Are oral cefuroxime axetil,cefixime and cefditoren pivoxil adequate to treat uncomplicated acute pyelonephritis after switching from intravenous therapy? A pharmacokinetic/pharmacodynamic perspective

ObjectivesThe goal of this study is to assess, by means of pharmacokinetic/pharmacodynamic (PK/PD) analysis using the Monte Carlo simulation, the adequacy of oral cephalosporins cefuroxime axetil, cefixime and cefditoren at different dosing regimens as switch therapy after intravenous cephalosporin treatment in uncomplicated acute pyelonephritis.MethodsThe methodology included: (i) dosing regimen selection and acquisition of pharmacokinetic data; (ii) microbiological data acquisition; and (iii) Monte Carlo simulation to estimate the PTA (probability of PK/PD target attainment) and CFR (cumulative fraction of response), as indicators of treatment success.ResultsAt the current susceptibility breakpoints defined by EUCAST and CLSI for either cefuroxime axetil or cefixime, the probability of bactericidal target attainment is zero for the dosage regimens simulated. Considering the bactericidal target %fT_>MIC > 70%, the likelihood of the cefuroxime 500-mg q8h regimen or the cefixime 200-mg q12h regimen producing this exposure or achieving this target is only above 90% for organisms yielding MICs ≤ 0.5 mg/l and MICs ≤ 0.25 mg/l, respectively. Cefditoren pivoxil 400 mg q12h provided probabilities of bactericidal target attainment of 80% or higher for MICs ≤ 0.03 mg/l, and ≤0.25 mg/l if considering total instead of free drug concentrations.ConclusionsThe results of the PK/PD target attainment analysis reveal that the likelihood of treatment success based upon the current breakpoints proposed by either EUCAST or CLSI is low. Of the three cephalosporins, cefixime 400 mg q12h prove to be the best option in oral APN treatment, although this regimen is currently off label.     

Pharmacokinetic/pharmacodynamic analysis as a tool for surveillance of the activity of antimicrobials against Pseudomonas aeruginosa strains isolated in critically ill patients

IntroductionTo evaluate the changes in the susceptibility of Pseudomonas aeruginosa over time (2000–2017) against antimicrobials used in an intensive care unit of a Spanish tertiary hospital, and to compare them with the antimicrobial activity considering theoretical pharmacokinetic/pharmacodynamic (PK/PD) criteria. The influence of the method for handling duplicate isolates to quantify susceptibility rates was also evaluated.MethodsThe susceptibility was studied considering the Clinical and Laboratory Standards Institute (CLSI) breakpoints. Monte Carlo simulations were conducted to calculate the cumulative fraction of response (CFR). Linear regression analysis was applied to determine the trends in susceptibility and in the CFR.ResultsA significant decrease in the susceptibility to gentamicin and imipenem was observed, and more recently the highest percentages of susceptible strains were found for amikacin, cephalosporins and piperacillin/tazobactam (>80%). The probability of success of an empiric treatment or CFR for most of the evaluated antimicrobials was lower than 70% during the last two-year period. Only meropenem provided high probabilities (>90%) to achieve the PK/PD target. Cephalosporins provided moderate probabilities (>80%) although for ceftazidime, the highest dose (2 g/8 h) was required. Moreover, a significant decrease in the CFR trend for ciprofloxacin, imipenem and levofloxacin was observed.ConclusionsBoth susceptibility rates and CFR values have to be considered together to optimize the antimicrobial dose regimen for clinical making-decisions. They are complementary tools and, they should be used jointly in surveillance programmes. In fact, susceptibility data are not always useful to detect changes in the CFR. No relevant differences were observed among the methods for handling repeated isolates.     

Susceptibility of Pseudomonas aeruginosa and antimicrobial activity using PK/PD analysis: an 18-year surveillance study

IntroductionWe analysed the changes in the susceptibility of Pseudomonas aeruginosa to antimicrobials over an 18-year period (2000-2017) in order to evaluate the adequacy of the antimicrobial therapy against this organism in patients admitted in a tertiary Spanish hospital (excluding the intensive care unit). In addition, the antimicrobial activity was evaluated using pharmacokinetic/pharmacodynamic (PK/PD) criteria as a microbiological surveillance tool.MethodsSusceptibility was studied according to the Clinical and Laboratory Standards Institute breakpoints. Monte Carlo simulations were conducted to calculate the cumulative fraction of response (CFR). Linear regression analysis was applied to determine the trends in susceptibility and in the CFR.ResultsIn 2017, susceptibility rates were: amikacin, penicillins and cephalosporins ≥85%, tobramycin 76%, meropenem 75% and gentamicin, imipenem and fluoroquinolones <70%. PK/PD analyses was able to identify changes in antimicrobial activity not detected by only assessing MICs; meropenem administered in extended infusion attained a CFR >90%, ceftazidime, piperacillin/tazobactam and imipenem provided CFRs between 80-90%, all of them administered at the highest doses.ConclusionsAnalysis of susceptibility and PK/PD modelling, should be considered together to select the most appropriate antimicrobial drug and dosage regimen. Empirical antipseudomonal therapy would vary considerably if both microbiological surveillance tools were considered. In this study, the PK/PD analysis made it possible to preserve the therapeutic value of antimicrobials with low susceptibility rates, such as carbapenems, and the selection of the most effective antimicrobials among those with high rates of susceptibility.     

Antimicrobial susceptibility of microorganisms that cause urinary tract infections in pediatric patients

Introduction

Cumulative susceptibility reports are a valuable tool for the empirical treatment of urinary tract infections, especially in the current context of increasing resistance rates. Our objective was to analyze the antimicrobial susceptibility of bacterial isolates in urine cultures of pediatric patients during a five-year period.

In vitro activity of delafloxacin against highly levofloxacin-resistant invasive isolates of Streptococcus pneumoniae

IntroductionWe report the activity of delafloxacin, a new fluoroquinolone with high affinity for both topoisomerase IV and DNA gyrase, against highly-levofloxacin-resistant invasive strains of Streptococcus pneumoniae.MethodsA total of 173 highly-levofloxacin-resistant (MIC >32 mg/L) S. pneumoniae invasive isolates were studied. The strains were isolated from blood (n = 162) and other sterile fluids (n = 11). Serotyping was performed by the Pneumotest-Latex and Quellung reaction.Delafloxacin, levofloxacin, penicillin, cefotaxime, erythromycin and vancomycin MICs were determined by the gradient diffusion method following EUCAST guidelines and breakpoints.ResultsAmong the isolates, 32.9% were penicillin non-susceptible, 19.7% cefotaxime non-susceptible, and 76.9% erythromycin resistant. All were susceptible to vancomycin. Delafloxacin MIC₅₀ and MIC₉₀ (mg/L) values were 0.064 and 0.12, respectively; 60% (15/25) of serotype 9V isolates showed delafloxacin MICs ≥ 0.12 mg/L.ConclusionsDelafloxacin was very active against highly-levofloxacin-resistant invasive isolates of S. pneumoniae. Isolates belonging to serotype 9V showed higher delafloxacin MIC values.     

Comparative in vitro activity of a pharmacokinetically enhanced oral formulation of amoxicillin/clavulanic acid (2000/125 mg twice daily) against 9172 respiratory isolates collected worldwide in 2000.

OBJECTIVES: A new, pharmacokinetically enhanced, oral formulation of amoxicillin/clavulanic acid has been developed to overcome resistance in the major bacterial respiratory pathogen Streptococcus pneumoniae, while maintaining excellent activity against Haemophilus influenzae and Moraxella catarrhalis, including beta-lactamase producing strains. This study was conducted to provide in vitro susceptibility data for amoxicillin/clavulanic acid and 16 comparator agents against the key respiratory tract pathogens. METHODS: Susceptibility testing was performed on 9172 isolates collected from 95 centers in North America, Europe, Australia, and Hong Kong by broth microdilution MIC determination, according to NCCLS methods, using amoxicillin/clavulanic acid and 16 comparator antimicrobial agents. Results were interpreted according to NCCLS breakpoints and pharmacokinetic/pharmacodynamic (PK/PD) breakpoints based on oral dosing regimens. RESULTS: Overall, 93.5% of Streptococcus pneumoniae isolates were susceptible to amoxicillin/clavulanic acid at the current susceptible breakpoint of < or =2 microg/mL and 97.3% at the PK/PD susceptible breakpoint of < or =4 microg/mL for the extended release formulation. Proportions of isolates that were penicillin intermediate and resistant were 13% and 16.5%, respectively, while 25% were macrolide resistant and 21.8% trimethoprim/sulfamethoxazole resistant. 21.9% of Haemophilus influenzae were beta-lactamase producers and 16.8% trimethoprim/sulfamethoxazole resistant, >99% of isolates were susceptible to amoxicillin/clavulanic acid, cefixime, ciprofloxacin and levofloxacin at NCCLS breakpoints. The most active agents against Moraxella catarrhalis were amoxicillin/clavulanic acid, macrolides, cefixime, fluoroquinolones, and doxycycline. Overall, 13% of Streptococcus pyogenes were resistant to macrolides. CONCLUSION: The extended release formulation of amoxicillin/clavulanic acid has potential for empiric use against many respiratory tract infections worldwide due to its activity against species resistant to many agents currently in use.     

The efficacy of Helicobacter pylori eradication regimen with and without vitamin C supplementation

BackgroundVitamin C in gastric juice and in vitro has been shown to inhibit the growth of Helicobacter pylori (H. pylori).AimsThe purpose of this study was to investigate the effect of addition of vitamin C to eradication regimen on H. pylori eradication rate.PatientsThis randomised controlled clinical trial was conducted on 312 patients with H. pylori infection who had referred to the Taleghani Research Center of Gastroenterology and Liver Disease.MethodsPatients were randomly divided into two groups. Group A patients (162 patients) received amoxicillin 1 g and metronidazole 500 mg b.i.d., bismuth 240 mg b.i.d. and omeprazole 40 mg q.i.d. in two divided doses. Patients in group B (150 patients) received the same regimen plus 500 mg vitamin C per day. All patients received therapy for 2 weeks. Four weeks later all patients underwent urea breath test and results were compared.ResultsA total of 140 patients in group A and 141 in group B completed the study. On intention-to-treat analysis 48.8% of patients in group A in comparison to 78% in group B responded to eradication therapy and had negative urea breath test (p < 0.0001).ConclusionAddition of vitamin C to H. pylori treatment regimen of amoxicillin, metronidazole and bismuth can significantly increases H. pylori eradication rate.     

Impaired coronary microvascular and left ventricular diastolic functions in patients with ankylosing spondylitis

BackgroundIt has been shown that the patients with inflammatory rheumatic diseases such as systemic lupus erythematosus and rheumatoid arthritis have an increased risk of developing atherosclerosis. However, the association of ankylosing spondylitis (AS) to atherosclerosis and related diseases is still controversial. Accordingly, we investigated coronary flow reserve (CFR) and left ventricular (LV) diastolic function in patients with AS using transthoracic Doppler echocardiography.MethodsCFR and LV diastolic function were studied in 40 patients with AS (38.9 ± 10.2 years, 26 males) and 35 healthy volunteers (37.5 ± 6.4 years, 23 males). Coronary diastolic peak flow velocities (DPFV) were measured at baseline and after dipyridamole infusion. CFR was calculated as the ratio of hyperemic to baseline DPFV. LV diastolic function was assessed by both standard and tissue Doppler imaging.ResultsDemographic features and coronary risk factors except diastolic blood pressure were similar between the groups. CFR were significantly lower in the AS group than in the control group (2.20 ± 0.46 versus 3.02 ± 1.50, P < 0.0001). Reflecting LV diastolic function mitral A-wave and E/A ratio were borderline significant, and mitral E-wave deceleration time and isovolumic relaxation time were significantly different between the groups. Serum hsCRP and TNF-α levels were significantly higher in the patients with AS, and hsCRP and TNF-α levels independently correlated with CFR.ConclusionThese findings show that CFR reflecting coronary microvascular function and LV diastolic function are impaired in patients with AS, and severity of these impairments correlate well with hsCRP and TNF-α. These results suggest that impaired CFR may be an early manifestation of cardiac involvement in patients with AS.     

Comparison of levofloxacin-containing sequential and standard triple therapies for the eradication of Helicobacter pylori

BackgroundThere is an important concern about the success of standard triple treatment for Helicobacter pylori (H. pylori) in recent years. Better eradication rates have been reported with sequential treatment in current studies. This study aimed to compare the success of a novel levofloxacin-containing sequential regimen with standard triple therapy.MethodsH. pylori-positive patients with non-ulcer dyspepsia were randomly allocated to one of the study groups. The patients on sequential arm were given esomeprazole 40 mg BID and amoxicillin 1 g BID for the first week followed by esomeprazole 40 mg BID, levofloxacin 500 mg QD and metronidazole 500 mg TID for the second week. The patients on standard triple arm were given esomeprazole 40 mg BID, amoxicillin 1 g BID and clarithromycin 500 mg BID for 2 weeks. Eradication was assessed by urea breath test on 6th weeks.ResultsSeventy-five patients were enrolled in each group; 72 in sequential arm and 67 in standard arm completed the protocols. H. pylori eradication rate of per protocol was 90% in sequential versus 57% in standard treatment groups with a statistical significance (p < 0.000). Both regimens were similarly well tolerated and side effects were comparable. Only one patient in sequential arm stopped the treatment because of side effects.ConclusionThe levofloxacin-containing sequential therapy is a significantly better strategy than the standard triple treatment for H. pylori eradication. Standard triple treatment is no more effective for H. pylori in our population and levofloxacin-containing sequential regimen might be used as a first-line eradication option.     

A simple double differential centrifugation-wash procedure to rapidly obtain bacterial identification and direct antimicrobial susceptibility testing from positive blood cultures

IntroductionThis study proposes a simple and rapid method for both bacterial identification and direct antimicrobial susceptibility testing (AST) by using MALDI-TOF and a double differential centrifugation-wash procedure from positive blood cultures.MethodsFifty-two positive blood cultures (37 gramnegative bacilli and 15 grampositive cocci) were studied by two methods for identification and AST: a reference method, and the rapid MALDI-TOF method obtaining a purified pellet by using a double differential centrifugation procedure.ResultsA total of 1101 MIC values (mg/l) were interpreted according to EUCAST clinical breakpoints and compared using the two methods simultaneously. Discrepancies in 81 MIC values (7.35%) were detected. By analyzing standard parameters, we obtained 98.28% essential agreement and 92.65% categorical agreement considering all isolates tested.ConclusionThis method provides rapid bacterial identification and AST, offering definitive results 24–48 h earlier than the conventional method (p < 0.001) and improving the turnaround time in blood culture diagnostics, especially in laboratories without 24-h on-call.     

Effect of Helicobacter pylori eradication on glycaemia control in patients with type 2 diabetes mellitus and comparison of two therapeutic regimens

Background and study aimsThe eradication rate of Helicobacter pylori (H. pylori) has been reported as being lower in patients with type 2 diabetes mellitus (DM) than in those without DM. The aim of the study was to assess the efficacy of the two H. pylori eradication regimens in patients without and with type 2 DM and to study the effect of H. pylori treatment on glycaemia control.Patients and MethodsA total of 93 consecutive type 2 DM (non-insulin users) and 98 non-diabetic age- and sex-matched patients were enrolled. Patients were randomly assigned to one of the two treatment protocols all given twice daily: (a) a 14-day quadruple therapy comprising of omeprazole 20 mg, metronidazole 500 mg, amoxicillin 1 g and bismuth subcitrate 240 mg (OMAB) and (b) a 14-day triple regimen comprising of omeprazole 20 mg plus clarithromycin 500 mg and amoxicillin 1 g (OCA). Cure was defined as a negative ¹³C-urea breath test at least 6 weeks after treatment.ResultsThe H. pylori eradication rate with the OCA regimen was 63% in patients with type 2 DM (non-insulin users) and 87.7% in the control group (p = 0.017). The H. pylori eradication rate with the OMAB regimen was 38.2% in patients with type 2 DM and 55.1% in the control group (p < 0.001). Mean decrease of fasting plasma glucose and HbA1c level shows no statistically significant difference after H. pylori eradication.ConclusionThis study suggests that the eradication rate of H. pylori with OCA or OMAB treatment is lower in patients with type 2 diabetes than in non-diabetics and H. pylori treatment in patients with type 2 DM has no role in the control of the glycaemia. The triple therapy (OCA) is superior to the quadruple protocol (OMAB) in H. pylori eradication of both DM and non-DM cases.     

Low ankle-brachial index is an independent predictor of poor functional outcome in acute cerebral infarction

ObjectiveOur study aimed to evaluate the effects of psoriasis (Pso) on coronary microvascular function and whether there is a relationship between disease activity scores and coronary blood flow abnormalities.Methods56 young patients (pts) with Pso (42 M, aged 37 ± 3 years) without clinical evidence of cardiovascular diseases, and 56 controls matched for age and gender were studied. Coronary flow velocity in the left anterior descending coronary artery was detected by transthoracic echocardiography at rest and during adenosine infusion. Coronary flow reserve (CFR) was the ratio of hyperaemic diastolic flow velocity (DFV) to resting DFV. A CFR ≤ 2.5 was considered abnormal.ResultsIn pts with Pso, CFR was lower than in controls (3.2 ± 0.9 vs. 3.7 ± 0.7, p = 0.02). CFR was abnormal (≤2.5) in 12 pts (22% vs. 0% controls, p < 0.0001). Moreover, in pts with CFR ≤ 2.5, Psoriasis Area Severity Index (PASI), a clinical score for Pso severity, was higher (11 ± 6 vs. 7 ± 3, p = 0.006) compared to pts with CFR > 2.5. At multivariable analysis PASI remained the only determinant of CFR ≤ 2.5 (p = 0.02).ConclusionCFR in young pts with severe Pso without coronary disease is reduced suggesting a coronary microvascular dysfunction, independently related to the severity and extension of Pso. This early microvascular impairment might be hypothesized as the consequence of prolonged and sustained systemic inflammation and might explain the increased cardiovascular risk conferred by Pso.     

The efficacy of ranitidine bismuth citrate,amoxicillin and doxycycline or tetracycline regimens as a first line treatment for Helicobacter pylori eradication

BackgroundThe eradication rates of Helicobacter pylori (H. pylori) clearly decreased with standard PPI-based triple therapies.AimTo assess the efficacy of two different triple therapies consisting of ranitidine bismuth citrate–amoxicillin–doxycycline and ranitidine bismuth citrate–amoxicillin–tetracycline combinations as a first line treatment option.MethodsOne hundred and fifteen consecutive dyspeptic patients in whom H. pylori infection was diagnosed for the first time were enrolled in this study. The patients were randomized into two groups. Group 1 (n = 57) was assigned to receive a 14-day triple therapy consisting of ranitidine bismuth citrate 400 mg (b.i.d), amoxicillin 1 g (b.i.d) and doxycycline 100 mg (b.i.d). Group 2 (n = 58) was assigned to receive a 14-day triple therapy consisting of ranitidine bismuth citrate 400 mg (b.i.d), amoxicillin 1 g (b.i.d) and tetracycline 500 mg (q.i.d).ResultsThe eradication was achieved in 45.7% (21/46) and 40.8% (20/49) of the patients in group 1 and group 2, according to per protocol analysis. The intention-to-treat eradication rates were 36.8% (21/57) and 34.5% (20/58) in group 1 and group 2, respectively.ConclusionsTwo-week therapy with neither ranitidine bismuth citrate–amoxicillin–doxycycline nor ranitidine bismuth citrate–amoxicillin–tetracycline is adequately effective for H. pylori eradication as a first line therapy.     

Hypoadiponectinemia in lipodystrophic HIV individuals: A metabolic marker of subclinical cardiac damage

Background and aimTo evaluate cardiovascular abnormalities in highly active antiretroviral therapy (HAART) treated HIV patients with no signs or symptoms of cardiovascular impairment, and to assess the relative role of multiple concomitant risk factors.Methods and resultsForty-four consecutive HIV subjects (mean age 41 ± 6 yrs) were enrolled. Inclusion criteria were HIV infection, CD4 + cell count > 150/ml, HAART treatment for at least 4 years. Metabolic serum levels, morphological and functional echocardiographic parameters were assessed in all subjects. Sixteen healthy age and sex matched subjects with no cardiovascular risk factors were recruited as controls.HIV patients showed increased left ventricular mass index with reduced mid-wall fractional shortening (mFS) when compared to controls (50.2 ± 10.5 vs. 38.6 ± 14.4, p = 0.05 and 18.3 ± 0.6 vs. 21.9 ± 0.7, p < 0.05, respectively). Twenty-nine patients were lipodystrophic (LD) and showed a longer HAART period (p = 0.0004) and greater use of protease inhibitors (PI) (p = 0.001). Coronary flow reserve (CFR) was significantly reduced in HIV patients as compared to controls (p < 0.0001), as it was in LD subjects when compared to non-lipodystrophic ones (NLD) (p < 0.001). Adiponectin concentrations were found to be significantly lower in LD subjects than in NLD ones (7.8 ± 0.8 vs. 13.8 ± 1.2 μg/ml, p = 0.01), and showed a direct correlation with CFR. In multiple regression analysis, insulin, HDL and adiponectin accounted for 63% of CFR variations.ConclusionsLeft ventricular hypertrophy, depressed mFS and reduced CFR represent the main signs of subclinical cardiac damage in HIV subjects treated with HAART. Hypoadiponectinemia in these subjects seems to be a metabolic risk factor of cardiovascular impairment.     

Penbactam for Helicobacter pylori eradication: A randomised comparison of quadruple and triple treatment schedules in an Iranian population

Background & study aimsSelection of the best drug regimens for eradication of Helicobacter pylori infection especially in patients at risk of peptic ulcer relapses and the development of complications is challenging. This study assessed and compared the efficacy of the two common PPI based triple therapies to a quadruple therapy including PPI, metronidazole, amoxicillin and a bismuth compound in Iranian population.Patients & MethodsThree hundred and thirty patients with peptic ulcer and H. pylori infection were included in the study. Patients were randomly assigned to one of the three treatment protocols all given twice daily: (a) A 14-day quadruple therapy (OMAB group) comprising omeprazole 20 mg, metronicazole 500 mg, amoxicillin 1 g, and bismuth subcitrate 240 mg; (b) A 14-day triple regimen (OCP group) comprising omeprazole 20 mg plus clarithromycine 500 mg and penbactam 750 mg and (c) A 14-day triple regimen (OCA group) comprising omeprazole 20 mg plus clarithromycine 500 mg and amoxicillin 1 g. Cure was defined as a negative urea breath test at least six weeks after treatment.ResultsThe per-protocol eradication rates achieved with both OCP regimen (87.0%) and OCA treatment (90.8%) were significantly higher than the OMAB treatment protocol (56.0%); however, no significant difference emerged in eradication rates between the two triple treatment schedules. No significant differences between the groups were found in most side-effects.ConclusionTwo-week quadruple therapy showed a lower eradication rate compared to common triple treatment schedules when used as first-line eradication treatment for H. pylori infection in Iranian population.     

Auditory disorders in patients with systemic lupus erythematosus: Relation to clinical parameters

Aim of the workTo evaluate the hearing disorders in SLE patients with particular regard to their frequency and relationship to disease duration and activity.Patients and methodsTwenty female SLE patients were enrolled in the study. Assessment of disease activity was done using the SLE disease activity index (SLEDAI). Another 20 otologically healthy subjects of matched age and sex served as controls. Auditory assessment was performed and included otoscopic examination, pure tone audiometry (PTA), acoustic immittance testing and speech audiometry.ResultsThe PTA was abnormal in 13 (65%) patients; 4 had tinnitus and 1 vertigo. The PTA results showed a highly significant statistical difference from the control (p < 0.001). Otoscopic examination, acoustic immittance testing and speech audiometry of all patients were normal. A significant difference was found in the age at disease onset between those with and without abnormal PTA (p = 0.023). Moreover, there was a significantly lower hearing level (right ear) at 12,000 Hz in juvenile-onset (N = 6) (20.83 ± 3.76 db) compared to adult-onset cases (32.5 ± 15.66 db) (p = 0.02). No significant difference was present in the audiovestibular manifestations (p = 0.114), clinical, laboratory parameters or disease activity between those with or without hearing loss. However, hearing levels were significantly lower in those with lupus nephritis and those receiving hydroxychloroquine.ConclusionPure tone audiometry revealed SNHL in 65% of SLE patients. Absence of audiovestibular manifestations does not exclude inner ear affection. Age at disease onset is remarkably associated with hearing loss in SLE. Lupus nephritis and hydroxychloroquine use are associated with lower hearing levels and possible early hearing loss.     

An explorative data-analysis to support the choice between hepatic resection and radiofrequency ablation in the treatment of hepatocellular carcinoma

BackgroundWhether to prefer hepatic resection or radiofrequency ablation as first line therapy for hepatocellular carcinoma is a matter of debate.AimsTo compare outcomes of resection and ablation, in the treatment of early hepatocellular carcinoma, through a decision-making analysis.MethodsData of 388 cirrhotic patients undergoing resection and of 207 undergoing radiofrequency ablation were reviewed. Two distinct regression models were devised and used to perform sensitivity and probabilistic analyses, to overcome biases of covariate distributions.ResultsActuarial survival curves showed no difference between resection and ablation (P = 0.270) despite the fact that ablated patients were older, with worse liver function and smaller, unifocal tumours (P < 0.05), suggesting a complex, non-linear relationship between clinical, tumoral variables and treatments. Sensitivity and probabilistic analyses suggested that the superiority of resection over ablation decreased at higher Model for-End stage Liver Disease scores, and that ablation provided better results for smaller tumours and higher Model for-End stage Liver Disease scores. In patients with 2–3 tumours up to 3 cm, the two treatments produced opposite comparative results in relation to the Model for-End stage Liver Disease score.ConclusionsThe superiority, or the equivalence, of resection and ablation depends on the non-linear relationship existing between treatment, tumour number, size and degree of liver dysfunction.     

Coronary vasoreactivity is not altered in young people with type 1 diabetes

Background and aimAbnormal coronary microvascular circulation has been demonstrated in diabetes and is associated with increased rate of cardiovascular events. Our objective was to evaluate coronary vasoreactivity in young people with type 1 diabetes with and without microvascular complications.Methods and resultsTwenty-five type 1 diabetic patients without microvascular complications (DC–), 23 with microvascular complications (DC+), and 18 control subjects (C) were studied. Coronary vasoreactivity was assessed by means of coronary flow reserve (CFR). Blood flow velocity in the left anterior descending coronary artery was measured at rest and after high-dose dipyridamole using transthoracic color-guided pulsed Doppler echocardiography. CFR was defined as the ratio of hyperaemic to resting diastolic peak flow velocities.The three groups had similar cardiac function parameters, and also systolic and diastolic blood pressure at rest, which remained unchanged during dipyridamole infusion. Resting coronary flow velocity was comparable in C, DC–, and DC+ (p = ns). Dipyridamole infusion produced a threefold increase in coronary diastolic peak velocity, which reached similar values in C (0.69 ± 0.16 m/s), DC– (0.69 ± 0.18 m/s), and DC+ (0.66 ± 0.11 m/s). Mean CFR ratio was similar in C (3.33 ± 0.66), DC– (3.30 ± 0.51), and DC+ (3.24 ± 0.60). At multiple linear regression analysis, no association was found between CFR and age, sex, HbA_1c, duration of diabetes, and complications.ConclusionCoronary vasodilatory function is preserved in young D patients, even those with early microvascular complications, suggesting that coronary vasoreactivity deteriorates at more advanced stages of microvascular complications and/or in the presence of other cardiovascular risk factors.     

Effect of cilostazol on arteriovenous fistula in hemodialysis patients

BackgroundThe maturation and patency of permanent vascular access are critical in patients requiring hemodialysis. Although numerus trials have been attempted to achieve permanently patent vascular access, little have been noticeable. Cilostazol, a phosphodiesterase-3 inhibitor, has been shown to be effective in peripheral arterial disease including vascular injury-induced intimal hyperplasia. We therefore aimed to determine the effect of cilostazol on the patency and maturation of permanent vascular access.MethodsThis single-center, retrospective study included 194 patients who underwent arteriovenous fistula surgery to compare vascular complications between the cilostazol (n = 107) and control (n = 87) groups.ResultsThe rate of vascular complications was lower in the cilostazol group than in the control group (36.4% vs. 51.7%; p = 0.033), including maturation failure (2.8% vs. 11.5%; p = 0.016). The rate of reoperation due to vascular injury after hemodialysis initiation following fistula maturation was also significantly lower in the cilostazol group than in the control group (7.5% vs. 28.7%; p < 0.001). However, there were no significant differences in the requirement for percutaneous transluminal angioplasty (PTA), rate of PTA, and the interval from arteriovenous fistula surgery to PTA between the cilostazol and control groups.ConclusionCilostazol might be beneficial for the maturation of permanent vascular access in patients requiring hemodialysis.     

Implicaciones pronósticas de los índices fisiológicos coronarios en pacientes con diabetes mellitus

Introduction and objectivesNo thorough investigation has been performed of the prognostic value of coronary physiological indices in patients with diabetes mellitus (DM) after coronary revascularization deferral.MethodsWe analyzed 714 patients (235 with DM) with deferred revascularization according to fractional flow reserve (> 0.80). A comprehensive physiological evaluation including coronary flow reserve (CFR), index of microcirculatory resistance, and fractional flow reserve was performed at the time of revascularization deferral. The median values of the CFR (2.88), fractional flow reserve (0.88), and index of microcirculatory resistance (17.85) were used to classify patients into high- or low-index groups. The primary outcome was the patient-oriented composite outcome (POCO) at 5 years, comprising all-cause death, any myocardial infarction, and any revascularization.ResultsCompared with the non-DM population, the DM population showed higher risk of POCO (HR, 2.49; 95%CI, 1.64-3.78; P < .001). In the DM population, the low-CFR group had a higher risk of POCO than the high-CFR group (HR, 3.22; 95%CI, 1.74-5.97; P < .001). In contrast, CFR values could not differentiate the risk of POCO in the non-DM population. There was a significant interaction between CFR and the presence of DM regarding the risk of POCO (P for interaction = .025). Independent predictors of POCO were a low CFR and family history of coronary artery disease in the DM population and percent diameter stenosis and multivessel disease in the non-DM population.ConclusionsThe association between coronary physiological indices and clinical outcomes differs according to the presence of DM. In deferred patients, CFR is the most important prognostic factor in patients with DM, but not in those without DM.