ΔKi67 proliferation index as independent predictive and prognostic factor of outcome in luminal breast cancer: data from neoadjuvant letrozole-based treatment.

A key tool for monitoring breast cancer patients under neoadjuvant treatment is the identification of reliable predictive markers. Ki67 has been identified as a prognostic and predictive marker in ER-positive breast cancer. Ninety ER-positive, HER2 negative locally advanced breast cancer patients received letrozole (2.5 mg daily) and cyclophosphamide (50 mg daily) with/without Sorafenib (400 mg/bid daily) for 6 months before undergoing surgery. Ki67 expression and tumor size measured with caliber were determined at baseline, after 30 days of treatment and at the end of treatment. Patients were assigned to a clinical response category according to Response Evaluation Criteria in Solid Tumors, both at 30 days and before surgery and further classified as high-responder and low-responder according to the median variation of Ki67 values between biopsy and 30 days and between biopsy and surgery time. The predictive role of Ki67 and its changes with regard to clinical response and survival was analyzed. No differences in terms of survival outcomes emerged between the arms of treatment, while we observed a higher percentage of women with progression or stable disease in arm with the combination containing Sorafenib (20.5% vs 7.1%, p = 0.06). Clinical complete responders experienced a greater overall variation in Ki67 when compared with partial responders and patients with progressive/stable disease (66.7% vs 30.7%, p = 0.009). High responders showed a better outcome than low responders in terms of both disease-free survival (p = 0.009) and overall survival (p = 0.002). ΔKi67 score evaluated between basal and residual tumor at definitive surgery showed to be highly predictive of clinical complete response, and a potential parameter to be used for predicting disease-free survival and overall survival in luminal breast cancer treated with neoadjuvant endocrine-based therapy.

Efficacy of extended aromatase inhibitors for hormone-receptor-positive breast cancer: A literature-based meta-analysis of randomized trials.

BACKGROUND: Endocrine treatment with Tamoxifen and aromatase inhibitors (AIs) is a staple in the management of hormone receptor positive breast cancer (HR + BC). It has become clear that HR + BC carries a consistent risk of relapse up to 15 years post-diagnosis. While increasing evidence supports the use of extended adjuvant Tamoxifen over 5 years, controversial data are available on the optimal duration of extended AIs adjuvant treatment. We performed a meta-analysis to assess the real impact of extended adjuvant therapy with AIs on disease-free survival (DFS). METHODS: A literature-based meta-analysis of randomized controlled trials (RCTs) was undertaken. Relevant publications from PubMed, the Cochrane Library, and abstracts from American Society of Clinical Oncology (ASCO) and San Antonio Breast Cancer (SABCS) symposia were searched. Primary and secondary endpoints were Disease Free Survival (DFS) and overall survival (OS) respectively. A subgroup analysis was also performed to elucidate the impact of nodal involvement. RESULTS: The pooled analysis revealed a significant increase in DFS in the extended AIs group (hazard ratio (HR): 0.78, 95% CI: 0.68-0.90; P = 0.0006). The subgroup analysis according to nodal status showed a greater DFS benefit with extended AIs in patients with positive nodes (HR = 0.67 versus 0.80). Our analysis also demonstrated no improvement in OS with extended AIs (HR = 0.99, 95%CI: 0.87-1.12; P = 0.84). CONCLUSION: This work confirmed the efficacy of extended adjuvant treatment with AIs for HR + early breast cancer, with a 22% increase in DFS, but no impact on OS. Greater efficacy was observed in women with positive nodal status.

Brain unidentified bright objects ("UBO") in systemic lupus erythematosus: sometimes they come back. A study of microembolism by cMRI and Transcranial Doppler ultrasound.

OBJECTIVES: The objectives of this report are to assess the occurrence of microembolic signals (MES) detected by transcranial Doppler ultrasound (TCD) in systemic lupus erythematosus (SLE) patients with (NPSLE) and without (SLE) neuropsychiatric involvement, and to verify the correlation between MES, clinical characteristics, especially the patent foramen ovale (PFO), and the presence of punctuate T2-hyperintense white matter lesions (WMHLs) detected by conventional magnetic resonance imaging (cMRI). METHODS: A TCD registration to detect MES from the middle cerebral artery was carried out in SLE and NPSLE patients after exclusion of aortic and/or carotid atheromatous disease. In all patients conventional brain magnetic resonance imaging (cMRI) and transesophageal echocardiography were performed. Patients were stratified in two groups, with and without WMHLs, and compared. RESULTS: Twenty-three SLE patients (16 NPSLE and seven SLE) were enrolled in the study. Overall MES were detected in 12 patients (52.1%), WHMLs were detectable in 15 patients (13 NPSLE and two SLE) while eight patients had normal cMRI (three NPSLE and five SLE). Matching TCD ultrasound and neuroimaging data, MES were detected in 10 (nine NPSLE and one SLE) out of 15 patients with WHMLs and in only two out of eight patients (two NPSLE and six SLE) with normal cMRI, both with NP involvement. A PFO was confirmed in all cases of MES detection. CONCLUSION: MES are frequent findings in SLE patients, especially in those with focal WMHLs detected by cMRI and correlating with PFO. These findings should be taken into account and suggest caution in the interpretation of cMRI pictures along with a careful evaluation of MES in patients with cMRI abnormalities that should be included in the workup of SLE patients.

Very Early Carotid Endarterectomy After Intravenous Thrombolysis.

OBJECTIVE/BACKGROUND: The timing of carotid endarterectomy (CEA) after thrombolysis is still a matter of debate. The aim of this study was to analyse a cohort of patients undergoing urgent endarterectomy after intravenous thrombolysis for acute ischaemic stroke. METHODS: This was an observational study. Prospective databases were reviewed and matched to identify patients who underwent CEA early after intravenous thrombolysis (2009-14). The focus was carotid surgery performed within 12 hours of stroke onset in patients with a high grade (≥70%) symptomatic carotid stenosis, associated with vulnerable plaques or stroke in evolution, and evidence of a significant salvageable ischaemic penumbra on perfusion computed tomography scan. Demographic and clinical information, as well as data on relevant outcomes were extracted. RESULTS: Thirty four consecutive stroke patients who underwent CEA within 2 weeks of thrombolysis for acute ischaemic stroke and ipsilateral high grade carotid stenosis were identified. In 11 patients the surgical procedure was performed within 12 hours of the onset of symptoms. All patients showed a clinical improvement after combined treatment. The 3 month outcome was favourable (modified Rankin Scale ≤ 2) in 10 patients. No haemorrhagic complications were registered. There was neither peri-operative stroke nor stroke within 3 months of surgery. One patient died from acute myocardial infarction 3 days after intervention. CONCLUSION: This experience suggests that very early CEA after thrombolysis, aimed at removing the source of potential embolisation and restoring blood flow, may be safe and can lead to a favourable outcome.

Evaluation of acute perihematomal regional apparent diffusion coefficient abnormalities by diffusion-weighted imaging.

In this study, we investigated 40 patients (18 male, 22 female; mean age = 64.5 +/- 11.0; GCS = 9 to 14) with acute supratentorial spontaneous intracerebral hemorrhage (SICH) at admission by using a 1-tesla magnetic resonance imaging (MRI) unit equipped for single-shot echo-planar spin-echo isotropic diffusion-weighted imaging (DWI) sequences. All DWI studies were obtained within 48 hours after symptom onset. Regional apparent diffusion coefficient (rADC) values were measured in 3 different regions of interest (ROIs) drawn freehand on the T2-weighted images at b 0 s/mm2 on every section in which hematoma was visible: 1) the perihematomal hyperintense area; 2) 1 cm of normal appearing brain tissue surrounding the perilesional hyperintense rim; 3) an area mirroring the region including the clot and perihematomal hyperintense area placed in the contralateral hemisphere. rADC mean values were higher in perihematomal hyperintense and in contralateral than in normal appearing areas (p < 0.001), with increased rADC mean levels in all regions examined. Our findings show that rADC values indicative of vasogenic edema were present in the perihematomal area and in normal appearing brain tissue located both ipsilateral and contralateral to the hematoma, with lower levels in non-injured areas located in the T2 hyperintense rim around the clot.

Elevated plasma homocysteine in acute stroke was not associated with severity and outcome: stronger association with small artery disease.

Homocysteine increases in the acute phase of ischaemic stroke and from the acute to the convalescent phase, suggesting that hyper-homocysteinaemia may be a consequence rather than a causal factor. Therefore we measured homocysteine plasma levels in stroke patients in order to investigate possible correlations of homocysteine with stroke severity and clinical outcome. Further we looked for eventual differences in stroke subtypes. We prospectively studied plasma homocysteine levels in acute stroke patients admitted to the stroke unit of our department. Seven hundred and seventy-five ischaemic stroke patients, 39 cerebral haemorrhages and 421 healthy control subjects have been enrolled. Stroke severity and clinical outcome were measured with the Scandinavian Stroke Scale, the Rankin Scale and the Barthel Index. Stroke severity by linear stepwise regression analysis was not an independent determinant of plasma homocysteine levels. Homocysteine was not correlated with outcome measured by the Barthel Index. Mean plasma homocysteine of both ischaemic and haemorrhagic stroke was significantly higher than controls (p<0.05). Homocysteine had an adjusted odds ratios (OR) of 4.2 (95% CI 2.77-6.54) for ischaemic stroke and of 3.69 (95% CI 1.90-7.17) for haemorrhagic stroke. Compared with the lowest quartile, the upper quartile was associated with an adjusted OR of ischaemic stroke due to small artery disease of 17.4 (95% CI 6.8-44.3). Homocysteine in the acute phase of stroke was not associated with stroke severity or outcome. Elevated plasma homocysteine in the acute phase of stroke was associated with both ischaemic and haemorrhagic stroke. Higher levels are associated with higher risk of small artery disease subtype of stroke.

Assessment of acute spontaneous intracerebral hematoma by CT perfusion imaging.

A single-section deconvolution-derived computerized tomographic perfusion imaging was performed in 45 patients (22 male and 23 female; mean age=69.89+/-10.07 years) with acute supratentorial spontaneous intracerebral hemorrhage. Mean rCBF and rCBV were lower in the hemorrhagic core than in the perihematomal low density area (p<0.001), and in the perihematomal low density area than in normal appearing brain parenchyma (p<0.001). Mean rMTT values were higher in perihematomal low density area than in normal appearing area (p<0.01) and in both hemorrhagic and perihematomal area than in controlateral ROI (p<0.001). There were no differences in rMTT mean values between hemorrhagic core and perihematomal area, as well as between normal appearing and controlateral areas. We found a concentric distribution of all CT perfusion parameters characterized by an improvement from the core to the periphery, with low perihematomal rCBF and rCBV values suggesting edema formation.

Incidence of myasthenia gravis in the province of Ferrara: a community-based study.

BACKGROUND: The reported annual incidence of myasthenia gravis (MG) ranges from 0.25 to 15 per million. The sex- and age-related pattern of disease incidence is still debated. METHODS: An intensive descriptive study was performed in the province of Ferrara (mean population 360,950 people) over the period 1985 through 2000. RESULTS: The average crude annual incidence rate was 2 per 100,000. We confirm a female preponderance in the total population, particularly in the youngest age groups. CONCLUSIONS: We observed an early increase in incidence in females, partly due to thymoma-associated MG, while MG without thymoma showed increasing incidence with age nonsignificantly different in the two sexes.

Posatirelin for the treatment of late-onset Alzheimer's disease: a double-blind multicentre study vs citicoline and ascorbic acid.

INTRODUCTION: Posatirelin (L-pyro-2-aminoadipyl-L-leucil-L-prolinamide) a new synthetic tripeptide with cholinergic, catecholaminergic and neurotrophic properties, was investigated in the treatment of Alzheimer's disease. MATERIAL AND METHODS: A multicentre, double-blind study vs citicoline (reference drug) and ascorbic acid (inactive drug) was carried out in elderly patients suffering from late-onset Alzheimer's disease. The once daily intramuscular treatment lasted for three months followed by one-month oral treatment with a placebo. Subscales and factors of GBS (Gottfries-Bråne-Steen) Rating Scale were identified as primary measures for efficacy assessment. RESULTS: At the end of the treatment, GBS subscale and factor scores assessing intellectual and emotional impairments, orientation and memory, ability to perform activities of daily living, depression-anxiety, attention and motivation were improved in the postatirelin group, showing significant differences with respect to the citicoline and/or ascorbic acid groups. Tolerability was good in all groups. CONCLUSIONS: The improvement in the GBS Rating Scale score observed in the posatirelin group is clinically relevant. It is worth verifying the drug-induced functional improvements, in further studies with large samples.

Effect of age on gastric acid, pepsin, pepsinogen group A and gastrin secretion in peptic ulcer patients.

To verify the effect of age on gastric secretions in gastric (GU) and duodenal ulcer (DU) patients, we carried out a retrospective study evaluating basal and stimulated gastric acid secretion in 427 peptic ulcer subjects aged between 12 and 73 years (GU = 74, DU = 353) in addition to studying gastric juice pepsin, serum pepsinogen group A (PGA) and gastrin in 175 patients (GU = 28, DU = 147). All subjects were then divided into groups according to their sex and age (< 30, 30-39, 40-49, 50-59 and > 60 years). Basal, maximal and peak acid outputs (BAO, MAO, PAO) were unchanged in the various age groups, though MAO and PAO were higher in males than females and in DU than in those with GU, even in the elderly (> 60 years). Pepsin and gastrin levels were unchanged at the various ages in GU and DU, while PGA was higher in males with DU aged 50 or over. This demonstrates that acid, pepsin and gastrin secretions do not change with age in ulcer patients. Acid secretion retains its typical distribution according to pathology (DU > GU) and sex (males > females), and also appears to have a fundamental pathogenetic role in peptic ulcer in the elderly.