ICG lymphography is a lymphatic imaging tool that can inform lymphedema treatment, including self-management. Self-management requires patient engagement in a multimodal treatment program. However, lack of knowledge about lymphedema, challenges maintaining motivation, and lack of confidence in ability to perform self-management are barriers to engagement. This study aimed to determine if there was any change (immediate and/or delayed) to patient knowledge, motivation, confidence in lymphedema self-management, or lymphedema distress after undergoing ICG lymphography. A secondary aim was to observe health-related quality of life. A prospective observational repeated measures study followed 25 consecutive participants with limb lymphedema at three timepoints: pre; directly post; and, 12-months post ICG lymphography. A questionnaire exploring knowledge, motivation and confidence in self-management, along with lymphedema distress and a health-related quality of life tool were completed at each timepoint. Patients' knowledge about lymph-edema improved over all timepoints (p<0.001). Motivation for lymphedema self-management improvements trended toward significance directly post ICG lymphography (p=0.053), but was not maintained at 12-months. No other variables demonstrated significant change. Patients described the experience of undergoing ICG lymphography as positive and reported key learnings and changes to their self-management. ICG lymphography could be a useful tool to improve a person's knowledge of their lymphedema and may positively influence motivation to engage in self-management. Further exploration to sustaining motivation over time and potential im-pacts to lymphedema outcomes is necessary.

The primary study aim compared upper extremity (UE) functionality between breast cancer- related lymphedema (BCRL) patients and healthy controls. A secondary aim compared UE functionality based on lymphedema stage. The study included 50 women with unilateral BCRL and 50 healthy controls. UE functionality was assessed using the following measurement tools: the universal goniometer for range of motion (ROMs), digital inclinometer for proprioception, Semmes-Weinstein monofilament (SWM) test for light touch sensation, Upper Limb Functional Test (ULIFT) score for functionality and mobility, Disability of the Arm, Shoulder and Hand (DASH) for UE disability level, hand grip strength for peripheral muscle strength, and Upper Extremity Lymphedema Quality of Life questionnaire 27 (ULL-27) and Short Form 36-item Health Survey (SF-36) for quality of life (QoL). BCRL patients had reduced UE ROMs, UE functionality and mobility, hand grip strength, worse DASH score, impaired proprioception, light touch sensation and poorer quality of life compared to healthy controls (p<0.05). Significant between-group differences were detected in UE ROMs, ULIFT, DASH outcomes, proprioception, light touch sensation and physical and mental sub-scores of QoL assessments (p<0.05), while no significant differences were detected for hand grip strength, ULL-27 global score (p>0.05) according to lymphedema stage. Findings exhibited that patients with BCRL present with worse UE mobility, increased disability, loss of proprioception, impaired light touch sensation, and lower QoL compared to their healthy controls. UE functions and QoL may also vary between patients according to lymphedema severity.

Recently, increased interest has focused on the phenomenon of lymphatic contractility. The thoracic duct and other lymph vessels appear to contract spontaneously to facilitate lymph flow with rate of contractions and their amplitude variable and dependent on different factors including fluid, concentration of ions or acidity, aging, drugs, or pathology. Not every lymph vessel remains contracting continuously with some seeming to completely stop their contractions due to various reasons. This may occur with no lymph flow within the vessel, or with very high flow, or it may be due to pathology or completely physiological conditions. Numerous studies have been conducted on this topic; however, their results may some-times seem contradictory. In this review, up-to-date publications have been collected and summarized to provide insights into the challenging topic of spontaneous lymphatic contractility and factors affecting it. This area remains of high research interest and newer techniques such as sonography may help to continue to shed light on the phenomenon of lymphatic contractility.

This study assessed responsiveness of the Lymphedema Life Impact Scale (LLIS), Upper Limb Functional Index (ULFI), and Shoulder Pain and Disability Index (SPADI) instruments in patients with upper limb lymphedema undergoing complete decongestive therapy (CDT). The prospective cohort study was conducted from March 2024 to May 2025. Participants were patients with unilateral upper limb lymphedema secondary to breast cancer. All patients completed the LLIS, ULFI, and SPADI at baseline and again after 10 sessions of physiotherapy delivered over a 20-day period. Additionally, a 7-point Global Rating of Change scale (GRC) was administered as an external anchor. Paired t-tests or Wilcoxon tests were utilized to examine differences between pre- and post-intervention scores. A total of 110 patients were enrolled. The ULFI, LLIS, and SPADI demonstrated acceptable responsiveness, as indicated by an area under the curve (AUC) exceeding 0.70. Furthermore, the change scores for all three instruments exhibited strong correlations with patients' GRC scales, with Spearman correlation coefficients greater than 0.60. The results support the use of the LLIS, ULFI, and SPADI as reliable tools to monitor treatment outcomes in patients with upper limb lymphedema due to breast cancer.

Bioimpedance analysis constitutes noninvasive, low-cost intervention for early diagnosis and evaluation of breast cancer-related lymphedema (BCRL). In this study, we investigated the frequency dependence of capacitance, a marker of disease progression, in patients with BRCL. Pseudo membrane capacitance of the affected and unaffected sides of upper limbs was calculated from reactance values obtained at 5, 50, and 250 kHz. At all frequencies, pseudo membrane capacitance differed significantly between affected and unaffected limbs, with the most pronounced difference observed at 5 kHz. The Weibull analysis of the 5 kHz data demonstrated linear distributions for both limbs, with high correlation coefficients (affected: r = 0.97; unaffected: r = 0.98). The shape parameter derived from the Weibull plot indicated that pseudo membrane capacitance on the unaffected side followed a Gaussian-like distribution (α = 3.90), whereas that on the affected side was characterized by a Rayleigh distribution (α = 2.04). These distributional differences suggest distinct underlying tissue characteristics between affected and unaffected limbs. These findings indicate that capacitance measured using commonly available bioimpedance devices can differentiate affected from unaffected limbs and may provide clinically relevant information for identifying early or subclinical lymphedema prior to the development of overt clinical edema.

This study evaluated the quality and readability of responses provided by ChatGPT and Gemini to frequently asked questions related to lymphedema. Ten frequently asked questions about lymphedema were selected by expert therapists for submission to ChatGPT and Gemini. The initial responses from ChatGPT and Gemini were recorded without follow-up queries. Five independent experts (therapists) specialized in this field evaluated responses from ChatGPT and Gemini using a four-point rating scale. Readability levels were analyzed using the Flesch-Kincaid Grade Level through WordCalc software. Results indicated that except for questions 3 and 6, ChatGPT and Gemini provided similar responses, with significant differences observed in those two questions (p = 0.014). ChatGPT's answers to questions 1, 2, 3, 4, 8, 9, and 10 were found to be more readable than Gemini's, while Gemini's answers to questions 5, 6, and 7 were more readable. Overall, approximately 70% of ChatGPT's responses were found to be easier to read compared to Gemini. The results of this study indicate that both AI search engines offer comparable responses to research questions. However, when evaluating clarity and accessibility of the answers, ChatGPT was found to be more understandable and user-friendly than Gemini.

Early detection of early-stage lymphedema resulting from breast cancer treatment enables prompt intervention and can potentially slow disease progression. To support this, various methods have been developed that use quantitative criteria sensitive to excess tissue fluid, which is a hallmark of lymphedema. One such method involves measuring the dielectric constant (TDC) of arm tissue in both the at-risk and contralateral arms to calculate their ratio. This communication aims to estimate what constitutes an interarm TDC ratio likely to serve as a threshold for arm lymphedema. Data from 403 healthy women were used to calculate the ratio of the highest to the lowest forearm TDC values (β). The distribution of β was analyzed, and estimated lymphedema thresholds were calculated as the mean β plus 2.0, 2.5, and 3.0 standard deviations, producing less and more conservative thresholds. Values ranged from approximately 1.15 to 1.20, with only 0.74% of cases exceed-ing a β value of 1.20. The β values were not affected by age, which ranged from 18 to 87, or body mass index, ranging from 14.7 to 49.9 kg/m². These data represent the most comprehensive reference values available to help physicians and therapists determine appropriate thresholds.

Prox-1 (prospero homeobox protein 1) is a master control gene for lymphatic vessel development and it has been widely used as a marker to detect lymphatic vessels inside and outside the eye. We herein report a novel finding of Prox-1 expression on the astrocytes of the optic nerve, a critical structure that conveys visual information from the retina to the brain. We identified that Prox-1 expressing cells were widely distributed inside the optic nerve. These cells co-expressed both GFAP (glial fibrillary acidic protein) and AQP4 (aquaporin-4) which are typical markers for astrocytes. Interestingly, some of the Prox-1+ cells ensheath CD31+ blood vessels inside the optic nerve and these cells are part of the glymphatic system utilized for ocular fluid circulation. This study not only reveals a novel expression pattern of Prox-1 in the optic nerve but also identifies a new marker for the glymphatic system in this critical structure. Further exploration on this novel phenomenon may re-veal new mechanisms and therapeutic targets for optic nerve-related diseases that affect many patients worldwide.

Lymphovenous anastomosis (LVA) and stellate ganglion block (SGB) have been reported as effective treatments for breast cancer-related lymphedema (BCRL). However, no studies have evaluated the efficacy of ultrasound-guided SGB in patients undergoing LVA. This study aimed to assess whether adding SGB to LVA improves outcomes in BCRL patients. Thirty BCRL patients were randomly assigned to either the control (LVA only, n = 15) or SGB group (n = 15). The SGB group received ultrasound-guided SGBs at 2 days, 2 weeks, and 4 weeks postoperatively. Arm circumferences were measured at four points (5 cm and 10 cm above and below the elbow) at baseline and at 1-, 3-, and 6-months post-surgery. Treatment-related variables were also analyzed to identify potential predictors of success. Repeated-measures analysis of variance showed no significant differences in circumferential changes between groups over time, although a decreasing trend was observed within groups. However, significant reductions in circumferential differences compared with baseline were observed at several measurement sites in the SGB group. Logistic regression analysis revealed no significant predictors of treatment success. In conclusion, ultrasound-guided SGB performed postoperatively may enhance the therapeutic effect of LVA in BCRL, further reducing arm circumferential differences.

Understanding lymphatic anatomy of the upper extremity is necessary for treatment of upper extremity lymphedema (UEL). This study aimed to clarify the watershed of upper arm lymphosomes using fluorescent lymphography with multi-site injection of indocyanine green (ICG). Limbs contralateral to breast cancer treatment side of breast cancer survivors were included to evaluate upper arm lymphosomes. 0.1ml of ICG was injected intra-dermally at these 3 points in the mid-lateral upper arm: at the level of one (U1), two (U2), and three quarters (U3) from the lateral edge of the acromion to the lateral epicondyle of the humerus. Fluorescent images were obtained to determine the upper arm lymphatic pathway patterns. An injection site with multiple lymphatic pathways was evaluated as a watershed point. A total of twenty-one limbs were included. The lymphatic pathways from the U1/ U2/ U3 were anteromedial patterns in 20/13/6 (95.2%/90.5%/28.6%), and posterolateral pat-terns in 3/13/19 (14.3%/61.9%/90.5%), respectively. Both patterns were identified in 2/12/5 (9.5%/57.1%/23.8%), and no pattern in 0/1/1 (0%/4.8%/4.8%). Based on study results, the true watershed was determined as an approximate line from the posterolateral side of the lateral edge of the acromion to the anteromedial side of the lateral epicondyle of the humerus rather than a mid-arm line.

Lymphedema is a chronic, progressive impairment of the lymphatic system that can impact activities and quality of life. Research regarding conservative management of lymphedema primarily consists of complete decongestive therapy (CDT) and compression devices intended to promote lymphatic and venous return. Advanced pneumatic compression devices (APCDs) contain multiple programmable sleeves designed to mimic manual lymph drainage at home. This study aims to determine the effectiveness of APCDs in the treatment of lymphedema through the completion of a systematic review and meta-analysis. A systematic search of five databases was conducted, spanning the years 2010-2021. Only experimental designs of moderate or strong quality were chosen and final review set consists of twelve articles. APCDs are found to be effective for lymphedema treatment based on differences in pre- and post-intervention limb volumes and patient-reported outcomes. Two meta-analyses evaluated the impact of APCDs on both rates of cellulitis and manual therapy. Both analyses demonstrated significant decreases in rates after the APCD interventions. The data showed consistent reduction of limb volume and improved patient-reported outcomes, indicating that APCDs are generally effective as a complementary intervention to CDT in the maintenance phase of lymphedema treatment.

Lymphedema is a chronic inflammatory disease caused by defective lymphatic system function or development that proceeds in ab-normal fluid drainage and edema of the peripheral tissues. This retrospective study evaluates the potential role of transcription factors in the development of primary lymphedema. We analyzed 408 Italian primary lymphedema patients for pathogenic variants in genes related to the transcription factor network. Eighteen likely pathogenic genetic variants were identified in 5 genes - FOXC1, FOXC2, NOTCH1, RORC, and SOX18 - most of which have not been previously reported in the literature. Although majority of these genetic variants resulted in premature termination of the proteins, a single missense variant was identified in FOXC2 and analyzed in this study using molecular modeling approaches to evaluate its structural changes. These results suggested possible deleterious effects of the analyzed variant and supported its potential pathogenicity. Our findings provide additional evidence that associates variants in transcription factors to the onset of lymphedema and support the addition of the candidate genes FOXC1, NOTCH1, and RORC in primary lymphedema diagnostic practice.

The Ketogenic Diet (KD) is currently the most widely studied nutritional approach for patients with lipedema, although its use may cause important drawbacks especially in case of comorbidities. A Modified Mediterranean Diet (MMed) is more easily adaptable, better tolerated, and can be temporarily replaced by a ketogenic diet for a short period of time if necessary using a sort of "sandwich" approach. We report 10 clinical cases with lipedema and comorbidities subjected to a hypocaloric MMed for 6 months. All patients were properly assessed by anthropometric measurements and body composition before and at the end of nutritional treatment. Only 2 patients needed a short period of KD due to poor response to MMed. At the end of 6-month follow-up, patients showed weight loss with reduction in body circumferences and improvement in body composition. In the two cases where it was necessary to resort to a period of KD, good results were achieved allowing a return to the MMed for the maintenance. In patients suffering from lipedema with associated comorbidities and concomitant pharmacological treatments, the use of MMed as first line treatment allows achievement of better metabolic balance, greater compliance, and improved body composition.

This study explored differences in morphology and distribution of myocardial lymphatic drainage ducts in patients with dilated cardiomyopathy (DCM), ischemic cardiomyopathy (ICM), and hypertrophic cardiomyopathy (HCM) in end-stage heart failure to reveal the relationship between the morphological distribution characteristics of myocardial lymphatic drainage ducts and different etiologies and these disease courses. Hearts of 24 patients (transplant recipients) who underwent heart transplantation and 1 normal heart were collected. Myocardial tissue from the anterior wall of the ventricle was taken and quickly frozen. Immunohistochemical and Western blotting techniques were used to detect the expression of LYVE-1, Podoplanin, and VEGFR-3 in cardiac tissue. Ink injection, immunohistochemical staining, and immunofluorescence double labeling techniques were used to detect the co-localization of three antibodies in hu-man heart tissue. Masson staining was used to observe the distribution and content of collagen fibers in the heart tissue of transplant recipients. Compared with the normal group, expression levels of LYVE-1 (p<0.05) and VEGFR-3 (p<0.001) in the DCM group were significantly increased. Expression level of LYVE-1 (p<0.05) was significantly increased in the ICM and HCM groups, but there was no significant change in the expression level of VEGFR-3. The expression level of Podoplanin in the normal group was higher than that in the heart failure groups, but the protein ex-pression results were the opposite. The expression levels of LYVE-1 and VEGFR-3 in the DCM and ICM groups showed an increasing trend with the progression of the disease, while the expression levels of Podoplanin showed a decreasing trend. The immunofluorescence results showed that on larger lymphatic vessels, LYVE-1 and VEGFR-3 were expressed on the inner side of the lymphatic lumen, while Podoplanin was expressed on the outer side, and there was co-localization between the two layers. Masson's staining results showed that the degree of myocardial fibrosis in the DCM group (p<0.01) and HCM group (p<0.001) increased, while there was no significant change in the ICM group (p<0.05). Positive expression intensity of LYVE-1, Podoplanin, and VEGFR-3 does not have a consistent quantitative relationship with different types of heart failure and the duration of the disease. The expression of three biomarkers confirms that DCM, ICM, and HCM have increased lymphatic vessel architecture compared to normal hearts, and the number of lymphatic vessels increases with prolongation of disease course.

Kikuchi-Fujimoto disease (KFD) shares similar clinical manifestations and ultrasonic features with non-specific reactive lymphadenopathy (NSRL). This study aims to elucidate the independent predictors distinguishing these two diseases. A total of 136 lymph nodes (136 patients) with pathologically proven KFD from January 2015 to December 2019 were included. The control group comprised 117 NSRL lymph nodes (117 patients). Clinical information and imaging features were collected and analyzed. The main complaints of KFD were fever (84.6%). The patients with KFD and immune system diseases were older and had longer duration of symptoms. No significant differences (p< 0.05) were observed in sex, white blood cell count, short and long axis, shape, and margin. A binary logistic regression analysis revealed that the independent diagnostic factors were patient age (odds ratio [OR]=3.120, p=0.008), fever or pain (OR=0.100, p=0.038), failure of empirical antibiotic or antiviral therapy (OR= 305.88, p<0.001), vascular pattern (OR=0.049, p=0.042), CRP (OR=2.679, p=0.035), laterality (OR=0.352, p=0.020), and loose conglomeration (OR=3.605, p=0.019). The combined diagnosis effectiveness was 88.9%. Fever/pain, age range of 20-32 years, increased CRP, ineffective empirical treatment, loose conglomeration, unilateral, and non-abnormal vascular pattern were independent predictors.