Improving pneumococcal vaccine uptake in veterans with chronic lymphocytic leukemia through a virtual clinic.

Through a "virtual clinic," we used the electronic medical record to identify and intervene upon patients with chronic lymphocytic leukemia (cll) who were not current for pneumococcal vaccines. Within 180 days, 100/160 patients (62%) received the recommended pneumococcal vaccine. A virtual clinic may improve vaccination rates among high-risk patient populations.

Evolving gene banks: improving diverse populations of crop and exotic germplasm with optimal contribution selection.

We simulated pre-breeding in evolving gene banks - populations of exotic and crop types undergoing optimal contribution selection for long-term genetic gain and management of population genetic diversity. The founder population was based on crosses between elite crop varieties and exotic lines of field pea (Pisum sativum) from the primary genepool, and was subjected to 30 cycles of recurrent selection for an economic index composed of four traits with low heritability: black spot resistance, flowering time and stem strength (measured on single plants), and grain yield (measured on whole plots). We compared a small population with low selection pressure, a large population with high selection pressure, and a large population with moderate selection pressure. Single seed descent was compared with S0-derived recurrent selection. Optimal contribution selection achieved higher index and lower population coancestry than truncation selection, which reached a plateau in index improvement after 40 years in the large population with high selection pressure. With optimal contribution selection, index doubled in 38 years in the small population with low selection pressure and 27-28 years in the large population with moderate selection pressure. Single seed descent increased the rate of improvement in index per cycle but also increased cycle time.

Erratum to: Frailty has a stronger association with inflammation than age in older veterans.

[This corrects the article DOI: 10.1186/s12979-016-0082-z.].

International cancer seminars: a focus on kidney cancer.

Recent years have seen important advances in our understanding of the etiology, biology and genetics of kidney cancer. To summarize important achievements and identify prominent research questions that remain, a workshop was organized by IARC and the US NCI. A series of 'difficult questions' were formulated, which should be given future priority in the areas of population, genomic and clinical research.

Frailty has a stronger association with inflammation than age in older veterans.

BACKGROUND: Upregulation of pro-inflammatory cytokines has not only been associated with increased morbidity and mortality in older adults but also has been linked to frailty. In the current study we aimed to compare the relative relationship of age and frailty on inflammation and thrombosis in older veterans. RESULTS: We analyzed 117 subjects (age range 62-95 years; median 81) divided into 3 cohorts: non-frail, pre-frail and frail based on the Fried phenotype of frailty. Serum inflammatory markers were determined using commercially available ELISA kits. Frail and pre-frail (PF) subjects had higher levels than non-frail (NF) subjects of IL-6 (NF vs. PF: p = 0.002; NF vs. F: p < 0.001), TNFR1 (NF vs. F: p = 0.012), TNFRII (NF vs. F: 0.002; NF vs. PF: p = 0.005) and inflammatory index: = 0.333*log(IL-6) + 0.666*log(sTNFR1) (NF vs. F: p = 0.009; NF vs. PF: p < 0.001). Frailty status explained a greater percent of variability in markers of inflammation than age: IL-6 (12 % vs. 0.3 %), TNFR1 (5 % vs. 4 %), TNFR2 (11 % vs. 6 %), inflammatory index (16 % vs. 8 %). Aging was significantly associated with higher fibrinogen (p = 0.04) and D-dimer levels (p = 0.01) but only among NF subjects. CONCLUSION: In conclusion, these data suggest that among older veterans, frailty status has a stronger association with inflammation and the inflammatory index than age does. Larger studies, in more diverse populations are needed to confirm these findings.

miR-210 is a target of hypoxia-inducible factors 1 and 2 in renal cancer, regulates ISCU and correlates with good prognosis.

BACKGROUND: Clear cell renal cancer frequently harbours von Hippel-Lindau (VHL) gene mutations, leading to stabilisation of the hypoxia-inducible factors (HIFs) and expression of their target genes. We investigated HIF-1 and HIF-2 in the regulation of microRNA-210 (miR-210), and its clinical relevance in renal tumours. METHODS: RCC4 and 786-O renal cancer cell lines transfected with either an empty vector or functional VHL and incubated in normoxia or hypoxia were examined for miR-210 expression. Hypoxia-inducible factor siRNAs were used to examine their regulation of miR-210. Seventy-one clear cell renal tumours were sequenced for VHL mutations. Expression of miR-210, VHL, CA9, ISCU and Ki-67 were determined by immunohistochemistry and qRT-PCR. RESULTS: In addition to HIF-1 regulating miR-210 in renal cancer, HIF-2 can regulate this microRNA in the absence of HIF-1. MicroRNA-210 is upregulated in renal cancer compared with normal renal cortex tissue. MicroRNA-210 correlates negatively with its gene target ISCU at the protein and mRNA level. MicroRNA-210 correlated with positive outcome variables and negatively with Ki-67. CONCLUSION: We provide further evidence of miR-210 activity in vivo, and show that high miR-210 expression is associated with better clinico-pathological prognostic factors.

Acceptability of anxiety management within UK armed forces.

BACKGROUND: The Department of Community Mental Health (DCMH) at RAF Brize Norton runs a regular anxiety management day (AMD) which is a group intervention for regular military personnel who have been diagnosed with anxiety-related disorders. The AMD is a 1 day course for up to 20 participants run by two community mental health nurses based at the DCMH. It contains a combination of psycho-education and generic anxiety management techniques. AIMS: To establish whether the AMD is acceptable to full time regular military personnel who have been referred to the DCMH. METHODS: The acceptability of the AMD was assessed using a standardized feedback form, which asked about the patient's perception of the quality of the AMD and the course content. Feedback data were collected over a 12 month period between September 2010 and August 2011. RESULTS: Clinical and sociodemographic data were available for 91 of the 97 (94%) participants who participated in the AMD over the period from September 2010 to August 2011. Ninety-two per cent (89/97) of participants completed a post course survey immediately after they completed the AMD. Respectively, 95 and 93% considered the format and content of the AMD to be of good quality. CONCLUSIONS: The AMD fits well with the stepped care approach of the Improving Access to Psychological Therapies programme and resulted in a good level of patient satisfaction.

Extra-mandibular Osteoradionecrosis after the Treatment of Head and Neck Cancer.

AIMS: Osteoradionecrosis (ORN) is a serious toxicity of head and neck radiotherapy. It predominantly affects the mandible. Extra-mandibular ORN is rare. The aim of this study was to report the incidence and outcomes of extra-mandibular ORNs from a large institutional database. MATERIALS AND METHODS: In total, 2303 head and neck cancer patients were treated with radical or adjuvant radiotherapy. Of these, extra-mandibular ORN developed in 13 patients (0.5%). RESULTS: Maxillary ORNs (n = 8) were a consequence of the treatment of various primaries (oropharynx = 3, sinonasal = 2, maxilla = 2, parotid = 1). The median interval from the end of radiotherapy to the development of ORN was 7.5 months (range 3-42 months). The median radiotherapy dose in the centre of the ORN was 48.5 Gy (range 22-66.5 Gy). Four patients (50%) healed in 7, 14, 20 and 41 months. All temporal bone ORNs (n = 5) developed after treatment to the parotid gland (of a total of 115 patients who received radiotherapy for parotid gland malignancy). The median interval from the end of radiotherapy to the development of ORN was 41 months (range 20-68 months). The median total dose in the centre of the ORN was 63.5 Gy (range 60.2-65.3 Gy). ORN healed in only one patient after 32 months of treatment with repeated debridement and topical betamethasone cream. CONCLUSION: Extra-mandibular ORN is a rare late toxicity and this current study provides useful information on its incidence and outcome. The risk of temporal bone ORN should be considered in the treatment of parotid malignancies and patients should be counselled. More research is required to determine the optimal management of extra-mandibular ORN, particularly on the role of the PENTOCLO regimen.

Prognostic utility of pre-operative circulating osteopontin, carbonic anhydrase IX and CRP in renal cell carcinoma.

BACKGROUND: Objectively measured circulating biomarkers of prognosis complementing existing clinicopathological models are needed in renal cell carcinoma (RCC). METHODS: Blood samples collected from 216 RCC patients in Leeds before nephrectomy (median follow-up 7 years) were analysed for C-reactive protein (CRP), osteopontin (OPN) and carbonic anhydrase IX (CA9) and prognostic significance determined. RESULTS: CA9, OPN and CRP were univariately prognostic for overall survival (OS), cancer-specific survival (CSS) and disease-free survival (DFS) with CRP and CA9 being independently prognostic for OS/CSS and OS, respectively. Including CA9, OPN and CRP with other conventional prognostic factors gave a superior predictive capacity when compared with a previously published pre-operative clinical nomogram (Karakiewicz et al, 2009). Osteopontin outperformed this nomogram and the post-operative SSIGN score for OS but not for CSS, being significantly predictive for non-cancer deaths. Osteopontin, CRP and CA9 outperformed stage (c-index 76% compared with 70% for stage) and OPN or CA9 identified several subsets of poor prognosis patients including in T1 patients, who may benefit from adjuvant therapy and increased surveillance. CONCLUSION: Circulating CA9, OPN and CRP add value to existing clinicopathological prognostic factors/models and support further studies to investigate their potential use in improving the clinical management of RCC.

Characterization of MHC-II antigen presentation by B cells and monocytes from older individuals.

In this study we examine the effects of aging on antigen presentation of B cells and monocytes. We compared the antigen presentation function of peripheral blood B cells from young and old subjects using a system that specifically measures the B cell receptor (BCR)-mediated MHC-II antigen presentation. Monocytes were studied as well. Overall the mean magnitude of antigen presentation of soluble antigen and peptide was not different in older and younger subjects for both B cells and monocytes. Older subjects, however, showed increased heterogeneity of BCR-mediated antigen presentation by their B cells. The magnitude and variability of peptide presentation, which do not require uptake and processing, were the same between groups. Presentation by monocytes had similar variability between the older and younger subjects. These data suggest that poor B cell antigen processing, which results in diminished presentation in some older individuals may contribute to poor vaccine responses.

Patient perceptions of costs in the NHS: an evaluation.

The cost of the NHS, wastage within it and how much trusts have overspent is a national obsession. Despite these widespread opinions, the costs of individual treatments and impacts of non-attendance appear to be little understood. There is a paucity of literature with regards to patients' awareness of costs associated with services provided by the NHS. The authors aim to ascertain whether patients are aware of the costs associated with care services provided, and if these data could aid educating patients on NHS costs to reduce missed appointments. A questionnaire was randomly distributed to new and review patients in our Oral and Maxillofacial outpatient and emergency departments from November-December 2017 asking them to estimate the cost of common services they may encounter, such as an outpatient appointment, an orthopantomogram (OPT), a CT head, and a full blood count test (FBC). The results demonstrate that 81% of patients surveyed underestimated the cost of their new patient appointment, with 34% underestimating the cost of their review appointment. The cost of an overnight stay in hospital was underestimated by 65% of patients, with 89% of patients underestimating the cost of an hours's operating. The costs of a full blood count, an OPT and a CT head have been mostly overestimated by 89%, 77%, and 54% of patients respectively. The results show there is a wide variation in patients' estimates of costs, with over 50% of patients overestimating the costs of investigations but underestimating the cost of their appointment/A&E attendance.

Association of serum amyloid A protein and peptide fragments with prognosis in renal cancer.

BACKGROUND: In renal cell carcinoma (RCC), the discovery of biomarkers for clinical use is a priority. This study aimed to identify and validate diagnostic and prognostic serum markers using proteomic profiling. METHODS: Pre-operative sera from 119 patients with clear cell RCC and 69 healthy controls was analysed by surface-enhanced laser desorption/ionisation time-of-flight mass spectrometry with stringent in-house quality control and analysis routines. Following identification of one prognostic peak as a fragment of serum amyloid A (SAA), total serum SAA and CRP were also determined by immunoassay for further validation. RESULTS: Several peptides were identified as having independent prognostic but not diagnostic significance on multivariable analysis. One was subsequently identified as a 1525 Da fragment of SAA (hazard ratio (HR)=0.26, 95% CI 0.08-0.85, P=0.026). This was weakly negatively correlated with total SAA, which was also of independent prognostic significance (HR=2.46, 95% CI 1.17-5.15, P=0.017). Both potentially strengthened prognostic models based solely on pre-operative variables. CONCLUSIONS: This is the first description of the prognostic value of this peptide in RCC and demonstrates proof of principle of the approach. The subsequent examination of SAA protein considerably extends previous studies, being the first study to focus solely on pre-operative samples and describing potential clinical utility in pre-operative prognostic models.

Improving the accuracy of pre-operative survival prediction in renal cell carcinoma with C-reactive protein.

BACKGROUND: Validated objective biomarkers are needed for patients with renal cell carcinoma (RCC) to guide patient management and define high-risk populations for follow-up or for therapeutic purposes. METHODS: Patients undergoing nephrectomy for RCC (n=286 all stages, 84% with conventional clear cell type) were included with a median duration follow-up of 5 years. The prognostic significance of pre-operative haematological and biochemical variables, including C-reactive protein (CRP) values were examined and whether they added additional information to a recently published pre-operative scoring system was determined. RESULTS: C-reactive protein was the most significant predictor of overall survival (OS; χ(2)=50.9, P<0.001). Five-year OS for patients with CRP ≤ 15 mg l(-1) vs >15 mg l(-1) was 72% (95% CI 65-78%) and 33% (95% CI 23-44%), respectively. Similar results were seen for cancer-specific survival (CSS) and disease-free survival. On multivariate analysis, CRP remained highly significant for CSS (χ(2)=17.3, P<0.0001) and OS (χ(2)=9.8, P<0.002), in addition to other pre-operative variables including log of neutrophil/lymphocyte ratio, red blood cell count and white cell count. C-reactive protein was significant in addition to the pre-operative nomogram score (χ(2)=12.5, P=0.0004 for OS, χ(2)=16.2, P=0.0001 for CSS and χ(2)=8.6, P=0.003 for DFS) and was still significant when other pre-operative variables were included. CONCLUSION: C-reactive protein and other haematological and biochemical variables have independent prognostic significance in RCC and may enhance pre-operative scoring systems.

The real penalty: number of OMFS patients presenting to the emergency department at Sunderland Royal Hospital after England fixtures before and during the 2018 FIFA Football World Cup.

The aim of this study was to establish a link between a large televised sporting event and the incidence of patients presenting to the emergency department with oral and maxillofacial injuries. When compared with daily attendances throughout the year, the mean (SD) number rose from 2.53 (1.69) to 4.00 (1.53) (p=0.005) between 1 November 2017 and 31 July 2018 on the day after an England fixture, an increase of 58%. These data show the need for workforce planning during large-scale national sporting events because of the rise in the number of patients presenting. They show that the increase in workload is caused by a higher number of both traumatic and non-traumatic injuries.

The future of OMFS lies in creating pathways to implement the PMETB recommendations and inspiring our trainees. Enough time has been spent debating, we need to deliver!: Re: Newman L, Brown J, Kerawala C, et al. Our specialty. The future. Is the writing on the wall? Br J Oral Maxillofac Surg 2020 (online ahead of print).

The British Association of Oral and Maxillofacial Surgeons (BAOMS) has been at the centre of the transition of our specialty in the UK from a branch of dentistry to one of the 10 UK surgical specialties. In this role it has, at different times, pushed boundaries against resistance from other specialties, and redirected the ambitions of the deputy chair of the Postgraduate Medical Education and Training Board (PMETB) review to produce recommendations that were exactly what OMFS needed. The editorial Our specialty. The future. Is the writing on the wall? is just the most recent iteration of half a century of internal debate. Whilst there are some issues with how the authors have presented recruitment data (their figures omit ST1 run-through and do not recognise that the same single, unfilled post may be present for two or more national selection rounds) their first paragraph A debate that we feel is long overdue presents the greatest concern. In this short communication, we illustrate that in the last 20 years the specialty has not been short of debate. In the absence of new and specific evidence that any other route forward would be supported by our national training committee (OMFS SAC), our regulator (GMC), the breadth of our specialty (including our current specialists and our current and future trainees) and, most importantly, would actually address our problems, we should avoid putting energy into an empty debate. Our focus should be on delivering the PMETB recommendations and inspiring our future trainees.

Changing the Oral and Maxillofacial Surgery (OMFS) training pathway in the United Kingdom - an illustrative retrospective.

OMFS training is perceived as a long and expensive pathway although papers have shown it compares favourably with other surgical specialties. Every OMFS clinician has a vested interest and duty continually to improve the quality of training and minimise costs, especially to trainees at junior levels. Any serious proposal to fundamentally change the format of training, must be given due consideration by all stakeholders. In 2016, a British Medical Journal article whose authors included the BAOMS President of that year and OMFS Specialty Advisory Committee (SAC) Chair, posed the question - should the future of OMFS training revert to single dental degree, change to single medical degree - or continue as a dual degree specialty? The BMJ publication was discussed at the British Association of Oral and Maxillofacial Surgeons (BAOMS) Council in March 2016 and all present unanimously supported the dual degree pathway. Later that year a formal proposal was made by the BAOMS immediate past President that training in the UK change to single medical degree 'Maxillofacial Surgery' similar to the training in Spain, France or Italy. Evidence around the risks and benefits of making this change to OMFS training was assembled and reviewed by BAOMS Council in March 2017. BAOMS Council once again unanimously supported continuing OMFS as a dual degree specialty with the observation that the quality of patient care which this training provided was the specialty's Unique Selling Point or USP. The requirement for both degrees to provide care for OMFS patients had been confirmed by external scrutiny on two separate occasions by the responsible regulators. In this paper, we outline the key steps to be considered when making major changes in the OMFS training pathways using this event as an example and the suggestion that those proposing changes should assemble and present evidence to support their proposal using the template provided.

Choosing the best method to utilise single positron emission computed tomography (SPECT) scans in the management of unilateral condylar hyperplasia.

Facial asymmetry secondary to unilateral condylar hyperplasia can be a diagnostic challenge to oral and maxillofacial surgeons. Single positron emission computed tomography (SPECT) scans provide a useful adjunct. We report a brief summary of the evidence describing the effectiveness of different methods of analysing SPECT scans and compare it with the results of a 10-year study at Sunderland Royal Hospital. Overall, both the evidence base and our study strongly favour use of the condyle:condyle ratio over the condyle:reference bone ratio, suggesting that no further comparisons are needed.

Pre-operative urinary cathepsin D is associated with survival in patients with renal cell carcinoma.

BACKGROUND: No circulating markers are routinely used for renal cancer. The objective of this pilot study was to investigate whether conditioned media (CM) from renal cancer cell lines contains potential biomarkers that, when measured in clinical fluids, have diagnostic or prognostic utility. METHODS: Comparative 2D PAGE profiling of CM from renal cell carcinoma (RCC) and normal renal cultures identified cathepsin D that was subsequently validated in urine samples from 239 patients and healthy and benign disease subjects. RESULTS: Urinary cathepsin D was found to be significantly associated with overall (OS) (hazard ratio, HR, 1.33, 95%CI [1.09-1.63], P=0.005) and cancer-specific survival (HR 1.36, 95%CI [1.07-1.74], P=0.013) in RCC patients on univariate analysis. An optimal cut point (211 ng ml(-1) micromolCr(-1)) around which to stratify patients by OS was determined. Five-year OS equal to/above and below this value was 47.0% (95%CI 35.4%, 62.4%) and 60.9% (48.8%, 76.0%), respectively. On multivariable analysis using pre-operative variables, cathepsin D showed some evidence of independent prognostic value for OS (likelihood ratio test P-value=0.056) although requiring further validation in larger patient numbers with sufficient statistical power to determine independent significance. CONCLUSION: These data establish an important proof of principle and show the potential of proteomics-based studies. Cathepsin D may be of value as a pre-operative urinary biomarker for RCC, alone or in combination.

A comparative analysis of the encapsulated end-organs of mammalian skeletal muscles and of their sensory nerve endings.

The encapsulated sensory endings of mammalian skeletal muscles are all mechanoreceptors. At the most basic functional level they serve as length sensors (muscle spindle primary and secondary endings), tension sensors (tendon organs), and pressure or vibration sensors (lamellated corpuscles). At a higher functional level, the differing roles of individual muscles in, for example, postural adjustment and locomotion might be expected to be reflected in characteristic complements of the various end-organs, their sensory endings and afferent nerve fibres. This has previously been demonstrated with regard to the number of muscle-spindle capsules; however, information on the other types of end-organ, as well as the complements of primary and secondary endings of the spindles themselves, is sporadic and inconclusive regarding their comparative provision in different muscles. Our general conclusion that muscle-specific variability in the provision of encapsulated sensory endings does exist demonstrates the necessity for the acquisition of more data of this type if we are to understand the underlying adaptive relationships between motor control and the structure and function of skeletal muscle. The present quantitative and comparative analysis of encapsulated muscle afferents is based on teased, silver-impregnated preparations. We begin with a statistical analysis of the number and distribution of muscle-spindle afferents in hind-limb muscles of the cat, particularly tenuissimus. We show that: (i) taking account of the necessity for at least one primary ending to be present, muscles differ significantly in the mean number of additional afferents per spindle capsule; (ii) the frequency of occurrence of spindles with different sensory complements is consistent with a stochastic, rather than deterministic, developmental process; and (iii) notwithstanding the previous finding, there is a differential distribution of spindles intramuscularly such that the more complex ones tend to be located closer to the main divisions of the nerve. Next, based on a sample of tendon organs from several hind-foot muscles of the cat, we demonstrate the existence in at least a large proportion of tendon organs of a structural substrate to account for multiple spike-initiation sites and pacemaker switching, namely the distribution of sensory terminals supplied by the different first-order branches of the Ib afferent to separate, parallel, tendinous compartments of individual tendon organs. We then show that the numbers of spindles, tendon organs and paciniform corpuscles vary independently in a sample of (mainly) hind-foot muscles of the cat. Grouping muscles by anatomical region in the cat indicated the existence of a gradual proximo-distal decline in the overall average size of the afferent complement of muscle spindles from axial through hind limb to intrinsic foot muscles, but with considerable muscle-specific variability. Finally, we present some comparative data on muscle-spindle afferent complements of rat, rabbit and guinea pig, one particularly notable feature being the high incidence of multiple primary endings in the rat.