Associations between levels of insulin-like growth factor 1 and sinusoidal obstruction syndrome after allogeneic haematopoietic stem cell transplantation.

Allogeneic myeloablative haematopoietic stem cell transplantation (HSCT) is challenged by severe adverse events, as cytotoxic effects of the conditioning may result in systemic inflammation, leaky epithelial barriers and organ toxicities, contributing to treatment-related morbidity and mortality. We hypothesised that insulin-like growth factor-1 (IGF-1), a mediator of growth and proliferation of various tissues, may attenuate chemotherapy-induced tissue damage after HSCT. We prospectively measured plasma levels of IGF-1 and its binding protein 3 (IGFBP-3) in 41 patients undergoing myeloablative HSCT. IGF-1 and IGFBP-3 levels were inversely correlated with C-reactive protein and interleukin-6 levels post HSCT. In multivariate analyses, low levels of IGF-1 and IGFBP-3 before conditioning were associated with increased risk of developing sinusoidal obstruction syndrome (SOS; OR=5.00 per 1 SDS decrease in IGF-1 (95% CI: 1.45-16.67), P=0.011 and OR=5.00 (1.37-20.00), P=0.015, respectively). Furthermore, low pre-transplant levels of IGF-1 and IGFBP-3 were associated with increased fluid retention during the first 21 days post transplant (OR=7.69 (95% CI: 1.59-33.33), P=0.012, and OR=2.94 (1.03-8.33), P=0.045). These data suggest that high levels of IGF-1 and IGFBP-3 may have a protective effect against fluid retention and SOS, possibly by attenuating systemic inflammation, and may prove useful as predictive biomarkers of SOS.

T cell reconstitution in allogeneic haematopoietic stem cell transplantation: prognostic significance of plasma interleukin-7.

Infections and acute graft-versus-host disease (aGVHD) are major causes of treatment-related mortality and morbidity following allogeneic haematopoietic stem cell transplantation (HSCT). Both complications depend on reconstitution of the T-lymphocyte population based on donor T cells. Although it is well established that Interleukin-7 (IL-7) is a cytokine essential for de novo T cell development in the thymus and homoeostatic peripheral expansion of T cells, associations between circulating levels of IL-7 and T cell reconstitution following HSCT have not been investigated previously. We prospectively measured IL-7 levels in 81 patients undergoing myeloablative HSCT with either sibling donor or an unrelated donor. Plasma IL-7 levels peaked at day +7 post-transplant (1.3-82.4 pg/ml), at the time of maximal lymphopaenia. In multivariate analysis, peak levels of IL-7 were significantly higher in patients treated with anti-thymocyte globulin (ATG) compared with those not treated with ATG (P = 0.0079). IL-7 levels at day +7 were negatively associated with T cell counts at day +30 to +60 (at day +60: CD3(+) : ß = -10.6 × 10(6) cells/l, P = 0.0030; CD8(+) : ß = -8.4 × 10(6) cells/l, P = 0.061; CD4(+) : ß = -2.1 × 10(6) cells/l, P = 0.062) in multivariate analyses. In adults, high IL-7 levels were associated with increased risk of grade II-IV aGVHD (OR = 5.4, P = 0.036) and reduced overall survival (P = 0.046). The present data indicate that high plasma levels of IL-7 in the early post-transplant period are predictive for slow T cell reconstitution, increased risk of aGVHD and increased mortality following HSCT.

Pretransplant C-reactive protein as A prognostic marker in allogeneic stem cell transplantation.

We evaluated the prognostic role of baseline levels of C-reactive protein (CRP) as well as CRP levels during conditioning in patients undergoing myeloablative allogeneic stem cell transplantation (SCT). Furthermore, we studied the impact of baseline clinical factors and conditioning regimens on CRP levels in the same period. We conducted a population-based retrospective study of 349 patients undergoing SCT at the National Danish SCT centre between January 2000 and January 2009. CRP levels increased significantly during the conditioning and peaked at day -3 before infusion of the graft. Elevated CRP was associated with older age, non-malignant disease, reduced pretransplant Karnofsky score and high-risk leukaemia. By univariate and multivariate analyses, increased CRP levels (>10 mg/l) before the start of treatment (day -7) and at the day of graft infusion (day 0) were associated with decreased overall survival [HR 1.35 (95%CL) (1.18-1.54); P < 0.0001] and increased treatment-related mortality [1.5 (1.24-1.82); P < 0.0001]. Similar findings were seen for mean CRP levels during the conditioning. CRP was not associated with risk of relapse or aGvHD in multivariate analysis. This study suggests that increased CRP levels before and during the conditioning are associated with baseline clinical factors and that elevated pretransplant CRP levels predict a poorer survival in SCT.

Bronchiolitis obliterans after allo-SCT: clinical criteria and treatment options.

Bronchiolitis obliterans (BO) following allogeneic haematopoietic SCT (HSCT) is a serious complication affecting 1.7-26% of the patients, with a reported mortality rate of 21-100%. It is considered a manifestation of chronic graft-versus-host disease, but our knowledge of aetiology and pathogenesis is still limited. Diagnostic criteria are being developed, and will allow more uniform and comparable research activities between centres. At present, no randomised controlled trials have been completed that could demonstrate an effective treatment. Steroids in combination with other immunosuppressive drugs still constitute the backbone of the treatment strategy, and results from our and other centres suggest that monthly infusions of high-dose pulse i.v. methylprednisolone (HDPM) might stabilise the disease and hinder progression. This article provides an overview of the current evidence regarding treatment options for BO and presents the treatment results with HDPM in a paediatric national HSCT-cohort.

Using interaction graphs for analysing the therapy process.

BACKGROUND: Therapy processes are complex dynamical systems where several variables are constantly interacting with each other. In general, the underlying mechanisms are difficult to assess. Our approach is to identify the dependency structure of relevant variables within the therapy process using interaction graphs. These are instruments for multivariate time series which are based on the analysis of partial spectral coherences. We used interaction graphs in order to investigate the therapy process of a multimodal therapy concept for fibromyalgia patients. Our main hypothesis was that self-efficacy plays a central role in the therapy process. METHODS: Patients kept an electronic diary for 13 weeks. Pain intensity, depression, sleep quality, anxiety and self-efficacy were assessed via visual analogue scales. The resulting multivariate time series were aggregated over individuals, and partial spectral coherences between each pair of the variables were calculated. From the partial coherences, interaction graphs were plotted. RESULTS: Within the resulting graphical model, self-efficacy was strongly related to pain intensity, depression and sleep quality. All other relations were substantially weaker. There was no direct relationship between pain intensity and sleep quality. CONCLUSIONS: The relations between two variables within the therapy process are mainly induced by self-efficacy. Interaction graphs can be used to pool time series data of several patients and thus to assess the common underlying dependency structure of a group of patients. The graphical representation is easily comprehensible and allows to distinguish between direct and indirect relationships.

[Shared decision making (SDM) with chronic pain patients. The patient as a partner in the medical decision making process]. / Partizipative Entscheidungsfindung (PEF) mit chronischen Schmerzpatienten. Der Patient als Partner im medizinischen Entscheidungsprozess.

Fibromyalgia syndrome (FMS) is an exemplary condition of chronic widespread pain that is difficult to control and often leads to frustration and resignation on the part of both the patient and the doctor. Shared decision making (SDM) could be a means to facilitate doctor-patient interaction and might therefore influence therapeutic decisions taken. We conducted a prospective study to evaluate the effects of SDM with FMS patients. We developed a communication train-ing program for physicians and a computer-based information tool on FMS for patients. The study included 133 FMS patients. Intervention group I (IG I) was treated by communication-trained doctors and had access to a computer-based information tool on FMS,intervention group II (IG II) was treated by standard doctors and received the information tool, and the control group (CG) was treated by standard doctors and got no additional information. All three groups we-re offered the same evidence-based treatment options for FMS. Patients of the IGs were more willing to become involved in exercise, to enroll in integrated group therapy for FMS patients (IGTF), and to take analgesics. Patients of the CG preferred anti-depressants. More patients from IG II and CG opted for relaxation techniques. Patients in IG I and IG II choose significantly more therapeutic options than patients in the CG. SDM is one means to increase FMS patients' readiness for treatment. Especially the element of providing sufficient medical information seems to account for this effect. The readiness to enroll in physical activities, to take analgesics, and to participate in psychotherapeutic elements was most likely to be raised through SDM.

[Psychosocial factors in a fibromyalgia syndrome patient. Assessment by means of electron pain diaries--casuistics and multivariate time series analysis]. / Psychosoziale Faktoren bei einer Fibromyalgiepatientin. Erfassung mittels eines elektronischen Schmerztagebuchs-Kasuistik und multivariate Zeitreihenanalyse.

OBJECTIVE: Fibromyalgia syndrome (FMS) is a condition of chronic widespread pain. In its process of chronification psychosocial factors play an important role. A multimodal treatment including integrated group therapy has been proved to be effective. Yet little attention has been paid so far to the exact sequence of changes and interrelation between psychosocial factors, functional capacity, and level of pain under integrated group therapy for FMS patients. METHODS: One FMS patient was exemplarily monitored with an electronic diary over 13 weeks while undergoing integrated group therapy. On a daily basis we assessed the level of pain, functional capacity, and other disease-related variables (anxiety, depression, quality of sleep, self-efficacy) via visual analog scales. By the means of multivariate time series analysis the timing of changes in psychosocial factors and their effects on perceived functional capacity was identified. RESULTS: Under integrated group therapy all assessed variables gradually changed in the predicted way. Pain, depression, anxiety could be reduced, whereas self-efficacy, quality of sleep, and functional capacity improved. 71% of the variance could be explained by the multiple regression model. Self-efficacy was, beside pain intensity and depression, an important predictor for functional capacity on the same day. High self-efficacy correlated negatively with the level of functional capacity 3 days later. CONCLUSION: Integrated group therapy proved to be effective. Self-efficacy played an important role regarding the improvement of functional capacity. Depicting the exact timing of changes in the assessed variables helped to detect patterns of influence and indicate directions for further treatment.

Design and test of a simple high-temperature laser microrefractometer.

The design of a laser microrefractometer that is suitable for temperature-dependent measurements is described. The refractive index of methylene iodide is measured in the temperature range of 22-92 °C for laser wavelengths covering almost the entire visible range of the spectrum: 442, 488, 515, 543, 594, and 633 nm. A detailed analysis of the temperature-related experimental error is made.

Divinylsulphone-activated agarose. Formation of stable and non-leaking affinity matrices by immobilization of immunoglobulins and other proteins.

Divinylsulphone-activated agarose is an attractive alternative to several of the activated supports usually used. Unlike CNBr-activated gels, it does not leak the immobilized protein at high pH. It reacts readily with proteins at near-neutral pH (unlike the epoxy-activated supports). Generally, divinylsulphone-activated agarose reacts with amino, hydroxyl, and sulphydryl groups, thus allowing immobilization of a wide spectrum of ligands. Moreover, it is available in an aqueous suspension free of organic solvents and neither requires time-consuming swelling nor washing.