ICM Partners

About: ICM Partners is a based out in . It is known for research contribution in the topics: Population & Breast cancer. The organization has 1311 authors who have published 1521 publications receiving 33745 citations. The organization is also known as: International Creative Management Partners.

Patterns of response and relapse in primary CNS lymphomas after first-line chemotherapy: imaging analysis of the ANOCEF-GOELAMS prospective randomized trial

Abstract: Background Our aim was to review MRI characteristics of patients with primary CNS lymphoma (PCNSL) enrolled in a randomized phase II trial and to evaluate their potential prognostic value and patterns of relapse, including T2 fluid attenuated inversion recovery (FLAIR) MRI abnormalities. Methods Neuroimaging findings in 85 patients with PCNSL enrolled in a prospective trial were reviewed blinded to outcomes. MRI characteristics and responses according to International PCNSL Collaborative Group (IPCG) criteria were correlated with progression-free survival (PFS) and overall survival (OS). Results Multivariate analysis showed that objective response at 2 months (P 11.4 cm3) enhancing tumor volume (P = .006) were associated with poor OS and PFS, respectively. Ratio of change in product of largest diameters at early MRI evaluation but not timing of complete response achievement (early vs delayed) was prognostic for OS. Sixty-nine patients relapsed. Relapse in the brain (n = 52) involved an initial enhancing site, a different site, or both in 46%, 40%, and 14% of patients, respectively. At baseline, non-enhancing T2-FLAIR hypersignal lesions distant from the enhancing tumor site were detected in 18 patients. These lesions markedly decreased (>50%) in 16 patients after chemotherapy, supporting their neoplastic nature. Of these patients, 10/18 relapsed, half (n = 5) in the initially non-enhancing T2-FLAIR lesions. Conclusions Baseline tumor size and infratentorial localization are of prognostic value in PCNSL. Our findings provide evidence that non-enhancing FLAIR abnormalities may add to overall tumor burden, suggesting that response criteria should be refined to incorporate evaluation of T2-weighted/FLAIR sequences.

Spinal cord multi‐parametric magnetic resonance imaging for survival prediction in amyotrophic lateral sclerosis

Abstract: Background: Assessing survival is a critical issue in patients with Amyotrophic Lateral Sclerosis (ALS). Neuroimaging seems to be promising in the assessment of disease severity and several studies also suggest a strong relationship between spinal cord (SC) atrophy described by MRI and disease progression. Aim of the study was than to determine the predictive added value of multimodal SC MRI on survival. Methods: 49 ALS patients were recruited and clinical data collected. Patients were scored on ALSFRS-R and manual muscle testing. They were followed longitudinally to assess survival. Cervical spinal cord was imaged using 3T MRI system. Cord volume and cross-sectional area (CSA) at each vertebral level were computed. DTI metrics were measured. Imaging metrics and clinical variables were used as inputs for a multivariate Cox regression survival model. Results: When building a multivariate Cox regression model with clinical and MRI parameters, FA, MTR, and CSA at C2-C3, C4-C5, C5-C6 and C6-C7 vertebral levels were significant. Moreover, hazard ratio (HR) calculated for CSA at C3-C4 and C5-C6 levels indicated an increased risk for patients with SC atrophy (respectively 0.66 and 0.68). In our cohort, MRI parameters seem to be more predictive than clinical variables, which had HR very close to 1. Conclusions: We suggest that multimodal SC MRI could be a useful tool in survival prediction especially if used at the beginning of the disease and when combined with clinical variables. To validate it as a biomarker, results confirmation in independent bigger cohorts of patients is warranted.

A recurrent point mutation in PRKCA is a hallmark of chordoid gliomas

Abstract: Chordoid glioma (ChG) is a characteristic, slow growing, and well-circumscribed diencephalic tumor, whose mutational landscape is unknown. Here we report the analysis of 16 ChG by whole-exome and RNA-sequencing. We found that 15 ChG harbor the same PRKCA$^{D463H}$ mutation. PRKCA encodes the Protein kinase C (PKC) isozyme alpha (PKC$\alpha$) and is mutated in a wide range of human cancers. However the hot spot PRKCA$^{D463H}$ mutation was not described in other tumors. PRKCA$^{D463H}$ is strongly associated with the activation of protein translation initiation (EIF2) pathway. PKC$\alpha$$^{D463H}$ mRNA levels are more abundant than wild-type PKC$\alpha$ transcripts, whilePKC$\alpha$$^{D463H}$ is less stable than the PCK$\alpha$WT protein. Compared to PCK$\alpha$WT, the PKC$\alpha$$^{D463H}$ protein is depleted from the cell membrane. The PKC$\alpha$$^{D463H}$ mutant enhances proliferation of astrocytes and tanycytes, the cells of origin of ChG. In conclusion, our study identifies the hallmark mutation for chordoid gliomas and provides mechanistic insights on ChG oncogenesis.

Recombinant factor VIIa in the management of postpartum bleeds: an audit of clinical use.

Abstract: Background. This paper presents an analysis of 25 patient cases in which recombinant factor VIIa was used in the management of postpartum hemorrhage, including severe and/or life-threatening bleeds. Anecdotal experiences in the empirical use of this agent are described and dosing regimens, effects on bleeding, and safety data are presented.Methods. Data were extracted from the international, internet-based, voluntary registry, haemostasis.com. Search results were manually cross-checked against monthly summary reports and cases of confirmed postpartum hemorrhage were analyzed by the authors. Case providers were contacted individually to approve the use of their cases, supply any missing data, and validate the data already held.Results. Of 43 reported gynecological admissions for hemorrhage, 13 were excluded as they did not relate to childbirth, and 5 due to insufficient data. The remaining 25 records, all associated with postpartum hemorrhage, were submitted by 14 doctors from 5 countries. Following admini...