Pattern of employment and associated factors in long-term lymphoma survivors 10 years after high-dose chemotherapy with autologous stem cell transplantation.

Background This study examined employment patterns and associated factors in lymphoma survivors treated with high-dose chemotherapy with autologous stem cell transplantation (HDT-ASCT) from diagnosis to a follow-up survey at a mean of 10 years after HDT-ASCT. Patients and methods All lymphoma survivors aged ≥18 years at HDT-ASCT in Norway from 1987 to 2008, and alive at the end of 2011 were eligible for this cross-sectional study performed in 2012/2013. Participants completed a mailed questionnaire. Job status was dichotomized as either employed (paid work) or not-employed (disability and retirement pension, on economic support, home-makers, or students). Results The response rate was 78%, and the sample (N = 312) contained 60% men. Mean age at HDT-ASCT was 44.3 and at survey 54.0 years. At diagnosis 85% of survivors were employed, 77% before and 77% after HDT-ASCT, and 58% at follow-up. Forty seven percent of the survivors were employed at all time points. The not-employed group at survey was significantly older and included significantly more females than the employed group. No significant between-group differences were observed for lymphoma-related variables. Fatigue, mental distress and type D personality were significantly higher among those not-employed, while quality of life was significantly lower compared to the employed group. Older age at survey, being female, work ability and presence of type D personality remained significantly related to being not-employed at survey in the multivariable analysis. Conclusions Our findings show that not-employed long-term survivors after HDT-ASCT for lymphoma have more comorbidity, cognitive problems and higher levels of anxiety/depression than employed survivors. These factors should be checked and eventually treated in order to improve work ability.

Serum/glucocorticoid-regulated kinase 1 (SGK1) is a prominent target gene of the transcriptional response to cytokines in multiple myeloma and supports the growth of myeloma cells.

Multiple myeloma (MM) is a paradigm for a malignant disease that exploits external stimuli of the microenvironment for growth and survival. A thorough understanding of the complex interactions between malignant plasma cells and their surrounding requires a detailed analysis of the transcriptional response of myeloma cells to environmental signals. We determined the changes in gene expression induced by interleukin (IL)-6, tumor necrosis factor-α, IL-21 or co-culture with bone marrow stromal cells in myeloma cell lines. Among a limited set of genes that were consistently activated in response to growth factors, a prominent transcriptional target of cytokine-induced signaling in myeloma cells was the gene encoding the serine/threonine kinase serum/glucocorticoid-regulated kinase 1 (SGK1), which is a down-stream effector of PI3-kinase. We could demonstrate a rapid, strong and sustained induction of SGK1 in the cell lines INA-6, ANBL-6, IH-1, OH-2 and MM.1S as well as in primary myeloma cells. Pharmacologic inhibition of the Janus kinase/signal transducer and activator of transcription (JAK/STAT) pathway abolished STAT3 phosphorylation and SGK1 induction. In addition, small hairpin RNA (shRNA)-mediated knock-down of STAT3 reduced basal and induced SGK1 levels. Furthermore, downregulation of SGK1 by shRNAs resulted in decreased proliferation of myeloma cell lines and reduced cell numbers. On the molecular level, this was reflected by the induction of cell cycle inhibitory genes, for example, CDKNA1/p21, whereas positively acting factors such as CDK6 and RBL2/p130 were downregulated. Our results indicate that SGK1 is a highly cytokine-responsive gene in myeloma cells promoting their malignant growth.

Elevated serum concentrations of activated hepatocyte growth factor activator in patients with multiple myeloma.

OBJECTIVES: Hepatocyte growth factor (HGF) is a potential key factor in multiple myeloma. Conversion of pro-HGF to its active form is a critical limiting step for its biological effects. We aimed to examine the levels of the most potent activator, the hepatocyte growth factor activator (HGFA), in serum and bone marrow plasma of patients with multiple myeloma. METHODS: The activated form of HGFA was measured by an enzyme-linked immunosorbent assay in serum (n = 49) and bone marrow plasma (n = 16) from multiple myeloma patients, and in serum from healthy controls (n = 24). RESULTS: The median concentrations of activated HGFA in myeloma and control sera were 39.7 (range 6.2-450.0) and 17.6 ng/mL (range 4.8-280.6), respectively. The difference was statistically significant (P = 0.037). The median concentration of activated HGFA in bone marrow plasma was 6.1 ng/mL (range 3.5-30.0). CONCLUSION: We here show for the first time that the activated form of HGFA is present at high levels in serum and bone marrow of myeloma patients, thus providing a necessary prerequisite for the activation of HGF.

[Injuries in handball players]. / Skader hos håndballspillere.

The study involves 421 patients who had suffered injury while playing handball. It describes mechanism and trauma, the injuries and their consequences, and data on training and technical conditions. 2/3 of the injured were female and one half belonged to the younger age-classes. The incidence of injury was highest among senior players. Distortion was the most frequent type of injury, followed by contusions and fractures. Half of the injuries were to the upper limbs, but the most frequent single injury was injury to the ankle joint. Many fractures were seen in fingers, forearm, hand and ribs. Wounds occurred most frequently to the face. The most serious injuries were ruptures of the ligaments in the knee joint. Protective equipment, such as braces, was seldom used. A small minority of the players were given adequate first aid. Important measures to prevent injury include better basic training, better technical training conditions, good first aid, and some changes in the rules of competition.