MOZ/TIF2-induced acute myeloid leukaemia in transgenic fish

The inv(8)(p11q13) chromosomal abnormality, described in acute myeloid leukaemias (AML), fuses the histone acetyl-transferase (HAT) MYST3 (MOZ) gene with another HAT gene, NCOA2 (TIF2). We generated a transgenic zebrafish in which the MYST3/NCOA2 fusion gene was expressed under control of the spi1 promoter. An AML developed in 2 of 180 MYST3/NCOA2-EGFP-expressing embryos, 14 and 26 months after injection of the fusion gene in a one-cell embryo, respectively. This leukaemia was characterised by an extensive invasion of kidneys by myeloid blast cells. This model, which is the first zebrafish model of AML, demonstrates the oncogenic potency of MYST3/NCOA2 fusion gene.     

CD20‐positive plasmablastic lymphoma with excellent response to bortezomib combined with rituximab

As a distinct type of aggressive mature large B‐cell lymphoma, plasmablastic lymphoma (PBL) poses diagnostic and treatment challenges. PBL is distinguished from other B‐cell lymphomas by the presence of plasmacytic differentiation markers such as CD38, CD138, and MUM1. Clinically, PBLs from oral and extra‐oral sites are rapidly progressive tumors with frequent relapse after treatment with standard diffuse large B‐cell lymphoma regimens. Here, we report a near‐complete response of one patient with relapsed PBL following treatment with a non‐cytotoxic regimen containing bortezomib, rituximab, and dexamethasone.     

Early decline in cancer antigen 125 as a surrogate for progression-free survival in recurrent ovarian cancer

We used data from 886 patients from the CAELYX in Platinum Sensitive Ovarian Patients (CALYPSO) trial, recruited between April 2005 and September 2007, to examine the role of early decline in cancer antigen 125 (CA125) and early tumor response as prognostic factors and surrogates for superiority of treatment with carboplatin-pegylated liposomal doxorubicin (CPLD) compared with carboplatin-paclitaxel (CP) in a landmark analysis. Progression-free survival (PFS) was estimated by Kaplan-Meier analyses. We used univariate and multivariable Cox proportional hazards analyses to assess early decline and early response as surrogates for CPLD treatment benefit compared with CP. All statistical tests were two-sided. Early decline (defined as rate of CA125 decrease of at least 50% per month) was associated with improved PFS (adjusted hazard ratio [HR] for progression = 0.81, 95% confidence interval [CI] = 0.67 to 0.97, P = .02) but early response (complete or partial responses) was not. CPLD was associated with improved PFS compared with CP (HR = 0.82, 95% CI = 0.69 to 0.96, P = .01). However, fewer CPLD patients had an early decline (161 [37.4%] vs 233 [51.2%], P < .001) or an early response (146 [33.9%] vs 176 [38.7%], P = .14) compared with CP patients. The PFS for CPLD patients did not change statistically significantly after adjustment for early decline (adjusted HR = 0.80, 95% CI = 0.68 to 0.94, P = .007). These findings are opposite to what would be expected if these markers were good surrogates for treatment benefit.     

Clozapine-induced seizures: recognition and treatment.

OBJECTIVES: To inform clinicians about the types of seizures that can be induced by clozapine and to provide recommendations for treatment. METHODS: We identified articles on clozapine-induced seizures from a MEDLINE search of the English-language literature from 1978 to July 2006. The frequency of each type of seizure and the dosages of clozapine associated with seizures were compiled. In addition to this review, we report a new case illustrating the challenge of diagnosing subtle seizure activity. RESULTS: The tonic-clonic variety is the most frequently described clozapine-induced seizure. Myoclonic and atonic seizures together constitute about one-quarter of the reported seizures. The mean dosage of clozapine associated with seizures is not high (less than 600 mg daily). CONCLUSIONS: It may be difficult for clinicians to recognize subtle types of clozapine-induced seizures, such as myoclonic, atonic, or partial seizures. Clinicians should not place excessive reliance on the plasma level of clozapine or electroencephalogram findings to predict the occurrence of seizures. When a first seizure occurs, it is recommended that the dosage of clozapine be reduced or an alternative antipsychotic agent be employed. If a second seizure occurs, an anticonvulsant drug should be started. Special attention should be paid when commencing or discontinuing concurrent medication that may affect the plasma level of clozapine.     

Intralymphocyte magnesium decrease in patients with primary aldosteronism. Possible links with cardiac remodelling.

Our group have described a group of patients with primary aldosteronism which is characterized by significantly decreased intralymphocyte ionized magnesium concentration. Some models of experimental hyperaldosteronism are characterized by cardiovascular fibrosis but despite this fact the link between a negative magnesium balance and fibrosis is lacking. Consequently, to shed some light on the relationships between magnesium and tissue fibrosis we tested the in vitro effects of incubating human fibroblasts in low magnesium medium on mRNA collagen I and III gene expression by northern blot analysis. Both collagen I and III mRNA gene expression were increased by magnesium deprivation. The increase in collagen expression was similar for both collagen I and III. These data are in favour of a potential link between magnesium homeostasis and collagen synthesis. A physiopathologic mechanism linking magnesium homeostasis to the state of collagen turnover may have important clinical correlates such as cardiac remodelling in congestive heart failure.     

Sociodemographic,socioeconomic, and clinical determinants of survival in patients with cancer: A systematic review of the literature focused on the elderly

Studies on cancer survival have revealed disparities not only between the elderly and their younger counterparts, but also among the elderly themselves. The aim of this work was to identify sociodemographic, socioeconomic, clinical, and care-related determinants of survival or mortality in older patients with cancer by a systematic synthesis of the literature. Understanding these factors is of great value for guiding health policies and programs aimed at reducing cancer survival disparities.We conducted a search of MEDLINE and SCOPUS databases under PRISMA guidelines. Results were limited to articles published in English and French from 2005 to 2015, and focused on elderly patients with cancer. The article selection was performed in a stepwise fashion: title, abstract, and full-text selection. Studied determinants and results of each article were synthesized. Forty-five articles were eligible and included in the study. We observed different ways of measuring socioeconomic status, comorbidities, and treatment among studies. Cancer-specific and overall survival were the main studied outcomes. Advanced age, low income, low socioeconomic status, presence of comorbidities, advanced stage, and poor tumor grade were found to be associated with lower survival or higher mortality. On the other hand, female gender and being married were predictive of increased survival or lower mortality.The next logical step is to carry out studies on elderly patients from different countries and to incorporate pertinent factors in a unique model. Moreover, specific geriatric health impairments should be taken into account in further research because of their association with survival.