Development and internal validation of clinical prediction models for outcomes of complicated intra-abdominal infection.

BACKGROUND: Complicated intra-abdominal infections (cIAIs) are associated with significant morbidity and mortality. The aim of this study was to describe the clinical characteristics of patients with cIAI in a multicentre study and to develop clinical prediction models (CPMs) to help identify patients at risk of mortality or relapse. METHODS: A multicentre observational study was conducted from August 2016 to February 2017 in the UK. Adult patients diagnosed with cIAI were included. Multivariable logistic regression was performed to develop CPMs for mortality and cIAI relapse. The c-statistic was used to test model discrimination. Model calibration was tested using calibration slopes and calibration in the large (CITL). The CPMs were then presented as point scoring systems and validated further. RESULTS: Overall, 417 patients from 31 surgical centres were included in the analysis. At 90 days after diagnosis, 17.3 per cent had a cIAI relapse and the mortality rate was 11.3 per cent. Predictors in the mortality model were age, cIAI aetiology, presence of a perforated viscus and source control procedure. Predictors of cIAI relapse included the presence of collections, outcome of initial management, and duration of antibiotic treatment. The c-statistic adjusted for model optimism was 0.79 (95 per cent c.i. 0.75 to 0.87) and 0.74 (0.73 to 0.85) for mortality and cIAI relapse CPMs. Adjusted calibration slopes were 0.88 (95 per cent c.i. 0.76 to 0.90) for the mortality model and 0.91 (0.88 to 0.94) for the relapse model; CITL was -0.19 (95 per cent c.i. -0.39 to -0.12) and - 0.01 (- 0.17 to -0.03) respectively. CONCLUSION: Relapse of infection and death after complicated intra-abdominal infections are common. Clinical prediction models were developed to identify patients at increased risk of relapse or death after treatment, these now require external validation.

SLC19A3 encodes a second thiamine transporter ThTr2.

Recently, a new family of facilitative carriers has been cloned consisting of the reduced folate (SLC19A1) and the thiamine (SLC19A2) transporters. Despite a high level of sequence identity and similarity there is essentially no functional overlap between these carriers. The former transports folates and the latter thiamine. In this paper we describe the function of SLC19A3, another member of this transporter family most recently cloned, after transient transfection of the cDNA into HeLa cells. Uptake of [3H]thiamine, but not of methotrexate nor folic acid, was enhanced in SLC19A3 transfectants relative to vector control. Similarly, in the transfectants thiamine transport increased with an increase in pH with peak activity at pH approximately 7.5. While [3H]thiamine uptake was markedly inhibited by nonlabeled thiamine it was not inhibited by several organic cations in 100-fold excess. Hence this carrier has a high degree of specificity for vitamin B1. The data indicate that SLC19A3 has the characteristics of SLC19A2 (ThTr1) and represents a second thiamine transporter (ThTr2) in this family of facilitative carriers.

Stenotrophomonas maltophilia contamination of nebulizers used to deliver aerosolized therapy to inpatients with cystic fibrosis.

There is circumstantial evidence that nebulizer equipment may be a source of Stenotrophomonas maltophilia for patients with cystic fibrosis. Eighty-nine inpatient nebulizers were examined for evidence of S. maltophilia contamination of which nine (10%) yielded 14 strains of the bacterium. Environmental samples were obtained from 73 different sites on the ward, of which 17 (23%) yielded a further 21 strains. Positive sites included taps, sink drains, and potable water. Genotyping using ERIC-PCR and pulsed-field gel electrophoresis revealed that two pairs of patients' nebulizers were contaminated with closely related strains. None of the S. maltophilia isolates obtained from the ward environment shared genotypes with those obtained from the nebulizers. The frequency of isolation of S. maltophilia from potable water sources on the ward suggests that contamination may result from using it to clean reusable nebulizer equipment, particularly if this is followed by inadequate drying. Although the actual source of S. maltophilia contamination of hospital-use nebulizer equipment in this study remained elusive, these results have important infection control implications.

Transmission of colistin-resistant Pseudomonas aeruginosa between patients attending a pediatric cystic fibrosis center.

We report on an outbreak of colistin-resistant Pseudomonas aeruginosa (CRPA) that occurred in a United Kingdom pediatric cystic fibrosis (CF) unit and involved six children over a period of 5 years. All CRPA-positive children had received aerosolized colistin therapy before first isolation of resistant organisms (mean duration, 3.1 years). Four of the 6 had also received courses of intravenous colistin in the year before the first isolation of CRPA. No impact of CRPA acquisition on respiratory function, clinical condition, or radiological parameters could be demonstrated. Four of the 6 children carried isolates of CRPA indistinguishable on genotyping. Two of these 4 children were sisters. The other 2 were on the same ward together at time of first isolation, and subsequently shared overlapping admissions with one of the sisters. While there is no conclusive evidence for the route of transmission, the frequency of overlapping in-patient admissions between 3 of these patients is suggestive of patient-to-patient transfer in the nosocomial setting.CF clinicians should be aware that colistin resistance can occur in P. aeruginosa, and some of these strains are capable of spread within CF units.

Histological changes and neural elements in the posterior cruciate ligament in osteoarthritic knees.

PURPOSE: To evaluate histological changes and neural elements in 100 posterior cruciate ligaments (PCLs) in patients with osteoarthritis. METHODS: 100 PCLs were obtained from a consecutive series of 46 women and 16 men aged 49 to 91 (mean, 67) years who underwent primary PCL-retaining total knee replacement for osteoarthritis. Histology was examined using conventional light microscopy. The PCLs were graded histologically in terms of parallel orientation of collagen fibres, mucoid degeneration, inflammation, and haemosiderin deposition. Histological changes were graded as normal, mild degeneration, moderate degeneration, and severe degeneration. The neural elements were assessed using immunohistochemical staining for S100 protein and neurofilaments. The histopathologist was blinded to the age, gender, and clinical and radiological grades of osteoarthritis. RESULTS: One specimen was excluded from analysis owing to inadequate tissue. In the remaining 99 specimens, histology was normal in 72, mildly degenerative in 4, moderately degenerative in 4, and severely degenerative in 15. 76 specimens were positive for S100 protein or neurofilament or both by immunohistochemical staining, indicating the presence of neural elements. CONCLUSION: Most knees with osteoarthritis present with viable PCLs. Retaining the PCL in total knee replacement is a good option for better kinematics, stability, and proprioception.

Expression of the reduced folate carrier SLC19A1 in IEC-6 cells results in two distinct transport activities.

Intestinal absorption of folates has been characterized as a facilitative process with a low pH optimum. Studies with intestinal epithelial cells have suggested that this activity is mediated by the reduced folate carrier (RFC1). In this paper, we report on folate transport characteristics in an immortalized rat IEC-6 cell line that was found to exhibit the predominant influx activity for methotrexate (MTX) at pH 5.5 with a low level of activity at pH 7.4. Transfection of this cell line with an RFC1 construct resulted in clones exhibiting increased MTX uptake at both the pHs and high folic acid uptake only at the low pH. For the two clones with the highest level of transport activity, relative MTX influx at the two pHs was reversed. Moreover, the low pH MTX influx activity ([MTX](e) = 0.5 microM) was markedly inhibited by 20 microM folic acid while influx at neutral pH was not. Furthermore, in the presence and absence of glucose at low pH, MTX and folic acid influx activity was inhibited by azide, while MTX influx at pH 7.4 was stimulated by azide in the absence of glucose but was unchanged in the presence of glucose and azide. This was contrasted with the results of transfection of the same RFC1 construct into an L1210 murine leukemia cell line bearing a nonfunctional endogenous carrier. In this case, the activity expressed was only at pH 7.4. These data indicate that RFC1 can exhibit two distinct types of folate transport activities in intestinal cells that must depend on tissue-specific modulators.