Search Results (67)

Background and clinical significance: Lymphedema is a relatively common clinical manifestation in patients and has a broad differential diagnosis, the main concern being the exclusion of malignancy. However, a rare constellation of lymphedema with systemic features and no underlying malignancy is yellow nail syndrome (YNS). YNS is a lymphatic abnormality, characterized by a triad of yellow nails, primary lymphedema and respiratory manifestations. Case presentation: Here, we report a 74-year-old male patient who presented to us with massive chylous ascites, cough, yellow nails and recurrent bilateral leg edema. During the last 10 years, he had thrice undergone thoracocentesis, which revealed chylous pleural effusion, although there was no documented diagnosis of yellow nail syndrome. We pursued a thorough work-up to rule out underlying cirrhosis and malignancy (the main causes of chylous ascites). There are only few cases of yellow nail syndrome reported in the literature with chylous ascites as a manifestation of YNS. Conclusions: The co-existence of chylous ascites with the classical triad of pleural effusion, lymphedema and yellow nail changes in the same patient has to be included in the diagnostic process to differentiate this entity from liver cirrhosis and solid or hematological cancer. Full article

Background: Lymphatic malformations (LM) are rare congenital vascular anomalies caused by abnormal development and growth of lymphatic vessels. These malformations can lead to a wide range of symptoms, from mild swelling to more severe complications. Treatment options remain limited, especially for complex cases. Recent research has suggested that PIK3CA mutations play a key role in the pathogenesis of LM, potentially offering new possibilities for targeted treatment strategies. Methods: In this study, a cohort of 36 patients diagnosed with LM, Klippel-Trenaunay syndrome (KTS), and Proteus syndrome was analyzed. PIK3CA mutations were assessed in tissue samples obtained from the LM during clinically indicated procedures using digital droplet polymerase chain reaction (ddPCR), targeting five hotspots. Results: PIK3CA mutations were found in 18 patients (50%). The most frequent mutation was p.E542K (c.1624G>A), found in 19.44% of patients, followed by p.H1047R (c.3149A>G), p.E545K (c.1633G>A), and p.H1047L (c.3140A>T) each occurring in 11.11% of the cases. Mutations were more common in isolated LMs, with 63.16% of patients exhibiting PIK3CA mutations. Conclusions: PIK3CA mutations are common in LM, supporting the potential for targeted therapies like PI3K inhibitors in treating complex cases. This research highlights the importance of genetic analysis in the management of LM and offers a new therapeutic approach. Full article

Background/Objectives: Lipedema is a chronic, progressive disorder of the adipo-fascial tissue characterized by abnormal subcutaneous fat accumulation, inflammation, fibrosis, pain, and edema. Despite its considerable impact on patients’ quality of life, it remains underdiagnosed. Recent studies have suggested a potential overlap between lipedema and hypermobility spectrum disorders (HSDs), both involving connective tissue dysfunction. This work explores the shared pathophysiological features of lipedema and HSD, highlighting clinical correlations, comorbidities, and the need for integrated diagnostic and therapeutic approaches. Methods: A cross-sectional observational study was conducted through an online survey targeting individuals with lipedema and a control group with lymphedema. The questionnaire assessed symptoms typically associated with HSD, including musculoskeletal, gastrointestinal, urogynecological, vascular, and neuropsychological manifestations. Descriptive statistics were used to evaluate clinical patterns in both groups. Results: Among the lipedema patients, 44% reported joint hypermobility and 60% recalled being hypermobile during childhood. High rates of pediatric overweight (50%), low muscle tone (55%), and exercise-induced fatigue (70%) were observed. Adult symptoms included joint pain (notably in the ankles, knees, cervical spine, sacrum, and feet), digestive issues (50%), and thyroid disorders (24.4%). Compared with the control group, patients with lipedema showed significantly more connective tissue-related motor deficits and systemic symptoms. Conclusions: Connective tissue laxity may play a critical role in the pathogenesis of lipedema, contributing to multisystemic manifestations through vascular, lymphatic, gastrointestinal, and musculoskeletal involvement. The high prevalence of HSD-like features calls for a paradigm shift in the understanding of lipedema as a systemic disorder. Early identification of connective tissue alterations, especially in children with familial predisposition, could enable timely interventions, potentially mitigating disease progression. A multidisciplinary, evidence-based approach is essential for accurate diagnosis and effective management. Full article

Background/Objectives: Cystic hygroma is a congenital lymphatic malformation often identified during early pregnancy and frequently associated with chromosomal abnormalities and adverse outcomes. We aimed to appraise the genetic and clinical characteristics of fetuses diagnosed with cystic hygroma in the first/early second trimester, assess the resolution patterns in chromosomally normal cases, and provide insights into prognosis—based on data collected over a 30-year period. Methods: A retrospective cohort study was conducted on 405 consecutive fetuses diagnosed with nuchal cystic hygroma between 8.0 and 14.0 weeks of gestation from 1993 to 2023 at two tertiary care centers. Diagnoses were established using high-resolution transabdominal and transvaginal 3D/4D ultrasonography. All cases underwent prenatal cytogenetic analysis, including karyotyping. Fetuses with a normal karyotype were observed through serial ultrasounds through the remainder of the pregnancy to verify the eventual resolution of hygromas. Both descriptive and inferential statistical methods were used, with p < 0.05 as a cut-off (two-tailed). Results: Of the 405 fetuses, 210 (51.9%) had chromosomal abnormalities, most commonly trisomy 21, while 195 (48.1%) had a normal karyotype. A significantly higher frequency of trisomy 21 was observed compared to other identified chromosomal abnormalities (p < 0.001). In the chromosomally normal group, 85 (43.6%) showed spontaneous resolution of the hygroma within four weeks, and these pregnancies resulted in phenotypically normal live births. Septated hygromas were significantly more frequent in the abnormal karyotype group (71.4%). Conclusions: The finding and diagnosis of cystic hygroma in first trimester and early second-trimester pregnancy represent a strong predictor of chromosomal aneuploidy and warrant comprehensive prenatal genetic testing and close follow-up. However, in the absence of genetic abnormalities and additional malformations, spontaneous resolution is common, and neonatal outcomes are generally favorable. Health systems should provide equitable access to genetic testing and fetal imaging to support accurate diagnosis and informed decisions. Full article

Background and Clinical Significance: Papillary Fibroelastoma is a benign primary cardiac tumor, commonly located in a valvular position, predominantly on the aortic valve. Case Presentation: We present a 73-year-old male patient with a medical history of chronic lymphatic leukemia, kidney failure, diabetes, and obstructive sleep apnea. In a routinely performed echocardiogram an abnormal structure in the left ventricle was found. The patient presented completely asymptomatically at the time of examination. A cardiac magnetic resonance-scan provided further information about the size and localization of the tumor in the left ventricle, which seemed to be attached to a papillary muscle and was about 1.6 cm in diameter. Due to visible scarring of the myocardia, which was identified in the scan, a cardiac catheter examination was performed. A coronary artery disease was detected with a severe stenosis in three vessels. During an elective bypass-operation, the removal of the structure was performed with an approach through the left atrium, passing the mitral valve using a valve sizer for better exposure. The tumor of 1 cm presented macroscopically with an anemone-like shape. The histopathological examination confirmed the intraoperative assumption of a papillary fibroelastoma, found in an aberrant location. Conclusions: Unexpectedly challenging surgical removals of structures in the left ventricle require innovative techniques with available instruments for better exposure. Full article

Background/Objectives: Idiopathic normal-pressure hydrocephalus (iNPH) is a potentially reversible neurological disorder characterized by gait disturbance, cognitive impairment, and urinary incontinence. Its pathophysiology involves impaired cerebrospinal fluid (CSF) absorption, and recent research has highlighted the role of the glymphatic and meningeal lymphatic systems in this process. However, the factors that trigger the clinical manifestations of iNPH in subclinical cases remain poorly understood. Case Presentation: Herein, we report two rare cases of iNPH in which clinical symptoms only became apparent following systemic infections. An 82-year-old man presented with transient neurological deficits during a course of sepsis caused by Klebsiella pneumoniae. Neuroimaging revealed periventricular changes and mild ventricular enlargement. Shunting and a tap test led to significant improvements to both his gait and cognition. An 80-year-old man with a history of progressive gait disturbance and cognitive decline developed worsening urinary incontinence and acute cerebral infarction caused by Staphylococcus haemolyticus bacteremia. Magnetic resonance imaging revealed a ventriculomegaly with features of disproportionally enlarged subarachnoid space hydrocephalus and a corona radiata infarct. Clinical improvement was achieved after a ventriculoperitoneal shunt was placed. Conclusions: Our two present cases suggest that systemic inflammatory states may act as catalysts for the manifestation of iNPH in patients with predisposing cerebral ischemia or subclinical abnormalities in CSF flow, highlighting the need for higher clinical awareness of iNPH in older patients who present with neurological deterioration during systemic infections. Early diagnosis and timely shunting after appropriate infection control may facilitate significant functional recovery in such patients. Full article

Background: Vascular malformations (VAMs) impose multifaceted burdens extending beyond physical impairments to psychosocial dysfunction. While prior studies predominantly utilized generic quality-of-life instruments, disease-specific tools are critical for addressing heterogeneous symptom profiles and sociocultural variability, particularly in understudied Asian populations. This study investigated psychosocial impacts across pediatric and adult VAM patients via validated, condition-specific measures. Methods: A prospective cohort of 233 hospitalized VAM patients (114 pediatric patients, 119 adult patients) completed the OVAMA questionnaire, and 114 adult, 68 pediatric patients, and 115 parent-proxies completed corresponding PROMIS questionnaires. The subtypes included arteriovenous malformations (AVMs), venous/lymphatic/lymphovenous malformations (VMs/LMs/LVMs), port-wine stains (PWSs), and other vascular malformations. Statistical analyses (Mann–Whitney U test, Kruskal–Wallis test, linear regression) were used to evaluate associations between demographics, clinical characteristics, and psychosocial outcomes. Results: Compared with children, adults reported significantly greater distress related to general (p = 0.004) and appearance (p = 0.003) problems. Compared with AVM (p = 0.01) and PWS (p = 0.041) patients, VM/LM/LVM patients presented elevated general problem scores. Pain and bleeding were related to general problems, whereas temporary enlargement was related togeneral and appearance problems. The PROMIS results revealed that 42.1% of adults had below-normal psychosocial-positive scores, whereas 33% demonstrated abnormal psychosocial-negative scores. Pediatric self-reports were associated with higher anxiety and depression rates than parent proxies were, with the VM/LM/LVM subgroups reporting poorer family relationships (p = 0.0062) and life purposes (p = 0.0075). Treatment frequency was correlated with increased psychological stress in children (p = 0.007). Conclusion: VAMs significantly impair psychosocial functioning across all ages, with adults experiencing heightened distress and social role deficits. Pediatric patients with low-flow malformations (VMs/LMs/LVMs) face compound depressive symptoms and familial strain. Disease-specific tools such as OVAMA and PROMIS are essential for comprehensive assessments, guiding tailored interventions to address both physical and psychosocial burdens. Full article

Objectives: To investigate the diagnostic value of various lymphatic imaging techniques for thoracic duct (TD) outlet obstruction in patients with chylous leakage. Methods: A retrospective analysis was conducted on 23 patients with chylous leakage who were radiologically diagnosed with a TD outlet obstruction and underwent a TD exploration and reconstruction between January 2022 and February 2025. Non-enhanced magnetic resonance lymphangiography (MRL), ⁹⁹Tc^m-DX lymphoscintigraphy, and intranodal lymphangiography were employed to detect abnormalities in the central lymphatic vessels. The Receiver Operating Characteristic (ROC) curve was utilized to analyze the diagnostic performance of these imaging methods for TD outlet obstruction in lymphatic disorders. Results: Twenty-three patients (fifteen males and eight females) with chylous leakage were included in this study, with an average age of 59.78 ± 13.08 years. Non-enhanced MRL, ⁹⁹Tc^m-DX lymphoscintigraphy, and intranodal lymphangiography revealed TD outlet obstructions in 13, 17, and 18 patients, respectively. Twenty patients exhibited findings consistent with preoperative imaging during TD explorations; the intraoperative microscopic visualization demonstrated the difficulty of white chyle entering the bloodstream for these patients. The ROC curve analysis indicated that “at least two imaging modalities were positive” and had the highest Area Under the Curve (AUC) value (0.90); “intranodal lymphangiography” and “non-enhanced magnetic resonance lymphangiography” followed closely with respective AUC values of 0.76 and 0.73, and ⁹⁹Tc^m-DX lymphoscintigraphy exhibited a lower AUC value 0.63. Conclusions: The combined utilization of multimodal lymphatic imaging techniques demonstrated a high diagnostic accuracy in identifying TD outlet obstruction in patients with chylous leakage. Full article

The immune system is a vital defense network within the body, where lymph and lymph nodes play pivotal roles. Lymph is a transparent fluid containing white blood cells, specifically lymphocytes, which circulate through the lymphatic system, rapidly multiplying to fight viruses and bacteria. Lymph nodes function as filters, capturing and eliminating infections and abnormal cells found in the lymphatic fluid prior to its reentry into the circulatory system. A thorough meta-analysis of research publications in the topic is conducted utilizing Bibliometrix to comprehensively assess the current literature. The paper is centered on understanding the intricate relationship between interferons, dendritic cells, and macrophages in the lymphatic system during hepatitis virus infection. A nonlinear model for the development of the virus is used, together with the initial conditions, for a much better understanding of a hepatitis-C infection. The associated Cauchy problem is numerically solved and graphs are depicted. The interpretation of the figures explains the dynamics of interferons, dendritic cells, and macrophages as well as their interaction with other factors. By adopting an interdisciplinary approach, this study offers fresh perspectives and uncovers new research areas to better comprehend and battle hepatitis virus infections. Full article

Background/Objectives: Cardiovascular diseases (CVDs) are the leading cause of global mortality. Major adverse cardiovascular events (MACEs)—such as acute myocardial infarction, stroke, and heart failure—are critical endpoints in the clinical research. The existing research has shown metal ions are important regulators of cardiovascular functioning, and defective metal handling may be associated with an increased risk of CVD. This study examines the association of the plasma/serum levels of magnesium, copper, and zinc with MACE incidence and the prevalence of circulatory system diseases, by using electronic health records from a subset of the Scottish population. Methods: We categorised individuals by high, low, or normal plasma/serum metal levels, and calculated the percentage of those who subsequently developed a MACE, identified using related International Classification of Diseases, 10th Revision codes from hospital admission records. Logistic regression was employed to analyse the association between pre-event metal ion levels and the development of specific circulatory system disease subgroups. Results: This study found abnormal magnesium, high copper, and low zinc were associated with a higher risk of developing MACEs. Low magnesium, high copper, or low zinc were associated with increased risks of various circulatory diseases, with specific variations, like low copper increasing venous and lymphatic disease risk. Conclusions: Our findings suggest abnormal plasma metal profiles are associated with the development of MACEs and circulatory disease events, underscoring the importance of monitoring plasma metal levels for cardiovascular risk management and prevention. Full article

Tumor-associated macrophages (TAMs) are known to induce epithelial–mesenchymal transition (EMT) and angiogenesis in areas with a high density of accumulation in the submucosal (SM) layer. However, lymphatic vessels, which are important routes for lymph node metastasis, have rarely been analyzed, and their relationship to TAM accumulation is unknown. In this study, paraffin-embedded sections from 11 cases of human early-stage colorectal cancer (SM invasive carcinoma) were stained with CD34 antibody for vascular endothelium and podoplanin antibody for lymphatic endothelium at the deepest, central, and marginal sites of tumor invasion. Tumor blood vessels increased in the deepest invasive areas, and a positive correlation was observed between the number of TAMs and tumor blood vessels. Interestingly, lymphatic vessels with CD34-positive endothelial cells (CD34-positive lymphatic vessels) were observed within the tumor. The number of CD34-positive lymphatic vessels was significantly higher in the metastasis-positive group. These results suggest that abnormalities in the vascular and lymphatic systems are observed from the early stage of colorectal cancer development and that VEGF-A derived from TAMs is important for tumor angiogenesis. In addition, CD34-positive lymphatic vessels observed in the deepest areas of tumor invasion have not been reported in Japan, with initial reports indicating that they are neoplastic lymphatic vessels. Full article

Background: Lipedema is an adipose tissue disorder in women, with an abnormal fat deposition in lower limbs and occasionally upper limbs. The condition is characterized by pain, bruising, heaviness, and mobility impairment. Objectives: This study aims to evaluate the effects of a modified Complete Decongestive Therapy protocol using the Godoy Method in the postoperative period following lipedema surgery. Methods: In total, 293 participants who underwent liposuction for lipedema were studied. The postoperative physiotherapy protocol included Godoy cervical stimuli, Manual Lymphatic Drainage based on Godoy maneuvers, mechanical lymphatic drainage with RAGodoy^®, compression with bandages, skin care, and therapeutic education. Results: This study found that the number of physiotherapy sessions significantly reduced pain (p = 0.000) and other complications (p = 0.007) and increased mobility (p = 0.003). The number of physiotherapy sessions showed significant differences in pain intensity at 90 days post-treatment (p = 0.000). In total, 47.24% of the participants became functionally independent on the third day of the physiotherapy intervention (p = 0.003). A total of 40.96% of the participants developed some complications, although a relationship between inadequate compression and the occurrence of complications was also found in 36.52% of patients. Conclusions: The success of surgical treatment for lipedema not only depends on the surgery itself but also on the proper management of the patient in the perioperative period to minimize complications and prevent recurrence. The Complete Decongestive Therapy protocol modified with the Godoy Method showed effects on pain reduction, mobility increase, edema reabsorption, and prevention of complications, consequently enhancing functionality and quality of life for patients undergoing lipedema surgery. Full article

Background: Vulvar lymphangiectasia (VLA) is a rare condition characterized by the abnormal dilation of lymphatic vessels in the vulvar region, often secondary to surgery or radiation therapy for malignancies. Its clinical presentation closely resembles other dermatological conditions, posing challenges for accurate diagnosis and appropriate management. This study aims to present a rare case of VLA occurring decades after cervical carcinoma surgery, contributing to the limited literature on this condition and offering insights into its differential diagnosis and management. Methods: A 70-year-old female patient presented with multiple fluid-filled vesicles in the vulvar region appearing 36 years after undergoing radical hysterectomy with pelvic lymphadenectomy for cervical carcinoma. The lesions were biopsied, and histopathological and immunohistochemical analyses were performed to confirm the diagnosis. A review of the existing literature on VLA was conducted to contextualize this case. Results: A histopathological examination revealed papillomatous lesions with hyper-keratosis, dilated lymphatic vessels, and no signs of atypia, consistent with VLA. An immunohistochemical analysis confirmed the lymphatic nature of the lesions. Due to the patient’s comorbidities, asymptomatic presentation, and lesion stability, conservative management with regular follow-up was chosen. No progression or complications were observed during the 12-month follow-up period. Conclusions: This case highlights the importance of considering VLA in patients presenting with vulvar vesicles, especially those with a history of lymphatic disruption. An accurate diagnosis through histopathological and immunohistochemical techniques is essential to distinguish VLA from other conditions. Conservative management may be appropriate for asymptomatic cases, but tailored therapeutic strategies are needed to address symptomatic or disfiguring lesions. Full article

A 30-year-old woman presented with progressive edema and mild diarrhea. Laboratory examination revealed hypoalbuminemia. She underwent ^99mTc-antimony sulphide colloid (^99mTc-ASC) lymphoscintigraphy to evaluate potential loss of protein through gastrointestinal tract caused by lymphatic leakage and detect abnormalities in the lymphatic systems. The images showed abnormal leakage of radiotracers in the bowel, suggestive of protein loss through the gastrointestinal tract. Abnormal visualization of the lower part of thoracic duct and bilateral venous angle was also demonstrated on ^99mTc-ASC scintigraphy. It suggested secondary intestinal lymphangiectasis caused by lymphatic obstruction and reflux. Enhanced CT reconstruction of the small intestine revealed roughness and thickening of intestinal wall, consistent with the diagnosis of protein-losing enteropathy. Full article

Chronic wounds (CWs) in humans affect millions of people in the US alone, cost billions of dollars, cause much suffering, and still there are no effective treatments. Patients seek medical care when wound chronicity is already established, making it impossible to investigate factors that initiate chronicity. In this study, we used a diabetic mouse model of CWs that mimics many aspects of chronicity in humans. We performed scRNAseq to compare the cell composition and function during the first 72 h post-injury and profiled 102,737 cells into clusters of all major cell types involved in healing. We found two types of fibroblasts. Fib 1 (pro-healing) was enriched in non-CWs (NCWs) whereas Fib 2 (non-healing) was in CWs. Both showed disrupted proliferation and migration, and extracellular matrix (ECM) deposition in CWs. We identified several subtypes of keratinocytes, all of which were more abundant in NCWs, except for Channel-related keratinocytes, and showed altered migration, apoptosis, and response to oxidative stress (OS) in CWs. Vascular and lymphatic endothelial cells were both less abundant in CWs and both had impaired migration affecting the development of endothelial and lymphatic microvessels. Study of immune cells showed that neutrophils and mast cells are less abundant in CWs and that NCWs contained more proinflammatory macrophages (M1) whereas CWs were enriched in anti-inflammatory macrophages (M2). Also, several genes involved in mitochondrial function were abnormally expressed in CWs, suggesting impaired mitochondrial function and/or higher OS. Heat shock proteins needed for response to OS were downregulated in CWs, potentially leading to higher cellular damage. In conclusion, the initiation of chronicity is multifactorial and involves various cell types and cellular functions, indicating that one type of treatment will not fix all problems, unless the root cause is fundamental to the cell and molecular mechanisms of healing. We propose that such a fundamental process is high OS and its association with wound infection/biofilm. Full article