Management of acute aortic syndrome with evolving individualized precision medicine solutions: Lessons learned over two decades and literature review

BackgroundThoracoabdominal acute aortic syndrome is associated with high morbidity and mortality. We aim to scrutinize our evolving strategies for acute aortic syndrome (AAS) management using minimally invasive and adaptive surgical techniques over two decades.MethodsThis is a longitudinal observational study at our tertiary vascular centre from 2002 to 2021. Out of 22,349 aortic referrals, we performed 1,555 aortic interventions over twenty years. Amongst 96 presented with symptomatic aortic thoracic pathology, 71 patients had AAS. Our primary endpoint is combined aneurysm-related and cardiovascular-related mortality.ResultsThere were 43 males and 28 females (5 Traumatic Aortic Transection (TAT), 8 Acute Aortic Intramural Hematoma (IMH), 27 Symptomatic Aortic Dissection (SAD) and 31 Thoracic Aortic Aneurysm (TAA) post-SAD) with a mean age of 69. All the patients with AAS received optimal medical therapy (OMT), but TAT patients underwent emergency thoracic endovascular aortic repair (TEVAR). Fifty-eight patients had an aortic dissection, of which 31 developed TAA. These 31 patients with SAD and TAA received OMT initially and interval surgical intervention with TEVAR or sTaged hybrId sinGle lumEn Reconstruction (TIGER). To increase our landing area, we performed a left subclavian chimney graft with TEVAR in twelve patients. The average follow-up duration was 78.2 months, and eleven patients (15.5%) had combined aneurysm and cardiovascular-related mortality. Twenty-six percentage of the patients developed endoleaks (EL), of which 15% required re-intervention for type II and III. Four patients who had paraplegia (5.7%) and developed renal failure died. None of our patients had a stroke or bowel ischaemia. Twenty patients had OMT, eight of these were patients with acute aortic hematoma, and all eight died within 30 days of presentation.ConclusionAcute aortic hematoma is a sinister finding, which must be closely monitored, and consideration is given to early intervention. Paraplegia and renal failure result in an increased mortality rate. TIGER technique with interval TEVAR has salvaged complex situations in young patients. Left subclavian chimney increases our landing area and abolishes SINE. Our experience shows that minimally invasive techniques could be a viable option for AAS

Management of retroperitoneal fibrosis with endovascular aneurysm repair in patients refractory to medical management

BackgroundEarly diagnosis and treatment of under-recognized retroperitoneal fibrosis (RPF) are essential before reaching the poorly responsive fibrotic stage. Although most patients respond to medical therapy, relapses and unresponsiveness are common. However, open surgery in medically resistant patients is associated with major adverse clinical events.MethodsThis is a single-centre longitudinal study of optimal medical therapy (OMT) vs. endovascular aneurysm repair (EVAR) in patients presenting with RPF to our tertiary referral vascular centre. Out of 22,349 aortic referrals, we performed 1,555 aortic interventions over twenty years. Amongst them, 1,006 were EVAR, TEVAR and BEVAR. Seventeen patients (1.09%) had documented peri-aortic RPF.ResultsOut of the 17 RPF patients, 11 received OMT only, while 6 underwent EVAR after the failure of OMT. 82% (n = 14) were male, and the median follow-up was 62.7 months (IQR: 28.2–106). Nine (52%) had immunoglobulin G4-related disease (4 OMT vs. 5 EVAR). EVAR patients had 100% technical success without perioperative mortality. Furthermore, all the EVAR patients were symptom-free following the intervention. Pre-operative aortic RPF index (maximum peri-aortic soft tissue diameter/maximum aortic diameter) was higher in the EVAR than in OMT. However, there was a significant decrement in the aortic RPF index following EVAR (P = 0.04).ConclusionWe believe that when optimal medical therapy fails in RPF, EVAR provides a promising outcome. Further studies are recommended to establish the role of endovascular repair

Two decades of experience in explantation and graft preserving strategies following primary endovascular aneurysm repair and lessons learned

ObjectivesWe aim to scrutinize our evolving re-intervention strategies following primary endovascular aortic aneurysm repair (EVAR) - EVAR GORE SalvAge Fabric Technique (ARAFAT), aortic sac double breasting with endograft preservation, and stent-graft explantation.MethodsWe performed 1,555 aortic interventions over the study period, including 910 EVARs. Factors associated with the need for reintervention and the likelihood of chronic fabric fatigue failure (CFFF) were investigated. Using conventional and innovative diagnostic modalities with Prone contrASt enHanced computed tomography Angiography (PASHA), 136 endoleaks (ELs) were identified (15 type I, 98 type II; 18 type III; 5 type IV).ResultsForty-four (4.84%) patients underwent re-intervention post-primary EVAR; 18 ARAFATs, 12 double breastings, and 14 explantations. Choice of re-intervention was based on patient fitness and mode of failure. Mean EL detection duration following primary EVAR was 53.3 ± 6.82 months, while mean time to re-intervention was 70.20 ± 6.98 months. The mean sac size before the primary EVAR and re-intervention was 6.00 ± 1.75 cm and 7.51 ± 1.94 cm, respectively. Polyester (61.40%) was the most commonly employed stent-graft material. Use of more than three modular stent-graft components (3.42 ± 1.31, p = 0.846); with the proximal stent-graft diameter of 31.6 ± 3.80 cm (p = 0.651) and the use of iliac limbs more than 17 mm (p = 0.364), all added together are contributing factors. We had one peri-operative mortality following explantation due to sepsis-induced multiorgan failure.ConclusionsOur re-intervention strategies matured from stent graft explantation to graft preservation with endovascular relining of the stent-graft. Graft preservation with aortic sacotomy and double breasting were used to manage concealed ELs due to aortic hygroma

Impact of Baseline Steroids on Efficacy of Programmed Cell Death-1 and Programmed Death-Ligand 1 Blockade in Patients With Non-Small-Cell Lung Cancer

Treatment with programmed cell death-1 or programmed death ligand 1 (PD-(L)1) inhibitors is now standard therapy for patients with lung cancer. The immunosuppressive effect of corticosteroids may reduce efficacy of PD-(L)1 blockade. On-treatment corticosteroids for treatment of immune-related adverse events do not seem to affect efficacy, but the potential impact of baseline corticosteroids at the time of treatment initiation is unknown. Clinical trials typically excluded patients who received baseline corticosteroids, which led us to use real-world data to examine the effect of corticosteroids at treatment initiation. We identified patients who were PD-(L)1-naïve with advanced non-small-cell lung cancer from two institutions-Memorial Sloan Kettering Cancer Center and Gustave Roussy Cancer Center-who were treated with single-agent PD-(L)1 blockade. Clinical and pharmacy records were reviewed to identify corticosteroid use at the time of beginning anti-PD-(L)1 therapy. We performed multivariable analyses using Cox proportional hazards regression model and logistic regression. Ninety (14%) of 640 patients treated with single-agent PD-(L)1 blockade received corticosteroids of ≥ 10 mg of prednisone equivalent daily at the start of the PD-(L)1 blockade. Common indications for corticosteroids were dyspnea (33%), fatigue (21%), and brain metastases (19%). In both independent cohorts, Memorial Sloan Kettering Cancer Center (n = 455) and Gustave Roussy Cancer Center (n = 185), baseline corticosteroids were associated with decreased overall response rate, progression-free survival, and overall survival with PD-(L)1 blockade. In a multivariable analysis of the pooled population, adjusting for smoking history, performance status, and history of brain metastases, baseline corticosteroids remained significantly associated with decreased progression-free survival (hazard ratio, 1.3; P = .03), and overall survival (hazard ratio, 1.7; P Baseline corticosteroid use of ≥ 10 mg of prednisone equivalent was associated with poorer outcome in patients with non-small-cell lung cancer who were treated with PD-(L)1 blockade. Prudent use of corticosteroids at the time of initiating PD-(L)1 blockade is recommended

Prevalence of problem alcohol use among patients attending primary care for methadone treatment

<p>Abstract</p> <p>Background</p> <p>Problem alcohol use is associated with adverse health outcomes among current or former heroin users and primary care is providing methadone treatment for increasing numbers of this population. This study aimed todetermine the prevalence of problem alcohol use among current or former heroin users attending primary care for methadone treatment and to describe the socio-demographic characteristics and health service utilisation characteristics associated with problem alcohol uses.</p> <p>Methods</p> <p>We conducted a cross sectional survey of patients sampled from a national database of patients attending general practice for methadone treatment. Participants were recruited by their general practitioner and data was collected using an interviewer-administered questionnaire, which included the Alcohol Use Disorders Identification Test ('AUDIT'), with a score of >7 considered abnormal (ie 'AUDIT positive cases') and socio-demographic, medical and substance use characteristics.</p> <p>Results</p> <p>We interviewed 196 patients (71% of those invited, 31% of those sampled, 11% of the national database). The median age was 32 years, 55% were hepatitis C positive, 79% had used illicit drugs in the previous month and 68% were male. Sixty-eight 'AUDIT positive' cases were identified (prevalence of 35%, 95% CI = 28–41%) and these were more likely to have attended a local Emergency Department in the previous year (p < 0.05) and less likely to have attended a hospital clinic in the previous year (p < 0.05). Twenty-seven (14%) scored 20 or higher indicating possible alcohol dependence.</p> <p>Conclusion</p> <p>Problem alcohol use has a high prevalence among current or former heroin users attending primary care for methadone treatment and interventions that address this issue should be explored as a priority. Interventions that address problem alcohol use in this population should be considered as a priority, although the complex medical and psychological needs of this population may make this challenging.</p

Volatility as a concept to understand the impact of stress on the microbiome

The microbiome-gut-brain-axis is a complex phenomenon spanning several dynamic systems in the body which can be parsed at a molecular, cellular, physiological and ecological level. A growing body of evidence indicates that this axis is particularly sensitive to the effects of stress and that it may be relevant to stress resilience and susceptibility. Although stress-induced changes in the composition of the microbiome have been reported, the degree of compositional change over time, which we define as volatility, has not been the subject of in-depth scrutiny. Using a chronic psychosocial stress paradigm in male mice, we report that the volatility of the microbiome significantly correlated with several readouts of the stress response, including behaviour and corticosterone response. We then validated these findings in a second independent group of stressed mice. Additionally, we assessed the relationship between volatility and stress parameters in a cohort of health volunteers who were undergoing academic exams and report similar observations. Finally, we found inter-species similarities in the microbiome stress response on a functional level. Our research highlights the effects of stress on the dynamic microbiome and underscores the informative value of volatility as a parameter that should be considered in all future analyses of the microbiome

Antibody-Based Sensors: Principles, Problems and Potential for Detection of Pathogens and Associated Toxins

Antibody-based sensors permit the rapid and sensitive analysis of a range of pathogens and associated toxins. A critical assessment of the implementation of such formats is provided, with reference to their principles, problems and potential for ‘on-site’ analysis. Particular emphasis is placed on the detection of foodborne bacterial pathogens, such as Escherichia coli and Listeria monocytogenes, and additional examples relating to the monitoring of fungal pathogens, viruses, mycotoxins, marine toxins and parasites are also provided

Characterisation of the pro-inflammatory cytokine signature in severe COVID-19

Clinical outcomes from infection with SARS-CoV-2, the cause of the COVID-19 pandemic, are remarkably variable ranging from asymptomatic infection to severe pneumonia and death. One of the key drivers of this variability is differing trajectories in the immune response to SARS-CoV-2 infection. Many studies have noted markedly elevated cytokine levels in severe COVID-19, although results vary by cohort, cytokine studied and sensitivity of assay used. We assessed the immune response in acute COVID-19 by measuring 20 inflammatory markers in 118 unvaccinated patients with acute COVID-19 (median age: 70, IQR: 58-79 years; 48.3% female) recruited during the first year of the pandemic and 44 SARS-CoV-2 naïve healthy controls. Acute COVID-19 was associated with marked elevations in nearly all pro-inflammatory markers, whilst eleven markers (namely IL-1β, IL-2, IL-6, IL-10, IL-18, IL-23, IL-33, TNF-α, IP-10, G-CSF and YKL-40) were associated with disease severity. We observed significant correlations between nearly all markers elevated in those infected with SARS-CoV-2 consistent with widespread immune dysregulation. Principal component analysis highlighted a pro-inflammatory cytokine signature (with strongest contributions from IL-1β, IL-2, IL-6, IL-10, IL-33, G-CSF, TNF-α and IP-10) which was independently associated with severe COVID-19 (aOR: 1.40, 1.11-1.76, p=0.005), invasive mechanical ventilation (aOR: 1.61, 1.19-2.20, p=0.001) and mortality (aOR 1.57, 1.06-2.32, p = 0.02). Our findings demonstrate elevated cytokines and widespread immune dysregulation in severe COVID-19, adding further evidence for the role of a pro-inflammatory cytokine signature in severe and critical COVID-19