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The relationship between serum 25-hydroxyvitamin D (25(OH)D) levels, genomic response to vitamin D (Vit.D), and positivity to SARS-CoV-2 remains understudied. In this pilot study, during the follow-up of patients with Inflammatory Bowel Disease (IBD) and COVID-19, we investigated this issue by analyzing the molecular contents of serum extracellular vesicles (EVs) from six groups of IBD patients (n = 32), classified according to anti-SARS-CoV-2 status, 25(OH)D level, and Vit.D supplementation, by small RNA-seq. This analysis revealed differentially expressed miRNAs, PIWI-RNA, transfer RNA, small nucleolar RNAs, and protein-coding RNAs in the EVs obtained from these cohorts of IBD patients. Experimental validation evidenced a statistically significant increase in miR30d-5p, miR150-5p, Let-7f-5p, and Let-7a-5p in the anti-SARS-CoV-2-positive and low 25(OH)D and Vit.D supplemented groups with respect to the non-Vit.D supplemented group, indicating their responsiveness to Vit.D treatment. Bioinformatics analysis highlighted the regulation of these validated miRNAs by oxidative stress and inflammation, hallmarks of IBD and COVID-19. Our study reports an unprecedented panel of circulating EV-enclosed inflammation- and oxidative stress-related miRNAs, the potentiality of which, as biomarkers for Vit.D responsivity in IBD patients, needs to be explored in future studies on larger cohorts in order to allow clinicians to optimize current treatment strategies upon viral infection.

The coronavirus disease (COVID-19) pandemic represents a global health challenge, particularly considering concomitant diseases. Patients with inflammatory bowel diseases (IBD) can be considered a population at risk. On the other hand, the risk of developing IBD and COVID-19 have both been described as modulated by vitamin D (VD) levels. In this work, a cohort of 106 adult patients affected by IBD was prospectively enrolled, during the second wave of the pandemic in Italy. In these patients, VD plasma levels, demographic, and clinical characteristics were tested for a correlation/an association with the risk of infection with SARS-CoV-2 in the study period (anti-spike IgG positivity) and the severity of COVID-19 symptoms. By multivariate logistic regression analysis, VD supplementation (Odds Ratio; OR 0.116, p = 0.002), therapy with monoclonal antibodies (OR 0.227, p = 0.007), and the use of mesalazine (OR 2.968, p = 0.046) were found to be independent predictors of SARS-CoV-2 positivity. Moreover, hypertension was associated with severe disease ( p = 0.019), while a VD level higher than 30 ng/mL ( p = 0.031, OR 0.078) was associated with asymptomatic infection. No interplay between IBD activity and COVID-19 risk of infection or symptoms was observed. These results confirm the importance of VD levels in defining the risk of COVID-19 and give encouraging data about the safety of maintaining immunomodulatory treatments for IBD during the COVID-19 pandemic.

Background & Aims: In France, liver grafts that have been refused at least 5 times can be "rescued" and allocated to a centre which chooses a recipient from its own waiting list, outside the patient-based allocation framework. We explored whether these "rescued" grafts were associated with worse graft/patient survival, as well as assessing their effect on survival benefit., Methods: Among 7,895 candidates, 5,218 were transplanted between 2009 and 2014 (336 centre-allocated). We compared recipient/graft survival between patient allocation and centre allocation, considering a selection bias and the distribution of centre-allocation recipients among the transplant teams. We used a propensity score approach and a weighted Cox model using the inverse probability of treatment weighting method. We also explored the survival benefit associated with centre-allocation grafts., Results: There was a significantly higher risk of graft loss/death in the centre allocation group compared to the patient allocation group (hazard ratio 1.13; 95% CI 1.05-1.22). However, this difference was no longer significant for teams that performed more than 7% of the centre-allocation transplantations. Moreover, receiving a centre-allocation graft, compared to remaining on the waiting list and possibly later receiving a patient-allocation graft, did not convey a poorer survival benefit (hazard ratio 0.80; 95% CI 0.60-1.08)., Conclusions: In centres which transplanted most of the centre-allocation grafts, using grafts repeatedly refused for top-listed candidates was not detrimental. Given the organ shortage, our findings should encourage policy makers to restrict centre-allocation grafts to targeted centres., Lay Summary: "Centre allocation" (CA) made it possible to save 6 out of 100 available liver grafts that had been refused at least 5 times for use in the top-listed candidates on the national waiting list. In this series, the largest on this topic, we showed that, in centres which transplanted most of the CA grafts, using grafts repeatedly refused for top-listed candidates did not appear to be detrimental. In the context of organ shortage, our results, which could be of interest for any country using this CA strategy, should encourage policy makers to reassess some aspects of graft allocation by restricting CA grafts to targeted centres, fostering the "best" matching between grafts and candidates on the waiting list., Competing Interests: Please refer to the accompanying ICMJE disclosure forms for further details., (© 2020 The Author(s).)

Background: The French transplant governing system defined "Rescue" (the so-called "Hors Tour") livers as those livers which were declined for the five top-listed patients. This study compares the outcomes following liver transplantation (LT) in patients who received a donor liver through a rescue allocation (RA) procedure or according to MELD score priority (standard allocation, SA) and evaluates the impact on the graft pool of a proactive policy to accept RA grafts., Methods: Data from all consecutive patients who underwent LT with SA or RA grafts from 2011 to 2015 were compared in terms of short- and long-term outcomes., Results: The 249 elective first LTs were performed with 64 (25.7%) RA and 185 (74.3%) SA grafts. RA grafts were obtained from older donors and were associated with a longer cold ischemia time. Recipients of RA livers were older and had lower MELD scores. The rates of delayed graft function, primary nonfunction, retransplantation, complications, and mortality were similar between the RA and SA groups. At 1 and 3 and 5 years, graft and patient survival rates were similar between the groups. These results were maintained after matching on recipient characteristics. Our proactive policy to accept RA grafts increased the liver pool for elective first transplantation by 25%., Conclusions: RA livers can be safely transplanted into selected recipients and significantly expand the liver pool.

Background: Emergency digestive surgery is being increasingly performed in elderly patients. The aim of the present study was to identify the predictors of mortality and morbidity following emergency digestive surgery in patients aged 80 years and older., Methods: A single-center retrospective review was performed of consecutive patients aged ≥65 years operated for a digestive surgical emergency between January 2011 and December 2013. Two groups were compared: group A (aged 65-79 years) and group B (aged ≥80 years)., Results: The study population included 185 patients: 76 patients in group A and 109 in group B. The mean age was 79.9 years (65-104 years). The overall 90-day mortality rate was 23.2 and 31.9% at 1 year, which was similar between groups. The overall morbidity was 28.6%. No differences were noted between the two groups in overall, minor (Dindo I-II) or major (Dindo III-IV) morbidity rates. Multivariate analysis identified pulmonary disease (odds ratio, OR = 6.43, p = 0.02), bowel ischemia (OR = 11.41, p = 0.01), postoperative ICU stay (OR = 7.37, p < 0.0001) and the occurrence of postoperative complications (OR = 2.66, p = 0.03) as predictors of 90-day mortality. Predictors of in-hospital morbidity were preoperative hemoglobin <12 g/dL (OR = 2.49, p = 0.02) and postoperative intensive care unit (ICU) stay (OR = 6.69, p < 0.0001). An age ≥80 year was not associated with mortality or morbidity in this study., Conclusions: The decision to perform abdominal surgery in the emergency setting should be based on physiological status, which accounts for a patient's comorbidities and health status, rather than on chronological age per se.

Background: Control of warm ischemia (WI) lesions that occur with donation after circulatory death (DCD) would significantly increase the donor pool for liver transplantation. We aimed to determine whether a novel, oxygenated and hypothermic machine perfusion device (HMP Airdrive system) improves the quality of livers derived from DCDs using a large animal model., Methods: Cardiac arrest was induced in female large white pigs by intravenous injection of potassium chloride. After 60 minutes of WI, livers were flushed in situ with histidine-tryptophan-ketoglutarate and subsequently preserved either by simple cold storage (WI-SCS group) or HMP (WI-HMP group) using Belzer-MPS solution. Liver grafts procured from heart-beating donors and preserved by SCS served as controls. After 4 hours of preservation, all livers were transplanted., Results: All recipients in WI-SCS group died within 6 hours after transplantation. In contrast, the HMP device fully protected the liver against lethal ischemia/reperfusion injury, allowing 100% survival rate. A postreperfusion syndrome was observed in all animals of the WI-SCS group but none of the control or WI-HMP groups. After reperfusion, HMP-preserved livers functioned better and showed less hepatocellular and endothelial cell injury, in agreement with better-preserved liver histology relative to WI-SCS group. In addition to improved energy metabolism, this protective effect was associated with an attenuation of inflammatory response, oxidative load, endoplasmic reticulum stress, mitochondrial damage, and apoptosis., Conclusions: This study demonstrates for the first time the efficacy of the HMP Airdrive system to protect liver grafts from lethal ischemic damage before transplantation in a clinically relevant DCD model.

This study compared robotic (RR) and laparoscopic resection (LR) for primary gastrointestinal stromal tumors (GISTs) of the stomach >5 cm. Twelve consecutive patients who underwent RR from 2012 to 2015 were matched for tumor size and location with 24 patients who underwent LR from 2000 to 2012. The median tumor size was 7.1 cm (range, 5.5 to 11.5). GISTs were resected by wedge resection (91.7%) or distal gastrectomy. The median RR operative time was longer than that of LR (162.5 vs. 130 min, respectively; P=0.004). Only 1 LR patient required conversion. The time to flatus and hospital stay were similar between groups. Overall, 3 patients developed minor postoperative complications that were medically treated. Mortality was nil. All resections were R0. No difference was observed in the incidence of recurrence. RR was significantly more expensive (+21.6%) than LR. RR appears to be safe and feasible for GISTs>5 cm, but is associated with longer operative times and greater costs.

Purpose: The aim of the study was to compare the short- and long-term outcomes of laparoscopic extended right colectomy (ER) versus laparoscopic left colectomy (LC) for splenic flexure carcinomas., Methods: Patients with stage 0-III adenocarcinoma of the splenic flexure who underwent laparoscopy between 2000 and 2013 were identified from a prospectively maintained database. Twenty-seven patients who underwent ER were matched by age, gender, BMI, ASA score, and tumor stage with 27 patients who underwent LC., Results: The ER procedures were significantly longer than LC (235 ± 49.2 min vs. 192 ± 43.4 min, p = 0.001, respectively). Post-operatively, time to flatus and return to regular diet were observed to average 2.4 ± 0.8 days (1-4 days) and 4.6 ± 1.05 days (3-8 days), respectively, without differences between the groups. Overall, 14 complications were observed in 12 patients and 90-day mortality was nil. The length of hospitality stay was not different between ER and LC, with an overall mean of 8.3 ± 2.7 days. All procedures were classified as R0 resections, but ER was associated with a higher number of lymph nodes retrieved (21.4 ± 4.9) compared with LC (16.6 ± 5.5, p = 0.001). The 1-, 3-, and 5-year cumulative survival rates were 92.6, 85.8, and 72.8% for the ER group and 96.3, 91.9, and 75.1% for the LC group (p = 0.851). The 1-, 3-, and 5-year disease-free survival rates were 85.2, 76.7, and 67.1% for the ER group and 96.2, 75.5, and 66.7% for the LC group (p = 0.636)., Conclusions: Laparoscopic ER and LC procedures performed for splenic flexure carcinomas appear to have similar short- and long-term oncologic outcomes.

Objectives: The aim of the study was to compare the long-term oncologic results of laparoscopic liver resection (LLR) versus open liver resection (OLR) for colorectal liver metastasis (CRLM) using a propensity score analysis., Subjects and Methods: This propensity score matching (PSM) study was based on a prospective database of a single tertiary-care center. Patients with primarily resectable CRLM were selected for a 1:1 PSM between LLR and OLR. Covariates for PSM estimation were age, gender, body mass index, American Society of Anesthesiologists score, primary tumor location, CRLM presentation, location, size, and number. Moreover, the year of surgery was included in the PSM model. Operative, postoperative, and survival rates were compared between groups., Results: From 2000 to 2013, in total, 339 liver resections for CRLM met the selection criteria. Among these, 52 LLR patients were matched with 52 OLR patients. The two surgical approaches showed similar postoperative morbidity and mortality rates. LLR was associated with significantly less blood loss, less frequent need for and shorter duration of pedicle clamping, faster recovery, and shorter hospital stay. Moreover, the overall 3- and 5-year survival rates were, respectively, 83% and 76% for LLR and 87% and 62% for OLR (P=.51). The 3- and 5-year disease-free survival rates were, respectively, 28% and 21% for LLR and 31% and 21% for OLR (P=.71)., Conclusions: The LLR achieves similar oncological results to those of the standard open surgery for CRLM, with the additional benefit of significantly faster recovery.

Right colon cancer rarely presents as an emergency, in which bowel occlusion and massive bleeding are the most common clinical presentations. Although there are no definite guidelines, the first line treatment for massive right colon cancer bleeding should ideally stop the bleeding using endoscopy or interventional radiology, subsequently allowing proper tumor staging and planning of a definite treatment strategy. Minimally invasive approaches for right and left colectomy have progressively increased and are widely performed in elective settings, with laparoscopy chosen in the majority of cases. Conversely, in emergent and urgent surgeries, minimally invasive techniques are rarely performed. We report a case of an 86-year-old woman who was successfully treated for massive rectal bleeding in an urgent setting by robotic surgery (da Vinci Intuitive Surgical System®). At admission, the patient had severe anemia (Hb 6 g/dL) and hemodynamic stability. A computer tomography scanner with contrast enhancement showed a right colon cancer with active bleeding; no distant metastases were found. A colonoscopy did not show any other bowel lesion, while a constant bleeding from the right pre-stenotic colon mass was temporarily arrested by endoscopic argon coagulation. A robotic right colectomy in urgent setting (within 24 hours from admission) was indicated. A three-armed robot was used with docking in the right side of the patient and a fourth trocar for the assistant surgeon. Because of the patient's poor nutritional status, a double-barreled ileocolostomy was performed. The post-operative period was uneventful. As the neoplasia was a pT3N0 adenocarcinoma, surveillance was decided after a multidisciplinary meeting, and restoration of the intestinal continuity was performed 3 months later, once good nutritional status was achieved. In addition, we reviewed the current literature on minimally invasive colectomy performed for colon carcinoma in emergent or urgent setting. No study on robotic approach was found. Seven studies evaluating the role of laparoscopic colectomy concluded that this technique is a safe and feasible option associated with lower blood loss and shorter hospital stay. It may require longer operative time, but morbidity and mortality rates appeared comparable to open colectomy. However, the surgeon's experience and the right selection of candidate patients cannot be understated.

We report a case of a three month young pregnant woman (In Vitro Fertilization and Embryo Transfer - IVF-ET - twin pregnancy) with situs viscerum inversus totalis affected by acute cholecystitis. As already happened in other pregnant women, we use laparoscopic approach and cholecystectomy is performed successfully without any morbidity for mother and fetuses.