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BACKGROUND AND PURPOSE: Endothelin-1 (ET-1) receptor A (ETA) antagonists reduce proteinuria and prevent renal outcomes in chronic kidney disease (CKD) patients, but their utility has been limited because of associated fluid retention, resulting in increased heart failure risk. Understanding the mechanisms responsible for fluid retention could result in solutions that preserve renoprotective effects while mitigating fluid retention, but the complexity of the endothelin system has made identification of the underlying mechanisms challenging. APPROACH: We utilized a previously developed mathematical model of ET-1 kinetics, ETA receptor antagonism, kidney function, haemodynamics, and sodium and water homeostasis to evaluate hypotheses for mechanisms of fluid retention with ETA antagonism. To do this, we simulated the RADAR clinical trial of atrasentan in patients with type 2 diabetes and CKD and evaluated the ability of the model to predict the observed decreases in haematocrit, urine albumin creatinine ratio (UACR), mean arterial pressure (MAP), and estimated glomerular filtration rate (eGFR). BACKGROUND AND KEY RESULTS: An effect of ETA antagonism on venodilation and increased venous capacitance was found to be the critical mechanism necessary to reproduce the simultaneous decrease in both MAP and haematocrit observed in RADAR. CONCLUSIONS AND IMPACT: These findings indicate that fluid retention with ETA antagonism may not be caused by a direct antidiuretic effect within the kidney but is instead be an adaptive response to venodilation and increased venous capacity, which acutely tends to reduce cardiac filling pressure and cardiac output, and that fluid retention occurs in an attempt to maintain cardiac filling and cardiac output.

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INTRODUCTION: Docetaxel plus ramucirumab (DTX + RAM) therapy is a standard treatment for previously treated lung cancer, but many adverse events have been reported. This retrospective study was conducted to examine if the side effects of DTX + RAM therapy can be minimized by the combined use of oral dexamethasone (DEX), and to assess the therapeutic effect of DTX + RAM in patients with recurrent lung cancer. METHODS: Forty patients with relapsed non-small cell lung cancer who underwent DTX + RAM therapy were divided into two groups based on the concomitant use of oral DEX, and the therapeutic effects and toxicities in the two groups were compared. RESULTS: The objective response rate (ORR) was significantly better in the DEX group (P = 0.0203). The median progression-free survival (PFS) was 5.20 months vs 2.87 months (P = 0.064) in the DEX and non-DEX groups, respectively. However, the median overall survival (OS) was significantly better in the DEX group (15.17 months vs 7.37 months, P = 0.0317). The frequency of fluid retention within six months of the start of treatment was 10.0% vs 42.5% in the DEX and non-DEX groups, respectively, with the fluid retention rate being significantly higher in the non-DEX group (P = 0.039).Conclusion: Concomitant use of oral DEX during DTX + RAM therapy may facilitate the long-term continuation of treatment and contribute to OS prolongation.

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Anticuerpos Monoclonales Humanizados , Protocolos de Quimioterapia Combinada Antineoplásica , Carcinoma de Pulmón de Células no Pequeñas , Dexametasona , Docetaxel , Neoplasias Pulmonares , Ramucirumab , Humanos , Docetaxel/administración & dosificación , Docetaxel/uso terapéutico , Masculino , Femenino , Dexametasona/administración & dosificación , Dexametasona/uso terapéutico , Estudios Retrospectivos , Anticuerpos Monoclonales Humanizados/administración & dosificación , Anticuerpos Monoclonales Humanizados/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Persona de Mediana Edad , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/patología , Neoplasias Pulmonares/mortalidad , Anciano , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Carcinoma de Pulmón de Células no Pequeñas/patología , Carcinoma de Pulmón de Células no Pequeñas/mortalidad , Adulto , Administración Oral , Recurrencia Local de Neoplasia/tratamiento farmacológico , Resultado del Tratamiento

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BACKGROUND & AIMS: Early identification of worsening HF enables timely adjustments to prevent hospitalization. Recent studies show the HeartLogic™ algorithm detects congestion and reduces HF events. However, it is unclear which patients benefit most. Therefore, this study aims to identify and characterize HF patients who benefit most from CIED-based remote monitoring with HeartLogic™. METHODS: In this multicenter retrospective study, patients with a CIED and HeartLogic™ algorithm under structured follow-up were included. Patients were classified as having "substantial benefit" or "no benefit" from monitoring. RESULTS: In total, 242 patients were included (male n = 190, 79%, median age 61 years [IQR 61-77]). Median follow-up was 1.2 years [IQR 1.1-2.7]. Among 378 alerts, 266 were true positive (70%) and 112 false positive (30%). Of the 242 patients, 69 (29%) were classified as having "substantial benefit", while 173 (71%) had "no benefit" from HeartLogic™ monitoring. Univariate and multivariate analysis showed that patients with "substantial benefit" had higher NYHA functional class (OR 2.64, P = 0.004), higher NT-ProBNP (OR 1.02, P = 0.003), higher serum creatinine (OR 1.10, P < 0.001), lower LVEF (OR 1.19, P = 0.004), more severe mitral regurgitation (OR 2.16, P = 0.006), higher right ventricular end diastolic volume (OR 1.05, P = 0.040), higher pulmonary artery pressures (OR 1.19, P = 0.003), and were more likely to use loop diuretics (OR 2.79, P = 0.001). Among patients with "substantial benefit," the positive predictive value (PPV) of HeartLogic™ to detect congestion was 92%. CONCLUSION: The utilization of CIED-based HeartLogic™ driven HF care demonstrated pronounced efficacy, predominantly in patients exhibiting characteristics of HF at a more advanced disease stage.

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Algoritmos , Insuficiencia Cardíaca , Humanos , Masculino , Femenino , Persona de Mediana Edad , Estudios Retrospectivos , Insuficiencia Cardíaca/diagnóstico , Anciano , Estudios de Seguimiento

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We previously reported that sodium-glucose cotransporter 2 (SGLT2) inhibitors exert sustained fluid homeostatic actions through compensatory increases in osmotic diuresis-induced vasopressin secretion and fluid intake. However, SGLT2 inhibitors alone do not produce durable amelioration of fluid retention. In this study, we examined the comparative effects of the SGLT2 inhibitor dapagliflozin (SGLT2i group, n = 53) and the combined use of dapagliflozin and conventional diuretics, including loop diuretics and/or thiazides (SGLT2i + diuretic group, n = 23), on serum copeptin, a stable, sensitive, and simple surrogate marker of vasopressin release and body fluid status. After six months of treatment, the change in copeptin was significantly lower in the SGLT2i + diuretic group than in the SGLT2i group (-1.4 ± 31.5% vs. 31.5 ± 56.3%, p = 0.0153). The change in the estimated plasma volume calculated using the Strauss formula was not significantly different between the two groups. Contrastingly, changes in interstitial fluid, extracellular water, intracellular water, and total body water were significantly lower in the SGLT2i + diuretic group than in the SGLT2i group. Changes in renin, aldosterone, and absolute epinephrine levels were not significantly different between the two groups. In conclusion, the combined use of the SGLT2 inhibitor dapagliflozin and conventional diuretics inhibited the increase in copeptin levels and remarkably ameliorated fluid retention without excessively reducing plasma volume and activating the renin-angiotensin-aldosterone and sympathetic nervous systems.

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Introduction Prolonged sitting-induced blood pooling in the lower legs can increase blood pressure through increased sympathetic nerve activity and peripheral vascular resistance, an aspect that has been understudied as a primary outcome. This study compared the effects of prolonged sitting with those of prolonged supination on blood pressure in healthy young men. Methods This randomized crossover study included 16 healthy young men (mean age: 21.6 ± 0.7 years) who were randomly assigned to a three-hour supine (CON) or three-hour sitting (SIT) condition, followed by a washout period of at least one week. Systolic blood pressure (SBP), diastolic blood pressure (DBP), mean arterial pressure (MAP), heart rate (HR), low-frequency/high-frequency (LF/HF) ratio derived from heart rate variability, and leg circumference were measured at 60, 120, and 180 minutes from baseline. These indices were compared by two-way (time × conditions) analysis of variance (ANOVA). Results In the SIT condition, DBP, MAP, HR, LF/HF ratio, and leg circumference increased significantly over time (P < 0.05) and were significantly higher than those in the CON condition (P < 0.05). However, SBP showed no significant change over time and between conditions. Conclusions The findings indicate the involvement of sympathetic nerve activity and increased peripheral vascular resistance induced by fluid retention in the lower legs with increased DBP and MAP in healthy young men.

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BACKGROUND & AIMS: The international cancer cachexia criteria with a cutoff of 5% weight loss (WL) was proposed in Western patients. The Asian Working Group for Cachexia (AWGC) developed new criteria in Asian patients. The AWGC criteria are not cancer-specific and employ a cutoff of 2% WL. However, it is unclear whether both criteria are useful in patients with very advanced cancer because WL can be underestimated owing to fluid retention. Therefore, this study aimed to investigate the impacts of fluid retention on the prognostic abilities of both criteria in cancer patients with weeks of survival. METHODS: This study involved a secondary analysis of a prospective cohort study. The inclusion criteria constrained the study to adult patients with advanced cancer. Patients were divided into Non-cachexia and Cachexia groups using the international criteria and AWGC criteria. We performed time-to-event analyses using the Kaplan-Meier method and log-rank tests, and by conducting univariate and multivariate Cox regression analyses. RESULTS: A total of 402 patients were included in the analysis. Using the international criteria, the p-values for the log-rank test and stratified log-rank test for the mixed patients with and without fluid retention were 0.55 and 0.18, respectively. Using the AWGC criteria, the p-values for the log-rank test and stratified log-rank test for the mixed patients with and without fluid retention were 0.38 and 0.12, respectively. Without considering the impacts of fluid retention, no significant differences were observed between the Non-cachexia and Cachexia groups for both criteria. After adjusting for the status of fluid retention, significantly higher risks of mortality were not observed in the Cox proportional hazard model for the Cachexia group compared with the Non-cachexia group, for both criteria. However, significant associations were observed between fluid retention and overall survival. CONCLUSIONS: The international criteria and AWGC criteria lost their prognostic abilities in cancer patients with weeks of survival. Since measurements of %WL were significantly confounded by fluid retention, fluid retention-adjusted criteria for cachexia need to be developed for cancer patients with refractory cachexia.

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Caquexia , Neoplasias , Adulto , Humanos , Caquexia/complicaciones , Caquexia/diagnóstico , Pronóstico , Estudios Prospectivos , Pérdida de Peso , Neoplasias/complicaciones

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INTRODUCTION: Docetaxel can cause fluid retention reactions (FRRs) and hypersensitivity reactions (HSRs). The manufacturer recommends a multi-day oral dexamethasone premedication to prevent these toxicities, but steroid related side effects and regimen compliance remain a concern. This study aimed to determine if modified dexamethasone premedication regimens resulted in differences in HSRs or FRRs to docetaxel. We also examined side effects of dexamethasone and delays in chemotherapy. METHODS: A retrospective chart review was conducted on 82 early breast cancer patients treated with docetaxel. Three steroid regimens were examined: IV 20 mg single-dose dexamethasone, or IV 12 mg dexamethasone with either dexamethasone 8 mg BID for three days starting the day before chemotherapy or dexamethasone 4 mg BID for three days following chemotherapy. Adverse effects, delays in chemotherapy, and reasons for delays in chemotherapy were recorded. RESULTS: The incidence and severity of FRRs and HSRs was low, with less than 10% incidence of HSRs or FRRs in any group. Delays were most common in the group receiving dexamethasone 8 mg BID for 3 days starting the day before chemotherapy (63.3%) (p < 0.05) and were most commonly due to patient noncompliance (26%). CONCLUSION: A single dose of intravenous dexamethasone alone or followed by lower doses of oral dexamethasone may improve patient compliance and avoid delays in chemotherapy, without an increase in docetaxel toxicity.

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Neoplasias de la Mama , Mastectomía , Humanos , Femenino , Neoplasias de la Mama/cirugía , Mastectomía Radical , Músculos Pectorales , Abdomen

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BACKGROUND: Urine output < 1 L per 24 h is a clinical warning sign that requires attention from hospital staff, who should determine whether the low flow is due to low habitual intake of water or disease-induced dehydration. The incidence of this condition is unclear. METHODS: A cohort of 20 healthy volunteers (mean age 42 years, range 23-62 years) recorded their food and water intakes daily for 8 days. They also collected and measured all urine and delivered first morning urine samples for analysis of osmolality and creatinine. Optimal cutoffs for these biomarkers to indicate urine output of < 1 L or 15 mL/kg during the preceding 24 h were applied with and without correction for age to cross-sectional data from 1,316 subjects in various clinical settings, including healthy volunteers, preoperative patients, patients seeking acute care at a hospital, and patients receiving institutional geriatric care. RESULTS: The urine output amounted to < 1 L during 22 of the 159 evaluable study days and was indicated by urine osmolality > 760 mosmol/kg or urine creatinine > 13 mmol/L, which had sensitivity and specificity of approximately 80%. Days with urine output < 1 L were associated with significantly less intake of both water (-41%) and calories (-22%) compared to other days. Application of age-corrected biomarker cutoffs to the 1,316 subjects showed a stronger dependency of low urine output on age than the clinical setting, occurring in 44% of the 72 participants aged 15-30 years and 18% of the 62 patients aged 90-104 years. CONCLUSION: Biomarkers measured in morning urine of young and middle-aged volunteers indicated urine output of < 1 L with good precision, but the cutoffs should be validated in older age groups to yield reliable results. TRIAL REGISTRATIONS: ISRCTN12215472 at http://www.isrctn.com ; NCT01458678 at ClinicalTrials.gov, and ChiCTR-TNRC-14,004,479 at the chictr.org/en.

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ObjectiveTo investigate the effects of Linggui Zhugantang （LGZGT）-containing serum on primary astrocytes （AS） induced by β amyloid 1-42 （Aβ1-42） in a rat model of Alzheimer's disease （AD） and explore the phagocytic and degradative effects of LGZGT on Aβ. MethodAn AD model was established by inducing AS with Aβ1-42. The cells were divided into normal group， model group， LGZGT low-， medium-， and high-dose （LGZGT-L， LGZGT-M， and LGZGT-H） groups， and donepezil hydrochloride group. The model group was treated with Aβ1-42 at a final concentration of 10 μmol∙L-1. The LGZGT-L， LGZGT-M， and LGZGT-H groups were treated with 10% serum containing LGZGT on the basis of the model group. Cell viability was assessed using a cell counting kit-8 （CCK-8）， lactate dehydrogenase （LDH） activity was measured using an LDH assay kit， and cell morphology was observed using an inverted microscope. The expression of Aβ-related degradation enzymes insulin-degrading enzyme （IDE） and cathepsin D （CTSD） was detected using Western blot， and the fluorescence intensity of cathepsin B （CTSB） was measured using immunofluorescence. The content of Aβ1-42 in cells was determined using an enzyme-linked immunosorbent assay （ELISA）. ResultCompared with the normal group， the viability of AS in all groups decreased， and Aβ1-42 at different concentrations had inhibitory effects on AS proliferation. After administration， compared with the normal group， the cell survival rate of the model group decreased significantly （P<0.05）. Compared with the model group， the cell survival rates of the LGZGT-H group and donepezil hydrochloride group increased significantly （P<0.05）. The LDH activity of cells in the model group was significantly increased compared with that in the normal group （P<0.05）， and cell bodies were swollen and enlarged with increased protrusions and elongation， suggesting more obvious cell damage. Compared with the model group， the LDH activity of cells in the donepezil hydrochloride， LGZGT-L， LGZGT-M， and LGZGT-H groups decreased significantly （P<0.05）. After administration， the cell swelling in the LGZGT-M， LGZGT-H， and donepezil hydrochloride groups improved， cell protrusions shortened， and cell clustering decreased. Compared with the normal group， the expression of IDE and CTSD in the model group decreased significantly （P<0.05）. Compared with the model group， the expression of IDE increased significantly in the LGZGT-M and LGZGT-H groups （P<0.05）. Compared with the model group， the expression of CTSD increased significantly in the LGZGT-L， LGZGT-M， LGZGT-H， and donepezil hydrochloride groups （P<0.05）. The average fluorescence intensity of CTSB in the model group was significantly lower than that in the normal group （P<0.05）. Compared with the model group， the average fluorescence intensity of CTSD in the LGZGT-L， LGZGT-M， LGZGT-H， and donepezil hydrochloride groups increased significantly （P<0.05）. The intracellular content of Aβ1-42 in cells in the model group was significantly higher than that in the normal group （P<0.05）. After administration， compared with the model group， the intracellular content of Aβ1-42 in cells in the LGZGT-L， LGZGT-M， LGZGT-H， and donepezil hydrochloride groups decreased significantly （P<0.05）， and LGZGT-containing serum reduced Aβ1-42 in a dose-dependent manner （P<0.05）. ConclusionLGZGT has a protective effect on Aβ1-42-induced AS and can promote the degradation of Aβ. Its mechanism may be related to reducing Aβ toxicity， enhancing cell viability， promoting the expression of IDE， CTSD， and CTSB， and restoring lysosomal function.

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To date, there have been limited reports on the efficacy of Kampo medicine in treating obsessive compulsive behaviors. To the best of our knowledge, there have been no previous reports on the efficacy of ryokeijutsukanto for obsessive compulsive behaviors. Here, we describe 2 cases of obsessive-compulsive behavior successfully treated with ryokeijutsukanto. Case 1 involved a 30-year-old female patient who presented with vague anxiety. As a result, she spent significant time engaging in compulsive behavior related to checking and was frequently tardy to work. She met the diagnostic criteria for obsessive compulsive disorder. We prescribed ryokeijutsukanto. Her compulsive behavior then improved from 40 minutes to 5 minutes in 56 days. Case 2 involved 57-year-old female patient who complained of not feeling refreshed in the morning. In addition, she had a feeling of gloom, daytime sleepiness and compulsive behavior of checking about 5 times whether windows were locked. We prescribed ryokeijutsukanto. In 14 days, her checking behavior then improved from 5 times to once. Other troublesome symptoms also improved. Ryokeijutsukanto is usually utilized for patients with fluid retention, dizziness, and qi counterflow. However, these 2 cases have qi stagnation rather than qi counterflow. These results suggested that ryokeijutsukanto could also be utilized to treat compulsive behaviors when patients had fluid retention, dizziness and qi stagnation.

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Sodium and fluid retention in liver disease is classically thought to result from reduced effective circulating volume and stimulation of the renin-angiotensin-aldosterone system (RAAS). Aldosterone dives Na+ retention by activating the mineralocorticoid receptor and promoting the maturation and apical surface expression of the epithelial Na+ channel (ENaC), found in the aldosterone-sensitive distal nephron. However, evidence of fluid retention without RAAS activation suggests the involvement of additional mechanisms. Liver disease can greatly increase plasma and urinary bile acid concentrations and have been shown to activate ENaC in vitro. We hypothesize that elevated bile acids in liver disease activate ENaC and drive fluid retention independent of RAAS. We therefore increased circulating bile acids in mice through bile duct ligation (BDL) and measured effects on urine and body composition, while using spironolactone to antagonize the mineralocorticoid receptor. We found BDL lowered blood [K+] and hematocrit, and increased benzamil-sensitive natriuresis compared to sham, consistent with ENaC activation. BDL mice also gained significantly more body water. Blocking ENaC reversed fluid gains in BDL mice but had no effect in shams. In isolated collecting ducts from rabbits, taurocholic acid stimulated net Na+ absorption but had no effect on K+ secretion or flow-dependent ion fluxes. Our results provide experimental evidence for a novel aldosterone-independent mechanism for sodium and fluid retention in liver disease which may provide additional therapeutic options for liver disease patients.

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Protein ingestion is known to enhance post-exercise hydration. Whether the type of protein (i.e., whey, casein) can alter this response is unknown. Accordingly, this study aimed to compare the effects of the addition of milk-derived whey isolate or casein protein to carbohydrate-electrolyte (CE) drinks on post-exercise rehydration and endurance capacity. Thirty male soldiers (age: 24 ± 2.1 y; VO2max: 49.3 ± 4.7 mL/kg/min) were recruited. Upon losing ~2.2% of body mass by running in warm and humid conditions (32.3 °C, 76% relative humidity [RH]), participants ingested either a CE solution (66 g/L carbohydrate [CHO]), or CE plus isolate whey protein (CEW, 44 g/L CHO, 22 g/L isolate whey), or CE plus isolate casein protein (CEC, 44 g/L CHO, 22 g/L isolate casein) beverage in a volume equal to 150% of body mass loss. At the end of the 3 h rehydration period, a positive fluid balance was higher with CEW (0.22 L) compared to CEC (0.19 L) and CE (0.12 L). Overall mean fluid retention was higher in CEW (80.35%) compared with the CE (76.67%) and CEC trials (78.65%). The time of the endurance capacity test [Cooper 2.4 km (1.5 miles) run test] was significantly higher in CEC (14.25 ± 1.58 min) and CE [(12.90 ± 1.01 min; (p = 0.035)] than in CEW [(11.40 ± 1.41 min); (p = 0.001)]. The findings of this study indicate that the inclusion of isolate whey protein in a CE solution yields superior outcomes in terms of rehydration and enhanced endurance capacity, as compared to consuming the CE solution alone or in conjunction with isolate casein protein.

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Caseínas , Carbohidratos de la Dieta , Masculino , Humanos , Adulto Joven , Adulto , Proteína de Suero de Leche , Carbohidratos de la Dieta/farmacología , Ejercicio Físico/fisiología , Equilibrio Hidroelectrolítico , Electrólitos , Resistencia Física

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Docetaxel, a taxoid chemotherapy agent, may induce fluid retention. We present a case of metastatic breast cancer in which high output caused by docetaxel-induced fluid retention resulted in heart failure due to left ventricular outflow tract (LVOT) obstruction. A 58-year-old woman presented with exertional dyspnea and anasarca. The jugular venous pressure was elevated, and the carotid pulse was pulsus bisferiens with a spike-and-dome configuration. On auscultation, a mid-late systolic murmur that did not radiate to the neck but increased with the Valsalva maneuver was noted. Echocardiography revealed a left ventricular ejection fraction of 63% with systolic anterior motion (SAM) of the mitral valve, resulting in LVOT obstruction with a resting pressure gradient of 64 mmHg and moderate to severe mitral regurgitation. Treatment with carvedilol, trichlormethiazide, and an increased dose of furosemide gradually improved her symptoms, physical findings, and echocardiographic abnormalities. This case highlights the importance of recognizing high-output heart failure along with LVOT obstruction in patients scheduled to receive docetaxel.

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BACKGROUND: Endothelin A receptor antagonists (ETARA) slow chronic kidney disease (CKD) progression but their use is limited due to fluid retention and associated clinical risks. Sodium-glucose co-transporter 2 inhibitors (SGLT2i) cause osmotic diuresis and improve clinical outcomes in CKD and heart failure. We hypothesized that co-administration of the SGLT2i dapagliflozin with the ETARA zibotentan would mitigate the fluid retention risk using hematocrit (Hct) and bodyweight as proxies for fluid retention. METHODS: Experiments were performed in 4% salt fed WKY rats. First, we determined the effect of zibotentan (30, 100 or 300 mg/kg/day) on Hct and bodyweight. Second, we assessed the effect of zibotentan (30 or 100 mg/kg/day) alone or in combination with dapagliflozin (3 mg/kg/day) on Hct and bodyweight. RESULTS: Hct at Day 7 was lower in zibotentan versus vehicle groups [zibotentan 30 mg/kg/day, 43% (standard error 1); 100 mg/kg/day, 42% (1); and 300 mg/kg/day, 42% (1); vs vehicle, 46% (1); P < .05], while bodyweight was numerically higher in all zibotentan groups compared with vehicle. Combining zibotentan with dapagliflozin for 7 days prevented the change in Hct [zibotentan 100 mg/kg/day and dapagliflozin, 45% (1); vs vehicle 46% (1); P = .44] and prevented the zibotentan-driven increase in bodyweight (zibotentan 100 mg/kg/day + dapagliflozin 3 mg/kg/day = -3.65 g baseline corrected bodyweight change; P = .15). CONCLUSIONS: Combining ETARA with SGLT2i prevents ETARA-induced fluid retention, supporting clinical studies to assess the efficacy and safety of combining zibotentan and dapagliflozin in individuals with CKD.

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Diabetes Mellitus Tipo 2 , Insuficiencia Renal Crónica , Inhibidores del Cotransportador de Sodio-Glucosa 2 , Simportadores , Animales , Ratas , Inhibidores del Cotransportador de Sodio-Glucosa 2/farmacología , Inhibidores del Cotransportador de Sodio-Glucosa 2/uso terapéutico , Antagonistas de los Receptores de la Endotelina A , Receptor de Endotelina A , Ratas Endogámicas WKY , Compuestos de Bencidrilo/farmacología , Compuestos de Bencidrilo/uso terapéutico , Glucosa , Sodio , Diabetes Mellitus Tipo 2/tratamiento farmacológico

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BACKGROUND: There is little evidence that supports the registered high dose of dexamethasone used around docetaxel. However, this high dose is associated with considerable side effects. This study evaluates the feasibility of reducing the prophylactic oral dosage of dexamethasone around docetaxel infusion. PATIENTS AND METHODS: Eligible patients had a histologically confirmed diagnosis of prostate or breast cancer and had received at least three cycles of docetaxel as monotherapy or combination therapy. Prophylactic dexamethasone around docetaxel infusion was administered in a de-escalating order per cohort of patients. Primary endpoint was the occurrence of grade III/IV fluid retention and hypersensitivity reactions (HSRs). RESULTS: Of the 46 enrolled patients, 39 were evaluable (prostate cancer (n = 25), breast cancer (n = 14). In patients with prostate cancer, the dosage of dexamethasone was reduced to a single dose of 4 mg; in patients with breast cancer, the dosage was reduced to a 3-day schedule of 4 mg-8 mg-4 mg once daily, after which no further reduction has been tested. None of the 39 patients developed grade III/IV fluid retention or HSR. One patient (2.6%) had a grade 1 HSR, and there were six patients (15.4%) with grade I or II edema. There were no differences in quality of life (QoL) between cohorts. CONCLUSIONS: It seems that the prophylactic dose of dexamethasone around docetaxel infusion can be safely reduced with respect to the occurrence of grade III/IV HSRs or the fluid retention syndrome.

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BACKGROUND: The hydration status can be indicated by biomarkers in the urine. However, the sensitivity and specificity of single measurements of biomarkers in morning urine and spot urine samples to quantify previous and current daily water ingestion is unclear. METHODS: The water content of food and liquid consumed by 20 volunteers (mean age 42 years) was calculated daily for two weeks. The volunteers increased their consumption of water by approximately 30% during the second week. They measured their excreted urine volume and sampled the morning urine and 24-h collections of urine for analysis of osmolality and creatinine during the first four days of both weeks (N = 157). The same biomarkers of hydration were measured in spot samples taken at every voiding on the other days (N = 762). Receiver operating characteristic (ROC) curves were used to study the ability of pre-specified ranges of biomarkers to quantify the water intake. RESULTS: The biomarkers in the morning urine obtained during normal fluid intake quantified the water consumption with an average area under the ROC curve (AUC) of 0.72 for osmolality and 0.66 for creatinine. Spot urine yielded an AUC of 0.74 for osmolality and 0.70 for creatinine. The AUCs obtained for days of increased fluid intake were approximately 10% lower. Large intakes (3-4 L daily) were identified with a sensitivity of 50-80% and low intakes (< 1.5-2 L) with a sensitivity of 20-50%, while false positives occurred in approximately 10%. CONCLUSION: Biomarkers in morning urine and spot urine samples distinguished between large and small daily water intakes. Osmolality was slightly superior to creatinine. The indications were less useful during days of increased fluid intake.

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The burden of chronic kidney disease is increasing worldwide, largely due to the increasing global prevalence of diabetes mellitus and hypertension. While renin angiotensin system inhibitors and sodium-glucose cotransporter two inhibitors are the management cornerstone for reducing kidney and cardiovascular complications in patients with diabetic and non-diabetic kidney disease (DKD), they are partially effective and further treatments are needed to prevent the progression to kidney failure. Endothelin receptor antagonism represent a potential additional therapeutic option due to its beneficial effect on pathophysiological processes involved in progressive kidney disease including proteinuria, which are independently associated with progression of kidney disease. This review discusses the biological mechanisms of endothelin receptor antagonists (ERA) in kidney protection, the efficacy and safety of ERA in randomised controlled trials reporting on kidney outcomes, and its potential future use in both diabetic and non-DKDs.

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Diabetes Mellitus , Nefropatías Diabéticas , Insuficiencia Renal Crónica , Humanos , Antagonistas de los Receptores de Endotelina/efectos adversos , Riñón , Nefropatías Diabéticas/tratamiento farmacológico , Nefropatías Diabéticas/etiología , Nefropatías Diabéticas/prevención & control , Insuficiencia Renal Crónica/complicaciones , Insuficiencia Renal Crónica/tratamiento farmacológico , Antihipertensivos/uso terapéutico , Antagonistas de Receptores de Angiotensina/uso terapéutico , Diabetes Mellitus/tratamiento farmacológico

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Imatinib is a crucial therapeutic strategy against chronic myeloid leukemia. Though superficial edema is a common adverse effect of imatinib, massive fluid retention is rarely reported. Here, we report the case of an adolescent who had tolerated imatinib for a long time, and then presented with massive pleural/pericardial effusion during an episode of Campylobacter jejuni bacteremia. A stepwise and comprehensive survey excluded all other plausible causes of disease. The Naranjo scale was used to assess the probability of an adverse effect of medication, and the score turned out to be 9, indicating severe fluid retention to be a definite reaction to imatinib. Drug discontinuation, antibiotic administration, and invasive procedures improved this condition. After this episode, the patient could tolerate imatinib again, illustrating the transient and reversible nature of this reaction. Since prolonged imatinib usage is crucial for chronic myeloid leukemia control, alertness to drug-related adverse effects is recommended, even if the subject has previously shown a good tolerance to the drug due to various physical conditions, especially physiological stressors, like infection or inflammation.

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Antineoplásicos , Bacteriemia , Campylobacter , Leucemia Mielógena Crónica BCR-ABL Positiva , Derrame Pericárdico , Adolescente , Antineoplásicos/efectos adversos , Bacteriemia/tratamiento farmacológico , Dasatinib/uso terapéutico , Humanos , Mesilato de Imatinib/efectos adversos , Leucemia Mielógena Crónica BCR-ABL Positiva/tratamiento farmacológico

RESUMEN

This paper examines evidence implicating migraine headache as a withdrawal symptom of excessive sodium chloride intake. Emerging research in food addiction posits that food and drug addictions share common features, such as withdrawal symptoms. Salt (sodium chloride) meets the criteria for the diagnosis of substance dependence, including withdrawal in which the substance is used to relieve withdrawal symptoms. The premonitory symptoms of migraine include food cravings for salty foods, which can alleviate migraine pain. Edema, possibly related to large amounts of salt consumed in binge eating, can cause approximately four pounds of retained fluid. This amount of fluid is similar to the fluid retained before the onset of migraine headache, which may be accompanied by polyuria. This paper proposes that inhibited withdrawal from highly processed food intake, rich in salt, mediates an association between increased sodium chloride intake and relief from migraine headache pain. The relief from withdrawal symptoms could also be a mediating factor that explains the controversial findings inversely associating dietary sodium intake with migraine history. Moreover, the withdrawal of retained sodium and edema related to the use of nonsteroidal anti-inflammatory drugs may elucidate a potential mechanism in medication overuse headache. Further research is needed to investigate the pain experienced from sodium chloride withdrawal in migraine headache.

Asunto(s)

Cefaleas Secundarias , Trastornos Migrañosos , Síndrome de Abstinencia a Sustancias , Trastornos Relacionados con Sustancias , Humanos , Trastornos Migrañosos/tratamiento farmacológico , Dolor , Cloruro de Sodio/efectos adversos , Cloruro de Sodio Dietético/efectos adversos