Accuracy of comprehensive PCR analysis of nasopharyngeal and oropharyngeal swabs for CT-scan-confirmed pneumonia in elderly patients: a prospective cohort study.

OBJECTIVES: We aimed to assess the accuracy of PCR detection of viruses and bacteria on nasopharyngeal and oropharyngeal swabs (NPS) for the diagnosis of pneumonia in elderly individuals. METHODS: We included consecutive hospitalized elderly individuals suspected of having pneumonia. At inclusion, NPS were collected from all participants and tested by PCR for the presence of viral and bacterial respiratory pathogens (index test, defined as comprehensive molecular testing). Routine diagnostic tests (blood and sputum culture, urine antigen detection) were also performed. The reference standard was the presence of pneumonia on a low-dose CT scan as assessed by two independent expert radiologists. RESULTS: The diagnosis of pneumonia was confirmed in 127 of 199 (64%) included patients (mean age 83 years, community-acquired pneumonia in 105 (83%)). A pathogen was identified by comprehensive molecular testing in 114 patients (57%) and by routine methods in 22 (11%). Comprehensive molecular testing was positive for viruses in 62 patients (31%) and for bacteria in 73 (37%). The sensitivity and specificity were 61% (95% CI 53%-69%) and 50% (95% CI 39%-61%) for comprehensive molecular testing, and 14% (95% CI 82%-21%) and 94% (95% CI 86%-98%) for routine testing, respectively. Positive likelihood ratio was 2.55 for routine methods and 1.23 for comprehensive molecular testing. CONCLUSION: Comprehensive molecular testing of NPS increases the number of pathogens detected compared with routine methods, but results are poorly predictive of the presence of pneumonia. Hence, comprehensive molecular testing is unlikely to impact clinical decision-making (NCT02467192). CLINICAL TRIALS REGISTRATION: NCT02467192.

Pancreatic ß-cell imaging in humans: fiction or option?

Diabetes mellitus is a growing worldwide epidemic disease, currently affecting 1 in 12 adults. Treatment of disease complications typically consumes ∼10% of healthcare budgets in developed societies. Whilst immune-mediated destruction of insulin-secreting pancreatic ß cells is responsible for Type 1 diabetes, both the loss and dysfunction of these cells underly the more prevalent Type 2 diabetes. The establishment of robust drug development programmes aimed at ß-cell restoration is still hampered by the absence of means to measure ß-cell mass prospectively in vivo, an approach which would provide new opportunities for understanding disease mechanisms and ultimately assigning personalized treatments. In the present review, we describe the progress towards this goal achieved by the Innovative Medicines Initiative in Diabetes, a collaborative public-private consortium supported by the European Commission and by dedicated resources of pharmaceutical companies. We compare several of the available imaging methods and molecular targets and provide suggestions as to the likeliest to lead to tractable approaches. Furthermore, we discuss the simultaneous development of animal models that can be used to measure subtle changes in ß-cell mass, a prerequisite for validating the clinical potential of the different imaging tracers.

Early detection of lung cancer: a statement from an expert panel of the Swiss university hospitals on lung cancer screening.

The discussion about setting up a program for lung cancer screening was launched with the publication of the results of the National Lung Screening Trial, which suggested reduced mortality in high-risk subjects undergoing CT screening. However, important questions about the benefit-harm balance and the details of a screening program and its cost-effectiveness remain unanswered. A panel of specialists in chest radiology, respiratory medicine, epidemiology, and thoracic surgery representing all Swiss university hospitals prepared this joint statement following several meetings. The panel argues that premature and uncontrolled introduction of a lung cancer screening program may cause substantial harm that may remain undetected without rigorous quality control. This position paper focuses on the requirements of running such a program with the objective of harmonizing efforts across the involved specialties and institutions and defining quality standards. The underlying statement includes information on current evidence for a reduction in mortality with lung cancer screening and the potential epidemiologic implications of such a program in Switzerland. Furthermore, requirements for lung cancer screening centers are defined, and recommendations for both the CT technique and the algorithm for lung nodule assessment are provided. In addition, related issues such as patient management, registry, and funding are addressed. Based on the current state of the knowledge, the panel concludes that lung cancer screening in Switzerland should be undertaken exclusively within a national observational study in order to provide answers to several critical questions before considering broad population-based screening for lung cancer.

Deficiency in the NADPH oxidase 4 predisposes towards diet-induced obesity.

OBJECTIVE: NADPH oxidase 4 (NOX4) is a reactive oxygen species (ROS) producing NADPH oxidase that regulates redox homeostasis in diverse insulin-sensitive cell types. In particular, NOX4-derived ROS is a key modulator of adipocyte differentiation and mediates insulin receptor signaling in mature adipocytes in vitro. Our study was aimed at investigating the role of NOX4 in adipose tissue differentiation, whole body metabolic homeostasis and insulin sensitivity in vivo. DESIGN: Mice with genetic ablation of NOX4 (NOX4-deficient mice) were subjected to chow or high-fat-containing diet for 12 weeks. Body weight gain, adiposity, insulin sensitivity, and adipose tissue and liver gene and protein expression were analyzed and compared with similarly treated wild-type mice. RESULTS: Here, we report that NOX4-deficient mice display latent adipose tissue accumulation and are susceptible to diet-induced obesity and early onset insulin resistance. Obesity results from accelerated adipocyte differentiation and hypertrophy, and an increase in whole body energy efficiency. Insulin resistance is associated with increased adipose tissue hypoxia, inflammation and adipocyte apoptosis. In the liver, more severe diet-induced steatosis was observed due to the lack of proper upregulation of mitochondrial fatty acid ß-oxidation. CONCLUSION: These findings identify NOX4 as a regulator of metabolic homeostasis. Moreover, they indicate an anti-adipogenic role for NOX4 in vivo and reveal its function as a protector against the development of diet-induced obesity, insulin resistance and hepatosteatosis.

Chronic mTOR inhibition by rapamycin induces muscle insulin resistance despite weight loss in rats.

BACKGROUND AND PURPOSE: mTOR inhibitors are currently used as immunosuppressants in transplanted patients and as promising anti-cancer agents. However, new-onset diabetes is a frequent complication occurring in patients treated with mTOR inhibitors such as rapamycin (Sirolimus). Here, we investigated the mechanisms associated with the diabetogenic effects of chronic Sirolimus administration in rats and in in vitro cell cultures. EXPERIMENTAL APPROACH: Sirolimus was administered to rats fed either a standard or high-fat diet for 21 days. Metabolic parameters were measured in vivo and in ex vivo tissues. Insulin sensitivity was assessed by glucose tolerance tests and euglycaemic hyperinsulinaemic clamps. Rapamycin effects on glucose metabolism and insulin signalling were further evaluated in cultured myotubes. KEY RESULTS: Sirolimus induced a decrease in food intake and concomitant weight loss. It also induced specific fat mass loss that was independent of changes in food intake. Despite these beneficial effects, Sirolimus-treated rats were glucose intolerant, hyperinsulinaemic and hyperglycaemic, but not hyperlipidaemic. The euglycaemic hyperinsulinaemic clamp measurements showed skeletal muscle is a major site of Sirolimus-induced insulin resistance. At the molecular level, long-term Sirolimus administration attenuated glucose uptake and metabolism in skeletal muscle by preventing full insulin-induced Akt activation and altering the expression and translocation of glucose transporters to the plasma membrane. In rats fed a high-fat diet, these metabolic defects were exacerbated, although Sirolimus-treated animals were protected from diet-induced obesity. CONCLUSIONS AND IMPLICATIONS: Taken together, our data demonstrate that the diabetogenic effect of chronic rapamycin administration is due to an impaired insulin action on glucose metabolism in skeletal muscles.

The role of imaging and molecular imaging in the early detection of metabolic and cardiovascular dysfunctions.

Despite intense effort, obesity is still rising throughout the world. Links between obesity and cardiovascular diseases are now well established. Most of the cardiovascular changes related to obesity can be followed by magnetic resonance imaging (MRI) or by magnetic resonance spectroscopy (MRS). In particular, we will see in this review that MRI/MRS is extremely well suited to depict (1) changes in cardiac mass and function, (2) changes in stroke volume, (3) accumulation of fat inside the mediastinum or even inside the cardiomyocytes, (4) cell viability and (5) molecular changes during early cardiovascular diseases.

Hyperpolarizing gases via dynamic nuclear polarization and sublimation.

A high throughput method was designed to produce hyperpolarized gases by combining low-temperature dynamic nuclear polarization with a sublimation procedure. It is illustrated by applications to 129Xe nuclear magnetic resonance in xenon gas, leading to a signal enhancement of 3 to 4 orders of magnitude compared to the room-temperature thermal equilibrium signal at 7.05 T.

Overeruption of periodontally affected unopposed molars in adult rats.

BACKGROUND AND OBJECTIVE: In clinical practice, anterior teeth with periodontal disease exhibiting signs of overeruption are occasionally encountered. However, the influence of periodontitis on unopposed teeth needs to be further elucidated. This study investigated, in rats, the overeruption pattern of unopposed mandibular molars with experimentally induced periodontitis. MATERIAL AND METHODS: Sixty adult male rats were divided equally into four groups. In two groups, periodontitis was induced by a silk thread placed around the cervix of the right mandibular molar. In two groups with and without experimentally induced periodontitis, the crowns of the right maxillary molars were reduced occlusally by grinding to simulate unopposed teeth. After 4 wk, the animals were killed and scanned using micro-computed tomography to measure the vertical position of molars and the buccal and lingual alveolar bone levels. RESULTS: There were no significant differences in the overeruption of opposed molars with and without periodontitis. However, the alveolar bone level of opposed molars with periodontitis was lower than that of healthy molars. Healthy unopposed molars were extruded when compared to molars with an antagonist. The alveolar bone level of healthy unopposed molars was not influenced by molar overeruption. Unopposed molars with periodontitis exhibited significantly larger extrusion than healthy unopposed molars. The lingual alveolar bone level of unopposed molars with periodontitis was lower than that of other healthy and periodontally affected teeth. CONCLUSION: The loss of antagonist causes overeruption of the unopposed tooth, which becomes more prominent in the presence of periodontitis.

Female hydrocele: the cyst of Nuck.

The canal of Nuck is the portion of the processus vaginalis within the inguinal canal in women. A hydrocele of the canal of Nuck is equivalent to an encysted hydrocele of the cord in men. The literature reveals very little about this rare condition in the adult female patient. In this paper, we report a case of hydrocele of the canal of Nuck in a young female. The diagnosis was made with ultrasound and magnetic resonance imaging and then confirmed preoperatively and by histopathology. Although rare, a hydrocele of the canal of Nuck has to be included in the differential diagnosis of a groin lump in female patients.

Analysis of contrast-enhanced MR images to assess renal function.

The image analysis and kinetic modeling methods used in dynamic contrast-enhanced magnetic resonance imaging of the kidney are reviewed. Image analysis includes various techniques of coregistration and segmentation. Few methods have been completely implemented. Nevertheless, the use of coregistration may become a standard to decrease the effect of motion on abdominal images and improve the quality of the renal signals. Kinetic models are classified into three categories: enhancement-based, external and internal representations. Enhancement-based representations are limited to a basic analysis of the tracer concentration curves in the kidneys. Their relationship to the underlying physiology is complex and undefined. However, they can be used to evaluate the split renal function. External representations assess the kidney input and output. An external representation based on the up-slope of the renal enhancement to calculate the renal perfusion is commonly used because of its simplicity. In contrast, external representation based on deconvolution or identification methods remain underexploited. For glomerular filtration, an internal representation based on a two-compartmental model is mostly used. Internal representations based on multi-compartmental models describe the renal function in a more realistic way. Because of their numerical complexity, these models remain rarely used.

Parametric and quantitative analysis of MR renographic curves for assessing the functional behaviour of the kidney.

The aim of this study was to refine the description of the renal function based on MR images and through transit-time curve analysis on a normal population and on a population with renal failure, using the quantitative model of the up-slope. Thirty patients referred for a kidney MR exam were divided in a first population with well-functioning kidneys and in a second population with renal failure from ischaemic kidney disease. The perfusion sequence consisted of an intravenous injection of Gd-DTPA and of a fast GRE sequence T1-TFE with 90 degrees magnetisation preparation (Intera 1.5 T MR System, Philips Medical System). To convert the signal intensity into 1/T1, which is proportional to the contrast media concentration, a flow-corrected calibration procedure was used. Following segmentation of regions of interest in the cortex and medulla of the kidney and in the abdominal aorta, outflow curves were obtained and filtered to remove the high frequency fluctuations. The model of the up-slope method was then applied. Significant reduction of the cortical perfusion (Qc = 0.057+/-0.030 ml/(s 100 g) to Qc = 0.030 +/- 0.017 ml/(s 100 g), P < 0.013) of the medullary perfusion (Qm = 0.023 +/- 0.018 ml/(s 100 g) to Qm = 0.011 +/- 0.006 ml/(s 100 g), P < 0.046) and of the accumulation of contrast media in the medulla (Qa = 0.005 +/- 0.003 ml/(s 100 g) to Qa = 0.0009 +/- 0.0008 ml/(s 100 g), P < 0.001) were found in presence of renal failure. High correlations were found between the creatinine level and the accumulation Qa in the medulla (r2 = 0.72, P < 0.05), and between the perfusion ratio Qc/Qm and the accumulation Qa in the medulla (r2 = 0.81, P < 0.05). No significant difference was found in times to peak between both populations despite a trend showing Ta the time to the end of the increasing contrast accumulation period in the medulla, arriving later for renal failure. Advances in MR signal calibration with the building of quantitative model such as the up-slope allow to assess kinetic and haemodynamic and functional parameters of the diseased kidney.

Specificity of SPIO particles for characterization of liver hemangiomas using MRI.

We investigated the specificity of superparamagnetic iron oxide (SPIO)-enhanced T1-weighted spin-echo (SE) magnetic resonance (MR) images for the characterization of liver hemangiomas. When imaging liver hemangiomas, which are the most frequent benign liver tumors, a method with very high specificity is required, which will obviate other studies, follow-up, or invasive diagnostic procedures such as percutaneous biopsy. Eighty-three lesions were examined by MR imaging at 1.5 T before and after intravenous injection of SPIO particles. Lesions were categorized as follows according to the final diagnosis: 37 hemangiomas, nine focal nodular hyperplasias (FNHs), 19 hepatocellular carcinomas (HCCs), and 18 metastases. Their signal intensity values were normalized to muscle and compared. The only lesions showing a significant increase in signal intensity ratio (lesion to muscle) on postcontrast T1-weighted SE images were hemangiomas (p < 0.001). The signal intensity ratio of hemangiomas increased on average by 70%. Based on receiver operating characteristic analysis and using a cutoff level of 50% signal increase, the specificity and sensitivity of SPIO-enhanced MR imaging for the characterization of hemangiomas would be 100% and 70%, respectively. The T1 effect of SPIO particles can help differentiate hemangiomas from other focal liver lesions such as FNHs, HCCs, and metastases and may obviate biopsy. When using SPIO particles for liver imaging, it is useful to add a T1-weighted sequence to T2-weighted images, thereby providing additional information for lesion characterization.

[Sonography of the hand and wrist]. / Hand- und Handwurzel-Ultraschall.

In the recent years US has gained wide diffusion as a useful imaging tool in the evaluation of musculoskeletal disorders. Recognized advantages of US over the other imaging modalities are low costs, non-invasiveness, possibility to perform a dynamic examination and readiness. Unfortunately, US has a long learning curve and allows good results only when performed by well-trained and experienced examiners. Specifically, utilization of the recent small transducers allows to perform dynamic examination of the hand during flexion-extension movements of the fingers, while their high frequency (till 15 MHz) have increased the possibility to evaluate small anatomic structures of the hand and wrist as well as to detect subtle pathologic changes. The purpose of this article is to present first the normal basic anatomy and US appearance. Then the main pathological conditions including joint and tendon disorders, foreign bodies and other traumatic lesions, entrapment neuropathies and expansible lesions will be presented.