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Multiple sclerosis is the leading non-traumatic cause of disability in young adults, affecting up to 100,000 Canadians. This chronic inflammatory and neurodegenerative disease of the central nervous system leads to irreversible neurologic disability if inadequately controlled. Though many current medications are available that reduce inflammatory damage, most patients continue to show some evidence of disease activity and accrue disability. In this review, we discuss the role of immune ablation followed by autologous hematopoietic stem cell transplantation (AHSCT), a therapeutic option for select patients with a more aggressive disease course. By “resetting” the immune system with a variety of ablative conditioning regimens, followed by immune reconstitution, this therapy has shown a durable response in halting evidence of inflammatory activity in most patients, without the need for continued disease-modifying therapies (DMT). Since the introduction of this therapy, there have been advances in patient selection and supportive care, such that morbidity has significantly declined and treatment-related mortality is minimized. Recent phase-II trials have shown excellent results in efficacy and safety of AHSCT; however, challenges exist which require ongoing study. The future challenges include comparing the variety of AHSCT conditioning regimens with each other as well as with existing highly effective DMT; identifying patients with an aggressive disease course through novel biomarkers who may benefit the most from AHSCT; and surveillance of long-term outcomes of different treatment protocols. In select patients, replacing the immune system with AHSCT holds promise of fundamentally altering the trajectory of their aggressive disease course.
Background: There is an unmet need for blood-based biomarkers that can reliably detect MS disease activity. Serum Biomarkers of interest includ Neurofilament-light-chain (NfL), Glial-fibrillary-strocyte-protein(GFAP) and Tau. Bone Marrow Transplantation (BMT) is reserved for aggressive forms of MS and has been shown to halt detectable CNS inflammatory activity for prolonged periods. Significant pre-treatment tissue damage at followed by inflammatory disease abeyance should be reflected longitudinal sera collected from these patients. Methods: Sera were collected from 23 MS patients pre-treatment, and following BMT at 3, 6, 9 and 12-months in addition from 33 non-inflammatory neurological controls. Biomarker quantification was performed with SiMoA. Results: Pre-AHSCT levels of serum NfL and GFAP but not Tau were elevated compared to controls (p=0.0001), and NfL correlated with lesion-based disease activity (6-month-relapse, MRI-T2 and Gadolinium-enhancement). 3-months post-treatment, while NfL levels remained elevated, Tau/GFAP paradoxically increased (p=0.0023/0.0017). These increases at 3m correlated with MRI ‘pseudoatrophy’ at 6-months. NfL/Tau levels dropped to that of controls by 6-months (p=0.0036/0.0159). GFAP levels dropped progressively after 6-months although even at 12-months remained higher than controls (p=0.004). Conclusions: NfL was the closest correlate of MS disease activity and treatment response. Chemotherapy-related toxicity may account for transient increases in NfL, Tau and MRI brain atrophy post-BMT.
Towards a comprehensive revision of Gesneriaceae in Sri Lanka, 12 names are here typified, of which 11 are lectotypifications, including one second-step lectotypification, and the other is a neotypification.
Two new species of Oreocharis, O. tribracteata and O. rufescens, are described and a key to the species in Vietnam is provided. The new species have distinct features not previously, or rarely, observed in the genus, both showing the partial fusion of the calyx lobes into a tube, and the presence of three bracts in Oreocharis tribracteata.
Dietary patterns are a major risk factor for cardiovascular morbidity and mortality; however, few studies have examined this relationship in older adults. We examined prospective associations between dietary patterns and the risk of CVD and all-cause mortality in 3226 older British men, aged 60–79 years and free from CVD at baseline, from the British Regional Heart Study. Baseline FFQ data were used to generate thirty-four food groups. Principal component analysis identified dietary patterns that were categorised into quartiles, with higher quartiles representing higher adherence to the dietary pattern. Cox proportional hazards examined associations between dietary patterns and risk of all-cause mortality and cardiovascular outcomes. We identified three interpretable dietary patterns: ‘high fat/low fibre’ (high in red meat, meat products, white bread, fried potato, eggs), ‘prudent’ (high in poultry, fish, fruits, vegetables, legumes, pasta, rice, wholemeal bread, eggs, olive oil) and ‘high sugar’ (high in biscuits, puddings, chocolates, sweets, sweet spreads, breakfast cereals). During 11 years of follow-up, 899 deaths, 316 CVD-related deaths, 569 CVD events and 301 CHD events occurred. The ‘high-fat/low-fibre’ dietary pattern was associated with an increased risk of all-cause mortality only, after adjustment for confounders (highest v. lowest quartile; hazard ratio 1·44; 95 % CI 1·13, 1·84). Adherence to a ‘high-sugar’ diet was associated with a borderline significant trend for an increased risk of CVD and CHD events. The ‘prudent’ diet did not show a significant trend with cardiovascular outcomes or mortality. Avoiding ‘high-fat/low-fibre’ and ‘high-sugar’ dietary components may reduce the risk of cardiovascular events and all-cause mortality in older adults.
Genji monogatari or The Tale of Genji was composed by Murasaki Shikibu around the first decade of the eleventh century. Genji monogatari is divided into two major sections: chapters 1 to 41, which describe the story of Genji and the women in his life, and chapters 42 to 54, which deals with Genji's progeny. The first section is subdivided into: chapters 1 to 33, narrating the rise, fall, and rise again of the young Genji, and chapters 34 to 41, which portray him becoming increasingly introspective and contemplative. The story begins with a love affair between the emperor and Kiritsubo. Captivated by her close resemblance to the late Kiritsubo, Genji's father takes in a new consort, known to as Fujitsubo. The earliest documented evidence of Genji reading is found in the diary of the author herself, which claims that figures like the poet Fujiwara no Kinto, Fujiwara no Michinaga, and the Ichijo Emperor read at least parts of Genji monogatari.
Dermoid cysts in the floor of the mouth are relatively uncommon developmental lesions. They are thought to arise in the midline and along the lines of embryonic fusion of the facial processes containing ectodermal tissue.
A 17-year-old female presented with a 3-month history of a growing, progressive swelling in the mouth floor. Clinical examination revealed a rather large symmetrical, soft swelling in the mouth floor, displacing the tongue superiorly. The fast growing nature and size of the lesion raised suspicion of potential compromise to the airway. Surgical excision was therefore performed.
Differential diagnosis of cystic lesions in the floor of the mouth is of paramount importance, as the recommended surgical techniques vary depending on the anatomical position of the lesions. The intraoral approach is preferred for those lesions that do not extend beyond the mylohyoid muscle boundaries; this leads to a satisfactory cosmetic and functional outcome.
Obesity is a major public health problem with increasing prevalence worldwide. It is well recognized as a risk factor for cardiovascular morbidity and mortality in adult populations. Obesity prevalence is also increasing with age, and this may be particularly important in an ageing population. Ageing is associated with an increase in visceral fat and a progressive loss of muscle mass. Sarcopenia has been defined as the age-associated loss of skeletal muscle mass and has been associated with metabolic impairment, cardiovascular disease (CVD) risk factors, physical disability and mortality. Sarcopenia is often associated with obesity. Sarcopenic obesity is a new category of obesity in older adults who have high adiposity coupled with low muscle mass. Thus sarcopenia with obesity may synergistically increase their effect on metabolic disorders, CVD and mortality. This review focuses on the effects of sarcopenic obesity on the risk of cardiovascular disease and mortality in older adults.
This paper reviews the health implications of obesity, sarcopenia and sarcopenic obesity on CVD and mortality in older adults and discusses the obesity paradox seen in patients with CVD. Obesity is a major public health problem with increasing prevalence worldwide. It is an established risk factor for cardiovascular morbidity and mortality in adult populations. However, there is controversy surrounding the effects of obesity as measured by BMI in older people, and overweight and obesity (BMI ⩾ 25 kg/m2) are apparently associated with increased survival in those with CVD (obesity paradox). Ageing is associated with an increase in visceral fat and a progressive loss of muscle mass which have opposing effects on mortality. Thus BMI is not a good indicator of obesity in older adults. Sarcopenia, the age-associated loss of skeletal muscle mass, is a major concern in ageing populations and has been associated with metabolic impairment, CVD risk factors, physical disability and mortality. Sarcopenia often coexists with obesity. Sarcopenic obesity is a new category of obesity in older adults who have high adiposity coupled with low muscle mass. To fully understand the effect of obesity on mortality in the elderly it is important to take muscle mass into account. The evidence suggests that sarcopenia with obesity may be associated with higher levels of metabolic disorders and an increased risk of mortality than obesity or sarcopenia alone. Efforts to promote healthy ageing should focus on both preventing obesity and maintaining or increasing muscle mass.
Socio-economic gradients in diet quality are well established. However, the influence of material socio-economic conditions particularly in childhood, and the use of multiple disaggregated socio-economic measures on diet quality have been little studied in the elderly. In the present study, we examined childhood and adult socio-economic measures, and social relationships, as determinants of diet quality cross-sectionally in 4252 older British men (aged 60–79 years). A FFQ provided data on daily fruit and vegetable consumption and the Elderly Dietary Index (EDI), with higher scores indicating better diet quality. Adult and childhood socio-economic measures included occupation/father's occupation, education and household amenities, which combined to create composite scores. Social relationships included social contact, living arrangements and marital status. Both childhood and adult socio-economic factors were independently associated with diet quality. Compared with non-manual social class, men of childhood manual social class were less likely to consume fruit and vegetables daily (OR 0·80, 95 % CI 0·66, 0·97), as were men of adult manual social class (OR 0·65, 95 % CI 0·54, 0·79), and less likely to be in the top EDI quartile (OR 0·73, 95 % CI 0·61, 0·88), similar to men of adult manual social class (OR 0·66, 95 % CI 0·55, 0·79). Diet quality decreased with increasing adverse adult socio-economic scores; however, the association with adverse childhood socio-economic scores diminished with adult social class adjustment. A combined adverse childhood and adulthood socio-economic score was associated with poor diet quality. Diet quality was most favourable in married men and those not living alone, but was not associated with social contact. Diet quality in older men is influenced by childhood and adulthood socio-economic factors, marital status and living arrangements.
The role of total thyroidectomy in the management of patients with Graves' disease remains controversial. However, there is increasing evidence to support the role of the procedure as a safe and definitive treatment for Graves' disease.
Patients were identified from a prospective thyroid database of the multidisciplinary thyroid clinic at Hull Royal Infirmary. All case notes were independently reviewed to confirm the data held on the database.
Over a 7-year period, the senior author has performed 206 total thyroidectomies for Graves' disease. The incidence of temporary recurrent laryngeal nerve palsy and hypoparathyroidism was 3.4 per cent and 24 per cent respectively. There was one case of permanent unilateral recurrent laryngeal nerve palsy, and 3.9 per cent of patients developed permanent hypoparathyroidism. There has been no relapse of thyrotoxicosis.
In the context of a multidisciplinary thyroid clinic, total thyroidectomy should be offered as a safe and effective first-line treatment option for Graves' disease.
The aim of this study was to retrospectively assess the value of whole genome sequencing (WGS) compared to conventional typing methods in the investigation and control of an outbreak of Shigella sonnei in the Orthodox Jewish (OJ) community in the UK. The genome sequence analysis showed that the strains implicated in the outbreak formed three phylogenetically distinct clusters. One cluster represented cases associated with recent exposure to a single strain, whereas the other two clusters represented related but distinct strains of S. sonnei circulating in the OJ community across the UK. The WGS data challenged the conclusions drawn during the initial outbreak investigation and allowed cases of dysentery to be implicated or ruled out of the outbreak that were previously misclassified. This study showed that the resolution achieved using WGS would have clearly defined the outbreak, thus facilitating the promotion of infection control measures within local schools and the dissemination of a stronger public health message to the community.
To identify the cause of operative failure in patients who have undergone parathyroid surgery for primary hyperparathyroidism.
Retrospective case review.
Patients who had undergone a primary procedure for primary hyperparathyroidism between July 2003 and December 2007. Cases with incomplete post-operative serum calcium data were excluded.
Main outcome measure:
Operative failure was defined as failure to achieve normalisation of serum adjusted calcium levels post-operatively.
A total of 220 primary procedures were conducted over 4.5 years. Data were not available for 16 patients. Thirteen procedures (6.4 per cent) were considered failures, and these cases were individually reviewed and classified according to the reason for failure.
Establishing the cause of failure following surgery for primary hyperparathyroidism can be a complex task. In some instances, diagnostic uncertainty remains despite detailed biochemical and radiological assessment. This paper outlines our approach to maximising the cure rate at primary surgery.
To explore why there is a lack of acceptance among Western Australian (WA) adults of the Go for 2&5®fruit and vegetable social marketing message to consume at least five servings of vegetables per day.
A series of focus group discussions comprised of homogeneous groups varied by sex and age, until saturation of themes was achieved, followed by thematic analysis.
Part of qualitative research for the Go for 2&5® fruit and vegetable social marketing campaign in WA (2009 population: 2·2 million).
WA adults stratified by sex and age groups (18–29 and 30–55 years) drawn from the second and third quartiles of socio-economic disadvantage.
Familiarity with the Go for 2&5® message was excellent. Understanding of what constitutes ‘two servings of fruit’ was excellent and regarded by participants as highly achievable. Understanding of what constitutes ‘five servings of vegetables’ was suboptimal with widespread overestimation contributing to the belief that it is unrealistic. Participants did not know how the 2&5 recommendation was formulated and believed that daily consumption of two servings of fruit and five of vegetables would confer no greater health benefit than one of fruit and three of vegetables. Participants assumed that the 2&5 recommendation was ‘aspirational’ in the sense that it was purposely exaggerated to simply encourage greater overall consumption.
A convincing case needs to be presented to WA adults as to why they should consume five servings of vegetables per day. Continuing efforts to educate incorporating what constitutes a serving will assist perceptions that the recommendation is realistic.
To consolidate the key features of carcinoma showing thymus-like element, including its management.
We present our experience of the difficult diagnosis and management of this rare tumour. We also present the results of an extensive literature search, documenting those aspects of the clinical picture, natural history and management of carcinoma showing thymus-like element which are relevant to head and neck surgeons.
Intrathyroidal, epithelial carcinoma showing thymus-like element is a rare, malignant tumour of the thyroid gland, with histopathological features similar to squamous cell carcinoma but a more favourable prognosis. It is usually treated surgically using a combination of total thyroidectomy and selective neck dissection, with radiotherapy and chemotherapy in selected cases.
Carcinoma showing thymus-like element of the thyroid gland is a rare condition. Head and neck surgeons with a thyroid interest should be aware of this tumour, because of its close histological resemblance to other, commoner malignancies of the thyroid gland.