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Journal of Cardiothoracic Surgery Jun 2024About 10% of patients after cardiopulmonary bypass (CPB) would undergo acute liver injury, which aggravated the mortality of patients. Ac2-26 has been demonstrated to...
OBJECTIVE
About 10% of patients after cardiopulmonary bypass (CPB) would undergo acute liver injury, which aggravated the mortality of patients. Ac2-26 has been demonstrated to ameliorate organic injury by inhibiting inflammation. The present study aims to evaluate the effect and mechanism of Ac2-26 on acute liver injury after CPB.
METHODS
A total of 32 SD rats were randomized into sham, CPB, Ac, and Ac/AKT1 groups. The rats only received anesthesia, and rats in other groups received CPB. The rats in Ac/AKT1 were pre-injected with the shRNA to interfere with the expression of AKT1. The rats in CPB were injected with saline, and rats in Ac and Ac/AKT1 groups were injected with Ac2-26. After 12 h of CPB, all the rats were sacrificed and the peripheral blood and liver samples were collected to analyze. The inflammatory factors in serum and liver were detected. The liver function was tested, and the pathological injury of liver tissue was evaluated.
RESULTS
Compared with the sham group, the inflammatory factors, liver function, and pathological injury were worsened after CPB. Compared with the CPB group, the Ac2-26 significantly decreased the pro-inflammatory factors and increased the anti-inflammatory factor, improved liver function, and ameliorated the pathological injury. All the therapeutic effects of Ac2-26 were notably attenuated by the shRNA of AKT1. The Ac2-26 increased the GSK3β and eNOS, and this promotion was inhibited by the shRNA.
CONCLUSION
The Ac2-26 significantly treated the liver injury, inhibited inflammation, and improved liver function. The effect of Ac2-26 on liver injury induced by CPB was partly associated with the promotion of AKT1/GSK3β/eNOS.
Topics: Animals; Cardiopulmonary Bypass; Proto-Oncogene Proteins c-akt; Rats, Sprague-Dawley; Glycogen Synthase Kinase 3 beta; Rats; Nitric Oxide Synthase Type III; Male; Disease Models, Animal; Liver; Signal Transduction
PubMed: 38824570
DOI: 10.1186/s13019-024-02801-z -
Journal of Cardiothoracic Surgery Jun 2024Post-operative atrial fibrillation (POAF) occurs in up to 40% of patients following coronary artery bypass grafting (CABG) and is associated with a higher risk of stroke... (Observational Study)
Observational Study
Epicardial placement of human placental membrane allografts in coronary artery bypass graft surgery is associated with reduced postoperative atrial fibrillation: a pilot study for a future multi-center randomized controlled trial.
BACKGROUND
Post-operative atrial fibrillation (POAF) occurs in up to 40% of patients following coronary artery bypass grafting (CABG) and is associated with a higher risk of stroke and mortality. This study investigates how POAF may be mitigated by epicardial placement of aseptically processed human placental membrane allografts (HPMAs) before pericardial closure in CABG surgery. This study was conducted as a pilot feasibility study to collect preliminary for a forthcoming multi-center randomized controlled trial.
METHODS
This retrospective observational study of patients undergoing CABG surgery excluded patients with pre-operative heart failure, chronic kidney disease, or a history of atrial fibrillation. The "treatment" group (n = 24) had three HPMAs placed epicardially following cardiopulmonary bypass decannulation but before partial pericardial approximation and chest closure. The only difference in clinical protocol for the control group (n = 54) was that they did not receive HPMA.
RESULTS
HPMA-treated patients saw a significant, greater than four-fold reduction in POAF incidence compared to controls (35.2-8.3%, p = 0.0136). Univariate analysis demonstrated that HPMA treatment was associated with an 83% reduction in POAF (OR = 0.17, p = 0.0248). Multivariable analysis yielded similar results (OR = 0.07, p = 0.0156) after controlling for other covariates. Overall length of stay (LOS) between groups was similar, but ICU LOS trended lower with HPMA treatment (p = 0.0677). Post-operative inotrope and vasopressor requirements were similar among groups. There was no new-onset post-operative heart failure, stroke, or death reported up to thirty days in either group.
CONCLUSIONS
Epicardial HPMA placement can be a simple intervention at the end of CABG surgery that may provide a new approach to reduce post-operative atrial fibrillation by modulating local inflammation, possibly reducing ICU and hospital stay, and ultimately improving patient outcomes.
Topics: Humans; Atrial Fibrillation; Coronary Artery Bypass; Female; Pilot Projects; Male; Retrospective Studies; Middle Aged; Postoperative Complications; Aged; Placenta; Pregnancy; Allografts; Pericardium; Feasibility Studies
PubMed: 38824517
DOI: 10.1186/s13019-024-02822-8 -
Cardiovascular Revascularization... May 2024Coronary collateral circulation is a common finding in patients with chronic total occlusions (CTOs) resulting from chronic coronary artery disease (CAD). Regional wall...
BACKGROUND
Coronary collateral circulation is a common finding in patients with chronic total occlusions (CTOs) resulting from chronic coronary artery disease (CAD). Regional wall motion abnormalities (RWMA) on transthoracic echocardiography (TTE) can be used for the diagnosis of CAD. However, little work has been done to investigate the impact of collateral vessels on the diagnostic accuracy of resting TTE for CAD.
METHODS
A retrospective chart review was conducted of adults who received a resting TTE and cardiac catheterization within 30 days over a 4-year period at the Temple Baylor Scott & White echocardiography laboratory. Exclusion criteria included catheterization without coronary angiography and prior history of CAD, percutaneous coronary intervention (PCI), or coronary artery bypass graft (CABG). We analyzed RWMA on TTE in patients with CAD and coronary collateral circulation on cardiac catheterization to assess for correlation.
RESULTS
Of the 753 patients were included in this study, 453 had CAD, 272 had both CAD and RWMA, 111 had collateral circulation, and 73 had collateral circulation and RWMA. There was no significant difference in RWMA in patients with CAD with and without collateral circulation. There was no significant difference in the sensitivity (60.0 % vs 59.2 %) and specificity (78.4 % vs 73.9 %) after collateral-adjusted interpretation of RWMA and CAD (p = 0.3).
DISCUSSION
Our results suggest the average coronary collateral system is of insufficient clinical significance to prevent the development of RWMA on resting TTE.
PubMed: 38824113
DOI: 10.1016/j.carrev.2024.05.023 -
The Annals of Thoracic Surgery May 2024Recent randomized trial data showed fewer strokes with left atrial appendage occlusion (LAAO) following cardiac surgery in patients with atrial fibrillation. We...
BACKGROUND
Recent randomized trial data showed fewer strokes with left atrial appendage occlusion (LAAO) following cardiac surgery in patients with atrial fibrillation. We developed a quality initiative to increase LAAO adoption.
METHODS
Among 11,099 patients undergoing isolated CABG between January 2019-March 2021 at 33 hospitals in Michigan, those with atrial fibrillation undergoing first-time, on-pump CABG were eligible (n=1,241). A goal LAAO rate of 75% was selected as a quality improvement target through a statewide collaborative. An interrupted time series analysis evaluated the change in LAAO rate before (January-December 2019) versus after (January 2020-March 2021) implementation.
RESULTS
Implementation of the quality metric improved LAAO rate from 61% (357/581) before to 79% (520/660) after implementation (p<0.001). Compared to patients not undergoing concomitant LAAO, LAAO patients (71%, 877/1,241) were older, more frequently male, and had a lower STS-PROM (2.9±3.5% vs. 3.7±5.7%, p=0.003), while other baseline characteristics including CHADS-VASc scores were similar. Mean bypass and cross-clamp times were 7 and 6 minutes longer, respectively, in the LAAO group among those who did not undergo concomitant ablation. Operative mortality, major morbidity, blood product administration, and thromboembolic events were similar between groups. Interrupted time series analysis showed a significant increase in LAAO rate after implementation (p=0.009).
CONCLUSIONS
LAAO in patients with atrial fibrillation undergoing isolated CABG did not add operative risk versus isolated CABG without LAAO. A statewide quality improvement initiative was successful in increasing the rate of concomitant LAAO and could be further evaluated as a potential quality metric in cardiac surgery.
PubMed: 38823757
DOI: 10.1016/j.athoracsur.2024.05.020 -
The Canadian Journal of Cardiology May 2024Coronary artery disease is a common etiology of ischemic left ventricular systolic dysfunction (LVSD), for which the optimal revascularization strategy remains unclear.... (Review)
Review
BACKGROUND
Coronary artery disease is a common etiology of ischemic left ventricular systolic dysfunction (LVSD), for which the optimal revascularization strategy remains unclear. We aimed to determine whether percutaneous coronary intervention (PCI) or coronary artery bypass grafting (CABG) results in greater survival advantage in patients with LVSD.
METHODS
A study-level (SLMA) and reconstructed individual patient data meta-analysis (rIPDMA) from Kaplan-Meier (KM) survival curves were performed. A systematic search of MEDLINE, EMBASE, and Cochrane was conducted for observational and randomized studies published after 2010 that compared PCI to CABG in patients with left ventricular ejection fraction ≤40%. The primary outcome was all-cause mortality at longest follow-up. The secondary outcomes were myocardial infarction (MI), stroke, repeat revascularization, cardiovascular mortality, and major adverse cardiovascular and cerebrovascular events (MACCE) at longest follow-up.
RESULTS
Fourteen studies (11 observational, three randomized, 13,063 patients) were eligible for SLMA. Seven contained digitizable KM curves from which individual patient data could be reconstructed. Study-level analysis found PCI associated with increased all-cause mortality (Hazard Ratio 1.41 [95% Confidence Interval 1.18-1.69]), MI (2.10 [1.62-2.72]), repeat revascularization (2.39 [1.37-4.17]) and MACCE (1.58 [1.23-2.03]), without significant differences in stroke (0.86 [0.39-1.92]) or cardiovascular mortality (1.42 [0.78-2.59]). In the rIPDMA, PCI resulted in increased all-cause mortality (1.57 [1.34-1.87]) and repeat revascularization (3.63 [3.12-4.21]) but overall lower risk of stroke (0.62 [0.39-0.99]) due to fewer events during initial follow-up.
CONCLUSIONS
In patients with ischemic LVSD, PCI was associated with higher risk of all-cause mortality and repeat revascularization than CABG but lower risk of short-term stroke.
PubMed: 38823634
DOI: 10.1016/j.cjca.2024.05.023 -
International Journal of Cardiology May 2024
PubMed: 38823532
DOI: 10.1016/j.ijcard.2024.132215 -
The natural history of isolated common femoral endarterectomy for chronic limb-threatening ischemia.Journal of Vascular Surgery May 2024Occlusive disease of the common femoral artery can generate profound lower extremity ischemia as the normal collateral pathways from the profunda to the superficial...
OBJECTIVE
Occlusive disease of the common femoral artery can generate profound lower extremity ischemia as the normal collateral pathways from the profunda to the superficial femoral artery cannot adequately develop. In patients with lifestyle-limiting claudication, isolated endarterectomy of the common femoral artery (CFE) is highly effective. As CFE does not provide direct, in-line flow to the plantar arch, it has been felt to provide inadequate revascularization to patients with chronic limb-threatening ischemia (CLTI). The purpose of this retrospective clinical study was to report and assess the natural history of selected patients with CLTI treated with isolated CFE (without concomitant infrainguinal revascularization).
METHODS
Consecutive CFE performed in a large, urban hospital for CLTI between 2014-2021 were reviewed. Patient characteristics, limb, and anatomic stages using the Wound, Ischemia, foot Infection (WIfI) and Global Anatomic Staging Systems (GLASS) were tabulated. Limb-specific and survival-related endpoints were analyzed.
RESULTS
58 patients presenting with CLTI underwent isolated CFE (mean age 74±10 years; 62% male, 90% current or prior smoker). Comorbidities included diabetes (52%), coronary artery disease (55%), congestive heart failure (22%), and end-stage renal failure on hemodialysis (5%). Patients presented with either rest pain (36%) or tissue loss (64%); the latter group exhibited advanced limb threat (68% in WIfI stage 3 or 4). The majority of patients had associated severe infrainguinal disease (50% GLASS 3). After a median follow-up of 17 months (range 10-29 months), vascular reintervention was required in 7 patients (12%). One patient (2%) required major limb amputation after presentation in WIfI stage 4 (W3I3fI0). Indeed, WIfI stage 4 was a significant univariate predictor of the need for subsequent infrainguinal bypass (p=0.034).
CONCLUSIONS
Isolated CFE as primary therapy in highly selected patients with CLTI was safe and effective. Index limb stage is predictive of the need for associated infrainguinal revascularization in this complex population.
PubMed: 38823529
DOI: 10.1016/j.jvs.2024.05.050 -
Neurosurgical Focus Jun 2024Neurosurgical targeting of the cerebellar dentate nucleus via ablative dentatotomy and stimulation of the dentate nucleus was historically used for effective treatment... (Review)
Review
OBJECTIVE
Neurosurgical targeting of the cerebellar dentate nucleus via ablative dentatotomy and stimulation of the dentate nucleus was historically used for effective treatment of spasticity. Yet for decades, neurosurgical treatment of spasticity targeting the cerebellum was bypassed in favor of alternative treatments such as intrathecal baclofen pumps and selective dorsal rhizotomies. Cerebellar neuromodulation has recently reemerged as a promising and effective therapy for spasticity and related movement disorders.
METHODS
In this narrative review, the authors contextualize the historical literature of cerebellar neuromodulation, comparing it with modern approaches and exploring future directions with regard to cerebellar neuromodulation for spasticity.
RESULTS
Neurosurgical intervention on the cerebellum dates to the use of dentatotomy in the 1960s, which had progressed to electrical stimulation of the cerebellar cortex and dentate nucleus by the 1980s. By 2024, modern neurosurgical approaches such as tractography-based targeting of the dentate nucleus and transcranial magnetic stimulation of cerebellar cortex have demonstrated promise for treating spasticity.
CONCLUSIONS
Cerebellar neuromodulation of the dentate nucleus and cerebellar cortex are promising therapies for severe cases of spasticity. Open areas for exploration in the field include the following: tractography-based targeting, adaptive cerebellar stimulation, and investigations into the network dynamics between the cerebellar cortex, deep cerebellar nuclei, and the subcortical and cortical structures of the cerebrum.
Topics: Humans; Muscle Spasticity; Neurosurgical Procedures; Cerebellum; Cerebellar Nuclei; Transcranial Magnetic Stimulation; Baclofen
PubMed: 38823055
DOI: 10.3171/2024.3.FOCUS2446 -
Obesity Surgery Jun 2024Bariatric surgery patients may develop common bile duct stones, and the alterations in their anatomy present challenges in treating this condition. Methods such as...
BACKGROUND
Bariatric surgery patients may develop common bile duct stones, and the alterations in their anatomy present challenges in treating this condition. Methods such as laparoscopic bile duct exploration is impractical in many healthcare facilities, due to the absence of a choledochoscope. This study assesses the feasibility of laparoscopic exploration of the common bile duct using a disposable bronchoscope in these individuals.
METHOD
The study involved 32 participants who had undergone gastric bypass surgery. These participants presented with both bile duct stones and bile ducts exceeding 8 mm in diameter, diagnosed through either MRCP or cholangiography conducted during the surgery. Stone extraction was carried out through either choledotomy or transcystic routes using a disposable bronchoscope and endoscopic baskets.
RESULTS
The patients' ages ranged from 27 to 66 years, with a mean bile duct diameter of 11.6 mm (SD 3.1 mm). A 100% stone clearance rate was achieved for all patients. None of the patients required conversion to open surgery. No T-tubes were placed. One patient developed biloma and intra-abdominal abscesses, which were successfully treated with a percutaneous drain over the course of a week. No mortalities were recorded during the course of this study.
CONCLUSION
Our study results demonstrate that laparoscopic bile duct exploration is both feasible and safe in patients who have undergone gastric bypass surgery. The utilization of a disposable bronchoscope emerges as a practical and cost-effective alternative to a choledochoscope in this procedure.
PubMed: 38822904
DOI: 10.1007/s11695-024-07317-y -
ACS Chemical Neuroscience Jun 2024Spontaneous aggregation of amyloid beta (Aβ) leads to the formation of neurotoxic senile plaque considered as the most crucial event in Alzheimer's disease (AD)...
Spontaneous aggregation of amyloid beta (Aβ) leads to the formation of neurotoxic senile plaque considered as the most crucial event in Alzheimer's disease (AD) progression. Inhibition or disruption of this deadly aggregate formation is one of the most efficient strategies for the development of potential therapeutics, and extensive research is in progress by various research groups. In this direction, the development of a peptide analogous to that of the native Aβ peptide is an attractive strategy. Based on this rationale, β-sheet breakers were developed from the Aβ central hydrophobic core. These peptide derivatives will bind to the full length of the parent Aβ and interfere in self-recognition, thereby preventing the folding of the Aβ peptide into cross β-sheet neurotoxic aggregates. However, this approach is effective in the inhibition of fibrillar aggregation, but this strategy is ineffective in the Aβ neurotoxic oligomer formation. Therefore, an alternative and efficient approach is to use the Aβ peptide analogous to the C-terminal region, which arbitrates fibrillation and oligomerization. Herein, we developed the Aβ C-terminal fragment (ACT-1 to ACT-7) for inhibition of oligomerization as well as fibrillar aggregation. Screening of these seven peptides resulted in an efficient anti-Aβ peptide aggregative agent (ACT-7), which was evaluated by the ThT assay peptide. The ThT assay reveals complete inhibition and showed significant neuroprotection of PC-12-derived neurons from Aβ-induced toxicity and reduced cell apoptosis. Further, analysis using CD and FTIR spectroscopy reveals that the ACT-7 peptide efficiently inhibits the formation of the β-sheet secondary structure content. HR-TEM microscopic analysis confirmed the inhibition of formation. Therefore, the inhibition of β-sheet Aβ fibrillary aggregation by the protease-stable ACT-7 peptide may provide a beneficial effect on AD treatment to control the Aβ aggregates. Finally, we anticipate that our newly designed ACT peptides may also assist as a template molecular scaffold for designing potential anti-AD therapeutics.
PubMed: 38822790
DOI: 10.1021/acschemneuro.4c00032