Novel strategies for improving hematopoietic reconstruction after allogeneic hematopoietic stem cell transplantation or intensive chemotherapy.

High-dose conditioning regimens for allogeneic hematopoietic cell transplantation (allo-HCT) as well as intensive poly-chemotherapy for acute myeloid leukemia (AML) induce prolonged periods of neutropenia. The duration of the neutropenia is particularly long following umbilical cord blood transplantation (UCBT). Areas covered: After briefly reviewing the impact of hematopoietic growth factors administration to hasten hematologic reconstitution after allo-HCT or intensive AML chemotherapy, this article summarizes recent approaches that have been investigated to prompt hematologic reconstruction after UCBT or intensive AML chemotherapy.

Glucocorticoid-induced leucine zipper (GILZ) is involved in glucocorticoid-induced and mineralocorticoid-induced leptin production by osteoarthritis synovial fibroblasts.

Background: Glucocorticoid-induced leucine zipper (GILZ) is a mediator of the anti-inflammatory activities of glucocorticoids. However, GILZ deletion does not impair the anti-inflammatory activities of exogenous glucocorticoids in mice arthritis models and GILZ could also mediate some glucocorticoid-related adverse events. Osteoarthritis (OA) is a metabolic disorder that is partly attributed to adipokines such as leptin, and we previously observed that glucocorticoids induced leptin secretion in OA synovial fibroblasts.

Novel approaches for preventing acute graft-versus-host disease after allogeneic hematopoietic stem cell transplantation.

Introduction: Allogeneic hematopoietic stem cell transplantation (alloHSCT) offers potential curative treatment for a wide range of malignant and nonmalignant hematological disorders. However, its success may be limited by post-transplant acute graft-versus-host disease (aGVHD), a systemic syndrome in which donor's immune cells attack healthy tissues in the immunocompromised host. aGVHD is one of the main causes of morbidity and mortality after alloHSCT.

SRC kinase inhibition with saracatinib limits the development of osteolytic bone disease in multiple myeloma.

Multiple myeloma (MM)-associated osteolytic bone disease is a major cause of morbidity and mortality in MM patients and the development of new therapeutic strategies is of great interest. The proto-oncogene SRC is an attractive target for such a strategy. In the current study, we investigated the effect of treatment with the SRC inhibitor saracatinib (AZD0530) on osteoclast and osteoblast differentiation and function, and on the development of MM and its associated bone disease in the 5TGM.

Methods of ex vivo expansion of human cord blood cells: challenges, successes and clinical implications.

More than 40,000 unrelated cord blood transplantations (UCBT) have been performed worldwide as treatment for patients with malignant or non-malignant life threatening hematologic disorders. However, low absolute numbers of hematopoietic stem and progenitor cells (HSPCs) within a single cord blood unit has remained a limiting factor for this transplantation modality, particularly in adult recipients. Further, because UCB contains low numbers of mostly naïve T cells, immune recovery after UCBT is slow, predisposing patients to severe infections.

What is important in being cured from depression? Discordance between physicians and patients (1).

Aims: The comparison of what physicians and patients consider important in being cured from depression.

Methods: 426 outpatients (in primary care and in psychiatric care) with a clinical diagnosis of major depression were included: at the start of antidepressant treatment, the importance of a range of items for being cured from depression (depressive, anxious and somatic symptoms, positive affect, functional impairment, quality of life) was assessed in physicians and patients separately and a ranking was made; after 3 months of treatment, the importance of these items for being cured from depression was re-assessed in the patients.

Results: The items ranked top 10 by physicians mainly contain depressive symptoms while those ranked top 10 by patients mainly contain positive affect items and this attention to positive affect even increases at 3 months follow-up and is higher in patients with recurrent depression than in patients with a first episode of depression.

What is important in being cured from: does discordance between physicians and patients matter? (2).

Aims: The influence of discordance in what is important in being cured from depression on clinical outcome at 6 months, assessed with a divergence index.

Methods: 304 outpatients treated for depression by general practitioners or by psychiatrists and completing a 6-month treatment period: a divergence index (divergence between physician and patient view on what is important in being cured from depression) was calculated for each physician-patient pair. The relation between this index and outcome at 6 months was analyzed (including depressive, anxious and somatic symptom severity, positive effect, functional impairment and quality of life (psychological and social relations).

Umbilical cord fibroblasts: Could they be considered as mesenchymal stem cells?

In cell therapy protocols, many tissues were proposed as a source of mesenchymal stem cells (MSC) isolation. So far, bone marrow (BM) has been presented as the main source of MSC despite the invasive isolation procedure related to this source. During the last years, the umbilical cord (UC) matrix was cited in different studies as a reliable source from which long term ex vivo proliferating fibroblasts were isolated but with contradictory data about their immunophenotype, gene expression profile, and differentiation potential.

Cellular immunotherapy in multiple myeloma: lessons from preclinical models.

The majority of multiple myeloma patients relapse with the current treatment strategies, raising the need for alternative therapeutic approaches. Cellular immunotherapy is a rapidly evolving field and currently being translated into clinical trials with encouraging results in several cancer types, including multiple myeloma. Murine multiple myeloma models are of critical importance for the development and refinement of cellular immunotherapy.

Comprehensive plasma profiling for the characterization of graft-versus-host disease biomarkers.

Acute graft-versus-host disease (aGVHD) remains a life-threatening complication of hematopoietic stem cell transplantation (HSCT) therefore limiting its application. To optimize the management of aGVHD and reduce therapy-related toxicity, early specific markers are needed. The main objective of this study was to uncover diagnostic biomarkers by comparing plasma protein profiles of patients at the time of acute GVHD diagnosis with those of patients undergoing HSCT without aGVHD.

Thinking out of the box--new approaches to controlling GVHD.

Graft-versus-host disease (GVHD) remains a major limitation of allogeneic hematopoietic cell transplantation (allo-HCT). Despite major advances in the understanding of GVHD pathogenesis, standard GVHD prophylaxis regimens continue to be based on the combination of a calcineurin inhibitor with an antimetabolite, while first line treatments still rely on high-dose corticosteroids. Further, no second line treatment has emerged thus far in acute or chronic GVHD patients who failed to respond with corticosteroid treatment.

Emerging drugs for prevention of graft failure after allogeneic hematopoietic stem cell transplantation.

Introduction: Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is the treatment of choice for many patients suffering from hematological malignancies, severe hemoglobinopathies, bone marrow failures or severe primary immunodeficiencies. Graft rejection/failure (GF) is a life-threatening complication following allo-HSCT that is most commonly caused by the reactivity of recipient T cells, natural killer (NK) cells or antibodies against donor grafted hematopoietic cells. The increasing use of allo-HSCT following reduced-intensity conditioning (RIC) and the increasing use of alternative donors (unrelated cord blood and human leukocyte antigen (HLA)-mismatched donor) have resulted in higher frequency of GF.

Differential signalling through ALK-1 and ALK-5 regulates leptin expression in mesenchymal stem cells.

Leptin plays a central role in maintaining energy balance, with multiple other systemic effects. Despite leptin importance in peripheral regulation of mesenchymal stem cells (MSC) differentiation, little is known about its expression mechanism. Leptin is often described as adipokine, while it is expressed by other cell types.

Mesenchymal stromal cells: a new tool against graft-versus-host disease?

Mesenchymal stromal cells (MSCs) represent a heterogeneous subset of multipotent cells that can be isolated from several tissues including bone marrow and fat. MSCs exhibit immunomodulatory and anti-inflammatory properties that prompted their clinical use as prevention and/or treatment for severe graft-versus-host disease (GVHD). Although a number of phase I-II studies have suggested that MSC infusion was safe and might be effective for preventing or treating acute GVHD, definitive proof of their efficacy remains lacking thus far.

Isokinetic assessment of the shoulder rotators: a study of optimal test position.

Background:   Isokinetic assessment of the shoulder rotator cuff is a common component of shoulder muscles assessment. Nevertheless, the extensive mobility of the shoulder poses great difficulty in finding a consensus protocol for evaluation.

Objective:   To select an optimal protocol, among three, based on the best reproducibility and reliability of strength scores derived from internal and external rotator tests.

Shoulder function after latissimus dorsi transfer in breast reconstruction.

Background/aims: Latissimus dorsi (LD) transfer in the case of breast reconstruction remains frequently used because this muscle provides a good size source of tissue in reconstructive surgery. Given that, the consequences of the LD removal on shoulder function and the actual loss of maximal strength developed must be investigated.

Methods: Twenty women (50 ± 7.

Gait analysis in elderly adult patients with mild cognitive impairment and patients with mild Alzheimer's disease: simple versus dual task: a preliminary report.

Unlabelled: SUMMARY BACKGROUND/AIMS: The aim of this study was to assess gait characteristics during simple and dual task in patients with mild cognitive impairment (MCI) and compare them with those of healthy elderly subjects and mild Alzheimer's disease (AD) patients.

Methods: We proposed a gait analysis to appreciate walking (simple task and dual task) in 14 MCI, 14 controls and six AD subjects who walked at their preferred speed. A 20-second period of stabilized walking was used to calculated stride frequency, stride length, symmetry and regularity.

Strength imbalances and prevention of hamstring injury in professional soccer players: a prospective study.

Background: The relationship between muscle injury and strength disorders remains a matter of controversy.

Purpose: Professional soccer players performed a preseason isokinetic testing aimed at determining whether (1) strength variables could be predictors of subsequent hamstring strain and (2) normalization of strength imbalances could reduce the incidence of hamstring injury.

Study Design: Cohort study (prognosis); Level of evidence, 1.