Role of NT-proBNP and lung ultrasound in diagnosing and classifying heart failure in a hospitalized oldest-old population: a cross-sectional study.

AIM: Diagnosing and classifying heart failure (HF) in the oldest-old patients has technical and interpretation issues, especially in the acute setting. We assessed the usefulness of both N-terminal pro-brain natriuretic peptide (NT-proBNP) and lung ultrasound (LUS) for confirming HF diagnosis and predicting, among hospitalized HF patients, those with reduced ejection fraction (HFrEF). METHODS: We performed a cross-sectional study on 148 consecutive patients aged ≥ 80 years admitted to our Internal Medicine and Geriatrics ward with at least one symptom/sign compatible with HF and NT-proBNP ≥ 125 pg/mL. We measured serum NT-proBNP levels and performed LUS and transthoracic echocardiography (TTE) on admission before diuretic therapy. We divided our cohort into three subgroups according to the left ventricular ejection fraction (LVEF): reduced (LVEF ≤ 40%), mildly-reduced (LVEF = 41-49%) and preserved (LVEF ≥ 50%). RESULTS: The mean age was 88±5 years. Male prevalence was 42%. Patients with HFrEF were 19%. Clinical features and laboratory parameters did not differ between the three subgroups, except for higher NT-proBNP in HFrEF patients, which also had a higher number of total B-lines and intercostal spaces of pleural effusion at LUS. Overall, NT-proBNP showed an inverse correlation with LVEF (r = -0.22, p = 0.007) and a direct correlation with age, total pulmonary B-lines, and intercostal spaces of pleural effusion. According to the ROCs, NT-proBNP levels, pulmonary B-lines and pleural effusion extension were poorly predictive for HFrEF. The best-performing cut-offs were 9531 pg/mL for NT-proBNP (SP 0.70, SE 0.50), 13 for total B-lines (SP 0.69, SE 0.85) and one intercostal space for pleural effusion (SP 0.55, SE 0.89). Patients with admission NT-proBNP ≥ 9531 pg/mL had a 2-fold higher risk for HFrEF (OR 2.5, 95% CI 1.3-4.9), while we did not find any association for total B-lines ≥ 13 or pleural effusion ≥ 1 intercostal space with HFrEF. A significant association with HFrEF emerged for the combination of NT-proBNP ≥ 9531 pg/mL, total B-lines ≥ 13 and intercostal spaces of pleural effusion ≥ 1 (adjusted OR 4.3, 95% CI 1.5-12.9). CONCLUSIONS: Although NT-proBNP and LUS help diagnose HF, their accuracy in discriminating HFrEF from non-HFrEF was poor in our real-life clinical study on oldest-old hospitalized patients, making the use of TTE still necessary to distinguish HF phenotypes in this peculiar setting. These data require confirmation in more extensive and longer prospective studies.

Blood circulating bacterial DNA in hospitalized old COVID-19 patients.

BACKGROUND: Coronavirus disease COVID-19 is a heterogeneous condition caused by SARS-CoV-2 infection. Generally, it is characterized by interstitial pneumonia that can lead to impaired gas-exchange, acute respiratory failure, and death, although a complex disorder of multi-organ dysfunction has also been described. The pathogenesis is complex, and a variable combination of factors has been described in critically ill patients. COVID-19 is a particular risk for older persons, particularly those with frailty and comorbidities. Blood bacterial DNA has been reported in both physiological and pathological conditions and has been associated with some haematological and laboratory parameters but, to date, no study has characterized it in hospitalized old COVID-19 patients The present study aimed to establish an association between blood bacterial DNA (BB-DNA) and clinical severity in old COVID-19 patients. RESULTS: BB-DNA levels were determined, by quantitative real-time PCRs targeting the 16S rRNA gene, in 149 hospitalized older patients (age range 65-99 years) with COVID-19. Clinical data, including symptoms and signs of infection, frailty status, and comorbidities, were assessed. BB-DNA was increased in deceased patients compared to discharged ones, and Cox regression analysis confirmed an association between BB-DNA and in-hospital mortality. Furthermore, BB-DNA was positively associated with the neutrophil count and negatively associated with plasma IFN-alpha. Additionally, BB-DNA was associated with diabetes. CONCLUSIONS: The association of BB-DNA with mortality, immune-inflammatory parameters and diabetes in hospitalized COVID-19 patients suggests its potential role as a biomarker of unfavourable outcomes of the disease, thus it could be proposed as a novel prognostic marker in the assessment of acute COVID-19 disease.

Role of Cardio-Renal Dysfunction, Inflammation Markers, and Frailty on In-Hospital Mortality in Older COVID-19 Patients: A Cluster Analysis.

Our study aimed to identify clusters of hospitalized older COVID-19 patients according to their main comorbidities and routine laboratory parameters to evaluate their association with in-hospital mortality. We performed an observational study on 485 hospitalized older COVID-19 adults (aged 80+ years). Patients were aggregated in clusters by a K-medians cluster analysis. The primary outcome was in-hospital mortality. Medical history and laboratory parameters were collected on admission. Frailty, defined by the Clinical Frailty Scale (CFS), referred to the two weeks before hospitalization and was used as a covariate. The median age was 87 (83-91) years, with a female prevalence (59.2%). Three different clusters were identified: cluster 1 (337), cluster 2 (118), and cluster 3 (30). In-hospital mortality was 28.5%, increasing from cluster 1 to cluster 3: cluster 1 = 21.1%, cluster 2 = 40.7%, and cluster 3 = 63.3% (p < 0.001). The risk for in-hospital mortality was higher in clusters 2 [HR 1.96 (95% CI: 1.28-3.01)] and 3 [HR 2.87 (95% CI: 1.62-5.07)] compared to cluster 1, even after adjusting for age, sex, and frailty. Patients in cluster 3 were older and had a higher prevalence of atrial fibrillation, higher admission NT-proBNP and C-reactive protein levels, higher prevalence of concurrent bacterial infections, and lower estimated glomerular filtration rates. The addition of CFS significantly improved the predictive ability of the clusters for in-hospital mortality. Our cluster analysis on older COVID-19 patients provides a characterization of those subjects at higher risk for in-hospital mortality, highlighting the role played by cardio-renal impairment, higher inflammation markers, and frailty, often simultaneously present in the same patient.

Effect of Cytomegalovirus Reactivation on Inflammatory Status and Mortality of Older COVID-19 Patients.

Herpesviridae reactivation such as cytomegalovirus (CMV) has been described in severe COVID-19 (COronaVIrusDisease-2019). This study aimed to understand if CMV reactivation in older COVID-19 patients is associated with increased inflammation and in-hospital mortality. In an observational single-center cohort study, 156 geriatric COVID-19 patients were screened for CMV reactivation by RT-PCR. Participants underwent a comprehensive clinical investigation that included medical history, functional evaluation, laboratory tests and cytokine assays (TNF-α, IFN-α, IL-6, IL-10) at hospital admission. In 19 (12.2%) of 156 COVID-19 patients, CMV reactivation was detected. Multivariate Cox regression models showed that in-hospital mortality significantly increased among CMV positive patients younger than 87 years (HR: 9.94, 95% CI: 1.66-59.50). Other factors associated with in-hospital mortality were C-reactive protein (HR: 1.17, 95% CI: 1.05-1.30), neutrophil count (HR: 1.20, 95% CI: 1.01-1.42) and clinical frailty scale (HR:1.54, 95% CI: 1.04-2.28). In patients older than 87 years, neutrophil count (HR: 1.13, 95% CI: 1.05-1.21) and age (HR: 1.15, 95% CI: 1.01-1.31) were independently associated with in-hospital mortality. CMV reactivation was also correlated with increased IFN-α and TNF-α serum levels, but not with IL-6 and IL-10 serum changes. In conclusion, CMV reactivation was an independent risk factor for in-hospital mortality in COVID-19 patients younger than 87 years old, but not in nonagenarians.

Radiological lung sequelae, functional status and symptoms in older patients 3 and 6 months after hospitalization for COVID-19 pneumonia.

The aim of our study was to assess the lung sequelae and clinical consequences 3 and 6 months after hospitalization for COVID-19 pneumonia in older patients. An observational study was conducted on 55 patients aged 65 years and older. Activities of daily living (ADL) and clinical frailty scale (CFS) were assessed at baseline and after 3 months. Both quantitative assessment at chest high-resolution computed tomography (CT) and semi-quantitative severity score (CTSS) were performed at baseline and after 3 and 6 months. Mean age: 82.3 ± 7.1 years. Male prevalence: 56.4%. After 6 months, ground-glass opacities (GGO) were still detectable in 22% of subjects, while consolidations were no longer appreciable. During follow-up, CTSS reached an overall median score of zero after 6 months. Fibrotic-like changes were found in 40% of subjects with an overall median score of 0 (0-5) points, being more prevalent in males. Patients reporting worsening ADL and CFS were 10.9% and 45.5%, respectively. They were associated with the burden of comorbidities, especially history of heart failure and chronic obstructive pulmonary disease at baseline. Amnesic disorders, exertional dyspnea, and fatigue were the most relevant symptoms reported. No association emerged between persistent or new-onset symptoms and evidence of fibrotic-like changes. The typical chest CT abnormalities of the COVID-19 pneumonia acute phase resolved in most of our older patients. Mild fibrotic-like changes persisted in less than half of the patients, especially males, without significantly affecting the functional status and frailty condition, which instead were more likely associated with pre-existing comorbidities.

Renin-Angiotensin-System Inhibitors Are Associated With Lower In-hospital Mortality in COVID-19 Patients Aged 80 and Older.

Background: Older adults are at higher risk of morbidity and mortality for coronavirus disease 2019 (COVID-19). Renin-angiotensin-system inhibitors (RASi) were found to have a neutral or protective effect against mortality in COVID-19 adult patients. Aims: We investigated whether this association was confirmed also in COVID-19 older patients. Methods: This is a prospective observational study on 337 hospitalized older adults (aged 80 years and older). We classified the study population according to usage of RASi before and during hospitalization. A propensity score analysis was also performed to confirm the findings. Results: The mean age was 87.4 ± 6.1 years. Patients taking RASi at home were 147 (43.6%). During hospitalization, 38 patients (11.3% of the entire study population) discontinued RASi, while 57 patients (16.9% of the entire study population) started RASi. In-hospital mortality was 43.9%. Patients taking RASi during hospitalization (patients who maintained their home RASi therapy + patients who started RASi during hospitalization) had a significantly lower in-hospital mortality than untreated patients [HR 0.48 (95% CI: 0.34-0.67)], even after adjustment for required respiratory support, functional status, albumin, inflammation, and cardiac biomarkers. The analysis of the groups derived from the "propensity score matching" (58 patients in each group) confirmed these results [HR 0.46 (95% CI: 0.23-0.91)]. Discussion: Despite the high risk of death in older COVID-19 patients, RASi therapy during hospitalization was associated with a clinically relevant lower in-hospital mortality, likely due to the benefit of RAS modulation on the cardiopulmonary system during the acute phase of the disease. Conclusion: Our findings confirm the protective role of RASi even in COVID-19 patients aged 80 years and older.

Routine laboratory parameters, including complete blood count, predict COVID-19 in-hospital mortality in geriatric patients.

To reduce the mortality of COVID-19 older patients, clear criteria to predict in-hospital mortality are urgently needed. Here, we aimed to evaluate the performance of selected routine laboratory biomarkers in improving the prediction of in-hospital mortality in 641 consecutive COVID-19 geriatric patients (mean age 86.6 ± 6.8) who were hospitalized at the INRCA hospital (Ancona, Italy). Thirty-four percent of the enrolled patients were deceased during the in-hospital stay. The percentage of severely frail patients, assessed with the Clinical Frailty Scale, was significantly increased in deceased patients compared to the survived ones. The age-adjusted Charlson comorbidity index (CCI) score was not significantly associated with an increased risk of death. Among the routine parameters, neutrophilia, eosinopenia, lymphopenia, neutrophil-to-lymphocyte ratio (NLR), C-reactive protein, procalcitonin, IL-6, and NT-proBNP showed the highest predictive values. The fully adjusted Cox regressions models confirmed that high neutrophil %, NLR, derived NLR (dNLR), platelet-to-lymphocyte ratio (PLR), and low lymphocyte count, eosinophil %, and lymphocyte-to-monocyte ratio (LMR) were the best predictors of in-hospital mortality, independently from age, gender, and other potential confounders. Overall, our results strongly support the use of routine parameters, including complete blood count, in geriatric patients to predict COVID-19 in-hospital mortality, independent from baseline comorbidities and frailty.

Circulating miR-320b and miR-483-5p levels are associated with COVID-19 in-hospital mortality.

The stratification of mortality risk in COVID-19 patients remains extremely challenging for physicians, especially in older patients. Innovative minimally invasive molecular biomarkers are needed to improve the prediction of mortality risk and better customize patient management. In this study, aimed at identifying circulating miRNAs associated with the risk of COVID-19 in-hospital mortality, we analyzed serum samples of 12 COVID-19 patients by small RNA-seq and validated the findings in an independent cohort of 116 COVID-19 patients by qRT-PCR. Thirty-four significantly deregulated miRNAs, 25 downregulated and 9 upregulated in deceased COVID-19 patients compared to survivors, were identified in the discovery cohort. Based on the highest fold-changes and on the highest expression levels, 5 of these 34 miRNAs were selected for the analysis in the validation cohort. MiR-320b and miR-483-5p were confirmed to be significantly hyper-expressed in deceased patients compared to survived ones. Kaplan-Meier and Cox regression models, adjusted for relevant confounders, confirmed that patients with the 20% highest miR-320b and miR-483-5p serum levels had three-fold increased risk to die during in-hospital stay for COVID-19. In conclusion, high levels of circulating miR-320b and miR-483-5p can be useful as minimally invasive biomarkers to stratify older COVID-19 patients with an increased risk of in-hospital mortality.

Possible harm from glucocorticoid drugs misuse in the early phase of SARS-CoV-2 infection: a narrative review of the evidence.

Since the publication of the RECOVERY trial, the use of glucocorticoid drugs (GC) has spread for the treatment of severe COVID-19 worldwide. However, the benefit of dexamethasone was largest in patients who received mechanical ventilation or supplemental oxygen therapy, while no benefit was found among patients without hypoxemia. In addition, a positive outcome was found in patients who received dexamethasone after several days of symptoms, while possible harm could exist if administered early. The right time interval for GC administration is still a matter of debate. Previous studies showed that an early GC use during the first phase of the disease, when viral replication peaks, may negatively affect the innate immune response through several mechanisms, such as the inhibition of pro-inflammatory and antiviral cytokine production and signaling pathway, including type I interferon, that is fundamental to counteract the virus and that was found to be impaired in several patients with life-threatening COVID-19. The GC misuse can lead to a more severe disease even in patients who do not have the established risk factors, such as obesity and cardiovascular diseases. In our focused review, we describe the role of immune response in viral infections, especially SARS-CoV-2, and discuss the potential harms of GC misuse in COVID-19.

The Identikit of Patient at Risk for Severe COVID-19 and Death: The Dysregulation of Renin-Angiotensin System as the Common Theme.

Since the first months of the coronavirus disease 2019 (COVID-19) pandemic, several specific physiologic traits, such as male sex and older age, or health conditions, such as overweight/obesity, arterial hypertension, metabolic syndrome, and type 2 diabetes mellitus, have been found to be highly prevalent and associated with increased risk of adverse outcomes in hospitalized patients. All these cardiovascular morbidities are widespread in the population and often coexist, thus identifying a common patient phenotype, characterized by a hyper-activation of the "classic" renin-angiotensin system (RAS) and mediated by the binding of angiotensin II (Ang II) to the type 1-receptor. At the same time, the RAS imbalance was proved to be crucial in the genesis of lung injury after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, where angiotensin-converting-enzyme-2 (ACE2) is not only the receptor for SARS-CoV-2, but its down-regulation through internalization and shedding, caused by the virus binding, leads to a further dysregulation of RAS by reducing angiotensin 1-7 (Ang 1-7) production. This focused narrative review will discuss the main available evidence on the role played by cardiovascular and metabolic conditions in severe COVID-19, providing a possible pathophysiological link based on the disequilibrium between the two opposite arms of RAS.

Chest X-ray Score and Frailty as Predictors of In-Hospital Mortality in Older Adults with COVID-19.

BACKGROUND: The purpose of this study was to evaluate the prognostic impact of chest X-ray (CXR) score, frailty, and clinical and laboratory data on in-hospital mortality of hospitalized older patients with COVID-19. METHODS: This retrospective study included 122 patients 65 years or older with positive reverse transcription polymerase chain reaction for severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) and with availability to CXRs on admission. The primary outcome of the study was in-hospital mortality. Statistical analysis was conducted using Cox regression. The predictive ability of the CXR score was compared with the Clinical Frailty Scale (CFS) and fever data using Area Under the Curve (AUC) and net reclassification improvement (NRI) statistics. RESULTS: Of 122 patients, 67 died during hospital stay (54.9%). The CXR score (HR: 1.16, 95% CI, 1.04-1.28), CFS (HR: 1.27; 95% CI, 1.09-1.47), and presence of fever (HR: 1.75; 95% CI, 1.03-2.97) were significant predictors of in-hospital mortality. The addition of both the CFS and presence of fever to the CXR score significantly improved the prediction of in-hospital mortality (NRI, 0.460; 95% CI, 0.102 to 0.888; AUC difference: 0.117; 95% CI, 0.041 to 0.192, p = 0.003). CONCLUSIONS: CXR score, CFS, and presence of fever were the main predictors of in-hospital mortality in our cohort of hospitalized older patients with COVID-19. Adding frailty and presence of fever to the CXR score statistically improved predictive accuracy compared to single risk factors.

Disequilibrium between the classic renin-angiotensin system and its opposing arm in SARS-CoV-2-related lung injury.

A dysregulation of the renin-angiotensin system (RAS) has been involved in the genesis of lung injury and acute respiratory distress syndrome from different causes, including several viral infections. The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection of pneumocytes, the hallmark of the pandemic coronavirus disease 2019 (COVID-19) involving both alveolar interstitium and capillaries, is linked to angiotensin-converting enzyme 2 (ACE2) binding and its functional downregulation. ACE2 is a key enzyme for the balance between the two main arms of the RAS: the ACE/angiotensin (Ang) II/Ang II type 1 receptor axis ("classic RAS") and the ACE2/Ang(1-7)/Mas receptor (MasR) axis ("anti-RAS"). The ACE2 downregulation, as a result of SARS-coronaviruses binding, enhances the classic RAS, leading to lung damage and inflammation with leaky pulmonary blood vessels and fibrosis, when the attenuation mediated by the anti-RAS arm is reduced. ACE inhibitors (ACE-I) and Ang II type 1 receptor blockers (ARB), effective in cardiovascular diseases, were found to prevent and counteract acute lung injury in several experimental models by restoring the balance between these two opposing arms. The evidence of RAS arm disequilibrium in COVID-19 and the hypothesis of a beneficial role of RAS modulation supported by preclinical and clinical studies are the focus of the present review. Preclinical and clinical studies on drugs balancing RAS arms might be the right way to counter COVID-19.

Pharmacological Approach to Smoking Cessation: An Updated Review for Daily Clinical Practice.

Tobacco use is one of the major public health concerns and it is the most preventable cause of morbidity and mortality worldwide. Smoking cessation reduces subsequent cardiovascular events and mortality. Smoking is a real chronic disorder characterized by the development of an addiction status mainly due to nicotine. This condition makes the smokers generally unable to quit smoking without help. Different strategies are available to treat smoking dependence that include both non-pharmacological (behavioral counselling) and pharmacological therapies. Currently, it is well accepted that smoking cessation drugs are effective and safe in real-world settings. Nicotine replacement therapy (NRT), varenicline, bupropion and cytisine are the main pharmacological strategies available for smoking cessation. Their efficacy and safety have been proved even in patients with chronic cardiovascular disease. Each of these drugs has peculiar characteristics and the clinician should customize the smoking cessation strategy based on currently available scientific evidence and patient's preference, paying particular attention to those patients having specific cardiovascular and psychiatric comorbidities. The present document aims to summarize the current viable pharmacological strategies for smoking cessation, also discussing the controversial issue regarding the use of alternative tobacco products, in order to provide useful practical indications to all physicians, mainly to those involved in cardiovascular prevention.

A 95-year-old patient with unexpected coronavirus disease 2019 masked by aspiration pneumonia: a case report.

BACKGROUND: Severe acute respiratory syndrome coronavirus-2 infection has become a pandemic disease (coronavirus disease 2019). The infection has moved from China to the rest of the world and Italy represents one of the most affected countries. Older adults are more susceptible to develop complications with the consequent highest mortality rates. CASE PRESENTATION: We report a case of a 95-year-old Caucasian woman affected by pneumonia, initially defined as common aspiration pneumonia in a bedridden patient with vascular dementia, which later turned out to be coronavirus disease 2019 pneumonia during the initial spread of severe acute respiratory syndrome coronavirus-2 in our district. Some features of a computed tomography scan of her chest and her clinical history with known dysphagia had led at first to a different diagnosis with a consequent exposure of health professionals to infectious risk in two distinct hospitals. In this case report, we describe the clinical/imaging features of coronavirus disease 2019 pneumonia and the diagnostic process that led to a correct diagnosis in a nonagenarian with multiple comorbidities. CONCLUSIONS: This case report highlights both the possible pitfalls in diagnosing coronavirus disease 2019 pneumonia in very old patients with comorbidities and the greater than expected spread of the infection, even in individuals with reduced interpersonal contacts and no defined epidemiological link.

Prevalence of Subclinical Carotid Atherosclerosis and Role of Cardiovascular Risk Factors in Older Adults: Atherosclerosis and Aging are Not Synonyms.

INTRODUCTION: Age is traditionally considered a major cardiovascular (CV) risk factor, but its real weight in the absence of other modifiable risk factors is not clear. AIM: To compare the prevalence of subclinical carotid atherosclerosis, and its association with the main CV risk factors, between older adults and hypertensive adults. METHODS: Cross-sectional study on 210 consecutive patients: 70 older adults (age ≥ 80 years), and 140 hypertensive adults having at least another CV risk factor. Patients had no history of peripheral artery disease or major CV events. RESULTS: Mean age was 54.2 ± 7.2 years in hypertensive adults and 88.5 ± 5.5 years in older adults with a female prevalence in the latter group. Dyslipidemia and smoking were more prevalent in hypertensive adults, while chronic kidney disease was more prevalent in older adults. Prevalence of carotid plaques did not differ between hypertensive adults and older adults (48.2% vs 55.6%, respectively, p = 0.311). Age ≥ 80 years was not associated with a higher risk of carotid plaques even after adjusting for other risk factors (p = 0.204). Hypertension and dyslipidemia were the risk factors more strongly associated with carotid plaques in older adults and hypertensive adults, respectively. When older adults with hypertension were excluded from the analysis, prevalence of carotid plaques was significantly higher in hypertensive adults (p = 0.042). CONCLUSION: Hypertension and dyslipidemia are the major determinant of atherosclerosis regardless of age in our study. Our findings support the concept that aging is not necessarily synonymous with atherosclerosis and highlight the key role played by superimposed CV risk factors on arterial ''bad aging''.

Acute Exacerbation of Chronic Obstructive Pulmonary Disease in Oldest Adults: Predictors of In-Hospital Mortality and Need for Post-acute Care.

OBJECTIVES: Older age is associated with higher risk of death during acute exacerbations of chronic obstructive pulmonary disease (AE-COPD). Older patients hospitalized for AE-COPD often require post-acute care after acute phase. The aim of this study was to evaluate components of a comprehensive geriatric assessment and clinical/laboratory parameters, in order to find predictors of in-hospital mortality and need for post-acute care in patients aged 80 and older hospitalized for AE-COPD. DESIGN: Prospective observational study. SETTING: Hospital assessment. PARTICIPANTS: 121 patients consecutively admitted to an internal medicine and geriatrics department for AE-COPD. MEASURES: Activities of Daily Living (ADL) Hierarchy scale, Geriatric Index of Comorbidity, cognitive impairment, and clinical and laboratory parameters were collected. RESULTS: Mean age: 87.0 ± 4.9 years; male: 54.5%. In-hospital mortality (18.2% of patients) was significantly associated with functional disability, high comorbidity, cognitive impairment, anemia, older age, lower albumin, higher N-terminal pro-B-type natriuretic peptide (NT-proBNP) and white blood cell levels, oral corticosteroids taken before admission, and no angiotensin-converting enzyme inhibitors or angiotensin receptor blockers taken before admission. In a stepwise logistic regression, functional dependence (P = .006), cognitive impairment (P = .038), and oral corticosteroids therapy before hospitalization (P = .035) were independently associated with a higher risk of in-hospital mortality. Among laboratory parameters, only NT-proBNP remained significantly associated with in-hospital mortality (P = .026). The need for post-acute care (18.2% of survivors) was associated with older age, higher admission Pco2, greater comorbidity, and cognitive impairment. In a stepwise logistic regression, only cognitive impairment (P = .016) and ln_Pco2 (P = .056) confirmed their association with the need for post-acute care. CONCLUSIONS/IMPLICATIONS: Preadmission functional dependence, cognitive impairment, and corticosteroid use, plus elevated NT-proBNP at admission are risk factors for mortality during an AE-COPD in the oldest old. Therefore, medical providers should consider these, as well as the patient's advance directives, in planning hospital care. Furthermore, providers should arrange especially careful posthospitalization monitoring and frequent follow-up of individuals with cognitive impairment and baseline hypercapnia.

Combination Therapy of Inhaled Indacaterol/Glycopyrronium for Chronic Obstructive Pulmonary Disease in the Very Elderly: Is It Safe? An Electrocardiographic Evaluation.

Cardiovascular (CV) comorbidities in patients with chronic obstructive pulmonary disease (COPD) are associated with increased morbidity and mortality, especially in old and very old subjects. The question if long-acting beta-agonist and long-acting muscarinic antagonist could be associated with the increased prevalence of CV-related adverse effects has puzzled, particularly in the past, specialists involved in the management of respiratory diseases. The safety of these compounds has scarcely been tested in patients aged ≥ 65 years with CV comorbidities, since randomized controlled trials rarely include this subpopulation. However, the fixed combination indacaterol/glycopyrronium has shown a favorable CV safety profile in both healthy volunteers and COPD patients. Thus, we aimed to assess the CV safety pro-- file of the fixed combination indacaterol/glycopyrronium 110/50 µg in a series of COPD patients aged ≥ 80 years with several comorbidities. Our results indicate that this combination is safe in the comorbid elderly, since no significant electrocardiographic abnormalities were recorded after the administration of the inhaled therapy. Only rare and nonclinically significant changes in heart rate and corrected QT interval duration were evident, mainly in females and in patients with concomitant impaired kidney function.

Hb Olivet (HBA1: C.40G > A; p.Ala14Thr), a Novel Silent Hemoglobin Variant in Two Families of Distinct Origin.

We report two families, members of which are carriers of a novel hemoglobin (Hb) variant that was named Hb Olivet [α13(A11)Ala→Thr (α1) (GCC > ACC); HBA1: c.40G > A; p.Ala14Thr]. The analysis of these cases allowed a clear description of this anomaly that behaves as a silent Hb. In the first family, of Portuguese ethnicity living in France, the proband, a 24-year-old male and his 57-year-old mother, both appeared to be carriers. The son presented with borderline mean corpuscular volume (MCV), while the mother was normocytic and normochromic. Hemoglobin separation on capillary electrophoresis (CE) was normal, while a slightly asymmetric peak was observed on high performance liquid chromatography (HPLC). In a second family, originally from Surinam but living in The Netherlands, the proband, a 6-year-old girl, showed a mild microcytosis at low ferritin levels. The abnormal Hb was inherited from the mother who was clearly iron depleted, was not present in the sister and brother of the proband. The microcytic hypochromic anemia was only shown in two out of a total of four carriers. It therefore seems likely that iron depletion is causative as two carriers are completely normal. Characterization and genotype/phenotype correlation are briefly described.