Evaluation of a real-time PCR assay for rectal screening of OXA-48-producing Enterobacteriaceae in a general intensive care unit of an endemic hospital.

Carbapenemase-producing Enterobacteriaceae are increasing worldwide. Rectal screening for these bacteria can inform the management of infected and colonized patients, especially those admitted to intensive care units (ICUs). A laboratory developed, qualitative duplex real-time polymerase chain reaction assay for rapid detection of OXA-48-like and VIM producing Enterobacteriaceae, performed on rectal swabs, was designed and evaluated in an intensive care unit with endemic presence of OXA-48. During analytical assay validation, no cross-reactivity was observed and 100% sensitivity and specificity were obtained for both blaOXA-48-like and blaVIM in all spiked clinical samples. During the clinical part of the study, the global sensitivity and specificity of the real-time PCR assay for OXA-48 detection were 95.7% and 100% (P=0.1250), respectively, in comparison with culture; no VIM-producing Enterobacteriaceae were detected. Clinical features of patients in the ICU who were colonized or infected with OXA-48 producing Enterobacteriaceae, including outcome, were analyzed. Most had severe underlying conditions, and had risk factors for colonization with carbapenemase-producing Enterobacteriaceae before or during ICU admission, such as receiving previous antimicrobial therapy, prior healthcare exposure (including long-term care), chronic disease, immunosuppression and/or the presence of an intravascular catheter and/or mechanical ventilation device. The described real-time PCR assay is fast (~2-3hours, if DNA extraction is included), simple to perform and results are easy to interpret, features which make it applicable in the routine of clinical microbiology laboratories. Implementation in endemic hospitals could contribute to early detection of patients colonized by OXA-48 producing Enterobacteriaceae and prevention of their spread.

Azathioprine: tolerability, efficacy, and predictors of benefit in neuromyelitis optica.

OBJECTIVE: To evaluate the efficacy, tolerability, optimal dosing, and monitoring of azathioprine in patients with neuromyelitis optica (NMO). METHODS: This was a chart review and telephone follow-up study of 99 patients with NMO spectrum of disorders (NMOSD) treated with azathioprine (1994-2009). NMOSD were NMO (2006 diagnostic criteria) or partial NMO forms (NMO-immunoglobulin G seropositive). Wilcoxon signed rank test was used to compare pretreatment and postinitiation of azathioprine (posttreatment) annualized relapse rates (ARR), Expanded Disability Status Scale (EDSS) score, and visual acuity outcome. Linear regression was used to assess the effects of various factors on ARR change and disability. RESULTS: The median duration of NMOSD symptoms prior to initiation of azathioprine was 2 years (range 1-27); 79 patients were women. Eighty-six patients had NMO and 13 limited NMO versions, including transverse myelitis in 8 and optic neuritis in 5. Median posttreatment follow-up was 22 months. Thirty-eight patients discontinued drug (side effects, 22; no efficacy, 13; lymphoma, 3). Among 70 patients with >12 months follow-up, 48 received ≥2.0 mg/kg/day (ARR: pretreatment, 2.20; posttreatment, 0.52); 22 received <2.0 mg/kg/day (ARR: pretreatment, 2.09; posttreatment, 0.82); 52 received concomitant prednisone (ARR: pretreatment, 2.20; posttreatment, 0.89) and 18 did not (ARR: pretreatment, 1.54; posttreatment, 0.23); p < 0.0001 for each comparison. EDSS was stable or improved despite ongoing attacks in 22 patients (31%). Twenty-six patients tolerated azathioprine and were relapse-free (37%, median follow-up 24 months; range 12-151). Mean corpuscular volume increase influenced ARR change (p = 0.049). CONCLUSIONS: Azathioprine is generally effective and well-tolerated. Early initiation, adequate dosing, and hematologic parameter monitoring may optimize efficacy. CLASSIFICATION OF EVIDENCE: This study provides Class IV evidence that azathioprine is effective for reducing relapse rates and improving EDSS and visual acuity scores in patients with NMO spectrum of disorders.

Optimal presentation modes for detecting brain tumor progression.

BACKGROUND AND PURPOSE: A common task in radiology interpretation is visual comparison of images. The purpose of this study was to compare traditional side-by-side and in-place (flicker) image presentation modes with advanced methods for detecting primary brain tumors on MR imaging. MATERIALS AND METHODS: We identified 66 patients with gliomas and 3 consecutive brain MR imaging examinations (a "triplet"). A display application that presented images in side-by-side mode with or without flicker display as well as display of image subtraction or automated change detection information (also with and without flicker display) was used by 3 board-certified neuroradiologists. They identified regions of brain tumor progression by using this display application. Each case was reviewed using all modes (side-by-side presentation with and without flicker, subtraction with and without flicker, and change detection with and without flicker), with results compared via a panel rating. RESULTS: Automated change detection with or without flicker (P < .0027) as well as subtraction with or without flicker (P < .0027) were more sensitive to tumor progression than side-by-side presentation in cases where all 3 raters agreed. Change detection afforded the highest interrater agreement, followed by subtraction. Clinically determined time to progression was longer for cases rated as nonprogressing by using subtraction images and change-detection images both with and without flicker display mode compared with side-by-side presentation. CONCLUSIONS: Automated change detection and image subtraction, with and without flicker display mode, are superior to side-by-side image comparison.

The Geneva prognostic score and mortality in patients diagnosed with pulmonary embolism by CT pulmonary angiogram.

This study prospectively evaluates whether a previously established adverse outcome score (the Geneva prognostic score) predicts 3 and 12-month overall mortality among the patients diagnosed with pulmonary embolism (PE) by a CT pulmonary angiogram (CTPA). Five hundred twenty-three consecutive patients who had CTPA for suspected PE were recruited prospectively from March 2003 to October 2004. The Geneva prognostic score was calculated for all patients. Twelve-month follow up was completed in all patients in December 2005. There were 105 patients diagnosed with PE. The mean score was 2.71 (standard deviation (SD) 1.25) for those patients who had died (n = 7) and 1.14 (SD 1.19) for those patients who were alive (n = 98) at 3-month follow up (P < 0.001). The mean scores were 2.69 (SD 0.95) for those who had died (n = 13) and 1.04 (SD 1.15) for those patients who were alive (n = 92) at 12-month follow up (P < 0.001). At 3-month follow up, among the 88 patients with a score of 2 or less, three patients (3.4%) died and among 17 patients with a score of greater than 2, four patients (23.5%) died (P = 0.01). At 12-month follow up, five patients (5.7%) with a score of 2 or less died and eight patients (47.1%) with a score of three or more died (P < 0.0001). The Geneva prognostic score stratifies patients with low and high risk for overall mortality at 3 and 12 months among patients diagnosed with PE by CTPA.

Clinical and radiographic spectrum of pathologically confirmed tumefactive multiple sclerosis.

Atypical imaging features of multiple sclerosis lesions include size >2 cm, mass effect, oedema and/or ring enhancement. This constellation is often referred to as 'tumefactive multiple sclerosis'. Previous series emphasize their unifocal and clinically isolated nature, however, evolution of these lesions is not well defined. Biopsy may be required for diagnosis. We describe clinical and radiographic features in 168 patients with biopsy confirmed CNS inflammatory demyelinating disease (IDD). Lesions were analysed on pre- and post-biopsy magnetic resonance imaging (MRI) for location, size, mass effect/oedema, enhancement, multifocality and fulfilment of Barkhof criteria. Clinical data were correlated to MRI. Female to male ratio was 1.2 : 1, median age at onset, 37 years, duration between symptom onset and biopsy, 7.1 weeks and total disease duration, 3.9 years. Clinical course prior to biopsy was a first neurological event in 61%, relapsing-remitting in 29% and progressive in 4%. Presentations were typically polysymptomatic, with motor, cognitive and sensory symptoms predominating. Aphasia, agnosia, seizures and visual field defects were observed. At follow-up, 70% developed definite multiple sclerosis, and 14% had an isolated demyelinating syndrome. Median time to second attack was 4.8 years, and median EDSS at follow-up was 3.0. Multiple lesions were present in 70% on pre-biopsy MRI, and in 83% by last MRI, with Barkhof criteria fulfilled in 46% prior to biopsy and 55% by follow-up. Only 17% of cases remained unifocal. Median largest lesion size on T2-weighted images was 4 cm (range 0.5-12), with a discernible size of 2.1 cm (range 0.5-7.5). Biopsied lesions demonstrated mass effect in 45% and oedema in 77%. A strong association was found between lesion size, and presence of mass effect and/or oedema (P < 0.001). Ring enhancement was frequent. Most tumefactive features did not correlate with gender, course or diagnosis. Although lesion size >5 cm was associated with a slightly higher EDSS at last follow-up, long-term prognosis in patients with disease duration >10 years was better (EDSS 1.5) compared with a population-based multiple sclerosis cohort matched for disease duration (EDSS 3.5; P < 0.001). Given the retrospective nature of the study, the precise reason for biopsy could not always be determined. This study underscores the diagnostically challenging nature of CNS IDDs that present with atypical clinical or radiographic features. Most have multifocal disease at onset, and develop RRMS by follow-up. Although increased awareness of this broad spectrum may obviate need for biopsy in many circumstances, an important role for diagnostic brain biopsy may be required in some cases.

Vancomycin-resistant enterococcal colonization appears associated with increased mortality among allogeneic hematopoietic stem cell transplant recipients.

There are no cohort studies describing outcomes of patients colonized with vancomycin-resistant enterococci (VRE) undergoing allogeneic hematopoietic stem cell transplantation (AHSCT). We therefore conducted a retrospective cohort study of 217 consecutive adults undergoing AHSCT at the Mayo Clinic (Rochester, MN, USA) from 1998 to 2004. We analyzed the association between VRE colonization prior to transplant and 100-day post transplant mortality and morbidity. We identified 22 pretransplant VRE colonized patients and 195 non-colonized patients. Both groups had similar baseline characteristics with the following six exceptions. Colonized patients were more likely to have had pretransplant Clostridium difficile-associated diarrhea, pretransplant acute renal failure, AML, Cy/TBI conditioning, decreased platelet count at time of transplantation and myeloablative conditioning regimens. Overall, patients colonized with VRE were twice as likely to die by day 100 post transplant compared to non-colonized patients (hazard ratio: 2.1, P=0.028). This association persisted even after adjusting for differences in baseline characteristics. Increased mortality in the colonized group correlated with the presence of VRE bacteremia. Overall, pretransplant VRE colonization appears to be an independent risk factor for increased mortality post-AHSCT.