Primary hemiarthroplasty for treatment of proximal humeral fractures

Background: Primary hemiarthroplasty of the shoulder is used to treat complex proximal humeral fractures, although the reported functional results following this method of treatment have varied widely. The aim of this study was to prospectively assess the prosthetic survival and functional outcomes in a large series of patients treated with shoulder hemiarthroplasty for a proximal humeral fracture. By determining the factors that affected the outcome, we also aimed to produce models that could be used clinically to estimate the functional outcome at one year following surgery.Methods: A thirteen-year observational cohort study of 163 consecutive patients treated with hemiarthroplasty for a proximal humeral fracture was performed. Twenty-five patients died or were lost to follow-up in the first year after treatment, leaving 138 patients who had assessment of shoulder function with use of the modified Constant score at one year postinjury.Results: The overall rate of prosthetic survival was 96.9% at one year, 95.3% at five years, and 93.9% at ten years. The overall median modified Constant score was 64 points at one year, with a typically good score for pain relief (median, 15 points) and poorer scores, with a greater scatter of values, for function (median, 12 points), range of motion (median, 24 points), and muscle power (median, 14 points). Of the factors that were assessed immediately after the injury, only patient age, the presence of a neurological deficit, tobacco usage, and alcohol consumption were significantly predictive of the one-year Constant score (p &lt; 0.05). Of the factors that were assessed at six weeks postinjury, those that predicted the one-year Constant score included the age of the patient, the presence of a persistent neurological deficit, the need for an early reoperation, the degree of displacement of the prosthetic head from the central axis of the glenoid seen radiographically, and the degree of displacement of the tuberosities seen radiographically.Conclusions: Primary shoulder hemiarthroplasty performed for the treatment of a proximal humeral fracture in medically fit and cooperative adults is associated with satisfactory prosthetic survival at an average of 6.3 years. Although the shoulder is usually free of pain following this procedure, the overall functional result, in terms of range of motion, function, and power, at one year varies. A good functional outcome can be anticipated for a younger individual who has no preoperative neurological deficit, no postoperative complications, and a satisfactory radiographic appearance of the shoulder at six weeks. The results are poorer in the larger group of elderly patients who undergo this procedure, especially if they have a neurological deficit, a postoperative complication requiring a reoperation, or an eccentrically located prosthesis with retracted tuberosities.<br /

‘Sadly I think we are sort of still quite white, middle-class really’ – Inequities in access tobereavement support: Findings from a mixed methods study

Background:Voluntary and community sector bereavement services are central to bereavement support in the UK.Aim:To determine service providers’ perspectives on access to their support before and during the COVID-19 pandemic.Design:Mixed methods study using an explanatory sequential design: (1) Cross-sectional online survey of UK bereavement services; (2) Qualitative interviews with staff and volunteers at selected services.Settings/participants:147 services participated in the survey; 24 interviews were conducted across 14 services.Results:67.3% of services reported there were groups with unmet needs not accessing their services before the pandemic; most frequently people from minoritised ethnic communities (49%), sexual minority groups (26.5%), deprived areas (24.5%) and men (23.8%). Compared with before the pandemic, 3.4% of services were seeing more people from minoritised ethnic groups, while 6.1% were seeing fewer. 25.2% of services did not collect ethnicity data. Qualitative findings demonstrated the disproportionate impact of the pandemic on minoritised ethnic communities, including disruption to care/mourning practices, and the need for culturally appropriate support. During the pandemic outreach activities were sometimes deprioritised; however, increased collaboration was also reported. Online provision improved access but excluded some. Positive interventions to increase equity included collecting client demographic data; improving outreach, language accessibility and staff representation; supporting other professionals to provide bereavement support; local collaboration and co-production.Conclusions:Service providers report inequities in access to bereavement support. Attention needs to be paid to identifying, assessing and meeting unmet needs for appropriate bereavement support. Identified positive interventions can inform service provision and research

Therapeutic options for mucinous ovarian carcinoma

OBJECTIVE: Mucinous ovarian carcinoma (MOC) is an uncommon ovarian cancer histotype that responds poorly to conventional chemotherapy regimens. Although long overall survival outcomes can occur with early detection and optimal surgical resection, recurrent and advanced disease are associated with extremely poor survival. There are no current guidelines specifically for the systemic management of recurrent MOC. We analyzed data from a large cohort of women with MOC to evaluate the potential for clinical utility from a range of systemic agents. METHODS: We analyzed gene copy number (n = 191) and DNA sequencing data (n = 184) from primary MOC to evaluate signatures of mismatch repair deficiency and homologous recombination deficiency, and other genetic events. Immunohistochemistry data were collated for ER, CK7, CK20, CDX2, HER2, PAX8 and p16 (n = 117-166). RESULTS: Molecular aberrations noted in MOC that suggest a match with current targeted therapies include amplification of ERBB2 (26.7%) and BRAF mutation (9%). Observed genetic events that suggest potential efficacy for agents currently in clinical trials include: KRAS/NRAS mutations (66%), TP53 missense mutation (49%), RNF43 mutation (11%), ARID1A mutation (10%), and PIK3CA/PTEN mutation (9%). Therapies exploiting homologous recombination deficiency (HRD) may not be effective in MOC, as only 1/191 had a high HRD score. Mismatch repair deficiency was similarly rare (1/184). CONCLUSIONS: Although genetically diverse, MOC has several potential therapeutic targets. Importantly, the lack of response to platinum-based therapy observed clinically corresponds to the lack of a genomic signature associated with HRD, and MOC are thus also unlikely to respond to PARP inhibition

Beginning teacher agency in the enactment of fundamental British values: A multi-method case study.

There has been significant discussion and debate about the meaning and implementation of the requirement for schools to promote fundamental British values. While much of the research in this area focuses on surveying teachers’ attitudes, this paper set out to understand the processes of professional enactment through which beginning teachers interpret the policy agenda across sites and contexts in initial teacher education. A multi-method case study was undertaken at a large provider of initial teacher education in the North of England, following beginning teachers on project placement in primary schools. Theorising awareness and agency as axes of professional formation, the paper identifies three key thematic foci: community partnership, the treatment of inclusiveness and diversity and the professional understanding, interpretation and performance of value language. Context shapes enactment of each theme, with reflective space for criticality required if beginning teachers are to develop professional agency with regard to their role as values educators. This is a feature of the culture of placement schools, and while university-based teaching can ameliorate the effects of unreflective compliance, it cannot provide a replacement for professional acculturation. The paper explores the implications of reflection on enactment for the professional acculturation of beginning teachers, making recommendations for teacher education

Gene expression profiling of mucinous ovarian tumors and comparison with upper and lower gastrointestinal tumors identifies markers associated with adverse outcomes.

PURPOSE: Advanced-stage mucinous ovarian carcinoma (MOC) has poor chemotherapy response and prognosis and lacks biomarkers to aid stage I adjuvant treatment. Differentiating primary MOC from gastrointestinal (GI) metastases to the ovary is also challenging due to phenotypic similarities. Clinicopathologic and gene-expression data were analyzed to identify prognostic and diagnostic features. EXPERIMENTAL DESIGN: Discovery analyses selected 19 genes with prognostic/diagnostic potential. Validation was performed through the Ovarian Tumor Tissue Analysis consortium and GI cancer biobanks comprising 604 patients with MOC (n = 333), mucinous borderline ovarian tumors (MBOT, n = 151), and upper GI (n = 65) and lower GI tumors (n = 55). RESULTS: Infiltrative pattern of invasion was associated with decreased overall survival (OS) within 2 years from diagnosis, compared with expansile pattern in stage I MOC [hazard ratio (HR), 2.77; 95% confidence interval (CI), 1.04–7.41, P = 0.042]. Increased expression of THBS2 and TAGLN was associated with shorter OS in MOC patients (HR, 1.25; 95% CI, 1.04–1.51, P = 0.016) and (HR, 1.21; 95% CI, 1.01–1.45, P = 0.043), respectively. ERBB2 (HER2) amplification or high mRNA expression was evident in 64 of 243 (26%) of MOCs, but only 8 of 243 (3%) were also infiltrative (4/39, 10%) or stage III/IV (4/31, 13%). CONCLUSIONS: An infiltrative growth pattern infers poor prognosis within 2 years from diagnosis and may help select stage I patients for adjuvant therapy. High expression of THBS2 and TAGLN in MOC confers an adverse prognosis and is upregulated in the infiltrative subtype, which warrants further investigation. Anti-HER2 therapy should be investigated in a subset of patients. MOC samples clustered with upper GI, yet markers to differentiate these entities remain elusive, suggesting similar underlying biology and shared treatment strategies

Large-scale association analysis identifies new lung cancer susceptibility loci and heterogeneity in genetic susceptibility across histological subtypes.

Although several lung cancer susceptibility loci have been identified, much of the heritability for lung cancer remains unexplained. Here 14,803 cases and 12,262 controls of European descent were genotyped on the OncoArray and combined with existing data for an aggregated genome-wide association study (GWAS) analysis of lung cancer in 29,266 cases and 56,450 controls. We identified 18 susceptibility loci achieving genome-wide significance, including 10 new loci. The new loci highlight the striking heterogeneity in genetic susceptibility across the histological subtypes of lung cancer, with four loci associated with lung cancer overall and six loci associated with lung adenocarcinoma. Gene expression quantitative trait locus (eQTL) analysis in 1,425 normal lung tissue samples highlights RNASET2, SECISBP2L and NRG1 as candidate genes. Other loci include genes such as a cholinergic nicotinic receptor, CHRNA2, and the telomere-related genes OFBC1 and RTEL1. Further exploration of the target genes will continue to provide new insights into the etiology of lung cancer

Case Reports1. A Late Presentation of Loeys-Dietz Syndrome: Beware of TGFβ Receptor Mutations in Benign Joint Hypermobility

Background: Thoracic aortic aneurysms (TAA) and dissections are not uncommon causes of sudden death in young adults. Loeys-Dietz syndrome (LDS) is a rare, recently described, autosomal dominant, connective tissue disease characterized by aggressive arterial aneurysms, resulting from mutations in the transforming growth factor beta (TGFβ) receptor genes TGFBR1 and TGFBR2. Mean age at death is 26.1 years, most often due to aortic dissection. We report an unusually late presentation of LDS, diagnosed following elective surgery in a female with a long history of joint hypermobility. Methods: A 51-year-old Caucasian lady complained of chest pain and headache following a dural leak from spinal anaesthesia for an elective ankle arthroscopy. CT scan and echocardiography demonstrated a dilated aortic root and significant aortic regurgitation. MRA demonstrated aortic tortuosity, an infrarenal aortic aneurysm and aneurysms in the left renal and right internal mammary arteries. She underwent aortic root repair and aortic valve replacement. She had a background of long-standing joint pains secondary to hypermobility, easy bruising, unusual fracture susceptibility and mild bronchiectasis. She had one healthy child age 32, after which she suffered a uterine prolapse. Examination revealed mild Marfanoid features. Uvula, skin and ophthalmological examination was normal. Results: Fibrillin-1 testing for Marfan syndrome (MFS) was negative. Detection of a c.1270G > C (p.Gly424Arg) TGFBR2 mutation confirmed the diagnosis of LDS. Losartan was started for vascular protection. Conclusions: LDS is a severe inherited vasculopathy that usually presents in childhood. It is characterized by aortic root dilatation and ascending aneurysms. There is a higher risk of aortic dissection compared with MFS. Clinical features overlap with MFS and Ehlers Danlos syndrome Type IV, but differentiating dysmorphogenic features include ocular hypertelorism, bifid uvula and cleft palate. Echocardiography and MRA or CT scanning from head to pelvis is recommended to establish the extent of vascular involvement. Management involves early surgical intervention, including early valve-sparing aortic root replacement, genetic counselling and close monitoring in pregnancy. Despite being caused by loss of function mutations in either TGFβ receptor, paradoxical activation of TGFβ signalling is seen, suggesting that TGFβ antagonism may confer disease modifying effects similar to those observed in MFS. TGFβ antagonism can be achieved with angiotensin antagonists, such as Losartan, which is able to delay aortic aneurysm development in preclinical models and in patients with MFS. Our case emphasizes the importance of timely recognition of vasculopathy syndromes in patients with hypermobility and the need for early surgical intervention. It also highlights their heterogeneity and the potential for late presentation. Disclosures: The authors have declared no conflicts of interes

BHPR research: qualitative1. Complex reasoning determines patients' perception of outcome following foot surgery in rheumatoid arhtritis

Background: Foot surgery is common in patients with RA but research into surgical outcomes is limited and conceptually flawed as current outcome measures lack face validity: to date no one has asked patients what is important to them. This study aimed to determine which factors are important to patients when evaluating the success of foot surgery in RA Methods: Semi structured interviews of RA patients who had undergone foot surgery were conducted and transcribed verbatim. Thematic analysis of interviews was conducted to explore issues that were important to patients. Results: 11 RA patients (9 ♂, mean age 59, dis dur = 22yrs, mean of 3 yrs post op) with mixed experiences of foot surgery were interviewed. Patients interpreted outcome in respect to a multitude of factors, frequently positive change in one aspect contrasted with negative opinions about another. Overall, four major themes emerged. Function: Functional ability & participation in valued activities were very important to patients. Walking ability was a key concern but patients interpreted levels of activity in light of other aspects of their disease, reflecting on change in functional ability more than overall level. Positive feelings of improved mobility were often moderated by negative self perception ("I mean, I still walk like a waddling duck”). Appearance: Appearance was important to almost all patients but perhaps the most complex theme of all. Physical appearance, foot shape, and footwear were closely interlinked, yet patients saw these as distinct separate concepts. Patients need to legitimize these feelings was clear and they frequently entered into a defensive repertoire ("it's not cosmetic surgery; it's something that's more important than that, you know?”). Clinician opinion: Surgeons' post operative evaluation of the procedure was very influential. The impact of this appraisal continued to affect patients' lasting impression irrespective of how the outcome compared to their initial goals ("when he'd done it ... he said that hasn't worked as good as he'd wanted to ... but the pain has gone”). Pain: Whilst pain was important to almost all patients, it appeared to be less important than the other themes. Pain was predominately raised when it influenced other themes, such as function; many still felt the need to legitimize their foot pain in order for health professionals to take it seriously ("in the end I went to my GP because it had happened a few times and I went to an orthopaedic surgeon who was quite dismissive of it, it was like what are you complaining about”). Conclusions: Patients interpret the outcome of foot surgery using a multitude of interrelated factors, particularly functional ability, appearance and surgeons' appraisal of the procedure. While pain was often noted, this appeared less important than other factors in the overall outcome of the surgery. Future research into foot surgery should incorporate the complexity of how patients determine their outcome Disclosure statement: All authors have declared no conflicts of interes

Global assessment of marine plastic exposure risk for oceanic birds

Plastic pollution is distributed patchily around the world’s oceans. Likewise, marine organisms that are vulnerable to plastic ingestion or entanglement have uneven distributions. Understanding where wildlife encounters plastic is crucial for targeting research and mitigation. Oceanic seabirds, particularly petrels, frequently ingest plastic, are highly threatened, and cover vast distances during foraging and migration. However, the spatial overlap between petrels and plastics is poorly understood. Here we combine marine plastic density estimates with individual movement data for 7137 birds of 77 petrel species to estimate relative exposure risk. We identify high exposure risk areas in the Mediterranean and Black seas, and the northeast Pacific, northwest Pacific, South Atlantic and southwest Indian oceans. Plastic exposure risk varies greatly among species and populations, and between breeding and non-breeding seasons. Exposure risk is disproportionately high for Threatened species. Outside the Mediterranean and Black seas, exposure risk is highest in the high seas and Exclusive Economic Zones (EEZs) of the USA, Japan, and the UK. Birds generally had higher plastic exposure risk outside the EEZ of the country where they breed. We identify conservation and research priorities, and highlight that international collaboration is key to addressing the impacts of marine plastic on wide-ranging species