Clinical associations and prognostic value of MRI-visible perivascular spaces in patients with ischemic stroke or TIA: a pooled analysis

BACKGROUND AND OBJECTIVES: Visible perivascular spaces are an MRI marker of cerebral small vessel disease and might predict future stroke. However, results from existing studies vary. We aimed to clarify this through a large collaborative multicenter analysis. METHODS: We pooled individual patient data from a consortium of prospective cohort studies. Participants had recent ischemic stroke or transient ischemic attack (TIA), underwent baseline MRI, and were followed up for ischemic stroke and symptomatic intracranial hemorrhage (ICH). Perivascular spaces in the basal ganglia (BGPVS) and perivascular spaces in the centrum semiovale (CSOPVS) were rated locally using a validated visual scale. We investigated clinical and radiologic associations cross-sectionally using multinomial logistic regression and prospective associations with ischemic stroke and ICH using Cox regression. RESULTS: We included 7,778 participants (mean age 70.6 years; 42.7% female) from 16 studies, followed up for a median of 1.44 years. Eighty ICH and 424 ischemic strokes occurred. BGPVS were associated with increasing age, hypertension, previous ischemic stroke, previous ICH, lacunes, cerebral microbleeds, and white matter hyperintensities. CSOPVS showed consistently weaker associations. Prospectively, after adjusting for potential confounders including cerebral microbleeds, increasing BGPVS burden was independently associated with future ischemic stroke (versus 0-10 BGPVS, 11-20 BGPVS: HR 1.19, 95% CI 0.93-1.53; 21+ BGPVS: HR 1.50, 95% CI 1.10-2.06; = 0.040). Higher BGPVS burden was associated with increased ICH risk in univariable analysis, but not in adjusted analyses. CSOPVS were not significantly associated with either outcome. DISCUSSION: In patients with ischemic stroke or TIA, increasing BGPVS burden is associated with more severe cerebral small vessel disease and higher ischemic stroke risk. Neither BGPVS nor CSOPVS were independently associated with future ICH

Serum cardiolipin antibodies in cancer patients with thromboembolic events

This study was undertaken to investigate a possible association of anticardiolipin antibodies (ACLAs) in cancer patients with thromboembolic events. Twenty-five patients with solid tumors complicated with acute thrombosis, 36 cancer patients without any thrombotic events, and a group of 20 healthy volunteers without thrombosis or malignancy were included. The mean age of the cancer patients with and without thrombosis and healthy subjects were 50 years (range 20-75), 45 years (range 23-66), and 40 years (range 20-68), respectively Deep venous thrombosis (n = 16) and thrombosis of the central venous port-catheter systems (n = 9) were confirmed by Doppler sonography in all patients. Ige and IgM isotypes of ACLAs were: quantitated by enzyme-linked immunosorbent assay with normal levels of <23 GPL and <11 MPL, respectively. Mean values of IgG ACLAs were found similar in cancer patients with acute thrombosis (13.8 +/- 4.9 GPL), without thrombosis (12.8 +/- 5.4 GPL) or in healthy subjects (14.8 +/- 5.5 GPL). Although the mean values of IgM ACLAs were within normal limits in all groups, cancer patients with thrombotic events had higher levels of IgM ACLAs (mean = 10.5 +/- 2.2 MPL) than cancer patients without thrombosis (mean = 4.6 +/- 2.3 MPL) (p = .01). Healthy subjects also had lower levels of IgM ACLAs (mean = 7.1 +/- 3.2 MPL) than cancer patients with thrombosis (p = .16). In addition, a higher percentage of cancer patients with or without thrombosis had IgM and IgG ACLA levels above normal limits compared with healthy controls. In conclusion, our study suggests an association between ACLAs or Ige and particularly IgM isotypes and venous thrombosis in malignancy. Identification of cancer patients who are at higher risk for developing thromboembolic events might lead to a better selection of patients for prophylactic anticoagulant therapy

Development of co-dominant SCAR markers linked to resistant gene against the Fusarium oxysporum f. sp. radicis-lycopersici

PubMed ID: 26037087Key message: We developed highly reliable co-dominant SCAR markers linked to the Frl gene. FORL testing is difficult. The marker is expected to be quickly adapted for MAS by tomato breeders. Abstract: Fusarium oxysporum f. sp. radicis-lycopersici causes Fusarium crown and root rot (FCR), an economically important soil-borne disease of tomato. The resistance against FCR is conferred by a single dominant gene (Frl) located on chromosome 9. The aim of this study was to develop molecular markers linked to the Frl gene for use in marker-assisted breeding (MAS) programs. The FCR-resistant ‘Fla. 7781’ and susceptible ‘B560’ lines were crossed, and F1 was both selfed and backcrossed to ‘B560’ to generate segregating F2 and BC1 populations. The two conserved set II (COSII) markers were found linked to the Frl gene, one co-segregated with FCR resistance in both F2 and BC1 populations and the other was 8.5 cM away. Both COSII markers were converted into co-dominant SCAR markers. SCARFrl marker produced a 950 and a 1000 bp fragments for resistant and susceptible alleles, respectively. The linkage of SCARFrl marker was confirmed in BC2F3 populations developed by backcrossing the resistant ‘Fla. 7781’ to five different susceptible lines. The SCARFrl marker has been in use in the tomato breeding programs in BATEM, Antalya, Turkey, since 2012 and has proved highly reliable. The SCARFrl marker is expected to aid in the development of FCR-resistant lines via marker-assisted selection (MAS). © 2015, Springer-Verlag Berlin Heidelberg

Clinical significance of p95HER2 overexpression, PTEN loss and PI3K expression in p185HER2-positive metastatic breast cancer patients treated with trastuzumab-based therapies

BACKGROUND: Overexpression of p185HER2 is an established poor prognostic factor in breast cancer, portending an aggressive course and potential for early metastasis. On the other hand, monoclonal antibody trastuzumab is widely used in the clinic to target this overexpressed oncogene. Unfortunately, ∼30–40% of all patients overexpressing HER2 respond to trastuzumab, warranting further research regarding the structure and additional modulation of the receptor. In this study, we aimed to investigate the response to trastuzumab in terms of the potential roles of several oncogenic pathways (phosphatase and tensin homologue (PTEN) and phosphatidylinositol 3-kinase (PI3K)) and a truncated receptor protein, p95HER2, retrospectively. MATERIALS AND METHODS: Paraffin-embedded primary tumour tissues of 100 HER2-positive metastatic breast cancer patients who received trastuzumab with combination cytotoxic chemotherapy were analysed with immunohistochemical method for p95HER2, p85 (PI3K) and PTEN. Relationship between variables were tested via χ(2), Fischer's exact test and Mann–Whitney U tests, wherever appropriate. Progression-free survival (PFS) and overall survival (OS) periods were calculated with Kaplan–Meier method and survival curves of subgroups were compared with log-rank test. RESULTS: Percentage of patients was found to be 33%, 57% and 42% positive for p95 expression, PTEN and PI3K, respectively. p95-expressing tumours had statistically lower response rates for trastuzumab than tumours not expressing p95 (P=0.001). On the contrary, PTEN-expressing tumours had statistically higher response rates for trastuzumab than tumours not expressing PTEN (P=0.012). PI3K expression had no significant effect on trastuzumab response. Median PFS for p95-expressing and not expressing tumours were 8 months (95% CI, 2.5–13.4 months) and 22 months (95% CI, 9.9–34 months), respectively (P=0.0001). Median PFS for PTEN-expressing and not expressing tumours were 15.3 months (95% CI, 12.6–34 months) and 12.1 months (95% CI, 7.9–16.2 months), respectively (P=0.04). Median OS for p95-expressing and not expressing tumours were 24 months (95% CI, 8.3–40.4 months) and 29.1 months (95% CI, 8.6–43.2 months), respectively (P=0.045). Median OS for PTEN-expressing and not expressing tumours were 25.1 months (95% CI, 7.5–40.1 months) and 26.8 months (95% CI, 8.1–42 months), respectively, which was not statistically significant (P=0.5). Level of PI3K expression had no effect on PFS and OS in our patient population. Presence of visceral metastases HR=2.38 ((95% CI, 1.2–4.5), P=0.009), p95 expression HR=2.1 ((95% CI, 1.1–3.7), P=0.03) and response to trastuzumab HR=2.2 ((95% CI, 1.18–4.47), P=0.014) are identified as factors independently affecting PFS. Response to trastuzumab HR=1.7 ((95% CI, 1.14–3.47), P=0.013) was identified as the single parameter influencing survival by Cox regression analysis. CONCLUSIONS: Presence of p95 predicted a poorer response to trastuzumab treatment, shorter PFS and OS in our HER2-positive metastatic breast cancer cohort. In addition, loss of PTEN predicted a poorer response to trastuzumab treatment and shorter PFS but not OS. We could not find an effect of PI3K expression on the above-mentioned parameters

The effect of breastfeeding on spontan resolution of monosymptomatic enuresis

Aykac, Aykut/0000-0001-7078-0135WOS: 000380066200022PubMed: 27286120Purpose: The aim of this study was to examine whether the duration of breastfeeding during infancy was associated with the time of spontaneous resolution of monosymptomatic enuresis (SRME). Materials and Methods: A total of 1500 people were surveyed at four centers. One hundred and eighty-one people with a history of monosymptomatic enuresis (ME) who received no treatment and had no day time symptoms were included in the study. The relationship between the duration of breastfeeding and SRME was assessed by considering the duration of breastfeeding as both continuous and categorical (cut-off value 5 months) variable. The multivariate general linear model was used to identify independent predictors such as gender, family history, and educational status of parents. Results: Pearson correlation analysis of the age of SRME and duration of breastfeeding found no statistically significant relationship. However, there was a significant difference in the age of SRME of those who were breastfed for 5 months or less compared to those who were breastfed for more than 5 months. According to the multivariate analysis, gender and educational status of parents were not effective on the age of SRME. Stepwise linear regression model showed that breastfeeding for five months or less and family history could affect the age of SRME. The regression formula was: age of SRME= 9.599 + (3.807xfive months or less of breastfeeding) + (1.258xpositive family history). Conclusions: It was found that when breastfeeding lasted for more than 5 months, there was a positive contribution to SRME