Bone health and body composition in transgender adults before gender-affirming hormonal therapy: data from the COMET study.

PURPOSE: Preliminary data suggested that bone mineral density (BMD) in transgender adults before initiating gender-affirming hormone therapy (GAHT) is lower when compared to cisgender controls. In this study, we analyzed bone metabolism in a sample of transgender adults before GAHT, and its possible correlation with biochemical profile, body composition and lifestyle habits (i.e., tobacco smoke and physical activity). METHODS: Medical data, smoking habits, phospho-calcic and hormonal blood tests and densitometric parameters were collected in a sample of 125 transgender adults, 78 Assigned Females At Birth (AFAB) and 47 Assigned Males At Birth (AMAB) before GAHT initiation and 146 cisgender controls (57 females and 89 males) matched by sex assigned at birth and age. 55 transgender and 46 cisgender controls also underwent a complete body composition evaluation and assessment of physical activity using the International Physical Activity Questionnaire (IPAQ). RESULTS: 14.3% of transgender and 6.2% of cisgender sample, respectively, had z-score values < -2 (p = 0.04). We observed only lower vitamin D values in transgender sample regarding biochemical/hormonal profile. AFAB transgender people had more total fat mass, while AMAB transgender individuals had reduced total lean mass as compared to cisgender people (53.94 ± 7.74 vs 58.38 ± 6.91, p < 0.05). AFAB transgender adults were more likely to be active smokers and tend to spend more time indoor. Fat Mass Index (FMI) was correlated with lumbar and femur BMD both in transgender individuals, while no correlations were found between lean mass parameters and BMD in AMAB transgender people. CONCLUSIONS: Body composition and lifestyle factors could contribute to low BMD in transgender adults before GAHT.

Sleep and circadian rhythms in hospitalized patients with decompensated cirrhosis: effect of light therapy.

Patients with liver cirrhosis often exhibit sleep-wake abnormalities, which are, at least to some extent, circadian in origin. A relatively novel non-pharmacological approach to circadian disruption is appropriately timed bright light therapy. The aims of this pilot study were to investigate sleep-wake characteristics of a well-characterized population of inpatients with cirrhosis, and to evaluate the efficacy of bright light therapy in the hospital setting. Twelve consecutive inpatients with cirrhosis underwent complete sleep-wake assessment, to include qualitative and semi-quantitative (actigraphic) indices of night-time sleep quality, daytime sleepiness, diurnal preference, habitual sleep timing, quality of life, mood and circadian rhythmicity [i.e. urine collections for measurement of the melatonin metabolite 6-sulphatoxymelatonin (aMT6s)]. Patients showed extremely impaired night sleep quality (Pittsburg Sleep Quality Index global score: 16.3 ± 2.1) and daytime sleepiness was common (Epworth Sleepiness Scale: 8.3 ± 3.2). Five patients were randomly assigned to a single room in which lighting was controlled in relation to timing, spectral composition and intensity (lights on at 06:30 and off at 22:30, blue-enriched, more intense light in the morning, red-enriched, less intense light in the afternoon/evening); the others stayed in identical rooms with standard lighting. Sleep diaries revealed poor sleep quality, prolonged sleep latency (67 ± 138 min) and a reduced sleep efficiency (69 ± 21%). These features were confirmed by actigraphy (sleep efficiency: 71 ± 13%; fragmentation index: 55 ± 15%). Quality of life was globally impaired, and mood moderately depressed (Beck Depression Inventory: 19.4 ± 7.9). Seven patients underwent serial urine collections: no circadian aMT6s rhythm was detected in any of them, neither at baseline, nor during the course of hospitalization in either room (n = 4). In conclusion, sleep and circadian rhythms in hospitalized, decompensated patients with cirrhosis are extremely compromised. Treatment with bright light therapy did not show obvious, beneficial effects, most likely in relation to the severity of disturbance at baseline.

New Perspectives in the Association between Anthropometry and Mortality: The Role of Calf Circumference.

AIMS: Considering the impact of sarcopenia on mortality, and the difficulty to assessment of body composition, the hypothesis of the study is that calf circumference (CC) is closely related to mortality in older patients. The aim of the study was to analyze the potential role of CC to predict mortality in old individuals at 3, 6 and 12 months after discharge from hospital. METHODS: Patients aged >65 years were recruited for this retrospective study from September 2021 to March 2022. Their physical and body composition characteristics (including Body Mass Index-BMI and Mini Nutritional Assessment-MNA) were measured; data on mortality at 3 (T3), 6 (T6) and 12 (T12) months after discharge were recorded. Sarcopenia was diagnosed according to the 2019 European Consensus criteria. RESULTS: Participants were 192 older adults (92 women), with a mean age of 82.8±7.0 years. Sarcopenic people were 41. The mortality rate was higher in sarcopenic people only at T3 and T6. CC had comparable validity in predicting mortality to that of MNA and ASMMI (Appendicular Skeletal Muscle Mass), and was better than BMI and serum albumin at each time point. Youden's index showed that the best cut-off for CC for predicting mortality was 30.6 cm both at T3 (sensitivity: 74%; specificity: 75%) and T6 (sensitivity: 75%; specificity: 67%). At the Cox regression model for mortality, high values of CC (HR 0.73, CI95% 0.60-0.89/p<0.001) and ADL scores (HR 0.72, CI95% 0.54-0.96/p=0.04) were protective factors at T6 and T12 respectively; at T12 high comorbidity rate was a risk factor (HR 1.28, IC95% 1.02-1.62/p=0.04). CONCLUSIONS: CC has a validity comparable to MNA and ASMMI in predicting mortality at 3, 6 and 12 months after hospital discharge. Moreover, it can be considered an independent predictor of medium-term mortality in the hospitalized older population. CC can be an effective method for the prognostic stratification of these patients, due to its simplicity and immediacy.

Micronutrient Deficiency and Its Potential Role in Delirium Onset in Older Adults: A Systematic Review.

BACKGROUND AND OBJECTIVES: One of the pathogenetic hypotheses of delirium is the "neuroinflammatory theory" with consequent neurotoxicity of brain connectivity networks. Micronutrients may play a significant role in the prevention of neuroinflammation. This systematic review addresses the role of micronutrients in the development of delirium in older populations. METHODS: The EBSCO, Cochrane, PubMed, and Web of Science databases were searched for articles on delirium and micronutrients. The methodological quality of the studies included in the review was evaluated with the Newcastle-Ottawa Scales for observational studies and for case-control studies. RESULTS: 1326 papers were identified from the searches, 7 of which met the inclusion criteria (see section 2.3). All the papers included were written in English. Delirium was predominantly secondary to post-operative dysfunction or acute medical conditions. By altering the production of neurotransmitters resulting in an imbalance, and by reducing their immunomodulatory role with a consequent increase in inflammatory oxidative stress, micronutrient deficiency seems to be associated with an increased incidence of delirium. CONCLUSIONS: This review supports the existence of an association between micronutrient deficiency (i.e. cobalamin, thiamine, and vitamin D) and an increased incidence of delirium, with a greater prevalence in hospitalized patients.

Neuropsychological tools in hepatology: a survival guide for the clinician.

Neuropsychological assessment has three main applications in clinical hepatology: (i) to detect, grade and monitor liver failure-related cognitive alterations in end-stage liver disease (hepatic encephalopathy), (ii) to substantiate complaints of attention or concentration difficulties in patients with non-cirrhotic chronic hepatitis C viral infection, and (iii) to screen patients who are being considered for liver transplantation for early signs of dementia. However, there is limited agreement on how cognitive assessment should be conducted in these patients, and how results should be interpreted and used to implement clinical decisions. In this review, we summarize the available literature on neuropsychological dysfunction in patients with cirrhosis and with chronic hepatitis C viral infection and provide some guidance on how to utilize neuropsychological assessment in practice.

Factors Influencing Serum-Hydroxivitamin D Levels and Other Bone Metabolism Parameters in Healthy Older Women.

OBJECTIVE: Older women have frequently low serum 25-hydroxivitamin D (25[OH]D) concentrations, high parathormone (PTH) levels and low bone mineral density (BMD) values. Endogenous synthesis, dietary habits, sunlight exposure and fat-mass-mediated storage may influence 25(OH)D levels and bone metabolism, but the relevance of these factors in the elderly has yet to be fully elucidated. We aimed to investigate the influence of dietary vitamin D intake and fat mass on serum 25(OH)D levels and bone metabolism in older women. DESIGN: Cross-sectional. SETTING: Community. PARTICIPANTS: 218 fit older women attending a biweekly mild fitness program. MEASUREMENTS: Dietary habits was investigated through a 3-day record questionnaire. Serum 25(OH)D and intact parathormone (PTH) concentrations were measured by radioimmunoassay and by a 2-step immunoradiometric assay, respectively. BMD and body composition were estimated using dual-energy X-ray absorptiometry with fan-beam technology. RESULTS: Only fat mass showed a significant negative association with 25(OH)D (ß=-3.76, p<0.001), and positive associations with whole body, lumbar, femoral neck and total hip BMD. Binary logistic analysis revealed a protective effect of adiposity on secondary hyperparathyroidism (OR=0.42, 95%CI:0.19-0.92, p=0.03). Dietary vitamin D intake was not associated to any of these outcomes. CONCLUSION: Fat mass has a greater influence on serum 25(OH)D than dietary vitamin D intake.

Recent developments in the diagnosis and treatment of covert/minimal hepatic encephalopathy.

The terms minimal hepatic encephalopathy and covert hepatic encephalopathy are defined. Clinical assessment is unreliable and both require the use of diagnostic tools. Of these, psychometric tests are the most widely used. They require proper standardization and may be biased by patient cooperation or lack thereof. The measure of the critical flicker frequency and of the electroencephalogram, possibly quantified, are also useful. The alteration of any of them is not strictly parallel in size and may vary from patient to patient. When possible, the use of multiple measures might increase diagnostic reliability. These functional measures should be interpreted within the clinical/biochemical profile of the patient to exclude other disorders. A flow chart for treatment is proposed on the basis of current knowledge.

Hypovitaminosis D and fat mass in healthy older people.

Prospective studies have suggested that hypovitaminosis D can predict the onset of obesity, but they relied mainly on body mass index, which could be scarcely reliable in older people. We investigated whether baseline hypovitaminosis D could predict higher fat mass (FM) levels using dual-energy X-ray absorptiometry in a sample of 116 fit and healthy older subjects. Although no significant differences in FM estimates emerged between subjects with and without hypovitaminosis D at the baseline, abdominal FM was found significantly higher in the former group (with hypovitaminosis D at the baseline) than in the latter after 3 years of follow-up. Adjusted logistic regression analysis confirmed these findings: hypovitaminosis D coincided with an approximately sixfold higher risk of subjects having higher abdominal FM levels at the follow-up. In conclusion, hypovitaminosis D predicts higher abdominal FM levels in the elderly.

Effect of weight loss on mortality in overweight and obese nursing home residents during a 5-year follow-up.

BACKGROUND/OBJECTIVES: The objective of this study was to ascertain the effect of weight loss over the course of 1 year on 5-year mortality in old nursing home (NH) residents in different classes of body mass index (BMI). SUBJECTS/METHODS: A longitudinal study was conducted on 161 NH residents aged ⩾ 70 years at the Istituto di Riposo per Anziani, Padova, Italy. Data were collected using a comprehensive geriatric assessment at baseline and at a 1-year follow-up visit. Mortality was recorded over a 5-year follow-up. We divided our sample into four groups using as cutoffs a BMI of 25 and a weight gain or loss of 5% at 1 year (BMI ⩾ 25 and weight stable/gain, BMI ⩾ 25 and weight loss, BMI<25 and weight stable/gain and BMI <25 and weight loss). RESULTS: People with a BMI ⩾ 25 and weight loss suffered the worst decline in activities of daily living, whereas those with a BMI <25 and weight loss had the most significant decline in nutritional status, which coincided with the worst decline in the Multidimensional Prognostic Index among the groups whose weight changed. Compared with those with a BMI ⩾ 25 and weight stable/gain (reference group), those with a BMI <25 were at the highest risk of dying (in association with weight loss: hazard ratio HR=3.60, P=0.005; in association with weight stable/gain: HR=2.45, P=0.01), and the mortality risk was also increased in people with a BMI ⩾ 25 and weight loss (HR=1.74, P=0.03). CONCLUSIONS: In conclusion, weight loss increases the mortality risk in frail, disabled NH residents, even if they are overweight or obese.

WITHDRAWN: Short- and long-term efficacy of cholinesterase inhibitors in older adults with alzheimer's disease and mixed dementia: results of a 21-month observational study.

Ahead of Print article withdrawn by publisher.

Duration of breastfeeding as a risk factor for vertebral fractures.

PURPOSE: Among the risk factors for osteoporosis and fractures, gynecological history (fertile period, parity and breastfeeding) play an important part. Changes in calcium metabolism to enable an adequate mineral transfer to the milk have a prominent role in bone loss during breastfeeding. Data on the influence of breastfeeding in postmenopausal osteoporosis are inconsistent. The aim of the present study was to identify any association between duration of breastfeeding and vertebral fractures in postmenopausal women. METHODS: All patients underwent the following tests: bone mineral density measurements of the lumbar spine (L1-L4) and the total and femoral neck using dual-energy X-ray absorptiometry and antero-posterior and lateral radiography of the thoracic and lumbar spine to identify vertebral fractures. RESULTS: The study involved 752 women with a mean age of 64.5±9.3; 23% of them reported vertebral osteoporotic fractures. The women with vertebral fractures had breastfed for longer periods (11.8±12.9 vs. 9.3±11.2months, p=0.03) and had more pregnancies (2.6±2.2 vs. 2.2±1.3, p=0.002). Breastfeeding for more than 18months was associated with a two-fold risk of developing vertebral fractures (OR 2.12, 95% CI 1.14-5.38, p=0.04), particularly in those without current or past use of drugs positively affecting bone. CONCLUSIONS: Our study showed an association between long periods of breastfeeding and vertebral fractures, supporting a role for lengthy lactation as a risk factor for osteoporotic fractures after menopause. Bearing in mind all the benefits of breastfeeding, this finding suggests the importance of an adequate calcium and vitamin D intake during pregnancy and breastfeeding, with the aid of dietary supplements if necessary.

Association between dietary folate intake and serum insulin-like growth factor-1 levels in healthy old women.

OBJECTIVE: High serum levels of insulin-like growth factor-1 (IGF-1) seem to coincide with higher rates of some types of cancer and the risk of all-cause mortality in old people. Eating vegetables seems to reduce IGF-1 levels because they are rich in micronutrients such as vitamins. This study investigates the possible association between vitamin intake and IGF-1 levels in a representative group of healthy elderly women with Mediterranean dietary habits. DESIGN: This cross-sectional study included 124 healthy women with a mean age of 71.3 ± 4.2 years and a mean body mass index (BMI) of 27.37 ± 3.48 kg/m(2) attending a mild fitness program twice a week at public gyms in Padova. The main parameters considered were IGF-1 (measured by chemiluminescence) and diet, assessed on the basis of a 3-day record and a questionnaire on the frequency with which they usually ate certain foods. RESULTS: The mean IGF-1 level for the sample as a whole was 136.2 ± 38.9 µg/l, and was significantly lower in women with a higher folate intake (p = 0.04). On simple linear analysis, the vitamins found associated with serum IGF-1 levels were: folates (r: -0.25; p = 0.003); vitamin E (r: -0.21; p = 0.01); vitamin D (r: -0.17; p = 0.03); and riboflavin (r: -0.16; p=0.03). After removing the effect of calorie, protein, carbohydrate and fat intake, and other known potential confounders (age, BMI, alcohol intake), only folate intake correlated with IGF-1 levels (r = -0.17; p = 0.04). CONCLUSION: A folate-rich diet could have the effect of lowering circulating IGF-1 levels in elderly women.

Relationship between increased endogenous parathormone levels and bone density in postmenopausal women treated with bisphosphonates.

AIM: Bisphosphonates increase bone mineral density (BMD) and also increase parathyroid hormone (PTH): the rule of increased PTH on BMD is not well known. The aim of our study was to assess the relationship between endogenous PTH levels and BMD after 18 months of antiresorptive therapy in a group of post-menopausal women with normal baseline PTH levels. METHODS: A retrospective study was conducted on 62 women with normal baseline PTH levels (mean age 62.7 ± 8.6 years) who underwent dual-energy X-ray absorptiometry, thoracic-lumbar radiography, and blood and urine sampling at the baseline and after 18 months. All patients were treated with bisphosphonates and received calcium and vitamin D3 supplementation. RESULTS: In the whole group, after 18 months, mean BMD improved both at lumbar spine (0.53 ± 0.09 vs. 0.49 ± 0.09 g/cm2; P<0.05) and at femur (0.66 ± 0.08 vs. 0.65 ± 0.09 g/cm2; P<0.05); PTH levels (56.80 ± 19.07 vs. 48.74 ± 14.99 pg/mL; P<0.001) and serum 25-hydroxyvitamin D (60.73 ± 29.87 vs. 49.81 ± 26.56 ng/mL; P<0.05) increased. Dividing the patients according PTH variation (>0 or ≤ 0), the group with ΔPTH>0 had higher percentage increase of BMD at spine (8.0 ± 9% vs. 4 ± 7.5%; P<0.001) and at total hip (3 ± 9% vs. 0.49 ± 8.9%; P<0.001) while the bone alkaline phosphatase significantly decreased (-11.80 ± 2.19 vs. -4.05 ± 3.08 ug/L; P<0.001) than the other group. CONCLUSION: Increased endogenous PTH levels seems to be associated with a higher BMD increase in patients treated with bisphosphonates for postmenopausal osteoporosis. The increase of PTH must be clarified by further investigations.

Nutritional predictors of cognitive impairment severity in demented elderly patients: the key role of BMI.

INTRODUCTION: The body mass index (BMI) is commonly used to assess nutritional status and the Mini Mental State Examination (MMSE) is a validated tool for assessing cognitive status in elderly people. Nutritional and cognitive aspects are closely related in dementia. OBJECTIVES: To establish whether BMI predicts cognitive decline in demented patients and whether an "alarm" BMI cut-off exists for declining MMSE scores. SUBJECTS AND METHODS: 82 elderly demented patients underwent clinical, bio-chemical and functional assessment. DESIGN: Transversal study. RESULTS: The mean BMI was 26.08±4.48 kg/m² and the mean MMSE 18.68±5.38. Patients with BMI<25 kg/m² had significantly lower MMSE scores (16.5±5.53 vs 20.38±4.64; p 0.001), fat-free mass (FFM; 27.76±8.99 vs 37.38±10.58 kg; p<0.001), fat-free mass index (FFMI; 11.52±3.03 vs 14.67±2.89 kg/m²; p<0.001), and fat mass (FM; 24.90±6.89 vs 36.86±6.77 kg; p<0.001), as well as lower Mini Nutritional Assessment (MNA) scores (23.80±2.50 vs 25.00±2.29; p=0.03) and higher vitamin B12 levels (460.95±289.80 vs 332.43±82.07 pg/ml; p=0.01). In the sample as a whole, MMSE scores significantly correlated with scores for MNA (r=0.27, p=0.01), FFM (r=0.27, p=0.01), BMI (r=0.19, p=0.05), ADL (r=0.28, p=0.01) and instrumental activities of daily living (IADL; r=0.34, p=0.002). On multiple logistic regression, BMI<25 kg/m² was independently associated with the risk of moderate-severe cognitive impairment (OR=2.96; 95% CI; 1.16-7.55) and female gender was independently associated with severity of dementia (OR=3.14; 95% CI; 1.09-9.03). CONCLUSION: BMI seems to indicate global health status in elderly demented people and a BMI of 25 kg/m² can be considered an "alarm" cut-off, lower values coinciding with a worse cognitive status based on MMSE scores.