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Surgery remains the only recommended intervention for patients with native aortic regurgitation. A transcatheter therapy to treat patients at high risk for mortality and complications with surgical aortic valve replacement represents an unmet need. Commercial transcatheter heart valves in pure aortic regurgitation are hampered by unacceptable rates of embolisation and paravalvular regurgitation. The Trilogy transcatheter heart valve (JenaValve Technology, Irvine, CA, USA) provides a treatment option for these patients. We report outcomes with transfemoral transcatheter aortic valve implantation (TAVI) in patients with pure aortic regurgitation using this dedicated transcatheter heart valve.

Atrial fibrillation (AF) is a common comorbidity in patients with heart failure with preserved ejection fraction (HFpEF) and in heart failure with mildly reduced ejection fraction (HFmrEF).

IMPORTANCE: The frequency and clinical importance of structural valve deterioration (SVD) in patients undergoing self-expanding transcatheter aortic valve implantation (TAVI) or surgery is poorly understood. OBJECTIVE: To evaluate the 5-year incidence, clinical outcomes, and predictors of hemodynamic SVD in patients undergoing self-expanding TAVI or surgery. DESIGN, SETTING, AND PARTICIPANTS: This post hoc analysis pooled data from the CoreValve US High Risk Pivotal (n = 615) and SURTAVI (n = 1484) randomized clinical trials (RCTs); it was supplemented by the CoreValve Extreme Risk Pivotal trial (n = 485) and CoreValve Continued Access Study (n = 2178). Patients with severe aortic valve stenosis deemed to be at intermediate or increased risk of 30-day surgical mortality were included. Data were collected from December 2010 to June 2016, and data were analyzed from December 2021 to October 2022. INTERVENTIONS: Patients were randomized to self-expanding TAVI or surgery in the RCTs or underwent self-expanding TAVI for clinical indications in the nonrandomized studies. MAIN OUTCOMES AND MEASURES: The primary end point was the incidence of SVD through 5 years (from the RCTs). Factors associated with SVD and its association with clinical outcomes were evaluated for the pooled RCT and non-RCT population. SVD was defined as (1) an increase in mean gradient of 10 mm Hg or greater from discharge or at 30 days to last echocardiography with a final mean gradient of 20 mm Hg or greater or (2) new-onset moderate or severe intraprosthetic aortic regurgitation or an increase of 1 grade or more. RESULTS: Of 4762 included patients, 2605 (54.7%) were male, and the mean (SD) age was 82.1 (7.4) years. A total of 2099 RCT patients, including 1128 who received TAVI and 971 who received surgery, and 2663 non-RCT patients who received TAVI were included. The cumulative incidence of SVD treating death as a competing risk was lower in patients undergoing TAVI than surgery (TAVI, 2.20%; surgery, 4.38%; hazard ratio [HR], 0.46; 95% CI, 0.27-0.78; P = .004). This lower risk was most pronounced in patients with smaller annuli (23 mm diameter or smaller; TAVI, 1.32%; surgery, 5.84%; HR, 0.21; 95% CI, 0.06-0.73; P = .02). SVD was associated with increased 5-year all-cause mortality (HR, 2.03; 95% CI, 1.46-2.82; P < .001), cardiovascular mortality (HR, 1.86; 95% CI, 1.20-2.90; P = .006), and valve disease or worsening heart failure hospitalizations (HR, 2.17; 95% CI, 1.23-3.84; P = .008). Predictors of SVD were developed from multivariate analysis. CONCLUSIONS AND RELEVANCE: This study found a lower rate of SVD in patients undergoing self-expanding TAVI vs surgery at 5 years. Doppler echocardiography was a valuable tool to detect SVD, which was associated with worse clinical outcomes. TRIAL REGISTRATION: ClinicalTrials.gov Identifiers: NCT01240902, NCT01586910, and NCT01531374

IMPORTANCE: In patients with severe aortic valve stenosis at intermediate surgical risk, transcatheter aortic valve replacement (TAVR) with a self-expanding supra-annular valve was noninferior to surgery for all-cause mortality or disabling stroke at 2 years. Comparisons of longer-term clinical and hemodynamic outcomes in these patients are limited. OBJECTIVE: To report prespecified secondary 5-year outcomes from the Symptomatic Aortic Stenosis in Intermediate Risk Subjects Who Need Aortic Valve Replacement (SURTAVI) randomized clinical trial. DESIGN, SETTING, AND PARTICIPANTS: SURTAVI is a prospective randomized, unblinded clinical trial. Randomization was stratified by investigational site and need for revascularization determined by the local heart teams. Patients with severe aortic valve stenosis deemed to be at intermediate risk of 30-day surgical mortality were enrolled at 87 centers from June 19, 2012, to June 30, 2016, in Europe and North America. Analysis took place between August and October 2021. INTERVENTION: Patients were randomized to TAVR with a self-expanding, supra-annular transcatheter or a surgical bioprosthesis. MAIN OUTCOMES AND MEASURES: The prespecified secondary end points of death or disabling stroke and other adverse events and hemodynamic findings at 5 years. An independent clinical event committee adjudicated all serious adverse events and an independent echocardiographic core laboratory evaluated all echocardiograms at 5 years. RESULTS: A total of 1660 individuals underwent an attempted TAVR (n = 864) or surgical (n = 796) procedure. The mean (SD) age was 79.8 (6.2) years, 724 (43.6%) were female, and the mean (SD) Society of Thoracic Surgery Predicted Risk of Mortality score was 4.5% (1.6%). At 5 years, the rates of death or disabling stroke were similar (TAVR, 31.3% vs surgery, 30.8%; hazard ratio, 1.02 [95% CI, 0.85-1.22]; P = .85). Transprosthetic gradients remained lower (mean [SD], 8.6 [5.5] mm Hg vs 11.2 [6.0] mm Hg; P < .001) and aortic valve areas were higher (mean [SD], 2.2 [0.7] cm2 vs 1.8 [0.6] cm2; P < .001) with TAVR vs surgery. More patients had moderate/severe paravalvular leak with TAVR than surgery (11 [3.0%] vs 2 [0.7%]; risk difference, 2.37% [95% CI, 0.17%- 4.85%]; P = .05). New pacemaker implantation rates were higher for TAVR than surgery at 5 years (289 [39.1%] vs 94 [15.1%]; hazard ratio, 3.30 [95% CI, 2.61-4.17]; log-rank P < .001), as were valve reintervention rates (27 [3.5%] vs 11 [1.9%]; hazard ratio, 2.21 [95% CI, 1.10-4.45]; log-rank P = .02), although between 2 and 5 years only 6 patients who underwent TAVR and 7 who underwent surgery required a reintervention. CONCLUSIONS AND RELEVANCE: Among intermediate-risk patients with symptomatic severe aortic stenosis, major clinical outcomes at 5 years were similar for TAVR and surgery. TAVR was associated with superior hemodynamic valve performance but also with more paravalvular leak and valve reinterventions.

For mental health nurses, a core component of the nurse–patient relationship is compassion. Bearing witness to patients' distress may lead to the manifestation of compassion fatigue; a decrease in compassionate and empathic responses because of prolonged contact with patients with mental ill health issues. Mental health nurses, particularly those who work in areas where they are exposed to frequent crisis presentations, such as inpatient settings and crisis teams, are at risk of developing compassion fatigue, yet there remains a paucity of research into the impact on those delivering mental health care in the UK. This article highlights the importance of identifying compassion fatigue, advocates for open honest and supportive discussions without fear of reprimand, and argues that possible workplace causes should be effectively addressed by nurse leaders and organisations, not just for sake of the mental health nurse and their employers, but also to ensure positive patient outcomes.

IMPORTANCE: The outcomes of transcatheter aortic valve replacement (TAVR) in low-risk patients with bicuspid aortic valve stenosis have not been studied in a large scale, multicentered, prospective fashion. OBJECTIVE: To evaluate the procedural safety, efficacy, and 30-day outcomes of TAVR in patients with bicuspid aortic stenosis at low surgical risk. DESIGN, SETTING, AND PARTICIPANTS: The Low Risk Bicuspid Study is a prospective, single-arm trial study with inclusion/exclusion criteria developed from the Evolut Low Risk Randomized Trial. Follow-up is planned for 10 years. Patients underwent TAVR at 25 centers in the United States who were also participating in the Evolut Low Risk Randomized Trial from December 2018 to October 2019. Eligible patients had severe bicuspid aortic valve stenosis and met American Heart Association/American College of Cardiology guideline indications for aortic valve replacement. INTERVENTIONS: Patients underwent attempted implant of an Evolut or Evolut PRO transcatheter aortic valve, with valve size based on annular measurements. MAIN OUTCOMES AND MEASURES: The prespecified primary end point was the incidence of all-cause mortality or disabling stroke at 30 days. The prespecified primary efficacy end point was device success defined as the absence of procedural mortality, the correct position of 1 bioprosthetic heart valve in the proper anatomical location, and the absence of more than mild aortic regurgitation postprocedure. RESULTS: A total of 150 patients underwent an attempted implant. Baseline characteristics include mean age of 70.3 (5.5) years, 48.0% female (n = 72), and a mean Society of Thoracic Surgeons score of 1.4 (0.6%). Most patients (136; 90.7%) had Sievers type I valve morphology. The incidence of all-cause mortality or disabling stroke was 1.3% (95% CI, 0.3%-5.3%) at 30 days. The device success rate was 95.3% (95% CI, 90.5%-98.1%). At 30 days, the mean (SD) AV gradient was 7.6 (3.7) mm Hg and effective orifice area was 2.3 (0.7) cm2. A new permanent pacemaker was implanted in 22 patients (15.1%). No patients had greater than mild paravalvular leak. CONCLUSIONS AND RELEVANCE: Transcatheter aortic valve replacement in low–surgical risk patients with bicuspid aortic valve stenosis achieved favorable 30-day results, with low rates of death and stroke and high device success rate. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03635424

•SBCE has a high sensitivity in delineating macroscopic changes of CD.•Severity of malabsorption on blood parameters (vitamin B12 and folate levels) correlate with extent of CD.•Patients with CD with a normal SBCE, are unlikely to have significant active disease as an explanation for their symptoms.

When an unexpected event occurs in a hybrid cardiac operating room, a minimally invasive heart surgery may need to be transitioned to open-heart surgery emergently. In such cases, an interspecialty team must dynamically shift roles quickly and seamlessly, without compromising patient safety. During this transition, appropriate response can be delayed because there are multiple teams carrying out critical, urgent, interdependent tasks. This paper describes human-factors efforts that employed task analysis, cognitive in-situ walk-throughs, and in-situ simulation to develop operational protocols to address the high-risk event. This series of interventions helped to create safe, effective protocols for seamless transition of leadership in this complex procedure.

Molecular dissection of inborn errors of immunity can help to elucidate the nonredundant functions of individual genes. We studied 3 children with an immune dysregulation syndrome of susceptibility to infection, lymphadenopathy, hepatosplenomegaly, developmental delay, autoimmunity, and lymphoma of B-cell (n = 2) or T-cell (n = 1) origin. All 3 showed early autologous T-cell reconstitution following allogeneic hematopoietic stem cell transplantation. By whole-exome sequencing, we identified rare homozygous germline missense or nonsense variants in a known epigenetic regulator of gene expression: ten-eleven translocation methylcytosine dioxygenase 2 (TET2). Mutated TET2 protein was absent or enzymatically defective for 5-hydroxymethylating activity, resulting in whole-blood DNA hypermethylation. Circulating T cells showed an abnormal immunophenotype including expanded double-negative, but depleted follicular helper, T-cell compartments and impaired Fas-dependent apoptosis in 2 of 3 patients. Moreover, TET2-deficient B cells showed defective class-switch recombination. The hematopoietic potential of patient-derived induced pluripotent stem cells was skewed toward the myeloid lineage. These are the first reported cases of autosomal-recessive germline TET2 deficiency in humans, causing clinically significant immunodeficiency and an autoimmune lymphoproliferative syndrome with marked predisposition to lymphoma. This disease phenotype demonstrates the broad role of TET2 within the human immune system.

Molecular dissection of inborn errors of immunity can help to elucidate the nonredundant functions of individual genes. We studied 3 children with an immune dysregulation syndrome of susceptibility to infection, lymphadenopathy, hepatosplenomegaly, developmental delay, autoimmunity, and lymphoma of B-cell (n = 2) or T-cell (n = 1) origin. All 3 showed early autologous T-cell reconstitution following allogeneic hematopoietic stem cell transplantation. By whole-exome sequencing, we identified rare homozygous germline missense or nonsense variants in a known epigenetic regulator of gene expression: ten-eleven translocation methylcytosine dioxygenase 2 (TET2). Mutated TET2 protein was absent or enzymatically defective for 5-hydroxymethylating activity, resulting in whole-blood DNA hypermethylation. Circulating T cells showed an abnormal immunophenotype including expanded double-negative, but depleted follicular helper, T-cell compartments and impaired Fas-dependent apoptosis in 2 of 3 patients. Moreover, TET2-deficient B cells showed defective class-switch recombination. The hematopoietic potential of patient-derived induced pluripotent stem cells was skewed toward the myeloid lineage. These are the first reported cases of autosomal-recessive germline TET2 deficiency in humans, causing clinically significant immunodeficiency and an autoimmune lymphoproliferative syndrome with marked predisposition to lymphoma. This disease phenotype demonstrates the broad role of TET2 within the human immune system.

Inflammatory bowel disease (IBD) places a significant burden on health-care systems because of its chronicity and need for expensive therapies and surgery. With increasing use of biological therapies, contemporary data on IBD health-care costs are important for those responsible for allocating resources in Europe. To our knowledge, no prospective long-term analysis of the health-care costs of patients with IBD in the era of biologicals has been done in Europe. We aimed to investigate cost profiles of a pan-European, community-based inception cohort during 5 years of follow-up.

ObjectiveIn England, the National Health Service commissioned a National Management Service for children with primary ciliary dyskinesia (PCD). The aims of this study were to describe the health of children seen in this Service and compare lung function to children with cystic fibrosis (CF).DesignMulti-centre service evaluation of the English National Management PCD Service.SettingFour nationally commissioned PCD centres in England.Patients333 children with PCD reviewed in the Service in 2015; lung function data were also compared with 2970 children with CF.ResultsMedian age at diagnosis for PCD was 2.6 years, significantly lower in children with situs inversus (1.0 vs 6.0 years, p<0.001). Compared with national data from the CF Registry, mean (SD) %predicted forced expiratory volume in one second (FEV1) was 76.8% in PCD (n=240) and 85.0% in CF, and FEV1was lower in children with PCD up to the age of 15 years. Approximately half of children had some hearing impairment, with 26% requiring hearing aids. Children with a lower body mass index (BMI) had lower FEV1(p<0.001). One-third of children had positive respiratory cultures at review, 54% of these grew Haemophilus influenzae.ConclusionsWe provide evidence that children with PCD in England have worse lung function than those with CF. Nutritional status should be considered in PCD management, as those with a lower BMI have significantly lower FEV1. Hearing impairment is common but seems to improve with age. Well-designed and powered randomised controlled trials on management of PCD are needed to inform best clinical practice.

Traffic conditions in signalized junctions are highly dynamic and may be subject to abrupt changes due to unanticipated traffic incidents or network obstructions. These abrupt changing conditions are represented as different regimes or modes where each mode is represented by its own distinct model, forming a set of multiple models. At any instance in time, only one model of the set has the potential of representing the physical system dynamics at that time. However the dynamics may arbitrarily jump over to a different regime when an abnormal condition arises. Furthermore, it might be impossible to identify these models a priori. Hence, a multiple model approach is developed to self-detect these abrupt changes, identify which member of the set best represents the actual system and automatically self-configure and add a new model to the set when a previously unmodelled regime arises. This approach makes use of a real-time joint (dual) estimation algorithm to estimate traffic state variables such as queue lengths and traffic flow, as well as model parameters such as turning ratios, saturation flow values and noise covariance resulting from unmodelled dynamics and measurement errors. The proposed algorithm is validated through simulations on signalized 3-arm and 4-arm junctions with typical day-to-day traffic conditions including several network irregularities occuring at different times of the day such as arm closures as a result of traffic incidents. This work is aimed to form part of adaptive control loops for traffic light systems that are able to autonomously adjust to changing traffic conditions so as to ensure efficient vehicle flows.

Altered drive to socially engage is a transdiagnostic feature across multiple psychopathologies. Yet, lack of clarity regarding specific processes that constitute social drive, along with insufficient measurement methods, has hindered understanding in this area. This study ascertained the feasibility of approximating difficulties within specific fine-grained social drive processes as proposed by 2 theoretical frameworks: “orienting,” “wanting,” “pursuing,” “liking,” “learning,” and “reticence” within a reward processing framework and “orienting,” “seeking and maintaining,” and “liking” within a social motivation framework.

Great interest exists in the potential efficacy of prediagnostic interventions within the autism spectrum disorder prodrome, but available evidence relates to children at high familial risk. We aimed to test the efficacy of a pre-emptive intervention designed for infants showing early behavioural signs of autism spectrum disorder.

Motus (Lingo) is a TV show based on a word game where each player has to guess a word, of which she knows only the length and the first letter. To do this, the player makes different proposals and she is given some hints based on the positions of the letters. We first show in this article that there is no strategy to find all the words with the available number of proposals. Next, we study different strategies based on aggregate functions and tie-breaks. All these strategies were tested on all the 5 to 10 letter French words, which finally leads us to discuss the respective performance of these strategies. We show that the criteria of average number of tries used, worst case and number of fails are conflicting.

ObjectiveThe Epi-IBD cohort is a prospective population-based inception cohort of unselected patients with inflammatory bowel disease from 29 European centres covering a background population of almost 10 million people. The aim of this study was to assess the 5-year outcome and disease course of patients with Crohn’s disease (CD).DesignPatients were followed up prospectively from the time of diagnosis, including collection of their clinical data, demographics, disease activity, medical therapy, surgery, cancers and deaths. Associations between outcomes and multiple covariates were analysed by Cox regression analysis.ResultsIn total, 488 patients were included in the study. During follow-up, 107 (22%) patients received surgery, while 176 (36%) patients were hospitalised because of CD. A total of 49 (14%) patients diagnosed with non-stricturing, non-penetrating disease progressed to either stricturing and/or penetrating disease. These rates did not differ between patients from Western and Eastern Europe. However, significant geographic differences were noted regarding treatment: more patients in Western Europe received biological therapy (33%) and immunomodulators (66%) than did those in Eastern Europe (14% and 54%, respectively, P<0.01), while more Eastern European patients received 5-aminosalicylates (90% vs 56%, P<0.05). Treatment with immunomodulators reduced the risk of surgery (HR: 0.4, 95% CI 0.2 to 0.6) and hospitalisation (HR: 0.3, 95% CI 0.2 to 0.5).ConclusionDespite patients being treated early and frequently with immunomodulators and biological therapy in Western Europe, 5-year outcomes including surgery and phenotype progression in this cohort were comparable across Western and Eastern Europe. Differences in treatment strategies between Western and Eastern European centres did not affect the disease course. Treatment with immunomodulators reduced the risk of surgery and hospitalisation.

The Lindelöf degree and extent were studied in Buhagiar et al. (Cent Eur J Math 12(8):1249–1264, 2014) in relation to lexicographic products of linearly ordered spaces. In this paper we consider the behaviour of other important cardinal functions, such as spread, density, weight and character, in such lexicographic products. Namely, we study the relation between a particular cardinal function on a lexicographic product of linearly ordered spaces and that cardinal function on each factor of the product.

•Patients with small bowel bleeding from angioectasia requring increasing therapy are in increasingly co-morbid patients.•Somatostatin analogues may be a useful adjunct to endoscopic therapy for transfusion dependent bleeding.•In the first year, they reduced bleeding episodes while being cost neutral.

Introduction:Screening is an effective means for colorectal cancer prevention and early detection. Family history is strongly associated with colorectal cancer risk. We describe the rationale, evidence and recommendations for colorectal cancer screening by family history for people without a genetic syndrome, as reported in the 2017 revised Australian guidelines. Main recommendations:Based on 10-year risks of colorectal cancer, people at near average risk due to no or weak family history (category 1) are recommended screening by immunochemical faecal occult blood test (iFOBT) every 2 years from age 50 to 74 years. Individuals with moderate risk due to their family history (category 2) are recommended biennial iFOBT from age 40 to 49 years, then colonoscopy every 5 years from age 50 to 74 years. People with a high risk due to their family history (category 3) are recommended biennial iFOBT from age 35 to 44 years, then colonoscopy every 5 years from age 45 to 74 years. Changes in management as a result of the guidelines:By 2019, the National Bowel Cancer Screening Program will offer all Australians free biennial iFOBT screening from age 50 to 74 years, consistent with the recommendations in these guidelines for category 1. Compared with the 2005 guidelines, there are some minor changes in the family history inclusion criteria for categories 1 and 2; the genetic syndromes have been removed from category 3 and, as a consequence, colonoscopy screening is now every 5 years; and for categories 2 and 3, screening begins with iFOBT for people aged 40 and 35 years, respectively, before transitioning to colonoscopy after 10 years.

IMPORTANCE: In patients with heart failure (HF) and left ventricular ejection fraction (LVEF) equal to or greater than 40%, a transcatheter interatrial shunt device (IASD; Corvia Medical) reduces exercise pulmonary capillary wedge pressure (PCWP) and is safe compared with sham control treatment at 1 month of follow-up. The longer-term safety and patency of the IASD has not yet been demonstrated in the setting of a randomized clinical trial (RCT). OBJECTIVE: To evaluate the 1-year safety and clinical outcomes of the IASD compared with a sham control treatment. DESIGN, SETTING, AND PARTICIPANTS: This phase 2, double-blind, 1-to-1 sham-controlled multicenter RCT of IASD implantation vs a sham procedure (femoral venous access and imaging of the interatrial septum without IASD) was conducted in 22 centers in the United States, Europe, and Australia on patients with New York Heart Association (NYHA) class III or ambulatory class IV HF, LVEF equal to or greater than 40%, exercise PCWP equal to or greater than 25 mm Hg, and PCWP-right atrial pressure gradient equal to or greater than 5 mm Hg. MAIN OUTCOMES AND MEASURES: Safety was assessed by major adverse cardiac, cerebrovascular, or renal events (MACCRE). Exploratory outcomes evaluated at 1 year were hospitalizations for HF, NYHA class, quality of life, a 6-minute walk test, and device patency. RESULTS: After 1 year, shunts were patent in all IASD-treated patients; MACCRE did not differ significantly in the IASD arm (2 of 21 [9.5%]) vs the control arm (5 of 22 [22.7%]; P = .41), and no strokes occurred. The yearly rate of hospitalizations for HF was 0.22 in the IASD arm and 0.63 in the control arm (P = .06). Median improvement in NYHA class was 1 class in the IASD arm (IQR, −1 to 0) vs 0 in the control arm (IQR, −1 to 0; P = .08). Quality of life and 6-minute walk test distance were similar in both groups. At 6 months, there was an increase in right ventricular size in the IASD arm (mean [SD], 7.9 [8.0] mL/m2) vs the control arm (−1.8 [9.6] mL/m2; P = .002), consistent with left-to-right shunting through the device; no further increase occurred in the IASD arm at 12 months. CONCLUSIONS AND RELEVANCE: The REDUCE LAP-HF I phase 2, sham-controlled RCT confirms the longer-term patency of the IASD. Through 1 year of follow-up, IASD treatment appears safe, with no significant differences in MACCRE in patients receiving IASD compared with those who received sham control treatment. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT02600234

Coeliac disease is a common autoimmune disorder induced by ingesting gluten, the protein component of wheat, barley, and rye. It is estimated that one-in-hundred people worldwide have coeliac disease, of whom the majority remain undiagnosed. Coeliac disease is characterized by a wide range of gastrointestinal and extraintestinal symptoms but can also present asymptomatically. Diagnosing coeliac disease depends on the concordance of clinical, serological and histopathological data. However, the diagnosis can be challenging and frequently overlooked. Undiagnosed coeliac disease is associated with an increased risk of complications and detrimental effects on quality of life. Early diagnosis and treatment of coeliac disease are necessary to reduce the risk of long-term complications.

Cardiac computed tomography angiography was used to identify anatomical characteristics of the aortic root in patients with severe aortic regurgitation (AR) as compared to those with aortic stenosis (AS) to judge feasibility of transcatheter aortic valve replacement (TAVR) with the JenaValve Trilogy system.

IMPORTANCE: Transcatheter aortic valve replacement (TAVR) is now a well-accepted alternative to surgical AVR (SAVR) for patients with symptomatic aortic stenosis at increased operative risk. There is interest in whether TAVR would benefit patients at lower risk. OBJECTIVE: The Society of Thoracic Surgeons Predicted Risk of Mortality (STS PROM) has trended downward in US TAVR trials and the STS/American College of Cardiology Transcatheter Valve Therapy Registry. We hypothesized that if the Society of Thoracic Surgeons Predicted Risk of Mortality (STS PROM) alone is sufficient to define decreased risk, the contribution to survival based on the degree of invasiveness of the TAVR procedure will decrease, making it more difficult to show improved survival and benefit over SAVR. DESIGN, SETTING, AND PARTICIPANTS: The CoreValve US Pivotal High Risk Trial was a multicenter, randomized, noninferiority trial. This retrospective analysis evaluated patients who underwent an attempted implant and had an STS PROM of 7% or less. The trial was performed at 45 US sites. Patients had severe aortic stenosis and were at increased surgical risk based on their STS PROM score and other risk factors. INTERVENTIONS: Eligible patients were randomly assigned (1:1) to self-expanding TAVR or to SAVR. MAIN OUTCOMES AND MEASURES: We retrospectively stratified patients by the overall median STS PROM score (7%) and analyzed clinical outcomes and quality of life using the Kansas City Cardiomyopathy Questionnaire in patients with an STS PROM score of 7% or less. RESULTS: The mean (SD) ages were 81.5 (7.6) years for the TAVR group and 81.2 years (6.6) for the SAVR group. A little more than half were men (57.9% in the TAVR group and 55.8% in the SAVR group). Of 750 patients who underwent attempted implantation, 383 (202 TAVR and 181 SAVR) had an STS PROM of 7% or less (median [interquartile range]: TAVR, 5.3% [4.3%-6.1%]; SAVR, 5.3% [4.1%-5.9%]). Two-year all-cause mortality for TAVR vs SAVR was 15.0% (95% CI, 8.9-10.0) vs 26.3% (95% CI, 19.7-33.0) (log rank P = .01). The 2-year rate of stroke for TAVR vs SAVR was 11.3% vs 15.1% (log rank P = .50). Quality of life by the Kansas City Cardiomyopathy Questionnaire summary score showed significant and equivalent increases in both groups at 2 years (mean [SD] TAVR, 20.0 [25.0]; SAVR, 18.6 [23.6]; P = .71; both P &lt; .001 compared with baseline). Medical benefit, defined as alive with a Kansas City Cardiomyopathy Questionnaire summary score of at least 60 and a less than 10-point decrease from baseline, was similar between groups at 2 years (TAVR, 51.0%; SAVR, 44.4%; P = .28). CONCLUSIONS AND RELEVANCE: Self-expanding TAVR compares favorably with SAVR in high-risk patients with STS PROM scores traditionally considered intermediate risk. TRIAL REGISTRATION: Clinicaltrials.gov Identifier: NCT01240902.

Neck sonography is frequently encountered on ultrasound lists in the paediatric patient population. Anecdotally, one of the most frequent clinical indications is the investigation of a neck lump. While performing an ultrasound of the neck, structures other than those routinely assessed, such as the thyroid cartilage and mandibular cortex also come into view. Occasionally, pathology in these structures is also encountered, albeit less frequently. The purpose of this case report and review is to illustrate the ultrasound, computed tomography and magnetic resonance imaging appearances of cyst-like changes in the thyroid cartilage that are encountered in children, particularly in early adolescence.

Objective To evaluate short and long term effects of giving nebulised budesonide early in respiratory syncytial viral (RSV) bronchiolitis. Design A multicentre randomised double blind placebo controlled trial. Subjects Infants admitted to hospital with their first episode of RSV positive bronchiolitis. Intervention Randomisation to receive either 1 mg of nebulised budesonide (Bud) or placebo (Pla) twice daily from admission until 2 weeks after discharge. Follow up was for 12 months. Main outcome measures Duration of hospital admission, time taken to become symptom free, re-admission rates, general practitioner consultation rates, and use of antiwheeze medication during follow up. Results 161 infants were studied. Both arms were similar with respect to initial clinical severity, age, sex, socioeconomic class, and tobacco exposure. Median time from first nebulisation to discharge: Bud and Pla, 2 days. Median number of days for 50% of infants to be symptom free for 48 hours: Bud, 10 days; Pla, 12 days. Respiratory re-admission rates in the 12 month follow up: Bud, 16%; Pla, 18%; median difference (95% confidence interval (CI)), -2 (-14 to 10). Median respiratory related general practitioner attendances: Bud, 4.0; Pla, 4.5; median difference (95% CI), -1 (-2 to 0). Percentage of infants receiving at least one prescription for antiwheeze medication during follow up, corticosteroids: Bud, 50%; Pla, 60%; difference (95% CI), -10 (-26 to 6); bronchodilators: Bud, 60%; Pla, 67%; difference (95% CI), -7 (-22 to 8). Conclusions There are no short or long term clinical benefits from the administration of nebulised corticosteroids in the acute phase of RSV bronchiolitis.

Introduction: The correlations between salivary hormone testing and the manual muscle test have not to our knowledge been reported before. Methods: Correlations between manual muscle tests and salivary hormone tests for 110 participants (83 female, 17 male) experiencing adrenal stress disorder (ASD) are described. Saliva samples were collected and screened for cortisol and dehydroepiandrosterone (DHEA). Results: We observed that patients with signs and symptoms of ASD and abnormal hormone levels on salivary hormone testing demonstrate distinct neuromuscular impairments that could be detected using the MMT. Discussion: Evidence for the linkages between neurohormonal imbalances and muscular imbalances are presented. Conclusion: This physical examination procedure, used within a number of health professions, may warrant further investigation given its utility, noninvasiveness, rapidity, and cost-effectiveness as a day-to-day clinical evaluation and management tool in cases of ASD. [ABSTRACT FROM AUTHOR]

Objective:Guidelines for swab use at our centre cover lower-limb wounds, ulcers and postoperative wound infections but not all types of wound. The objective of this study was to assess current practices in wound management at Mater Dei Hospital and to identify areas for improvement.Method:Wound swabs received at the microbiology department between February and April 2013 from adult inpatients departments were included. Wound swabs from the ophthalmology and paediatric departments were excluded. Patient comorbidities, detailed wound descriptions, acknowledgement of and documentation of culture and sensitivity results, and antibiotic changes during treatment were collected. Indictors of infection including white cell counts (WCCs) and C-reactive protein (CRP) were recorded.Results:The study included 134 patients. Diabetes mellitus (61.9%, n=83) was the most common underlying comorbidity. Postoperative wounds were the most common type of wounds swabbed (34.3%). The wound swab characteristics were not fully documented in 27 patients (20.1%). The CRP results were not recorded in 39.6% and WCCs were not taken in 10.4% of patients. Wound swab results were not acknowledged in the medical notes of 76% of cases.Conclusion:Wound swabs that were not indicated, lack of documentation and untimely acknowledgement of results were evident. This suggests that a significant proportion of wound swabs may not have been justified and had no impact on wound management. Our study clearly underlines the need for a more comprehensive guideline.Declaration of interest:There was no sponsorship of this study. The authors have no conflict of interest to declare.

Ultrasound is the primary imaging modality for testicular and scrotal assessment, with no risk of ionising radiation to radiosensitive tissue. Scrotal ultrasound is reliable in distinguishing between intratesticular and extratesticular lesions and characterising them as cystic or solid. High-resolution images are reproducible with the added advantage of further characterisation by using colour Doppler assessment or Valsalva manoeuvres. This pictorial review covers the anatomy of the epididymis and adnexa, and describes the ultrasound appearances of a range of extratesticular pathologies including congenital, benign, post-surgical, infective and vascular conditions collated over a two-year period at our institution.

Diagnostic ultrasound is considered to be the gold standard imaging modality for testicular assessment. As a result, it is frequently encountered by general radiologists and sonographers on daily ultrasound lists as well as by radiology residents out of hours. The main strength of diagnostic ultrasound in testicular assessment is that the high-frequency linear transducers utilized reproduce high-resolution images allowing accurate assessment of the testicular parenchyma. The fact that no ionizing radiation is utilized is particularly important as many patients on whom a testicular scan is requested are young or middle aged and the testis as an organ is very radiosensitive. This pictorial review comprises a range of illustrated images of congenital, benign, malignant, infection, polyorchidism and prosthesis-related pathologies collated over a two-year period at our institution.

The in situgenerated nickel hydride complex, [Ni(Mes2NHC)HCp], and its cationic analogue, [Ni(Mes2NHC)(NCMe)Cp](PF6), are efficient and chemoselective pre-catalysts for the hydrosilylation of both aldimines and ketimines under mild conditions.

The optimal degree of heparin anticoagulation for peripheral vascular interventions (PVIs) has not been defined. We sought to correlate total heparin dose and peak procedural activated clotting time (ACT) with postprocedural outcomes in patients undergoing PVI.

The reactions of selected primary amines with the unsaturated heterodimetallic complex [ηC5Me5NiμCOMoCO2ηC5H5]Ni[pb2]Mo1a were investigated. Primary aminesreact with this heterodimetallic complex to form unstable adducts, which are in equilibrium with the free amine and complex 1ain solution. Complex 1b, the nickel–tungsten analogue of 1a, reacts similarly with benzylamine. The position of the equilibrium shifts in favour of the adducts at low temperature, and crystals of the allylamine and benzylamine complexes [ηC5Me5RNH2Ni–MoCO3ηC5H5], 2a, R = C3H5; 4a, R = PhCH2 could be isolated. Their structures were established by singlecrystal Xray diffraction studies. The primary amines in complexes 2aand 4aare each coordinated, by means of their respective nitrogen atoms, to the nickel atom and thus provide the first structurally characterised examples of primary amine organometallic nickel complexes. The bonding of the amine to the heterodimetallic centre is in contrast to what has been observed with phosphoruscontaining 2electron donor ligands, in which the phosphane ligand is coordinated to the group 6 metal atom. A measure of the Ni–N bond dissociation enthalpy for the benzylaminenickel–tungsten complex 4bwas obtained from a VT 1H NMR spectroscopic study and was found to be –149 ± 10 kJ mol–1. NBonded hydrogen atoms in both 2aand 4aexhibit intermolecular hydrogenbonding interactions in the solid state with carbonyl oxygen atoms of adjacent molecules. These molecules exist as loosely bound dimers in the solid state. Complex 2aC21H27MoNNiO3 crystallises in the monoclinic space group P21nwith a= 10.19222, b= 11.15383, c= 18.80534 Å, β= 90.7772° and Z= 4. Complex 4aC25H29MoNNiO3 also crystallises in the monoclinic space group P21nwith a= 12.08404, b= 10.94904, c= 17.49306 Å, β= 90.3963° and Z= 4.

Antipsychotic drugs are the most effective treatment for the psychotic symptoms of schizophrenia, yet their mechanism of action remains largely unknown.

Even after five decades of use, the mood stabilizer lithium continues to be the mainstay of treatment for bipolar disorder in many countries. The mechanism of action for lithium, however, remains unclear.

Abstract In this note we give a measure-theoretic criterion for the completeness of an inner product space. We show that an inner product space S is complete if and only if there exists a s-additive state on C(S), the orthomodular poset of complete-cocomplete subspaces of S. We then consider the problem of whether every state on E(S), the class of splitting subspaces of S, can be extended to a Hilbertian state on E( ); we show that for the dense hyperplane S (of a separable Hilbert space) constructed by P. Pták and H. Weber in Proc. Am. Math. Soc. 129 (2001), 2111–2117, every state on E(S) is a restriction of a state on E( ).

AbstractWe introduce sign-preserving charges on the system of all orthogonally closed subspaces, F(S), of an inner product space S, and we show that it is always bounded on all the finite-dimensional subspaces whenever dim S= ?. When Sis finite-dimensional this is not true. This fact is used for a new completeness criterion showing that Sis complete whenever F(S) admits at least one non-zero sign-preserving regular charge. In particular, every such charge is always completely additive.

The notion of a strongly dense inner product space is introduced and it is shown that, for such an incomplete space $S$ (in particular, for each incomplete hyperplane of a Hilbert space), the system $F(S)$ of all orthogonally closed subspaces of $S$ is not stateless, and the state-space of $F(S)$ is affinely homeomorphic to the face consisting of the free states on the projection lattice corresponding to the completion of $S$. The homeomorphism is determined by the extension of the states. In particular, when $S$ is complex, the state-space of $F(S)$ is affinely homeomorphic to the state-space of the Calkin algebra associated with $\skew3\overline S$.

Background: Direct factor (F)Xa inhibition is an attractive method to limit thrombotic complications during percutaneous coronary intervention (PCI). Objectives: To investigate drug levels achieved, effect on coagulation markers, and preliminary efficacy and safety of several doses of DX‐9065a, an intravenous, small molecule, direct, reversible FXa inhibitor during PCI. Patients and methods: Patients undergoing elective, native‐vessel PCI (n= 175) were randomized 4 : 1 to open‐label DX‐9065a or heparin in one of four sequential stages. DX‐9065a regimens in stages I–III were designed to achieve concentrations of > 100 ng mL−1, > 75 ng mL−1, and > 150 ng mL−1. Stage IV used the stage III regimen but included patients recently given heparin. Results: At 15 min median (minimum) DX‐9065a plasma levels were 192 (176), 122 (117), 334 (221), and 429 (231) ng mL−1in stages I–IV, respectively. Median whole‐blood international normalized ratios (INRs) were 2.6 (interquartile range 2.5, 2.7), 1.9 (1.8, 2.0), 3.2 (3.0, 4.1), and 3.8 (3.4, 4.6), and anti‐FXa levels were 0.36 (0.32, 0.38), 0.33 (0.26, 0.39), 0.45 (0.41, 0.51), and 0.62 (0.52, 0.65) U mL−1, respectively. Stage II enrollment was stopped (n= 7) after one serious thrombotic event. Ischemic and bleeding events were rare and, in this small population, showed no clear relation to DX‐9065a dose. Conclusions: Elective PCI is feasible using a direct FXa inhibitor for anticoagulation. Predictable plasma drug levels can be rapidly obtained with double‐bolus and infusion DX‐9065a dosing. Monitoring of DX‐9065a may be possible using whole‐blood INR. Direct FXa inhibition is a novel and potentially promising approach to anticoagulation during PCI that deserves further study.

The heterobimetallic complexes [(η-C5H5)(OC)Ni−M(CO)3(η-C5H4Me)] (Ni−M, M = Mo, W) react with 3-methoxy-3-methyl-1-butyne [HC&tbd1;CMe2(OMe)] to afford the enantiomeric μ-alkyne complexes [CpNi(μ-η²,η²-HC2R)M(CO)2Cp‘] [Ni−M, M = Mo, W; R = CMe2(OMe)], which have chiral dimetalatetrahedrane cores, and the metallacycles [(η-C5H5)Ni{μ-η³(Ni),η¹(M)−C(O)−C(R)−C(H)}M(CO)2(η-C5H4Me)] [Ni−M, M = Mo, W; R = CMe2(OMe)], formed via highly regioselective alkyne−CO coupling. All complexes react with HBF4·Et2O. The Ni−Mo μ-alkyne complex generated the propargylic cationic species [(η-C5H5)Ni(μ-HC2CMe2)Mo(CO)2(η-C5H4Me)]⁺BF4^- (Ni−Mo) by protonation, followed by rapid methanol elimination. Attempted protonation of the Ni−W μ-alkyne complex led to intractable products. However cationic Ni−W (μ-HC2CMe2) complexes, and their Ni−Mo analogues, are accessible by direct protonation with HBF4·Et2O of the metallacycles [(η-C5H5)Ni{μ-η³(Ni),η¹(M)-C(O)−C(R)−C(H)}M(CO)2(η-C5H4Me)] [Ni−M, M = Mo, W; R = CMe2(OMe)]. Proton migration and CO and MeOH elimination reactions rapidly follow to generate heterobimetallic μ-HC2CMe2 cationic complexes. An intermediate was isolated from the slower Ni−W reaction. Spectroscopic data suggest that the stabilized HC2CMe2⁺ ions are π-coordinated to the group 6 metal atoms and not to the nickel. Differences in dynamic behavior are observed between the Ni−Mo and Ni−W cations:  rotation about the C−CMe2 bond occurs at ambient temperature for the Ni−Mo allenyl complex on the ¹H NMR time scale, but the Ni−W allenyl species is static.