T cell lymphoproliferative disorders associated with anti-tumor necrosis factor alpha antibody therapy for ulcerative colitis: literature summary

The enhanced risk of development of lymphoproliferative disorders in patients with inflammatory bowel disease has been attributed to immunosuppressive/immunomodulatory therapies. Infliximab is a chimeric monoclonal immunoglobulin G1 antibody directed against tumor necrosis factor alpha (TNF-α) that was approved by the Food and Drug Administration (FDA) in 1998 as an effective therapeutic agent against inflammatory bowel disease. Malignant lymphomas of both B and T cell lineage have been described in patients undergoing therapy involving TNF-α blockade. To date, eight cases of Epstein–Barr virus (EBV)-negative hepatosplenic T cell lymphoma associated with infliximab have been reported to the FDA’s Adverse Event Reporting System, as well as several other T cell lymphoproliferative disorders with aggressive clinical outcomes. We present the histologic, immunophenotypic, and molecular features of a T cell lymphoproliferative disorder involving the axillary lymph node of a 33-year-old male following infliximab treatment for ulcerative colitis. These EBV-negative lymphomas suggest that lymphoproliferative disorders following infliximab treatment for inflammatory bowel disease may involve EBV-independent immune dysregulation. The spectrum of lymphoproliferative disorders associated with infliximab and the potential mechanisms by which they occur are discussed

The ProPrems trial: investigating the effects of probiotics on late onset sepsis in very preterm infants

BACKGROUND: Late onset sepsis is a frequent complication of prematurity associated with increased mortality and morbidity. The commensal bacteria of the gastrointestinal tract play a key role in the development of healthy immune responses. Healthy term infants acquire these commensal organisms rapidly after birth. However, colonisation in preterm infants is adversely affected by delivery mode, antibiotic treatment and the intensive care environment. Altered microbiota composition may lead to increased colonisation with pathogenic bacteria, poor immune development and susceptibility to sepsis in the preterm infant.Probiotics are live microorganisms, which when administered in adequate amounts confer health benefits on the host. Amongst numerous bacteriocidal and nutritional roles, they may also favourably modulate host immune responses in local and remote tissues. Meta-analyses of probiotic supplementation in preterm infants report a reduction in mortality and necrotising enterocolitis. Studies with sepsis as an outcome have reported mixed results to date.Allergic diseases are increasing in incidence in "westernised" countries. There is evidence that probiotics may reduce the incidence of these diseases by altering the intestinal microbiota to influence immune function. METHODS/DESIGN: This is a multi-centre, randomised, double blinded, placebo controlled trial investigating supplementing preterm infants born at < 32 weeks' gestation weighing < 1500 g, with a probiotic combination (Bifidobacterium infantis, Streptococcus thermophilus and Bifidobacterium lactis). A total of 1,100 subjects are being recruited in Australia and New Zealand. Infants commence the allocated intervention from soon after the start of feeds until discharge home or term corrected age. The primary outcome is the incidence of at least one episode of definite (blood culture positive) late onset sepsis before 40 weeks corrected age or discharge home. Secondary outcomes include: Necrotising enterocolitis, mortality, antibiotic usage, time to establish full enteral feeds, duration of hospital stay, growth measurements at 6 and 12 months' corrected age and evidence of atopic conditions at 12 months' corrected age. DISCUSSION: Results from previous studies on the use of probiotics to prevent diseases in preterm infants are promising. However, a large clinical trial is required to address outstanding issues regarding safety and efficacy in this vulnerable population. This study will address these important issues. TRIAL REGISTRATION: Australia and New Zealand Clinical Trials Register (ANZCTR): ACTRN012607000144415The product "ABC Dophilus Probiotic Powder for Infants®", Solgar, USA has its 3 probiotics strains registered with the Deutsche Sammlung von Mikroorganismen und Zellkulturen (DSMZ--German Collection of Microorganisms and Cell Cultures) as BB-12 15954, B-02 96579, Th-4 15957

The effect of lateral wedge insoles in patients with medial compartment knee osteoarthritis: balancing biomechanics with pain neuroscience

Results on the effects of lateral wedge insoles (LWIs) in patients with medial knee osteoarthritis (OA) are ambiguous and not fully understood. Because of the low cost of this intervention and its clinical utility, attention to LWIs is worth considering. Current insights on the efficacy of LWIs are mainly focused on changing biomechanical aspects, such as the external knee adduction moment, in an attempt to influence pain, functional ability and structural progression. It is however appropriate to interpret the effectiveness of LWIs in a broader concept than the pure biomechanical approach. Given our current understanding of OA-related pain, including the involvement of the central nervous system and nociception-motor interactions, concepts of pain neuroscience should be taken into account. The purpose of this review is to summarize the current state of knowledge regarding the biomechanical effect of LWIs. It aims to discuss the degree to which such biomechanical effect translates to clinical effects (symptom relief, function recovery and reduction of structural progression). In order to explain these clinical effects, this paper balances biomechanics with pain neuroscience. A literature search was performed and reviewed using a narrative approach. Many studies investigated the effect of LWIs on dynamic knee joint loading, and beneficial biomechanical effects (reduction in knee adduction moment) were observed in patients with mild to moderate medial knee OA, in particular when using full-length LWIs. However, despite beneficial biomechanical effects, there is insufficient evidence for clinically important effects or significant reductions in disease progression. Evaluating the effects of LWIs, our current understanding of OA pain should be taken into account, as LWIs may be part of a comprehensive biopsychosocial treatment. Future work on all of the variables that could influence clinical outcomes in order to decide in which subgroups of patients LWIs are (most) effective is necessary

Inter- and intrarater reliability of two proprioception tests using clinical applicable measurement tools in subjects with and without knee osteoarthritis

Background: The therapeutic value of proprioceptive-based exercises in knee osteoarthritis (KOA) management warrants investigation of proprioceptive testing methods easily accessible in clinical practice. Objective: To estimate inter-and intrarater reliability of the knee joint position sense (KJPS) test and knee force sense (KFS) test in subjects with and without KOA. Design: Cross-sectional test-retest design. Method: Two blinded raters performed independently repeated measures of the KJPS and KFS test, using an analogue inclinometer and handheld dynamometer, respectively, in eight KOA patients (12 symptomatic knees) and 26 healthy controls (52 asymptomatic knees). Intraclass correlation coefficients (ICCs; model 2,1), standard error of measurement (SEM) and minimal detectable change with 95% confidence bounds (MDC95) were calculated. Results: For KJPS, results showed good to excellent test-retest agreement (ICCs 0.70-0.95 in KOA patients; ICCs 0.65-0.85 in healthy controls). A 2 degrees measurement error (SEM 1 degrees) was reported when measuring KJPS in multiple test positions and calculating mean repositioning error. Testing KOA patients pre and post therapy a repositioning error larger than 4 degrees (MDC95) is needed to consider true change. Measuring KFS using handheld dynamometry showed poor to fair interrater and poor to excellent intrarater reliability in subjects with and without KOA. Conclusions: Measuring KJPS in multiple test positions using an analogue inclinometer and calculating mean repositioning error is reliable and can be used in clinical practice. We do not recommend the use of the KFS test to clinicians. Further research is required to establish diagnostic accuracy and validity of our KJPS test in larger knee pain populations

Dynamic and static knee alignment at baseline predict structural abnormalities on MRI associated with medial compartment knee osteoarthritis after 2 years

Dynamic and static varus alignment, both, have been reported as risk factors associated with structural progression of knee osteoarthritis. However the association of none of the static and dynamic alignment with structural, clinical, and functional progression associated with knee osteoarthritis has not been assessed yet in a longitudinal study.publisher: Elsevier articletitle: Dynamic and static knee alignment at baseline predict structural abnormalities on MRI associated with medial compartment knee osteoarthritis after 2 years journaltitle: Gait & Posture articlelink: http://dx.doi.org/10.1016/j.gaitpost.2017.05.024 content_type: article copyright: © 2017 Elsevier B.V. All rights reserved.status: publishe

Changes in gait characteristics of women with early and established medial knee osteoarthritis: Results from a 2-years longitudinal study

Despite the large number of cross-sectional studies on gait in subjects with knee osteoarthritis, there are scarcely any longitudinal studies on gait changes in knee osteoarthritis.status: publishe

Varus thrust in women with early medial knee osteoarthritis and its relation with the external knee adduction moment

Varus thrust, defined as an abrupt increase of the knee varus angle during weight-bearing in gait, has been shown to be present in patients with moderate to severe knee osteoarthritis and is considered to be one of the risk factors for progression of symptomatic medial knee osteoarthritis. We evaluated the presence and magnitude of varus thrust and its relation with the Knee Adduction Moment in women with early medial knee osteoarthritis, and compared it to that in a group of controls and in a group of subjects with established medial knee osteoarthritis.publisher: Elsevier articletitle: Varus thrust in women with early medial knee osteoarthritis and its relation with the external knee adduction moment journaltitle: Clinical Biomechanics articlelink: http://dx.doi.org/10.1016/j.clinbiomech.2016.10.006 content_type: article copyright: © 2016 Elsevier Ltd. All rights reserved.status: publishe