RESUMEN
Developmental and functional defects in the lymphatic system are responsible for primary lymphoedema (PL). PL is a chronic debilitating disease caused by increased accumulation of interstitial fluid, predisposing to inflammation, infections and fibrosis. There is no cure, only symptomatic treatment is available. Thirty-two genes or loci have been linked to PL, and another 22 are suggested, including Hepatocyte Growth Factor (HGF). We searched for HGF variants in 770 index patients from the Brussels PL cohort. We identified ten variants predicted to cause HGF loss-of-function (six nonsense, two frameshifts, and two splice-site changes; 1.3% of our cohort), and 14 missense variants predicted to be pathogenic in 17 families (2.21%). We studied co-segregation within families, mRNA stability for non-sense variants, and in vitro functional effects of the missense variants. Analyses of the mRNA of patient cells revealed degradation of the nonsense mutant allele. Reduced protein secretion was detected for nine of the 14 missense variants expressed in COS-7 cells. Stimulation of lymphatic endothelial cells with these 14 HGF variant proteins resulted in decreased activation of the downstream targets AKT and ERK1/2 for three of them. Clinically, HGF-associated PL was diverse, but predominantly bilateral in the lower limbs with onset varying from early childhood to adulthood. Finally, aggregation study in a second independent cohort underscored that rare likely pathogenic variants in HGF explain about 2% of PL. Therefore, HGF signalling seems crucial for lymphatic development and/or maintenance in human beings and HGF should be included in diagnostic genetic screens for PL.
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Factor de Crecimiento de Hepatocito , Linfedema , Humanos , Factor de Crecimiento de Hepatocito/genética , Factor de Crecimiento de Hepatocito/metabolismo , Masculino , Femenino , Niño , Adulto , Linfedema/genética , Linfedema/patología , Adolescente , Persona de Mediana Edad , Animales , Mutación Missense/genética , Mutación con Pérdida de Función , Edad de Inicio , Preescolar , Células COS , Chlorocebus aethiops , Células Endoteliales/metabolismo , Células Endoteliales/patología , Adulto JovenRESUMEN
BACKGROUND: Primary lymphoedema (PL) syndromes are increasingly recognised as presentations of complex genetic disease, with at least 20 identified causative genes. Recognition of clinical patterns is key to diagnosis, research and therapeutics. The defining criteria for one such clinical syndrome, 'WILD syndrome' (Warts, Immunodeficiency, Lymphoedema and anogenital Dysplasia), have previously depended on a single case report. METHODS AND RESULTS: We present 21 patients (including the first described case) with similar clinical and immunological phenotypes. All had PL affecting multiple segments, with systemic involvement (intestinal lymphangiectasia/pleural or pericardial effusions) in 70% (n=14/20). Most (n=20, 95%) had a distinctive cutaneous lymphovascular malformation on the upper anterior chest wall. Some (n=10, 48%) also had hyperpigmented lesions resembling epidermal naevi (but probably lymphatic in origin). Warts were common (n=17, 81%) and often refractory. In contrast to the previous case report, anogenital dysplasia was uncommon-only found in two further cases (total n=3, 14%). Low CD4 counts and CD4:CD8 ratios typified the syndrome (17 of 19, 89%), but monocyte counts were universally normal, unlike GATA2 deficiency. CONCLUSION: WILD syndrome is a previously unrecognised, underdiagnosed generalised PL syndrome. Based on this case series, we redefine WILD as 'Warts, Immunodeficiency, andLymphatic Dysplasia' and suggest specific diagnostic criteria. The essential criterion is congenital multisegmental PL in a 'mosaic' distribution. The major diagnostic features are recurrent warts, cutaneous lymphovascular malformations, systemic involvement (lymphatic dysplasia), genital swelling and CD4 lymphopaenia with normal monocyte counts. The absence of family history suggests a sporadic condition, and the random distribution of swelling implicates mosaic postzygotic mutation as the cause.
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Síndromes de Inmunodeficiencia , Linfedema , Verrugas , Humanos , Verrugas/diagnóstico , Verrugas/genética , Linfedema/diagnóstico , Linfedema/genéticaRESUMEN
Primary lymphatic anomalies may present in a myriad of ways and are highly heterogenous. Careful consideration of the presentation can lead to an accurate clinical and/or molecular diagnosis which will assist with management. The most common presentation is lymphoedema, swelling resulting from failure of the peripheral lymphatic system. However, there may be internal lymphatic dysfunction, for example, chylous reflux, or lymphatic malformations, including the thorax or abdomen. A number of causal germline or postzygotic gene mutations have been discovered. Some through careful phenotyping and categorisation of the patients based on the St George's classification pathway/algorithm. The St George's classification algorithm is aimed at providing an accurate diagnosis for patients with lymphoedema based on age of onset, areas affected by swelling and associated clinical features. This has enabled the identification of new causative genes. This update brings the classification of primary lymphatic disorders in line with the International Society for the Study of Vascular Anomalies 2018 classification for vascular anomalies. The St George's algorithm considers combined vascular malformations and primary lymphatic anomalies. It divides the types of primary lymphatic anomalies into lymphatic malformations and primary lymphoedema. It further divides the primary lymphoedema into syndromic, generalised lymphatic dysplasia with internal/systemic involvement, congenital-onset lymphoedema and late-onset lymphoedema. An audit and update of the algorithm has revealed where new genes have been discovered and that a molecular diagnosis was possible in 26% of all patients overall and 41% of those tested.
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Anomalías Linfáticas/genética , Enfermedades Linfáticas/genética , Linfedema/genética , Enfermedades Vasculares/genética , Humanos , Anomalías Linfáticas/clasificación , Anomalías Linfáticas/patología , Enfermedades Linfáticas/clasificación , Enfermedades Linfáticas/patología , Linfedema/clasificación , Linfedema/patología , Enfermedades Vasculares/clasificación , Enfermedades Vasculares/patología , Malformaciones Vasculares/clasificación , Malformaciones Vasculares/genéticaRESUMEN
BACKGROUND: Lymphoedema develops after axillary clearance (ANC) in 25% of patients. This prospective, multi-centre study compared multi-frequency bioimpedance spectroscopy (BIS) with arm volume measurement to: (1) determine which test has better diagnostic accuracy, (2) identify factors predicting development of lymphoedema, and its effect on quality-of-life. METHODS: Participants (N = 1100) underwent measurements pre and post-ANC surgery for breast cancer. Relative arm volume increase (RAVI) of >10% diagnosed lymphoedema. Predictors of lymphoedema were determined using logistic regression. Optimal diagnostic method was assessed using diagnostic accuracy. Quality-of-life was assessed using the FACT B + 4 questionnaire. RESULTS: Lymphoedema was diagnosed in 22.8% women using RAVI > 10%, 45.6% using BIS criteria, while 24.5% underwent compression sleeve application by 24 months. BMI > 30 was an independent factor for both development (p = 0.005) and progression (p = 0.015) of lymphoedema. RAVI at 1 month, BMI > 30 and number of involved nodes contributed to a novel scoring model to predict lymphoedema by 36 months. Larger decreases in QoL scores post-surgery occurred in lymphoedema patients (p < 0.001). Progression to moderate lymphoedema occurred in 15% patients after sleeve application. CONCLUSIONS: RAVI measurement was the best diagnostic tool for lymphoedema. BIS alone is not appropriate for lymphoedema screening or diagnosis. BMI > 30 predicted lymphoedema diagnosis and progression.
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Axila/cirugía , Neoplasias de la Mama/epidemiología , Escisión del Ganglio Linfático/efectos adversos , Linfedema/epidemiología , Adulto , Anciano , Anciano de 80 o más Años , Brazo/patología , Brazo/cirugía , Axila/patología , Neoplasias de la Mama/complicaciones , Neoplasias de la Mama/patología , Neoplasias de la Mama/cirugía , Femenino , Humanos , Linfedema/etiología , Linfedema/patología , Persona de Mediana Edad , Estudios Prospectivos , Calidad de Vida , Encuestas y Cuestionarios , Reino Unido/epidemiologíaRESUMEN
Sotos syndrome is an overgrowth-intellectual disability (OGID) syndrome caused by NSD1 pathogenic variants and characterized by a distinctive facial appearance, an intellectual disability, tall stature and/or macrocephaly. Other associated clinical features include scoliosis, seizures, renal anomalies, and cardiac anomalies. However, many of the published Sotos syndrome clinical descriptions are based on studies of children; the phenotype in adults with Sotos syndrome is not yet well described. Given that it is now 17 years since disruption of NSD1 was shown to cause Sotos syndrome, many of the children first reported are now adults. It is therefore timely to investigate the phenotype of 44 adults with Sotos syndrome and NSD1 pathogenic variants. We have shown that adults with Sotos syndrome display a wide spectrum of intellectual ability with functioning ranging from fully independent to fully dependent. Reproductive rates are low. In our cohort, median height in adult women is +1.9 SD and men +0.5 SD. There is a distinctive facial appearance in adults with a tall, square, prominent chin. Reassuringly, adults with Sotos syndrome are generally healthy with few new medical issues; however, lymphedema, poor dentition, hearing loss, contractures and tremor have developed in a small number of individuals.
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Fenotipo , Síndrome de Sotos/fisiopatología , Adulto , Niño , Facies , Femenino , Humanos , Discapacidad Intelectual/genética , Masculino , Síndrome de Sotos/genética , Síndrome de Sotos/psicologíaAsunto(s)
Linfedema , Calidad de Vida , Brazo , Axila , Humanos , Linfedema/diagnóstico , Linfedema/epidemiología , Linfedema/etiología , Estudios ProspectivosRESUMEN
The importance of early detection of lymphoedema by arm volume measurements before surgery and repeated measurements after surgery in women undergoing axillary node clearance (ANC) in order to enable early intervention is recognised. A prospective multi-centre study was performed which studied the difference between multi-frequency bioimpedance electrical analysis (BIS) and perometer arm measurement in predicting the development of lymphoedema. Women undergoing ANC underwent pre-operative and regular post-operative measurements of arm volume by both methods. The primary endpoint is the incidence of lymphoedema (≥10 % arm volume increase compared to contralateral arm by perometer) at 2 and 5 years after ANC. The threshold for intervention in lymphoedema was also assessed. Out of 964 patients recruited, 612 had minimum 6 months follow-up data. Using 1-month post-operative measurements as baseline, perometer detected 31 patients with lymphoedema by 6 months (BIS detected 53). By 6 months, 89 % of those with no lymphoedema reported at least one symptom. There was moderate correlation between perometer and BIS at 3 months (r = 0.40) and 6 months (r = 0.60), with a sensitivity of 73 % and specificity of 84 %. Univariate and multivariate analyses revealed a threshold for early intervention of ≥5 to <10 % (p = 0.03). Threshold for early intervention to prevent progression to lymphoedema is ≥5 to <10 % but symptoms alone do not predict lymphoedema. The modest correlation between methods at 6 months indicates arm volume measurements remain gold standard, although longer term follow-up is required.
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Neoplasias de la Mama/patología , Espectroscopía Dieléctrica , Detección Precoz del Cáncer , Ganglios Linfáticos/patología , Linfedema/patología , Adulto , Anciano , Anciano de 80 o más Años , Neoplasias de la Mama/complicaciones , Neoplasias de la Mama/cirugía , Progresión de la Enfermedad , Femenino , Humanos , Escisión del Ganglio Linfático , Linfedema/complicaciones , Linfedema/cirugía , Persona de Mediana Edad , Periodo Posoperatorio , Pronóstico , Estudios Prospectivos , Calidad de VidaAsunto(s)
Edema , Sociedades Médicas/tendencias , Servicios de Salud Comunitaria , Humanos , Medicina Estatal , Reino UnidoRESUMEN
Background: Lymphedema and lipedema are debilitating conditions with no proven drug or surgical therapy. Effective treatment requires self-management through movement and compression to reduce limb volume and the incidence of cellulitis. The addition of personalized everyday physical activity (PA) could be transformative, increasing the therapy window to include all waking hours per week and enabling an increased dose of PA. Aim: This service evaluation aimed to determine the feasibility of LymphActiv as a treatment option for lymphedema and lipedema patients. Methods: This service evaluation followed an open observational cohort design, including 55 patients who participated in LymphActiv over 24 weeks. Patients wore an objective PA monitor and interacted with their data in an online dashboard, alongside remote mentor support. Primary outcomes were changes to PA, body weight, limb volume and quality of life. Clinical assessments occurred at baseline and after the 24-week program. Noncompleters were used as a quasi-control group for comparison. Results: Thirty-seven patients completed, of which 81% improved PA. On average, completers reduced their right and left lower limb volumes by -1.8% and -2.1%, respectively. Completers also experienced small average weight losses of -1.2 kg. Noncompleters experienced small average increases in each of these outcome measures. Discussion: These results establish the value of LymphActiv, providing benefit to patients who might otherwise have deteriorated. For services, this could lead to substantial cost-savings through reduced admissions, greater patient independence, and less need for community health care input. The next step is to undertake a randomized, controlled trial comparing the intervention with standard care.
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Lipedema , Linfedema , Humanos , Calidad de Vida , Linfedema/etiología , Resultado del Tratamiento , Ejercicio FísicoRESUMEN
Background: Optimal frequency and duration of pneumatic compression device (PCD) therapy for lymphedema is undetermined. This prospective, randomized preliminary study evaluated the impact of different PCD dosing protocols on physiological and patient-reported outcomes (PROs) to estimate treatment effects, assess the responsiveness of various measurement techniques, and identify endpoints for a definitive PCD dosing trial. Methods and Results: Twenty-one patients with lower extremity lymphedema were randomized into three groups for treatment with the Flexitouch advanced PCD: (A) once per day for 1 hour, 12 consecutive days; (B) twice per day in 1-hour treatments, 5 consecutive days; or (C) twice per day in 2-hour treatments, 5 consecutive days. Outcomes measured were changes in limb volume (LV), tissue fluid, tissue tone, and PROs. Those in group A experienced mean (standard deviation) LV reductions of 109 (58) mL (p = 0.003) on day 1 and of 97 (86) mL (p = 0.024) on day 5. Group A also showed possible single-treatment decreases in extracellular fluid volume by bioimpedance spectroscopy (BIS) on day 5. There were no consistent changes in groups B and C. Long-term assessment of LV and BIS showed no clear change. Tonometry, ultrasound, local tissue water, and PROs showed wide variation among participants. Conclusions: LV measurements showed potential benefit for 1-hour daily PCD treatment. A definitive dosing trial should include LV, BIS, and PROs in a comparison of 1- and 2-hour daily treatment protocols conducted over a study period of 4 weeks. These data may inform appropriate outcome measures for other intervention studies in lymphedema.
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Linfedema , Autocuidado , Humanos , Estudios Prospectivos , Manometría , Aparatos de Compresión Neumática Intermitente , Linfedema/diagnóstico , Linfedema/terapia , Extremidad Inferior , Resultado del TratamientoRESUMEN
Lymphedema can develop after treatment for breast cancer (BCRL). Lymphedema of the breast is not well studied. Currently, the main techniques used to diagnose and monitor the effectiveness of treatment are subjective clinician assessment and patient reports. Eighty-nine women who had undergone breast cancer treatment were recruited with and without breast lymphedema. Blinded clinical assessment determined the presence or absence of breast lymphedema. Measurement of skin thickness by ultrasound scanning, local tissue water by tissue dielectric constant (TDC) and tissue indentation by tonometry was recorded. Breast cancer treatment and demographic details were documented. Descriptive statistics were undertaken to compare sample characteristics, including the Chi-squared test, Odds Ratio (OR) and Relative Risks (RR) calculated. Increased body mass index (BMI), larger bra size, increased number of positive lymph nodes, axillary surgery, chemotherapy and increased Nottingham Prognostic Index (NPI) were all associated with breast lymphedema (p < 0.05). Ultrasound and TDC measurements were significantly higher in the lymphedema group (p < 0.05). Receiver Operator Characteristic (ROC) curves demonstrated that ultrasound and TDC measurements could distinguish between edematous and non-edematous breasts. Threshold levels were produced, which demonstrated good levels of sensitivity and specificity. These findings have the potential to improve the diagnosis of breast lymphedema.
RESUMEN
Around 25% of women undergoing Axillary Clearance (ANC) develop lymphedema (LE). Intervention with a compression garment is recommended to prevent LE but no randomised evidence exists to support this strategy. METHODS: A randomised trial tested standard management versus application of graduated compression garments (20-24 mmHg) to affected arm, for 1 year. Women with node positive breast cancer (n = 1300) undergoing ANC consented to arm volume measurements and those developing a 4-9% relative arm volume increase (RAVI) (subclinical LE) within 9 months post-surgery were randomised. Primary outcome was proportion of patients developing LE (RAVI > 10%) by 24-months in each group. Secondary endpoints included Quality of life in each group. RESULTS: In total 143 patients were randomised (74 no sleeve: 69 compression sleeve) between October 2010 and November 2015. The lymphoedema rate at 24 months in the 'no sleeve' group was at 41%, similar to the 'sleeve' group (30%: p = 0.32). Thirtytwo patients randomised to the 'no sleeve' group had a sleeve applied within 24 months. Body Mass Index (BMI) at randomisation predicted LE at any time point HR 1.04 (CI 1.01-1.08; p = 0.01). Patients with obesity (BMI > 30) had higher rates of LE in both groups (46%) compared to those with BMI < 30 (24%). No difference between patients was found in either group in changes in QoL. Compression sleeves applied after development of LE improved QoL scores (FACT-B p = 0.007:TOI p = 0.042). CONCLUSION: Early intervention with External Compression garments does not prevent clinical LE, particularly in women with a high BMI > 30. The use of prophylactic garments in subclinical LE (RAVI < 9%) is unwarranted.
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Neoplasias de la Mama , Linfedema , Humanos , Femenino , Índice de Masa Corporal , Calidad de Vida , Linfedema/etiología , Linfedema/prevención & control , Neoplasias de la Mama/cirugía , Neoplasias de la Mama/complicacionesRESUMEN
Superficial erythematous cutaneous vascular malformations are assumed to be blood vascular in origin, but cutaneous lymphatic malformations can contain blood and appear red. Management may be different and so an accurate diagnosis is important. Cutaneous malformations were investigated through 2D histology and 3D whole-mount histology. Two lesions were clinically considered as port-wine birthmarks and another 3 lesions as erythematous telangiectasias. The aims were (i) to demonstrate that cutaneous erythematous malformations including telangiectasia can represent a lymphatic phenotype, (ii) to determine if lesions represent expanded but otherwise normal or malformed lymphatics, and (iii) to determine if the presence of erythrocytes explained the red color. Microscopy revealed all lesions as lymphatic structures. Port-wine birthmarks proved to be cystic lesions, with nonuniform lymphatic marker expression and a disconnected lymphatic network suggesting a lymphatic malformation. Erythematous telangiectasias represented expanded but nonmalformed lymphatics. Blood within lymphatics appeared to explain the color. Blood-lymphatic shunts could be detected in the erythematous telangiectasia. In conclusion, erythematous cutaneous capillary lesions may be lymphatic in origin but clinically indistinguishable from blood vascular malformations. Biopsy is advised for correct phenotyping and management. Erythrocytes are the likely explanation for color accessing lymphatics through lympho-venous shunts.
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Telangiectasia , Malformaciones Vasculares , Humanos , Malformaciones Vasculares/diagnóstico , Capilares , Venas , Telangiectasia/diagnósticoRESUMEN
Little is known about the overall prevalence of lymphoedema in children and the types of paediatric lymphoedema seen by specialist centres. Therefore, this study was aimed to provide a profile of children with primary or secondary lymphoedema seen by the expert centres of the paediatric and primary lymphoedema working group (PPL-WG) of VASCERN and to compare the profile between the different countries. A retrospective review of all children (aged up to 18 years) seen for the first time by the expert centres over one year (2019) was carried out. Lymphoedema-, patient- and genetics-related data was collected and described for the whole group and compared between the different European countries/UK. In 2019, a total of 181 new children were seen by eight expert centres. For primary lymphoedema, the phenotype was based on the St George's classification of lymphatic anomalies. The percentages diagnosed according to each category were: 7.2% for syndromic lymphoedema, 2.8% for systemic/visceral involvement, 30.4% for congenital, 35.9% for late-onset lymphoedema and 19.3% for vascular/lymphatic malformations. 4.4% had secondary lymphoedema. Nearly 10% of all children had had at least one episode of cellulitis. The median delay from onset of symptoms to being seen by an expert centre was 2.4 years. In 44.4% of the children with primary lymphoedema a genetic test was performed, of which 35.8% resulted in a molecular diagnosis. Across the different centres, there was a wide variety in distribution of the different categories of paediatric lymphoedema diagnosed and the frequency of genetic testing. In conclusion, this paper has demonstrated that there is a large delay between the onset of paediatric lymphoedema and the first visit in the expert centres and that an episode of cellulitis is a relatively common complication. Diagnostic variation across the centres may reflect different referral criteria. Access to genetic testing was limited in some centres. It is recommended that these issues are addressed in the future work of the PPL-WG to improve the referral to the expert centres and the consistency in service provision for paediatric lymphoedema in Europe.
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Celulitis (Flemón) , Linfedema , Humanos , Linfedema/diagnóstico , Linfedema/epidemiología , Linfedema/genética , Pruebas Genéticas , Prevalencia , Estudios RetrospectivosRESUMEN
Lipoedema is a chronic adipose tissue disorder mainly affecting women, causing excess subcutaneous fat deposition on the lower limbs with pain and tenderness. There is often a family history of lipoedema, suggesting a genetic origin, but the contribution of genetics is currently unclear. A tightly phenotyped cohort of 200 lipoedema patients was recruited from two UK specialist clinics. Objective clinical characteristics and measures of quality of life data were obtained. In an attempt to understand the genetic architecture of the disease better, genome-wide single nucleotide polymorphism (SNP) genotype data were obtained, and a genome wide association study (GWAS) was performed on 130 of the recruits. The analysis revealed genetic loci suggestively associated with the lipoedema phenotype, with further support provided by an independent cohort taken from the 100,000 Genomes Project. The top SNP rs1409440 (ORmeta ≈ 2.01, Pmeta ≈ 4 x 10-6) is located upstream of LHFPL6, which is thought to be involved with lipoma formation. Exactly how this relates to lipoedema is not yet understood. This first GWAS of a UK lipoedema cohort has identified genetic regions of suggestive association with the disease. Further replication of these findings in different populations is warranted.
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Estudio de Asociación del Genoma Completo , Lipedema , Femenino , Genotipo , Humanos , Polimorfismo de Nucleótido Simple , Calidad de Vida , Reino UnidoRESUMEN
Background: Chronic edema (CO) is a complex condition, arising from different factors, including immobility and obesity. Edema and obesity can have a significant impact on quality of life of patients and their families. Understanding how to manage edema in obese patients is an increasing challenge for both patients and clinicians. As effective treatment options are limited for this population, it is more cost-effective for patients to lose weight before starting treatment. When patients cannot maintain weight loss, one option is to have bariatric surgery. This study was part of LIMPRINT: Lymphedema IMpact and PRevalence INTernational, a study with the aim of identifying the prevalence and impact of CO in different countries and health care settings. Study Purpose: To evaluate the prevalence and impact of CO among patients in a United Kingdom bariatric surgical service. Methods and Results: The gold standard pitting test assessed the presence of edema. General (EuroQOL-5 Dimensions [EQ-5D], RAND 36-Item Short Form Health Survey, Version 1.0 [SF-36], Generalized Anxiety Disorder 7-Item Scale [GAD-7] and Patient Health Questionnaire-9 [PHQ-9]), and edema-specific (Lymphedema Quality of Life [LYMQOL]) quality-of-life questionnaires were used to evaluate impact of edema. The prevalence of edema was 52.1% (25 of 48 participants had edema), potentially linked to obesity, immobility, and medications. Most participants had International Society of Lymphology (ISL) Stage I edema. There were no statistically significant differences between the quality of life of participants with and without edema. However, comparing SF-36 results and normative population data indicated that quality of life was much lower than those in the normative population. Conclusions: This study highlights the high prevalence of edema and low quality of life of this bariatric population. ClinicalTrials.gov ID: NCT03154593.
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Bariatria , Calidad de Vida , Enfermedad Crónica , Diagnóstico Diferencial , Edema/diagnóstico , Edema/epidemiología , Edema/etiología , Humanos , Sistema Linfático , Prevalencia , Encuestas y CuestionariosRESUMEN
Background: More research is needed in lymphedema management to strengthen the evidence base and ensure patients receive clinically and cost-effective treatment. It is critical that patients and clinicians are involved in prioritizing research to ensure that it reflects their needs and is not biased by commercial interests. This study aimed to set the research priorities for lymphedema management in the United Kingdom, through collaboration with patients, carers, and clinicians. Methods and Results: Following the James Lind Alliance's methodology, a national survey was conducted to identify unanswered questions about lymphedema management from the perspective of patients, carers, and clinicians. These were collated and verified against an in-depth evidence review. Unanswered questions were formatted into broad research questions, which were prioritized by a purposive sample of patients, carers, and clinicians, using an online Delphi survey. The initial survey generated 631 submissions from 213 participants, including 108 patients, 9 carers, and 88 clinicians. Of these, 485 met inclusion criteria and were grouped into 12 overarching themes. The evidence review demonstrated that 101 submissions were answered by existing research and identified an additional 78 questions. The remaining unanswered submissions were collated into 126 broad research questions, which were prioritized over four rounds of the Delphi survey to produce the top 10 priorities. Conclusions: This study is the first to attempt to systematically identify research priorities for lymphedema management in the United Kingdom, from the perspective of patients, carers, and clinicians. The results provide guidance for researchers and funders to ensure future research meets the needs of those living with lymphedema.
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Investigación Biomédica , Linfedema/diagnóstico , Linfedema/terapia , Práctica Asociada , Investigación , Manejo de la Enfermedad , Humanos , Colaboración Intersectorial , Linfedema/etiología , Reino UnidoRESUMEN
Turner syndrome is a complex disorder caused by an absent or abnormal sex chromosome. It affects 1/2000-1/3000 live-born females. Congenital lymphoedema of the hands, feet and neck region (present in over 60% of patients) is a common and key diagnostic indicator, although is poorly described in the literature. The aim of this study was to analyse the medical records of a cohort of 19 Turner syndrome patients attending three specialist primary lymphoedema clinics, to elucidate the key features of the lymphatic phenotype and provide vital insights into its diagnosis, natural history and management. The majority of patients presented at birth with four-limb lymphoedema, which often resolved in early childhood, but frequently recurred in later life. The swelling was confined to the legs and hands with no facial or genital swelling. There was only one case of suspected systemic involvement (intestinal lymphangiectasia). The lymphoscintigraphy results suggest that the lymphatic phenotype of Turner syndrome may be due to a failure of initial lymphatic (capillary) function.