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A range of procedural errors can occur when performing endodontic treatment on posterior teeth. These errors may decrease the success rate in endodontic practice. This study assessed the prevalence of procedural errors and the quality of endodontic treatments in maxillary molars and premolars using cone-beam computed tomography (CBCT). CBCT scans from two private radiology centers were assessed retrospectively to ensure the same calculated sample size of 327 teeth for each of the four maxillary posterior tooth types (a total of 1,308 endodontically treated teeth). Image sets were evaluated for procedural errors categorized as follows: obturation length (overfilling or underfilling by >2 mm short of the root apex), missed canals, perforations, strip perforations (with extrusion of material into the furcation area), separated instruments in the root canal space, and root fracture. Data were analyzed with SPSS version 20 (SPSS Inc., Chicago, IL, USA), and frequency data was assessed using the Monte Carlo test at the 0.05 level of significance. The procedural errors most commonly reported in the present study were from most frequent to least frequent: underfilled canals (50.0%), missed canals (27.5%), overfilled canals (12.5%), apical perforations (5.0%), separated instruments (3.1%), and root fractures (1.9%). No strip perforations (with extrusion of material into the furcation area) were seen in the study (0%). Underfilled and missed root canals were the most frequent procedural errors identified in the present study. These findings underline the importance of more consideration of critical working length management during all stages of root canal treatment, greater awareness of root canal anatomy, and the use of imaging and diagnostic devices that enhance the ability to identify and treat root canals both safely and effectively.

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Background Prior studies have shown an association between myocardial injury after noncardiac surgery (MINS) and all-cause mortality in patients following noncardiac surgery. However, the association between preoperative risk assessments, Revised Cardiac Risk Index and American College of Surgeons National Surgical Quality Improvement Program, and postoperative troponin elevations and long-term mortality is unknown. Methods and Results A retrospective chart review identified 548 patients who had a troponin I level drawn within 14 days of noncardiac surgery that required an overnight hospital stay. Patients aged 40 to 80 years with at least 2 cardiovascular risk factors were included, while those with trauma, pulmonary embolism, and neurosurgery were excluded. Kaplan-Meier survival and odds ratio (OR) with sensitivity/specificity analysis were performed to assess the association between preoperative risk and postoperative troponin elevation and all-cause mortality at 1 year. Overall, 69%/31% were classified as low-risk/high-risk per the Revised Cardiac Risk Index and 66%/34% per American College of Surgeons National Surgical Quality Improvement Program. Comparing the low-risk versus high-risk groups, preoperative risk assessment was not associated with either postoperative troponin elevation or 1-year mortality. MINS portended a 1-year mortality of OR, 3.9 (95% CI, 2.44-6.33) in the total population. Patients classified as low risk preoperatively with MINS had the highest risk of 1-year mortality (OR, 9.6; 95% CI, 4.27-24.38), with a low prevalence of statin use. Conclusions Current preoperative risk stratification tools do not prognosticate the risk of postoperative troponin elevation and all-cause mortality at 1 year. Interestingly, patients classified as low risk preoperatively with MINS had a markedly higher 1-year mortality risk compared with the general population, and most of them are not taking a statin. Our results suggest that evaluating preoperatively low-risk patients for MINS presents an opportunity for prognostication, risk reclassification, and initiating therapies such as statins to mitigate long-term risk.

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INTRODUCTION: Patients suffering ankle fractures provide a common economic and time burden to modern healthcare in the UK. They continue to be admitted to await operative intervention and may have to wait days before an operation occurs. Unnecessary bed stay is one are that may be subject to cost savings if the safety of the patient is maintained. PATIENT AND METHODS: We prospectively collected data on 23 patients over a four-month period identifying their admission status, length of stay, and time to operative intervention. We were able to cost analyse the patients journey from admission to discharge, postoperative intervention. We then instilled the Ankle Home Stay Programme, identifying patients safe to be discharged who were able to re-attend for their operation. Seventeen patients were enrolled in this and a subsequent cost-analysis was compared to the pre-intervention cohort. RESULTS: Pre Ankle Home Stay Programme demonstrated cost per patient of admitted patients to be £2690 and £1347 for patients managed in the outpatient setting. Implementation of the pathway maintained this cost saving with those in the outpatient setting costing £1781 per patient and those admitted costing £2855. CONCLUSIONS: Patients can be safely managed in the outpatient setting, with regular clinic review before formal operative intervention as opposed to blanket admission to an acute inpatient bed. This is cost saving in a healthcare system with finite resources focussed on improving use of economic resources. It also maintains patient care with select admission criteria onto the pathway and regular review to ensure standards are maintained.

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Introduction: Azithromycin stabilises and improves lung function forced expiratory volume in one second (FEV1) in lung transplantation patients with bronchiolitis obliterans syndrome (BOS). A post hoc analysis was performed to assess the long-term effect of azithromycin on FEV1, BOS progression and survival . Methods: Eligible patients recruited for the initial randomised placebo-controlled trial received open-label azithromycin after 3 months and were followed up until 6 years after inclusion (n=45) to assess FEV1, BOS free progression and overall survival. Results: FEV1 in the placebo group improved after open-label azithromycin and was comparable with the treatment group by 6 months. FEV1 decreased after 1 and 5 years and was not different between groups. Patients (n=18) with rapid progression of BOS underwent total lymphoid irradiation (TLI). Progression-free survival (log-rank test p=0.40) and overall survival (log-rank test p=0.28) were comparable. Survival of patients with early BOS was similar to late-onset BOS (log-rank test p=0.74). Discussion: Long-term treatment with azithromycin slows down the progression of BOS, although the effect of TLI may affect the observed attenuation of FEV1 decline. BOS progression and long-term survival were not affected by randomisation to the placebo group, given the early cross-over to azithromycin and possibly due to TLI in case of further progression. Performing randomised placebo-controlled trials in lung transplantation patients with BOS with a blinded trial duration is feasible, effective and safe.

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Type-2 biomarkers and related cytokines (IL-5, IL-13), lung function and asthma symptoms were measured in 44 poorly-controlled severe oral corticosteroid (OCS)-dependent asthmatics for up to 88 days after a 7-day prednisolone boost (0.5 mg/kg). High-dose OCS reduced median blood eosinophils (-60 cells/µl; 95% CI -140 to 10), periostin (-8.4 ng/mL; -11.6 to -2.8), FeNO (-19.0 ppb; -28.5 to -4.0), IL-5 (-0.17 pg/mL; -0.28 to -0.08) and IL-13 (-0.15 pg/mL; -0.27 to -0.03). There were small improvements in mean FEV1 (0.16 L; 0.05 to 0.27) and (Asthma Control Questionnaire) ACQ-7 score (0.3; 0.0 to 0.7). Study measures returned to baseline 1-month postintervention. Following rescue OCS, 1 month is sufficient before using type-2 biomarkers to guide long-term treatment. TRIAL REGISTRATION NUMBER: NCT01948401.

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BACKGROUND: The demand for lung transplantation vastly exceeds the availability of donor organs. This translates into long waiting times and high waiting list mortality. We set out to examine factors influencing patient outcomes from the time of listing for lung transplantation in the UK, examining for differences by patient characteristics, lung disease category and transplant centre. METHODS: Data were obtained from the UK Transplant Registry held by NHS Blood and Transplant for adult lung-only registrations between 1January 2004 and 31 March 2014. Pretransplant and post-transplant outcomes were evaluated against lung disease category, blood group and height. RESULTS: Of the 2213 patient registrations, COPD comprised 28.4%, pulmonary fibrosis (PF) 26.2%, cystic fibrosis (CF) 25.4% and other lung pathologies 20.1%. The chance of transplantation after listing differed by the combined effect of disease category and centre (p<0.001). At 3 years postregistration, 78% of patients with COPD were transplanted followed by 61% of patients with CF, 59% of other lung pathology patients and 48% of patients with PF, who also had the highest waiting list mortality (37%). The chance of transplantation also differed by height with taller patients having a greater chance of transplant (HR: 1.03, 95% CI: 1.02 to 1.04, p<0.001). Patients with blood group O had the highest waiting mortality at 3 years postregistration compared with all other blood groups (27% vs 20%, p<0.001). CONCLUSIONS: The way donor lungs were allocated in the UK resulted in discrepancies between the risk profile and probability of lung transplantation. A new donor lung allocation scheme was introduced in 2017 to try to address these shortcomings.

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PURPOSE: To survey the practice of orthopaedic consultants in the Greater London area for treating Achilles tendon ruptures. METHODS: 221 orthopaedic consultants working in 28 hospitals within the Greater London area were identified. A questionnaire regarding conservative treatment for acute Achilles tendon ruptures was sent. The choice of immobilisation, the period of immobilisation, the time to weight bearing, the use of heel raises, and the use of diagnostic ultrasonography were enquired about. RESULTS: 62 of 86 respondents treated Achilles tendon ruptures conservatively by below-knee casts (n=51), above-knee casts (n=5), or functional braces (n=6). The most common immobilisation regimen (n=7) was to keep the foot in a sequence of an equinus position, a semi-equinus position, and a neutral position (3 weeks in each position). After cast removal, 45 of respondents preferred to use a heel raise for a median duration of 4 (range, 2-36) weeks. Respectively for foot and ankle specialists (n=24) and other orthopaedic specialists (n=38), the median immobilisation period prescribed was 8 (range, 3-13) and 9 (range, 6-36) weeks, respectively (p=0.625), whereas the median time to weight bearing prescribed was 6 (range, 0-9) and 6 (range, 0-12) weeks, respectively (p=0.402). CONCLUSION: Functional bracing was not as widely used as below-knee cast immobilisation. There was no consensus on the optimal immobilisation regimen.

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BACKGROUND: Necrotizing enterocolitis (NEC) is a disease in neonates, often resulting in death or serious medical or neurodevelopmental complications. The rate of NEC is highest in the smallest babies and many efforts have been tried to reduce the rate of NEC. In neonates born below 1500 grams, the rate of NEC has been significantly reduced with the use of various probiotics. This study examines the impact of routine use of a probiotic, Lactobacillus reuteri DSM 17938 (BioGaia®), on the rate of NEC in neonates at highest risk for developing NEC, those with birth weight ≤1000 grams. METHODS: This is a retrospective cohort study comparing the rates of NEC in neonates with birth weight ≤ 1000 grams. The groups are separated into those neonates born from January 2004 to June 30, 2009, before introduction of L. reuteri , and neonates born July 2009 through April 2011 who received routine L. reuteri prophylaxis. The chart review study was approved by our institutional review board and exempted from informed consent.Neonates were excluded if they died or were transferred within the first week of life. The remainder were categorized as having no NEC, medical NEC, surgical NEC, or NEC associated death. Since no major changes occurred in our NICU practice in recent years, and the introduction of L. reuteri as routine prophylaxis was abrupt, we attributed the post-probiotic changes to the introduction of this new therapy. Rates of NEC were compared using Chi square analysis with Fisher exact t-test. RESULTS: Medical records for 311 neonates were reviewed, 232 before- and 79 after-introduction of L. reuteri prophylaxis. The incidence of NEC was significantly lower in the neonates who received L. reuteri (2 of 79 neonates [2.5%] versus 35 of 232 untreated neonates [15.1%]). Rates of late-onset gram-negative or fungal infections (22.8 versus 31%) were not statistically different between treated and untreated groups. No adverse events related to use of L reuteri were noted. CONCLUSIONS: Prophylactic initiation of L. reuteri as a probiotic for prevention of necrotizing enterocolitis resulted in a statistically significant benefit, with avoidance of 1 NEC case for every 8 patients given prophylaxis.

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The skeletal response to short-term exercise training remains poorly described. We thus studied the lower limb skeletal response of 723 Caucasian male army recruits to a 12-wk training regime. Femoral bone volume was assessed using magnetic resonance imaging, bone ultrastructure by quantitative ultrasound (QUS), and bone mineral density (BMD) using dual-energy X-ray absorptiometry (DXA) of the hip. Left hip BMD increased with training (mean ± SD: 0.85 ± 3.24, 2.93 ± 4.85, and 1.89 ± 2.85% for femoral neck, Ward's area, and total hip, respectively; all P < 0.001). Left calcaneal broadband ultrasound attenuation rose 3.57 ± 0.5% (P < 0.001), and left and right femoral cortical volume by 1.09 ± 4.05 and 0.71 ± 4.05%, respectively (P = 0.0001 and 0.003), largely through the rise in periosteal volume (0.78 ± 3.14 and 0.59 ± 2.58% for right and left, respectively, P < 0.001) with endosteal volumes unchanged. Before training, DXA and QUS measures were independent of limb dominance. However, the dominant femur had higher periosteal (25,991.49 vs. 2,5572 mm(3), P < 0.001), endosteal (6,063.33 vs. 5,983.12 mm(3), P = 0.001), and cortical volumes (19,928 vs. 19,589.56 mm(3), P = 0.001). Changes in DXA, QUS, and magnetic resonance imaging measures were independent of limb dominance. We show, for the first time, that short-term exercise training in young men is associated not only with a rise in human femoral BMD, but also in femoral bone volume, the latter largely through a periosteal response.

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Benzophenone photophores are employed widely for photoaffinity-labeling studies. Photolabeling with benzophenone, however, is hardly a routine experiment. Even when a photoprobe binds to its target, photocrosslinking does not necessarily occur. This is because photolabeling by benzophenone is affected by many factors other than target-binding, such as conformational flexibility of photoligand. Despite the widespread recognition of such complications, there has been no systematic study to assess the relative importance of individual factors that can affect photolabeling efficiency. In order to gain an insight into this problem, we conducted a structure-activity relationship (SAR) study of benzophenone photoligands for Lck kinase, in which photoligands with varying target-binding affinity and conformational flexibility were compared. The study found that binding-affinity, as indicated by kinase inhibitory potency, did not correlate with photolabeling efficiency. Instead, conformational flexibility was found to be the determining factor for efficient photolabeling by our photoligands. Implication of the current findings, in particular, with regard to selection and optimization of benzophenone photoligands, is discussed.

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BACKGROUND: Left ventricular mass is a risk factor for cardiovascular morbidity and mortality. Although factors associated with elevated left ventricular mass have been sought and studied extensively in elderly and in diseased subjects, few studies have examined the young and healthy. The aim of this study was to examine the possible influence of lifestyle on left ventricular mass in a large group of young men. METHODS: Left ventricular mass was assessed using cardiovascular magnetic resonance in 541 healthy Caucasian male army recruits. Anthropometric, lifestyle and blood pressure data were collected. RESULTS: Mean unadjusted left ventricular mass and left ventricular mass indexed to body surface area were 163.8+/-24.9 g and 86.6+/-10.2 g m(-2) respectively. In univariate analysis, age, height, weight, alcohol consumption, systolic blood pressure, diastolic blood pressure and indices of physical activity were positively associated with unadjusted left ventricular mass (all P<0.02). By contrast, smoking was associated with lower mean left ventricular mass; never smoked 167.5+/-25.8 g vs ex-smokers 159.1+/-25.2 g vs current smokers 161.0+/-23.1 g (P=0.007). Multivariate analysis revealed weight, systolic blood pressure, smoking status and indices of physical activity to be independent predictors of left ventricular mass. CONCLUSIONS: Our data confirm an association of age, body weight, height, physical activity, diastolic and systolic blood pressure with left ventricular mass. In addition, unexpectedly, we have found smoking is associated with lower left ventricular mass in a large sample of young healthy men. Although the latter association may result from confounding effects, such an interesting observation deserves further investigation.

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A molecular probe that selectively tags Lck, a Src-family kinase, was developed. This probe was one of many compounds originally designed to target the active site of tyrosine kinases in general. To our surprise, however, the probe almost exclusively labeled Lck even in a lysate of Jurkat cells. This finding led us to further characterize this probe-Lck complex by a series of photolabeling and mass spectrometric analyses. The probe-binding site on Lck was located within the well-conserved region of Src-family kinases, as we originally expected. However, the unexpected selectivity of this probe toward Lck suggests that subtle factors, which are difficult to predict based on static crystal structures, play important roles in probe recognition.

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The objective of this study was to examine the relationship between the interleukin-6 (IL-6) -174 G>C promoter polymorphism and exercise-induced femoral cortical bone resorption. Skeletal response to exercise was assessed in 130 male Caucasian army recruits. Five cross-sectional magnetic resonance images of the right femur were obtained before and after a 10-week period of basic physical training, and changes in cross-sectional cortical area were calculated. Recruits were genotyped for the -174 G>C IL-6 promoter polymorphism. Genotype frequencies (GG 36%, GC 47%, CC 22.17%) were in Hardy-Weinberg equilibrium. The mean percentage change in proximal femoral cross-sectional cortical area was strongly IL-6 genotype-dependent, with GG homozygotes losing 6.8 (3.82)% in cortical area, GC gaining+5.5 (4.88)% and CC gaining+17.3 (9.46)% (P=0.007 for linear trend). These changes persisted throughout the right femur and were significant in the femur as a whole (P=0.03). This study demonstrates an association between a functional polymorphism in the IL-6 gene and femoral cortical remodelling during strenuous physical exercise. Previous studies have suggested an important role for IL-6 in the regulation of bone mass in postmenopausal women, and in the invasion of bone by metastatic tumour deposits. These data extend these observations to the regulation of bone mass in healthy males, supporting a fundamental role for IL-6 in the regulation of bone mass and bone remodelling in humans.

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