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The European Forum for Research and Education in Allergy and Airways diseases (EUFOREA) organized its bi-annual forum EUFOREUM in Berlin in November 2023. The aim of EUFOREUM 2023 was to highlight pediatric action plans for prevention and optimizing care for type 2 inflammatory conditions starting in childhood, with a focus on early-stage diagnosis, ensuring neither under- nor overdiagnosis, optimal care, and suggestions for improvement of care. EUFOREA is an international not-for-profit organization forming an alliance of all stakeholders dedicated to reducing the prevalence and burden of chronic respiratory diseases through the implementation of optimal patient care via educational, research, and advocacy activities. The inclusive and multidisciplinary approach of EUFOREA was reflected in the keynote lectures and faculty of the virtual EUFOREUM 2023 (www.euforea.eu/euforeum) coming from the pediatric, allergology, pulmonology, ENT, dermatology, primary health care fields and patients around the central theme of type 2 inflammation. As most type 2 inflammatory conditions may start in childhood or adolescence, and most children have type 2 inflammation when suffering from a respiratory or skin disease, the moment has come to raise the bar of ambitions of care, including prevention, remission and disease modification at an early stage. The current report provides a comprehensive overview of key statements by the faculty of the EUFOREUM 2023 and the ambitions of EUFOREA allowing all stakeholders in the respiratory field to be updated and ready to join forces in Europe and beyond., (© 2024 The Author(s). Pediatric Allergy and Immunology published by European Academy of Allergy and Clinical Immunology and John Wiley & Sons Ltd.)

Angiogenesis and endothelial activation and dysfunction have been associated with acute graft-vs.-host disease (aGVHD), pointing to the endothelium as a potential target for pharmacological intervention. Defibrotide (DF) is a drug with an endothelium-protective effect that has been approved for the treatment of veno-occlusive disease/sinusoidal obstruction syndrome after allogeneic hematopoietic cell transplantation. Clinical data suggest that DF also reduces the incidence of aGVHD; however, the mechanisms of DF-mediated aGVHD regulation have not been examined. To investigate possible DF-mediated prophylactic and therapeutic mechanisms in aGVHD, we performed in vitro studies using endothelial cell (EC) lines. We found that DF significantly and dose-dependently suppressed EC proliferation and notably reduced their ability to form vascular tubes in Matrigel. To explore whether DF administered prophylactically or therapeutically has a significant effect on aGVHD endothelial dysfunction, ECs were exposed to media containing sera from patients with aGVHD ( n = 22) in the absence or presence of DF and from patients that did not develop aGVHD ( n = 13). ECs upregulated adhesion molecules (vascular cell adhesion molecule 1, intercellular adhesion molecule 1), the adherence junction protein VE-cadherin, von Willebrand factor (VWF), and Akt phosphorylation in response to aGVHD sera. These responses were suppressed upon treatment with DF. In summary, DF inhibits vascular angiogenesis and endothelial activation induced by sera from aGVHD patients. Our results support the view that DF has notable positive effects on endothelial biology during aGVHD., (Copyright © 2019 Martinez-Sanchez, Hamelmann, Palomo, Mir, Moreno-Castaño, Torramade, Rovira, Escolar, Cordes, Kalupa, Mertlitz, Riesner, Carreras, Penack and Diaz-Ricart.)

Controversial results have been reported regarding the importance of the duodenal food passage after total gastrectomy. There are a number of experimental and clinical studies showing an advantage for the jejunal interposition between esophagus and duodenum. Others favor the Roux-en-Y reconstruction, as it is technically less demanding. The purpose of this study was the randomized comparison between two major reconstruction principles after total gastrectomy for gastric cancer (i.e., jejunal interposition with pouch versus Roux-en-Y pouch reconstruction). A group of 120 patients with gastric cancer were randomized and operated on during a 5-year period according to standardized operative protocols, using either a jejunal interposition with pouch (JIP) or the Roux-en-Y reconstruction with pouch (RYP). Endpoints of this study were operation time, intra- and postoperative problems and complications, patients' body weight, functional assessment, and quality of life. Of the 120 patients, 14 had to be withdrawn during the operation because only the Roux-en-Y reconstruction was technically possible. Finally, 53 patients with JIP were compared with 53 patients with RYP for the perioperative course. There were no significant differences between the two procedures (RYP and JIP) regarding complications (24.5% and 26.4%, respectively), mortality (3.8% and 1.9%, respectively), and operation time (4.35 hours and 4.40 hours, respectively). For long-term functional comparison 46 (RYP, n = 26; JIP, n = 20) patients were without recurrence after 3 years of survival. Comparison of body weight, Visick scoring, and the Spitzer Index also did not reveal any significant difference between the two operation methods.(ABSTRACT TRUNCATED AT 250 WORDS)

Extensive small bowel resection may become necessary for several reasons in children and adults. The only causal therapy of short bowel syndrome is small bowel transplantation. So far severe immunological problems have caused deleterious results despite technically successful transplantation. A clinical case of small bowel transplantation in a child is reported. The 3-year-old boy had been operated on for volvulus which had led to nearly total gangrene of the whole small bowel. Finally, only 4 cm of jejunum could be saved. Total parenteral nutrition (TPN) therefore became necessary. Small bowel transplantation was carried out with the mother as donor; transplantation technique is described in detail. Postoperative immunosuppression was performed by administration of cyclosporin A and prednisolone. Because of graft rejection, the graft had to be removed on the 12th postoperative day. At present, the child is well and on TPN again. This case shows that small bowel transplantation by living related organ donation is technically possible without impairment of the donor's quality of life. Further experimental and clinical work should be encouraged.

Heterotopic auxiliary liver transplantations were performed in rats using the method of Hess et. al. [6]. Oxygen pressure of liver tissue was measured with a Pt-surface electrode of Kessler and Lübbers [10]. After ligation of the hepatic artery, liver tissue PO2 decreased and remained low during further preparation. Only two of the seven lobes of the rat liver (= 30% of the parenchyma) were used as a graft. After revascularization and application of a gelatine plasma substitute, tissue PO2 of the graft increased to values of normal rat liver, although the graft was supplied with portal blood only. We suggest that one reason for this is the increase of portal perfusion rate, for the whole amount of portal blood perfuses only 30% of liver parenchyma. In the first month after transplantation PO2 of the graft parenchyma was low, but increased continually in the following months, reaching PO2 values of normal rat livers after 1 year.

A fatal case of overwhelming postsplenectomy pneumococcal sepsis is presented occurring in a 37-year-old female 11 years after removal of the spleen because of traumatic rupture. The patient died 11 h after admission to hospital and about 32 h after sudden onset of illness. At necropsy splenic tissue, splenosis, disseminated intravascular coagulation, and thrombi within the arterioles consisting of gram-positive cocci and adrenal hemorrhage were found. The clinical, laboratory, and postmortem findings are described. Reports had been published of 41 other cases of overwhelming postsplenectomy infection (OPSI) in patients aged 20 years or more, but only three of these cases of OPSI syndrome occurred in spite of remaining splenic tissue. The longest interval between extirpation of spleen and subsequent sepsis was 42 years, indicating a small but lifelong risk of severe infection in asplenic patients. In view of the literature, the role of spleen in infection defence, the splenic function in blood clearance, and the prevention of postsplenectomy infections by antibiotic prophylaxis, pneumococcal vaccine, and reimplantation of autochthonous splenic tissue or infrared contact coagulation are discussed.

Using an immunohistochemical attempt to immunostain thyroid related autoantibodies, 30 specimens of autonomous adenomas of the thyroid were investigated. Twelve out of 23 inflammatory infiltrates surrounding the 'hot' nodules contained plasma cells, which gave a positive staining reaction for thyroid related autoantibodies. Seven adenomas showed no significant lymphoplasmacellular infiltration. It is concluded that this phenomenon might be due to an autoimmune pathogenesis in a part of patients with autonomous adenomas, indicating that there is no sharp line between autoimmune and non autoimmune thyroid disorder.

Ten thyroid specimens from patients with Graves' disease were investigated immunohistologically with respect to the localisation of thyrotropin (TSH) receptor related autoantibodies. After conventional preparation of formalin-fixed and paraffin-embedded thyroid slices for immunostaining, 3-5 micron tissue sections were incubated with a porcine thyrotropin receptor containing membrane preparation (pTSH-R). The TSH receptor containing membrane fragments bound to the thyroid tissue were revealed with a slightly modified unlabelled PAP technique according to Sternberger, using an antiserum to pTSH-R obtained from immunized rabbits. This technique resulted in a staining of a considerable portion of plasma cells within the lymphoplasmacellular infiltrates of all the Graves thyroids. No staining occurred if for negative control either pTSH-R or its antiserum from rabbit was omitted. In addition, the staining reaction was markedly reduced by pretreatment of pTSH-R with serum from patients with Graves' disease in order to occupy its binding sites for autoantibodies prior to the staining procedure. It is concluded that the staining of the intrathyroidal plasma cells is due to their synthesis of autoantibodies directed against TSH receptor related structures of thyroid epithelia. The results are in keeping with the concept that the thyroid as the target organ itself is the site of autoantibody synthesis in Graves' disease.

Histamine release by modified gelatin (Haemaccel) and dextran (Macrodex) has been demonstrated in volunteers by direct and indirect methods. In a pilot study of Haemaccel, histamine release was observed in six of seven volunteers. The highest plasma histamine concentration was 4.8 ng/ml, the lowest 1.7 ng/ml: two of the subjects showed slight allergic reactions. Using Haemaccel batch 2551, 10 out of 12 subjects reacted to the rapid infusion of Haemaccel with increased plasma histamine concentrations, whereas none reacted to Ringer's solution. None of the 10 subjects had an allergic reaction, but an increase in gastric secretion was observed in eight. Changes in the venous basophil granulocyte count were found in both those who reacted and those who did not react to Haemaccel. After the rapid infusion of dextran the highest plasma histamine concentration was 5.0 ng/ml, the lowest 1.3 ng/ml. The withdrawal of blood had no influence on plasma histamine concentration. The incidences of histamine release produced by Haemaccel varied with different batches. Thus, it seems unlikely that immunological mechanisms are principally responsible. Nine instances of allergic and anaphylactoid reactions to plasma substitutes have been reported, seven after Haemaccel infusion, and two after dextran administration. One of the patients who received dextran died. Histamine release was always associated with Haemaccel infusion and corresponded in extent to the clinical symptoms observed, but there was no significant histamine release associated with the reactions to dextran.