The lymphatic system plays a crucial, yet often overlooked, role in maintaining fluid homeostasis, and its dysregulation is a key feature of heart failure (HF). Lymphatic dysregulation in patients with HF typically results from a combination of self-perpetuating congestive mechanisms, such as increased fluid filtration, decreased lymph drainage into the central venous system, impaired lymph vessel integrity, dysfunctional lymphatic valves, and dysfunctional renal lymphatic system. These pathomechanisms collectively overwhelm the lymphatic system and hinder its ability to decongest the interstitial space with subsequent manifestation and progression of clinical congestion. Targeting the lymphatic system to counteract these congestive pathomechanisms and facilitate interstitial fluid removal represents a novel pathway to treat congestion in HF. In this study, we discuss the physiological roles of the lymphatic system in fluid homeostasis and the pathophysiological alteration of these roles in HF. We also discuss innovative technologies that aim to use the lymphatic system pathway to treat congestion in HF and provide future directions related to these approaches.

Background: The thoracic duct (TD) and the cisterna chyli (CC) exhibit a high degree of variability in their topographical and morphometric properties. Materials and Methods: PubMed, Scopus, Embase, Web of Science, Cochrane Library, and Google Scholar were searched to identify all studies that included information regarding the morphometric and topographical characteristics of the TD and CC. Results: The most frequent location of the TD termination was the left venous angle, with a pooled prevalence of 45.29% (95% CI: 25.51-65.81%). Moreover, the TD terminated most commonly as a single vessel (pooled prevalence = 78.41%; 95% CI: 70.91-85.09%). However, it divides into two or more terminating branches in approximately a quarter of the cases. The pooled prevalence of the CC was found to be 55.49% (95% CI: 26.79-82.53%). Conclusions: Our meta-analysis reveals significant variability in the anatomy of the TD and CC, particularly regarding TD termination patterns. Despite the predominance of single-vessel terminations, almost a quarter of cases exhibit branching, highlighting the complexity of the anatomy of the TD. These findings demonstrate the importance of detailed anatomical knowledge for surgeons to minimize the risk of accidental injury during head and neck, as well as thoracic surgeries. Our study provides essential insights that can enhance surgical safety and efficacy, ultimately improving patient outcomes.

Lymphoscintigraphy is a nuclear medicine procedure that uses a small quantity of radioactive particles for visualizing the lymphatic system. Traditionally, the radiotracer was injected subcutaneously, but the quality of lymphatic path imaging was scarce due to high background. Intradermal radiotracer injection is considered the modern-day intralymphatic injection. We propose rest/stress intradermal lymphoscintigraphy for the diagnosis, staging and surgical planning of lymphedema. Major and minor findings were described in primary and secondary lymphedema. Based on the in-depth information of the lymphatic pathways, physiotherapists and microsurgeons can obtain important functional information in patients\' selection to treat with physical treatments and/or undergo microsurgery.

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Currently, there is unavailability of disease-modifying medication for Alzheimer\'s disease (AD), a debilitating neurological disorder. The pathogenesis of AD appears to be complex and could be influenced by the glymphatic system present in the central nervous system (CNS). Amyloid-beta (Aβ) and other metabolic wastes are eliminated from the brain interstitium by the glymphatic system, which encompasses perivascular channels and astroglial cells. Dysfunction of the glymphatic system, which could occur due to decreased aquaporin 4 (AQP4) expression, aging-related alterations in the human brain, and sleep disruptions, may contribute to the pathogenesis of AD and also accelerate the development of AD by causing a buildup of harmful proteins like Aβ. Promising approaches have been examined for reducing AD pathology, including non-pharmacological therapies that target glymphatic function, like exercise and sleep regulation. In addition, preclinical research has also demonstrated the therapeutic potential of pharmaceutical approaches targeted at augmenting AQP4-mediated glymphatic flow. To identify the precise processes driving glymphatic dysfunction in AD and to find new treatment targets, more research is required. Innovative diagnostic and treatment approaches for AD could be made possible by techniques such as dynamic contrast-enhanced MRI, which promises to evaluate glymphatic function in neurodegenerative diseases. Treatment options for AD and other neurodegenerative diseases may be improved by comprehending and utilizing the glymphatic system\'s function in preserving brain homeostasis and targeting the mechanisms involved in glymphatic functioning. This review intends to enhance the understanding of the complex link between AD and the glymphatic system and focuses on the function of AQP4 channels in promoting waste clearance and fluid exchange.

Lymphedema occurs as a result of lymphatic vessel damage or obstruction, leading to the lymphatic fluid stasis, which triggers inflammation, tissue fibrosis, and adipose tissue deposition with adipocyte hypertrophy. The treatment of lymphedema is divided into conservative and surgical approaches. Among surgical treatments, methods like lymphaticovenular anastomosis and vascularized lymph node transfer are gaining attention as they focus on restoring lymphatic flow, constituting a physiologic treatment approach. Lymphatic endothelial cells form the structure of lymphatic vessels. These cells possess button-like junctions that facilitate the influx of fluid and leukocytes. Approximately 10% of interstitial fluid is connected to venous return through lymphatic capillaries. Damage to lymphatic vessels leads to lymphatic fluid stasis, resulting in the clinical condition of lymphedema through three mechanisms: Inflammation involving CD4+ T cells as the principal contributing factor, along with the effects of immune cells on the VEGF-C/VEGFR axis, consequently resulting in abnormal lymphangiogenesis; adipocyte hypertrophy and adipose tissue deposition regulated by the interaction of CCAAT/enhancer-binding protein α and peroxisome proliferator-activated receptor-γ; and tissue fibrosis initiated by the overactivity of Th2 cells, leading to the secretion of profibrotic cytokines such as IL-4, IL-13, and the growth factor TGF-β1. Surgical treatments aimed at reconstructing the lymphatic system help facilitate lymphatic fluid drainage, but their effectiveness in treating already damaged lymphatic vessels is limited. Therefore, reviewing the pathophysiology and molecular mechanisms of lymphedema is crucial to complement surgical treatments and explore novel therapeutic approaches.

This paper studies the transport of monoclonal antibodies through skin tissue and initial lymphatics, which impacts the pharmacokinetics of monoclonal antibodies. Our model integrates a macroscale representation of the entire skin tissue with a mesoscale model that focuses on the papillary dermis layer. Our results indicate that it takes hours for the drugs to disperse from the injection site to the papillary dermis before entering the initial lymphatics. Additionally, we observe an inhomogeneous drug distribution in the interstitial space of the papillary dermis, with higher drug concentrations near initial lymphatics and lower concentrations near blood capillaries. To validate our model, we compare our numerical simulation results with experimental data, finding a good alignment. Our parametric studies on the drug molecule properties and injection parameters suggest that a higher diffusion coefficient increases the transport and uptake rate while binding slows down these processes. Furthermore, shallower injection depths lead to faster lymphatic uptake, whereas the size of the injection plume has a minor effect on the uptake rate. These findings advance our understanding of drug transport and lymphatic absorption after subcutaneous injection, offering valuable insights for optimizing drug delivery strategies and the design of biotherapeutics.

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Over the past several centuries, the integration of contemporary medical techniques and innovative technologies, like genetic sequencing, have played a pivotal role in enhancing our comprehension of congenital vascular and lymphatic disorders. Nonetheless, the uncommon and complex characteristics of these disorders, especially considering their formation during the intrauterine stage, present significant obstacles in diagnosis and treatment. Here, we review the intricacies of these congenital abnormalities, offering an in-depth examination of key diagnostic approaches, genetic factors, and therapeutic methods.

Cystic Hygroma (CH) also referred to as lymphangioma, is a cystic malformation of the lymphatic vessels that can occur anywhere in the body. Its incidence in adulthood is considered rare and its occurrence in the neck is even rarer and only a few case reports are available till date. We present a case of adult CH of the neck and the literature review of the same. A 30-year-old male presented with painless swelling in the left side of the neck of 2 years duration. Investigations showed a cystic mass on the left lower anterior part of the neck which was surgically removed in-toto with the intact capsule. The biopsy report confirmed the diagnosis. A differential diagnosis of CH should be considered when a cystic lesion is encountered in the neck of an adult, cytological and radiological evaluation is necessary for defining its location and diagnosis. Although various conservative modalities of management are available, they are employed only in certain situations, and surgical excision of CH is considered the gold standard. The chances of recurrence range from 15 to 20%.