Rapid detection of periprosthetic joint infection using a combination of 16s rDNA polymerase chain reaction and lateral flow immunoassay: A Pilot Study.

OBJECTIVES: The objective of this study was to develop a test for the rapid (within 25 minutes) intraoperative detection of bacteria from synovial fluid to diagnose periprosthetic joint infection (PJI). METHODS: The 16s rDNA test combines a polymerase chain reaction (PCR) for amplification of 16s rDNA with a lateral flow immunoassay in one fully automated system. The synovial fluid of 77 patients undergoing joint aspiration or primary or revision total hip or knee surgery was prospectively collected. The cohort was divided into a proof-of-principle cohort (n = 17) and a validation cohort (n = 60). Using the proof-of-principle cohort, an optimal cut-off for the discrimination between PJI and non-PJI samples was determined. PJI was defined as detection of the same bacterial species in a minimum of two microbiological samples, positive histology, and presence of a sinus tract or intra-articular pus. RESULTS: The 16s rDNA test proved to be very robust and was able to provide a result in 97% of all samples within 25 minutes. The 16s rDNA test was able to diagnose PJI with a sensitivity of 87.5% and 82%, and a specificity of 100% and 89%, in the proof-of-principle and validation cohorts, respectively. The microbiological culture of synovial fluid achieved a sensitivity of 80% and a specificity of 93% in the validation cohort. CONCLUSION: The 16s rDNA test offers reliable intraoperative detection of all bacterial species within 25 minutes with a sensitivity and specificity comparable with those of conventional microbiological culture of synovial fluid for the detection of PJI. The 16s rDNA test performance is independent of possible blood contamination, culture time and bacterial species.Cite this article: V. Janz, J. Schoon, C. Morgenstern, B. Preininger, S. Reinke, G. Duda, A. Breitbach, C. F. Perka, S. Geissler. Rapid detection of periprosthetic joint infection using a combination of 16s rDNA polymerase chain reaction and lateral flow immunoassay: A Pilot Study. Bone Joint Res 2018;7:12-19. DOI: 10.1302/2046-3758.71.BJR-2017-0103.R2.

Feasibility of noninvasive single-channel automated differentiation of obstructive and central hypopneas with nasal airflow.

BACKGROUND: The identification of obstructive and central hypopneas is considered challenging in clinical practice. Presently, obstructive and central hypopneas are usually not differentiated or scores lack reliability due to the technical limitations of standard polysomnography. Esophageal pressure measurement is the gold-standard for identifying these events but its invasiveness deters its usage in daily practice. OBJECTIVES: To determine the feasibility and efficacy of an automatic noninvasive analysis method for the differentiation of obstructive and central hypopneas based solely on a single-channel nasal airflow signal. The obtained results are compared with gold-standard esophageal pressure scores. METHODS: A total of 41 patients underwent full night polysomnography with systematic esophageal pressure recording. Two experts in sleep medicine independently differentiated hypopneas with the gold-standard esophageal pressure signal. Features were automatically extracted from the nasal airflow signal of each annotated hypopnea to train and test the automatic analysis method. Interscorer agreement between automatic and visual scorers was measured with Cohen's kappa statistic (ĸ). RESULTS: A total of 1,237 hypopneas were visually differentiated. The automatic analysis achieved an interscorer agreement of ĸ = 0.37 and an accuracy of 69% for scorer A, ĸ = 0.40 and 70% for scorer B and ĸ = 0.41 and 71% for the agreed scores of scorers A and B. CONCLUSIONS: The promising results obtained in this pilot study demonstrate the feasibility of noninvasive single-channel hypopnea differentiation. Further development of this method may help improving initial diagnosis with home screening devices and offering a means of therapy selection and/or control.

Comparison of upper airway respiratory resistance measurements with the esophageal pressure/airflow relationship during sleep.

Measurement of upper airway resistance is of interest in sleep disordered breathing to estimate upper airway patency. Resistance is calculated with the airflow and respiratory effort signals. However, there is no consensus on a standard for upper airway resistance measurement. This study proposes a new benchmarking method to objectively compare different upper airway resistance measurement methods by objectively differentiating between breaths with inspiratory flow limitation (high resistance) and non-limited breaths (low resistance). Resistance was measured at peak-Pes, at peak-flow, at the linear portion of a polynomial equation, as an area comparative and as average resistance for an inspiration. A total of 20 patients with systematic, gold-standard esophageal pressure and nasal airflow acquisition were analyzed and 109,955 breaths were automatically extracted and evaluated. Relative resistance values in relationship to a reference resistance value obtained during wakefulness were also analyzed. The peak-Pes measurement method obtained the highest separation index with significant (p < 0.001) differences to the other methods, followed by the area comparative and the peak-flow methods. As expected, average resistances were significantly (p < 0.001) lower for the non-IFL than for the IFL group. Hence, we recommend employing the peak-Pes for accurate upper airway resistance estimation.

Automatic non-invasive differentiation of obstructive and central hypopneas with nasal airflow compared to esophageal pressure.

The differentiation of obstructive and central respiratory events is a major challenge in the diagnosis of sleep disordered breathing. Esophageal pressure (Pes) measurement is the gold-standard method to identify these events but its invasiveness deters its usage in clinical routine. Flattening patterns appear in the airflow signal during episodes of inspiratory flow limitation (IFL) and have been shown with invasive techniques to be useful to differentiate between central and obstructive hypopneas. In this study we present a new method for the automatic non-invasive differentiation of obstructive and central hypopneas solely with nasal airflow. An overall of 36 patients underwent full night polysomnography with systematic Pes recording and a total of 1069 hypopneas were manually scored by human experts to create a gold-standard annotation set. Features were automatically extracted from the nasal airflow signal to train and test our automatic classifier (Discriminant Analysis). Flattening patterns were non-invasively assessed in the airflow signal using spectral and time analysis. The automatic non-invasive classifier obtained a sensitivity of 0.71 and an accuracy of 0.69, similar to the results obtained with a manual non-invasive classification algorithm. Hence, flattening airflow patterns seem promising for the non-invasive differentiation of obstructive and central hypopneas.

Automatic differentiation of obstructive and central hypopneas with esophageal pressure measurement during sleep.

The differentiation between obstructive and central respiratory events is one of the most recurrent tasks in the diagnosis of sleep disordered breathing. Esophageal pressure measurement is the gold-standard method to assess respiratory effort and identify these events. But as its invasiveness discourages its use in clinical routine, non-invasisve systems have been proposed for differentiation. However, their adoption has been slow due to their limited clinical validation, as the creation of manual, gold-standard validation sets by human experts is a cumbersome procedure. In this study, a new system is proposed for an objective automatic, gold-standard differentiation between obstructive and central hypopneas with the esophageal pressure signal. First, an overall of 356 hypopneas of 16 patients were manually scored by a human expert to create a gold-standard validation set. Then, features were extracted from each hypopnea to train and test classifiers (Discriminant Analysis, Support Vector Machines and adaboost classifiers) to differentiate between central and obstructive hypopneas with the gold-standard esophageal pressure signal. The automatic differentiation system achieved promising results, with a sensitivity of 0.88, a specificity of 0.93 and an accuracy of 0.90. Hence, this system seems promising for an automatic, gold-standard differentiation between obstructive and central hypopneas.

Automatic classification of inspiratory flow limitation assessed non-invasively during sleep.

Detection of inspiratory flow limitation (IFL) is being recognized of increasing importance in order to diagnose pathologies related to sleep disordered breathing. Currently, IFL is usually identified with the help of invasive esophageal pressure measurement, still considered the gold-standard reference to assess respiratory effort. But the invasiveness of esophageal pressure measurement and its impact on sleep discourages its use in clinical routine. In this study, a new noninvasive automatic system is proposed for objective IFL classification. First, an automatic annotation system for IFL based on pressure/flow relationship was developed. Then, classifiers (Support Vector Machines and adaboost classifiers) were trained with these gold-standard references in order to objectively classify breaths non-invasively, solely based on the breaths' flow contours. The new non-invasive automatic classification system seems to be promising, as it achieved a sensitivity of 0.92 and a specificity of 0.89, outperforming prior classification results obtained by human experts.

Characterization of inspiratory flow limitation during sleep with an exponential model.

Assessing incidence and severity of inspiratory flow limitation (IFL) is of importance for patients suffering of sleep disordered breathing (SDB) in order to diagnose a spectrum of different pathologies. In this study a new exponential equation is proposed to characterize the pressure/flow relationship of IFL and non-IFL breaths. Classical and alternative criteria are applied on the model's predictions in order to assess IFL, and its outcome is compared to the outcome of other models. The newly proposed exponential model seems to be promising, as it outperforms other models by achieving a global average sensitivity of 93% and specificity of 91%, and the lowest mean square error when estimating resistance at peak pressure. Additional statistical tests were performed on the exponential model's coefficients in order to determine if a coefficient based classification is possible.

[Accidental cannulation of the hepatic artery following needle-knife sphincterotomy]. / Akzidentelle Sondierung der A. hepatica im Rahmen der Nadelmessersphincterotomie.

The use of needle-knife sphincterotomy has become an established technique for precut sphincterotomy to achieve am otherwise inaccessible bile duct. The present case report describes an accidental cannulation of the proper hepatic artery following needle-knife sphincterotomy. The endoscopic retrograde cholangiopancreaticography (ERCP) was performed for diagnosis and treatment of a pancreatitis presumably caused by cholelithiasis. After guide-wire placement and angiography of the artery through the papilla, there were no further complications. The distance between the catheter and the hepatic hilus was seen under X-ray control.

The efficacy of Ginkgo special extract EGb 761 in patients with tinnitus.

OBJECTIVE: The objective of the present study in 60 patients with chronic tinnitus aurium was to confirm the efficacy of oral treatment with 2 x 80 mg Ginkgo special extract EGb 761 per day subsequent to 10-day EGb 761 infusion treatment. METHODS: Patients with chronic tinnitus aurium underwent 10 days of in-patient infusion treatment with 200 mg/day EGb 761, after which they were randomized to double-blind, oral out-patient treatment with either 2 x 80 mg/day EGb 761 or placebo, given over a scheduled treatment period of 12 weeks. The primary outcome measure was the change in tinnitus volume in the more severely affected ear during randomized treatment. RESULTS: Fifty-two of 60 patients (89.7%) completed the infusion treatment; complete sets of data were available for 40 (66.7%), 30 (50.0%) and 22 (36.7%) patients after 4, 8 and 12 weeks of randomized treatment, respectively. For the primary outcome measure, significant superiority of EGb 761 over placebo was demonstrated in the intention-to-treat analysis data set after 4, 8 and 12 weeks of out-patient treatment (p < 0.05, 1-tailed), although the absolute treatment group difference was moderate. The results were supported by the secondary outcome measures for efficacy (e.g. decreased hearing loss, improved self-assessment of subjective impairment). During out-patient treatment, there were no attributable adverse events under EGb 761. CONCLUSIONS: A combination of infusion therapy followed by oral administration of Ginkgo special extract EGb 761 appears to be effective and safe in alleviating the symptoms associated with tinnitus aurium.

Transcranial power-mode duplex ultrasound in two patients with moyamoya syndrome.

Moyamoya syndrome is characterized by the reticulated collateralization of the intracranial vasculature distal to an occlusion of proximal intracranial vessels. In the present study this pathology was visualized in 2 patients, aged 29 and 32 years, using transcranial color Doppler imaging (TCDI). Digital subtraction angiography in both patients revealed stenosis of the intracranial portion of the internal carotid arteries, occlusion and stenosis of several cerebral arteries, and a bilateral reticulated collateral network particularly in the region of both basal ganglia, typical of moyamoya syndrome. TCDI with power-mode Doppler depicted parts of the intracranial collateral network, not possible using conventional color-flow Doppler. TCDI with power-mode Doppler permitted better visualization of intracranial vascular pathology in comparison to conventional color-flow Doppler, enabling a rapid and noninvasive diagnosis of rare cerebrovascular anomalies.

Three-dimensional ultrasound angiography (power mode) for the quantification of carotid artery atherosclerosis.

Three-dimensional (3D) ultrasound angiography was performed to diagnose carotid artery atherosclerosis. Thirty-five patients (15 women, 20 men) with a history of cerebrovascular disease were examined using conventional color-coded Doppler ultrasound and 3D ultrasound angiography. Carotid stenosis was initially diagnosed using continuous-wave Doppler ultrasound. To determine intraobserver and interobserver reliabilities, 21 patients were evaluated using 3D ultrasound on three occasions. Sixty-five percent of patients were diagnosed with stenosis of more than 50%. Twenty-two percent of plaques had a smooth surface, 72.9% were ulcerated, and 5.1% were indeterminate. Data collection for 3D imaging required 5 minutes per patient, whereas image processing and plaque volume quantification required 30 minutes. Plaque volume ranged from 0.053 to 0.685 ml. The intraobserver and interobserver variabilities were 4.16 and 5.87%, respectively (r = 0.96, p < 0.0001; r = 0.89, p < 0.0001). 3D Color Doppler and 3D ultrasound angiography assessments of plaque volume differed by 8.5%. Plaques were more precisely differentiated using 3D ultrasound, and plaque volume quantification was less affected by echo shadowing after 3D reconstruction. In comparison to other techniques for the quantification of atherosclerotic lesions. 3D ultrasound angiography offers a more precise quantitative method for prospective, clinical studies of atherosclerosis.

Cerebrovascular disease assessed by color-flow and power Doppler ultrasonography. Comparison with digital subtraction angiography in internal carotid artery stenosis.

BACKGROUND AND PURPOSE: An understanding of carotid atherosclerosis is important to further our knowledge regarding the etiology of cerebral ischemia, and therefore it is necessary to accurately visualize carotid stenosis. The purpose of the present study was to compare different imaging techniques to determine their advantages and disadvantages in the diagnosis and quantification of middle- and high-grade internal carotid artery stenosis. In particular, we were interested in evaluating the effectiveness of the new ultrasound technique power Doppler. METHODS: Fifty-four patients with greater than 50% extracranial internal carotid artery stenosis, as determined by continuous-wave Doppler, were recruited prospectively to serve as subjects. All subjects were examined with color-flow Doppler, power Doppler, and digital subtraction angiography to enable visualization of carotid stenosis and plaque surface morphology. RESULTS: Thirty-four middle-grade stenoses (50% to 69%), 32 high-grade stenoses (70% to 99%), and 7 complete occlusions of the internal carotid artery were diagnosed with the use of digital subtraction angiography. Power Doppler visualized stenosis significantly more frequently and accurately than color-flow Doppler. Color-flow Doppler tended to overestimate and underestimate in patients with both middle- and high-grade stenosis. Power Doppler was superior to both color-flow Doppler and angiography with regard to differentiation of plaque surface morphology. CONCLUSIONS: This study demonstrates that power Doppler is an important, noninvasive imaging technique that has several advantages over color-flow Doppler in diagnosing carotid artery stenosis and visualizing plaque surface. Power Doppler, used in concert with other ultrasound techniques, should enable a more accurate detection and treatment of cerebrovascular disease.

The efferent innervation of outer hair cells in humans: physiological investigations.

We report on a case of reversible pontine deafness caused by multiple sclerotic lesions in the pons, and describe six experiments in humans, in whom we recorded transient otoacoustic emissions and distortion products. Our findings indicate an inhibitory effect of efferent innervation on the motility of outer hair cells in humans. Otoacoustic emissions increased in patients with unilateral deafness after the central part of the efferent pathway was destroyed (pontine deafness). Otoacoustic emissions also increased in patients with myasthenia gravis after the administration of an acetylcholinesterase inhibitor. General myotonia (Batter-Curschmann-Steinert Syndrome) resulted in mild sensorineural hearing loss, and in the absence of contralateral inhibition of otoacoustic emissions. Otoacoustic emissions decreased gradually under general anesthesia with muscle relaxation. Contralateral acoustic stimulation was seen during anaesthesia with muscle relaxation.

Immunohistochemical findings of IgG recognized in the planum semilunatum of the guinea pig.

The planum semilunatum is located on the lateral side of the crista ampullaris of the semicircular canal. With regard to the functions of the planum semilunatum, some researchers assume the existence of secretory activity based on the microstructural features observed in isotopic experiments. In the present study, in order to confirm the existence of an immunological mechanism in the ampulla of the semicircular canal, the distribution of immunoglobulins in the semi-circular canal of guinea pigs was investigated immunohistochemically. Positivity of IgG was observed in the constituent cells of the planum semilunatum or beneath the basement membrane of the cells. It is concluded that ample IgG, which is an important constituent of the body fluids, is collected within this region. The planum semilunatum containing such ample amounts of IgG might be involved in the immunological mechanism operating in the ampullar of the semicircular canal.

[Assessment of central disorders of the statoacusticus nerve using high resolution imaging procedures (PET and MRI)]. / Beurteilung von zentralen Störungen des N. statoacusticus mittels hochauflösender bildgebender Verfahren (PET und MRT).

Disorders of the auditory and vestibular central nervous system can be diagnosed more precisely by high resolution magnetic resonance imaging (MRI) and positron emission tomography (PET). MRI is mostly used for small intrameatal acoustic neuromas up to 10 mm, intracranial cholesteatomas, and multiple sclerosis. Positron emission tomography has advantages after acoustic or electric stimulation in the auditory cortex. PET is not yet a routine procedure in clinical diagnosis.

Immune response of the endolymphatic sac to horseradish peroxidase: immunologic route from the middle ear to the inner ear.

Twenty guinea pigs were immunized with horseradish peroxidase (HRP) intradermally and challenged with 5 mg of the same antigen in the tympanic bulla. The appearance of immunoglobulin-producing cells (plasma cells) in the inner ear structure was examined immunohistochemically in frozen sections. Four to 10 days following antigen challenge, 5 of the 20 animals showed significantly increased plasma cells in the subepithelial connective tissue of the endolymphatic sac (ES). Those cells showed positive reactions, mainly with IgG followed by IgM. The cells that reacted positively with IgA were few. Some of these plasma cells were considered to contain the specific antibody against HRP. The results indicate the role of the ES as a local immune response region for the inner ear complex, as well as the existence of an immunologic route from the middle ear cavity to the inner ear, particularly to the ES.

[Cytomegalovirus infection and inner ear deafness]. / Zytomegalieinfektion und Innenohrschwerhörigkeit.

Bilateral sensorineural hearing loss of patients is correlated with elevated antibody titres against cytomegaly virus in serum in children as well as in adults. Unilateral deafness correlates with mumps infection. This is shown in a German population as well as in a Mediterranean group of patients. There is no evidence between antibody titer of Coxsackie virus, adenovirus and herpes virus or toxoplasma gondii interaction and sensorineural hearing loss neither unilaterally nor bilaterally.