Lymphedema pathogenesis involves antigen-driven expansion of CD4+ T cells in skin.

Introduction: Lymphedema, a progressive condition involving unresolved swelling and inflammation, affects as many as 1 in 1000 Americans. Although CD4+ T cells are implicated in the chronic inflammatory process, antigen-specific responses are understudied.

Methods: Using high-throughput sequencing, we studied the T cell receptors (TCRs) of CD4+ T cells in paired normal and lymphedema skin biopsies of 11 patients.

Inhibition of Th2 Differentiation Accelerates Chronic Wound Healing by Facilitating Lymphangiogenesis.

: Chronic wounds pose a significant healthcare burden, and there remains no effective animal model for study. We aimed to develop a mouse model of chronic wounds that remain open for at least 4 weeks and to investigate the role of the lymphatic system in wound healing. : Full-thickness excisional wounds were created on the dorsal surface of mouse tails to simulate chronic wounds.

Metformin Use and Risk of Breast Cancer-Related Lymphedema: A Retrospective Analysis.

Background: Over 30% of breast cancer patients develop lymphedema following axillary lymph node dissection (ALND), significantly impacting their quality of life. Comorbid conditions like diabetes mellitus (DM), which contribute to endothelial dysfunction and inflammation, may also affect lymphatic endothelium. Preclinical studies suggest that metformin, a common DM treatment, may reduce lymphedema risk.

Maternal and neonatal outcomes after delayed vs early cord clamping at cesarean delivery: a systematic review and meta-analysis.

Objective: This study aimed to systematically review maternal and neonatal outcomes after delayed cord clamping compared with early cord clamping at the time of cesarean delivery.

Data Sources: MEDLINE, Embase, and ClinicalTrials.gov were searched from inception through October 5, 2023.

Regulation of VEGFR3 signaling in lymphatic endothelial cells.

The receptor tyrosine kinase vascular endothelial growth factor (VEGF) receptor 3 (VEGFR3) is the principal transmembrane receptor responsible for sensing and coordinating cellular responses to environmental lymphangiogenic stimuli in lymphatic endothelial cells (LECs). VEGFC and D (VEGFC/D) function as the cognate ligands to VEGFR3 by stimulating autophosphorylation of intracellular VEGFR3 tyrosine kinase domains that activate signal cascades involved in lymphatic growth and survival. VEGFR3 primarily promotes downstream signaling through the phosphoinositide 3-kinase (PI3K) and Ras signaling cascades that promote functions including cell proliferation and migration.

Racial and Ethnic Differences in Breast Inflammation and Its Association with Lymphedema Risk After Axillary Lymph Node Dissection.

Background: Chronic inflammatory responses initiated by lymphatic injury play a key role in the pathophysiology of secondary lymphedema; however, it is unknown if these responses vary by race/ethnicity. We assessed whether baseline differences in inflammation, characterized by crown-like structures of the breast (CLS-B), contributed to lymphedema risk in a diverse cohort of patients treated with axillary lymph node dissection (ALND).

Methods: Between 11/2016-03/2020, patients undergoing ALND were enrolled in a prospective lymphedema screening study.

Role of inducible nitric oxide (iNOS) and nitrosative stress in regulating sex differences in secondary lymphedema.

Secondary lymphedema is a common complication following surgical treatment of solid tumors. Although more prevalent in women due to higher breast cancer rates, men also develop lymphedema, often with more severe manifestations. Despite these differences in clinical presentation, the cellular mechanisms underlying sex differences are poorly understood.

Impact of Treatment of Pudendal Neuralgia on Pain: A Systematic Review and Meta-Analysis.

Introduction And Hypothesis: Pudendal neuralgia is chronic pelvic pain associated with the pudendal nerve. Unfortunately, the best treatment approach is unknown. Our objective was to systematically assess interventions for pudendal neuralgia for improvement in pain.

Breast Cancer-Related Lymphedema Results in Impaired Epidermal Differentiation and Tight Junction Dysfunction.

Breast cancer-related lymphedema (BCRL) is characterized by skin changes, swelling, fibrosis, and recurrent skin infections. Clinical studies have suggested that lymphedema results in skin barrier defects; however, the underlying cellular mechanisms and the effects of bacterial contamination on skin barrier function remain unknown. In matched biopsies from patients with unilateral BCRL, we observed decreased expression of FLG and the tight junction protein ZO-1 in skin affected by moderate lymphedema or by subclinical lymphedema in which dermal backflow of lymph was identified by indocyanine green lymphography, relative to those in the controls (areas without backflow and from the unaffected arm).

Active Compared With Passive Voiding Trials After Midurethral Sling Surgery: A Systematic Review.

Objective: To compare active with passive voiding trials on the rate of passing a trial of void and discharge rates with catheter in women who have undergone midurethral sling for treatment of stress urinary incontinence (SUI).

Data Sources: MEDLINE, EMBASE, and ClinicalTrials.gov were searched through February 24, 2023.

Dysregulation of Lymphatic Endothelial VEGFR3 Signaling in Disease.

Vascular endothelial growth factor (VEGF) receptor 3 (VEGFR3), a receptor tyrosine kinase encoded by the gene, plays a significant role in the morphogenesis and maintenance of lymphatic vessels. Under both normal and pathologic conditions, VEGF-C and VEGF-D bind VEGFR3 on the surface of lymphatic endothelial cells (LECs) and induce lymphatic proliferation, migration, and survival by activating intracellular PI3K-Akt and MAPK-ERK signaling pathways. Impaired lymphatic function and VEGFR3 signaling has been linked with a myriad of commonly encountered clinical conditions.

Permanent Compared With Absorbable Suture in Apical Prolapse Surgery: A Systematic Review and Meta-analysis.

Objective: To explore how permanent compared with absorbable suture affects anatomic success in native tissue vaginal suspension (uterosacral ligament suspension and sacrospinous ligament suspension) and sacrocolpopexy with mesh.

Data Sources: MEDLINE, EMBASE, and ClinicalTrials.gov were searched through March 29, 2022.