Increased mortality in acromegaly is due to vascular and respiratory disease and is normalised by control of GH levels-A retrospective analysis from the UK Acromegaly Register 1970-2016.

CONTEXT: Epidemiological studies involving patients with acromegaly have yielded conflicting results regarding cancer incidence and causes of mortality in relation to control of growth hormone (GH) excess. OBJECTIVE: The objective of this retrospective cohort study is to clarify these questions and identify goals for treatment and monitoring patients. METHODS: We studied 1845 subjects from the UK Acromegaly Register (1970-2016), obtaining cancer standardised incidence rates (SIR) and all causes standardised mortality rates (SMR) from UK Office for National Statistics, to determine the relationship between causes of mortality-age at diagnosis, duration of disease, post-treatment and mean GH levels. RESULTS: We found an increased incidence of all cancers (SIR, 1.38; 95% CI: 1.06-1.33, p < .001), but no increase in incidence of female breast, thyroid, colon cancer or any measure of cancer mortality. All-cause mortality rates were increased (SMR, 1.35; 95% CI: 1.24-1.46, p < .001), as were those due to vascular and respiratory diseases. All-cause, all cancer and cardiovascular deaths were highest in the first 5 years following diagnosis. We found a positive association between post-treatment and mean treatment GH levels and all-cause mortality (p < .001 and p < .001), which normalised with posttreatment GH levels of <1.0 µg/L or meantreatment GH levels of <2.5 µg/L. CONCLUSION: Acromegaly is associated with increased incidence of all cancers but not thyroid or colon cancer and no increase in cancer mortality. Excess mortality is due to vascular and respiratory disease. The risk is highest in the first 5 years following diagnosis and is mitigated by normalising GH levels.

Contemporary Use of the Femoropopliteal Vein in Vascular Reconstructions.

INTRODUCTION: Current practice patterns favor endovascular treatment, resulting in fewer open procedures. When needed, greater saphenous vein and/or prosthetic conduits are considered the first choice for open vascular bypass. However, there is a cohort of patients in which these conduits are either not available or not suitable to address the surgical requirements. One alternative is to use femoropopliteal vein (FPV), an often-overlooked conduit. We report on the contemporary use of FPV in a tertiary vascular institution. METHODS: All patients who underwent FPV harvest, as defined by CPT code 35572, between 2005 and 2019 were identified. Patient demographics (sex, age, baseline laboratory values, medical co-morbidities), indication for use of FPV, complications specific to vein harvest, operative details, post-operative course, and outcomes were recorded. RESULTS: Ninety patients had harvest of FPV for creation of 123 conduits. In this study, a conduit was defined as a segment of vein used to perfuse a distinctly separate vascular bed. We identified four cohorts in which FPV was used: aorto-iliac reconstruction in 38 patients for infected graft (19), occlusive disease (8), aortitis (5), mycotic aneurysm (5), and malignancy (1); peripheral artery revascularization in 26 patients for ilio-femoral reconstruction (15), femoropopliteal reconstruction (4), upper extremity/cerebrovascular reconstruction (6), and coronary bypass (1); mesenteric revascularization in 20 patients for acute or acute on chronic ischemia (12), chronic ischemia (7) or aneurysm (1); and dialysis access in 6 patients. There was a high incidence of pre-existing comorbid conditions in all groups, but most notably those patients who underwent aorto-iliac reconstruction. Harvest-related or conduit-related complications included compartment syndrome, graft-associated hemorrhage, surgical site infection, and lymphatic complications. Primary graft patency at 3 years was 83% ± 4% (aorto-iliac), 83% ± 6% (peripheral), 100% (mesenteric), and 23% ± 19% (dialysis access, P < 0.001). CONCLUSIONS: While use of FPV has potential significant harvest-related, conduit-related, or systemic complications, FPV is useful for a variety of needs, almost universally available, and durable. In the current era where endovascular approach is the focus, FPV should not be forgotten as a potential conduit that can be used for a variety of vascular reconstruction indications.

Exploring the Utility of Brain Natriuretic Peptide Measurement in Vascular Surgery.

BACKGROUND: The Canadian Cardiovascular Society 2016 guidelines recommend pre-operative measurement of brain natriuretic peptide (BNP) to risk-stratify patients for a 30-day composite outcome of death, myocardial infarction, or asymptomatic myocardial injury after noncardiac surgery (MINS). Whether this practice affects outcomes is unclear. The aim of this study was to examine the clinical utility of brain natriuretic peptide and myocardial injury after noncardiac surgery. METHODS: Analysis of a prospectively maintained database identified all elective open vascular surgery cases at an academic teaching hospital from January 2015 to December 2018. Pre-operative BNP values were available from June 2018 onward after becoming institutionally mandated. Co-morbidities were also collected to stratify patients using the Revised Cardiac Risk Index. The composite outcome of 30-day mortality, myocardial infarction, or MINS was determined. RESULTS: Prior to BNP becoming an institutionally required test, data was available from 1176 open cases. The 30-day mortality was 1.3% (15/1176) and post-operative myocardial infarction rate was 2.3% (27/1176). BNP measurements were collected in 91 consecutive patients. Ten patients (11%) experienced the composite outcome of mortality, myocardial infarction, or MINS. Elevated BNP was associated with increased odds of the composite outcome (P = 0.04), but not with mortality or myocardial infarction. Revised Cardiac Risk Index score was not predictive of outcomes. The majority of patients who qualified for the composite outcome experienced only an asymptomatic troponin rise (80%). Two patients met the universal definition of myocardial infarction, one of whom died. No other deaths occurred within 30 days. Detection of MINS did not result in any significant changes to patient management. CONCLUSIONS: Elevated BNP correlates with increased MINS. An asymptomatic troponin rise is the most commonly observed event, with unclear clinical implications. BNP may over-estimate surgical risk. Further studies on the long-term outcomes of patients with elevated BNP and MINS are required before widely adopting this strategy in vascular surgery patients.

Treatment of systemic sclerosis.

Systemic sclerosis (SSc) is a rare connective tissue disease characterized by skin and visceral fibrosis, vascular hyperreactivity and obliterative vasculopathy. Some of its complications such as interstitial lung disease (ILD), pulmonary arterial hypertension (PAH) and heart involvement can be life-threatening and are associated with a high mortality and a poor prognosis. Many clinical trials were carried out in order to improve the survival and prognosis of SSc patients. The management of SSc is based on the frequent and regular assessment of the potential organ damage, and if present, the establishment of graduated pharmacological therapeutic strategies, associated with non-pharmacological procedures. Several randomized clinical trials have showed significant positive outcomes regarding some specific involvements. Many advances have been made, especially in the field of targeted therapies and personalized medicine, based on specific characteristics of the patient and the SSc.

Decision Science Can Inform Clinical Trade-Offs Regarding Cardiotoxic Cancer Treatments.

Cancer treatment-related cardiotoxicity (ie, heart failure, coronary artery disease, vascular diseases, arrhythmia) is a growing cancer survivorship concern within oncology practice; heart disease is the leading cause of noncancer death in cancer survivors and surpasses cancer as the leading cause of death for some cancers with higher survival rates. The issue of cardiotoxicity introduces a critical tradeoff that must be acknowledged and reconciled in clinical oncology practice: treating cancer aggressively and effectively in the present vs preventing future cardiotoxicity. Although many cancers must be treated as aggressively as possible, for others, multiple treatment options are available. Yet even when effective and less cardiotoxic treatments are available, they are not always chosen. Wariness to choose equally effective but less cardiotoxic treatment options may result in part from providers' and patients' reliance on "cognitive heuristics," or mental shortcuts that people (including, research shows, medical professionals) use to simplify complex judgments. These heuristics include delay discounting, availability and affect heuristics, and default bias. In the current commentary, we describe relevant research that illuminates how use of heuristics leads to biased medical decision making and translate how this research may apply when the tradeoff between aggressive cancer treatment and preventing future cardiotoxicity is considered. We discuss the implications of these biases in oncology practice, offer potential solutions to reduce bias, and call for future research in this area.

Ten-Year All-Cause Death According to Completeness of Revascularization in Patients With Three-Vessel Disease or Left Main Coronary Artery Disease: Insights From the SYNTAX Extended Survival Study.

BACKGROUND: Ten-year all-cause death according to incomplete (IR) versus complete revascularization (CR) has not been fully investigated in patients with 3-vessel disease and left main coronary artery disease undergoing percutaneous coronary intervention (PCI) versus coronary artery bypass grafting (CABG). METHODS: The SYNTAX Extended Survival study (Synergy Between PCI With TAXUS and Cardiac Surgery: SYNTAX Extended Survival [SYNTAXES]) evaluated vital status up to 10 years in patients who were originally enrolled in the SYNTAX trial. In the present substudy, outcomes of the CABG CR group were compared with the CABG IR, PCI CR, and PCI IR groups. In addition, in the PCI cohort, the residual SYNTAX score (rSS) was used to quantify the extent of IR and to assess its association with fatal late outcome. The rSS of 0 suggests CR, whereas a rSS>0 identifies the degree of IR. RESULTS: IR was more frequently observed in patients with PCI versus CABG (56.6% versus 36.8%) and more common in those with 3-vessel disease than left main coronary artery disease in both the PCI arm (58.5% versus 53.8%) and the CABG arm (42.8% versus 27.5%). Patients undergoing PCI with CR had no significant difference in 10-year all-cause death compared with those undergoing CABG (22.2% for PCI with CR versus 24.3% for CABG with IR versus 23.8% for CABG with CR). In contrast, those with PCI and IR had a significantly higher risk of all-cause death at 10 years compared with CABG and CR (33.5% versus 23.7%; adjusted hazard ratio, 1.48 [95% CI, 1.15-1.91]). When patients with PCI were stratified according to the rSS, those with a rSS≤8 had no significant difference in all-cause death at 10 years as the other terciles (22.2% for rSS=0 versus 23.9% for rSS>0-4 versus 28.9% for rSS>4-8), whereas a rSS>8 had a significantly higher risk of 10-year all-cause death than those undergoing PCI with CR (50.1% versus 22.2%; adjusted hazard ratio, 3.40 [95% CI, 2.13-5.43]). CONCLUSIONS: IR is common after PCI, and the degree of incompleteness was associated with 10-year mortality. If it is unlikely that complete (or nearly complete; rSS<8) revascularization can be achieved with PCI in patients with 3-vessel disease, CABG should be considered. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT00114972. URL: https://www.clinicaltrials.gov; Unique identifier: NCT03417050.

Understanding value and patient complexity among common inpatient vascular surgery procedures.

OBJECTIVE: Vascular surgery patients are highly complex, second only to patients undergoing cardiac procedures. However, unlike cardiac surgery, work relative value units (wRVU) for vascular surgery were undervalued based on an overall patient complexity score. This study assesses the correlation of patient complexity with wRVUs for the most commonly performed inpatient vascular surgery procedures. METHODS: The 2014 to 2017 National Surgical Quality Improvement Program Participant Use Data Files were queried for inpatient cases performed by vascular surgeons. A previously developed patient complexity score using perioperative domains was calculated based on patient age, American Society of Anesthesiologists class of ≥4, major comorbidities, emergent status, concurrent procedures, additional procedures, hospital length of stay, nonhome discharge, and 30-day major complications, readmissions, and mortality. Procedures were assigned points based on their relative rank and then an overall score was created by summing the total points. An observed to expected ratio (O/E) was calculated using open ruptured abdominal aortic aneurysm repair (rOAAA) as the referent and then applied to an adjusted median wRVU per operative minute. RESULTS: Among 164,370 cases, patient complexity was greatest for rOAAA (complexity score = 128) and the least for carotid endarterectomy (CEA) (complexity score = 29). Patients undergoing rOAAA repair had the greatest proportion of American Society of Anesthesiologists class of ≥IV (84.8%; 95% confidence interval [CI], 82.6%-86.8%), highest mortality (35.5%; 95% CI, 32.8%-38.3%), and major complication rate (87.1%; 95% CI, 85.1%-89.0%). Patients undergoing CEA had the lowest mortality (0.7%; 95% CI, 0.7%-0.8%), major complication rate (8.2%; 95% 95% CI, 8.0%-8.5%), and shortest length of stay (2.7 days; 95% CI, 2.7-2.7). The median wRVU ranged from 10.0 to 42.1 and only weakly correlated with overall complexity (Spearman's ρ = 0.11; P < .01). The median wRVU per operative minute was greatest for thoracic endovascular aortic repair (0.25) and lowest for both axillary-femoral artery bypass (0.12) and open femoral endarterectomy, thromboembolectomy, or reconstruction (0.12). After adjusting for patient complexity, CEA (O/E = 3.8) and transcarotid artery revascularization (O/E = 2.8) had greater than expected O/E. In contrast, lower extremity bypass (O/E = 0.77), lower extremity embolectomy (O/E = 0.79), and open abdominal aortic repair (O/E = 0.80) had a lower than expected O/E. CONCLUSIONS: Patient complexity varies substantially across vascular procedures and is not captured effectively by wRVUs. Increased operative time for open procedures is not adequately accounted for by wRVUs, which may unfairly penalize surgeons who perform complex open operations.

Functional Status and Out-of-Hospital Outcomes in Different Types of Vascular Surgery Patients.

BACKGROUND: We aimed to determine the correlation between the functional status at discharge in non-cardiac vascular surgery patients and the out-of-hospital mortality. METHODS: We performed a retrospective cohort study including adult non-cardiac vascular surgery patients (open, endovascular and venous procedures) surviving hospitalization in Boston, Massachusetts, USA. The exposure of interest was functional status determined by a licensed physical therapist at hospital discharge and rated based on qualitative categories adapted from the Functional Independence Measure. The primary outcome was all cause 90-day mortality after hospital discharge. The secondary outcome was readmission within 30days. Adjusted odds ratios were estimated by multivariable logistic regression models. RESULTS: This cohort included 2318 patients (male 51%; mean age 61 ± 17.7). After evaluation by a physiotherapist, 425 patients scored the lowest functional status, 631 scored moderately low, 681 moderately high and 581 scored the highest functional status. The lowest functional status was associated with a 3.41-fold increased adjusted odds for 90-day mortality (95%CI, 1.70-6.84) compared to patients with the highest functional status. When excluding venous intervention patients, the adjusted odds ratio was 6.76 (95%CI, 2.53-18.12) for the 90-day mortality post-discharge. The adjusted odds for readmission within 30-days was 1.5-fold increase in patients with the lowest functional status (95%CI, 1.04-2.20). CONCLUSIONS: In vascular surgery patients surviving hospitalization, functional status is strongly associated with out-of-hospital mortality and readmission rate. Future trials could provide evidence if improvement of functional status could prevent adverse outcomes in the postoperative setting.

Frailty leads to poor long-term survival in patients undergoing elective vascular surgery.

OBJECTIVE: Frailty has persistently been associated with unfavorable short-term outcomes after vascular surgery, including an increased complication risk, greater readmission rate, and greater short-term mortality. However, a knowledge gap remains concerning the association between preoperative frailty and long-term mortality. In the present study, we aimed to determine this association in elective vascular surgery patients. METHODS: The present study was a part of a large prospective cohort study initiated in 2010 in our tertiary referral teaching hospital to study frailty in elderly elective vascular surgery patients (Vascular Ageing Study). A total of 639 patients with a minimal follow-up of 5 years, who had been treated from 2010 to 2014, were included in the present study. The Groningen Frailty Indicator, a 15-item self-administered questionnaire, was used to determine the presence and degree of frailty. RESULTS: Of the 639 patients, 183 (28.6%) were considered frail preoperatively. For the frail patients, the actuarial survival after 1, 3, and 5 years was 81.4%, 66.7%, and 55.7%, respectively. For the nonfrail patients, the corresponding survival was 93.6%, 83.3%, and 75.2% (log-rank test, P < .001). Frail patients had a significantly greater risk of 5-year mortality (unadjusted hazard ratio, 2.09; 95% confidence interval, 1.572-2.771; P < .001). After adjusting for surgical- and patient-related risk factors, the hazard ratio was 1.68 (95% confidence interval, 1.231-2.286; P = .001). CONCLUSIONS: The results of our study have shown that preoperative frailty is associated with significantly increased long-term mortality after elective vascular surgery. Knowledge of a patient's preoperative frailty state could, therefore, be helpful in shared decision-making, because it provides more information about the procedural benefits and risks.

Lessons Learned from the Impact of the COVID-19 Pandemic in a Vascular Surgery Department and Preparation for Future Outbreaks.

OBJECTIVES: This study aims to report the changes and adaptations of a vascular tertiary center during a global pandemic and the impact on its activity and patients. METHODS: We conducted a retrospective cohort study within the Vascular Surgery ward in Centro Hospitalar Universitário Lisboa Norte, Portugal. All data from surgical, inpatient and outpatient activity were collected from February to June 2020 and compared to the same 5-month period in 2018 and 2019. We ran a descriptive analysis of all data and performed statistical tests for the variation of procedures and admissions between February and June 2018 and the same time period in 2020. RESULTS: During the outbreak, our staff had to be readapted. Six nurses were transferred to COVID-19 units (out of a total of 33 nurses) while 1 of the 7 residents was transferred to an intensive care unit and 1 senior surgeon was put on prophylactic leave. In the outpatient clinic, there was an increase in the number of telemedicine consultations with a greater focus on first-time referrals and urgent cases. There was a significant increase in the total number of elective admissions whereas there were significantly less admissions from an emergency setting (+57% and -54%, respectively, P < 0.001). The vascular surgery team performed a total number of 584 procedures between February and June 2020 (-17.8% compared to 2018 and 2019), with a significant increase in the number of endovascular procedures (P < 0.001) and in the use of local and regional anesthesia (P < 0.001), especially in the Angio Suite (+600%, P < 0.001). Comparing with 2018 and 2019, the surgical team performed less outpatient procedures in early 2020. We reported a significant increase in the total number of procedures for patients with a chronic limb-threatening ischemia (CLTI) diagnosis (+21%, P < 0.001). We did not report significant changes in the proportion of other vascular conditions. Regarding mortality, we observed a 16% decrease in the intraoperative mortality (P 0.67). CONCLUSIONS: In this study, we assessed the impact of the COVID-19 outbreak in daily activity during the contingency period. During the outbreak, there was an overall decline in outpatient clinics and inpatient admissions. Nevertheless, and despite the restrictions imposed by the pandemic and health authorities, we managed to maintain most procedures for most vascular diseases, particularly for CLTI urgent cases, without a significant increase in the mortality rate. Stringent protective measures for patient and staff or higher use of endovascular techniques and local anesthesia are some of the successful changes implemented in the department. These learned lessons are to be pursued as the pandemic evolves with future outbreaks of COVID-19, such as the current second outbreak currently spreading through Europe.

Impact of COVID-19 on vascular patients worldwide: analysis of the COVIDSurg data.

BACKGROUND: The COVIDSurg collaborative was an international multicenter prospective analysis of perioperative data from 235 hospitals in 24 countries. It found that perioperative COVID-19 infection was associated with a mortality rate of 24%. At the same time, the COVER study demonstrated similarly high perioperative mortality rates in vascular surgical patients undergoing vascular interventions even without COVID-19, likely associated with the high burden of comorbidity associated with vascular patients. This is a vascular subgroup analysis of the COVIDSurg cohort. METHODS: All patients with a suspected or confirmed diagnosis of COVID-19 in the 7 days prior to, or in the 30 days following a vascular procedure were included. The primary outcome was 30-day mortality. Secondary outcomes were pulmonary complications (adult respiratory distress syndrome, pulmonary embolism, pneumonia and respiratory failure). Logistic regression was undertaken for dichotomous outcomes. RESULTS: Overall, 602 patients were included in this subgroup analysis, of which 88.4% were emergencies. The most common operations performed were for vascular-related dialysis access procedures (20.1%, N.=121). The combined 30-day mortality rate was 27.2%. Composite secondary pulmonary outcomes occurred in half of the vascular patients (N.=275, 45.7%). CONCLUSIONS: Mortality following vascular surgery in COVID positive patients was significantly higher than levels reported pre-pandemic, and similar to that seen in other specialties in the COVIDSurg cohort. Initiatives and surgical pathways that ensure vascular patients are protected from exposure to COVID-19 in the peri-operative period are vital to protect against excess mortality.

Differences in hub and spoke vascular units practice during the novel Coronavirus-19 (COVID-19) outbreak in Lombardy, Italy.

BACKGROUND: To highlight differences in clinical practice among referral (hub, HH) or satellite (spoke, SH) hospital vascular surgery units (VSUs) in Lombardy, during the COVID-19 pandemic "phase 1" period (March 8 - May 3, 2020). METHODS: The Vascular Surgery Group of Regione Lombardia Register, a real-word, multicenter, retrospective register was interrogated. All patients admitted with vascular disease were included. Patients' data on demographics, COVID-19 positivity, comorbidities and outcomes were extrapolated. Two cohorts were obtained: patients admitted to HH or SH. Primary endpoint was 30-day mortality rate. Secondary outcomes were 30-day complications and amputation (in case of peripheral artery disease [PAD]) rates. Univariate and multivariate analysis were used to compare HH and SH groups and predictors of poor outcomes. RESULTS: During the study period, 659 vascular patients in 4 HH and 27 SH were analyzed. Among these, 321 (48.7%) were admitted to a HH. No difference in COVID-19 positive patients was described (21.7% in HH vs. 15.9% in SH; P=0.058). After 30 days from intervention, HH and SH experienced similar mortality and no-intervention-related complication rate (12.1% vs. 10.0%; P=0.427 and 10.3% vs. 8.3%; P=0.377, respectively). Conversely, in HH postoperative complications were higher (23.4% vs. 16.9%, P=0.038) and amputations in patients treated for PAD were lower (10.8% vs. 26.8%; P<0.001) than in SH. Multivariate analysis demonstrated in both cohorts COVID-19-related pneumonia as independent predictor of death and postoperative complications, while age only for death. CONCLUSIONS: HH and SH ensured stackable results in patients with vascular disease during COVID-19 "phase 1." Despite this, poor outcomes were observed in both HH and SH cohorts, due to COVID-19 infection and its related pneumonia.

Long-Term Impact of Vascular Surgery Stress on Frail Older Patients.

BACKGROUND: Frailty is a syndrome where the ability to cope with acute physiological stress is compromised, although it is unclear what impact this stress has on long-term outcomes. Vascular-Physiological and Operative Severity Score for enumeration of Mortality and Morbidity is a validated method for calculating levels of stress associated with vascular procedures. We designed this study to evaluate the long-term impact of different levels of surgical stress among frail older patients undergoing vascular surgery procedures. METHODS: We identified all independently living patients who underwent prospective frailty assessment followed by an elective vascular surgery procedure captured in the Vascular Quality Initiative registry (endovascular abdominal aortic aneurysm [AAA] repair, thoracic endovascular aortic repair, suprainguinal and infrainguinal bypass, peripheral vascular intervention, carotid endarterectomy, and open AAA) at an academic institution between January 2016 and July 2018. Patient- and procedure-level data were obtained from our institutional data warehouse and Vascular Quality Initiative database, and used to calculate Vascular-Physiological and Operative Severity Score for enumeration of Mortality and Morbidity scores. The association between frailty and composite outcome of any major complications (surgical site infection; graft thrombectomy; major amputation; adverse cardiac, pulmonary, or neurologic event; acute renal insufficiency; and/or reoperation related to the index procedure), nonhome living status, or death within 1 year after low-, medium-, and high-stress vascular procedures was evaluated using bivariate and logistic regression models. RESULTS: A total of 163 patients were identified (70% male, mean age 67.8 years) who underwent open AAA repair (6%), endovascular AAA repair (21%), thoracic endovascular aortic repair (7%), suprainguinal bypass (5%), infrainguinal bypass (18%), carotid endarterectomy (18%), or peripheral vascular interventions (25%), which included 44 (27%) patients diagnosed with frailty before surgery. Overall, frail patients had significantly higher rates of the 1-year composite outcome (48% frail versus 27% nonfrail; P = 0.012) when compared with nonfrail patients, with a significant dose-dependent effect as the level of stress increased. In comparison, increasing levels of surgical stress had a negligible effect on long-term outcomes among nonfrail patients. The interaction between frailty and high surgical stress was found in adjusted regression models to be a significant predictor of adverse outcomes within 1 year after vascular surgery (odds ratio, 3.3; 95% confidence interval, 1.3-8.6; P < 0.01). CONCLUSIONS: Frail patients who undergo high-stress vascular procedures have a significantly higher rate of complications leading to loss of functional independence and mortality within the year after their surgery. These data suggest that estimates of surgical stress should be incorporated into clinical decision making for frail older patients before and after surgery.

Vascular Surgery During COVID-19 Emergency in Hub Hospitals of Lombardy: Experience on 305 Patients.

OBJECTIVE: During the most aggressive phase of the COVID-19 outbreak in Italy, the Regional Authority of Lombardy identified a number of hospitals, named Hubs, chosen to serve the whole region for highly specialised cases, including vascular surgery. This study reports the experience of the four Hubs for Vascular Surgery in Lombardy and provides a comparison of in hospital mortality and major adverse events (MAEs) according to COVID-19 testing. METHODS: Data from all patients who were referred to the Vascular Surgery Department of Hubs from 9 March to 28 April 2020 were collected prospectively and analysed. A positive COVID-19 polymerase chain reaction swab test, or symptoms (fever > 37.5 °C, upper respiratory tract symptoms, chest pain, and contact/travel history) associated with interstitial pneumonia on chest computed tomography scan were considered diagnostic of COVID-19 disease. Patient characteristics, operative variables, and in hospital outcomes were compared according to COVID-19 testing. A multivariable model was used to identify independent predictors of in hospital death and MAEs. RESULTS: Among 305 included patients, 64 (21%) tested positive for COVID-19 (COVID group) and 241 (79%) did not (non-COVID group). COVID patients presented more frequently with acute limb ischaemia than non-COVID patients (64% vs. 23%; p < .001) and had a significantly higher in hospital mortality (25% vs. 6%; p < .001). Clinical success, MAEs, re-interventions, and pulmonary and renal complications were significantly worse in COVID patients. Independent risk factors for in hospital death were COVID (OR 4.1), medical treatment (OR 7.2), and emergency setting (OR 13.6). COVID (OR 3.4), obesity class V (OR 13.5), and emergency setting (OR 4.0) were independent risk factors for development of MAEs. CONCLUSION: During the COVID-19 pandemic in Lombardy, acute limb ischaemia was the most frequent vascular disease requiring surgical treatment. COVID-19 was associated with a fourfold increased risk of death and a threefold increased risk of major adverse events.

Meta-Analysis of the Effect of Vascular Complications on Mortality in Patients Undergoing Femoral Venoarterial Extracorporeal Membrane Oxygenation.

BACKGROUND: Extracorporeal membrane oxygenation (ECMO) has become an accepted treatment modality in the management of select patients with cardiopulmonary failure. As a result, its use has increased significantly over the past decade. However, the effect of complications on mortality is not clearly established. We performed a comprehensive, up-to-date meta-analysis of peer-reviewed literature focusing on the effect of vascular complications (VCs) on the survival of patients receiving venoarterial ECMO (VA-ECMO) with femoral cannulation. METHODS: A systematic search of 4 different databases (PubMed, Embase, Scopus, and Web of Science) was conducted from their inception to mid-September of 2019. To keep the pooled analysis current, only studies published within the past 5 years were included. Mortality was analyzed based on presence or absence of VCs. Studies with less then 10 patients, with incomplete mortality data, and not accessible in the English language were excluded. RESULTS: Ten studies were included in the analysis encompassing 1,643 patients over a 5-year period. There were 369 patients with a cumulative VC rate of 22.5% (range 9.4 to 43.9%). The pooled mortality rate for patients with and without VCs was 69.6% and 56.8%, respectively. Meta-analysis demonstrated a significant correlation between VCs and mortality with a relative risk (RR) of 1.36 (95% confidence interval (CI), 1.15-1.60; P = 0.0004). Covariate-adjusted meta-regression analysis revealed an inverse relationship between age and mortality for VCs, with an RR of 1.33 (95% CI, 1.15-1.54; P = 0.0184), and direct relationship between female gender and mortality from VCs, RR 1.39 (95% CI, 1.21-1.59; P = 0.0165). CONCLUSIONS: The most recently available data published in the literature demonstrate a significant correlation of VCs with mortality. Therefore, aggressive attempts should be made to minimize VCs in patients with femoral VA-ECMO cannulation.

Relation of Age to Risk of Major Rejections, Allograft Vasculopathy, and Long-Term Mortality in a Contemporary Cohort of Patients Undergoing Heart Transplantation.

OBJECTIVES: To investigate the impact of recipient age on the occurrence of rejections, vasculopathy, and mortality after HTx. METHODS: Study population comprised all consecutive 291 patients who underwent HTx between 1991-2016 and were followed at our center. Patients were categorized by age tertiles: < 46 years (mean 31.4 ± 11.7, range 16-45, n=90), 46-57 years (mean 51.4 ± 3.2, range 46-56, n=92), and ≥ 57 years (mean 61.6 ± 3.4, range 57-73, n=109). RESULTS: Patients aged ≥ 57 years were more often males and had more pre-HTx co-morbidities including hypertension, diabetes, dyslipidemia, and history of smoking (P < 0.05) compared to the younger age groups. Kaplan-Meier analysis by age tertiles showed the rates of major rejections and vasculopathy at 15 years were similar among the three age groups. Mortality rates at 15 years were directly related to the age groups (39%, 52%, 62% log-rank, P = 0.01). However, the association between age and mortality was no longer statistically significant after multivariate analysis (hazard ratio 1.01, 95% confidence interval 1.00-1.03). CONCLUSIONS: In a contemporary cohort of patients undergoing HTx, recipient age does not significantly impact the risk of major rejections, vasculopathy, and long-term mortality.

Prognostic Significance of Preoperative Neutrophil-Lymphocyte Ratio in Vascular Surgery: Systematic Review and Meta-Analysis.

OBJECTIVE: The global burden of surgical vascular disease is increasing and with it, the need for cost-effective, accessible prognostic biomarkers to aid optimization of peri-operative outcomes. The neutrophil-lymphocyte ratio (NLR) is emerging as a potential candidate biomarker for perioperative risk stratification. We therefore performed this systematic review and meta-analysis on the prognostic value of elevated preoperative NLR in vascular surgery. METHODS: We searched Embase (Ovid), Medline (Ovid), and the Cochrane Library database from inception to June 2019. Screening was performed, and included all peer-reviewed original research studies reporting preoperative NLR in adult emergent and elective vascular surgical patients. Studies were assessed for bias and quality of evidence using a standardized tool. Meta-analysis was performed by general linear (mixed-effects) modelling where possible, and otherwise a narrative review was conducted. Between-study heterogeneity was estimated using the Chi-squared statistic and explored qualitatively. RESULTS: Fourteen studies involving 5,652 patients were included. The overall methodological quality was good. Elevated preoperative NLR was associated with increased risk of long-term mortality (HR 1.40 [95%CI: 1.13-1.74], Chi-squared 60.3%, 7 studies, 3,637 people) and short-term mortality (OR: 3.08; 95%CI: 1.91-4.95), Chi-squared 66.59%, 4 studies, 945 people). Outcome measures used by fewer studies such as graft patency and amputation free survival were assessed via narrative review. CONCLUSIONS: NLR is a promising, readily obtainable, prognostic biomarker for mortality outcomes following vascular surgery. Heterogeneity in patient factors, severity of vascular disease, and type of vascular surgery performed renders direct comparison of outcomes from the current literature challenging. This systematic review supports further investigation for NLR measurement in pre-vascular surgical risk stratification. In particular, the establishment of a universally accepted NLR cut-off value is of importance in real-world implementation of this biomarker.

Endothelial Dysfunction and Thrombosis in Patients With COVID-19-Brief Report.

OBJECTIVE: Alveolar-capillary endothelial cells can be activated by severe acute respiratory syndrome coronavirus 2 infection leading to cytokine release. This could trigger endothelial dysfunction, pyroptosis, and thrombosis, which are the vascular changes, commonly referred to as coronavirus disease 2019 (COVID-19) endotheliopathy. Thus, this study aimed to identify tissue biomarkers associated with endothelial activation/dysfunction and the pyroptosis pathway in the lung samples of patients with COVID-19 and to compare them to pandemic influenza A virus H1N1 subtype 2009 and control cases. Approach and Results: Postmortem lung samples (COVID-19 group =6 cases; H1N1 group =10 cases, and control group =11 cases) were analyzed using immunohistochemistry and the following monoclonal primary antibodies: anti-IL (interleukin)-6, anti-TNF (tumor necrosis factor)-α, anti-ICAM-1 (intercellular adhesion molecule 1), and anticaspase-1. From the result, IL-6, TNF-α, ICAM-1, and caspase-1 showed higher tissue expression in the COVID-19 group than in the H1N1 and control groups. CONCLUSIONS: Our results demonstrated endothelial dysfunction and suggested the participation of the pyroptosis pathway in the pulmonary samples. These conditions might lead to systemic thrombotic events that could impair the clinical staff's efforts to avoid fatal outcomes. One of the health professionals' goals should be to identify the high risk of thrombosis patients early to block endotheliopathy and its consequences.