Positional contrastive learning for improved thigh muscle segmentation in MR images.

The accurate segmentation of individual muscles is essential for quantitative MRI analysis of thigh images. Deep learning methods have achieved state-of-the-art results in segmentation, but they require large numbers of labeled data to perform well. However, labeling individual thigh muscles slice by slice for numerous volumes is a laborious and time-consuming task, which limits the availability of annotated datasets. To address this challenge, self-supervised learning (SSL) emerges as a promising technique to enhance model performance by pretraining the model on unlabeled data. A recent approach, called positional contrastive learning, exploits the information given by the axial position of the slices to learn features transferable on the segmentation task. The aim of this work was to propose positional contrastive SSL for the segmentation of individual thigh muscles from MRI acquisitions in a population of elderly healthy subjects and to evaluate it on different levels of limited annotated data. An unlabeled dataset of 72 T1w MRI thigh acquisitions was available for SSL pretraining, while a labeled dataset of 52 volumes was employed for the final segmentation task, split into training and test sets. The effectiveness of SSL pretraining to fine-tune a U-Net architecture for thigh muscle segmentation was compared with that of a randomly initialized model (RND), considering an increasing number of annotated volumes (S = 1, 2, 5, 10, 20, 30, 40). Our results demonstrated that SSL yields substantial improvements in Dice similarity coefficient (DSC) when using a very limited number of labeled volumes (e.g., for S = 1, DSC 0.631 versus 0.530 for SSL and RND, respectively). Moreover, enhancements are achievable even when utilizing the full number of labeled subjects, with DSC = 0.927 for SSL and 0.924 for RND. In conclusion, positional contrastive SSL was effective in obtaining more accurate thigh muscle segmentation, even with a very low number of labeled data, with a potential impact of speeding up the annotation process in clinics.

Dopamine Pharmacodynamics: New Insights.

Dopamine is a key neurotransmitter involved in physiological processes such as motor control, motivation, reward, cognitive function, and maternal and reproductive behaviors. Therefore, dysfunctions of the dopaminergic system are related to a plethora of human diseases. Dopamine, via different circuitries implicated in compulsive behavior, reward, and habit formation, also represents a key player in substance use disorder and the formation and perpetuation of mechanisms leading to addiction. Here, we propose dopamine as a model not only of neurotransmission but also of neuromodulation capable of modifying neuronal architecture. Abuse of substances like methamphetamine, cocaine, and alcohol and their consumption over time can induce changes in neuronal activities. These modifications lead to synaptic plasticity and finally to morphological and functional changes, starting from maladaptive neuro-modulation and ending in neurodegeneration.

Advancing healthcare through thoracic ultrasound research in older patients.

This paper reports the proceedings of a meeting convened by the Research Group on Thoracic Ultrasound in Older People of the Italian Society of Gerontology and Geriatrics, to discuss the current state-of-the-art of clinical research in the field of geriatric thoracic ultrasound and identify unmet research needs and potential areas of development. In the last decade, point-of-care thoracic ultrasound has entered clinical practice for diagnosis and management of several respiratory illnesses, such as bacterial and viral pneumonia, pleural effusion, acute heart failure, and pneumothorax, especially in the emergency-urgency setting. Very few studies, however, have been specifically focused on older patients with frailty and multi-morbidity, who frequently exhibit complex clinical pictures needing multidimensional evaluation. At the present state of knowledge, there is still uncertainty on the best requirements of ultrasound equipment, methodology of examination, and reporting needed to optimize the advantages of thoracic ultrasound implementation in the care of geriatric patients. Other issues regard differential diagnosis between bacterial and aspiration pneumonia, objective grading of interstitial syndrome severity, quantification and monitoring of pleural effusions and solid pleural lesions, significance of ultrasonographic assessment of post-COVID-19 sequelae, and prognostic value of assessment of diaphragmatic thickness and motility. Finally, application of remote ultrasound diagnostics in the community and nursing home setting is still poorly investigated by the current literature. Overall, the presence of several open questions on geriatric applications of thoracic ultrasound represents a strong call to implement clinical research in this field.

Prognostic Significance of Chest Imaging by LUS and CT in COVID-19 Inpatients: The ECOVID Multicenter Study.

BACKGROUND: Point-of-care lung ultrasound (LUS) score is a semiquantitative score of lung damage severity. High-resolution computed tomography (HRCT) is the gold standard method to evaluate the severity of lung involvement from the novel coronavirus disease (COVID-19). Few studies have investigated the clinical significance of LUS and HRCT scores in patients with COVID-19. Therefore, the aim of this study was to evaluate the prognostic yield of LUS and of HRCT in COVID-19 patients. METHODS: We carried out a multicenter, retrospective study aimed at evaluating the prognostic yield of LUS and HRCT by exploring the survival curve of COVID-19 inpatients. LUS and chest CT scores were calculated retrospectively by 2 radiologists with >10 years of experience in chest imaging, and the decisions were reached in consensus. LUS score was calculated on the basis of the presence or not of pleural line abnormalities, B-lines, and lung consolidations. The total score (range 0-36) was obtained from the sum of the highest scores obtained in each region. CT score was calculated for each of the 5 lobes considering the anatomical extension according to the percentage parenchymal involvement. The resulting overall global semiquantitative CT score was the sum of each single lobar score and ranged from 0 (no involvement) to 25 (maximum involvement). RESULTS: One hundred fifty-three COVID-19 inpatients (mean age 65 ± 15 years; 65% M), including 23 (15%) in-hospital deaths for any cause over a mean follow-up of 14 days were included. Mean LUS and CT scores were 19 ± 12 and 10 ± 7, respectively. A strong positive linear correlation between LUS and CT scores (Pearson correlation r = 0.754; R2 = 0.568; p < 0.001) was observed. By ROC curve analysis, the optimal cut-point for mortality prediction was 20 for LUS score and 4.5 for chest CT score. According to Kaplan-Meier survival analysis, in-hospital mortality significantly increased among COVID-19 patients presenting with an LUS score ≥20 (log-rank 0.003; HR 9.87, 95% CI: 2.22-43.83) or a chest CT score ≥4.5 (HR 4.34, 95% CI: 0.97-19.41). At multivariate Cox regression analysis, LUS score was the sole independent predictor of in-hospital mortality yielding an adjusted HR of 7.42 (95% CI: 1.59-34.5). CONCLUSION: LUS score is useful to stratify the risk in COVID-19 patients, predicting those that are at high risk of mortality.

The role of the Sunfrail tool in the screening of frailty and in integrated community-hospital care pathways: a retrospective observational study.

BACKGROUND: One of the most problematic expression of ageing is frailty, and an approach based on its early identification is mandatory. The Sunfrail-tool (ST), a 9-item questionnaire, is a promising instrument for screening frailty. AIMS: To assess the diagnostic accuracy and the construct validity between the ST and a Comprehensive Geriatric Assessment (CGA), composed by six tests representative of the bio-psycho-social model of frailty; To verify the discriminating power of five key-questions of the ST; To investigate the role of the ST in a clinical-pathway of falls' prevention. METHODS: In this retrospective study, we enrolled 235 patients from the Frailty-Multimorbidity Lab of the University-Hospital of Parma. The STs' answers were obtained from the patient's clinical information. A patient was considered frail if at least one of the CGAs' tests resulted positive. RESULTS: The ST was associated with the CGA's judgement with an Area Under the Curve of 0.691 (CI 95%: 0.591-0.791). Each CGA's test was associated with the ST total score. The five key-question showed a potential discriminating power in the CGA's tests of the corresponding domains. The fall-related question of the ST was significantly associated with the Short Physical Performance Battery total score (OR: 0.839, CI 95%: 0.766-0.918), a proxy of the risk of falling. DISCUSSION: The results suggest that the ST can capture the complexity of frailty. The ST showed a good discriminating power, and it can guide a second-level assessment to key frailty domains and/or clinical pathways. CONCLUSIONS: The ST is a valid and easy-to-use instrument for the screening of frailty.

Gait characteristics in community-dwelling older persons with low skeletal muscle mass and low physical performance.

BACKGROUND: Demographic changes in the western world entail new clinical approaches and challenges in older persons. Low skeletal muscle mass and low physical performance in older persons are both predisposing conditions for disability and obtaining knowledge in this cohort is essential. AIM: The primary aim of the study was to analyze a broader spectrum of gait characteristics within this specific population and differentiate them across different test conditions. METHODS: Two centers participating at the SPRINTT project with hi-tech gait analysis available conducted a cross-sectional descriptive study on N = 115 community-dwelling older persons with low muscle mass and physical performance. Reference values of 13 gait parameters were collected across different conditions: usual gait speed, fast gait speed, and usual gait speed while simultaneously naming animals. RESULTS AND DISCUSSION: This study shows the first spatio-temporal reference values in a community-dwelling older population composed of individuals with low skeletal muscle mass and low physical performance. In comparison to the normative spatio-temporal gait parameters in older persons reported in the literature, this population showed some differences. The mean gait speed was lower than 1 m/s, considered as a cutoff for vulnerable community-dwelling individuals, which corresponds to a greater risk of falls, hospitalization, and mortality. The stride length variability was higher, exposing to a greater risk of falling, and was also associated with a higher risk of developing cognitive decline. CONCLUSION: This study represents the first step in the development of quantitative reference values in community-dwelling older persons with low physical performance and low skeletal muscle mass.

Gut microbiota and motoric-cognitive frailty in hospitalized older persons.

PURPOSE OF REVIEW: In older people, many systems spontaneously change without diseases. Because of the ageing process, the gut microbiota undergoes a reduced species richness, altered balance between species, with an increased interindividual variability. The result is the reduced resilience in the presence of diseases and medications. These changes are more evident in older persons with neurodegenerative diseases and cognitive-motoric frailty. RECENT FINDINGS: A relationship between liver alteration, gut microbiota and the presence of viruses and gram-bacteria is conceivable. They determine the acceleration of neurodegenerative diseases with cognitive and motoric frailty. Hospitalization represents one of the stressors for the gut microbiota, producing dysbiosis and increasing the representation of pathobionts. The gut microbiota alterations during hospitalization may be associated with negative clinical outcomes. This phenomenon together with liver dysfunction could produce an acceleration of the trajectory of cognitive-motoric frailty towards disability and mortality. The observation that predisability is associated of both losses of cognition and motoric performance, has allowed introducing a new syndrome, the motoric-cognitive risk syndrome, which is a condition of increased risk of dementia and mobility-disability. SUMMARY: The interaction between liver and gut microbiota may accelerate the neurodegenerative diseases and represents a promising marker of prognostic trajectories in older patients.

Relationship between comprehensive geriatric assessment and amyloid PET in older persons with MCI.

BACKGROUND: The association between amyloid deposition and cognitive, behavioral and physical performance in mild cognitive impairment (MCI) due to Alzheimer's disease (AD) has been poorly investigated, especially in older persons. METHODS: We studied the in vivo correlation between the amyloid deposition at Positron Emission Tomography (amyloid-PET) and the presence of memory loss, reduced executive function, neuropsychiatric symptoms and physical performance in older persons with MCI. Amyloid-PET was performed with 18F-flutemetamol and quantitatively analyzed. RESULTS: We evaluated 48 subjects, 21 men and 27 women. We performed in each patient a comprehensive geriatric assessment (CGA) including Mini Mental State Examination (MMSE), Clock Drawing Test (CDT), Activity Daily Living (ADL), Instrumental Activity of Daily Living (IADL), Neuropsychiatric inventory (NPI) questionnaire, 15 Geriatric Depression Scale (GDS), Short Physical Performance Battery (SPPB) and Hand Grip strength. Then, each patient underwent amyloid-PET. Mean age of the enrolled subjects was 74.6 ± 7.8 years. All of these subjects showed preserved cognitive function at MMSE > 24, while 29 of 48 subjects (61.0%) had altered CDT. Mean NPI score was 6.9 ± 5.9. The mean value of SPPB score was 9.0 ± 2.6, while the average muscle strength of the upper extremities measured by hand grip was 25.6 ± 7.7 Kg. CT/MRI images showed cortical atrophic changes in 26 of the 48 examined subjects (54.0%), while cerebrovascular modifications were present in 31 subjects (64.5%). Pathological burden of amyloid deposits was detected in 25 of 48 (52.0%) patients with a mean value of global z-score of 2.8 (subjects defined as MCI due to AD). After stratifying subjects in subclasses of clinical alterations, more probability of pathological amyloid deposition was found in subjects with impaired CDT and higher NPI score (O.R. = 3.45 [1.01-11.2], p = 0.04), with both impaired CDT and low physical performance (O.R. = 5.80 [1.04-32.2], p = 0.04), with altered CDT and high NPI score (O.R. = 7.98 [1.38-46.0], p = 0.02), and finally in those subjects with altered CDT, high NPI and low physical performance (O.R. = 5.80 [1.05-32.2], p = 0.04). CONCLUSION: Our findings support the recent hypothesis that amyloid deposition could be associated with multiple cerebral dysfunction, mainly affecting executive, behavioral and motor abilities.

Delirium in COVID-19: epidemiology and clinical correlations in a large group of patients admitted to an academic hospital.

BACKGROUND: Delirium incidence and clinical correlates in coronavirus disease-19 (COVID-19) pneumonia are still poorly investigated. AIM: To describe the epidemiology of delirium in patients hospitalized for suspect COVID-19 pneumonia during the pandemic peak in an academic hospital of Northern Italy, identify its clinical correlations and evaluate the association with mortality. METHODS: The clinical records of 852 patients admitted for suspect COVID-19 pneumonia, defined as respiratory symptoms or fever or certain history of contact with COVID-19 patients, plus chest CT imaging compatible with alveolar-interstitial pneumonia, were retrospectively analyzed. Delirium was defined after careful revision of daily clinical reports in accordance with the Confusion Assessment Method criteria. Data on age, clinical presentation, comorbidities, drugs, baseline lab tests and outcome were collected. The factors associated with delirium, and the association of delirium with mortality, were evaluated through binary logistic regression models. RESULTS: Ninety-four patients (11%) developed delirium during stay. They were older (median age 82, interquartile range, IQR 78-89, vs 75, IQR 63-84, p < 0.001), had more neuropsychiatric comorbidities and worse respiratory exchanges at baseline. At multivariate models, delirium was independently and positively associated with age [odds ratio (OR) 1.093, 95% confidence interval (CI) 1.046-1.143, p < 0.001], use of antipsychotic drugs (OR 4.529, 95% CI 1.204-17.027, p = 0.025), serum urea and lactate-dehydrogenase at admission. Despite a higher mortality in patients with delirium (57% vs 30%), this association was not independent of age and respiratory parameters. CONCLUSIONS: Delirium represents a common complication of COVID-19 and a marker of severe disease course, especially in older patients with neuropsychiatric comorbidity.

Treatment of Delirium in Older Persons: What We Should Not Do!

The presentation of common acute diseases in older age is often referred to as "atypical". Frequently, the symptoms are neither single nor tissue related. In most cases, the onset of symptoms and diseases is the expression of a diminished reserve with a failure of the body system and imbalance of brain function. Delirium is one of the main devastating and prevalent atypical symptoms and could be considered as a geriatric syndrome. It encompasses an array of neuropsychiatric symptoms and represents a disarrangement of the cerebral function in response to one or more stressors. The most recent definition, reported in the DSM-V, depicts delirium as a clear disturbance in attention and awareness. The deficit is to be developed in a relatively short time period (usually hours or days). The attention disorder must be associated with another cognitive impairment in memory, orientation, language, visual-spatial or perception abilities. For the treatment, it is imperative to remove the potential causes of delirium before prescribing drugs. Even a non-pharmacological approach to reducing the precipitating causes should be identified and planned. When we are forced to approach the pharmacological treatment of hyperactive delirium in older persons, we should select highly cost-effective drugs. High attention should be devoted to the correct balance between improvement of psychiatric symptoms and occurrence of side effects. Clinicians should be guided in the correct choice of drugs following cluster symptoms presentation, excluding drugs that could potentially produce complications rather than advantages. In this brief point-of-view, we propose a novel pharmacological flow-chart of treatment in relation to the basic clusters of diseases of an older patient acutely admitted to the hospital and, in particular, we emphasize "What We Should Not Do!", with the intention of avoiding possible side effects of drugs used.

The Gut-Muscle Axis in Older Subjects with Low Muscle Mass and Performance: A Proof of Concept Study Exploring Fecal Microbiota Composition and Function with Shotgun Metagenomics Sequencing.

The gut microbiota could influence the pathophysiology of age-related sarcopenia through multiple mechanisms implying modulation of chronic inflammation and anabolic resistance. The aim of this study was to compare the fecal microbiota composition and functionality, assessed by shotgun metagenomics sequencing, between two groups of elderly outpatients, differing only for the presence of primary sarcopenia. Five sarcopenic elderly subjects and twelve non-sarcopenic controls, classified according to lower limb function and bioimpedance-derived skeletal muscle index, provided a stool sample, which was analyzed with shotgun metagenomics approaches, to determine the overall microbiota composition, the representation of bacteria at the species level, and the prediction of bacterial genes involved in functional metabolic pathways. Sarcopenic subjects displayed different fecal microbiota compositions at the species level, with significant depletion of two species known for their metabolic capacity of producing short-chain fatty acids (SCFAs), Faecalibacterium prausnitzii and Roseburia inulinivorans, and of Alistipes shahii. Additionally, their fecal metagenome had different representation of genes belonging to 108 metabolic pathways, namely, depletion of genes involved in SCFA synthesis, carotenoid and isoflavone biotransformation, and amino acid interconversion. These results support the hypothesis of an association between microbiota and sarcopenia, indicating novel possible mediators, whose clinical relevance should be investigated in future studies.

Exercise and immune system as modulators of intestinal microbiome: implications for the gut-muscle axis hypothesis.

Exercise is a possible modulator of intestinal microbiome composition, since some investigations have shown that it is associated with increased biodiversity and representation of taxa with beneficial metabolic functions. Conversely, training to exhaustion can be associated with dysbiosis of the intestinal microbiome, promoting inflammation and negative metabolic consequences. Gut microbiota can, in turn, influence the pathophysiology of several distant organs, including the skeletal muscle. A gut-muscle axis may in fact regulate muscle protein deposition and muscle function. In older individuals, this axis may be involved in the pathogenesis of muscle wasting disorders through multiple mechanisms, involving transduction of pro-anabolic stimuli from dietary nutrients, modulation of inflammation and insulin sensitivity. The immune system plays a fundamental role in these processes, being influenced by microbiome composition and at the same time contributing to shape microbial communities. In this review, we summarize the most recent literature acquisitions in this field, disentangling the complex relationships between exercise, microbiome, immune system and skeletal muscle function and proposing an interpretative framework that will need verification in future studies.

Physical performance across the thyroid function values within the normal range in adult and older persons.

BACKGROUND: Thyroid hormone variation may be correlated with adverse health outcomes, even within the normal reference range in euthyroid individuals. AIMS: To determine the association between plasma thyroid-stimulating hormone (TSH), free triiodothyronine (FT3), and free thyroxine (FT4) levels and physical performance score in middle age and older adults who had levels of all three hormones in the normal range. METHODS: In this community-based, cross-sectional study, euthyroid participants of the Invecchiare in Chianti study, aged 23-102 years (N = 1060), were considered. Physical performance was evaluated by the Summary Physical Performance Battery (SPPB) score. Plasma TSH, FT3, and FT4 levels were predictors, and SPPB score was the outcome. RESULTS: At the univariate analyses, TSH, FT4, and FT3 were not significantly associated with SPPB score in young individuals, whereas, in older participants, SBBP score was positively (P < 0.001) associated with FT3, and negatively associated with both TSH (P < 0.02) and FT4 (P < 0.001). After adjusting for multiple confounders, FT3 remained significantly associated with SPPB (beta ± SE, 0.35 ± 0.17, P = 0.04), but FT4 and TSH were not. Results did not change when all the three hormones FT3, FT4, and TSH were simultaneously considered in the fully adjusted model (beta ± SE for FT3, 0.37 ± 0.18, P = 0.04). DISCUSSION: The results of this study demonstrate that SPPB score is positively associated with circulating FT3 but not with FT4 or with TSH, in older euthyroid individuals. CONCLUSIONS: In euthyroid older adults, circulating FT3 may play an important role in the thyroid effects on physical function.

Short-Physical Performance Battery (SPPB) score is associated with falls in older outpatients.

BACKGROUND: The capacity of Short-Physical Performance Battery (SPPB) test to discriminate between fallers and non-fallers is controversial, and has never been compared with fall risk assessment-specific tools, such as Performance-Oriented Mobility Assessment (POMA). AIM: To verify the association of SPPB and POMA scores with falls in older outpatients. METHODS: 451 older subjects (150 males, mean age 82.1 ± 6.8) evaluated in a geriatric outpatient clinic for suspected frailty were enrolled in this cross-sectional study. Self-reported history of falls and medication history were carefully assessed. Each participant underwent comprehensive geriatric assessment, including SPPB, POMA, Geriatric Depression Scale (GDS), mini-mental state examination (MMSE) and mini-nutritional assessment-short form (MNA-SF). Multivariate logistic regression and receiver-operating characteristic (ROC) analyses were performed to determine the factors associated with the status of faller. RESULTS: 245 (54.3%) subjects were identified as fallers. They were older and had lower SPPB and POMA test scores than non-fallers. At ROC analysis, SPPB (AUC 0.676, 95% CI 0.627-0.728, p < 0.001) and POMA (AUC 0.677, 95% CI 0.627-0.726, p < 0.001) scores were both associated with falls. At multivariate logistic regression models, SPPB total score (OR 0.83, 95% CI 0.76-0.92, p < 0.001), POMA total score (OR 0.94, 95% CI 0.91-0.98, p = 0.002) and SPPB balance score alteration (OR 2.88, 95% CI 1.42-5.85, p = 0.004), but not POMA balance subscale score alteration, were independently associated with recorded falls, as also GDS, MMSE and MNA-SF scores. CONCLUSIONS: SPPB total score was independently associated with reported falls in older outpatients, resulting non-inferior to POMA scale. The use of SPPB for fall risk assessment should be implemented.

Understanding the gut-kidney axis in nephrolithiasis: an analysis of the gut microbiota composition and functionality of stone formers.

OBJECTIVES: The involvement of the gut microbiota in the pathogenesis of calcium nephrolithiasis has been hypothesised since the discovery of the oxalate-degrading activity of Oxalobacter formigenes, but never comprehensively studied with metagenomics. The aim of this case-control study was to compare the faecal microbiota composition and functionality between recurrent idiopathic calcium stone formers (SFs) and controls. DESIGN: Faecal samples were collected from 52 SFs and 48 controls (mean age 48±11). The microbiota composition was analysed through 16S rRNA microbial profiling approach. Ten samples (five SFs, five controls) were also analysed with deep shotgun metagenomics sequencing, with focus on oxalate-degrading microbial metabolic pathways. Dietary habits, assessed through a food-frequency questionnaire, and 24-hour urinary excretion of prolithogenic and antilithogenic factors, including calcium and oxalate, were compared between SFs and controls, and considered as covariates in the comparison of microbiota profiles. RESULTS: SFs exhibited lower faecal microbial diversity than controls (Chao1 index 1460±363vs 1658±297, fully adjusted p=0.02 with stepwise backward regression analysis). At multivariate analyses, three taxa (Faecalibacterium, Enterobacter, Dorea) were significantly less represented in faecal samples of SFs. The Oxalobacter abundance was not different between groups. Faecal samples from SFs exhibited a significantly lower bacterial representation of genes involved in oxalate degradation, with inverse correlation with 24-hour oxalate excretion (r=-0.87, p=0.002). The oxalate-degrading genes were represented in several bacterial species, whose cumulative abundance was inversely correlated with oxaluria (r=-0.85, p=0.02). CONCLUSIONS: Idiopathic calcium SFs exhibited altered gut microbiota composition and functionality that could contribute to nephrolithiasis physiopathology.

Low incidence of pneumonia in COPD patients treated with inhaled corticosteroids undergoing pulmonary rehabilitation.

BACKGROUND: Based on meta-analyses results, it is currently acknowledged that there is an increased risk of pneumonia in patients with chronic obstructive pulmonary disease (COPD) undergoing inhaled corticosteroids (ICS) treatment. However, this is not found to be true in those with asthma. No data on this risk are available for COPD patients involved in pulmonary rehabilitation program (PR). METHODS: For 1 year, we prospectively studied 2 cohorts of COPD patients-undergoing PR and not undergoing PR. The first group included 438 patients undergoing PR of which 353 were treated with ICS, and 85 were treated with bronchodilators only. The second group was comprised of 76 COPD patients who were treated with ICS, but not PR. The control group consisted of 49 ICS-treated patients with asthma. The diagnosis of pneumonia, when suspected, had to be confirmed with a chest x-ray. RESULTS: Overall, 6 cases of pneumonia were diagnosed in the first study group: 5 ICS-treated patients and 1 patient treated only with bronchodilators. This corresponded to a rate of 1.41 and 1.17%, respectively, compared to a rate of 6.6% in COPD patients not treated with PR, which was significantly higher (p = 0.029) than that in the first study group. No case of pneumonia was registered among patients with asthma. CONCLUSIONS: These findings suggest that a significantly lower incidence of pneumonia is found in COPD patients treated with ICS and PR than in patients treated with ICS but not with PR. This observation deserves to be investigated in large populations of PR-treated COPD patients, possibly in multi-centric cohort studies.

Assessing sarcopenia with vastus lateralis muscle ultrasound: an operative protocol.

BACKGROUND: Muscle ultrasound (MUS) has so far not been implemented for sarcopenia assessment in clinical geriatric practice due to allegedly low reproducibility of results in the absence of standardization of procedures. However, rigorous and standardized application of this technique yields highly reproducible results. Its application, especially if integrated with clinical evaluation and comprehensive geriatric assessment, proofs very useful for rapidly obtaining information on muscle mass and architecture. OBJECTIVE: Here, we present a standardized protocol for performing right vastus lateralis (RVL) MUS and measuring parameters of muscle size and architecture. METHODS: RVL muscle thickness (MT), fascicle length (FL), pennation angle (PA), echo-intensity (EI) and cross-sectional area (CSA) can be assessed with this protocol. A portable instrument equipped with a 5-cm long 3-11 mHz linear probe should be used with both B-mode real-time and extended-field-of-view (EFOV) techniques. Longitudinal B-mode and transverse EFOV images should be acquired during each exam, and analyzed with NIH-ImageJ software. CONCLUSIONS: This operative protocol represents a good compromise between the feasibility of MUS in clinical settings and the need of obtaining precise measurements of muscle parameters. Future studies should verify the reproducibility of the proposed technique, and its correlation with appendicular lean mass and parameters of muscle function.

Molecular and Clinical Issues about the Risk of Venous Thromboembolism in Older Patients: A Focus on Parkinson's Disease and Parkinsonism.

Venous thromboembolism (VTE) is a common and potentially life-threatening condition which includes both deep-vein thrombosis (DVT) and pulmonary embolism (PE). VTE has a significant clinical and epidemiological impact in the elderly, and its incidence increases to more than 1% per year in older patients, suggesting the presence of specific age-related risk factors in this population. Immobilization seems to predominate as the main cause in patients admitted for medical acute illness in medicine wards, and there is evidence of a high risk in older patients with immobilization resulting from advanced forms of Parkinson’s disease (PD), regardless of the presence of an acute medical condition. In this review, we would to discuss the recent evidence on clinical, molecular and epidemiological features of VTE in older frail subjects focusing on patients with PD and parkinsonism. We also discuss some therapeutic issues about the risk prevention and we suggest a thorough comprehensive geriatric assessment that can represent an optimal strategy to identify and prevent the VTE risk in these patients.

"Brain-muscle loop" in the fragility of older persons: from pathophysiology to new organizing models.

BACKGROUND: The imperative action of the geriatric medicine is to prevent disability in older persons. Many epidemiological studies have been conducted in the last decades for improving knowledge of the aging process and their interactions with age-related diseases, especially for the identification of the relationship between sarcopenia and loss of mobility. Factors influencing muscle integrity can be classified into six main physiologic subsystems, but the central nervous system certainly plays a crucial role for maintaining muscle integrity in older persons. Recent data show that the reduced muscle strength and not muscle mass could be considered the core of the fragility in predicting changes of gait velocity and mobility and conferring a higher risk of mortality in older persons. Sarcopenia and cognitive decline could, therefore, produce slow gait velocity in older persons, with devastating effect and consequences. Perhaps the most notorious corollary is falling, which is often caused by an underlying gait problem. Injuries caused by accidental falls range from relatively innocent bruises to major fractures or head trauma. Another important consequence is reduced mobility, which leads to loss of independence. This immobility is often compounded by a fear of falling, which further immobilises patients and affects their quality of life and physical performance. HYPOTHESIS: When we search the association between brain pathology and muscle function in older persons, we amazingly find that established composite measure of physical frailty is associated with brain pathology. Sarcopenia, which produces muscle dysfunction, slow gait velocity and cognitive decline, could share a strong bidirectional relationship, and this suggests the coexistence of both cognitive and motor dysfunctions in older persons to characterize a new syndrome characterized by slow gait and cognitive complaints, the motoric-cognitive risk syndrome (MRC). AIM: In this review, we want to emphasize the relationship between memory complaints with muscle function integrating cognitive and physical evaluation, even with amyloid PET study, to identify older patients at high risk of cognitive and physical decline.

The association of serum procalcitonin and high-sensitivity C-reactive protein with pneumonia in elderly multimorbid patients with respiratory symptoms: retrospective cohort study.

BACKGROUND: Serum procalcitonin and high-sensitivity C-reactive protein (hs-CRP) elevations have been associated with pneumonia in adults. Our aim was to establish their diagnostic usefulness in a cohort of hospitalized multimorbid patients ≥65 years old admitted to hospital with acute respiratory symptoms. METHODS: With a retrospective cohort study design, all multimorbid patients ≥65 years-old with acute respiratory symptoms admitted to an internal medicine hospital ward in Italy from January to August 2013 were evaluated. Pneumonia diagnosis, comorbidities expressed through Cumulative Illness Rating Scale (CIRS), setting of living, length of stay, serum hs-CRP and procalcitonin at admission were collected for each patient. Data were analyzed with Mann-Whitney's U test and multivariate Cox logistic regression analysis. A Receiver Operating Characteristic (ROC) curve was used to verify each biomarker's association with pneumonia diagnosis. RESULTS: Four hundred fifty five patients (227 M) were included in the study, of whom 239 with pneumonia (138 M, mean age 80 ± 13) and 216 without pneumonia (89 M, mean age 80 ± 14). After adjustment for age and sex, median levels of hs-CRP were significantly higher in patients with pneumonia (116 mg/L, IQR 46.5-179.0, vs 22.5 mg/dl, IQR 6.9-84.4, p < 0.0001), while procalcitonin median levels were not (0.22 ng/ml IQR 0.12-0.87, vs 0.15 ng/ml, IQR 0.10-0.35, p = 0.08). The ROC analysis showed that, unlike procalcitonin, hs-CRP values were predictive of pneumonia (AUC 0.76, 95% CI 0.72-0.79, p < 0.0001, cut-off value 61 mg/L), even after adjustment for possible confounders including nursing home residence and dementia. Serum hs-CRP levels >61 mg/L were independently associated with a 3.59-fold increased risk of pneumonia (OR 3.59, 95% CI 2.35-5.48, p < 0.0001). CONCLUSION: In elderly multimorbid patients who require hospital admission for respiratory symptoms, serum hs-CRP testing seems to be more useful than procalcitonin for guiding the diagnostic process when clinical suspicion of pneumonia is present. Procalcitonin testing might hence be not recommended in this setting.