A phase II multicenter study of two different dosages of pemetrexed given in combination with cyclophosphamide as first-line treatment in patients with locally advanced or metastatic breast cancer

Pemetrexed/cyclophosphamide was evaluated as first-line treatment for patients with locally advanced/metastatic breast cancer. In this randomized phase II study (NCT00190671), therapy consisted of either 600 mg/m(2) (P600) or 1,800 mg/m(2) (P1800) pemetrexed, followed by 600 mg/m(2) cyclophosphamide, every 21 days; 103 females (42 P600; 61 P1800) were enrolled. P600 was discontinued, as response rate (19.1%) was lower than targeted. In the P1800 arm, 20 patients had partial response (32.8%; 95% CI: 21.0-44.6) and 26 (42.6%) had stable disease. Median progression-free survival was 6.3 months (range: 0.3-31.1). P1800 plus cyclophosphamide 600 represents a regimen of reasonable efficacy and acceptable tolerability.     

Experience of young women diagnosed with breast cancer who undergo fertility preservation consultation

BackgroundFertility preservation (FP) is of increasing concern to young patients with breast cancer. The American Society of Clinical Oncology has recommended referral to a reproductive specialist as early as possible before beginning systemic adjuvant therapy.AimTo gather information from young patients with breast cancer about their experiences with FP referral, consultation, and decision making.MethodsAn anonymous questionnaire was mailed to consecutive patients with breast cancer who were referred, from January 2005 to January 2010, from our center to the CReATe fertility clinic. Topics included demographics; cancer stage and treatment; previous fertility problems; referral source and timing; options presented and chosen; and satisfaction with the referral, consultation, and decision-making processes.ResultsOf the 53 women identified, 27 (51%) participated. The mean age was 31 years (range, 24-41 years). Fifteen (56%) women opted for embryo or oocyte cryopreservation, 2 for ovarian suppression, and 10 for no FP. The choice was not affected by disease stage or by already having a child. Of the 22 women who responded, 14 (64%) were satisfied or very satisfied overall. Eighteen out of 23 (78%) respondents felt that the right amount of information was given. Thirty-nine percent had difficulty with decision making, but only 1 (4%) woman indicated that cost was a deciding factor. A common theme among respondents was inadequate time for decision making. A common complaint was the lack of written material before and/or after their consultation. Sixty-three percent expressed an interest in meeting with a psychosocial counselor.Conclusions(1) FP referral should be initiated by the surgeon as soon as a diagnosis of invasive cancer is made, (2) women need written materials before and after FP consultation is needed, and (3) a FP counselor who is able to spend additional time after the consultation could help with decision making.     

Wool Keratin Hydrolysates for Bioactive Additives Preparation

The aim of this paper was to select keratin hydrolysate with bioactive properties by using the enzymatic hydrolysis of wool. Different proteolytic enzymes such as Protamex, Esperase, and Valkerase were used to break keratin molecules in light of bioactive additive preparation. The enzymatic keratin hydrolysates were assessed in terms of the physico-chemical characteristics related to the content of dry substance, total nitrogen, keratin, ash, cysteic sulphur, and cysteine. The influence of enzymatic hydrolysis on molecular weight and amino acid composition was determined by gel permeation chromatography (GPC) and gas chromatography-mass spectrometry (GC-MS) analyses. Antimicrobial activity of keratin hydrolysates was analysed against Fusarium spp., a pathogenic fungus that can decrease the quality of plants. The bioactivity of enzymatic hydrolysates was tested on maize plants and allowed us to select the keratin hydrolysates processed with the Esperase and Valkerase enzymes. The ratio of organised structures of hydrolysate peptides was analysed by attenuated total reflectance-Fourier transform infrared (ATR-FTIR) deconvolution of the amide I band and may explain the difference in their bioactive behaviour. The most important modifications in the ATR spectra of maize leaves in correlation with the experimentally proven performance on maize development by plant length and chlorophyll index quantification were detailed. The potential of enzymatic hydrolysis to design additives with different bioactivity was shown in the case of plant growth stimulation.     

Cerebral lesions of multiple sclerosis: is gadolinium always irreplaceable in assessing lesion activity?

PURPOSE

We aimed to identify imaging characteristics on conventional magnetic resonance imaging that could predict multiple sclerosis (MS) brain lesion activity without contrast media administration.

MATERIALS AND METHODS

Magnetic resonance data sets of forty-two patients with relapsing-remitting MS who presented symptoms or signs suggestive of new disease activity were retrospectively reviewed. We classified the MS lesions into three types according to different patterns present on T2-weighted images and evaluated their relationship with the contrast uptake. Evolving aspects of each type of lesion were observed in 18 patients during a follow-up period ranging from nine to 36 months.

RESULTS

On T2-weighted images, only the pattern consisting of a thin border of decreased intensity compared with the lesion’s center and perifocal edema (Type II) reached diagnostic accuracy in terms of its relationship with gadolinium enhancement (P = 0.006). The sensitivity was 0.461, and the specificity was 0.698. In contrast, enhancement was not significantly related to the pattern consisting of a lesion center that was homogeneously brighter than its periphery (Type I) or less-hyperintense T2 focal lesions with either homogeneous or inhomogeneous center (Type III) (P > 0.05 for both).

CONCLUSION

The assessment of MS lesion activity should include a careful evaluation of T2-weighted images in addition to contrast enhancement assessment. The presence of an accompanying peripheral thin rim of hypointensity on T2-weighted images related best with contrast enhancement and subsequent lesion activity and may represent an additional pattern for disease activity assessment when gadolinium examination is contraindicated or influenced by prior therapy.Multiple sclerosis (MS) is a chronic inflammatory disease characterized by demyelination and widespread tissue damage in the white and grey matter in the central nervous system (CNS) and spinal cord (1). MS has a very heterogeneous neurological presentation. In diagnosing MS, magnetic resonance imaging (MRI) studies with and without gadolinium contrast are required, according to McDonald 2005 (2) and the modified McDonald criteria 2010 (3), to provide information about the CNS involvement of demyelinating lesions. A decreased incidence of clinical relapse in MS is commonly used as a measure of therapeutic intervention efficacy. Despite their generalized use in clinical trials of relapsing-remitting and progressive multiple sclerosis, the current MRI measures add little if anything to the clinically relevant relapse and disability outcomes when used independently (4). At the present time, there is limited association between the lesions detected with conventional MRI and clinical status (5), with a low reported sensitivity to diffuse grey-matter and white matter disease (6, 7). Therefore, there is a sustained need for research to find better MRI markers of disease activity.It is generally believed that because acute MS lesions are associated with a transient breakdown of the blood-brain barrier (BBB), gadolinium contrast agents would produce enhancement of these lesions on T1-weighted images. Beginning with the earliest magnetic resonance studies of MS, it became clear that the correlation between enhanced lesions and clinical disease activity is modest at best (8). Nevertheless, contrast enhancement remains a sensitive method for detecting active MS lesions, with all the implications derived from its presence (from diagnosis to treatment trial monitoring). However, there are conditions under which the administration of gadolinium-based agents is prohibited (9). Additionally, contrast administration cannot help document disease activity following steroid treatment when variable degrees of enhancing lesions suppression occurs (10).Still, is the information offered by the administration of contrast really irreplaceable? Certainly, a less invasive and more cost-effective method is needed in clinical practice to assess MS lesion activity. Ideally, this assessment method would also work for patients in whom gadolinium agents cannot be used or are influenced by medication. Furthermore, the confidence intervals for correlations between contrast-enhanced lesions and MS relapses exclude the possibility that contrast enhanced lesions can be a good surrogate outcome for the occurrence MS relapses (11). Furthermore, when studies centered their analysis on the morphological characteristics of the conventional MRI lesions of MS (rim lesions and ring enhancement) and the patients’ clinical characteristics (12), only ring-enhancing lesions seemed to be associated with a worse prognosis.Therefore, the present study aimed to identify imaging characteristics that could predict lesion activity without the administration of contrast media by analyzing the morphology and signal patterns of brain MS lesions on T2-weighted images that are present in all routine MRI protocols for MS surveillance and correlating these results with the findings obtained from contrast-enhanced T1-weighted images.     

The changing epidemic of pediatric hiv infection in romania

PURPOSE: By the late 1980s, over 100,000 infants and children were living in public institutions in Romania. It was not uncommon for children in these facilities to receive one or more 'micro-transfusions' of blood, unscreened for HIV, as therapy for anemia or malnutrition. To assess the impact of pediatric HIV infection in Romania, the European country with the most pediatric cases, cross-sectional and cohort studies were implemented in Constanta (the epi-center of pediatric HIV in Romania) in April 1999.METHODS: Demographic, clinical and social data are collected once for all cross-sectional subjects. Similar data are collected every 11-13 months for subjects in the cohort. The cross-sectional study population was defined as all living HIV-infected infants and children, 0-18 years, known to the investigators from April to September 1999. The cohort consists of subjects diagnosed with HIV between 1995 and 1999.RESULTS: Enrolled are 791 subjects, of which 357 are in the cohort study. The majority (83%) are Romanian, vs Gypsy or Turkish/Hun and their mean age is 11 years (SD = 1.3). Biologic parents are the primary caretakers of 77% and 86% attend school. Mode of transmission was perinatal for 8%; blood transfusion/parental therapy modes account for 89% of the transmission and the presumed timing was between 1-12 months of age. Mean age at HIV confirmation was 5 years (SD = 3.2). AIDS has been diagnosed in 40% and 52% are receiving antiretroviral therapy.CONCLUSIONS: The Romanian pediatric HIV epidemic differs vastly from that in the US. Fewer children are with their biologic parent(s) and attending school. Early diagnosis of infection is rare, as therapy did not become available until the late 1990's. Perinatal transmission is increasing, however, which supports the need for HIV education and intervention in Eastern Europe.     

Effect of Intensive Compared With Standard Glycemia Treatment Strategies on Mortality by Baseline Subgroup Characteristics: The Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial

OBJECTIVE

To determine if baseline subgroups in the Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial can be identified for whom intensive compared with standard glycemia treatment had different effects on all-cause mortality.

RESEARCH DESIGN AND METHODS

Exploratory post hoc intention-to-treat comparisons were made between intensive and standard glycemia groups on all-cause mortality by subgroups defined by baseline characteristics.

RESULTS

There were few significant interactions between baseline characteristics and effects of intensive versus standard glycemia treatment on mortality: self-reported history of neuropathy (hazard ratio [HR] 1.95, 95% CI 1.41–2.69) versus no history of neuropathy (0.99, 0.79–1.26; P value for interaction 0.0008), higher A1C (A1C >8.5%: HR 1.64, 95% CI 1.22–2.22; A1C 7.5–8.4%: 1.00, 0.75–1.34; A1C <7.5%: 1.00, 0.67–1.50; P value for interaction 0.04), and aspirin use (HR 1.45, 95% CI 1.13–1.85, compared with 0.96, 0.72–1.27, in nonusers; P value for interaction 0.03).

CONCLUSIONS

We found a remarkable similarity of effect from intensive compared with standard glycemia treatment on mortality across most baseline subgroups. No differential effect was found in subgroups defined by variables anticipated to have an interaction: age, duration of diabetes, and previous history of cardiovascular disease. The three baseline characteristics that defined subgroups for which there was a differential effect on mortality may help identify patients with type 2 diabetes at higher risk of mortality from intensive regimens for glycemic control. Further research is warranted.Numerous epidemiological studies have demonstrated a relationship between elevated A1C and a greater risk of cardiovascular (CVD) events and mortality in type 2 diabetes (1–3). Therefore, it has been hypothesized that a reduction to near-normal levels of A1C in patients with type 2 diabetes would reduce the risk of these adverse outcomes. Three large randomized controlled clinical trials testing this hypothesis in individuals with longstanding type 2 diabetes reported their main results in the past 2 years (4–6).The Data Safety Monitoring Board of the Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial discontinued the intensive glycemia arm because of an increase in all-cause mortality in the intensive glycemia arm compared with the standard glycemia arm. The finding of excess mortality in the intensive arm of the ACCORD trial has led to controversy about implementation of intensive glucose control in patients with type 2 diabetes (7,8). Adding to the controversy were results of the Action in Diabetes and Vascular Disease: Preterax and Diamicron MR Controlled Evaluation (ADVANCE) and Veterans Affairs Diabetes Trial (VADT), demonstrating that although there was no significant reduction in the primary end point of CVD events, there was no increase in mortality with the intensive glycemia arm compared with the standard glycemia arm (4,6), which has raised questions about reasons for these discrepancies (9–12).A critical question relates to the applicability and generalizability of the conclusions of the ACCORD trial to the broader population or to specific subgroups of patients with type 2 diabetes. Indeed, prespecified subgroup analyses in ACCORD did suggest a significant benefit of intensive glycemic control on CVD events in those participants with lower A1C at entry or absence of CVD event by history, but there was no suggestion of a differential effect on mortality (5). However, these observations are based on only a few subgroup analyses at the time of the primary publication. The effect on mortality of intensive compared with standard glycemia treatment may have been modified by other possible characteristics of patients at entry. We have therefore carried out exploratory post hoc analyses of the effects of intensive compared with standard glycemia treatment in ACCORD participants categorized by various baseline characteristics on all-cause mortality at the time of discontinuation of the intensive glycemia treatment of ACCORD, with the goal to determine if particular subgroups at higher or lower risk from the intensive intervention can be identified.     

Ocular migraine and antiphospholipid antibodies--where we stand?

There is no doubt that ocular migraine also known as retinal migraine or ophthalmic migraine should not to be confused with ophthalmoplegic migraine. The hallmark of ocular migraine is the unilateral visual loss or "monocular transient loss of vision" associated or followed by the headache. Better safe than sorry, therefore an ophthalmologic examination during the migraine attack is the most diagnostic method. age with typical history for ocular migraine. Importantly supportive data sustain that different neuro-ophthalmologic manifestations as amaurosis fugax, retinal vascular thrombosis and optic neuropathy, may be considered as the ocular hallmarks of the Hughes's syndrome. Clues for the evaluating of antiphospholipid antibodies include recurrent thrombosis especially in young people, recurrent fetal loss, and thrombocytopenia. There are no studies that focus exclusively on the prophylaxis of ocular migraine. Ocular features due to antiphospholipid antibodies - induced thrombosis or Hughes's syndrome should be treated with anticoagulant therapy.     

Expression of β1 adrenergic receptor in vascular anomalies in children

ObjectiveControversial, heterogeneous, and inconsistent responses to beta-blockers have been reported in some cases of infantile proliferative hemangiomas. On the basis of these clinical observations, we aimed to examine the β1 adrenergic receptor (β1-AR) protein expression distribution among different types of pediatric vascular anomalies.MethodsImmunohistochemistry (IHC) was performed for β1-AR on 43 surgical specimens.ResultsWe found positive β1-AR IHC staining in all intramuscular hemangiomas, capillary–lymphatic, lymphatic, venous, and combined malformations, and Masson’s tumor cases, as well as in 7 of 10 cases of proliferative infantile hemangiomas.ConclusionsOur research demonstrates, for the first time, the degree of heterogeneous expression of β1-AR among pediatric vascular malformations. Our results support the need for β1-AR assessment in pediatric vascular anomalies to select cases with a robust response to β1-selective blockers. β1-AR assessment may have a strong impact on therapeutic refinement for pediatric vascular anomalies by selecting cases with a stronger response to beta-blockers.