-
American Family Physician Nov 2022Edema is a common clinical sign that may indicate numerous pathologies. As a sequela of imbalanced capillary hemodynamics, edema is an accumulation of fluid in the...
Edema is a common clinical sign that may indicate numerous pathologies. As a sequela of imbalanced capillary hemodynamics, edema is an accumulation of fluid in the interstitial compartment. The chronicity and laterality of the edema guide evaluation. Medications (e.g., antihypertensives, anti-inflammatory drugs, hormones) can contribute to edema. Evaluation should begin with obtaining a basic metabolic panel, liver function tests, thyroid function testing, brain natriuretic peptide levels, and a urine protein/creatinine ratio. Validated decision rules, such as the Wells and STOP-Bang (snoring, tired, observed, pressure, body mass index, age, neck size, gender) criteria, can guide decision-making regarding the possibility of venous thromboembolic disease and obstructive sleep apnea, respectively. Acute unilateral lower-extremity edema warrants immediate evaluation for deep venous thrombosis with a d-dimer test or compression ultrasonography. For patients with chronic bilateral lower-extremity edema, duplex ultrasonography with reflux can help diagnose chronic venous insufficiency. Patients with pulmonary edema or elevated brain natriuretic peptide levels should undergo echocardiography to assess for heart failure. Lymphedema is often a clinical diagnosis; lymphoscintigraphy can be performed if the diagnosis is unclear. Treatment of edema is specific to the etiology. Diuretics are effective but should be used only for systemic causes of edema. Ruscus extract and horse chestnut seed demonstrate moderate-quality evidence to improve edema from chronic venous insufficiency. Compression therapy is effective for most causes of edema.
Topics: Humans; Natriuretic Peptide, Brain; Edema; Venous Insufficiency; Lymphedema; Primary Health Care
PubMed: 36379502
DOI: No ID Found -
The New England Journal of Medicine Sep 2020Among patients with non-small-cell lung cancer (NSCLC), exon 14 skipping mutations occur in 3 to 4% and amplifications occur in 1 to 6%. Capmatinib, a selective...
BACKGROUND
Among patients with non-small-cell lung cancer (NSCLC), exon 14 skipping mutations occur in 3 to 4% and amplifications occur in 1 to 6%. Capmatinib, a selective inhibitor of the MET receptor, has shown activity in cancer models with various types of MET activation.
METHODS
We conducted a multiple-cohort, phase 2 study evaluating capmatinib in patients with -dysregulated advanced NSCLC. Patients were assigned to cohorts on the basis of previous lines of therapy and status ( exon 14 skipping mutation or amplification according to gene copy number in tumor tissue). Patients received capmatinib (400-mg tablet) twice daily. The primary end point was overall response (complete or partial response), and the key secondary end point was response duration; both end points were assessed by an independent review committee whose members were unaware of the cohort assignments.
RESULTS
A total of 364 patients were assigned to the cohorts. Among patients with NSCLC with a exon 14 skipping mutation, overall response was observed in 41% (95% confidence interval [CI], 29 to 53) of 69 patients who had received one or two lines of therapy previously and in 68% (95% CI, 48 to 84) of 28 patients who had not received treatment previously; the median duration of response was 9.7 months (95% CI, 5.6 to 13.0) and 12.6 months (95% CI, 5.6 to could not be estimated), respectively. Limited efficacy was observed in previously treated patients with amplification who had a gene copy number of less than 10 (overall response in 7 to 12% of patients). Among patients with amplification and a gene copy number of 10 or higher, overall response was observed in 29% (95% CI, 19 to 41) of previously treated patients and in 40% (95% CI, 16 to 68) of those who had not received treatment previously. The most frequently reported adverse events were peripheral edema (in 51%) and nausea (in 45%); these events were mostly of grade 1 or 2.
CONCLUSIONS
Capmatinib showed substantial antitumor activity in patients with advanced NSCLC with a exon 14 skipping mutation, particularly in those not treated previously. The efficacy in -amplified advanced NSCLC was higher in tumors with a high gene copy number than in those with a low gene copy number. Low-grade peripheral edema and nausea were the main toxic effects. (Funded by Novartis Pharmaceuticals; GEOMETRY mono-1 ClinicalTrials.gov number, NCT02414139.).
Topics: Adult; Aged; Aged, 80 and over; Antineoplastic Agents; Benzamides; Carcinoma, Non-Small-Cell Lung; Edema; Exons; Female; Gene Dosage; Humans; Imidazoles; Lung Neoplasms; Male; Middle Aged; Mutation; Nausea; Protein Kinase Inhibitors; Proto-Oncogene Proteins c-met; Triazines
PubMed: 32877583
DOI: 10.1056/NEJMoa2002787 -
Advances in Kidney Disease and Health Mar 2023The development of peripheral edema can often pose a significant diagnostic and therapeutic challenge for practitioners due to its association with a wide variety of... (Review)
Review
The development of peripheral edema can often pose a significant diagnostic and therapeutic challenge for practitioners due to its association with a wide variety of underlying disorders ranging in severity. Updates to the original Starling's principle have provided new mechanistic insights into edema formation. Additionally, contemporary data highlighting the role of hypochloremia in the development of diuretic resistance provide a possible new therapeutic target. This article reviews the pathophysiology of edema formation and discusses implications for treatment.
Topics: Humans; Causality; Acid-Base Imbalance; Diuretics; Edema
PubMed: 36868727
DOI: 10.1053/j.akdh.2022.12.002 -
Critical Care (London, England) May 2023Fluid normally exchanges freely between the plasma and interstitial space and is returned primarily via the lymphatic system. This balance can be disturbed by diseases... (Review)
Review
Fluid normally exchanges freely between the plasma and interstitial space and is returned primarily via the lymphatic system. This balance can be disturbed by diseases and medications. In inflammatory disease states, such as sepsis, the return flow of fluid from the interstitial space to the plasma seems to be very slow, which promotes the well-known triad of hypovolemia, hypoalbuminemia, and peripheral edema. Similarly, general anesthesia, for example, even without mechanical ventilation, increases accumulation of infused crystalloid fluid in a slowly equilibrating fraction of the extravascular compartment. Herein, we have combined data from fluid kinetic trials with previously unconnected mechanisms of inflammation, interstitial fluid physiology and lymphatic pathology to synthesize a novel explanation for common and clinically relevant examples of circulatory dysregulation. Experimental studies suggest that two key mechanisms contribute to the combination of hypovolemia, hypoalbuminemia and edema; (1) acute lowering of the interstitial pressure by inflammatory mediators such as TNFα, IL-1β, and IL-6 and, (2) nitric oxide-induced inhibition of intrinsic lymphatic pumping.
Topics: Humans; Hypovolemia; Hypoalbuminemia; Edema; Respiration, Artificial; Crystalloid Solutions
PubMed: 37245039
DOI: 10.1186/s13054-023-04496-5 -
The New England Journal of Medicine Sep 2020A splice-site mutation that results in a loss of transcription of exon 14 in the oncogenic driver occurs in 3 to 4% of patients with non-small-cell lung cancer (NSCLC)....
BACKGROUND
A splice-site mutation that results in a loss of transcription of exon 14 in the oncogenic driver occurs in 3 to 4% of patients with non-small-cell lung cancer (NSCLC). We evaluated the efficacy and safety of tepotinib, a highly selective MET inhibitor, in this patient population.
METHODS
In this open-label, phase 2 study, we administered tepotinib (at a dose of 500 mg) once daily in patients with advanced or metastatic NSCLC with a confirmed exon 14 skipping mutation. The primary end point was the objective response by independent review among patients who had undergone at least 9 months of follow-up. The response was also analyzed according to whether the presence of a exon 14 skipping mutation was detected on liquid biopsy or tissue biopsy.
RESULTS
As of January 1, 2020, a total of 152 patients had received tepotinib, and 99 patients had been followed for at least 9 months. The response rate by independent review was 46% (95% confidence interval [CI], 36 to 57), with a median duration of response of 11.1 months (95% CI, 7.2 to could not be estimated) in the combined-biopsy group. The response rate was 48% (95% CI, 36 to 61) among 66 patients in the liquid-biopsy group and 50% (95% CI, 37 to 63) among 60 patients in the tissue-biopsy group; 27 patients had positive results according to both methods. The investigator-assessed response rate was 56% (95% CI, 45 to 66) and was similar regardless of the previous therapy received for advanced or metastatic disease. Adverse events of grade 3 or higher that were considered by investigators to be related to tepotinib therapy were reported in 28% of the patients, including peripheral edema in 7%. Adverse events led to permanent discontinuation of tepotinib in 11% of the patients. A molecular response, as measured in circulating free DNA, was observed in 67% of the patients with matched liquid-biopsy samples at baseline and during treatment.
CONCLUSIONS
Among patients with advanced NSCLC with a confirmed exon 14 skipping mutation, the use of tepotinib was associated with a partial response in approximately half the patients. Peripheral edema was the main toxic effect of grade 3 or higher. (Funded by Merck [Darmstadt, Germany]; VISION ClinicalTrials.gov number, NCT02864992.).
Topics: Adult; Aged; Aged, 80 and over; Antineoplastic Agents; Carcinoma, Non-Small-Cell Lung; Edema; Exons; Female; Humans; Lung Neoplasms; Male; Middle Aged; Mutation; Piperidines; Protein Kinase Inhibitors; Proto-Oncogene Proteins c-met; Pyridazines; Pyrimidines
PubMed: 32469185
DOI: 10.1056/NEJMoa2004407 -
Journal of Surgical Orthopaedic Advances 2016Complex regional pain syndrome (CRPS) is a neurological disorder producing peripheral neurogenic inflammatory process in hands and feet distal to injury, which may lead... (Review)
Review
Complex regional pain syndrome (CRPS) is a neurological disorder producing peripheral neurogenic inflammatory process in hands and feet distal to injury, which may lead to severe disability. Symptoms are often out of proportion to the initiating event and not limited to a single peripheral nerve. There is no gold standard in diagnosis of this entity, and a multidisciplinary approach is necessary for proper diagnosis. Magnetic resonance imaging (MRI) is one of the most useful diagnostic modalities in early stages of CRPS (when clinical diagnosis is most difficult), the most desirable time to diagnose this disorder to expedite treatment and improve function. This article discusses MRI findings of CRPS, particularly in the early phase, and differential considerations.
Topics: Bone Marrow; Complex Regional Pain Syndromes; Cumulative Trauma Disorders; Edema; Fractures, Stress; Humans; Magnetic Resonance Imaging; Peripheral Nerve Injuries; Reflex Sympathetic Dystrophy
PubMed: 27518298
DOI: No ID Found -
British Journal of Clinical Pharmacology Aug 2021Many drugs are responsible, through different mechanisms, for peripheral oedema. Severity is highly variable, ranging from slight oedema of the lower limbs to anasarca... (Review)
Review
Many drugs are responsible, through different mechanisms, for peripheral oedema. Severity is highly variable, ranging from slight oedema of the lower limbs to anasarca pictures as in the capillary leak syndrome. Although most often noninflammatory and bilateral, some drugs are associated with peripheral oedema that is readily erythematous (eg, pemetrexed) or unilateral (eg, sirolimus). Thus, drug-induced peripheral oedema is underrecognized and misdiagnosed, frequently leading to a prescribing cascade. Four main mechanisms are involved, namely precapillary arteriolar vasodilation (vasodilatory oedema), sodium/water retention (renal oedema), lymphatic insufficiency (lymphedema) and increased capillary permeability (permeability oedema). The underlying mechanism has significant impact on treatment efficacy. The purpose of this review is to provide a comprehensive analysis of the main causative drugs by illustrating each pathophysiological mechanism and their management through an example of a drug.
Topics: Edema; Heart Failure; Humans; Lymphedema; Pharmaceutical Preparations; Vasodilation
PubMed: 33506982
DOI: 10.1111/bcp.14752 -
Journal of Clinical Hypertension... May 2022Dihydropyridine calcium channel blockers (DHPCCBs) are widely used to treat hypertension and chronic coronary artery disease. One common adverse effect of DHPCCBs is... (Meta-Analysis)
Meta-Analysis
Dihydropyridine calcium channel blockers (DHPCCBs) are widely used to treat hypertension and chronic coronary artery disease. One common adverse effect of DHPCCBs is peripheral edema, particularly of the lower limbs. The side effect could lead to dose reduction or discontinuation of the medication. The combination of DHPCCBs and renin-angiotensin system blockers has shown to reduce the risk of DHPCCBs-associated peripheral edema compared with DHPCCBs monotherapy. We performed the current systematic review and network meta-analysis of randomized controlled trials (RCTs) to estimate the rate of peripheral edema with DHPCCBs as a class and with individual DHPCCBs and the ranking of the reduction of peripheral edema. The effects of renin-angiotensin system blockers on DHPCCBs network meta-analysis were created to analyze the ranking of the reduction of peripheral edema. A total of 3312 publications were identified and 71 studies with 56,283 patients were included. Nifedipine ranked highest in inducing peripheral edema (SUCRA 81.8%) and lacidipine (SUCRA 12.8%) ranked the least. All DHPCCBs except lacidipine resulted in higher relative risk (RR) of peripheral edema compared with placebo. Nifedipine plus angiotensin receptor blocker (SUCRA: 92.3%) did not mitigate peripheral edema and amlodipine plus angiotensin-converting enzyme inhibitors (SUCRA: 16%) reduced peripheral edema the most. Nifedipine ranked the highest and lacidipine ranked the lowest amongst DHPCCBs for developing peripheral edema when used for cardiovascular indications. The second or higher generation of DHPCCBs combination with ACEIs or ARBs or diuretics lowered the chance of peripheral edema development compared to single DHPCCB treatment.
Topics: Antihypertensive Agents; Calcium Channel Blockers; Dihydropyridines; Edema; Humans; Hypertension; Network Meta-Analysis; Nifedipine
PubMed: 35234349
DOI: 10.1111/jch.14436 -
Eye (London, England) Aug 2023Diabetic retinopathy (DR) may lead to vision-threatening complications in people living with diabetes mellitus. Decades of research have contributed to our understanding... (Review)
Review
Diabetic retinopathy (DR) may lead to vision-threatening complications in people living with diabetes mellitus. Decades of research have contributed to our understanding of the pathogenesis of diabetic retinopathy from non-proliferative to proliferative (PDR) stages, the occurrence of diabetic macular oedema (DMO) and response to various treatment options. Multimodal imaging has paved the way to predict the impact of peripheral lesions and optical coherence tomography-angiography is starting to provide new knowledge on diabetic macular ischaemia. Moreover, the availability of intravitreal anti-vascular endothelial growth factors has changed the treatment paradigm of DMO and PDR. Areas of research have explored mechanisms of breakdown of the blood-retinal barrier, damage to pericytes, the extent of capillary non-perfusion, leakage and progression to neovascularisation. However, knowledge gaps remain. From this perspective, we highlight the challenges and future directions of research in this field.
Topics: Humans; Diabetic Retinopathy; Macular Edema; Neovascularization, Pathologic; Fluorescein Angiography; Blood-Retinal Barrier; Tomography, Optical Coherence; Diabetes Mellitus
PubMed: 36494431
DOI: 10.1038/s41433-022-02335-5