Machine-learning algorithm in acute stroke: real-world experience.

AIM: To assess the clinical performance of a commercially available machine learning (ML) algorithm in acute stroke. MATERIALS AND METHODS: CT and CT angiography (CTA) studies of 104 consecutive patients (43 females, age range 19-93, median age 62) performed for suspected acute stroke at a single tertiary institution with real-time ML software analysis (RAPID™ ASPECTS and CTA) were included. Studies were retrospectively reviewed independently by two neuroradiologists in a blinded manner. RESULTS: The cohort included 24 acute infarcts and 16 large vessel occlusions (LVO). RAPID™ ASPECTS interpretation demonstrated high sensitivity (87.5%) and NPV (87.5%) but very poor specificity (30.9%) and PPV (30.9%) for detection of acute ischaemic parenchymal changes. There was a high percentage of false positives (51.1%). In cases of proven LVO, RAPID™ ASPECTS showed good correlation with neuroradiologists' blinded independent interpretation, Pearson correlation coefficient = 0.96 (both readers), 0.63 (RAPID™ vs reader 1), 0.69 (RAPID™ vs reader 2). RAPID™ CTA interpretation demonstrated high sensitivity (92.3%), specificity (85.3%), and negative predictive (NPV) (98.5%) with moderate positive predictive value (PPV) (52.2%) for detection of LVO (N=13). False positives accounted for 12.5% of cases, of which 27.3% were attributed to arterial stenosis. CONCLUSION: RAPID™ CTA was robust and reliable in detection of LVO. Although demonstrating high sensitivity and NPV, RAPID™ ASPECTS interpretation was associated with a high number of false positives, which decreased clinicians' confidence in the algorithm. However, in cases of proven LVO, RAPID™ ASPECTS performed well and had good correlation with neuroradiologists' blinded interpretation.

Identification of Chlamydial species in crocodiles and chickens by PCR-HRM curve analysis.

Recently, a PCR protocol (16SG), targeting 16S rRNA gene coupled with high resolution melt (HRM) curve analysis was developed in our laboratory and shown to reliably detect and identify the seven different Chlamydiaceae spp. In this study, the potential of this method was assessed for detection and differentiation of Chlamydiosis in clinical specimens. Of the total number of 733 specimens from a range of animal species, 219 (30%) were found positive by 16SG PCR. When a sufficient amount of DNA was available (64 submissions), amplicons generated by the 16SG PCR were subjected to HRM curve analysis and results were compared to that of nucleotide sequencing. In all instances, the infecting Chlamydiaceae spp. was genotyped according to the identity of its nucleotide sequence to a reference species. Analysis of the HRM curves and nucleotide sequences from 16SG PCR amplicons also revealed the occurrence of a Chlamydophila-like, a Parachlamydia-like and a variant of Chlamydophila psittaci in chickens. These results reveal the potential of 16SG PCR-HRM curve analysis for rapid and simultaneous detection and identification of Chlamydiaceae spp. in animals and demonstrate the capacity of this system for rapid identification of new Chlamydiaceae spp. in animals during routine diagnostic testings.

Association between leukotriene receptor antagonist therapy and Churg-Strauss syndrome: an analysis of the FDA AERS database.

BACKGROUND: The possible role of leukotriene receptor antagonist (LTRA) therapy in the pathogenesis of Churg-Strauss syndrome (CSS) is uncertain. The aim was to examine the association between LTRA therapy and CSS in cases registered in the FDA Adverse Event Reporting System (AERS) database. METHODS: All cases of suspected drug-induced CSS reported to the AERS database between November 1997 and April 2003 were reviewed. Subjects in whom LTRAs were the suspected medication and sufficient documentation existed to confirm the diagnosis of CSS were sequentially categorised into one of the following groups: (A) CSS before treatment initiation; (B) oral or inhaled corticosteroids reduced or stopped within 6 months of CSS onset; (C) possible prodromal phase of CSS at treatment initiation; (D) unstable asthma at treatment initiation; (E) stable asthma at treatment initiation. RESULTS: There were 181 case reports of suspected drug-induced CSS with sufficient documentation to confirm a diagnosis of CSS; in 163 (90%) an LTRA was a suspect medication. In 140 of these 163 cases there was sufficient documentation to sequentially categorize the case into groups, with 13 (9%) in A, 27 (19%) in B, 11 (8%) in C, 28 (20%) in D and 61 (44%) in E. CONCLUSION: LTRA therapy was a suspect medication in most confirmed cases of CSS reported in the AERS database. In the majority of cases treated with an LTRA, CSS could not be explained by either corticosteroid withdrawal or pre-existing CSS. These findings are informative in considering the potential associations between LTRA therapy and CSS.

Characterization of Chlamydiaceae species using PCR and high resolution melt curve analysis of the 16S rRNA gene.

AIM: To design a rapid diagnostic test to differentiate species belonging to the family Chlamydiaceae. METHODS AND RESULTS: Five oligonucleotide sets each targeting various conserved regions of the genome of six species (Chlamydia muridarum, C. suis, C. trachomatis, Chlamydophila felis, Cp. pneumoniae and Cp. psittaci) belonging to the family Chlamydiaceae were tested for their suitability for polymerase chain reaction (PCR) and high resolution melt (HRM) curve analysis to differentiate Chlamydiaceae species. Three of the oligonucleotide sets were able to detect all six reference species used in this study, but only one set (16SG) could clearly differentiate between them by HRM curve analysis. The PCR-HRM curve analysis confidence percentages correlated strongly with the nucleotide sequence identities. Clinical specimens from a number of animal species suspected of chlamydiosis were tested with the newly developed 16SG PCR-HRM curve analysis and sequenced to confirm the infecting species. It was demonstrated that PCR-HRM using the 16SG oligonucleotide set could relate the infecting Chlamydiaceae species to the most similar (based on 16S rRNA gene nucleotide sequence) reference species tested. Although Cp. pecorum was not included initially as a reference species in this assay, inclusion of a field isolate of Cp. pecorum as a reference allowed two koala specimens to be correctly identified. CONCLUSION: PCR-HRM analysis using the oligonucleotide set 16SG is a robust, simple and rapid technique for differentiation of at least the Chlamydiaceae species used in this study. SIGNIFICANCE AND IMPACT OF THE STUDY: This technique allowed for the rapid detection and identification of the six Chlamydiaceae reference species and may be useful for identification of uncharacterized Chlamydiaceae species or for use in animal species where occurrence of the disease has not been fully investigated.

Effect of nutrient deprivation on the viability of intervertebral disc cells.

There is evidence that a fall in nutrient supply leads to disc degeneration but little understanding of the effects of nutrient deprivation on the physiology of disc cells which govern the composition of the disc. We examined the effects of changes in glucose and oxygen concentration and pH on the viability and metabolism of cells from bovine nucleus pulposus. Cells isolated from bovine discs and embedded in alginate beads were cultured under oxygen and glucose concentrations from zero to physiological levels and maintained at pH 7.4, pH 6.7, or pH 6.2 for up to 3 days. Interactions between nutrient concentrations were examined in relation to cell viability and lactic acid production. Cell viability was significantly reduced in the absence of glucose, with or without oxygen. Disc cells survived at 0% oxygen, provided that glucose was present, as seen previously. Cell viability decreased if the medium was acidic, more so when combined with low glucose concentrations. The rate of lactic acid production also fell as the pH became acidic and after 24 h or more at low glucose concentrations, but it did not appear to vary with oxygen concentration under the culture conditions used here. Glucose, rather than oxygen, appears to be the nutrient critical for maintaining disc cell viability. However, in an avascular tissue such as the disc, it is unlikely that glucose deprivation will occur alone; it will almost certainly correlate with a fall in oxygen concentration and pH. These results indicate that the combined nutrient and metabolite environment, rather than concentrations of any single nutrient, should be considered when studying cellular physiology in the disc.

Isolation of Ross River virus from mosquitoes and from horses with signs of musculo-skeletal disease.

OBJECTIVE: To report clinical and clinicopathological findings in horses naturally infected with Ross River virus (RRV) and identify likely mosquito arbovirus vector species. PROCEDURES: Veterinarians submitted serum samples from 750 horses because they suspected Ross River virus (RRV) infection. The samples were tested for the presence of IgM and IgG antibody to RRV and for the presence of virus. Mosquitoes were trapped, differentiated to species level and tested for the presence of RRV by virus isolation. RESULTS: RRV was isolated from six species of mosquitoes (Ochlerotatus camptorhyncus, Culex globocoxitus, Cx. australicus, Cx. annulirostris, Cx. quinquefasciatus, Anopheles annulipes) and from 13 horses with clinical signs of musculo-skeletal disease. Antibody to RRV was detected in 420 of the 750 serum samples; 307 contained IgG only; 76 contained both IgM and IgG and 37 contained only IgM antibody to RRV. Virus was isolated from horses with IgM antibody only. CONCLUSIONS: RRV can be isolated from infected horses during the short time period when there is an overlap of clinical signs, positive IgM serology and viraemia. Early spring infections of horses may occur if RRV infected mosquito vectors are present. RRV has not been shown to cause clinical disease in horses. This is the first report of isolation of RRV from Oc. camptorhyncus in the Murray region and indicates a potential for infection of humans and animals in autumn as well as in spring.

Intervertebral disc composition in neuromuscular scoliosis: changes in cell density and glycosaminoglycan concentration at the curve apex.

STUDY DESIGN: An analysis of the variation in glycosaminoglycan, water content, and cell density with disc level in patients with neuromuscular scoliosis. OBJECTIVES: To determine whether the composition of the apical disc differed from that of adjacent discs in the same spine. SUMMARY OF BACKGROUND DATA: Compositional differences between the convex and concave sides of scoliotic discs have been noted and are thought to be secondary to altered loading. However, there is little information on changes relative to the apex. METHODS: Intact wedges of disc obtained during anterior fusion procedures were taken from 23 discs of 6 patients with neuromuscular scoliosis. Radial profiles of glycosaminoglycan, water content, and cell density were measured. Concentrations were compared at a standard distance (5 mm) into the disc and plotted versus spinal level. RESULTS: Glycosaminoglycan and water content were lowest in the outer annulus and increased steadily toward the disc center, whereas the cell density was highest in the outer 2 mm, fell steeply and then remained constant. At 5 mm from the annulus edge, cell density was lowest in apical discs and, in most cases, was noticeably higher in adjacent discs of the same spine. At the same point, there was no consistent change in glycosaminoglycan/dry weight from disc to disc, indicating no significant proteoglycan loss. However, glycosaminoglycan/tissue water, and therefore swelling pressure, was highest in the apical discs, suggesting that these discs were the most heavily loaded. CONCLUSIONS: The loss of cells from the disc at the curve apex probably arose because this disc experiences greater mechanical stress or is more deformed than its neighbors. The decrease in cell density was not associated with major changes in tissue composition, possibly because rates of degradation and of synthesis were reduced, leaving the matrix largely unchanged.

The pathophysiology of the intervertebral disc.

After a review of disk structure, the pivotal role of disk cells in producing and renewing the extracellular disk matrix is emphasized. Disk cells rely on nutrients that diffuse through the vertebral endplates. Microelectrode methods have been developed to study nutrient diffusion and endplate permeability. Mechanical stimuli modify disk cell activity. Scoliosis is associated with decreased endplate permeability, a factor that may play a role in disk degeneration and scoliosis progression.

Efficacy of continuous extrapleural intercostal nerve block on post-thoracotomy pain and pulmonary mechanics.

To assess the efficacy of continuous extrapleural intercostal nerve block on postoperative pain and pulmonary function, a prospective, randomized, double-blind, placebo-controlled trial was conducted on 56 patients undergoing elective thoracotomy. Infusion was started before closing the chest and was continued for 5 days. Subjective pain relief was assessed on a linear visual analogue scale. Pulmonary function was measured on the day before operation and daily for 5 days. There were 29 patients in a group which received bupivacaine and 27 in a control group which received saline. The bupivacaine group had lower pain scores (P less than 0.01) and required less papaveretum (P less than 0.01) than the control group. Forced vital capacity, forced expiratory volume in 1 s and peak expiratory flow rate were maximally reduced at 24 h to median values of 56, 60 and 57 per cent, respectively, of preoperative control values in the bupivacaine group, and to 25, 30 and 32 per cent in the control group. These differences are highly significant (P less than 0.01). Restoration of pulmonary function was superior in the bupivacaine group (P less than 0.01). There were no infusion-related complications. After thoracotomy, continuous intercostal blockade with bupivacaine is a safe and effective method of pain relief which reduces the early loss of postoperative pulmonary function significantly and more rapidly restores respiratory mechanics.

Teicoplanin: Part 1. An evaluation of the concentrations seen in serum and the subcutaneous fat of the relatively ischaemic lower limb following a single intravenous bolus.

Teicoplanin is a new antibiotic currently undergoing clinical evaluation. Consecutive patients undergoing elective vascular surgery (n = 28) were randomised to receive a single intravenous bolus of 400 mg teicoplanin 1, 3, 6 or 12 h prior to surgery as prophylaxis against Gram-positive infection. Serum and fat antibiotic levels were measured and found to exceed the established MICs for common staphylococcal and streptococcal infections for at least 12 h following administration. This suggests that teicoplanin would be a useful choice of antibiotic in the prophylaxis and treatment of appropriate infections in elective surgery. By extrapolation, teicoplanin would also be of use in the prophylaxis and treatment of suitable infections seen in traumatised patients.

Teicoplanin: Part 2. Evaluation of its use in the biliary system.

Teicoplanin is a new antibiotic currently undergoing extensive investigation to evaluate its potential use in the prophylaxis and treatment of appropriate infection. To ascertain its penetration into the biliary system, 24 patients undergoing elective cholecystectomy were randomised to receive an intravenous bolus of 400 mg teicoplanin 1, 3, 6 or 12 h prior to surgery. During the operation, blood, gall bladder bile and tissue and common bile duct bile were removed for teicoplanin estimation. The results show that teicoplanin penetrates well into the gall bladder wall and bile, though less well into common bile duct bile. These results show that teicoplanin would seem to be a suitable antibiotic for the treatment of biliary infections that are known to be sensitive to the antibiotic.

The spring in the arch of the human foot.

Large mammals, including humans, save much of the energy needed for running by means of elastic structures in their legs and feet. Kinetic and potential energy removed from the body in the first half of the stance phase is stored briefly as elastic strain energy and then returned in the second half by elastic recoil. Thus the animal runs in an analogous fashion to a rubber ball bouncing along. Among the elastic structures involved, the tendons of distal leg muscles have been shown to be important. Here we show that the elastic properties of the arch of the human foot are also important.