A pas de deux of osteoporosis and sarcopenia: osteosarcopenia.

The musculoskeletal conditions osteoporosis and sarcopenia are highly prevalent in older adults. Osteoporosis is characterized by low bone mass and microarchitectural deterioration of bone, whereas sarcopenia is identified by the loss of muscle strength, function and mass. Osteoporosis represents a major health problem contributing to millions of fractures worldwide on an annual basis, whereas sarcopenia is associated with a range of adverse physical and metabolic outcomes. They both affect physical and social function, confidence and quality of life as well as contributing to high health-care costs worldwide. Osteosarcopenia is the term given when both conditions occur concomitantly and it has been suggested that interactions between these two conditions may accelerate individual disease progression as co-existence of osteoporosis and sarcopenia is associated with higher morbidity from falls, fracture, disability as well as mortality. In this review, we will outline the epidemiology, pathogenesis and clinical consequences of osteosarcopenia and discuss available management strategies.

COVID-19 and associations with frailty and multimorbidity: a prospective analysis of UK Biobank participants.

BACKGROUND: Frailty and multimorbidity have been suggested as risk factors for severe COVID-19 disease. AIMS: We investigated, in the UK Biobank, whether frailty and multimorbidity were associated with risk of hospitalisation with COVID-19. METHODS: 502,640 participants aged 40-69 years at baseline (54-79 years at COVID-19 testing) were recruited across UK during 2006-10. A modified assessment of frailty using Fried's classification was generated from baseline data. COVID-19 test results (England) were available for 16/03/2020-01/06/2020, mostly taken in hospital settings. Logistic regression was used to discern associations between frailty, multimorbidity and COVID-19 diagnoses, after adjusting for sex, age, BMI, ethnicity, education, smoking and number of comorbidity groupings, comparing COVID-19 positive, COVID-19 negative and non-tested groups. RESULTS: 4510 participants were tested for COVID-19 (positive = 1326, negative = 3184). 497,996 participants were not tested. Compared to the non-tested group, after adjustment, COVID-19 positive participants were more likely to be frail (OR = 1.4 [95%CI = 1.1, 1.8]), report slow walking speed (OR = 1.3 [1.1, 1.6]), report two or more falls in the past year (OR = 1.3 [1.0, 1.5]) and be multimorbid (≥ 4 comorbidity groupings vs 0-1: OR = 1.9 [1.5, 2.3]). However, similar strength of associations were apparent when comparing COVID-19 negative and non-tested groups. However, frailty and multimorbidity were not associated with COVID-19 diagnoses, when comparing COVID-19 positive and COVID-19 negative participants. DISCUSSION AND CONCLUSIONS: Frailty and multimorbidity do not appear to aid risk stratification, in terms of positive versus negative results of COVID-19 testing. Investigation of the prognostic value of these markers for adverse clinical sequelae following COVID-19 disease is urgently needed.

Approaches to the diagnosis and prevention of frailty.

An individual who is living with frailty has impairments in homeostasis across several body systems and is more vulnerable to stressors that may ultimately predispose them to negative health-related outcomes, disability and increased healthcare use. Approximately a quarter of individuals aged > 85 years are living with frailty and as such the identification of those who are frail is a public health priority. Given that the syndrome of frailty is defined by progressive and gradual loss of physiological reserves there is much scope to attempt to modify the trajectory of the frailty syndrome via physical activity and nutritional interventions. In this review we give an up to date account on the identification of frailty in clinical practice and offer insights into physical activity and nutritional strategies that may be beneficial to modify or reverse the frailty syndrome.

A systematic review of the provision and efficacy of patient and carer information and support (PCIS) interventions for patients with dementia and their informal carers.

BACKGROUND: The NHS dementia strategy identifies patient and carer information and support (PCIS) as a core component of gold-standard dementia care. This is the first systematic review of PCIS, performed to analyse the literature and evidence for these interventions. AIMS: To systematically review literature evaluating the effectiveness of the provision of PCIS for people with dementia and their informal carers, in inpatient and outpatient settings. METHODS: Searches of four online biomedical databases, accessed in September 2018. Studies were selected if they were: relating to people with dementia or their informal carers, based in inpatient or outpatient settings, published in English-language peer-reviewed journals no earlier than the year 2000 and assessed dementia-related information or social support interventions, by measuring qualitative or quantitative carer or patient-reported outcomes. Standardised data extraction and quality appraisal forms were used. RESULTS: 7 of 43 full-text papers analysed were eligible for analysis. 3 papers were different arms of one original study. Trends were present in the quantitative results towards reduced patient and carer depression and anxiety and the themes in the qualitative analysis were in favour of the intervention. CONCLUSIONS: The studies analysed were too heterogeneous in design, population and outcomes measured to make a conclusive opinion about the efficacy of these interventions. It is surprising that for such a common condition, a gold-standard evidence-based intervention and standardised delivery for provision of PCIS for people living with dementia in the UK does not exist. Further research is therefore vital.

A systematic review of specialist inpatient dementia care services versus standard inpatient dementia care in acute hospitals.

BACKGROUND: Specialist inpatient dementia units (SIDU) have been developed to address adverse outcomes often experienced by people living with dementia admitted to acute hospitals. However, the evidence base of their effectiveness remains limited. AIM: To review the current literature to establish the comparative effectiveness of acute hospital SIDU vs. standard ward care (SWC). METHODS: We did an online search of 12 biomedical databases from inception to 31st October 2017. Studies of inpatients with any form of dementia in acute hospitals, published in English language peer-reviewed journals, using experimental, observational or qualitative study designs, comparing SIDU with SWC and which measured any qualitative or quantitative outcome of the patient or carer experience were included in the search criteria. We used a standardised data extraction and appraisal form. RESULTS: Three of 46 full-text studies evaluated were suitable for analysis. Due to study heterogeneity, pooled odds ratios were only possible for mortality [OR 1.06 (CI 1.0-1.4)]. Otherwise, a narrative synthesis was performed. Although quantitative measures of length of stay, mortality and behavioural and psychiatric symptoms of dementia are not significantly lower, SIDU are associated with greater patient and carer satisfaction, reduced readmission rates, more accurate and comprehensive assessment processes, documentation of resuscitation decisions, and increased rates of discharge to the patient's own home. CONCLUSIONS: Although SIDU may be associated with improved care outcomes, the current evidence of their effectiveness is markedly limited. Further research and service evaluation of SIDU as a method for providing high-quality dementia care in acute NHS Trusts is needed. PROSPERO: CRD42017078364.

Muscle Mass, Muscle Morphology and Bone Health Among Community-Dwelling Older Men: Findings from the Hertfordshire Sarcopenia Study (HSS).

Sarcopenia and osteoporosis are associated with poor health outcomes in older people. Relationships between muscle and bone have typically been reported at a functional or macroscopic level. The aims of this study were to describe the relationships between muscle morphology and bone health among participants of the Hertfordshire Sarcopenia Study (HSS). 105 older men, mean age 72.5 (SD 2.5) years, were recruited into the HSS. Whole body lean mass as well as appendicular lean mass, lumbar spine and femoral neck bone mineral content (BMC) and bone mineral density (BMD) were obtained through dual-energy X-ray absorptiometry scanning. Percutaneous biopsy of the vastus lateralis was performed successfully in 99 participants. Image analysis was used to determine the muscle morphology variables of slow-twitch (type I) and fast-twitch (type II) myofibre area, myofibre density, capillary and satellite cell (SC) density. There were strong relationships between whole and appendicular lean body mass in relation to femoral neck BMC and BMD (r ≥ 0.43, p < 0.001). Type II fibre area was associated with both femoral neck BMC (r = 0.27, p = 0.01) and BMD (r = 0.26, p = 0.01) with relationships robust to adjustment for age and height. In unadjusted analysis, SC density was associated with whole body area (r = 0.30, p = 0.011) and both BMC (r = 0.26, p = 0.031) and area (r = 0.29, p = 0.017) of the femoral neck. We have demonstrated associations between BMC and changes in muscle at a cellular level predominantly involving type II myofibres. Interventions targeted at improving muscle mass, function and quality may improve overall musculoskeletal health. Larger studies that include women are needed to explore these relationships further.

Skeletal muscle morphology in sarcopenia defined using the EWGSOP criteria: findings from the Hertfordshire Sarcopenia Study (HSS).

BACKGROUND: Sarcopenia is defined as the loss of muscle mass and function with age and is associated with decline in mobility, frailty, falls and mortality. There is considerable interest in understanding the underlying mechanisms. Our aim was to characterise muscle morphology changes associated with sarcopenia among community dwelling older men. METHODS: One hundred and five men aged 68-76 years were recruited to the Hertfordshire Sarcopenia Study (HSS) for detailed characterisation of muscle including measures of muscle mass, strength and function. Muscle tissue was obtained from a biopsy of the vastus lateralis for 99 men and was processed for immunohistochemical studies to determine myofibre distribution and area, capillarisation and satellite cell (SC) density. RESULTS: Six (6 %) men had sarcopenia as defined by the European Working Group on Sarcopenia in Older People (EWGSOP) criteria. These men had lower SC density (1.7 cells/mm(2) vs 3.8 cells/mm(2), p = 0.06) and lower SC/fibre ratio (0.02 vs 0.06, p = 0.06) than men without sarcopenia. Although men with sarcopenia tended to have smaller myofibres and lower capillary to fibre ratio, these relationships were not statistically significant. CONCLUSION: We have shown that there may be altered muscle morphology parameters in older men with sarcopenia. These results have the potential to help identify cell and molecular targets for therapeutic intervention. This work now requires extension to larger studies which also include women.

Pitfalls in microdialysis methodology: an in vitro analysis of temperature, pressure and catheter use.

Microdialysis of macromolecules within the brain provides a unique insight into physiological and pathological processes occurring within an otherwise inaccessible cranial cavity. The physically restricted nature of the intracranial compartment may present wider variations of pressure and temperature than those experienced in the rest of the body. In this study we attempted to determine the effect of variation of temperature and pressure on a cytokine recovery in vitro. Our results demonstrate that the wide variation of recovery attributable to different catheter use outweighed any effects caused by temperature or pressure. Investigators performing cytokine microdialysis using the CMA 71 system should be aware of the wide inter-catheter variability and potential effects of temperature on recovery.

Primary hyperparathyroidism: an analysis of failure of parathyroidectomy.

BACKGROUND: Preoperative imaging in patients undergoing surgery for primary hyperparathyroidism (PHPT) is used primarily to facilitate targeted parathyroidectomy. Failure of preoperative localisation mandates a bilateral exploration. It is thought that the results of imaging may also predict the success of surgery. The aims of this study were to assess whether the findings on preoperative localisation influenced outcomes following parathyroidectomy for PHPT and to explore factors underlying failure to cure at surgery. METHODS: We analysed outcomes of all patients who underwent first-time surgery for PHPT in two centres over a 5-year period to determine an association with demographic characteristics and findings on preoperative imaging. Records of patients not cured by initial surgery were reviewed to explore factors underlying failure to cure. RESULTS: The failure rate (persistent disease) in the entire cohort was 5 % (25/541) (bilateral neck explorations, 5 %; unilateral exploration, 7 %; targeted approach, 4 %), while two patients developed recurrent disease. In patients who had undergone dual imaging with an ultrasound scan and (99m)Tc-sestamibi scintigraphy, failure rates with "lateralised and concordant" imaging, "nonconcordant" imaging, and "dual-negative" imaging were 2, 9, and 11 %, respectively (p = 0.01). Of the 25 patients with persistent disease, multigland disease (MGD) was present in 52 % (13/25) and ectopic adenoma in 24 % (6/12). CONCLUSIONS: Patients with PHPT who do not have lateralised and concordant dual imaging are at higher risk of persistent disease. A significant proportion of failures are due to the inability to recognise the presence and/or extent of MGD.

Is grip strength a good marker of physical performance among community-dwelling older people?

INTRODUCTION: There is increasing interest in physical performance as it relates to both the current and future health of older people. It is often characterised using the Short Physical Performance Battery including assessment of gait speed, chair rises and standing balance. However this battery of tests may not be feasible in all clinical settings and simpler measures may be required. As muscle strength is central to physical performance, we explored whether grip strength could be used as a marker of the Short Physical Performance Battery. OBJECTIVE: To examine associations between grip strength and components of the Short Physical Performance Battery in older community dwelling men and women. METHODS: Grip strength measurement and the Short Physical Performance Battery were completed in 349 men and 280 women aged 63-73 years taking part in the Hertfordshire Cohort Study (HCS). Relationships between grip strength and physical performance (6m timed-up-and-go [TUG], 3m walk, chair rises and standing balance times) were analysed using linear and logistic regression, without and with adjustment for age, anthropometry, lifestyle factors and co-morbidities. RESULTS: Among men, a kilo increase in grip strength was associated with a 0.07s (second) decrease in 6m TUG, a 0.02s decrease in 3m walk time, and a 1% decrease in chair rises time (p<0.001 for all). Among women, a kilo increase in grip strength was associated with a 0.13s decrease in 6m TUG, a 0.03s decrease in 3m walk time, and a 1% decrease in chair rises time (p<0.001). Higher grip strength was associated with better balance among men (p=0.01) but not women (p=0.57). Adjustment for age, anthropometry, lifestyle and co-morbidities did not alter these results. CONCLUSIONS: Grip strength is a good marker of physical performance in this age group and may be more feasible than completing a short physical performance battery in some clinical settings.

Systematic review of intravenous methylene blue in parathyroid surgery.

BACKGROUND: Methylene blue is an intraoperative adjunct for localization of enlarged parathyroid glands. The availability of preoperative and other intraoperative localization methods, and the reported adverse effects of methylene blue make its routine use debatable. The aim of this study was to perform a systematic review of the use of methylene blue in parathyroidectomy. METHODS: A systematic review of English-language literature in MEDLINE and Scopus databases on the use of intravenous methylene blue in parathyroid surgery was carried out. RESULTS: There were no randomized clinical trials. Thirty-nine observational studies were identified, of which 33 did not have a control arm. The overall median staining rate for abnormal parathyroid glands was 100 per cent. The median cure rates in the methylene blue and no-methylene blue arms were 100 and 98 per cent respectively. Neurotoxicity was reported in 25 patients, all of whom were taking serotonergic medication. CONCLUSION: Observational evidence suggests that methylene blue is efficacious in identifying enlarged parathyroid glands. Toxicity appears to be mild in the absence of concomitant use of serotonin reuptake inhibitors. The effectiveness of methylene blue in the context of currently used preoperative and intraoperative localization techniques has yet to be shown.

Making sense of postoperative CT imaging following laparoscopic partial nephrectomy.

The increasing popularity of laparoscopic partial nephrectomy (LPN) necessitates radiologists to become familiar with the operative techniques as well as normal and abnormal postoperative findings. Due to the varying presentation of abnormal changes following LPN and their similarities with other disease entities, radiologists should be cognizant of common pitfalls to avoid inadvertent misdiagnosis. A few common pitfalls discussed in this paper are the identification of laparoscopic port placement issues, recognizing a myriad of post-surgical materials, differentiating haemostatic materials from postoperative abscess and infection, non-absorbable suture material mimicking rim calcifications, as well as hints for differentiating exuberant granulation tissue from tumour recurrence.

Developmental influences, muscle morphology, and sarcopenia in community-dwelling older men.

BACKGROUND: Sarcopenia is associated with disability, morbidity, and mortality. Lower birth weight is associated with reduced muscle mass and strength in older people, suggesting that developmental influences are important in sarcopenia. However, underlying mechanisms are unknown. Our objective was to determine whether low birth weight is associated with altered skeletal muscle morphology in older men. METHODS: Ninety-nine men with historical records of birth weight (≤3.18 kg and ≥3.63 kg), aged 68-76 years, consented for detailed characterization of muscle, including a biopsy of the vastus lateralis. Tissue was processed for immunohistochemical studies and analyzed to determine myofibre density, area, and score. RESULTS: Muscle fibre score (fibres kilograms per square millimeter) was significantly reduced in those with lower birth weight: 1.5 × 10(3) vs 1.7 × 10(3), p = .04 unadjusted; p = .09 adjusted for age, height, and physical activity. In addition, there was a trend for reduced myofibre density (fibres per square millimeter) in those with lower birth weight: total fibre density: 176 vs 184, type I myofibre density: 77 vs 80, and type II myofibre density: 99 vs 105. Types I and II myofibre areas (square micrometers) were larger in those with lower birth weight: type I: 4903 vs 4643 and type II: 4046 vs 3859. However, none of these differences were statistically significant. CONCLUSIONS: This is the first study showing that lower birth weight is associated with a significant decrease in muscle fibre score, suggesting that developmental influences on muscle morphology may explain the widely reported associations between lower birth weight and sarcopenia. However, the study may have been underpowered and did not include women supporting replication in larger cohorts of older men and women.

Cephalometric determinants of successful functional appliance therapy.

This retrospective study was undertaken to determine the presence of any features on a pretreatment lateral cephalogram that may be used to predict the success of improvement in the sagittal dental base relationship during functional appliance therapy in patients with a Class II skeletal pattern. Seventy-two patients judged to have been successfully treated with a functional appliance were selected for the study. Pre- and posttreatment radiographs were analyzed and the change in the ANB angle was used to determine the skeletal response to treatment. Within the total sample size of 72 patients, two groups were selected. One group of 13 patients who demonstrated a reduction in ANB angle of 3.0 degrees or more were identified as the skeletal group. A second group of 15 patients who demonstrated a change in ANB angle equal to or less than 0.5 degrees were identified as the nonskeletal group. Statistical analysis of these two groups revealed the presence of skeletal and dentoalveolar differences on the pretreatment lateral cephalogram. In the skeletal group, which responded with a favorable skeletal change, the mandible was smaller both in length (P < .01) and ramus height (P < .05) and the anterior and posterior lower face heights were smaller (P < .05). The cranial base was also smaller when compared with the respective lengths in the nonskeletal group.

Hematuria in children.

Children with hematuria require a thorough history and physical examination. Not all children with hematuria require the same investigations. The only laboratory test uniformly required for children with the various presentations of hematuria is a complete urinalysis with a microscopic examination. The rest of the evaluation is tailored according to the pertinent history, physical examination, and other abnormalities on the urinalysis. This article has provided a brief summary of the more common causes of pediatric hematuria and suggestions for tailoring the patient's evaluation according to the presentation. Most causes of hematuria in pediatrics represent medical conditions that often require referral to a pediatric nephrologist. Indications for referral to a urologist are more limited and include stones that do not pass spontaneously or are more than 5 mm in diameter, renal injury from trauma, anatomic abnormalities, or gross hematuria that seems to originate from the urinary tract and is without an identified cause.

Malignant lymphoma of the gastrointestinal tract.

AIMS: The gastrointestinal tract (GIT) is the most common site of extra-nodal lymphoma. Most of these lymphomas arise from mucosa associated lymphoid tissue (MALT). We attempt in this study to define the natural history and treatment outcome of this type of lymphoma. METHODS: We carried out a retrospective study of patients presenting at our centre with histopathological diagnosis of primary GIT lymphoma between 1990 and 1994. RESULTS: Equal numbers of cases of stomach and small bowel lymphoma were found. Vomiting and feeling of fullness were the two most common presenting symptoms. Large cell type and high grade tumours were found to be the commonest histological types. All the patients were treated with surgery followed by chemotherapy. A 5-year disease-free survival (DFS) rate of 73%) was observed with a confidence interval of 0.65-1.35. Survival in stomach cancer was 73.5% (95% CI 0.26-1.74) while it was 76.4% in small bowel tumours (95% CI 0.54-1.46). The difference in survival was not statistically significant. CONCLUSIONS: Although there is no consensus regarding treatment of primary GI lymphoma, surgery and adjuvant chemotherapy yield good survival.

An autoantibody in pemphigus serum, specific for the 59 kD keratin, selectively binds the surface of keratinocytes: evidence for an extracellular keratin domain.

We have identified a novel IgG antikeratin autoantibody in the serum of a Brazilian pemphigus foliaceus patient (Cascas-42). This antibody is specific for the 59 kD acidic murine keratin and its 56.5 kD human counterpart (Moll's catalogue #10), and is distinct from the pemphigus antibody system. Antikeratin autoantibodies present in the Cascas-42 serum were purified by affinity chromatography with a 59 kD murine keratin-agarose column (IAP-Cascas-42 antibodies). The specificity of the IAP-Cascas-42 antibodies was tested by indirect immunofluorescence and immunoelectron microscopy against epidermal cryosections, trypsin-dissociated keratinocytes, and epidermal cell cultures. The serum was also tested with extracts from unlabeled and surface 125I-labeled keratinocytes (Iodo-Gen method) by immunoblot analysis of one- and two-dimensional polyacrylamide gel electrophoresis. The IAP-Cascas-42 antibodies bind the intercellular spaces of murine epidermis, and the cell surfaces of viable, dissociated murine keratinocytes, as well as murine epidermal cells in culture by immunofluorescence and immunoelectron microscopy. These autoantibodies did not stain cytoplasmic keratins and did not react with parallel human epidermal substrates. The Cascas-42 serum identified the 59 kD murine acidic keratin and its 56.5 kD human counterpart in epidermal extracts by two-dimensional polyacrylamide gel electrophoresis and immunoblot analysis. In addition, surface radioiodination of viable murine keratinocytes selectively labeled the 59 kD keratin suggesting that a domain of this molecule is exposed on the cell surface. The 125I-labeled 59 kD keratin was also recognized by the Cascas-42 serum by immunoblotting and autoradiography. These studies suggest that in murine epidermis, the 59 kD keratin is a transmembrane protein with an extracellular domain recognized by the IAP-Cascas-42 antibodies.