Generation of donor-specific Tr1 cells to be used after kidney transplantation and definition of the timing of their in vivo infusion in the presence of immunosuppression

Background: Operational tolerance is an alternative to lifelong immunosuppression after transplantation. One strategy to achieve tolerance is by T regulatory cells. Safety and feasibility of a T regulatory type 1 (Tr1)-cell-based therapy to prevent graft versus host disease in patients with hematological malignancies has been already proven. We are now planning to perform a Tr1-cell-based therapy after kidney transplantation. Methods: Upon tailoring the lab-grade protocol to patients on dialysis, aims of the current work were to develop a clinical-grade compatible protocol to generate a donor-specific Tr1-cell-enriched medicinal product (named T10 cells) and to test the Tr1-cell sensitivity to standard immunosuppression in vivo to define the best timing of cell infusion. Results: We developed a medicinal product that was enriched in Tr1 cells, anergic to donor-cell stimulation, able to suppress proliferation upon donor- but not third-party stimulation in vitro, and stable upon cryopreservation. The protocol was reproducible upon up scaling to leukapheresis from patients on dialysis and was effective in yielding the expected number of T10 cells necessary for the planned infusions. The tolerogenic gene signature of circulating Tr1 cells was minimally compromised in kidney transplant recipients under standard immunosuppression and it eventually started to recover 36weeks post-transplantation, providing rationale for selecting the timings of the cell infusions. Conclusions: These data provide solid ground for proceeding with the trial and establish robust rationale for defining the correct timing of cell infusion during concomitant immunosuppressive treatment

INDEPENDENT PATIENT DATA META-ANALYSIS OF PROPHYLACTIC MESH PLACEMENT FOR INCISIONAL HERNIA PREVENTION (AFTER ABDOMINAL AORTIC ANEURYSM SURGERY): A COLLABORATIVE EUROPEAN HERNIA SOCIETY PROJECT (I-PREVENT-AAA)

peer reviewedAbstract Introduction Incisional hernia (IH) is a prevalent and potentially dangerous complication after abdominal surgery, especially in high-risk groups. Prophylactic mesh augmentation (PMA) of the abdominal wall has been studied as a preventive measure for IH-formation, but strong recommendations are lacking. Our primary aim was to evaluate the effectiveness of the use of PMA after open abdominal aortic aneurysm (AAA)-surgery for the prevention of IH by performing an individual patient-data meta-analysis (IPDMA). Secondary aims include evaluation of postoperative complications, and identification of subgroups that benefit most from PMA. Methods A systematic literature search to identify Randomized-Controlled Trials (RCTs) that compare PMA after open AAA surgery to primary suturing (PS), was conducted. Lead authors of eligible studies were asked to share individual participant-data. A one-stage analysis was performed and Cox-regression analyses were used to assess time-to-event outcomes. Results Five RCTs were included in our IPDMA, which resulted in 488 analysed patients. PMA resulted in a Hazard Ratio (HR) of 0.25 (95%CI 0.12–0.50) for the reduction of IH occurrence. No significant differences were present when comparing onlay with sublay mesh (HR 0.56, 95%CI 0.24–1.28). Patients treated with an onlay mesh had significantly more seroma formation in comparison to PS (OR 22.1,95%CI 1.88–259.58) and patients with a sublay mesh had fewer re-operations than those treated with PS (OR 0.47,95%CI 0.43–0.51). Subgroup analyses showed the effectiveness of PMA in various subgroups (e.g., high BMI patients). Conclusion PMA after open AAA surgery is an effective measure to reduce IH formation in a wide variety of patients

Appendectomy during the COVID-19 pandemic in Italy: a multicenter ambispective cohort study by the Italian Society of Endoscopic Surgery and new technologies (the CRAC study)

Major surgical societies advised using non-operative management of appendicitis and suggested against laparoscopy during the COVID-19 pandemic. The hypothesis is that a significant reduction in the number of emergent appendectomies was observed during the pandemic, restricted to complex cases. The study aimed to analyse emergent surgical appendectomies during pandemic on a national basis and compare it to the same period of the previous year. This is a multicentre, retrospective, observational study investigating the outcomes of patients undergoing emergent appendectomy in March-April 2019 vs March-April 2020. The primary outcome was the number of appendectomies performed, classified according to the American Association for the Surgery of Trauma (AAST) score. Secondary outcomes were the type of surgical technique employed (laparoscopic vs open) and the complication rates. One thousand five hundred forty one patients with acute appendicitis underwent surgery during the two study periods. 1337 (86.8%) patients met the inclusion criteria: 546 (40.8%) patients underwent surgery for acute appendicitis in 2020 and 791 (59.2%) in 2019. According to AAST, patients with complicated appendicitis operated in 2019 were 30.3% vs 39.9% in 2020 (p = 0.001). We observed an increase in the number of post-operative complications in 2020 (15.9%) compared to 2019 (9.6%) (p < 0.001). The following determinants increased the likelihood of complication occurrence: undergoing surgery during 2020 (+ 67%), the increase of a unit in the AAST score (+ 26%), surgery performed > 24 h after admission (+ 58%), open surgery (+ 112%) and conversion to open surgery (+ 166%). In Italian hospitals, in March and April 2020, the number of appendectomies has drastically dropped. During the first pandemic wave, patients undergoing surgery were more frequently affected by more severe appendicitis than the previous year's timeframe and experienced a higher number of complications. Trial registration number and date: Research Registry ID 5789, May 7th, 202

Mobilità multiscalare e territorio multimodale al centro del Piano Territoriale degli Orari

Esiti analitica derivati dalla recente esperienza del Piano Territoriale degli Orari del Comune di Bergamo: fenomeni di mobilità, usi del territorio, accessibilità ai servizi nello spazio-tempo del sistema urbano

Barilla

In un contesto economico incerto, in uno scenario internazionale sempre più competitivo, diventa estremamente importante rafforzare il primato del Made in Italy. Oltre a investimenti su brand e qualità dei prodotti, le aziende devono utilizzare la leva dell'innovazione dei processi operativi. Il libro documenta - attraverso casi aziendali espressione dell’eccellenza italiana - il contributo dei processi di Supply Chain Management alla competitività delle aziende e identifica le aree di innovazione in grado di accrescere il differenziale competitivo basato su riconoscibilità e qualità. Emerge in modo univoco che l’adozione di prassi di integrazione dei processi e lo sviluppo di logiche di collaborazione con gli attori a monte e a valle della supply chain consente di consolidare la competitività in modo significativo. Lo sviluppo di relazioni inter-organizzative - finalizzato alla ricerca di razionalizzazioni operative di breve termine, ma anche di soluzioni innovative per favorire la riorganizzazione delle modalità di gestione dei processi - permette di conseguire miglioramenti sensibili sul fronte delle prestazioni sia di carattere economico-finanziario sia di natura operativ