Frequent utilization of the emergency department for acute exacerbation of chronic obstructive pulmonary disease

Background: Little is known about patients who frequently visit the emergency department (ED) for acute exacerbation of chronic obstructive pulmonary disease (AECOPD). We aimed to quantify the proportion and characteristics of patients with frequent ED visits for AECOPD and associated healthcare utilization. Methods: We conducted a retrospective cohort study of adults aged ≥40 years with at least one ED visit for AECOPD between 2010 and 2011, derived from population-based all-payer data of State ED and Inpatient Databases for two large and diverse states: California and Florida. Outcome measures were frequency of ED visits for AECOPD, 30-day ED revisits, subsequent hospitalizations, near-fatal events (AECOPD involving mechanical ventilation), and charges for both ED and inpatient services (available only for Florida) during the year after the first ED visit. Results: The analytic cohort comprised 98,280 unique patients with 154,736 ED visits for AECOPD. During the 1-year period, 29.4% (95% CI, 29.1%-29.7%) of the patients had two or more (frequent) visits, accounting for 55.2% (95% CI, 54.9%-55.4%) of all ED visits for AECOPD. In the multivariable model, significant predictors of frequent ED visits were age 55–74 years (vs. 40–54 years), male sex, non-Hispanic white or black race, Medicaid insurance (vs. private), and lower median household income (all P < 0.001). At the visit-level, 12.3% of ED visits for AECOPD were 30-day revisit events (95% CI, 12.1%-12.4%). Additionally, 62.8% of ED visits for AECOPD (95% CI, 62.6%-63.0%) resulted in a hospitalization; patients with frequent ED visits comprised 55.5% (95% CI, 55.2%-55.8%) of all hospitalizations. Furthermore, 7.3% (95% CI, 7.3%-7.5%) of ED visits for AECOPD led to a near-fatal event; patients with frequent ED visits accounted for 64.4% (95% CI, 63.5%-65.3%) of all near-fatal events. Total charges for AECOPD were $1.94 billion (95$1.90-1.97 billion) in Florida; patients with frequent ED visits accounted for $1.07 billion (95$1.04-1.09 billion). Conclusions: In this large cohort study, we found that 29% had frequent ED visits for AECOPD and that lower socioeconomic status was significantly associated with a higher frequency of ED visits. Individuals with frequent ED visits for AECOPD accounted for a substantial amount of healthcare utilization and financial burden

Brain hypoperfusion in adolescents dependent of multiple drugs

Brain SPECT imaging (BSI) with statistical parametric mapping (SPM) offers a clear and accurate vision of perfusion changes. Objective: To study brain perfusion abnormalities in adolescents' dependent of multiple drugs. Method: Sixteen male patients (15.1 +/- 2.1 years) were submitted to (99m)Tc-HMPAO BSI with SPM. Results: Cortical hypoperfusion occurred in 7/16 patients (44%). There was a significant inverse correlation between the number of hypoperfused regions and the patient's age (p= -0.6737; p=0.004) and with the age when the drug dependence began (p= -0.5616; p=0.023). There was also a tendency towards an inverse correlation between regions of hypoperfusion and the duration of the drug dependence. Conclusion: BSI with SPM can help detect hypoperfusion in adolescents dependent on multiple drugs. The younger the patients, the more regions of hypoperfusion are noted. Probably, the neuronal plasticity has an important role in this phenomenon because the highest neural activity occurs in childhood.68216116

Immunological imbalance between IFN-³ and IL-10 levels in the sera of patients with the cardiac form of Chagas disease

The immune response is crucial for protection against disease; however, immunological imbalances can lead to heart and digestive tract lesions in chagasic patients. Several studies have evaluated the cellular and humoral immune responses in chagasic patients in an attempt to correlate immunological findings with clinical forms of Chagas disease. Moreover, immunoglobulins and cytokines are important for parasitic control and are involved in lesion genesis. Here, cytokine and IgG isotype production were studied, using total epimastigote antigen on sera of chagasic patients with indeterminate (IND, n = 27) and cardiac (CARD, n = 16) forms of the disease. Samples from normal, uninfected individuals (NI, n = 30) were use as controls. The results showed that sera from both IND and CARD patients contained higher levels of Trypanosoma cruzi-specific IgG1 (IgG1) antibodies than sera from NI. No difference in IgG2 production levels was observed between NI, IND and CARD patients, nor was a difference in IL-10 and IFN-³ production detected in the sera of IND, CARD and NI patients. However, IND patients displayed a positive correlation between IL-10 and IFN-³ levels in serum, while CARD patients showed no such correlation, indicating an uncontrolled inflammatory response in CARD patients. These findings support the hypothesis that a lack of efficient regulation between IFN-³ and IL-10 productions in CARD patients may lead to cardiac immunopathology.CNP

Stem cells and repair of lung injuries

Fueled by the promise of regenerative medicine, currently there is unprecedented interest in stem cells. Furthermore, there have been revolutionary, but somewhat controversial, advances in our understanding of stem cell biology. Stem cells likely play key roles in the repair of diverse lung injuries. However, due to very low rates of cellular proliferation in vivo in the normal steady state, cellular and architectural complexity of the respiratory tract, and the lack of an intensive research effort, lung stem cells remain poorly understood compared to those in other major organ systems. In the present review, we concisely explore the conceptual framework of stem cell biology and recent advances pertinent to the lungs. We illustrate lung diseases in which manipulation of stem cells may be physiologically significant and highlight the challenges facing stem cell-related therapy in the lung

Whole Genome Characterization of the Mechanisms of Daptomycin Resistance in Clinical and Laboratory Derived Isolates of Staphylococcus aureus

Background: Daptomycin remains one of our last-line anti-staphylococcal agents. This study aims to characterize the genetic evolution to daptomycin resistance in S. aureus. Methods: Whole genome sequencing was performed on a unique collection of isogenic, clinical (21 strains) and laboratory (12 strains) derived strains that had been exposed to daptomycin and developed daptomycin-nonsusceptibility. Electron microscopy (EM) and lipid membrane studies were performed on selected isolates. Results: On average, six coding region mutations were observed across the genome in the clinical daptomycin exposed strains, whereas only two mutations on average were seen in the laboratory exposed pairs. All daptomycin-nonsusceptible strains had a mutation in a phospholipid biosynthesis gene. This included mutations in the previously described mprF gene, but also in other phospholipid biosynthesis genes, including cardiolipin synthase (cls2) and CDP-diacylglycerol-glycerol-3-phosphate 3-phosphatidyltransferase (pgsA). EM and lipid membrane composition analyses on two clinical pairs showed that the daptomycin-nonsusceptible strains had a thicker cell wall and an increase in membrane lysyl-phosphatidylglycerol. Conclusion: Point mutations in genes coding for membrane phospholipids are associated with the development of reduced susceptibility to daptomycin in S. aureus. Mutations in cls2 and pgsA appear to be new genetic mechanisms affecting daptomycin susceptibility in S. aureus

Conservation and divergence within the clathrin interactome of <i>Trypanosoma cruzi</i>

Trypanosomatids are parasitic protozoa with a significant burden on human health. African and American trypanosomes are causative agents of Nagana and Chagas disease respectively, and speciated about 300 million years ago. These parasites have highly distinct life cycles, pathologies, transmission strategies and surface proteomes, being dominated by the variant surface glycoprotein (African) or mucins (American) respectively. In African trypanosomes clathrin-mediated trafficking is responsible for endocytosis and post-Golgi transport, with several mechanistic aspects distinct from higher organisms. Using clathrin light chain (TcCLC) and EpsinR (TcEpsinR) as affinity handles, we identified candidate clathrin-associated proteins (CAPs) in Trypanosoma cruzi; the cohort includes orthologs of many proteins known to mediate vesicle trafficking, but significantly not the AP-2 adaptor complex. Several trypanosome-specific proteins common with African trypanosomes, were also identified. Fluorescence microscopy revealed localisations for TcEpsinR, TcCLC and TcCHC at the posterior region of trypomastigote cells, coincident with the flagellar pocket and Golgi apparatus. These data provide the first systematic analysis of clathrin-mediated trafficking in T. cruzi, allowing comparison between protein cohorts and other trypanosomes and also suggest that clathrin trafficking in at least some life stages of T. cruzi may be AP-2-independent