Clinical and microbiological characteristics of bacterial infections in patients with cirrhosis. A prospective cohort study from Argentina and Uruguay.

INTRODUCTION AND OBJECTIVES: there is insufficient data regarding bacterial infections in patients with cirrhosis to support recommendations for empiric antibiotic treatments, particularly in Latin America. This study aimed to evaluate bacterial infection's clinical impact and microbiological characteristics, intending to serve as a platform to revise current practices. MATERIALS AND METHODS: multicenter prospective cohort study of patients with cirrhosis and bacterial infections from Argentina and Uruguay. Patient and infection-related information were collected, focusing on microbiology, antibiotic susceptibility patterns, and outcomes. RESULTS: 472 patients were included. Spontaneous bacterial infections and urinary tract infections (UTIs) were registered in 187 (39.6%) and 116 (24.6%) patients, respectively, representing the most common infections. Of the 256 culture-positive infections, 103 (40.2%) were caused by multidrug-resistant organisms (reaching 50% for UTI), and 181 (70.7%) received adequate initial antibiotic treatment. The coverage of cefepime and ceftriaxone was over 70% for the empirical treatment of community-acquired spontaneous infections, but ceftazidime´s coverage was only 40%. For all UTI cases and for healthcare-associated or nosocomial spontaneous bacterial infections, the lower-spectrum antibiotics that covered at least 70% of the isolations were imipenem and meropenem. During hospitalization, a second bacterial infection was diagnosed in 9.8% of patients, 23.9% required at least one organ support, and 19.5% died. CONCLUSIONS: short-term mortality of bacterial infections in patients with cirrhosis is very high, and a high percentage were caused by multidrug-resistant organisms, particularly in UTIs. The information provided might serve to adapt recommendations, particularly related to empirical antibiotic treatment in Argentina and Uruguay. The study was registered in Clinical Trials (NCT03919032).

The use of proton pump inhibitors in an Italian hospital: focus on oncologic and critical non-ICU patients.

BACKGROUND: Proton pump inhibitors (PPIs) are among the most misused drugs both at the community and hospital level. Recently, possible risks have been underscored, suggesting the importance of limiting PPI use to proven indications. OBJECTIVE: To survey the appropriateness of PPI use in a University hospital in Italy. Setting Azienda Ospedaliera Universitaria Policlinico 'P. Giaccone', in Palermo, Italy. METHOD: A one day-observational study, reviewing patients' medical records to identify treatments with PPIs and the indications for their use. After discharge, a subgroup of the cohort was followed up to assess the continuation of therapy at home. Appropriateness was evaluated according to the indications stated in the official product information sheet and supported by the AIFA notes. MAIN OUTCOME MEASURE: Prevalence and appropriateness of PPI use in the hospital and after discharge. RESULTS: In the index day 62.9 % of 343 evaluable patients received a PPI. In only 29.1 % of these, the treatment could be considered appropriate. The most frequent reasons for inappropriate treatment were stress ulcer prophylaxis in low risk patients and unwarranted gastro-protection in drug treated patients. 30.9 % of patients received PPIs for uncertain indications: of these, 25.7 % were "critical" patients admitted in non-ICU wards. Furthermore, as much as 88.2 % of anticancer drug treated patients received PPIs as gastroprotective agents. At discharge 48.6 % of patients received a prescription to continue PPI therapy at home and 75.9 % of the 83 followed up patients were found to be still taking these drugs after on average 3 months from discharge. CONCLUSION: This study confirms a high proportion of inappropriate PPI therapy into the hospital that translates in a prolonged unnecessary administration in the community setting. Further studies are needed to assess the cost-effectiveness of PPI therapy in subgroups of patients at moderate risk for gastric complications to optimize current guidelines.

Permeability properties of a three-cell type in vitro model of blood-brain barrier.

We previously found that RBE4.B brain capillary endothelial cells (BCECs) form a layer with blood-brain barrier (BBB) properties if co-cultured with neurons for at least one week. As astrocytes are known to modulate BBB functions, we further set a culture system that included RBE4.B BCECs, neurons and astrocytes. In order to test formation of BBB, we measured the amount of 3H-sucrose able to cross the BCEC layer in this three-cell type model of BBB. Herein we report that both neurons and astrocytes induce a decrease in the permeability of the BCEC layer to sucrose. These effects are synergic as if BCECs are cultured with both neurons and astrocytes for 5 days, permeability to sucrose decreases even more. By Western analysis, we also found that, in addition to the canonical 60 kDa occludin, anti-occludin antibodies recognize a smaller protein of 48 kDa which accumulates during rat brain development. Interestingly this latter protein is present at higher amounts in endothelial cells cultured in the presence of both astrocytes and neurons, that is in those conditions in which sucrose permeation studies indicate formation of BBB.

Synergistic effects of neurons and astrocytes on the differentiation of brain capillary endothelial cells in culture.

Brain capillary endothelial cells form a functional barrier between blood and brain, based on the existence of tight junctions that limit paracellular permeability. Occludin is one of the major transmembrane proteins of tight junctions and its peripheral localization gives indication of tight junction formation. We previously reported that RBE4.B cells (brain capillary endothelial cells), cultured on collagen IV, synthesize occludin and correctly localize it at the cell periphery only when cocultured with neurons. In the present study, we describe a three-cell type-culture system that allowed us to analyze the combined effects of neurons and astrocytes on differentiation of brain capillary endothelial cells in culture. In particular, we found that, in the presence of astrocytes, the neuron-induced synthesis and localization of occludin is precocious as compared to cells cocultured with neurons only.

Asociacion de hemocromatosis y esferocitosis hereditaria / Association of hemochromatosis and hereditary spherocytosis

La esferocitosis hereditaria es una anemia hemolítica crónica que raramente presenta sobrecarga férrica. Sólo 15 casos de esferocitosis hereditaria y hemocromatosis fueron descriptos cpn anterioridad. Inicialmente, se había propuesto que la hemocromatosis era el resultado del depósito exagerado de hierro secundario a la hemólisis crónica y al aumento de la eritropoyesis. Se vió, con posterioridad, que la sobrecarga aparecía en sujetos esplenectomizados, sugiriendo este hecho la posibilidad de una herencia independiente de la esfrocitosis y de la hemacromatosis. Se presenta un paciente de 45 años, de sexo masculino, con el antecedente de esfocitosis hereditaria, esplenectomizado a los 5 años, que desarrolló sobrecarga de hierro con afección cardíaca, hepática y pancreática.