Screening for carriage of methicillin-resistant Staphylococcus aureus shortly after exposure may lead to false-negative results

We evaluated a double screening strategy for carriage of methicillin-resistant Staphylococcus aureus (MRSA) in patients exposed to a newly detected MRSA carrier. If the first screening of the exposed patient yielded negative results, screening was repeated 4 days later. This strategy detected 12 (28%) of the 43 new MRSA carriers identified during the study period. The results suggest that there is an incubation period before MRSA carriage is detectable.

Testing an alternative search algorithm for compound identification with the 'Wiley Registry of Tandem Mass Spectral Data. MSforID'

A tandem mass spectral database system consists of a library of reference spectra and a search program. State-of-the-art search programs show a high tolerance for variability in compound-specific fragmentation patterns produced by collision-induced decomposition and enable sensitive and specific 'identity search'. In this communication, performance characteristics of two search algorithms combined with the 'Wiley Registry of Tandem Mass Spectral Data, MSforID' (Wiley Registry MSMS, John Wiley and Sons, Hoboken, NJ, USA) were evaluated. The search algorithms tested were the MSMS search algorithm implemented in the NIST MS Search program 2.0g (NIST, Gaithersburg, MD, USA) and the MSforID algorithm (John Wiley and Sons, Hoboken, NJ, USA). Sample spectra were acquired on different instruments and, thus, covered a broad range of possible experimental conditions or were generated in silico. For each algorithm, more than 30,000 matches were performed. Statistical evaluation of the library search results revealed that principally both search algorithms can be combined with the Wiley Registry MSMS to create a reliable identification tool. It appears, however, that a higher degree of spectral similarity is necessary to obtain a correct match with the NIST MS Search program. This characteristic of the NIST MS Search program has a positive effect on specificity as it helps to avoid false positive matches (type I errors), but reduces sensitivity. Thus, particularly with sample spectra acquired on instruments differing in their Setup from tandem-in-space type fragmentation, a comparably higher number of false negative matches (type II errors) were observed by searching the Wiley Registry MSMS.

Biomarker-guided personalised emergency medicine for all - hope for another hype?

Polymorbid patients, diverse diagnostic and therapeutic options, more complex hospital structures, financial incentives, benchmarking, as well as perceptional and societal changes put pressure on medical doctors, specifically if medical errors surface. This is particularly true for the emergency department setting, where patients face delayed or erroneous initial diagnostic or therapeutic measures and costly hospital stays due to sub-optimal triage. A "biomarker" is any laboratory tool with the potential better to detect and characterise diseases, to simplify complex clinical algorithms and to improve clinical problem solving in routine care. They must be embedded in clinical algorithms to complement and not replace basic medical skills. Unselected ordering of laboratory tests and shortcomings in test performance and interpretation contribute to diagnostic errors. Test results may be ambiguous with false positive or false negative results and generate unnecessary harm and costs. Laboratory tests should only be ordered, if results have clinical consequences. In studies, we must move beyond the observational reporting and meta-analysing of diagnostic accuracies for biomarkers. Instead, specific cut-off ranges should be proposed and intervention studies conducted to prove outcome relevant impacts on patient care. The focus of this review is to exemplify the appropriate use of selected laboratory tests in the emergency setting for which randomised-controlled intervention studies have proven clinical benefit. Herein, we focus on initial patient triage and allocation of treatment opportunities in patients with cardiorespiratory diseases in the emergency department. The following five biomarkers will be discussed: proadrenomedullin for prognostic triage assessment and site-of-care decisions, cardiac troponin for acute myocardial infarction, natriuretic peptides for acute heart failure, D-dimers for venous thromboembolism, C-reactive protein as a marker of inflammation, and procalcitonin for antibiotic stewardship in infections of the respiratory tract and sepsis. For these markers we provide an overview on physiopathology, historical evolution of evidence, strengths and limitations for a rational implementation into clinical algorithms. We critically discuss results from key intervention trials that led to their use in clinical routine and potential future indications. The rational for the use of all these biomarkers, first, tackle diagnostic ambiguity and consecutive defensive medicine, second, delayed and sub-optimal therapeutic decisions, and third, prognostic uncertainty with misguided triage and site-of-care decisions all contributing to the waste of our limited health care resources. A multifaceted approach for a more targeted management of medical patients from emergency admission to discharge including biomarkers, will translate into better resource use, shorter length of hospital stay, reduced overall costs, improved patients satisfaction and outcomes in terms of mortality and re-hospitalisation. Hopefully, the concepts outlined in this review will help the reader to improve their diagnostic skills and become more parsimonious laboratory test requesters.

Multicentre validation study of nucleic acids extraction from FFPE tissues

In most pathology laboratories worldwide, formalin-fixed paraffin embedded (FFPE) samples are the only tissue specimens available for routine diagnostics. Although commercial kits for diagnostic molecular pathology testing are becoming available, most of the current diagnostic tests are laboratory-based assays. Thus, there is a need for standardized procedures in molecular pathology, starting from the extraction of nucleic acids. To evaluate the current methods for extracting nucleic acids from FFPE tissues, 13 European laboratories, participating to the European FP6 program IMPACTS (www.impactsnetwork.eu), isolated nucleic acids from four diagnostic FFPE tissues using their routine methods, followed by quality assessment. The DNA-extraction protocols ranged from homemade protocols to commercial kits. Except for one homemade protocol, the majority gave comparable results in terms of the quality of the extracted DNA measured by the ability to amplify differently sized control gene fragments by PCR. For array-applications or tests that require an accurately determined DNA-input, we recommend using silica based adsorption columns for DNA recovery. For RNA extractions, the best results were obtained using chromatography column based commercial kits, which resulted in the highest quantity and best assayable RNA. Quality testing using RT-PCR gave successful amplification of 200 bp-250 bp PCR products from most tested tissues. Modifications of the proteinase-K digestion time led to better results, even when commercial kits were applied. The results of the study emphasize the need for quality control of the nucleic acid extracts with standardised methods to prevent false negative results and to allow data comparison among different diagnostic laboratories.

Indocyanine green fluorescence-guided sentinel lymph node biopsy in dermato-oncology

Sentinel lymph node biopsy (SLNB) for cutaneous malignancies usually carried out with radioactive nanocolloids (Tc-99m). The SLNE is controversially discussed internationally. This is especially given to the high false-negative rate up to 44 %. An alternative could be the fluorescent dye indocyanine green (ICG).

Intraobserver and interobserver agreement for results of low-field magnetic resonance imaging in dogs with and without clinical signs of disk-associated wobbler syndrome

OBJECTIVE: To determine interobserver and intraobserver agreement for results of low-field magnetic resonance imaging (MRI) in dogs with and without disk-associated wobbler syndrome (DAWS). DESIGN: Validation study. ANIMALS: 21 dogs with and 23 dogs without clinical signs of DAWS. PROCEDURES: For each dog, MRI of the cervical vertebral column was performed. The MRI studies were presented in a randomized sequence to 4 board-certified radiologists blinded to clinical status. Observers assessed degree of disk degeneration, disk-associated and dorsal compression, alterations in intraspinal signal intensity (ISI), vertebral body abnormalities, and new bone formation and categorized each study as originating from a clinically affected or clinically normal dog. Interobserver agreement was calculated for 44 initial measurements for each observer. Intraobserver agreement was calculated for 11 replicate measurements for each observer. RESULTS: There was good interobserver agreement for ratings of disk degeneration and vertebral body abnormalities and moderate interobserver agreement for ratings of disk-associated compression, dorsal compression, alterations in ISI, new bone formation, and suspected clinical status. There was very good intraobserver agreement for ratings of disk degeneration, disk-associated compression, alterations in ISI, vertebral body abnormalities, and suspected clinical status. There was good intraobserver agreement for ratings of dorsal compression and new bone formation. Two of 21 clinically affected dogs were erroneously categorized as clinically normal, and 4 of 23 clinically normal dogs were erroneously categorized as clinically affected. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggested that variability exists among observers with regard to results of MRI in dogs with DAWS and that MRI could lead to false-positive and false-negative assessments.

Different fever definitions and the rate of fever and neutropenia diagnosed in children with cancer: a retrospective two-center cohort study

Background. The definition of fever, and thus fever and neutropenia (FN), varies between different pediatric oncology centers. Higher temperature limit should reduce FN rates, but may increase rates of FN with complications by delaying therapy. This study determined if different fever definitions are associated with different FN rates. Procedure. Two pediatric oncology centers had used three fever definitions in 2004–2011: ear temperature >=38.5°C persisting >=2 hours (low definition); axillary temperature >=38.5°C >=2 hours or >=39.0°C once (middle); and ear temperature >=39.0°C once (high). Clinical information was retrospectively extracted from charts. FN rates were compared using mixed Poisson regression. Results. In 521 pediatric patients with cancer, 783 FN were recorded during 6,009 months cumulative chemotherapy exposure time (501 years; rate, 0.13/month [95% CI, 0.12–0.14]), 124 of them with bacteremia (16%; 0.021/month [0.017–0.025]). In univariate analysis, the high versus low fever definition was associated with a lower FN rate (0.10/month [0.08–0.11] vs. 0.15/month [0.13–0.16]; rate ratio, 0.66 [0.45–0.97]; P ¼ 0.036), the middle definition was intermediate (0.13/month [0.11–0.15]). This difference was not confirmed in multivariate analysis (rate ratio, 0.94 [0.67–1.33]; P ¼ 0.74). The high versus low definition was not associated with an increased rate of FN with bacteremia (multivariate rate ratio, 1.39 [0.53–3.62]; P ¼ 0.50). Conclusion. A higher fever definition was not associated with a lower FN rate, nor with an increased rate of FN with bacteremia. These may be false negative findings due to methodological limitations. These questions, with their potential impact on health-related quality of life, and on costs, need to be assessed in prospective studies.

Is there an indication for frozen section examination of the ureteral margins during cystectomy for transitional cell carcinoma of the bladder?

PURPOSE: We evaluated the incidence of pathological findings of the ureter at cystectomy for transitional cell carcinoma of the bladder and assessed the usefulness of intraoperative frozen section examination of the ureter. MATERIALS AND METHODS: Histopathological findings of ureteral frozen section examination were compared to the corresponding permanent sections and the diagnostic accuracy of frozen section examination was evaluated. These segments were then compared to the more proximal ureteral segments resected at the level where they cross over the common iliac arteries. The histopathological findings of the ureteral segments were then correlated for upper urinary tract recurrence and overall survival. RESULTS: Transitional cell carcinoma or carcinoma in situ was found on frozen section examination of the distal ureter in 39 of 805 patients (4.8%) and on permanent sections in 29 (3.6%). In 755 patients the false-negative rate of frozen section examination of the ureters was 0.8%. Of the patients with carcinoma in situ diagnosed on the first frozen section examination 80% also had carcinoma in situ in the bladder. Transitional cell carcinoma or carcinoma in situ in the most proximally resected ureteral segments was found in 1.2% of patients. After radical cystectomy there was tumor recurrence in the upper urinary tract in 3% of patients with negative ureteral frozen section examination and in 17% with carcinoma in situ on frozen section examination. CONCLUSIONS: Routine frozen section examination of the ureters at radical cystectomy is only recommended for patients with carcinoma in situ of the bladder, provided the ureters are resected where they cross the common iliac arteries.

Ultrasound diagnosis of spontaneous carotid dissection with isolated Horner syndrome

BACKGROUND AND PURPOSE: Isolated Horner syndrome without associated cranial nerve palsies or ischemic symptoms is an important presentation of spontaneous internal carotid artery dissection (sICAD). Ultrasound is often used as a screening method in these patients because cervical MRI is not always available on an emergency basis. Current knowledge on ultrasound findings in patients with sICAD presenting with isolated Horner syndrome is limited. METHODS: Patients were recruited from prospective cervical artery dissection databases of 3 tertiary care centers. Diagnosis of sICAD was confirmed by cervical MRI and MR angiography or digital subtraction angiography in all patients. Data on Doppler sonography and color duplex sonography examinations performed within 30 days of symptom onset were analyzed. RESULTS: We identified 88 patients with Horner syndrome as the only sign of sICAD. Initial ultrasound examination was performed in 72 patients after a mean time interval from symptom onset to examination of 11 (SD 8) days. The overall frequency of false-negative ultrasound findings was 31% (22 of 72 patients). It showed stenosis >or=80% or occlusion in 34 (47%) patients, and stenosis

Comparison of tendency-oriented perimetry and dynamic strategy in octopus perimetry as a screening tool in a clinical setting: a prospective study

OBJECTIVE: The aim of this study was to compare the results of tendency-oriented perimetry (TOP) and a dynamic strategy in octopus perimetry as screening methods in clinical practice. DESIGN: A prospective single centre observational case series was performed. PARTICIPANTS AND METHODS: In a newly opened general ophthalmologic practice 89 consecutive patients (171 eyes) with a clinical indication for octopus static perimetry testing (ocular hypertension or suspicious optic nerve cupping) were examined prospectively with TOP and a dynamic strategy. The visual fields were graded by 3 masked observers as normal, borderline or abnormal without any further clinical information. RESULTS: 83% eyes showed the same result for both strategies. In 14% there was a small difference (with one visual field being abnormal or normal, the other being borderline). In only 2.9% of the eyes (5 cases) was there a contradictory result. In 4 out of 5 cases the dynamic visual field was abnormal and TOP was normal. 4 of these cases came back for a second examination. In all 4 the follow-up examination showed a normal second dynamic visual field. CONCLUSIONS: Octopus static perimetry using a TOP strategy is a fast, patient-friendly and very reliable screening tool for the general ophthalmological practice. We found no false-negative results in our series.

Laryngeal and hypopharyngeal carcinomas after (chemo)radiotherapy: a diagnostic dilemma

PURPOSE OF REVIEW: During recent years, (chemo)radiotherapy has evolved into a primary treatment modality for both early and advanced laryngeal and hypopharyngeal carcinomas. Head and neck surgeons will be concerned more frequently with patients presenting symptoms and signs suggesting recurrent tumor or complications of (chemo)radiotherapy. RECENT FINDINGS: Analysis of histologic characteristics and tumor spread of recurrent carcinomas on whole-organ slices of salvage laryngectomy specimens showed that recurrent laryngeal carcinomas are often present with multiple tumor foci dispersed in different regions; furthermore, they may develop beneath an intact mucosa. Only a few articles analyze the reliability of laryngoscopy and biopsy in detecting recurrences after (chemo)radiotherapy: the number of false negative biopsies is relatively high. The differentiation between radionecrosis and tumor recurrence is difficult by computed tomography scan and magnetic resonance imaging in many cases. Positron emission tomography-computed tomography and diffusion-weighted magnetic resonance imaging are promising diagnostic modalities to detect or exclude persistent or recurrent disease after (chemo)radiotherapy. SUMMARY: Endoscopy with biopsy, computed tomography scan and conventional magnetic resonance imaging present several deficiencies in diagnosing recurrent disease after (chemo)radiotherapy. New imaging modalities such as positron emission tomography-computed tomography and diffusion-weighted magnetic resonance imaging show promising results, increasing the diagnostic efficacy.

[Goiter and nodular thyroid disease: clinical guidelines for diagnosis and treatment. (Waiting? Hormone therapy? Surgery? radioiodine?)]

Nodular thyroid disease is a common problem. We present clinical guidelines for the management of patients with thyroid nodules, multinodular goiters and thyroid cysts for use by primary physicians. In the initial evaluation ultrasonography of the thyroid and fine-needle aspiration biopsy (FNAB) is recommended. FNAB has become the cornerstone in the evaluation of solitary thyroid nodules, cysts and dominant nodules within multinodular goiters. If the procedure is done properly, it should have a false-negative rate of less than 5% and a false-positive rate of not more than 1%. Thyroid radionuclide scans are less frequently used in the initial evaluation of a nodular goiter. Surgery is the primary therapy for patients with nodular thyroid disease. Other available treatment options are radioiodine and TSH-suppression with thyroxine. The main indications for surgery in euthyroid patients with thyroid nodule or with nontoxic multinodular goiter are recently documented or suspected malignancy, compression of the trachea and esophagus, significant growth of the nodule, recurrence of a cyst after aspiration, neck discomfort and cosmetic concern.

The accuracy of FAST in relation to grade of solid organ injuries: a retrospective analysis of 226 trauma patients with liver or splenic lesion

BACKGROUND: This study investigated the role of a negative FAST in the diagnostic and therapeutic algorithm of multiply injured patients with liver or splenic lesions. METHODS: A retrospective analysis of 226 multiply injured patients with liver or splenic lesions treated at Bern University Hospital, Switzerland. RESULTS: FAST failed to detect free fluid or organ lesions in 45 of 226 patients with spleen or liver injuries (sensitivity 80.1%). Overall specificity was 99.5%. The positive and negative predictive values were 99.4% and 83.3%. The overall likelihood ratios for a positive and negative FAST were 160.2 and 0.2. Grade III-V organ lesions were detected more frequently than grade I and II lesions. Without the additional diagnostic accuracy of a CT scan, the mean ISS of the FAST-false-negative patients would be significantly underestimated and 7 previously unsuspected intra-abdominal injuries would have been missed. CONCLUSION: FAST is an expedient tool for the primary assessment of polytraumatized patients to rule out high grade intra-abdominal injuries. However, the low overall diagnostic sensitivity of FAST may lead to underestimated injury patterns and delayed complications may occur. Hence, in hemodynamically stable patients with abdominal trauma, an early CT scan should be considered and one must be aware of the potential shortcomings of a "negative FAST".

Forget the blood, not the stone! Microhaematuria in acute urolithiasis and the role of early CT scanning

BACKGROUND: Although urinalysis is simple and inexpensive to perform, the finding of microhaematuria on urinalysis may be unreliable for diagnosing urolithiasis. OBJECTIVE: To evaluate microhaematuria as a diagnostic marker for urolithiasis compared with low-dose unenhanced multidetector computed tomography (MDCT) as the "gold standard". SETTING: A level 1 emergency department in a tertiary referral university teaching hospital. DESIGN: Retrospective analysis. METHODS: A study was undertaken to assess whether the finding of microhaematuria was diagnostic for urolithiasis using a low-dose unenhanced MDCT-based diagnosis as the reference standard by reviewing the records of all patients who presented to the emergency department with colicky flank pain and underwent a CT scan between January 2003 and December 2005. RESULTS: Urolithiasis was present (as defined by low-dose unenhanced MDCT) in 507/638 patients (79%); 341/638 (53%) were true positive for urolithiasis, 76 (12%) were true negative, 55 (9%) were false positive and 166 (26%) were false negative. Microhaematuria as a test for urolithiasis in patients presenting to the emergency department therefore has a sensitivity, specificity, positive predictive value and negative predictive value of 67%, 58%, 86% and 31%, respectively. 58% of the urinalysis results were negative for haematuria in the subset of patients with significant alternative diagnoses. CONCLUSIONS: The sensitivity, specificity and negative predictive value of microhaematuria on urinalysis for urolithiasis using unenhanced MDCT as the reference standard were low. This suggests that, when urolithiasis is clinically suspected, unenhanced MDCT is indicated without urinalysis being a prerequisite.

Pelvic radiography in ATLS algorithms: A diminishing role?

ABSTRACT: BACKGROUND: Pelvic x-ray is a routine part of the primary survey of polytraumatized patients according to Advanced Trauma Life Support (ATLS) guidelines. However, pelvic CT is the gold standard imaging technique in the diagnosis of pelvic fractures. This study was conducted to confirm the safety of a modified ATLS algorithm omitting pelvic x-ray in hemodynamically stable polytraumatized patients with clinically stable pelvis in favour of later pelvic examination by CT scan. METHODS: We conducted a retrospective analysis of all polytraumatized patients in our emergency room between 01.07.2004 and 31.01.2006. Inclusion criteria were blunt abdominal trauma, initial hemodynamic stability and a stable pelvis on clinical examination. We excluded patients requiring immediate intervention because of hemodynamic instability. RESULTS: We reviewed the records of n = 452 polytraumatized patients, of which n = 91 fulfilled inclusion criteria (56% male, mean age = 45 years). The mechanism of trauma included 43% road traffic accidents, 47% falls. In 68/91 (75%) patients, both a pelvic x-ray and a CT examination were performed; the remainder had only pelvic CT. In 6/68 (9%) patients, pelvic fracture was diagnosed by pelvic x-ray. None of these 6 patients was found having a false positive pelvic x-ray, i.e. there was no fracture on pelvic CT scan. In 3/68 (4%) cases a fracture was missed in the pelvic x-ray, but confirmed on CT (false negative on x-ray). None of the diagnosed fractures needed an immediate therapeutic intervention. 5 (56%) were classified type A fractures, and another 4 (44%) B 2.1 in computed tomography (AO classification). One A 2.1 fracture was found in a clinically stable patient who only received CT scan (1/23). CONCLUSION: While pelvic x-ray is an integral part of ATLS assessment, this retrospective study suggests that in hemodynamically stable patients with clinically stable pevis, its sensitivity is only 67% and it may safely be omitted in favor of a pelvic CT examination if such is planned in adjunct assessment and available. The results support the safety and utility of our modified ATLS algorithm. A randomized controlled trial using the algorithm can safely be conducted to confirm the results.