Simultaneous assessment of liver volume and whole liver fat content: a step towards one-stop shop preoperative MRI protocol

Objective  

The purpose of this study was to evaluate the ability of a whole liver volume (WLV) segmentation algorithm to measure fat fraction (FF).     

Quorum sensing inhibitors increase the susceptibility of bacterial biofilms to antibiotics in vitro and in vivo

Although the exact role of quorum sensing (QS) in various stages of biofilm formation, maturation, and dispersal and in biofilm resistance is not entirely clear, the use of QS inhibitors (QSI) has been proposed as a potential antibiofilm strategy. We have investigated whether QSI enhance the susceptibility of bacterial biofilms to treatment with conventional antimicrobial agents. The QSI used in our study target the acyl-homoserine lactone-based QS system present in Pseudomonas aeruginosa and Burkholderia cepacia complex organisms (baicalin hydrate, cinnamaldehyde) or the peptide-based system present in Staphylococcus aureus (hamamelitannin). The effect of tobramycin (P. aeruginosa, B. cepacia complex) and clindamycin or vancomycin (S. aureus), alone or in combination with QSI, was evaluated in various in vitro and in vivo biofilm model systems, including two invertebrate models and one mouse pulmonary infection model. In vitro the combined use of an antibiotic and a QSI generally resulted in increased killing compared to killing by an antibiotic alone, although reductions were strain and model dependent. A significantly higher fraction of infected Galleria mellonella larvae and Caenorhabditis elegans survived infection following combined treatment, compared to treatment with an antibiotic alone. Finally, the combined use of tobramycin and baicalin hydrate reduced the microbial load in the lungs of BALB/c mice infected with Burkholderia cenocepacia more than tobramycin treatment alone. Our data suggest that QSI may increase the success of antibiotic treatment by increasing the susceptibility of bacterial biofilms and/or by increasing host survival following infection.     

No loss of chance of diabetic retinopathy screening by endocrinologists with a digital fundus camera

OBJECTIVE

To compare the efficacy of the diabetic retinopathy (DR) screening with digital camera by endocrinologists with that by specialist and resident ophthalmologists in terms of sensitivity, specificity, and level of “loss of chance.”

RESEARCH DESIGN AND METHODS

In a cross-sectional study, 500 adult diabetic patients (1,000 eyes) underwent three-field retinal photography with a digital fundus camera following pupillary dilatation. Five endocrinologists and two ophthalmology residents underwent 40 h of training on screening and grading of DR and detection of associated retinal findings. A κ test compared the accuracy of endocrinologist and ophthalmology resident screening with that performed by experienced ophthalmologists. Screening efficiency of endocrinologists was evaluated in terms of “loss of chance,” i.e., missed diagnoses that required ophthalmologist referrals.

RESULTS

The mean weighted κ of DR screening performed by endocronologists was similar to that of ophthalmology residents (0.65 vs. 0.73). Out of 456 DR eyes, both endocrinologists and ophthalmology residents misdiagnosed only stage 1 DR (36 and 14, respectively), which did not require ophthalmologist referral. There were no significant differences between endocrinologists and ophthalmology residents in terms of diabetic maculopathy and incidental findings except for papillary cupping and choroidal lesions, which were not the main purpose of the study or of the training.

CONCLUSIONS

The endocrinologist with specific training for DR detection using a three-field digital fundus camera with pupillary dilatation can perform a reliable DR screening without any loss of chance for the patients when compared with identical evaluation performed by experienced ophthalmologists.Diabetic retinopathy (DR) is one of the main causes of blindness in industrialized nations (1). The worldwide prevalence of diabetes in adults is estimated to rise to 7.7%, affecting 439 million adults by 2030 (2). In France, the increasing number of patients with diabetes, coupled with the lack of a national screening program, results in a steady rise in the visual handicaps related to the disease (3).Annual screening of DR is recommended as an effective approach to prevent visual loss related to diabetes (4,5). Currently, digital nonmydriatic fundus photography is increasingly used as a method of screening for ophthalmologists worldwide (5–7). According to consensus classifications (4,5), DR at a stage higher than 1 needs further ophthalmological management. Despite these recommendations, only 30% of the diabetic patients in France undergo DR screening each year. Partly, this is due to the lack of ophthalmologists and insufficient awareness about the visual consequences of the disease (3,8). The situation is slowly changing after implementation of telemedical screening networks using digital fundus photography (9–11). Further increase in screening coverage can be achieved with the involvement of allied medical professionals.Since the 1980s, the concept of “loss of chance” has emerged in medicine and law. The misdiagnosis during DR screening can lead to a loss of chance for patients requiring referral to an ophthalmologist for further examinations and management (12,13).Two studies have shown that screening performed by an endocrinologist using an ophthalmoscope (14) and a mydriatic camera (15), respectively, were reliable, although they didn’t evaluate the loss of chance. Furthermore, no endocrinologists’ team approach was evaluated so far.This clinical research trial has been designed to compare the efficacy of the DR screening with digital camera by a team of previously trained endocrinologists (7) with that of residents and specialist ophthalmologists, in terms of sensitivity, specificity and level of “loss of chance.”     

Prevalence and risk factors of sleep bruxism and wake-time tooth clenching in a 7- to 17-yr-old population

Carra MC, Huynh N, Morton P, Rompré PH, Papadakis A, Remise C, Lavigne GJ. Prevalence and risk factors of sleep bruxism and wake‐time tooth clenching in a 7‐ to 17‐yr‐old population.
Eur J Oral Sci 2011; 119: 386–394. © 2011 Eur J Oral Sci Sleep‐related bruxism (SB) and wake‐time tooth clenching (TC) have been associated with temporomandibular disorders (TMDs), headache, and sleep and behavioral complaints. This study aimed to assess the prevalence and risk factors of these signs and symptoms in a 7‐ to 17‐yr‐old population (n = 604) seeking orthodontic treatment. Data were collected by questionnaire and by a clinical examination assessing craniofacial morphology and dental status. Sleep‐related bruxism was reported by 15% of the population and TC was reported by 12.4%. The SB group (n = 58) was mainly composed of children (67.3% were ≤12 yr of age) and the TC group (n = 42) was mainly composed of adolescents (78.6% were ≥13 yr of age). The craniofacial morphology of over 60% of SB subjects was dental class II and 28.1% were a brachyfacial type. Compared with controls (n = 220), SB subjects were more at risk of experiencing jaw muscle fatigue [adjusted OR (AOR) = 10.5], headache (AOR = 4.3), and loud breathing during sleep (AOR = 3.1). Compared with controls, TC subjects reported more temporomandibular joint clicking (AOR = 5), jaw muscle fatigue (AOR = 13.5), and several sleep and behavioral complaints. Sleep‐ and wake‐time parafunctions are frequently associated with signs and symptoms suggestive of TMDs, and with sleep and behavioral problems. Their clinical assessment during the planning of orthodontic treatment is recommended.     

Myocardial infarction: Role of new antiplatelet agents

Thienopyridines have become the cornerstone of treatment of percutaneous coronary intervention although no survival benefit has ever been shown with clopidogrel despite increasing loading doses. Newly developed P2Y(12)?inhibitors are more potent, more predictable and have a faster onset of action than clopidogrel, characteristics that make them particularly attractive for high-risk PCI. Four new P2Y(12)?inhibitors have been tested each of them having particular individual properties. Prasugrel is an oral prodrug leading to irreversible blockade of the P2Y(12)?receptor and is approved worldwide for ACS PCI. Ticagrelor is a direct-acting and reversible inhibitor of the P2Y(12)?receptor with potentially more pleiotropic effects. Cangrelor is an intravenous direct and reversible inhibitor of the P2Y(12)?receptor providing the highest level of inhibition and elinogrel is an intravenous and oral P2Y(12)?antagonist with a direct and reversible action. Both prasugrel and ticagrelor, opposed to clopidogrel, have shown that stronger P2Y(12)?inhibition led respectively to significant 19?% and 16?% relative risk reduction of a similar primary endpoint combining cardiovascular death, nonfatal myocardial infarction, or nonfatal stroke. Both drugs showed a significant 0.6?% absolute excess of TIMI major bleeding not related to CABG surgery. The effect of these new compounds is prompt, predictable and powerful as compared to clopidogrel. Their net benefit is particularly marked in PCI for STEMI patients, in which there is no significant increase in major bleeding when compared with clopidogrel. However, because in clinical trials patients perceived to be at higher risk for bleeding usually are excluded, the risk of major and even fatal bleeding might even be higher in a "real-world" setting i.e. in the elderly patient with comorbidities.     

A phase I/IIa clinical trial of a recombinant Rho protein antagonist in acute spinal cord injury

Multiple lines of evidence have validated the Rho pathway as important in controlling the neuronal response to growth inhibitory proteins after central nervous system (CNS) injury. A drug called BA-210 (trademarked as Cethrin(?)) blocks activation of Rho and has shown promise in pre-clinical animal studies in being used to treat spinal cord injury (SCI). This is a report of a Phase I/IIa clinical study designed to test the safety and tolerability of the drug, and the neurological status of patients following the administration of a single dose of BA-210 applied during surgery following acute SCI. Patients with thoracic (T2-T12) or cervical (C4-T1) SCI were sequentially recruited for this dose-ranging (0.3?mg to 9?mg Cethrin), multi-center study of 48 patients with complete American Spinal Injury Association assessment (ASIA) A. Vital signs; clinical laboratory tests; computed tomography (CT) scans of the spine, head, and abdomen; magnetic resonance imaging (MRI) of the spine, and ASIA assessment were performed in the pre-study period and in follow-up periods out to 1 year after treatment. The treatment-emergent adverse events that were reported were typical for a population of acute SCI patients, and no serious adverse events were attributed to the drug. The pharmacokinetic analysis showed low levels of systemic exposure to the drug, and there was high inter-patient variability. Changes in ASIA motor scores from baseline were low across all dose groups in thoracic patients (1.8±5.1) and larger in cervical patients (18.6±19.3). The largest change in motor score was observed in the cervical patients treated with 3?mg of Cethrin in whom a 27.3±13.3 point improvement in ASIA motor score at 12 months was observed. Approximately 6% of thoracic patients converted from ASIA A to ASIA C or D compared to 31% of cervical patients and 66% for the 3-mg cervical cohort. Although the patient numbers are small, the observed motor recovery in this open-label trial suggests that BA-210 may increase neurological recovery after complete SCI. Further clinical trials with Cethrin in SCI patients are planned, to establish evidence of efficacy.     

Percutaneous coronary intervention after fibrinolysis: a multiple meta-analyses approach according to the type of strategy.

OBJECTIVES: We performed a meta-analysis of randomized trials that enrolled ST-segment elevation myocardial infarction patients treated with fibrinolysis to assess the potential benefits of: 1) rescue percutaneous coronary intervention (PCI) versus no PCI; 2) systematic and early (< or =24 h) PCI versus delayed or ischemia-guided PCI; 3) fibrinolysis-facilitated PCI versus primary PCI alone. BACKGROUND: The impact of PCI strategies after fibrinolysis on mortality or reinfarction remains to be established. METHODS: The meta-analysis was performed using the odds ratio (OR) as the parameter of efficacy with a random effect model. Fifteen randomized trials (5,253 patients) were selected. The primary end point was mortality or the combined end point of death or reinfarction. RESULTS: Rescue PCI for failed fibrinolysis reduced mortality (6.9% vs. 10.7%) (OR, 0.63; 95% confidence interval [CI], 0.39 to 0.99; p = 0.055) and the rate of death or reinfarction (10.8% vs. 16.8%) (OR, 0.60; 95% CI, 0.41 to 0.89; p = 0.012) compared with a conservative approach. Systematic and early PCI performed during the "stent era" led to a nonsignificant reduction in mortality compared with delayed or ischemia-guided PCI (3.8% vs. 6.7%) (OR, 0.56; 95% CI, 0.29 to 1.05; p = 0.07) and to a 2-fold reduction in the rate of death or reinfarction (7.5% vs. 13.2%) (OR, 0.53; 95% CI, 0.33 to 0.83; p = 0.0067). This benefit contrasted with a nonsignificant increase in the rate of both mortality (5.5% vs. 3.9%, p = 0.33) or death or reinfarction (9.6% vs. 5.7%, p = 0.06) observed in the "balloon era." Fibrinolysis-facilitated PCI was associated with more reinfarction as compared with primary PCI alone (5.0% vs. 3.0%) (OR, 1.68; 95% CI, 1.12 to 2.51; p = 0.013) without significant impact on mortality (OR, 1.30; 95% CI, 0.92 to 1.83; p = 0.13). CONCLUSIONS: Our findings support rescue PCI and systematic and early PCI after fibrinolysis. However, the current data do not support fibrinolysis-facilitated PCI in lieu of primary PCI alone.