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

Neutron personal dosimetry using polyallyl diglycol carbonate (PADC): Current status, best practices and proposed research

The objective of this paper is to provide an overview of the current status in neutron personal dosimetry based on poly allyl diglycol carbonate (PADC), also commonly known by the commercial name CR-39, to summarize the best practices in the field, and to point future research directions. An overview of the fundamentals of the technique is given, including a discussion on the PADC material, main parameters and characteristics, practical considerations, dosimetry approaches, and relevant standards. This work also summarizes the best practices adopted by individual monitoring services (IMSs) and discusses the research needed to improve the performance of this type of neutron dosimetry technique, as well as the challenges that make progress difficult. This work is based on the knowledge and experience of several laboratories and investigators and is part of the activities of the European Radiation Dosimetry Group (EURADOS) Working Group 2 – Harmonization of Individual Monitoring in Europe (WG2)

Defining the characteristics of certified hernia centers in Italy: The Italian society of hernia and abdominal wall surgery workgroup consensus on systematic reviews of the best available evidences

Background: The terms “Hernia Center” (HC) and Hernia Surgeon” (HS) have gained more and more popularity in recent years. Nevertheless, there is lack of protocols and methods for certification of their activities and results. The Italian Society of Hernia and Abdominal Wall Surgery proposes a method for different levels of certification. Methods: The national board created a commission, with the task to define principles and structure of an accreditation program. The discussion of each topic was preceded by a Systematic Review, according to PRISMA Guidelines and Methodology. In case of lack or inadequate data from literature, the parameter was fixed trough a Commission discussion. Results: The Commission defined a certification process including: “FLC - First level Certification”: restricted to single surgeon, it is given under request and proof of a formal completion of the learning curve process for the basic procedures and an adequate year volume of operations. “Second level certification”: Referral Center for Abdominal Wall Surgery. It is a public or private structure run by at least two already certified and confirmed FLC surgeons. “Third level certification”: High Specialization Center for Abdominal Wall Surgery. It is a public or private structure, already confirmed as Referral Centers, run by at least three surgeons (two certified and confirmed with FLC and one research fellow in abdominal wall surgery). Both levels of certification have to meet the Surgical Requirements and facilities criteria fixed by the Commission. Conclusion: The creation of different types of Hernia Centers is directed to create two different entities offering the same surgical quality with separate mission: the Referral Center being more dedicated to clinical and surgical activity and High Specialization Centers being more directed to scientific tasks

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

Poor nutritional status is associated with other geriatric domain impairments and adverse postoperative outcomes in onco-geriatric surgical patients – a multicentre cohort study

Background: Nutritional status (NS), though frequently affected in onco-geriatric patients, is no standard part of a geriatric assessment. The aim of this study was to analyse the association between a preoperatively impaired NS and geriatric domain impairments and adverse postoperative outcomes in onco-geriatric surgical patients. Methods: 309 patients ≥70 years undergoing surgery for solid tumours were prospectively recruited. Nine screening tools were preoperatively administered as part of a geriatric assessment. NS was based on BMI, weight loss and food intake. Odds ratio’s (OR) and 95% confidence intervals (95%CI) were estimated using logistic regression analysis. The occurrence of 30-day adverse postoperative outcomes was recorded. Results: At a median age of 76 years, 107 patients (34.6%) had an impaired NS. Decreased performance status and depression were associated with an impaired NS, when adjusted for tumour characteristics and comorbidities (ORPS>1 3.46; 95%CI 1.56-7.67. ORGDS>5 2.11; 95%CI 1.05-4.26). An impaired NS was an independent predictor for major complications (OR 3.3; 95%CI 1.6-6.8). Ten out of 11 patients who deceased had an impaired NS. Conclusion: An impaired NS is prevalent in onco-geriatric patients considered to be fit for surgery. It is associated with decreased performance status and depression. An impaired NS is a predictor for adverse postoperative outcomes. NS should be incorporated in a geriatric assessment

EHS Rapid Guideline: Evidence-Informed European Recommendations on Parastomal Hernia Prevention—With ESCP and EAES Participation

Background: Growing evidence on the use of mesh as a prophylactic measure to prevent parastomal hernia and advances in guideline development methods prompted an update of a previous guideline on parastomal hernia prevention.Objective: To develop evidence-based, trustworthy recommendations, informed by an interdisciplinary panel of stakeholders.Methods: We updated a previous systematic review on the use of a prophylactic mesh for end colostomy, and we synthesized evidence using pairwise meta-analysis. A European panel of surgeons, stoma care nurses, and patients developed an evidence-to-decision framework in line with GRADE and Guidelines International Network standards, moderated by a certified guideline methodologist. The framework considered benefits and harms, the certainty of the evidence, patients’ preferences and values, cost and resources considerations, acceptability, equity and feasibility.Results: The certainty of the evidence was moderate for parastomal hernia and low for major morbidity, surgery for parastomal hernia, and quality of life. There was unanimous consensus among panel members for a conditional recommendation for the use of a prophylactic mesh in patients with an end colostomy and fair life expectancy, and a strong recommendation for the use of a prophylactic mesh in patients at high risk to develop a parastomal hernia.Conclusion: This rapid guideline provides evidence-informed, interdisciplinary recommendations on the use of prophylactic mesh in patients with an end colostomy. Further, it identifies research gaps, and discusses implications for stakeholders, including overcoming barriers to implementation and specific considerations regarding validity

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

ERNIE INGUINO-CRURALI : ANATOMIA E CLASSIFICAZIONE

Nella riparazione delle ernie inguino-crurali, le tecniche protesiche, introdotte negli anni \u201990 hanno determinato una semplificazione nell\u2019esecuzione della procedura chirurgica rendendo meno stringente la necessit\ue0 di isolare le varie strutture muscolo-aponeurotiche. Tuttavia la genesi delle ernie della regione inguino-crurale, la loro corretta classificazione e la loro riparazione, indipendentemente dall\u2019accesso utilizzato, sono strettamente correlate all\u2019anatomia di questa regione. Gli autori descrivono dettagliatamente le strutture anatomiche coinvolte e le varie classificazioni proposte negli ultimi 40 anni basate su dati anatomici, fisiopatologici o chirurgici. I vari sistemi classificativi proposti risultano per\uf2 il pi\uf9 delle volte difficili da ricordare per l\u2019estrema esasperazione del dettaglio, poco intuitivi e dipendenti dal tipo di accesso chirurgico effettuato. In conclusione sembra che il sistema di classificazione oggi pi\uf9 utilizzato sia ancora quello concepito quasi 200 anni fa che identifica le ernie in indirette, dirette e femorali. Proprio in quest\u2019ottica semplificativa, appare assai valida la classificazione proposta dalla European Hernia Society nel 2004, nella quale le ernie vengono suddivise in primitive e ricorrenti, viene mantenuta l\u2019identificazione del difetto erniario (ernie mediali, laterali e femorali) e la misurazione della porta erniaria ha come riferimento il dito indice dell\u2019operatore