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PURPOSE OF REVIEW: The regulation of blood pressure is conventionally conceptualised into the product of "circulating blood volume" and "vasoconstriction components". Over the last few years, however, demonstration of tissue sodium storage challenged this dichotomous view. RECENT FINDINGS: We review the available evidence pertaining to this phenomenon and the early association made with blood pressure; we discuss open questions regarding its originally proposed hypertonic nature, recently challenged by the suggestion of a systemic, isotonic, water paralleled accumulation that mirrors absolute or relative extracellular volume expansion; we present the established and speculate on the putative implications of this extravascular sodium excess, in either volume-associated or -independent form, on blood pressure regulation; finally, we highlight the prevalence of high tissue sodium in cardiovascular, metabolic and inflammatory conditions other than hypertension. We conclude on approaches to reduce sodium excess and on the potential of emerging imaging technologies in hypertension and other conditions.

Volume overload, defined as excess total body sodium and water with expansion of extracellular fluid volume, characterizes common disorders such as congestive heart failure, end-stage liver disease, chronic kidney disease, and nephrotic syndrome. Diuretics are the cornerstone of therapy for volume overload and comprise several classes whose mechanisms of action, pharmacokinetics, indications, and adverse effects are essential principles of nephrology. Loop diuretics are typically the first-line treatment in the management of hypervolemia, with additional drug classes indicated in cases of diuretic resistance and electrolyte or acid-base disorders. Separately, clinical trials highlight improved outcomes in some states of volume overload, such as loop diuretics and sodium/glucose cotransporter 2 inhibitors in patients with congestive heart failure. Resistance to diuretics is a frequent, multifactorial clinical challenge that requires creative and physiology-based solutions. In this installment of AJKD's Core Curriculum in Nephrology, we discuss the pharmacology and therapeutic use of diuretics in states of volume overload and strategies to overcome diuretic resistance.

Lipedema PubMed published article

El lipedema es un trastorno crónico que se presenta en mujeres durante la pubertad u otros momentos de cambios hormonales como en el embarazo o la menopausia.  Es caracterizado por una obesidad desproporcionada de las extremidades, especialmente en caderas y piernas, asociado a hematomas con mínimo trauma y dolor espontáneo o inducido por presión. Usualmente es mal diagnoticado e infratratado y suele confundirse con otras enfermedades como la obesidad y linfedema. Su causa aún se sigue estudiando, existen hipótesis sobre su origen poligenético regulado por los estrógenos, por el inicio de la enfermedad en etapas de cambio hormonal y debido a que se presenta mayormente en mujeres. Los tratamiento para el lipedema se basa en seis pilares: 1) Fisioterapia-ejercicios, 2) Terapia compresiva, 3) Control de peso, 4) Liposucción, 5) Terapia psicosocial-6) Automanejo.

The quantitative assessment of lymphatic dermal clearance using NIR fluorescent tracers is particularly important for the early diagnosis of several potential disabling diseases. Currently, half-life values are computed using a mono-exponential mathematical model, neglecting diffusion of the tracer within the dermis after injection. The size and position of the region of interest are subjectively manually selected around the point of injection on the skin surface where the fluorescence signal intensity is averaged, neglecting any spatial information contained in the image. In this study we present and test a novel mathematical model allowing the objective quantification of dermal clearance, taking into consideration potential dermal diffusion. With only two parameters, this "clearance-diffusion" model is simple enough to be applied in a variety of settings and requires almost no prior information about the system. We demonstrate that if dermal diffusion is low, the mono-exponential approach is suitable but still lacking objectivity. However, if dermal diffusion is substantial, the clearance-diffusion model is superior and allows the accurate calculation of half-life values.

OBJECTIVE: Upper extremity lymphedema (UEL) is a burdensome disease with significant impact on quality of life underscoring the importance of quality of life measurements in this patient population. Only recently, the LYMPH Q Upper Extremity Module, a new patient-reported outcome measurement (PROM), has been developed. The aim of the study was to translate the LYMPH Q Upper Extremity Module from English to German and perform a comprehensive validation. METHODS: Translation was performed in accordance with the International Society for Pharmacoeconomics and Outcomes Research (ISPOR) best-practice guidelines. To validate the German LYMPH Q, a multicenter study was conducted. Internal consistency was determined by Cronbach's alpha. Reliability was assessed by the intra-class correlation coefficient (ICC). To analyse construct validity, a Pearson correlation coefficient between the LYMPH Q, quickDASH and SF-36 was calculated. Responsiveness was assessed by comparing the pre- and postoperative LYMPH Q scores in five patients receiving lymphatic reconstructive surgery. RESULTS: Validation was performed in a cohort of 65 patients. Internal consistency of the different domains was good to excellent (α: 0.87-0.97). ICC ranged from 0.74 to 0.92. The domains of the LYMPH Q correlated significantly with the corresponding domains of the SF-36 and quick DASH. Construct validity was good with eight of ten hypotheses confirmed. Significant improvements of function (46.4 ± 13.3 vs. 77.8 ± 11.5; p= 0.03), symptoms (42.0 ± 10.7 vs. 70.6 ± 11.6; p= 0.02) and psychological well-being (40.4 ± 14.6 vs. 78.0 ± 17.3; p= 0.03) were observed after lymphatic reconstructive surgery. CONCLUSION: The German version of The LYMPH Q Upper Extremity Module is conceptually equivalent to the original English version. It is a reliable and valid PROM to assess physical and psychological impairments in patients with UEL.

Lipedema is a disabling disease characterized by symmetric enlargement of the lower and/or upper limbs due to deposits of subcutaneous fat, that is easily misdiagnosed. Lipedema can be primary or syndromic, and can be the main feature of phenotypically overlapping disorders. The aim of this study was to design a next-generation sequencing (NGS) panel to help in the diagnosis of lipedema by identifying genes specific for lipedema but also genes for overlapping diseases, and targets for tailored treatments. We developed an NGS gene panel consisting of 305 genes potentially associated with lipedema and putative overlapping diseases relevant to lipedema. The genomes of 162 Italian and American patients with lipedema were sequenced. Twenty-one deleterious variants, according to 3 out of 5 predictors, were detected in PLIN1, LIPE, ALDH18A1, PPARG, GHR, INSR, RYR1, NPC1, POMC, NR0B2, GCKR, PPARA in 17 patients. This extended NGS-based approach has identified a number of gene variants that may be important in the diagnosis of lipedema, that may affect the phenotypic presentation of lipedema or that may cause disorders that could be confused with lipedema. This tool may be important for the diagnosis and treatment of people with pathologic subcutaneous fat tissue accumulation.

BACKGROUND: Despite an increasing demand for surgical treatment of lipedema, the evidence for liposuction is still limited to five peer-reviewed publications. Little is known about the influence of disease stage, patient age, body mass index, or existing comorbidities on clinical outcomes. Considering the chronically progressive nature of lipedema, it was hypothesized that younger patients with lower body mass index and stage would report better results. METHODS: This retrospective, single-center, noncomparative study included lipedema patients who underwent liposuction between July of 2009 and July of 2019. After a minimum of 6 months since the last surgery, all patients completed a disease-related questionnaire. The primary endpoint was the need for complex decongestive therapy based on a composite score. Secondary endpoints were the severity of complaints (i.e., spontaneous pain, sensitivity to pressure, feeling of tension, bruising, impairment of body image) measured on a visual analogue scale. RESULTS: One hundred six patients underwent a total of 298 large-volume liposuctions (mean lipoaspirate, 6355 ± 2797 ml). After a median follow-up of 20 months (interquartile range, 10 to 42 months), a median complex decongestive therapy score reduction of 37.5 percent (interquartile range, 0 to 88.8 percent; p < 0.0001) was observed. An improvement in lipedema-associated symptoms was also observed (p < 0.0001). The percentage reduction in complex decongestive therapy scores was greater in patients with a body mass index less than or equal to 35 kg/m2; (compared to higher body mass index; p < 0.0001) and in stage I and II patients (compared to stage III patients; p = 0.0019). CONCLUSION: Liposuction reduces the severity of symptoms and the need for conservative treatment in lipedema patients, especially if it is performed in patients with a body mass index below 35 kg/m2; at an early stage of the disease. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, IV.

Lymphatic drainage is the main form of therapy for lymphedema, as it affects the pathophysiology of this clinical condition. The two main objectives of lymphatic drainage are the formation and drainage of lymph. In recent years, Godoy &amp; Godoy developed a novel concept of mechanical lymphatic drainage involving a device denominated RAGodoy®, which performs passive exercises of the lower and upper limbs as a form of lymphatic drainage. The aim of the present study was to address the concept of this therapy as well as perform a literature review on its forms of use and the results obtained. All studies analyzed show that this technique used as monotherapy enables the treatment of lymphedema, but superior results are achieved when combined with compression mechanisms.

Background: There is insufficient clear epidemiological and clinical knowledge about lymphedema patient’s population in Mexico, this limits its investigation. The objective of this study is to present basic lymphedema epidemiological data and its clinical characteristics based on the analysis of lymphedema patients’ data collected from a specialized rehabilitation clinic in Mexico. Methods: This is a cohort study developed between 2015 and 2021. The study was carried ou in a private clinic specialized in oncological and peripheral vascular patients’ rehabilitation. Clinical assessments and interviews were performed to collect each case’s clinical history, considering its medical characteristics, physical activity and functionality and socio-demographic information, classified in a matrix, and later statistically evaluated. Results: Among 446 lymphedema patients, gender distribution was represented by 81% female and 19% male with a mean age of 50.5 years (±44.5). The population was categorized into the following three different study groups according to diagnosis: Cancer-Related Lymphedema (CRL), Non-Cancer-Related Secondary Lymphedema (NCRSL) and Primary Lymphedema. 60.08% of the patients had CRL; 25.11% had NCRSL and 14.79% had Primary Lymphedema. Among the patients with CRL, 81% of them corresponded to breast cancer diagnosis, the rest were associated to 19 different cancer diagnoses. The most prevalent diagnosis was breast CRL 48.6%; phlebolymphedema 19.4%; congenital and praecox lymphedema 14.1%; lipo-lymphedema 4.8%. The BMI of 64% of the patients ranged in overweight and obesity. 37.6% of patients reported that had experienced pain in limbs affected by lymphedema and 45% of all patients reported some disability to perform one or more activities associated to their limb volume or limb discomfort. 82% of patients had no physical activity or performed less physical activity than what is suggested to their population group’s recommendation. Conclusion: This study stablishes a precedent on reporting the broadest available epidemiological and clinical data of lymphedema in Mexico. Further studies are needed to report with a higher precision the epidemiological, clinical, and demographical data about each etiological group for a better understanding of lymphedema in Mexico and Latin America.

In daily practice, medical history and physical examination are commonly coupled with anthropometric measurements for the diagnosis and management of patients with lymphatic diseases. Herein, considering the current progress of ultrasound imaging in accurately assessing the superficial soft tissues of the human body; it is noteworthy that ultrasound examination has the potential to augment the diagnostic process. In this sense/report, briefly revisiting the most common clinical maneuvers described in the pertinent literature, the authors try to match them with possible (static and dynamic) sonographic assessment techniques to exemplify/propose an 'ultrasound-guided' physical examination for different tissues in the evaluation of lymphedema.

Left ventricular (LV) twist is defined as the wringing motion of the LV around its long-axis during systole generated by rotation of the LV apex in a counterclockwise direction, as viewed from the apex, while the LV base moves in a clockwise direction. In several cases, the LV apex and base move in the same direction during ejection demonstrating a special condition called as LV 'rigid body rotation'. The present review aimed to summarize our knowledge about this rare but not fully understood entity demonstrating its theoretic pathophysiologic background, clinical significance, associated diseases, and reversibility based on available literature.

BACKGROUND: Lipedema often remains undiagnosed in patients with obesity, leading to mismanagement of treatment. Because of this, despite remarkable weight loss after bariatric surgery and decreases in hip and abdomen circumference, some patients show only small decreases in circumference of the extremities and report persistent limb pain. OBJECTIVE: The goal of this work is to raise awareness of lipedema coincident with obesity, mistakenly diagnosed as obesity alone, in order to ensure the correct diagnosis of the condition and to achieve better treatment outcomes for people with lipedema and coincident obesity. SETTING: CG Lympha Clinic, Cologne, and Ernst von Bergmann Clinic, Potsdam. METHODS: From clinical records, we identified 13 patients who were diagnosed with lipedema only after undergoing bariatric surgery. We describe the course of their pain before and after bariatric surgery, focusing on the long-term progression of symptoms accompanying the disease. RESULTS: Lipedema cannot be cured by bariatric surgery, and although the patients in this study lost an average of more than 50 kg of weight, they displayed no improvement in the pain symptoms typical of lipedema. CONCLUSIONS: Because of the different etiologies of lipedema and obesity, lipedema requires its own specific treatment. Patients suffering from obesity should always be assessed for pain and lipedema. If coincident lipedema is diagnosed, we suggest that bariatric surgery only be performed first if diet and exercise have failed, the patient's body mass index is >40 kg/m2, and the patient has been informed of the possible persistence of pain. Lipedema, like a coincident disease, must be additionally treated conservatively or preferably surgically. This optimized treatment may help to better manage patient expectations after weight loss.

Background: Lipedema is a chronic and progressive adipose tissue disorder that causes significant morbidity and negatively influences mental health and quality of life, and increases the risk of depression, anxiety, and eating disorders. One construct of relevance to better understanding psychological disorders is emotion regulation (ER). Therefore, the aim of this study is to investigate the difficulties in ER among lipedema patients compared to healthy people without lipedema. Methods: This cross-sectional study assessed differences in ER and anxiety between two groups: 26 female patients with lipedema and 26 sex- and age-matched healthy controls. The Difficulties in Emotion Regulation Scale (DERS) assessed emotional regulation across six dimensions: Impulse control, goal-directed behavior, awareness, clarity, non-acceptance, and strategies. Anxiety was assessed by the Hamilton Anxiety Scale (HAM-A). ANOVA assessed differences in measures between lipedema and healthy control groups. Results: Lipedema patients presented with significantly more difficulties in ER and a higher level of anxiety than those without lipedema. Specifically, the lipedema group showed higher and significant differences in total DERS and anxiety scores and all DERS subscales scores compared to those without lipedema. Conclusions: Lipedema patients showed significant difficulties with ER, and were associated with anxiety symptoms, indicating that ER difficulties may play a role in developing emotional disorders, such as anxiety, for patients with lipedema. The health care provider should pay more attention to ER difficulties and psychological status among lipedema patients.

Lipedema patients suffer not only from visual stigma but also reduction in their quality of life through pain and performance loss in daily life. In clinical practice, it is still difficult to reliably diagnose the disease. This study aims to provide further insights into the characteristics of lipedema patients of all stages and provide a baseline prior to surgery for a surgical treatment evaluation by means of patient-reported outcome measures. Methods: Patients completed a lipedema-specific questionnaire containing 50 items, the World Health Organization Quality of Life BREF (WHOQOL-BREF) and the Patient Health Questionnaire 9 (PHQ-9). The data were analyzed using SPSS statistics 27. Patients who had already received liposuction were excluded. Results: Five hundred and eleven patients were included, of whom 337 completed the PHQ9 and 333 completed the WHOQOL-BREF questionnaires. The general characteristics of lipedema patients, especially the daily symptoms, are described. Previous observations, such as the frequent occurrence of hypothyroidism and the low rate of type 2 diabetes, were confirmed. Over 49% suffer from severe impairments in their jobs, whereby the disease shows a familial accumulation. The results of the WHOQOL-BREF and the PHQ-9 suggest a high level of mental stress. Discussion: As surgical intervention in lipedema patients is gaining traction, its effects should be well-documented. Therefore, a comprehensive baseline needs to be established prior to surgical treatment. The psychological components are just as important as the inclusion of daily impairments.

Abstract Background Lipedema is characterized as an abnormal deposition of fat in the buttocks and legs bilaterally that may be accompanied by swelling, pain, and tenderness. It is still often confused with more frequent conditions such as obesity and lymphedema. The estimated prevalence in Europe varies between 0.06% and 39%. Objectives To evaluate the prevalence of lipedema and identify health factors related to it in the Brazilian population. Methods Administration of a previously validated online screening questionnaire to a representative sample of the general population. The questionnaire was distributed and administered to anonymous volunteers representing the general Brazilian population using software designed for population analyses. Results 253 women answered the questionnaire, 12.3 ± 4% (Confidence Interval [CI] 95%) of whom presented symptoms compatible with a high probability of being diagnosed with lipedema. Furthermore, anxiety, depression, hypertension, and anemia were also correlated with a high probability of the diagnosis. Conclusions The estimated prevalence of lipedema in the population of Brazilian women is 12.3%. , Resumo Contexto O lipedema é caracterizado por deposição anormal de gordura em glúteos e pernas bilateralmente, que pode ser acompanhada por edema, dor e sensibilidade ao toque. Ainda é frequentemente confundido com condições mais frequentes, como obesidade e linfedema. A prevalência estimada na Europa varia entre 0,06% e 39%. Objetivos Avaliar a prevalência do lipedema na população brasileira e identificar fatores de saúde relacionados a essa doença. Métodos Foi aplicado um questionário de rastreamento on-line, previamente validado em amostra representativa da população geral. O questionário de rastreamento foi distribuído e aplicado em voluntárias anônimas representativas da população geral brasileira por software dedicado a análises populacionais. Resultados Um total de 253 mulheres respondeu ao questionário, e 12,3 ± 4% (intervalo de confiança de 95%) apresentaram sintomatologia compatível com alta probabilidade de diagnóstico de lipedema. Ansiedade, depressão, hipertensão e anemia foram correlacionadas com a alta probabilidade diagnóstica da doença. Conclusões A prevalência estimada do lipedema na população de mulheres brasileiras é de 12,3%.

Lipohyperplasia dolorosa (LiDo) - commonly referred to as lipedema - is a painful disproportionate but symmetrical fat distribution disorder of the extremities. An accompanying proportional symmetrical adipose tissue proliferation in the sense of coincident obesity can complicate the diagnosis and therapy of LiDo. Surprisingly, no valid anthropometric parameters are used to determine this obesity percentage. The often used parameter body mass index (BMI) lacks construct validity. An alternative is the waist-toheight ratio (WHtR).