Clinical features and outcomes of elderly hospitalised patients with chronic obstructive pulmonary disease, heart failure or both

Background and objective: Chronic obstructive pulmonary disease (COPD) and heart failure (HF) mutually increase the risk of being present in the same patient, especially if older. Whether or not this coexistence may be associated with a worse prognosis is debated. Therefore, employing data derived from the REPOSI register, we evaluated the clinical features and outcomes in a population of elderly patients admitted to internal medicine wards and having COPD, HF or COPD + HF. Methods: We measured socio-demographic and anthropometric characteristics, severity and prevalence of comorbidities, clinical and laboratory features during hospitalization, mood disorders, functional independence, drug prescriptions and discharge destination. The primary study outcome was the risk of death. Results: We considered 2,343 elderly hospitalized patients (median age 81 years), of whom 1,154 (49%) had COPD, 813 (35%) HF, and 376 (16%) COPD + HF. Patients with COPD + HF had different characteristics than those with COPD or HF, such as a higher prevalence of previous hospitalizations, comorbidities (especially chronic kidney disease), higher respiratory rate at admission and number of prescribed drugs. Patients with COPD + HF (hazard ratio HR 1.74, 95% confidence intervals CI 1.16-2.61) and patients with dementia (HR 1.75, 95% CI 1.06-2.90) had a higher risk of death at one year. The Kaplan-Meier curves showed a higher mortality risk in the group of patients with COPD + HF for all causes (p = 0.010), respiratory causes (p = 0.006), cardiovascular causes (p = 0.046) and respiratory plus cardiovascular causes (p = 0.009). Conclusion: In this real-life cohort of hospitalized elderly patients, the coexistence of COPD and HF significantly worsened prognosis at one year. This finding may help to better define the care needs of this population

Analysis of shared common genetic risk between amyotrophic lateral sclerosis and epilepsy

Because hyper-excitability has been shown to be a shared pathophysiological mechanism, we used the latest and largest genome-wide studies in amyotrophic lateral sclerosis (n = 36,052) and epilepsy (n = 38,349) to determine genetic overlap between these conditions. First, we showed no significant genetic correlation, also when binned on minor allele frequency. Second, we confirmed the absence of polygenic overlap using genomic risk score analysis. Finally, we did not identify pleiotropic variants in meta-analyses of the 2 diseases. Our findings indicate that amyotrophic lateral sclerosis and epilepsy do not share common genetic risk, showing that hyper-excitability in both disorders has distinct origins

Secretory cells of the airway express molecules of the chemoreceptive cascade

Airway secretion is maintained by specialized non-ciliated epithelial cells whose phenotype varies with their topographical location. In addition, specialized epithelial cells located in the airway contain the molecular machinery of chemoreceptive elements. Our aim has been to evaluate whether the secretory cells themselves possess a chemoreceptive capability, which requires the simultaneous presence of chemosensory and secretory mechanisms. We performed immunohistochemical analysis with antibodies against the Clara-cell-specific secretory proteins, CC10 and CC26, as secretory markers. As chemoreceptive markers, we employed antibodies against alpha-gustducin and phospholipase C beta 2 (PLCbeta2), two components of the taste transduction pathway. We also attempted to characterize further the secretory cell type by using a marker of chloride secretion, cystic fibrosis transmembrane regulator (CFTR). We found alpha-gustducin localized in non-ciliated cells of the epithelium lining the trachea and bronchioles of adult rats, where it was also co-expressed with CC10 and CC26. Ultrastructural immunohistochemistry revealed alpha-gustducin in the apical cytoplasm of secretory cells, concentrated around and inside the granules. CFTR was also observed in a subpopulation of non-ciliated epithelial cells, co-localized with some alpha-gustducin- and PLCbeta2-immunoreactive cells, at all levels of the airway epithelium. We conclude that non-ciliated epithelial cells of the rat airway express components of distinct signaling mechanisms and suggest that secretory events are driven by a molecular mechanism activated by the binding of luminal substances to G-protein-coupled receptors

Immunolocalization of leptin and leptin receptor in colorectal mucosa of ulcerative colitis, Crohn's disease and control subjects with no inflammatory bowel disease

The expression of leptin and leptin receptor (Ob-R) has been partially elucidated in colon of patients with inflammatory bowel diseases (IBDs), even though leptin is involved in angiogenesis and inflammation. We previously reported overexpression of GLUT5 fructose transporter, in aberrant clusters of lymphatic vessels in lamina propria of IBD and controls. Here, we examine leptin and Ob-R expression in the same biopsies. Specimens were obtained from patients with ulcerative colitis (UC), Crohn's disease (CD) and controls who underwent screening for colorectal cancer, follow-up after polypectomy or with a history of lower gastrointestinal symptoms. Immunohistochemistry revealed leptin in apical and basolateral membranes of short epithelial portions, Ob-R on the apical pole of epithelial cells. Leptin and Ob-R were also identified in structures and cells scattered in the lamina propria. In UC, a significant correlation between leptin and Ob-R in the lamina propria was found in all inflamed samples, beyond non-inflamed samples of the proximal tract, while in CD, it was found in inflamed distal samples. Most of the leptin and Ob-R positive areas in the lamina propria were also GLUT5 immunoreactive in inflamed and non-inflamed mucosa. A significant correlation of leptin or Ob-R expression with GLUT5 was observed in the inflamed distal samples from UC. Our findings suggest that there are different sites of leptin and Ob-R expression in large intestine and those in lamina propria do not reflect the status of mucosal inflammation. The co-localization of leptin and/or Ob-R with GLUT5 may indicate concomitance effects in colorectal lamina propria areas

High Resolution and High Definition Anorectal Manometry

Th e book provides a comprehensive overview of high resolution and high definition anorectal manometry (HRAM/HDAM), showing the possible benefits of a wider use of these techniques in clinical practice, as well as their limitations. Although these techniques provide fresh insights into anorectal function and off er a new perspective on the pathophysiologic mechanisms of many defecation disturbances, there is a need to clarify whether their use has beneficial effects on clinical management compared to conventional manometry. There is still a considerable way to go to gain the clinical diffusion of esophageal HRM, which has become the gold standard in studying esophageal motility. Indeed, many gastroenterologists and surgeons are convinced that further studies are necessary in order to be able to recommend HRAM and HDAM over and above conventional anorectal manometry. The first part of the book presents anorectal anatomy and pathophysiology, highlighting the indications and limitations of conventional anorectal manometry. Th e second part then focuses on the general concepts of high resolution manometry and the difference between conventional anorectal manometry and HRAM/HDAM, including technical aspects and different equipment. The third part explains how to perform, analyze and interpret HRAM and HDAM recordings, and describes the parameters study protocol, normal values and how to formulate a particular diagnosis. Lastly, the fourth part includes a collection of normal and pathological images with a glossary of the most frequently terms. Written by experts in the fi eld of anorectal manometry and defecation disorders, this book is of interest to specialists and residents dealing with these conditions

Brain metabolic changes across King's stages in amyotrophic lateral sclerosis: a(18)F-2-fluoro-2-deoxy-d-glucose-positron emission tomography study

PURPOSE: To assess the brain metabolic correlates of the different regional extent of ALS, evaluated with the King's staging system, using brain 18F-2-fluoro-2-deoxy-D-glucose-PET (18F-FDG-PET). METHODS: Three hundred ninety ALS cases with King's stages 1, 2, and 3 (n = 390), i.e., involvement of 1, 2, and 3 body regions respectively, underwent brain 18F-FDG-PET at diagnosis. King's stage at PET was derived from ALSFRS-R and was regressed out against whole-brain metabolism in the whole sample. The full factorial design confirmed the hypothesis that differences among groups (King's 1, King's 2, King's 3, and 40 healthy controls (HC)) existed overall. Comparisons among stages and between each group and HC were performed. We included age at PET and sex as covariates. RESULTS: Brain metabolism was inversely correlated with stage in medial frontal gyrus bilaterally, and right precentral and postcentral gyri. The full factorial design resulted in a significant main effect of groups. There was no significant difference between stages 1 and 2. Comparing stage 3 to stage 1+2, a significant relative hypometabolism was highlighted in the former in the left precentral and medial frontal gyri, and in the right medial frontal, postcentral, precentral, and middle frontal gyri. The comparisons between each group and HC showed the extension of frontal metabolic changes from stage 1 to stage 3, with the larger metabolic gap between stages 2 and 3. CONCLUSIONS: Our findings support the hypothesis that in ALS, the propagation of neurodegeneration follows a corticofugal, regional ordered pattern, extending from the motor cortex to posterior and anterior regions.status: publishe

Murine cerebral organoids develop network of functional neurons and hippocampal brain region identity

Brain organoids are in vitro three-dimensional (3D) self-organized neural structures, which can enable disease modeling and drug screening. However, their use for standardized large-scale drug screening studies is limited by their high batch-to-batch variability, long differentiation time (10–20 weeks), and high production costs. This is particularly relevant when brain organoids are obtained from human induced pluripotent stem cells (iPSCs). Here, we developed, for the first time, a highly standardized, reproducible, and fast (5 weeks) murine brain organoid model starting from embryonic neural stem cells. We obtained brain organoids, which progressively differentiated and self-organized into 3D networks of functional neurons with dorsal forebrain phenotype. Furthermore, by adding the morphogen WNT3a, we generated brain organoids with specific hippocampal region identity. Overall, our results showed the establishment of a fast, robust and reproducible murine 3D in vitro brain model that may represent a useful tool for high-throughput drug screening and disease modeling.publishedVersionPeer reviewe