Hypoxia in uterine fibroids: role in pathobiology and therapeutic opportunities.

Uterine fibroids are the most common tumors in females affecting up to 70% of women world-wide, yet targeted therapeutic options are limited. Oxidative stress has recently surfaced as a key driver of fibroid pathogenesis and provides insights into hypoxia-induced cell transformation, extracellular matrix pathophysiology, hypoxic cell signaling cascades, and uterine biology. Hypoxia drives fibroid tumorigenesis through (1) promoting myometrial stem cell proliferation, (2) causing DNA damage propelling transformation of stem cells to tumor initiating cells, and (3) driving excess extracellular matrix (ECM) production. Common fibroid-associated DNA mutations include MED12 mutations, HMGA2 overexpression, and Fumarate hydratase loss of function. Evidence suggests an interaction between hypoxia signaling and these mutations. Fibroid development and growth are promoted by hypoxia-triggered cell signaling via various pathways including HIF-1, TGFß, and Wnt/ß-catenin. Fibroid-associated hypoxia persists due to antioxidant imbalance, ECM accumulation, and growth beyond adequate vascular supply. Current clinically available fibroid treatments do not take advantage of hypoxia-targeting therapies. Growing pre-clinical and clinical studies identify ROS inhibitors, anti-HIF-1 agents, Wnt/ß-catenin inhibition, and TGFß cascade inhibitors as agents that may reduce fibroid development and growth through targeting hypoxia.

Common Beverage Consumption and Benign Gynecological Conditions.

The purpose of this article is to review the effects of four commonly consumed beverage types-sugar-sweetened beverages (SSBs), caffeinated beverages, green tea, and alcohol-on five common benign gynecological conditions: uterine fibroids, endometriosis, polycystic ovary syndrome (PCOS), anovulatory infertility, and primary dysmenorrhea (PD). Here we outline a plethora of research, highlighting studies that demonstrate possible associations between beverage intake and increased risk of certain gynecological conditions-such as SSBs and dysmenorrhea-as well as studies that demonstrate a possible protective effect of beverage against risk of gynecological condition-such as green tea and uterine fibroids. This review aims to help inform the diet choices of those with the aforementioned conditions and give those with uteruses autonomy over their lifestyle decisions.

Multicenter CT Image-Based Anatomic Assessment of Patients with Aortoiliac Aneurysm Undergoing Endovascular Repair with Iliac Branch Devices.

BACKGROUND: The Global Iliac Branch Study (NCT05607277) is an international, multicenter, retrospective cohort study of anatomic predictors of adverse iliac events (AIEs) in aortoiliac aneurysms treated with iliac branch devices (IBDs). METHODS: Patients with pre-IBD and post-IBD computed tomography imaging were included. We measured arterial diameters, stenosis, calcification, bifurcation angles, and tortuosity indices using a standardized, validated protocol. A composite of ipsilateral AIE was defined, a priori, as occlusion, type I or III endoleak, device constriction, or clinical event requiring reintervention. Paired t-test compared tortuosity indices and splay angles pretreatment and post-treatment for all IBDs and by device material (stainless steel and nitinol). Two-sample t-test compared anatomical changes from pretreatment to post-treatment by device material. Logistic regression assessed associations between AIE and anatomic measurements. Analysis was performed by IBD. RESULTS: We analyzed 297 patients (286 males, 11 females) with 331 IBDs (227 stainless steel, 104 nitinol). Median clinical follow-up was 3.8 years. Iliac anatomy was significantly straightened with all IBD treatment, though stainless steel IBDs had a greater reduction in total iliac artery tortuosity index and aortic splay angle compared to nitinol IBDs (absolute reduction -0.20 [-0.22 to -0.18] vs. -0.09 [-0.12 to -0.06], P < 0.0001 and -19.6° [-22.4° to -16.9°] vs. -11.2° [-15.3° to -7.0°], P = 0.001, respectively). There were 54 AIEs in 44 IBDs in 42 patients (AIE in 13.3% of IBD systems), requiring 35 reinterventions (median time to event 41 days; median time to reintervention 153 days). There were 18 endoleaks, 29 occlusions, and 5 device constrictions. There were no strong associations between anatomic measurements and AIE overall, though internal iliac diameter was inversely associated with AIE in nitinol devices (nAIE, nitinol = 8). CONCLUSIONS: Purpose-built IBDs effectively treat aortoiliac disease, including that with tortuous anatomy, with a high patency rate (91.5%) and low reintervention rate (9.1%) at 4 years. Anatomic predictors of AIE are limited.

Comparing Functional Frailty and Radiographic Sarcopenia as Predictors of Outcomes After Liver Transplant.

INTRODUCTION: Frailty and sarcopenia are associated with an increased risk of hospitalization and mortality in patients with end-stage liver disease. The ability to identify frail patients at risk of adverse outcomes could help optimize liver transplant (LT) evaluations and pre-transplant care. This study compared sarcopenia, via L3-psoas muscle index (L3-PMI), to frailty, via liver frailty index (LFI) and analyzed associated outcomes after liver transplantation (LT). METHODS: A retrospective review of consecutive LT-recipients with cross-sectional abdominal/pelvic imaging were reviewed over 5 years at a single transplant center. RESULTS: Four hundred and twenty-six patients underwent transplant during this study interval; 31% of patients were sarcopenic. Two hundred eight patients underwent LFI evaluation: 25% were frail, 59% were prefrail, and 16% were robust. Sarcopenic patients had higher LFI scores indicating greater frailty (p = 0.02). Both sarcopenia and LFI-frailty were associated with significantly higher MELD-Na scores. Length of post-LT hospital stay was increased in sarcopenic (mean 14 vs. nonsarcopenic 11 days, p = 0.02) and LFI-frail patients (mean 13 vs. 10 prefrail, 8 robust, p = 0.04). As a categorical variable, neither LFI-frailty nor sarcopenia were significantly associated with reduced survival at 1-year (robust 100%, prefrail 93.5%, frail 91.1%, p = 0.31) (nonsarcopenic 94.4%, sarcopenic 91.4%, p = 0.30). However, LFI score was significantly associated with mortality at 1-year (OR 2.133, p = 0.047). CONCLUSIONS: Radiographic sarcopenia is a suitable proxy for in-person frailty assessment as both L3-PMI and LFI capture frail patients' pre-LT. However, physical assessment with frailty better predicts 1-year mortality post-LT than the measurement of muscle mass.

Image-based assessment of aortoiliac aneurysm anatomical characteristics in patients from the global iliac branch study.

OBJECTIVE: Endovascular repair is the preferred treatment for aortoiliac aneurysm, with preservation of at least one internal iliac artery recommended. This study aimed to assess pre-endovascular repair anatomical characteristics of aortoiliac aneurysm in patients from the Global Iliac Branch Study (GIBS, NCT05607277) to enhance selection criteria for iliac branch devices (IBD) and improve long-term outcomes. METHODS: Pre-treatment CT scans of 297 GIBS patients undergoing endovascular aneurysm repair were analyzed. Measurements included total iliac artery length, common iliac artery length, tortuosity index, common iliac artery splay angle, internal iliac artery stenosis, calcification score, and diameters in the device's landing zone. Statistical tests assessed differences in anatomical measurements and IBD-mediated internal iliac artery preservation. RESULTS: Left total iliac artery length was shorter than right (6.7 mm, P = .0019); right common iliac artery less tortuous (P = .0145). Males exhibited greater tortuosity in the left total iliac artery (P = .0475) and larger diameter in left internal iliac artery's landing zone (P = .0453). Preservation was more common on right (158 unilateral, 34 bilateral) than left (105 unilateral, 34 bilateral). There were 192 right-sided and 139 left-sided IBDs, with 318 IBDs in males and 13 in females. CONCLUSION: This study provides comprehensive pre-treatment iliac anatomy analysis in patients undergoing endovascular repair with IBDs, highlighting differences between sides and sexes. These findings could refine patient selection for IBD placement, potentially enhancing outcomes in aortoiliac aneurysm treatment. However, the limited number of females in the study underscores the need for further research to generalize findings across genders.