The M694V mutation in Armenian‐Americans: a 10‐year retrospective study of MEFV mutation testing for familial Mediterranean fever at UCLA

Familial Mediterranean fever (FMF), inherited in an autosomal recessive manner, is a systemic auto‐inflammatory disorder characterized by recurrent attacks of fever with peritonitis, pleuritis, synovitis and erysipeloid rash. The marenostrin‐encoding fever (MEFV) gene, located on chromosome 16p13.3, is the only gene in which mutations are currently known to cause FMF. To correlate specific genotypes with adverse phenotypes of affected populations residing in the Western United States, a retrospective case series review was conducted of all MEFV gene mutation testing completed at UCLA Clinical Molecular Diagnostic Laboratory between February 2002 and February 2012, followed by clinical chart review of all subjects who either have a single or double mutation. All 12 common mutations in the MEFV gene were analyzed and the M694V variant was found to be associated with an adverse FMF clinical outcome in the Armenian‐American population, manifested by earlier onset of disease, increased severity of disease, and renal amyloidosis.     

An evidence-based review of enhanced recovery interventions in knee replacement surgery

IntroductionTotal knee replacement (TKR) is a very common surgical procedure. Improved pain management techniques, surgical practices and the introduction of novel interventions have enhanced the patient’s postoperative experience after TKR. Safe, efficient pathways are needed to address the increasing need for knee arthroplasty in the UK. Enhanced recovery programmes can help to reduce hospital stays following knee replacements while maintaining patient safety and satisfaction. This review outlines common evidence-based pre, intra and postoperative interventions in use in enhanced recovery protocols following TKR.MethodsA thorough literature search of the electronic healthcare databases (MEDLINE^®, Embase™ and the Cochrane Library) was conducted to identify articles and studies concerned with enhanced recovery and fast track pathways for TKR.ResultsA literature review revealed several non-operative and operative interventions that are effective in enhanced recovery following TKR including preoperative patient education, pre-emptive and local infiltration analgesia, preoperative nutrition, neuromuscular electrical stimulation, pulsed electromagnetic fields, perioperative rehabilitation, modern wound dressings, different standard surgical techniques, minimally invasive surgery and computer assisted surgery.ConclusionsEnhanced recovery programmes require a multidisciplinary team of dedicated professionals, principally involving preoperative education, multimodal pain control and accelerated rehabilitation; this will be boosted if combined with minimally invasive surgery. The current economic climate and restricted healthcare budget further necessitate brief hospitalisation while minimising costs. These non-operative interventions are the way forward to achieve such requirements.     

A review of outcomes of the surgical management of femoroacetabular impingement

Introduction

Femoroacetabular impingement (FAI) resulting from abnormal contact between the acetabulum and femur has been studied extensively in recent years owing to its association with acetabular labrum tears and possible contribution to the development of osteoarthritis.

Methods

A comprehensive PubMed, MEDLINE^® and Embase™ literature search was conducted. Search terms included ‘femoroacetabular impingement’, ‘pathophysiology’, ‘diagnosis’, ‘dGEMRIC’, ‘arthroscopic’, ‘open’, ‘mini-open’ and ‘outcome measure’.

Results

A range of radiographic features have been described, and computed tomography and magnetic resonance imaging are both commonly used in the diagnosis of the bony abnormalities in FAI. Treatment of FAI is surgical with methods of treatment ranging from open surgical hip dislocation to arthroscopic osteochondroplasty.

Conclusions

In recent years, a trend towards the use of arthroscopic treatment for FAI has been seen, with promising results from a range of studies. However, only short-term outcome data are available and a range of different outcome measures have been used in studies to date. We present an overview of the outcomes for a range of surgical treatment methods for FAI and discuss the outcome measures used.     

In vivo relationship of interleukin-2 and soluble IL-2 receptor to blood-brain barrier impairment in patients with active multiple sclerosis

Interleukin (IL)-2 has well-recognized effects on cerebral endothelial cells and, therefore, may mediate disruption of the blood-brain barrier in patients with multiple sclerosis (MS). To evaluate the in vivo relationship of the IL-2 system to blood-brain barrier impairment in MS, levels of IL-2 and soluble IL-2 receptors (sIL-2R) in cerebrospinal fluid (CSF) and serum samples from 50 patients with active MS and 49 controls were correlated with values of the CSF to serum albumin ratio. Intrathecal levels of IL-2 and sIL-2R were significantly higher in MS compared with the control groups and correlated with albumin ratios in MS patients. Intrathecal levels of IL-2 and sIL-2R also correlated with the degree of barrier damage in these patients. It is suggested that intrathecal levels of IL-2 and sIL-2R are related to barrier impairment in MS and may be important in understanding some of the pathological changes of this condition.     

Correlation of interleukin-2 and soluble interleukin-2 receptor with clinical activity of multiple sclerosis.

Concentrations of interleukin-2 (IL-2) and soluble IL-2 receptor (sIL-2R) in serum and CSF samples were measured in 63 patients with multiple sclerosis (MS) to evaluate their usefulness as markers of disease activity. CSF concentrations of IL-2 and sIL-2R were significantly higher in MS relapse compared with MS patients in remission or with control subjects. These concentrations correlated with the clinical score by which disease severity was assessed, with the number of relapses per year, and with the total disease duration. Furthermore, there was evidence of intrathecal release of IL-2 and sIL-2R in clinically active MS. The results extend the notion that an activated cellular immune state parallels the evolution of the pathological process in MS and suggest that measurement of IL-2 and sIL-2R concentrations may provide an objective marker of disease activity in patients with MS.     

Hypokalaemic myopathy in alcoholism

We describe the clinical and pathological features of a patient with an acute painless proximal myopathy due to hypokalaemia associated with alcoholism. There was an excellent response to treatment with potassium supplements. The importance of recognition of low potassium states in alcohol-dependent patients with muscular weakness is emphasized.