The impact of acetabular labral tears on sexual activity in women.

A healthy sex-life is an important component of a good quality of life. However, sexual function may be inhibited in women with acetabular labral tears because of the labrum being caught between the femoral head neck junction and the acetabular rim during flexion and/or abduction of the hip. The aim of this article is to quantify the effect that acetabular labral tears may have on the sexual lives of women and to establish the extent to which they may be expected to resolve after arthroscopic intervention. The article also highlights the importance of including questions related to the impact on sexual activity as a routine part of our taking history for a young adult with hip pain, to gain a true appreciation of the impact the symptoms have on the day-to-day lives of our patients.

ISHA-Richard Villar Best Clinical Paper Award: Acetabular labral tears in sexually active women: an evaluation of patient satisfaction following hip arthroscopy.

The aim of this study was to evaluate the effect of symptomatic labral tears on the sex lives of women and the effect of surgical intervention on hip symptoms during sexual intercourse. One hundred and twenty consecutive women who had undergone hip arthroscopy under a single surgeon at a tertiary referral centre were identified. A specific questionnaire was designed and sent to each of the patients. Data were collected on the nature of symptoms, if they experienced any hip pain during sexual intercourse and if this had impacted on their sex lives and the degree of resolution of hip symptoms after the procedure, on a scale of 1-10. One hundred and four responses were available. Ninety-two women reported that they were sexually active. Of these, 87 (94%) reported pain during intercourse affecting their sex life. Eight women reported hip pain for a few days following intercourse and four stated that they are often not able to continue on account of the pain. Mean patient satisfaction with a resolution of symptoms during intercourse was 7.8 out of the 10. Seventy-seven women reported a post-operative improvement in the hip symptoms experienced during sex. Labral tears do have a significant effect on the sex life of women. Hip arthroscopy to address the labral tear as well as any underlying pathology relieves the pain experienced by women during intercourse with, a resultant improvement in their sex lives.

Discovery of 1-(1H-Pyrazolo[4,3-c]pyridin-6-yl)urea Inhibitors of Extracellular Signal-Regulated Kinase (ERK) for the Treatment of Cancers.

The ERK/MAPK pathway plays a central role in the regulation of critical cellular processes and is activated in more than 30% of human cancers. Specific BRAF and MEK inhibitors have shown clinical efficacy in patients for the treatment of BRAF-mutant melanoma. However, the majority of responses are transient, and resistance is often associated with pathway reactivation of the ERK signal pathway. Acquired resistance to these agents has led to greater interest in ERK, a downstream target of the MAPK pathway. De novo design efforts of a novel scaffold derived from SCH772984 by employing hydrogen bond interactions specific for ERK in the binding pocket identified 1-(1H-pyrazolo[4,3-c]pyridin-6-yl)ureas as a viable lead series. Sequential SAR studies led to the identification of highly potent and selective ERK inhibitors with low molecular weight and high LE. Compound 21 exhibited potent target engagement and strong tumor regression in the BRAF(V600E) xenograft model.

Medium to long term follow up of a consecutive series of 604 Exeter Trauma Stem Hemiarthroplasties (ETS) for the treatment of displaced intracapsular femoral neck fractures.

The aim of this study was to evaluate the medium to long term follow up results for the Exeter Trauma Stem (ETS) in the treatment of displaced femoral neck fractures. We retrospectively evaluated 604 consecutive cemented ETS hemiarthroplasties performed at our institution between 2007 and 2012. The range of follow up was 2-7 years with a mean follow-up of 4.1 years for the surviving patients. The mean age of the patient population was 84 years (range 46-106) with 81.3% female patients. 382 patients (63.2%) died within the follow up period. Postoperative superficial soft tissue infection occurred in 11 patients and deep prosthetic infection in 5 patients. Dislocation occurred in 11 patients and periprosthetic fracture occurred in 7 patients. 11 patients underwent Girdlestone excision arthroplasty and 6 patients were revised to total hip replacement. This paper represents the largest consecutive series for this implant, with the longest follow up currently available. The results confirm that the prosthesis is an excellent implant for these patients with a low risk of needing revision surgery.

Integrated care pathways in lower-limb arthroplasty: are they effective in reducing length of hospital stay?

PURPOSE: The aim of this study was to examine the effect of an integrated care pathway (ICP) for total hip and knee arthroplasty (THA/TKA) on length of stay (LOS), day of surgery admission rate (DOSA) and postoperative length of stay (POLOS). METHODS: Three hundred and eight THAs and 299 TKAs were assessed in a retrospective before-after trial design. LOS, POLOS and DOSA were recorded for patients before and after introduction of the ICP. The ICP encompassed a patient education programme, specific daily management goals, variance mapping, daily facilitated meetings and a DOSA policy. Subgroup analysis according to age and gender was also performed. RESULTS: Mean LOS was significantly reduced by 1.4 (from 6.9 to 5.5) days for THA and 0.8 (from 6.4 to 5.6) days for TKA. Elderly patients and men achieved greater LOS reductions than their counterparts for both operations. Younger patients undergoing THA achieved a significantly higher DOSA rate than older patients (89 % vs 71 %, p = 0.010); however, this difference was not observed in the TKA population. Mean POLOS for THA was reduced by 0.6 (from 5.9 to 5.3) days, again with the greatest benefit seen in elderly and male patients. POLOS for TKA patients was not significantly affected by the ICP. CONCLUSIONS: The introduction of an ICP reduced LOS by 1.4 days for THA and 0.8 days for TKA. Elderly and male patients benefitted most.

Factors associated with prolonged length of stay following a total knee replacement in patients aged over 75.

PURPOSE: The aim of this study was to examine factors associated with a prolonged length of stay (LOS) in patients over 75 undergoing a total knee replacement (TKR). METHODS: Patients over 75 undergoing a TKR at our institution from January 2008 to February 2009 were identified (n = 112). Patient and operative factors previously shown to affect length of stay were identified. Patient notes were reviewed for details on each of these and data analysed for their effect on length of stay. Discrete data were analysed for their effect on post-operative length of stay using either the Mann-Whitney U test or the Kruskall-Wallis test and continuous data analysed with the Spearman's rank correlation coefficient. RESULTS: The following factors were associated with length of stay at the 95 % confidence level: patient age, pre-operative mobility and the use of walking aids, BMI, whether the patient was able to mobilise within 24 or 48 hours of the surgery, the day on which the patient first walked ten metres and achieved 90° active knee flexion, pre and post-operative haemoglobin and the need for a blood transfusion. CONCLUSIONS: Pre-operative use of walking aids, peri-operative haemoglobin concentration, failure to mobilise early following the operation and post-operative complications (including the need for a blood transfusion) seem to be the significant factors associated with a prolonged stay in hospital in the over 75 year olds.

Fibrin-mediated lentivirus gene transfer: implications for lentivirus microarrays.

We employed fibrin hydrogel as a bioactive matrix for lentivirus mediated gene transfer. Fibrin-mediated gene transfer was highly efficient and exhibited strong dependence on fibrinogen concentration. Efficient gene transfer was achieved with fibrinogen concentration between 3.75 and 7.5mg/ml. Lower fibrinogen concentrations resulted in diffusion of virus out of the gel while higher concentrations led to ineffective fibrin degradation by target cells. Addition of fibrinolytic inhibitors decreased gene transfer in a dose-dependent manner suggesting that fibrin degradation by target cells may be necessary for successful gene delivery. Under these conditions transduction may be limited only to cells interacting with the matrix thereby providing a method for spatially-localized gene delivery. Indeed, when lentivirus-containing fibrin microgels were spotted in an array format gene transfer was confined to virus-containing fibrin spots with minimal cross-contamination between neighboring sites. Collectively, our data suggest that fibrin may provide an effective matrix for spatially-localized gene delivery with potential applications in high-throughput lentiviral microarrays and in regenerative medicine.

Melatonin improves placental efficiency and birth weight and increases the placental expression of antioxidant enzymes in undernourished pregnancy.

Melatonin participates in circadian, seasonal and reproductive physiology. Melatonin also acts as a potent endogenous antioxidant by scavenging free radicals and upregulating antioxidant pathways. The placenta expresses melatonin receptors and melatonin protects against oxidative damage induced in rat placenta by ischemia-reperfusion. One of the most common complications in pregnancy is a reduction in fetal nutrient delivery, which is known to promote oxidative stress. However, whether melatonin protects placental function and fetal development in undernourished pregnancy is unknown. Here, we investigated the effects of maternal treatment with melatonin on placental efficiency, fetal growth, birth weight and protein expression of placental oxidative stress markers in undernourished pregnancy. On day 15 of pregnancy, rats were divided into control and undernourished pregnancy (35% reduction in food intake), with and without melatonin treatment (5 microg/mL drinking water). On day 20 of gestation, fetal biometry was carried out, the placenta was weighed and subsequently analyzed by Western blot for xanthine oxidase, heat shock protein (HSP) 27 and 70, catalase, manganese superoxide dismutase (Mn-SOD) and glutathione peroxidase 1 (GPx-1). A separate cohort was allowed to deliver to assess effects on birth weight. Maternal undernutrition led to a fall in placental efficiency, disproportionate intrauterine growth retardation and a reduction in birth weight. Maternal treatment with melatonin in undernourished pregnancy improved placental efficiency and restored birth weight, and it increased the expression of placental Mn-SOD and catalase. The data show that in pregnancy complicated by undernutrition, melatonin may improve placental efficiency and birth weight by upregulating placental antioxidant enzymes.