Systematic review of existing guidelines for NAFLD assessment

Aim: In this systematic review, guidelines on non-alcoholic fatty liver disease (NAFLD) were evaluated, aiming at a guideline synthesis focusing on diagnosis an...     

Evaluation of Reduced Susceptibility to Quaternary Ammonium Compounds and Bisbiguanides in Clinical Isolates and Laboratory-Generated Mutants of Staphylococcus aureus

The MICs and minimum bactericidal concentrations (MBCs) for the biocides benzalkonium chloride and chlorhexidine were determined against 1,602 clinical isolates of Staphylococcus aureus. Both compounds showed unimodal MIC and MBC distributions (2 and 4 or 8 mg/liter, respectively) with no apparent subpopulation with reduced susceptibility. To investigate further, all isolates were screened for qac genes, and 39 of these also had the promoter region of the NorA multidrug-resistant (MDR) efflux pump sequenced. The presence of qacA, qacB, qacC, and qacG genes increased the mode MIC, but not MBC, to benzalkonium chloride, while only qacA and qacB increased the chlorhexidine mode MIC. Isolates with a wild-type norA promoter or mutations in the norA promoter had similar biocide MIC distributions; notably, not all clinical isolates with norA mutations were resistant to fluoroquinolones. In vitro efflux mutants could be readily selected with ethidium bromide and acriflavine. Multiple passages were necessary to select mutants with biocides, but these mutants showed phenotypes comparable to those of mutants selected by dyes. All mutants showed changes in the promoter region of norA, but these were distinct from this region of the clinical isolates. Still, none of the in vitro mutants displayed fitness defects in a killing assay in Galleria mellonella larvae. In conclusion, our data provide an in-depth comparative overview on efflux in S. aureus mutants and clinical isolates, showing also that plasmid-encoded efflux pumps did not affect bactericidal activity of biocides. In addition, current in vitro tests appear not to be suitable for predicting levels of resistance that are clinically relevant.     

Neuroendocrine effects of citalopram infusion in anorexia nervosa

Because of the role of serotonin (5HT) in regulating food intake and mood, several studies have focused their attention on the assessment of serotonergic activity in eating disorders, and in particular in anorexia nervosa, but the results have been inconsistent. Citalopram, a highly selective 5HT reuptake inhibitor, has been recently reported as a neuroendocrine probe to assess the serotonergic function in physiological and pathological conditions. We evaluated the adrenocorticotropic hormone (ACTH), cortisol, prolactin (PRL) and growth hormone (GH) secretion during placebo or citalopram IV infusion (20 mg over 120 min), in six women with anorexia nervosa restricter type, and in six healthy women, in order to test the hypothesis that this neurotransmitter system is abnormal in this group of patients. ACTH and PRL secretion was higher during citalopram infusion compared to placebo (p<0.05) in both groups, while cortisol secretion was higher during citalopram infusion only in healthy controls (p<0.05), but not in anorexic patients. GH levels were unaffected by citalopram in both groups. These results demonstrate that serotonergic activation by citalopram affects corticotroph and lactotroph but not somatotroph secretion in anorexic as well as in normal subjects. Our preliminary findings do not support the existence of remarkable alterations in the serotonergic control of anterior pituitary function in anorexia nervosa, while there seems to be an impairment of the adrenal function in this group of patients.     

Advances in magnetic resonance imaging: how they are changing the management of prostate cancer

Context

Although magnetic resonance imaging (MRI) is emerging as the most commonly used imaging modality for prostate cancer (PCa) detection, treatment planning, and follow-up, its acceptance has not been uniform. Recently, great interest has been shown in multiparametric MRI, which combines anatomic T2-weighted (T2W) imaging with MR spectroscopic imaging (MRSI), dynamic contrast-enhanced MRI (DCE-MRI), and diffusion-weighted imaging (DWI).

Objective

The aim of this article is to review the current roles of these MR techniques in different aspects of PCa management: initial diagnosis, biopsy strategies, planning of radical prostatectomy (RP) and external radiation therapy (RT), and implementation of alternative focal therapies.

Evidence acquisition

The authors searched the Medline and Cochrane Library databases (primary fields: prostatic neoplasm, magnetic resonance). The search was performed without language restriction from January 2008 to November 2010.

Evidence synthesis

Initial diagnosis: The data suggest that the combination of T2W MRI and DWI or MRSI with DCE-MRI has the potential to guide biopsy to the most aggressive cancer foci in patients with previously negative biopsies, increasing the accuracy of the procedure. Transrectal MR-guided prostate biopsy can improve PCa detection, but its availability is still limited and the examination time is rather long. Planning of RP: It appears that adding MRSI, DWI, and/or DCE-MRI to T2W MRI can facilitate better preoperative characterization of cancer with regard to location, size, and relationship to prostatic and extraprostatic structures, and it may also facilitate early detection of local recurrence. Thus, use of these MR techniques may improve surgical, oncologic, and functional management. Planning of external RT and focal therapies: MR techniques have similar potential in these areas, but the published data remain very limited.

Conclusions

MRI technology is continuously evolving, and more extensive use of MRI technology in clinical trials and practice will help to improve PCa diagnosis and treatment planning.     

Breast abnormalities: a retrospective study of 208 patients

Ectopic breast tissue occurs in 0.4-6% of the general population. Usually, these tissues develop along the embryonic milk line but other sites are reported in the literature. Accessory breasts are commonly axillary and may undergo hormonal changes. Some pathologies of normally positioned breasts can occur in ectopic breast tissue, including carcinoma, and therefore require traditional senological flow-charts and imaging strategies. Supernumerary nipples are generally asymptomatic but may sometimes be associated with urological malformations. In our 10-year experience, 208 patients were observed (138 polythelia and 70 polymastia) and 159 surgical procedures were performed, 97 for supernumerary nipple excision and 67 for accessory breast ablation. Five neoplastic lesions and 25 fibrocystic mastopathies were detected in specimens; normal nipple or breast tissue was found in 129. In view of the potentially malignant transformation of accessory breasts, thorough physician evaluation is needed. Surgery is currently suggested in cases of suspected malignancy, in symptomatic cases and for cosmetic problems.     

Liraglutide, a long-acting glucagon-like peptide-1 analog, reduces body weight and food intake in obese candy-fed rats, whereas a dipeptidyl peptidase-IV inhibitor, vildagliptin, does not

Metabolic effects of the glucagon-like peptide-1 analog liraglutide and the dipeptidyl peptidase-IV inhibitor vildagliptin were compared in rats made obese by supplementary candy feeding. Female Sprague-Dawley rats were randomized to 12-week diets of chow or chow plus candy. The latter were randomized for 12 further weeks to continue their diet while receiving 0.2 mg/kg liraglutide twice daily subcutaneously, 10 mg/kg vildagliptin twice daily orally, or vehicle or to revert to chow-only diet. Energy expenditure was measured, and oral glucose tolerance tests (OGTTs) were performed. Body composition was determined by dual-energy X-ray absorptiometry scanning, and pancreatic beta-cell mass was determined by histology. Candy feeding increased weight, fat mass, and feeding-associated energy expenditure. Liraglutide or reversal to chow diet fully reversed weight and fat gains. Liraglutide was associated with decreased calorie intake and shifted food preference (increased chow/decreased candy consumption). Despite weight loss, liraglutide-treated rats did not decrease energy expenditure compared with candy-fed controls. Vildagliptin affected neither weight, food intake, nor energy expenditure. OGTTs, histology, and blood analyses indirectly suggested that both drugs increased insulin sensitivity. Liraglutide and vildagliptin inhibited obesity-associated increases in beta-cell mass. This was associated with weight and fat mass normalization with liraglutide, but not vildagliptin, where the ratio of beta-cell to body mass was low.     

A new priority policy for patients with hepatocellular carcinoma awaiting liver transplantation within the model for end-stage liver disease system.

The best prioritization of patients with hepatocellular carcinoma (HCC) waiting for liver transplantation under the model for end-stage liver disease (MELD) allocation system is still being debated. We analyzed the impact of a MELD adjustment for HCC, which consisted of the addition of an extra score (based on the HCC stage and waiting time) to the native MELD score. The outcome was analyzed for 301 patients with chronic liver disease listed for liver transplantation between March 1, 2001 and February 28, 2003 [United Network for Organ Sharing (UNOS)-Child-Turcotte-Pugh (CTP) era, 163 patients, 28.8% with HCC] and between March 1, 2003 and February 28, 2004 (HCC-MELD era, 138 patients, 29.7% with HCC). In the HCC-MELD era, the cumulative dropout risk at 6 months was 17.6% for patients with HCC versus 22.3% for those patients without HCC (P = NS), similar to that in the UNOS-CTP era. The cumulative probability of transplantation at 6 months was 70.3% versus 39.0% (P = 0.005), being higher than that in the UNOS-CTP era for patients with HCC (P = 0.02). At the end of the HCC-MELD era, 12 patients with HCC (29.3%) versus 57 without HCC (58.8%) were still on the list (P = 0.001). Both native and adjusted MELD scores were higher (P < 0.05) and progressed more in patients with HCC who dropped out than in those who underwent transplantation or remained on the list (the initial-final native MELD scores were 17.3-23.1, 15.5-15.6, and 12.8-14.1, respectively). The patients without HCC remaining on the list showed stable MELD scores (initial-final: 15.1-15.4). In conclusion, the present data support the strategy of including the native MELD scores in the allocation system for HCC. This model allows the timely transplantation of patients with HCC without severely affecting the outcome of patients without HCC.