Incidence,risk factors and management of pleural effusions during dasatinib treatment in unselected elderly patients with chronic myelogenous leukaemia

To assess the most important features and clinical impact of pleural effusions, which are a common toxicity during dasatinib treatment and often impair its high efficacy, 172 unselected consecutive patients with chronic myelogenous leukaemia in chronic phase treated in 27 Italian centres, with dasatinib when aged >60 years for resistance/intolerance to imatinib, were examined. During treatment, 52/172 patients (30.2%) presented pleural effusion, which was grades 1–2 in 38 patients and grades 3–4 in 14 patients (8.1% of the entire cohort of patients), according to the WHO scale; in 14/52 patients (26.9%), there was a concomitant pericardial effusion. Pleural effusion was recurrent in 25/52 patients (48.0%). Median time from dasatinib to first pleural effusion was 11.0 months (interquartile range 3.6–18.6). Eleven patients (6.4%) required permanent dasatinib discontinuation. Only presence of concomitant pulmonary disease ( p = 0.035) and initial daily dose of dasatinib (140 mg vs 100 mg, p = 0.014) were significantly associated with pleural effusions. There were no differences among patients with or without pleural effusions as concerns response rates and overall survival. Pleural effusions were common in our unselected ‘real‐life’ population of elderly patients but were clinically manageable and did not seem to affect treatment results. Copyright © 2012 John Wiley & Sons, Ltd.     

Mid-trimester fetal-placental velocimetry response to nifedipine may predict early the onset of pre-eclampsia

The effect of nifedipine on fetal-placental blood flow at 22-24 weeks in patients with pregnancy-induced hypertension (PIH) was evaluated. Twenty patients with PIH were submitted to the Doppler evaluation of fetal-placental perfusion at 22-24 weeks. The systo-diastolic (SID) ratio and the pulsatility index (PI) of uterine, umbilical and middle cerebral arteries and systemic blood pressure were recorded before and 7 days after nifedipine administration (10 mg/ per os 3 times/day until delivery). Statistical analysis was performed with paired and unpaired t-test and the two-tailed Fisher exact test. Nifedipine significantly (p < 0.05) decreased the mean systolic pressure in all patients (from 146 to 135 mmHg): 8 patients developed pre-eclampsia (PE) complicated by fetal growth restriction (FGR) (PE group), whilst the remaining were only affected by PIH (PIH group). The gestational age at delivery, neonatal birthweight and 1- and 5-min Apgar scores were significantly (p < 0.001) lower in PE than in PIH women. Nifedipine treatment significantly changed the PI and S/D ratio (mean +/- SEM) of the uterine (PI from 0.66 +/- 0.01 to 0.51 + 0.01; SID ratio: from 2.00 +/- 0.09 to 1.79 + 0.05) and umbilical (PI: from 1.55 +/- 0.04 to 1.40 +/- 0.02; S/D ratio: from 2.45 +/- 0.09 to 2.31+/- 0.09) arteries and the middle cerebral PI (from 1.45 +/- 0.03 to 1.61 +/- 0.01) artery only in PIH, but not in PE patients. Fetal-placental blood flow changes after nifedipine may early identify patients at risk of PE.     

Pigmented mammary Paget's disease mimicking melanoma

Our case of pigmented mammary Paget's disease simulated melanoma clinically and dermoscopically. Histologically, the lesion was characterized by microscopic features similar to those seen in malignant melanoma and, to a lesser extent, in Bowen's disease (intra-epidermal squamous cell carcinoma). Immunohistochemical studies demonstrated that the tumor cells were positive for keratins (Cam 5.2+MNF 116) and AE1-AE3 and negative for HMB-45 and S-100 proteins. In conclusion clinical and dermoscopic examination cannot reliably distinguish melanoma from epithelial pre-neoplastic or neoplastic disease, therefore the differentiation of pigmented Paget's disease from superficial spreading of melanoma and Bowen's disease is based on histopathologic integrated with immunohistochemical criteria.     

In Vitro Activity of Tea Tree Oil Vaginal Suppositories against Candida spp. and Probiotic Vaginal Microbiota

The aim of this work is to evaluate the in vitro microbicidal activity of vaginal suppositories (VS) containing tea tree oil (TTO‐VS) towards Candida spp. and vaginal probiotics. A total of 20 Candida spp. strains, taken from patients with vaginitis and from an established type collection, including reference strains, were analysed by using the CLSI microdilution method. To study the action of VS towards the beneficial vaginal microbiota, the sensitivity of Bifidobacterium animalis subsp. lactis (DSM 10140) and Lactobacillus spp. (Lactobacillus casei R‐215 and Lactobacillus acidophilus R‐52) was tested. Both TTO‐VS and TTO showed fungicidal activity against all strains of Candida spp. whereas placebo‐VS or the Aloe gel used as controls were ineffective. The study of fractional fungicidal concentrations (FFC) showed synergistic interaction with the association between Amphotericin B and TTO (0.25 to 0.08 µg/ml, respectively) against Candida albicans. Instead, the probiotics were only affected by TTO concentration ≥ 4% v/v, while, at concentrations < 2% v/v, they remained viable. TTO‐VS exhibits, in vitro, a selective fungicidal action, slightly affecting only the Bifidobacteriun animalis strain growth belonging to the vaginal microbiota. In vivo studies are needed to confirm the efficacy to prevent acute or recurrent vaginal candidiasis. Copyright © 2015 John Wiley & Sons, Ltd.     

Stereoselective synthesis of new beta-lactams by cyclocondensation of 1-methoxy-3-(trimethylsilyloxy)-1,3-butadiene with 4-formyl substituted azetidinones

The BF3.OEt2 or LiClO4 catalyzed hetero Diels-Alder reaction of 1-methoxy-3-(trimethylsilyloxy)-1,3-butadiene (Danishefsky's diene) with enantiomerically pure 4-formylazetidin-2-ones affords the corresponding cycloadducts in fair to good yields and in diastereoisomeric ratios of up to 98:2.     

Single territory incomplete surgical revascularization improves regional wall motion of remote ventricular areas: results from a propensity-matched study

Objective Basic science studies demonstrated a general intramyocardial angiogenetic response potentially responsible for the creation of a microvascular neocapillaries network assisting myocardial function. We hypothesized that the benefit provided by the reperfusion of left anterior descending (LAD) territories and the biological angiogenetic drive triggered by the revascularization could translate in a global improvement in ventricular contractility, not restricted to the grafted area. Methods High-risk patients with multivessel coronary artery disease and preoperative wall motion abnormalities were retrospectively analysed to compare outcomes and regional ventricular function of those who received optimal medical therapy (OMT) versus those who underwent off-pump coronary artery bypass grafting (CABG) and received an incomplete myocardial revascularization using left internal mammary artery (LIMA) on LAD (off-pump CABG group). From January 2007 to December 2014, 206 patients (OMT n = 136, OPCAB n = 70) were propensity-score matched to have 70 matched pairs. Variables included in propensity score analyses were ejection fraction (EF), left ventricular end diastolic volume (LVEDVi), EuroSCORE II. Primary endpoint was the variation in the global wall motion score index (ΔWMSI) as evaluated by transthoracic echocardiography. Follow up was completed at 3 years from surgery or hospital discharge. Results Regional analysis of ventricular function revealed a regional WMSI improvement in the OPCABG group not only for LAD territories but also for non-LAD regions, associated with a reduction in the negative left ventricular ischemic remodeling, compared to patients discharged in optimal medical therapy. Global ΔWMSI was negative in OPCAB group (-3.4 ± 2.8%) and positive in the OMT group (5.9 ± 3.1%), indicating a better wall motion score for OPCAB patients. Surprisingly, regional WMSI improved also in non-grafted territories in the OPCAB group with a delta value of -3.7 ± 5.3% for left circumflex artery (LCX) area and -3.5 ± 5.4% for right coronary artery (RCA) area. Conclusions In patients with multivessel coronary artery disease, LIMA-to-LAD grafting is associated with an improvement in the WMSI involving also the surrounding non-LAD ungrafted segments and with the attenuation of negative global and regional ischemic ventricular remodelling.