De novo AML patients with favourable–intermediate karyotype may benefit from the addition of low-dose gemtuzumab ozogamicin (GO) to fludarabine, Ara-C and idarubicin (FLAI): a contribution to the reopened “GO question”

We report the final results of a prospective trial testing the combination of fludarabine, Ara-C and idarubicin (FLAI) followed by low-dose gemtuzumab ozogamicin (FLAI-GO) in 85 patients aged 60 years or more with CD33+ acute myeloid leukaemia (AML). Median age was 68 years (60–82); karyotype was unfavourable in 21 patients (24 %), intermediate in 63 (74 %) and favourable in 1 (2 %). There were five therapy-related deaths. Of the 80 evaluable patients, 47 achieved complete response (CR) (58 %); CR rates were 65 and 32 % in good-intermediate/poor karyotype patients, respectively. Median length of CR was 7 months (3–76). The cumulative incidence of relapse was 84 % with an actuarial survival of 50.3 % at 1 year and 14.4 % at 2 years. The study control population is an unselected consecutive historic cohort of 104 patients treated with the FLAI regimen, who were matched for age and prognostic factors. CR rates after FLAI-GO and FLAI were comparable. However, patients with de novo AML and intermediate–favourable karyotype receiving GO had a significantly lower risk of relapse at 2 years as compared to patients not receiving GO (n?=?77) (40 vs 80 %, p?=?0.01) and significantly better disease-free survival (p?=?0.018) and overall survival (p?=?0.022).     

Body composition changes and cardiometabolic benefits of a balanced Italian Mediterranean Diet in obese patients with metabolic syndrome

Metabolic syndrome (MS) is a cluster of metabolic alteration associated with a higher risk of cardiovascular disease and overall mortality than the single alterations alone. The Italian Mediterranean Diet (IMD) can exert a positive effect on cardiovascular risk and related morbidity and mortality. The aim was to evaluate the benefits of dietary intervention based on a typical IMD on body composition, cardiometabolic changes and reduction in cardiovascular disease in patients with MS. Eighty White Italian subjects with MS were prescribed a balanced hypocaloric IMD. We investigated dietary habits and impact of the diet on health status, blood biochemical markers, anthropometric measurements and body composition during a 6-month follow-up period. Body composition, fat mass and distribution were assessed by Dual X-ray absorptiometry. Adherence to the IMD led to a decrease in body weight (102.59 ± 16.82 to 92.39 ± 15.94 kg, p < 0.001), body mass index (BMI) (38.57 ± 6.94 to 35.10 ± 6.76, <0.001) and waist circumference (112.23 ± 12.55 vs 92.42 ± 18.17 cm, p < 0.001). A significant loss of total body fat especially in waist region was observed. The MS was resolved in 52 % of the patients. Significant improvements in systolic and diastolic blood pressure and fasting glucose occurred. Low-density lipoprotein cholesterol was reduced from 128.74 ± 33.18 to 108.76 ± 38.61 mg/dl (p < 0.001), triglycerides from 169.81 ± 80.80 to 131.02 ± 63.88 mg/dl (p < 0.001). The present results suggest that a dietary intervention based on a typical IMD effectively promotes weight loss and reduces the growing burden of cardiovascular risk factors that typifies patients with MS.     

Excessive daytime sleepiness and hepatic encephalopathy: it is worth asking

The relationship between hepatic encephalopathy (HE) and the sleep-wake disturbances exhibited by patients with cirrhosis remains debated. The aim of this study was to examine the usefulness of sleep-wake interview within the context of HE assessment. One-hundred-and-six cirrhotic patients were asked three yes/no questions investigating the presence of difficulty falling asleep, night awakenings and daytime sleepiness. All underwent formal HE assessment, quantitative electroencephalography and standardised psychometry. Fifty-eight were monitored for 8?±?6 months in relation to the occurrence of HE. Patients complaining of daytime sleepiness (n?=?75, 71 %) had slower EEGs than those who did not report it (relative alpha power: 37?±?19 vs. 48?±?17 %, p?<?0.05). In addition, daytime sleepiness was associated with the presence of portal-systemic shunt (79 vs. 57 %, p?<?0.05) and HE history (72 vs. 45 %, p?<?0.05). Finally, the absence of excessive daytime sleepiness had a Negative Predictive Value of 92 % (64–100) in relation to the development of HE during the follow-up period. These data support the appropriateness of adding a yes/no question on the presence of excessive daytime sleepiness to routine assessment of patients with cirrhosis, to help identify those who do not need further, formal HE screening.     

“Ischemic” ST elevation in a woman with left ventricular hypertrophy

We report the case of a woman who presented with ST elevation and episodes of chest pain, mimicking an acute myocardial infarction. At coronary angiography no sign of coronary stenosis was found and ECG anomalies were related to asymmetric left ventricular hypertrophy and aortic stenosis.     

Correlation between some metabolic markers of vascular risk and carotid artery intima-media thickness in postmenopausal women

AIM AND SETTING: This study investigated correlations between insulinemia, insulin sensitivity, body mass index, lipids and lipoproteins with intima-media thickness in a group of 25 (age range 40-55 years) postmenopausal women (minimum duration of menopause 2 years) not on hormone replacement treatment. METHODOLOGY: Uni and multivariate correlations showed a direct relationship between insulin pattern, insulin sensitivity, body mass index, low density lipoproteins and increased intima-media thickness. RESULTS: Our multivariate correlation results revealed that intima-media thickness is influenced by the associations of the different metabolic functions investigated. Therefore, carotid wall intima-media thickness represents a dependent variable in postmenopausal women for some metabolisms whose dysfunction leads to atherosclerosis. CONCLUSION: This multielement synergy is able to detect cardiovascular risk and may underlie cardiovascular mortality in postmenopausal women.     

Endothelial cell binding by systemic lupus antibodies: functional properties and relationship with anti-DNA activity

Anti-DNA antibodies and anti-endothelial cell antibodies (AECA) are often detected in systemic lupus erythematosus (SLE). Anti-DNA antibodies can also bind the membrane of human umbilical vein endothelial cells (HUVEC), but little is known about the presence of AECA in the population of immunoglobulins from SLE sera that do not bind DNA. The aim of this study is to analyse the ability of anti-DNA and non-anti-DNA antibodies from SLE sera to bind endothelial cell antigens and to investigate their pathogenic potential. Both anti-DNA and non-anti-DNA antibodies display AECA activity by immunoprecipitation and flow cytometry and in some patients recognize antigens of identical molecular weight. Complement-dependent cytotoxicity on HUVEC was not detected with either anti-DNA or non-anti-DNA antibodies. Similarly, apoptosis was not induced in HUVEC and HL60 incubated with anti-DNA or non-anti-DNA antibodies, as shown by the DNA hypodiploid content. These data indicate that AECA are highly heterogeneous, as they recognize a wide variety of surface molecules on HUVEC and equally present in anti-DNA and non-anti-DNA antibodies from SLE patients.     

Relationship between salivary flow rates and Candida counts in subjects with xerostomia

OBJECTIVE: This study evaluated the relationship between salivary flow and Candida colony counts in the saliva of patients with xerostomia. STUDY DESIGN: Sialometry and Candida colony-forming unit (CFU) counts were taken from 112 subjects who reported xerostomia in a questionnaire. Chewing-stimulated whole saliva was collected and streaked in Candida plates and counted in 72 hours. Species identification was accomplished under standard methods. RESULTS: There was a significant inverse relationship between salivary flow and Candida CFU counts (P =.007) when subjects with high colony counts were analyzed (cutoff point of 400 or greater CFU/mL). In addition, the median sialometry of men was significantly greater than that of women (P =.003), even after controlling for confounding variables like underlying disease and medications. Sj?gren's syndrome was associated with low salivary flow rate (P =.007). There was no relationship between the median Candida CFU counts and gender or age. There was a high frequency (28%) of mixed colonization. Candida albicans was the most frequent species, followed by C parapsilosis, C tropicalis, and C krusei. CONCLUSIONS: In subjects with high Candida CFU counts there was an inverse relationship between salivary flow and Candida CFU counts.     

Baseline-Dependent Effects of Cocaine Pre-Exposure on Impulsivity and D2/3 Receptor Availability in the Rat Striatum: Possible Relevance to the Attention-Deficit Hyperactivity Syndrome

We have previously shown that impulsivity in rats predicts the emergence of compulsive cocaine seeking and taking, and is coupled to decreased D_2/3 receptor availability in the ventral striatum. As withdrawal from cocaine normalises high impulsivity in rats, we investigated, using positron emission tomography (PET), the effects of response-contingent cocaine administration on D_2/3 receptor availability in the striatum. Rats were screened for impulsive behavior on the five-choice serial reaction time task. After a baseline PET scan with the D_2/3 ligand [¹⁸F]fallypride, rats were trained to self-administer cocaine for 15 days under a long-access schedule. As a follow-up, rats were assessed for impulsivity and underwent a second [¹⁸F]fallypride PET scan. At baseline, we found that D_2/3 receptor availability was significantly lower in the left, but not right, ventral striatum of high-impulsive rats compared with low-impulsive rats. While the number of self-administered cocaine infusions was not different between the two impulsivity groups, impulsivity selectively decreased in high-impulsive rats withdrawn from cocaine. This effect was accompanied by a significant increase in D_2/3 receptor availability in the left, but not right, ventral striatum. We further report that D_2/3 receptor availability was inversely related to baseline D_2/3 receptor availability in the ventral striatum of high-impulsive rats, as well as to the left and right dorsal striatum of both low-impulsive and high-impulsive rats. These findings indicate that the reduction in impulsivity in high-impulsive rats by prior cocaine exposure may be mediated by a selective correction of deficient D_2/3 receptor availability in the ventral striatum. A similar baseline-dependent mechanism may account for the therapeutic effects of stimulant drugs in clinical disorders such as ADHD.     

Pharmacotherapeutic management of macular edema in diabetic subjects undergoing cataract surgery

ABSTRACT

Introduction: Cataracts and diabetes are widespread pathologies that are of growing concern to the global population. In diabetic patients who have had cataract surgery, the worsening of preexisting diabetic macular edema or occurrence of pseudophakic cystoid macular edema are common causes of visual impairment even with the most advanced surgical techniques available today for phacoemulsification.

Areas covered: In this review, the authors assess the available literature to evaluate and compare different drugs, with the aim of establishing the best pharmacological strategies for the prevention and treatment of macular edema in diabetic patients undergoing cataract surgery.

Expert opinion: Guidelines for the optimal management of diabetic macular edema in conjunction with cataract surgery or treatment of pseudophakic cystoid macular edema in diabetic patients are still lacking. To treat these conditions, clinicians need to understand the pharmacokinetics, posology, and efficacy of available drugs: topical non-steroidal anti-inflammatory drugs (NSAIDs), intravitreal anti-vascular endothelial growth factors (VEGFs), and both topical and intravitreal steroids. Diabetic patients undergoing cataract surgery should receive topical NSAIDs to prevent pseudophakic cystoid macular edema. Intravitreal anti-VEGFs and steroids, in association with cataract surgery, are indicated for patients with preexisting diabetic macular edema or those at high risk of macular edema after surgery.