Interventions that cause weight loss and the impact on cardiovascular risk factors: a systematic review and meta‐analysis

Overweight and obesity increase the risks of diabetes and cardiovascular disease (CVD). This has been shown to be reversed with weight loss. A systematic review and meta‐analysis were performed to determine the effect of weight loss in the primary prevention of CVD. PubMed, Embase and the Cochrane Library databases were searched electronically through to May 2013. Randomized controlled trials assessing weight loss and cardiovascular risk factors and outcomes were included. A random effects meta‐analysis, with sub‐group analyses for degree of weight loss, and age were performed. Because few studies reported clinical outcomes of CVD, analyses were limited to cardiovascular risk factors (83 studies). Interventions that caused any weight loss significantly reduced systolic blood pressure (?2.68 mmHg, 95% CI ?3.37, ?2.11), diastolic blood pressure (?1.34 mmHg, 95% CI ?1.71, ?0.97), low‐density lipoprotein cholesterol (?0.20 mmol L^?1, 95% CI ?0.29, ?0.10), triglycerides (?0.13 mmol L^?1, 95% CI ?0.22, ?0.03), fasting plasma glucose (?0.32 mmol L^?1, 95% CI ?0.43, ?0.22) and haemoglobin A1c(?0.40%, 95% CI ?0.52, ?0.28) over 6–12 months. Significant changes remained after 2 years for several risk factors. Similar results were seen in sub‐group analyses. Interventions that cause weight loss are effective at improving cardiovascular risk factors at least for 2 years. © 2016 World Obesity     

Spatial coordination of cell-adhesion molecules and redox cycling of iron in the microvascular inflammatory response to pulmonary injury

Transmigration of phagocytic leukocytes (PLCs) from the peripheral blood into injured lung requires a conversion of the microvascular endothelial cells (ECs) to the proinflammatory phenotypes and spatiotemporal interplay of different types of cell adhesion molecules (CAMs) on PLC and endothelium. The present report is focused on involvement of iron-dependent redox signaling in spatial coordination of lung CAM due to either a pulmonary trauma or endotracheal iron administration in rats. Redox alterations, deposition of 3-nitrotyrosine, expression of VE-cadherin, ICAM-1, and the PLC integrins, and the status of thioredoxin, Ref-1, NF-kappaB and Nrf2 redox-sensitive elements in the alveolar microvasculature were assessed with EPR spectroscopy, immunobloting, and confocal microscopy. We demonstrated for the first time in vivo that the presence of catalytically active iron, deposition of myeloperoxidase, and induction of the oxidative stress in the lung-injury models were accompanied by (a) downregulation of VE-cadherin, (b) upregulation and polarization of ICAM-1 and the PLC integrins, and (c) nuclear translocation and interaction of thioredoxin, Ref-1, and NF-kappaB and complex structural changes in EC and PLC at the sites of their contacts. The studies suggested that a part of the proinflammatory action of iron in the lung resulted from its stimulation of the redox-sensitive factors.     

Cemented versus uncemented hemiarthroplasty for hip fractures: a systematic review of randomised controlled trials

We performed a systematic review of randomised controlled trials in order to identify the best available evidence to compare the outcome between cemented and uncemented hemiarthroplasty for treatment of intracapsular hip fractures. We searched the Cochrane Bone, Joint and Muscle Trauma Group Specialised Register, the Cochrane Central Register of Controlled Trials, EMBASE, CINAHL, MEDLINE and the National Research Register (UK) to retrieve all of the published randomised controlled trials designed to address these issues, in order to perform a meta-analysis. Eight studies involving 1169 patients were determined to be appropriate for meta-analysis. The following statistically significant differences were found between the cemented and uncemented prostheses: (1) longer operative time for cemented prosthesis; (2) lower reduction in mobility score for those treated with cemented prosthesis; (3) fewer patients with residual pain in the hip and lower pain score (signifying less pain) for those treated with a cemented prosthesis. Our meta-analysis has shown that there is good evidence that the use of cement during hemiarthroplasty will reduce the amount of residual hip pain and also allow better restoration of function. There is no evidence of significant adverse effects of cement on mortality or other complications encountered. These observations apply to older designs, and there is a need for randomised trials comparing hydroxyapatite-coated modern stems with cemented prostheses.     

Targeted delivery of low molecular drugs using chitosan and its derivatives

Chitosan has prompted the continuous impetus for the development of safe and effective drug delivery systems because of its unique physicochemical and biological characteristics. The primary hydroxyl and amine groups located on the backbone of chitosan allow for chemical modification to control its physical properties. When the hydrophobic moiety is conjugated to a chitosan molecule, the resulting amphiphile may form self-assembled nanoparticles that can encapsulate a quantity of drugs and deliver them to a specific site of action. Chemical attachment of the drug to the chitosan throughout the functional linker may produce useful prodrugs, exhibiting the appropriate biological activity at the target site. Mucoadhesive and absorption enhancement properties of chitosan increase the in vivo residence time of the dosage form in the gastrointestinal tract and improve the bioavailability of various drugs. The main objective of this review is to provide an insight into various target-specific carriers, based on chitosan and its derivatives, towards low molecular weight drug delivery. The first part of the review is concerned with the organ-specific delivery of low molecular drugs using chitosan and its derivatives. The subsequent section considers the recent developments of drug delivery carriers for cancer therapy with special focus on various targeting strategies.     

Meta‐analysis of randomized controlled trials on the safety and effectiveness of early versus delayed laparoscopic cholecystectomy for acute cholecystitis

Background:

In many countries laparoscopic cholecystectomy for acute cholecystitis is mainly performed after the acute episode has settled because of the anticipated increased risk of morbidity and higher conversion rate from laparoscopic to open cholecystectomy.

Methods:

A systematic review was performed with meta‐analysis of randomized clinical trials of early laparoscopic cholecystectomy (ELC; performed within 1 week of onset of symptoms) versus delayed laparoscopic cholecystectomy (performed at least 6 weeks after symptoms settled) for acute cholecystitis. Trials were identified from The Cochrane Library trials register, Medline, Embase, Science Citation Index Expanded and reference lists. Risk ratio (RR) or mean difference was calculated with 95 per cent confidence intervals (c.i.) based on intention‐to‐treat analysis.

Results:

Five trials with 451 patients were included. There was no significant difference between the two groups in terms of bile duct injury (RR 0·64 (95 per cent c.i. 0·15 to 2·65)) or conversion to open cholecystectomy (RR 0·88 (95 per cent c.i. 0·62 to 1·25)). The total hospital stay was shorter by 4 days for ELC (mean difference ?4·12 (95 per cent c.i. ?5·22 to ?3·03) days).

Conclusion:

ELC during acute cholecystitis appears safe and shortens the total hospital stay. Copyright © 2009 British Journal of Surgery Society Ltd. Published by John Wiley & Sons, Ltd.     

Hemiarthroplasty versus internal fixation for displaced intracapsular hip fractures: A long-term follow-up of a randomised trial

In a prospective randomised trial, 455 patients presenting to one hospital with a displaced intracapsular fracture were randomised to either closed reduction and internal fixation with three cancellous screws or replacement with an uncemented hemiarthroplasty. Follow-up of surviving patients was for between 9 and 15 years to determine the long-term outcome for the two treatment methods. 93% of patients died during this follow-up period. There was no difference in mortality between the two procedures. The need for revision surgery to the hip was increased for those treated by internal fixation (93% versus 62% implant survival rate; hazard ratio: 0.14, 95% CI 0.08-0.24). 91% of revision's operations occurred within 2 years from injury. There was no difference in the degree of residual pain between groups neither was there any difference in the number of patients requiring institutional care. These results demonstrate that both treatment methods produce comparable final outcomes but internal fixation is associated with an increased re-operation rate.     

Estrogen receptor alpha deletion enhances the metastatic phenotype of Ron overexpressing mammary tumors in mice

Background  

The receptor tyrosine kinase family includes many transmembrane proteins with diverse physiological and pathophysiological functions. The involvement of tyrosine kinase signaling in promoting a more aggressive tumor phenotype within the context of chemotherapeutic evasion is gaining recognition. The Ron receptor is a tyrosine kinase receptor that has been implicated in the progression of breast cancer and evasion of tamoxifen therapy.     

Lymphatic Filariasis: Perspectives on Lymphatic Remodeling and Contractile Dysfunction in Filarial Disease Pathogenesis

Lymphatic filariasis, one of the most debilitating diseases associated with the lymphatic system, affects over a hundred million people worldwide and manifests itself in a variety of severe clinical pathologies. The filarial parasites specifically target the lymphatics and impair lymph flow, which is critical for the normal functions of the lymphatic system in maintenance of body fluid balance and physiological interstitial fluid transport. The resultant contractile dysfunction of the lymphatics causes fluid accumulation and lymphedema, one of the major pathologies associated with filarial infection. In this review, we take a closer look at the contractile mechanisms of the lymphatics, its altered functions, and remodeling during an inflammatory state and how it relates to the severe pathogenesis underlying a filarial infection. We further elaborate on the complex host–parasite interactions, and molecular mechanisms contributing to the disease pathogenesis. The overall emphasis is on elucidating some of the emerging concepts and new directions that aim to harness the process of lymphangiogenesis or enhance contractility in a dysfunctional lymphatics, thereby restoring the fluid imbalance and mitigating the pathological conditions of lymphatic filariasis.     

Techniques for liver parenchymal transection: a meta-analysis of randomized controlled trials

Background:

Different techniques of liver parenchymal transection have been described, including the finger fracture, sharp dissection, clamp–crush methods and, more recently, the Cavitron ultrasonic surgical aspirator (CUSA), the hydrojet and the radiofrequency dissection sealer (RFDS). This review assesses the benefits and risks associated with the various techniques.

Methods:

Randomized clinical trials were identified from the Cochrane Library Trials Register, MEDLINE, EMBASE, Science Citation Index Expanded and reference lists. Odds ratio (ORs), mean difference (MDs) and standardized mean differences (SMDs) were calculated with 95% confidence intervals based on intention-to-treat analysis or available-case analysis.

Results:

We identified seven trials including a total of 556 patients. Blood transfusion requirements were lower with the clamp–crush technique than with the CUSA or hydrojet. The clamp–crush technique was quicker than the CUSA, hydrojet or RFDS. Infective complications and transection blood loss were greater with the RFDS than with the clamp–crush method. There was no significant difference between techniques in mortality, morbidity, liver dysfunction or intensive therapy unit and hospital stay.

Conclusions:

The clamp–crush technique is more rapid and is associated with lower rates of blood loss and otherwise similar outcomes when compared with other methods of parenchymal transection. It represents the reference standard against which new methods may be compared.