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

Laparoscopic right hemicolectomy: the SICE (Societ\ue0 Italiana di Chirurgia Endoscopica e Nuove Tecnologie) network prospective trial on 1225 cases comparing intra corporeal versus extra corporeal ileo-colic side-to-side anastomosis

Background: While laparoscopic approach for right hemicolectomy (LRH) is considered appropriate for the surgical treatment of both malignant and benign diseases of right colon, there is still debate about how to perform the ileo-colic anastomosis. The ColonDxItalianGroup (CoDIG) was designed as a cohort, observational, prospective, multi-center national study with the aims of evaluating the surgeons\u2019 attitude regarding the intracorporeal (ICA) or extra-corporeal (ECA) anastomotic technique and the related surgical outcomes. Methods: One hundred and twenty-five Surgical Units experienced in colorectal and advanced laparoscopic surgery were invited and 85 of them joined the study. Each center was asked not to change its surgical habits. Data about demographic characteristics, surgical technique and postoperative outcomes were collected through the official SICE website database. One thousand two hundred and twenty-five patients were enrolled between March 2018 and September 2018. Results: ICA was performed in 70.4% of cases, ECA in 29.6%. Isoperistaltic anastomosis was completed in 85.6%, stapled in 87.9%. Hand-sewn enterotomy closure was adopted in 86%. Postoperative complications were reported in 35.4% for ICA and 50.7% for ECA; no significant difference was found according to patients\u2019 characteristics and technologies used. Median hospital stay was significantly shorter for ICA (7.3 vs. 9 POD). Postoperative pain in patients not prescribed opioids was significantly lower in ICA group. Conclusions: In our survey, a side-to-side isoperistaltic stapled ICA with hand-sewn enterotomy closure is the most frequently adopted technique to perform ileo-colic anastomosis after any indications for elective LRH. According to literature, our study confirmed better short-term outcomes for ICA, with reduction of hospital stay and postoperative pain. Trial registration: Clinical trial (Identifier: NCT03934151)

Three-row versus two-row circular staplers for left-sided colorectal anastomosis: a propensity score-matched analysis of the iCral 2 and 3 prospective cohorts

Background: Since most anastomoses after left-sided colorectal resections are performed with a circular stapler, any technological change in stapling devices may influence the incidence of anastomotic adverse events. The aim of the present study was to analyze the effect of a three-row circular stapler on anastomotic leakage and related morbidity after left-sided colorectal resections. Materials and methods: A circular stapled anastomosis was performed in 4255 (50.9%) out of 8359 patients enrolled in two prospective multicenter studies in Italy, and, after exclusion criteria to reduce heterogeneity, 2799 (65.8%) cases were retrospectively analyzed through a 1:1 propensity score-matching model including 20 covariates relative to patient characteristics, to surgery and to perioperative management. Two well-balanced groups of 425 patients each were obtained: group (A) – true population of interest, anastomosis performed with a three-row circular stapler; group (B) – control population, anastomosis performed with a two-row circular stapler. The target of inferences was the average treatment effect in the treated (ATT). The primary endpoints were overall and major anastomotic leakage and overall anastomotic bleeding; the secondary endpoints were overall and major morbidity and mortality rates. The results of multiple logistic regression analyses for the outcomes, including the 20 covariates selected for matching, were presented as odds ratios (OR) and 95% confidence intervals (95% CI). Results: Group A versus group B showed a significantly lower risk of overall anastomotic leakage (2.1 vs. 6.1%; OR 0.33; 95% CI 0.15–0.73; P = 0.006), major anastomotic leakage (2.1 vs. 5.2%; OR 0.39; 95% CI 0.17–0.87; P = 0.022), and major morbidity (3.5 vs. 6.6% events; OR 0.47; 95% CI 0.24–0.91; P = 0.026). Conclusion: The use of three-row circular staplers independently reduced the risk of anastomotic leakage and related morbidity after left-sided colorectal resection. Twenty-five patients were required to avoid one leakage

Antiinflammatory Therapy with Canakinumab for Atherosclerotic Disease

Background: Experimental and clinical data suggest that reducing inflammation without affecting lipid levels may reduce the risk of cardiovascular disease. Yet, the inflammatory hypothesis of atherothrombosis has remained unproved. Methods: We conducted a randomized, double-blind trial of canakinumab, a therapeutic monoclonal antibody targeting interleukin-1β, involving 10,061 patients with previous myocardial infarction and a high-sensitivity C-reactive protein level of 2 mg or more per liter. The trial compared three doses of canakinumab (50 mg, 150 mg, and 300 mg, administered subcutaneously every 3 months) with placebo. The primary efficacy end point was nonfatal myocardial infarction, nonfatal stroke, or cardiovascular death. RESULTS: At 48 months, the median reduction from baseline in the high-sensitivity C-reactive protein level was 26 percentage points greater in the group that received the 50-mg dose of canakinumab, 37 percentage points greater in the 150-mg group, and 41 percentage points greater in the 300-mg group than in the placebo group. Canakinumab did not reduce lipid levels from baseline. At a median follow-up of 3.7 years, the incidence rate for the primary end point was 4.50 events per 100 person-years in the placebo group, 4.11 events per 100 person-years in the 50-mg group, 3.86 events per 100 person-years in the 150-mg group, and 3.90 events per 100 person-years in the 300-mg group. The hazard ratios as compared with placebo were as follows: in the 50-mg group, 0.93 (95% confidence interval [CI], 0.80 to 1.07; P = 0.30); in the 150-mg group, 0.85 (95% CI, 0.74 to 0.98; P = 0.021); and in the 300-mg group, 0.86 (95% CI, 0.75 to 0.99; P = 0.031). The 150-mg dose, but not the other doses, met the prespecified multiplicity-adjusted threshold for statistical significance for the primary end point and the secondary end point that additionally included hospitalization for unstable angina that led to urgent revascularization (hazard ratio vs. placebo, 0.83; 95% CI, 0.73 to 0.95; P = 0.005). Canakinumab was associated with a higher incidence of fatal infection than was placebo. There was no significant difference in all-cause mortality (hazard ratio for all canakinumab doses vs. placebo, 0.94; 95% CI, 0.83 to 1.06; P = 0.31). Conclusions: Antiinflammatory therapy targeting the interleukin-1β innate immunity pathway with canakinumab at a dose of 150 mg every 3 months led to a significantly lower rate of recurrent cardiovascular events than placebo, independent of lipid-level lowering. (Funded by Novartis; CANTOS ClinicalTrials.gov number, NCT01327846.

Prevalence and quantitative assessment of macrophages in coronary plaques

Although optical coherence tomography (OCT) proved to be able to identify macrophage clusters, there are no available data on the possibility to obtain reproducible measurements of their circumferential extension and location. The purpose of the present post-hoc analysis of the CLIMA study was to revise the clinical and demographic variables of patients having coronary plaques with macrophages and to investigate the reproducibility of their quantitative assessment. A total of 577 patients out of 1003 undergoing OCT showed macrophage accumulation. Three groups were identified; group 1 (426 patients) without macrophages, group 2 (296) patients with low macrophage content (less than median value [67\ub0] of circumferential arc) and group 3 (281) with high macrophage content arc [> 67\ub0]. Patients with macrophages (groups 2 and 3) showed a higher prevalence of family history for coronary artery disease and hypercholesterolemia and had a significantly larger body mass index. Furthermore, group 3 had more commonly triple vessel disease and higher value of LDL cholesterol levels compared to the two other groups. The inter-observer agreement for macrophage interpretation was good: R values were 0.97 for the circumferential arc extension, 0.95 for the minimum distance and 0.98 for the mean distance. A non-significant correlation between circumferential extension of macrophages and hsCRP values was found (R = 0.013). Quantitative assessment of macrophage accumulations can be obtained with high reproducibility by OCT. The presence and amount of macrophages are poorly correlated with hsCRP and identify patients with more advanced atherosclerosis and higher LDL cholesterol levels

Laparoscopic right hemicolectomy: the SICE (Società Italiana di Chirurgia Endoscopica e Nuove Tecnologie) network prospective trial on 1225 cases comparing intra corporeal versus extra corporeal ileo-colic side-to-side anastomosis

Background: While laparoscopic approach for right hemicolectomy (LRH) is considered appropriate for the surgical treatment of both malignant and benign diseases of right colon, there is still debate about how to perform the ileo-colic anastomosis. The ColonDxItalianGroup (CoDIG) was designed as a cohort, observational, prospective, multi-center national study with the aims of evaluating the surgeons’ attitude regarding the intracorporeal (ICA) or extra-corporeal (ECA) anastomotic technique and the related surgical outcomes. Methods: One hundred and twenty-five Surgical Units experienced in colorectal and advanced laparoscopic surgery were invited and 85 of them joined the study. Each center was asked not to change its surgical habits. Data about demographic characteristics, surgical technique and postoperative outcomes were collected through the official SICE website database. One thousand two hundred and twenty-five patients were enrolled between March 2018 and September 2018. Results: ICA was performed in 70.4% of cases, ECA in 29.6%. Isoperistaltic anastomosis was completed in 85.6%, stapled in 87.9%. Hand-sewn enterotomy closure was adopted in 86%. Postoperative complications were reported in 35.4% for ICA and 50.7% for ECA; no significant difference was found according to patients’ characteristics and technologies used. Median hospital stay was significantly shorter for ICA (7.3 vs. 9 POD). Postoperative pain in patients not prescribed opioids was significantly lower in ICA group. Conclusions: In our survey, a side-to-side isoperistaltic stapled ICA with hand-sewn enterotomy closure is the most frequently adopted technique to perform ileo-colic anastomosis after any indications for elective LRH. According to literature, our study confirmed better short-term outcomes for ICA, with reduction of hospital stay and postoperative pain. Trial registration: Clinical trial (Identifier: NCT03934151)

Relationship betweeen the amount and location of macrophages and clinical outcome: subanalysis of the CLIMA-study

Background: The ability of optical coherence tomography (OCT) to recognize intraplaque macrophage infiltration is now well acknowledged. This post-hoc analysis of the CLIMA study aimed to address the clinical impact of the circumferential extension of OCT-defined macrophages and their location at one year follow-up. Methods: The multicentre CLIMA study enrolled 1003 patients undergoing OCT evaluation of the untreated proximal left anterior descending (LAD) coronary artery. Measurements of circumferential extension of macrophages and measurements of the distance from intima-lumen contour to macrophages string were performed at the plaque cross-section judged as containing the greatest amount of macrophages. The main study endpoint was a composite of cardiac death, myocardial infarction (MI) and/or target vessel revascularization (TVR). Results: Patients with large macrophage arc (p = 0.001) and superficial macrophage arc (p < 0.001) showed a higher one-year incidence of the main one-year composite endpoint. Consistently hypertension (p = 0.018), family history of CAD (p = 0.046), diabetes mellitus (p = 0.036), lower ejection fraction (p = 0.009) and chronic kidney disease (p = 0.019) were more frequently found in patients experiencing the main composite endpoint. At multivariate Cox regression analysis, fibrous cap thickness < 75 μm (HR 2.51, 95% 1.46–4.32), presence of large (HR 1.97, 95%CI 1.16–3.35, p = 0.012) and superficial (HR 1.72, 95%CI 1.02–2.90; p = 0.040) macrophage arc remained independent predictors of the main composite endpoint. Large macrophage arc was associated with target LAD related MI. Conclusion: The present post-hoc analysis of the CLIMA showed that the circumferential extension of macrophages and their location are related to a composite endpoint of cardiac death, MI and/or TVR