Luigia Scudeller

Rapid on-site evaluation of transbronchial aspirates in the diagnosis of hilar and mediastinal adenopathy: a randomized trial.

BACKGROUND Rapid on-site evaluation (ROSE) of transbronchial needle aspirates has long been used during flexible bronchoscopy, but its usefulness in the diagnosis of hilar and mediastinal adenopathy is controversial. The aim of the present study was to evaluate the extent to which ROSE can be valuable in patients undergoing transbronchial needle aspiration (TBNA) for the diagnosis of hilar and mediastinal adenopathy. METHODS A total of 168 consecutive patients with enlarged lymph nodes were randomized to undergo TBNA with or without ROSE. The primary outcome measure of the study was the diagnostic yield of TBNA on a per-patient basis. Secondary outcome measures included the percentage of adequate specimens on a per-lymph node basis, the number of biopsy sites on a per-patient basis, and the complication rate of bronchoscopy on a per-patient basis. RESULTS We found no significant difference between the TBNA group and the ROSE group in terms of diagnostic yield (75.3% vs 78.3%, respectively; P = .64), and percentage of adequate specimens (86.5% vs 78.4%, respectively; P = .11). The median (interquartile range) number of biopsy sites was significantly lower in the ROSE group (1 [1-2] vs 2 [1-2], respectively; P = .0005). The complication rate of bronchoscopy was significantly lower in patients undergoing on-site review (6% vs 20%; P = .01), whereas the complication rate of TBNA was similar among the study groups. CONCLUSIONS ROSE of transbronchial aspirates from hilar and mediastinal nodes enables avoidance of additional biopsy without loss in diagnostic yield and reduces the complication rate of bronchoscopy. TRIAL REGISTRY ClinicalTrials.gov; No.: NCT00915330; URL: www.clinicaltrials.gov

Extracorporeal photochemotherapy in graft-versus-host disease: a longitudinal study on factors influencing the response and survival in pediatric patients.

BACKGROUND: Extracorporeal photochemotherapy (ECP) is a valid therapeutic option in the treatment of acute and chronic graft‐versus‐host disease (aGVHD and cGVHD, respectively). No standard clinical and laboratory criteria of response to ECP treatment are available at the moment.

Hyperlactacidemia Potentially Due to Linezolid Overexposure in a Liver Transplant Recipient

Sir—A 59-year-old white liver transplant recipient developed bilateral pneumonia on day 4 after the operation. After performing bronchoscopy with bronchoalveolar lavage, empirical therapy with piperacillin-tazobactam (4.5 g every 6 h) and levofloxacin (500 mg every 12 h) was commenced. During the subsequent 24 h, the patient’s clinical condition worsened until he developed severe sepsis. Drotrecogin-a was administered, but because of the persistence of the patient’s critical condition, and because no bacteria were isolated, antibiotic therapy was shifted 48 h later to meropenem (500 mg every 6 h) plus linezolid (600 mg every 12 h). Over the subsequent days, the patient’s clinical condition slowly improved. However, despite there being no evidence of graft dysfunction or renal failure, a progressive asymptomatic increase in the plasma lactate level was noted (peak level, 8.4 mmol/L) (figure 1). On day 10 of the second-line antibiotic regimen, therapy was de-escalated by withdrawing meropenem. In accordance with our institution’s antibiotic policy, which is oriented at optimizing therapy for critically ill patients [1], multiple blood samples were obtained to assess linezolid exposure during a dosing interval and were subsequentlyanalyzed by high-performance liquid chromatography [2]. Pharmacokinetic analysis revealed significant plasma overexposure to linezolid (12-h area under the curve, 412.55 /L; maximum concentration, 43.32 mg h mg/L; minimum concentration, 26.99 mg/ L) because of impaired clearance (1.51 L/ h) with a prolonged elimination half-life (16.57 h) [3]. We hypothesized that the patient potentially had drug-induced hyperlactacidemia. On day 12 of hospitalization, linezolid was withdrawn, and blood samples were obtained to determine whether plasma drug levels were decreasing. During the subsequent 2 days, concomitantly with a decrease in the plasma linezolid level, a progressive decrease of the plasma lactate level (until complete normalization occurred) was documented (figure 1). Hyperlacticidemia during linezolid therapy has been previously reported to be an adverse event that mainly develops after long treatment periods and that slowly resolves after withdrawal of the drug [4–6]. Conversely, in the case we report, lactate levels started increasing just after the first week of treatment, rapidly achieved the maximum level, and returned to a normal level within 48 h after drug withdrawal. It has been suggested that, on the basis of its mechanism of action, linezolid may cause hyperlacticidemia by inhibiting mitochondrial protein synthesis [6]. Therefore, hyperlacticidemia should be expected to occur earlier in the course of treatment and to be more severe in patients who

Comparison between Rules-Based Human Immunodeficiency Virus Type 1 Genotype Interpretations and Real or Virtual Phenotype: Concordance Analysis and Correlation with Clinical Outcome in Heavily Treated Patients

We compared 2 rules-based genotype interpretation systems and real or virtual phenotype through a retrospective analysis of a prospective trial. Genotypes were determined with VircoGEN II (VIRCO) and were interpreted with either RetroGram 1.4 or TRUGENE HIV-1 (guidelines 3.0) or original virtual phenotype (Virtual Phenotype; VIRCO), as available in the year 2000. Among 188 human immunodeficiency virus (HIV) type 1 isolates, overall concordance (kappa agreement) was observed for the 2 rules-based systems, whereas striking discordances were noted between them and real and virtual phenotype interpretations for stavudine, didanosine, zalcitabine, abacavir, and amprenavir (kappa<0.4). Clinical evaluation of a subset of 173 patients showed that both rules-based sensitivity scores were independently associated with HIV RNA loads <400 copies/mL at week 16 of during-treatment analysis (TRUGENE: odds ratio [OR], 2.90; 95% confidence interval [CI], 1.52-5.52; P=.001; RetroGram: OR, 2.34; 95% CI, 1.21-4.55; P=.012), whereas, in contrast to real or virtual phenotype, interpretations according to biological cut-offs were not (OR, 1.91; 95% CI, 0.77-4.76; P=.162).

Do adherence rates and glaucomatous visual field progression correlate

Purpose TO assess the relation between visual field progression and adherence rate in patients with glaucoma using Travatan Dosing Aid® (TDA). Methods In this 36-month retrospective study, 35 patients with primary open-angle glaucoma on travoprost or travoprost/timolol fixed combination monotherapy were submitted to ophthalmic examination and to visual field (VF) test from 2007 to 2009. Adherence was recorded with TDA. The association between VF progression (from 2007 to the end of the follow-up period) and a number of predictors (adherence rates at 12 months) was tested by means of chi-square test (or Fisher exact test) or Mann-Whitney test as appropriate. Results The mean (±SD) adherence rates were 71.9%±27.8% after 1 month of follow-up and 76.8%±20.9% at 12 months. A total of 25 (71.4%) patients with stable VF had a median adherence rate (IQR) of 85% (75%-97%); patients who worsened (n=10; 28.6%) recorded a median (IQR) adherence of 21% (9%-45%) (p<0.001). No association was found between VF progression and any of the other variables (age, sex, schooling, visual acuity, intraocular pressure (IOP) at baseline and over time, other ocular diseases, time since diagnosis and actual therapy, number of concomitant systemic therapies). Patients who were at least 90% adherent did not progress, while 43.5% of the patients with lower adherence worsened (p=0.01). Conclusions Our data suggest that adherence rate may play a role in glaucomatous damage and/or progression; the target IOP therefore should be adjusted by adherence rates. Monitoring tools, educational programs, use of videos, a better doctor-patient relationship, or other means to improve adherence are desirable and necessary to preserve visual function.

Platelet lysate formulations based on mucoadhesive polymers for the treatment of corneal lesions

Objectives  Growth factors contained in platelet α‐granules initiate and modulate tissue repair and are proposed for the treatment of soft and hard‐tissue surgical conditions and in the management of non‐healing wounds. Platelet lysate is a hemoderivative obtained from platelet‐rich plasma and is capable of releasing a pool of growth factors. Many medical and surgical techniques have been proposed for the treatment of corneal lesions; management of these conditions remains problematic and healing with standard protocols is unattainable. The aim of this study was to develop formulations suitable for prolonging the contact of platelet lysate with the damaged cornea for the time necessary to exert a therapeutic effect.

Lack of a correlation between portal vein flow and pressure: toward a shared interpretation of hemodynamic stress governing inflow modulation in liver transplantation

The portal vein flow (PVF), portal vein pressure (PVP), and hepatic venous pressure gradient (HVPG) were prospectively assessed to explore their relationships and to better define hyperflow and portal hypertension (PHT) during liver transplantation (LT). Eighty‐one LT procedures were analyzed. No correlation between PVF and PVP was observed. Increases in the central venous pressure (CVP) were transmitted to the PVP (58%, range = 25%‐91%, P = 0.001). Severe PHT (HVPG ≥ 15 mm Hg) showed a significant reciprocal association with high PVF (P = 0.023) and lower graft survival (P = 0.04). According to this initial experience, an HVPG value ≥ 15 mm Hg is a promising tool for the evaluation of hemodynamic stress potentially influencing outcomes. An algorithm for graft inflow modulation based on flows, gradients, and systemic hemodynamics is provided. In conclusion, the evaluation of PHT severity with PVP could be delusive because of the influence of CVP. PVF and PVP do not correlate and should not be used individually to assess hyperflow and PHT during LT. Liver Transpl 17:836‐848, 2011.

Autologous platelet lysate for treatment of refractory ocular GVHD

Current treatment of ocular GVHD (oGVHD), represented by systemic immunosuppressive regimens and local therapies (mainly artificial tears and corticosteroids), gives unsatisfactory results. We investigated the safety and efficacy of autologous plasma rich in PDGFs to treat oGVHD unresponsive to standard medications. A total of 23 patients with refractory oGVHD (grade II–IV) unresponsive to standard therapy were treated with autologous plasma rich in PDGFs eye drops (PRGD) four times/day for 6 months. Symptoms and signs (best visual acuity, Schirmer’s test and tear break up time (TBUT), evaluation of the anterior segment and fluorescein and lissamine staining) were always assessed by the same ophthalmologist. Patients were defined as ‘responders’ when showing improvement for total complaints and at least one sign. At 30 days of treatment, 17 patients (73.9%) were classified as responders. The symptom that improved most was photophobia (improved in 19 patients, 82.6%). TBUT improved in 20 patients (86.9%) and anterior segment score in 19 patients (82.6%). Response was maintained over time. No serious adverse events occurred. PRGD proved to be safe and effective in treating oGVHD and may be a valid treatment option from the early stages of the disease to avoid irreversible ocular damage.

Prospective evaluation of intraoperative hemodynamics in liver transplantation with whole, partial and DCD grafts

The interaction of systemic hemodynamics with hepatic flows at the time of liver transplantation (LT) has not been studied in a prospective uniform way for different types of grafts. We prospectively evaluated intraoperative hemodynamics of 103 whole and partial LT. Liver graft hemodynamics were measured using the ultrasound transit time method to obtain portal (PVF) and arterial (HAF) hepatic flow. Measurements were recorded on the native liver, the portocaval shunt, following reperfusion and after biliary anastomosis. After LT HAF and PVF do not immediately return to normal values. Increased PVF was observed after graft implantation. Living donor LT showed the highest compliance to portal hyperperfusion. The amount of liver perfusion seemed to be related to the quality of the graft. A positive correlation for HAF, PVF and total hepatic blood flow with cardiac output was found (p = 0.001). Portal hypertension, macrosteatosis >30%, warm ischemia time and cardiac output, independently influence the hepatic flows. These results highlight the role of systemic hemodynamic management in LT to optimize hepatic perfusion, particularly in LDLT and split LT, where the highest flows were registered.

Treatment of pyogenic (non-tuberculous) spondylodiscitis with tailored high-dose levofloxacin plus rifampicin

The purpose of this study was to assess the clinical efficacy of high-dose levofloxacin plus rifampicin in the empirical treatment of non-tuberculous spondylodiscitis in an epidemiological context of low incidence of staphylococcal fluoroquinolone resistance. All consecutive adult patients with spondylodiscitis (January 2003 to December 2006) were empirically treated with high-dose levofloxacin (500 mg every 12 h normalised to renal function and optimised by means of therapeutic drug monitoring whenever feasible) plus rifampicin 600 mg every 24 h. Trough and peak plasma concentrations were targeted at 1-3 mg/L and 6-9 mg/L, respectively, to maximise the concentration-dependent activity of levofloxacin in bone. Follow-up was performed until 9 months after the end of therapy. Forty-eight patients were included. Eleven patients underwent a surgical approach for spine stabilisation. Among the 29 bacterial isolates, Staphylococcus aureus was the most frequent (65.5%) (all meticillin-susceptible strains). Tailored levofloxacin plasma exposure over time was ensured in most cases. Median treatment duration was 15.1 weeks. Overall response rates were: 77.1% at the intent-to-treat analysis; 84.1% among patients who completed therapy (N=44); and 96.3% among those receiving targeted therapy against documented levofloxacin-susceptible isolates (N=27). No patient had evidence of disease relapse at follow-up. Our findings suggest that high-dose levofloxacin regimens may be highly effective in the treatment of non-tuberculous spondylodiscitis and support its putative role in combination with rifampicin against S. aureus.