Unraveling the role of ectopic thymic tissue in patients undergoing thymectomy for myasthenia gravis

Extended thymectomy has been considered the goal of surgery for myasthenia gravis (MG) mainly due to the existence of ectopic thymic tissue. Recently, ectopic thymic tissue has attracted increasing attention in patients with MG following thymectomy. However, the specific role of ectopic thymic tissue in patients with MG is still under debate. A systematic search of the literature was performed on PubMed and Medline according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISM) statement. Studies evaluating the rate of ectopic thymic tissue in patients with MG with or without thymoma were included. Extraction was performed for all eligible studies and the rate of ectopic thymic tissue at common locations was calculated. Eighteen out of fifty-nine studies were eligible for inclusion, of which ten studies reported the common locations of ectopic thymic tissue in mediastinal fat. Of these ten studies, the presence of ectopic thymic tissue was investigated in different anatomical locations in 882 patients, of whom, 509 patients (58%) have at least one positive location with the most common ones being anterior mediastinal fat, pericardiophrenic angles, aortopulmonary window, cervical region (pretracheal fat) and lateral to phrenic nerves. On the other hand, nine studies analyzed the influence of the presence of ectopic thymic tissue on the clinical outcomes of MG patients. Of these, six found that the presence of ectopic thymic tissue in MG patients is a significant predictor of poor outcome after thymectomy, however, the other three did not find a significance. Altogether, ectopic thymic tissue is likely to present in more than a half of patients undergoing thymectomy for MG. Besides, MG patients who have ectopic thymic tissue after thymectomy do not seem to have as good outcome as those who have not

Thrombus in the Non-aneurysmal, Non-atherosclerotic Descending Thoracic Aorta – An Unusual Source of Arterial Embolism

AbstractIntroductionMural thrombus of the thoracic aorta is a rare clinical finding in the absence of aneurysm or atherosclerosis.MethodsThe medical records of all patients diagnosed with a thrombus of a non-aneurysmatic and non-atherosclerotic descending thoracic aorta (NAADTA) and treated by the senior author between 04/1997 and 04/2010 were reviewed.ResultsEight patients with mural thrombus of the NAADTA were identified. Arterial embolism was the main clinical finding in all cases and involved the lower extremities (n = 6), mesenteric (n = 3) or renal arteries (n = 2). Hypercoagulable disorders were present in 3 cases and a concurrent malignancy in another 3. Two patients underwent open surgery while 4 patients were treated conservatively with anticoagulation. Of the remaining 2 patients, one was treated with a thoracic stent-graft and aorto-biiliac bypass and the other one with transfemoral thrombectomy. Technical success was achieved in all surgical cases and thrombus resolution or stable disease in the conservative management group. No thrombus recurrence was observed during a mean follow-up of 49 months.ConclusionThe management of mural thrombus in NAADTA represents a challenge, especially in case of malignant disease or hypercoagulable disorder as a potential underlying pathology and should be individualized. Although no consensus exists in the literature, therapeutic anticoagulation is proposed as first-line therapy. The indication for surgical intervention results from contraindication to anticoagulation, mobile thrombus or recurrent embolism. Whenever possible, endovascular therapy should be preferred

Transpiration of grapevines and co-habitating cover crop and weed species in a vineyard. A “snapshot” at diurnal trends

The objective of this study was to quantify transpiration rates of two cover crops, Festuca rubra subsp. rubra  (red fescue) and Medicago lupulina (black medick) and 4 weeds, Chenopodium album (fat hen), Cirsium arvense (creeping thistle), Malva neglecta (common mallow) and Taraxacum officinale (dandelion) occurring in a mixed stand in a commercial steep-slope, North-South oriented vineyard as compared to vines, cv. Riesling near Johannisberg (Rheingau), Germany. Leaf transpiration (E) was measured directly on the cover crop and weed species with a portable gas exchange measurement system. Grapevine transpiration was measured concomitantly using custommade Granier-type xylem sap flow gauges. Measurements were conducted on two days in August (15th and 22nd) in 2001 under hot and sunny conditions. All herbaceous species presented a similar diurnal pattern of E, with low values in the morning and afternoon and peak values between 12 and 15 h. In contrast E of grapevines peaked mid-morning (between 8 and 10 h) remained relatively stable until mid-afternoon (16 h) before decreasing continuously until darkness. Significant differences in E between the herbaceous species were observed throughout the day. In general transpiration rates were highest for M. neglecta and lowest for C. arvense, T. officinale and F. rubra subsp. rubra. We estimated the projected leaf area indices (leaf area per surface area covered) for each species and calculated possible transpiration rates for pure stands assuming that all leaves were well exposed. Potential transpiration rates ranged from about 1 mm d-1 (one l m-2 of soil surface) for F. rubra subsp. rubra to = 5 mm d-1 for M. neglecta as compared to only 0.9 mm d-1 for grapevine. These results underline the importance of appropriate cover crop species and the control of some weed species with respect to water use.

Off-label use in germany - a current appraisal of gynaecologic university departments

<p>Abstract</p> <p>Objective</p> <p>The off-label use, referring to the applicability of pharmaceutical drugs beyond the submitted and from the Federal Institute for Drugs and Medical Devices (BfArM, Bundesamt für Arzneimittel und Medizinprodukte) certified and approved administration, is the subject of controversial discussions. the application can be considered in case of severe illness - if no therapeutic alternatives are available - or it exists as a founded perspective for achieving therapeutic success.</p> <p>Methods</p> <p>A latitudinal study for evaluating the application of off-label use supplements was performed at 43 German university and academic teaching hospitals. Five doctors at each hospital applied off-label pharmaceutical drugs and were called upon to share their personal experience to the application of those medications.</p> <p>Results</p> <p>75 (35%) questionnaires were returned out of 22 (51%) medical centres with 215 contacted physicians. Off-label use was common for 65 (91%) of the physicians. Only 9% of them obviate the application of off-label drugs. About a half of the medication is related to application in obstetrics (54%) and in most cases on an every day basis. Uterotonics were the most commonly used off-label medications (34%). The main part of information about off-label use is obtained from personal information of colleagues (66%) and personal experience (58%). 34% of physicians think that off label use is risky. Interestingly, the view about off label use of medication varies considerably among physicians from various hospitals.</p> <p>Conclusions</p> <p>The application of off-label pharmaceutical drugs in Germany seems to be a well established practice. More than 90% of participators of our trial use at least one medication outside the administration. This includes particularly prostaglandins, anti-hyper-tonic therapeutics and chemotherapeutics.</p

Clonal expansion and epigenetic inheritance of long-lasting NK cell memory

Clonal expansion of cells with somatically diversified receptors and their long-term maintenance as memory cells is a hallmark of adaptive immunity. Here, we studied pathogen-specific adaptation within the innate immune system, tracking natural killer (NK) cell memory to human cytomegalovirus (HCMV) infection. Leveraging single-cell multiomic maps of ex vivo NK cells and somatic mitochondrial DNA mutations as endogenous barcodes, we reveal substantial clonal expansion of adaptive NK cells in HCMV(+) individuals. NK cell clonotypes were characterized by a convergent inflammatory memory signature enriched for AP1 motifs superimposed on a private set of clone-specific accessible chromatin regions. NK cell clones were stably maintained in specific epigenetic states over time, revealing that clonal inheritance of chromatin accessibility shapes the epigenetic memory repertoire. Together, we identify clonal expansion and persistence within the human innate immune system, suggesting that these mechanisms have evolved independent of antigen-receptor diversification

GATA3-driven Th2 responses inhibit TGF-beta1-induced FOXP3 expression and the formation of regulatory T cells.

Transcription factors act in concert to induce lineage commitment towards Th1, Th2, or T regulatory (Treg) cells, and their counter-regulatory mechanisms were shown to be critical for polarization between Th1 and Th2 phenotypes. FOXP3 is an essential transcription factor for natural, thymus-derived (nTreg) and inducible Treg (iTreg) commitment; however, the mechanisms regulating its expression are as yet unknown. We describe a mechanism controlling iTreg polarization, which is overruled by the Th2 differentiation pathway. We demonstrated that interleukin 4 (IL-4) present at the time of T cell priming inhibits FOXP3. This inhibitory mechanism was also confirmed in Th2 cells and in T cells of transgenic mice overexpressing GATA-3 in T cells, which are shown to be deficient in transforming growth factor (TGF)-beta-mediated FOXP3 induction. This inhibition is mediated by direct binding of GATA3 to the FOXP3 promoter, which represses its transactivation process. Therefore, this study provides a new understanding of tolerance development, controlled by a type 2 immune response. IL-4 treatment in mice reduces iTreg cell frequency, highlighting that therapeutic approaches that target IL-4 or GATA3 might provide new preventive strategies facilitating tolerance induction particularly in Th2-mediated diseases, such as allergy