Dementia, osteoporosis and fragility fractures: Intricate epidemiological relationships, plausible biological connections, and twisted clinical practices.

Dementia, osteoporosis, and fragility fractures are chronic diseases, often co-existing in older adults. These conditions pose severe morbidity, long-term disability, and mortality, with relevant socioeconomic implications. While in the research arena, the discussion remains on whether dementia is the cause or the consequence of fragility fractures, healthcare professionals need a better understanding of the interplay between such conditions from epidemiological and physiological standpoints. With this review, we summarized the available literature surrounding the relationship between cognitive impairment, dementia, and both low bone mineral density (BMD) and fragility fractures. Given the strength of the bi-directional associations and their impact on the quality of life, we shed light on the biological connections between brain and bone systems, presenting the main mediators, including gut microbioma, and pathological pathways leading to the dysregulation of bone and brain metabolism. Ultimately, we synthesized the evidence about the impact of available pharmacological treatments for the prevention of fragility fractures on cognitive functions and individuals' outcomes when dementia coexists. Vice versa, the effects of symptomatic treatments for dementia on the risk of falls and fragility fractures are explored. Combining evidence alongside clinical practice, we discuss challenges and opportunities related to the management of older adults affected by cognitive impairment or dementia and at high risk for fragility fracture prevention, which leads to not only an improvement in patient health-related outcomes and survival but also a reduction in healthcare cost and socio-economic burden.

Advances in management of periprosthetic joint infections: an historical prospective study.

OBJECTIVE: The purpose of our study is to assess the incidence of prosthetic joint infection (PJI) after total Knee arthroplasty (TKA), total Hip arthroplasty (THA) and total Shoulder arthroplasty (TSA), to identify risk factors, determine the microbial spectrum and management's outcome. PATIENTS AND METHODS: A case-control, retrospective observational study was performed analyzing patients who developed a PJI after TKA, THA, and TSA from 2000 to 2017 at our hospital. The patient's risk profile was defined extracting from clinical records the following data: sex, age, BMI, type of implant, comorbidity, year of surgery, year of infection, previous intra-articular injection, microbial isolation, medical and surgical management outcome. We include in the "control group" for each "case" at least 3 patients who didn't have a PJI after TJA. RESULTS: 28 patients met all inclusion and exclusion criteria. Comparing the "cases" with "controls" demographics parameters, medical comorbidities and previous intra-articular injection were not associated with an increased risk of PJI. Comparing the "early/delayed group" with "late group", BMI was associated with an increased risk of early/delayed PJI, while demographics parameters, medical comorbidities, and previous intra-articular injection did not significantly increase the risk of PJI. Logistic regression showed that for each BMI unit there was a 20-fold increased risk of early prosthetic infection (OR 1.19, IC 1.03-1.38, p=0.01). Staphylococci were isolated most frequently from pre-operative and intra-operative cultures. Two-stage arthroplasty exchange and surgical debridement resulted in the most performed surgical treatment with a success rate of 88 and 87%. CONCLUSIONS: Obesity is a risk factor for "early/delayed infection" of TJA. Two-stage arthroplasty exchange, debridement, antibiotics, and implant retention in patients are treatments with a high rate of success in terms of reinfection.

The role of procalcitonin outside of the Intensive Care Unit (ICU): a multidisciplinary approach.

OBJECTIVE: Biochemical markers are commonly used in medicine to guide diagnostic investigation or therapy duration and/or monitor treatment efficacy. Due to the emergence and spread of antimicrobial resistance, markers able to prompt a more rational use of antimicrobial therapy are regarded with the greatest attention. Procalcitonin (PCT) certainly stands out among others, yet its role must be better established especially outside of the critical care area. Data about PCT utilization in non-critical patients, optimal negativity cut-offs as well as a protocol for measurement timing are all lacking. MATERIALS AND METHODS: To address these issues, a focus group was set up to propose and endorse shared statements regarding the most beneficial use of PCT in real life as infection marker for non-critical patients, based on the authors' experience and a review of recent literature. RESULTS: A group of nine experts in the fields of Infectious Diseases, Internal Medicine, Microbiology, Clinical Chemistry, Surgery and Medical Economics participated in the discussion of nine pre-specified statements. CONCLUSIONS: The potential role for PCT in differentiating infectious and non-infectious clinical syndromes and guiding antimicrobial therapy discontinuation was acknowledged. Moreover, a shared measurement protocol and desirable cut-offs for the non-critical area were proposed. Finally, observations were made about a reasonable selection of the patient population to be tested.

The use of SAMe in chemotherapy-induced liver injury.

Drug-induced liver injury (DILI) remains the most common cause of acute liver failure in the Western world. Chemotherapy is one of the major class of drugs most frequently associated with idiosyncratic DILI. For this reason, patients who receive chemotherapy require careful assessment of liver function prior to treatment to determine which drugs may not be appropriate and which drug doses should be modified. S-adenosylmethionine (SAMe) is an endogenous agent derived from methionine. Its supplementation is effective in the treatment of liver disease, in particular intrahepatic cholestasis (IHC). The target of this review is to analyze the mechanisms of hepatotoxicity of the principal anticancer agents and the role of SAMe in the prevention of this complication.

Occurrence of nocturia is not mediated by nocturnal hypoxia length and severity in patients with sleep-disordered breathing.

BACKGROUND: Nocturia is highly prevalent in subjects with respiratory sleep disturbances (ie obstructive sleep apnea). The aim of our study is to evaluate whether nocturia is associated with intermittent desaturations or hypoxia length and severity in people undergoing polysomnography. METHODS: We recruited 275 consecutive subjects attending the outpatient clinic for respiratory diseases at Campus Bio-Medico Teaching Hospital. Nocturia was defined as a self-reported voiding frequency ≥ two per night. The groups with and without nocturia were compared with parametric and non-parametric tests, as appropriated. Multivariable logistic regression analysis was used to assess the association of nocturia with patients' characteristics, including oxygen desaturation index (ODI), respiratory efforts (RE) and oxygen saturation below 90% (TST90). RESULTS: Sixty-six (24%) subjects reported nocturia, the median ODI was 15 (8-31), the median RE was 22 (12-38) and the median TST90 was 4.7 (0.3-20.6). ODI and RE were significantly higher in subjects with nocturia as compared with controls. In the multivariable model, ODI was associated with an increased probability of nocturia (OR = 1.03; 95% CI = 1.01-1.06), and the higher the ODI score, the higher the probability to have nocturia (P for trend = 0.038). No significant association was found between TST90 and the occurrence of nocturia. CONCLUSIONS: Intermittent desaturations and not hypoxia length and severity, expressed by TST90, are associated with the occurrence of nocturia in subjects complaining sleep disturbances.

Inflammation as a mediator of the association between osteoporosis and hearing loss in older subjects: a population-based study.

OBJECTIVE: Due to the aging of populations, the prevalence of hearing loss and osteoporosis is increasing. Previous studies have found an association between these conditions. Nevertheless, the pathophysiologic pathway of such an association has not yet been established. The present study aimed at evaluating the association, if any, of hearing loss with osteoporosis in an older unselected population, and whether this association varied according to inflammatory status. PATIENTS AND METHODS: We assessed the association of osteoporosis with a self-reported hearing loss in all 310 subjects aged 75+ living in Tuscania (Italy), without exclusion criteria. Bone density was assessed by calcaneal quantitative ultrasound; osteoporosis was defined as a T-score ≤ -2.5 Standard Deviation. RESULTS: Hearing loss was associated with osteoporosis (OR = 1.84, 95% CI = 1.03-3.28; p = 0.40) in multivariable logistic regression analysis, after adjusting for potential confounders. Analysis of the interaction term indicated that this association varied according to the erythrocyte sedimentation rate, ERS (p = 0.030), and high-sensitivity C reactive protein, hs-CRP (p = 0.017) but not sex (p = 0.832). Of notice, this association was significant only for higher levels of inflammatory parameters (OR = 2.82; 95% CI = 1.15-6.90; p = 0.023 for the higher ERS tertile; and OR = 3.81; 95% CI = 1.36-10.63; p = 0.011 for the higher hs-CRP tertile vs. lower tertiles). CONCLUSIONS: Hearing loss is associated with osteoporosis in community dwelling elderly. Such an association seems to depend upon higher inflammation levels.

Management of diabetes in older adults.

Type 2 diabetes prevalence is high in older adults and is expected to rise in the next decades. Diabetes in the population of frail older adults is accompanied by functional disability, several comorbidities, and premature mortality. A comprehensive geriatric assessment, including functional, cognitive, mental and social status, is advisable for identifying the glycemic targets and glucose-lowering therapies, focused on patient preferences, needs, and risks. The therapeutic options for older adults with diabetes are like those for the adult population. However, the pharmacological treatments must be carefully prescribed and monitored, taking into consideration the patient cognitive capacities, the potentially life-threatening drug-drug interactions, the cardiovascular risk, and with the main goal of avoiding hypoglycemia. Also, a careful nutritional evaluation with appropriate tools, as well as a balanced and periodically monitored physical activity, contribute to an effective tailored care plan, as needed by older adults with diabetes. This review evaluates the currently available hypoglycemic drugs and the current indications to the Italian diabetology community, specifically with regard to the treatment of adults aged 75 years or older with diabetes, including the unmet needs by the guidelines.

Characterization of circadian COPD symptoms by phenotype: Methodology of the STORICO observational study.

Chronic obstructive pulmonary disease (COPD) is one of the leading causes of morbidity and mortality worldwide. The symptoms of COPD are troublesome, variable, can occur during all parts of the 24-h day and have a substantial impact on patients' health status, quality of life and healthcare resource utilization. Reducing symptoms, improving health status and increasing physical activity are major goals in the management of stable COPD. In order to provide effective, patient-oriented care, patients should be evaluated on the basis of lung function, frequency of symptoms and patient-perceived impact of symptoms on their lives and treatment decisions made on a case-by-case basis. The identification of COPD phenotypes is an evolving debate and literature data about the circadian variation of COPD symptoms according to phenotypes are nowadays lacking. The ongoing STORICO (STudio Osservazionale sulla caratteRizzazione dei sIntomi delle 24 ore nei pazienti con BPCO) study (NCT03105999) is aimed to describe by clinically defined phenotypes the frequency and 12-month evolution of early-morning, day- and night-time COPD symptoms in a cohort of 600 Italian patients with stable COPD. Secondary objectives include the description of the 12-month variation of outcomes of interest according to phenotypes and of the healthcare resources utilization (overall and by phenotype) during 12-month observation. An exploratory analysis will be conducted aimed to phenotype COPD patients in an alternative researcher-independent way based on circadian pattern of symptoms combined with measures of respiratory function, health-related quality of life and comorbidity. The present paper describes the methodology of the STORICO study.

Prototypical versus contemporary Mediterranean Diet.

BACKGROUND AND AIMS: To investigate the evolution of the Mediterranean Diet (MD) in a delimited area of Southern Italy, by comparing the diet adopted 60-70 years ago (Prototypical Mediterranean Diet, PMD) with the contemporary one (Contemporary Mediterranean Diet, CMD), and to verify to what extent they fitted the recommendations of the Italian and the USDA dietary guidelines. METHODS: We recruited a total of 106 participants, divided in two groups. PMD group included 52 women aged >80 years, with a good cognitive function and full independence in basic and instrumental activities of daily living. CMD group included 20 men and 34 women aged 50-60 years. Food intake was assessed by administering the EPIC food frequency questionnaire to each participant, and an additional survey to the PMD subjects only. RESULTS: Both PMD and CMD showed adequate intakes of macronutrients, although some deficiencies related to micronutrient requirements were evident. CMD showed a slightly greater use of animal products, processed and sugary foods, and higher intakes of simple sugars, animal proteins (49.6 vs 28.3 g/day), animal lipids (37.8 vs 20.1 g/day), saturated fats (25.0 vs 15.8 g/day) and cholesterol (305.0 vs 258.5 g/day). PMD showed many similarities to the original version of the MD in terms of macronutrients distribution and food choices. CONCLUSION: The documented evolution of the dietary habits over a 70 years timespan suggests that nowadays Mediterranean regions adhere less strictly to the original MD, although nutrients intakes are adequate to LARN and USDA recommendations.

Endoscopic treatment of primary benign central airway tumors: Results from a large consecutive case series and decision making flow chart to address bronchoscopic excision.

BACKGROUND: Benign tracheo-bronchial neoplasms are rare, but potentially dangerous conditions with life threatening consequences. Tumor removal should be pursued by methods minimizing the procedural stress. The role of endoscopic treatment, as an alternative to open surgery, remains controversial. OBJECTIVES: report the twelve-years endoscopic experience in Rome, Italy. Fifty-seven benign tracheo-bronchial tumors were diagnosed and 130 tracheo-bronchial resections by rigid bronchoscopy performed. METHODS: we identified histotypes associated with higher recurrence rate and assessed their relationship with gender, age and tracheo-bronchial location. We provided data on safety and complications and suggested a decision making flow chart to address the patients to endoscopic resection. RESULTS: complete eradication after a single procedure without recurrence at 2 years was obtained in 63.1% of cases (36/57). Need of a second intervention within few months but no further recurrence at follow up was seen in a further 8.8% (5/57). Histotypes associated with recurrence were papillomas and inflammatory polyp. Seven patients (12.3%) were addressed to surgery because of multiple recurrence. Ten patients (17.5%) were lost at follow up. In case of recurrence, the bronchial biopsy was always repeated and no malignant transformation was observed. No major complications, pneumothorax or pneumomediastinum occurred. CONCLUSIONS: endoscopic treatment of benign tracheo bronchial tumors is safe and effective, provided that the procedure is carefully and systematically planned. The rate of eradication is satisfactory and the incidence of complications negligible. This will encourage this approach as first line treatment especially in patients, frequently elderly people, having increased surgical risk due to concomitant respiratory failure or major comorbidities.

Flavonoids and arterial stiffness: promising perspectives.

BACKGROUND AND AIMS: Flavonoids are a group of polyphenol compounds, ubiquitously found in plants. Great emphasis has been given to their possible benefits for cardiovascular health. These beneficial effects may be mediated by a specific action on arterial walls. Arterial stiffness is a marker of vascular aging, increasingly used in the clinical setting and assessed by pulse wave velocity. It has shown to be a robust predictor of cardiovascular events and mortality. This review aims at providing a comprehensive evaluation of available intervention and observational studies examining the relationship between flavonoid consumption and arterial stiffness. DATA SYNTHESIS: A Medline(®) literature search was performed using the keywords "arterial stiffness" and "flavonoids". As a result, 2 cross-sectional and 16 intervention studies assessing the relationship between flavonoids intake and arterial stiffness were retained. Four intervention trials reported a significant decrease of arterial stiffness after a flavonoid-based intervention, independently from blood pressure changes. The two observational studies reported significant associations between a higher flavonoid consumption and a lower arterial stiffness. In this review, isoflavones, anthocyanins and to a lesser extent cocoa flavan-3-ols appeared to be the more efficient to improve vascular function. CONCLUSIONS: Despite their heterogeneity, preliminary data seem to support an improvement of the arterial stiffness related to flavonoid intake. However, further research on absorption and dose-response effects of the specific flavonoid subclasses on arterial structure is warranted.

Colistin bladder instillation, an alternative way of treating multi-resistant Acinetobacter urinary tract infection: a case series and review of literature.

The multiresistant Acinetobacter species bacteria are frequently involved in urinary or respiratory tract infections, and one of the most effective drugs, colistine, is associated with significant nephrotoxicity and neurotoxicity. Given that very high concentrations of colistine into biological fluids are safe for the human organism, attempts have been made at delivering the drug topically, by aerosol, or, occasionally, intratechally or intraventricularly for meningitis. These topical treatments could eradicate the Pseudomonas sp. from the lung of patients with cystic fibrosis or bronchiectasis and the Acinetobacter baumannii from lung and meninges. However, only one case of colistin topic treatment in urinary tract infection is described. We report a case series of three patients successfully undergone colistin bladder instillations for multi drug resistant Acinetobacter urinary tract infection, and we review the literature about colistin topic treatment.

The oxygen therapy.

Oxygen (O(2)) is a vital element. Shortage of O(2) results in deranged metabolism and important changes in vascular tone with opposite effects on the systemic and pulmonary circulation. During hypoxemia, oxidative stress exposes the organism to a sort of accelerated senescence as well as to several acute untoward effects. Thus, hypoxemia should be promptly recognized and treated, hopefully by measures tailored to the pathophysiological mechanisms underlying hypoxemia. However, O(2) therapy remains the most common therapy of hypoxemia, but it must be carefully tailored to relieve hypoxemia without provoking hyperoxia or hypercarbia. Then, the individual response to O(2) as well as changing needs of O(2) during sleep or exercise must be evaluated to provide the best O(2) therapy. Hyperoxia, the effect of overcorrection of hypoxia, can dramatically impact the health status and threaten the survival of the newborn and, through different mechanisms and effects, the adult. A thorough knowledge of the pathophysiological bases of hypoxemia and O(2) storage and delivery devices is then mandatory to administer O(2) therapy guaranteeing for optimal correction of hypoxemia and minimizing the risk of hyperoxia. Consistent with this aim also is a careful scrutiny of instruments and procedures for monitoring the individual response to O(2) over time. Thus, at variance from classical pharmacological therapy, performing O(2) therapy requires a vast array of clinical and technical competences. The optimal integration of these competences is needed to optimize O(2) therapy on individual bases.

Pulmonary diffusing capacity for carbon monoxide: a marker of depressed hypercapnic drive in type 1 diabetes mellitus?

AIMS: Decreased chemosensitivity to hypercapnia, a common finding in Type 1 diabetes mellitus, seems related to autonomic neuropathy. We proposed to verify whether simple neuroautonomic cardiovascular tests or indexes of severity of diabetes and respiratory impairment can identify patients with such a dysfunction, but no clinical evidence of autonomic neuropathy. METHODS: Forty patients with Type 1 diabetes, 20 with autonomic neuropathy according to the results of a standardized test battery, were studied and compared with 40 normal subjects matched by age and sex. Spirometry and pulmonary diffusing capacity for carbon monoxide were performed. The chemosensitivity to hypercapnia was tested by the rebreathing method. RESULTS: There was no significant difference between patients with and without autonomic neuropathy in chemosensitivity to hypercapnia, as expressed by the ventilation response to increasing end-tidal pressure of carbon dioxide; however, it was lower in the whole group of patients with diabetes than in control subjects (1.71 ± 0.80 vs. 2.45 ± 1.11 l⁻¹ min⁻¹ mmHg, respectively, P=0.002). No significant correlation was found between ventilation response to increasing end-tidal pressure of carbon dioxide and the results of autonomic tests. In patients with diabetes mellitus, the ventilatory response to hypercapnia significantly correlated with pulmonary diffusing capacity for carbon monoxide (Spearman's rho=0.387, P=0.013) and this was the only variable significantly associated with ventilation response to increasing end-tidal pressure of carbon dioxide in a multiple regression model. CONCLUSIONS: Chemosensitivity to hypercapnia was depressed in patients with diabetes mellitus, irrespective of autonomic neuropathy, in comparison with control subjects. The correlation with pulmonary diffusing capacity for carbon monoxide suggests that microcirculatory damage might contribute to depress the central chemosensitivity.

Effect of local and remote ischemic preconditioning on endothelial function in young people and healthy or hypertensive elderly people.

To verify whether age affects remote preconditioning, we compared healthy young people (mean age = 28.0 years, SD: 7.2), healthy elderly people (age = 69.2 years, SD: 5.0), and hypertensive elderly people (group 3, age = 72.8 years, SD: 3.9). Each group included 10 participants. The flow-mediated-dilation (FMD) was measured after local (same arm) and remote (leg) ischemic preconditioning. Healthy elderly people had the greatest increase of FMD after ischemic preconditioning compared to baseline (173% after local and 181% after remote preconditioning) and young participants the smallest increase (77% after local and 69% after remote preconditioning) while hypertensive elderly had an intermediate increase (P for comparison across groups: 0.347 for local and 0.064 for remote preconditioning). However, absolute values of FMD after preconditioning were much lower in elderly hypertensive than in healthy young adults. Remote preconditioning increases endothelial reactivity in healthy and hypertensive elderly. The potential clinical relevance of this finding deserves consideration.

Ageing and COPD affect different domains of nutritional status: the ECCE study.

Chronic obstructive pulmonary disease (COPD) and ageing may contribute to malnutrition. We aimed to explore whether COPD and ageing determine malnutrition in different manners. 460 stable COPD outpatients (376 males and 84 females) from the Extrapulmonary Consequences of COPD in the Elderly (ECCE) study database were investigated (age 75.0±5.9 yrs; forced expiratory volume in 1 s 54.7±18.3% predicted). Nutritional status was evaluated using the Mini Nutritional Assessment® (MNA) questionnaire. From the MNA, three scores exploring the domains of the nutritional status were calculated: body composition, energy intake and body functionality scores. Global Initiative for Chronic Obstructive Lung Disease (GOLD) stages were negatively correlated with five MNA items exploring mobility, patient's perception of own nutrition and health status, and arm and calf circumferences (lowest Spearman's rho (rs)=-0.011; highest p=0.039). GOLD stages were independently correlated with body composition and body functionality scores (model r2=0.073). Age was negatively correlated with four MNA items exploring loss of appetite, fluid intake, mobility and autonomy in daily life (lowest rs=-0.013; highest p=0.030). Age was independently correlated with body functionality score (model r2=0.037). Severe COPD and ageing are independent and probably concurrent conditions leading to malnutrition. The MNA questionnaire allows a valuable insight into the complexity of components of nutritional status and may provide useful clues for treatment strategies.

Ultrasound imaging of the sural nerve: ultrasound anatomy and rationale for investigation.

BACKGROUND: Damage to the sural nerve (SuN) may arise from surgical stripping or thermal ablation of the small saphenous vein (SSV). OBJECTIVE: This study aims to demonstrate that visualisation of the SuN and its point of contact with the SSV ('risk point') using ultrasound imaging can be achieved in routine clinical practice. TYPE OF STUDY: This is a cohort study. PATIENTS: Fifteen normal subjects and five patients with chronic venous insufficiency (CVI) (two with a dilated, incompetent SSV). METHOD: The SuN was identified using high-resolution ultrasound imaging using 14- and 18-MHz probes. Two manoeuvres were found to improve visualisation: (1) the contrast of the nerve was increased compared with the other tissues by varying the angle of insonation; and (2) the transducer was moved up and down the limb for a short distance during transverse imaging of the calf. The muscles and other soft tissues appeared 'out of focus', whereas the SuN retained both shape and echogenicity. Once the nerve has been identified, proceeding proximally, the point of separation of the two components is often detectable. It is then possible to follow the two different nerves observing the medial sural cutaneous nerve (MSCN) inside the 'triangle' of connective tissue below the SSV joining the tibial nerve and the lateral sural cutaneous nerve (LCSN) joining the common peroneal nerve, which runs inside a tiny fascial duplication. The extent of nerves, which were identified, was recorded in each limb as well as their anatomical distribution. RESULTS: The SuN and the point at which it might be at risk were identified on ultrasound images in 39 of 40 limbs (97%) studied. In transverse section, it was readily identified within the saphenous compartment. It lies in close proximity to the SSV only in the distal third of the limb, where the two components of the nerve: MSCN, a branch of the tibial nerve; and LSCN, a branch of the common peroneal nerve join together. The relationship between the SuN and the SSV is very variable, with the nerve running separately or in close contact with the vein for variable distances, in many different combinations. CONCLUSIONS: The SuN and 'risk point' can be identified by ultrasonography (US). We propose that this technique could be used to prevent damage to the SuN during surgical or thermal ablation of the SSV and during Achilles tendon surgery.