Heart failure with comorbid dementia: Association with clinical characteristics and outcomes.

BACKGROUND: Heart failure (HF) and dementia both have profound effects on function and mortality in older persons. However, we have limited knowledge about the impact of co-occurring HF and dementia. Our goal was to understand how often persons with HF have dementia and the impact of their co-occurrence. METHODS: Retrospective analysis of participants (age > 65) in the 2015 wave of the nationally representative Health and Aging Trends Study (NHATS) with linkage to Medicare claims. 912 participants with HF (45% older than 80, 51% women) using Medicare claims. We used the validated NHATS dementia algorithm to identify those with probable dementia. Outcomes of interest included the need for help with activities of daily living (ADLs) and instrumental activities of daily living (IADLs) at baseline, functional decline, hospitalization over 1 year, and mortality over 2-years. Baseline functional status, functional decline, and hospitalization were compared using adjusted logistic regression, mortality was analyzed using adjusted Cox regression models adjusted for demographics, socio-economic status, baseline health, and baseline functional status. RESULTS: 200 (21%) of the participants with HF also had dementia. For each I/ADL, patients with both HF and dementia were more likely to need help than those with HF without dementia. 71.8% of participants with HF and dementia needed help with medications versus 16.6% with HF without dementia (p < 0.001). Having HF and dementia was associated with an increased risk of requiring help with additional ADLs after one year (aOR = 2.69, 95% CI 1.53, 4.73). Participants with HF and dementia had an increased risk of being hospitalized within one year (aOR = 2.02 95% CI 1.16, 3.54), or dying within two years (aHR = 1.52 95% CI 1.03, 2.26). CONCLUSIONS: One-fifth of persons over age 65 with HF also have comorbid dementia. Co-occurring HF and dementia markedly increase functional impairment and subsequent ADL decline, hospitalization, and death. These results highlight the need for physician awareness for signs of dementia, and appropriate adjustments in the management of HF.

Effect of telemonitoring on readmissions for acute exacerbation of chronic obstructive pulmonary disease: A randomized clinical trial.

INTRODUCTION: Acute exacerbations of chronic obstructive pulmonary disease are associated with high morbidity and mortality. Telemonitoring may reduce the frequency of hospitalization. The aim of this study was to investigate the effect of telemonitoring on hospitalization rates for acute exacerbations of chronic obstructive pulmonary disease. METHODS: Patients were recruited during hospitalization and equally randomized to telemonitoring or usual care. Telemonitoring participants recorded symptoms and monitored oxygen saturation, heart rate, peak expiratory flow, and body weight. Alerts were generated if readings breached thresholds. Acute exacerbations of chronic obstructive pulmonary disease hospitalizations during the 6 months intervention were compared using logistic regression, and time to first hospitalization was assessed using Cox proportional hazard modeling. The incidence rates for acute exacerbations of chronic obstructive pulmonary disease hospitalization were compared using a negative binomial regression model with between-group comparisons expressed as incidence rate ratios. The telemonitoring group was used as reference. RESULTS: A total of 222 patients were randomized. 37/112 (33%) in the control group and 31/110 (28%) in the telemonitoring group experienced acute exacerbations of chronic obstructive pulmonary disease hospitalization during the intervention period, odds ratio of 1.26, confidence interval 0.71-2.23, p = 0.4. No difference was seen in time to first hospitalization, hazard ratio 1.23, CI 0.77-1.99, p = 0.4. The number of hospitalizations in the intervention period was 66 in the control group and 42 in the telemonitoring group, with incidence rate ratio 1.42, confidence interval 1.04-1.95, p = 0.03. Adjustment for dyspnea score, smoking, and cohabitation status did not change the results, incidence rate ratio 1.44, confidence interval 1.05-1.99, p = 0.02. DISCUSSION: Patients who received telemonitoring experienced significantly fewer acute exacerbations of chronic obstructive pulmonary disease hospitalizations, although the overall risk of having at least one hospitalization and the time to first hospitalization was similar between the two groups.

Incidence and severity of asymptomatic ocular injury in adult and pediatric orbital fractures.

PURPOSE: To evaluate the incidence of severe ocular injury requiring emergent ophthalmic evaluation in visually asymptomatic patients presenting with orbital fractures. METHODS: We performed a retrospective chart review of all adult and pediatric orbital fractures between 2012-2022 at a level 1 trauma center. Ocular injuries were categorized into severe, moderate, and mild. We evaluated symptoms, mechanism of injury, visual acuity (VA), and severity of injuries using the Cochran-Armitage and linear-by-linear tests. RESULTS: Of the 2495 cases, 1534 had ophthalmology evaluation. The mean ± standard deviation age was 40.4 ± 20.4 years. Most patients were male (73.1%) and Caucasian (75.9%). The mean time to evaluation was 0.6 ± 2.5 days. 486 (31.7%) were visually symptomatic, 760 (49.5%) were asymptomatic, and 288 (18.8%) were unknown. Of the symptomatic, 135 (27.8%) had severe injuries, 108 (22.2%) had moderate injuries, 216 (44.4%) had mild injuries, and 27 (5.6%) had no injuries. Of the asymptomatic, 67 (8.8%) had severe injuries, 183 (24.1%) had moderate injuries, 468 (61.6%) had mild injuries, and 42 (5.5%) had no injuries. Symptoms correlated with injury severity (p-value <.001). The most common mechanism of injury were falls (24.0%), assaults (22.2%), and motor vehicle accidents (14.8%). CONCLUSIONS: Visually asymptomatic orbital fractures were less likely to have severe ocular injuries; however, many patients were unable to express symptoms. Emergent ophthalmology evaluation should be considered in all patients presenting with orbital fractures, especially patients with visual symptoms or are unable to report symptoms.

Predictive Value of Precision-Cut Kidney Slices as an Ex Vivo Screening Platform for Therapeutics in Human Renal Fibrosis.

Animal models are a valuable tool in preclinical research. However, limited predictivity of human biological responses in the conventional models has stimulated the search for reliable preclinical tools that show translational robustness. Here, we used precision-cut kidney slices (PCKS) as a model of renal fibrosis and investigated its predictive capacity for screening the effects of anti-fibrotics. Murine and human PCKS were exposed to TGFß or PDGF pathway inhibitors with established anti-fibrotic efficacy. For each treatment modality, we evaluated whether it affected: (1) culture-induced collagen type I gene expression and interstitial accumulation; (2) expression of markers of TGFß and PDGF signaling; and (3) expression of inflammatory markers. We summarized the outcomes of published in vivo animal and human studies testing the three inhibitors in renal fibrosis, and drew a parallel to the PCKS data. We showed that the responses of murine PCKS to anti-fibrotics highly corresponded with the known in vivo responses observed in various animal models of renal fibrosis. Moreover, our results suggested that human PCKS can be used to predict drug efficacy in clinical trials. In conclusion, our study demonstrated that the PCKS model is a powerful predictive tool for ex vivo screening of putative drugs for renal fibrosis.

Metformin modulates immune cell infiltration into the kidney during unilateral ureteral obstruction in mice.

Metformin is today the first choice treatment for type-2 diabetes, but has also protective effects in several renal disease models. Previously, we have demonstrated that the protective effects in response to unilateral ureteral obstruction (UUO) are independent of organic cation transporters (OCTs), the transporters responsible for the metformin uptake into the renal cells. The mechanisms behind the renoprotective effects are incompletely understood, but our previous results indicate that the renoprotective effects at least partly could be dependent on actions of metformin outside the renal cells. In this study, we investigate whether the renoprotective effects of metformin can be mediated via systemic immunomodulatory actions. We demonstrated that metformin can affect the immune system in the kidney as well as in the peripheral blood and spleen following UUO. UUO kidneys showed infiltration of immune cells including monocytes, B cells, and T cells, but metformin limited infiltration of all cell types. UUO animals had increased spleen sizes, but this increase was attenuated by metformin. Metformin treatment surprisingly resulted in a higher proportion of monocytes with infiltratory capacity 7 days after UUO. Other studies have suggested that metformin regulates monocyte maturation through signal transducer and activator of transcription 3 (STAT3) activation, as also indicated by our results. In conclusion, our results demonstrate that metformin limits the infiltration of immune cells into the kidney, as well as modulates immune cell composition at a systemic level.

HLA-G polymorphisms and HLA-G expression in sarcoidosis.

BACKGROUND: The MHC class Ib molecule Human Leukocyte Antigen (HLA)-G may be important in induction and maintenance of immunological tolerance, and HLA-G expression may have a role in different cancers, in certain diseases with associations to HLA, and in organ transplantation. Sarcoidosis is a systemic granulomatous disease with unknown etiology but at the molecular level several studies have shown HLA associations. METHODS: In the present study, HLA-G alleles/polymorphisms were studied in sarcoidosis patients (n = 47) and controls (n = 129) by PCR techniques and HLA-G protein expression was investigated in granulomas from sarcoidosis patients with the use of immunohistochemistry. RESULTS: The HLA-G*010102/-G*0106 alleles were observed more often in sarcoidosis patients (39.4%) than in controls (26.4%), p = 0.025 (Fisher's exact test); however, not significant after correction (p(c) = 0.15). When HLA-G expression was investigated by immunohistochemistry in granulomas from sarcoidosis patients, weak HLA-G expression was observed in only one patient. CONCLUSIONS: HLA-G alleles that include a 14-bp sequence polymorphism in exon 8 of the HLA-G gene are observed more often in sarcoidosis patients than in controls. The sequence variation may influence HLA-G mRNA stability and influence the expression of soluble isoforms of HLA-G. Only rare and weak expression of HLA-G was observed in granulomas from sarcoidosis patients. More studies are needed to further elucidate the possible role for HLA-G in sarcoidosis.