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Frontiers in Veterinary Science 2021Fluid overload (FO) is characterized by hypervolemia, edema, or both. In clinical practice it is usually suspected when a patient shows evidence of pulmonary edema,... (Review)
Review
Fluid overload (FO) is characterized by hypervolemia, edema, or both. In clinical practice it is usually suspected when a patient shows evidence of pulmonary edema, peripheral edema, or body cavity effusion. FO may be a consequence of spontaneous disease, or may be a complication of intravenous fluid therapy. Most clinical studies of the association of FO with fluid therapy and risk of harm define it in terms of an increase in body weight of at least 5-10%, or a positive fluid balance of the same magnitude when fluid intake and urine output are measured. Numerous observational clinical studies in humans have demonstrated an association between FO, adverse events, and mortality, as have two retrospective observational studies in dogs and cats. The risk of FO may be minimized by limiting resuscitation fluid to the smallest amount needed to optimize cardiac output and then limiting maintenance fluid to the amount needed to replace ongoing normal and pathological losses of water and sodium.
PubMed: 34268347
DOI: 10.3389/fvets.2021.668688 -
Frontiers in Cardiovascular Medicine 2022Congestive heart failure (HF) is a complex disease state characterized by impaired ventricular function and insufficient peripheral blood supply. The resultant reduced... (Review)
Review
Congestive heart failure (HF) is a complex disease state characterized by impaired ventricular function and insufficient peripheral blood supply. The resultant reduced blood flow characterizing HF promotes activation of neurohormonal systems which leads to fluid retention, often exhibited as pulmonary congestion, peripheral edema, dyspnea, and fatigue. Despite intensive research, the exact mechanisms underlying edema formation in HF are poorly characterized. However, the unique relationship between the heart and the kidneys plays a central role in this phenomenon. Specifically, the interplay between the heart and the kidneys in HF involves multiple interdependent mechanisms, including hemodynamic alterations resulting in insufficient peripheral and renal perfusion which can lead to renal tubule hypoxia. Furthermore, HF is characterized by activation of neurohormonal factors including renin-angiotensin-aldosterone system (RAAS), sympathetic nervous system (SNS), endothelin-1 (ET-1), and anti-diuretic hormone (ADH) due to reduced cardiac output (CO) and renal perfusion. Persistent activation of these systems results in deleterious effects on both the kidneys and the heart, including sodium and water retention, vasoconstriction, increased central venous pressure (CVP), which is associated with renal venous hypertension/congestion along with increased intra-abdominal pressure (IAP). The latter was shown to reduce renal blood flow (RBF), leading to a decline in the glomerular filtration rate (GFR). Besides the activation of the above-mentioned vasoconstrictor/anti-natriuretic neurohormonal systems, HF is associated with exceptionally elevated levels of atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP). However, the supremacy of the deleterious neurohormonal systems over the beneficial natriuretic peptides (NP) in HF is evident by persistent sodium and water retention and cardiac remodeling. Many mechanisms have been suggested to explain this phenomenon which seems to be multifactorial and play a major role in the development of renal hyporesponsiveness to NPs and cardiac remodeling. This review focuses on the mechanisms underlying the development of edema in HF with reduced ejection fraction and refers to the therapeutic maneuvers applied today to overcome abnormal salt/water balance characterizing HF.
PubMed: 36237903
DOI: 10.3389/fcvm.2022.933215 -
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