Data errors in the National Hip Fracture Database: a local validation study.

AIMS: We present an audit comparing our level I major trauma centre's data for a cohort of patients with hip fractures in the National Hip Fracture Database (NHFD) with locally held data on these patients. PATIENTS AND METHODS: A total of 2036 records for episodes between July 2009 and June 2014 were reviewed. RESULTS: The demographics of nine patients were recorded incorrectly. The rate of incorrect data in operation codes was most significant with overall accuracy of 0.637 (95% CI 0.615 to 0.658). The sensitivity of NHFD coding ranged from 0.250 to 1.000 and the specificity 0.879 to 0.999. The recording of cementation had a sensitivity of 0.932 and specificity of 0.713. The recording of total hip arthroplasty had a sensitivity of 0.739 and specificity of 0.983. The overall accuracy of mortality data was 0.942 (95% CI 0.931 to 0.952), with sensitivity of 0.967 and specificity of 0.419. CONCLUSION: This paper highlights the need for local audit of the integrity of data uploaded to the NHFD. Cite this article: Bone Joint J 2016;98-B:1406-9.

A prospective, randomised study comparing two techniques of autologous chondrocyte implantation for osteochondral defects in the knee: Periosteum covered versus type I/III collagen covered.

INTRODUCTION: The results for autologous chondrocyte implantation (ACI) in the treatment of full thickness chondral defects in the knee are encouraging. At present two techniques have been described to retain the chondrocyte suspension within the defect. The first involves using a periosteal cover (ACI-P) and the second involves using a type I/III collagen membrane (ACI-C). To the authors knowledge there are no comparative studies of these two techniques in the current literature. We have therefore undertaken such a study to establish if there is a difference between the 2 techniques based on a clinical and arthroscopic assessment. METHODS: A total of 68 patients with a mean age of 30.52 years with symptomatic articular cartilage defects were randomised to have either ACI-P (33 patients) or ACI-C (35 patients). The mean defect size was 4.54 cm2. All patients were followed up at 24 months. RESULTS: A clinical and functional assessment showed that 74% of patients had a good or excellent result following the ACI-C compared with 67% after the ACI-P at 2 years. Arthroscopy at 1 year also demonstrated similar results for both techniques. However, 36.4% of the ACI-P grafts required shaving for hypertrophy compared with none for the ACI-C grafts at 1 year. DISCUSSION: This study has shown no statistical difference between the clinical outcome of ACI-C versus ACI-P at 2 years. A significant number of patients who had the ACI-P required shaving of a hypertrophied graft. We conclude that there is no advantage in using periosteum as a cover for retaining chondrocytes within an osteochondral defect; as a result we advocate the use of an alternative cover such as a manufactured type I/III collagen membrane.

The use of autologous chondrocyte implantation following and combined with anterior cruciate ligament reconstruction.

We report our experience of using autologous chondrocyte implantation (ACI) to treat osteochondral defects of the knee in combination with anterior cruciate ligament (ACL) reconstruction. The outcome of symptomatic osteochondral lesions treated with ACI following previous successful ACL reconstruction is also reviewed. Patients were followed for a mean of 23 months. Nine patients underwent ACL reconstruction in combination with ACI. Mean modified Cincinnati knee scores improved from 42 to 69 following surgery. Seven patients described their knee as better and two as the same. A second group of nine patients underwent ACI for symptomatic articular cartilage defects following previous ACL reconstruction. In this group, the mean modified Cincinnati knee score improved from 53 to 62 after surgery. Six patients described their knee as better and three as worse. Combined treatment using ACI with ACL reconstruction is technically feasible and resulted in sustained improvement in pain and function. The results following previous ACL reconstruction also resulted in clinical improvement, although results were not as good as following the combined procedure.

The role of the Short Form 36 Health Survey in autologous chondrocyte implantation.

The purpose of this study was to examine the use of the Short Form 36 Health Survey (SF-36) in the preoperative assessment and postoperative review of patients undergoing autologous chondrocyte implantation (ACI) of the knee. We used the SF-36, a validated health related quality of life survey, and The Modified Cincinnati Knee score, a commonly used knee function scoring system, to evaluate 25 consecutive patients preoperatively and 1 year following surgery. Before surgery, patients scored lower for all aspects of general health and level of functioning compared to a normalised general population. We demonstrated significant increases of overall SF-36 scores following surgery, reflecting improvements to perceived general health. Most significant improvements were seen in the physical categories of "Physical Functioning" (44.8 to 56.2, p=0.014), "Role Physical"(35.0 to 52.2, p=0.044) and "Bodily Pain"(33.6 to 50.9, p=0.001). Higher preoperative SF-36 scores were found to correlate significantly with greater increases of Modified Cincinnati Knee scores. Postoperative knee function scores correlated well with physical categories of the SF-36. However, we found poor correlation between postoperative Modified Cincinnati Knee scores and SF-36 scores for vitality, social functioning and emotional domains. This suggests that knee function scores alone do not incorporate all the benefits to patient health following ACI surgery. We recommend using a knee function scoring system and the SF-36 for both the preoperative assessment and postoperative review of ACI patients.

Regulation of alternative splicing by PTB and associated factors.

PTB (polypyrimidine tract-binding protein) is a repressive regulator of alternative splicing. We have investigated the role of PTB in three model alternative splicing systems. In the alpha-actinin gene, PTB represses the SM (smooth muscle) exon by binding to key sites in the polypyrimidine tract. Repressive binding to these sites is assisted by co-operative binding to additional downstream sites. SM exon splicing can be activated by CELF proteins, which also bind co-operatively to interspersed sites and displace PTB from the pyrimidine tract. Exon 11 of PTB pre-mRNA is repressed by PTB in an autoregulatory feedback loop. Exon 11-skipped RNA gets degraded through nonsense-mediated decay. Less than 1% of steady-state PTB mRNA is represented by this isoform, but inhibition of nonsense-mediated decay by RNA interference against Upf1 shows that at least 20% of PTB RNA is consumed by this pathway. This represents a widespread but under-appreciated role of alternative splicing in the quantitative regulation of gene expression, an important addition to its role as a generator of protein isoform diversity. Repression of alpha-tropomyosin exon 3 is an exceptional example of PTB regulation, because repression only occurs at high levels in SM cells, despite the fact that PTB is widely expressed. In this case, a PTB-interacting cofactor, raver1, appears to play an important role. By the use of 'tethering' assays, we have identified discrete domains within both PTB and raver1 that mediate their repressive activities on this splicing event.

Autologous chondrocyte implantation versus matrix-induced autologous chondrocyte implantation for osteochondral defects of the knee: a prospective, randomised study.

Autologous chondrocyte implantation (ACI) is used widely as a treatment for symptomatic chondral and osteochondral defects of the knee. Variations of the original periosteum-cover technique include the use of porcine-derived type I/type III collagen as a cover (ACI-C) and matrix-induced autologous chondrocyte implantation (MACI) using a collagen bilayer seeded with chondrocytes. We have performed a prospective, randomised comparison of ACI-C and MACI for the treatment of symptomatic chondral defects of the knee in 91 patients, of whom 44 received ACI-C and 47 MACI grafts. Both treatments resulted in improvement of the clinical score after one year. The mean modified Cincinnati knee score increased by 17.6 in the ACI-C group and 19.6 in the MACI group (p = 0.32). Arthroscopic assessments performed after one year showed a good to excellent International Cartilage Repair Society score in 79.2% of ACI-C and 66.6% of MACI grafts. Hyaline-like cartilage or hyaline-like cartilage with fibrocartilage was found in the biopsies of 43.9% of the ACI-C and 36.4% of the MACI grafts after one year. The rate of hypertrophy of the graft was 9% (4 of 44) in the ACI-C group and 6% (3 of 47) in the MACI group. The frequency of re-operation was 9% in each group. We conclude that the clinical, arthroscopic and histological outcomes are comparable for both ACI-C and MACI. While MACI is technically attractive, further long-term studies are required before the technique is widely adopted.

Autologous chondrocyte implantation at the knee using a bilayer collagen membrane with bone graft. A preliminary report.

Autologous chondrocyte implantation (ACI) is a technique used for the treatment of symptomatic osteochondral defects of the knee. A variation of the original periosteum membrane technique is the matrix-induced autologous chondrocyte implantation (MACI) technique. The MACI membrane consists of a porcine type-I/III collagen bilayer seeded with chondrocytes. Osteochondral defects deeper than 8 to 10 mm usually require bone grafting either before or at the time of transplantation of cartilage. We have used a variation of Peterson's ACI-periosteum sandwich technique using two MACI membranes with bone graft which avoids periosteal harvesting. The procedure is suture-free and requires less operating time and surgical exposure. We performed this MACI-sandwich technique on eight patients, five of whom were assessed at six months and one year post-operatively using the modified Cincinnati knee, the Stanmore functional rating and the visual analogue pain scores. All patients improved within six months with further improvement at one year. The clinical outcome was good or excellent in four after six months and one year. No significant graft-associated complications were observed. Our early results of the MACI-sandwich technique are encouraging although larger medium-term studies are required before there is widespread adoption of the technique.

Comparison of microporous and nonporous membrane bioreactor systems for the treatment of BTEX in vapor streams.

Increased regulatory constraints on industrial releases of atmospheric volatile organic compounds (VOCs) have resulted in an interest in using biofilters, bioscrubbers and air/liquid membranes for treatment of vapor phase waste streams. In this report, we describe the comparison of the use of two fundamentally different types of membrane module systems that allow the rapid diffusion of vapor phase aromatics and oxygen to an active biofilm for subsequent biodegradation. One system used a commercial membrane module containing microporous polypropylene fibers while the other used a nonporous silicone tubing membrane module for the delivery of substrate (a mixture of benzene, ethylbenzene, toluene, and xylenes [BTEX]) and electron acceptor (O(2)). Tests of the systems under similar conditions with BTEX in the vapor feed stream showed significant performance advantages for the silicone membrane system. The average surface-area-based BTEX removal rate for the microporous membrane system over 500 h of operation was 7.88 microg h(-1) cm(-2) while the rate for the silicone membrane system was 23.87 microg h(-1) cm(-2). The percentages of BTEX removal were also consistently better in the silicone membrane system versus the microporous system. Part of the performance problem associated with the microporous membrane system appeared to be internal water condensation and possible plugging of the pores with biomass over time that could not be resolved with vapor phase backflushing.

Focal fatty infiltration of the liver: analysis of prevalence and CT findings in children and young adults.

OBJECTIVE: Focal fatty infiltration of the liver, a benign entity that can be confused with a malignant lesion, is well characterized in adults but not in children. The goal of this study was to determine by CT the prevalence and characteristics of focal fatty infiltration in children and young adults. MATERIALS AND METHODS: We retrospectively analyzed 305 consecutive contrast-enhanced abdominal CT examinations of 218 children and young adults with no known liver disease, performed during 2 years at our institution, to identify focal fatty infiltration of the liver. The imaging criterion for focal fatty infiltration of the liver on helical CT was a geometric or ovoid low-attenuation area adjacent to the falciform ligament, gallbladder fossa, or porta hepatis. If a patient's findings met the CT criterion for focal fatty infiltration of the liver, all previous abdominal CT and MR imaging examinations performed for that patient were reviewed to assess the evolution of focal fatty infiltration of the liver. RESULTS: Of 218 children and young adults, 20 (9.2%) met the CT criterion for focal fatty infiltration of the liver. In our population, focal fatty infiltration of the liver was identified only adjacent to the falciform ligament. The prevalence of focal fatty infiltration of the liver increased significantly with advancing age: 0% for ages 1 month-4 years; 7.3% for 5-9 years; 10.2% for 10-14 years, and 25.6% for 15-19 years (p < 0.0001). CONCLUSION: Focal fatty infiltration of the liver was identified in 9.2% of patients in our population, and occurrence of this lesion in children increases significantly with advancing age. However, focal fatty infiltration of the liver is uncommon in infants and young children and should be a diagnosis of exclusion.

Biodegradation of BTEX vapors in a silicone membrane bioreactor system.

The biotreatment of complex mixtures of volatile organic compounds (VOCs) such as benzene, toluene, ethylbenzene, and xylene isomers (BTEX) has been investigated by many workers. However, the majority of the work has dealt with the treatment of aqueous or soil phase contamination. The biological treatment of gas and vapor phase sources of VOC wastes has recently received attention with increased usage of biofilters and bioscrubbers. Although these systems are relatively inexpensive, performance problems associated with biomass plugging, gas channeling, and support media acidification have limited their adoption. In this report we describe the development and evaluation of an alternative biotreatment system that allows rapid diffusion of both BTEX and oxygen through a silicone membrane to an active biofilm. The bioreactor system has a rapid liquid recycle, which facilitates nutrient medium mixing over the biofilm and allows for removal of sloughing cell mass. The system removed BTEX at rates up to 30 microg h(-1) cm(-2) of membrane area. BTEX removal efficiencies ranged from 75% to 99% depending on the BTEX concentration and vapor flowrate. Consequently, the system can be used for continuous removal and destruction of BTEX and other potential target VOCs in vapor phase streams.

Differential alternative splicing activity of isoforms of polypyrimidine tract binding protein (PTB).

Polypyrimidine tract binding protein (PTB) is an RNA-binding protein that regulates splicing by repressing specific splicing events. It also has roles in 3'-end processing, internal initiation of translation, and RNA localization. PTB exists in three alternatively spliced isoforms, PTB1, PTB2, and PTB4, which differ by the insertion of 19 or 26 amino acids, respectively, between the second and third RNA recognition motif domains. Here we show that the PTB isoforms have distinct activities upon alpha-tropomyosin (TM) alternative splicing. PTB1 reduced the repression of TM exon 3 in transfected smooth muscle cells, whereas PTB4 enhanced TM exon 3 skipping in vivo and in vitro. PTB2 had an intermediate effect. The PTB4 > PTB2 > PTB1 repressive hierarchy was observed in all in vivo and in vitro assays with TM, but the isoforms were equally active in inducing skipping of alpha-actinin exons and showed the opposite hierarchy of activity when tested for activation of IRES-driven translation. These findings establish that the ratio of PTB isoforms could form part of a cellular code that in turn controls the splicing of various other pre-mRNAs.

Pulmonary metastases at diagnosis of neuroblastoma in pediatric patients: CT findings and prognosis.

OBJECTIVE: We undertook this study to determine the frequency, CT appearance, and clinical implications of the rare occurrence of pulmonary metastases among children presenting with neuroblastoma. MATERIALS AND METHODS: A search of the Children's Cancer Group database revealed 21 of 567 children with reported lung metastases at original diagnosis of neuroblastoma. CT examinations available for 17 of these patients were analyzed retrospectively to determine if lung metastases were present, and if so, to characterize their radiographic features. RESULTS: Seventeen (3%) of 567 patients presenting with Evans stage IV neuroblastoma had confirmed pulmonary metastases at diagnosis. All had metastases to at least one site other than the lungs. The most common CT appearance of pulmonary lesions was of up to five, small, bilateral, noncalcified nodules. In nine patients (53%), the pulmonary nodules initially resolved with treatment. In this cohort, six children developed progressive disease and died, and three are still alive. All eight children whose lung lesion did not completely respond to treatment died. Overall, children with pulmonary metastases had unfavorable Shimada histology, a higher association with amplification of the MYCN oncogene (p = 0.0002), and a decreased event-free survival (p < 0.001) when compared with all children with stage IV neuroblastoma without pulmonary metastases. CONCLUSION: The search for neuroblastoma lung metastases, which occur more frequently than previously reported, is clinically important because their presence portends a poor prognosis.

Comparison of different primers for rapid detection of Salmonella using the polymerase chain reaction.

Salmonella is the leading cause of food-borne diarrhoeas in the US. In recent years polymerase chain reaction (PCR) has become the method of choice for rapid and sensitive detection of Salmonellae in contaminated foods. As a result, several different primer sets have been reported for use in PCR-based assay systems. In order to identify an optimal primer set from among the wide range of primers reported in the literature, we synthesized five different pairs and evaluated their relative performance in PCR under uniform assay conditions using a common panel of the target (Salmonella) and non-target (non- Salmonella) bacterial strains. Of the five sets of primers tested, the one designed on the basis of a 199 bp repeat sequence of S. weltevreden[Jitrapakdee et al. (1995) Molecular and Cellular Probes 9, 375-382] gave optimal results with most bacterial strains examined.

The vascular vise causing TAPVR type I to radiographically mimic TAPVR type III.

A subtype of supracardiac total anomalous pulmonary venous return (TAPVR) consists of the vertical vein passing between the left pulmonary artery and the left mainstem bronchus resulting in relative obstruction to pulmonary venous return. This has been termed the vascular vise. In this situation, the supracardiac type of TAPVR (Type I) may mimic radiographically the infradiaphragmatic type (Type 3).

Direct coronal CT scanning of the neonatal chest.

BACKGROUND: The purpose of this study was to attempt to improve upon conventional coronal computed tomographic (CT) images of neonatal chest which to date have been made by reformatting thinly spaced axial images. MATERIALS AND METHODS: Nine neonates were studied by direct coronal CT scans with the patients' long axis 90 degrees to the scanning table. They were studied to further define their thoracic abnormalities detected on plain film. Spiral CT and cine scan (Imatron) were utilized. RESULTS: Congenital lung lesions such as congenital cystic adenomatoid malformation could not be diagnosed but their anatomical location could be accurately depicted, enabling easier surgical planning. The arterial supply to bronchopulmonary sequestrations was also identifiable. Tracheobronchial abnormalities such as tracheobronchus and bronchial atresia were also identifiable. Causing of air trapping, both intrinsic such as an atretic bronchus and extrinsic such as vascular compression were readily demonstrated. CONCLUSION: With neither special devices nor paraphernalia, the described method of direct coronal CT scans were both feasible and provided significant information. This technique allows for improved assessment of the tracheobronchial tree and more accurate detection, localization, and characteristics of lesions adjacent to the diaphragm.

Polypyrimidine tract binding protein functions as a repressor to regulate alternative splicing of alpha-actinin mutally exclusive exons.

The smooth muscle (SM) and nonmuscle (NM) isoforms of alpha-actinin are produced by mutually exclusive splicing of an upstream NM exon and a downstream SM-specific exon. A rat alpha-actinin genomic clone encompassing the mutually exclusive exons was isolated and sequenced. The SM exon was found to utilize two branch points located 382 and 386 nucleotides (nt) upstream of the 3' splice site, while the NM exon used a single branch point 191 nt upstream. Mutually exclusive splicing arises from the proximity of the SM branch points to the NM 5' splice site, and this steric repression could be relieved in part by the insertion of spacer elements. In addition, the SM exon is repressed in non-SM cells and extracts. In vitro splicing of spacer-containing transcripts could be activated by (i) truncation of the transcript between the SM polypyrimidine tract and exon, (ii) addition of competitor RNAs containing the 3' end of the actinin intron or regulatory sequences from alpha-tropomyosin (TM), and (iii) depletion of the splicing extract by using biotinylated alpha-TM RNAs. A number of lines of evidence point to polypyrimidine tract binding protein (PTB) as the trans-acting factor responsible for repression. PTB was the only nuclear protein observed to cross-link to the actinin RNA, and the ability of various competitor RNAs to activate splicing correlated with their ability to bind PTB. Furthermore, repression of alpha-actinin splicing in the nuclear extracts depleted of PTB by using biotinylated RNA could be specifically restored by the addition of recombinant PTB. Thus, alpha-actinin mutually exclusive splicing is enforced by the unusual location of the SM branch point, while constitutive repression of the SM exon is conferred by regulatory elements between the branch point and 3' splice site and by PTB.

Worsening enterocolitis in neonates: diagnosis by CT examination of urine after enteral administration of iohexol.

Perforation, a severe complication of necrotizing enterocolitis (NEC), has a high mortality rate. Recently, we presented a new technique for evaluation of NEC: measuring the CT attenuation coefficient of urine after oral administration of iohexol. We present three cases of neonates with NEC who demonstrated serial increases in urine CT attenuation coefficients, all of whom subsequently deteriorated clinically and radiographically. Surgery in all three cases confirmed severe necrosis and/or perforation. These three cases suggest that the CT attenuation coefficient of urine after oral administration of iohexol may be a more sensitive indicator of NEC severity, progression, and perforation than clinical evaluation and radiography. More investigation is necessary, but eventually, this noninvasive technique may be able to decrease morbidity and mortality by predicting the need for surgical intervention or more aggressive medical management of NEC before perforation occurs.

Co-transcriptional commitment to alternative splice site selection.

Production of mRNA in eukaryotic cells involves not only transcription but also various processing reactions such as splicing. Recent experiments have indicated that there are direct physical connections between components of the transcription and processing machinery, supporting previous suggestions that pre-mRNA splicing occurs co-transcriptionally. Here we have used a novel functional approach to demonstrate co-transcriptional regulation of alternative splicing. Exon 3 of the alpha-tropomyosin gene is specifically repressed in smooth muscle cells. By delaying synthesis of an essential downstream inhibitory element, we show that the decision to splice or repress exon 3 occurs during a limited window of opportunity following transcription, indicating that splice site selection proceeds rapidly after transcription.

Systemic spread of meconium peritonitis.

Meconium peritonitis is a chemical peritonitis which occurs following bowel perforation during fetal life. It is generally looked upon as benign, resulting in no long-term sequelae. We present a case of a newborn infant with meconium peritonitis who developed infarcts in several organs. At autopsy the infarcts proved to be caused by emboli as a result of intravascular dissemination of meconium. To our knowledge, this is the first reported case of systemic spread of meconium peritonitis in the literature and suggests that meconium peritonitis may have more serious implications than generally thought.