Osteoprotegerin as a marker of atherosclerosis: A systematic update

Abstract

Objective. Osteoprotegerin (OPG) may be involved in development of atherosclerosis. To evaluate plasma concentrations of OPG in individuals with stable coronary artery disease (CAD), acute coronary syndrome (ACS), peripheral artery disease (PAD), and cerebrovascular disease (CBVD) a systematic literature review was performed. Design and methods. Studies investigating OPG concentrations in stable CAD, ACS, PAD, and CBVD were extracted from PubMed and the Cochrane Library, retrieving 280 articles. Nonrelevant articles were excluded and after thorough evaluation, and only 14 studies with clearly defined cohorts qualified for this review. Results. In 11 studies, OPG concentrations were elevated. Severity of atherosclerosis was significantly associated with higher OPG concentrations compared to healthy controls. No association between PAD and OPG concentrations was observed. Conclusion. OPG concentrations are associated with the presence and severity of stable CAD, ACS, and CBVD. Larger studies are needed to reach conclusions concerning OPG concentrations in PAD. Studies addressing a putative role for OPG in suspected CAD and CBVD are warranted.     

Hyponatremia as a marker of complicated appendicitis: A systematic review

BackgroundAcute appendicitis, the most common cause of acute surgical abdomen, is associated with intra-abdominal complications, such as perforation, that increase morbidity and mortality. Early and accurate preoperative diagnosis of complicated appendicitis mandates the identification of new diagnostic markers. This systematic review summarizes current literature on the adoption of hyponatremia as an early diagnostic and predictive marker of complicated appendicitis.MethodsPubmed, Cochrane Library, Scopus, Google Scholar, WHO Global Health Library, System for Information on Grey Literature, ISI Web of Science, EBSCOHost and Virtual Health Library were searched in accordance with the PRISMA guidelines in order to identify original human studies investigating the association between hyponatremia and the presence or development of complicated appendicitis.ResultsA total of 7 studies conducted in 6 different countries were identified. A prospective diagnostic accuracy study reported a strong association between hyponatremia and complicated appendicitis in children. The largest sample size study performed in adults reported a significant association between hyponatremia and perforated or gangrenous appendicitis.ConclusionsThe admission serum sodium level measurement, a routinely performed, low-cost test, should be taken into account in patients with clinical presentation compatible with acute appendicitis and suspicion of underlying complications. Future well-designed prospective diagnostic accuracy studies are required to further establish the association between hyponatremia and perforated appendicitis.     

Osteoprotegerin: a valid new marker of bone turnover in post-menopausal osteoporosis?

Abstract An increase of setum osteoprotegerin has been found in post-menopausal women, that is positively correlated with age and bone markers, negatively with bone mass. In 25 post-menopausal women (mean age, 63±8 years) we measured serum levels of osteoprotegerin, total and bone alkaline phosphatase, osteocalcin, urinary deoxypyridinoline and bone mineral density of the lumbar spine and femur.Osteoprotegerin and bone markers did not differ from range of normal values. Bone mineral density appeared markedly reduced both at the spine and the femur.A significant correlation between osteoprotegerin and age, duration of menopause, osteocalcin and bone alkaline phosphatase was found. No correlation was found between osteoprotegerin and bone mineral density in all measured skeletal sites. In conclusion, osteoprotegerin does not appear to be an interesting parameter for the evaluation of bone turnover in post-menopausal osteoporosis.     

Osteoprotegerin as a potential therapy for osteoporosis

The discovery and characterization of the RANKL/RANK/ OPG signaling pathway and the identification of its role in the pathogenesis of bone loss have provided the rationale for the development of drugs with the ability to modulate RANK-induced osteoclastogenesis. In vivo studies have identified interfering with the RANKL/RANK interaction as a potential therapeutic target in the management of osteoporosis. Two agents capable of blocking the binding of RANKL to RANK have been so far tested in clinical studies—osteoprotegerin (Fc-OPG fusion molecule) and the RANKL-antibody (AMG 162). Both have been found to have profound inhibitory effects on bone resorption, with AMG 162 appearing to be overall superior to OPG. Data are still very scarce, however, and much remains to be uncovered before novel strategies capable of modulating the RANKL/OPG signaling pathway could be safely and effectively used in the management of osteoporosis.     

CT-defined low-skeletal muscle mass as a prognostic marker for survival in prostate cancer: A systematic review and meta-analysis

BackgroundLow-skeletal muscle mass (LSMM) is defined as progressive skeletal muscle loss, which can be assessed by imaging modalities. It was shown that this parameter is predictive and prognostic of several clinically relevant factors in several tumor entities. Our aim was to establish the effect of LSMM on overall survival (OS) in prostate cancer patients based on a large patient sample.MethodsMEDLINE library, EMBASE and SCOPUS databases were screened for the associations between LSMM and mortality in prostate cancer patients up to April 2021. The primary endpoint of the systematic review was the hazard ratio of LSMM on OS. In total, five studies were suitable for the analysis and included into the present study.ResultsThe included studies comprised over all 1221 patients. The identified frequency of LSMM was 61.02%. The pooled hazard ratio for the effect of LSMM on OS was 1.4 [95% CI 0.7-2.5] in univariate analysis and was 1.6 [95% CI 1.2-2.1] in multivariate analysis.ConclusionCT-defined LSMM has a frequency of 61% in patients with PC and shows a positive association with the overall survival with a hazard ratio of 1.4. LSMM assessment should therefore be included into clinical routine as a relevant prognostic biomarker.     

Oxidized low density lipoprotein (Ox-LDL) as a marker of atherosclerosis in hemodialysis (HD) patients

AIM: To characterize the relationship between oxidative stress and atherosclerosis in HD patients. METHODS: Seventy-five HD patients were entered into the study. Ox-LDL was measured as a probe for peroxidation and compared to clinical atherosclerotic parameters. Prospective studies were also performed to assess the effects of vitamin E-bonded membrane on oxidative stress. RESULTS: Elderly patients tended to show elevated Ox-LDL (alpha = 0.060+/-0.021 ng/microg LDL protein/year, r = 0.35, p < 0.05). Levels of Ox-LDL in the patients with positive history for atherosclerotic diseases (3.1+/-0.4 ng/microg LDL protein, n = 36) were higher than those with a negative history (1.6+/-0.2, n = 39, p < 0.01). Further-more, ankle/brachial pressure index was negatively correlated to Ox-LDL (alpha = -0.052+/-0.012/ng/microg LDL protein, r = 0.42, p < 0.01). Application of vitamin E-bonded membrane for 10 months (-38+/-11%, n = 14, p < 0.05), but not synthetic membrane, ameliorated Ox-LDL. CONCLUSIONS: Our results indicate that Ox-LDL is elevated in aged HD patients. In addition, the present data provide evidence that vitamin E-bonded dialyzers attenuate oxidative stress. Finally, our findings suggest that Ox-LDL correlates to the magnitude of peripheral arterial diseases in HD patients.     

Evidence‐based therapy in hypertrophic scars: An update of a systematic review

Hypertrophic scars are still a major burden for numerous patients, especially after burns. Many treatment options are available; however, no evidence‐based treatment protocol is available with recommendations mostly emerging from experience or lower quality studies. This review serves to discuss the currently available literature. A systematic review was performed and the databases PubMed and Web of Science were searched for suitable publications. Only original articles in English that dealt with the treatment of hypertrophic scars in living humans were analyzed. Further, studies with a level of evidence lower than 1 as defined by the American Society of Plastic Surgeons were excluded. After duplicate exclusion, 1638 studies were screened. A qualitative assessment yielded 163 articles eligible for evidence grading. Finally nine studies were included. Four of them used intralesional injections, four topical therapeutics and one assessed the efficacy of CO₂‐laser. Intralesional triamcinolone + fluorouracil injections, and topical pressure and/or silicone therapy revealed significant improvements in terms of scar height, pliability, and pigmentation. This systematic review showed that still few high‐quality studies exist to evaluate therapeutic means and their mechanisms for hypertrophic scars. Among these, most of them assessed the efficacy of intralesional triamcinolone injections with the same treatment protocol. Intralesional injection appears to be the best option for hypertrophic scar treatment. Future studies should focus on a possible optimization of infiltrative therapies, consistent end‐point evaluations, adequate follow‐up periods, and possibly intraindividual treatments.     

The effects of antimuscarinic treatments in overactive bladder: an update of a systematic review and meta-analysis

CONTEXT: Antimuscarinic agents are currently the first-line pharmacotherapy for overactive bladder. OBJECTIVES: A systematic review published in 2005 was updated, including data on a newly licensed antimuscarinic (fesoterodine). The primary aim of this study was to systematically review evidence on the efficacy of licensed administration of antimuscarinic treatments in overactive bladder from randomised controlled trials. Secondary aims were to review evidence on tolerability and safety and health-related quality of life (HRQL). EVIDENCE ACQUISITION: All relevant data sources from randomised controlled trials were searched, and two independent reviewers considered publications for inclusion and extracted relevant data. Meta-analysis was used to pool efficacy, tolerability, safety, and HRQL outcomes by treatment. Efficacy was measured by continent days, mean voided volume, urgency episodes, and micturition frequency. Tolerability and safety were measured by means of adverse event and withdrawal rates. HRQL was measured by various instruments. EVIDENCE SYNTHESIS: An additional 1118 references were retrieved with data on 83 studies extracted. Antimuscarinics were found to be more effective than placebo. Tolerability was good; few of the antimuscarinics were found to have significantly higher withdrawal rates in comparison to placebo. No serious adverse event for any product was statistically significant compared to placebo. Dry mouth (mild, moderate, severe) was the most commonly reported adverse event (29.6% on treatment vs 7.9% on placebo), followed by pruritus (15.4% on treatment vs 5.2% on placebo). Improvements were seen in HRQL with treatment by darifenacin, fesoterodine, oxybutynin transdermal delivery system, propiverine extended release (ER), solifenacin, tolterodine ER and immediate release, and trospium. Limitations of the study include restrictions on the types of patients typically included in overactive bladder trials and topics that have not been adequately addressed in the current antimuscarinic literature. CONCLUSIONS: Antimuscarinics are efficacious, safe, and well-tolerated treatments that improve HRQL. Profiles of each drug and dosage differ and should be considered in making treatment choices.     

Elasticity as a biomarker for prostate cancer: a systematic review

• To systematically review the range of methods available for assessing elasticity in the prostate and to examine its use as a biomarker for prostate cancer.

• A systematic review of the electronic database PubMed was performed up to December 2012.
• All relevant studies assessing the use of elasticity as a biomarker for prostate cancer were included except those not studying human prostates or reporting a sensitivity, specificity or quantitative elasticity value.

• There has been much interest in the use of elasticity in the detection of prostate cancer and there have been many publications using various methods of detection. The most common method of assessment is an imaging method, called sonoelastography. Further imaging methods include ultrasound (US), three‐dimensional US and magnetic resonance elastography. These methods are reviewed for sensitivity and specificity.
• The other method of assessment is the mechanical method. These use quantitative elasticity values to differentiate benign from malignant areas of the prostate. This method of assessment has shown that the elasticity changes for differing Gleason grades and T stages of disease within the prostate. Quantitative elasticity values offer the potential of using ‘threshold’ elasticity values under which the prostate is benign.

• Tissue elasticity has great potential as a diagnostic and prognostic biomarker for prostate cancer and can be assessed using various methods. Currently transrectal sonoelastography has the most evidence supporting its use in clinical practice.