The use of the RegJoint™ implant for base of thumb osteoarthritis: Results with a minimum follow-up of 2 years.

The RegJoint™ (Scaffdex Oy, Finland) implant is a bio-absorbable poly-L/D-lactide implant which acts as a temporary support in resected joint spaces. It can be used in base of thumb surgery as a spacer to prevent first metacarpal subsidence. However, high rates of adverse tissue reactions and bone osteolysis have been reported recently by one group. The objective of this study was to investigate the outcome of patients treated in our institution with this implant. Patients underwent a postoperative clinical and radiological assessment. The QuickDASH questionnaire, Patient Evaluation Measure (PEM) and a visual analogue scale for pain assessment were used. Grip strength, key pinch, pinch strength, thumb palmar and radial abduction and opposition were measured. Trapeziometacarpal height was used to evaluate thumb shortening compared with the preoperative value. Periprosthetic bone-erosion of the trapezium and metacarpal were measured. Subluxation of the joint was evaluated by measuring the step-off between the radial edge of the trapezium and the base of the first metacarpal bone. Twenty-two patients from 2013-2016 were included. There were no postoperative wound complications. There was no significant difference in grip strength, key pinch or pinch between the operated and the contralateral hand. There was no significant difference in the trapeziometacarpal height, trapezial height or the degree of subluxation pre-or post-operatively. Contrary to recent reports, we did not find any adverse soft tissue reactions or significant bone erosion. There was no significant change in hand function. We consider the RegJoint™ a useful adjunct in the management of a select cohort of patients with base of thumb arthritis.

Correlations between contouring similarity metrics and simulated treatment outcome for prostate radiotherapy.

Many similarity metrics exist for inter-observer contouring variation studies, however no correlation between metric choice and prostate cancer radiotherapy dosimetry has been explored. These correlations were investigated in this study. Two separate trials were undertaken, the first a thirty-five patient cohort with three observers, the second a five patient dataset with ten observers. Clinical and planning target volumes (CTV and PTV), rectum, and bladder were independently contoured by all observers in each trial. Structures were contoured on T2-weighted MRI and transferred onto CT following rigid registration for treatment planning in the first trial. Structures were contoured directly on CT in the second trial. STAPLE and majority voting volumes were generated as reference gold standard volumes for each structure for the two trials respectively. VMAT treatment plans (78 Gy to PTV) were simulated for observer and gold standard volumes, and dosimetry assessed using multiple radiobiological metrics. Correlations between contouring similarity metrics and dosimetry were calculated using Spearman's rank correlation coefficient. No correlations were observed between contouring similarity metrics and dosimetry for CTV within either trial. Volume similarity correlated most strongly with radiobiological metrics for PTV in both trials, including TCPPoisson (ρ = 0.57, 0.65), TCPLogit (ρ = 0.39, 0.62), and EUD (ρ = 0.43, 0.61) for each respective trial. Rectum and bladder metric correlations displayed no consistency for the two trials. PTV volume similarity was found to significantly correlate with rectum normal tissue complication probability (ρ = 0.33, 0.48). Minimal to no correlations with dosimetry were observed for overlap or boundary contouring metrics. Future inter-observer contouring variation studies for prostate cancer should incorporate volume similarity to provide additional insights into dosimetry during analysis.

Video gaming enhances psychomotor skills but not visuospatial and perceptual abilities in surgical trainees.

INTRODUCTION: There is considerable interest in the identification and assessment of underlying aptitudes or innate abilities that could potentially predict excellence in the technical aspects of operating. However, before the assessment of innate abilities is introduced for high-stakes assessment (such as competitive selection into surgical training programs), it is essential to determine that these abilities are stable and unchanging and are not influenced by other factors, such as the use of video games. The aim of this study was to investigate whether experience playing video games will predict psychomotor performance on a laparoscopic simulator or scores on tests of visuospatial and perceptual abilities, and to examine the correlation, if any, between these innate abilities. METHODS: Institutional ethical approval was obtained. Thirty-eight undergraduate medical students with no previous surgical experience were recruited. All participants completed a self-reported questionnaire that asked them to detail their video game experience. They then underwent assessment of their psychomotor, visuospatial, and perceptual abilities using previously validated tests. The results were analyzed using independent samples t tests to compare means and linear regression curves for subsequent analysis. RESULTS: Students who played video games for at least 7 hours per week demonstrated significantly better psychomotor skills than students who did not play video games regularly. However, there was no difference on measures of visuospatial and perceptual abilities. There was no correlation between psychomotor tests and visuospatial or perceptual tests. CONCLUSIONS: Regular video gaming correlates positively with psychomotor ability, but it does not seem to influence visuospatial or perceptual ability. This study suggests that video game experience might be beneficial to a future career in surgery. It also suggests that relevant surgical skills may be gained usefully outside the operating room in activities that are not related to surgery.

The management of rectal cancer in Ireland in 2007--room for improvement?

INTRODUCTION: Effective management of rectal cancer relies on accurate pre-operative assessment, surgical technical excellence and integrated neoadjuvant and adjuvant chemo and/or radiotherapy. The aim of this study was to examine the management of rectal cancer in Ireland. METHODS: This was a retrospective chart review. All cases of rectal cancer (15 cm or less from the anal verge) diagnosed in Ireland in the year 2007 were included in the audit. RESULTS: In total data for 585 patients were included, under the care of 87 consultant surgeons operating in 48 hospitals. Only data recorded in medical charts were included. Pre-operative investigations were less utilised than recommended by current guidelines and consequently many cancers were inadequately staged. In total 52.5% of cases were discussed at a multi-disciplinary meeting. Overall, 88% of the patients had surgery, and the 30-day mortality rate was 1.7%. The quality of post-operative pathology reporting was variable, with adequacy of total mesorectal excision status unclear or unknown in 74% of cases. Cases were managed in a large number of centres, and in lower volume centres (<5 cases per annum) patients appeared to be less adequately investigated. CONCLUSION: This study gives a snapshot of recent practice in the management of rectal cancer in Ireland but is of necessity limited as the audit was retrospective and long term outcomes have not been assessed. In 2007 rectal cancer was managed in a large number of centres and best practice was frequently not adhered to. The impending centralisation of cancer services is likely to impact on the management of rectal cancer in Ireland.

Coping with stress in surgery: the difficulty of measuring non-technical skills.

BACKGROUND: Non-technical skills are relevant to surgical performance but are difficult to quantify. The aim of this study was to investigate the relationship between self-efficacy, which is a measure of stress-coping ability, and surgical performance. METHODS: Two hundred and sixteen basic surgical trainees were assessed on their performance of three bench model-type open and laparoscopic surgical tasks. They also completed a 10-item General Self-Efficacy (GSE) questionnaire to assess their stress-coping abilities. Their assessment scores were correlated with the GSE scores. RESULTS: The mean GSE score of 31.39 was higher than the recorded population norms. There was no significant correlation between GSE and surgical performance for open or laparoscopic tasks. CONCLUSION: Junior surgical trainees have high self-belief scores, but these abilities are difficult to measure and quantify. More refined methods may be necessary to measure non-technical skills relevant to surgery.

A case of villoglandular papillary adenocarcinoma of the cervix with vaginal skip metastasis.

► First case of cervical villoglandular cancer with concurrent vaginal skip metastasis. ► Rapid progression to advanced stage with good response to adjuvant therapy.

Objective assessment of surgical performance and its impact on a national selection programme of candidates for higher surgical training in plastic surgery.

OBJECTIVE: The objective of this study was to develop and validate a transparent, fair and objective assessment programme for the selection of surgical trainees into higher surgical training (HST) in plastic surgery in the Republic of Ireland. METHODS: Thirty-four individuals applied for HST in plastic surgery at the Royal College of Surgeons in Ireland (RCSI) in the academic years 2005-2006 and 2006-2007. Eighteen were short-listed for interview and further assessment. All applicants were required to report on their undergraduate educational performance and their postgraduate professional development. Short-listed applicants completed validated objective assessment simulations of surgical skills, an interview and assessment of their suitability for a career in surgery. RESULTS: When applicants' short-listing scores were combined with their interview scores and assessment of their suitability for a career in surgery, individuals who were selected for HST in plastic surgery performed significantly better than those who were not (P<0.002). However, when the assessment of technical skills scores were added the significance level of this difference increased further (P<0.0001) as did the statistical power of the difference to 99.9%, thus increasing the robustness of the selection package. CONCLUSION: The results from this study suggest that the assessment protocol we used to select individuals for HST in plastic surgery reliably and statistically significantly discriminated between the performances of candidates.

Toward using delta13C of ecosystem respiration to monitor canopy physiology in complex terrain.

In 2005 and 2006, air samples were collected at the base of a Douglas-fir watershed to monitor seasonal changes in the delta13CO2 of ecosystem respiration (delta13C(ER)). The goals of this study were to determine whether variations in delta13C(ER) correlated with environmental variables and could be used to predict expected variations in canopy-average stomatal conductance (Gs). Changes in delta13C(ER) correlated weakly with changes in vapor pressure deficit (VPD) measured 0 and 3-7 days earlier and significantly with soil matric potential (psi(m)) (P value <0.02) measured on the same day. Midday G (s) was estimated using sapflow measurements (heat-dissipation method) at four plots located at different elevations within the watershed. Values of midday Gs from 0 and 3-7 days earlier were correlated with delta13C(ER), with the 5-day lag being significant (P value <0.05). To examine direct relationships between delta13C(ER) and recent Gs, we used models relating isotope discrimination to stomatal conductance and photosynthetic capacity at the leaf level to estimate values of stomatal conductance ("Gs-I") that would be expected if respired CO2 were derived entirely from recent photosynthate. We compared these values with estimates of Gs using direct measurement of transpiration at multiple locations in the watershed. Considering that the approach based on isotopes considers only the effect of photosynthetic discrimination on delta13C(ER), the magnitude and range in the two values were surprisingly similar. We conclude that: (1) delta13C(ER) is sensitive to variations in weather, and (2) delta13C(ER) potentially could be used to directly monitor average, basin-wide variations in Gs in complex terrain if further research improves understanding of how delta13C(ER) is influenced by post-assimilation fractionation processes.

Backyard burning.

This study was undertaken to determine whether changes had occurred in the numbers of burns that could be related to backyard burning subsequent to the introduction of the council tax throughout Eire for the collection of household refuse. Numbers of patients admitted to our unit who had sustained burns by burning rubbish were recorded prospectively over a period of 12 months. A random control group was taken as three years prior to this and results found by retrospective chart review. Between January and November 2005, 168 patients were admitted to the National Burns Unit, St James's Hospital Dublin, Ireland. Nineteen of these patients sustained flame burns from backyard burning. One hundred and seventy patients were admitted in the comparative period of 2002; Seven of these from backyard burning. The total number of inpatient days for these patients in 2005 (255) was significantly more than in 2002 (68) (p=0.024). The numbers in our study show a marked increase in the number of patients sustaining burns in this manner, and appear to correlate with the introduction of bin charges by a number of county councils around the country last year. This study demonstrates that the introduction of legislation can have an unforeseen adverse affect on the population if not introduced in correlation with appropriate public education. While the introduction of waste charges represents a very necessary move forward in waste disposal in Ireland, public awareness campaigns should be implemented to prevent further such injuries from occurring.

Terminal myelocystocele and sacrococcygeal teratoma: a comparison of fetal ultrasound presentation and perinatal risk.

This case exemplifies the difficulty in differentiating cystic sacrococcygeal teratoma and terminal myelocystocele. Fetal sonography presentation and perinatal risks of sacrococcygeal teratoma and terminal myelocystocele are compared, and we emphasize the importance of obtaining fetal MR imaging to establish an accurate diagnosis.

Parafibromin is a nuclear protein with a functional monopartite nuclear localization signal.

Parafibromin is a nuclear protein with a tumour suppressor role in the development of non-hereditary and hereditary parathyroid carcinomas, and the hyperparathyroidism-jaw tumour (HPT-JT) syndrome, which is associated with renal and uterine tumours. Nuclear localization signal(s), (NLS(s)), of the 61 kDa parafibromin remain to be defined. Utilization of computer-prediction programmes, identified five NLSs (three bipartite (BP) and two monopartite (MP)). To investigate their functionality, wild-type (WT) and mutant parafibromin constructs tagged with enhanced green fluorescent protein or cMyc were transiently expressed in COS-7 cells, or human embryonic kidney 293 (HEK293) cells, and their subcellular locations determined by confocal fluorescence microscopy. Western blot analyses of nuclear and cytoplasmic fractions from the transfected cells were also performed. WT parafibromin localized to the nucleus and deletions or mutations of the three predicted BP and one of the predicted MP NLSs did not affect this localization. In contrast, deletions or mutations of a MP NLS, at residues 136-139, resulted in loss of nuclear localization. Furthermore, the critical basic residues, KKXR, of this MP NLS were found to be evolutionarily conserved, and over 60% of all parafibromin mutations lead to a loss of this NLS. Thus, an important functional domain of parafibromin, consisting of an evolutionarily conserved MP NLS, has been identified.

White particulate matter found in blood collection bags consist of platelets and leukocytes.

BACKGROUND: In late January 2003, some blood centers and hospitals throughout the US voluntarily sus-pended the use of some RBC and plasma units for trans-fusion due to the presence of unknown white particulate matter (WPM) in these units. To better understand the WPM phenomena, a number of technologies were used to establish the nature of the particulates observed in Terumo Collection sets. STUDY DESIGN AND METHODS: All AS-5 nonleuko-reduced RBCs and plasma units were visually inspected for WPM by placing the bags on a flat counter, undisturbed, for approximately 10 minutes and then perform-ing a visual examination for particles. Particles were isolated and placed on microscope slides or in plastic tubes for further analysis. Electron microscopy, bright field microscopy, differential interference contrast microscopy, infrared spectroscopy, and flow cytometry procedures were performed to establish the nature of the particulate matter. In addition, leukoreduction filters and blood transfusion sets were used on RBCs units with WPM. RESULTS: The particles were mostly composed of PLTs and WBCs, and fragments of these cells. All macroscopic WPM was removed from RBCs with leukoeduction and transfusion filters. CONCLUSIONS: WPM originated from PLTs and WBCs. Foreign matter (e.g., plastic) was not observed in any of the units. Leukoreduction and transfusion filters can be used to remove macroscopic WPM.

Multiple endocrine neoplasia type 1 (MEN1) germline mutations in familial isolated primary hyperparathyroidism.

BACKGROUND: Familial isolated hyperparathyroidism (FIHP) is an autosomal dominant disorder characterized by uniglandular or multiglandular parathyroid tumours that occur in the absence of other endocrine tumours. The disorder may represent either an early stage of multiple endocrine neoplasia type 1 (MEN1), or an allelic variant of MEN1, or a distinct entity involving another locus. We have explored these possibilities in seven families in whom primary hyperparathyroidism occurred as the sole endocrinopathy. METHODS: Seven FIHP families were ascertained and venous blood samples obtained from 35 members (17 affected and 18 unaffected) for DNA sequence analysis of the MEN1 gene. The mean (+/- SD) follow-up period in the 17 affected members was 15.06 (+/- 8.83) years. RESULTS: Four heterozygous germline mutations of the MEN1 gene were identified. These consisted of two 4-bp intragenic deletions that would result in prematurely truncated proteins, and two missense (Asp153Val and Ala411Pro) mutations. Furthermore, analysis of parathyroid tumour DNA from one individual revealed a loss of the wild-type allele and retention of the mutant allele, consistent with Knudson's 'two-hit' model of hereditary cancer and a tumour suppressor role for MEN1 in FIHP. CONCLUSIONS: Our results provide further support for FIHP being a distinct allelic variant of MEN1, and an analysis of the 16 mutations reported to date indicate that FIHP is associated with a higher frequency of missense MEN1 mutations.

HRPT2, encoding parafibromin, is mutated in hyperparathyroidism-jaw tumor syndrome.

We report here the identification of a gene associated with the hyperparathyroidism-jaw tumor (HPT-JT) syndrome. A single locus associated with HPT-JT (HRPT2) was previously mapped to chromosomal region 1q25-q32. We refined this region to a critical interval of 12 cM by genotyping in 26 affected kindreds. Using a positional candidate approach, we identified thirteen different heterozygous, germline, inactivating mutations in a single gene in fourteen families with HPT-JT. The proposed role of HRPT2 as a tumor suppressor was supported by mutation screening in 48 parathyroid adenomas with cystic features, which identified three somatic inactivating mutations, all located in exon 1. None of these mutations were detected in normal controls, and all were predicted to cause deficient or impaired protein function. HRPT2 is a ubiquitously expressed, evolutionarily conserved gene encoding a predicted protein of 531 amino acids, for which we propose the name parafibromin. Our findings suggest that HRPT2 is a tumor-suppressor gene, the inactivation of which is directly involved in predisposition to HPT-JT and in development of some sporadic parathyroid tumors.

2-methoxyestradiol induces interferon gene expression and apoptosis in osteosarcoma cells.

2-Methoxyestradiol (2-ME), a naturally occurring mammalian metabolite of 17beta-estradiol, has been implicated as a physiological inhibitor of tumor cell proliferation. In this study, the effects of 2-ME on cultured osteosarcomatous cells were investigated. Dose-dependent growth inhibition was observed in MG63 and TE85 human osteosarcoma cells exposed to 2-ME. The cell killing by 2-ME was ligand-specific; the immediate precursor (2-hydroxyestradiol), the parent compound (17beta-estradiol), and the equivalent metabolite of estrone (2-methoxyestrone) exhibited less potency and efficacy. Furthermore, 2-ME was similarly effective at killing immortalized human fetal osteoblastic cells (hFOB) with and without estrogen receptor-alpha and -beta and rat osteosarcoma cells (ROS17/2.8). The cytotoxicity of 2-ME was selective to transformed and immortalized osteoblastic cells; 2-ME (2 microm) had no effect on the proliferation of primary cultures of human osteoblasts. Co-treatment with the potent estrogen receptor ligand, ICI-182,780, did not reduce 2-ME-induced osteosarcoma cell death, implying that this action is not mediated by conventional estrogen receptors. The expression levels of bone matrix protein genes, type 1 collagen and osteonectin, were transiently reduced after 2-ME treatment, suggesting that the surviving cells are capable of producing bone matrix. The 2-ME-mediated killing of osteosarcoma cells was due to the induction of apoptosis; treatment induced expression of interferon genes within 12 h and histological evidence of apoptosis within 48 h of 2-ME treatment. Thus, our results demonstrate that 2-ME is highly cytotoxic to osteosarcoma cells but not normal osteoblasts. These findings suggest that further study of 2-ME as a potential intervention for treatment of osteosarcoma is warranted.

In-vivo measurement of activated microglia in dementia.

BACKGROUND: Activated microglia have a key role in the brain's immune response to neuronal degeneration. The transition of microglia from the normal resting state to the activated state is associated with an increased expression of receptors known as peripheral benzodiazepine binding sites, which are abundant on cells of mononuclear phagocyte lineage. We used brain imaging to study expression of these sites in healthy individuals and patients with Alzheimer's disease. METHODS: We studied 15 normal individuals (age 32-80 years), eight patients with Alzheimer's disease, and one patient with minimal cognitive impairment. Quantitative in-vivo measurements of glial activation were obtained with positron emission tomography (PET) and carbon-11-labelled (R)-PK11195, a specific ligand for the peripheral benzodiazepine binding site. FINDINGS: In normal individuals, regional [11C](R)-PK11195 binding did not significantly change with age, except in the thalamus, where an age-dependent increase was found. By contrast, patients with Alzheimer's disease showed significantly increased regional [11C](R)-PK11195 binding in the entorhinal, temporoparietal, and cingulate cortex. INTERPRETATION: In-vivo detection of increased [11C](R)-PK11195 binding in Alzheimer-type dementia, including mild and early forms, suggests that microglial activation is an early event in the pathogenesis of the disease.

Neuropsychological profiles of familial Alzheimer's disease associated with mutations in the presenilin 1 and amyloid precursor protein genes.

Patients with familial Alzheimer's disease and a subset known to have presenilin mutations were compared with sporadic cases on a comprehensive battery of cognitive tests. These included measures of memory, intelligence, language and perception. The three groups were very comparable, in terms of severity, on global measures of dementia. However, their profiles/patterns of cognitive impairment differed in two respects; the group with sporadic Alzheimer's disease were significantly more impaired on tests of object naming and object perception than either the group with familial Alzheimer's disease or group with familial Alzheimer's disease and presenilin mutations, yet they scored at a significantly higher level on the measure of verbal intelligence. This study provides further evidence of the heterogeneity of the disease process.