were correlated to one another and to the amounts of CD3+ and CD20+ cells, respectively. Abnormal TCR-Vβ repertoires were found with different degrees of clonality or reduced expression in these AT patients. There was no clear clustering of expansions to specific TCR-Vβ genes. PCR spectratyping analysis of the FR2 IgH BCR gene rearrangements in peripheral blood was abnormal in 50 % of the patients.

Conclusion

The immunodeficiency associated with AT is combined, remains low over time and not progressive. It is characterized by low TREC and KREC copies suggestive of abnormal T and B cell neogenesis.