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BioRxiv : the Preprint Server For... Jun 2024Oxidative stress is implicated in the pathogenesis and progression of abdominal aortic aneurysm (AAA). Antioxidant delivery as a therapeutic for AAA is of substantial...
BACKGROUND
Oxidative stress is implicated in the pathogenesis and progression of abdominal aortic aneurysm (AAA). Antioxidant delivery as a therapeutic for AAA is of substantial interest although clinical translation of antioxidant therapy has met with significant challenges due to limitations in achieving sufficient antioxidant levels at the site of AAA. We posit that nanoparticle-based approaches hold promise to overcome challenges associated with systemic administration of antioxidants.
METHODS
We employed a peptide-based nanoplatform to overexpress a key modulator of oxidative stress, superoxide dismutase 2 (SOD2). The efficacy of systemic delivery of SOD2 mRNA as a nanotherapeutic agent was studied in two different murine AAA models. Unbiased mass spectrometry-enabled proteomics and high-dimensional bioinformatics were used to examine pathways modulated by SOD2 overexpression.
RESULTS
The murine SOD2 mRNA sequence was mixed with p5RHH, an amphipathic peptide capable of delivering nucleic acids to form self-assembled nanoparticles of ∼55 nm in diameter. We further demonstrated that the nanoparticle was stable and functional up to four weeks following self-assembly when coated with hyaluronic acid. Delivery of SOD2 mRNA mitigated the expansion of small AAA and largely prevented rupture. Mitigation of AAA was accompanied by enhanced SOD2 protein expression in aortic wall tissue. Concomitant suppression of nitric oxide, inducible nitric oxide synthase expression, and cell death was observed. Proteomic profiling of AAA tissues suggests that SOD2 overexpression augments levels of microRNAs that regulate vascular inflammation and cell apoptosis, inhibits platelet activation/aggregation, and downregulates mitogen-activated protein kinase signaling. Gene set enrichment analysis shows that SOD2 mRNA delivery is associated with activation of oxidative phosphorylation, lipid metabolism, respiratory electron transportation, and tricarboxylic acid cycle pathways.
CONCLUSIONS
These results confirm that SOD2 is key modulator of oxidative stress in AAA. This nanotherapeutic mRNA delivery approach may find translational application in the medical management of small AAA and the prevention of AAA rupture.
PubMed: 38948794
DOI: 10.1101/2024.06.17.599454 -
Journal of Orthopaedics Nov 2024Anterior cruciate ligament (ACL) rupture is a prevalent sports injury with rising rates attributed to increased population participation in sports activities. ACL... (Review)
Review
BACKGROUND
Anterior cruciate ligament (ACL) rupture is a prevalent sports injury with rising rates attributed to increased population participation in sports activities. ACL rupture can lead to severe knee complications including cartilage damage, torn meniscus, and osteoarthritis. Current treatment options include conservative measures and surgical interventions. However, debates persist regarding the optimal approach.
PURPOSE
This analysis intended to compare the function, knee stability, and incidence rate of secondary surgery between conservative and surgical treatments in ACL rupture patients.
METHODS
A systematic search was performed via Embase, Ovid Medline, PubMed, Cochrane Library, Web of Science, and Google Scholar for reporting outcomes of conservative and surgical treatments after ACL rupture. The outcomes included patient-reported outcome measures (PROMs), knee stability, the need for secondary meniscal surgery, delayed ACL reconstruction surgery, and revision ACL reconstruction surgery. Outcomes were analyzed using mean differences or odd ratios (OR) with 95 % CIs.
RESULTS
11 studies were included with 1516 patients. For PROMs, our evidence indicated no differences in KOOS Pain, KOOS Symptoms, KOOS Sport/Rec, KOOS ADL, and KOOS QOL. (all p > 0.05). for knee stability, pivot shift (OR, 0.14; p < 0.001), Lachman test (OR, 0.06; p < 0.001), and tibia translation (p < 0.001) were evaluated, and the available evidence favored surgical treatment over conservative treatment. For the incidence rate of any secondary surgery after the first diagnosis, the surgical group showed a lower rate of meniscal surgery with statistical significance (OR, 0.37; p < 0.001). The average rate of revision ACL reconstruction is 5.80 %, while the rate of delayed ACL reconstruction after conservative treatment is 18.51 %.
CONCLUSION
Currently, there is insufficient empirical evidence to advocate a systematic surgical reconstruction for any patient who tore his ACL. This review found no differences in function outcomes between conservative and surgical treatments. Regarding knee stability and secondary meniscal surgery, the results prefer the surgical treatments. The occurrence rate of revision and delayed ACL reconstruction are non-negligible factors that must be fully understood by both surgeons and patients before choosing a suitable treatment.
PubMed: 38948499
DOI: 10.1016/j.jor.2024.05.026 -
JACC. Case Reports Jul 2024Single coronary artery, giant coronary artery aneurysm, and coronary cameral fistula are rare congenital anomalies, and can cause a range of presentations. To our...
Single coronary artery, giant coronary artery aneurysm, and coronary cameral fistula are rare congenital anomalies, and can cause a range of presentations. To our knowledge, this is the first reported case of all 3 entities occurring simultaneously in 1 patient, with largely unknown implications. Multimodal imaging was essential in prompt diagnosis and management.
PubMed: 38948493
DOI: 10.1016/j.jaccas.2024.102396 -
Frontiers in Surgery 2024This study aimed to compare the short-term outcomes of surgical treatment for acute type A aortic dissection between patients undergoing cardiopulmonary arrest at the...
BACKGROUND
This study aimed to compare the short-term outcomes of surgical treatment for acute type A aortic dissection between patients undergoing cardiopulmonary arrest at the time of entry into the operating room and patients who received successful preoperative cardiopulmonary resuscitation before entering the operating room or patients who had cardiopulmonary arrest on the operating room table after entering the operating room without cardiopulmonary arrest. In the present study, we focused on the circulatory status at the time of entering the operating room because it is economically and emotionally difficult to cease intervention once the patient has entered the operating room, where surgeons, anesthesiologists, nurses, and perfusionists are already present, all necessary materials are packed off and cardiopulmonary bypass have already been primed.
METHODS
Twenty (5.5%) of 362 patients who underwent surgical treatment for acute type A aortic dissection between January 2016 and March 2022 had preoperative cardiopulmonary arrest. To compare the early operative outcomes, the patients were divided into the spontaneous circulation group ( = 14, 70.0%) and the non-spontaneous circulation group ( = 6, 30.0%) based on the presence or absence of spontaneous circulation upon entering the operating room. The primary endpoint was postoperative 30-day mortality. The secondary endpoints included in-hospital complications and persistent neurological disorders.
RESULTS
Thirty-day mortality was 65% ( = 13/20) in the entire cohort; 50% ( = 7/14) in the spontaneous circulation group and 100% ( = 6/6) in the non-spontaneous circulation group. The major cardiopulmonary arrest causes were aortic rupture and cardiac tamponade ( = 16; 80.0%), followed by coronary malperfusion ( = 4; 20.0%). Seven patients (50.0%) survived in the spontaneous circulation group, and none survived in the non-spontaneous circulation group (= .044). Five survivors walked unaided and were discharged home; the remaining two were comatose and paraplegic.
CONCLUSIONS
The outcomes were extremely poor in patients with acute type A aortic dissection who had preoperative cardiopulmonary arrest and received ongoing cardiopulmonary resuscitation at entry into the operating room. Therefore, surgical treatment might be contraindicated in such patients.
PubMed: 38948478
DOI: 10.3389/fsurg.2024.1404825 -
Biotechnology Reports (Amsterdam,... Jun 2024The antioxidant and antiproliferative activity of red tilapia ( spp.) viscera hydrolysates (RTVH) was evaluated. For that, the hydrolysates was applied to three cancer...
The antioxidant and antiproliferative activity of red tilapia ( spp.) viscera hydrolysates (RTVH) was evaluated. For that, the hydrolysates was applied to three cancer cell lines (HepG2, Huh7 and SW480) and the control (CCD-18Co). Finally, the line on which the hydrolysate had the greatest effect (SW480) and the control (CCD-18Co) were subjected to the ApoTox-Glo Triplex Assay to determine apoptosis, toxicity, and cell viability. The result showed that hydrolysate had a dose-dependent cytotoxic effect selective on the three cancer cell lines, compared to the control cells. There is a relationship between the antioxidant capacity of RTVHs and their antiproliferative capacity on cancer cells evaluated, which achieved cell viability by action of RTVH of 34.68 and 41.58 and 25.41 %, to HepG2, Huh7 and SW480, respectively. The action of RTVH on cancer cell line SW480 is not due to the induction of apoptosis but to the rupture of the cell membrane.
PubMed: 38948352
DOI: 10.1016/j.btre.2024.e00832 -
Journal of Inflammation Research 2024Inflammation triggers atherosclerotic plaque rupture, leading to acute myocardial infarction (AMI). Following AMI, peri-coronary adipose tissue (PCAT) undergoes a...
BACKGROUND
Inflammation triggers atherosclerotic plaque rupture, leading to acute myocardial infarction (AMI). Following AMI, peri-coronary adipose tissue (PCAT) undergoes a transition from lipid-rich to hydrophilic characteristics due to vascular inflammation. This study investigates PCAT changes and neutrophil-to-lymphocyte ratio levels during AMI.
PATIENTS AND METHODS
60 AMI patients undergoing coronary computed tomography angiography and angiography (Jan 2020-Jun 2022) were studied 60 age, gender, BMI-matched stable angina, and 60 non-coronary artery disease patients were included. Siemens VB20.0 measured PCAT-volume and fat attenuation index (FAI). Neutrophil-to-lymphocyte ratio levels were calculated by peripheral blood tests.
RESULTS
The PCAT volume and PCAT-FAI gradually increased across the control, stable angina, and AMI groups, with a corresponding gradual rise in NLR. NLR exhibited weak positive correlation with PCAT-FAI (r=0.35) and PCAT-volume (r=0.24). Multivariable logistic regression identified increased PCAT-volume, PCAT-FAI and neutrophil-to-lymphocyte ratio as possible independent AMI risk factors. No significant PCAT-volume difference was observed between infarct-related artery (IRA) and non-IRA for all three coronary arteries. Only PCAT-FAI around IRA-LAD was higher than non-IRA-LAD (-74.84±6.93 HU vs -79.04±8.68 HU). PCAT-FAI around culprit vessels in AMI was higher than corresponding lesion related vessel in SA. PCAT-volume around narrowed non-IRA in AMI was higher than that of corresponding LRV in SA. PCAT-FAI of narrowed non-IRA-LADs and non-IRA-LCXs in AMI were elevated compared to LADs (-78.46±8.56HU vs -83.13±8.34 HU) and LCXs (-73.83±10.63 HU vs -81.38±7.88 HU) of lesion related vessel in stable angina.
CONCLUSION
We found an association between AMI and inflammation in the coronary perivascular adipose tissue and systemic inflammatory response.
PubMed: 38948196
DOI: 10.2147/JIR.S465605 -
Endoscopic Ultrasound 2024
PubMed: 38947745
DOI: 10.1097/eus.0000000000000049 -
Cureus May 2024This study highlights a case of late open conversion repair (OCR) for persistent Type II endoleak after endovascular aneurysm repair (EVAR), presenting a 78-year-old...
This study highlights a case of late open conversion repair (OCR) for persistent Type II endoleak after endovascular aneurysm repair (EVAR), presenting a 78-year-old male with a history of EVAR for an infrarenal abdominal aortic aneurysm. Despite conservative management of the initial endoleak, the aneurysm sac's progressive growth necessitated open reconstruction to salvage the graft. Successful postoperative outcomes emphasize the critical need for meticulous intervention strategies and surveillance in managing persistent Type II endoleaks. This case underlines the importance of a tailored approach, leveraging both endovascular and open surgical techniques, to optimize long-term outcomes and prevent aneurysm rupture in complex cases.
PubMed: 38947720
DOI: 10.7759/cureus.61420 -
Cureus May 2024A cesarean scar pregnancy (CSP) is a rare form of ectopic pregnancy. Proper diagnosis and management of CSP are incredibly important secondary to the risk of uterine...
A cesarean scar pregnancy (CSP) is a rare form of ectopic pregnancy. Proper diagnosis and management of CSP are incredibly important secondary to the risk of uterine rupture and life-threatening hemorrhage. Various medical and surgical management have been described previously. This report looks at two cases of CSP diagnosed at an urban hospital in Atlanta, Georgia. The first woman was 30 years old with a history of five prior CS. She was referred from an abortion clinic for CSP at 6 weeks 2 days gestation. She did not desire future fertility and opted for a hysterectomy. The second woman was 38 years old with a history of three prior CS presenting with vaginal bleeding and abdominal pain and found to have a CSP with a gestation sac measuring 5 weeks 1 day. Given the patient's desires for future fertility, she was treated with a two-dose regimen of systemic intramuscular methotrexate (MTX) at 1 mg/kg with successful resolution of CSP and subsequent intrauterine pregnancy. Due to the high risk of uterine rupture and hemorrhage with CSP, it is important to have a high index of suspicion for diagnosis. Due to the rarity of CSP, and thus difficulty creating quality prospective trials, there is no consensus on the best management yet. Although conservative treatment carries high failure risk, shared decision-making incorporating future fertility desires should be considered when determining management of CSP, and when surgical management is considered a minimally invasive approach should be the standard of care in surgical management.
PubMed: 38947697
DOI: 10.7759/cureus.61311 -
Cureus May 2024Coronary artery disease continues to remain the leading cause of mortality worldwide. Coronary blood supply is provided through the right and left main coronary...
Coronary artery disease continues to remain the leading cause of mortality worldwide. Coronary blood supply is provided through the right and left main coronary arteries. The left main coronary artery (LMCA) in turn gives rise to the left anterior descending (LAD) and left circumflex (LCX) arteries. In some cases, LMCA may trifurcate into the ramus intermedius (RI) in addition to the LAD and LCX arteries. Atherosclerotic plaque formation and rupture with subsequent clot formation and occlusion of coronary arteries are the underlying mechanisms of myocardial infarction. Though the clinical implications of the presence of ramus intermedius (RI) are controversial some data suggest that the RI is associated with an increased risk of atherosclerotic plaque formation in the LMCA and the proximal LAD. Conversely, it has been proposed that the RI provides an additional collateral source of blood supply to the myocardium and may potentially contribute to improved survival. Case reports tout the benefits of RI, specifically in the setting of multivessel coronary artery occlusions. Whether it increases the risk of atherosclerotic plaque formation or whether it is protective has yet to be determined. We present a case of a 58-year-old male who presented with acute coronary syndrome and cardiogenic shock due to total ostial occlusion of LAD. The patient had also chronic total occlusions of the right coronary artery and LCX but a patent RI, which was the only source of blood supply to the myocardium and practically determined the patient's survival. Additionally, we performed a literature review to identify similar cases, to support RI's potentially protective role in enhancing survival.
PubMed: 38947610
DOI: 10.7759/cureus.61288