Epidemiology of glenohumeral dislocation and subsequent instability in an urban population

Background: Glenohumeral dislocation is the most commonly encountered adult joint instability. The epidemiology in the United Kingdom and worldwide is unclear and often limited to young, active groups that are not representative of general populations. Information regarding epidemiology and outcome from a first dislocation is useful for trauma service planning and patient counseling. We calculated the incidence of shoulder instability after a first dislocation in our urban population and investigated predictors of recurrent instability. Methods: A prospectively collected trauma database was retrospectively examined to identify patients with a first-time dislocation. Demographics, subsequent dislocation, and instability details were collected from electronic patient records. Results: In a 38-month study period, 329 first dislocations occurred in a population of 475,147 with mean follow-up 28.5 months (range, 10-50 months). The overall incidence for first-time dislocations in this population was 21.9 per 100,000 population, of which 7.9% sustained a redislocation and 6.1% had further symptomatic instability. There were 18.8% with associated greater tuberosity fractures, 8.8% sustained a nerve injury, and 2.7% were posterior dislocations. A bimodal distribution was observed for males (peak incidence per 100,000 of 42.1 and 50.9 in 15-24 and ≥85 age groups, respectively), and unimodal for females (peak 45.7 in the 65-74 age group). Conclusion: We demonstrate a previously unreported burden of dislocation in older age groups and suggest a rate of recurrence lower than previously reported in the United Kingdom. The group aged 15 to 19 years was at the highest risk of recurrent dislocation and instability. Gender was not a significant predictor of instability

Post-Operative Radiotherapy for Soft Tissue Sarcoma of the Anterior Compartment of the Thigh: Should the Sartorius Muscle be Included?

Purpose: The clinical target volume (CTV) of post-operative radiotherapy for soft tissue sarcoma of the limbs conventionally includes the whole of the transverse cross-section of the affected anatomical compartment. In the anterior thigh sartorius appears to lie within its own fascial compartment and can be safely excluded. We investigated the potential impact of omitting sartorius from the anterior muscle compartment on patients with soft tissue sarcoma of the thigh

The Anatomy of Sartorius Muscle and its Implications for Sarcoma Radiotherapy

Purpose: Controversy exists as to whether sartorius muscle is completely invested in fascia. If it is, then direct tumour involvement from soft tissue sarcoma of the anterior thigh would be unlikely and would justify omitting sartorius from the radiotherapy volume

Death or survival from invasive pneumococcal disease in Scotland: associations with serogroups and multilocus sequence types

We describe associations between death from invasive pneumococcal disease (IPD) and particular serogroups and sequence types (STs) determined by multilocus sequence typing (MLST) using data from Scotland. All IPD episodes where blood or cerebrospinal fluid (CSF) culture isolates were referred to the Scottish Haemophilus, Legionella, Meningococcal and Pneumococcal Reference Laboratory (SHLMPRL) from January 1992 to February 2007 were matched to death certification records by the General Register Office for Scotland. This represented 5959 patients. The median number of IPD cases in Scotland each year was 292. Deaths, from any cause, within 30 days of pneumococcal culture from blood or CSF were considered to have IPD as a contributing factor. Eight hundred and thirty-three patients died within 30 days of culture of Streptococcus pneumoniae from blood or CSF [13.95%; 95% confidence interval (13.10, 14.80)]. The highest death rates were in patients over the age of 75. Serotyping data exist for all years but MLST data were only available from 2001 onward. The risk ratio of dying from infection due to particular serogroups or STs compared to dying from IPD due to all other serogroups or STs was calculated. Fisher's exact test with Bonferroni adjustment for multiple testing was used. Age adjustment was accomplished using the Cochran-Mantel-Haenszel test and 95% confidence intervals were reported. Serogroups 3, 11 and 16 have increased probability of causing fatal IPD in Scotland while serogroup 1 IPD has a reduced probability of causing death. None of the 20 most common STs were significantly associated with death within 30 days of pneumococcal culture, after age adjustment. We conclude that there is a stronger association between a fatal outcome and pneumococcal capsular serogroup than there is between a fatal outcome and ST

Post-Operative Radiotherapy for Soft Tissue Sarcoma of the Anterior Compartment of the Thigh: Should the Sartorius Muscle be Included?

PURPOSE: The clinical target volume (CTV) of post-operative radiotherapy for soft tissue sarcoma of the limbs conventionally includes the whole of the transverse cross-section of the affected anatomical compartment. In the anterior thigh sartorius appears to lie within its own fascial compartment and can be safely excluded. We investigated the potential impact of omitting sartorius from the anterior muscle compartment on patients with soft tissue sarcoma of the thigh. PATIENTS AND METHODS: We used the planning CT data from six patients who had previously received post-operative radiotherapy for soft tissue sarcoma of the thigh. The anterior compartments were outlined twice, initially including and then excluding the sartorius muscle. The volumes of the anterior compartment (i.e., the CTVs), both with and without sartorius, and the corresponding planning target volumes (PTVs) were calculated. Treatment plans were prepared for each PTV. For both volumes the unirradiated normal tissue corridor was outlined on each CT slice. The volume and circumference of the unirradiated corridor were then calculated. RESULTS: For all six patients there was an important improvement in normal tissue sparing by excluding sartorius. The mean reduction in volume of the anterior compartment when sartorius was excluded was 10% (95% Confidence Interval 8-12%), whilst the mean decrease in PTV was 11% (95% CI 7-14%). There was a substantial increase in the volume of the unirradiated normal tissue corridor, with a mean value of 77% (95% CI 41-114%) when sartorius was excluded. In addition, the percentage increase in the size of the unirradiated normal tissue corridor, expressed as a percentage of the whole leg circumference, was 10% (95% CI 8-13%). When sartorius was included in the anterior compartment, the circumference of the unirradiated corridor was less than one-third of the whole leg circumference in four of the six patients. When sartorius was excluded, the circumference of the unirradiated corridor was greater than one-third of the leg circumference over the entire length of the target volume in all patients. DISCUSSION: It is essential to know the anatomy of the sartorius muscle to be able to exclude it from the anterior compartment. The increase in the size of the normal tissue corridor when sartorius is excluded should deliver clinical advantage by decreasing the normal tissue adverse effects.Peer Reviewe

The anatomy of sartorius muscle and its implications for sarcoma radiotherapy.

PURPOSE: Controversy exists as to whether sartorius muscle is completely invested in fascia. If it is, then direct tumour involvement from soft tissue sarcoma of the anterior thigh would be unlikely and would justify omitting sartorius from the radiotherapy volume. SUBJECTS AND METHODS: Eight thighs in six cadavers were examined in the dissecting room. Using a previous case, conformal radiotherapy plans were prepared to treat the anterior compartment of the thigh including and excluding sartorius. The corridor of unirradiated normal tissue was outlined separately. RESULTS: In all cases, sartorius was enclosed within a fascial sheath of its own. In four of the six cadavers, there was clear evidence of a fascial envelope surrounding sartorius, fused to the fascia lata and medial intermuscular septum. In two, sartorius was fully ensheathed in the upper half of the thigh; in the lower half the intermuscular septum became thin, and blended with the tendinous aponeurosis on the surface of vastus medialis in an example case. By excluding sartorius, the volume of the anterior compartment was reduced by 8%, but the volume of the unirradiated normal tissue corridor increased by 134%. With sartorius included, the unirradiated corridor became very small inferiorly, only 6% of the circumference of the whole leg, compared to 27% with sartorius excluded. DISCUSSION: The anatomy suggests that sartorius could be safely omitted from the clinical target volume of anterior compartment soft tissue sarcomas. This substantially increases the size of the unirradiated normal tissue corridor, expressed as a volume and a circumference, which could give a clinical advantage by reducing normal tissue complications.Peer Reviewe

Presence of Nonhemolytic Pneumolysin in Serotypes of Streptococcus pneumoniae Associated with Disease Outbreaks

Pneumolysin is an important virulence factor of the human pathogen Streptococcus pneumoniae. Sequence analysis of the ply gene from 121 clinical isolates of S. pneumoniae uncovered a number of alleles. Twenty-two strains were chosen for further analysis, and 14 protein alleles were discovered. Five of these had been reported previously, and the remaining 9 were novel. Cell lysates were used to determine the specific hemolytic activities of the pneumolysin proteins. Six strains showed no hemolytic activity, and the remaining 16 were hemolytic, to varying degrees. We report that the nonhemolytic allele reported previously in serotype 1, sequence type (ST) 306 isolates is also present in a number of pneumococcal isolates of serotype 8 that belong to the ST53 lineage. Serotype 1 and 8 pneumococci are known to be associated with outbreaks of invasive disease. The nonhemolytic pneumolysin allele is therefore associated with the dominant clones of outbreak-associated serotypes of S. pneumonia

Trends in serotypes and sequence types among cases of invasive pneumococcal disease in Scotland, 1999-2010.

INTRODUCTION: The 7-valent pneumococcal conjugate vaccine (Prevenar(®), Wyeth; PCV7) was introduced to the UK paediatric immunisation schedule in 2006. This study investigates trends in serotypes and multi locus sequence types (STs) among cases of invasive pneumococcal disease (IPD) in Scotland prior to, and following, the introduction of PCV7. METHODS: Scottish Invasive Pneumococcal Disease Enhanced Surveillance has records of all cases of IPD in Scotland since 1999. Cases diagnosed from blood or cerebrospinal fluid isolates until 2010 were analysed. Logistic and poisson regression modelling was used to assess trends prior to and following the introduction of PCV7. RESULTS: Prior to PCV7 use, on average 650 cases of IPD were reported each year; 12% occurred in those aged <5 years and 35% affected those aged over 65 years. Serotypes in PCV7 represented 47% of cases (68% in <5 year olds). The serotype and ST distribution was relatively stable with only serotype 1 and associated ST 306 showing an increasing trend. PCV7 introduction was associated with a 69% (95% CI: 50%, 80%) reduction in the incidence of IPD among those aged <5 years, a 57% (95% CI: 47%, 66%) reduction among those aged 5-64 years but no significant change among those aged 65 years and over where increases in non-PCV7 serotypes were observed. Serotypes which became more prevalent post-PCV7 are those which were associated with STs related to the PCV7 serotypes. CONCLUSIONS: Routine serotyping and sequence typing in Scotland allowed the assessment of the relationship between the capsule and the clones in the post vaccination era. Changes in the distribution of serotypes post PCV7 introduction appear to be driven by associations between serotypes and STs prior to PCV7 introduction. This has implications for the possible effects of the introduction of higher valency vaccines and could aid in predicting replacement serotypes in IPD

The PIKfyve Inhibitor YM201636 Blocks the Continuous Recycling of the Tight Junction Proteins Claudin-1 and Claudin-2 in MDCK cells

Tight junctions mediate the intercellular diffusion barrier found in epithelial tissues but they are not static complexes; instead there is rapid movement of individual proteins within the junctions. In addition some tight junction proteins are continuously being endocytosed and recycled back to the plasma membrane. Understanding the dynamic behaviour of tight junctions is important as they are altered in a range of pathological conditions including cancer and inflammatory bowel disease. In this study we investigate the effect of treating epithelial cells with a small molecule inhibitor (YM201636) of the lipid kinase PIKfyve, a protein which is involved in endocytic trafficking. We show that MDCK cells treated with YM201636 accumulate the tight junction protein claudin-1 intracellularly. In contrast YM201636 did not alter the localization of other junction proteins including ZO-1, occludin and E-cadherin. A biochemical trafficking assay was used to show that YM201636 inhibited the endocytic recycling of claudin-1, providing an explanation for the intracellular accumulation. Claudin-2 was also found to constantly recycle in confluent MDCK cells and treatment with YM201636 blocked this recycling and caused accumulation of intracellular claudin-2. However, claudin-4 showed negligible endocytosis and no detectable intracellular accumulation occurred following treatment with YM201636, suggesting that not all claudins show the same rate of endocytic trafficking. Finally, we show that, consistent with the defects in claudin trafficking, incubation with YM201636 delayed formation of the epithelial permeability barrier. Therefore, YM201636 treatment blocks the continuous recycling of claudin-1/claudin-2 and delays epithelial barrier formation

Quantitative Assessment of the Sensitivity of Various Commercial Reverse Transcriptases Based on Armored HIV RNA

The in-vitro reverse transcription of RNA to its complementary DNA, catalyzed by the enzyme reverse transcriptase, is the most fundamental step in the quantitative RNA detection in genomic studies. As such, this step should be as analytically sensitive, efficient and reproducible as possible, especially when dealing with degraded or low copy RNA samples. While there are many reverse transcriptases in the market, all claiming to be highly sensitive, there is need for a systematic independent comparison of their applicability in quantification of rare RNA transcripts or low copy RNA, such as those obtained from archival tissues.We performed RT-qPCR to assess the sensitivity and reproducibility of 11 commercially available reverse transcriptases in cDNA synthesis from low copy number RNA levels. As target RNA, we used a serially known number of Armored HIV RNA molecules, and observed that 9 enzymes we tested were consistently sensitive to ∼1,000 copies, seven of which were sensitive to ∼100 copies, while only 5 were sensitive to ∼10 RNA template copies across all replicates tested. Despite their demonstrated sensitivity, these five best performing enzymes (Accuscript, HIV-RT, M-MLV, Superscript III and Thermoscript) showed considerable variation in their reproducibility as well as their overall amplification efficiency. Accuscript and Superscript III were the most sensitive and consistent within runs, with Accuscript and Superscript II ranking as the most reproducible enzymes between assays.We therefore recommend the use of Accuscript or Superscript III when dealing with low copy number RNA levels, and suggest purification of the RT reactions prior to downstream applications (eg qPCR) to augment detection. Although the results presented in this study were based on a viral RNA surrogate, and applied to nucleic acid lysates derived from archival formalin-fixed paraffin embedded tissue, their relative performance on RNA obtained from other tissue types may vary, and needs future evaluation