Evaluation of the influence of platelet-rich plasma (PRP), platelet lysate (PL) and mechanical loading on chondrogenesis in vitro.

The aim of this work is to investigate the capability of PRP as an adjuvant therapy to autologous chondrocyte implantation (ACI) in combination with multi-axial load with respect to cartilage regeneration. Articular cartilage shows poor repair capacity and therapies for cartilage defects are still lacking. Well-established operative treatments include ACI, and growing evidence shows the beneficial effects of PRP.

Changes in Gastrointestinal Microbiome Composition in PD: A Pivotal Role of Covariates.

Altered gut microbiota may trigger or accelerate alpha-synuclein aggregation in the enteric nervous system in Parkinson's disease (PD). While several previous studies observed gut microbiota alterations in PD, findings like diversity indices, and altered bacterial taxa itself show a considerable heterogeneity across studies. We recruited 179 participants, of whom 101 fulfilled stringent inclusion criteria.

The Potential for Synovium-derived Stem Cells in Cartilage Repair.

Background: Articular cartilage defects often result in pain, loss of function and finally osteoarthritis. Developing cell-based therapies for cartilage repair is a major goal of orthopaedic research. Autologous chondrocyte implantation is currently the gold standard cell-based surgical procedure for the treatment of large, isolated, full thickness cartilage defects.

Prospective Clinical Trial for Septic Arthritis: Cartilage Degradation and Inflammation Are Associated with Upregulation of Cartilage Metabolites.

. Intra-articular infections can rapidly lead to osteoarthritic degradation. The aim of this clinical biomarker analysis was to investigate the influence of inflammation on cartilage destruction and metabolism.

The trans-well coculture of human synovial mesenchymal stem cells with chondrocytes leads to self-organization, chondrogenic differentiation, and secretion of TGFβ.

Background: Synovial mesenchymal stem cells (SMSC) possess a high chondrogenic differentiation potential, which possibly supports natural and surgically induced healing of cartilage lesions. We hypothesized enhanced chondrogenesis of SMSC caused by the vicinity of chondrocytes (CHDR).

Methods: Human SMSC and CHDR interactions were investigated in an in-vitro trans-well monolayer coculture over a time period of up to 21 days.

Clinical Trial and In Vitro Study for the Role of Cartilage and Synovia in Acute Articular Infection.

Objective: Osteoarthritis is a long-term complication of acute articular infections. However, the roles of cartilage and synovia in this process are not yet fully understood.

Methods: Patients with acute joint infections were enrolled in a prospective clinical trial and the cytokine composition of effusions compared in patients with arthroplasty (n = 8) or with intact joints (n = 67).

Features of cell death, mitochondrial activation and caspase dependence of rabbit anti-T-lymphocyte globulin signaling in lymphoblastic Jurkat cells are distinct from classical apoptosis signaling of CD95.

Rabbit anti-T-lymphocyte-globulin (ATG) is used for immunosuppression in organ and stem cell transplantation. The aim of this study was to investigate ATG-induced cell death compared to CD95-signaling of apoptosis. We measured features of cell death at the cell membrane, mitochondria, nuclei and caspase-3 cleavage.

Dissociable attentional and inhibitory networks of dorsal and ventral areas of the right inferior frontal cortex: a combined task-specific and coordinate-based meta-analytic fMRI study.

The right inferior frontal cortex (rIFC) is frequently activated during executive control tasks. Whereas the function of the dorsal portion of rIFC, more precisely the inferior frontal junction (rIFJ), is convergingly assigned to the attention system, the functional key role of the ventral portion, i.e.

Practical execution of defect preparation prior to surgical cartilage intervention: results from a representative meeting survey among experts.

During a specialised orthopedic meeting held on 'the state of the art in cartilage defect repair', all previously fully-registered participants were requested to participate in an electronic survey by the use of a moderator-presented "Power Point Presentation-based" 9-item questionnaire. The aim of this survey was to assess indication, approach, and treatment execution of cartilage defect debridement prior to planned microfracture (MFX) or autologous chondrocyte implantation (ACI). All participants completed the questionnaire (n = 146) resulting in a return rate of 100 %.

Data-driven analysis of simultaneous EEG/fMRI using an ICA approach.

Due to its millisecond-scale temporal resolution, EEG allows to assess neural correlates with precisely defined temporal relationship relative to a given event. This knowledge is generally lacking in data from functional magnetic resonance imaging (fMRI) which has a temporal resolution on the scale of seconds so that possibilities to combine the two modalities are sought. Previous applications combining event-related potentials (ERPs) with simultaneous fMRI BOLD generally aimed at measuring known ERP components in single trials and correlate the resulting time series with the fMRI BOLD signal.

Early intra-articular complement activation in ankle fractures.

Cytokine regulation possibly influences long term outcome following ankle fractures, but little is known about synovial fracture biochemistry. Eight patients with an ankle dislocation fracture were included in a prospective case series and matched with patients suffering from grade 2 osteochondritis dissecans (OCD) of the ankle. All fractures needed external fixation during which joint effusions were collected.

Rabbit anti-T-lymphocyte globulin (ATG) persists with differential reactivity in patients' sera after full hematopoetic regeneration from allogeneic stem cell transplantation.

Background: Rabbit polyclonal anti-T-lymphocyte Globulin (ATG-F®, Fresenius) is widely used for GvHD prophylaxis in allogeneic stem cell transplantation (SCT). ATG has a wide epitope spectrum and has been shown to react with all compartments of peripheral blood mononuclear cells (PBMNCs). ATG induces apoptosis in all cellular compartments.

Suppression of granzyme B activity and caspase-3 activation in leukaemia cells constitutively expressing the protease inhibitor 9.

Immune surveillance against malignant cells is mediated by cytotoxic T-lymphocytes and NK-cells (CTL/NK) that induce apoptosis through the granzyme-B-dependent pathway. The serine protease inhibitor serpinB9/protease inhibitor-9 (PI-9) is a known inhibitor of granzyme B. Ectopic expression of PI-9 in tumour cells has been reported.

Body mass index and bioelectrical impedance phase angle as potentially modifiable nutritional markers are independent risk factors for outcome in allogeneic hematopoietic cell transplantation.

Beside many risk factors in patients considered for alloHCT, only body mass index (BMI) as a broad marker of nutritional status has prognostic value in these patients. This is the first prospective study to investigate the validity of further nutritional markers: adjusted BMI, normalized for gender and age; Subjective Global Assessment questionnaire and standardized phase angle, normalized for gender, age and BMI in 105 patients as independent risk factors for outcomes [overall survival (OS), non-relapse mortality (NRM), relapse mortality (RM), progression-free survival (PFS)] until 2 years after alloHCT. In Cox proportional-hazards regression models, we included a variety of accepted risk factors.

Longitudinal follow-up of nutritional status and its influencing factors in adults undergoing allogeneic hematopoietic cell transplantation.

There are few longitudinal data on nutritional status and body composition of patients undergoing allogeneic hematopoietic cell transplantation (alloHCT). We assessed nutritional status of 105 patients before alloHCT and its course during the early post-transplant period to day +30 and day +100 via weight history, body mass index (BMI) normalized for gender and age, Subjective Global Assessment, phase angle normalized for gender, age, and BMI, and fat-free and body fat masses. Furthermore, we present a multivariate regression model investigating the impact of factors on body weight.

Marrow versus blood-derived stem cell grafts for allogeneic transplantation from unrelated donors in patients with active myeloid leukemia or myelodysplasia.

Peripheral blood stem cells (PBSCs) are increasingly used as the graft source in allogeneic hematopoietic cell transplantation. We compared long-term outcome after unrelated donor transplantation of 85 consecutive patients with acute myelogenous leukemia or myelodysplastic syndrome regarding disease status (early disease [CR1, refractory anemia); n = 25 and advanced/active disease [>CR1, >refractory anemia]; n = 60) who were treated with conventional conditioning regimens followed by bone marrow (BM) or PBSC grafts. Graft-versus-host disease prophylaxis consisted mainly of cyclosporine A, short-course methotrexate, and anti-T-lymphocyte globulin.

Course of serum 25-hydroxyvitamin D(3) status and its influencing factors in adults undergoing allogeneic hematopoietic cell transplantation.

Hypovitaminosis D (<30 ng/ml) is highly prevalent in allogeneic hematopoietic cell transplantation (alloHCT), but the relevance of influencing factors for serum 25-hydroxyvitamin D(3) [25(OH)D(3)] status in adult patients remains unknown. We are the first to have prospectively assessed 25(OH)D(3) status and its influencing factors in 102 patients before and at days +30 and +100 after alloHCT. Among others, we evaluated age, gender, weight, fat mass, season, sun exposure habits, and dietary and supplemental vitamin D intake as factors potentially influencing baseline vitamin D status in uni- and multivariate linear regression analysis.

Role of antioxidants in buccal mucosa cells and plasma on the incidence and severity of oral mucositis after allogeneic haematopoietic cell transplantation.

Purpose: Oral mucositis (OM) is known to be a significant complication of chemotherapy preceding haematopoietic cell transplantation (HCT). Antioxidants (AOX) scavenge free radicals, which play a major role in the initiation of OM and may reduce the OM risk.

Study Design: The primary objective of this prospective study was to investigate the association between the incidence and severity of OM (WHO oral toxicity scale) and the AOX status in buccal mucosa cells (BMC) and plasma.

A novel GVHD-prophylaxis with low-dose alemtuzumab in allogeneic sibling or unrelated donor hematopoetic cell transplantation: the feasibility of deescalation.

Prophylaxis of acute graft-versus-host disease (aGVHD), while maintaining the graft-versus-leukemia (GVL)/lymphoma effect and preventing severe infectious diseases, remains the main challenge in allogeneic hematopoetic cell transplantation (allo-HCT). To evaluate this, we examined the feasibility of deescalating the dose of alemtuzumab (MabCampath) in combination with cyclosporine (CsA) as the sole GVHD-prophylaxis in patients after fludarabine (Flu)-based reduced-intensity conditioning (RIC) in an observational cohort study. We included 127 consecutive patients (median age 63 years) with an unrelated (UD; n=69) or related donor (SIB; n=58) after their first transplantation, mostly presenting with advanced disease.

Successful treatment of severe acute intestinal graft-versus-host resistant to systemic and topical steroids with alemtuzumab.

Development of severe steroid-resistant acute graft-versus-host disease (GVHD) after allogeneic hematopoietic cell transplantation (HCT) is associated with poor outcome. The humanized monoclonal antibody alemtuzumab was shown to be effective in GVHD prophylaxis in conditioning regimens before allogeneic HCT. We evaluated the efficacy and safety of alemtuzumab in 20 patients with histologically confirmed steroid refractory grade III and IV intestinal GVHD after related and unrelated HCT.

Rabbit anti T-lymphocyte globulin induces apoptosis in peripheral blood mononuclear cell compartments and leukemia cells, while hematopoetic stem cells are apoptosis resistant.

Polyclonal anti-T-lymphocyte globulins (ATG) are used in allogeneic stem cell transplantation (SCT) for the prophylaxis of graft versus host disease (GVHD) by in vivo T cell depletion. In this study we investigated the complement independent induction of apoptosis by rabbit ATG in peripheral blood mononuclear cell (PBMNC) compartments and hematopoetic stem cells (HSC). We also detected antileukemic activity of ATG by measuring apoptosis in myeloid and lymphatic leukemia cell lines and primary leukemia cells.

Ex vivo detection of primary leukemia cells resistant to granule cytotoxin-induced cell death: a rapid isolation method to study granzyme-B-mediated cell death.

Cytotoxic T lymphocytes and natural killer cells (CTL/NK) induce cell death in leukemia cells by the granzyme B (grB)-dependent granule cytotoxin (GC) pathway. Resistance to GC may be involved in immune evasion of leukemia cells. The delivery of active grB into the cytoplasma is dependent on the presence of perforin (PFN) and grB complexes.

A fludarabine, thiotepa reduced toxicity conditioning regimen designed specifically for allogeneic second haematopoietic cell transplantation after failure of previous autologous or allogeneic transplantation.

We present a phase II study of fludarabine 5 x 30 mg/m(2), thiotepa 3 x 5 mg/kg as preparative regimen specifically for allogeneic second haematopoietic stem cell transplantation (HCT) after failure of previous HCT. Forty-nine patients (median age 52 years, range 27-68) received an allogeneic second HCT after failed autologous (n=29) or allogeneic (n=20) HCT. Diagnoses were AML (n=18), ALL (n=3), multiple myeloma (n=11), lymphoma (n=16) and CML (n=1).

Immunopathogenesis of acute graft-versus-host disease: implications for novel preventive and therapeutic strategies.

Acute graft-versus-host disease (GVHD) is a primary T-cell-mediated complication of allogeneic hematopoietic stem cell transplantation (HSCT), occurring when donor-derived T cells are stimulated by host antigen-presenting cells (APCs), enhanced by proinflammatory cytokines such as interleukin (IL)-1, IL-6, IL-8, and tumor necrosis factor (TNF)-alpha. Recent data indicate that besides differences in major histocompatibility and minor histocompatibility antigens, cytokine gene polymorphisms have a predictive value for the complication of GVHD. Patients with a high anti-inflammatory IL-10 production have been demonstrated to be protected from GVHD while patients with high TNF-alpha serum levels were more at risk for GVHD.

Donor lymphocyte infusions for multiple myeloma: clinical results and novel perspectives.

Donor lymphocyte infusions (DLIs) provide effective therapy for patients with various hematological malignancies who have relapsed after allogeneic hematopoietic stem cell transplantation (HSCT). In patients with multiple myeloma (MM), DLIs can induce response rates of 40-52%. DLIs were employed as treatment for MM relapse or as prophylaxis for relapse in MM patients undergoing allo-HSCT.