Treatment-limiting decisions, comorbidities, and mortality in the emergency departments: a cross-sectional elderly population-based study

BACKGROUND: Older adults experience a higher risk of death in the emergency departments (EDs), in part, as a result of their comorbidities. A treatment-limiting decision is often reported for older adults who die in the EDs. The Charlson Comorbidity Index (CCI) is a validated method for the scoring of comorbidities. Whether an association between the CCI and treatment-limiting decisions exists remains unknown. OBJECTIVE: To determine whether the CCI was associated with the treatment-limiting decisions made for older patients who die in the EDs. METHODS: A total of 2,095 patients >/=65 years old who died in the EDs in France and Belgium were prospectively included between 2004 and 2005. The recorded data included: 1) the CCI score; 2) patient age; 3) gender; 4) living in senior housing facilities; 5) hospitalizations occurring in the previous year; 6) presence of functional limitations (according to the Knaus classification); 7) chronic diseases; and 8) presence of organ failure(s). A treatment-limiting decision was defined as a predetermined choice not to implement therapies that would otherwise be required to sustain life. RESULTS: A treatment-limiting decision was identified in 993 (47%) patients. Fully-adjusted logistic regression model showed that a CCI >/= 5 (OR=25.56 with P=0.037), age >/=85years (OR=20.33 with P<0.001), living in an institution (OR=0.15 with P=0.017), hematologic (OR=6.92 with P=0.020) and respiratory disease (OR=0.17 with P=0.046), and neurologic causes (OR=0.20 with P=0.010) of organ failure were significantly associated with treatment-limiting decisions. CONCLUSION: An elevated CCI score (>/=5) was associated with a treatment-limiting decision in elderly patients evaluated in the EDs. Further research is needed to corroborate this finding

Analysis of iatrogenic risk related to anticholinergic effects using two scales in acute geriatric inpatient unit

Anticholinergic medications are responsible for most frequent adverse drug effects. Two scales have been elaborated as tools for prescribers: the Anticholinergic Drug Scale (ADS) of Carnahan et al., and the Anticholinergic Risk Scale (ARS) of Rudolph et al. The objective of this study was to analyze the diagnostic performance of both scales for predicting signs related to an anticholinergic effect. Method: Medical records of 1379 patients aged 75 years or older hospitalized in a geriatric acute care unit between 2002 and 2005 were studied. The analyze was made retrospectively, but data were collected prospectively. Results: Risk of appearance of total anticholinergic signs (ADS : OR 1,45, CI 95% [1,03-2,03], p=0,037 and ARS : OR 1,98, CI 95% [1,19-3,28] p<0,01) and peripheral signs (ADS: OR 1,66, CI 95% [1,22-2,26], p<0,01 and ARS : OR 1,81, CI 95% [1,19-2,75], p<0,01) increased when score was >= 3 with both scales, which wasn\u27t the case for central signs. Conclusion: Both scales permitted to detect an increased risk of appearance of total and peripheral anticholinergic signs, but not the centrals as delirium. Interest of total anticholinergic burden remains to be demonstrated, especially for delirium risk assessment

Extracellular calcium antagonizes forskolin-induced aquaporin 2 trafficking in collecting duct cells

BACKGROUND: Urinary concentrating defects and polyuria are the most important renal manifestations of hypercalcemia and the resulting hypercalciuria. In this study, we tested the hypothesis that hypercalciuria-associated polyuria in kidney collecting duct occurs through an impairment of the vasopressin-dependent aquaporin 2 (AQP2) water channel targeting to the apical membrane possibly involving calcium-sensing receptor (CaR) signaling. METHODS: AQP2-transfected collecting duct CD8 cells were used as experimental model. Quantitation of cell surface AQP2 immunoreactivity was performed using an antibody recognizing the extracellular AQP2 C loop. Intracellular cyclic adenosine monophosphate (cAMP) accumulation was measured in CD8 cells using a cAMP enzyme immunoassay kit. To study the translocation of protein kinase C (PKC), membranes or cytosol fractions from CD8 cells were subjected to Western blotting using anti-PKC isozymes antibodies. The amount of F-actin was determined by spectrofluorometric techniques. Intracellular calcium measurements were performed by spectrofluorometric analysis with Fura-2/AM. RESULTS: We demonstrated that extracellular calcium (Ca2+ o) (5 mmol/L) strongly inhibited forskolin-stimulated increase in AQP2 expression in the apical plasma membrane. At least three intracellular pathways activated by extracellular calcium were found to contribute to this effect. Firstly, the increase in cAMP levels in response to forskolin stimulation was drastically reduced in cells pretreated with Ca2+ o compared to untreated cells. Second, Ca2+ o activated PKC, known to counteract vasopressin response. Third, quantification of F-actin demonstrated that Ca2+ o caused a nearly twofold increase in F-actin content compared with basal conditions. All these effects were mimicked by a nonmembrane permeable agonist of the extracellular CaR, Gd3+. CONCLUSION: Together, these data demonstrate that extracellular calcium, possibly acting through the endogenous CaR, antagonizes forskolin-induced AQP2 translocation to the apical plasma membrane in CD8 cells. In hypercalciuria, this mechanism might blunt water reabsorption and prevent further calcium concentration, thus protecting against a potential risk of urinary calcium-containing stone formation

Invasive Bacterial Infections in Children With Sickle Cell Disease: 2014–2019

Background: Children with sickle cell disease (SCD) are at a high risk of invasive bacterial infections (IBI). Universal penicillin prophylaxis and vaccination, especially against Streptococcus pneumoniae, have deeply changed its epidemiology. Analysis of IBI in children with SCD in a post-13-valent pneumococcal vaccine era is limited. Methods: Twenty-eight pediatric hospitals from 5 European countries retrospectively collected IBI episodes in SCD children aged 1 month to 18 years between 2014 and 2019. IBI was defined as a positive bacterial culture or polymerase chain reaction from a normally sterile fluid: blood, cerebrospinal, joint, or pleural fluid and deep surgical specimen. Results: We recorded 169 IBI episodes. Salmonella spp. was the main isolated bacteria (n = 44, 26%), followed by Streptococcus pneumonia (Sp; n = 31, 18%) and Staphylococcus aureus (n = 20, 12%). Salmonella prevailed in osteoarticular infections and in primary bacteremia (45% and 23% of episodes, respectively) and Sp in meningitis and acute chest syndrome (88% and 50%, respectively). All Sp IBI occurred in children ≤10 years old, including 35% in children 5 to 10 years old. Twenty-seven (17%) children had complications of infection and 3 died: 2 because of Sp, and 1 because of Salmonella. The main risk factors for a severe IBI were a previous IBI and pneumococcal infection (17 Sp/51 cases). Conclusions: In a post-13-valent pneumococcal vaccine era, Salmonella was the leading cause of bacteremia in IBI in children with SCD in Europe. Sp came second, was isolated in children ≤10 years old, and was more likely to cause severe and fatal cases.info:eu-repo/semantics/publishedVersio

Circadian Integration of Glutamatergic Signals by Little SAAS in Novel Suprachiasmatic Circuits

Neuropeptides are critical integrative elements within the central circadian clock in the suprachiasmatic nucleus (SCN), where they mediate both cell-to-cell synchronization and phase adjustments that cause light entrainment. Forward peptidomics identified little SAAS, derived from the proSAAS prohormone, among novel SCN peptides, but its role in the SCN is poorly understood.Little SAAS localization and co-expression with established SCN neuropeptides were evaluated by immunohistochemistry using highly specific antisera and stereological analysis. Functional context was assessed relative to c-FOS induction in light-stimulated animals and on neuronal circadian rhythms in glutamate-stimulated brain slices. We found that little SAAS-expressing neurons comprise the third most abundant neuropeptidergic class (16.4%) with unusual functional circuit contexts. Little SAAS is localized within the densely retinorecipient central SCN of both rat and mouse, but not the retinohypothalamic tract (RHT). Some little SAAS colocalizes with vasoactive intestinal polypeptide (VIP) or gastrin-releasing peptide (GRP), known mediators of light signals, but not arginine vasopressin (AVP). Nearly 50% of little SAAS neurons express c-FOS in response to light exposure in early night. Blockade of signals that relay light information, via NMDA receptors or VIP- and GRP-cognate receptors, has no effect on phase delays of circadian rhythms induced by little SAAS.Little SAAS relays signals downstream of light/glutamatergic signaling from eye to SCN, and independent of VIP and GRP action. These findings suggest that little SAAS forms a third SCN neuropeptidergic system, processing light information and activating phase-shifts within novel circuits of the central circadian clock

The Role for HNF-1β-Targeted Collectrin in Maintenance of Primary Cilia and Cell Polarity in Collecting Duct Cells

Collectrin, a homologue of angiotensin converting enzyme 2 (ACE2), is a type I transmembrane protein, and we originally reported its localization to the cytoplasm and apical membrane of collecting duct cells. Recently, two independent studies of targeted disruption of collectrin in mice resulted in severe and general defects in renal amino acid uptake. Collectrin has been reported to be under the transcriptional regulation by HNF-1α, which is exclusively expressed in proximal tubules and localized at the luminal side of brush border membranes. The deficiency of collectrin was associated with reduction of multiple amino acid transporters on luminal membranes. In the current study, we describe that collectrin is a target of HNF-1β and heavily expressed in the primary cilium of renal collecting duct cells. Collectrin is also localized in the vesicles near the peri-basal body region and binds to γ-actin-myosin II-A, SNARE, and polycystin-2-polaris complexes, and all of these are involved in intracellular and ciliary movement of vesicles and membrane proteins. Treatment of mIMCD3 cells with collectrin siRNA resulted in defective cilium formation, increased cell proliferation and apoptosis, and disappearance of polycystin-2 in the primary cilium. Suppression of collectrin mRNA in metanephric culture resulted in the formation of multiple longitudinal cysts in ureteric bud branches. Taken together, the cystic change and formation of defective cilium with the interference in the collectrin functions would suggest that it is necessary for recycling of the primary cilia-specific membrane proteins, the maintenance of the primary cilia and cell polarity of collecting duct cells. The transcriptional hierarchy between HNF-1β and PKD (polycystic kidney disease) genes expressed in the primary cilia of collecting duct cells has been suggested, and collectrin is one of such HNF-1β regulated genes