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We formulate a compartmental model of the murine lymphatic system with the transfer rate parameters derived from the data on the geometric characteristics of the lymphatic system (LS) graph structure and the Hagen–Poiseuille-based values of the lymph flows through the system components, i.e., vertices and edges. It is supplemented by the physics-based model of lymph node draining-related function which considers a paradigmatic view of its geometry with one- and three-afferent lymphatic vessels and one efferent vessel, and the lymph flow described by the Darcy–Starling equations. We discuss further modelling work needed to gain a predictive understanding of the LS function in response to various perturbations including infections and therapeutic treatments. [ABSTRACT FROM AUTHOR]

Background While substantial anatomical study has been pursued throughout the human body, anatomical study of the human lymphatic system remains in its infancy. For microsurgeons specializing in lymphatic surgery, a better command of lymphatic anatomy is needed to further our ability to offer surgical interventions with precision. In an effort to facilitate the dissemination and advancement of human lymphatic anatomy knowledge, our teams worked together to create a map. The aim of this paper is to present our experience in mapping the anatomy of the human lymphatic system. Methods Three steps were followed to develop a modern map of the human lymphatic system: (1) identifying our source material, which was "Anatomy of the human lymphatic system," published by Rouvière and Tobias (1938), (2) choosing a modern platform, the Miro Mind Map software, to integrate the source material, and (3) transitioning our modern platform into The Human BioMolecular Atlas Program (HuBMAP). Results The map of lymphatic anatomy based on the Rouvière textbook contained over 900 data points. Specifically, the map contained 404 channels, pathways, or trunks and 309 lymph node groups. Additionally, lymphatic drainage from 165 distinct anatomical regions were identified and integrated into the map. The map is being integrated into HuBMAP by creating a standard data format called an Anatomical Structures, Cell Types, plus Biomarkers table for the lymphatic vasculature, which is currently in the process of construction. Conclusion Through a collaborative effort, we have developed a unified and centralized source for lymphatic anatomy knowledge available to the entire scientific community. We believe this resource will ultimately advance our knowledge of human lymphatic anatomy while simultaneously highlighting gaps for future research. Advancements in lymphatic anatomy knowledge will be critical for lymphatic surgeons to further refine surgical indications and operative approaches. [ABSTRACT FROM AUTHOR]

Introduction: Botulinum toxin A (BoTA) is a neurotoxin formed by Clostridium botulinum, with a broad medical application spectrum. While the primary effect of BoTA is on the muscles, the effects of BoTA in other systems including the blood vasculature have already been examined, revealing unexpected actions. However, no studies exist to the best of our knowledge regarding the potential effects of BoTA on the lymphatic vascular system, possessing a critical role in health and disease. Isolated human lymphatic endothelial cells (LECs) were cultured in dedicated in vitro culture systems. The analysis including imaging and cell culture approaches as well as molecular biology techniques is performed to examine the LEC alterations occurring upon exposure to different concentrations of BoTA. Materials and Methods: Human LECs were cultured and expanded on collagen-coated petri dishes using endothelial basal medium and the commercial product Botox from Allergan as used for all our experiments. Harvested cells were used in various in vitro functional tests to assess the morphologic and functional properties of the BoTA-treated LECs. Gene expression analysis was performed to assess the most important lymphatic system-related genes and pathways. Results: Concentrations of 1, 5 or 10 U of BoTA did not demonstrate a significant effect regarding the proliferation and migration capacity of the LECs versus untreated controls. Interestingly, even the smallest BoTA dose was found to significantly decrease the cord-like-structure formation capacity of the seeded LECs. Gene expression analysis was used to underpin possible molecular alterations, suggesting no significant effect of BoTA in the modification of gene expression versus the starvation medium control. Conclusion: LECs appear largely unaffected to BoTA treatment, with an isolated effect on the cord-like-structure formation capacity. Further work needs to assess the effect of BoTA on the smooth-muscle-cell-covered collecting lymphatic vessels and the possible aesthetic implications of such an effect, due to edema formation. Level of Evidence V: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266. [ABSTRACT FROM AUTHOR]

The vascular and lymphatic systems are integral to maintaining skeletal homeostasis and responding to pathological conditions in bone and joint tissues. This review explores the interplay between blood vessels and lymphatic vessels in bones and joints, focusing on their roles in homeostasis, regeneration, and disease progression. Type H blood vessels, characterized by high expression of CD31 and endomucin, are crucial for coupling angiogenesis with osteogenesis, thus supporting bone homeostasis and repair. These vessels facilitate nutrient delivery and waste removal, and their dysfunction can lead to conditions such as ischemia and arthritis. Recent discoveries have highlighted the presence and significance of lymphatic vessels within bone tissue, challenging the traditional view that bones are devoid of lymphatics. Lymphatic vessels contribute to interstitial fluid regulation, immune cell trafficking, and tissue repair through lymphangiocrine signaling. The pathological alterations in these networks are closely linked to inflammatory joint diseases, emphasizing the need for further research into their co-regulatory mechanisms. This comprehensive review summarizes the current understanding of the structural and functional aspects of vascular and lymphatic networks in bone and joint tissues, their roles in homeostasis, and the implications of their dysfunction in disease. By elucidating the dynamic interactions between these systems, we aim to enhance the understanding of their contributions to skeletal health and disease, potentially informing the development of targeted therapeutic strategies. [ABSTRACT FROM AUTHOR]

Background One major barrier to HIV cure is the persistence of virus, possibly linked to an insufficient antiretroviral drug (ARV) distribution into tissues. Objectives To draw the whole-body distribution of three antiretroviral drugs—tenofovir disoproxil fumarate, emtricitabine and dolutegravir—in non-human primates (NHPs). Methods Eight uninfected NHPs received a single injection of a solution containing the three ARVs. Forty-five different tissues were sampled 24 h after injection. Results Median tissue penetration factors (TPFs) were 45.4, 5.8 and 0.5 for tenofovir, emtricitabine and dolutegravir, respectively, and were statistically different between the three ARVs. Tissues were grouped by system, because TPFs were consistent according to these groups, and ranked in order of decreasing TPFs. The digestive system was the system with the highest tissue concentrations. Next came the two main sites of elimination, the liver and the kidney, as well as the tissues of the cardiopulmonary and urinary systems. Then, it was the whole lymphatic system. The next group included the reproductive system, the adipose tissue and the skin. The last two systems were the muscle and the CNS. The intra-tissue variability was rather low with a median coefficient of variation of the concentrations around 15% and no value greater than 80%. Conclusions Overall, this study determines the first whole-body distribution in a validated NHP model. These data have important implications for future preclinical and clinical studies for the development of novel HIV therapies towards an HIV cure. [ABSTRACT FROM AUTHOR]

The glial lymphatic system is a recently discovered anatomical structure in the field of neuroscience, with functions such as regulation of interstitial fluid movement, waste removal and potentially brain immunity, playing an important role in physiology and pathology of the central nervous system. With the development of imaging technology, more and more magnetic resonance imaging (MRI) techniques have been applied to the study of the glial lymphatic system of the human brain. Currently, the commonly used imaging techniques include dynamic contrast-enhanced MRI, diffusion tensor image analysis along the perivascular space, and novel multimodal ultra-fast magnetic resonance techniques, etc. This article summarizes and reviews the application of these techniques in the brain glymphatic system, in order to provide a reference for the imaging study of the glymphatic system.

Cystic lymphangioma is a benign lymphatic malformation that primarily affects children, with rare occurrences in adults. These malformations are most commonly found in the head and neck region, though their presence in the abdominal cavity is infrequent. In this report, we present the case of 71-year-old women with a cystic lymphangioma located in the omental bursa. The rarity of this condition in adults, combined with its unusual abdominal location, highlights the unique aspects of this case. This report explores the clinical presentation, diagnostic challenges, and management strategies for these uncommon lymphatic malformations.

Purpose Assessing the severity of breast cancer-related lymphedema (BCRL) requires various clinical tools, yet no standardized methodology is available. Ultrasonography shows promise for diagnosing lymphedema and evaluating its severity. This study explored the clinical utility of ultrasonography in patients with BCRL. Methods In this retrospective cross-sectional study, patients with unilateral BCRL were examined. The analyzed data included demographics, lymphedema location, International Society of Lymphology (ISL) stage, surgical history, treatment regimens, and arm circumference. Skin, subcutis, and muscle thicknesses were assessed ultrasonographically at predetermined sites, and the percentage of excess thickness was calculated. Multivariate logistic regression analysis was employed to identify associations between ultrasonographic measurements and advanced lymphedema (ISL 2 or 3). The Lymphedema Quality of Life arm questionnaire was used to evaluate patient-reported outcomes regarding lymphedema and their correlations with ultrasonographic findings. Results Among 118 patients, 71 were classified as ISL 0-1 and 47 as ISL 2-3. Patients with advanced lymphedema were older, had higher nodal stages, underwent more axillary lymph node dissections, and had higher rates of dominant-arm lymphedema. Multivariate logistic regression revealed significant associations of greater skin thickness (adjusted odds ratio [OR], 4.634; 95% confidence interval [CI], 1.233 to 17.419), subcutis thickness (adjusted OR, 7.741; 95% CI, 1.649 to 36.347), and subcutis echogenicity (adjusted OR, 4.860; 95% CI, 1.517 to 15.566) with advanced lymphedema. Furthermore, greater skin thickness (P=0.016) and subcutis echogenicity (P=0.023) were correlated with appearance-related discomfort. Conclusion Ultrasonographic measurements were significantly associated with advanced lymphedema in BCRL. Ultrasonography represents a valuable diagnostic and severity assessment tool for lymphedema.

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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%. [ABSTRACT FROM AUTHOR]

The pre-collecting and collecting lymph vessels have smooth muscle cells, and sufficient perfusion is vital to maintain their function. Although the vasa vasorum of the collecting lymph vessels (VVCL) have been histologically investigated, little is known about their physiology. This study aimed to investigate the relationship between morphology and blood flow of the VVCL in lymphoedematous limbs. Medical records of lower extremity lymphoedema patients who underwent video capillaroscopy observation during supermicrosurgical lymphaticovenous anastomosis (LVA) surgery were reviewed. The collecting lymph vessels, dissected for LVA, were examined under video capillaroscopy (GOKO Bscan-ZD, GOKO Imaging Devices Co., Japan) with a magnification of 175x and 620x. Blood flow velocity of the VVCL was calculated by measuring the red blood cell movement using software (GOKO-VIP ver. 1.0.0.4, GOKO Imaging Devices Co., Japan). Based on the video capillaroscopy findings, the VVCL were grouped according to their morphology; the VVCL morphology types and blood flow velocity were then compared according to the lymphosclerosis severity grade. Sixty-seven lymph vessels in 20 lower extremity lymphoedema patients were evaluated, including s0 in 19 (28.4%), s1 in 34 (50.7%), s2 in 10 (14.9%), and s3 in four (6.0%) lymph vessels. The VVCLs were grouped into four types: type 1 (n = 4), type 2 (n = 37), type 3 (n = 19), and type 4 (n = 7). Blood flow velocity of the VVCL ranged 0 – 189.3 μm/sec (average 26.40 μm/sec). There were statistically significant differences in VVCL morphology (p <.001) and blood flow velocity (p <.001) according to lymphosclerotic severity. Vasa vasorum of the collecting lymph vessels could be grouped into four types with different characteristics. Morphological and physiological changes of the VVCL were related to sclerotic changes of the collecting lymph vessels. [ABSTRACT FROM AUTHOR]

Diagnosis of renal fibrosis can only be verified by kidney biopsy, but biomarkers for non-invasive evaluation remain unsatisfactory. Patients with fibrosis often have abnormalities of the lymphatic vascular system and associated immune function. We describe here a lymphatic marker as a candidate biomarker for fibrosis. After assessing and grading the fibrosis scores, testing serum soluble lymphatic vessel endothelial hyaluronan receptor1 (sLYVE1) level, and collecting clinical information, the association between sLYVE1 and renal fibrosis was analyzed. Logistic regression analysis was used to screen variables. Diagnosis models with or without sLYVE1 were built, and nomograms were plotted. Calibration curve, C-index, and DCA were performed to assess the models. A total of 298 patients were enrolled in the study, of which 199 were included in the training cohort and 99 patients in the validation cohort. Serum sLYVE1 levels markedly elevated with increasing fibrosis grade (p<0.05). ROC analysis of sLYVE1 showed an AUC of 0.791 and 0.846 with optimal cut-off value of 405.25 ng/mL and 498.55 ng/mL for the prediction of moderate-to-severe renal fibrosis (MSF) and severe renal fibrosis (SF), respectively. The diagnostic nomogram model without sLYVE1 (model 1) included traditional clinical determinants (C-index: 0.658 for MSF; 0.603 for SF). A combination of model 1 and sLYVE1 (model 2) improved predictive performance (C-index: 0.847 for MSF; 0.856 for SF). Calibration curve and DCA demonstrated a better consistency accuracy and clinical benefit of model 2 than model 1. Serum sLYVE1 may be identified as a potential biomarker of renal fibrosis. Models incorporating sLYVE1 may be beneficial for a more accurate non-invasive diagnosis of renal fibrosis. [ABSTRACT FROM AUTHOR]

IntroductionThe lymphatic system is a multifaceted regulator of tissue homeostasis and an integral part of immune responses. Previous studies had shown that subsets of lymphatic endothelial cells (LEC) express PTX3, an essential component of humoral innate immunity and tissue homeostasis.MethodsIn the present study using whole-mount imaging and image-based morphometric quantifications, Ptx3-targeted mice and in vivo functional analysis, we investigated the involvement of PTX3 in shaping and function of the lymphatic vasculature.ResultsWe found that PTX3 is localized in the extracellular matrix (ECM) surrounding human and murine lymphatic vessels (LV). In murine tissues, PTX3 was localized in the ECM close to LV terminals and sprouting. Ptx3-deficient mice showed LV abnormalities in the colon submucosa and diaphragm, including a disorganized pattern and hyperplasia of initial LV capillaries associated with altered distribution of tight junction-associated molecules. Mice with LEC-restricted PTX3 gene inactivation showed morphological and organization abnormalities similar to those observed in Ptx3-deficient animals. Ptx3-deficient mice showed defective fluid drainage from footpads and defective dendritic cell (DC) trafficking.DiscussionThus, PTX3 is strategically localized in the ECM of specialized LV, playing an essential role in their structural organization and immunological function.

Optimal management of breast cancer-related lymphoedema (BCRL), a common and debilitating complication of surgery and radiotherapy, depends on early detection, personalised risk assessment and proactive intervention. For instance, a recent review advises healthcare professionals to reframe the narrative about the daily-living skin trauma risks away from 'what to avoid' to 'what to do'. Another review recommends daily, or nearly daily, exercise at home to reduce lymphoedema severity. However, several questions await full answers. There is, for instance, no consensus regarding the most appropriate surgical technique for preventing BCRL. This feature summarises some recent papers updating healthcare professionals about BCRL. [ABSTRACT FROM AUTHOR]

The human gastrointestinal tract, boasting the most diverse microbial community, harbors approximately 100 trillion microorganisms comprising viruses, bacteria, fungi, and archaea. The profound genetic and metabolic capabilities of the gut microbiome underlie its involvement in nearly every facet of human biology, from health maintenance and development to aging and disease. Recent recognition of microbiota – gut – brain axis, referring to the bidirectional communication network between gut microbes and their host, has led to a surge in interdisciplinary research. This review begins with an overview of the current understandings regarding the influence of gut microbes on intestinal and blood-brain barrier integrity. Subsequently, we discuss the mechanisms of the microbiota – gut – brain axis, examining the role of gut microbiota-related neural transmission, metabolites, gut hormones and immunity. We propose the concept of microbiota-mediated multi-barrier modulation in the potential treatment in gastrointestinal and neurological disorders. Furthermore, the role of lymphatic network in the development and maintenance of barrier function is discussed, providing insights into lesser-known conduits of communication between the microbial ecosystem within the gut and the brain. In the final section, we conclude by describing the ongoing frontiers in understanding of the microbiota – gut – brain axis’s impact on human health and disease.

Soft tissue injuries are common in the military, generally producing simple hematomas without the need for intensive evaluation and management. In certain situations, a shearing effect between fascial planes whereby a disruption of the vasculature and lymphatic systems creates a "closed degloving injury" is more generally referred to as a Morel-Lavallée Lesion (MLL). With a consistent pool of blood, lymph, and pieces of soft tissue, an M7LL can cause significant poor cosmesis, chronic pain, and risk secondary infection if left undetected and untreated. Proper diagnosis can be made through the effective use of ultrasound and, if detected early enough, through conservative measures to include needle aspiration and compression sleeves. Prior cases describe chronic MLLs existing for extended periods of time, in some cases years, requiring operative intervention, and in some cases poor outcomes. We present two cases of active duty soldiers presenting with seemingly innocuous injuries found on closer evaluation to have MLL, treated in one case with needle aspiration and compression, in the other with operative management. [ABSTRACT FROM AUTHOR]

This chronic condition is potentially distressing for patients. Margaret Perry explains what nurses working in primary care need to know about diagnosis and management of this condition. Lymphoedema is a long-term chronic disease which can have a devastating effect on the affected persons quality of life. The condition can be classified as primary or secondary, the latter being the commonest type. This article will therefore focus on secondary lymphoedema and will look at causes, diagnosis, treatment and complications, with the hope that the information given will give nurses and non-medical prescribers more confidence in assessing patients presenting with symptoms of this unpleasant disease. [ABSTRACT FROM AUTHOR]

The primary objective of the review is to assess the potential of lymphatic-targeted drug delivery systems, with a particular emphasis on their role in tumour therapy and vaccination efficacy. The lymphatic system's crucial functions in maintaining bodily equilibrium, regulating metabolism, and orchestrating immune responses make it an ideal target for drug delivery. Lymph nodes, being primary sites for tumour metastasis, underscore the importance of targeting the lymphatic system for effective treatment. Nanotechnologies and innovative biomaterials have facilitated the development of lymphatic-targeted drug carriers, leveraging endogenous macromolecules to enhance drug delivery efficiency. Various systems such as liposomes, micelles, inorganic nanomaterials, hydrogels, and nano-capsules demonstrate significant potential for delivering drugs to the lymphatic system. Understanding the physiological functions of the lymphatic system and its involvement in diseases underscores the promise of targeted drug delivery in improving treatment outcomes. The strategic targeting of the lymphatic system presents opportunities to enhance patient prognosis and advance therapeutic interventions across various medical contexts, indicating the importance of ongoing research and development in this area. [ABSTRACT FROM AUTHOR]

Lymphedema is a chronic and progressive disease of the lymphatic system characterized by inflammation, increased adipose deposition, and tissue fibrosis. Despite early hypotheses identifying lymphedema as a disease of mechanical lymphatic disruption alone, the progressive inflammatory nature underlying this condition is now well-established. In this review, we provide an overview of the various inflammatory mechanisms that characterize lymphedema development and progression. These mechanisms contribute to the acute and chronic phases of lymphedema, which manifest clinically as inflammation, fibrosis, and adiposity. Furthermore, we highlight the interplay between current therapeutic modalities and the underlying inflammatory microenvironment, as well as opportunities for future therapeutic development. [ABSTRACT FROM AUTHOR]

Vascular cognitive impairment and dementia (VCID) represents a broad spectrum of cognitive decline secondary to cerebral vascular aging and injury. It is the second most common type of dementia, and the prevalence continues to increase. Nuclear factor erythroid 2-related factor 2 (NRF2) is enriched in the cerebral vasculature and has diverse roles in metabolic balance, mitochondrial stabilization, redox balance, and anti-inflammation. In this review, we first briefly introduce cerebrovascular aging in VCID and the NRF2 pathway. We then extensively discuss the effects of NRF2 activation in cerebrovascular components such as endothelial cells, vascular smooth muscle cells, pericytes, and perivascular macrophages. Finally, we summarize the clinical potential of NRF2 activators in VCID. [ABSTRACT FROM AUTHOR]

The lymphatic kidney system plays a crucial role in managing interstitial fluid removal, regulating fluid balance, and tuning immune response. It also assists in the reabsorption of proteins, electrolytes, cytokines, growth factors, and immune cells. Pathological conditions, including tissue damage, excessive interstitial fluid, high blood glucose levels, and inflammation, can initiate lymphangiogenesis—the formation of new lymphatic vessels. This process is associated with various kidney diseases, including polycystic kidney disease, hypertension, ultrafiltration challenges, and complications post-organ transplantation. Although lymphangiogenesis has beneficial effects in removing excess fluid and immune cells, it may also contribute to inflammation and fibrosis within the kidneys. In this review, we aim to discuss the biology of the lymphatic system, from its development and function to its response to disease stimuli, with an emphasis on renal pathophysiology. Furthermore, we explore how innovative treatments targeting the lymphatic system could potentially enhance the management of kidney diseases. [ABSTRACT FROM AUTHOR]

Background: In breast cancer survivors at risk for lymphedema, variation in lymphatic function and arm volume has been observed related to a bout of exercise, with potential for prediction of breast cancer-related arm lymphedema (BCRaL). This novel, exploratory study examined the acute lymphatic response to resistance exercise and later development of BCRaL in women at high risk for BCRaL. Methods: One year after participation in a cross-over trial evaluating the acute lymphatic response to upper-extremity resistance exercise (low-and heavy-load), participants were assessed for BCRaL (n ​= ​16). The response to exercise was assessed before and after (post, 24- and 72-hrs) each exercise bout as extracellular fluid (L-Dex; bioimpedance spectroscopy (BIS)), interarm volume % difference (IVD; Dual-energy x-ray absorptiometry (DXA)) and symptoms (Numeric rating scale, 0–10 (NRS)). BCRaL at follow-up was defined as presence of one objective indicator (L-Dex >10, change ≥+6.5, IVD >5%) plus one objective or subjective indicator (interarm symptom ≥1 or visual inspection). Descriptive statistics were used to compare the acute response between participants with and without BCRaL at follow-up. Results: No trends indicating a similar acute response to exercise was observed in participants who later developed BCRaL (n ​= ​5). There were no observable differences in acute lymphatic response between participants that developed BCRaL and those who did not, both at an individual and group level. Conclusions: Findings from this exploratory study showed no evidence to suggest that the acute response to resistance exercise can predict BCRaL development.

Background: Leishmaniasis, caused by the protozoan Leishmania sp., infects phagocyte cells present in lymphatic organs. This study demonstrates the influence of nanostructured lipid carrier-loaded hydroxymethylnitrofurazone (NLC-NFOH) on lymphatic uptake using a chylomicron-blocking flow model in rats. Method: Lymphatic uptake of NFOH was assessed 1 h after oral administration of dimethyl sulfoxide with NFOH or NLC-NFOH with and without cycloheximide pretreatment. Result: Dimethyl sulfoxide with NFOH and NLC-NFOH showed NFOH serum concentrations of 0.0316 and 0.0291 μg/ml, respectively. After chylomicron blocking, NFOH was not detected. Conclusion: Despite log P below 5, NFOH was successfully taken up by the lymphatic system. Long-chain fatty acids and particle size might be main factors in these findings. NLC-NFOH is a promising and convenient platform for treating leishmaniasis via oral administration. [ABSTRACT FROM AUTHOR]

Study of the lymphatic system, compared to that of the other body systems, has been historically neglected. While scientists and clinicians have, in recent decades, gained a better appreciation of the functionality of the lymphatics as well as their role in associated diseases (and consequently investigated these topics further in their experimental work), there is still much left to be understood of the lymphatic system. In this review article, we discuss the role lymphatic imaging techniques have played in this recent series of advancements and how new imaging techniques can help bolster this wave of discovery. We specifically highlight the use of lymphatic imaging techniques in understanding the fundamental anatomy and physiology of the lymphatic system; investigating the development of lymphatic vasculature (using techniques such as intravital microscopy); diagnosing, staging, and treating lymphedema and cancer; and its role in other disease states. [ABSTRACT FROM AUTHOR]

Historically, research into the lymphatic system has been overlooked due to both a lack of knowledge and limited recognition of its importance. In the last decade however, lymphatic research has gained substantial momentum and has included the development of a variety of computational models to aid understanding of this complex system. This article reviews existing computational fluid dynamic models of the lymphatics covering each structural component including the initial lymphatics, pre-collecting and collecting vessels, and lymph nodes. This is followed by a summary of limitations and gaps in existing computational models and reasons that development in this field has been hindered to date. Over the next decade, efforts to further characterize lymphatic anatomy and physiology are anticipated to provide key data to further inform and validate lymphatic fluid dynamic models. Development of more comprehensive multiscale- and multi-physics computational models has the potential to significantly enhance the understanding of lymphatic function in both health and disease. [ABSTRACT FROM AUTHOR]

Postmenopausal osteoporosis refers to a metabolic bone disease characterized by a decrease in bone mass and bone strength in postmenopausal women. It has received attention because of the gradual increase trend of its prevalence. Relevant studies have confirmed that microcirculatory disorders are closely related to bone loss and that modulation of the lymphatic system relieves microcirculatory disorders. However, the importance of the lymphatic system in the study of osteoporosis has not received sufficient attention. Based on the characteristics of postmenopausal patients with osteoporosis, which is characterized by deficiency and stasis, Professor Xiaolin Shi created a strong-bone formula, which takes into account the stasis while tonifying the kidney, spleen, and liver, thus achieving the effect of benefiting Qi and tonifying the kidney, activating blood circulation, removing stasis, and warming the meridians. In this paper, we discuss the treatment of postmenopausal osteoporosis by improving lymphatic circulation with benefiting Qi and warming channel method based on the theory of deficiency and stasis, in order to provide new research ideas for the clinical treatment of postmenopausal osteoporosis. [ABSTRACT FROM AUTHOR]

The lymphatic system maintains tissue homeostasis by transporting the excess fluid from the interstitium and ultimately returning it to the venous circulation against an adverse pressure gradient and gravitational force. The spontaneous contractions of lymphangions, the building blocks of collecting vessels, and the secondary lymphatic valves play key roles in lymph propulsion. The aim of this study was to investigate lymph propulsion in a series of three contracting lymphangions in a 3D reconstructed model segmented from micro-CT scans of the collecting lymphatics in the hind limb of mice. Computational Fluid Dynamics and Fluid–Structure Interaction were used to study the behavior of flow within the collecting vessel, as well as the behavior and deformations of the vessel wall and the poroelastic interstitium. The secondary valves were modelled as porous membranes with closed or open states depending on their permeability. A sensitivity study revealed that the parameters having the most impact on the total volume of lymph propelled by active contraction of the lymphangions were the elastic modulus of the interstitium and the permeability of the secondary valves during the open states. [ABSTRACT FROM AUTHOR]

Abstract Photoacoustic imaging (PAI) is a successful clinical imaging platform for management of cancer and other health conditions that has seen significant progress in the past decade. However, clinical translation of PAI based methods are still under scrutiny as the imaging quality and clinical information derived from PA images are not on par with other imaging methods. Hence, to improve PAI, exogenous contrast agents, in the form of nanomaterials, are being used to achieve better image with less side effects, lower accumulation, and improved target specificity. Nanomedicine has become inevitable in cancer management, as it contributes at every stage from diagnosis to therapy, surgery, and even in the postoperative care and surveillance for recurrence. Nanocontrast agents for PAI have been developed and are being explored for early and improved cancer diagnosis. The systemic stability and target specificity of the nanomaterials to render its theranostic property depends on various influencing factors such as the administration route and physico-chemical responsiveness. The recent focus in PAI is on targeting the lymphatic system and nodes for cancer diagnosis, as they play a vital role in cancer progression and metastasis. This review aims to discuss the clinical advancements of PAI using nanoparticles as exogenous contrast agents for cancer theranostics with emphasis on PAI of lymphatic system for diagnosis, cancer progression, metastasis, PAI guided tumor resection, and finally PAI guided drug delivery. Graphical Abstract

Abstract The lymphatic system maintains tissue homeostasis by transporting the excess fluid from the interstitium and ultimately returning it to the venous circulation against an adverse pressure gradient and gravitational force. The spontaneous contractions of lymphangions, the building blocks of collecting vessels, and the secondary lymphatic valves play key roles in lymph propulsion. The aim of this study was to investigate lymph propulsion in a series of three contracting lymphangions in a 3D reconstructed model segmented from micro-CT scans of the collecting lymphatics in the hind limb of mice. Computational Fluid Dynamics and Fluid–Structure Interaction were used to study the behavior of flow within the collecting vessel, as well as the behavior and deformations of the vessel wall and the poroelastic interstitium. The secondary valves were modelled as porous membranes with closed or open states depending on their permeability. A sensitivity study revealed that the parameters having the most impact on the total volume of lymph propelled by active contraction of the lymphangions were the elastic modulus of the interstitium and the permeability of the secondary valves during the open states.

Imaging of the lymphatic system has always encountered difficulties, such as high costs, timeconsuming procedures, and low-resolution images. Each method of imaging provides its own challenges. The use of high-resolution ultrasonography (HR-US) and microvascular flow imaging (MVFI) may prove to be the most effective method for visualizing the superficial lymphatic vessels. This study investigated the utilization of HR-US and MVFI in imaging inguinal lymph nodes and vessels, as well as the innovative use of an intranodal saline injection that acted as a contrast agent. This technical note aims to demonstrate that HR-US and MVFI, in combination with an intranodal saline injection, are applicable to the dynamic imaging of superficial inguinal lymph nodes and vessels.

The article is dedicated to the 400th anniversary of the birth of the outstanding French anatomist, physician and philosopher Jean Pecquet (1622–1674). Pecquet’s biography is connected with the city of Dieppe, where the future scientist was born and got his primary education, and with Paris, where he made his main discoveries in anatomy. Throughout his life, Pecquet collaborated with many prominent scientists of that time (Jacques Mentel, Louis Gayant, Jean Riolan (the Younger)), including not only physicians and anatomists, but also physicists such as Blaise Pascal, Edme Mariotte, Marin Mersenne and Evangelista Torricelli. Pecquet’s most famous discovery is the chyle cictern, or cisterna chyli. The structure was named after of the scientist – “Pecquet’s reservoir (cistern)”. But more revolutionary discovery made by Pecquet is revealing and proving the fact that the lymphatic ducts flow into the superior vena cava indirectly through the venous angles and refuting the conventional opinion on the drainage of lymph into the liver. An important help in Pecquet’s anatomical research and experiments was his passion for the physical and mathematical sciences. In collaboration with Edme Marriott, Pecquet studied the structure of the eyeball and turned out to be more foresighted, because, unlike Marriott, he correctly understood the role of the retina in the functioning of the eye as an organ of vision. Pecquet was one of William Harvey’s supporters regarding his concept of blood circulation. He introduced cutting-edge at that moment technologies into the anatomy methodology, including animal experiments in vivo, and made a fateful contribution to the progress of anatomical science.

The subject of lymphatics and cancer had been in the air for a lot of time. The Editor, Paolo Zamboni, came up at first with the idea of writing about this issue and was good enough to ask me to attempt this work after I provided him with images of mesenteric, intestinal and hepatic metastases from a young patient I treated for a malignant melanoma of the skin, in the last year of my surgical practice.

The glory of having discovered the lymphatic vessels belongs undoubtedly to the Italian Gaspare Aselli from Cremona; he established itself as an excellent anatomist and surgeon, also military, in Milan, where the first true description of the lymphatic system can really begin; later, he moved to Pavia, where in 1624 he obtained the chair of anatomy.

Little progress has been made in modern lymphatic medicine since Dr. Kinmonth first described pedal lymphangiography in the 1950s. The clinical need for an effective treatment modality for managing lymphatic leakage greatly increased only after intranodal lymphangiography, which enabled the depiction of the exact location of the leakage. This review introduces five hypotheses that have been proposed while addressing various clinical scenarios involving lymphatic leakage: (1) various embolization techniques can be used to prevent lymphatic leakage; (2) lymph node embolization can treat postoperative pelvic lymphoceles that are refractory to sclerotherapy; (3) the technical success rate of thoracic duct cannulation can be improved by using retrograde thoracic duct access as a bail-out method; (4) non-traumatic chylothorax can be managed by understanding the underlying pathophysiology; and (5) chylous ascites can be managed by understanding the underlying pathophysiology. Five retrospective observational studies, one randomized prospective clinical trial, and two case reports (letters to the editor) were published after the hypotheses were validated. We provide a new systematic approach to lymphatic intervention by describing the process of the current comprehensive research.

Photoacoustic imaging (PAI) is a successful clinical imaging platform for management of cancer and other health conditions that has seen significant progress in the past decade. However, clinical translation of PAI based methods are still under scrutiny as the imaging quality and clinical information derived from PA images are not on par with other imaging methods. Hence, to improve PAI, exogenous contrast agents, in the form of nanomaterials, are being used to achieve better image with less side effects, lower accumulation, and improved target specificity. Nanomedicine has become inevitable in cancer management, as it contributes at every stage from diagnosis to therapy, surgery, and even in the postoperative care and surveillance for recurrence. Nanocontrast agents for PAI have been developed and are being explored for early and improved cancer diagnosis. The systemic stability and target specificity of the nanomaterials to render its theranostic property depends on various influencing factors such as the administration route and physico-chemical responsiveness. The recent focus in PAI is on targeting the lymphatic system and nodes for cancer diagnosis, as they play a vital role in cancer progression and metastasis. This review aims to discuss the clinical advancements of PAI using nanoparticles as exogenous contrast agents for cancer theranostics with emphasis on PAI of lymphatic system for diagnosis, cancer progression, metastasis, PAI guided tumor resection, and finally PAI guided drug delivery. [ABSTRACT FROM AUTHOR]

Purpose: This study aimed to compare the distribution and drainage pathway of sentinel lymph nodes between high- and low-risk endometrial cancers. Methods: In total, 429 patients with endometrial cancer who underwent sentinel lymph node biopsy in Peking University People's Hospital from July 2015 to April 2022 were retrospectively enrolled. There were 148 patients in the high-risk group and 281 patients in the low-risk group. Results: The unilateral and bilateral detection rates of sentinel lymph nodes were 86.5% and 55.9%, respectively. The highest detection rate was achieved in the subgroup with a combined use of indocyanine green (ICG) and carbon nanoparticles (CNP) (94.4% for unilateral detection and 66.7% for bilateral detection). The upper paracervical pathway (UPP) was detected in 93.3% of cases in the high-risk group and 96.0% of cases in the low-risk group (p = 0.261). The lower paracervical pathway (LPP) was detected in 10.0% of cases in the high-risk group and 17.9% of cases in the low-risk group (p = 0.048). Remarkably increased detection rates of SLN in the common iliac (7.5%) and para-aortic or precaval areas (2.9%) were observed in the high-risk group. In contrast, a markedly decreased detection rate of SLN in the internal iliac area (1.9%) was observed in the high-risk group. Conclusion: The highest detection rate of SLN was observed in the subgroup with a combined use of ICG and CNP. The detection of UPP is important for both high-risk and low-risk cases, while LPP detection plays a more important role in the low-risk group. Lymphadenectomy in the common iliac and para-aortic or precaval areas is essential for patients with high-risk EC. Removal of internal iliac lymph nodes is essential for patients with low-risk EC, in case of ineffective SLN mapping. [ABSTRACT FROM AUTHOR]

Dysfunctions in the lymphatic system can cause primary or secondary lymphedema, derived from chronic edema, when the lymphatic system is unable to adequately drain lymph from the tissues, resulting in swelling and pain. Through a cross-sectional experimental clinical study, we sought to evaluate the effect of the Adapted Lymphatic Protocol of Medicinal Biomagnetism on pain in the lower limbs of patients with peripheral edema of lymphatic origin. Medicinal Biomagnetism is a therapeutic system developed in 1988 by Dr. Isaac Goiz Durán that uses static magnetic fields generated by medium intensity magnets. These magnets are applied in pairs, one with a north pole, with a calming effect, and the other with a south pole, which activates areas with organic deficiencies, known as Biomagnetic Pairs. Carried out on four female participants, the study applied the protocol in three sessions, spaced weekly. The results demonstrated a reduction in the measurements of the lower limbs, relief in the intensity of pain and discomfort in the legs, although the lymphedema did not disappear completely. It was concluded that Medicinal Biomagnetism proved to be a non-invasive, accessible approach with few side effects, with the potential to alleviate pain and improve quality of life in patients with peripheral edema of lymphatic origin. [ABSTRACT FROM AUTHOR]

The lymphatic system is an integral part of the circulatory system and plays an important role in the fluid homeostasis of the human body. Accumulating evidence has recently suggested the involvement of lymphatic dysfunction in the pathogenesis of cardio-reno-vascular (CRV) disease. However, how the sophisticated contractile machinery of lymphatic vessels is modulated and, possibly impaired in CRV disease, remains largely unknown. In particular, little attention has been paid to the effect of the renin-angiotensin-system (RAS) on lymphatics, despite the high concentration of RAS mediators that these tissue-draining vessels are exposed to and the established role of the RAS in the development of classic microvascular dysfunction and overt CRV disease. We herein review recent studies linking RAS to lymphatic function and/or plasticity and further highlight RAS-specific signaling pathways, previously shown to drive adverse arterial remodeling and CRV organ damage that have potential for direct modulation of the lymphatic system. [ABSTRACT FROM AUTHOR]

Over sixty years, laser technologies have undergone a technological revolution and become one of the main tools in biomedicine, particularly in neuroscience, neurodegenerative diseases and brain tumors. Glioblastoma is the most lethal form of brain cancer, with very limited treatment options and a poor prognosis. In this study on rats, we demonstrate that glioblastoma (GBM) growth can be suppressed by photosensitizer-free laser treatment (PS-free-LT) using a quantum-dot-based 1267 nm laser diode. This wavelength, highly absorbed by oxygen, is capable of turning triplet oxygen to singlet form. Applying 1267 nm laser irradiation for a 4 week course with a total dose of 12.7 kJ/cm2 firmly suppresses GBM growth and increases survival rate from 34% to 64%, presumably via LT-activated apoptosis, inhibition of the proliferation of tumor cells, a reduction in intracranial pressure and stimulation of the lymphatic drainage and clearing functions. PS-free-LT is a promising breakthrough technology in non- or minimally invasive therapy for superficial GBMs in infants as well as in adult patients with high photosensitivity or an allergic reaction to PSs. [ABSTRACT FROM AUTHOR]

Small extracellular vesicles (sEVs) are small, cell-derived particles with sizes of approximately 100 nm. Since these particles include cargos such as host cell-derived proteins, messenger RNAs, and micro RNAs, they serve as mediators of cell-cell communication. While the analysis of the pharmacokinetic of sEVs after the intravenous injection have been reported, the lymphatic transport of sEVs remains unclear. The objective of this study was to provide insights into the intra-lymphatic trafficking and distribution of sEVs when they are injected into an interstitial space both in normal skin tissue and in cancerous tissue. When sEVs were Subcutaneously administered into the tail base and the tumor tissue, they preferably accumulated in the lymph nodes (LNs), rather than in the liver and the spleen. The findings reported herein show that the lymphatic transport of sEVs was drastically changed in model mice, in which a surgical treatment was used to modify to allow the dominant lymphatic flow from the footpad directly to the axillary LN via the inguinal LN. Based on the results, we conclude that when sEVs are injected into the subcutis space, they are preferably delivered to the LN via the lymphatic system. Further, the extent of accumulation of sEVs in the LN after subcutaneous injection was reduced when they were preliminarily incubated with Proteinase K. These results suggest that the lymphatic drainage of sEVs in normal skin tissue is regulated by membrane proteins on their surface. This reduction, however, was not observed in the case of cancer tissue. This discrepancy can be attributed to the presence of highly permeable lymphatic vessels in the tumor tissue. Further, the major cell subtypes that captured sEVs in the LN were LN-resident medullary sinus macrophages. These collective findings indicate that the lymphatic drainage of sEVs are mediated by proteins and, that they may appear to contribute to the control of the function of immune-responsive cells in the LNs. [Display omitted] [ABSTRACT FROM AUTHOR]

Copyright of Mersin University School of Medicine Lokman Hekim Journal of History of Medicine & Folk Medicine is the property of Mersin University School of Medicine and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Chylous ascites (CA) is a rare form of ascites that results from the leakage of lipid-rich lymph into the peritoneal cavity. This usually occurs due to trauma and rupture of the lymphatics or increased peritoneal lymphatic pressure secondary to obstruction. The underlying etiologies for CA have been classified as traumatic, congenital, infectious, neoplastic, postoperative, cirrhotic or cardiogenic. Since malignancy and cirrhosis account for about two-thirds of all the cases of CA in Western countries. The diagnosis of CA is based on the distinct characteristic of the ascitic fluid which includes a milky appearance and a triglyceride level of 200 mg/dL. The management consists of identifying and treating the underlying disease process, dietary modification, and diuretics. Treatment with nutritional optimization and management of the underlying etiology are the cornerstones of therapy. When conservative measures fail, other interventions such as octreotide/somatostatin analogues, surgical ligation, embolization and transjugular intrahepatic portosystemic shunt in patients with cirrhosis can be considered.

Copyright of China Journal of Oral & Maxillofacial Surgery is the property of Shanghai Jiao Tong University, College of Stomatology and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Contractile function of the collecting lymphatic vessels depend on smooth muscle cells, one-way valves, surrounding tissues, and regulation by the autonomic nervous system. The potentially deleterious effects of the Fontan procedure and elevated central venous pressure on lymphatic function leading to life-threatening complications are described. Presented at the 2023 ISL International Congress of Lymphology, Genoa, Italy in a special symposium on central and regional lymphatic system in health and disease. [ABSTRACT FROM AUTHOR]

Despite being rarely discussed, perinephric lymphatics are involved in many pathological and benign processes. The lymphatic system in the kidneys has a harmonious dynamic with ureteral and venous outflow, which can result in pathology when this dynamic is disturbed. Although limited by the small size of lymphatics, multiple established and emerging imaging techniques are available to visualize perinephric lymphatics. Manifestations of perirenal pathology may be in the form of dilation of perirenal lymphatics, as with peripelvic cysts and lymphangiectasia. Lymphatic collections may also occur, either congenital or as a sequela of renal surgery or transplantation. The perirenal lymphatics are also intimately involved in lymphoproliferative disorders, such as lymphoma as well as the malignant spread of disease. Although these pathologic entities often have overlapping imaging features, some have distinguishing characteristics that can suggest the diagnosis when paired with the clinical history. [ABSTRACT FROM AUTHOR]

Copyright of Die Dermatologie is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Imaging of the lymphatic system has always encountered difficulties, such as high costs, timeconsuming procedures, and low-resolution images. Each method of imaging provides its own challenges. The use of high-resolution ultrasonography (HR-US) and microvascular flow imaging (MVFI) may prove to be the most effective method for visualizing the superficial lymphatic vessels. This study investigated the utilization of HR-US and MVFI in imaging inguinal lymph nodes and vessels, as well as the innovative use of an intranodal saline injection that acted as a contrast agent. This technical note aims to demonstrate that HR-US and MVFI, in combination with an intranodal saline injection, are applicable to the dynamic imaging of superficial inguinal lymph nodes and vessels. [ABSTRACT FROM AUTHOR]

Adverse ventricular remodeling after myocardial infarction (MI) is progressive ventricular dilatation associated with heart failure for weeks or months and is currently regarded as the most critical sequela of MI. It is explained by inadequate tissue repair due to dysregulated inflammation during the acute stage; however, its pathophysiology remains unclear. Tenascin-C (TNC), an original member of the matricellular protein family, is highly up-regulated in the acute stage after MI, and a high peak in its serum level predicts an increased risk of adverse ventricular remodeling in the chronic stage. Experimental TNC-deficient or -overexpressing mouse models have suggested the diverse functions of TNC, particularly its pro-inflammatory effects on macrophages. The present study investigated the roles of TNC during human myocardial repair. We initially categorized the healing process into four phases: inflammatory, granulation, fibrogenic, and scar phases. We then immunohistochemically examined human autopsy samples at the different stages after MI and performed detailed mapping of TNC in human myocardial repair with a focus on lymphangiogenesis, the role of which has recently been attracting increasing attention as a mechanism to resolve inflammation. The direct effects of TNC on human lymphatic endothelial cells were also assessed by RNA sequencing. The results obtained support the potential roles of TNC in the regulation of macrophages, sprouting angiogenesis, the recruitment of myofibroblasts, and the early formation of collagen fibrils during the inflammatory phase to the early granulation phase of human MI. Lymphangiogenesis was observed after the expression of TNC was down-regulated. In vitro results revealed that TNC modestly down-regulated genes related to nuclear division, cell division, and cell migration in lymphatic endothelial cells, suggesting its inhibitory effects on lymphatic endothelial cells. The present results indicate that TNC induces prolonged over-inflammation by suppressing lymphangiogenesis, which may be one of the mechanisms underlying adverse post-infarct remodeling. [ABSTRACT FROM AUTHOR]