Safety and Effect of Bariatric Metabolic Surgeries for Psychiatric Patients with Obesity: A Retrospective Matched Case-control Trial.

INTRODUCTION: Patients living with psychiatric illnesses (PIs) have a high prevalence of obesity. In a 2006 survey, 91.2% of professionals in the bariatric field identified "psychiatric issues" as clear contraindications to weight-loss surgery. METHODS: This retrospective matched case-control study investigated the impact, safety, and possible relapse after bariatric metabolic surgery (BMS) in patients with PIs. Also, we tested the incidence of patients who developed PI after BMS and compared the post-procedural weight loss with that in a matched control group without PIs. The cases were matched in a ratio of 1:4 to the control patients standardized for age, sex, preoperative BMI, and type of BMS. RESULTS: Of 5987 patients, 2.82% had a preoperative PI; postoperative de novo PI was present in 0.45%. Postoperative BMI was significantly different between the groups when compared to preoperative BMI (p < 0.001). Percentage of total weight loss (%TWL) after six months was not significantly different between the case (24.6% ± 8.9) and control groups (24.0% ± 8.4, p = 1.000). Early and late complications were not significantly different between the groups. The psychiatric drug use and dosage changes did not differ significantly pre- and postoperatively. Of the psychiatric patients, 5.1% were postoperatively admitted to a psychiatric hospital (p = 0.06) unrelated to BMS, and 3.4% had a prolonged absence from work after surgery. CONCLUSION: BMS is an effective weight loss treatment and a safe procedure for patients with psychiatric disorders. We found no change in the patients' psychiatric status outside the usual disease course. Postoperative de novo PI was rare in the present study. Furthermore, patients with severe psychiatric illness were excluded from undergoing surgery and, therefore, from the study. Careful follow-up is necessary to guide and protect patients with PI.

C/EBPγ deregulation results in differentiation arrest in acute myeloid leukemia.

C/EBPs are a family of transcription factors that regulate growth control and differentiation of various tissues. We found that C/EBPγ is highly upregulated in a subset of acute myeloid leukemia (AML) samples characterized by C/EBPα hypermethylation/silencing. Similarly, C/EBPγ was upregulated in murine hematopoietic stem/progenitor cells lacking C/EBPα, as C/EBPα mediates C/EBPγ suppression. Studies in myeloid cells demonstrated that CEBPG overexpression blocked neutrophilic differentiation. Further, downregulation of Cebpg in murine Cebpa-deficient stem/progenitor cells or in human CEBPA-silenced AML samples restored granulocytic differentiation. In addition, treatment of these leukemias with demethylating agents restored the C/EBPα-C/EBPγ balance and upregulated the expression of myeloid differentiation markers. Our results indicate that C/EBPγ mediates the myeloid differentiation arrest induced by C/EBPα deficiency and that targeting the C/EBPα-C/EBPγ axis rescues neutrophilic differentiation in this unique subset of AMLs.

The expression of the peripheral cannabinoid receptor CB2 has no effect on clinical outcome in diffuse large B-cell lymphomas.

BACKGROUND: The peripheral cannabinoid receptor (CB2) is mainly detected on B cells in the germinal centers (GCs) of the immune system, using an antibody directed against the extra cellular N-terminal domain of the receptor. We retrospectively investigated the CB2 receptor expression in diffuse large B-cell lymphomas (DLBCL) and its clinical relevance for treatment outcome. PATIENTS AND METHODS: We have constructed a tissue micro-array (TMA) using lymphoma tissue of a large cohort of patients with DLBCL (N = 104) who were treated with CHOP. RESULTS: Forty-five out of 79 evaluable cases (57%) were CB2 positive. The expression of CB2 receptors was variably present in both the germinal center B cell (GCB) (n = 31) and the non-GCB/activated B-cell (ABC) (n = 43) DLBCL subtypes. CB2 positivity was not associated with a different outcome in this patient cohort (CR; P = 0.87, EFS; P = 0.32, DFS; P = 0.06 and OS; P = 0.18). Implementation of CB2 expression in the Hans algorithm using the markers CD10, BCL6, and MUM1 did not result in added prognostic value (all P-values >0.1). CONCLUSIONS: We hypothesize that although CB2 is normally expressed in GCs, the expression in one of the malignant counterparts such as DLBCL is aberrant. This may be an explanation for the absence of prognostic relevance for the expression of this protein.

Prognostic relevance of immunohistochemical subclassification of diffuse large B-cell lymphoma in two prospective phase III clinical trials.

PURPOSE: Until now molecular biologic techniques have not been easily used in daily clinical practice to stratify patients for therapeutic purposes. Therefore, we have investigated the prognostic relevance of the immunohistochemical (IHC) germinal center B-cell (GCB) versus non-GCB diffuse large B-cell lymphoma (DLBCL) subtypes. PATIENTS AND METHODS: We have analyzed tumor samples from patients treated in 2 prospective multicenter phase III trials, ie HOVON 25 (patients≥65 years, n=153) and HOVON 26 (patients<65 years, n=144) using whole sections (WS) or tissue microarray (TMA). CD10, BCL6, and MUM1 were applied in a specific IHC algorithm. The effect on clinical outcome using WS or TMA and variations in cut-off levels of these markers was also investigated. RESULTS: The GCB subtype was not associated with a better OS in either trial. Small differences were observed in the HOVON 25 trial between techniques, with TMA showing a better outcome for GCB than did WS. Variation of cut-off levels in the specific algorithm did not improve the prediction of clinical outcome. CONCLUSION: We did not observe a consistent predictive power of the GCB and non-GCB classification by IHC in this large series of DLBCL patients treated with CHOP. This underscores the need to determine the biologic variation and the standardization of the protein expression levels and to further study the relevance of prognostic IHC classifications, preferably in phase III clinical trials.

Gene expression profiling for improved dissection of acute leukemia: a recently identified immature myeloid/T-lymphoid subgroup as an example.

In this concise overview, we discuss recent findings concerning a distinct subgroup of acute myeloid/T-lymphoid leukemia. We describe how we identified these leukemias in multiple cohorts of acute myeloid leukemia (AML) using a combination of gene expression profiling and additional analytic approaches, and how we obtained insight in possible mechanisms leading to their phenotype.