Journals at the University of Arizona
Not a member yet
18839 research outputs found
Sort by
LYMPHOVENOUS ANASTOMOSIS FOR THE TREATMENT OF LYMPHEDEMA: A SYSTEMATIC REVIEW OF THE LITERATURE AND META-ANALYSIS
No full textLymphovenous anastomosis (LVA) hasbeen described as an effective treatment forearly stages of lymphedema (LE). The aim ofthis study was to deepen the evaluation of theeffectiveness of LVA by performing a metaanalysisto provide information about its utilityin specific anatomical sites, clinical stages,duration of lymphedema, and surgical technique.A systematic literature search usingPubMed/Medline, Google Scholar, and CochraneDatabase was performed in November2019. Only original studies in which exclusivelyLVA was performed for primary and/or secondarylymphedema in humans were eligible fordata extraction. A meta-analysis was performedon articles with a well-defined endpointand a subgroup analysis was conductedin relation to surgical technique, duration oflymphedema, stage of pathology. Forty-eightstudies, including 6 clinical trials and 42 lowriskbias observational studies were included inour meta-analysis. 1,281 subjects were includedand the majority of articles reported a pre-postanalysis. Lymphaticovenular anastomosisappears to result effectively in treatment oflymphedema with an odds ratio of 0.07 (CI:0.04, 0.13, p0.001). All subgroup metaanalyseswere statistically significant for LVAsspecifically with regard to anatomical site,clinical stage, duration of LE, or type ofmicrosurgical procedure (p0.05).Our meta-analysis confirmed the efficacyof LVAs for the treatment of lymphedema,even when subgroup analysis was performedfor clinical stage, duration of pathology, anatomicalsite of lymphedema, or type of microsurgicalprocedure. Further prospective trialswith a common clearly defined outcome measureare warranted for an unbiased evaluation
RARE PECAM1 VARIANTS IN THREE FAMILIES WITH LYMPHEDEMA
No full textPECAM1 is a member of the immunoglobulin superfamily and is expressed in monocytes, neutrophils, macrophages and other types of immune cells as well as in endothelial cells. PECAM1 function is crucial for the development and maturation of B lymphocytes. The aim of this study was to link rare PECAM1 variants found in lymphedema patients with the development of lymphatic system malformations. Using NGS, we previously tested 246 Italian lymphedema patients for variants in 29 lymphedema-associated genes and obtained 235 negative results. We then tested these patients for variants in the PECAM1 gene. We found three probands with rare variants in PECAM1. All variants were heterozygous missense variants. In Family 1, the unaffected mother and brother of the proband were found to carry the same variant as the proband. Lymphoscintigraphy was performed to determine possible lymphatic malformations and showed that in both cases a bilateral slight reduction in the speed and lymphatic clearance of the lower limbs. PECAM1 function is important for lymphatic vasculature formation. We found variants in PECAM1 that may be associated with susceptibility to lymphedema
ABNORMAL LYMPHATIC PHENOTYPE IN A CRISPR MOUSE MODEL OF THE HUMAN LYMPHEDEMA-CAUSING CONNEXIN47 R260C POINT MUTATION
No full textConnexin proteins form gap junctionscontrolling exchange of ions and small moleculesbetween cells and play an important rolein movement of lymph within lymphatic vessels.Connexin47 (CX47) is highly expressed inlymphatic endothelial cells and CX47 missensemutations, i.e., R260C, cosegregate with primarylymphedema in humans. However, studiesutilizing CX47 knockout mice have failedto demonstrate any lymphatic anomalies. Tounravel the lymphatic consequences of expressinga mutant CX47 protein, we used CRISPRtechnology to create a mouse carrying a Cx47missense mutation (Cx47R259C) equivalent tothe human CX47R260C missense mutationassociated with human primary lymphedema.Intradermal Evans Blue dye injection identifieda 2-fold increase in regional lymph nodesin homozygous Cx47R259C mice compared towildtype, particularly in the jugular region (4.8± 0.4 and 2.0 ± 0.0, respectively, p0.01).Associated lymphatic channels were increasedin Cx47R259C mice and mesenteric lymphreflux occurred in homozygous Cx47R259Cmice but not in wildtype. Contractility ofsuperficial cervical lymphatics, assessed bypressure myography, was reduced in homozygousCx47R259C mice compared to wildtype.In conclusion, our data are the first to demonstratea role for the Cx47 protein in lymphaticanatomy and function. This phenotype is similarto that found with other valve deficientmouse mutants, e.g., in Foxc2. Of significance,this study is the first to use CRISPR technologyto develop a pre-clinical model of primarylymphedema and demonstrates the importanceof distinguishing between lack of and presenceof mutant protein when developing clinicallyrelevant animal models for translation ofpre-clinical findings
SVEP1 IS IMPORTANT FOR MORPHOGENESIS OF LYMPHATIC SYSTEM: POSSIBLE IMPLICATIONS IN LYMPHEDEMA
No full textSVEP1, also known as Polydom, is alarge extracellular mosaic protein with functionsin protein interactions and adhesion.Since Svep1 knockout animals show severeedema and lymphatic system malformations, theaim of this study is to evaluate the presence ofSVEP1 variants in patients with lymphedema.We analyzed DNA from 246 lymphedemapatients for variants in known lymphedemagenes, 235 of whom tested negative and underwenta second testing for new candidate genes,including SVEP1, as reported here. We foundthree samples with rare heterozygous missensesingle-nucleotide variants in the SVEP1 gene.In one family, healthy members were found tocarry the same variants and reported somesubclinical edema. Based on our findings and areview of the literature, we propose SVEP1 as acandidate gene that should be sequenced inpatients with lymphatic malformations, with orwithout lymphedema, in order to investigateand add evidence on its possible involvement inthe development of lymphedema
COMPARISON OF PEROMETRY-BASED VOLUMETRIC ARM MEASUREMENTS AND BIOIMPEDANCE SPECTROSCOPY FOR EARLY IDENTIFICATION OF LYMPHEDEMA IN A PROSPECTIVELY-SCREENED COHORT OF BREAST CANCER PATIENTS
No full textBreast cancer-related lymphedema(BCRL) affects more than one in five womentreated for breast cancer, and women remain atlifelong risk. Screening for BCRL is recommendedby several national and internationalorganizations for women at risk of BCRL, andmultiple methods of objective screening measurementexist. The goal of this study was tocompare the use of perometry and bioimpedancespectroscopy (BIS) for early identificationof BCRL in a cohort of 138 prospectivelyscreenedpatients. At each screening visit, apatient's relative volume change (RVC) fromperometer measurements and change in L-Dexfrom baseline (ΔL-Dex) using BIS wascalculated. There was a negligible correlationbetween RVC and ΔL-Dex (r=0.195). Multiplethresholds of BCRL were examined: RVC ≥5%and ≥10% as well as and ΔL-Dex ≥6.5 and ≥10.While some patients developed an elevatedRVC and ΔL-Dex, many demonstratedelevations in only one threshold category.Moreover, the majority of patients with RVC≥5%, ΔL-Dex ≥6.5, or ΔL-Dex ≥10 regressed tonon-elevated measurements without intervention.These findings suggest a role forcombining multiple screening methods for earlyidentification of BCRL; furthermore, BCRLdiagnosis must incorporate patient symptomsand clinical evaluation with objective measurementsobtained from techniques such asperometry and bioimpedance spectroscopy
A NEW ERA OF SEEKING KNOWLEDGE FOR #LYMPHEDEMA ON SOCIAL MEDIA: A DETAILED INSTAGRAM HASHTAG ANALYSIS
No full textInstagram® is one of the most activesocial media platforms with over a billion usersworldwide. Since the importance of educationon lymphedema has been established due to thechronic nature of the disease, seeking knowledgeattracts much attention not only clinicallybut also on social platforms such as Instagram®. Our aim was to examine content byanalyzing posts tagged with hashtags on Instagram® related to lymphedema. Nine predefinedhashtags related to lymphedema were used tosearch posts uploaded to Instagram® via theApify tool. Retrieved public posts were classifiedand analyzed by four researchers for theircontent and post-type. We found that the vastmajority of sharing on Instagram® in thecontext of lymphedema and its related aspectshave relatively low scores for both relevancyand accuracy with a 77% irrelevancy rate. Thebest posts were those determined to be educational,which were found 57% relevant andcorrect. Medical professionals should considerthat disseminating true guidance and therapycarries importance for patients with lymphedemaand treatment success. The ability forpatients to reach knowledge via social mediamight also be an important aspect in relivingsuffering due to lymphedema. However, ourresults demonstrate that Instagram® might notbe a good platform for patients to discoverreliable information about lymphedema
