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Time for \u27The Change\u27: Increasing Awareness of the Menopause Transition in Dermatological Training and Practice
Review of Cerebral Collateral Circulation and Insight Into Cardiovascular Strategies to Limit Collateral Damage in Ischemic Stroke
Cerebral collateral circulation is a dynamic and adaptive process by which alternative vascular pathways supply perfusion to ischemic brain tissue in the event of an arterial occlusion. This complicated network of blood vessels that acts as a natural bypass plays a pivotal role in stroke pathophysiology and has become a key area of study given its significance in stroke treatment and patient outcomes. In this review, we will study the factors influencing the formation, recruitment, and endurance of collateral vessels; discuss imaging modalities for quantitative and qualitative assessment of this network; explore the role of collaterals in stroke management; and highlight several cardiovascular strategies to minimize damage to collaterals and optimize stroke outcomes
En-Bloc Excision of Sacral Squamous Cell Carcinoma With Immediate Reconstruction
Sacral squamous cell carcinoma is an uncommon condition that may arise in scars following burns or in chronic wounds, such as an untreated pilonidal cyst. The aim of the present technical note is to describe a surgical technique aimed at minimizing local recurrence rates by en-bloc resection as well as providing immediate plastic reconstruction: 1. right-sided extended vertical rectus abdominis myo-cutaneous (VRAM) flap; 2. abdomino-perineal excision of the rectum with end colostomy; 3. en-bloc excision of the mass inclusive of gluteus maximus muscles and distal sacrectomy; 4. sacrectomy defect covered with VRAM flap; 5. bilateral gluteal defects covered with single-layer dermal substitute of bovine collagen and elastin hydrolysate followed by immediate split-thickness skin grafting from bilateral thigh donor sites, and negative pressure wound therapy dressings. This approach resulted in a favorable outcome at 2-year follow-up in a male patient presenting with a large locally advanced sacral squamous cell carcinoma involving the external anal sphincter muscle
Utilization of Liver Machine Perfusion Is Associated With Increase in Center Level Liver Transplant Volume
Cardiac Manifestations of Viral Infections, Including Covid-19: A Review
Viral infections have been linked to a variety of cardiac pathology, which may include acute myocarditis, dilated cardiomyopathy, heart failure, cardiogenic shock, pericarditis, acute coronary syndromes, and arrhythmias. We performed a systematic review of literature focusing on the cardiovascular effects of various viral infections, as well as providing an update on the current understanding of the pathophysiology of Coronavirus disease-2019 (COVID-19). Cardiac manifestations of viral illnesses are usually self-limiting, have variable clinical presentations, and require sufficient clinical suspicion for diagnosis and optimal management
Trends and Disparities in Valvular Heart Disease Mortality in the United States From 1999 to 2020
BACKGROUND: Percutaneous heart valve procedures have been increasingly performed over the past decade, yet real-world mortality data on valvular heart disease (VHD) in the United States remain limited.
METHODS AND RESULTS: We queried the Centers for Disease Control and Prevention\u27s Wide-Ranging Online Data for Epidemiologic Research database among patients ≥15 years old from 1999 to 2020. VHD and its subtypes were listed as the underlying cause of death. We calculated age-adjusted mortality rate (AAMR) per 100 000 individuals and determined overall trends by estimating the average annual percent change using the Joinpoint regression program. Subgroup analyses were performed based on demographic and geographic factors. In the 22-year study, there were 446 096 VHD deaths, accounting for 0.80% of all-cause mortality (56 014 102 people) and 2.38% of the total cardiovascular mortality (18 759 451 people). Aortic stenosis recorded the highest mortality of VHD-related death in both male (109 529, 61.74%) and female (166 930, 62.13%) populations. The AAMR of VHD has declined from 8.4 (95% CI, 8.2-8.5) to 6.6 (95% CI, 6.5-6.7) per 100 000 population. Similar decreasing AAMR trends were also seen for the VHD subtypes. Men recorded higher AAMR for aortic stenosis and aortic regurgitation, whereas women had higher AAMR for mitral stenosis and mitral regurgitation. Mitral regurgitation had the highest change in average annual percent change in AAMR.
CONCLUSIONS: The mortality rate of VHD among the US population has declined over the past 2 decades. This highlights the likely efficacy of increasing surveillance and advancement in the management of VHD, resulting in improved outcomes
The Efficacy & Molecular Mechanisms of a Terpenoid Compound Ganoderic Acid C1 on Corticosteroid-Resistant Neutrophilic Airway Inflammation: In Vivo and In Vitro Validation
INTRODUCTION: Neutrophil predominant airway inflammation is associated with severe and steroid-resistant asthma clusters. Previously, we reported efficacy of ASHMI, a three-herb TCM asthma formula in a steroid-resistant neutrophil-dominant murine asthma model and further identified Ganoderic Acid C1 (GAC1) as a key ASHMI active compound in vitro. The objective of this study is to investigate GAC1 effect on neutrophil-dominant, steroid-resistant asthma in a murine model.
METHODS: In this study, Balb/c mice were systematically sensitized with ragweed (RW) and alum and intranasally challenged with ragweed. Unsensitized/PBS challenged mice served as normal controls. Post sensitization, mice were given 4 weeks of oral treatment with GAC1 or acute dexamethasone (Dex) treatment at 48 hours prior to challenge. Pulmonary cytokines were measured by ELISA, and lung sections were processed for histology by H&E staining. Furthermore, GAC1 effect on MUC5AC expression and on reactive oxygen species (ROS) production in human lung epithelial cell line (NCI-H292) was determined by qRT-PCR and ROS assay kit, respectively. Computational analysis was applied to select potential targets of GAC1 in steroid-resistant neutrophil-dominant asthma. Molecular docking was performed to predict binding modes between GAC1 and Dex with TNF-α.
RESULTS: The result of the study showed that chronic GAC1 treatment, significantly reduced pulmonary inflammation (P \u3c 0.01-0.001 vs Sham) and airway neutrophilia (P \u3c 0.01 vs Sham), inhibited TNF-α, IL-4 and IL-5 levels (P \u3c 0.05-0.001 vs Sham). Acute Dex treatment reduced eosinophilic inflammation and IL-4, IL-5 levels, but had no effect on neutrophilia and TNF-α production. GAC1 treated H292 cells showed decreased MUC5AC gene expression and production of ROS (P \u3c 0.001 vs stimulated/untreated cells). Molecular docking results showed binding energy of complex GAC1-TNF was -10.8 kcal/mol.
DISCUSSION: GAC1 may be a promising anti-asthma botanical drug for treatment of steroid-resistant asthma
Foxa2 Rewires Ap-1 for Transcriptional Reprogramming and Lineage Plasticity in Prostate Cancer
FOXA family proteins act as pioneer factors by remodeling compact chromatin structures. FOXA1 is crucial for the chromatin binding of the androgen receptor (AR) in both normal prostate epithelial cells and the luminal subtype of prostate cancer (PCa). Recent studies have highlighted the emergence of FOXA2 as an adaptive response to AR signaling inhibition treatments. However, the role of the FOXA1 to FOXA2 transition in regulating cancer lineage plasticity remains unclear. Our study demonstrates that FOXA2 binds to distinct classes of developmental enhancers in multiple AR-independent PCa subtypes, with its binding depending on LSD1. Moreover, we reveal that FOXA2 collaborates with JUN at chromatin and promotes transcriptional reprogramming of AP-1 in lineage-plastic cancer cells, thereby facilitating cell state transitions to multiple lineages. Overall, our findings underscore the pivotal role of FOXA2 as a pan-plasticity driver that rewires AP-1 to induce the differential transcriptional reprogramming necessary for cancer cell lineage plasticity
Redo Partial Aortic Root Remodelling in Type a Dissection With an Aorto-Left Atrial Fistula
A 72-year-old male with a history of a triple-vessel coronary artery bypass graft years ago presented with a DeBakey type 2 aortic dissection and an aorto-left atrial fistula with patent bypass grafts (left internal mammary artery and saphenous vein grafts). He developed pulmonary oedema and required intubation. The right axillary artery was cannulated. After the ascending aorta and left internal mammary artery were clamped, the aorta was transected, leaving aortic tissue around two saphenous vein grafts as two separate patches. An entry tear was found adjacent to the proximal anastomosis of the saphenous vein graft to the posterior descending artery. A fistula, which was located between a false lumen in the non-coronary sinus and the dome of the left atrium, was primarily closed. Because the adventitia was thinned out in the non-coronary sinus due to aortic dissection, partial aortic root remodelling was performed with resuspension of the commissures. Hemiarch repair was performed under moderate hypothermia and unilateral antegrade cerebral perfusion. After systemic perfusion was resumed, the locations of the saphenous vein graft buttons were determined. The ascending graft was cross-clamped again; the saphenous vein graft to the obtuse marginal branch graft was reimplanted using the Carrel patch technique while a saphenous vein graft to the posterior descending artery required interposition of a 10-mm Dacron graft to accommodate the length
Stroke After Acute Type a Dissection Repair Using Right Axillary Cannulation First Approach
BACKGROUND: This study sought to analyze the details of strokes after acute type A dissection repair (ATAD) using a right axillary artery (RAX) first approach. METHODS: A total of 356 consecutive ATAD repairs from 2005 to 2022 were analyzed on the basis of arterial cannulation site. Strokes were evaluated by head computed tomography. RESULTS: The rate of RAX cannulation was 82.6% (n = 294), with a 38.2% rate of antegrade cerebral perfusion use, both of which had increased over the years. The non-RAX group had more cardiogenic shock (RAX, 16.3% vs non-RAX, 37.1%; P \u3c .001), cerebral malperfusion (8.8% vs 25.8%, respectively; P \u3c .001), and innominate artery dissection (45.9% vs 69.2%, respectively; P = .007). Eight patients died before undergoing a full neurologic assessment. The overall stroke rate was 8.4% (n = 30), and it was lower in the RAX group (5.1% vs 24.2%; P \u3c .001). All strokes were ischemic, with concomitant hemorrhagic strokes occurring in 6 patients. Strokes diagnosed immediately after surgery (perioperative stroke) accounted for 70% (n = 21 of 30) of cases. Strokes predominantly affected the right anterior circulation (right anterior, 80% vs left anterior, 46.7% vs left posterior, 26.7%; P = .013), independent of arterial cannulation site. The proposed mechanism of perioperative strokes was not uniform (embolism, 33.3%; hypoperfusion, 42.8%; embolism and hypoperfusion, 14.3%; lacunar infarct, 10%), whereas most postoperative strokes were embolic (77.8%). The mean National Institutes of Health Stroke Scale score was 20.6 ± 9.9, and the modified Rankin score at discharge was 4.1±2.2. CONCLUSIONS: Most strokes in ATAD occurred perioperatively from various mechanisms predominantly affecting the right anterior circulation irrespective of the arterial cannulation site. This complication is most likely the result of unstable hemodynamics and dissection of the innominate artery (IA) or its downstream vessels