Immunotherapy of Crohn's disease.

Although the initiating events of Crohn's disease are unknown, models of experimental colitis have provided new insights in the immunologically mediated pathways of mucosal inflammation. In Crohn's disease activated mucosal T lymphocytes produce proinflammatory cytokines within the mucosal compartment. With this understanding, there has been a shift in past years from the use of unspecific anti-inflammatory agents (corticosteroids, aminosalicylates) to the use of immunomodulatory drugs (azathioprine, methotrexate). Moreover, novel strategies have been designed for specific targets in Crohn's disease, in particular T lymphocytes and cytokines. In an open label study treatment of steroid-refractory Crohn's disease with anti- CD4+ antibodies was well tolerated and showed clinical benefit. However, a sustained depletion of the CD4+ cells precluded further clinical trials. In controlled clinical studies, anti-tumour necrosis factor (TNF-alpha) antibodies induced complete remissions and few side effects were observed. One study suggested efficacy in active Crohn's disease of recombinant interleukin-10. Long term treatment studies will have to answer questions about the indications for use, benefit and toxicity. Altogether, these results hold promise for future management of Crohn's disease, where disease-modifying interventions and strategies that effectively maintain disease remission will play a key role

Infliximab treatment induces apoptosis of lamina propria T lymphocytes in Crohn's disease

Background and aims: Treatment with infliximab induces remission in about 70% of patients with steroid refractory Crohn's disease. Because Crohn's disease is considered to be mediated by uncontrolled activation of mucosal T lymphocytes, we hypothesised that infliximab could induce apoptosis of T lymphocytes. Methods: Induction of apoptosis in vivo was studied in 10 patients with therapy refractory Crohn's disease. In vitro, resting or stimulated Jurkat T cells were incubated with infliximab. Results: Infusion of infliximab (5 mg/kg) in steroid refractory patients with Crohn's disease induced a clinical response in 9/10 patients but did not influence expression of activation markers, homing receptors, memory cells, Fas expression, or Bax/Bcl-2 expression on peripheral blood T lymphocytes. In contrast, a significant increase in CD3 and TUNEL positive cells within colonic biopsies was detected 24 hours after infusion of infliximab, suggesting that infliximab stimulates apoptosis of activated T lymphocytes but not of resting T cells. To test this hypothesis, the effects of infliximab on Jurkat T cells were investigated. We observed that infliximab induced apoptosis and an increase in the Bax/Bcl-2 ratio of CD3/CD28 stimulated Jurkat T cells but not of unstimulated Jurkat cells. Conclusions: Our data indicate that infliximab treatment causes a rapid and specific increase in apoptosis of T lymphocytes in the gut mucosa. These findings may explain the rapid and sustained therapeutic effects of infliximab in Crohn's disease

Effect of exercise after a deep venous thrombosis:A systematic review

Post-thrombotic syndrome (PTS) is a common complication after deep vein thrombosis (DVT) and has a major impact on physical symptoms, quality of life (QoL) and economic costs. Relatively simple lifestyle interventions as physical exercise might reduce PTS severity and increase QoL. To evaluate the direct and long-term effects of physical activity in patients with an acute or previous DVT. We conducted a systematic review through an additional search from 2007 up to March 2022, to complement the comprehensive systematic review of Kahn et al. Articles evaluating the effect of exercise after a DVT including symptoms, QoL and the incidence and severity of PTS, were included. Quality of the studies was assessed using a GRADE-like checklist and results were reported according to the PRISMA Statement. Ten studies were included, seven randomized controlled trials and three cohort studies. We identified three types of physical activity based on timing and duration; (1) early mobilisation in the acute phase of the DVT; (2) short duration exercise 1 year after DVT and (3) prolonged exercise during follow-up after a previous DVT. Early mobilisation showed improvement in QoL and pain reduction and after 2 years it resulted in a significant reduction of PTS severity. Prolonged supervised exercise resulted in improvement of QoL. In addition, positive effects on symptoms of venous insufficiency and muscle functions were observed. None of the included studies reported an increased risk of PTS or worsening of symptoms due to physical activity. Physical exercise after a DVT is safe, improves QoL, reduces pain and decreases PTS severity. Lifestyle intervention such as guided individualized training programs can be a useful supplementary therapy for patients after a DVT or for PTS patients. Optimal training programs may be identified by further studies that improve patient-oriented outcomes for both adults and children after a DVT.</p

High salt meals in staff canteens of salt policy makers: observational study

Objective To assess the salt content of hot meals served at the institutions of salt policy makers in the Netherlands

Student Outcomes from the Collective Design and Delivery of Culturally Relevant Engineering Outreach Curricula in Rural and Appalachian Middle Schools

Middle school is a pivotal time for career choice, and research is rich with studies on how students perceive engineering, as well as corresponding intervention strategies to introduce younger students to engineering and inform their conceptions of engineering. Unfortunately, such interventions are typically not designed in culturally relevant ways. Consequently, there continues to be a lack of students entering engineering and a low level of diverse candidates for this profession. The purpose of this study was to explore how students in rural and Appalachian Virginia conceive of engineering before and after engagement with culturally relevant hands-on activities in the classroom. We used student responses to the Draw an Engineer Test (DAET), consisting of a drawing and several open-ended prompts administered before and after the set of engagements, to answer our research questions related to changes in students’ conceptions of engineering. We used this study to develop recommendations for teachers for the use of such engineering engagement practices and how to best assess their outcomes, including looking at the practicality of the DAET. Overall, we found evidence that our classroom engagements positively influenced students’ conceptions of engineering in these settings

Neonatal sepsis and transient immunodeficiency: Potential for novel immunoglobulin therapies?

Neonates, especially preterm neonates, have the highest risk of sepsis of all age groups. Transient immaturity of the neonatal immune system is an important risk factor. Neonates suffer from hypogammaglobulinemia as nor IgA nor IgM is transferred over the placenta and IgG is only transferred over the placenta late in gestation. In addition, neutrophil numbers and complement function are also decreased. This mini-review focuses on strategies to improve neonatal host-defense. Both clinical and preclinical studies have attempted to boost neonatal immunity to lower the incidence of sepsis and improve outcome. Recent advances in the development of (monoclonal) antibodies show promising results in preclinical studies but have yet to be tested in clinical trials. Strategies to increase complement activity seem efficient in vitro but potential disadvantages such as hyperinflammation have held back further clinical development. Increase of neutrophil numbers has been tested extensively in clinical trials but failed to show improvement in mortality. Future research should focus on clinical applicability of promising new prevention strategies for neonatal sepsis

Assessing health-related quality of life using the Wound-QoL-17 and the Wound-QoL-14—Results of the cross-sectional European HAQOL study using item response theory

For assessing health-related quality of life in patients with chronic wounds, the Wound-QoL questionnaire has been developed. Two different versions exist: the Wound-QoL-17 and the Wound-QoL-14. For international and cross-cultural comparisons, it is necessary to demonstrate psychometric properties in an international study. Therefore, the aim of this study was to test both questionnaires in a European sample, using item response theory (IRT). Participants were recruited in eight European countries. Item characteristic curves (ICC), item information curves (IIC) and differential item functioning (DIF) were calculated. In both questionnaires, ICCs for most items were well-ordered and sufficiently distinct. For items, in which adjacent response categories were not sufficiently distinct, response options were merged. IICs showed that items on sleep and on pain, on worries as well as on day-to-day and leisure activities had considerably high informational value. In the Wound-QoL-14, the item on social activities showed DIFs regarding the country and age. The same applied for the Wound-QoL-17, in which also the item on stairs showed DIFs regarding age. Our study showed comparable results across both versions of the Wound-QoL. We established a new scoring method, which could be applied in international research projects. For clinical practice, the original scoring can be maintained.</p

What Works When Treating Granulomatous Disease in Genetically Undefined CVID? A Systematic Review

Background: Granulomatous disease is reported in at least 8–20% of patients with common variable immunodeficiency (CVID). Granulomatous disease mainly affects the lungs, and is associated with significantly higher morbidity and mortality. In half of patients with granulomatous disease, extrapulmonary manifestations are found, affecting e.g. skin, liver, and lymph nodes. In literature various therapies have been reported, with varying effects on remission of granulomas and related clinical symptoms. However, consensus recommendations for optimal management of extrapulmonary granulomatous disease are lacking. Objective: To present a literature overview of the efficacy of currently described therapies for extrapulmonary granulomatous disease in CVID (CVID+EGD), compared to known treatment regimens for pulmonary granulomatous disease in CVID (CVID+PGD). Methods: The following databases were searched: Embase, Medline (Ovid), Web-of-Science Core Collection, Cochrane Central, and Google Scholar. Inclusion criteria were 1) CVID patients with granulomatous disease, 2) treatment for granulomatous disease reported, and 3) outcome of treatment reported. Patient characteristics, localization of granuloma, treatment, and association with remission of granulomatous disease were extracted from articles. Results: We identified 64 articles presenting 95 CVID patients with granulomatous disease, wherein 117 different treatment courses were described. Steroid monotherapy was most frequently described in CVID+EGD (21 out of 53 treatment courses) and resulted in remission in 85.7% of cases. In CVID+PGD steroid monotherapy was described in 15 out of 64 treatment courses, and was associated with remission in 66.7% of cases. Infliximab was reported in CVID+EGD in six out of 53 treatment courses and was mostly used in granulomatous disease affecting the skin (four out of six cases). All patients (n = 9) treated with anti-TNF-α therapies (infliximab and etanercept) showed remission of extrapulmonary granulomatous disease. Rituximab with or without azathioprine was rarely used for CVID+EGD, but frequently used in CVID+PGD where it was associated with remission of granulomatous disease in 94.4% (17 of 18 treatment courses). Conclusion: Although the number of CVID+EGD patients was limited, data indicate that steroid monotherapy often results in remission, and that anti-TNF-α treatment is effective for granulomatous disease affecting the skin. Also, rituximab with or without azathioprine was mainly described in CVID+PGD, and only in few cases of CVID+EGD