BACKGROUND AND PURPOSEPharmacological preconditioning (PPC) with mitochondrial ATP-sensitive K + (mitoKATP) channel openers such as diazoxide, leads to cardioprotection against ischaemia. However, effects on Ca 2+ homeostasis during PPC, particularly changes in Ca 2+ channel activity, are poorly understood. We investigated the effects of PPC on cardiac L-type Ca 2+ channels. EXPERIMENTAL APPROACHPPC was induced in isolated hearts and enzymatically dissociated cardiomyocytes from adult rats by preincubation with diazoxide. We measured reactive oxygen species (ROS) production and Ca 2+ signals associated with action potentials using fluorescent probes, and L-type currents using a whole-cell patch-clamp technique. Levels of the a1c subunit of L-type channels in the cellular membrane were measured by Western blot. KEY RESULTSPPC was accompanied by a 50% reduction in a1c subunit levels, and by a reversible fall in L-type current amplitude and Ca 2+ transients. These effects were prevented by the ROS scavenger N-acetyl-L-cysteine (NAC), or by the mitoKATP channel blocker 5-hydroxydecanoate (5-HD). PPC signficantly reduced infarct size, an effect blocked by NAC and 5-HD. Nifedipine also conferred protection against infarction when applied during the reperfusion period. Downregulation of the a1c subunit and Ca 2+ channel function were prevented in part by the protease inhibitor leupeptin. CONCLUSIONS AND IMPLICATIONSPPC downregulated the a1c subunit, possibly through ROS. Downregulation involved increased degradation of the Ca 2+ channel, which in turn reduced Ca 2+ influx, which may attenuate Ca 2+ overload during reperfusion. Abbreviations

Among the currently available antiretroviral drugs, the novel integrase inhibitor raltegravir (RAL) is an oral agent without cross-resistance to any other antiretroviral family and it provides an option with easier administration and better tolerability than enfuvirtide (ENF). There is no experience in routine clinical practice with RAL as a simplification strategy. We evaluate the efficacy and safety of switching ENF to RAL as a simplification strategy for a follow-up of 24 and 48 weeks in patients with an HIV-1 viral load (VL) < 50 copies/mL. MethodsIn this retrospective cohort, patients from routine clinical practice on a suppressive ENF-containing regimen were selected. The patients were switched from ENF to RAL while the rest of the antiretroviral regimen remained unchanged. According to standard clinical practice, we assessed the VL, CD4+ T-cell count, hepatic enzymes and fasted lipid profile. Results after a 24-week period of follow-up are shown in this analysis. Sixteen patients were included in this analysis. At baseline, the median number of prior antiretrovirals was 12 (9-16). The means of time on ENF treatment and time with viral suppression were 126 (SD: 62) and 98 (SD: 57) weeks, respectively. The concurrent treatments included DRV/r in 10 (62.5%) patients, TPV/r in five (31.2%) and ETV in two (12.5%) more subjects. The 100% of patients achieved 24 weeks with sustained viral suppression. Median CD4+ T-cell count increased from 374 (272-466) cells/mL at baseline to 408 (308-541) cells/mL at week 24 of follow-up (p = 0.087). There were no significant changes in total cholesterol, HDL cholesterol, LDL cholesterol and triglycerides (p = 0.103, p = 0.934, p = 0.978 and p = 0.696, retrospectively). Similarly, there were no significant changes in AST, ALT and ALP (p = 0.156, p = 0.475 and p = 0.487, respectively). Only the gamma-GT improved significantly, showing a reduction from 58.5 (32.2-78.7) U/L at baseline to 37 (22.5-54) U/L at week 24 of follow-up (p = 0.023). Injection site reactions were solved in all patients after switching and there were no significant adverse events related with RAL administration. ConclusionSwitching ENF to RAL seems to be safe and effective in the short-term in patients with viral suppression despite a prior high antiretroviral experience. Its long-term impact on patient's adherence, quality of life, safety and efficacy should be evaluated in clinical trials.

BackgroundOur antimicrobial stewardship programme was introduced in 2016 in the quality certification system of our hospital and different indicators were designed to evaluate the quality of the process, establishing a limit of acceptability (LA) for each of them.PurposeThe objective of this study is to determine the indicators from January 2016 to June 2017 and to analyse if they are within the established limit.Material and methodsIndicators have been analysed semiannually except antimicrobial resistance that has been determined annually. Indicators and LA for each case are:Antimicrobial consumption: DDD/1000 stays (LA=100).Toxicity: carbapenem neurotoxicity (LA=2%) and clostridium difficile isolates (LA=5%).Clinical results: mortality in patients with bacteraemia, both global (LA=20%) and attributable to bacteraemia (LA=10%).Resistance to antimicrobials: variation from the previous year (LA=5%).ResultsResults obtained for each of the indicators in the first and second half of 2016 and the first half of 2017 are:DDD/1000 stays: 77.92 and 65.7Neurotoxicity: None, 0.5% and 0.17%.Clostridium difficile: 0.5%, 0.4% and 0.34%.Global mortality in patients with bacteraemia: 10%, 17% and 14%.Mortality attributable to bacteraemia: 5%, 3.6% and 10%.Resistances: a slight improvement in enterobacteria susceptibility is observed, while in P. aeruginosa there is an upward tendency of resistance, especially to carbapenems and ciprofloxacin. For Gram + bacteria, the sensitivity in S. aureus and E. faecalis increases, but also the resistance to ampicillin in E. faecium. The cumulative nosocomial incidence of ESBL–E. coli and P. aeruginosa resistant to carbapenemics has remained stable and has increased in ESBL–K. pneumoniae, carbapenemase producing enterobacteria and extremely resistant enterobacteria.The acceptability limits have been fulfilled in all cases except for K. pneumoniae and P. aeruginosa resistances.ConclusionIt is essential to establish indicators to evaluate the quality of the processes to analyse their evolution in detecting problems and design improvement strategies. Our revision shows that all parameters analysed are within the limit of acceptability except some resistance data for Gram – bacteria, mainly due to the appearance in our hospital of an outbreak of extremely resistant K. pneumoniae and the appearance of carbapenemases. The impact on the resistances is expected to be obtained later.No conflict of interest

BackgroundSeveral studies indicate that 96% of patients with symptomatic C. difficile infection had received antibiotics within 14 days prior to the onset of diarrhoea. Complications include dehydration, electrolyte disturbances, toxic megacolon, hypotension, renal failure, systemic inflammatory response syndrome, sepsis and death.PurposeTo analyse patients admitted to our hospital testing positive for toxins A + B of C. difficile over 4½ years and to determine the associated mortality.Material and methodsDescriptive retrospective study conducted between 1 January 2010 and 30 June 2014 that included all hospitalised patients testing positive for C. difficile toxins A + B. Dara recorded were antimicrobial treatments before detection of toxins, condition for which they were prescribed, treatment to eradicate C. difficile and its duration. The percentage of patients who died during that admission or within 10 days of discharge was also determined.ResultsResults were positive in 60 samples from 54 patients, 51.7% women and 48.3% men, with a mean age of 76.2 years. The most common pathologies for which antibiotics were prescribed were respiratory infection (36.4%), urinary tract infection (27.3%), intra-abdominal infection (16.4%), unspecified febrile syndrome (7.3%) and others (12.6%). 35 patients (64.8%) received more than one antimicrobial prior to detection of C. difficile, mainly ß-lactams (63.0%) and fluoroquinolones (27.8%).Treatments prescribed for eradication of C. difficile were:Metronidazole (63.3%): <7 days in 4 isolates, 7–10 days in 18 of them, >10 days for 15 and five patients died during treatment.Oral vancomycin (20%): <7 days in 1 patient, 7–10 days in 3 isolates and >10 days for 8 of them.No treatment: 10 patients (16.7%).Of the patients evaluated, 18 died (32.7%).ConclusionThe number of patients in whom toxins A + B of C. difficile were positively identified was low, probably due to the low degree of clinical suspicion and not too satisfactory sensitivity of the technique. Prescribing for treatments for eradication was not appropriate in 27.8% of patients (10 received no treatment and 5 for insufficient time). The mortality rates found in our study agree with data from the literature (22–40%).References and/or acknowledgementsNo conflict of interest.