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Physiological Reports Jun 2023Physiological properties and function of the lymphatic system is still somewhat of a mystery. We report the current knowledge about human lymphatic vessel contractility... (Review)
Review
Physiological properties and function of the lymphatic system is still somewhat of a mystery. We report the current knowledge about human lymphatic vessel contractility and capability of adaptation. A literature search in PubMed identified studies published January 2000-September 2022. Inclusion criteria were studies investigating parameters related to contraction frequency, fluid velocity, and lymphatic pressure in vivo and ex vivo in human lymphatic vessels. The search returned 2885 papers of which 28 met the inclusion criteria. In vivo vessels revealed baseline contraction frequencies between 0.2 ± 0.2 and 1.8 ± 0.1 min , velocities between 0.008 ± 0.002 and 2.3 ± 0.3 cm/s, and pressures between 4.5 (range 0.5-9.2) and 60.3 ± 2.8 mm Hg. Gravitational forces, hyperthermia, and treatment with nifedipine caused increases in contraction frequency. Ex vivo lymphatic vessels displayed contraction frequencies between 1.2 ± 0.1 and 5.5 ± 1.2 min . Exposure to agents affecting cation and anion channels, adrenoceptors, HCN channels, and changes in diameter-tension properties all resulted in changes in functional parameters as known from the blood vascular system. We find that the lymphatic system is dynamic and adaptable. Different investigative methods yields alternating results. Systematic approaches, consensus on investigative methods, and larger studies are needed to fully understand lymphatic transport and apply this in a clinical context.
Topics: Humans; Lymphatic System; Lymphatic Vessels; Adaptation, Physiological; Acclimatization
PubMed: 37269161
DOI: 10.14814/phy2.15697 -
International Journal of Surgery... May 2023Microsurgical treatment options for lymphedema consist mainly of lymphovenous anastomosis (LVA) and vascularized lymph node transfers (VLNTs). There are no standard... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Microsurgical treatment options for lymphedema consist mainly of lymphovenous anastomosis (LVA) and vascularized lymph node transfers (VLNTs). There are no standard measurements of the effectiveness of these interventions and reported outcomes vary among studies.
METHODS
A systematic review and meta-analysis were performed based on a structured search in Embase, Medline, PubMed, Cinahl, Cochrane, and ProQuest in October 2020, with an update in February 2022. Firstly, a qualitative summary of the main reported outcomes was performed, followed by a pooled meta-analysis of the three most frequently reported outcomes using a random effects model. Randomized controlled trials, prospective cohorts, retrospective cohorts, and cross-sectional and case-control studies that documented outcomes following microsurgery in adult patients were included. Studies of other surgical treatments (liposuction, radical excision, lymphatic vessel transplantation) or without reported outcomes were excluded. The study protocol was registered on PROSPERO (International Prospective Register of Systematic Reviews) (ID: CRD42020202417). No external funding was received for this review.
RESULTS
One hundred fifty studies, including 6496 patients, were included in the systematic review. The qualitative analysis highlighted the three most frequently reported outcomes: change in circumference, change in volume, and change in the number of infectious episodes per year. The overall pooled change in excess circumference across 29 studies, including 1002 patients, was -35.6% [95% CI: -30.8 to -40.3]. The overall pooled change in excess volume across 12 studies including 587 patients was -32.7% [95% CI: -19.8 to -45.6], and the overall pooled change in the number of cutaneous infections episodes per year across 8 studies including 248 patients was -1.9 [95% CI: -1.4 to -2.3]. The vast majority of the studies included were case series and cohorts, which were intrinsically exposed to a risk of selection bias.
CONCLUSION
The currently available evidence supports LVA and vascularized lymph node transfers as effective treatments to reduce the severity of secondary lymphedema. Standardization of staging method, outcomes measurements, and reporting is paramount in future research in order to allow comparability across studies and pooling of results.
Topics: Adult; Humans; Retrospective Studies; Cross-Sectional Studies; Lymphedema; Lymphatic Vessels; Treatment Outcome; Randomized Controlled Trials as Topic
PubMed: 37057889
DOI: 10.1097/JS9.0000000000000210 -
Cureus Dec 2019It is estimated that one in every six patients undergoing solid cancer treatment will develop secondary lymphedema. We conducted a systematic review of publications... (Review)
Review
It is estimated that one in every six patients undergoing solid cancer treatment will develop secondary lymphedema. We conducted a systematic review of publications assessing the potential use of pharmacotherapy agents in lymphedema treatment. The search was conducted on PubMed and eligibility criteria excluded papers that investigated other therapies or focused on primary lymphedema. From 285 potential papers found in the literature, seven studies fulfilled the eligibility criteria. Different types of therapies were proposed, but all of them interfered with inflammation in the lymphedema tissue. Interestingly, the majority of publications were clinical, and three authors conducted randomized, placebo-controlled, double-blinded clinical studies. Promising results were observed for the oral administration of ketoprofen or selenium and topical tacrolimus. Pharmacotherapy agents were successfully described in lymphedema treatment in clinical and experimental studies. The benefits of delivering ketoprofen, selenium, or tacrolimus in lymphedema were noticed, and these therapies were easily delivered and well-tolerated.
PubMed: 31815082
DOI: 10.7759/cureus.6300 -
European Archives of... Jun 2023This systematic review aimed to provide a comprehensive overview of the validity and reliability of existing measurement instruments for quantifying head and neck... (Review)
Review
PURPOSE
This systematic review aimed to provide a comprehensive overview of the validity and reliability of existing measurement instruments for quantifying head and neck lymphedema.
METHODS
Four databases were searched on January 31st, 2022. The COnsensus-based Standards for selecting health Measurement INstruments (COSMIN) checklists were used for the risk of bias (ROB) assessment.
RESULTS
Out of 3362 unique records, eight studies examined the reliability and validity of five measurement instruments of which one patient reported outcome. The Patterson scale for internal lymphedema and the patient reported head and neck external lymphedema and fibrosis (LIDS-H&N) demonstrated validity and reliability. For external lymphedema, none of the instruments had good reliability for all measuring points.
CONCLUSION
There is a lack of sufficiently reliable and valid measurement instruments for external head and neck lymphedema. The Patterson scale and the patient reported LIDS-H&N seem reliable for clinical practice and research.
Topics: Humans; Reproducibility of Results; Neck; Head; Head and Neck Neoplasms; Lymphedema
PubMed: 36763153
DOI: 10.1007/s00405-023-07841-0 -
Journal of Magnetic Resonance Imaging :... Jun 2021Clinical examination and lymphoscintigraphy are the current standard for investigating lymphatic function. Magnetic resonance imaging (MRI) facilitates three-dimensional...
BACKGROUND
Clinical examination and lymphoscintigraphy are the current standard for investigating lymphatic function. Magnetic resonance imaging (MRI) facilitates three-dimensional (3D), nonionizing imaging of the lymphatic vasculature, including functional assessments of lymphatic flow, and may improve diagnosis and treatment planning in disease states such as lymphedema.
PURPOSE
To summarize the role of MRI as a noninvasive technique to assess lymphatic drainage and highlight areas in need of further study.
STUDY TYPE
Systematic review.
POPULATION
In October 2019, a systematic literature search (PubMed) was performed to identify articles on magnetic resonance lymphangiography (MRL).
FIELD STRENGTH/SEQUENCE
No field strength or sequence restrictions.
ASSESSMENT
Article quality assessment was conducted using a bespoke protocol, designed with heavy reliance on the National Institutes of Health quality assessment tool for case series studies and Downs and Blacks quality checklist for health care intervention studies.
STATISTICAL TESTS
The results of the original research articles are summarized.
RESULTS
From 612 identified articles, 43 articles were included and their protocols and results summarized. Field strength was 1.5 or 3.0 T in all studies, with 25/43 (58%) employing 3.0 T imaging. Most commonly, imaging of the peripheries, upper and lower limbs including the pelvis (32/43, 74%), and the trunk (10/43, 23%) is performed, including two studies covering both regions. Imaging protocols were heterogenous; however, T -weighted and contrast-enhanced T -weighted images are routinely acquired and demonstrate the lymphatic vasculature. Edema, vessel, quantity and morphology, and contrast uptake characteristics are commonly reported indicators of lymphatic dysfunction.
DATA CONCLUSION
MRL is uniquely placed to yield large field of view, qualitative and quantitative, 3D imaging of the lymphatic vasculature. Despite study heterogeneity, consensus is emerging regarding MRL protocol design. MRL has the potential to dramatically improve understanding of the lymphatics and detect disease, but further optimization, and research into the influence of study protocol differences, is required before this is fully realized.
LEVEL OF EVIDENCE
2 TECHNICAL EFFICACY: Stage 2.
Topics: Contrast Media; Humans; Lymphatic Vessels; Lymphedema; Lymphography; Magnetic Resonance Imaging; Magnetic Resonance Spectroscopy
PubMed: 33625795
DOI: 10.1002/jmri.27542 -
Cureus Mar 2024Rosacea is a common cutaneous condition caused by persistent, recurring lesions in facial skin vessels. It is a chronic skin condition with a variety of clinical... (Review)
Review
Rosacea is a common cutaneous condition caused by persistent, recurring lesions in facial skin vessels. It is a chronic skin condition with a variety of clinical symptoms and an unknown cause. Rosacea begins with the widening of capillaries and a flushed appearance. Following that, telangiectasia appears, and reddened patches persist, particularly on the cheeks and nose. Erythema persists due to repeated vasodilation and telangiectasia. In addition, skin inflammation manifests as papules, pustules, lymphedema, and fibrosis. Despite recent advances in treatment, rosacea, a chronic inflammatory relapsing central facial dermatosis, can be extremely difficult to manage. The purpose of this meta-analysis and systematic review was to evaluate the effectiveness of low-dose isotretinoin in the treatment of rosacea. Following the guidelines set forth by the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA), the researcher employed the following search terms in the EMBASE, Web of Science, PubMed, Cochrane Library, and Google Scholar databases to provide a therapeutic update relevant to clinical practice: "low dose isotretinoin," "isotretinoin and rosacea," "isotretinoin treatment of rosacea," and "effectiveness of isotretinoin in treating rosacea". The search was carried out by the researcher for articles published from February 2019 to February 2024. The articles included were all published in the English language. The overall frequency of patients with adverse events differed significantly between the groups treated with low-dose isotretinoin and the comparators (minocycline, pulsed dye laser, evening primrose oil, , doxycycline, combined dose or placebo) (0.80, 95% CI 0.73 to 0.88, p = 0.0001). Sub-group analysis indicated that there was a difference between the interventions used in the treatments all in favor of low-dose isotretinoin treatment. The results showed that the moderate group had RR: 0.76, 95% CI: 0.44-1.30, I2 = 0%; the mild group had RR: 0.94, 95% CI: 0.56-1.57, I2 = 0%; and the group with severe rosacea had RR: 0.73, 95% CI: 0.47-1.13, I2 = 0%. According to this study, rosacea can be treated effectively with low-dose isotretinoin even in patients at severe stages of the disease by using the recommended dose once a week. Further, the intervention has also been shown to have fewer side effects on the patients. Therefore, this study recommends randomized controlled trials to be done to fully investigate the best combination options for isotretinoin on mild to severe rosacea based on the fact that some of the treatments combined have shown to be effective on treatment.
PubMed: 38681262
DOI: 10.7759/cureus.57085 -
Cancers Feb 2020Analysis of quality of life (QOL) outcomes is an important aspect of lymphedema treatment since this disease can substantially impact QOL in affected individuals. There... (Review)
Review
INTRODUCTION
Analysis of quality of life (QOL) outcomes is an important aspect of lymphedema treatment since this disease can substantially impact QOL in affected individuals. There are a growing number of studies reporting patient-reported outcomes (PROMs) for patients with lymphedema. The purpose of this study was to conduct a systematic review of outcomes and utilization of PROMs following surgical treatment of lymphedema.
METHODS
A literature search of four databases was performed up to and including March, 2019. Studies included reported on QOL outcomes after physiologic procedures, defined as either lymphovenous bypass (LVB) or vascularized lymph node transplant (VLNT), to treat upper and/or lower extremity primary or secondary lymphedema.
RESULTS
In total, 850 studies were screened-of which, 32 studies were included in this review. Lymphovenous bypass was the surgical intervention in 16 studies, VLNT in 11 studies, and both in 5 studies. Of the 32 total studies, 16 used validated survey tools. The most commonly used PROM was the lymph quality of life measure for limb lymphedema (LYMQOL) (12 studies). In the remaining four studies, the upper limb lymphedema 27 scale (ULL27), the short form 36 questionnaire (SF-36), the lymphedema functioning, disability and health questionnaire (Lymph-ICF), and lymphedema life impact scale (LLIS) were each used once. QOL improvement following surgical treatment was noted in all studies.
CONCLUSIONS
Physiologic surgical treatment of lymphedema results in improved QOL outcomes in most patients. The use of validated PROM tools is increasing but there is no current consensus on use. Future research to evaluate the psychometric properties of PROMs in lymphedema is needed to guide the development and use of lymphedema-specific tools.
PubMed: 32121343
DOI: 10.3390/cancers12030565 -
Journal of Clinical and Translational... Jun 2022Lymph node transfer surgery (LNTS) is indicated in secondary lymphedema (LE) patients who do not respond to conservative therapy. Animal models are the spearhead of LE... (Review)
Review
BACKGROUND AND AIM
Lymph node transfer surgery (LNTS) is indicated in secondary lymphedema (LE) patients who do not respond to conservative therapy. Animal models are the spearhead of LE research and were used to pioneer most of the surgical interventions currently in practice. We conducted a systematic review of the literature to explore animal models dedicated to LNTS to compare different species, techniques, and outcomes.
METHODS
Four databases were searched: PubMed, Cumulative Index of Nursing and Allied Health Literature, Scopus, and Web of Science. We used the Preferred Reporting Items for Systematic Reviews and Meta-Analysis as our basis of organization.
RESULTS
Avascular lymph node graft (ALNG) and vascularized lymph node transfer (VLNT) effectively treated LE and lead to better outcomes than controls. Whole ALNGs are superior to fragmented ALNGs. Larger fragments are more likely to be reintegrated into the lymphatic system than small fragments. VLNT was superior to whole and fragmented ALNG. Increasing the number of VLNT resulted in better outcomes. Adipose-derived stem cells improved outcomes of VLNT; vascular endothelial growth factor C and D and platelet-rich plasma improved outcomes for ALNG. Cryopreservation of lymph nodes (LNs) did not affect outcomes for ALNG. The critical ischemia and venous occlusion time for LN flaps were 4-5 and 4 h, respectively. The critical time for reperfusion injury was 2 h. Some of the novel models included venous LNT, and cervical adipocutaneous flap to groin.
CONCLUSION
Current evidence from animals favors VLNT over other surgical interventions. Several pharmacological therapies significantly improved outcomes of ALNG and VLNT.
RELEVANCE TO PATIENTS
LE is a chronic condition affecting millions of patients worldwide. LNTS is becoming more popular as a LE treatment. Animal models have led the LE research for decades and developing new models for LE are essential for LE research. This systematic review aims to summarize the existing animal models dedicated to LNTS. We believe that this review is critical to guide researchers in the selection of the model that is best fit for their hypothesis-driven experiments.
PubMed: 35813893
DOI: No ID Found -
Advances in Wound Care Aug 2022Secondary lymphedema is a debilitating disease caused by lymphatic dysfunction characterized by chronic swelling, dysregulated inflammation, disfigurement, and... (Review)
Review
Secondary lymphedema is a debilitating disease caused by lymphatic dysfunction characterized by chronic swelling, dysregulated inflammation, disfigurement, and compromised wound healing. Since there is no effective cure, animal model systems that support basic science research into the mechanisms of secondary lymphedema are critical to advancing the field. Over the last decade, lymphatic research has led to the improvement of existing animal lymphedema models and the establishment of new models. Although an ideal model does not exist, it is important to consider the strengths and limitations of currently available options. In a systematic review adhering to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, we present recent developments in the field of animal lymphedema models and provide a concise comparison of ease, cost, reliability, and clinical translatability. The incidence of secondary lymphedema is increasing, and there is no gold standard of treatment or cure for secondary lymphedema. As we iterate and create animal models that more closely characterize human lymphedema, we can achieve a deeper understanding of the pathophysiology and potentially develop effective therapeutics for patients.
Topics: Animals; Disease Models, Animal; Humans; Lymphatic System; Lymphatic Vessels; Lymphedema; Reproducibility of Results
PubMed: 34128396
DOI: 10.1089/wound.2021.0033 -
Stem Cell Research & Therapy Nov 2021Lymphedema, the accumulation of interstitial fluid caused by poor lymphatic drainage, is a progressive and permanent disease with no curative treatment. Several studies... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Lymphedema, the accumulation of interstitial fluid caused by poor lymphatic drainage, is a progressive and permanent disease with no curative treatment. Several studies have evaluated cell-based therapies in secondary lymphedema, but no meta-analysis has been performed to assess their efficacy.
METHODS
We conducted a systematic review and meta-analysis of all available preclinical and clinical studies, with assessment of their quality and risk of bias.
RESULTS
A total of 20 articles using diverse cell types were selected for analysis, including six clinical trials and 14 pre-clinical studies in three species. The meta-analysis showed a positive effect of cell-based therapies on relevant disease outcomes (quantification of edema, density of lymphatic capillaries, evaluation of the lymphatic flow, and tissue fibrosis). No significant publication bias was observed.
CONCLUSION
Cell-based therapies have the potential to improve secondary lymphedema. The underlying mechanisms remain unclear. Due to relevant heterogeneity between studies, further randomized controlled and blinded studies are required to substantiate the use of these novel therapies in clinical practice.
Topics: Cell- and Tissue-Based Therapy; Humans; Lymphedema
PubMed: 34801084
DOI: 10.1186/s13287-021-02632-y