Age differentially impacts adaptive immune responses induced by adenoviral versus mRNA vaccines against COVID-19.

Adenoviral and mRNA vaccines encoding the viral spike (S) protein have been deployed globally to contain severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Older individuals are particularly vulnerable to severe infection, probably reflecting age-related changes in the immune system, which can also compromise vaccine efficacy. It is nonetheless unclear to what extent different vaccine platforms are impacted by immunosenescence. Here, we evaluated S protein-specific immune responses elicited by vaccination with two doses of BNT162b2 or ChAdOx1-S and subsequently boosted with a single dose of BNT162b2 or mRNA-1273, comparing age-stratified participants with no evidence of previous infection with SARS-CoV-2. We found that aging profoundly compromised S protein-specific IgG titers and further limited S protein-specific CD4+ and CD8+ T cell immunity as a probable function of progressive erosion of the naive lymphocyte pool in individuals vaccinated initially with BNT162b2. Our results demonstrate that primary vaccination with ChAdOx1-S and subsequent boosting with BNT162b2 or mRNA-1273 promotes sustained immunological memory in older adults and potentially confers optimal protection against coronavirus disease 2019.

Polypharmacy and Antibody Response to SARS-CoV-2 Vaccination in Residents of Long-Term Care Facilities: The GeroCovid Vax Study.

BACKGROUND AND OBJECTIVE: Polypharmacy is common in older adults, particularly among those living in long-term care facilities. This condition represents a marker of clinical complexity and might directly affect the immunological response. However, there are limited data on the association of polypharmacy with vaccine immunogenicity. This study evaluated the immune response to anti-SARS-CoV-2 vaccines in older residents of long-term care facilities as a function of the number of medications used. METHODS: In 478 long-term care facility residents participating in the GeroCovid Vax study, we assessed SARS-CoV-2 trimeric S IgG levels through chemiluminescent assays before the vaccination and after 2, 6, and 12 months. A booster dose was administered between 6- and 12-month assessments. Sociodemographic information and data on chronic diseases and medications were derived from medical records. Based on the number of daily medications, residents were classified into the no polypharmacy (zero to four medications), polypharmacy (five to nine medications), and hyperpolypharmacy (ten or more medications) groups. RESULTS: In the sample (mean age 82.1 years, 69.2% female), 200 (41.8%) residents were taking five or fewer medications/day (no polypharmacy), 229 (47.9%) had polypharmacy, and 49 (10.3%) had hyperpolypharmacy. Using linear mixed models adjusted for potential confounders, we found that hyperpolypharmacy was associated with a steeper antibody decline after 6 months from the first vaccine dose administration (ß = - 0.29, 95% confidence interval - 0.54, - 0.03, p = 0.03) than no polypharmacy, while no significant differences were observed at 12 months. CONCLUSIONS: The humoral immune response to SARS-CoV-2 vaccination of older residents showed only slight changes as a function of the number of medications taken. Although it seemed less durable among older residents with hyperpolypharmacy, the booster dose administration equalized such a difference.

Strategies and Tools for Supporting the Appropriateness of Drug Use in Older People.

Through this structured review of the published literature, we aimed to provide an up-to-date description of strategies (human-related) and tools (mainly from the digital field) facilitating the appropriateness of drug use in older adults. The evidence of each strategy and tool's effectiveness and sustainability largely derives from local and heterogeneous experiences, with contrasting results. As a general framework, three main steps should be considered in implementing measures to improve appropriateness: prescription, acceptance by the patient, and continuous monitoring of adherence and risk-benefit profile. Each step needs efforts from specific actors (physicians, patients, caregivers, healthcare professionals) and dedicated supporting tools. Moreover, how to support the appropriateness also strictly depends on the particular setting of care (hospital, ambulatory or primary care, nursing home, long-term care) and available economic resources. Therefore, it is urgent assigning to each approach proposed in the literature the following characteristics: level of effectiveness, strength of evidence, setting of implementation, needed resources, and issues for its sustainability.

Prevalence and impact of polypharmacy in older patients with type 2 diabetes.

BACKGROUND: Polypharmacy is a prevalent condition in older adults, especially those with multiple chronic diseases, and has been largely associated with adverse outcomes, including disability, hospitalizations, and death. AIMS: This systematic review focused on diabetes and aimed to investigate the prevalence and impact of polypharmacy in older adults affected by such disease. METHODS: Observational (either cross-sectional or longitudinal) or experimental studies investigating the frequency and impact of polypharmacy in older adults with diabetes were identified from scientific databases and grey literature until August 2021. The prevalence and the 95% Confidence Interval (95% CI) of polypharmacy in older people with diabetes were summarized by a random-effects meta-analysis. RESULTS: From a total of 1465 records, 9 were selected for the qualitative synthesis, and 8 for the quantitative synthesis. Most studies defined polypharmacy using a cut-off for the minimum number of medications ranging from 4 to 6 drugs/day. The pooled prevalence of polypharmacy in older people with diabetes was 64% (95% CI 45-80%). Considering studies that used the same definition of polypharmacy (i.e. ≥ 5 drugs/day), the pooled prevalence was 50% (95% CI 37-63%). The between-studies heterogeneity was high. Across the selected studies, polypharmacy seemed to negatively influence both diabetes-specific (poor glycemic control and risk of hypoglycemia) and health-related (risk of incident falls, syncope, hospitalization, and death) outcomes. CONCLUSION: This systematic review confirms the high prevalence of polypharmacy in older people with diabetes and its strong impact on several health-related outcomes, including mortality. These results strengthen the need to improve care strategies for management of these patients.

Congestive heart failure and comorbidity as determinants of colorectal cancer perioperative outcomes.

There has been an increase in surgical interventions in frailer elderly with concomitant chronic diseases. The purpose of this paper was to evaluate the impact of aging and comorbidities on outcomes in patients who underwent surgery for the treatment of colorectal cancer (CRC) in Veneto Region (Northeastern Italy). This is a retrospective cohort study in patients ≥ 40 years who underwent elective or urgent CRC surgical resection between January 2013 and December 2015. Independent variables included: age, sex, and comorbidities. We analyzed variables associated with the surgical procedure, such as stoma creation, hospitalization during the year before the index surgery, the surgical approach used, the American Society of Anesthesiologists (ASA) score, and the Charlson Comorbidity Index score. Eight thousand four hundred and forty-seven patients with CRC underwent surgical resection. Patient age affected both pre- and post-resection LOS as well as the overall survival (OS); however, it did not affect the 30-day readmission and reoperation rates. Multivariate analysis showed that age represented a risk factor for longer preoperative and postoperative LOS as well as for 30-day and 365-day mortality, but it was not associated with an increased risk of 30-day reoperation and 30-day readmission. Chronic Heart Failure increased the 30-day mortality risk by four times, the preoperative LOS by 51%, and the postoperative LOS by 33%. Chronic renal failure was associated with a 74% higher 30-day readmission rate. Advanced age and comorbidities require a careful preoperative evaluation and appropriate perioperative management to improve surgical outcomes in older patients undergoing elective or urgent CRC resection.

Post-Operative All-Cause Mortality in Elderly Patients Undergoing Abdominal Emergency Surgery: Role of Charlson Comorbidity Index.

(1) Background: The Charlson comorbidity index (CCI) score has been shown to predict 10-year all-cause mortality, but its validity is a matter of debate in surgical patients. We wanted to evaluate CCI on predicting all-cause mortality in elderly patients undergoing emergency abdominal surgery (EAS); (2) Methods: This retrospective single center study included all patients aged 65 years or older consecutively admitted from January 2017 to December 2019, who underwent EAS and were discharged alive. CCI was calculated by using of the International Classification of Diseases, 9th Revision, Clinical Modification codes. Our outcome was all-cause death recorded during the 20.8 ± 8.8 month follow-up; (3) Results: We evaluated 197 patients aged 78.4 ± 7.2 years of whom 47 (23.8%) died. Mortality was higher in patients who underwent open abdominal surgery than in those treated with laparoscopic procedure (74% vs. 26%, p < 0.001), and in those who needed colon, small bowel, and gastric surgery. Mean CCI was 4.98 ± 2.2, and in subjects with CCI ≥ 4 survival was lower. Cox regression analysis showed that CCI (HR 1.132, 95% CI 1.009-1.270, p = 0.035), and open surgery (HR 10.298, 95%CI 1.409-75.285, p = 0.022) were associated with all-cause death independently from age and sex; (4) Conclusions: Calculation of CCI, could help surgeons in the preoperative stratification of risk of death after discharge in subjects aged ≥65 years who need EAS. CCI ≥ 4, increases the risk of all-causes mortality independently from age.

Perioperative Management of Elderly patients (PriME): recommendations from an Italian intersociety consensus.

BACKGROUND: Surgical outcomes in geriatric patients may be complicated by factors such as multiple comorbidities, low functional performance, frailty, reduced homeostatic capacity, and cognitive impairment. An integrated multidisciplinary approach to management is, therefore, essential in this population, but at present, the use of such an approach is uncommon. The Perioperative Management of Elderly patients (PriME) project has been established to address this issue. AIMS: To develop evidence-based recommendations for the integrated care of geriatric surgical patients. METHODS: A 14-member Expert Task Force of surgeons, anesthetists, and geriatricians was established to develop evidence-based recommendations for the pre-, intra-, and postoperative care of hospitalized older patients (≥ 65 years) undergoing elective surgery. A modified Delphi approach was used to achieve consensus, and the strength of recommendations and quality of evidence was rated using the U.S. Preventative Services Task Force criteria. RESULTS: A total of 81 recommendations were proposed, covering preoperative evaluation and care (30 items), intraoperative management (19 items), and postoperative care and discharge (32 items). CONCLUSIONS: These recommendations should facilitate the multidisciplinary management of older surgical patients, integrating the expertise of the surgeon, the anesthetist, the geriatrician, and other specialists and health care professionals (where available) as needed. These roles may vary according to the phase and setting of care and the patient's conditions.

Three-year National report from the Gruppo Italiano di Ortogeriatria (GIOG) in the management of hip-fractured patients.

BACKGROUND: Hip fractures (HF) are a major issue worldwide. We aimed at evaluating the practices in delivering care to patients with HF among several Italian Orthogeriatric centers. METHODS: The study took place from February 2016 to July 2018. Seven performance indicators (pre-surgical cognitive assessment, surgery performed ≤ 48 h from fracture, removal of urinary catheter/absence of delirium/start of physiotherapy on the first post-operative day, prescription of bone protection at discharge, and discharge toward rehabilitation) were collected. RESULTS: The 14 participating hospitals totally recruited 3.017 patients. Patients were old (median age 86 years; Inter Quartile Range [IQR] 80-90), mostly females (77%). Nearly 55% of them were already impaired in mobility and about 10% were nursing home residents. Median time-to-surgery was 41 h (IQR 23-62). Models of care greatly varied among centers, only 49.3% of patients being co-managed by geriatricians and orthopedics. There was high variability across centers in four indicators ("pre-surgical cognitive assessment", "bone protection prescription", "use of urinary catheter" and "start of physiotherapy"), moderate in two indicators ("surgery performed ≤ 48 h from fracture" and "discharge toward rehabilitation" and low in one ("absence of delirium on day following surgery"). Comparison with international studies suggests very different ways of providing care to HF Italian patients. CONCLUSIONS: The study results suggest high inter-center variability in the key-performance indicators, and different approaches in providing care to our HF patients in comparison to other countries. A National debate on the topic is required in Italy to harmonize practices of orthogeriatric care.

Polypharmacy and sarcopenia in hospitalized older patients: results of the GLISTEN study.

BACKGROUND: Recently the Berlin Aging Study II (BASE-II) showed that polypharmacy is associated with clinically relevant sarcopenia among community-dwelling older persons. Here we report findings from the GLISTEN study about the association of polypharmacy with sarcopenia among older medical in-patients. METHODS: The GLISTEN study investigated prevalence and clinical correlates of sarcopenia in older patients admitted to geriatric and internal medicine acute care wards of 12 Italian hospitals. RESULTS: In this sample of older medical in-patients with high prevalence of sarcopenia (34.7%) and polypharmacy (70.2%) we did not observe a significant association of polypharmacy with sarcopenia. CONCLUSIONS: Present findings demonstrate that the association of polypharmacy with sarcopenia, observed in the BASE-II study, is not evident in the GLISTEN sample, being our patients significantly older, more multi-morbid, with high prevalence of sarcopenia and polypharmacy, suggesting that this association might vary according to the heterogeneous health, functional, and nutritional characteristics of older people.

Relationship between low levels of circulating TRAIL and atheromatosis progression in patients with chronic kidney disease.

BACKGROUND: Chronic kidney disease (CKD) patients experience a high risk of cardiovascular disease (CV); however, the factors involved in CV-related morbidity and mortality in these patients have not been fully defined. Tumor necrosis factor related apoptosis-inducing ligand (TRAIL) is a cytokine, which exhibits pleiotropic activities on endothelial, vascular smooth muscle and inflammatory cells, with relevant effects on atheromatous plaque formation. On this basis, the present study aims to investigate the role of TRAIL in atheromatosis progression in CKD patients. METHODS: Circulating TRAIL levels were measured in 378 CKD patients belonging to the Spanish National Observatory of Atherosclerosis in Nephrology (NEFRONA) study. All patients were free of previous CV events. Carotid and femoral B-mode ultrasound was performed to detect the presence of plaque at baseline and after 24 months of follow-up. RESULTS: The lowest levels of TRAIL at baseline were significantly (p<0.05) associated with the appearance, after 24 months of follow-up, of at least two new atheromatous plaques in all territories and of one new plaque in the carotid artery, even after adjusting for CV risk factors. In addition, the patients with low levels of TRAIL at baseline were characterized by the presence of at least one hypoechoic plaque in the carotid artery. This association was significant (p<0.05) even after adjusting for CKD stage. CONCLUSIONS: Overall, the results of our study suggest TRAIL as an assertable independent prognostic biomarker for atheromatosis plaque formation in CKD patients. This observation further supports the potential role of TRAIL for the prevention/treatment of CV disease.

Association Between Gait Speed With Mortality, Cardiovascular Disease and Cancer: A Systematic Review and Meta-analysis of Prospective Cohort Studies.

OBJECTIVES: Slow gait speed may be associated with premature mortality, cardiovascular disease (CVD), and cancer, although a comprehensive meta-analysis is lacking. In this systematic review and meta-analysis, we explored potential associations between gait speed and mortality, incident CVD, and cancer. DESIGN: A systematic search in major databases was undertaken from inception until March 15, 2018 for prospective cohort studies reporting data on gait speed and mortality, incident CVD, and cancer. SETTING AND PARTICIPANTS: All available. MEASURES: The adjusted hazard ratios (HRs) and 95% confidence intervals (CIs), based on the model with the maximum number of covariates for each study between gait speed (categorized as decrease in 0.1 m/s) and mortality, incident CVD, and cancer, were meta-analyzed with a random effects model. RESULTS: Among 7026 articles, 44 articles corresponding to 48 independent cohorts were eligible. The studies followed up on a total of 101,945 participants (mean age 72.2 years; 55% women) for a median of 5.4 years. After adjusting for a median of 9 potential confounders and the presence of publication bias, each reduction of 0.1 m/s in gait speed was associated with a 12% increased risk of earlier mortality (45 studies; HR = 1.12, 95% CI: 1.09-1.14; I2 = 90%) and 8% increased risk of CVD (13 studies; HR = 1.08, 95% CI: 1.03-1.13; I2 = 81%), but no relationship with cancer was observed (HR = 1.00, 95% CI: 0.97-1.04; I2 = 15%). CONCLUSION/IMPLICATIONS: Slow gait speed may be a predictor of mortality and CVD in older adults. Because gait speed is a quick and inexpensive measure to obtain, our study suggests that it should be routinely used and may help identify people at risk of premature mortality and CVD.

A moderate 500-m treadmill walk for estimating peak oxygen uptake in men with NYHA class I-II heart failure and reduced left ventricular ejection fraction.

BACKGROUND: Maximal cardiopulmonary exercise testing (CPX) is the gold-standard for cardiorespiratory fitness assessment in chronic heart failure (CHF) patients. However, high costs, required medical supervision, and safety concerns make maximal exercise testing impractical for evaluating mobility-impaired adults. Thus, several submaximal walking protocols have been developed and currently used to estimate peak oxygen consumption (VO2peak) in CHF patients. However, these tests have to be performed at close to maximum exercise intensity. The aim of this study was to examine the validity of a 500-m treadmill-walking test carried out at moderate intensity for estimating VO2peak in community-dwelling adult and elderly patients with CHF and reduced left ventricular ejection fraction (HFrEF). METHODS: Forty-three clinically stable men with HFrEF (age 67.7 ± 9.2 years, and left ventricular ejection fraction, LVEF 38% ± 6%) underwent exercise testing during an outpatient cardiac rehabilitation/secondary prevention program. Each patients completed a CPX, and a moderate and self-paced (11-13/20 on the Borg scale) 500-m treadmill-walking test. Age, weight, height, walk time, and heart rate during the 500-m test were entered into prediction equations previously validated for VO2peak estimation from a 1000-m walking test in patients with cardiovascular disease and preserved LVEF. RESULTS: Directly measured and estimated VO2peak values were not different (21.6 ± 4.9 vs 21.7 ± 4.6 mL/kg/min). The comparison between measured and estimated VO2peak values yielded a correlation of R = 0.97 (SEE = 0.7 mL/kg/min, P < 0.0001). The slope and the intercept coincided with the line of identity (Passing and Bablock analysis, P = 0.50). Residuals were normally distributed, and the examination of the Bland-Altman analysis do not show systematic or proportional error. CONCLUSIONS: A moderate and self-regulated 500-m treadmill-walking test is a valid tool for VO2peak estimation in patients with HFrEF. These findings may have practical implications in the context of transitioning from clinically based programs to fitness facilities or self-guided exercise programs in adults and elderly men with HFrEF.

The incidence of sarcopenia among hospitalized older patients: results from the Glisten study.

BACKGROUND: New evidence is emerging on the importance of lean body mass during periods of illness and recovery. The preservation of lean body mass during such periods of intense stress impacts both patient and treatment outcomes. However, data concerning the incidence of sarcopenia among older people during hospitalization are scarce. The objective of this study was to evaluate the development of sarcopenia in a sample of hospitalized older subjects. METHODS: We used data of 394 participants from the multicentre Italian Study conducted by the Gruppo Lavoro Italiano Sarcopenia-Trattamento e Nutrizione (GLISTEN) in 12 Acute Care Wards (Internal Medicine and Geriatrics) of University Hospitals across Italy. This study was designed to determine the prevalence of sarcopenia at hospital admission and the change in muscle mass and strength during hospitalization. Sarcopenia was defined as low skeletal mass index (kg/m2 ) along with either low handgrip strength or slow walking speed [European Working Groups on Sarcopenia in Older People (EWGSOP) criteria]. Estimation of skeletal muscle mass was performed by bioelectrical impedance analysis (BIA). RESULTS: The mean age of the 394 enrolled patients (including 211 females who accounted for 53% of the sample) was 79.6 ± 6.4 years. Among those without sarcopenia at hospital admission, 14.7% of the study sample met the EWGSOP sarcopenia diagnostic criteria at discharge. The incidence of sarcopenia during hospitalization was significantly associated with the number of days spent in bed but was not correlated with the total length of hospital stay. In particular, patients who developed sarcopenia spent an average of 5.1 days in bed compared with 3.2 days for those with no sarcopenia at discharge (P = 0.02). Patients with sarcopenia showed a significantly lower body mass index compared with non-sarcopenic peers (25.0 ± 3.8 kg/m2 vs. 27.6 ± 4.9 kg/m2 , respectively; P < 0.001). Similarly, the skeletal mass index at admission was significantly lower among patients who developed sarcopenia during hospital stay. CONCLUSIONS: Incident sarcopenia during hospital stay is relatively common and is associated with nutritional status and the number of days of bed rest.

Combining LDL-C and HDL-C to predict survival in late life: The InChianti study.

BACKGROUND: While the relationship between total cholesterol (TC) and cardiovascular disease (CVD) progressively weakens with aging, several studies have shown that low TC is associated with increased mortality in older individuals. However, the possible additive/synergic contribution of the two most important cholesterol rich fractions (LDL-C and HDL-C) to mortality risk has not been previously investigated. Our study aimed to investigate the relationship between baseline LDL-C and HDL-C, both separately and combined, and 9-years mortality in a sample of community dwelling older individuals from the InCHIANTI study. METHODS AND FINDINGS: 1044 individuals over 64 years were included. CVD and cancer mortality were defined by ICD-9 codes 390-459 and 140-239, respectively. LDL-C <130 mg/dL (3.36 mmol/L) was defined as "optimal/near optimal". Low HDL-C was defined as <40/50 mg/dL (1.03/1.29 mmol/L) in males/females, respectively. Nine-years mortality risk was calculated by multivariate Cox proportional hazards model. We found that, compared to subjects with high LDL-C and normal HDL-C (reference group), total mortality was significantly increased in subjects with optimal/near optimal LDL-C and low HDL-C (H.R.:1.58; 95%CI:1.11-2.25). As regards the specific cause of death, CVD mortality was not affected by LDL-C/HDL-C levels, while cancer mortality was significantly increased in all subjects with optimal/near optimal LDL-C (with normal HDL-C: H.R.: 2.49; with low HDL-C: H.R.: 4.52). Results were unchanged after exclusion of the first three years of follow-up, and of subjects with low TC (<160 g/dL-4.13 mmol/L). CONCLUSIONS: Our findings suggest that, in community dwelling older individuals, the combined presence of optimal/near optimal LDL-C and low HDL-C represents a marker of increased future mortality.

Dynapenic Abdominal Obesity as a Predictor of Worsening Disability, Hospitalization, and Mortality in Older Adults: Results From the InCHIANTI Study.

BACKGROUND: There are relatively few prospective studies evaluating the combined effect of abdominal obesity and low muscle strength on mortality, hospitalization, and incident disability. The aim of this study was to prospectively evaluate the prognostic value of dynapenic abdominal obesity on incident disability, hospitalization, and mortality in the population of the InCHIANTI study. METHODS: In 370 men and 476 women aged between 65 and 95 years, handgrip strength, waist circumference (WC), body mass index, interleukin-6, C-reactive protein, education, medications, smoking status, and comorbidities were evaluated at the baseline. Difficulties in performing basic activities of daily living were assessed at baseline and at 3-, 6-, and 9-year follow-ups, using a standardized questionnaire. Hospitalization and mortality rates were evaluated during an 11-year follow-up. The study population was categorized as nondynapenic nonabdominal obese (ND/NAO, reference group), dynapenic nonabdominal obese (D/NAO), nondynapenic abdominal obese (ND/AO), and dynapenic abdominal obese (D/AO), according to handgrip strength/WC tertiles. RESULTS: D/AO participants presented more than a twofold increase in risk of worsening disability (odds ratio = 2.10; 95% confidence interval [CI]: 1.14-3.88) and significantly higher risk of hospitalization (1.36; 95% CI: 1.04-1.78) compared with ND/NAO participants. After adjustment for potential confounders, the relative risk of death was 1.47 (95% CI: 1.09-1.97) for D/NAO compared with the ND/NAO group. CONCLUSIONS: Dynapenic abdominal obese participants are at higher risk of worsening disability and hospitalization than ND/NAO participants. Mortality risk was higher in participants with dynapenia without central fat distribution compared with the reference group.

Serum Soluble Tumor Necrosis Factor-Related Apoptosis-Inducing Ligand Levels in Older Subjects with Dementia and Mild Cognitive Impairment.

BACKGROUND: The tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) has been involved in both physiological and pathological conditions, including vascular pathologies and pathologies of the central nervous system. Nonetheless, the knowledge about the role of systemic TRAIL in patients affected by different types of dementia and mild cognitive impairment (MCI) is still limited. OBJECTIVE: We assessed serum TRAIL levels in a large cohort of older individuals (n = 644) including patients with late-onset Alzheimer's disease (LOAD), vascular dementia (VAD), 'mixed' dementia (MIX), MCI, and healthy controls. METHODS: Circulating TRAIL was measured by ELISA. RESULTS: At univariate analysis, TRAIL levels were higher in VAD, MIX, and MCI patients compared with LOAD patients and controls. Using the multiple linear regression model, we found that TRAIL levels were associated with VAD and MCI, but not MIX, independent of potential confounding factors. CONCLUSION: The finding of high levels of circulating TRAIL in VAD and MCI seems to suggest that both of these conditions are characterized by a significant vascular damage with respect to LOAD.

Change in the Multidimensional Prognostic Index Score During Hospitalization in Older Patients.

We investigated and describe change in the Multidimensional Prognostic Index (MPI) score between admission and discharge in 960 older patients admitted to 20 geriatric units for an acute disease or a relapse of a chronic disease. The MPI was calculated at admission and at discharge. Subjects were divided into three groups of MPI score, low risk (MPI-1 value ≤0.33), moderate risk (MPI-2 value 0.34-0.66), and severe risk of mortality (MPI-3 value ≥0.67), on the basis of previously established cutoffs. Variation of MPI values over length of hospital stay (LOS) was analyzed with a multivariable longitudinal linear model for repeated measurements. At admission, 23.5% subjects had an MPI-1 score, 33.3% had an MPI-2 score, and 43.0% had an MPI-3 score. Overall, for almost 60% of the patients, MPI score at hospital discharge was different compared with the score at admission, although the difference was not statistically significant (-0.003; p = 0.708). Patients with high and intermediate MPI scores at admission had a decrease of MPI score at discharge (delta-MPI -0.026, p < 0.001, and delta-MPI -0.066, p = 0.569, respectively), whereas patients in the MPI-low group, experienced a significant increase in MPI score (delta-MPI 0.041, p < 0.001). The evolution of MPI score as a function of LOS had a curvilinear shape because it significantly decreased for patients with short hospitalization (1-6 days) and tended to increase for those with longer LOS. The MPI, a well-established prognostic tool, is sensitive to change of patient's health status and might be used to objectively track and monitor the clinical evolution of acutely ill geriatric patients admitted to the hospital.

The Multidimensional Prognostic Index predicts in-hospital length of stay in older patients: a multicentre prospective study.

BACKGROUND: prediction of length of stay (LOS) may be useful to optimise care plans to reduce the negative outcomes related to hospitalisation. OBJECTIVE: to evaluate whether the Multidimensional Prognostic Index (MPI), based on a Comprehensive Geriatric Assessment (CGA), may predict LOS in hospitalised older patients. DESIGN: prospective multicentre cohort study. SETTING: twenty Geriatrics Units. PARTICIPANTS: patients aged 65 and older consecutively admitted to Geriatrics Units. MEASUREMENT: at admission, the CGA-based MPI was calculated by using a validated algorithm that included information on basal and instrumental activities of daily living, cognitive status, nutritional status, the risk of pressures sores, co-morbidity, number of drugs and co-habitation status. According to validated cut-offs, subjects were divided into three groups of risk, i.e. MPI-1 low risk (value ≤0.33), MPI-2 moderate risk (value 0.34-0.66) and MPI-3 severe risk of mortality (value ≥0.67). RESULTS: two thousand and thirty-three patients were included; 1,159 were women (57.0%). Age- and sex-adjusted mean LOS in patients divided according to the MPI grade was MPI-1 = 10.1 (95% CI 8.6-11.8), MPI-2 = 12.47 (95% CI 10.7-14.68) and MPI-3 = 13.41 (95% CI 11.5-15.7) days (P for trend <0.001). The overall accuracy of the MPI to predict LOS was good (C-statistic 0.74, 95% CI 0.72-0.76). Moreover, a statistically significant trend of LOS means was found even in patients stratified according to their International Classification of Diseases, 9th revision, Clinical Modification (ICD-9-CM) main diagnosis. CONCLUSIONS: the MPI is an accurate predictor of LOS in older patients hospitalised with the most frequent diseases.

Absolute quantification of cell-free microRNAs in cancer patients.

The hypothesis to use microRNAs (miRNAs) circulating in the blood as cancer biomarkers was formulated some years ago based on promising initial results. After some exciting discoveries, however, it became evident that the accurate quantification of cell-free miRNAs was more challenging than expected. Difficulties were linked to the strong impact that many, if not all, pre- and post- analytical variables have on the final results. In this study, we used currently available high-throughput technologies to identify miRNAs present in plasma and serum of patients with breast, colorectal, lung, thyroid and melanoma tumors, and healthy controls. Then, we assessed the absolute level of nine different miRNAs (miR-320a, miR-21-5p, miR-378a-3p, miR-181a-5p, miR-3156-5p, miR-2110, miR-125a-5p, miR-425-5p, miR-766-3p) in 207 samples from healthy controls and cancer patients using droplet digital PCR (ddPCR) technology. We identified miRNAs specifically modulated in one or more cancer types, according to tissue source. The significant reduction of miR-181a-5p levels in breast cancer patients serum was further validated using two independent cohorts, one from Italy (n = 70) and one from US (n = 90), with AUC 0.66 and 0.73 respectively. This study finally powers the use of cell-free miRNAs as cancer biomarkers and propose miR-181a-5p as a diagnostic breast cancer biomarker.