Comparison of sporadic and familial behavioral variant frontotemporal dementia (FTD) in a North American cohort.

INTRODUCTION: Behavioral variant frontotemporal dementia (bvFTD) may present sporadically or due to an autosomal dominant mutation. Characterization of both forms will improve understanding of the generalizability of assessments and treatments. METHODS: A total of 135 sporadic (s-bvFTD; mean age 63.3 years; 34% female) and 99 familial (f-bvFTD; mean age 59.9; 48% female) bvFTD participants were identified. f-bvFTD cases included 43 with known or presumed chromosome 9 open reading frame 72 (C9orf72) gene expansions, 28 with known or presumed microtubule-associated protein tau (MAPT) mutations, 14 with known progranulin (GRN) mutations, and 14 with a strong family history of FTD but no identified mutation. RESULTS: Participants with f-bvFTD were younger and had earlier age at onset. s-bvFTD had higher total Neuropsychiatric Inventory Questionnaire (NPI-Q) scores due to more frequent endorsement of depression and irritability. DISCUSSION: f-bvFTD and s-bvFTD cases are clinically similar, suggesting the generalizability of novel biomarkers, therapies, and clinical tools developed in either form to the other.

Active lifestyles moderate clinical outcomes in autosomal dominant frontotemporal degeneration.

INTRODUCTION: Leisure activities impact brain aging and may be prevention targets. We characterized how physical and cognitive activities relate to brain health for the first time in autosomal dominant frontotemporal lobar degeneration (FTLD). METHODS: A total of 105 mutation carriers (C9orf72/MAPT/GRN) and 69 non-carriers reported current physical and cognitive activities at baseline, and completed longitudinal neurobehavioral assessments and brain magnetic resonance imaging (MRI) scans. RESULTS: Greater physical and cognitive activities were each associated with an estimated >55% slower clinical decline per year among dominant gene carriers. There was also an interaction between leisure activities and frontotemporal atrophy on cognition in mutation carriers. High-activity carriers with frontotemporal atrophy (-1 standard deviation/year) demonstrated >two-fold better cognitive performances per year compared to their less active peers with comparable atrophy rates. DISCUSSION: Active lifestyles were associated with less functional decline and moderated brain-to-behavior relationships longitudinally. More active carriers "outperformed" brain volume, commensurate with a cognitive reserve hypothesis. Lifestyle may confer clinical resilience, even in autosomal dominant FTLD.

Generation of an induced pluripotent stem cell line (UBCi001-A) from a presymptomatic individual carrying the R418X progranulin gene mutation.

Induced pluripotent stem cells (iPSCs) were generated from peripheral blood-derived erythroid progenitor cells obtained from a presymptomatic female carrying the heterozygous R418X progranulin (GRN) nonsense mutation, known to cause autosomal dominant frontotemporal lobar degeneration. Erythroid progenitor cells were reprogrammed into iPSCs using integration free episomal plasmids which enables exogenous expression of the Yamanaka factors. The pluripotent potential of the iPSCs was validated through expression of pluripotency factors and their capacity to differentiate into the three primary germ layers. The cells were confirmed to carry the described mutation and shown to have a normal karyotype.

Review: Neuropathology of non-tau frontotemporal lobar degeneration.

Frontotemporal dementia (FTD) is a heterogeneous clinical syndrome associated with frontotemporal lobar degeneration (FTLD) as a relatively consistent neuropathological hallmark feature. However, the discoveries in the past decade of many of the relevant pathological proteins aggregating in human FTD brains in addition to several new FTD causing gene mutations underlined that FTD is a diverse condition on the neuropathological and genetic basis. This resulted in a novel molecular classification of these conditions based on the predominant protein abnormality and allows most cases of FTD to be placed now into one of three broad molecular subgroups; FTLD with tau, TAR DNA-binding protein 43 or FET protein accumulation (FTLD-tau, FTLD-TDP and FTLD-FET respectively). This review will provide an overview of the molecular neuropathology of non-tau FTLD, insights into disease mechanisms gained from the study of human post mortem tissue as well as discussion of current controversies in the field.

Retrospective study to investigate the possible relationship between excess blood loss at caesarean section and reduced intra-operative oxytocin dose.

OBJECTIVE: To investigate a possible relationship between the oxytocin dose at caesarean section and blood loss. STUDY DESIGN: Retrospective analysis of computerised data for all caesarean sections in a UK maternity unit delivering 6000 women annually during 1995-2009 and thus for seven years before and after the 2001 recommended change in oxytocin dose. Validation of computerised and hand-checked clinical data for 1996 and 2006 was performed and annual frequency of blood loss >1000 ml was observed. RESULTS: Validation showed most variables recorded were similar for both acquisition methods. For 17,405 (98.9%) caesarean sections with blood loss recorded, excess or severe loss occurred in 127 (1.6%) of 7177 cases during 1995-2001 compared with 362 (4.0%) of 9035 during 2003-2009 (OR 2.317, CI 1.888-2.843). It was significantly more frequent with multiple than singleton pregnancies (OR 1.946, CI 1.417-2.673), with general than neuraxial anaesthesia (OR 4.296, CI 3.479-5.305) and with non-longitudinal than longitudinal fetal lie (OR 1.942, CI 1.501-2.512). Excluding these three groups, excess blood loss was still more frequent during 2003-2009 than 1995-2001 (OR 3.181, CI 2.374-4.263). Oxytocin given during labour did not influence the frequency of excess blood loss. CONCLUSIONS: The increased rate of excess blood loss at caesarean section during the latter period could be the result of the reduced oxytocin dose. If similar observations are made by others, this possible relationship should be investigated with appropriate objective randomised studies.

The effect of future ambient air pollution on human premature mortality to 2100 using output from the ACCMIP model ensemble.

Ambient air pollution from ground-level ozone and fine particulate matter (PM2.5) is associated with premature mortality. Future concentrations of these air pollutants will be driven by natural and anthropogenic emissions and by climate change. Using anthropogenic and biomass burning emissions projected in the four Representative Concentration Pathway scenarios (RCPs), the ACCMIP ensemble of chemistry-climate models simulated future concentrations of ozone and PM2.5 at selected decades between 2000 and 2100. We use output from the ACCMIP ensemble, together with projections of future population and baseline mortality rates, to quantify the human premature mortality impacts of future ambient air pollution. Future air pollution-related premature mortality in 2030, 2050 and 2100 is estimated for each scenario and for each model using a health impact function based on changes in concentrations of ozone and PM2.5 relative to 2000 and projected future population and baseline mortality rates. Additionally, the global mortality burden of ozone and PM2.5 in 2000 and each future period is estimated relative to 1850 concentrations, using present-day and future population and baseline mortality rates. The change in future ozone concentrations relative to 2000 is associated with excess global premature mortality in some scenarios/periods, particularly in RCP8.5 in 2100 (316 thousand deaths/year), likely driven by the large increase in methane emissions and by the net effect of climate change projected in this scenario, but it leads to considerable avoided premature mortality for the three other RCPs. However, the global mortality burden of ozone markedly increases from 382,000 (121,000 to 728,000) deaths/year in 2000 to between 1.09 and 2.36 million deaths/year in 2100, across RCPs, mostly due to the effect of increases in population and baseline mortality rates. PM2.5 concentrations decrease relative to 2000 in all scenarios, due to projected reductions in emissions, and are associated with avoided premature mortality, particularly in 2100: between -2.39 and -1.31 million deaths/year for the four RCPs. The global mortality burden of PM2.5 is estimated to decrease from 1.70 (1.30 to 2.10) million deaths/year in 2000 to between 0.95 and 1.55 million deaths/year in 2100 for the four RCPs, due to the combined effect of decreases in PM2.5 concentrations and changes in population and baseline mortality rates. Trends in future air pollution-related mortality vary regionally across scenarios, reflecting assumptions for economic growth and air pollution control specific to each RCP and region. Mortality estimates differ among chemistry-climate models due to differences in simulated pollutant concentrations, which is the greatest contributor to overall mortality uncertainty for most cases assessed here, supporting the use of model ensembles to characterize uncertainty. Increases in exposed population and baseline mortality rates of respiratory diseases magnify the impact on premature mortality of changes in future air pollutant concentrations and explain why the future global mortality burden of air pollution can exceed the current burden, even where air pollutant concentrations decrease.

Blood loss and blood transfusion at caesarean section: a prospective observational study covering 30 years.

OBJECTIVE: Attitudes to acute blood loss and transfusion have changed during the last 40 years. This study observed the trends in blood loss and transfusion rates at caesarean section during that period to identify any trends between 1976 and 2006. STUDY DESIGN: Prospective analysis of clinical notes of women delivered by caesarean sections in a major district hospital obstetric unit in the UK, delivering around 6000 annually during four 12-month periods every 10 years from 1976 to 2006. Details including demographic, pregnancy, delivery, blood loss, transfusion, and puerperal observations were recorded. RESULTS: 3222 of 22,998 women were delivered by caesarean section during the four study years, increasing from 7.2% in 1976 to 23.4% in 2006 (P<0.001). The median recorded blood loss was 500ml, which did not change significantly over the study years. The rate of excess blood loss however increased in low-risk cases in 2006 compared with 1996 (P<0.001); this increase followed the recommended restricted intra-operative oxytocin dose. Transfusion rates declined significantly from 22% in 1976 to 4-5% in 1996 and 2006 (P<0.001). CONCLUSIONS: Median blood loss remained steady for each of the study years but with an increase in excess blood loss cases in the last study year compared with the two previous study years. The explanation for this is presently uncertain, but was possibly influenced by the 2001 recommendation for a reduced dose of oxytocin at delivery. Transfusion rates declined, probably precipitated by anxieties over infections associated blood products. There was no indication of increased morbidity with the reduced transfusion rates accessed by the surrogate of post-delivery discharge times.

Incidence and prevalence of multiple sclerosis in the UK 1990-2010: a descriptive study in the General Practice Research Database.

OBJECTIVES: To estimate the incidence and prevalence of multiple sclerosis (MS) by age and describe secular trends and geographic variations within the UK over the 20-year period between 1990 and 2010 and hence to provide updated information on the impact of MS throughout the UK. DESIGN: A descriptive study. SETTING: The study was carried out in the General Practice Research Database (GPRD), a primary care database representative of the UK population. MAIN OUTCOME MEASURES: Incidence and prevalence of MS per 100 000 population. Secular and geographical trends in incidence and prevalence of MS. RESULTS: The prevalence of MS recorded in GPRD increased by about 2.4% per year (95% CI 2.3% to 2.6%) reaching 285.8 per 100 000 in women (95% CI 278.7 to 293.1) and 113.1 per 100 000 in men (95% CI 108.6 to 117.7) by 2010. There was a consistent downward trend in incidence of MS reaching 11.52 per 100 000/year (95% CI 10.96 to 12.11) in women and 4.84 per 100 000/year (95% CI 4.54 to 5.16) in men by 2010. Peak incidence occurred between ages 40 and 50 years and maximum prevalence between ages 55 and 60 years. Women accounted for 72% of prevalent and 71% of incident cases. Scotland had the highest incidence and prevalence rates in the UK. CONCLUSIONS: We estimate that 126 669 people were living with MS in the UK in 2010 (203.4 per 100 000 population) and that 6003 new cases were diagnosed that year (9.64 per 100 000/year). There is an increasing population living longer with MS, which has important implications for resource allocation for MS in the UK.

The receptor tyrosine kinase Axl regulates cell-cell adhesion and stemness in cutaneous squamous cell carcinoma.

Axl is a receptor tyrosine kinase (RTK) upregulated in various tumors including cutaneous squamous cell carcinoma (SCC). Axl expression correlates with poor prognosis and induction of epithelial-mesenchymal transition (EMT), hence we hypothesized that Axl is involved in the disruption of cell-cell adhesion to allow invasion and chemotherapy resistance of the cancer stem cell population. Cutaneous SCC cell lines with stable knockdown of Axl were generated using retroviral vectors. Axl depletion altered expression of intercellular junction molecules increasing cell-cell adhesion with downregulation of Wnt and TGFßR signaling. Furthermore, Axl expression correlated with the expression of putative cancer stem cell markers, CD44 and ALDH1, increased resistance to chemotherapy drugs, enhanced sphere formation ability and expression of EMT features by cancer stem cells. Axl depletion resulted in loss of tumor formation in an in vivo zebrafish xenograft model. In conclusion, these data suggest that abrogation of Axl results in loss of cancer stem cell properties indicating a role for Axl as a therapeutic target in chemotherapy-resistant cancer.

Laminar distribution of the pathological changes in sporadic frontotemporal lobar degeneration with transactive response (TAR) DNA-binding protein of 43 kDa (TDP-43) proteinopathy: a quantitative study using polynomial curve fitting.

AIMS: Previous data suggest heterogeneity in laminar distribution of the pathology in the molecular disorder frontotemporal lobar degeneration (FTLD) with transactive response (TAR) DNA-binding protein of 43 kDa (TDP-43) proteinopathy (FTLD-TDP). To study this heterogeneity, we quantified the changes in density across the cortical laminae of neuronal cytoplasmic inclusions, glial inclusions, neuronal intranuclear inclusions, dystrophic neurites, surviving neurones, abnormally enlarged neurones, and vacuoles in regions of the frontal and temporal lobe. METHODS: Changes in density of histological features across cortical gyri were studied in 10 sporadic cases of FTLD-TDP using quantitative methods and polynomial curve fitting. RESULTS: Our data suggest that laminar neuropathology in sporadic FTLD-TDP is highly variable. Most commonly, neuronal cytoplasmic inclusions, dystrophic neurites and vacuolation were abundant in the upper laminae and glial inclusions, neuronal intranuclear inclusions, abnormally enlarged neurones, and glial cell nuclei in the lower laminae. TDP-43-immunoreactive inclusions affected more of the cortical profile in longer duration cases; their distribution varied with disease subtype, but was unrelated to Braak tangle score. Different TDP-43-immunoreactive inclusions were not spatially correlated. CONCLUSIONS: Laminar distribution of pathological features in 10 sporadic cases of FTLD-TDP is heterogeneous and may be accounted for, in part, by disease subtype and disease duration. In addition, the feedforward and feedback cortico-cortical connections may be compromised in FTLD-TDP.

N-Acetylcysteine inhibits platelet-monocyte conjugation in patients with type 2 diabetes with depleted intraplatelet glutathione: a randomised controlled trial.

AIMS/HYPOTHESIS: The aim of this study was to determine whether oral dosing with N-acetylcysteine (NAC) increases intraplatelet levels of the antioxidant, glutathione (GSH), and reduces platelet-monocyte conjugation in blood from patients with type 2 diabetes. METHODS: In this placebo-controlled randomised crossover study, the effect of oral NAC dosing on platelet-monocyte conjugation and intraplatelet GSH was investigated in patients with type 2 diabetes (eligibility criteria: men or post-menopausal women with well-controlled diabetes (HbA(1c) < 10%), not on aspirin or statins). Patients (n = 14; age range 43-79 years, HbA(1c) = 6.9 ± 0.9% [52.3 ± 10.3 mmol/mol]) visited the Highland Clinical Research Facility, Inverness, UK on day 0 and day 7 for each arm of the study. Blood was sampled before and 2 h after oral administration of placebo or NAC (1,200 mg) on day 0 and day 7. Patients received placebo or NAC capsules for once-daily dosing on the intervening days. The order of administration of NAC and placebo was allocated by a central office and all patients and research staff involved in the study were blinded to the allocation until after the study was complete and the data fully analysed. The primary outcome for the study was platelet-monocyte conjugation. RESULTS: Oral NAC reduced platelet-monocyte conjugation (from 53.1 ± 4.5% to 42.5 ± 3.9%) at 2 h after administration and the effect was maintained after 7 days of dosing. Intraplatelet GSH was raised in individuals with depleted GSH and there was a negative correlation between baseline intraplatelet GSH and platelet-monocyte conjugation. There were no adverse events. CONCLUSIONS/INTERPRETATION: The NAC-induced normalisation of intraplatelet GSH, coupled with a reduction in platelet-monocyte conjugation, suggests that NAC might help to reduce atherothrombotic risk in type 2 diabetes. FUNDING: Chief Scientist Office (CZB/4/622), Scottish Funding Council, Highlands & Islands Enterprise and European Regional Development Fund. TRIAL REGISTRATION: isrctn.org ISRCTN89304265.

Multiple pathologies are common in Alzheimer patients in clinical trials.

OBJECTIVE: To determine the frequency of multiple pathology [Alzheimer Disease (AD) plus Vascular Dementia and/or Dementia with Lewy Bodies] in patients enrolled in clinical trials of AD therapy, and to compare the cognitive and functional assessments between patients with pure AD and AD with multiple pathology. METHODS: We conducted a retrospective analysis of patients with a clinical diagnosis of AD who were enrolled in AD therapy clinical trials and subsequently received an autopsy for confirmation of their diagnosis from 2000 to 2009. Performance on cognitive screening tests, namely Modified Mini Mental state (3MS) exam, Mini Mental state Exam (MMSE) and Functional Rating Scale (FRS) were compared between patients with pure AD and multiple pathology. RESULTS: Autopsy reports were available for 16/47 (34%) of deceased patients. Of these 16 patients, 5 (31%) had pure AD pathology, 10 (63%) had AD with other pathology, and 1 (6%) had non-AD pathology. Compared to patients with pure AD, patients with AD mixed with other pathology had poorer baseline FRS in problem-solving (p<0.01) and community affairs (p<0.02). CONCLUSION: While the strict enrollment criteria for clinical trials identified the presence of AD pathology in the majority of cases (15/16), multiple pathology was more common than pure AD in our series of autopsied patients. Premortem biomarkers that can distinguish between pure AD and AD with multiple pathology will be beneficial in future clinical trials and dementia patient management.

Evidence to support the single-dose over the two-dose protocol for routine antenatal anti-D Rhesus prophylaxis: a prospective observational study.

OBJECTIVE: To assess the potential benefit of the single-dose compared with two-dose protocol for routine antenatal anti-D prophylaxis (RAADP). STUDY DESIGN: Prospective observational study during February to October 2009 in a district teaching hospital delivering 6000 women annually. Obstetric notes of eligible RhD negative women were reviewed following delivery to identify gestation and dose for RAADP injections, with laboratory confirmation when necessary. The primary outcome was compliance administering RAADP at the appropriate gestation with the secondary analysis of compliance for nulliparae and multiparae. RESULTS: For 644 eligible women, there was no statistically significant difference in administering the 28 week injection between the two-dose (95%) and single-dose (98%) protocols (P=0.17, OR 2.47: 95%CI (0.73, 8.34)). Compliance giving the injection at the correct gestation at 28 ± 1 weeks was achieved in 78% and 77% respectively (P=0.72, OR 1.10: 95%CI (0.69, 1.74)). For the two-dose protocol the second injection was given to 96% of those who had received the first injection, but at the correct time point in only 67%. By eliminating the variability of the 34 week injection, the single-dose protocol resulted in significantly greater overall success in giving RAADP at the appropriate times compared with the two-dose protocol (P=0.021, OR 1.68: 95%CI (1.08, 2.64)). There were no differences between nulliparae and multiparae for both protocols. CONCLUSION: The single-dose protocol provides enhanced compliance over the two-dose protocol with the potential for reduced sensitisation combining economic and manpower benefits. There remains room for improvement in administering RAADP at the correct gestation.

A case-control study of nutritional factors associated with chronic suppurative otitis media in Yemeni children.

BACKGROUND/OBJECTIVES: Undernutrition and chronic suppurative otitis media (CSOM) in children are common in low resource settings, but there are few studies of their interactions. The aim is to evaluate nutritional factors associated with CSOM in Yemeni children. SUBJECTS/METHODS: A case-control study of 75 children with CSOM and 74 healthy controls. Assessment included dietary history, anthropometry, haemoglobin (Hb) and serum analytes zinc (Zn), copper (Cu), selenium (Se), iron, calcium, phosphate (PO(4)) and total 25-hydroxy vitamin D (25(OH)D). RESULTS: Cases had lower mean Z-scores for weight-for-age, weight-for-height, body mass index and mid-upper arm circumference (MUAC) (all P<0.05), and lower mean concentrations of serum Zn (P=0.032), Se (P<0.001) and calcium adjusted for albumin (P=0.026). Age-adjusted Hb and iron biomarkers did not differ between cases and controls. There was high prevalence of low serum Zn concentration (≥ 90%) and vitamin D deficiency in both cases (80%) and controls (96%). Duration of ear discharge was negatively correlated with total 25(OH)D (P=0.028), calcium adjusted for albumin (P<0.001), PO(4) (P=0.002), transferrin receptor/log ferritin ratio (P<0.001) and Cu (P<0.001), and positively correlated with child age and MUAC (both P<0.001). CONCLUSIONS: Children with CSOM were more undernourished than controls with lower mean serum Zn, Se and calcium concentrations. Vitamin D-deficient and iron-replete children had longer duration of infection, although this association was lost with age adjustment. Trials evaluating specific micronutrients are required in order to investigate specific nutrient-infection interactions in CSOM.

Deafness: malaria as a forgotten cause.

BACKGROUND: Ototoxicity from antimalarials is a well publicised cause of deafness and a great deal of time and resources are spent assessing it in relation to new drugs. The effect of the malaria parasite itself on hearing is, however, poorly documented and most evidence is anecdotal. This paper aims to collate existing evidence of this association. METHODS: Two systematic literature searches were performed on Ovid Medline, first for 'malaria' and 'hearing loss' or 'hearing impairment' or 'deafness', and secondly for 'cerebral malaria' and 'neurologic' or 'neurological' or 'neurocognitive sequelae'. The articles were then individually studied for relevance. RESULTS: Malaria has been implicated as a rare cause of hearing loss in various studies, but recommendations and hypotheses have not been taken seriously or investigated. Searches also returned numerous studies of neurological sequelae after cerebral malaria, a small proportion of which observed hearing impairments on follow-up. However, no attempt was made to distinguish between treatment and disease as the cause. A few antimalarial drug trials which assessed hearing before treatment found unexplained hearing loss which improved with elimination of the parasite. CONCLUSION: Evidence from this review suggests that the falciparum parasite is a potential cause of hearing loss. Malaria is a disease of such high prevalence that even if only a small proportion of survivors develop this impairment the effects on children's education could be detrimental. More attention should be focussed on investigating this association as the clinical and pathophysiological implications are potentially considerable.

Acupuncture for pain relief during induced labour in nulliparae: a randomised controlled study.

OBJECTIVE: To assess the role of acupuncture for analgesia during labour. DESIGN: Double-blind study of manual, electro and sham acupuncture, and single-blind study comparing acupuncture with a control group for analgesia for labour induction. SETTING: A major obstetric unit in the UK. POPULATION: A cohort of 105 nulliparae undergoing labour induction at term. METHODS: Twenty-three subjects needed to be randomised to each group to have an 80% power of detecting a 50% relative reduction in epidural rate with an alpha value of 0.05. MAIN OUTCOME MEASURES: The primary end point was the rate of intrapartum epidural analgesia, and the secondary end points were parenteral analgesia requirement, labour length, delivery mode, neonatal condition and postpartum haemorrhage. RESULTS: There was no difference in epidural analgesia between acupuncture and sham acupuncture, relative risk 1.18 (95% CI 0.8-1.74), or between acupuncture and control, relative risk 0.88 (95% CI 0.66-1.19). There were no significant differences in the secondary end points between the acupuncture groups and the control group. Side effects or complications of acupuncture were not identified. CONCLUSIONS: Using the protocols studied, there was no analgesic benefit with acupuncture for pain relief during induced labour in nulliparae.

A novel double mutation in FUS gene causing sporadic ALS.

It has been shown that mutations in the Fused in Sarcoma gene (FUS) could explain up to 5% of cases with familial amyotrophic lateral sclerosis (ALS). Our mutation analysis of FUS in a Canadian ALS patient of Chinese origin revealed an unusual novel heterozygous double point mutation (R514S/E516V) confirming that exon 15 is a mutation hot-spot. The substitutions are in cis position to each other and affect highly conserved codons in the RGG-rich region of the FUS protein. The absence of clinical signs of ALS in the relatives of the affected carrier could indicate that this mutation is incompletely penetrant or de novo. The pathologic significance of the R514S/E516V mutation was confirmed by immunohistochemistry. FUS-positive cytoplasmic inclusions were noted in a moderate number in neurons and abundantly in glial cells in the motor cortex and the brainstem. Of interest, a significant number of neuronal and glial FUS-positive inclusions were found in the tegmentum of the brainstem. Importantly, some neurons with inclusions showed retention of the normal nuclear FUS immunostaining.

The clinical outcome of UK military personnel who received a massive transfusion in Afghanistan during 2009.

OBJECTIVES: The UK Defence Medical Services has developed a Massive Transfusion Protocol (MTP) that forms part of the initial Damage Control Resuscitation process for severely injured combat casualties. The key objectives of this retrospective review of MTP recipients are to document the survival rates, level of critical care support required and the blood components transfused as part of the Massive Transfusion Protocol in Afghanistan during 2009. In addition to providing a measure of our current effectiveness it should also provide a reference point for future reviews as the MTP continues to evolve. METHODS: This was a collaborative project involving the Royal Centre for Defence Medicine and the Critical Care Department, University Hospitals Birmingham. It was limited to UK military personnel who were injured in 2009 and received massive transfusions (defined as the transfusion of 10 or more units of packed red blood cells over a 24-hour period) at Camp Bastion Role 3 Medical Facility, Afghanistan. RESULTS: During the 12-month period, 59 personnel received massive transfusions. 51 (86%) personnel survived to be discharged from hospital in the UK. 48 (92%) personnel required ventilatory support for a median of 3 (2-8) days. The longest period of ventilation was 40 days; 29 (55%) personnel required vasopressor support and eight personnel (15%) required renal replacement therapy. The median total transfusion of blood components was 45 (28.5-62) units. There were seven transfusions of more than 100 units. Five of the personnel in this group (including the recipient of a 237-unit transfusion) survived to be discharged from University Hospitals Birmingham. On average, 1.21 (SD 0.28) units of packed red blood cells were transfused for every unit of fresh frozen plasma. CONCLUSIONS: The use of the current MTP was associated with a high rate of survival. Survivors require a continuity of critical care with a median demand for 3 days. The early use of plasma and platelets can be successfully delivered in the battlefield despite operational and logistic constraints.