Radiation therapy and mode of propagation of non-Hodgkin lymphomas (author's transl)]

Out of a total number of 123 patients with non-Hodgkin lymphomas the result of local radiation therapy from 65 patients with lymphosarcomas or reticulosarcomas stage I or II are reported. In stage I, the tumor still being localized, there are good chances for recovery (3 or 4 years of survival without recurrenced in 75%). Already in stage II the percentages of a three-year survival without recurrences are reduced to 40% with lymphosarcomas and to 19% with recitulosarcomas. This most probably is due to an early, occult, already advanced cancerous spread, not having been recognized. More aggressive diagnostic measures for the staging, therefore, are recommandable. There are significant differences between lymphosarcomas and recitulosarcomas concerning their mode of propagation. Lymphosarcomas prefer the propagation into contiguous lymph node stations. With reticulosarcomas the generalisation to stage IV predominates at the first recurrence. For an improvement of the therapeutic results an irradiation is recommended which encompasses the adjacent lymphatics not yet being involved, the so-called "extended field technic". Early cytostatic therapy in stage II additionally has to be discussed, particularly for reticulosarcomas.     

Time course of satisfaction of search

"Satisfaction of search" (SOS) refers to the effect in which a second lesion remains undetected after detection of another lesion on the same radiograph. The objective of this study was to clarify our understanding of SOS by relating it to total time of inspection and time intervals before, between, and after discovery of lesions. Detection accuracy of native lesions in chest radiographs, before and after the addition of a simulated nodular lesion, was measured for ten observers. Analysis of data from this and a previous experiment showed that average perceptual accuracy of individual receiver operating characteristic curves was significantly reduced with the addition of the nodules. Plots and analyses of search time revealed that, on average, during a typical 46-second inspection of a case, simulated nodules were found at 18 seconds, native abnormalities at 25 seconds, and false positives occurred at 33 seconds. Time needed to find nodules did not depend on whether native lesions were present; time to find native lesions did not change with addition of nodules; and total search time was the same for images with one, two, or no lesions. The detection results show that the SOS effect was obtained, but that interrupting search in order to measure it also diminishes accuracy. Analysis of the time course data relates SOS to perceptual capture and strategic halting of search.     

Long-term outcome of superficialis-to-profundus tendon transfer in patients with clenched fist due to spastic hemiplegia

Background. Spastic hemiplegia is a common feature after stroke, which can result in a clenched fist deformity with secondary hygienic problems and pain. Operative treatment can improve these problems, although literature about its long-term effects is lacking.

Purpose. To determine whether Superficialis-to-Profundus tendon (StP-) transfer procedure leads to permanent improvement of hygiene and reduction of pain in patients with clenched fist due to spastic hemiplegia following stroke.

Method. Patients who underwent a StP-transfer in 2003 – 2005 were evaluated on skin condition, upper extremity joint mobility, resting position and muscle tone and with VAS scores on hygiene maintenance and pain in the hand.

Results. Six patients (mean age 54 years; duration after stroke 10 years) were included. Indications to operate were hygienic problems only (3) or combined with pain (3). The average follow-up period was 19 months. After 6 weeks of post-operative splinting, no standard follow-up was applied. Serious post-operative complications were not reported. At follow-up no hygienic problems were present and pain was decreased in all except one patient. All hands could passively be fully opened. In resting position, flexion was seen in the MCP-joints (60 – 90°). Muscle tone was raised in flexors of the wrist and fingers and m. adductor pollicis (Ashworth 1 – 2). Given the same pre- and post-operative circumstances, all patients would agree to have the surgery over again.

Conclusion. Even 19 months after the StP-transfer for clenched fist, all operated hands could still be fully opened and there was a permanent improvement of hygiene and pain reduction.     

Infliximab partially impairs the anti‐Mycobacterium tuberculosis immune responses of severe psoriasis patients with positive tuberculin skin‐test

Background Infliximab and etarnecept are now widely used for treating severe psoriasis. However, these drugs, especially infliximab, increased the risk of tuberculosis reactivation. Surprisingly, epidemiological data suggest that the tuberculosis rate in patients taking infliximab in São Paulo State, Brazil, is similar to that of some developed, non‐endemic countries. Objective The aim of this study was to better understand the effect of infliximab on Mycobacterium tuberculosis (Mtb) immune responses of psoriasis patients in an endemic setting (Brazil). Methods We evaluated the tuberculosis‐specific immune responses of severe psoriasis patients and healthy individuals, both tuberculin skin test (TST) positive, in the presence/absence of infliximab. Patients had untreated severe psoriasis, no co‐morbidities affecting the immune responses and a TST >10 mm. Healthy TST⁺ (>10 mm) individuals were evaluated in parallel. PBMC cultures from both groups were stimulated with different Mycobacterium tuberculosis (Mtb) antigens (ESAT‐6, 85B and Mtb lysate) and phytohemagglutinin, with or without infliximab (5 μg/mL). Parameters evaluated were TNF‐α, IFN‐γ and IL‐10 secretion by ELISA, overnight IFN‐γ ELISpot and lymphocyte proliferative response (LPR). Results Infliximab almost abolished TNF‐α detection in PBMC supernatants of both groups. It also significantly reduced the LPR to phytohemagglutinin and the Mtb antigens as well as the IFN‐γ levels secreted into day 5 supernatants in both groups. There was no concomitant exaggerated IL‐10 secretion that could account for the decreases in these responses. ELISpot showed that, contrasting with the central‐memory responses above, infliximab did not affect effector‐memory INF‐γ‐releasing T‐cell numbers. Conclusions Infliximab affected some, but not all aspects of the in vitro antituberculosis immune responses tested. The preserved effector‐memory responses, putatively related to exposure to environmental mycobacteria, may help to explain the lower than expected susceptibility to tuberculosis reactivation in our setting.     

The endophytic fungus Piriformospora indica reprograms barley to salt-stress tolerance, disease resistance, and higher yield

Disease resistance strategies are powerful approaches to sustainable agriculture because they reduce chemical input into the environment. Recently, Piriformospora indica, a plant-root-colonizing basidiomycete fungus, has been discovered in the Indian Thar desert and was shown to provide strong growth-promoting activity during its symbiosis with a broad spectrum of plants. Here, we report on the potential of P. indica to induce resistance to fungal diseases and tolerance to salt stress in the monocotyledonous plant barley. The beneficial effect on the defense status is detected in distal leaves, demonstrating a systemic induction of resistance by a root-endophytic fungus. The systemically altered "defense readiness" is associated with an elevated antioxidative capacity due to an activation of the glutathione-ascorbate cycle and results in an overall increase in grain yield. Because P. indica can be easily propagated in the absence of a host plant, we conclude that the fungus could be exploited to increase disease resistance and yield in crop plants.     

Natürlicher Verlauf bei Hüftdysplasie und Operationsergebnisse

Background

The prevalence of hip dysplasia in epidemiological studies ranges from 1–20%. The associated deformity is a risk factor for secondary osteoarthritis (OA) of the hip.

Objective

What is the natural course of hip dysplasia and is it influenced by cofactors? How successful are corrective surgical procedures?

Material and methods

Analysis of published investigations up to 2018 which provide data about the natural course of hip dysplasia and the results of the most important surgical treatment procedures.

Results

The vast majority of published studies confirm a correlation between hip dysplasia and OA. The risk of OA increases with reduced acetabular coverage and severity of instability (subluxation). Long-term survival and functional results after pelvic osteotomies are meanwhile very good, if the procedure is performed in young or middle-aged patients with good congruency of the joints and no relevant OA. Additional deformities (e.?g. cam deformity or femoral torsional malalignment) should be simultaneously addressed and the acetabular fragment needs optimal positioning. Only a few studies with small patient cohorts and short observation times are currently available on the isolated arthroscopic treatment of borderline dysplasia.

Discussion

The importance of hip dysplasia as an established risk factor for secondary OA and the good results of reorientation pelvic osteotomies justify surgical correction when considering the identified indication criteria. Due to a low but relevant potential for complications, surgery should currently not be recommended for asymptomatic patients in adulthood. Potentially relevant cofactors are important for estimation of the natural course as well as the indications for surgical correction.

     

Dendritic cells process synthetic long peptides better than whole protein,improving antigen presentation and T‐cell activation

The efficiency of antigen (Ag) processing by dendritic cells (DCs) is vital for the strength of the ensuing T‐cell responses. Previously, we and others have shown that in comparison to protein vaccines, vaccination with synthetic long peptides (SLPs) has shown more promising (pre‐)clinical results. Here, we studied the unknown mechanisms underlying the observed vaccine efficacy of SLPs. We report an in vitro processing analysis of SLPs for MHC class I and class II presentation by murine DCs and human monocyte‐derived DCs. Compared to protein, SLPs were rapidly and much more efficiently processed by DCs, resulting in an increased presentation to CD4⁺ and CD8⁺ T cells. The mechanism of access to MHC class I loading appeared to differ between the two forms of Ag. Whereas whole soluble protein Ag ended up largely in endolysosomes, SLPs were detected very rapidly outside the endolysosomes after internalization by DCs, followed by proteasome‐ and transporter associated with Ag processing‐dependent MHC class I presentation. Compared to the slower processing route taken by whole protein Ags, our results indicate that the efficient internalization of SLPs, accomplished by DCs but not by B or T cells and characterized by a different and faster intracellular routing, leads to enhanced CD8⁺ T‐cell activation.     

Synthetic Long Peptide Derived from Mycobacterium tuberculosis Latency Antigen Rv1733c Protects against Tuberculosis

Responsible for 9 million new cases of active disease and nearly 2 million deaths each year, tuberculosis (TB) remains a global health threat of overwhelming dimensions. Mycobacterium bovis BCG, the only licensed vaccine available, fails to confer lifelong protection and to prevent reactivation of latent infection. Although 15 new vaccine candidates are now in clinical trials, an effective vaccine against TB remains elusive, and new strategies for vaccination are vital. BCG vaccination fails to induce immunity against Mycobacterium tuberculosis latency antigens. Synthetic long peptides (SLPs) combined with adjuvants have been studied mostly for therapeutic cancer vaccines, yet not for TB, and proved to induce efficient antitumor immunity. This study investigated an SLP derived from Rv1733c, a major M. tuberculosis latency antigen which is highly expressed by “dormant” M. tuberculosis and well recognized by T cells from latently M. tuberculosis-infected individuals. In order to assess its in vivo immunogenicity and protective capacity, Rv1733c SLP in CpG was administered to HLA-DR3 transgenic mice. Immunization with Rv1733c SLP elicited gamma interferon-positive/tumor necrosis factor-positive (IFN-γ⁺/TNF⁺) and IFN-γ⁺ CD4⁺ T cells and Rv1733c-specific antibodies and led to a significant reduction in the bacterial load in the lungs of M. tuberculosis-challenged mice. This was observed both in a pre- and in a post-M. tuberculosis challenge setting. Moreover, Rv1733c SLP immunization significantly boosted the protective efficacy of BCG, demonstrating the potential of M. tuberculosis latency antigens to improve BCG efficacy. These data suggest a promising role for M. tuberculosis latency antigen Rv1733c-derived SLPs as a novel TB vaccine approach, both in a prophylactic and in a postinfection setting.