Chronic Edema Management of the Lower Extremities.

Peripheral edema is a prevalent condition affecting patients dealing with an assortment of health conditions, such as congestive heart failure (CHF), liver disease, venous insufficiency, and postoperative surgical complications. Edema can present in a variety of ways, ranging from mild localized symptoms to severely debilitating forms that impact patients' daily lives. Despite the vast number of publications addressing the underlying causes of peripheral edema, there seems to be an absence of literature that presents the effectiveness and compliance of current management techniques. This paper aims to condense the current literature on the effectiveness and compliance of current edema management approaches across various common etiologies, with the intention of identifying alternative therapies that could enhance the quality of care for patients with chronic lower extremity edema. Several promising new therapies such as exogenous calf muscle stimulation, leg raise exercises, high-dose albumin injections, and device-based negative pressure lymph drainage (NPLD), deviate from the current established standard of care. This scoping review revealed diverse treatment methods tailored to the specific underlying etiology of edema. The use of diuretics and vasodilators has shown benefits in treating CHF-induced edema but failed to alleviate and prevent the recurrence of edema in hospitalized and recently discharged patients. Albumin injections have emerged as a potential alternative treatment for edema due to liver disease, addressing hypoalbuminemia symptoms caused by liver failure. Patients with vascular causes of edema are efficaciously treated conservatively with compression stockings, although patient adherence remains a hurdle. For postoperative edema, device-based NPLD appears promising, with potential benefits over elastic bandage wraps and kinesiology taping.

Popliteal Cyst Compressive Tibial Neuropathy and Venous Insufficiency: A Case Report.

Popliteal cysts are a collection of synovial fluid found in the popliteal fossa that typically form in adults in association with traumatic injuries, degenerative conditions, or inflammatory arthritis of the knee. While often asymptomatic, popliteal cysts may become problematic as enlarging and ruptured cysts may compress surrounding neurovascular structures, resulting in lower extremity edema or peripheral neuropathy. We report a unique case of a symptomatic popliteal cyst in a patient with both compressive neuropathy and venous congestion in the setting of a non-ruptured popliteal cyst after a surgically repaired intraarticular injury. Magnetic resonance imaging (MRI) showed a synovial cyst abutting the posterior neurovascular bundle and evidence of avascular necrosis. An open posterior cyst decompression was done, and the patient was able to report significant symptomatic improvement over the course of two weeks postoperatively. The previously noted varicose veins also demonstrated noticeable resolution. While relatively common, popliteal cysts may require prompt surgical decompression in order to provide effective symptomatic relief.

Rapid response of thyroid eye disease, peripheral edema, and acropathy to teprotumumab infusion.

Purpose: We present a case of rapid improvement in symptoms of thyroid eye disease and amelioration of worsening peripheral edema and acropathy with infusion of teprotumumab, a monoclonal antibody targeting the insulin-like growth factor-1 receptor. Observations: A 66 year old female with history of Hashimoto thyroiditis developed progressive thyroid eye disease (TED), peripheral edema, and acropathy attributable to acute Graves disease. Her signs and symptoms, refractory to oral steroid and diuretic therapy, rapidly improved following a standard dosing regimen of teprotumumab (one infusion 10 mg/kg then seven infusions 20 mg/kg) to resolution. Conclusions & importance: Teprotumumab, a monoclonal antibody targeting the insulin-like growth factor-1 receptor, is the first medication approved by the FDA for use in TED. Teprotumumab may contribute to the treatment of extraocular manifestations of Graves disease, chief among these peripheral soft tissue manifestations.

Exercise-Induced Fluid Retention, Cardiac Volume Overload, and Peripheral Edema in Ultra-Distance Cyclists.

Introduction: Ultracyclists expose themselves to extreme physical challenges. This study aimed to elucidate the effects of ultracycling on electrolyte and fluid balance and investigate the potential occurrence of peripheral edema. Methods: A total of 4 clinical visits were performed before, during, and after a 6-day bicycle ride in 13 ultracyclists (5 female, 8 male) including serial laboratory analyses of blood and urine, bioelectrical impedance, and echocardiography. Throughout the ride, participants continuously tracked fluid intake, measured extremity circumferences daily, and self-tested urinary electrolytes using a point-of-care testing device. Portrait photos were judged by 20 physicians for occurrence of facial and eyelid edema. Results: Participants covered a mean distance of 1205 km and 19,417 vertical meters. From baseline to day 6, body weight remained stable (P = 0.479); however, body composition changed with increasing total body water (TBW) (+1.98 l ± 1.37, P = 0.003) and plasma volume (+18.86 % ± 10.7, P < 0.001). A significant increase in N-terminal pro brain natriuretic peptide (NT-proBNP) (+297.99 ng/l ± 190.42, P < 0.001) until day 6 indicates concomitant cardiac volume overload. Swelling of face and eyelids peaked on day 5 (both P ≤ 0.033). On recovery, changes partly resolved. Although urinary sodium concentration showed a nadir on day 4 (-32.18 mmol/l ± 23.88, P = 0.022), plasma osmolality (+5.69 mmosmol/kg ± 5.88, P = 0.004) and copeptin (+38.28 pg/ml ± 18.90, P < 0.001) increased steadily until day 6. Conclusion: Ultracycling over multiple days induces extracellular volume expansion, peripheral edema, and cardiac volume overload. Renal sodium and water retention is likely contributing to this condition.

A Rare Case of Constrictive Pericarditis: Inflammatory Myofibroblastic Tumor.

A previously healthy 15-year-old adolescent female presented with dependent edema, ascites, and dyspnea on exertion. The result of her initial evaluation was consistent with constrictive pericarditis in the setting of local low-grade spindle cell sarcoma. She was unresponsive to traditional medical management and required concurrent mass resection and radical pericardiectomy for definitive treatment. (Level of Difficulty: Intermediate.).

Chronic Venous Insufficiency With Emphasis on the Geriatric Population.

The underpinning of Chronic Venous Insufficiency (CVI) is valvular dysfunction, which manifests on a spectrum depending on the severity of insufficiency and duration of the disease. The mainstay of treatment relies on compression therapy of a proper type and intensity. In older adults, special consideration must be taken during the patient encounter to account for age-related factors. This review discusses the clinical presentation, diagnosis, and mimicking of CVI, focusing mainly on older adults. The epidemiology, risk factors, disease burden, and grave complications -- such as thrombosis and ulceration, are reviewed. The physiological impacts of CVI are described, providing the background for treatment strategies, including non-invasive, medical, and surgical therapies. The findings show advanced age to be an important risk factor contributing to CVI and that other age-related factors add to the risk of severe complications. Clinical assessments combined with objective measurements that assess localized skin water using tissue dielectric constant values or whole limb assessments may aid in the differential diagnosis. Furthermore, understanding the mechanism of action of compression therapy, the mainstay of CVI treatment, and its physiological impacts, allows for its informed use in geriatric patients with increased risks of potential compression-related side effects.

Case report: Non-thrombotic iliac vein lesion: an unusual cause of unilateral leg swelling in a patient with endometrial carcinoma.

81-year-old female presented with subacute right lower extremity edema due to iliac vein compression by a markedly enlarged external iliac lymph node later identified as newly relapsed metastatic endometrial carcinoma. The patient underwent a full evaluation of the iliac vein lesion and cancer and had an intravenous stent placed with complete resolution of symptoms post-procedure.

Not So Transient Effusive-Constrictive Pericarditis.

A 63-year-old male patient presented with chest pain and signs of volume overload. His work-up revealed a diagnosis of transient effusive constrictive pericarditis of idiopathic etiology. Despite treatment with optimal medical therapy, he continued to experience persistent symptoms eventually requiring radical pericardiectomy.

Tepotinib: Management of Adverse Events in Patients With MET Exon 14 Skipping Non-Small Cell Lung Cancer.

BACKGROUND: Tepotinib, a highly selective, oral, once-daily MET inhibitor, has been approved for treatment of metastatic MET exon 14 skipping non-small cell lung cancer. OBJECTIVES: This article provides nurse-specific recommendations for identification and management of tepotinib adverse events (AEs). METHODS: Guidance on monitoring and proactive/reactive AE management was developed based on published literature and real-world nursing experience. Case studies of VISION trial participants were summarized to illustrate key principles. FINDINGS: Tepotinib AEs are generally mild to moderate and manageable, and can include peripheral edema, hypoalbuminemia, nausea, diarrhea, and creatinine increase. Alongside supportive care, tepotinib interruption and dose reduction is recommended for grade 3 AEs. For peripheral edema, proactive monitoring is crucial, and treatment interruption (including frequent, short treatment holidays) should be considered early. Nursing management of tepotinib AEs includes proactive monitoring, patient education, and interprofessional team coordination.

Acute Onset of Remitting Seronegative Symmetrical Synovitis With Pitting Edema (RS3PE) Two Weeks After COVID-19 Vaccination With mRNA-1273 With Possible Activation of Parvovirus B19: A Case Report With Literature Review.

Remitting seronegative symmetrical synovitis with pitting edema (RS3PE) is a rare clinical entity characterized by "remitting," "seronegative," and "symmetrical" synovitis with pitting edema on the dorsum of the hands and feet. Although rheumatic or malignant diseases are diseases that are known to coexist with RS3PE, other factors such as medication, infection, and vaccination have been reported to be associated with RS3PE. Here, we present a case of RS3PE syndrome that satisfied all four diagnostic criteria of RS3PE (pitting edema in the limbs, acute onset, age ≥ 50 years, and/or rheumatoid factor negativity) after mRNA-1273 SARS-CoV-2 vaccination.

Massive adrenocortical carcinoma presenting as peripheral edema: a case report.

BACKGROUND: Adrenocortical carcinoma is a rare, but potentially lethal, malignancy that is usually detected as an incidental finding on abdominal imaging studies or owing to hormonal complications. This report recounts an unusual presentation with leg edema due to compression of the inferior vena cava. The dearth of proven effective treatment is also addressed. CASE PRESENTATION: A 65-year-old White male physician presented with severe, bilateral pitting edema that extended from the toes to the thighs. It progressed over several months. He also experienced paroxysmal dyspnea. Evaluation of cardiac, hepatic, and renal function failed to determine a cause. Computed tomography revealed a tumor above the right kidney, with compression of the intrahepatic inferior vena cava and upstream distension. Serum cortisol and dehydroepiandrosterone sulfate concentrations were elevated, 24-hour urinary cortisol level was elevated, and serum adrenocorticotropic hormone and testosterone concentrations were suppressed. A 27-cm tumor, the right lobe of the liver, the right kidney, and 26 lymph nodes were resected. Histological study confirmed the diagnosis of adrenocortical carcinoma. Ki67 proliferation index was 26.7% (worse prognosis associated with index > 10%). Lymph nodes were negative for malignancy, but a separate 2.7-cm tumor was found near the renal hilum. Adjuvant mitotane chemotherapy was prescribed. Serum testosterone concentration returned to normal. High-dose hydrocortisone administration was needed because of adrenal suppression and CYP 3A4 induction by mitotane. CONCLUSION: Imaging of the abdomen and pelvis should be conducted in cases of unexplained leg edema. In this case, a large adrenal cancer compressed the vena cava. Iron deficiency followed resection of the large tumor. Advanced stages of adrenocortical carcinoma are associated with poor prognosis. Mitotane chemotherapy is a standard but unproven adjuvant treatment that is associated with many complications, and its induction of hepatic CYP 3A4 enzymes necessitates adjustment of other medications.

Safety of MET Tyrosine Kinase Inhibitors in Patients With MET Exon 14 Skipping Non-small Cell Lung Cancer: A Clinical Review.

MET exon 14 (METex14) skipping mutations occur in 3% to 4% of non-small cell lung cancer (NSCLC) cases. Currently, four oral MET tyrosine kinase inhibitors (TKIs) are in use for the treatment of patients with METex14 skipping NSCLC (tepotinib, capmatinib, savolitinib, and crizotinib). To support optimal management of METex14 skipping NSCLC in this typically older patient population, the safety profiles of these treatment options are reviewed here. Published safety data from prospective clinical trials with MET TKIs in patients with METex14 skipping NSCLC were reviewed. Treatment-related adverse events (TRAEs) occurring in ≥ 10% of patients were reported where feasible. Guidance on clinical monitoring and management of key MET TKI TRAEs and drug-drug interactions is provided. Across the clinical trials, safety data for MET TKIs were reported for 442 patients with METex14 skipping. Peripheral edema was the most reported TRAE (50%-63% of patients; grade ≥ 3: 1%-11%), followed by nausea (26%-46% of patients; grade ≥ 3: 0%-1%). TRAEs led to dose reductions in 33% to 38% of patients and to discontinuation in 7% to 14% of patients, across the MET TKIs. Considerations on interpreting available safety data are provided, along with insights into monitoring and managing specific MET TKI TRAEs of interest and drug-drug interactions. Overall, MET TKIs are tolerable treatment options for patients with METex14 skipping NSCLC, an older population for whom chemo- or immuno-therapy may not be an effective nor tolerable option. More data regarding the effectiveness of safety interventions and management strategies are needed.

Combined Use of Calcium-channel Blockers With Ombitasvir/Paritaprevir/Ritonavir Exacerbates Peripheral Edema in Elderly Japanese Patients.

BACKGROUND/AIM: The antiviral agent ritonavir is a substrate for cytochrome P450 3A4 (CYP3A4); therefore, concomitant use of CYP3A4-metabolising drugs might cause adverse reactions to this drug. We investigated the plasma level of calcium channel blockers (CCBs) as CYP3A4 substrates and peripheral edema as a potential adverse drug reaction possibly caused by the anti-hepatitis C virus (HCV) regimen of ombitasvir/paritaprevir/ritonavir (OPR) and CCBs. PATIENTS AND METHODS: We enrolled Japanese patients prescribed OPR for HCV infection. Peripheral edema was graded according to the Common Terminology Criteria for Adverse Events ver. 4. Plasma samples were collected on days 0, 7, 14, 28, and 42 after antiviral treatment, at the trough level. RESULTS: Out of 52 patients, 64% experienced grade 1 or grade 2 peripheral edema, but not grade 3. Concomitant use of CCBs significantly increased the emergence of grade 2 edema (62%), compared with patients treated solely with OPR (48%). The use of OPR significantly increased the plasma concentration of amlodipine. CONCLUSION: Peripheral edema in patients treated with OPR and CCBs, although tolerable, should be closely monitored.

A rare presentation of peripheral edema and ascites in a 10-year-old child with brucellosis: A case report.

INTRODUCTION: and importance: Brucellosis is a common infection in Mediterranean region that manifests with various symptoms. Brucellosis should be considered as a possible cause of recurrent fever even if the symptoms are not suggestive of brucellosis. CASE PRESENTATION: We report a case of 10-year-old child with no significant past medical history who presented with a 4-day period peripheral edema and ascites without fever, arthralgia or abdominal pain. CLINICAL DISCUSSION: Proper investigations showed normal cardiac and renal functions; ultrasonography showed no portal vein hypertension. Albumin and total protein were also within normal. Complete blood count revealed pancytopenia; bone marrow aspiration and biopsy revealed hypercellularity that could be attributed to hypersplenism as a possible cause. Liver biopsy revealed non-specific inflammatory findings and also did not lead to a definite diagnosis. While broadening the scope of deferential diagnosis in order to reach a final diagnosis, Wright serum agglutination was tested positive (1/640) and we diagnosed a brucellosis infection. A proper management with Antibiotics ensued; the patient had uneventful recovery on treatment until complete clinical and imaging resolution of signs and symptoms. CONCLUSION: Although brucellosis is considered a multi-systemic disease with atypical presentations, early diagnosis of brucellosis with management causes rapid recovery and favorable prognosis. We report a case of ascites and edema in context of Brucella infection which was completely resolved after treatment. This condition is rare especially in previously healthy child and after excluding other possible causes. We aim to share our case to keep brucellosis in mind as a differential diagnosis when dealing with infectious diseases with non-specific symptoms.

Asociación del signo de Godet con la medición por ultrasonido del edema periférico y balance de líquidos. El resurgir de la clínica / Association of the Godet's sign with ultrasound measurement of peripheral edema and fluid balance. The resurrection of the clinic / Associação do sinal de Godet com medida de ultrassom de edema periférico e equilíbrio hidrográfico. O ressurgimento da clínica

Resumen: Introducción: la administración de líquidos representa una intervención terapéutica de primera línea. Sin embargo, con frecuencia esto conduce a sobrecarga de líquidos, lo que se asocia con alta mortalidad. Objetivo: describir la asociación del edema periférico medido por ultrasonido con el balance hídrico acumulado diario y comparar su correlación con el signo de Godet. Material y métodos: pacientes adultos que ingresaron a la unidad de terapia intensiva (UTI) con más de 24 h de estancia y datos clínicos de sobrecarga hídrica. Diseño: es un estudio observacional, prospectivo, longitudinal, simple ciego, piloto. Cálculo de muestra n = 72 pacientes. Resultados: la mediana de edad fue de 45 años, 96.6% estuvo con ventilación mecánica, todos los pacientes presentaron desenlace en el análisis multivariado ajustado y se detectó que hay asociación del signo de Godet con la medición del edema por ultrasonido, observando una fuerte correlación explicada por una R2 87% p = 0.0001. Por último, se realizó otra regresión de los mililitros del balance hídrico acumulado asociada con los milímetros del edema medidos por ultrasonido, encontrando una R2 82% (IC 95% 1.47-3.70 p = 0.0001) interpretado como una fuerte asociación. Conclusiones: el signo de Godet se asoció fuertemente con los milímetros del edema medido por ultrasonido, además tiene una fuerte asociación entre el balance de líquido acumulado por día con los milímetros de edema que se incrementan en el tejido periférico por sobrecarga al día.

Abstract: Introduction: the administration of fluids represents a first-line therapeutic intervention. However, this often leads to fluid overload, which is associated with high mortality. Objective: to describe the association of peripheral edema measured by ultrasound with daily accumulated water balance and to compare its correlation with Godet's sign. Material and methods: adult patients admitted to the intensive care unit with more than 24 hours of stay and clinical data of fluid overload. Design: this is an observational, prospective, longitudinal, single-blind, pilot study. Sample calculation n = 72 patients. Results: the median age was 45 years, 96.6% were on mechanical ventilation, all patients presented their outcome in the adjusted multivariate analysis, and it was found that there is an association of Godet's sign with the measurement of edema by ultrasound, finding a strong correlation explained by an R2 87% p = 0.0001. Finally, another regression of milliliters of accumulated water balance associated with milliliters of edema measured by ultrasound was performed, finding an R2 82% (95% CI 1.47-3.70 p = 0.0001) interpreted as a strong association. Conclusions: Godet's sign was strongly associated with the millimeters of edema measured by ultrasound; it also has a strong association between the balance of fluid accumulated per day with the millimeters of edema that increase in the peripheral tissue due to overload per day.

Resumo: Introdução: a administração de fluidos representa uma intervenção terapêutica de primeira linha. No entanto, isso freqüentemente leva à sobrecarga hidríca, que está associada a alta mortalidade. Objetivo: descrever a associação do edema periférico medido pela ultrassonografia com o balanço hídrico diário acumulado e comparar sua correlação com o sinal de Godet. Material e métodos: pacientes adultos admitidos na unidade de terapia intensiva (UTI) com mais de 24 horas de internação e com quadro clínico de sobrecarga hídrica. Desenho: é um estudo observacional, prospectivo, longitudinal, simples-cego, piloto. Cálculo amostra n = 72 pacientes. Resultados: a idade média foi de 45 anos, 96.6% estavam em ventilação mecânica, todos os pacientes apresentaram seu desfecho na análise multivariada ajustada e constatou-se que há associação do sinal de Godet com a medida do edema pela ultrassonografia, encontrando forte correlação explicado por um R2 87% p = 0.0001. Finalmente, realizou-se outra regressão dos mililitros de balanço hídrico acumulado associado aos milímetros de edema medidos por ultrassom, encontrando um R2 82% (IC 95% 1.47-3.70 p = 0.0001) interpretado como uma forte associação. Conclusões: o sinal de Godet foi fortemente associado com os milímetros de edema medidos por ultrassom, também tem forte associação entre o balanço hídrico acumulado por dia com os milímetros de edema que aumentam nos tecidos periféricos devido à sobrecarga por dia.

Edema-like symptoms are common in ultra-distance cyclists and driven by overdrinking, use of analgesics and female sex - a study of 919 athletes.

BACKGROUND: Ultra-endurance cyclists regularly report various extents of bodily decline during long-distance bicycle rides, including potential kidney function-related symptoms such as swelling of body parts and urine changes. This study aimed to assess the prevalence of these symptoms in a representative cohort of ultra-endurance cyclists and shed light on potential predictors related to the ride, the rider and the rider's behavior. METHODS: Between November 26 and December 14, 2020, 1350 people participated in an online survey investigating potential kidney-related symptoms of ultra-distance cycling. Frequency and severity of edema-like ("swelling") symptoms and perceived changes in urine output, concentration and quality were associated with ride-related factors, demographic parameters and rider behavior-related variables. RESULTS: A total of 919 participants met the predefined inclusion criteria. The majority (N = 603, 65.6%) stated that they suffered from at least one potential kidney function-related symptom, out of which 498 (54.2%) stated one or more edema-like ("swelling") symptoms. In correlational and multiple regression analyses, female sex, intake of analgesics and drinking strategies correlated with swelling symptoms. Further analyses indicated that drinking due to thirst and/or drinking adapted to ambient sweating and temperature negatively correlated with swelling symptoms, whereas "drinking as much as possible" enhanced these. Intake of analgesics was moderately positively correlated with swelling symptoms. CONCLUSIONS: According to our survey, edema-like symptoms occur in the majority of ultra-distance cyclists and female sex, drinking strategy and intake of analgesic drugs are major predictors thereof. Studies are needed to investigate the underlying pathophysiological processes of such symptoms.

Objective determination of peripheral edema in heart failure patients using short-wave infrared molecular chemical imaging.

SIGNIFICANCE: Peripheral pitting edema is a clinician-administered measure for grading edema. Peripheral edema is graded 0, 1 + , 2 + , 3 + , or 4 + , but subjectivity is a major limitation of this technique. A pilot clinical study for short-wave infrared (SWIR) molecular chemical imaging (MCI) effectiveness as an objective, non-contact quantitative peripheral edema measure is underway. AIM: We explore if SWIR MCI can differentiate populations with and without peripheral edema. Further, we evaluate the technology for correctly stratifying subjects with peripheral edema. APPROACH: SWIR MCI of shins from healthy subjects and heart failure (HF) patients was performed. Partial least squares discriminant analysis (PLS-DA) was used to discriminate the two populations. PLS regression (PLSR) was applied to assess the ability of MCI to grade edema. RESULTS: Average spectra from edema exhibited higher water absorption than non-edema spectra. SWIR MCI differentiated healthy volunteers from a population representing all pitting edema grades with 97.1% accuracy (N = 103 shins). Additionally, SWIR MCI correctly classified shin pitting edema levels in patients with 81.6% accuracy. CONCLUSIONS: Our study successfully achieved the two primary endpoints. Application of SWIR MCI to monitor patients while actively receiving HF treatment is necessary to validate SWIR MCI as an HF monitoring technology.

Capmatinib successfully overcomes tepotinib-induced intolerable peripheral edema.

In May 2020 and February 2021, capmatinib and tepotinib, respectively were approved by the Food and Drug Administration (FDA) for the treatment of metastatic non-small cell lung carcinoma harboring mesenchymal-epithelial transition (MET) exon 14 skipping alterations. Herein, we present a case of intolerable peripheral edema caused by tepotinib, in which MET inhibitor could be continued by switching to capmatinib. Peripheral edema has been identified as one of the most common adverse events in capmatinib and tepotinib; however, there is no unified management for this adverse event. This is the first report that two MET inhibitors have different effects on the development of peripheral edema, and that the MET inhibitors can be continued by switching these drugs.

Evaluation of the Accuracy of a Video and AI Solution to Measure Lower Leg and Foot Volume.

BACKGROUND AND OBJECTIVES: Peripheral edema, change in foot volume, is a marker of congestion which is regularly assessed in routine clinical care. A novel video and Artificial Intelligence (AI)-based solution used to measure anatomical parameters, including volume and foot length, Heartfelt HF-1, is compared to the laboratory gold standard (water displacement) and a medical disposable measuring tape. DESIGN SETTING PARTICIPANTS AND MEASUREMENTS: 58 healthy volunteers were measured with the Heartfelt device; 22 were also measured with the water displacement method and 19 with the medical tape. Bland-Altman analysis was performed for both volumes and foot lengths. Left/right foot differences provided covariance-corrected standard error of measurement (ccSEM) and minimum detectable difference (MDD) for each measurement method. RESULTS: Heartfelt device measured volumes displayed excellent correlation to the gold standard (water displacement), with Bland-Altman bias of +32mL ±81mL (1 std.dev). Clinically important change in foot volume is approximately 13%. Water displacement yielded ccSEM of ± 32.1mL and MDD of 90mL (6.7% of average foot volume), while the Heartfelt device measurements yielded ccSEM of ±12.6mL and MDD of 35.3mL (2.6% of average foot volume). The majority of differences were attributable to manual positioning of the patient foot in the waterbath. CONCLUSION: This study finds that in clinical and non-clinical settings, the Heartfelt device measures foot volume and length more precisely than either the water displacement technique or manual foot length measurements using a medical disposable tape, while having an excellent agreement with these methods.

Selumetinib side effects in children treated for plexiform neurofibromas: first case reports of peripheral edema and hair color change.

BACKGROUND: Plexiform neurofibromas (PNs) are congenital tumors that affect around 50 % of the subjects with neurofibromatosis type 1. Despite being histologically benign, PNs can grow rapidly, especially in the pediatric age, and cause severe morbidities. In the past, various therapeutic approaches have been proposed to treat these masses, none of which obtained valuable results. Selumetinib, an inhibitor of mitogen-activated protein kinase (MEK) 1 and 2, has been the first molecule to demonstrate the ability of tackling the growth of PNs. The drug's most common side effects, which usually are mild or moderate, include gastrointestinal symptoms (diarrhea, abdominal pain), dermatologic manifestations (maculo-papular and acneiform rash, paronychia, mucositis), and various laboratory test abnormalities (elevation of creatine kinase and aminotransferase). CASES PRESENTATION: We report two previously undescribed adverse events in pediatric patients: peripheral edema and hair color change. The first case of peripheral edema occurred in a 7-year-old boy affected by a severe form of NF1, after two years of treatment with selumetinib at the standard dose (25 mg/m2twice a day). The edema involved the right leg, and the patient did not complain of pain. The second case of peripheral edema occurred in a 12-year-old girl after six months of therapy with selumetinib at the standard dose, involving her lower left leg. The patient initially complained of pain in that area, but it gradually and spontaneously resolved. In both patients, all the radiological exams, including lymphoscintigraphy, pelvic and abdominal ultrasound, and doppler ultrasound of the affected limb, as well as blood tests, revealed no abnormalities. Hair color change appeared in a 4-year-old boy after six months of therapy at the standard dose. The boy's hair, whose natural color was dark blonde, became lighter in some areas. Despite the appearance of these side effects, all the patients and their families decided to continue the treatment with selumetinib, in considerations of its clinical benefits. CONCLUSIONS: Since the use of selumetinib to treat plexiform neurofibromas is increasing in the pediatric population, clinicians should be aware of its side effects, so to decide whether continuing the treatment, reducing the dose or even interrupting it, when appropriate.