Adipokines and proinflammatory cytokines,the key mediators in the pathogenesis of nonalcoholic fatty liver disease

Nonalcoholic fatty liver disease (NAFLD) is a condition in which excess fat accumulates in the liver of a patient with no history of alcohol abuse or other causes for secondary hepatic steatosis. The pathogenesis of NAFLD and nonalcoholic steatohepatitis (NASH) has not been fully elucidated. The “two-hit“ hypothesis is probably a too simplified model to elaborate complex pathogenetic events occurring in patients with NASH. It should be better regarded as a multiple step process, with accumulation of liver fat being the first step, followed by the development of necroinflammation and fibrosis. Adipose tissue, which has emerged as an endocrine organ with a key role in energy homeostasis, is responsive to both central and peripheral metabolic signals and is itself capable of secreting a number of proteins. These adipocyte-specific or enriched proteins, termed adipokines, have been shown to have a variety of local, peripheral, and central effects. In the current review, we explore the role of adipocytokines and proinflammatory cytokines in the pathogenesis of NAFLD. We particularly focus on adiponectin, leptin and ghrelin, with a brief mention of resistin, visfatin and retinol-binding protein 4 among adipokines, and tumor necrosis factor-α, interleukin (IL)-6, IL-1, and briefly IL-18 among proinflammatory cytokines. We update their role in NAFLD, as elucidated in experimental models and clinical practice.     

Thymidylate synthase and cyclin d1 protein expression in lymph node negative colorectal cancer: role as prognostic factors?

Background/Aims: Thymidylate synthase (TS) is an enzyme for DNA-synthesis and the target for 5-fluorouracil whereas cyclin-D1 plays a critical role in the progression of cells through the G1 phase of the cell-cycle. There is evidence that expression of these markers may predict the outcome of patients with colorectal cancers. The aim of this study was to examine the prognostic value of TS and cyclin D1 protein expression in patients with node negative colorectal cancers. Methodology: TS and cyclin D1 protein expression from 140 patients with UICC stage I and II colorectal cancer was analyzed by immunhistochemistry in paraffin-embedded primary tumour specimens. Results: The 1-, 5- and 10-year overall-survival rates were 96%, 86% and 71%, respectively. Tumour stage and recurrence were associated with overall-survival. Low- and high TS immunoreactivity was present in 68 (48%) and 72 (52%) of cancers, respectively. Low- and high cyclin D1 immunoreactivity was present in 98 (70%) and 42 (30%) of the cancers, respectively. Patients (n=72) with high TS expressing tumours had a worse overall-survival than patients (n=68) with low TS expressing colorectal cancers (p=0.011). No difference in overall-survival was seen between patients with high and low cyclin D1 expressing cancers. Conclusions: TS may be helpful as a prognostic marker in lymph node negative colorectal cancer.     

Prediction of a Good Response to Cardiac Resynchronization Therapy in Patients with Severe Dilated Cardyomyopathy: Could Conventional Echocardiography Be the Answer after All?

Objectives: The aim of this study was to assess the performance of echocardiographic parameters to predict response to cardiac resynchronization therapy (CRT). Background: CRT reduces morbidity and mortality due to the proper selection of candidates for CRT. Methods: The 12‐month trial was performed on 70 optimally medicated patients with standard inclusion criteria: NYHA class III or IV heart failure, left ventricular ejection fraction (LVEF) ≤ 35%, and QRS ≥ 120 ms. All parameters were evaluated by conventional and tissue Doppler‐based methods. Indicator of positive CRT response was more than 20% in improvement of LVEF. Results: LVEF increased >20% in 42 patients. Out of 43 tested baseline echocardiographic parameters, 12 showed statistical difference between responders and nonresponders. Out of these 12 parameters, six (LVSV, LVSI, LVFS, RVd, VPMR, and PISA) had modest to moderately good ability to predict LVEF response with sensitivity ranging from 62.2% to 82.4%, and specificity ranging from 56.5% to 81.2%. For those parameters, the area under the receiver‐operating characteristic curve for positive response to CRT was ≤0.76. Multivariate regression analysis resulted in selection of LVSI and LVFS as possible predictive independent parameters for a good response. The cutoff value for LVSI was 38.7 mL/m² (P = 0.045) and for LVFS was 13% (P = 0.032). Conclusions: Contribution of LVSI and LVFS is to be confirmed in larger trials. Simplicity of their assessment by conventional echocardiography could be an argument for adding them to the inclusion criteria for CRT in severe heart failure patients. (Echocardiography 2012;29:267‐275)     

Orthopedic Jaw Movement Observations Part II: The Rotational Capacity of the Mandible

Using computerized axiography, particularly the electronic mandibular position indicator (EMPI), the mandibular opening movement was measured in 86 asymptomatic volunteers and temporomandibular joint (TMJ) patients. Terminal hinge-axis movement and hinge-axis rotation at maximum-guided mouth opening were recorded. The angle of hinge-axis rotation was used as a parameter for both movements, in accordance with the neutral-zero method. This is a well-established technique in orthopedics and is the standard tool for quantitative functional analysis of joints. An average group was defined, 50% being volunteers. The interquartile range for terminal hinge-axis movement in this study was 5.42°-7.41° in the volunteers and 4.73°-7.25° in the patients. The interquartile range for hinge-axis rotation at maximum opening was from 29.09°-34.87° in the volunteers and from 26.7°-35° in the patients. Computerized axiography is a refined tool for analyzing rotational and translational capacities of the mandible. It is a valid and practical method for orthopedic-diagnostic evaluation of mandibular movements and gives objective criteria for diagnosis in accident victims.     

Visual impairment and the prevalence of ocular pathology in homeless children and adults globally: a systematic review

BackgroundHomelessness is a global issue in developing and developed countries. This article is the first systematic review to explore its impact on visual health globally.MethodsA systematic literature search was conducted on OVID MEDLINE, EMBASE, and Cochrane CENTRAL. Peer-reviewed English-language studies with a focus on homeless children or adults that reported on ocular outcomes were included. Primary outcomes and secondary endpoints were reported via weighted averages. Primary outcomes between homeless children and homeless adults were compared using the Fisher exact test.ResultsThere were 5774 individuals across 23 full-text articles included in the review. For studies reporting primary outcomes, 36.8% of homeless individuals self-reported dissatisfaction with their vision, 26.8% self-reported a previous ocular pathology, 26.3% had uncorrected refractive error, 25.6% were functionally visually impaired, 9.2% had at least one previous eye surgery or procedure, and 4.0% had nonrefractive visual impairment. Upon screening, 25.1% of homeless individuals had some type of ocular pathology, which included cornea and external eye diseases (13.4%), glaucoma (7.4%), cataracts (6.3%), retinal diseases (5.3%), ocular motility disorders (4.7%), trauma (2.3%), neuro-ophthalmological conditions (1.7%), and oculoplastic conditions (0.7%). Homeless adults had significantly more visual impairment (p < 0.001), uncorrected refractive error (p < 0.001), ocular pathology (p < 0.001), cataracts (p < 0.001), retinal pathology (p < 0.001), and neuro-ophthalmological conditions (p < 0.001) relative to children.ConclusionsVisual impairment in homeless individuals is higher than the general population. Uncorrected refractive error is a leading cause of visual impairment in this population. Additionally, homeless adults have significantly more visual impairment and ocular pathology than homeless children. Future studies should also explore if these differences are consistent in developing countries and investigate ways to increase eye care access for homeless individuals.     

Multiple co-infections of rodents with hantaviruses, Leptospira, and Babesia in Croatia

Hantaviruses, Leptospira spp., and Babesia spp. are rodent-borne pathogens present worldwide. We studied multiple co-infections of small rodents in Croatia with all three pathogens. Twenty-eight Apodemus flavicollis and 16 Myodes glareolus were tested for the presence of hantavirus RNA by real-time RT-PCR, Leptospira strains by renoculture method and Babesia DNA by PCR. Anti-hantavirus antibodies and anti-Leptospira antibodies were detected by serological methods. Very high infection rates with each pathogen were found in A. flavicollis: 20 of 28 rodents (71%) were infected with Dobrava virus, 13 rodents (46%) were infected with Leptospira, and 5 rodents (18%) were infected with Babesia. Multiple co-infections with all three pathogens were found in 3 of 28 (11%) A. flavicollis animals, suggesting that the same rodent host can be infected with several pathogens at the same time. Dual infections with both hantaviruses and Leptospira were found in 7 of 44 rodents (16%), with hantaviruses and Babesia in 2 rodents (5%), and double infection with both Leptospira and Babesia were found in 1 rodent (2%). Since hantaviruses, Leptospira, and Babesia have similar geographical distributions, it is to be expected that in other parts of the world multiple co-infections, representing a serious threat to public health, can be found.     

ICUD-EAU International Consultation on Bladder Cancer 2012: Non–Muscle-Invasive Urothelial Carcinoma of the Bladder

Context

Our aim was to present a summary of the Second International Consultation on Bladder Cancer recommendations on the diagnosis and treatment options for non–muscle-invasive urothelial cancer of the bladder (NMIBC) using an evidence-based approach.

Objective

To critically review the recent data on the management of NMIBC to arrive at a general consensus.

Evidence acquisition

A detailed Medline analysis was performed for original articles addressing the treatment of NMIBC with regard to diagnosis, surgery, intravesical chemotherapy, and follow-up. Proceedings from the last 5 yr of major conferences were also searched.

Evidence synthesis

The major findings are presented in an evidence-based fashion. We analyzed large retrospective and prospective studies.

Conclusions

Urothelial cancer of the bladder staged Ta, T1, and carcinoma in situ (CIS), also indicated as NMIBC, poses greatly varying but uniformly demanding challenges to urologic care. On the one hand, the high recurrence rate and low progression rate with Ta low-grade demand risk-adapted treatment and surveillance to provide thorough care while minimizing treatment-related burden. On the other hand, the propensity of Ta high-grade, T1, and CIS to progress demands intense care and timely consideration of radical cystectomy.