Variable life adjusted display methodology for continuous performance monitoring of carotid endarterectomy.

Introduction The aim of this study was to use variable life-adjusted display (VLAD) methodology to monitor performance of six vascular surgeons undertaking carotid endarterectomy in a single institution. Materials and methods This was a prospective study with continuous analysis. A risk score model to predict 30-day stroke or death for individual patients was developed from data collected from 839 patients from 1992 to 1999. The model was used to monitor performance of six surgeons from 2000 to 2009. Individual risk factors and 30-day outcomes were analysed and VLAD plots were created for the whole unit and for each surgeon. Results Among the 941 carotid endarterectomies in the performance analysis, 28 adverse events were recorded, giving an overall stroke or death rate of 3.06%. The risk model predicted there would be 33 adverse events. There was no statistical difference between the predicted and the observed adverse events (P > 0.2, χ2 value 1.25, 4 degrees of freedom). The VLAD plot for the whole unit shows an overall net gain in operative performance, although this could have been chance variation. The individual VLAD plot showed that surgeons 1, 2, 3 and 6 to have an overall net gain in the number of successful operations. The changes observed between the surgeons was not significant (P > 0.05) suggesting chance variation only. Conclusions Performance of carotid endarterectomy can be continuously assessed using VLAD methodology for units and individual surgeons. Early identification and correction of performance variation could facilitate improved quality of care.

Room temperature plasmonic lasing in a continuous wave operation mode from an InGaN/GaN single nanorod with a low threshold.

It is crucial to fabricate nano photonic devices such as nanolasers in order to meet the requirements for the integration of photonic and electronic circuits on the nanometre scale. The great difficulty is to break down a bottleneck as a result of the diffraction limit of light. Nanolasers on a subwavelength scale could potentially be fabricated based on the principle of surface plasmon amplification by stimulated emission of radiation (SPASER). However, a number of technological challenges will have to be overcome in order to achieve a SPASER with a low threshold, allowing for a continuous wave (cw) operation at room temperature. We report a nano-SPASER with a record low threshold at room temperature, optically pumped by using a cw diode laser. Our nano-SPASER consists of a single InGaN/GaN nanorod on a thin SiO2 spacer layer on a silver film. The nanorod containing InGaN/GaN multi-quantum-wells is fabricated by means of a cost-effective post-growth fabrication approach. The geometry of the nanorod/dielectric spacer/plasmonic metal composite allows us to have accurate control of the surface plasmon coupling, offering an opportunity to determine the optimal thickness of the dielectric spacer. This approach will open up a route for further fabrication of electrically injected plasmonic lasers.

ESHRE PGD Consortium data collection XII: cycles from January to December 2009 with pregnancy follow-up to October 2010.

STUDY QUESTION: How do data in the 12th annual data collection (Data XII) of the European Society of Human Reproduction and Embryology Preimplantation Genetic Diagnosis (PGD) Consortium compare with the cumulative data for collections I-XI? SUMMARY ANSWER: Since the beginning of the data collections, there has been a steady increase in the number of cycles, pregnancies and babies reported annually. WHAT IS KNOWN ALREADY: The PGD Consortium has collected, analysed and published 11 previous data sets since 1997. STUDY DESIGN, SIZE, DURATION: Data were collected from each participating centre using a pre-designed FileMaker Pro database (versions 5-10). Separate FileMaker Pro files were used for the cycles, pregnancies and baby records. The study documented cycles performed during the calendar year 2009 and follow-up of the pregnancies and babies born which resulted from these cycles (until October 2010). PARTICIPANTS/MATERIALS, SETTING, METHODS: Data were submitted by 60 centres (full PGD Consortium members), and the blank files were distributed to each PGD Consortium member centre at the end of 2008. The submitted data were thoroughly analysed to identify incomplete data entries and corrections were requested from the participating centres. Records remaining with incomplete data were excluded from the calculations. Corrections, tables and calculations were made by expert co-authors. MAIN RESULTS AND THE ROLE OF CHANCE: For data collection XII, 60 centres reported data for 6160 cycles with oocyte retrieval (OR), along with details of the follow-up on 1607 pregnancies and 1238 babies born. A total of 870 OR were reported for chromosomal abnormalities, 113 OR for sexing for X-linked diseases, 1597 OR for monogenic diseases, 3551 OR for preimplantation genetic screening and 29 OR for social sexing. LIMITATIONS, REASONS FOR CAUTION: These data cannot include every PGD cycle performed annually, and only indicate the trends in PGD worldwide. WIDER IMPLICATION OF THE FINDINGS: The annual data collections provide an extremely valuable resource for data mining and for following trends in PGD practice. STUDY FUNDING/COMPETING INTEREST(S): None.

The ESHRE PGD Consortium: 10 years of data collection.

BACKGROUND: Since it was established in 1997, the ESHRE PGD Consortium has been collecting data from international preimplantation genetic diagnosis (PGD) centres. Ten papers have been published, including data from January 1997 to December 2007. METHODS: The data collection originally used a hard-copy format, then an excel database and finally a FileMaker Pro database. The indications are divided into five categories: PGD for chromosome abnormalities, sexing for X-linked disease, PGD for single gene defects, preimplantation genetic screening (PGS) and PGD for social sexing. The main end-points are pregnancy outcome and follow-up of deliveries. RESULTS: In data collection I, 16 centres contributed data, which increased to 57 centres by data X (average of 39 centres per data collection). These centres contributed data on over 27 000 cycles that reached oocyte retrieval. Of these cycles, 61% were for aneuploidy screening, 17% for single gene disorders, 16% for chromosomal abnormalities, 4% for sexing of X-linked disease and 2% for social sexing. Cumulatively, 5187 clinical pregnancies gave rise to 4140 deliveries and 5135 newborns (singletons: 3182, twins: 921, triplets: 37). CONCLUSIONS: In this paper, we present an overview of the first 10 years of PGD data, highlighting trends. These include the introduction of laser-assisted biopsy, an increase in polar body and trophectoderm biopsy, new strategies, methodologies and technologies for diagnosis, including recently arrays, and the more frequent use of freezing biopsied embryos. The Consortium data reports represent a valuable resource for information about the practice of PGD.

Recurrent familial malignant carotid body tumour presenting with lymph node metastasis: case report, and review of diagnosis and management of familial carotid body tumours.

OBJECTIVE: We report the case of a recurrent familial malignant carotid body tumour presenting with metastasis to local ipsilateral lymph nodes; the rarity of both recurrence combined with nodal spread is emphasised in this article. METHOD: We present a case report, and a review of the world literature concerning the diagnosis and management of carotid body tumours in the familial setting. CASE REPORT: A woman with a family history of succinate dehydrogenase complex subunit B gene mutation presented with right vocal fold palsy. A causative carotid body tumour was excised. Fifteen years later, the patient developed a right-sided swelling in the jugulo-digastric region, together with shooting pains towards her right ear. Imaging revealed right posterior triangle lymphadenopathy. Fine needle aspiration cytology of the node was equivocal. Computed tomography of her neck revealed, in addition, a mass within the right side of the larynx. Excision biopsy of the lymph node demonstrated metastatic paraganglioma. A carotid angiogram revealed a right-sided carotid body tumour. This was embolised prior to neck exploration and excision of the carotid body tumour with en bloc resection of adjacent nodes. Histological analysis confirmed the presence of lymph nodes containing metastatic paraganglioma. CONCLUSION: This case report demonstrates the need for extra vigilance to enable early disease detection in the familial setting of carotid body tumour, in order to reduce the surgical morbidity associated with disease progression. In addition, our report highlights the atypical aspects of presentation in the familial setting, together with the difficulty and lack of standardisation regarding monitoring of the disease.

Development and successful clinical application of preimplantation genetic haplotyping for Herlitz junctional epidermolysis bullosa.

BACKGROUND: Herlitz junctional epidermolysis bullosa (HJEB) is a severe, life-threatening, autosomal recessive blistering skin disease for which no cure is currently available. Prenatal diagnosis for couples at risk is feasible through fetal skin biopsy or analysis of DNA extracted from chorionic villi, but these methods can be applied only after pregnancy has been established. An alternative approach, which involves the analysis of single cells from embryos prior to establishment of pregnancy, is preimplantation genetic diagnosis (PGD). Until now, its clinical uptake has been hindered by lengthy delays in establishing mutation-specific protocols, and by the small amount of template DNA that can be obtained from a single cell. A new method that addresses these problems, preimplantation genetic haplotyping (PGH), relies on whole genome amplification followed by haplotyping of multiple polymorphic markers using standard DNA-based polymerase chain reaction (PCR) assays. OBJECTIVES: To design and validate a generic PGH assay for HJEB and to transfer this into clinical practice. MATERIALS AND METHODS: We established a multiplex PCR-based PGH assay involving 16 markers within and flanking the LAMB3 gene (the most frequently mutated gene in HJEB). The assay was then validated in 10 families with at least one previously affected offspring. After licensing by the Human Fertilisation and Embryology Authority (HFEA), the new test was used for PGD in a couple at risk of HJEB. RESULTS: The chromosome 1 LAMB3 markers within the assay were shown to be of sufficient heterogeneity to have widespread application for preimplantation testing of HJEB. In one couple that were heterozygous carriers of nonsense mutations in LAMB3, we used the new assay to identify unaffected embryos in a series of PGD cycles. Pregnancy was established in the third PGD cycle and a healthy, unaffected child was born. DNA analysis of cord blood confirmed the predicted single-cell mutation status of wild-type LAMB3 alleles. CONCLUSIONS: PGH represents a major step forward in widening the scope and availability of preimplantation testing for serious mapped single-gene disorders. We have established a generic test that is suitable for the majority of couples at risk of HJEB.

First use of preimplantation genotyping in prevention of recurrent diandric complete hydatidiform mole.

Complete hydatidiform moles have a diploid chromosome constitution, generally with only paternal genetic material present (diandry). Diandric complete moles are thought to arise either by fertilization of an anucleate oocyte by two spermatozoa or, more commonly, doubling of a single sperm genotype. Molar pregnancies are usually sporadic, and may be accompanied by malignant transformation; however, recurrence is associated with increased risk of further affected pregnancies and of persistent trophoblastic neoplasia or choriocarcinoma. This study presents the first use of preimplantation genotyping to ensure biparental inheritance in a woman presenting with recurrent diandric complete hydatidiform mole. Following an IVF cycle, a single cell from each of 11 embryos was tested by whole genome amplification and genotyping at 16 different simple tandem repeat loci. All embryos showed normal biparental inheritance; one blastocyst was transferred, resulting in the delivery of healthy monozygotic twin girls.

Four novel SPG3A/atlastin mutations identified in autosomal dominant hereditary spastic paraplegia kindreds with intra-familial variability in age of onset and complex phenotype.

Mutation of the atlastin gene (SPG3A) is responsible for approximately 10% of autosomal dominant hereditary spastic paraplegia (AD-HSP) cases. The goal of this study was to identify novel disease causing atlastin mutations. Atlastin nucleotide variations were detected by direct sequencing of all 14 exons in 70 autosomal dominant (AD), 16 single sibship and 14 sporadic spastic paraplegia patients. Six mis-sense mutations (four of which were novel) were identified in six unrelated AD-HSP kindreds in exons 4, 7 and 8 of the atlastin gene. One kindred with a novel mutation showed variability in clinical phenotype and age of onset. Mutations are predicted to decrease GTPase activity, cause morphological abnormalities of the endoplasmic reticulum and prevent maturation of the Golgi complex resulting in impaired vesicle trafficking. Our study significantly adds to the spectrum of mutations and clinical phenotype of SPG3A. We advocate that all spastin mutation negative AD-HSP kindreds should be screened for pathogenic atlastin mutations regardless of age of onset or phenotypic complexity.

Single cell PCR amplification of microsatellites flanking the COL7A1 gene and suitability for preimplantation genetic diagnosis of Hallopeau-Siemens recessive dystrophic epidermolysis bullosa.

BACKGROUND: Hallopeau-Siemens recessive dystrophic epidermolysis bullosa (HS-RDEB) is a severe inherited blistering skin disorder caused by mutations in the anchoring fibril type VII collagen gene, COL7A1. There is currently no effective treatment but DNA-based prenatal testing in families at risk of recurrence is possible, mostly involving chorionic villus sampling at 10-11 weeks' gestation. OBJECTIVES: An alternative method, for avoiding recurrence of HS-RDEB, is preimplantation genetic diagnosis (PGD). This involves DNA analysis of single blastomeres extracted from late cleavage stage embryos following in vitro fertilisation. METHODS: To establish PGD for HS-RDEB, we designed and optimised a sensitive single cell semi-duplex polymerase chain reaction (PCR) assay for two highly polymorphic dinucleotide repeat microsatellite markers, D3S1581 (telomeric) and D3S1289 (centromeric), close to the COL7A1 gene. RESULTS: We demonstrated high PCR efficiency, low allele drop out rates and no contamination in testing this assay on 50 single buccal cells of known heterozygous genotype and 13 research blastomeres from donated embryos. CONCLUSIONS: This semi-duplex PCR method provides robust, reproducible and informative amplification results for single cells. Moreover, this test has now been approved for clinical application by the UK Human Fertilisation and Embryology Authority (HFEA). As such, the development of PGD for HS-RDEB broadens the range of prenatal testing options and personal choice for couples at reproductive risk of this severe genetic skin disease.

The value of abdominal examination in the diagnosis of abdominal aortic aneurysm.

BACKGROUND: There is considerable variability in the reported value of clinical examination in the diagnosis of abdominal aortic aneurysms (AAA). This study aims to assess accuracy of abdominal examination by a doctor, a nurse and the patient in the diagnosis of AAA and whether this accuracy is related to the size of the aneurysm and/or the BMI of the patient. METHODS: 164 patients, 138 men and 26 women, median age 71 years, consented to participate in this prospective, single blind, controlled study. Thirty-nine patients attending for carotid duplex were used as controls. Abdominal examination was performed by a doctor and a nurse. Patients then performed self-examination. RESULTS: Examination by a doctor, a nurse and the patient were similar in accuracy in diagnosing/excluding AAA which was directly related to AAA size and patient BMI. The Negative Predicted Value of abdominal examination exceeds 0.9 with AAA diameters > or =4 cm and the Positive Predictive Value exceeds 0.8 with AAA diameters > or =5 cm. CONCLUSIONS: Abdominal examination by a doctor, a nurse and the patient is of value in the exclusion and diagnosis of significant AAA. It should be promoted and may represent a useful adjunct to population screening with ultrasound.

The role of hyperbaric oxygen therapy in ischaemic diabetic lower extremity ulcers: a double-blind randomised-controlled trial.

OBJECTIVE: ischaemic lower-extremity ulcers in the diabetic population are a source of major concern because of the associated high risk of limb-threatening complications. The aim of this study was to evaluate the role of hyperbaric oxygen in the management of these ulcers. METHOD: eighteen diabetic patients with ischaemic, non-healing lower-extremity ulcers were recruited in a double-blind study. Patients were randomly assigned either to receive 100% oxygen (treatment group) or air (control group), at 2.4 atmospheres of absolute pressure for 90 min daily (total of 30 treatments). RESULTS: healing with complete epithelialisation was achieved in five out of eight ulcers in the treatment group compared to one out of eight ulcers in the control group. The median decrease of the wound areas in the treatment group was 100% and in the control group was 52% (p=0.027). Cost-effectiveness analysis has shown that despite the extra cost involved in using hyperbaric oxygen, there was a potential saving in the total cost of treatment for each patient during the study. CONCLUSION: hyperbaric oxygen enhanced the healing of ischaemic, non-healing diabetic leg ulcers and may be used as a valuable adjunct to conventional therapy when reconstructive surgery is not possible.

POSSUM and P-POSSUM overpredict mortality for carotid endarterectomy.

OBJECTIVES: the aim was to test the predictive accuracy of POSSUM and P-POSSUM on patients undergoing CEA. DESIGN: retrospective and prospective study. MATERIALS: 499 CEAs performed by four vascular surgeons from a single unit from 1992-99. The median age was 68 (range 38-86) and 60% were men. METHODS: physiological parameters, operative parameters and the 30-day mortality were collected. Predicted mortality for each patient was calculated using POSSUM and P-POSSUM equations. Patients were stratified into risk groups and observed and predicted deaths were compared. Accuracy of the prediction was assessed using chi-squared analysis. RESULTS: the observed 30-day mortality was 1.8% (9/499). The predicted deaths using POSSUM and P-POSSUM analysis were 49 and 25 respectively compared to nine observed deaths. There was significant evidence of lack of fit of both models in predicting mortality (chi-squared analysis, p<0.05). CONCLUSIONS: POSSUM and P-POSSUM overpredict mortality and are unsuitable for comparative audit of CEA. Models developed specific for CEA might accurately predict mortality.

Risk modelling study for carotid endarterectomy.

BACKGROUND: The aims of this study were to identify factors that influence the risk of stroke or death following carotid endarterectomy (CEA) and to develop a model to aid in comparative audit of vascular surgeons and units. METHODS: A series of 839 CEAs performed by four vascular surgeons between 1992 and 1999 was analysed. Multiple logistic regression analysis was used to model the effect of 15 possible risk factors on the 30-day risk of stroke or death. Outcome was compared for four surgeons and two units after adjustment for the significant risk factors. RESULTS: The overall 30-day stroke or death rate was 3.9 per cent (29 of 741). Heart disease, diabetes and stroke were significant risk factors. The 30-day predicted stroke or death rates increased with increasing risk scores. The observed 30-day stroke or death rate was 3.9 per cent for both vascular units and varied from 3.0 to 4.2 per cent for the four vascular surgeons. Differences in the outcomes between the surgeons and vascular units did not reach statistical significance after risk adjustment. CONCLUSION: Diabetes, heart disease and stroke are significant risk factors for stroke or death following CEA. The risk score model identified patients at higher risk and aided in comparative audit.

Vascular surgical society of great britain and ireland: limb outcome following failed femoropopliteal polytetrafluoroethylene bypass for intermittent claudication

BACKGROUND: Femoropopliteal (FP) bypass using polytetrafluoroethylene (PTFE) is still considered by many surgeons to be a reasonable procedure for severe intermittent claudication (IC) without limb-threatening ischaemia. The consequences of FP graft failure were examined. METHODS: Over 8 years, 54 patients had 55 FP grafts (that subsequently occluded) inserted for severe IC (42 PTFE and 13 vein grafts) above (30) or below (25) the knee. There were no operative deaths. During the same interval a total of 191 FP grafts were placed, 100 of which were vein grafts. Patient demography and risk factor analysis was similar for both groups. RESULTS: Nineteen patients required amputation subsequent to a failed graft, all of these following PTFE grafts. Mean time to occlusion was 12.2 (range 0-79) months. For PTFE grafts, the mean(s. d.) ankle index rose from 0.51(0.14) to 0.95(0.15) after operation but fell to 0.25(0.15) after occlusion, confirming a highly significant deterioration from preoperative levels, which was not seen in vein graft occlusions. CONCLUSION: Long-term FP bypass patency rates with vein are superior to those obtained with PTFE. Failed PTFE grafts show a significant deterioration in pressure indices compared with preoperative values. FP grafts for IC carry an intrinsic risk of limb loss which is much greater when vein is not used (P < 0.001).

Vascular surgical society of great britain and ireland: influence of contralateral stenosis on long-term mortality rate following carotid surgery

BACKGROUND: Recent evidence suggests that high-grade contralateral stenosis has an adverse effect on perioperative morbidity in carotid endarterectomy (CEA). The relationship between contralateral high-grade stenosis and long-term survival after CEA was examined. METHODS: Three hundred and twenty-seven patients undergoing 333 CEA operations were entered prospectively into a database and long-term follow-up was instituted. Cardiac and stroke risk factors were identified before operation and correlated with long-term survival and cause of death. RESULTS: Mean age at operation was 68 (range 42-86) years. Median follow-up was 2 (range 1-8) years. There were 45 deaths (seven perioperative), 17 myocardial, 16 from stroke (four perioperative), five from neoplasia, three respiratory and four others. The cumulative 5-year survival rate was 75 per cent. Patients with high-grade contralateral stenosis (greater than 80 per cent) had a significantly reduced life expectancy after CEA (P < 0. 05). CONCLUSION: Severe contralateral carotid disease is not only an adverse perioperative risk factor but also has negative implications for survival of the patient in the longer term. Following CEA, patients in general have a lower life expectancy than a normal age-matched population.

Study of Alu sequences at the hypoxanthine phosphoribosyltransferase (hprt) encoding region of man.

The hypoxanthine phosphoribosyltransferase (hprt) encoding region of man is considered rich in Alu sequences: with 49 sequences present within 57 kilobases. Subfamily classification of the Alu sequences and identification of flanking direct repeats has been carried out to detect past rearrangements associated with their insertion into the region. Members of the Alu-J and three Alu-S subfamilies are present, along with the existence of free left arm sequences. Using available data, a comparison is made of the Alu subfamilies present at different gene regions. The heterogeneity in the number of each subfamily present at different genes shows that no one particular subfamily attained saturation in the genome. Several adjacent insertions of Alu sequences are seen at the hprt region. Furthermore two novel sequences are described, there is an incident where one Alu sequence has inserted into the middle poly(A) tract of an existing sequence at the hprt region; while another result from an Alu/Alu cross-over event elsewhere in the genome, before insertion into the hprt region. Once inserted, the Alu sequences are rarely subject to loss or rearrangement.