Diagnostic value of contrast-enhanced ultrasonography for patent foramen ovale detection.

Background: Patent foramen ovale (PFO) has been associated with migraine, cryptogenic stroke (CS), and hypoxemia. However, which examination method is most reliable remains controversial. This study sought to investigate the diagnostic value of contrast-enhanced ultrasonography (cU), including contrast-enhanced transcranial Doppler (cTCD), contrast transthoracic echocardiography (cTTE), and contrast transesophageal echocardiography (cTEE), for PFO; and to determine the best diagnostic strategy. Methods: This retrospective observational study included a total of 147 consecutive patients suspected PFO at The First Hospital of Shanxi Medical University between October 2019 and January 2022. The patients also underwent cTCD, cTTE, and cTEE examinations. The standard for the diagnosis of PFO was confirmation of the presence of PFO by color Doppler flow signals or contrast microbubbles (MBs) passing through the foramen ovale. Results: A total of 123 patients were diagnosed with PFO and 24 patients without PFO during the study period. The detectable rates of cTCD, cTTE, and cTEE were 120 (97.56%), 110 (89.43%), and 121 (98.37%), respectively. The sensitivity between cTCD and cTEE for PFO were comparable [97.56%, 95% confidence interval (CI): 92.5% to 99.4% vs. 98.37%, 95% CI: 93.7% to 99.7%; P>0.99], and the sensitivity of both were higher than that of cTTE (89.43%, 95% CI: 82.3% to 94.0%; P=0.02 and P=0.001, respectively). In addition, the specificity of cTEE for PFO was significantly higher than that of cTCD (100%, 95% CI: 82.3% to 100.0% vs. 75.00%, 95% CI: 53.0% to 89.4%; P<0.001) and cTTE (100%, 95% CI: 82.3% to 100.0% vs. 75.00%, 95% CI: 53.0% to 89.4%; P<0.001). Further, the semi-quantitative classification ability of cTCD for PFO with right-to-left shunt (RLS) was significantly higher than that of cTTE and cTEE (P=0.02 and P<0.001, respectively), and that of cTTE was significantly higher than that of cTEE (P=0.01). The Spearman analysis showed that the degree of RLS was positively correlated with the inner diameter of the PFO (r=0.695, P<0.001). Conclusions: The combination of cTCD and cTEE may provide a favorable strategy for the diagnosis of PFO.

Loss of anoctamin 1 reveals a subtle role for BK channels in lymphatic muscle action potentials.

Ca2+ signalling plays a crucial role in determining lymphatic muscle cell excitability and contractility through its interaction with the Ca2+-activated Cl- channel anoctamin 1 (ANO1). In contrast, the large-conductance (BK) Ca2+-activated K+ channel (KCa) and other KCa channels have prominent vasodilatory actions by hyperpolarizing vascular smooth muscle cells. Here, we assessed the expression and contribution of the KCa family to mouse and rat lymphatic collecting vessel contractile function. The BK channel was the only KCa channel consistently expressed in fluorescence-activated cell sorting-purified mouse lymphatic muscle cell lymphatic muscle cells. We used a pharmacological inhibitor of BK channels, iberiotoxin, and small-conductance Ca2+-activated K+ channels, apamin, to inhibit KCa channels acutely in ex vivo isobaric myography experiments and intracellular membrane potential recordings. In basal conditions, BK channel inhibition had little to no effect on either mouse inguinal-axillary lymphatic vessel (MIALV) or rat mesenteric lymphatic vessel contractions or action potentials (APs). We also tested BK channel inhibition under loss of ANO1 either by genetic ablation (Myh11CreERT2-Ano1 fl/fl, Ano1ismKO) or by pharmacological inhibition with Ani9. In both Ano1ismKO MIALVs and Ani9-pretreated MIALVs, inhibition of BK channels increased contraction amplitude, increased peak AP and broadened the peak of the AP spike. In rat mesenteric lymphatic vessels, BK channel inhibition also abolished the characteristic post-spike notch, which was exaggerated with ANO1 inhibition, and significantly increased the peak potential and broadened the AP spike. We conclude that BK channels are present and functional on mouse and rat lymphatic muscle cells but are otherwise masked by the dominance of ANO1. KEY POINTS: Mouse and rat lymphatic muscle cells express functional BK channels. BK channels make little contribution to either rat or mouse lymphatic collecting vessel contractile function in basal conditions across a physiological pressure range. ANO1 limits the peak membrane potential achieved in the action potential and sets a plateau potential limiting the voltage-dependent activation of BK. BK channels are activated when ANO1 is absent or blocked and slightly impair contractile strength by reducing the peak membrane potential achieved in the action potential spike and accelerating the post-spike repolarization.

Deep Parasternal Intercostal Plane Block for Intraoperative Pain Control in Cardiac Surgical Patients for Sternotomy: A Prospective Randomized Controlled Trial.

OBJECTIVES: Sternotomy pain is common after cardiac surgery. The deep parasternal intercostal plane (DPIP) block is a novel technique that provides analgesia to the anterior chest wall. The aim of this study was to investigate the analgesic effect of bilateral DPIP blocks on intraoperative pain control in cardiac surgery. DESIGN: This is a double-blinded, prospective randomized controlled trial (Oct 2020-Dec 2022). SETTINGS: This study was conducted in a single institution, which is an academic university hospital. PARTICIPANTS: Eighty-six elective cardiac surgical patients with median sternotomy were recruited. INTERVENTIONS: Patients were randomly divided into DPIP or control group. Either 20ml 0.25% levobupivacaine or 0.9% normal saline was injected for the DPIP under ultrasound guidance after induction of general anaesthesia. MEASUREMENTS AND MAIN RESULTS: The primary outcome was intraoperative opioids consumption and hemodynamic changes at sternotomy. Secondary outcomes included postoperative morphine consumption, postoperative pain and time to tracheal extubation. Intraoperative opioids requirement was reduced from a median (IQR) intravenous morphine equivalence of 21.4mg (13.8-24.3mg) in control group to 9.5mg (7.3-11.2mg) in the DPIP group (P<0.001). Hemodynamic parameters were more stable in DPIP group at sternotomy, as evidenced by lower percentage increase in systolic, diastolic and mean arterial blood pressure from baseline. No difference was observed in time to tracheal extubation, postoperative morphine consumption, postoperative pain score and spirometry. CONCLUSIONS: Bilateral DPIP block provides effective intraoperative analgesia and opioid-sparing. It may be included as part of the multimodal analgesia for enhanced recovery in cardiac surgery.

Effect of colchicine on perioperative atrial fibrillation and myocardial injury after non-cardiac surgery in patients undergoing major thoracic surgery (COP-AF): an international randomised trial.

BACKGROUND: Higher levels of inflammatory biomarkers are associated with an increased risk of perioperative atrial fibrillation and myocardial injury after non-cardiac surgery (MINS). Colchicine is an anti-inflammatory drug that might reduce the incidence of these complications. METHODS: COP-AF was a randomised trial conducted at 45 sites in 11 countries. Patients aged 55 years or older and undergoing major non-cardiac thoracic surgery were randomly assigned (1:1) to receive oral colchicine 0·5 mg twice daily or matching placebo, starting within 4 h before surgery and continuing for 10 days. Randomisation was done with use of a computerised, web-based system, and was stratified by centre. Health-care providers, patients, data collectors, and adjudicators were masked to treatment assignment. The coprimary outcomes were clinically important perioperative atrial fibrillation and MINS during 14 days of follow-up. The main safety outcomes were a composite of sepsis or infection, and non-infectious diarrhoea. The intention-to-treat principle was used for all analyses. This trial is registered with ClinicalTrials.gov, NCT03310125. FINDINGS: Between Feb 14, 2018, and June 27, 2023, we enrolled 3209 patients (mean age 68 years [SD 7], 1656 [51·6%] male). Clinically important atrial fibrillation occurred in 103 (6·4%) of 1608 patients assigned to colchicine, and 120 (7·5%) of 1601 patients assigned to placebo (hazard ratio [HR] 0·85, 95% CI 0·65 to 1·10; absolute risk reduction [ARR] 1·1%, 95% CI -0·7 to 2·8; p=0·22). MINS occurred in 295 (18·3%) patients assigned to colchicine and 325 (20·3%) patients assigned to placebo (HR 0·89, 0·76 to 1·05; ARR 2·0%, -0·8 to 4·7; p=0·16). The composite outcome of sepsis or infection occurred in 103 (6·4%) patients in the colchicine group and 83 (5·2%) patients in the placebo group (HR 1·24, 0·93-1·66). Non-infectious diarrhoea was more common in the colchicine group (134 [8·3%] events) than the placebo group (38 [2·4%]; HR 3·64, 2·54-5·22). INTERPRETATION: In patients undergoing major non-cardiac thoracic surgery, administration of colchicine did not significantly reduce the incidence of clinically important atrial fibrillation or MINS but increased the risk of mostly benign non-infectious diarrhoea. FUNDING: Canadian Institutes of Health Research, Accelerating Clinical Trials Consortium, Innovation Fund of the Alternative Funding Plan for the Academic Health Sciences Centres of Ontario, Population Health Research Institute, Hamilton Health Sciences, Division of Cardiology at McMaster University, Canada; Hanela Foundation, Switzerland; and General Research Fund, Research Grants Council, Hong Kong.

Initial Asian experience of the branched E-vita open NEO in complex aortic pathologies.

Background: Aortic arch pathology often requires staged segmental repairs. Total aortic arch replacement with frozen elephant trunk (FET) offers surgical options for these pathologies. The Jotec E-vita Open NEO™ branched prosthesis was introduced in 2020; we sought to share our initial experience focusing on the prosthesis selection strategies, surgical techniques, anastomosis-bleeding and graft-oozing control methods, and early clinical outcomes from two Asian centers. Methods: We performed a retrospective cohort study in patients with aortic arch pathologies who underwent total arch replacement using the FET procedure with Jotec E-vita Open NEO™ branched prosthesis from two Asian centers between October 2020 and August 2021. The primary outcome was overall 30-day mortality, and the secondary outcomes were operative complications. Results: Twenty-five consecutive patients underwent total arch replacement with FET with the novel hybrid prosthesis. Overall 30-day mortality from both centers was 0%. Overall mean operative, cardiopulmonary bypass, hypothermic circulatory arrest, and selective antegrade cerebral perfusion times were 353.4±80.5, 183.2±39.6, 57.2±14.7, and 138.2±28.6 minutes, respectively. No patient developed stroke. Permanent spinal cord injury (SCI) was recorded in one patient (4%) and one (4%) had transient lower limb weakness that resolved after spinal drainage. There was no requirement of re-sternotomy for hemostasis. Conclusions: We reported a multicenter Asian case series with the novel FET hybrid prosthesis demonstrating the feasibility and safety of promising initial clinical outcomes. The technique of circumferential reinforcement of vascular anastomosis for hemostasis may be one of the methods for lowering the rates of re-sternotomy for hemostasis, and proper surgical or transfusion strategies would overcome the excessive oozing of the prosthesis. Long-term follow-up is required for further evaluation of aortic pathology progression and device-related outcomes.

Dichotomous effects of in vivo and in vitro ionizing radiation exposure on lymphatic function.

On the one hand, lymphatic dysfunction induces interstitial edema and inflammation. On the other hand, the formation of edema and inflammation induce lymphatic dysfunction. However, informed by the earlier reports of undetected apoptosis of irradiated lymphatic endothelial cells (LECs) in vivo, lymphatic vessels are commonly considered inconsequential to ionizing radiation (IR)-induced inflammatory injury to normal tissues. Primarily because of the lack of understanding of the acute effects of IR exposure on lymphatic function, acute edema and inflammation, common sequelae of IR exposure, have been ascribed solely to blood vessel damage. Therefore, in the present study, the lymphatic acute responses to IR exposure were quantified to evaluate the hypothesis that IR exposure impairs lymphatic pumping. Rat mesenteric lymphatic vessels were irradiated in vivo or in vitro, and changes in pumping were quantified in isolated vessels in vitro. Compared with sham-treated vessels, pumping was lowered in lymphatic vessels irradiated in vivo but increased in vessels irradiated in vitro. Furthermore, unlike in blood vessels, the acute effects of IR exposure in lymphatic vessels were not mediated by nitric oxide-dependent pathways in either in vivo or in vitro irradiated vessels. After cyclooxygenase blockade, pumping was partially restored in lymphatic vessels irradiated in vitro but not in vessels irradiated in vivo. Taken together, these findings demonstrated that lymphatic vessels are radiosensitive and LEC apoptosis alone may not account for all the effects of IR exposure on the lymphatic system.NEW & NOTEWORTHY Earlier studies leading to the common belief that lymphatic vessels are radioresistant either did not characterize lymphatic pumping, deemed necessary for the resolution of edema and inflammation, or did it in vivo. By characterizing pumping in vitro, the present study, for the first time, demonstrated that lymphatic pumping was impaired in vessels irradiated in vivo and enhanced in vessels irradiated in vitro. Furthermore, the pathways implicated in ionizing radiation-induced blood vessel damage did not mediate lymphatic responses.

Midterm clinical outcome of a case of aortic arch aneurysm treated with a novel arch stentgraft system.

INTRODUCTION: Open surgery is the gold standard treatment for aortic arch disease. However, due to its complexity, open arch replacement is associated with considerable risk of mortality and morbidity. METHOD: We report a case of a 71-year-old gentleman with multiple comorbidities and symptomatic 7 cm aortic arch aneurysm who was treated with a single-stage carotid-carotid and left carotid-axillary bypass followed by zone 0 aortic arch stenting with bimodular Nexus™ stent graft. RESULTS: Post-operatively, the patient suffered from a minor stroke with full neurological recovery. Follow-up computed tomography of the aorta 3 years post-stenting showed excellent stent position with no endoleak and complete resolution of the saccular aneurysm. DISCUSSION: The midterm result of our patient who was successfully treated with an off-the-shelf single branch, bimodular stent graft system is excellent with complete resolution of the arch saccular aneurysm at 3-year after the operation.

Retrospective record review on timing of COVID-19 vaccination and cardiac surgery.

BACKGROUND: Novel clinical challenges are faced by cardiac surgeons under the coronavirus disease 2019 (COVID-19) pandemic. Amidst the uncertainties faced due to the socioeconomic and public health impact, there is little evidence surrounding COVID-19 vaccination in patients undergoing cardiac surgery. Timing of vaccination and postvaccination adverse effects are required parameters to discuss with cardiac surgical patients. METHODS: This is a single-center, retrospective observational study. All patients who underwent adult cardiac surgery at the Prince of Wales Hospital, Hong Kong from January 2021 to December 2021 were included. Postoperative clinical outcomes, COVID-19 vaccination status, and vaccination-related adverse effects were collected. RESULTS: A total of 426 patients; 117 (27%) underwent isolated coronary artery bypass grafting, 111 (26%) underwent valvular surgery, and 97 (23%) underwent aortic surgery. Patients received either Sinovac CoronaVac or Pfizer BNT162b2 vaccine. Overall vaccination rate with at least 1 dose was 52% (n = 212), 15% (n = 63) received the first dose before surgery, 36% (n = 149) received the first dose vaccination after surgery. Rate of completion with second and third doses of vaccination were 22% (n = 89) and 4.9% (n = 20), respectively. The mean timing of first dose of vaccine after surgery was 216 ± 84 days from operation. Three (1.4%) patients recorded vaccination-related complications. CONCLUSIONS: COVID-19 vaccination is safe in patients who received major cardiac surgery, with low adverse effects recorded and no vaccine-related mortality observed. A time frame of 3-6 months after cardiac surgery receiving COVID-19 vaccination is reasonable and could serve as a guidance for future COVID-19 vaccination booster programs.

Impact of the COVID-19 pandemic on American College of Surgeons-Accredited Education Institutes & American Society of Anesthesiologists-Simulation Education Network: Opportunities for interdisciplinary collaboration.

BACKGROUND: The COVID-19 pandemic presented challenges for simulation programs including American College of Surgeons Accredited Education Institutes and American Society of Anesthesiologists Simulation Education Network. American College of Surgeons Accredited Education Institutes and American Society of Anesthesiologists Simulation Education Network leadership were surveyed to identify opportunities to enhance patient safety through simulation. METHODS: Between January and June 2021, surveys consisting of 3 targeted domains: (I) Changing practice; (II) Contributions and recognition; and (III) Moving ahead were distributed to 100 American College of Surgeons Accredited Education Institutes and 54 American Society of Anesthesiologists Simulation Education Network centers. Responses were combined and percent frequencies reported. RESULTS: Ninety-six respondents, representing 51 (51%) American College of Surgeons Accredited Education Institutes, 17 (31.5%) American Society of Anesthesiologists Simulation Education Network, and 28 dually accredited centers, completed the survey. Change of practice. Although 20.3% of centers stayed fully operational at the COVID-19 onset, 82% of all centers closed: 32% were closed less than 3 months, 28% were closed 3 to 6 months, 8% were closed 7 to 9 months, and 32% remained closed as of June 6, 2021. Most impacted activities were large-group instruction and team training. Sixty-nine percent of programs converted in-person to virtual programs. Contributions. The top reported innovative contributions included policies (80%), curricula (80%), and scholarly work (74%), Moving ahead. The respondents' top concerns were returning to high-quality training to best address learners' deficiencies and re-engagement of re-directed training programs. When asked "How the American College of Surgeons/American Society of Anesthesiologists Programs could best assist your simulation center goals?" the top responses were "facilitate collaboration" and "publish best practices from this work." CONCLUSION: The Pandemic presented multiple challenges and opportunities for simulation centers. Opportunities included collaboration between American College of Surgeons Accredited Education Institutes and the American Society of Anesthesiologists Simulation Education Network to identify best practices and resources needed to enhance patient safety through simulation.

The misnomer of uncomplicated type B aortic dissection.

BACKGROUND: Acute type B aortic dissection (TBAD) is a rare condition that can be divided into complicated (CoTBAD) and uncomplicated (UnCoTBAD) based on certain presenting clinical and radiological features, with UnCoTBAD constituting the majority of TBAD cases. The classification of TBAD directly affects the treatment pathway taken, however, there remains confusion as to exactly what differentiates complicated from uncomplicated TBAD. AIMS: The scope of this review is to delineate the literature defining the intervention parameters for UnCoTBAD. METHODS: A comprehensive literature search was conducted using multiple electronic databases including PubMed, Scopus, and EMBASE to collate and summarize all research evidence on intervention parameters and protocols for UnCoTBAD. RESULTS: A TBAD without evidence of malperfusion or rupture might be classified as uncomplicated but there remains a subgroup who might exhibit high-risk features. Two clinical features representative of "high risk" are refractory pain and persistent hypertension. First-line treatment for CoTBAD is TEVAR, and whilst this has also proven its safety and effectiveness in UnCoTBAD, it is still being managed conservatively. However, TBAD is a dynamic pathology and a significant proportion of UnCoTBADs can progress to become complicated, thus necessitating more complex intervention. While the "high-risk" UnCoTBAD do benefit the most from TEVAR, yet, the defining parameters are still debatable as this benefit can be extended to a wider UnCoTBAD population. CONCLUSION: Uncomplicated TBAD remains a misnomer as it is frequently representative of a complex ongoing disease process requiring very close monitoring in a critical care setting. A clear diagnostic pathway may improve decision making following a diagnosis of UnCoTBAD. Choice of treatment still predominantly depends on when an equilibrium might be reached where the risks of TEVAR outweigh the natural history of the dissection in both the short- and long-term.

Open conversion with Crawford extent 3 thoracoabdominal aortic replacement after candy-plug implantation.

A patient who underwent candy-plug insertion in the year 2016 developed type 1B endoleak with rapid enlargement of distal descending thoracic aortic aneurysm in the year 2021 despite the initial successful false lumen occlusion and thrombosis. Open conversion with Crawford extent 3 thoracoabdominal aortic replacement was performed successfully and the patient was discharged home without any major complications.

A human pluripotent stem cell-based model of SARS-CoV-2 infection reveals an ACE2-independent inflammatory activation of vascular endothelial cells through TLR4.

To date, the direct causative mechanism of SARS-CoV-2-induced endotheliitis remains unclear. Here, we report that human ECs barely express surface ACE2, and ECs express less intracellular ACE2 than non-ECs of the lungs. We ectopically expressed ACE2 in hESC-ECs to model SARS-CoV-2 infection. ACE2-deficient ECs are resistant to the infection but are more activated than ACE2-expressing ones. The virus directly induces endothelial activation by increasing monocyte adhesion, NO production, and enhanced phosphorylation of p38 mitogen-associated protein kinase (MAPK), NF-κB, and eNOS in ACE2-expressing and -deficient ECs. ACE2-deficient ECs respond to SARS-CoV-2 through TLR4 as treatment with its antagonist inhibits p38 MAPK/NF-κB/ interleukin-1ß (IL-1ß) activation after viral exposure. Genome-wide, single-cell RNA-seq analyses further confirm activation of the TLR4/MAPK14/RELA/IL-1ß axis in circulating ECs of mild and severe COVID-19 patients. Circulating ECs could serve as biomarkers for indicating patients with endotheliitis. Together, our findings support a direct role for SARS-CoV-2 in mediating endothelial inflammation in an ACE2-dependent or -independent manner.

Pre-emptive BioGlue priming of the branched Evita Open NEO hybrid prosthesis: tackling excessive oozing.

Excessive oozing after total arch replacement with the frozen elephant trunk technique through the fabric of the E-vita Open NEO raised concern about its early adaptation. The mechanism is speculated to be multifactorial. Our goal was to report our approach using pre-emptive BioGlue priming on the fabric against the oozing phenomenon.

Paving the way for E-vita open NEO hybrid prosthesis implantation for complex aortic arch disease in Asia-Pacific.

We report first in man implantations of the newly designed Evita-open-NEO hybrid prosthesis for complex aortic arch disease from three different countries in Asia-Pacific including instructions on how to proceed with perioperative coagulation management.

Takotsubo syndrome after liver transplantation: An association with intraoperatively administered epinephrine and fentanyl.

Takotsubo syndrome (TTS) can develop after liver transplant (LT), but its predisposing factors are poorly understood. In this study, we aimed to determine if perioperative factors were associated with posttransplant TTS. Adult patients who underwent primary LT between 2006 and 2018 were included. Patients with and without TTS were identified and matched by propensity scores. Of 2181 LT patients, 38 developed postoperative TTS with a mean left ventricular ejection fraction of 25.5% (±7.8%). Multivariable logistic regression revealed two preoperative risk factors (alcoholic cirrhosis and model for end-stage liver disease-sodium scores) for TTS. Post-propensity match analyses showed that TTS patients had significantly higher doses of epinephrine and lower doses of fentanyl during LT compared with non-TTS patients. A higher dose of epinephrine and a lower dose of fentanyl was associated with a higher predicted probability of TTS. All TTS patients had full recovery of cardiac function and had comparable 1-year survival. In conclusion, TTS occurred at a rate of 1.7% after LT and was associated with two pretransplant risk factors. The higher doses of epinephrine and lower doses of fentanyl administered during LT were associated with posttransplant TTS. More studies on the relationship between intraoperative medications and TTS are warranted.

Algebraic formulas characterizing an alternative to Guyton's graphical analysis relevant for heart failure.

Although Guyton's graphical analysis of cardiac output-venous return has become a ubiquitous tool for explaining how circulatory equilibrium emerges from heart-vascular interactions, this classical model relies on a formula for venous return that contains unphysiological assumptions. Furthermore, Guyton's graphical analysis does not predict pulmonary venous pressure, which is a critical variable for evaluating heart failure patients' risk of pulmonary edema. Therefore, the purpose of the present work was to use a minimal closed-loop mathematical model to develop an alternative to Guyton's analysis. Limitations inherent in Guyton's model were addressed by 1) partitioning the cardiovascular system differently to isolate left ventricular function and lump all blood volumes together, 2) linearizing end-diastolic pressure-volume relationships to obtain algebraic solutions, and 3) treating arterial pressures as constants. This approach yielded three advances. First, variables related to morbidities associated with left ventricular failure were predicted. Second, an algebraic formula predicting left ventricular function was derived in terms of ventricular properties. Third, an algebraic formula predicting flow through the portion of the system isolated from the left ventricle was derived in terms of mechanical properties without neglecting redistribution of blood between systemic and pulmonary circulations. Although complexities were neglected, approximations necessary to obtain algebraic formulas resulted in minimal error, and predicted variables were consistent with reported values.