Inflammation in aortic surgery: postoperative evolution of biomarkers according pathologies and segments of the aorta.

OBJECTIVES: Aortic pathologies often present with elevated inflammatory biomarkers due to the nature of the disease. Open aortic surgery causes significant trauma to the body due to often mandatory ischemic periods, long cardiopulmonary bypass times and polytransfusion. We aim to determine postoperative trends on inflammation biomarkers for different aortic pathologies and type of surgery in different segments of the aorta. METHODS: Retrospective review of prospectively collected data of 193 consecutive patients who underwent aortic surgery in our centre between 2017 and 2021, grouped according to the type of aortic intervention: (1) Type A aortic dissection (AD) repair with ascending aorta/hemiarch replacement, (2) Aortic root replacement (ARR), (3) Aortic arch + Frozen elephant trunk (FET), (4) Descending thoracic aorta (DTA)/Thoraco-Abdominal aortic repair (TAA). Primary outcomes were daily values of white blood cells (WBC) and C-Reactive Protein (CRP) during the first 15 postoperative days. RESULTS: All groups had a similar inflammatory peak in the first 2-4 days (WBC 12-15 × 109 c/L). AD and FET groups show similar trends with WBC and CRP peaks on days 2 and 10. The ARR group didn't experience the 2nd peak as most patients were already discharged. DTA/TAA patients experienced a more prolonged inflammatory response, reaching a plateau by day 5-10. AD group shows the highest WBC levels and the DTA/TAAA group the highest CRP levels. CRP levels remain elevated (100-200 mg/L) in all groups after 15 postoperative days. CONCLUSIONS: Inflammatory biomarkers show different postoperative trends depending on the clinical presentation and complexity of the aortic procedure performed. Further understanding of the inflammatory response to different aortic pathologies and surgical procedures will permit reduction on the liberal use of antibiotics that this cohort of patients are usually exposed to. An earlier version of the data included in this manuscript was presented as Oral Abstract in the UK Society of Cardiothoracic Surgery Annual meeting in 2021.

Vascular Endothelial Growth Factor-C Treatment Enhances Cerebrospinal Fluid Outflow during Toxoplasma gondii Brain Infection but Does Not Improve Cerebral Edema.

Cerebral edema frequently develops in the setting of brain infection and can contribute to elevated intracranial pressure, a medical emergency. How excess fluid is cleared from the brain is not well understood. Previous studies have shown that interstitial fluid is transported out of the brain along perivascular channels that collect into the cerebrospinal fluid (CSF)-filled subarachnoid space. CSF is then removed from the central nervous system through venous and lymphatic routes. The current study tested the hypothesis that increasing lymphatic drainage of CSF would promote clearance of cerebral edema fluid during infection with the neurotropic parasite Toxoplasma gondii. Fluorescent microscopy and magnetic resonance imaging was used to show that C57BL/6 mice develop vasogenic edema 4 to 5 weeks after infection with T. gondii. Tracer experiments were used to evaluate how brain infection affects meningeal lymphatic function, which demonstrated a decreased rate in CSF outflow in T. gondii-infected mice. Next, mice were treated with a vascular endothelial growth factor (VEGF)-C-expressing viral vector, which induced meningeal lymphangiogenesis and improved CSF outflow in chronically infected mice. No difference in cerebral edema was observed between mice that received VEGF-C and those that rececived sham treatment. Therefore, although VEGF-C treatment can improve lymphatic outflow in mice infected with T. gondii, this effect does not lead to increased clearance of edema fluid from the brains of these mice.

An exploratory cost-effectiveness analysis of a novel tissue valve compared with mechanical valves for surgical aortic valve replacement in subgroups of people aged 55-64 and 65+ with aortic stenosis in the UK.

OBJECTIVE: Exploratory analysis to conceptualize and evaluate the potential cost-effectiveness and economic drivers of using a novel tissue valve compared with mechanical heart valves for surgical aortic valve replacement (SAVR) in people aged 55-64 and 65+ with aortic stenosis (AS) from a National Health Service (NHS) UK perspective. METHODS: A decision-analytic model was developed using a partitioned survival model. Parameter inputs were obtained from published literature. Deterministic and probabilistic sensitivity analyses (DSA and PSA) were conducted to explore the uncertainty around the parameters. RESULTS: The novel tissue valve was potentially associated with higher quality-adjusted life years (QALYs) of 0.01 per person. Potential cost savings were greatest for those aged 55-64 (£408) versus those aged 65+(£53). DSA indicated the results to be most dependent on relative differences in general mortality, procedure costs, and reoperation rates. PSA estimated around 75% of the iterations to be cost-effective at £20,000 per QALY for those aged 55-64, and 57% for those aged 65+. CONCLUSIONS: The exploratory analysis suggests that the novel tissue valve could be a cost-effective intervention for people over the age of 55 with AS who are suitable for SAVR in the UK.

Phagocytosis in the retina promotes local insulin production in the eye.

The retina is highly metabolically active, relying on glucose uptake and aerobic glycolysis. Situated in close contact to photoreceptors, a key function of cells in the retinal pigment epithelium (RPE) is phagocytosis of damaged photoreceptor outer segments (POS). Here we identify RPE as a local source of insulin in the eye that is stimulated by POS phagocytosis. We show that Ins2 messenger RNA and insulin protein are produced by RPE cells and that this production correlates with RPE phagocytosis of POS. Genetic deletion of phagocytic receptors ('loss of function') reduces Ins2, whereas increasing the levels of the phagocytic receptor MerTK ('gain of function') increases Ins2 production in male mice. Contrary to pancreas-derived systemic insulin, RPE-derived local insulin is stimulated during starvation, which also increases RPE phagocytosis. Global or RPE-specific Ins2 gene deletion decreases retinal glucose uptake in starved male mice, dysregulates retinal physiology, causes defects in phototransduction and exacerbates photoreceptor loss in a mouse model of retinitis pigmentosa. Collectively, these data identify RPE cells as a phagocytosis-induced local source of insulin in the retina, with the potential to influence retinal physiology and disease.

Open descending and thoracoabdominal aortic replacement: operative steps for patients with prior endovascular treatment.

Open surgery remains the gold standard for the treatment of the thoracoabdominal aorta. The rising number of endovascularly treated patients comes with an increase in the number of patients who require secondary open interventions due to the complex nature of the aortic disease or to treat endovascular complications. We describe our current approach to secondary open extent II thoracoabdominal aortic repair in patients with prior endovascular repair. In this case report, we show two different cases that exemplify this scenario.

Managing the Root in Acute Type A Aortic Dissections: Are We Ready for a Standardized Approach?

OBJECTIVES: Surgical repair of Type A aortic dissection (TAAD) requires exclusion of the primary entry tear and reestablishment of flow into the distal true lumen. Provided that the majority of tears occur within the ascending aorta (AA), replacing only that segment seems a safe option; however, this strategy leaves the root susceptible to dilatation and need for reintervention. We aimed to review the outcomes of the two strategies: aortic root replacement (ARR) and isolated ascending aortic replacement. METHODS: Retrospective analysis of prospectively collected data for all consecutive patients who underwent repair of acute TAAD at our institution from 2015 to 2020 was conducted. Patients were divided into two groups: (1) ARR and (2) isolated AA replacement as index operation for TAAD repair. Primary outcomes were mortality and need for reintervention during the follow-up. RESULTS: A total of 194 patients were included in the study; 68 (35%) in the ARR group and 126 (65%) in the AA group. There were no significant differences in postoperative complications or in-hospital mortality (23%; p = 0.51) between groups. Seven patients (4.7%) died during follow-up and eight patients underwent aortic reinterventions, including proximal aortic segments (two patients) and distal procedures (six patients). CONCLUSION: Both aortic root and AA replacement are acceptable and safe techniques. The growth of an untouched root is slow, and reintervention in this aortic segment is infrequent compared with distal aortic segments, hence preserving the root could be an option for older patients provided that there is no primary tear within the root.

The meningeal transcriptional response to traumatic brain injury and aging.

Emerging evidence suggests that the meningeal compartment plays instrumental roles in various neurological disorders, however, we still lack fundamental knowledge about meningeal biology. Here, we utilized high-throughput RNA sequencing (RNA-seq) techniques to investigate the transcriptional response of the meninges to traumatic brain injury (TBI) and aging in the sub-acute and chronic time frames. Using single-cell RNA sequencing (scRNA-seq), we first explored how mild TBI affects the cellular and transcriptional landscape in the meninges in young mice at one-week post-injury. Then, using bulk RNA-seq, we assessed the differential long-term outcomes between young and aged mice following TBI. In our scRNA-seq studies, we highlight injury-related changes in differential gene expression seen in major meningeal cell populations including macrophages, fibroblasts, and adaptive immune cells. We found that TBI leads to an upregulation of type I interferon (IFN) signature genes in macrophages and a controlled upregulation of inflammatory-related genes in the fibroblast and adaptive immune cell populations. For reasons that remain poorly understood, even mild injuries in the elderly can lead to cognitive decline and devastating neuropathology. To better understand the differential outcomes between the young and the elderly following brain injury, we performed bulk RNA-seq on young and aged meninges 1.5 months after TBI. Notably, we found that aging alone induced upregulation of meningeal genes involved in antibody production by B cells and type I IFN signaling. Following injury, the meningeal transcriptome had largely returned to its pre-injury signature in young mice. In stark contrast, aged TBI mice still exhibited upregulation of immune-related genes and downregulation of genes involved in extracellular matrix remodeling. Overall, these findings illustrate the dynamic transcriptional response of the meninges to mild head trauma in youth and aging.

Thoracoabdominal Aneurysm Repair During Early Stage of Pregnancy: Can and Should We Save the Baby?

Aortic dissection during pregnancy is a life-threatening condition for both mother and fetus. We present the case of a 34-year-old woman with a rapidly expanding abdominal aorta in the context of a chronic type B aortic dissection. A 4 to 6 weeks' viable pregnancy was incidentally diagnosed during the preoperative workup. She underwent urgent extent II thoracoabdominal aortic aneurysm repair with left-sided heart bypass. Postoperatively, vaginal ultrasound evaluation confirmed viability of the fetus, but the patient wished to terminate the pregnancy because of the possible unknown hypoxic effects on the fetus.

Fulminant Herpes Pneumonia Postaortic Surgery with Known Ankylosing Spondylitis.

Herpes simplex virus (HSV) pneumonitis is rare after cardiac surgery. A 36-year-old gentleman with ankylosing spondylitis underwent emergency surgery for a complex aortic aneurysmal disease. Preoperative treatment of aortitis with antitumor necrosis factor and steroid medication and surgical stress including cardiopulmonary bypass potentially created an immunosuppressive state and reactivation of undiagnosed HSV. Rapid HSV pneumonia ensued, culminating in fulminant organ failure and mortality. HSV pneumonia should be considered postoperatively in patients with severe respiratory distress, especially if immunocompromised.

Resternotomy aortic root and arch replacement following previous complex type A aortic dissection requiring endovascular repair for malperfusion.

A redo sternotomy, aortic root, and arch replacement in a patient following previous complex surgical and endovascular type A aortic dissection repair is presented in this video case report. Shortly after having the initial type A aortic dissection repair with replacement of the ascending aorta, the patient developed severe visceral malperfusion due to a compressed distal true lumen and underwent emergency endovascular repair with ascending arch and descending thoracic aorta stents and chimney grafts for the aortic arch vessels as well as fenestration of the intimal flap of the abdominal aorta. Unfortunately, the patient developed permanent paraplegia and progressive symptomatic severe aortic regurgitation. The patient underwent a redo sternotomy, aortic root, and arch replacement with explantation of the ascending stent graft and chimney stent grafts. Antegrade cerebral perfusion was maintained throughout the procedure. The aortic arch was replaced using a Terumo Aortic Plexus multibranched graft distally anastomosed to the endovascular stent graft, and the innominate and left common carotid arteries were reimplanted onto the graft. The aortic root was replaced with a Bioconduit graft, using a modified Cabrol technique to reimplant the left coronary artery. A satisfactory postoperative course and computed tomography imaging highlight the feasibility of this highly complex aortic arch repair with careful preoperative planning.

Retrograde type A aortic dissection: a different evil.

Retrograde type A aortic dissection (RTAAD) can be spontaneous or secondary to the instrumentation of the descending and thoraco-abdominal aorta. It has anatomical differences compared to antegrade type A aortic dissection that impact the management and prognosis. Treatment is not standardized. We report our approach to spontaneous RTAAD in our institution between 2018 and 2022 (n = 15). The mean age was 60.1 years and 93% were male. Aortic valve, coronary arteries and supra-aortic trunks were spared by the dissection in 80% of the cases; distal extension to iliacs was common and lower limb malperfusion was present in 4 cases (27%). The ascending aorta was dilated at presentation in 60% of the cases. Emergency surgery with arch/FET replacement was offered to 11 patients (73%); 3 patients (20%) received a limited proximal aortic repair; 1 patient was treated conservatively. Overall mortality was 47% (100% for limited proximal repair and 22% for those who received arch/FET). We advocate for aggressive treatment of RTAAD excluding the primary entry tear to prevent immediate- and mid-term complications.

Activated prothrombin complex concentrate to treat bleeding events in acquired hemophilia A: BAHAS study.

OBJECTIVE: Activated prothrombin complex concentrate (aPCC) is a bypassing agent indicated to treat bleeds in patients with acquired hemophilia A (AHA). Nevertheless, its efficacy and safety in the real-world setting have not often been addressed. METHODS: We report the experience of Spanish reference centers for coagulation disorders and from acquired hemophilia Spanish Registry (AHASR) from August 2012 to February 2021. Follow-up period of 30 days after aPCC withdrawal. RESULTS: Thirty patients with a median age of 70 years old, suffering from 51 bleeds treated with aPCC were finally evaluated. As first-line treatment, aPCC stopped bleeding in 13 of 14 (92.9%) cases. aPCC as the second line after recombinant factor VIIa failure, stopped bleeding in all cases. In 17 patients, aPCC was used far from initial bleed control as prophylaxis of rebleeding with 94% effectiveness. No thromboembolic episodes were communicated. One patient developed hypofibrinogenemia, which did not prevent aPCC from halting bleeding. No other serious adverse events possibly or probably associated with aPCC were reported. CONCLUSIONS: This data support aPCC as hemostatic treatment in AHA with high effectiveness and excellent safety profile in acute bleeds and as extended use to prevent rebleedings, even in aging people with high cardiovascular risk.

Effect of Hospital-associated SARS-CoV-2 Infections in Cardiac Surgery. A Multicenter Study.

BACKGROUND: The effect of hospital-associated SARS-CoV-2 infections in cardiac surgery patients remains poorly investigated, and current data are limited to small case series with conflicting results. METHODS: A multicenter European collaboration was organized to analyze the outcomes of patients who tested positive with hospital-associated SARS-CoV-2 infection after cardiac surgery. The study investigators hypothesized that early infection could be associated with worse postoperative outcomes; hence 2 groups were considered: (1) an early hospital-associated SARS-CoV-2 infection group comprising patients who had a positive molecular test result ≤7 days after surgery, with or without symptoms; and (2) a late hospital-associated SARS-CoV-2 infection group comprising patients whose test positivity occurred >7 days after surgery, with or without symptoms. The primary outcome was 30-day mortality. Secondary outcomes included all-cause mortality or morbidity at early follow-up and SARS-CoV-2-related hospital readmission. RESULTS: A total of 87 patients were included in the study. Of those, 30 were in the early group and 57 in the late group. Overall, 30-day mortality was 8%, and in-hospital mortality was 11.5%. The reintubation rate was 11.4%. Early infection was significantly associated with higher mortality (adjusted OR, 26.6; 95% CI, 2, 352.6; P < .01) when compared with the late group. At 6-month follow-up, survival probability was also significantly higher in the late infection group: 91% (95% CI, 83%, 98%) vs 75% (95% CI, 61%, 93%) in the early infection group (P = .036). Two patients experienced COVID-19-related rehospitalization. CONCLUSIONS: In this multicenter analysis, hospital-associated SARS-CoV-2 infection resulted in higher than expected postoperative mortality after cardiac surgery, especially in the early infection group.

A multi-centre prospective cohort study of patients on the elective waiting list for cardiac surgery during the COVID-19 pandemic.

OBJECTIVES: During the worldwide COVID-19 pandemic, elective cardiac surgery was suspended to provide ICU beds for COVID-19 patients and those requiring urgent cardiac surgery. The aim of this study is to assess the effect of the pandemic on outcomes of patients awaiting elective cardiac surgery. DESIGN: A multi-centre prospective cohort study. SETTING: The elective adult cardiac surgery waiting list as of 1 March 2020 across seven UK cardiac surgical centres. PARTICIPANTS: Patients on the elective adult cardiac surgery waiting list as of 1 March 2020 across seven UK cardiac surgical centres. MAIN OUTCOME MEASURES: Primary outcome was surgery, percutaneous therapy or death at one year. METHODS: Data were collected prospectively on patients on the elective adult cardiac surgery waiting list as of 1 March 2020 across seven UK cardiac surgical centres. Primary outcome was surgery, percutaneous therapy or death at one year. Demographic data and outcomes were obtained from local electronic records, anonymised and submitted securely to the lead centre for analysis. RESULTS: On 1 March 2020, there were 1099 patients on the elective waiting list for cardiac surgery. On 1 March 2021, 83% (n = 916) had met a primary outcome. Of these, 840 (92%) had surgery after a median of 195 (118-262) days on waiting list, 34 (3%) declined an offer of surgery, 23 (3%) had percutaneous intervention, 12 (1%) died, 7 (0.6%) were removed from the waiting list. The remainder of patients, 183 (17%) remained on the elective waiting list. CONCLUSIONS: This study has shown, for the first time, significant delays to treatment of patients awaiting elective cardiac surgery. Although there was a low risk of mortality or urgent intervention, important unmeasured adverse outcomes such as quality of life or increased perioperative risk may be associated with prolonged waiting times.

Ministernotomy repair of inadvertent proximal right subclavian artery injury following right internal jugular central venous catheter insertion.

A man in his 60s was referred for urgent coronary artery bypass grafting (CABG) procedure following acute coronary syndrome. After induction of general anaesthesia, right jugular venous catheterisation under two-dimensional ultrasound guidance was planned as part of perioperative management. While obtaining vascular access, the pulsatile flow was noted once the dilator was inserted, having to abandon the procedure and immediately apply manual pressure. CT angiogram showed proximal right subclavian artery injury with active contrast extravasation and resultant large haematoma in the neck. The patient underwent urgent exploration of the injured vessel through a J-shaped ministernotomy, and primary repair of the artery was performed. The patient recovered from the procedure without any complications. He continued to stay in the hospital for a few days, afterwards, he underwent the initially planned CABG surgery. He was discharged home on day 5 after surgery without further concerns.

The LINCE Project: A Pathway for Diagnosing NCL2 Disease.

Introduction: Neuronal Ceroid Lipofuscinosis (NCL) comprises a clinically and genetically heterogeneous group of 13 neurodegenerative lysosomal storage disorders. Neuronal Ceroid lipofuscinosis type 2 disease (NCL2), caused by the deficient lysosomal enzyme tripeptidyl peptidase 1 (TPP1), is the only one with an approved enzyme replacement treatment (ERT). Early initiation of ERT appears to modify significantly the natural history of the disease. We aimed to shorten the time to diagnosis of NCL2. Methods: In March 2017, we started per first time in Spain a selective screening program, the LINCE project, in pediatric patients with clinical symptoms compatible with NCL2 disease. The program covered the whole country. We distributed kits to pediatricians with the necessary material to assess patients. All samples in this study were received within one week of collection. Enzymatic activity determined on dried blood spots was the main method used to screen for TPP1 and palmitoyl protein thioesterase 1 (PPT1) for the differential diagnosis with neuronal ceroid lipofuscinosis type 1 (NCL1). Results: Over a period of three years, we received 71 samples. The analysis was minimally invasive, relatively cheap and fast-executing. Three cases identified as a direct result of the selective screening strategy were confirmed by genetic study of NCL2 disease with a median age of 4.5 years. Our screening method has a specificity of 100%, and, with the absence to date of false negatives. We did not detect any NCL1-positive cases. Conclusions: LINCE proved to be a simple, useful, and reliable tool for the diagnosis of NCL2, enabling clinicians to diagnose NCL2 faster. The presence of NCL2-positive cases in our population and availability of treatment may facilitate the inclusion of NCL2 in neonatal screening programs for early diagnosis.

Toxicity to bronchial cells and endocrine disruptive potentials of indoor air and dust extracts and their association with multiple chemical classes.

Pollution of indoor environment, where people spend much of their time, comprises complex mixtures of compounds with vastly understudied hazard potential. This study examined several important specific toxic effects and pollutant levels (177 compounds) of indoor samples (air gas phase, PM10 and dust) from different microenvironments after two extractions with focus on their gas/particle/dust distribution and polarity. The endocrine disruptive (ED) potential was assessed by human cell-based in vitro bioassays addressing anti-/estrogenicity, anti-/androgenicity, aryl hydrocarbon, thyroid and peroxisome proliferator-activated receptor-mediated activities. Potential toxicity to respiratory tract tissue was assessed using human bronchial cell line. The toxicological analyses pointed out the relevance of both inhalation and ingestion exposure, with significant effects detected after exposure to extracts from all three studied matrices with distinct gas/particle distribution patterns. Chemical analyses document the high complexity of indoor pollutant mixtures with greatest levels of phthalates, their emerging alternatives, and PAHs in dust. Despite the detection of up to 108 chemicals, effects were explained only to low extent. This emphasizes data gaps regarding ED potencies of many detected abundant indoor contaminants, but also potential presence of other unidentified ED compounds. The omnipresent ED potentials in indoor environment rise concern regarding associated human health risk.

Type A Aortic Dissection Masquerading as an Inferior Myocardial Infarction.

Type A aortic dissection is a life-threatening condition with a wide range of clinical manifestations. Dissection can sometimes mimic an acute myocardial infarction due to similar presenting symptoms and initial clinical investigations. We report the case of a 52-year-old male who presented with an inferior ST-segment elevation myocardial infarction with two drug-eluting stents inserted as a stabilizing intervention prior to surgical repair of an acute aortic dissection.