Long-term Functional Decline Research Articles

Provision of palliative care for people with chronic obstructive pulmonary disease: a narrative review.

Chronic obstructive pulmonary disease (COPD) is characterized by persistent and progressive airflow restriction and is the third leading cause of death and disability, globally. People with severe COPD generally experience long-term functional decline punctuated by periods of acute exacerbation. Symptom burden can be severe and debilitating, and typically includes breathlessness, cough, fatigue, pain, anxiety, depression, and overall reduced quality of life. Understanding current palliative care needs and provisions in this group is an essential step to expanding access in future. A narrative review of specialist and generalist (primary) palliative care provisions for people with COPD, with an emphasis on breathlessness symptom management. This paper aims to examine the current landscape of palliative care provision and highlight barriers and facilitators to palliative care access for people with severe COPD. People living with severe COPD, as well as the people who care for them, are routinely under-serviced in best-practice end-of-life care, despite having symptom burden that is comparable to that of people with advanced cancer. Barriers to palliative care in this group include lack of specialist palliative care resources, uncertainty surrounding prognostication, and poor recognition of need from both patients and clinicians. Routine early palliative care involvement, including integration of specialist palliative care into respiratory services and upskilling of other healthcare providers to adopt palliative care principals within usual care (primary palliative care), have been shown to improve outcomes indicative of high-quality end-of-life care in this group, including symptom control, place of death, and legal preparations. Ongoing integration of specialist palliative care and professional education for generalist and non-palliative care specialist healthcare providers in the recognition and management of unmet palliative care needs is required to increase capacity beyond traditional specialist palliative care models. Despite high level of symptom burden, many people with COPD miss out on palliative care. Expanding capacity of traditional specialist palliative care by upskilling generalist healthcare providers and integrating specialist palliative care into existing respiratory services is necessary to improve access for people with COPD.

Preoperative Age and Its Impact on Long-Term Renal Functional Decline after Robotic-Assisted Partial Nephrectomy: Insights from a Tertiary Referral Center.

Background and Objectives: to investigate the impact of age on renal function deterioration after robotic-assisted partial nephrectomy (RAPN) focusing on a decline to moderate and severe forms of chronic kidney disease (CKD). Materials and Methods: This is a single center prospective analysis of patients who underwent RAPN. The outcomes include the development of de novo CKD-S 3a [estimated glomerular filtration rate (eGFR) < 60 mL/min/1.73 m2)] and de novo CKD-S 3b (eGFR < 45 mL/min/1.73/m2). Multivariable analysis (MVA) via Cox regression identified predictors for CKD-S 3a/b. Kaplan -Meier Analyses (KMA) were fitted for survival assessment. Multivariable linear regression was utilized to identify the predictors of last-eGFR. Results: Overall, 258 patients were analyzed [low age (<50) n = 40 (15.5%); intermediate age (50-70) n = 164 (63.5%); high age (>70) n = 54 (20.9%)] with a median follow-up of 31 (IQR 20-42) months. MVA revealed an increasing RENAL score [Hazard Ratio (HR) 1.32, p = 0.009], age 50-70 (HR 6.21, p = 0.01), age ≥ 70 (HR 10.81, p = 0.001), increasing BMI (HR 1.11, p < 0.001) and preoperative CKD 2 (HR 2.43, p = 0.014) are independent risk factors associated with an increased risk of CKD-S 3a; conversely, post-surgical acute kidney injury was not (p = 0.83). MVA for CKD-S 3b revealed an increasing RENAL score (HR 1.51, p = 0.013) and age ≥ 70 (HR 2.73, p = 0.046) are associated with an increased risk of CKD-S 3b. Linear regression analysis revealed increasing age (Coeff. -0.76, p < 0.001), increasing tumor size (Coeff. -0.31, p = 0.03), and increasing BMI (Coeff. -0.64, p = 0.004) are associated with decreasing eGFR at last follow-up. We compare the survival distribution of our cohort stratified by age elderly patients experienced worsened CKD-S 3a/b disease-free survival (p < 0.001; p < 0.001, respectively). Conclusions: Age is independently associated with a greater risk of significant and ongoing decline in kidney function following RAPN. Recognizing the impact of aging on renal function post-surgery can guide better management practices. Further investigations are required.

Periodic discharges plus fast activity on EEG predict worse outcomes in post-stroke epilepsy.

Post-seizure functional decline is a concern in post-stroke epilepsy (PSE). However, data on electroencephalogram (EEG) markers associated with functional decline are scarce. Thus, we investigated whether periodic discharges (PDs) and their specific characteristics are associated with functional decline in patients with PSE. In this observational study, patients admitted with seizures of PSE and who had scalp EEGs were included. The association between the presence or absence of PDs and post-seizure short-term functional decline lasting 7 days after admission was investigated. In patients with PD, EEG markers were explored for risk stratification of short-term functional decline, according to the American Clinical Neurophysiology Society's Standardized Critical Care EEG Terminology. The association between EEG markers and imaging findings and long-term functional decline at discharge and 6 months after discharge, defined as an increase in the modified Rankin Scale score compared with the baseline, was evaluated. In this study, 307 patients with PSE (median age, 75; range, 35-97 years; 64% males; hemorrhagic stroke, 47%) were enrolled. Compared with 247 patients without PDs, 60 patients with PDs were more likely to have short-term functional decline (12 (20%) vs. 8 (3.2%), p < 0.001), with an adjusted odds ratio (OR) of 4.26 (95% confidence interval (CI), 1.44-12.6; p = 0.009). Patients with superimposed fast-activity PDs (PDs+F) had significantly more localized (rather than widespread) lesions (87% vs. 58%, p = 0.003), prolonged hyperperfusion (100% vs. 62%, p = 0.023), and a significantly higher risk of short-term functional decline than those with PDs without fast activity (adjusted OR, 22.0; 95% CI, 1.87-259.4; p = 0.014). Six months after discharge, PDs+F were significantly associated with long-term functional decline (adjusted OR, 4.21; 95% CI, 1.27-13.88; p = 0.018). In PSE, PDs+F are associated with sustained neuronal excitation and hyperperfusion, which may be a predictor of post-seizure short- and long-term functional decline.

Evaluation and Treatment of Acute Trauma Pain in Older Adults.

In the context of an ageing population, the demographic sands of trauma are shifting. Increasingly, trauma units are serving older adults who have sustained injuries in low-energy falls from a standing height. Older age is commonly associated with changes in physiology, as well as an increased prevalence of frailty and multimorbidity, including cardiac, renal and liver disease. These factors can complicate the safe and effective administration of analgesia in the older trauma patient. Trauma services therefore need to adapt to meet this demographic shift and ensure that trauma clinicians are sufficiently skilled in treating pain in complex older people. This article is dedicated to the management of acute trauma pain in older adults. It aims to highlight the notable clinical challenges of managing older trauma patients compared with their younger counterparts. It offers an overview of the evidence and practical opinion on the merits and drawbacks of commonly used analgesics, as well as more novel and emerging analgesic adjuncts. A search of Medline (Ovid, from inception to 7 November 2022) was conducted by a medical librarian to identifyrelevant articles using keyword and subject heading terms for trauma, pain, older adults and analgesics. Results were limited to articles published in the last 10years andEnglish language. Relevant articles' references were hand-screened to identify other relevant articles. There is paucity of dedicated high-quality evidence to guide management of trauma-related pain in older adults. Ageing-related changes in physiology, the accumulation of multimorbidity, frailty and the risk of inducing delirium secondary to analgesic medication present a suite of challenges in the older trauma patient. An important nuance of treating pain in older trauma patients is the challenge of balancing iatrogenic adverse effects of analgesia against the harms of undertreated pain, the complications and consequences of which include immobility, pneumonia, sarcopenia, pressure ulcers, long-term functional decline, increased long-term care needs and mortality. In this article, the role of non-opioid agents including short-course non-steroidal anti-inflammatory drugs (NSAIDs) is discussed. Opioid selection and dosing are reviewed for older adults suffering from acute trauma pain in the context of kidney and liver disease. The evidence base and limitations of other adjuncts such as topical and intravenous lidocaine, ketamine and regional anaesthesia in acute geriatric trauma are discussed.

How much does the postoperative delirium really count as a risk factor for poorer quality of life with long-term cognitive and functional decline after cardiac surgery?

How much does the postoperative delirium really count as a risk factor for poorer quality of life with long-term cognitive and functional decline after cardiac surgery?

Sex Differences in Long-Term Functional Decline after Ischemic Stroke: A Longitudinal Observational Study from the Fukuoka Stroke Registry

Introduction: Data on sex differences in poststroke functional status for a period longer than 1 year based on large cohorts are sparse. This study aimed to determine whether there are sex differences in long-term functional decline after ischemic stroke. Methods: We tracked functional status for 5 years among 3-month survivors of acute ischemic stroke and compared outcomes between women and men using a large-scale hospital-based stroke registry in Fukuoka, Japan. Functional status was assessed using the modified Rankin Scale (mRS). Functional dependency was defined as an mRS score of 3, 4, or 5. Logistic regression analysis was used to estimate odds ratios (ORs) and 95% confidence intervals of outcomes after adjusting for possible confounders. Results: A total of 8,446 patients (71.9 ± 12.5 years, 3,377 (40.0%) female patients) were enrolled in this study. Female sex was associated with a higher risk of functional dependency at 5 years poststroke even when adjusting for age, 3-month mRS score, and other confounding factors (multivariable-adjusted OR vs. men, 1.56 [95% confidence interval, 1.26–1.93]). This significant association of female sex with higher dependency at 5 years was also found among patients who were independent at 3 months poststroke. Subgroup analysis showed that increased risk of functional dependency in female patients was more marked in patients aged ≥75 years than in those aged <75 years (p for heterogeneity = 0.02). Conversely, female sex was associated with a lower risk of death. No sex difference was observed in stroke recurrence during 5 years poststroke. Discussion/Conclusion: This longitudinal observational study suggests that female sex was independently associated with an increased risk of functional decline in the chronic phase of stroke, especially in older patients. There was no sex difference in 5-year stroke recurrence, and thus, other factors might be involved in more significant deterioration of functional status in female survivors of ischemic stroke. Further studies are needed to elucidate underlying causes of sex differences in long-term functional decline after stroke.

Chronic Pulmonary Manifestations of COVID-19 Infection: Imaging Evaluation.

This case presents a patient with severe COVID-19 pneumonia requiring intensive care unit admission and a prolonged hospital stay. The infection resulted in long-term morbidity, functional decline, and abnormal chest CT findings. The mechanisms for long-term lung injury after COVID-19 infection, imaging appearances, and the role of imaging in follow-up are discussed.

Current Updates on the Diagnosis and Management of Multiple Sclerosis for the General Neurologist.

Multiple sclerosis (MS) is an immune-driven disease that affects the central nervous system and is characterized by acute-on-chronic demyelination attacks. It is a major cause of global neurological disability, and its prevalence has increased in the United States. Conceptual understandings of MS have evolved over time, including the identification of B cells as key factors in its pathophysiology. The foundation of MS management involves preventing flares so as to avoid long-term functional decline. Treatments may be categorized into low-, middle-, and high-efficacy medications based on their efficacy in relapse prevention. With 24 FDA-approved treatments for MS, individual therapy is chosen based on distinct mechanisms and potential side effects. This review provides a detailed update on the epidemiology, diagnosis, treatment advances, and major ongoing research investigations in MS.

Hyperacute immune responses associate with immediate neuropathology and motor dysfunction in large vessel occlusions.

Despite successful endovascular therapy, a proportion of stroke patients exhibit long-term functional decline, regardless of the cortical reperfusion. Our objective was to evaluate the early activation of the adaptive immune response and its impact on neurological recovery in patients with large vessel occlusion (LVO). Nineteen (13 females, 6 males) patients with acute LVO were enrolled in a single-arm prospective cohort study. During endovascular therapy (EVT), blood samples were collected from pre and post-occlusion, distal femoral artery, and median cubital vein (controls). Cytokines, chemokines,cellular and functional profiles were evaluated with immediate and follow-up clinical and radiographic parameters, including cognitive performance and functional recovery. In the hyperacute phase (within hours), adaptive immune activation was observed in the post-occlusion intra-arterial environment (post). Ischemic vascular tissue had a significant increase in T-cell-related cytokines, including IFN-γ and MMP-9, while GM-CSF, IL-17, TNF-α, IL-6, MIP-1a, and MIP-1b were decreased. Cellularity analysis revealed an increase in inflammatory IL-17+ and GM-CSF+ helper T-cells, while natural killer (NK), monocytes and B-cells were decreased. A correlation was observed between hypoperfused tissue, infarct volume, inflammatory helper, and cytotoxic T-cells. Moreover, helper and cytotoxic T-cells were also significantly increased in patients with improved motor function at 3 months. We provide evidence of the activation of the inflammatory adaptive immune response during the hyperacute phase and the association of pro-inflammatory cytokines with greater ischemic tissue and worsening recovery after successful reperfusion. Further characterization of these immune pathways is warranted to test selective immunomodulators during the early stages of stroke rehabilitation.

Postoperative delirium: An independent risk factor for poorer quality of life with long-term cognitive and functional decline after cardiac surgery

Study objectiveTo evaluate the influence of delirium on the functional and cognitive capacity of patients included in the DELIPRECAS study, as well as on their quality of life, in the 3–4 years after cardiac surgery. DesignProspective observational study. SettingAssessment of cognitive and functional status from hospital discharge to the present, 3 years after cardiac surgery. Patients313 patients undergoing cardiac surgery consecutively, aged 18 years or over. MeasurementsThe primary outcome measure was the cognitive and functional status of the patients 3 years after cardiac surgery, evaluated by telephone interview, and the possible influence on them of delirium diagnosed by the Confusion Assessment Method in Intensive Care Units (CAM-ICU) during their stay in the intensive care unit after cardiac surgery. Main resultsPostoperative delirium acts as an independent risk factor for the long-term development of memory problems (OR 6.11, 95% CI 2.54 to 14.68, p < 0.001), concentration (OR 11.20, 95% CI 3.58 to 35.09, p > 0.001), confusion/disorientation (OR 10.93, 95% CI 3.61 to 33.12, p > 0.001), sleep problems (OR 5.21, 95% CI 2 0.29 to 11.84, p < 0.001), nightmares (OR 8.99, 95% CI 1.98 to 40.90, p = 0.004), emotional problems (OR 4.30, 95% CI 1.87 to 9.91, p = 0.001) and poorer mobility after hospital discharge (OR 2.436, 95% CI 1.06 to 5.61, p = 0.037). The number of hospital readmissions was also significantly higher in those patients who developed delirium after cardiac surgery (27% vs 13.8%, p = 0.022). ConclusionPostoperative delirium is a risk factor for decreased quality of life in patients 3 years after heart surgery, being associated with greater cognitive and functional deterioration, as well as greater risk of hospital readmission. Therefore, emphasis should be placed on both prevention and early recognition and treatment of delirium to improve long-term outcomes for patients after cardiac surgery.

Patterns of change and factors associated with IADL function decline in community-dwelling older adults with arthritis

Arthritis is a major cause of functional decline, which affects the quality of life (QoL) of older adults. This study analyzed instrumental activities of daily living (IADL) patterns in older adults with arthritis and the risk factors of functional decline. Data from the Korean Longitudinal Study of Aging (KLoSA), in which the participants were community-dwelling older adults aged ≥ 65 years and conducted every two years, were used to examine patterns in IADL performance between 2006 and 2016. The participants comprised 1,822 older adults, divided into an arthritis group and a non-arthritis group. A Generalized Estimating Equations (GEE) model and Kaplan–Meier analysis was used for the data analysis. The arthritis groups showed a statistically significant decrease in IADL function in 2012 (β = 1.283, p = 0.026), 2014 (β = 1.323, p = 0.028), and 2016 (β = 1.484, p = 0.014). The GEE model identified psychological conditions (depressive symptoms, cognitive function) and number of chronic diseases in the arthritis group as risk factors for increased IADL dependence. Healthcare providers should develop strategies to manage long-term functional decline, including programs to manage and prevent chronic diseases, cognitive function decline, and keep depressive symptoms under control, beginning within six years of arthritis diagnosis.

Impact of frailty on risk of long-term functional decline following vascular surgery

ObjectiveFrailty is a clinical syndrome associated with slow recovery after vascular surgery. However, the degree and length of functional impairment frail patients experience after surgery is unclear. The objective of this study was to prospectively measure changes in functional status among frail and non-frail patients undergoing a spectrum of different vascular surgery procedures. MethodsPatients consented to undergo elective minor and major vascular surgery procedures at an academic medical center between May 2018 and March 2019 were prospectively identified. Prior to surgery, all patients underwent provider assessment of frailty using the validated Clinical Frailty Scale (CFS), as well as baseline assessment of functional status using the Katz Activities of Daily Living (ADL) index and the Lawton Instrumental Activities of Daily Living (iADL) index. These same instruments were used to evaluate each patient’s functional status at 2-weeks, 1-month, 1-year, and 2-year time points following surgery. Changes in iADL and ADL scores among frail (CFS ≥5) and non-frail patients were compared using paired Wilcoxon signed-rank tests and logistic regression models. ResultsA total of 126 patients were assessed before and after minor (55%) and major (45%) vascular procedures, of which 43 patients (34%) were determined to be frail prior to surgery. Frail patients were older and more likely than non-frail patients to have medical comorbidities including chronic kidney disease, chronic obstructive pulmonary disease, or diabetes (all P < .05). When compared with the non-frail cohort, frail patients had significantly lower ADL and iADL scores before surgery and experienced a greater decline in ability to independently complete ADL and iADL activities after surgery that was sustained at 2 years (P < .05 and P < .001, respectively). After risk-adjustment, frailty was associated with an increased likelihood of decline in ADLs (odds ratio, 5.4; 95% confidence interval, 1.9-15.4; P < .05) and iADLs (odds ratio, 6.3; 95% confidence interval, 2.6-15.1; P < .001) at 2 years following surgery. ConclusionsFrail patients experience a significant decline in ability to perform ADL and iADLs that persists 2 years following vascular surgery. These data highlight the degree of functional decline occurring immediately following surgery, as well as risk for long-term, sustained impairment that should be shared with frail patients before undergoing a procedure.

Peak ependymal cell stretch overlaps with the onset locations of periventricular white matter lesions

Deep and periventricular white matter hyperintensities (dWMH/pvWMH) are bright appearing white matter tissue lesions in T2-weighted fluid attenuated inversion recovery magnetic resonance images and are frequent observations in the aging human brain. While early stages of these white matter lesions are only weakly associated with cognitive impairment, their progressive growth is a strong indicator for long-term functional decline. DWMHs are typically associated with vascular degeneration in diffuse white matter locations; for pvWMHs, however, no unifying theory exists to explain their consistent onset around the horns of the lateral ventricles. We use patient imaging data to create anatomically accurate finite element models of the lateral ventricles, white and gray matter, and cerebrospinal fluid, as well as to reconstruct their WMH volumes. We simulated the mechanical loading of the ependymal cells forming the primary brain-fluid interface, the ventricular wall, and its surrounding tissues at peak ventricular pressure during the hemodynamic cycle. We observe that both the maximum principal tissue strain and the largest ependymal cell stretch consistently localize in the anterior and posterior horns. Our simulations show that ependymal cells experience a loading state that causes the ventricular wall to be stretched thin. Moreover, we show that maximum wall loading coincides with the pvWMH locations observed in our patient scans. These results warrant further analysis of white matter pathology in the periventricular zone that includes a mechanics-driven deterioration model for the ventricular wall.

Long-Term Functional Decline Following Vascular Surgery Among Vulnerable Adults

Identification of high-risk patients that may experience functional decline following surgery poses a challenge to healthcare providers. The Vulnerable Elders Survey (VES-13) is a patient-reported tool designed to identify risk for health deterioration based on age, self-rated health, physical function, and functional disabilities. This study was designed to determine whether VES-13 could predict long-term functional decline among patients undergoing vascular surgery procedures. Vascular surgery patients at an academic hospital were administered VES-13 between May 2018 and March 2019, and those scoring ≥3-points were classified as vulnerable. Each patient's functional status was assessed using the Katz Activities of Daily Living (ADL) and the Lawton-Brody Instrumental Activities of Daily Living (iADL) indices preoperatively and at 2-week, 1-month, and 1-year postoperative time points. Logistic regression models were used to identify independent predictors of functional decline. 126 patients (59% male) were assessed before and after minor (56%) and major (44%) vascular procedures, with 55 (43%) meeting criteria for vulnerability. Vulnerable patients were older, had lower baseline functional status, and were more likely than non-vulnerable patients to experience declines in ADLs and iADLs at all time-points (P < 0.05 for all time points). These findings were confirmed in risk-adjusted regression models where vulnerability was associated with an increased likelihood of decline in ADLs (OR:3.3; 95%CI:1.0-10.6; P < 0.05) and iADLs (OR:2.6; 95%CI:1.0-6.6; P = 0.05) at 1-year following surgery. The patient-reported VES-13 survey identifies vulnerable patients who are at risk for long-term functional decline following vascular surgery. This quick preoperative screening tool can allow surgeons to prepare older patients and caretakers for postoperative functional limitations.

Health-related quality of life, functional decline, and long-term mortality in older patients following hospitalisation due to COVID-19

BackgroundOlder people are particularly vulnerable to severe COVID-19. Little is known about long-term consequences of COVID-19 on health-related quality of life (HR-QoL) and functional status in older people, and the impact of age in this context. We aimed to study age-related change in health-related quality of life, functional decline and mortality among older patients 6 months following hospitalisation due to COVID-19.MethodsThis was a cohort study including patients aged 60 years and older admitted to four general hospitals in South-Eastern Norway due to COVID-19, from March 1 up until July 1, 2020. Patients who were still alive were invited to attend a six-month follow-up. Change in HR-QoL and functional status compared to before the COVID-19 hospitalisation were assessed using the EuroQol 5-dimensional-5 levels questionnaire (EQ. 5D-5L). A change in visual analogue scale (VAS) score of 7 or more was considered clinically relevant.ResultsOut of 216 patients aged 60 years and older that were admitted to hospital due to COVID-19 during the study period, 171 were still alive 180 days after hospital admission, and 106 patients (62%) attended the six-month follow-up. Mean age was 74.3 years, 27 patients (26%) had experienced severe COVID-19. Fifty-seven participants (54%) reported a decrease in the EQ. 5D-5L VAS score after 6 months, with no significant difference between persons aged 75 years and older compared to younger. Seventy participants (66%) reported a negative change in any of the dimensions of the EQ. 5D-5L, with impaired ability to perform activities of daily life (35%), reduced mobility (33%) and having more pain or discomfort (33%) being the most commonly reported changes. Forty-six participants (43%) reported a negative change in cognitive function compared to before the COVID-19 hospitalisation. Six-month mortality was 21%, and increased with increasing age.ConclusionsMore than half of the patients reported a negative change in HR-QoL 6 months following hospitalisation due to COVID-19, and one out of three experienced a persistently impaired mobility and ability to carry out activities of daily living. The results suggest awareness of long-term functional decline in older COVID-19 patients.

Long-Term Functional Decline Following Vascular Surgery Among Vulnerable Adults

Long-Term Functional Decline Following Vascular Surgery Among Vulnerable Adults

Mortality and Health Outcomes for Older Adults Screened by an Area Agency on Aging Over a 4.5-Year Period

Area Agencies on Aging (AAA) screen older adults and oversee delivery of a wide range of home- and community-based services (HCBS). We examined the assessment process, services, and mortality and health outcomes for older adults screened by an Area Agency on Aging in west-central Florida. Most were self/family referred (78.9%). Using data from July 2013-December 2018, 23,225 older adults were screened. Individuals had an average of 2.6 years follow-up in the dataset, during which time 63.6% received additional assessments: follow-up screening (50.6%), comprehensive assessment for enrollment in HCBS (35.7%), or assessments for congregate meals or other services (13.7%). Results revealed differences in mortality: 22.5% of clients receiving services died compared to 32.1% of clients prioritized as lower risk and on waiting lists for services. Long-term care placement and functional decline outcomes also will be reviewed, along with implications for service delivery and managing waitlists.

Cross-Priming Dendritic Cells Exacerbate Immunopathology After Ischemic Tissue Damage in the Heart.

Ischemic heart disease is a leading cause of heart failure and despite advanced therapeutic options, morbidity and mortality rates remain high. Although acute inflammation in response to myocardial cell death has been extensively studied, subsequent adaptive immune activity and anti-heart autoimmunity may also contribute to the development of heart failure. After ischemic injury to the myocardium, dendritic cells (DC) respond to cardiomyocyte necrosis, present cardiac antigen to T cells, and potentially initiate a persistent autoimmune response against the heart. Cross-priming DC have the ability to activate both CD4+ helper and CD8+ cytotoxic T cells in response to necrotic cells and may thus be crucial players in exacerbating autoimmunity targeting the heart. This study investigates a role for cross-priming DC in post-myocardial infarction immunopathology through presentation of self-antigen from necrotic cardiac cells to cytotoxic CD8+ T cells. We induced type 2 myocardial infarction-like ischemic injury in the heart by treatment with a single high dose of the β-adrenergic agonist isoproterenol. We characterized the DC population in the heart and mediastinal lymph nodes and analyzed long-term cardiac immunopathology and functional decline in wild type and Clec9a-depleted mice lacking DC cross-priming function. A diverse DC population, including cross-priming DC, is present in the heart and activated after ischemic injury. Clec9a-/- mice deficient in DC cross-priming are protected from persistent immune-mediated myocardial damage and decline of cardiac function, likely because of dampened activation of cytotoxic CD8+ T cells. Activation of cytotoxic CD8+ T cells by cross-priming DC contributes to exacerbation of postischemic inflammatory damage of the myocardium and corresponding decline in cardiac function. Importantly, this provides novel therapeutic targets to prevent postischemic immunopathology and heart failure.

Long-term functional decline of spontaneous intracerebral haemorrhage survivors

ObjectiveTo identify in patients who survived 6 months after a spontaneous intracerebral haemorrhage (ICH) baseline characteristics and new clinical events associated with functional decline.MethodsIn a single-centre study, we prospectively included...

Incident Impaired Cognitive Function in Sarcopenic Obesity: Data From the National Health and Aging Trends Survey

ObjectivesThe prevalence of obesity with sarcopenia is increasing in adults aged ≥65 years. This geriatric syndrome places individuals at risk for synergistic complications that leads to long-term functional decline. We ascertained the relationship between sarcopenic obesity and incident long-term impaired global cognitive function in a representative US population. DesignA longitudinal, secondary data set analysis using the National Health and Aging Trends Survey. SettingCommunity-based older adults in the United States. ParticipantsParticipants without baseline impaired cognitive function aged ≥65 years with grip strength and body mass index measures. MethodsSarcopenia was defined using the Foundation for the National Institutes of Health Sarcopenia Project grip strength cut points (men <35.5 kg; women <20 kg), and obesity was defined using standard body mass index (BMI) categories. Impaired global cognition was identified as impairment in the Alzheimer's Disease-8 score or immediate/delayed recall, orientation, clock-draw test, date/person recall. Proportional hazard models ascertained the risk of impaired cognitive function over 8 years (referent = neither obesity or sarcopenia). ResultsOf the 5822 participants (55.7% women), median age category was 75 to 80, and mean grip strength and BMI were 26.4 kg and 27.5 kg/m2, respectively. Baseline prevalence of sarcopenic obesity was 12.9%, with an observed subset of 21.2% participants having impaired cognitive function at follow-up. Compared with those without sarcopenia or obesity, the risk of impaired cognitive function was no different in obesity alone [hazard ratio (HR) 0.98; 95% confidence interval (CI) 0.82–1.16]), but was significantly higher in sarcopenia (HR 1.60; 95% CI 1.42–1.80) and sarcopenic obesity (HR 1.20; 95% CI 1.03–1.40). There was no significant interaction term between sarcopenia and obesity. ConclusionsBoth sarcopenia and sarcopenic obesity are associated with an increased long-term risk of impaired cognitive function in older adults.