Destination healthcare facility of patients with suspected traumatic brain injury in Scotland: Analysis of pre-hospital data

Background

Traumatic brain injury is common. Guidelines from the Brain Trauma Foundation and the Scottish Intercollegiate Guidelines Network recommend that patients with suspected severe traumatic brain injury should be treated in centres with neurosurgical expertise. Scotland does not have a framework for the delivery of trauma care. The aim of this study was to examine the demographic characteristics of incidents involving patients who have suffered a suspected traumatic brain injury, and to evaluate the level of the destination healthcare facility which patients are currently taken to.

Methods

Retrospective analysis of prospectively collected Scottish Ambulance Service data on incidents involving traumatic injury, between Nov 2008 and Oct 2010. Two groups of casualties were analysed: those who had a Glasgow coma scale of less than 14 (GCS < 14), and those who had a Glasgow coma scale of less than 9 (GCS < 9).

Results

126,934 incidents were identified and analysed. 3890 (3.1%) patients had a GCS of less than 14, and 657 (0.5% of total) had a GCS of less than 9. Almost one-third of incidents involving patients with either a GCS < 14 or GCS < 9 occurred in the greater Glasgow health board area. The Lothian health board region had the second-highest number of patients with either a GCS < 14 or GCS < 9. Only 13.8% of patients with a GCS < 14, and 16.7% of those with a GCS < 9, were taken to a hospital with a neurosurgical service.

Conclusions

Many patients who may harbour a traumatic brain injury are taken to a facility which may not be equipped or staffed to deal with such injuries. This mismatch needs to be addressed. However, the care of patients with head injuries is only one aspect of trauma care. The UK has long lagged behind North America in terms of the quality of trauma care provided, although the provision of trauma care in England is currently undergoing major changes. Scotland should consider the development of a similar service delivery framework.     

Minactivin expression in human monocyte and macrophage populations

Adherent monolayer cultures of human blood monocytes, peritoneal macrophages, bone marrow macrophages, and colonic mucosa macrophages were examined for their ability to produce and secrete minactivin, a specific inactivator of urokinase-type plasminogen activator. All except colonic mucosa macrophages produced and secreted appreciable amounts of minactivin, but only blood monocytes were stimulated by muramyl dipeptide (adjuvant peptide) to increase production. The minactivin from each of these populations could be shown to preferentially inhibit urokinase-type plasminogen activator and not trypsin, plasmin, or "tissue"-type plasminogen activator (HPA66). A plasminogen-activating enzyme present in monocyte cultures appeared unaffected by the presence of minactivin and could be shown to be regulated independently by dexamethasone.     

VEGF Improves Skeletal Muscle Regeneration After Acute Trauma and Reconstruction of the Limb in a Rabbit Model

Background

Complicated tibial fractures with severe soft tissue trauma are challenging to treat. Frequently associated acute compartment syndrome can result in scarring of muscles with impaired function. Several studies have shown a relationship between angiogenesis and more effective muscle regeneration. Vascular endothelial growth factor (VEGF) is associated with angiogenesis but it is not clear whether it would restore muscle force, reduce scarring, and aid in muscle regeneration after acute musculoskeletal trauma.

Questions/purposes

Therefore, we asked whether local application of VEGF (1) restores muscle force, (2) reduces scar tissue formation, and (3) regenerates muscle tissue.

Methods

We generated acute soft tissue trauma with increased compartment pressure in 22 rabbits and shortened the limbs to simulate fracture débridement. In the test group (n = 11), a VEGF-coated collagen matrix was applied locally around the osteotomy site. After 10 days of limb shortening, gradual distraction of 0.5 mm per 12 hours was performed to restore the original length. Muscle force was measured before trauma and on every fifth day after trauma. Forty days after shortening we euthanized the animals and histologically determined the percentage of connective and muscle tissue.

Results

Recovery of preinjury muscle strength was greater in the VEGF group (2.4 N; 73%) when compared with the control (1.8 N; 53%) with less connective and more muscle tissue in the VEGF group. The recovery of force was related to the percentage of connective tissue versus muscle fibers.

Conclusions

Local application of VEGF may improve restoration of muscle force by reducing connective tissue and increasing the relative amount of muscle fibers.

Clinical Relevance

VEGF may be useful to improve skeletal muscle repair by modulating muscle tissue regeneration and fibrosis reduction after acute trauma.     

The Influence of End‐of‐Life Care on Organ Donor Potential

Many patients with acute devastating brain injury die outside intensive care units and could go unrecognized as potential organ donors. We conducted a prospective observational study in seven hospitals in the Netherlands to define the number of unrecognized potential organ donors outside intensive care units, and to identify the effect that end‐of‐life care has on organ donor potential. Records of all patients who died between January 2013 and March 2014 were reviewed. Patients were included if they died within 72 h after hospital admission outside the intensive care unit due to devastating brain injury, and fulfilled the criteria for organ donation. Physicians of included patients were interviewed using a standardized questionnaire regarding logistics and medical decisions related to end‐of‐life care. Of the 5170 patients screened, we found 72 additional potential organ donors outside intensive care units. Initiation of end‐of‐life care in acute settings and lack of knowledge and experience in organ donation practices outside intensive care units can result in under‐recognition of potential donors equivalent to 11–34% of the total pool of organ donors. Collaboration with the intensive care unit and adjusting the end‐of‐life path in these patients is required to increase the likelihood of organ donation.     

Delayed plasma cholecystokinin and gallbladder responses to intestinal fat in patients with Billroth I and II gastrectomy

This study was undertaken to examine the intestinal phase of cholecystokinin (CCK) secretion and gallbladder contraction in patients who had undergone partial gastrectomy. Plasma CCK concentrations, measured by radioimmunoassay, and gallbladder contraction, measured by cholescintigraphy, were studied after intestinal administration of fat. Fasting plasma CCK concentrations were in the same range in nine patients who had undergone Billroth I gastrectomy (1.0 +/- 0.2 pmol/L), in nine patients who had undergone Billroth II gastrectomy (1.4 +/- 0.2 pmol/L), and in nine normal subjects (1.5 +/- 0.4 pmol/L). The peak increments in plasma CCK after intestinal fat were significantly (p less than 0.05) lower in patients with partial gastrectomy (5.4 +/- 0.6 pmol/L) compared with normal subjects (7.9 +/- 0.8 pmol/L). The integrated plasma CCK secretion was significantly (p less than 0.01 to p less than 0.05) reduced during the first 30 minutes in patients after Billroth I (74 +/- 11 pmol/1.30 min) and Billroth II gastrectomy (51 +/- 11 pmol/1.30 min) compared with normal subjects (122 +/- 18 pmol/1.30 min). Similarly, the start of gallbladder emptying was significantly (p less than 0.05) delayed in patients after partial gastrectomy. After 1 hour, however, the integrated plasma CCK response and gallbladder emptying were in the same range in Billroth I patients (186 +/- 34 pmol/1.60 min, 60% +/- 7%), Billroth II patients (175 +/- 17 pmol/1.60 min, 63% +/- 7%) and normal subjects (190 +/- 18 pmol/1.60 min, 55% +/- 6%). It is concluded that in patients who have undergone partial gastrectomy plasma CCK and gallbladder responses to intestinal fat are significantly delayed but reach normal levels beyond 30 minutes.     

Ustekinumab improves psoriasis‐related gene expression in noninvolved psoriatic skin without inhibition of the antimicrobial response

Background Ustekinumab is a fully human anti‐p40 monoclonal antibody which neutralizes interleukin (IL)‐12 and IL‐23, thereby interfering with T‐helper (Th)1/Th17 pathways and keratinocyte activation, and is highly effective in the treatment of psoriasis. During ustekinumab treatment, some of our patients noticed reduced koebnerization of noninvolved skin and less new plaque formation. Objectives To determine whether ustekinumab improves psoriasis‐related gene expression and tape‐strip responses in noninvolved skin. Methods Before and 4 weeks after ustekinumab treatment, noninvolved skin was tape‐stripped. After 5 h, biopsies were taken from untouched and tape‐stripped skin. The mRNA expression of psoriasis‐related markers such as NGF, GATA3 and IL‐22RA1, and several antimicrobial peptides (AMP) was quantified. Leucocyte counts and a broad range of inflammatory serum proteins were analysed to gain insight into the systemic alterations. Results Four weeks following a single ustekinumab injection, NGF showed a significant decrease, whereas GATA3 and IL‐22RA1 expression increased, indicative of reduced responsiveness to epidermal triggering. This was accompanied by an increase of the inflammation‐related serum proteins GPNMB, MST1 and TRADD. The baseline and tape‐strip‐induced mRNA expression of the AMP human β‐defensin‐2 (hBD‐2), S100A7 and LL‐37 remained unaltered. Clinically, after 4 weeks, eight out of 11 patients showed a 50% psoriasis area and severity index (PASI) improvement, which was accompanied by a significant reduction in serum hBD‐2 levels. No changes were noted in total leucocytes, C‐reactive protein and erythrocyte sedimentation rate. Conclusions These findings indicate that ustekinumab reduces psoriasis‐related gene expression in noninvolved psoriatic skin, making it more resistant to exogenous triggering, without disturbing its antimicrobial response. In parallel, ustekinumab modulates important circulating inflammation‐related proteins.     

Induction of proliferation of B prolymphocytic leukemia cells by phorbol ester and native or recombinant interferon-gamma

Phorbol ester phorbol myristate acetate (PMA) induces proliferation in nonmalignant human B cells and B cells from a patient with B prolymphocytic leukemia (B-PLL). Mitogen-free T cell-derived conditioned medium acts synergistically with PMA in inducing proliferation of B-PLL cells but does not enhance the PMA-stimulated outgrowth of nonmalignant B cells. Interleukin 2 (IL-2) has no effect on the outgrowth of B-PLL cells, and monoclonal antibodies against the IL-2 receptor do not influence the response to PMA and conditioned medium. Recombinant interferon-gamma (IFN-gamma), in contrast, is a potent enhancer of PMA-induced proliferation of B-PLL cells. With gel filtration techniques and with the use of anti-IFN-gamma antibodies, it is shown that IFN-gamma in the conditioned medium is responsible for the observed increase in B-PLL cell proliferation. Preincubation of B- PLL cells with IFN-gamma induces responsiveness to PMA, whereas IFN- gamma alone had no effect on these cells when pretreated with PMA. The combined data show that, in the presence of PMA, native and recombinant IFN-gamma are growth factors for B cells from a B-PLL patient and that IL-2 is not involved in this process.     

Ultraviolet irradiation induces cyclooxygenase-2 expression in keratinocytes

We examined the effect of ultraviolet (UV) irradiation on the expression of cyclooxygenases in cultured HaCaT keratinocytes and in human skin in vivo. UVB irradiation (10 and 50 mJ/cm2) and hydrogen peroxide (200 micromol/L) increased cyclooxygenase-2 mRNA expression in HaCaT keratinocytes. No clear expression of cyclooxygenase-1 mRNA was detected in either control or stimulated HaCaT cells. Genistein, a tyrosine kinase inhibitor, suppressed both the basal and stimulated expression of cyclooxygenase-2 in HaCaT cells. UVB-induced cyclooxygenase-2 mRNA expression was partly inhibited by the antioxidant N-acetylcysteine and by H-7, a non-specific inhibitor of protein kinase C. Solar-simulated irradiation (40 mJ/cm2) was found to induce in vivo both cyclooxygenase-2 mRNA and protein expression in human skin, whereas the expression of cyclooxygenase-1 mRNA remained at the basal level. Our results show that cyclooxygenase-2 expression is induced by UV irradiation and suggest that tyrosine kinases and reactive oxygen intermediates are involved in this induction of cyclooxygenase-2.