Low ASA Research Articles

Goodbye Hartmann trial: a prospective, international, multicenter, observational study on the current use of a surgical procedure developed a century ago

BackgroundLiterature suggests colonic resection and primary anastomosis (RPA) instead of Hartmann’s procedure (HP) for the treatment of left-sided colonic emergencies. We aim to evaluate the surgical options globally used to treat patients with acute left-sided colonic emergencies and the factors that leading to the choice of treatment, comparing HP and RPA.MethodsThis is a prospective, international, multicenter, observational study registered on ClinicalTrials.gov. A total 1215 patients with left-sided colonic emergencies who required surgery were included from 204 centers during the period of March 1, 2020, to May 31, 2020. with a 1-year follow-up.Results564 patients (43.1%) were females. The mean age was 65.9 ± 15.6 years. HP was performed in 697 (57.3%) patients and RPA in 384 (31.6%) cases. Complicated acute diverticulitis was the most common cause of left-sided colonic emergencies (40.2%), followed by colorectal malignancy (36.6%). Severe complications (Clavien-Dindo ≥ 3b) were higher in the HP group (P < 0.001). 30-day mortality was higher in HP patients (13.7%), especially in case of bowel perforation and diffused peritonitis. 1-year follow-up showed no differences on ostomy reversal rate between HP and RPA. (P = 0.127). A backward likelihood logistic regression model showed that RPA was preferred in younger patients, having low ASA score (≤ 3), in case of large bowel obstruction, absence of colonic ischemia, longer time from admission to surgery, operating early at the day working hours, by a surgeon who performed more than 50 colorectal resections.ConclusionsAfter 100 years since the first Hartmann’s procedure, HP remains the most common treatment for left-sided colorectal emergencies. Treatment’s choice depends on patient characteristics, the time of surgery and the experience of the surgeon. RPA should be considered as the gold standard for surgery, with HP being an exception.

Low dose aspirin prevents endothelial dysfunction in the aorta and foetal loss in pregnant mice infected with influenza A virus.

Influenza A virus (IAV) infection in pregnancy resembles a preeclamptic phenotype characterised by vascular dysfunction and foetal growth retardation. Given that low dose aspirin (ASA) is safe in pregnancy and is used to prevent preeclampsia, we investigated whether ASA or NO-conjugated aspirin, NCX4016, resolve vascular inflammation and function to improve offspring outcomes following IAV infection in pregnant mice. Pregnant mice were intranasally infected with a mouse adapted IAV strain (Hkx31; 104 plaque forming units) and received daily treatments with either 200µg/kg ASA or NCX4016 via oral gavage. Mice were then culled and the maternal lungs and aortas collected for qPCR analysis, and wire myography was performed on aortic rings to assess endothelial and vascular smooth muscle functionality. Pup and placentas were weighed and pup growth rates and survival assessed. IAV infected mice had an impaired endothelial dependent relaxation response to ACh in the aorta, which was prevented by ASA and NCX4016 treatment. ASA and NCX4016 treatment prevented IAV dissemination and inflammation of the aorta as well as improving the pup placental ratios in utero, survival and growth rates at post-natal day 5. Low dose ASA is safe to use during pregnancy for preeclampsia and this study demonstrates that ASA may prove a promising treatment for averting the significant vascular complications associated with influenza infection during pregnancy.

Endoscopic main duct stenting in refractory postoperative pancreatic fistula after distal pancreatectomy – a friend or a foe?

BackgroundClinically relevant (CR) postoperative pancreatic fistula (POPF) after distal pancreatectomy (DP) are common. Endoscopic treatment (ET) has only scarcely been explored. The aim of this study was to evaluate risk factors for CR POPF after DP and the efficacy of ET in adjunct to standard therapy.MethodsConsecutive patients without previous pancreatic surgery who underwent DP between 2011 and 2020 were evaluated, analyzing risk factors for CR POPF. The choice and performance of ET, main pancreatic duct (MPD) stenting, was not standardized. Healing time and complications after ET were registered.Results406 patients underwent DP, CR POPF occurred in 29.6%. ET was performed in 17 patients 27 days (median) after index surgery. Risk for CR POPF was increased in ASA-PS 1–2 patients, MPD ≤ 3 mm, procedure time ≥ 3 h, and CRP ≥ 180 on postoperative day 3. POPF resolved with standard treatment after 32 days and 59 days in the ET group (p < 0.001). There was one mortality in the ET-group (not procedure related). Mild post-ERCP pancreatitis occurred in three patients.ConclusionsCR POPF is common after DP. Long operating time, a narrow MPD, low ASA score, and high postoperative CRP were risk factors for CR POPF. ET was not beneficial but proper evaluation was not possible due to few patients and non-standardized treatment. Complications after ET appeared mild.

Association between reduced physical performance measures and short-term consequences after major emergency abdominal surgery: a prospective cohort study

BackgroundMajor emergency abdominal surgery is associated with high morbidity with outcomes worse than for similar elective surgery, including complicated physical recovery, increased need for rehabilitation, and prolonged hospitalisation.PurposeTo investigate whether low physical performance test scores were associated with an increased risk of postoperative complications, and, furthermore, to investigate the feasibility of postoperative performance tests in patients undergoing major emergency abdominal surgery. We hypothesize that patients with low performance test scores suffer more postoperative complications.MethodsThe study is a prospective observational cohort study including all patients who underwent major abdominal surgery at the Department of Surgery at Zealand University Hospital between 1st March 2017 and 31st January 2019. Patients were evaluated with De Morton Mobility Index (DEMMI) score, hand grip strength, and 30-s chair-stand test.ResultsThe study included 488 patients (median age 69, 50.6% male). Physiotherapeutic evaluation including physical performance tests with DEMMI and hand grip strength in the immediate postoperative period were feasible in up to 68% of patients undergoing major emergency abdominal surgery. The 30-s chair-stand test was less viable in this population; only 21% of the patients could complete the 30-s chair-stand test during the postoperative period. In logistic regression models low DEMMI score (< 40) and ASA classification and low hand grip strength (< 20 kg for women, < 30 kg for men were independent risk factors for the development of postoperative severe complications Clavien–Dindo (CD) grade ≥ 3.ConclusionsIn patients undergoing major emergency surgery low performance test scores (DEMMI and hand grip strength), were independently associated with the development of significant postoperative complications CD ≥ 3.

Twenty-four Hours Stay After Colorectal Surgery; A Systematic Review

Abstract Introduction The introduction of Enhanced Recovery After Surgery led to increasing twenty-four hours discharge pathways, for example in laparoscopic cholecystectomy and bariatric surgery. However, implementation in colorectal surgery still must set off. This systematic review assesses safety and feasibility of twenty-four hours discharge in colorectal surgery in terms of readmission and complications in current literature. Secondary outcome was identification of factors associated with success of twenty-four hours discharge. Methods Pubmed and EMBASE databases were searched to identify studies investigating twenty-four hours discharge in colorectal surgery, without restriction of study type. Search strategy included keywords relating to ambulatory management and colorectal surgery. Studies were scored according to MINORS score. Results Thirteen studies were included in this systematic review, consisting of six prospective and seven retrospective studies. Number of participants of the included prospective studies ranged from 5 to 157. Median success of discharge was 96% in the twenty-four hours discharge group. All prospective studies showed similar readmission and complication rates between twenty-four hours discharge and conventional postoperative management. Factors associated with success of twenty-four hours discharge were low ASA classification, younger age, minimally invasive approach, and relatively shorter operation time. Conclusions Twenty-four hours discharge in colorectal surgery seems feasible and safe, based on retro- and prospective studies. Careful selection of patients and establishment of a clear and adequate protocol are key items to assure safety and feasibility. Results should be interpreted with caution, due to heterogeneity. To confirm results, an adequately powered prospective randomized study is needed.

Aspirin use is associated with decreased inpatient mortality in patients with COVID-19: A meta-analysis

Thromboembolism is a major cause of death in patients who suffer from COVID-19. Studies examining the effects of aspirin (ASA) on mortality relating to this phenomenon have showed conflicting results with varying degrees and certainties of evidence. We performed an aggregate data meta-analysis of fourteen studies encompassing 164,539 COVID-19 patients, which showed a reduced risk of in-hospital mortality associated with ASA use in eight studies that reported risk ratios (RR 0.90; 95 % CI 0.82–0.98; I2 = 27.33 %, P = 0.01), six studies that reported hazard ratios (HR 0.56; 95 % CI 0.41–0.76, P ≤ 0.01; I2 = 85.92 %) and pooled effect size (0.71; 95 % CI 0.59–0.85, P = 0.00, I2 = 91.51 %). The objective of this study is to report the association between low dose ASA and a reduced risk of in-hospital mortality in patients with COVID-19.

High-Normal Preoperative Potassium Level Is Associated with Reduced 30-Day Morbidity and Shorter Hospital Stay after Radical Cystectomy.

Background: Radical cystectomy has high complication rates and, consequently, a high socioeconomic burden. The association between preoperative electrolyte levels and postoperative outcomes after radical cystectomy has not been investigated. Therefore, we aimed to investigate the association between preoperative potassium level and clinical (30-day morbidity) and economical (length of hospital stay) postoperative outcomes of patients undergoing radical cystectomy. Materials and Methods: We retrospectively evaluated clinical data of 317 patients who had undergone radical cystectomy for bladder cancer. Univariate and multivariate logistic regression analyses were performed to determine whether preoperative patient clinical factors influence clinical (30-day morbidity according to the Clavien-Dindo classification) and economical (length of hospital stay) postoperative outcomes. Results: In univariate analysis, low Charlson comorbidity score (p = 0.011), low ASA score (p = 0.015), no aspirin intake (p = 0.048) and high-normal preoperative potassium level (p = 0.034) were associated with reduced 30-day morbidity. In multivariate analysis, only high preoperative potassium remained an independent predictive factor for a reduced risk of postoperative complications (odds ratio 0.67, 95% confidence interval (0.48, 0.92), p = 0.014). Furthermore, high-normal preoperative potassium was the only preoperative factor associated with a shorter hospital stay ≤21 days (p = 0.007). Conclusions: High-normal preoperative potassium level was associated with better clinical (lower 30-day morbidity) and economical (shorter hospital stay) outcomes in patients undergoing radical cystectomy. We recommend that a randomized controlled trial be performed to investigate whether there is a causal relationship between preoperative potassium supplementation and postoperative complications and length of hospital stay.

Outcomes of Direct Oral Anticoagulants with Aspirin Versus Warfarin with Aspirin for Atrial Fibrillation and/or Venous Thromboembolic Disease

▪IntroductionThe direct oral anticoagulants (DOACs) including apixaban, dabigatran, edoxaban, and rivaroxaban are increasingly utilized for the management of venous thromboembolic disease (VTE) and/or non-valvular atrial fibrillation (NVAF). Adding aspirin (ASA) to warfarin or DOAC therapy increases bleeding risk. Patients on combination therapy with ASA and an anticoagulant were not well represented in clinical trials comparing DOACs to warfarin. We sought to compare bleeding and thrombotic outcomes with DOACs and ASA compared to warfarin and ASA in a non-trial setting.MethodsWe conducted a retrospective registry-based cohort study of adults on DOAC or warfarin therapy for VTE and/or NVAF. Warfarin treated patients were followed by six anticoagulation clinics. Four out of the six clinics contributed data on their patients that were on DOACs in the Michigan Anticoagulation Quality Improvement Initiative (MAQI 2) from January 2009 to June 2021. Patients were excluded if they had a history of heart valve replacement, recent myocardial infarction, or less than 3 months of follow-up. Two propensity matched cohorts (warfarin+ASA vs DOAC+ASA) of patients were analyzed based on ASA use at the time of study enrollment. The primary outcome was any new bleeding event. Secondary outcomes included new episodes of arterial or venous thrombosis, bleeding event type (major, fatal, life threatening, central nervous system, and non-major bleeding), emergency room visits, hospitalizations, transfusions, and death. Random chart audits were done to confirm the accuracy of the abstracted data. Event rates were compared using Poisson regression.ResultsWe identified a total of 1,139 patients on DOACs plus ASA and 4,422 patients on warfarin plus ASA. After propensity matching, we compared two groups of 1,114 matched patients. DOAC treated patients were predominately on apixaban (62.3%) and rivaroxaban (30.4%), most often at therapeutic doses (Table 1). Patients were largely (90.5%) on low dose ASA (≤ 100 mg). Patient demographics, co-morbidities, indication for anticoagulation, history of bleeding or clotting, medications, and duration of follow-up were well-balanced after matching. Patients were followed for a median of 11.7 months (interquartile range 4.4 and 34 months). Patients treated with DOAC+ASA had 2.4 thrombotic events per 100 patient years compared to 2.2 thrombotic events per 100 patient years with warfarin+ASA (P=0.78). There were no significant differences observed between groups by thrombotic subtype (stroke, transient ischemic attack, pulmonary embolism, deep vein thrombosis, table 1). Bleeding was also similar with 30.1 bleeding events per 100 patient years with DOAC+ASA compared to 27.8 bleeds per 100 patient years with warfarin+ASA (P=0.24). There were no significant differences by bleeding subtype (table 1). Hospitalizations for clotting occurred less frequently with DOAC+ASA (0.9 hospitalizations per 100 patient years) compared to warfarin+ASA (1.7 hospitalizations per 100 patient years, P=0.03). Mortality, transfusions, and healthcare utilization were otherwise similar between the two groups.ConclusionsFor patients on a DOAC versus warfarin with ASA for atrial fibrillation and/or venous thromboembolic disease without a recent myocardial infarction or heart valve replacement, bleeding and thrombotic outcomes were similar. [Display omitted] DisclosuresKaatz: Gilead: Consultancy; CSL Behring: Consultancy; Novartis: Consultancy; Bristol Myer Squibb: Consultancy, Research Funding; Pfizer: Consultancy; Alexion: Consultancy; Janssen: Consultancy, Research Funding; Osmosis Research: Research Funding. Kline-Rogers: Janssen: Consultancy; American College of Physicians: Consultancy. Sood: Bayer: Consultancy. Froehlich: Merck: Consultancy; Janssen: Consultancy; Novartis: Consultancy; Boehringer-Ingelheim: Consultancy; Pfizer: Consultancy; Blue Cross Blue Shield of Michigan: Research Funding; Fibromuscular Disease Society of America: Research Funding. Barnes: National Certification Board of Anticoagulation Providers: Membership on an entity's Board of Directors or advisory committees; Janssen: Consultancy; Acelis: Consultancy; AMAG Pharmaceuticals: Consultancy; Connected Health: Consultancy; Blue Cross Blue Shield of Michigan: Research Funding; AC Forum: Membership on an entity's Board of Directors or advisory committees; Pfizer: Consultancy; Bristol-Myers Squibb: Consultancy.

Assessing the applicability and outcomes of the COMPASS trial a large cohort of atherosclerotic disease patients

Abstract Background Atherosclerotic Cardiovascular disease (ASCVD) is the leading cause of morbidity and mortality worldwide with substantial impact on health care resources. Rivaroxaban 2.5 mg twice daily with low dose ASA reduced death, myocardial infarction and stroke compared to ASA alone in stable ASCVD patients studied in the COMPASS trial. Purpose To assess the applicability and potential outcomes of applying the COMPASS antithrombotic strategy in a population-based cohort of patients with ASCVD. Methods All patients with a new diagnosis of ASCVD identified during hospital admission or outpatient medical encounters using validated case definitions from 2008–2019 were included. We determined the proportion who met COMPASS eligibility criteria (Eligible), the proportion who met inclusion criteria but had exclusion criteria (Excluded), and the proportion who did not meet inclusion criteria (Ineligible). Primary outcomes of interest were CV death, myocardial infarction, and stroke (MACE), with secondary outcomes all cause death, CV hospitalization, PAD intervention, amputation, and all bleeding which were followed to end of study. Results Of 226,446 new ASCVD patients in the 11 years studied, 73% had coronary artery disease, 17% had peripheral artery disease including cerebral and peripheral vascular disease (PAD), and 10% had both. Of the 364,442 prevalent cases, 27% met COMPASS eligibility criteria, another 42% met inclusion criteria but would have been excluded and 31% were Ineligible. The main reasons for exclusion were high bleeding risk characteristics in 69% and concomitant medical therapy (CYP3A4 inducers 30%, oral anticoagulants 28%, and dual antiplatelet therapy 7%). The MACE event rates were approximately twice as high in the excluded group as those deemed COMPASS eligible (figures 1). COMPASS eligible patients in our cohort exhibited event rates similar to the ASA arm of COMPASS (figure 2). The other event rates per 100 person-years for Eligible, Excluded, and Ineligible patients respectively were: all-cause death 4.6, 10.6, 1.2,; CV hospitalization 4.8, 8.8, 3.0; PAD intervention 0.6, 0.6, 0.1; and all bleeding 1.9, 4.3, 1.1. If the COMPASS antithrombotic strategy of Rivaroxaban 2.5 twice daily with low dose ASA was given to patients deemed eligible in this population, there would have been a potential reduction of 87 MACE events, 34 CV death, 25 MI, 24 stroke, and 12 amputations per 10,000 patient years of treatment. Conclusion In a population of 4.4 million persons, there are approximately 20,000 incident ASCVD patients diagnosed yearly. Approximately 70% of patients with ASCVD in the real-world met COMPASS inclusion criteria, although more than half would be excluded due to high-bleed risk characteristics or concomitant medical therapy. Implementing the COMPASS antithrombotic strategy would result in substantial reduction in CV death and MACE events. Funding Acknowledgement Type of funding sources: Private company. Main funding source(s): Bayer MACE by COMPASS eligibilityEvent rates compared to COMPASS ASA

Predicting 30-day mortality after hip fracture: the G4A calibrated prognostic tool.

Proximal femoral fracture is common with a high mortality (7% mortality at 30 days). Accurate determination of mortality risk allows better consenting, clinical management and expectation management. Our study aim was to develop a prognostic tool to predict 30-day mortality after proximal femoral fracture, among patients treated within a dedicated hip fracture unit. We collected data from our hospital concerning 2210 patients with 2287 proximal femoral fractures. The clinical parameters of 97 patients who died within 30 days of surgery were analysed. We used logistic regression to determine if the parameters' relationship with 30-day mortality was statistically significant or not. The statistically significant parameters were used to create a prognostic model for predicting 30-day mortality. The 5 independent predictors of 30-day mortality were gender, age, admission source, preoperative Abbreviated Mental Test Score (AMTS) and American Society of Anesthesiologists Score (ASA). The highest risk was for males >85 years, admitted from institutional care, with low preoperative mental test score and high ASA grade. Using these predictors, we formulated the G4A score. The Hosmer-Lemeshow 'goodness of fit' test showed good concordance between observed and predicted mortality rates. We recommend the use of the G4A score to predict 30-day mortality after surgery for proximal femoral fracture, particularly within dedicated hip fracture units. Further research is needed to establish whether the findings of this study are applicable on a national scale.

A Less Than 81mg of Aspirin in Heart Mate 3 is Safe Irrespective of Amount of Platelet Inhibition

Purpose Optimal dose of aspirin for Heartmate 3 (HM 3) LVAD patients is still not known. Recently low dose aspirin (81mg compared to 325mg) has shown to be efficacious. Randomized control trial with no dose aspirin is underway. However, platelet inhibition can be still achieved with less than low dose aspirin. So we looked into safety and efficacy of a very low dose aspirin ( Methods We did retrospective analysis of HM3 patients implanted in our institution (2015- 2020). Patients who were on less than 81mg of aspirin/day were identified. Thromboelastogram (TEG) was used to assess response to aspirin. We compared the number of thromboembolic events, bleeding events, LDH, and hematocrit before and after the dose change, with the patients being their own controls, using paired t test. Results In our program, we follow 35 patients on HM3. Most of them 24(68.6%) receive > 81 mg of aspirin daily. We Identified 11 patients on less than 81mg of aspirin. The mean age of this cohort was 51.18 years, 7 were Male. Out of the 11, 3 patients were on aspirin 40.5 mg every other day, 3 on 40.5 mg every day, 4 on 81mg every other day and one patient was not on any aspirin. Reason for dose alteration was adequate inhibition noted on TEG in 5 patients and bleeding in 6 patients (4 out of 6 for gastrointestinal bleed). Mean duration of follow up was 22.57±18months. Six patients in this cohort were on standard warfarin protocol with the INR goal 2-3 and one patient was not on any warfarin. The follow-up on a very low ASA dose was 13.7±8.6 months. There were no pump thrombosis or other thromboembolic events either before or after the dose change. There was no significant difference in LDH levels before (225.2±24.3) or after (220.1±27.8) p=0.7, hematocrit before 33.6+/-9.9 or after 35.0+/-8.1, P=0.08, aspirin dose change. Arachidonic Acid inhibition on thromboelastogram was less than 80% in 7 patients and 5 of them had inhibition less than 50%. Conclusion A very low dose of aspirin (

1046 Assessing compliance to daily low dose aspirin for preeclampsia prevention using a validated questionnaire

Adherence is essential to the efficacy of ASA in preventing preeclampsia (PE). Our objective was to evaluate and compare the adherence of pregnant women at high risk for PE to different regimens of ASA using a validated questionnaire, the simplified medication adherence questionnaire (SMAQ). 33 pregnant women identified as high risk for developing PE using the Unites States Preventative Services Task Force (USPSF) criteria were randomized in an open-label setting to either ASA 81mg daily or ASA 162mg daily, to be initiated before 16 weeks’ gestation. The USPSF criteria include: PE in a prior pregnancy, chronic hypertension, pregestational diabetes, renal disease, autoimmune disease or multifetal gestation. Compliance to therapy was ascertained using the validated SMAQ at 20, 26 and 36 ± 2 weeks’ gestation (Table 1). Non-adherence was defined as: a positive response to any of the qualitative questions, >2 missed doses over the past week, or >2 days of non-use in the past 3 months. Compliance rates were compared across treatment groups using Chi-square with an alpha error level set at <0.05. The mean age of participants was 36.0±4.9 years, 16/33 (48.5%) were primiparous. Age and parity were similar for both treatment groups. 18/33 (54.5%) women were randomized to the ASA 81mg group and 15/33 (45.5%) to ASA 162mg. The SMAQ was completed by 93.9% of participants at 20±2 weeks, 87.9% at 26±2 weeks and 75.8% at 36±2 weeks. Table 2 outlines compliance rates with daily low dose aspirin, stratified by treatment group. Overall, medication adherence was higher in the ASA 81mg group, particularly after the mid-trimester. Reasons for non-adherence included gastrointestinal side effects (6.1%), vaginal spotting (3%) and non-intentional omission (9.1%). Aspirin compliance appears to be elevated in women at high risk for PE who are prescribed ASA 81mg daily and to be significantly lower in women on 162mg. This should be taken into consideration when prescribing and counseling women about low dose ASA for PE prevention.View Large Image Figure ViewerDownload Hi-res image Download (PPT)

Safety and efficacy of remimazolam in high risk colonoscopy: A randomized trial

BackgroundProcedural sedation of ASA III/IV patients has increased risk. Remimazolam (an ultra-short-acting benzodiazepine) has proven safe and efficient for outpatient colonoscopy sedation. MethodsA double-blind, randomized, multi-center, parallel group trial was performed, comparing remimazolam to placebo with an additional open-label arm for midazolam in procedural sedation of 79 ASA III/IV patients undergoing colonoscopy. This was the third of 3 Phase III trials for remimazolam in the procedural sedation program. The primary end point was the safety of remimazolam. ResultsOf 79 patients randomized at 3 US sites, 77 underwent sedation and colonoscopy (31 received remimazolam, 16 placebo and 30 midazolam). Incidence and frequency of treatment emergent adverse events (TEAEs) were comparable in all three treatment arms, and independent of ASA status. One TEAE leading to discontinuation and one serious TEAE were reported; both in the open label midazolam arm. The efficacy endpoint was achieved for remimazolam, placebo, and midazolam in 87.1%, 0%, and 13.3% of patients (p<0.00001 for remimazolam versus placebo and versus midazolam, respectively). ConclusionsRemimazolam is safe and efficient in procedural sedation of high risk ASA patients undergoing colonoscopy, showing a safety profile comparable to that in low risk ASA.

Pro-apoptotic properties and mitochondrial functionality in platelet-like-particles generated from low Aspirin-incubated Meg-01 cells

Long-term therapy with low Aspirin (ASA) dose is basis to prevent thrombotic acute events. However, the anti-platelet mechanisms of ASA remain not completely known. The aim was to analyze if in vitro exposure of human megakaryocytes to low ASA concentration may alter the apoptotic features of the newly formed platelets. Cultured Meg-01 cells, a human megakaryoblastic cell line, were stimulated to form platelets with 10 nmol/L phorbol 12-myristate-13-acetate (PMA) in the presence and absence of ASA (0.33 mmol/L). Results revealed that platelet-like particles (PLPs) derived from ASA-exposed Meg-01 cells, showed higher content of pro-apoptotic proteins Bax and Bak than PLPs from non-ASA incubated Meg-01 cells. It was accompanied of reduced cytochrome C oxidase activity and higher mitochondrial content of PTEN-induced putative kinase-1 in PLPs from ASA-incubated Meg-01 cells. However, only after calcium ionophore A23187 stimulation, caspase-3 activity, the cytosolic cytochrome C content, and reduction of mitochondrial membrane potential were higher in PLPs from ASA-incubated megakaryocytes than in those from Meg-01 without ASA. Nitric oxide synthase 3 content was higher in PLPs from ASA-exposed Meg-01 cells than in PLPs from non-ASA incubated Meg-01 cells. The L-arginine antagonist, NG-Nitro-L-arginine Methyl Ester, reduced caspase-3 activity in A23187-stimulated PLPs generated from ASA-incubated Meg-01 cells. As conclusions exposure of megakaryocyte to ASA promotes that the newly generated PLPs have, under stimulating condition, higher sensitivity to go into apoptosis than those PLPs generated from Meg-01 cells without ASA. It could be associated with differences in mitochondrial functionality and NO formation.

Feasibility assessment of outpatient colorectal resections at a tertiary referral center

Enhanced Recovery After Surgery (ERAS) protocols, particularly when paired with advanced laparoscopy, have reduced recovery time following colorectal procedures. The aim of this study was to determine if length of stay (LOS) could be reduced to an overnight observation stay (< 24h) with comparable perioperative morbidity. The secondary aim was to establish predictive factors contributing to early discharge. This is a retrospective cohort study of all colectomies at a tertiary care center between January 2016 and January 2019. Inclusion criteria included all colorectal resections with varying surgical approaches. Patients underwent a standardized ERAS protocol. A logistical regression model was conducted for predictive factors. Three hundred sixty patients were included (55.3% female). Of these, 78 (21.7%) patients were discharged within < 24h and 112 (31.1%) were discharged within 24-48h. The remainder comprised the > 48h group. Age differed significantly between the < 24h and 24-48h groups (p < 0.0001). Patients discharged within 24h were younger (59.4 ± 12.3years), had a lower CCI score (3.1; p = 0.0026), and lower ASA class (p < 0.0001). Emergency department visits (p = 0.3329) and readmissions (p = 0.6453) prior to POD 30 remained comparable among all groups. Younger age, low ASA, and minimally invasive surgical approach all contributed to ultra-fast discharge. ERAS protocols may allow for discharge within 24h following a major colorectal resection, all with low perioperative morbidity and mortality. The predictive factors for discharge within 24h include a low ASA (I or II), and a minimally invasive surgical approach.

Survival data on timing of resection of liver metastases in colorectal cancer patients.

Between 2007 and 2016, 140 consecutive patients who underwent resection of colorectal cancer with simultaneous liver metastases at a single university hospital were retrospectively analysed. In order to gather information regarding potential survival differences for n = 68 simultaneous versus n = 72 staged resections of the colorectal primary tumor and the liver metastases, Clinical, histopathological, serological, and survival data were compared for those two patient groups. The rate of simultaneous tumor resections increased from approximately 25% in 2007 to >75% in 2016. There was no difference in tumor specific survival for patients with simultaneous vs. staged resection (p = 0.631). This effect continued after excluding patients with extrahepatic metastases (p = 0.440). Further, neoadjuvant treatment did not lead to differences in the tumor-specific survival (p = 0.123). Factors associated with an increased tumor-specific survival were low ASA score (p < 0.001), low number of tumor-affected lymph nodes (p < 0.001), histological grading G1/2 (p = 0.001), and a low number of liver metastases (p = 0.044). There was no significant survival difference for the primary tumor stage (pT), the Clavien-Dindo complication rate, the resection status (R0), and minor versus major hepatectomies.

Retrospective analysis of acute left colon obstructions due to colorectal cancers

Amaç: Kolorektal tümörlere bağlı akut sol kolon tıkanıklığı bulguları gösteren olgularda acil koşullarda uygulanan rezeksiyon primer anastomoz sonuçlarının değerlendirilmesi ve bu sonuçların Hartmann Prosedür uygulanan hastaların sonuçlarıyla karşılaştırılması amaçlanmıştır. Gereç ve Yöntem: Ağustos 2005-Mart 2011 tarihleri arasında Ankara Numune Eğitim ve Araştırma Hastanesi Acil Cerrahi Servisi’ne yatış yapılan kolorektal kansere bağlı akut sol kolon obstrüksiyonu nedeniyle ameliyat edilen 84 hasta çalışmaya alındı ve retrospektif olarak incelendi. Hastaların tümü acil serviste değerlendirilip acil ameliyathanede opere edilmiştir. Hastaların tedavisinde Hartmann kolostomi ve rezeksiyon primer anastomoz cerrahi prosürleri kullanıldı. Barsak temizliği yapılmadan operasyona alındı ve intraoperatif rezeksiyon sonrası tüm hastalara manuel dekompresyon yapıldıktan sonra ya rezeksiyon primer anastomoz ya da Hartmann Prosedür yapıldı. Bulgular: Stoma açılan grupta postoperatif yoğun bakım ihtiyacı olan hasta sayısı 25, ventilatör ihtiyacı olanların sayısı 16, stoma revizyonu yapılan hasta sayısı 3 idi. Kardiyopulmoner morbidite sayısı 10, reoperasyon 9, mortalite sayısı 13 olarak saptandı. Anastomoz yapılan grupta ise postoperatif yoğun bakım ihtiyacı olan hasta sayısı 13, ventilatör ihtiyacı olanların sayısı 4’tü ve anastomoz yapılanların 2’sinde anastomoz kaçağı olduğu görüldü. Yeniden operasyona giren hasta sayısı 2 idi, mortalite sayısı 5 olarak saptandı. Her iki grup arasında postoperatif yoğun bakım ihtiyacı, ventilatör ihtiyacı, reoperasyon ve mortalite açısından p değerleri &amp;lt;0,05 olup anlamlı idi.Sonuç: Kolorektal kansere bağlı akut sol kolon obstrüksiyonu nedeniyle ameliyat edilecek hastalarda; genel durumu iyi, komorbiditesi ve ASA skoru düşük olan hastalara cerrahın tecrübesine dayanarak intraoperatif manuel dekompresyonla rezeksiyon-primer anastomoz yapılmasını önermekteyiz.

Continuing our work: transplant surgery and surgical oncology in a tertiary referral COVID-19 center.

COVID-19 is rapidly spreading worldwide. Healthcare systems are struggling to properly allocate resources while ensuring cure for diseases outside of the infection. The aim of this study was to demonstrate how surgical activity was affected by the virus outbreak and show the changes in practice in a tertiary referral COVID-19 center. The official bulletins of the Italian National Institute for the Infectious Diseases “L. Spallanzani” were reviewed to retrieve the number of daily COVID-19 patients. Records of consecutive oncological and transplant procedures performed during the outbreak were reviewed. Patients with a high probability of postoperative intensive care unit (ICU) admission were considered as high risk and defined by an ASA score ≥ III and/or a Charlson Comorbidity Index (CCI) ≥ 6 and/or a Revised Cardiac Risk Index for Preoperative Risk (RCRI) ≥ 3. 72 patients were operated, including 12 (16.6%) liver and kidney transplantations. Patients had few comorbidities (26.3%), low ASA score (1.9 ± 0.5), CCI (3.7 ± 1.3), and RCRI (1.2 ± 0.6) and had overall a low risk of postoperative ICU admission. Few patients had liver cirrhosis (12.5%) or received preoperative systemic therapy (16.6%). 36 (50%) high-risk surgical procedures were performed, including major hepatectomies, pancreaticoduodenectomies, total gastrectomies, multivisceral resections, and transplantations. Despite this, only 15 patients (20.8%) were admitted to the ICU. Only oncologic cases and transplantations were performed during the COVID-19 outbreak. Careful selection of patients allowed to perform major cancer surgeries and transplantations without further stressing hospital resources, meanwhile minimizing collateral damage to patients.

1681 Carotid screening prior to stress echocardiography, an opportunity to assess cardiovascular risk?

Abstract BACKGROUND Screening for atherosclerosis is an important method for assessing cardiovascular (CV) risk. Our data with carotid imaging shows a normal a carotid is associated with a very low 10-year CV risk of 1.6%. Even a low risk carotid still predicts a favourable outcome, 5.6-7.0% CV risk over 10 years. Increasing plaque burden as assessed by either total plaque area (&amp;gt;25mm2) or plaque score (&amp;gt;1) is associated with increasing CV risk, ranging from 20% to &amp;gt;30% over 10 years. PURPOSE This analysis was performed to estimate the prevalence and severity of carotid disease in men and women presenting for stress ECHO, with no prior documented evidence of CV disease. METHODS Data was collected from October 3, 2011 to January 22, 2019. Male patients aged 40-70yrs and female patients aged 50-75yrs undergoing stress ECHO underwent a screening carotid examination prior to the test. This involves only 2-3 images on each side to include, the CCA, carotid bulb and ICA. Maximal CCA IMT is measured using an automatic edge detection method, plaque score is calculated using the Rotterdam method and plaque area is measured in the carotid bulb and ICA bilaterally. Total plaque area being the sum of all area measurements. Apart from age criteria, patients were also excluded if they were diabetic, already taking a statin, or had a previous history of any vascular disease. A low-risk carotid was defined as a maximal CCA IMT &amp;lt;1.00m,with a plaque score of "0" or "1" providing the total plaque area was &amp;lt;25mm2. An unpaired t-test was used to detect differences between means and the Fisher’s exact test was used to detect differences between proportions. A p value of &amp;lt;0.05 was considered statistically significant. RESULTS There were 1683 patients, 1175 females and 508 males with a mean age of 60.9 ± 7.4 years. Of the 1683 patients 1058 had evidence of carotid plaque (62.9%), 368 males (72.4%) and 690 females (58.7%). 726 patients were classified as low-risk and 957 patients were classified as high-risk. See Table 1. CONCLUSIONS A brief screening carotid examination prior to stress ECHO reveals a large percentage of both men and women who have evidence of atherosclerosis, of which 56.9% are high-risk. These patients could be identified while in the ECHO laboratory. The patients could then be offered guideline therapy with statin therapy and low dose ASA. Table 1. Number Age CCA IMT PS 0-1 PS 2-3 PS 4-6 Low-risk High-risk Males 508 58.4 ± 7.8 1.14 ± 0.47 138 213 56 161 347 Females 1175 62.0 ± 7.0 0.99 ± 0.49 726 395 54 565 610 P value &amp;lt;0.0001 &amp;lt;0.0001 &amp;lt;0.0001 &amp;lt;0.005 &amp;lt;0.0001 &amp;lt;0.0001 &amp;lt;0.0001 PS = Plaque score.

BcERF070, a novel ERF (ethylene-response factor) transcription factor from non-heading Chinese cabbage, affects the accumulation of ascorbic acid by regulating ascorbic acid-related genes

L-Ascorbic acid (AsA) is an important nutrient in non-heading Chinese cabbage (Brassica rapa ssp. chinensis). To understand the regulatory mechanism of AsA accumulation, we crossed “Wutacai” and “Erqing” to obtain F2 plants and then constructed two pools (AsA-High and AsA-Low) of F2-generation plants to further analyze the differentially expressed genes (DEGs) by cDNA-amplified fragment length polymorphism (cDNA-AFLP) technology. Among the DEGs, BcERF070 showed a significantly higher expression level in “Wutacai” and F2 plants with high AsA than in “Erqing” and F2 plants with low AsA, suggesting that BcERF070 is involved in the accumulation of AsA. To further understand the function of BcERF070 in AsA accumulation, we obtained BcERF070-silenced plants and BcERF070-overexpressed Arabidopsis thaliana plants. It was found that the downregulation of BcERF070 resulted in a decrease in AsA content, and the upregulation of BcERF070 resulted in an increase in AsA content. To evaluate the mechanism of BcERF070 involvement in the accumulation of AsA, the leaves of BcERF070-silenced and control plants were subjected to transcriptome sequencing. Twelve DEGs including BrAPXs were found to be associated with ascorbic acid. The qRT-PCR analysis on BcERF070-silenced plants and BcERF070-overexpressed plants further demonstrated the reliability of the transcriptome sequencing. Finally, based on analysis of the cis-acting elements of the promoter of 12 AsA-related genes, we speculated that BcERF070 may act on the DRE (dehydration-responsive element) of seven target gene promoters to regulate AsA content. In conclusion, a novel transcription factor, BcERF070, was revealed in this study, which affected the accumulation of AsA by regulating genes involved in the ascorbate biosynthesis and metabolic pathway. This information will help in understanding the regulatory mechanism of BcERF070 involvement in the accumulation of AsA in plants.