Hands

societal wrec

Enhancement of anti-leukemia activity of NK cells in vitro and in vivo by inhibition of leukemia cell-induced NK cell damage

Acute myeloid leukemia (AML) cells induce, in vitro, NK cell abnormalities (NKCAs) including apoptosis and activating receptor down-regulation. The potential negative impact of AML cells on the therapeutic efficacy of NK cell-based strategies prompted us to analyze the mechanisms underlying NKCAs and to develop approaches to protect NK cells from NKCAs. NKCA induction by the AML leukemia cells target a subpopulation of peripheral blood NK cells and is interleukin-2 independent but is abrogated by a long-term culture of NK (LTNK) cells at 37°C. LTNK cells displayed a significantly enhanced ability to damage AML cells in vitro and inhibited the subcutaneous growth of ML-2 cells grafted into CB17 SCID mice. Actinomycin D restored the susceptibility of LTNK cells to NKCAs while TAPI-0, a functional analog of the tissue inhibitor of metalloproteinase (TIMP) 3, inhibits ML-2 cell-induced NKCAs suggesting that the generation of NK cell resistance to NKCAs involves RNA transcription and metalloproteinase (MPP) inactivation. This conclusion is supported by the reduced susceptibility to AML cell-induced NKCAs of LTNK cells in which TIMP3 gene and protein are over-expressed. This information may contribute to the rational design of targeted strategies to enhance the efficacy of NK cell-based-immunotherapy of AML with haploidentical NK cells

Asylum

The Hospital for Idiots and Imbecile

Minimally invasive approach to incisional hernia in elective and emergency surgery: a SICE (Italian Society of Endoscopic Surgery and new technologies) and ISHAWS (Italian Society of Hernia and Abdominal Wall Surgery) online survey

Minimally invasive abdominal wall surgery is growing worldwide, with a constant and fast improvement of surgical techniques and surgeons’ confidence in treating both primary and incisional hernias (IH). The Italian Society of Endoscopic Surgery and new technologies (SICE) and the ISHAWS (Italian Society of Hernia and Abdominal Wall Surgery) worked together to investigate state of the art in IH treatment in elective and emergency settings in Italy. An online open survey was designed, and Italian surgeons interested in abdominal wall surgery were invited to fill out a 20-point questionnaire on IH surgical procedures performed in their departments. Surgeons were asked to express their points of view on specific questions about technical and clinical variables in IH treatment. Preferred approach in elective IH surgery was minimally invasive (59.7%). Open surgery was the preferred approach in 40.3% of the responses. In emergency settings, open surgery was the preferred approach (65.4%); however, 34.5% of the involved surgeons declare to prefer the laparoscopic/endoscopic approach. Most respondents opted for conversion to open surgery in case of relevant surgical field contamination, with a non-mesh repair of abdominal wall defects. Among those that used the laparoscopic approach in the emergent setting, the majority (74%) used the size of the defect of 5 cm as a decisional cut-off. The spread of minimally invasive approaches to IH repair in emergency surgery in Italy is gaining relevance. Code-sharing through scientific societies can improve clinical practice in different departments and promote a tailored approach to IH surgery

Evaluation of a quality improvement intervention to reduce anastomotic leak following right colectomy (EAGLE): pragmatic, batched stepped-wedge, cluster-randomized trial in 64 countries

Background Anastomotic leak affects 8 per cent of patients after right colectomy with a 10-fold increased risk of postoperative death. The EAGLE study aimed to develop and test whether an international, standardized quality improvement intervention could reduce anastomotic leaks. Methods The internationally intended protocol, iteratively co-developed by a multistage Delphi process, comprised an online educational module introducing risk stratification, an intraoperative checklist, and harmonized surgical techniques. Clusters (hospital teams) were randomized to one of three arms with varied sequences of intervention/data collection by a derived stepped-wedge batch design (at least 18 hospital teams per batch). Patients were blinded to the study allocation. Low- and middle-income country enrolment was encouraged. The primary outcome (assessed by intention to treat) was anastomotic leak rate, and subgroup analyses by module completion (at least 80 per cent of surgeons, high engagement; less than 50 per cent, low engagement) were preplanned. Results A total 355 hospital teams registered, with 332 from 64 countries (39.2 per cent low and middle income) included in the final analysis. The online modules were completed by half of the surgeons (2143 of 4411). The primary analysis included 3039 of the 3268 patients recruited (206 patients had no anastomosis and 23 were lost to follow-up), with anastomotic leaks arising before and after the intervention in 10.1 and 9.6 per cent respectively (adjusted OR 0.87, 95 per cent c.i. 0.59 to 1.30; P = 0.498). The proportion of surgeons completing the educational modules was an influence: the leak rate decreased from 12.2 per cent (61 of 500) before intervention to 5.1 per cent (24 of 473) after intervention in high-engagement centres (adjusted OR 0.36, 0.20 to 0.64; P < 0.001), but this was not observed in low-engagement hospitals (8.3 per cent (59 of 714) and 13.8 per cent (61 of 443) respectively; adjusted OR 2.09, 1.31 to 3.31). Conclusion Completion of globally available digital training by engaged teams can alter anastomotic leak rates. Registration number: NCT04270721 (http://www.clinicaltrials.gov)