Prognosticating outcome using magnetic resonance imaging in patients with moderate to severe traumatic brain injury: a machine learning approach.

INTRODUCTION: Over the last decade advancements in computer processing have enabled the application of machine learning (ML) to complex medical problems. Convolutional neural networks (CNN), a type of ML, have been used to interrogate medical images for variety of purposes. In this study, we aimed to investigate the potential application of CNN in prognosticating patients with traumatic brain injury (TBI). METHODS: Patients with moderate to severe TBI and evidence of diffuse axonal injury (DAI) were selected retrospectively. A CNN model was developed using a training subgroup and a holdout subgroup was used as a testing dataset. We reported the model characteristics including area under the receiver operating characteristic curve (AUC). RESULTS: We included a total of 38 patient, of which we generated 725 MRI sections. We developed a CNN model based on a modified AlexNet architecture that interpreted the brain stem injury to generate outcome predictions. The model was able to predict GOS outcomes with a specificity of 0.43 and a sensitivity of 0.997. It showed an AUC of 0.917. CONCLUSION: The utilization of machine learning MRI analysis for prognosticating patients with TBI is a valued method that require further investigation. This will require multicentre collaboration to generate large datasets.

Spinal epidural hematoma caused by pseudogout: a case report and literature review.

Study Design Case report. Objective We present the first reported case of spontaneous spinal epidural hematoma secondary to calcium pyrophosphate crystal deposition disease (pseudogout) in a 75-year-old woman. Methods A retrospective review of the patient's case notes was undertaken and the limited literature on this subject reviewed. Results This patient presented with sudden-onset lower limb paresis, sensory loss, urinary retention, and back pain. Magnetic resonance imaging showed an epidural hematoma, which was evacuated. Histologic specimens of the clot showed calcium pyrophosphate dihydrate crystal deposits (pseudogout). Conclusion The importance of histopathologic review of surgical specimens is highlighted when considering the differential diagnosis of apparently spontaneous spinal epidural hematoma.

The two-week waiting time standard for cancer: a neurosurgical perspective.

The implementation of the two-week wait initiative for cancer referrals in the NHS has had a major impact on outpatient services. A low clinical detection rate among GPs for neurological cancer has resulted in a large number of urgent referrals with a low yield of positive diagnoses. We have devised a strategy for minimizing the impact on outpatient clinics: patients are scanned prior to clinical review and those with normal scans are referred back to the GP without a clinic appointment. Out of 69 referrals of suspected CNS cancer made in 2003, 61 were scanned and six resulted in a positive diagnosis. The equivalent of 10 clinics was saved, and an increased speed of diagnosis and treatment was achieved with no compromise in patient care. Our study illustrates the consequences of the 2-week wait initiative on the neurosurgical service, and proposes an effective and safe solution.

[The effect of the physico-chemical properties of suture materials and the surface structure on adherence of tumor cells]. / Vliv fyzikálne-chemických vlastností sicího materiálu a jeho povrchové struktury na adherenci nádorových bunek.

Local recurrence following curative resection for colorectal cancer may be caused by the seeding of free malignant cells at the anastigmatic site. This study investigated the influence of suture material on in vitro tumor cell adherence. Radiolabeled rat colonic cancer cells (RCC5) were incubated with a variety of suture materials, and the relative contribution of chemical composition and physical configuration to cell adherence was assessed. Nonadherent cells were washed free, and the cell adherence was determined by radioactive counting. Marked differences in adherence were observed, with cells preferentially adhering to protein-based and multifilament sutures. These observations were confirmed using scanning electron microscopy. These findings indicate that both chemical composition and physical configuration influence the adherence of tumor cells to sutures and suggest that the use of protein-based and multifilament sutures be carefully considered in situations where free malignant cells may be present following colorectal surgery.

CD44 expression in rejecting rat small bowel allografts.

CD44 is a widely expressed cell surface protein that recognizes multiple ligands and is involved in extra- and intercellular adhesion. The precise role of CD44 in immune interactions is currently unknown, but it is believed to be a homing receptor involved in lymphocyte trafficking and inflammatory responses. This study investigated CD44 expression in intestinal tissue after heterotopic rat small bowel transplantation and assessed the effect of transplantation on intestinal epithelial cell proliferation using an antibody to the nuclear activation Ag Ki67. Lamina propria and intestinal epithelial cell expression of CD44 was graded blindly by five observers, and villus epithelial cells were noted as being positive or negative for Ki67 staining. CD44 expression was high in the lamina propria of both allografted and isografted animals; however, there was no significant difference between the two groups. In contrast, the expression of CD44 on the villus epithelium was greater in allografted animals and progressed toward the villus tips as rejection developed, declining thereafter because of loss of villus integrity. Ki67 positivity was also greater in allografted animals but did not progress toward the villus tip. This is the first reported observation of CD44 expression on intestinal epithelium that is not restricted to the crypts. The findings indicate the involvement of CD44 in the rejection process and demonstrate changes in the proliferative profile of rejecting small intestinal epithelium. Further studies into adhesion molecules, such as CD44, may help to improve understanding of graft failure and promote the development of new therapeutic approaches for controlling and preventing graft rejection.

Differential expression of adhesion molecules during rat small bowel allograft rejection.

The adhesion molecules intercellular adhesion molecule 1 (ICAM-1), lymphocyte function-associated antigen-1 (LFA-1) (alpha and beta chains), and very late activation antigen-4 (VLA-4) have an essential role in cell-cell interactions and the initiation of immune responses. This study used an indirect immunoperoxidase technique to investigate the expression of these molecules in the lamina propria of allografts and isografts after heterotopic rat small bowel transplantation. Normal untransplanted small bowel served as additional controls. Overall, ICAM-1 and LFA-1 alpha expression was significantly higher in allografts, although there was variable expression of these molecules in isografted animals. There were temporal differences in the expression of ICAM-1 and LFA-1 alpha in that increased ICAM-1 expression was more pronounced in the the early posttransplant period, whereas there was a progressive increase in LFA-1 alpha as rejection developed. In contrast, there was no difference between allograft and isograft expression of LFA-1 beta and VLA-4. This study has demonstrated a preferential increase in adhesion molecule expression with developing rat small bowel allograft rejection and suggests that adhesion molecules are involved in the development and progression of allograft rejection. Although the observed differences in antigen expression are not as marked as those previously reported in other organ transplants, appropriate adhesion molecules may present suitable targets for immunotherapeutic protocols after small bowel transplantation.

CD44 exhibits a cell type dependent interaction with triton X-100 insoluble, lipid rich, plasma membrane domains.

CD44 is an abundant, widely expressed transmembrane glycoprotein which can act as a receptor for the extracellular matrix glycosaminoglycan, hyaluronan. Biochemical and morphological studies have demonstrated that in fibroblasts a significant of the CD44 population is resistant to Triton X-100 extraction and that the detergent insoluble protein is co-localized with components of the cortical cytoskeleton. Surprisingly, this distribution is not abrogated upon deletion of the CD44 cytoplasmic tail indicating that mechanisms other than a direct interaction with the cytoskeleton can regulate CD44. In this manuscript, the mechanisms underlying this detergent-insoluble association are further investigated. There was no evidence that the Triton X-100 insolubility of CD44 resulted from homotypic aggregation, an association with hyaluronan or from a direct, or indirect, association with the cytoskeleton. Instead, evidence is presented that the detergent insolubility of fibroblast CD44 at 4 degrees C results from an association of the CD44 transmembrane domain with Triton X-100 resistant, lipid rich, plasma membrane domains. The proportion of the CD44 found in these Triton X-100 insoluble structures is dependent upon cell type and cannot be altered by changing cell motility or extracellular matrix associations. These studies provide evidence for a novel mechanism regulating this adhesion protein in the plasma membrane.

Hyaluronan binding by CD44 is regulated by a phosphorylation-independent mechanism.

CD44 is an adhesion receptor for which the major characterized ligand is the extracellular matrix glycosaminoglycan, hyaluronan. This interaction underlies CD44-mediated cell attachment, cell migration, and matrix remodelling during development and wound healing. Truncation of the CD44 cytoplasmic domain does not prevent cell surface expression of this hyaluronan receptor but it dramatically impairs ligand binding. In this study we have examined the role of phosphorylation in regulating this function by mutating the target serine residues to either neutral amino acids with the aim of creating a phosphorylation-incompetent molecule, or to acidic residues to mimic a fully phosphorylated CD44. In transfected AKR1 cells the behavior of both the neutral and acidic mutants was indistinguishable from wild-type CD44, indicating that there is a phosphorylation-independent mechanism involved in regulating hyaluronan binding.

Influence of soluble suture factors on in vitro macrophage function.

Suture materials may interact with immune competent cells and thereby affect localized immunity. Macrophages are central to the inflammatory response and coordinate wound healing. They are also involved in the clearance of foreign material, bacteria and malignant cells. We studied the influence of soluble factors associated with silk, steel, nylon, polyglactin, polydioxanone and chromic catgut sutures on macrophage adherence, phagocytosis and the production of lysozyme and tumour necrosis factor. Soluble factors from suture materials influenced macrophage behaviour in vitro causing cellular activation, functional impairment and alterations in secreted levels of the cytokine tumour necrosis factor and the bactericidal agent lysozyme. Of the six materials studied, polyglactin had the most extreme effect, causing significant inhibition of cell adherence and lysozyme production. Silk also exerted a considerable effect on macrophages, significantly inhibiting adherence. In contrast, steel and polydioxanone media caused minimal inhibition of macrophage function although, as with all materials, they did activate the cells. This study has demonstrated that sutures release immunotoxic factors which considerably influence macrophage behaviour in vitro. These effects may have important clinical implications.

Influence of suture physicochemical and surface topographic structure on tumor cell adherence.

Local recurrence following curative resection for colorectal cancer may be caused by the seeding of free malignant cells at the anastomotic site. This study investigated the influence of suture material on in vitro tumor cell adherence. Radiolabeled rat colonic cancer cells (RCC5) were incubated with a variety of suture materials, and the relative contribution of chemical composition and physical configuration to cell adherence was assessed. Nonadherent cells were washed free, and the cell adherence was determined by radioactive counting. Marked differences in adherence were observed, with cells preferentially adhering to protein-based and multifilament sutures. These observations were confirmed using scanning electron microscopy. These findings indicate that both chemical composition and physical configuration influence the adherence of tumor cells to sutures and suggest that the use of protein-based and multifilament sutures be carefully considered in situations where free malignant cells may be present following colorectal surgery.

A rapid microplate-based fluorometric assay for phagocytosis.

A highly sensitive quantitative fluorometric assay for phagocytosis, previously measured using fluorescence spectrophotometry or flow cytometry, has been adapted for use with a 96-well fluorescence plate reader. The technique allows rapid analysis of large numbers of samples, and requires only a small sample volume. Comparison of plate types demonstrated that opaque white 96-well luminostrips produced a 100 fold greater fluorescent output, and were more sensitive than black fluoroplates. Intraplate variability was also significantly lower using white luminostrips. For the phagocytic assay, fluorescein conjugated polystyrene beads were incubated with macrophage monolayers in white luminostrips. After incubation, cells were washed, lysed and phagocytosis quantified by determining the fluorescent intensity using a fluorescence plate reader. The number of beads phagocytized was determined from a standard curve of bead number versus fluorescent output. The phagocytic activity of resident and thioglycollate-elicited peritoneal macrophages was compared using this technique.

Suppression of macrophage function by suture materials and anastomotic recurrence of Crohn's disease.

After surgical excision of bowel, Crohn's disease is likely to recur around the anastomosis. It is suggested that this may indicate a biological effect of suture materials on gastrointestinal immunology. To investigate this, the influence of six suture materials on the function of macrophages obtained from the rat peritoneal cavity and human intestinal mucosa was assessed. All materials significantly impaired macrophage function.

Experimental carcinogenesis at sutured and sutureless colonic anastomoses.

This study explores the role of sutures and the healing colonic wound in experimental carcinogenesis. One hundred sixty rats underwent surgery with colotomy and repair using silk, steel, or Vicryl (Ethicon, Somerville, NJ) sutures or a sutureless technique. Forty rats had a sham procedure. All animals received azoxymethane for 12 weeks at a dose of 10 mg/kg/week. Half the rats commenced carcinogen before surgery, and half commenced it eight weeks after surgery. Animals with anastomotic tumors were found in 46 percent of the sham group (P less than 0.05 cf. sutured), 41 percent of the sutureless group (P less than 0.02 cf. sutured), and 68 percent of the sutured group. The corresponding figures for anastomotic carcinoma were 9 percent (P less than 0.001 cf. sutured), 22 percent, and 38 percent. No significant differences in tumor yield were noted among the different sutures. However, several differences were noted between the two carcinogen models. In those animals that received surgery first, there was a higher incidence of anastomotic tumors (P less than 0.002) and cancers (P less than 0.0001) in the sutured and sutureless groups, and those tumors that occurred in the sutured group were considerably larger than in those that had carcinogen first (15.9 mm cf. 4.9 mm; P less than 0.0001). Overall, all sutures seem to enhance anastomotic tumor formation, and we would suggest that a sutureless anastomosis may diminish this risk.