Bone Loss and Fractures in Post-Menopausal Women Living with HIV: A Narrative Review.

INTRODUCTION: Post-menopausal women living with Human Immunodeficiency Virus (WLHIV) face an increased risk of bone fractures due to the relationship between HIV-related factors and menopause. This narrative review aims to summarise the current knowledge about fracture risk among post-menopausal WLHIV in particular looking at hormonal changes, combined antiretroviral therapy (cART), lifestyle factors, and psychosocial implications. We also profiled a summary of the significant, recent studies of post-menopausal WLHIV residing in low-income countries (LIC). METHODS: A thorough search of the literature was performed across PubMed, Medline, Scopus, and Google Scholar, focussing on studies published between 2000 and 2024. Inclusion criteria entailed original research, reviews, and meta-analyses addressing bone mineral density (BMD), fracture incidence, and related risk factors in post-menopausal WLHIV. RESULTS: The review identified 223 relevant studies. Post-menopausal WLHIV exhibit significantly lower BMD and higher fracture rates compared to both HIV-negative post-menopausal women and pre-menopausal WLHIV. cART, particularly tenofovir disoproxil fumarate (TDF), contributes to reduced BMD. Menopausal status exacerbates this risk through decreased oestrogen levels, leading to increased bone resorption. Moreover, lifestyle choices such as smoking, alcohol consumption, and low physical activity are more prevalent in PWHIV, which further elevates fracture risk. Different psychosocial factors may make WLWHIV more vulnerable at this stage of their life, such as depression, isolation, stigma, and housing and nutritional issues. Women living in LICs face a variety of challenges in accessing HIV care. There are gaps in research related to the prevalence of osteoporosis and bone loss in post-menopausal WLHIV in LICs. CONCLUSION: Post-menopausal women living with HIV face a significantly higher risk of bone loss and fractures due to the combined effects of HIV and menopause. Antiretroviral therapy (particularly TDF), lifestyle factors, and psychosocial challenges exacerbate this risk. There is a need for careful selection of cART, hormone replacement therapy (HRT), and emerging treatments such as Abaloparatide. A holistic approach including lifestyle changes and psychosocial support is crucial to reduce fracture risk in WLHIV, especially in low-income countries.

Primary Hyperparathyroidism and Pulmonary Embolism in Patients With a Fractured Neck of Femur.

Two patients aged 82 and 77, with a fractured neck of the femur, were found to have primary hyperparathyroidism, characterized by hypercalcemia and hypercalciuria. Post-surgery, both developed pulmonary embolism (PE), highlighting a possible link between hypercalcemia and increased hypercoagulation risk. There have been few case reports suggesting the association between hypercalcemia due to hyperparathyroidism and the increase in tendency of hypercoagulation and subsequent risk of venous thromboembolism (VTE). This case series offers insights into how ionized calcium influences thrombin formation, platelet activation and aggregation, and activation of clotting factors such as factor VII and factor X, raising questions about the role of chronic hypercalcemia in VTE. Further research is needed to 1) establish whether chronic hypercalcemia in the absence of fracture can modulate the risk of hypercoagulation; 2) determine whether chronic hypercalcemia in individuals with bone fracture may represent a significantly higher hypercoagulability risk during the postoperative periods.

Orthogeriatric Care Following Hip Fracture: Improving Post-Operative Outcomes in an Aged Population.

INTRODUCTION: Hip fractures globally are associated with high levels of morbidity, mortality, and significant financial burden. This audit aimed to assess the impact of orthogeriatric liaison care on post-operative outcomes following surgical management of neck or femur fractures. METHODS: Here, 258 patients who underwent hip fracture surgery over 1-year were included. Data were collected as an audit following the transition to an orthogeriatric liaison care model, involving regular orthogeriatric review (thrice weekly ward rounds, daily board rounds), superseding orthogeriatric review as requested. The audit is meant to assess the development of post-operative non-surgical site infection (NSSI) and mortality and duration of inpatient stay. Outcomes were compared to previous data from our hospital site in 2015/2016. RESULTS: Patients with severe cognitive impairment and systemic disease (Abbreviated Mental Test Score (AMTS) < 7 and American Society of Anesthesiologists (ASA) grade ≥ 3) showed significantly elevated NSSI risk, consistent across the study periods. Both periods demonstrated an increased risk of NSSI associated with admission from nursing homes. Despite the 2021/2022 cohort being notably older, NSSI risk decreased from 40.6% to 37.2% after implementing the orthogeriatric care model. NSSI risk was notably reduced for severe cognitive impairment (51.6% vs. 71%), and the p-value was 0.025. Average hospital stay decreased post-intervention (2.4 days shorter), with a notable reduction for NSSI patients (3.4 days shorter). Overall mortality rates were similar, although mortality due to infection was significantly reduced in 2021/2022 (44.4% vs. 93.3%), and the p-value was 0.003. CONCLUSION: The orthogeriatric liaison care model significantly decreased NSSI only in individuals with severe cognitive impairment and infection-associated mortality. This highlights the integral role of orthogeriatricians in the care of elderly hip fracture patients.

HIV and an Ageing Population-What Are the Medical, Psychosocial, and Palliative Care Challenges in Healthcare Provisions.

The continuing increase in patient numbers and improvement in healthcare provisions of HIV services in the UK, alongside the effectiveness of combined antiretroviral therapy (cART), has resulted in increasing numbers of the ageing population among people living with HIV (PLWH). It is expected that geriatricians will need to deal with many older people living with HIV (OPLWH) as life expectancy increases. Therefore, geriatric syndromes in OPLWH will be similar to the normal population, such as falls, cognitive decline, frailty, dementia, hypertension, diabetes and polypharmacy. The increase in the long-term use of cART, diabetes, dyslipidaemia and hypertension may lead to high prevalence of cardiovascular disease (CVD). The treatment of such conditions may lead to polypharmacy and may increase the risk of cART drug-drug interactions. In addition, the risk of developing infection and cancer is high. OPLWH may develop an early onset of low bone mineral density (BMD), osteoporosis and fractures. In this review, we have also provided potential psychosocial aspects of an ageing population with HIV, addressing issues such as depression, stigma, isolation and the need for comprehensive medical and psychosocial care through an interdisciplinary team in a hospital or community setting. OPLWH have a relatively high burden of physical, psychological, and spiritual needs and social difficulties, which require palliative care. The holistic type of palliative care that will improve physical, emotional and psychological wellbeing is discussed in this review.

Hyperacute synchronous cardiocerebral infarction in a patient with new-onset atrial fibrillation: a case of myocardial infarction with nonobstructive coronary arteries.

Hyperacute synchronous cardiocerebral infarction (CCI) is an extremely rare condition with an incidence of 0.009%. In the acute stage of ischemic stroke, there is a high prevalence of ECG abnormalities. Prolonged QTc, atrial fibrillation (AF) and ECG changes indicative of ischemic heart disease, such as Q waves, ST depression, and T wave inversion, were the most prevalent changes. There are three types of simultaneous CCI: cardiac conditions that cause cerebral infarction, cerebral infarction caused by cardiac conditions, and (c) dysregulation of the brain-heart axis or cerebral infarction causing myocardial infarction. Herein, we present a case of hyperacute synchronous CCI in an elderly patient with new-onset AF and myocardial infarction with nonobstructive coronary arteries (MINOCA).

Fracture Neck of the Femur: A Case of Two Pathologies.

We report a case of a 65-year-old woman who sustained a left neck of femur (NOF) fracture following low-energy trauma. Computed tomography (CT) scan for the neck, chest, abdomen and pelvis was normal apart from enlargement of the right lobe of the thyroid. Interestingly, thyroid function was normal. While waiting for the result of thyroid cytology and bone histology, the patient recovered well from the operation and started to engage well with physiotherapy. The result of the investigation showed presence of diffuse large B-cell lymphoma in the left NOF and right lobe of the thyroid. As the presence of lymphoma only in these two organs is extremely rare, it is not yet clear what is underlying mechanism for such association. Therefore, such observations may raise many future research questions as detailed in the discussion of this case report. This case also illustrates the importance of a multidisciplinary approach in identifying, evaluating, and treating unique and complex presentations of NOF fracture, with a focus on the patient's history, clinical examination and applying diagnostic tools.

Bone Health in People Living with HIV/AIDS: An Update of Where We Are and Potential Future Strategies.

The developments in Human Immunodeficiency Virus (HIV) treatment and in the care of people living with HIV (PLWHIV) and Acquired Immunodeficiency Syndrome (AIDS) over the last three decades has led to a significant increase in life expectancy, on par with HIV-negative individuals. Aside from the fact that bone fractures tend to occur 10 years earlier than in HIV-negative individuals, HIV is, per se, an independent risk factor for bone fractures. A few available antiretroviral therapies (ARVs) are also linked with osteoporosis, particularly those involving tenofovir disoproxil fumarate (TDF). HIV and hepatitis C (HCV) coinfection is associated with a greater risk of osteoporosis and fracture than HIV monoinfection. Both the Fracture Risk Assessment Tool (FRAX) and measurement of bone mineral density (BMD) via a DEXA scan are routinely used in the assessment of fracture risk in individuals living with HIV, as bone loss is thought to start between the ages of 40 and 50 years old. The main treatment for established osteoporosis involves bisphosphonates. Supplementation with calcium and vitamin D is part of clinical practice of most HIV centers globally. Further research is needed to assess (i) the cut-off age for assessment of osteoporosis, (ii) the utility of anti-osteoporotic agents in PLWHIV and (iii) how concomitant viral infections and COVID-19 in PLWHIV can increase risk of osteoporosis.

Recurrent abdominal laparotomy wound infection and dehiscence in a patient with zinc and selenium deficiency associated with Roux-en-Y gastric bypass: Case report and literature review.

We report a case of a 72-year-old woman who developed recurrent abdominal laparotomy wound dehiscence and infection following a hepatico-jejunostomy. Her surgical history included a Roux-en-Y gastric bypass (RYGB) that was carried out 11 years ago. Upon further assessment in the current admission, she was found to be deficient in both selenium and zinc. Daily multivitamin and mineral tablets and a nutritional supplement drink were prescribed to address her deficiencies. After 2 months of supplementation, the laparotomy wound had made significant healing progress and no further surgical input was required. This case illustrates the importance of assessing micronutrient levels in patients with a history of bariatric surgery who present with poor wound healing and infection. Bariatric patients should also be educated about the risks of nutritional deficiencies and encouraged to adhere to prescribed dietary and lifestyle changes. Importantly, family medicine and primary care physicians need to consider an adequate level of supplementation of micronutrients in all patients with RYGB surgery.

The frequency of Klotho KL-VS polymorphism in a large Italian population, from young subjects to centenarians, suggests the presence of specific time windows for its effect.

In mice a defect of Klotho gene expression results in multiple aging-like phenotypes including short lifespan, osteoporosis and atherosclerosis, while its over-expression suppresses aging and extends lifespan. Contrasting data have been reported as far as the importance of the functional variant of Klotho termed "KL-VS" on human longevity, depending on the average age of the old subjects that were compared with young controls. We therefore performed a study on a large Italian population sample including people from very young to very old age (centenarians). A total of 1,089 (669 women and 420 men) unrelated individuals from 19 to 109 years, born and residing in northern and central Italy, were subdivided into three age classes defined on the basis of the survival curve constructed using Italian demographic mortality data, and genotyped for the KL-VS allele. We found a significant increase of the heterozygous Klotho genotype in the class of elderly people compared to young controls. On the contrary, no difference was present between centenarians and young controls. Such a non monotonic trajectory is evident only when a large, comprehensive age range is investigated, and is compatible with the hypothesis that this KL-VS heterozygous genotype is favorable for survival in old people, its beneficial effect decreasing thereafter, and becoming no more evident at the extreme ages. Such unusual age-related changes in the Klotho KL-VS genotype frequency is compatible with the hypothesis that alleles and genotypes involved in aging and longevity may exert their biological effect at specific time windows.

Inflammaging and anti-inflammaging: a systemic perspective on aging and longevity emerged from studies in humans.

A large part of the aging phenotype, including immunosenescence, is explained by an imbalance between inflammatory and anti-inflammatory networks, which results in the low grade chronic pro-inflammatory status we proposed to call inflammaging. Within this perspective, healthy aging and longevity are likely the result not only of a lower propensity to mount inflammatory responses but also of efficient anti-inflammatory networks, which in normal aging fail to fully neutralize the inflammatory processes consequent to the lifelong antigenic burden and exposure to damaging agents. Such a global imbalance can be a major driving force for frailty and common age-related pathologies, and should be addressed and studied within an evolutionary-based systems biology perspective. Evidence in favor of this conceptualization largely derives from studies in humans. We thus propose that inflammaging can be flanked by anti-inflammaging as major determinants not only of immunosenescence but eventually of global aging and longevity.

Obesity and gastro-esophageal acid reflux: physiopathological mechanisms and role of gastric bariatric surgery.

BACKGROUND: Controversial findings about the relationships between obesity and gastro-esophageal reflux have been reported, as well as about the effects of weight loss and bariatric surgery on reflux. The aims of this study were to evaluate esophageal motility and gastro-esophageal acid circadian patterns in obese patients and to test the effects of vertical banded gastroplasty (VBG) on these parameters. METHODS: 14 obese subjects (BMI 36-53 kg/m2), 4 men, 10 women, 27-61 years old, admitted for elective bariatric surgery, underwent clinical evaluation, upper endoscopy, esophageal manometry and gastroesophageal pH monitoring. Evaluations were repeated 6 to 12 months after gastric surgery that consisted of a VBG (7 patients), accompanied in the other 7 patients with an anti-reflux procedure (fundoplication). Manometric and pH-metric findings in the obese patients were compared with a normal-weight control group before and after the two different surgical treatments. RESULTS: Gastro-esophageal reflux was significantly more frequent in obese (57.1%) than in control group (7.1%). Esophageal motility in obese subjects was not different from controls. After VBG alone, we found a reduction in basal lower esophageal sphincter (LES) pressure and an increase of acid reflux. When VBG was accompanied by fundoplication, basal LES pressure increased and acid reflux frequency decreased. CONCLUSIONS: Obesity is associated with gastroesophageal reflux. VBG reduced weight, but not gastro-esophageal acid reflux. Therefore, in our population, this operation cannot be considered as an antireflux procedure.

Relation between leptin and the metabolic syndrome in elderly women.

BACKGROUND: Leptin has been shown to be linked to adiposity and insulin resistance in middle-aged participants. However, the association between leptin and metabolic syndrome independently of body fat and body fat distribution has not been evaluated in healthy elderly people. METHODS: We studied the independent relation between leptin and the components of the metabolic syndrome in 107 women aged 67-78 years with body mass index (BMI) ranging from 18.19 to 36.16 kg/m2. In all participants, we evaluated BMI, waist and hip circumferences, body composition by dual energy X-ray absorptiometry, fasting, and 2-hour glucose, lipids, insulin, homeostasis model assessment of insulin resistance (HOMA), systolic (SBP), diastolic blood pressure (DBP), and leptin. RESULTS: Significant correlation was found between leptin, BMI, waist circumference, fat mass, DBP, SBP, cholesterol, triglycerides, insulin, and HOMA. After adjusting for age and waist circumference, as well for age and fat mass, leptin was significantly related to insulin levels, HOMA, and cholesterol. In a stepwise multiple regression analysis using insulin levels or HOMA as dependent variables and age, waist circumference, fat mass, leptin, SBP, DBP, cholesterol, and triglycerides as independent variables, leptin entered the regression first, waist circumference second, and age third. CONCLUSION: Our study shows that leptin is significantly related to indices of adiposity in elderly women, and leptin is significantly associated with insulin levels, HOMA, and cholesterol independent of age, body fat, and fat distribution. Leptin, waist circumference, and age together explained 31% and 33% of insulin levels and HOMA variance, respectively, in healthy elderly women.

Serum lipopotein (a) levels in a large sample of subjects affected by familial combined hyperlipoproteinaemia and in general population.

BACKGROUND: Serum lipoprotein (a) [Lp(a)] is a lipidic parameter, strictly under genetic control. Lp(a) levels vary in different dyslipidaemias according to the underlying disease. DESIGN: The aim of this study was to evaluate and compare serum Lp(a) mean levels distribution in a large familial combined hyperlipoproteinaemia (FCH) patients sample with a normolipidaemic group. METHODS: FCH group included 138 subjects (74 males and 65 females) aged from 16 to 88 years; the control group included 438 normolipidaemic subjects (238 males and 200 females) aged from 16 to 91 years. In both groups we have measured Lp(a) concentrations and other lipidic parameters. RESULTS: Serum lipid levels as well as Lp(a) log-transformed concentrations were on average higher in FCH patients than in control subjects. Lp(a) concentrations were not significantly different between sexes and among 20-year age classes in both groups. CONCLUSIONS: The relationship between FCH and Lp(a) remains controversial. However, since both are considered independent risk factors for premature CHD development, even if their pathogenic interaction is still unclear, we suggest that Lp(a) values should be carefully monitored in dyslipidaemic subjects and particularly in FCH ones. In FCH subjects with elevated Lp(a) levels, aggressive intervention could be required.

Asymptomatic massive hypertriglyceridemia in an octogenarian.

OBJECTIVE: To report the case of an 85-year-old man with asymptomatic massive hypertriglyceridemia (MHTG). CLINICAL PRESENTATION AND INTERVENTION: Our case was a non-smoker, healthy 85-year-old Caucasian male, with no excessive alcohol intake and no evidence of an excessive sedentary lifestyle, body mass index = 23.2 kg/m(2), BP = 125/85 mm Hg and plasma triglyceride (TG) >1,000 mg/dl. The MHTG was an incidental finding at the age of 70. He had no cardiovascular disease, xanthomas, xanthelasmas or keratic precipitate. During the last 15 years, his average TG plasma levels showed a significant variability independent of specific diet treatment and fibrate therapy. Liver ultrasound examination excluded hepatomegaly and fatty degeneration. Carotid artery ultrasound showed only intimal thickening in both carotid bifurcations. CONCLUSION: In this patient, MHTG had been silent for many years, with no evidence of coronary heart disease and liver fatty degeneration, both typical complications present in MHTG subjects with low high-density lipoprotein. Hence, this case must be considered as a rarity.

Effects of a new soy/beta-sitosterol supplement on plasma lipids in moderately hypercholesterolemic subjects.

Our aim was to test the hypocholesterolemic effect of a low-dose formulation of soy proteins supplemented with isolated b-sitosterol in a ratio of 4:1 in 20 moderately hypercholesterolemic subjects. The study has been divided in three different periods of forty days each: a stabilization diet period, then a treatment period during which all subjects assumed 10 g one time a day of the tested product and, finally, a wash out period. From the end of the stabilization diet period to the end of the soy protein added in b-sitosterol supplementation we observed a 0.45 +/- 0.30 mmol/L, 0.09 +/- 0.31 mmol/L and 0.17 +/- 0.22 mmol/L mean +/- SE decrease in respectively LDL-C, TG and apoB levels, associated with a 0.12 +/- 0.25 and 0.03 +/- 0.51 mg/dL mean increase respectively in HDL-C and apoA plasma concentrations. According to this recommends, low doses of soy protein added in b-sitosterol seems to be a practical and safe alternative for patients seeking modest reductions in LDL-C (< 15%).